Research Communities by Springer Nature

Behind the Paper: Teaching AI to See What the Eye Cannot

Yavuz Ünal — Mon, 18 May 2026 15:37:08 +0100

Can a deep learning model detect the subtle signs of diabetic retinopathy — before it's too late?

Diabetic retinopathy is one of those silent diseases that quietly steals vision while patients go about their daily lives. As a computer engineer working at the intersection of artificial intelligence and real-world problems, I've always been drawn to challenges where technology can make a tangible difference. This paper — Automated Seven-Stage Diabetic Retinopathy Grading Using Optimized Deep Networks Through Systematic Hyperparameter Tuning — represents my attempt to push automated DR diagnosis further than the conventional binary or five-stage approaches that dominate the literature.

Why Seven Stages Matter

Most existing studies simplify diabetic retinopathy into a binary problem (DR vs. no DR) or a five-class task. But clinicians don't think in binaries. The progression from mild non-proliferative DR to advanced proliferative DR involves subtle, gradual changes — each stage carrying different implications for treatment timing and strategy. A system that can distinguish all seven stages provides clinicians with the granular information they actually need to make decisions. That was the core motivation behind this work.

The Dataset Challenge

Working with a publicly available dataset of 1,437 fundus images sounds straightforward until you look at the class distribution. One of the most critical stages — Mild NPDR — had only six original images. Six. This is a common reality in medical imaging: the cases you most need to detect are often the rarest in your dataset.

Rather than giving up on fine-grained classification, I designed an extensive data augmentation pipeline — rotations, shifts, reflections, and scaling — that expanded the dataset to nearly 16,000 images while preserving the integrity of pathological features. The key was ensuring that augmentation didn't introduce artifacts that the model might learn instead of genuine disease markers.

Making the Invisible Visible with CLAHE

Fundus images can be deceptively uniform to the untrained eye. Subtle hemorrhages, tiny microaneurysms, and early exudates often hide in low-contrast regions. Before feeding images to any deep learning model, I applied Contrast Limited Adaptive Histogram Equalization (CLAHE) — a technique that enhances local contrast by processing the image in small tiles rather than globally. The difference was remarkable: features that were nearly invisible in the original images became clearly distinguishable after CLAHE preprocessing. This step alone significantly improved the model's ability to detect early-stage disease.

Letting the Algorithm Choose Its Own Architecture

Here's where the story gets interesting. Instead of hand-picking a deep learning architecture based on intuition or popularity, I used Optuna — a Bayesian optimization framework — to systematically evaluate nine pre-trained architectures: ResNet50, DenseNet121, EfficientNetB0, Xception, InceptionV3, VGG16, MobileNetV2, NASNetLarge, and InceptionResNetV2.

The winner? NASNetLarge — not the most commonly used architecture in DR literature, but the one that objectively performed best on this specific dataset. This finding reinforced an important lesson: the "best" model depends entirely on your data and task. There's no universal answer, and systematic search beats educated guessing.

Fine-Tuning with Grid Search

Once NASNetLarge was identified, I used Grid Search to exhaustively optimize hyperparameters: dropout rate, batch size, optimizer, learning rate, dense units, and the number of frozen layers. The optimal configuration — Adam optimizer, learning rate of 0.0001, dropout of 0.3, batch size of 64, and 713 frozen layers — achieved 98.39% classification accuracy, confirmed by 5-fold cross-validation at 98.50% ± 0.21%.

What struck me most was how sensitive the model was to batch size. Moving from 32 to 64 produced a dramatic accuracy jump, suggesting that the larger batch provided more stable gradient estimates during training — a detail easily overlooked but critical in practice.

Can We Trust What the Model Sees?

Accuracy numbers are important, but they don't tell the whole story. For a model to be clinically useful, we need to understand why it makes its decisions. Using saliency map visualization, I examined which regions of each fundus image most influenced the model's predictions.

The results were encouraging: in early DR stages, the model focused on central retinal areas around the optic disc and vasculature — exactly where microaneurysms and hemorrhages first appear. In advanced proliferative stages, attention patterns became more diffuse, reflecting the widespread retinal damage characteristic of severe disease. The model wasn't memorizing textures or dataset quirks; it was learning genuinely meaningful pathological features.

Honest Limitations

No study is without limitations, and I want to be transparent about mine. The Mild NPDR class, despite achieving perfect classification scores, started with only six original images. While augmentation addressed the imbalance effectively, there's always a risk that the model learned augmentation patterns rather than true disease features. External validation on independent datasets from different populations and imaging devices remains essential before any clinical deployment.

Looking Forward

This work demonstrates that systematic optimization — rather than manual trial-and-error — can push automated DR diagnosis to new levels of accuracy and reliability. But the real goal extends beyond numbers on a page. Diabetic retinopathy affects millions worldwide, and many patients in underserved regions lack access to specialist ophthalmologists. An AI system capable of reliable seven-stage grading could serve as a powerful screening tool, flagging patients who need urgent intervention and potentially saving countless eyes from preventable blindness.

The code and dataset are publicly available, and I hope this work encourages others to build upon it — with larger datasets, external validation, and ultimately, clinical trials that bring AI-assisted diagnosis from the laboratory to the clinic.

Yavuz Unal is a faculty member in the Department of Computer Engineering at Sinop University, Turkey. His research focuses on computer vision and deep learning applications in agricultural science, food quality assessment, and medical image analysis.

Read the full paper: Automated Seven-Stage Diabetic Retinopathy Grading Using Optimized Deep Networks Through Systematic Hyperparameter Tuning

Differential expression of long-noncoding RNAs under drought stress in tomato (Solanum lycopersicum)

Elif KARLIK URHAN — Mon, 18 May 2026 15:13:41 +0100

This study investigated the physiological and molecular responses of two tomato cultivars exposed to seven days of drought stress, with a particular focus on long non-coding RNAs (lncRNAs). Morphological and physiological analyses revealed significant differences between the drought-tolerant Falcon and drought-sensitive SC2121 cultivars in terms of shoot growth, root development, chlorophyll content, soluble protein accumulation, and water content. High-throughput RNA sequencing identified 269 drought-responsive lncRNAs, including 124 upregulated and 145 downregulated transcripts. Functional analyses suggested that several lncRNAs may regulate stress-related pathways associated with osmotic balance, transporter activity, and RNA splicing mechanisms. RT-qPCR validation confirmed the differential expression patterns of selected lncRNAs under drought conditions. Overall, the findings indicate that lncRNAs play important regulatory roles in tomato drought responses and may serve as potential targets for improving drought tolerance in crop breeding programs.

The Social Value of News

Tony Harcup — Mon, 18 May 2026 12:47:33 +0100

We get our news in a bewildering variety of ways these days, delivered 24/7 via platforms that can appear, alter and then sometimes disappear, all at dizzying speed. Whereas news once appeared as text circulating at regular intervals in printed form, augmented with the occasional illustration, we have now passed through a century of news being broadcast in sound and vision before coming out the other side with a pivot towards short-form video. The news industry now seems to be in a state of permanent flux.

It is true that many (usually older) people still get news from machines called TV sets and radios; also that a few of us (usually even older) still maintain print habits. But, increasingly, news is consumed in a fleeting fashion on smartphones. It flits past us, often without demanding deep levels of engagement. Even more worryingly, it can be hard at first glance to differentiate between news that has been carefully verified by reporters and lookalike ‘content’ that may have been generated by AI with little or nothing in the way of human input, let alone ethics.

Within this context of rapid changes to the ways in which news is produced and consumed, there is a need to stand back from chasing clicks and feeding the ‘for you’ algorithm to ask ourselves: what’s it all for? This is where news values come in. News values are the reason why I believe the book What’s the Point of News? remains as relevant for journalists and scholars today as on its publication day. Because the book’s focus is, unashamedly, on the democratic value of news to citizens rather than its commercial value to multimedia corporations.

It was primarily to explore the possibilities of this democratic function of news that I embarked upon my research in the first place. A second motivation was the gradual realisation that a lot of teaching around what academics typically call news values may be missing the point. It can be useful in helping journalism students identify the most common ingredients of news stories, or the ways in which different frames can be constructed around events, but where exactly do ‘values’ – especially human values - fit in? What are often labelled in scholarly literature as ‘news values’ seem more accurately to be lists of factors or components rather than values in the sense of principles, beliefs or worth. The actual values that might or might not underpin choices made in news selection, production and presentation are often left unexamined when taxonomies of so-called news values are discussed or reproduced.

That got me thinking, and then writing. The resulting monograph, What's the Point of News?, is as much a celebration of news as it is a critique. Sure, there is much to criticise, but the news industry is not monolithic. As well as highlighting some dubious practices, it is always important to record and celebrate more positive choices made by those journalists who, individually and collectively, go out of their way to listen carefully to those with the least power in any given situation, and to direct critical questions at those with the most power. As such, What’s the Point of News? is, unapologetically, a normative account of what news should be. And could be, more often than it is, notwithstanding the difficult conditions under which many journalists labour today.

Chief among the values that ought to guide news reporting is that it should serve the public good by providing people with societally important and useful information, emphasising the social utility of news for an audience comprising not just isolated individuals but (potentially) active citizens. Amid the horror stories and the quirky tales, alongside the sensational and the entertaining, there is an urgent need for what might be thought of as socially enabling and democratically empowering information that strengthens active citizenship by promoting understanding and imaginative empathy. That may seem a lot to ask of a rough trade such as journalism, yet examples exist around the world and are discussed at length in the book.

News informed by such values serves us as citizens by, among other things, better reflecting and representing the diversity of our lives, recording people’s myriad activities not just as passive victims or bystanders but as participants in a public, social sphere. Recognition of this crucial role is already embedded in the best journalism training, which is not content simply to reproduce industry norms but also to question them. However, there ought to be scope within journalism education – as well as within journalism itself - to think even more widely and deeply about the ethics of it all; hence the book’s subtitle, A study in ethical journalism.

To this end, there is much of value we can learn by considering the principles and practices – both historical and contemporary - of alternative journalism, peace journalism, feminism and other areas of critical praxis that have emerged from within small-scale (often local) forms of citizen-focussed journalism. After all, news has never been the preserve of the corporate news industry, however much proprietors might wish that to be so, and the defence of news values cannot be left to those whose primary motive is profit. News should serve us as citizens, not just consumers. And, when ruling politicians can blithely dismiss critical scrutiny as ‘fake news’, carefully reported news has arguably never been of greater social value than it is right now.

Tony Harcup is an Emeritus Fellow at the University of Sheffield, UK. He worked as a journalist within mainstream and alternative media before becoming a teacher, researcher and author. His books include the Oxford Dictionary of Journalism (2014); Alternative Journalism, Alternative Voices (2012); and Journalism: Principles and Practice (4^th ed, 2022). What’s the Point of News? is available in ebook, paperback and hardback. He can sometimes be found contributing to Bluesky as @writerlytone.

Opening the gate: how we learned to help antibiotics enter Pseudomonas aeruginosa

Muriel Masi — Mon, 18 May 2026 12:12:56 +0100

When we think about antibiotic resistance, we often focus on enzymes that degrade drugs or mutations that alter targets. But for Pseudomonas aeruginosa, one of the most problematic Gram-negative pathogens, the challenge starts even earlier: many antibiotics simply do not get in.

This question—how antibiotics enter bacterial cells—has been at the core of our work for several years. We have been particularly interested in the relationship between intracellular accumulation and antibacterial activity. In Escherichia coli, a set of physicochemical rules can often predict whether a compound will accumulate. But P. aeruginosa is different. Its outer membrane is much less permeable, its porins are highly selective, and its efflux systems are remarkably efficient. Together, these features create a formidable barrier.

This barrier has a striking consequence: antibiotics that are highly effective against other bacteria, such as doxycycline, are essentially inactive against P. aeruginosa. Not because they fail to hit their target, but because they never reach it in sufficient amounts.

Rather than designing entirely new antibiotics, we wondered whether it might be possible to help existing ones cross this barrier.

This is where NV716 comes in. This polyaminoisoprenyl compound had already been described as an antibiotic adjuvant capable of restoring the activity of several drugs in Gram-negative bacteria. However, its mechanism of action remained unclear. Did it inhibit efflux? Did it disrupt membranes? Or was something more subtle happening?

To address this, we decided to directly measure antibiotic accumulation and link it quantitatively to antibacterial activity. This required combining several approaches, from genetic models to fluorescence-based accumulation assays and advanced imaging techniques.

One of the first surprises came early. If NV716 were acting as an efflux inhibitor, we would expect to see a clear increase in the accumulation of antibiotics such as ciprofloxacin, which are strongly affected by efflux. But this was not the case. NV716 had little to no effect on ciprofloxacin accumulation under our conditions.

In contrast, the effect of doxycycline was immediate and striking. As soon as NV716 was added, intracellular accumulation increased dramatically in P. aeruginosa. Importantly, this effect was also observed in efflux-deficient strains, indicating that the mechanism was independent of efflux inhibition.

This pointed us toward the outer membrane.

Using a combination of biochemical assays and mutant strains, we found that NV716 interacts with lipopolysaccharides, the major components of the outer membrane. Rather than causing catastrophic damage, NV716 appears to induce controlled perturbation of membrane organization. This perturbation is sufficient to enhance antibiotic entry—particularly for doxycycline—without compromising the integrity of the inner membrane.

In other words, NV716 does not break the bacterial envelope; it subtly reshapes it.

To better understand what this perturbation looks like, we turned to imaging. This was one of the most exciting aspects of the project. By combining techniques such as cryo-soft X-ray tomography and nano-XRF, we were able to visualize membrane-associated changes and track the localization of the compound at the nanoscale.

One consistent observation was an increase in outer membrane vesicle production. These vesicles are known to be released in response to envelope stress, suggesting that the bacterial cell senses and responds to NV716-induced perturbation. Seeing this response emerging across different experimental scales—from population-level assays to single-cell imaging—was particularly rewarding.

Another important step was to move beyond qualitative observations and establish a quantitative framework. By measuring accumulation kinetics and applying a diffusion-based model, we could estimate changes in membrane permeability. This allowed us to directly connect a physical parameter—outer membrane permeability—to a biological outcome—antibiotic activity.

More broadly, our results support the idea that outer membrane permeability is a key determinant of antibiotic efficacy in Gram-negative bacteria and that it can be modulated in a controlled manner.

This has important implications. If we can tune membrane permeability, we may be able to broaden the range of compounds effective against intrinsically resistant bacteria such as P. aeruginosa. This includes not only existing antibiotics, but also new molecules that would otherwise fail to accumulate.

Of course, many questions remain. In our preliminary in vivo experiments, the NV716-doxycycline combination showed a trend toward improved survival, but it was not statistically significant under the tested conditions. Bridging the gap between enhanced accumulation and therapeutic efficacy will require further work and optimized models.

Nevertheless, this study provides a framework for thinking about antibiotic entry in a more quantitative and mechanistic way.

Ultimately, overcoming antibiotic resistance may not always require stronger drugs. Sometimes, it may simply require helping them get inside.

Do you want to know more? Take a look at our article in npj Antimicrobials and Resistance: https://doi.org/10.1038/s44259-026-00203-w

Welcome to our new Planetary Science Editors

Frank Schulz — Mon, 18 May 2026 12:09:27 +0100

We are happy to announce that renowned experts Jean-Michel Désert (AIP), Sonia Fornasier (LIRA), and Anni Määttänen (LATMOS/IPSL) join the Editorial Board of The Astronomy and Astrophysics Review to form a new planetary science team, which replaces former Editor Luisa M. Lara, who served in this role from 2021 to 2025.

What Brazilian hospitals taught me about resilience under pressure

Raimundo Nonato Diniz Rodrigues Filho — Mon, 18 May 2026 12:00:31 +0100

Several studies have associated emergency department overcrowding, operational fragmentation, and staff overload with patient safety risks, delayed care, communication failures, and burnout in healthcare systems worldwide. Discussions in quality improvement, resilience engineering, and healthcare operations research have increasingly reinforced the importance of governance structures, operational coordination, and organizational resilience in highly pressured environments.

Over the last few years, I have participated in projects involving Lean Healthcare, organizational maturity assessment, clinical governance, and emergency department overcrowding analysis in Brazilian hospitals.

These experiences — combined with operational work in intensive care units, emergency departments, and healthcare leadership — reinforced an important perception:

Resilience in healthcare systems is often misunderstood.

In many organizations, resilience becomes associated with the ability of professionals to continue operating despite chronic overload. However, operational experience and quality improvement initiatives increasingly demonstrate that sustainable healthcare systems cannot depend indefinitely on extraordinary individual effort alone.

Eventually, even highly committed teams become vulnerable when governance structures, operational visibility, communication flows, and decision-making processes become fragile.

In projects related to operational flow and organizational maturity, it became clear that resilient systems are characterized not only by technical competence, but by their ability to maintain coordination under pressure.

This includes:

reliable operational data;
governance structures capable of supporting decision-making;
communication alignment between teams;
organizational trust;
and operational models capable of functioning even during periods of saturation.

Many healthcare crises are not necessarily generated by lack of technical knowledge.

They emerge from fragmentation.

Fragmented communication.
Fragmented accountability.
Fragmented operational visibility.
Fragmented priorities.

Under pressure, fragmented systems collapse faster.

At the same time, I have also witnessed remarkable operational recoveries in hospitals capable of reorganizing flow, rebuilding governance mechanisms, and restoring alignment between teams even in highly constrained environments.

These experiences significantly changed the way I understand healthcare leadership and operational resilience.

Resilience is not the absence of pressure.

It is the capacity of the system to continue functioning safely, coherently, and predictably despite pressure.

And perhaps that is one of the most important lessons Brazilian hospitals have taught me.

References

To Err Is Human: Building a Safer Health System
Resilient Health Care
The association between emergency department crowding and adverse patient outcomes: a systematic review
Burnout in healthcare professionals: a call for organizational action
Goodhart’s Law and healthcare performance measurement

When organic dyes work better together

Luka Đorđević — Mon, 18 May 2026 10:43:39 +0100

Organic dyes absorb visible light strongly, can be synthesized and modified with precision, and are attractive building blocks for photocatalysis and artificial photosynthesis.^[1] Yet they often face two persistent problems: they degrade under irradiation and, when they aggregate, their excited states are usually quenched before they can do useful chemistry. For this reason, aggregation is often treated as something to avoid in molecular photocatalysis. In our work, we asked whether this assumption could be reversed. Could aggregation itself become the feature that activates an organic dye for photocatalysis?

The idea is conceptually simple. Some organic dyes lose absorbed energy through intramolecular motion: twisting, rotation or structural relaxation in the excited state. If these motions are restricted, more excited states survive long enough to react. This principle is well known in aggregation-induced emission,^[2,3] where molecules become brighter when they assemble. We wondered whether the same rigidification could also make them better photocatalysts (Figure 1a).

Figure 1. a, Overview of the rigidification in DSA molecules through supramolecular polymerization, obstructing otherwise rapid non-radiative decay of the photoexcited state. b, Aggregation leads to excited-states enhancement and photocatalysis (H₂ or H₂O₂ photoproduction), with improved dye properties such as stability and recovery. c, Chemical structure of distyrylanthracene (DSA2+) amphiphile where X⁻ indicates the counteranion. GS, ground state; ES, excited state; Sub, substrate; Pdt, product.

This project began from a serendipitous observation. Recently, we reported dye-based aggregates in which aggregation enhanced fluorescence and could be exploited for photocatalysis.^[4,5] These results suggested that emissive aggregation might be a powerful handle for light-driven chemistry, but they also revealed a limitation: both systems depended on rather specific packing motifs, making it difficult to generalize the concept. We therefore moved from serendipitous discovery to a deliberately designed system, choosing distyrylanthracene (DSA), as a tunable amphiphilic dye platform that self-assembles in water and whose aggregation could be controlled through counterions, concentration and salt addition (Figure 1b). By changing these parameters, we could tune whether the molecules remained dissolved or formed supramolecular nanostructures. The key observation was that the most emissive aggregates were also the most photocatalytically active. Fluorescence thus became a reporter of a deeper process: aggregation was increasing the population of reactive excited states (Figure 2).

Figure 2. Aggregation-induced photocatalysis in a nutshell.
a, Photographs of DSA in solution and in the aggregated state under ambient light and UV irradiation, showing aggregation-induced fluorescence. b, Light-driven H₂ evolution by DSA in solution and as aggregates, showing that photocatalytic activity is switched on upon aggregation.

The work was initiated by an undergraduate researcher (Luca Vaccarin) and then took over by two PhD students (Marianna Barbieri and David Cappelletti). A key aspect of the work was the collaboration needed to connect molecular design, supramolecular structure, excited-state dynamics and photocatalytic function. Synthetic chemistry and photocatalysis provided the first clues, but the full picture required microscopy, three-dimensional electron diffraction, transient absorption spectroscopy, and mechanistic photochemical experiments. Contributions from colleagues in Padova, Bologna, Modena and Rigaku Europe allowed us to move beyond the simple observation that the aggregates were brighter, and to understand why they became more reactive under irradiation.

The assembled dyes produced reactive oxygen species under light irradiation. Mechanistic experiments showed that oxygen was required and identified superoxide as a key intermediate. In the absence of a probe molecule, this reactivity could be channelled into hydrogen peroxide formation. The same aggregates could also support hydrogen evolution in the presence of Pt nanoparticles and a sacrificial donor. In the dissolved state, the dye was essentially inactive; upon salt-induced aggregation, hydrogen production turned on (Figure 2).

One of the most interesting parts of the study was that the “best” aggregates were not the most thermodynamically ordered ones. Kinetically trapped aggregates outperformed annealed, thermodynamic structures in both reactive oxygen species generation and hydrogen evolution. This was surprising because many supramolecular photocatalysts are designed to maximize extended order, exciton migration and charge separation. Here, the opposite lesson emerged: local excited-state confinement and pathway-dependent aggregation can be more important than long-range structural perfection. This point was important for us because it changes how one might design soft organic photocatalysts. Instead of asking only how to obtain the most crystalline or electronically coupled assembly, we can ask how to trap a packing arrangement that best preserves reactive excited states. In this sense, supramolecular pathway control becomes a functional photocatalytic parameter.

We also wanted to know whether the concept was limited to one dye scaffold. We therefore tested a structurally different tetraphenylethylene (TPE) derivative, a classic aggregation-induced emission motif. Even though this chromophore forms amorphous rather than crystalline aggregates, it also became fluorescent and photocatalytically active upon aggregation. This supported the broader idea that aggregation-induced rigidification can activate different organic chromophores for light-driven chemistry.

More broadly, this work suggests that aggregation does not need to be the enemy of molecular photocatalysis. When properly controlled, it can suppress unproductive decay, improve photostability, enable recovery of the active material and retain some of the molecular precision of homogeneous dyes while gaining features usually associated with heterogeneous photocatalysts.

Do you want to know more? Take a look at our article in Nature Chemistry:
Supramolecular dye polymers for aggregation-induced photocatalysis

https://doi.org/10.1038/s41557-026-02151-4. I hope you enjoy it!

References

[1] Romero, N. A. & Nicewicz, D. A. Organic photoredox catalysis. Chem. Rev. 116, 10075–10166 (2016).

[2] Würthner, F. Aggregation-induced emission (AIE): a historical perspective. Angew. Chem. Int. Ed. 59, 14192–14196 (2020).

[3] Mei, J., Leung, N. L. C., Kwok, R. T. K., Lam, J. W. Y. & Tang, B. Z. Aggregation-induced emission: together we shine, united we soar! Chem. Rev. 115, 11718–11940 (2015).

[4] Đorđević, L. et al. Mechanical and light activation of materials for chemical production. Adv. Mater. 37, 2418137 (2025). https://doi.org/10.1002/adma.202418137

[5] Barbieri, M. et al. Controlled aggregation of pyrene-based supramolecular nanostructures for light-driven switchable H₂ or H₂O₂ production. Adv. Funct. Mater. 36, 2505835 (2026). https://doi.org/10.1002/adfm.202505835

Information Security with Smart Hydrogels: Photo‑Patterning and Multi‑Stimuli Responsive Structural Color

Lillian Zhang — Mon, 18 May 2026 09:26:47 +0100

Introduction: The Need for Sophisticated Information Encryption

In the modern digital age, information security and anti-counterfeiting technologies are more critical than ever. Traditional printing methods and static security labels are increasingly vulnerable to sophisticated forgery. Photonic crystals, which produce vibrant structural colors through the periodic arrangement of nanostructures rather than chemical pigments, have emerged as a powerful alternative. These "structural colors" are fade-resistant and can be designed to respond to external stimuli, providing a dynamic layer of security.

However, many existing photonic crystal systems are limited by high manufacturing costs and a lack of color diversity within a single substrate. To address these challenges, a research team led by Professor Bingtao Tang has developed a novel multi-color patterning method using smart anti-opal hydrogels. Their work, published in Nano-Micro Letters, introduces a "film formation first, then patterning" approach that significantly enhances information capacity and encryption complexity.

Material Design: The Anti-Opal Hydrogel Framework

The core of this technology is an anti-opal structural color hydrogel (ASCH). Unlike standard opal structures (which are made of spheres), an anti-opal structure consists of an ordered array of air voids within a solid matrix.

In this study, the researchers used a silica (SiO₂) opal template to create an ordered porous network within a responsive poly(acrylamide-co-acrylic acid) hydrogel. This hydrogel is "smart" because its volume changes in response to various environmental stimuli, such as pH levels, solvent composition, and temperature. As the hydrogel swells or shrinks, the lattice constant of the internal air-void array changes, causing the reflected structural color to shift across the visible spectrum.

The Mechanism of Photo-Patterning: Light-Induced Crosslinking

The most significant innovation of this research is the use of UV light to control the crosslinking density of the hydrogel film after it has been formed.

Selective Swelling Control: The hydrogel precursor contains photo-initiators that allow for further crosslinking when exposed to UV light. By using a photomask or a programmed UV source, the researchers can create regions with different crosslinking densities on a single film. Areas with a high crosslinking degree have a "tight" network that restricts swelling, while areas with low crosslinking can swell more freely.
High-Resolution Multi-Color Output: When the film is immersed in a stimulus (like a specific pH buffer), each region swells to a different extent, reflecting a different color. This allows for the creation of complex, multi-colored patterns with a minimum line width of just 15 micrometers. Because the color is determined by the light dose during the "patterning" phase, the researchers can "print" high-resolution images and codes without using any ink.

Multi-Stimuli Responsiveness and Dynamic Encryption

The structural color of the hydrogel is not static; it is a "living" response to the environment. The ASCH films demonstrate sensitivity to multiple triggers:

pH Sensing: The presence of acrylic acid groups makes the hydrogel highly sensitive to pH changes. A pattern might be invisible at a neutral pH but reveal a vibrant, multi-colored QR code when exposed to an acidic or alkaline solution.
Solvent Response: The hydrogel responds differently to various ethanol-water mixtures. This can be used for "liquid-authenticated" security, where the correct message only appears when the film is wetted with a specific solvent.
Mechanical and Thermal Tuning: The elastic nature of the hydrogel allows the color to be tuned by physical stretching or temperature changes.

This multi-stimuli responsiveness enables a "layered encryption" strategy. Information can be hidden in plain sight and only "decrypted" when the correct sequence of environmental triggers is applied.

Information Capacity and Security Applications

By combining high-resolution photo-patterning with dynamic color shifts, this technology vastly increases information density. A single hydrogel film can store multiple "pages" of information that are revealed under different conditions. For example, a film could display a brand logo under normal light, a serial number when wetted, and a hidden warning code when the pH is altered.

The "film formation first" approach also simplifies the manufacturing process. Large-scale hydrogel films can be produced and stored, then customized with specific patterns using simple UV exposure whenever needed. This makes the technology highly adaptable for high-end packaging, identity documents, and secure data storage.

Conclusion and Future Outlook

The development of photo-patternable smart hydrogels marks a significant milestone in the field of photonic materials and information security. By leveraging the principles of light-induced crosslinking and anti-opal structural colors, the researchers have created a platform that is both highly secure and aesthetically striking.

Future research will likely focus on integrating these hydrogels with flexible electronic circuits or smartphone-based detection systems to create "smart" labels that can be verified instantly by consumers. As the battle against forgery continues, materials that can "think" and "react" like these smart hydrogels will be at the forefront of protecting global information and trade.

Graphene Aerogel‑Based Flexible Pressure Sensor for Physiological Signal Detection and Human–Machine Interaction

Lillian Zhang — Mon, 18 May 2026 09:16:10 +0100

Introduction: The Evolution of Tactile Sensing

The rapid development of soft robotics, wearable health monitoring, and human-machine interaction (HMI) has created an urgent need for flexible pressure sensors that mimic the sophisticated tactile capabilities of human skin. Ideally, these sensors should possess high sensitivity to detect subtle physiological signals (like a pulse) while maintaining a broad detection range for forceful interactions (like grasping). Traditional flexible sensors often struggle to balance these two requirements, frequently sacrificing sensitivity for durability or range.

A research team led by Professor Li Yang and Professor Gaofeng Shao has addressed this challenge by developing an anisotropic reduced graphene oxide aerogel (rGOA). Their work, published in Nano-Micro Letters, demonstrates how structural biomimicry and advanced freeze-casting techniques can produce a sensor with record-breaking performance and multi-functional integration capabilities.

Structural Innovation: Anisotropy via Freeze-Casting

The core of this sensor's excellence is its unique internal architecture. Unlike isotropic aerogels, which have a uniform, sponge-like structure in all directions, the rGOA developed in this study features a highly ordered, anisotropic cellular structure.

This structure was achieved through a bidirectional freeze-casting process. By controlling the temperature gradient during the freezing of the graphene oxide precursor, the researchers forced the ice crystals to grow in a specific orientation. This "template" dictated the arrangement of the graphene sheets, resulting in a micro-structured framework that resembles the lamellar structure of certain biological tissues. This anisotropy is crucial because it allows the aerogel to deform predictably and efficiently under external pressure, maximizing the change in contact area between graphene layers.

Sensing Mechanism: The Synergy of Contact and Geometry

The high sensitivity of the rGOA sensor is rooted in the "contact resistance" mechanism. As pressure is applied, the internal lamellar layers of the graphene aerogel come into contact with one another.

Micro-scale Contact Variations: Because the graphene sheets are ultra-thin and organized into a hierarchical structure, even a minute force causes a significant increase in the number of contact points. This leads to a dramatic drop in the material's overall electrical resistance, which is translated into a high-fidelity electronic signal.
Wide Detection Range: The anisotropic design ensures that the aerogel does not fully collapse under low pressure, preserving its structural "headroom" for higher loads. This allows the sensor to maintain linear sensitivity across a wide pressure range, from the delicate touch of a feather to the heavy weight of industrial manipulation.

From Physiological Monitoring to Human-Machine Interaction

The practical utility of the rGOA sensor was demonstrated across several high-impact scenarios:

Health Monitoring: Due to its exceptional sensitivity, the sensor can be integrated into wearable patches to monitor real-time physiological signals. It can accurately capture the subtle "D-wave" and "P-wave" features of the human radial artery pulse, providing critical data for cardiovascular health assessment.
Intelligent Robotics and Teleoperation: The researchers integrated the rGOA sensors into robotic manipulators to provide "force feedback." In a teleoperation setup, a human operator wearing a sensory glove could "feel" the resistance of objects being grasped by a distant robot arm. This enabled the stable grasping of fragile objects, such as eggs and tofu, without causing damage.
Artificial Intelligence and Recognition: By combining the sensor data with machine learning algorithms, the team developed a "smart finger" capable of food recognition. The sensor could distinguish between different types of food (e.g., bread, fruit, meat) with 100% accuracy based on the unique mechanical "signature" or stiffness of each item during a press-and-release cycle.

Durability and Environmental Stability

For wearable and robotic applications, long-term reliability is non-negotiable. The rGOA-based sensor exhibited remarkable cyclic stability, maintaining its performance over 20,000 compression cycles. The reduced graphene oxide framework is inherently stable and resistant to environmental degradation, ensuring that the sensor remains accurate even after prolonged use in varying conditions. Additionally, the ultra-light density of the aerogel ensures that it adds negligible weight to wearable devices, enhancing user comfort.

Conclusion and Future Outlook

The development of anisotropic graphene aerogels marks a significant milestone in the field of flexible electronics. By moving beyond simple material composition to sophisticated structural engineering, the researchers have created a tactile sensing platform that rivals biological systems in both sensitivity and versatility.

This work provides a blueprint for the future of "electronic skin." As AI and robotics continue to merge with our daily lives, these high-performance, graphene-based sensors will be the key to enabling machines to interact with the world—and with humans—more safely, delicately, and intelligently.

Call for papers: Phase Change Materials in Altered and Low Gravity — From Principles to Applications in Space and Beyond

Frank Schulz — Mon, 18 May 2026 09:06:11 +0100

Microgravity Science and Technology opened a new topical collection that aims to advance the fundamental understanding of heat and mass transfer processes in regimes where classical, buoyancy-driven behavior is altered or suppressed.

We particularly encourage contributions that reveal new physical mechanisms, quantify deviations from Earth-based expectations, and establish links between material properties and system performance. Experimental, theoretical, and numerical studies are all welcome. The collection also highlights the growing role of PCMs in space exploration, especially in thermal management and energy systems, and highlights the mutual benefits of space-driven research for terrestrial technologies.

We invite all researchers to submit relevant contributions, original research papers as well as review articles. All submissions are peer reviewed and will be published in this collection as soon as they are accepted. Please see our submission guidelines for further technical details.

Submission deadline: 1 November 2026

Editors: Xinyu Huang (National University of Singapore), Pablo Salgado Sánchez (Universidad Politécnica de Madrid, Spain), Berin Šeta (Technical University of Denmark)

Beyond Fragmented Leadership Models: A Conceptual Integrated Theory of Leadership Effectiveness in a VUCA World

Lindiwe Ndaba — Mon, 18 May 2026 07:54:01 +0100

Story Behind the Article by Millicent Lindiwe Ndaba

https://doi.org/10.1007/s42087-026-00615-0

This article is not merely an academic exercise; it is the culmination of a lifelong leadership journey shaped by experience, faith, relationships, and reflection. For me, leadership has never been a position or title, it has always been a lived reality.

From an early age, I was entrusted with opportunities to lead, beginning in school and extending into student governance at university. These experiences introduced me to the responsibility of influence, the discipline of accountability, and the complexity of representing diverse voices. I learned early that leadership is not defined by being heard, but by the ability to listen, understand, and act in ways that create meaningful impact.

At the core of this journey has been my spiritual foundation. My Christian faith shaped my understanding of leadership as stewardship, an obligation to serve with integrity, humility, and purpose. This perspective became the ethical anchor of my thinking, reinforcing the belief that leadership is not about power, but about responsibility and the elevation of others.

My upbringing further deepened this orientation. As the firstborn and only daughter, I developed a strong sense of responsibility and discipline. My parents instilled in me the values of integrity, perseverance, and respect, while my grandparents grounded me in resilience, cultural identity, and faith. These formative influences nurtured a conviction that leadership is inseparable from character and that no aspiration is beyond reach when pursued with commitment and belief.

Equally, my experiences within family life and marriage revealed leadership as deeply relational. They taught me that sustainable leadership is built on trust, empathy, partnership, and shared responsibility. These insights would later shape my understanding of leadership as fundamentally human-centred.

As my professional career evolved across governance, risk management, assurance, and digital governance, I encountered the realities of organizational life. I observed that institutions do not fail because of a lack of strategy or resources alone, but because of fragmented or ineffective leadership. I witnessed how leadership culture determines whether organizations thrive or decline, especially in complex and rapidly changing environments.

It was through these experiences that a critical realization emerged: existing leadership theories, while valuable, often explain leadership in isolation, focusing separately on ethics, agility, culture, or innovation. Yet, in practice, leadership unfolds at the intersection of all these dimensions simultaneously.

This realization became the foundation of this study. The article responds to what I observed as a gap between theory and reality; a fragmentation in leadership thinking that limits its effectiveness in a volatile, uncertain, complex, and ambiguous world. As reflected in the research, leadership effectiveness cannot be understood as the product of isolated competencies, but as an emergent outcome arising from the interaction of multiple, interdependent dimensions.

The Integrated Leadership Effectiveness Framework (ILEF) therefore emerged not only from academic synthesis, but from lived experience. It brings together ethical stewardship, humanity and cultural intelligence, transformational agility, and innovation enablement into a coherent system that reflects how leadership truly operates in practice.

Ultimately, this work is grounded in a simple but profound belief: leadership is stewardship. It is about safeguarding people, institutions, values, and future generations. It is about building trust, enabling transformative agility and innovation, and creating sustainable impact.

This article is both a reflection and a proposition: A reflection of a lived journey, and a proposition that leadership must be understood, taught, and practiced as an integrated and evolving system in order to remain effective in an increasingly complex world.

Caption

Mapping the hidden stable carbon reservoir beneath our feet

Zhaoxin Li — Mon, 18 May 2026 02:45:12 +0100

Soil carbon has long been central to climate mitigation discussions. However, while total soil organic carbon is widely mapped and reported, the more persistent fraction of soil carbon has received far less global attention. This gap motivated our study. We wanted to know not only where soil carbon is stored, but where it is stabilized and therefore more likely to contribute to long-term climate regulation.

The project started from a methodological challenge. Across the literature, stabilized soil carbon has been described using different terms, including recalcitrant, persistent, passive, or stable carbon. These terms are often used interchangeably, but they may reflect different measurement approaches. To make a global synthesis possible, we first needed to define what could be compared. We therefore adopted a unified operational definition: stabilized soil organic carbon was represented by hydrolysis-resistant organic carbon measured by acid hydrolysis, or, when direct measurements were unavailable, by total organic carbon minus explicitly reported labile carbon fractions. This step was essential because any global pattern would be meaningful only if the underlying measurements were analytically comparable.

After screening the literature, we built a georeferenced database covering croplands, forests, grasslands, and wetlands. The process was laborious because each record required not only carbon measurements, but also coordinates, soil depth, ecosystem type, and associated environmental information. Many potentially useful studies could not be included because they lacked coordinates, used incompatible methods, or did not report the necessary soil layers. This was one of the most important lessons from the project: global carbon science still depends heavily on careful field measurements and transparent reporting.

With the database established, we used a machine-learning framework to predict stabilized soil organic carbon across the globe. Among several candidate algorithms, XGBoost showed the strongest predictive performance and was used to generate global maps at fine spatial resolution. We also used SHAP analysis and moving-window partial correlations to identify the dominant controls of stabilized carbon across ecosystems. This combination allowed us to move beyond a single global average and explore how drivers varied spatially and among land-use types.

One of the clearest findings was the importance of wetlands. Wetlands stored much more stabilized soil carbon than forests, grasslands, or croplands. This pattern reflects the unique biogeochemical environment of wetland soils, where water saturation limits oxygen availability, slows decomposition, and promotes long-term carbon preservation. Cold-temperate regions also emerged as important hotspots, consistent with the role of low temperature in slowing microbial decomposition and supporting carbon persistence.

Figure 1. Global distribution of stabilized soil organic carbon pools

Another key result was that soil properties, rather than climate or human activities alone, explained most of the spatial variation in stabilized carbon. This does not mean that climate and management are unimportant. Instead, it suggests that their effects are often mediated through soil conditions such as organic carbon content, pH, texture, bulk density, and nutrient status. In croplands, for example, fertilizer use, straw return, tillage, irrigation, and cropping intensity all influenced stabilized carbon, but their effects depended on the soil context. This finding reinforces the idea that soil carbon management must be ecosystem-specific and regionally targeted.

Figure 2. Spatial patterns of dominant drivers of stabilized soil organic carbon across terrestrial ecosystems

A central contribution of the study is the concept of soil negative carbon potential, or SNCP. We define SNCP as the proportion of stabilized soil organic carbon within total soil organic carbon. This metric was designed to capture not just how much carbon is stored, but how much of it is likely to persist. Regions with higher SNCP may have greater potential to contribute to durable climate mitigation. Importantly, we found that higher SNCP was associated with lower greenhouse gas emissions and showed positive relationships with economic indicators, while crop yield trade-offs appeared limited. These relationships do not prove causality, but they suggest that soil carbon stabilization could be connected to broader climate and socioeconomic benefits.

Figure 3. Global estimates and vertical profiles of stabilized soil organic carbon stocks

For us, the broader message is that soil-based climate mitigation should not be assessed only by the size of the carbon pool. Durability matters. A soil that accumulates carbon rapidly but loses it easily may provide less long-term climate benefit than a soil that stores a larger fraction in stabilized forms. By mapping stabilized soil organic carbon and proposing SNCP, our study provides a framework for evaluating soil carbon through the lens of persistence.

This work also points to several future directions. First, more field measurements are needed in underrepresented ecosystems and regions, especially where global datasets remain sparse. Second, mechanistic studies are required to better understand how microbial processes, mineral protection, aggregation, and land management interact to control carbon stabilization. Third, Earth system models should better represent stabilized carbon pools rather than treating soil carbon as a single homogeneous reservoir. Finally, policy frameworks for carbon neutrality could benefit from indicators that distinguish short-term carbon accumulation from long-term carbon persistence.

In the end, this paper is about making the hidden part of soil carbon more visible. Stabilized soil carbon is not always the most dynamic or easily measured fraction, but it may be one of the most important for long-term climate mitigation. By identifying where this carbon is stored and what controls it, we hope this work provides a benchmark for future soil carbon research, Earth system modeling, and land-based climate strategies.

Beyond the Clot: Transauricular Vagus Nerve Stimulation in Hyperacute Stroke — A Conversation with Dr. Gareth Ackland

Hansen Chen — Mon, 18 May 2026 00:53:03 +0100

Mechanical thrombectomy has transformed acute stroke care, but recanalization does not address the autonomic and immune disturbances that follow reperfusion. In this phase 2 sham-controlled randomized trial (NCT05417009), Ackland and colleagues asked whether transcutaneous auricular vagus nerve stimulation (tVNS), delivered during and after thrombectomy, could reduce blood pressure variability and reverse early immunosuppression. The primary endpoint — coefficient of variation of systolic BP over 24 hours — was neutral, but exploratory HRV and whole-blood transcriptomic signals suggested a measurable biological effect. We invited Dr. Ackland to discuss the design, the results, and where the field should go next.

TSR: First, congratulations on this important study. What do you see as the central take-home message of this trial for the stroke field?

GA: Demonstrating feasibility and safety.

TSR: What motivated you to test tVNS in the hyperacute thrombectomy setting?

GA: Autonomic dysfunction is not only a dominant pathophysiologic feature of acute stroke, but potentially a therapeutic target. The focus has understandably been on “clot busting,” and rather less on the contribution of hemodynamic control.

TSR: What led you to focus on systolic blood pressure variability as the primary endpoint in this trial?

GA: Previous association studies identified this as a robust correlate of poorer outcomes, and it is also readily measurable from routinely collected data within EPRs.

TSR: The primary endpoint, systolic blood pressure variability over the first 24 hours, was neutral. How do you interpret that result in light of the accompanying changes in heart rate variability and whole-blood transcriptomic signals?

GA: First, this was a feasibility/safety study, so all the secondary outcomes reported are exploratory. Given the “pluripotent” therapeutic possibilities of the intervention, it is entirely possible that subclinical changes occur independent of the primary outcome. The disconnect between the two may reflect the secondary/exploratory outcomes being more sensitive biomarkers for the intervention, and an over-estimate of the possible separation in SBPV should that have occurred.

TSR: Looking ahead, what do you see as the most important next step for this line of work — refining stimulation timing and parameters, identifying the right biological responders, or moving toward imaging and functional outcomes such as edema, infarct evolution, and disability?

GA: If there is a role for modulating autonomic dysfunction, personalisation will likely be key. That may centre on stimulation timings, parameters (most likely frequency), and having a handle on acute versus chronic autonomic dysfunction in presenting patients. The likeliest target will be intermediate-term cardiovascular outcomes and restoring exercise capacity, both of which have a profound effect on the chances of recovery after stroke.

The full article, “Transauricular Vagus Nerve Stimulation in Acute Ischaemic Stroke Requiring Mechanical Thrombectomy: Sham-Controlled, Randomised Device Trial,” is published in Translational Stroke Research (2026) 17:10. doi: 10.1007/s12975-025-01404-7

Fighting darkness under the Sun: the story of melanoma research (5)

Chi-Ping Day — Mon, 18 May 2026 00:00:35 +0100

(1)
There is a particular cruelty to melanoma that distinguishes it from other cancers. It begins in the melanocyte, the pigment cell that colors skin and eye and hair, the cell whose very purpose is to protect the body from the sun's radiation by absorbing it. That a cell built to defend should become the agent of the body's destruction is one of the bitterest ironies that biology has to offer. Melanoma does not creep or linger. Once it decides to travel, it goes everywhere at once — lungs, liver, brain, bone — as though it has been planning the itinerary for years. By the time it announces itself, it has often been planning for exactly that long.

In the mid-twentieth century, medicine knew this much about melanoma and little else. It knew the tumor was dangerous. It knew that surgery, if performed early enough and with sufficient aggression, could remove it from the skin to cure the patient. What it did not know was how to stop it once it had left.

Thomas Anthony Dooley III arrived at his melanoma diagnosis in the autumn of 1959, by which point he had already lived at a velocity that most men do not approach. Born in St. Louis in 1927, the second son of an Irish-Catholic family, he had enlisted in the Navy at seventeen, trained as a hospital corpsman, and after the war earned his medical degree from St. Louis University in 1953. In 1954, assigned to Operation Passage to Freedom, he had spent months in the South China Sea on transport ships, treating nearly a million North Vietnamese refugees fleeing south after the fall of Dien Bien Phu — handling dysentery, tuberculosis, and trauma at a scale that medical school had never approached. He worked sixteen-hour days in the equatorial heat, his fair Irish skin accumulating the sun's radiation without thought, because there were patients coming to see him and the sun was simply there.

After discharge by Navy, he entered Laos and built a network of jungle hospitals. He wrote three bestselling books. He founded the Medical International Cooperation Organization (MEDICO), which by the time he died was running seventeen projects across twelve nations. He was a man of extraordinary output and inexhaustible public appetite. He was also, in the biological sense that would matter most, a Type I — pale, fair-haired, burning easily, never tanning, his melanocytes offering no more resistance to the accumulated ultraviolet radiation of the tropics than paper offers to a flame.

The lump appeared near his left shoulder. When a biopsy returned the verdict, it was malignant melanoma, arising from the sun-damaged skin of his upper chest, precisely the site and subtype one would predict in retrospect, in the way that retrospect always makes the terrible seem inevitable. He was thirty-two years old.

In the winter of 1960, Dooley agreed to let CBS News film his surgery at Memorial Sloan Kettering, the contemporary finest cancer institution of the country or the world. The cameras recorded the three-hour operation, his recovery, and an interview in which he spoke with a plainness that television was not accustomed to from such badly disease-stricken patient. The broadcast, Biography of a Cancer, aired nationally on April 21, 1960, hosted by Howard K. Smith. On camera, his physician offered a guarded optimism. Dooley, for his part, chose Walt Whitman: It's not important what you do with the years of your life, but how you use each hour. That's how I want to live.

He meant it. He returned to his hospitals in Laos. By the summer of 1960, the melanoma had reached his lungs, his liver, his spleen, his heart, and his brain — that systematic colonization which is the disease's signature, its most complete expression of itself. By December, his spine had failed. Physicians in Hong Kong fitted him with a steel and leather harness from shoulders to hips to hold him upright. He still saw patients and wrote letters.

In January 1961, he flew back to New York. There was no protocol left. On his thirty-fourth birthday, Cardinal Spellman came to his bedside, and a telegram arrived from President Eisenhower praising his service to distant peoples. He died the following evening, January 18, 1961.

The eulogies that followed spoke of the hospitals, the refugees, the three bestselling books, and the Peace Corps that Kennedy would soon found, citing Dooley's example. What the eulogies did not say was that Thomas Dooley had died into a void. Not a void of intelligence, effort, or institutional commitment. The physicians who attended him at Memorial Sloan Kettering were among the most capable oncologists in the world, working at its most formidably equipped cancer center. But capability and equipment mean nothing against a disease for which no effective systemic therapy exists, and for metastatic melanoma in 1959, none did. There was no chemotherapy, not to mention immunotherapy and targeted agent. There was surgery and radiation, whose responses could last for a few weeks to months; and beyond those two blunt treatments, there was nothing. Researchers had tried nitrogen mustard, actinomycin D, or their combinations, and the effects made patients desperately ill while leaving the tumors entirely unmoved. The disease ignored all of it with a disinterest that felt, to the physicians confronting it, almost personal.

Dacarbazine (DTIC), the alkylating agent that would eventually become the first chemotherapy approved for melanoma, was sixteen years from that moment. When it finally arrived, in 1975, it would produce objective responses in roughly one patient in seven and cures in essentially none. The survival curve for patients with distant metastatic disease, the disease Dooley died of, would hover near five percent at five years through the 1960s, the 1970s, and the 1980s: a figure so relentlessly grim that it ceased, after a time, to feel like a statistic and began to feel like a verdict. Median survival after a Stage IV diagnosis was measured in months. Six to nine, typically. For thirty more years after Dooley's death, oncologists would confront patients newly arrived at that diagnosis and offer them, with whatever grace they could manage, essentially what Dooley's physicians had offered him: surgery on accessible tumors, chemotherapy that sometimes helped and never cured, and the largely unanswered question of what to do next.

The incidence of melanoma, meanwhile, was rising at three to five percent each year. More patients, arriving steadily, into the same absence.

(2)
To understand why medicine was so helpless against melanoma for so long, it is necessary to understand what medicine did not know about the disease, not what it had failed to learn, but what it had not yet developed the conceptual vocabulary to even ask.

Before the middle of the twentieth century, melanoma was described primarily in appearance and outcome. A lesion was dark, irregular, spreading. A pathologist could confirm malignancy by looking at the cells under the microscope: their wild shapes, their disordered architectures, etc. What pathology could not do was distinguish, among malignant tumors, between the one that a surgeon's knife could cure and the one that could go out of control. It was Wallace Clark Jr. who first understood how to read their aggression.

Clark was a dermatopathologist, a physician who spent his professional life at the interface of the microscope slide and the patient chart, trying to read in the architecture of cells what the future held for the person those cells had come from. He was working at Massachusetts General Hospital (MGH) in the early 1960s when he began to look, with unusual systematic attention, at the relationship between melanoma cells and the anatomical layers of the skin they were invading. The skin is not a single structure. It is a series of discrete compartments; from the epidermis above, to the papillary dermis, the reticular dermis, and then to the subcutaneous fat below. Each has its own cellular composition and biological meaning in the context of tumor invasion. Clark reasoned that a tumor confined to the epidermis occupied a different biological position, and thus carried different consequences, from one that had pressed its way into the reticular dermis or beyond. Not different in nature, perhaps, but in degree and prognosis.
In a landmark paper published in 1966, Clark and his colleagues described five levels of melanoma invasion, each corresponding to an anatomical boundary the tumor had crossed or not yet crossed. Level I: confined to the epidermis, universally curable with surgery. Level II: into the papillary dermis, but not yet filling it. Level III: filling and expanding the papillary dermis, pressing against the deeper layer. Level IV: into the reticular dermis itself. Level V: through the dermis entirely, into the subcutaneous fat. The prognostic gradient was clear and steep. A Level I melanoma was a different disease, in almost every meaningful sense, from a Level V melanoma — different behavior, different biological activity, different survival probability, different clinical response required. The scale of levels gave pathologists a shared currency. For the first time, a number on a pathology report carried reproducible, communicable prognostic weight. Surgeons could plan margins with more information. Oncologists could discuss risk in terms patients could act on. Tumor boards could compare cases across institutions.

In 1959, Thomas Bernard Fitzpatrick arrived at Harvard Medical School, whose teaching hospital is MGH, as the new chairman of the Department of Dermatology. He was thirty-nine years old, had come up through biochemistry and photobiology, studied at the Mayo Clinic, done a fellowship at Oxford, collaborated with Aaron Lerner at the Army Chemical Center on the mechanisms of skin pigmentation. He brought to clinical dermatology a scientist's appetite for mechanism: for understanding not merely what a disease looked like but why it happened, at the molecular level, in the first place. He was, by nearly universal account among those who trained under him, an electrifying presence — a man whose enthusiasm for a difficult problem was so genuine and so contagious that it reorganized the priorities of those around him. He was also, in the most practical sense, a builder: of departments, of programs, of collaborations, of the conceptual infrastructure without which individual discoveries remain isolated facts rather than a field.

In 1966, Fitzpatrick and Clark established the world's first pigmented lesion clinic at MGH, in which the cases that accumulated could become data. The Clark levels paper was a direct product of that clinic. But the clinic also produced a continuous stream of clinical questions that pure pathology could not answer. What caused melanoma? Who was most likely to develop it? What did a dangerous lesion look like on the surface of the skin, before the biopsy, before the microscope — in the primary care office, at the dermatologist's first glance? What could be done, upstream of catastrophe, to prevent it?

These were the questions Fitzpatrick spent the better part of three decades trying to answer.
His photobiological research had given him a framework for the first one. Melanin, the pigment that had occupied his scientific attention since his early career, is not merely a coloring agent. It is a photoprotector that absorbs ultraviolet radiation before it can reach the cell nucleus, causing the DNA damage from which cancers arise. Fitzpatrick's research delineated these mechanisms, including the formation of pyrimidine dimers in keratinocytes following UVB exposure, the role of melanin in scavenging free radicals, the way that skin with high melanin content carries an inherent biological shield that paler skin simply does not possess. The implication — that fair-skinned individuals, with their relatively sparse melanin, faced substantially elevated melanoma risk under cumulative UV exposure — seems obvious in retrospect. In the early 1960s, it was a hypothesis requiring demonstration.

In 1975, Fitzpatrick translated this photobiological understanding into a clinical tool: the Fitzpatrick scale, a classification of six skin phototypes defined by their response to ultraviolet radiation. Type I always burned, never tanned; Type II burned easily, tanned minimally; and so on through Type VI, which never burned at all. The scale was not merely descriptive. It was a quantification of individual biological vulnerability — a way of placing each patient on the spectrum of risk, of connecting the laboratory understanding of melanin's photoprotective function to the practical question of how much sun exposure was too much for this particular person, with this particular skin. Dermatologists adopted it immediately. The sunscreen industry, which Fitzpatrick was simultaneously helping to develop and validate, used it as the framework for the sun protection factor rating system that would eventually appear on bottles in pharmacies everywhere. When a patient today reads an SPF number and chooses accordingly, they are acting on a logic that Fitzpatrick formalized.

Clark's levels and Fitzpatrick's scales addressed the problem from a different angle. A melanoma that is caught at Level I — confined to the epidermis, measuring a fraction of a millimeter — is, as Clark had shown, almost universally curable. The same tumor, allowed to thicken to four millimeters, to cross into the reticular dermis, to find a lymphatic channel and follow it outward, becomes something more dangerous entirely. The biology of the disease made early detection not merely preferable but the difference, for many patients, between life and death. Fitzpatrick's group worked to close that gap by systematically defining the surface characteristics of early melanomas — the asymmetry, the irregular border, the variegation of color from brown to black to red, the diameter greater than a pencil eraser — in terms that a physician without specialized training, or even a patient examining their own skin, could recognize and act on. These criteria would eventually be formalized and taught to every medical student; their derivation lay in the decades of clinical observation that Fitzpatrick and his colleagues had accumulated at that first pigmented lesion clinic.

Fitzpatrick was also, alongside Clark, among the first to recognize that melanoma's dangers were not distributed randomly across the population. Somewhere in the mid-1970s, both men began to notice the families. They appeared in the clinic with a characteristic presentation: patients with dozens of large, flat, irregularly bordered nevi scattered across their backs and shoulders and scalps — lesions that were not quite normal moles and not quite melanomas but something in between, something that no existing classification had a precise name for. What was more troubling than the lesions themselves was the family history that accompanied them. In certain pedigrees, melanoma appeared in siblings and parents and aunts at frequencies that no random distribution could account for. These were not clusters of bad luck. They were signals of hereditary predisposition — a systematic elevation of lifetime melanoma risk baked into the genome of certain families, expressed on the surface of the skin as a profusion of atypical nevi, waiting for the right mutation, the sufficient UV exposure, the critical moment of cellular instability.

Clark, working with David Elder and colleagues at Penn, documented these families with the methodical attention of a natural historian cataloguing a new species. The lesions he was recording showed, under the microscope, architectural disorder and cytological atypia that fell short of frank malignancy — the cells were aberrant, but they had not yet crossed the line. They were, he concluded, precursor lesions: not melanoma yet, but closer to it than anything else on the skin. In 1978, he published a paper describing what he called B-K mole syndrome — the initials drawn from two index families he had followed — characterizing for the first time the hereditary condition in which affected individuals carried a dramatically elevated lifetime melanoma risk. The syndrome would accumulate new names over the following decades, as clinical understanding refined itself: dysplastic nevus syndrome, familial atypical multiple mole melanoma syndrome, FAMMM. But the conceptual innovation belonged to that 1978 paper: the high-risk individual who could be identified before the melanoma appeared.

Fitzpatrick, approaching the same phenomenon from the clinical side, published his own landmark contribution in 1985 in the New England Journal of Medicine, as an advocacy for systematic screening and excision of dysplastic nevi in high-risk families, establishing criteria that would guide clinical practice for identifying melanoma susceptibility across generations. Where Clark had named the entity, Fitzpatrick had codified the response. Together they had invented, without quite using that word, the concept of melanoma surveillance: the practice of watching, periodically and systematically, the people most likely to develop the disease, in the hope of catching it at a moment when surgery could still reach it. It was not a cure. It was not even a treatment. But in a field where the survival curve had not moved in twenty years, it was the most powerful thing available: the knowledge of who to watch, and when to act.

There remained the question of how to read the primary tumor once it was in hand. Clark's levels measured depth of invasion anatomically; that is, which compartment of the skin the tumor had reached. In the early 1970s, in Nashville, a surgical pathologist named Alexander Breslow was mounting an ocular micrometer to his microscope and measuring something simpler and, as it would emerge, more powerful: the raw thickness of the tumor in millimeters, from the granular layer of the epidermis down to the deepest identifiable melanoma cell. Breslow demonstrated that this measurement — simple, direct, reproducible — carried even stronger prognostic power for most tumors than Clark's anatomical levels. The two systems were complementary rather than competing. Breslow thickness provided the primary prognostic gradient; Clark level supplied nuance in the cases where thickness alone was ambiguous. Both names entered the staging criteria that would govern melanoma management for the next three decades. A melanoma measuring less than 0.76 millimeters carried a five-year survival rate approaching ninety percent. A melanoma measuring more than four millimeters carried a figure that oncologists reported in flat numerals whose restraint barely contained the human devastation they described.

Pathology had given the disease a detailed verdict. What it could not give was a cure.

(3)
While Clark and Fitzpatrick were remaking the conceptual landscape of melanoma in America, a young physician in Scotland was beginning a parallel labor that would prove, in its own quiet and systematic way, equally consequential.

Rona MacKie was born in Dundee in 1940, the daughter of Norman Davidson, the Gardiner Professor of Biochemistry at the University of Glasgow. She grew up in a household where the habits of scientific inquiry were as natural as meals, where evidence and argument were the common currency of daily thought. She studied medicine at Glasgow, graduating in 1963, and completed her MD with commendation in 1970. She became a member of the Royal College of Physicians in 1971, the same year she published her first paper on melanoma. She would not stop for another four decades.

The Scotland into which MacKie brought her attention was a country with one of the higher melanoma incidence rates in the United Kingdom and almost no systematic apparatus for understanding it. Melanoma in Britain in the early 1970s was tracked inconsistently and managed even less consistently. Patients with clinically identical presentations received wildly different treatment depending on which hospital they arrived at, which surgeon happened to see them, what local tradition happened to prescribe. There was no shared database, no unified protocol, no way of knowing how many patients were being diagnosed, at what stage, with what outcomes. The disease was rising in the population, and medicine, in the sense of a collective, organized, self-correcting enterprise, could not quite see it.

MacKie could see it. This was partly temperamental, as she was a systematic thinker, a persistent builder of data records, and partly a consequence of where she stood. As a dermatologist in Glasgow, she was receiving the melanoma patients that the general practitioners and surgeons were sending her, and she was noticing, in the pattern of what arrived and when, the outlines of an epidemic that the numbers did not yet reflect.

In 1978, she was appointed Professor of Dermatology at the University of Glasgow, the first female professor across all disciplines in the institution's history. The appointment was beyond symbolism, because it gave MacKie the institutional standing to organize what she had been observing. In 1979, together with colleagues, she established the Scottish Melanoma Group, with a founding purpose that was as straightforward as it was essential: to obtain accurate epidemiological data on melanoma in Scotland. To count the patients. To record the tumors. To follow the outcomes. To build, from first principles, the kind of factual foundation without which no clinical progress is possible.

The Scottish Melanoma Group's database would eventually become one of the longest continuously maintained melanoma datasets in the world. From that archive, MacKie drew findings that would reshape how the disease was understood on both sides of the Atlantic. In 1982, she and Aitchison published a study establishing, at a population level, the relationship between severe sunburn and the subsequent risk of primary cutaneous malignant melanoma. This was rigorous epidemiological evidence that sunburn was not merely uncomfortable but carcinogenic, and that its consequences could arrive years or decades after the exposure. Fitzpatrick had traced the mechanism in the laboratory; MacKie confirmed the epidemiology in the population. They were, without formal collaboration, building the same case from opposite ends.

Her MD thesis had been built on something more intimate: the technique of dermatoscopy, the use of magnification and oblique illumination to examine pigmented lesions at the skin surface in ways that the naked eye could not. Dermatoscopy — or dermoscopy, as it would later be called — would not achieve widespread adoption for another two decades. MacKie saw its diagnostic potential in the 1970s, during years when most of her colleagues were not yet asking the question it was designed to answer. It was a pattern that would repeat itself in her work: the early sight, the patient documentation, the vindication arriving on a delay.

But the contribution that reached the widest audience was the seven-point checklist for melanoma, published with Doherty in 1991. The problem it addressed was the same one Fitzpatrick's group had attacked from the American side through the ABCD criteria: the diagnostic gap between a dangerous lesion and a noticed one. Melanoma's window of curability is early. The patient who arrives at a dermatologist with a Level I melanoma, thin and confined to the epidermis, faces an almost entirely different future than the patient who arrives at Level IV. But most patients do not go first to a dermatologist. They go to a general practitioner, whose exposure to melanoma pathology may be a fraction of a dedicated skin specialist's. The question MacKie was asking was not how to make dermatologists better at diagnosing melanoma. It was how to make everyone who saw patients better at knowing when to worry.

The checklist was the seven observable features of a suspicious pigmented lesion: change in size, irregular shape, irregular color, diameter greater than seven millimeters, inflammation, crusting or bleeding, sensory change. They were divided into major criteria, which alone warranted referral, and minor criteria, which contributed to a clinical score. The checklist required no specialized training, no dermatoscope, no laboratory equipment. It required only a physician paying attention and a tool simple enough to use in the midst of a full appointment schedule. The United Kingdom's National Health Service would eventually adopt it as the official clinical instrument for melanoma detection in primary care, a decision that translated, in the years that followed, into melanomas caught at earlier stages, tumors excised before they crossed from curable to lethal. The patients who survived because a GP in Edinburgh or Bristol or Manchester recognized the checklist's criteria and made the referral — they are, in the nature of these things, invisible statistics. Their melanomas were removed before they became stories.

MacKie understood that clinical tools without public awareness are tools with limited reach. She helped organize and sustain a Scottish public health campaign that carried the message of early detection into the population itself, urging people to look at their own skin, to notice change, to seek evaluation. The campaign produced a measurable shift: tumors being detected at earlier stages, the mortality curve beginning, with painful slowness, to bend. It was the most that could be offered, in a decade when therapy for advanced disease had essentially nothing new to offer. MacKie offered it methodically and without discouragement.

She served as editor of the British Journal of Dermatology from 1985 to 1988. She was elected a Fellow of the Royal Society of Edinburgh in 1983 and was appointed a Commander of the Order of the British Empire in 1999. Before these honors arrived, it was the thirty years of ledger-keeping, the thousands of cases followed from diagnosis to outcome, the checklists and campaigns and training sessions and database entries that, accumulated, constituted a campaign against a disease that was winning.

(4)
Diana Christine Merriweather was born in 1963, the same year Rona MacKie received her medical degree, the same year that melanoma's five-year survival rate for advanced disease was already settling into the grim territory it would occupy for the next three decades. She had long curly red hair and deep blue eyes and a close-lipped smile that tilted slightly, as if she were always on the verge of sharing a private observation. She had a gift for humor that her husband Jeff — a Navy pilot ascending toward a career as a NASA shuttle astronaut — found quietly endearing, and a compassion for small things and struggling creatures that was not sentiment but a genuine attunement, as if she heard frequencies that others could not quite register.
The mole on her back changed. This is how so many of these stories begin: a mole that changed. The dermatologist excised it and sent it to the laboratory, and the pathology report returned with its verdict. Melanoma. The margins were clear. She was assured that the removal was the end of the matter.

It was not. What followed was what thousands of melanoma patients experienced in the 1980s and 1990s — the sequence that oncologists privately called the roller coaster, though the phrase conceals more than it reveals. It was not a roller coaster. It was a series of retreats and returns, a disease that withdrew just far enough to seem defeated and then came back with a different angle, a different site, a different organ. Diana's melanoma recurred. Then it recurred again. By the summer of 1995, it had come back a third time.

She was not a scientist, but she brought to the literature of her own disease the same quality of attention she brought to everything else — precise, relentless, uncomfortable with comfortable answers. She read the papers. She called oncologists. She asked questions that the physicians around her found unusually exacting for someone without medical training. What she found, in that literature and in those conversations, was a field that had not moved. Dacarbazine had been approved in 1975, and it helped one patient in seven, and it cured none. High-dose interleukin-2 was in trials, producing dramatic responses in a small fraction of patients and punishing toxicity in many more. Interferon was being evaluated as adjuvant therapy, its benefit signal weak and contested. Therapeutic vaccines were being tested in a dozen variations, and failing in most of them. The researchers were not incompetent; they were working with the tools biology and chemistry had provided, and those tools were not yet adequate to the problem. The disease had, over the preceding decades, accumulated a grammar — Clark levels, Breslow thickness, the Fitzpatrick scale, the Scottish Melanoma Group's epidemiological archive, the seven-point checklist — but grammar is not a cure, and Diana Merriweather in 1995 needed a cure, or at least a treatment that worked, and there was none.

The internet that existed in 1995 was crude and slow and not yet understood as the thing it would become — but it had chat rooms, and in those chat rooms were melanoma patients, and Diana found them. She would sit up late into the night, the screen glowing in the dark while Jeff slept, typing to strangers who had the same disease and the same absence of options. She had an unusual capacity for that kind of intimacy — for making a person feel, even through a keyboard, that they were seen. As the disease spread to her organs and eventually to her brain, she continued. She was not searching, at that point, primarily for herself. She was searching for something she could do for the people she had met in those rooms, whose losses she had witnessed one by one, whose names had become real to her in a way that statistics are never real.
The frustration eventually transmuted into something harder and more useful. In 1996, Diana Merriweather Ashby founded the Melanoma Research Foundation (MRF). Its purposes were three: to fund research toward effective treatments and eventually a cure; to educate patients and physicians about prevention, diagnosis, and the still-limited tools of treatment; and to advocate for the melanoma community — to make the disease visible to the public and to Congress in proportion to the mortality it was delivering. She worked with a ferocity that her deteriorating condition made almost incomprehensible to those around her, stopping only when the cancer had taken her eyesight and then her voice.

She died on May 2, 1997. She was thirty-four years old. The MRF was eight months old.

Jeff Ashby flew his first shuttle mission in the years after her death and dedicated it to her name and to the awareness she had spent her last years trying to build. When he spoke about Diana, he came back always to the same image: a woman who had taken the full measure of what was absent — the treatments, the research, the funding, the public attention — and had turned, entirely and without remainder, toward others. It was pretty remarkable, he said, in the understated register of someone who has witnessed something that exceeds the vocabulary of ordinary admiration.

What the MRF became after her death — the research grants funded, the congressional appropriations negotiated, the scientists convened, the patients guided through a disease that, in the years that followed, would begin at last to yield — none of it was hers to see. The immunotherapy trials that would eventually reshape the survival curve, the targeted therapies that would follow the discovery of the BRAF mutation, the combination regimens that would produce durable remissions in patients who once had months to live — all of this was still gathering itself in the laboratories and the early-phase trials, still years away from the clinic. Diana Merriweather Ashby died at the edge of the dawn she had helped to assemble, in the last hour of the long dark.

(5)

The darkness lasted a long time. It lasted from the January evening in 1961 when Thomas Dooley died in his thirty-fourth year, through the decades of dacarbazine and interleukin-2 and the failed vaccine trials, to the May afternoon in 1997 when Diana Ashby, also thirty-four, was gone. Between those two deaths, the disease killed steadily and without interruption, and the survival curve for its most advanced form barely moved.

But the dark was not empty. Wallace Clark looked into the microscope and found a grammar in what had been noise — five levels of invasion, five anatomical sentences, each carrying different meaning and different consequence. Alexander Breslow mounted a micrometer to the same instrument and discovered that the simplest measurement of all, the raw thickness in millimeters, was often the most powerful predictor of what came next. Thomas Fitzpatrick, at Harvard, traced the molecular logic of how the sun damaged the skin, named the cell organelle that produced and housed pigment, built the scale that allowed physicians to quantify UV vulnerability, and helped to establish, alongside Clark, the concept of the high-risk individual who could be found before the melanoma arrived. Rona MacKie, in Glasgow, built a ledger that had not existed before she built it — recording thousands of cases, following outcomes, extracting patterns, and translating those patterns into a seven-point checklist that a general practitioner could use between appointments and a public health campaign that bent a mortality curve downward, slowly, against the grain of a disease that had not been asked to cooperate.

None of them could offer a drug that worked. None of them could save the patients who had already crossed into metastatic disease — not Dooley, not the thousands who followed him, not Diana Ashby herself. What they offered instead was the only thing that was available: the slow, costly, unglamorous accumulation of knowledge — knowledge of the disease's anatomy, its epidemiology, its surface signs, its familial patterns, its cellular mechanisms — that is the necessary precondition of every cure that has ever been found.

The physicians who would eventually break the plateau — who would map the BRAF mutation and build drugs to block it, who would understand how melanoma had learned to evade the immune system and build antibodies to interrupt that evasion — those physicians stood on foundations that Clark and Breslow and Fitzpatrick and MacKie had laid, in the years when standing on a foundation and building something from it were very different activities, when the foundation was real and the structure was not yet visible.

It is the nature of medical progress that its beneficiaries rarely know the names of those who made it possible. The patient who walked out of an oncology clinic in 2012, carrying a prescription for vemurafenib or ipilimumab, carrying with it a plausible chance of survival that would have seemed miraculous twenty years earlier — that patient did not know about the first pigmented lesion clinic, or the Scottish Melanoma Group's thirty-year database, or the seven-point checklist that sent a different patient to a different dermatologist a decade earlier, at a stage when surgery was still sufficient.

They didn't need to know. That is what the dark, which was not empty, had been for. Those who worked in it did not need to be remembered by those they could not yet save. They needed only to keep working — to keep the ledger, to keep measuring, to keep watching the skin of the people most likely to need watching — in the faith, which the evidence of history sometimes justifies, that the work itself was what the dawn required.

The dawn would come. But this is a story about the dark that preceded it, and about the men and women who refused, inside it, to stop.

Robotic retroperitoneal lymph node dissection: a stepwise technical guide

Juan Pablo Dugarte Del Burgo — Sun, 17 May 2026 20:07:09 +0100

Retroperitoneal lymph node dissection remains a critical operation in selected patients with testicular cancer, including patients with early metastatic disease, post-chemotherapy residual masses, and emerging indications for primary RPLND in carefully selected low-volume seminoma. Although survival outcomes in testicular cancer are excellent, RPLND remains one of the most technically demanding procedures in urologic oncology because it requires precise dissection around the vena cava, aorta, renal vessels, iliac vessels, lumbar branches, ureters, lymphatic channels, and sympathetic neural structures.

This article presents a standardized stepwise technical guide to robotic RPLND, emphasizing reproducible exposure, durable bowel exclusion, nerve-aware dissection, posterior plane development, and selective vascular and lymphatic control. The operative workflow includes patient positioning, port placement, mesenteric incision, creation of a broad L-shaped peritoneal flap, bilateral flap suspension, cephalad stay sutures, entry into the retroperitoneal template, early sympathetic nerve identification, split-and-roll dissection, posterior-first interaortocaval development, and clip-based control of vascular and lymphatic branches.

A central principle of the technique is that exposure should be treated as a formal operative step rather than an intermittent challenge. Broad peritoneal flap development and suspension provide a stable working field, allowing the surgeon to maintain orientation throughout the case. Early identification of the sympathetic trunk allows nerve preservation when oncologically appropriate, while posterior-first development of the interaortocaval space improves orientation and facilitates deliberate management of lumbar vessels. Mechanical clip control is favored for lymphatic channels and higher-risk vascular branches, particularly near the renal hilum, common iliac crossing, and posterior great-vessel planes.

The robotic platform may enhance visualization, countertraction, and precision during complex retroperitoneal dissection; however, the safety of the operation depends primarily on disciplined exposure, anatomic orientation, template adherence, neural preservation, and vascular control. By translating robotic RPLND into a structured operative sequence, this technical report aims to improve clarity, reproducibility, and educational value for surgeons performing this challenging procedure in experienced centers.

Unusual presentation of jejunal carcinoid tumor with intussusception and vertebral metastasis: a case report

Raghav Bansal — Sun, 17 May 2026 17:53:31 +0100

We report a fist of its kind case where patient with progressive back pain and neurological complications which after extensive diagnosis turned out to be an unusual complication of a rare gastrointestinal tumor. This case underscores the importance of detailed history taking and clinico-radiological correlation to reach at a certain diagnosis. A multidisciplinary team effort is required in cases like these. However, despite of best medical effort, patient failed to adhere to the treatment protocols, resulting in further complications. This highlights the role of patient compliance along with medical expertise, in order to successfully manage the case. These cases truly makes the abdomen a "Pandora's Box", surprising even the best of the surgeons. This case is an example for GI surgeons to not to ignore vague gastrointestinal symptoms and refer the patient to neuro, who'll probably just take care of the pain. After attending the case and following up, we decided to report this unusual presentation of a rare cancer, so that surgeons all around the world will be able to at least keep a differential diagnosis in mind, next time they come across something similar.

Surgical Determinants of Outcomes in Partial Nephrectomy: a Contemporary Review

Juan Pablo Dugarte Del Burgo — Sat, 16 May 2026 20:15:34 +0100

This contemporary review examines the key surgical determinants of outcomes in partial nephrectomy, with emphasis on modern minimally invasive and robotic approaches. It highlights how tumor complexity, ischemia strategy, resection technique, intraoperative imaging, parenchymal preservation, hemostasis, renorrhaphy, and surgeon experience influence oncologic control, renal functional preservation, and perioperative morbidity. The article provides an evidence-based framework to optimize outcomes in nephron-sparing surgery for localized renal masses.

Widespread DNA off-targeting confounds RNA chromatin occupancy studies

Igor Ulitsky — Sat, 16 May 2026 20:07:17 +0100

This project was conceived during my sabbatical at the Max Planck Institute for Molecular Genetics, hosted by Prof. Martin Vingron, a computational biologist. The Vingron lab conducted several studies that performed meta-analyses and comparisons of various tools for genomics research, which led me to think: What kinds of data or tools can be evaluated through such a lens in my field of long noncoding RNAs (lncRNAs)? The natural answer was datasets of lncRNA chromatin occupancy. Over the years, I’ve reviewed several manuscripts that included such experiments, and was often surprised by the discrepancy between the apparent low copy number of these RNAs in cells – often fewer than 5 copies per cell, and the reported number of genomic binding sites, often in the thousands, each of which seemed quite confident. When, as a reviewer, I raised questions about this apparent discrepancy, the reply was often citations of prior studies, using the same technique, which was most often ChIRP-seq, that also reported many binding sites for other non-abundant RNAs. Unfortunately, over the years, studies with such apparent discrepancies have accumulated. Importantly, the chromatin occupancy maps were often not the main experiment in these studies, but rather the last figure panel – the one aimed at connecting the phenotype observed upon lncRNA perturbation to the specific genes the lncRNA was suggested to regulate. The accumulation of such chromatin occupancy maps, dozens of which have been published in human and mouse cells, has fueled the notion that the task of ‘going to specific places in the genome’ is indeed something lncRNAs often carry out. Importantly, this was also a conceptually compelling model, as many chromatin-related complexes lack apparent sequence specificity yet regulate very specific genes across different developmental or physiological contexts. Recent studies have cast doubt on whether lncRNAs actually bind many of the complexes most often reported to act in this manner, such as Polycomb, but the evidence that lncRNAs often bind hundreds or thousands of discrete sites remains widespread in the literature.

During my sabbatical, I performed a rudimentary re-analysis of the data in some of the human studies, and after I returned to the Weizmann Institute, Micah Goldrich, a very talented PhD student in the lab, took over the project and injected substantial rigor and creativity into the analysis. Here, I need to explain shortly how the RNA chromatin occupancy are obtained. After cells are crosslinked, probes, typically short (~20 nucleotides), are used to pull on the RNA of interest, which is typically quite long (>1,000 nucleotides). DNA regions are extracted from the pulled-down material and prepared for sequencing. The recovered fragments are compared to an ‘input’ sample where the pulldown doesn’t take place. Together with Micah, we first found that the reported binding sites very often shared short sequence matches with the probes used in the pulldown experiments. For short matches of 7-12 nt or so, the number of sites that had such overlaps greatly exceeded (often by >10-fold) that expected by chance. While such matches might have been expected if the RNA of interest formed Watson-Crick base pairs with the target DNA, we found they occurred only in regions of the RNA bound by the probes, not elsewhere. This formed strong evidence that the probes, which were supposed to enrich the RNA, were instead directly enriching DNA fragments in an RNA-independent manner. Micah then cracked the mechanism through which this occurred – he found strong evidence that the probe matches were preferentially found at the ends of the sequenced reads, suggesting that the probes bound to single-stranded DNA fragments that can be formed during the process of library preparation.

After I presented our initial findings at the Noncoding Genome meeting at EMBL in October 2023 (a virtual presentation as I could not travel because of a war that had just broken out in Israel), I was contacted by Louis Delhaye and Pieter Mestdah from Ghent, who independently reached a similar conclusion. They studied a specific lncRNA, NESPR, and found that while it regulated the expression of a large number of genes, these genes were unrelated to the places where the lncRNA seemed to bind in the genome, and more concerningly, the bind sites reported by ChIRP-seq peristed even in cells where the lncRNA was not expressed at all, or in cells that did express the lncRNA but that were treated with RNase that was supposed to eliminate any RNA-related signal. We then decided to team up and present our independent findings in a joint manuscript that was a real pleasure to prepare and publish.

Beyond the findings on specific lncRNAs that our results cast a shadow on, our findings have broader implications for understanding how lncRNAs function, as they widen the gap in understanding whether lncRNAs, beyond a few well-studied examples such as Xist and Rox, indeed often target large numbers of distal chromatin sites. The mechanisms proposed for such targeting, such as triplex formation, have difficulty explaining how targeting specificity arises. We propose both computational and experimental methods to increase rigor in studying RNA-chromatin interactions, aiming to yield cleaner future maps that can expedite the study of lncRNA modes of action.

How a Scholarship Funding Setback Led to an Unexpected Publication

Nicholas Pranata — Sat, 16 May 2026 14:34:43 +0100

A Hopeful Beginning

The foundation of this paper began not as a journal submission, but as a research proposal for a Master degree program in sustainability. When I first inquired about the program after graduating with my bachelor's degree, full funding was not an option. However, a few months later in October, the university marketing team reached out to let me know a full-scholarship track had opened up. I was eager to try.

During the university open day, I had an incredibly encouraging conversation with one of the faculty professors. I shared my background with him, explaining that I had previously published a paper as a first author in a Q3 Scopus journal and had spent 1 year working in the green building sector. He was genuinely delighted to find an applicant interested in the demanding research track of their mixed-course program. This alignment felt especially meaningful because the university maintained a strict graduation requirement for students to publish in a Q1 journal.

During conversations with other candidates at the open day, I noticed many were content with accepting standard 30% or 50% partial grants without sitting for further examinations. Realizing that a partial scholarship would not be financially viable for me, I knew my only path forward was to aim for the 100% full-funding track. I chose to take the formal scholarship test instead. I put my absolute best effort into the examination with the hope of making my future studies financially feasible. Simultaneously, I also began drafting my research proposal.

An Unexpected Pivot

Unfortunately, administrative logistics can sometimes take unexpected turns. When the initial email notification arrived, it was for a 50% partial grant. Knowing this was not a suitable path for me, I politely informed the senior marketing representative that I would not be able to proceed with enrollment. The next day, I received a follow-up email clarifying that due to a miscommunication, the offer was actually a 50% scholarship for the 1st year only, which was half of what was offered the previous day.

It was a deeply disheartening moment. It is tough to navigate a process where you feel a strong mutual connection with the faculty, only to have the practical and financial framework shift so suddenly. The abrupt change in terms after such a welcoming open day experience felt incredibly confusing. Realizing the numbers simply did not work, I made the difficult decision to walk away and withdraw my application entirely.

Testing the Work Independently

With my application withdrawn, the research proposal sat idle in my file. I still believed in the core ideas regarding sustainable energy transitions, so I decided to reshape the framework into a full manuscript. I submitted it to a Q2 Scopus-indexed journal to see if the ideas could stand on their own merit within the global scientific community.

Then came the next twist in the rollercoaster ride: the Q2 journal declined the paper.

However, the editor kindly threw me a lifeline by suggesting a journal transfer. Looking through the publisher transfer options, I noticed several high-tier Q1 journals on the list. Because the transfer included a conditional APC waiver to one of the options, I figured there was no harm in trying. I remember thinking that if it got rejected again, I would still learn a lot from the peer review feedback for my next academic application.

I chose a Q1 journal, submitted the manuscript through the transfer network, and let it go. To my complete surprise, after a rigorous round of peer review and careful revisions, the reviewers and editors accepted the paper.

Lessons Learned Along the Way

It is a strange, humbling feeling to realize that I ended up meeting the exact Q1 publication milestone required by that program, just through a completely different door.

For fellow early-career researchers who might be facing funding hurdles or sudden changes in plans, my experience taught me that an apparent roadblock is often just a redirection. If a door closes due to administrative or financial mismatches, it does not mean your ideas lack value.

Academic paths are rarely linear. By staying open to unexpected opportunities and focusing on the research itself, we can often find a community ready to welcome our work, even if it is not the one we originally anticipated.

Call for papers: Intelligent Transport Systems: Ecology, Safety, Quality, Comfort

Stanislav Popov — Sat, 16 May 2026 13:25:33 +0100

"Intelligent Transport Systems: Ecology, Safety, Quality, Comfort ", organized by National Transport University with the support of leading European and global academic institutions.

📚 Key highlights of hashtag#ITSESQC: All accepted papers will be published in the Springer Nature Lecture Notes in Networks and Systems series (indexed in Elsevier | Scopus and Web of Science (Clarivate)) Strong international academic collaboration

✅ Participation and publication are completely free of charge It is always inspiring to exchange ideas in such a professional environment and contribute to shaping sustainable and intelligent transport systems. I would be glad to collaborate and warmly invite you to participate!

DOI: 10.13140/RG.2.2.27976.69127

Website: http://itsesqc.ntu.edu.ua