Fifty-six right-handed male participants with strength training experience performed dumbbell elbow flexion exercises while surface electrodes recorded biceps brachii activity. The researchers used two predefined exercise sequences performed in reversed order to reduce potential order and fatigue effects, a control measure intended to limit systematic bias in the acute EMG recordings.

The amplitude results followed a consistent pattern. In pronation, with palms facing down, right-arm EMG activity averaged 215 microvolts. Switching to a neutral grip raised the signal by 106 microvolts, and full supination added a further 100 microvolts. On the left side, pronation produced 249 microvolts, rising by 188 microvolts in neutral and by another 93 microvolts in supination.

Effect sizes, reported as Cohen’s dz, indicated moderate-to-large differences in recorded sEMG amplitude between the forearm positions, meaning the grip-related differences were not only statistically significant but also substantial in practical magnitude. Supination consistently elicited the highest biceps brachii activation and pronation the lowest across both arms, with neutral grips falling between the two extremes in every comparison.

The authors suggest that forearm position may be an important factor to consider when selecting dumbbell exercises aimed at increasing biceps brachii muscle activity, offering practical insight for coaches, athletes and rehabilitation specialists. They note, however, that the study examined acute EMG responses in a single muscle during one exercise type in a specific population, and that future research should explore additional muscle groups and exercise variations to refine training strategies and enhance performance outcomes.

Subject of Research: Acute effects of forearm position on biceps brachii electromyographic activity during dumbbell elbow flexion

Article Title: Optimizing hypertrophic strength training: electromyographic effects of forearm position on biceps brachii activity

Article References: Pakosz, P., Konieczny, M., & Domaszewski, P. (2026). Optimizing hypertrophic strength training: electromyographic effects of forearm position on biceps brachii activity. Scientific Reports. https://doi.org/10.1038/s41598-026-75583-0

Image Credits: AI Generated

DOI: 10.1038/s41598-026-75583-0

Keywords: electromyography, biceps brachii, forearm position, supination, pronation, strength training, hypertrophy, dumbbell exercise, muscle activation, surface EMG, Optimizing, hypertrophic

The research team, led by first author Kirsten Marchand and colleagues, recruited 17 participants purposefully through youth mental health and substance use services across the province. The group included six youth aged 16 to 24 with experience accessing opioid agonist treatment, four caregivers of such youth, five service providers, and two decision-makers. British Columbia was a deliberate choice of setting: overdose is one of the leading causes of accidental death among youth in the province, making the local urgency of the question acute.

Participants took part in semi-structured interviews, and the researchers applied a directed content analysis to the transcribed interviews to synthesize and describe the experts’ recommendations for improving the delivery of opioid agonist treatment to youth. This method allowed the team to organize what participants said into a coherent set of actionable guidance points drawn from across the four participant groups.

The analysis produced eight recommendations. First, services should establish and maintain trusting relationships with youth. Second, providers should regularly check in with young patients about their goals and about the benefits and challenges they experience with treatment. Third, all medication options should be presented alongside their respective benefits and challenges, rather than steering youth toward a single default. Fourth, induction plans for starting medication should be developed collaboratively with the young person rather than imposed on them.

The remaining four recommendations extend beyond the clinical encounter. Opioid agonist treatment should be delivered as part of a comprehensive approach to a young person’s health and life circumstances, not as an isolated prescription. Services should operate in low-barrier and non-judgmental settings that reduce the friction of staying in care. Tapering processes, when a young person chooses to reduce or stop medication, should likewise be developed collaboratively. Finally, caregivers should be empowered and supported, recognizing the role families play in sustaining youth engagement with treatment.

Underlying all eight recommendations, the researchers identified four foundational pillars. These emphasized positive relationships between youth and service providers, flexible treatment plans that can adapt to changing circumstances, and service delivery settings that are both low-barrier and holistic. Together, the pillars frame opioid agonist treatment for youth as a service built on relationships, flexibility, and accessibility rather than on medication alone.

The study’s design carries important limitations. It captured the perspectives of 17 purposively recruited participants in a single Canadian province, so the findings represent expert recommendations rather than tested outcomes. The authors are explicit that future research is needed to examine how youth-centred models of care actually perform once implemented, with specific attention to how these models address the diverse needs of youth across different communities, age ranges, genders, and clinical, social, and cultural contexts.

Even so, the recommendations offer a practical blueprint for services aiming to improve uptake and retention of opioid agonist treatment among young people. By centering trust, choice, collaboration, and caregiver support, the study reframes treatment for youth as a relationship-driven service rather than a purely pharmacological one. Whether these expert-grounded principles translate into measurable improvements in treatment engagement and outcomes will depend on the implementation research the authors call for next.

Subject of Research: Expert recommendations for youth-centred models of opioid agonist treatment in British Columbia

Article Title: Optimizing the quality of opioid agonist treatment for youth: experts’ recommendations for youth-centred models of care

Article References: Marchand, K., Turuba, R., Cameron, V., Eekhoudt, C. R., Fast, D., Knight, R., Marsh, D. C., Ignaszewski, M. J., Sassi, R., Mathias, S., & Barbic, S. (2026). Optimizing the quality of opioid agonist treatment for youth: experts’ recommendations for youth-centred models of care. Addiction Science & Clinical Practice. https://doi.org/10.1186/s13722-026-00729-4

Image Credits: AI Generated

DOI: 10.1186/s13722-026-00729-4

Keywords: opioid agonist treatment, opioid use disorder, youth health, qualitative research, British Columbia, overdose, models of care, addiction medicine, caregivers, service providers, Optimizing, quality

The intervention joined two mechanisms designed to address distinct problems in clinical decision-making. Its prospect-theory component focused on how patients evaluate uncertain outcomes, using clear reference points, balanced presentations of benefits and risks, and natural frequencies to explain low-probability complications. This was not a gain-versus-loss persuasion strategy. Instead, it aimed to help patients compare expected benefits, possible losses and the consequences of declining or delaying a procedure without allowing a severe but unlikely event to dominate the discussion. Its ultimatum-game component focused on interactional fairness through a four-stage sequence: a physician proposes a treatment, the patient responds with questions and personal priorities, the physician answers or revises the proposal, and both parties work toward a final shared decision. The two pathways were designed to connect cognitive accuracy, relational trust and decision quality.

Prospect theory provides a technical rationale for the risk-calibration component. It holds that people judge outcomes relative to a subjective reference point, treat losses asymmetrically relative to gains, and assign decision weights to probabilities through a nonlinear transformation. In this setting, the reference point was not monetary: it could be a patient’s baseline health, expected recovery time or clinical outcomes among similar patients. Loss aversion means that a possible complication may receive more psychological weight than an equivalent expected benefit, while nonlinear probability weighting can cause a low-probability event with severe consequences to appear more important than its stated frequency warrants. By presenting treatment benefits, potential harms and the consequences of no treatment together, the protocol sought to make these reference points and trade-offs explicit rather than attempting to steer patients through a preferred frame.

The ultimatum-game analogy supplied a different explanation for why a medically reasonable proposal might still encounter hesitation or refusal. In the classic economic game, a respondent may reject an advantageous offer when it is considered unfair. Clinical care is not an economic bargain, but the interaction has a comparable structure: a proposal, feedback, explanation or adjustment, and a decision. The study’s model operationalized this structure by asking clinicians to identify the procedure’s benefits, risks and alternatives; invite questions concerning risk tolerance, work, family responsibilities and other patient values; respond to the concerns raised; and revise the clinically feasible plan when appropriate. A four-step protocol does not itself prove that procedural fairness caused trust or acceptance to rise, and the study did not directly measure the proposed mediators. It nevertheless converted an abstract principle into steps that physicians could learn, audit and apply consistently.

The primary outcomes were risk understanding and trust in physicians. Risk understanding, rated by an assessor against predefined criteria, averaged 7.87 in the intervention group and 5.86 in the control group, an unadjusted difference of 2.01 points with a 95% confidence interval of 1.89–2.13. The standardized difference was unusually large at Cohen’s d of 3.66. Patient-reported trust averaged 8.41 versus 5.69, also a 2.72-point difference, with a 95% confidence interval of 2.61–2.84 and Cohen’s d of 5.03. Multivariable adjustment changed little: the adjusted coefficients were 2.001 for understanding and 2.703 for trust. Both measures were study-specific 0–10 tools with limited independent psychometric validation, so their numerical effect sizes should not be assumed to generalize to other instruments.

Treatment acceptance was more frequent in the intervention group: 148 of 160 patients, or 92.5%, accepted the proposed treatment, compared with 126 of 160, or 78.8%, under routine communication. The absolute difference was 13.7 percentage points. Adjusted odds of acceptance were 3.491 times those in the control group, with a 95% confidence interval of 1.638–7.442 and P = 0.001. That odds ratio should not be read as an equally large increase in probability, because odds and probability diverge when an outcome is common. Nor should higher acceptance automatically be equated with better decision-making. The intended interpretation is narrower: structured communication may help patients reach clear choices after they understand benefits, risks, alternatives and their own priorities. The study did not report whether increased acceptance represented less coercion, better alignment with patient values, or some combination of those outcomes.

The complication signal extended beyond communication and decision measures. During the 30 days after surgery or an invasive procedure, 18 intervention patients had complications, compared with 43 control patients. The unadjusted risk ratio was 0.419, with a 95% confidence interval of 0.253–0.693, while modified Poisson regression with robust standard errors produced an adjusted risk ratio of 0.413 and a 95% confidence interval of 0.248–0.688. Results remained directionally similar among 255 patients with a recorded procedure type and 173 patients known to have undergone surgery, with adjusted risk ratios of 0.407 and 0.333, respectively. One plausible pathway is that better-informed patients were more prepared for medication changes, postoperative activity, wound care and symptom monitoring, but those behaviors were not measured and therefore were not demonstrated as mediators. The magnitude of the difference is unusually large for a communication-only intervention, raising the possibility that unmeasured differences in physician teams, anesthesia, surgical pathways or perioperative care also contributed.

Medical disputes did not show a statistically supported reduction. Sixteen were recorded within three months—six in the intervention group and 10 in the control group—giving unadjusted rates of 3.8% and 6.3%. The adjusted odds ratio was 0.596, but its wide 95% confidence interval of 0.200–1.773 crossed 1 and the P value was 0.352. The event count was too small to support a firm conclusion, and the study did not distinguish complaints, liability disputes or other forms, or record their causes and resolution. Dispute frequency is also shaped by care quality, financial burden, expectations, complaint handling and mediation systems. The result therefore sets a clear limit to the intervention’s demonstrated reach: better communication may support conflict governance, but it cannot replace formal quality control and dispute-resolution systems.

Several design features also constrain what can be concluded. The study occurred at one hospital, and only two campuses participated, with one assigned to each condition. Because there was no independent randomization within campuses, campus characteristics and the intervention were perfectly aligned; patient-level adjustment could not remove unmeasured differences between sites. Baseline imbalances included payment method, occupation, procedure type and whether a patient had undergone a first procedure, although measured factors were included in the adjusted models. Education, household income, health literacy, physician seniority, team characteristics, communication duration and intervention fidelity were not fully recorded. Subgroup analyses were exploratory and not corrected for multiple comparisons. Although differences remained positive across age, sex and disease-severity groups, a nominal age interaction with risk understanding requires independent replication. Confirmation in multiple hospitals with more independently randomized units, validated outcome scales, longer follow-up and direct measurement of adherence and clinical pathways is needed before the complication association can be treated as causal or the approach can be judged for cost and sustainability in high-volume care.

Subject of Research: A controlled evaluation of structured preoperative physician-patient communication based on prospect theory and procedural-fairness principles.

Article Title: Optimizing physician-patient communication through an integrated perspective of prospect theory and the ultimatum game: a controlled study among patients undergoing elective surgery or invasive procedures in a Chinese tertiary hospital

Article References: Niu, M., & Liu, P. (2026). Optimizing physician-patient communication through an integrated perspective of prospect theory and the ultimatum game: a controlled study among patients undergoing elective surgery or invasive procedures in a Chinese tertiary hospital. Frontiers in Public Health, 14, Article 1937493. https://doi.org/10.3389/fpubh.2026.1937493

Image Credits: AI Generated

DOI: 10.3389/fpubh.2026.1937493

Keywords: preoperative communication, risk understanding, physician-patient trust, treatment acceptance, perioperative complications, prospect theory, shared decision-making, ultimatum game, patient safety, medical disputes, Optimizing, physician-patient

Researchers used two independently randomized cohorts of hospitalized patients aged 18 years or older who were admitted between January 1 and December 31, 2024. Patients had hospital stays lasting between 2 and 14 days. The validation set included 860 patients, while the test set included 886. Each model prediction assessed whether a patient would be discharged the same day, using clinical documentation from the 30 hours preceding a 06:00 index time. A baseline GPT-5 prompt produced an F1 score of 0.48 and sensitivity of 0.37 in the validation set.

The researchers evaluated three inference-time optimization strategies: test-time scaling, expert-led prompt engineering, and automated prompt optimization. On the hold-out test set, automated prompt optimization had higher F1 score and sensitivity than the basic prompt, but also lower positive predictive value and specificity. The abstract does not provide numerical test-set performance values. Test-time scaling and expert-led prompt engineering produced minimal improvement. Overall, automated optimization brought the model’s discharge-prediction performance into the range reported in the abstract for prior approaches.

Qualitative analysis, conducted from June through December 2025, identified operational workflows as the most common source of model errors. The study authors concluded that these workflows, rather than medical knowledge alone, accounted for most errors. The available evidence is limited to the journal abstract and does not report the number of errors reviewed, detailed examples, or the model’s operating characteristics beyond those listed above. Because the study was retrospective and based at one tertiary academic medical center, the abstract does not establish whether the observed performance would generalize to other hospitals or patient populations.

Subject of Research: Evaluation of large language models and prompt optimization for same-day hospital discharge prediction in adult inpatients

Article Title: Optimizing Large Language Models for Hospital Discharge Prediction

Article References: Spagnoli, J., Guzman, N. M., Desai, K., Chang, T. H., Bell, A., Gilbert, V., Lehn, S., Parekh, V. I., Sjoding, M. W., & Wong, A. (2026). Optimizing Large Language Models for Hospital Discharge Prediction. Journal of General Internal Medicine. https://doi.org/10.1007/s11606-026-10792-x

Image Credits: AI Generated

DOI: 10.1007/s11606-026-10792-x

Keywords: large language models, hospital discharge prediction, automated prompt optimization, GPT-5, retrospective cohort study, qualitative error analysis, inference-time optimization, electronic health records, Optimizing, Large, Language, Models

The field experiment was conducted in Bazaruto Archipelago National Park, where the largest known dugong subpopulation in the Western Indian Ocean occurs. Dugongs are large, mostly herbivorous marine mammals whose populations have declined throughout their range, and visual or aerial surveys can be difficult where animals are scarce, solitary, cryptic or avoid human activity. A positive eDNA result therefore offers a non-invasive way to supplement field observations, although the signal may reflect an animal that was present nearby or recently passed through the sampled area rather than one present at the exact sampling point and time.

During the campaign, the research team followed 12 non-linear boat tracks at an average speed of about 1.5 knots through known areas of dugong occurrence. The sampling design compared surface water with near-bottom water, filtered volumes of 1.5, 30 and 60 litres, and approximately 25 millilitres of sediment. Two filter configurations were used: 0.45-micrometre polyethersulfone Waterra cartridges for the 30- and 60-litre samples and 0.22-micrometre Millipore Sterivex filters for the 1.5-litre samples. Near-bottom water was collected about one metre above the seabed with a pump mounted on a manta tow frame, while surface samples were collected from the boat or from composite samples taken at the beginning and end of each track.

The investigators developed a species-specific qPCR assay, named Ddug01, targeting a 115-base-pair segment of the mitochondrial 16S ribosomal RNA gene. In silico analysis indicated amplification specific to dugongs and the extinct Steller’s sea cow. Testing with serial dilutions of dugong tissue DNA produced a linear response from undiluted DNA through a 10^-4 dilution, with a slope of -4.819, an R² of 0.984 and an amplification efficiency of 61.3%. The lowest concentration detected in all four technical replicates was 0.944 picograms of DNA per reaction, which was assigned as both the limit of detection and limit of quantification. Amplification became inconsistent at the next tenfold dilution and was absent at lower concentrations.

Each environmental sample was amplified in eight technical replicates, and a beta-binomial mixed-effects model accounted for positive versus negative replicates while including sampling batch as a random effect. Laboratory processing was associated with markedly stronger qPCR detection than field processing, with a significant treatment effect of χ² = 15.06 and p < 0.001. The comparison concerned complete operational workflows rather than extraction location alone: field samples were processed with smaller amounts of preservation buffer, lower centrifugation capacity and, for Sterivex filters, a different extraction kit. Positive results from field processing showed that the method functioned, but the lower yield indicates a practical limitation of the field protocol.

Filtration volume and vertical position interacted significantly, with χ² = 3.875 and p = 0.049. At the low volume of 1.5 litres, near-bottom samples had about 5.8 times higher odds of producing a positive qPCR replicate than surface samples, a statistically significant difference with p = 0.013. At 60 litres, however, detection was similar between the two vertical positions. The corresponding pattern appeared when volume was compared at each depth: increasing the filtered volume from 1.5 to 60 litres significantly improved detection in surface water, with an odds ratio of 5.49 and p = 0.012, whereas it did not significantly change detection near the bottom, with p = 0.917.

The highest sample-level detection rate came from 60-litre near-bottom samples processed in the laboratory, with 9 of 11 samples positive. The researchers also detected dugong DNA in samples collected 1 hour 40 minutes and 2 hours after the last visual sightings, and at two sites where no animals had been directly observed. One event without a visual sighting produced no eDNA detection, while a known feeding site with visible feeding trails also yielded no positive signal. These outcomes illustrate the complementary nature and limitations of the two approaches: eDNA may reveal animals missed by visual surveys, but absence of a detection does not necessarily establish that dugongs were absent, particularly where tides dilute signals or DNA disperses quickly.

Sediment did not outperform the water-based methods in this pilot. None of the 10 sediment samples produced a positive result, whereas every water-sampling and extraction combination produced at least one detection. The comparison is incomplete because sediment was processed only in the field, where overall detection was lower, and the extraction kit may have performed differently with sediment than with water. The result therefore does not establish that sediment is inherently unsuitable for dugong eDNA analysis. It shows only that the tested sediment workflow offered no advantage under the conditions encountered, while sediment eDNA may integrate signals over longer periods than water samples and could provide information about past rather than recent presence.

High-volume filtration also carried practical benefits. The 0.45-micrometre Waterra cartridge filtered water at an average rate of 25 seconds per litre, allowing a 60-litre sample to be processed in less than 25 minutes at the surface and underwater without clogging. Placing the cartridge directly on the pre-pump side of the system also reduced the amount of single-use tubing consumed, a relevant advantage for large monitoring programs. The field protocol used centrifugation limited to 5,000 g and could not process the full preservation-buffer volume processed in the laboratory. Such conditions are less effective for recovering free or weakly adsorbed DNA than higher-force centrifugation or precipitation methods involving reagents that are difficult to transport because of their toxicity and volatility.

The authors therefore favor mobile surface sampling with high-volume filtration as a practical approach for large-scale dugong monitoring, while acknowledging that the proof-of-concept study included only 12 sampling events and a limited number of positive detections. Sampling volume was also partly confounded with filter configuration and, in some laboratory comparisons, extraction kit, so the results cannot be attributed exclusively to volume. The study supports further testing across broader spatial, temporal and hydrodynamic conditions, including tidal cycles, and does not directly quantify DNA persistence or transport. Even with those limitations, the work shows that carefully chosen water sampling and processing conditions can improve the recovery of rare marine-mammal eDNA and could complement conventional surveys in tropical coastal habitats.

Subject of Research: Optimization of environmental DNA sampling and extraction for detecting rare dugongs in tropical coastal waters

Article Title: Optimizing Marine eDNA Protocols for Rare Megafauna: A Case Study on Dugongs in the Western Indian Ocean

Article References: Bernagou, L., Serval, A., Beudard, F., Mathey, J., Mercky, Y., Le Bozec, C., Trotzuk, E., Paunde, K., Garcia, M., Bellemain, E., & Corse, E. (2026). Optimizing Marine eDNA Protocols for Rare Megafauna: A Case Study on Dugongs in the Western Indian Ocean. Ecology and Evolution, 16(10), Article e74500. https://doi.org/10.1002/ece3.74500

Image Credits: AI Generated

DOI: 10.1002/ece3.74500

Keywords: dugong eDNA, environmental DNA, marine monitoring, qPCR, Bazaruto Archipelago, water filtration, molecular detection, Mozambique, sea mammal conservation, Optimizing, Marine, eDNA

Wet-fixed direct smears are a staple of cytology practice. In this technique, fresh cellular material is spread directly onto a glass slide and fixed while still wet, typically by immersion in 95% ethanol, before being stained, most commonly with the Papanicolaou method that has underpinned cervical cancer screening for decades. The wet-fixation approach preserves crisp nuclear detail, which is exactly what diagnosticians need. But it has an Achilles heel: the same aqueous steps that hydrate and stain the cells also loosen their grip on the slide. During the transitions between water and alcohol baths, and during the prolonged staining sequence itself, cells can detach in sheets or as single cells, reducing smear cellularity and potentially creating diagnostic uncertainty when the remaining material is thin.

The research team, led by Yinying Zou with colleagues Xin Wang, Yan Chen and Zihan Wu, set out to replace anecdote with evidence. Rather than simply asserting that one protocol works better than another, they designed a quantitative, paired comparison study that isolated three variables suspected of influencing cell detachment: the inclusion and concentration of an intermediate alcohol step, the duration of fixation, and the type of slide used. Detachment was scored semi-quantitatively using a streak-wiping method, a practical approach in which the smear surface is wiped and the amount of cellular material removed is graded, giving laboratories a reproducible way to measure what has historically been a subjective observation.

The statistical backbone of the study was appropriately matched to its paired design. Wilcoxon tests were used to compare detachment scores between paired conditions, while Friedman tests handled comparisons across blocks of related samples. This mattered because each experimental condition was evaluated against the others on matched material, controlling for the inherent variability between different smears. The results were striking. The intermediate alcohol step, a brief pass through diluted ethanol inserted between the water-based and high-percentage ethanol stages of processing, significantly reduced detachment compared with omitting it, with a p-value below 0.05. Even more interesting was the concentration effect: 50% ethanol outperformed 75% ethanol at this step, with the difference reaching statistical significance at p = 0.012.

The explanation for this concentration advantage lies in the physics of gradual dehydration. When a wet, water-saturated smear is plunged directly into 95% ethanol, the abrupt osmotic and surface-tension shift can destabilize the cell layer, encouraging cells to lift off the glass. A gentler transition through a more dilute alcohol softens this shock. The 50% ethanol step appears to hit a sweet spot, strong enough to begin dehydration and maintain the intermediate alcohol environment, yet mild enough to avoid the turbulence and shrinkage stresses that a stronger bath imposes. The studys recommendation is precise: include this intermediate alcohol step at every transition between water and 95% ethanol, not just once, but consistently throughout the staining sequence.

Fixation duration emerged as the second powerful lever. The team tested fixation times ranging from 30 minutes to 24 hours and found that prolonged fixation progressively decreased detachment, with the overall trend highly significant at p < 0.001. Cells that are given more time in fixative develop a firmer attachment to the slide surface, presumably because the fixative has fully penetrated and stabilized the cellular proteins and the cell-glass interface. However, the dose-response curve flattened out: beyond 3 hours of fixation, no further statistically significant reduction in detachment was observed. This is a crucial finding for busy laboratories, because it means the benefit of fixation saturates at a practically achievable time point. Extending fixation toward 3 hours captures nearly all of the available benefit, while the marginal gains of overnight fixation do not justify the workflow delay in most settings.

Perhaps the most workflow-friendly conclusion concerned slide type. Positively charged slides, which carry a surface treatment designed to attract and bind tissue sections, are often assumed to be superior for adhesion. The study tested ordinary glass slides against positively charged slides under the optimized protocol conditions and found that the two performed comparably, with p = 0.811. In other words, once the fixation and alcohol-step variables are properly controlled, the expensive specialty slides offer no measurable adhesion advantage for wet-fixed direct smears. Laboratories can confidently continue using ordinary slides, avoiding unnecessary cost without compromising quality, provided they implement the other elements of the optimized protocol.

Synthesized into a single evidence-based strategy, the studys recommendations are elegantly simple: extend fixation toward 3 hours, include an intermediate alcohol step, preferably 50% ethanol, at each transition between water and 95% ethanol, and use ordinary slides. Under these optimized conditions, the combination substantially reduces cell detachment, preserving smear cellularity and reducing the amount of loose cellular material available to contaminate shared staining baths. Because the interventions involve only changes to timing and reagent concentration, they can be implemented without new equipment, new consumables beyond standard ethanol dilutions, or disruptive workflow redesign, making this a rare example of a quality improvement measure that is simultaneously evidence-based and essentially free.

The implications reach beyond laboratory bench practice into patient safety and diagnostic reliability. Reduced detachment means fewer cells floating in staining solutions, which directly lowers the risk of cross-contamination between specimens, a recognized but underappreciated hazard in cytology laboratories. Preserved cellularity means diagnosticians see the full cellular picture the smear was intended to convey, reducing the chance that a paucity of remaining material forces an ambiguous interpretation or a repeat procedure. As laboratories worldwide search for low-cost, high-impact quality improvements, this Zhejiang University study provides a quantified template: three controllable variables, a validated semi-quantitative scoring method, and a statistically supported protocol that any cytology laboratory can adopt to make wet-fixed smears more reliable, one slide at a time.

Subject of Research: Cytology laboratory quality improvement

Article Title: Optimizing fixation and staining to reduce cell detachment in wet-fixed direct smears, a quantitative evidence-based quality improvement study

Article References: Zou, Y., Wang, X., Chen, Y., & Wu, Z. (2026). Optimizing fixation and staining to reduce cell detachment in wet-fixed direct smears, a quantitative evidence-based quality improvement study. Scientific Reports. https://doi.org/10.1038/s41598-026-76374-3

Image Credits: AI Generated

DOI: 10.1038/s41598-026-76374-3

Keywords: cytology, cell detachment, fixation, Papanicolaou stain, laboratory quality improvement, cross-contamination, Scientific Reports, Optimizing, staining, reduce, cell, detachment

The fecal immunochemical test works by detecting hemoglobin, the oxygen-carrying protein of red blood cells, that has leaked into the digestive tract from precancerous growths or tumors. Unlike the older guaiac-based stool tests, FIT does not react with hemoglobin from food, so it can be calibrated to a precise concentration, typically expressed in micrograms of hemoglobin per gram of feces. Lowering the threshold makes the test more sensitive, catching more cancers and precancerous lesions, but it also floods screening programs with false positives, each of which triggers an expensive and invasive colonoscopy. Raising the threshold does the opposite, sparing colonoscopy capacity but missing more early disease. For countries like China, where screening is being rolled out across enormous populations with limited endoscopy resources, that trade-off is not an academic curiosity; it determines whether a program is feasible at all.

To pin down the optimal balance, a team led by Yanxiu Liu and Nan Zhang of Shandong Cancer Hospital and Institute, together with collaborators at Shandong University and other provincial institutions, recruited asymptomatic residents aged 40 to 74 across 13 regions of Shandong Province. All participants were considered average risk, meaning they had no personal or family history suggesting elevated colorectal cancer risk and no symptoms that would already warrant diagnostic investigation. Each volunteer provided a stool sample for FIT analysis and then underwent a full colonoscopy, the gold standard against which the test’s performance could be measured. The researchers tracked three outcomes: colorectal cancer itself, advanced adenomas, which are precancerous polyps with a high potential to turn malignant, and the combined category of advanced colorectal neoplasia, which encompasses both.

The final analysis included 5,918 participants, a cohort in which 378 people, or 6.4 percent, turned out to have advanced adenomas and 28 people, or 0.5 percent, had colorectal cancers. Those numbers illustrate why screening matters: advanced adenomas were more than thirteen times as common as outright cancers, and detecting them early offers the chance to prevent malignancy rather than merely treat it. When the researchers evaluated FIT performance at a threshold of 25 micrograms of hemoglobin per gram of feces, the test detected 96.4 percent of the cancers found at colonoscopy, with a 95 percent confidence interval stretching from 89.3 to 100 percent. Sensitivity for advanced adenomas was considerably lower, at 40.2 percent, and for advanced colorectal neoplasia overall it was 44.1 percent, reflecting the well-known limitation that many precancerous polyps shed too little blood to trip even a low FIT cutoff.

Specificity, the proportion of people without disease who correctly test negative, remained impressively high at the same threshold: 95.6 percent for advanced adenoma, 93.8 percent for cancer, and 96.1 percent for advanced colorectal neoplasia. In practical terms, fewer than one in twenty average-risk residents without neoplasia would be falsely flagged at the 25 microgram cutoff. The researchers also calculated a measure called the number needed to scope, which quantifies the screening burden by counting how many colonoscopies must be performed to find one lesion. If everyone in the population went straight to colonoscopy without any preliminary stool testing, the program would need 211.4 colonoscopies to detect a single cancer and 14.6 to detect one case of advanced colorectal neoplasia. Using FIT at the 25 microgram threshold as a filter, those figures collapsed to 14.6 colonoscopies per cancer and just 2.2 per advanced neoplasia, a reduction of roughly ninety-three percent in the endoscopy burden per cancer detected.

That arithmetic is the heart of the study’s argument. FIT does not outperform colonoscopy in raw detection, but it transforms the economics of screening by concentrating endoscopy resources on the small fraction of people most likely to harbor disease. At a threshold of 25 micrograms per gram, the test misses some advanced adenomas, yet it still identifies the overwhelming majority of cancers while eliminating more than nine out of ten unnecessary colonoscopies. For a screening program, that means a fixed endoscopy budget can cover a vastly larger population, and the study’s authors argue that this balance between detection and resource use is what threshold selection is really about.

The Shandong team then took the analysis a step further by dividing the 13 regions into two groups according to their baseline colorectal cancer incidence, comparing relatively high-incidence areas with relatively low-incidence ones. The subgroup results point toward a strategy that has rarely been articulated so concretely: in regions where colorectal cancer is relatively common, the 25 microgram threshold appeared to provide a more favorable balance between detection and colonoscopy burden, because the higher sensitivity pays off when the underlying prevalence of disease is greater. In regions where the disease is relatively rare, a higher threshold of 50 micrograms per gram mainly improved specificity and screening efficiency, since lowering the cutoff in a low-prevalence population would generate a cascade of false positives that overwhelms endoscopy capacity without proportionally more cancers found.

This prevalence-dependent logic follows directly from the mathematics of predictive values. The positive predictive value of any test rises with disease prevalence, so the same FIT result carries more weight in a high-incidence region than in a low-incidence one. Conversely, when prevalence falls, the cost of each false positive grows relative to the benefit of each true positive, and a stricter threshold conserves resources. The Shandong data suggest that a one-size-fits-all national cutoff may leave efficiency on the table, and that region-specific calibration, informed by local cancer registries, could squeeze more screening value out of the same budget. The authors are careful to note, however, that these subgroup findings require further validation before region-specific strategies can be formally recommended, since the regional division was based on baseline incidence and the cohort, while large, was not designed to test regional strategies head-to-head.

The study arrives at a moment when colorectal cancer screening is expanding across China and other middle-income countries, and when health systems everywhere are grappling with the question of how to screen aging populations without exhausting endoscopy capacity. FIT is already the backbone of organized screening programs in many parts of the world, precisely because it is cheap, noninvasive, and can be administered by mail. But the new results underscore that the test’s value is not fixed; it is a dial that program designers must set according to local disease burden, endoscopy availability, and the goals of the program. A threshold that works well in a high-incidence province may squander resources in a low-incidence one, and the Shandong evidence provides a quantitative anchor for those decisions.

For average-risk residents, the practical takeaway is straightforward: a stool test at a carefully chosen cutoff can identify the great majority of colorectal cancers while sparing more than nine out of ten people an unnecessary colonoscopy, and the cutoff that achieves this balance may depend on where they live. The researchers conclude that a threshold of 25 micrograms of hemoglobin per gram appeared to provide a favorable overall balance in this average-risk population, while their further analyses suggest that optimization may vary across regions with different colorectal cancer incidence. As screening programs scale up, the study offers a template for evidence-based threshold selection, one that could help health systems detect more cancers with the endoscopies they already have, and it adds a compelling data point to the growing science of precision public health, where even a number printed on a stool test kit can shape who lives and who dies.

Subject of Research: Cancer Screening

Article Title: Optimizing thresholds of fecal immunochemical test for colorectal cancer screening in average-risk residents

Article References: Liu, Y., Feng, Y., Gao, Q., Ji, J., Lu, C., Zhang, X., Ma, H., Sun, X., & Zhang, N. (2026). Optimizing thresholds of fecal immunochemical test for colorectal cancer screening in average-risk residents. BMC Cancer. https://doi.org/10.1186/s12885-026-16967-3

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16967-3

Keywords: colorectal cancer, fecal immunochemical test, FIT threshold, colonoscopy, cancer screening, advanced adenoma, screening burden, Shandong Province, BMC Cancer, precision public health, Optimizing, thresholds

The central problem the team set out to solve is deceptively simple: ranches are not uniform. Soil types, slopes, drainage, and vegetation vary dramatically across a single property, and each patch responds differently to grazing, fire, flooding, or invasive species. Yet most existing assessment frameworks treat a ranch as a single unit, requiring one sampling site per 500 hectares regardless of how heterogeneous the landscape is. That standard, embedded in Argentina’s current guidelines for Manejo de Bosques con Ganadería Integrada (MBGI), the national framework for forest management with integrated livestock, has proven difficult to apply, particularly on smaller properties where the sampling density is too coarse to capture real ecological variation.

The new method begins in orbit. Using remote sensing imagery, the researchers delineated what ecologists call Ecological Sites: landscape units that share similar soil, topography, hydrology, climate, and potential vegetation, and are therefore expected to respond similarly to disturbances and management. At the Entre Ríos ranch, El Carayá, the team combined topographic and vegetation data in a geographic information system, drawing on earlier soil maps and vegetation surveys. At the two Patagonian ranches, Tres Lagos and El Jabalí, they used an open-access viewer built in Google Earth Engine that applies a random forest model to layers of mean annual precipitation and temperature, altitude, slope, aspect, meadow probabilities, and distance to rivers, alongside polygons from the most recent classification of native forests for Neuquén, Río Negro, and Chubut.

The classification worked. Six Ecological Sites emerged at El Carayá, eight at Tres Lagos, and four at El Jabalí. At El Carayá, the dominant site was a xerophytic forest of ñandubay (Neltuma affinis) and espinillo (Vachellia caven) covering 62 percent of the 12,450-hectare property, with hygrophilous forests along streams and lowlands accounting for another 28 percent. At Tres Lagos, a 22,224-hectare glaciofluvial valley between two lakes, herbaceous and subshrub communities dominated (36.8 percent), followed by ñire (Nothofagus antarctica) forests (24.6 percent) and Andean cypress (Austrocedrus chilensis) forests (17.3 percent). At the small 82-hectare El Jabalí ranch, wetlands covered 43.4 percent of the area, with Andean cypress, ñire, and mixed forests making up the remainder.

Once the sites were mapped, the team moved to the ground. They overlaid a regular grid of sampling points on each ranch, spacing points at least 250 meters apart and adjusting density to the property’s size and vegetation diversity. At each point they established circular plots of 20 to 25 meters in diameter and filled out a survey form recording qualitative and quantitative indicators of forest condition: herbaceous cover as a proxy for forage availability, indicator species, canopy cover, tree density and height, native tree regeneration, soil erosion assessed through physical crusts and litter cover, shrub encroachment, and signs of disturbance such as fire, flooding, and browsing. They also recorded the presence of exotic wildlife, including European rabbit (Oryctolagus cuniculus), European hare (Lepus europaeus), red deer (Cervus elaphus), and wild boar (Sus scrofa), estimating use intensity from footprints, feces, and direct observations.

In total, the researchers surveyed 92 plots at El Carayá, 227 at Tres Lagos, and 63 at El Jabalí, allocated proportionally across the Ecological Sites. The field data revealed telling contrasts. At El Carayá, soil hydric erosion was absent from 89 percent of plots and fire from 94 percent, but signs of overgrazing appeared in 70 percent of plots. At Tres Lagos, deer presence was recorded in 89 percent of plots, rabbit signs in 67 percent, and browsing evidence in 78 percent, while invasive herbaceous and shrub species were largely absent. At El Jabalí, the picture was more concerning: rosehip (Rosa eglanteria) appeared in 87 percent of plots, blackberry (Rubus ulmifolius) in 76 percent, shrub encroachment was moderate to high in 73 percent, and browsing signs were recorded in 65 percent of plots.

The indicators were then distilled into an Environmental Health Index (EHI). Variables were standardized using min-max normalization, transforming each indicator to a common scale between 0 and 1, where 1 represents the optimal or desired condition. Variables where absence indicated good condition, such as the absence of invasive species, were inverted so the summary index accurately reflected environmental significance. The researchers summed 23 variables at El Carayá and 24 at the Patagonian ranches, producing a gradient from worst (0) to best (1) at each sampling plot. The plots were grouped into three indicator categories, Soil, Vegetation, and Threats or Degradation processes, to allow a straightforward relationship between each recorded indicator and the corresponding ecosystem component.

To turn scattered plot values into continuous maps, the team applied ordinary kriging, a geostatistical interpolation method that accounts for the spatial correlation of observations. They randomly divided the sampling points into 70 percent for model calibration and 30 percent for independent validation, then compared five semi-variogram models: stable, circular, spherical, exponential, and Gaussian. The circular model performed best for El Carayá and Tres Lagos, the exponential model for El Jabalí. Cross-validation statistics showed mean squared errors close to zero for all three ranches, 0.027 for El Carayá, 0.046 for Tres Lagos, and 0.049 for El Jabalí, with corresponding root mean squared errors of 0.167, 0.214, and 0.222. The final EHI maps were generated at 10-meter resolution, fine enough to capture landscape detail while maintaining analytical integrity.

The mapped results showed that most land units across the three ranches exhibited intermediate to high environmental health. At El Carayá, average EHI values exceeded 0.50 across all sites, with 95 percent of the highland xerophytic forest ranging from 0.44 to 0.67, and the hygrophilous forest in streams showing the highest proportion of high values, with 90 percent of its area between 0.44 and 0.77. Less degraded forests clustered in the west and central-eastern regions, while degraded patches concentrated in the northeast and southwest. At Tres Lagos, all sites averaged between 0.49 and 0.55, with 88 percent of the ñire forest between 0.43 and 0.57. El Jabalí told a different story: all sites averaged below 0.45, with 48 percent of the coihue forest and 54 percent of the ñire forest falling between 0.16 and 0.32, the lowest values recorded in the study.

The researchers attribute El Jabalí’s poor showing to the pressures typical of small-scale ranching, where high stocking rates and visible overgrazing reflect the combined weight of livestock and forestry practices on limited land. More broadly, the predominance of intermediate EHI values across the ranches suggests a degree of resilience in these ecosystems, likely linked to the resprouting and regeneration capacity of native vegetation, despite a long history of grazing, forestry, and fire in the Espinal and Patagonian ecoregions. The team notes that the method has limitations: the Patagonian Ecological Site viewer is still under development, meadow classifications rely on a country-level probability map that may require field validation, and rapid assessment by design trades depth for speed. Still, the approach proved accurate across ranch sizes from under 100 to over 12,000 hectares, and the researchers argue it could scale up to landscape and regional levels, helping bridge the persistent mismatch between field-based ecological data and remote sensing. By pinpointing exactly where degradation is occurring within each ranch, the tool allows managers to direct scarce sampling effort and adaptive interventions to the patches that need them most, a capability the researchers say is essential as land-use pressures continue to rise on forested production systems worldwide.

Subject of Research: Environmental spatial assessment at ranch scale: a tool for optimizing livestock management in Argentine forests

Article Title: Environmental spatial assessment at ranch scale: a tool for optimizing livestock management in Argentine forests

Article References: Varela, S. A., Calamari, N. C., Trinco, F. D., Diez, J. P., Weigandt, M., Barzán, F. R., Lezana, L., Eclesia, R. P., López, D. R., Coria, R. D., Peri, P. L., Umaña, F. J., Raffo, F., Gazzotti, J. I., de la Peña, C., Wilson, M., Gabioud, E., Hernández, H., & Canavelli, S. B. (2025). Environmental spatial assessment at ranch scale: a tool for optimizing livestock management in Argentine forests. Vegetation Classification and Survey, 6, 163-179. https://doi.org/10.3897/vcs.141917

Image Credits: AI Generated

DOI: 10.3897/VCS.141917

Keywords: Environmental, spatial, assessment, ranch, scale, tool, optimizing, livestock, management, Argentine, forests, scientific research

The clinical stakes are considerable. Sepsis, defined as life-threatening acute organ dysfunction caused by infection, leaves survivors vulnerable to new cognitive impairment, worsening functional limitation, and exacerbation of chronic conditions. As many as 40 percent of survivors are rehospitalized within three months, and up to 30 percent die within the following year. Recovery is often prolonged and demands complex multidisciplinary care. Yet the Surviving Sepsis Campaign guidelines that address peri-discharge management rest largely on low-certainty or ungradable evidence, and the few randomized trials of sepsis recovery have evaluated complex multi-component interventions, making it difficult to isolate which individual practices drive benefit. Health systems have therefore implemented recovery programs in a fragmented manner, often without a strong empirical basis for their choices.

To close that gap, the research team, working within the Optimizing Veteran Recovery from Sepsis (OVeR-Sepsis) study funded by VA Health Systems Research, assembled practices from the Surviving Sepsis Campaign guidelines, hospital discharge guidelines, prior literature, and interviews with Veterans Health Administration clinicians. The panel that evaluated them included experts in sepsis, critical care, hospital medicine, primary care, geriatrics, inpatient and outpatient nursing, physical therapy, quality improvement, and post-critical illness recovery, as well as three Veteran patient representatives. Panel meetings ran from January through March 2025. For each practice, panelists independently rated validity, importance, and resource intensity on a nine-point Likert scale using Slido software before discussing the evidence and rerating. Disagreement was assessed statistically using the InterPercentile Range Adjusted for Symmetry, and practices with a median validity score of 7 to 9 without disagreement were rated valid.

Of the 18 practices considered, 10 were rated valid, eight uncertain, and none not valid, with no disagreement in the final ratings. Five practices emerged as the highest-value targets: scheduling recommended follow-up visits and testing before discharge; screening for limitations in basic and instrumental activities of daily living and need for durable medical equipment; educating patients on sepsis itself; educating patients on common post-sepsis symptoms such as fatigue, shortness of breath, and brain fog; and counseling patients or caregivers on discharge medications and their indications. All five were rated highly important yet only moderately resource-intensive, a combination the authors say should guide systematic implementation, quality improvement, and resource allocation.

Several of the panel’s judgments departed from existing guidelines in technically revealing ways. Scheduling outpatient follow-up within two weeks of discharge, and requiring that such visits be in-person, were both downgraded to uncertain validity. Panelists argued that reflex scheduling of every sepsis survivor, regardless of need, could erode clinic access for patients with more urgent problems, and noted that no evidence establishes a specific follow-up interval as outcome-improving or in-person visits as superior to virtual care. The final position aligns with the 2021 Surviving Sepsis Campaign guidelines, which issued no recommendation on early follow-up due to insufficient evidence, and with AHRQ’s Project RED toolkit, which recommends scheduling follow-up before discharge but does not specify timing.

The panel was similarly skeptical of systematic screening for cognitive impairment, anxiety, depression, and post-traumatic stress disorder after sepsis, a notable divergence from prior consensus recommendations. Panelists acknowledged that these conditions are common among survivors but questioned whether proactive screening improves management. Lingering delirium, they observed, may resolve with time, and an early screen risks an inaccurate diagnosis of cognitive impairment that could distress the patient, persist in the medical record, and alter care without benefit. Anxiety and depression after acute medical illness may likewise resolve with supportive care, and annual mental health screening is already recommended by the US Preventive Services Task Force and embedded in VHA practice. The panel concluded that the benefits of additional post-sepsis screening may not outweigh potential harms.

Other practices earned valid ratings but at high resource cost, placing them in a second implementation tier. Physical therapy evaluation before discharge was rated valid and highly important, with panelists suggesting that the AM-PAC

The panel’s reasoning also illustrates how resource intensity was defined expansively rather than narrowly. When panelists scored a screening practice, they were instructed to count not only the cost of administering the screen itself but also the downstream work it triggers, including any confirmatory testing, referrals, or treatment that a positive result would set in motion. This framing matters because practices that appear inexpensive at the bedside can become substantially more burdensome once their full cascade of follow-up is accounted for. Conversely, practices like medication counseling require little more than clinician time and careful communication, which helps explain why they clustered in the favorable high-importance, moderate-resource quadrant of the panel’s final ratings.

The composition of the panel itself shaped these judgments, and the authors are candid about its limits. Fifteen voting members included eight clinicians from the Veterans Health Administration, four clinicians from outside that system, and three Veteran patient representatives drawn from the Ann Arbor VA Veterans Research Engagement Council. Panelists were affiliated with seven VHA facilities across seven geographic regions and four national program offices covering hospital medicine, quality and patient safety, primary care, and nursing. The study team participated in deliberations but did not vote. Notably, the panel included no social work representation, a gap the authors flag as potentially influential, since several of the practices under consideration—particularly those touching on social support and care coordination—depend heavily on social work expertise. The predominance of VHA clinicians also raises questions about how ratings might differ in settings with different staffing models, payment structures, or patient populations.

The deliberative process itself changed outcomes in measurable ways. Five practices shifted between the initial and final rounds of rating, with four moving from valid to uncertain and one moving in the opposite direction, from uncertain to valid. These reversals followed structured discussion of the evidence, during which panelists reviewed literature summaries circulated before each meeting and debated practices where initial scores showed disagreement or wide spread. The audio-recorded and transcribed discussions were later mined for illustrative quotes that document the panel’s rationale. This dynamic—where expert consensus can erode as well as build under scrutiny—underscores that the ratings reflect collective judgment about the state of evidence rather than settled proof of effectiveness. A rating of uncertain validity is not a claim that a practice is useless; it is a statement that the panel lacked confidence it reliably improves recovery.

That distinction has practical consequences for how health systems should read the results. The five prioritized practices share a common character: they are largely informational and organizational interventions that connect patients to appropriate care rather than diagnostic or therapeutic maneuvers in themselves. Scheduling follow-up before discharge removes a well-known failure point in transitions of care, since patients who leave the hospital without an appointment in hand frequently fail to establish one. Screening for limitations in basic and instrumental activities of daily living, and for durable medical equipment needs, addresses the functional decline that sepsis survivors commonly experience and that often goes unrecognized until it causes a crisis. Education about sepsis itself, including the signs and symptoms of recurrence, equips survivors to recognize deterioration early, while education about expected post-sepsis symptoms such as fatigue, shortness of breath, and brain fog can normalize the recovery trajectory and prompt appropriate care-seeking. Counseling on discharge medications and their indications targets the medication errors and unintentional discontinuations that frequently accompany complex post-hospital regimens.

The panel’s emphasis on patient-centered scheduling deserves particular attention. In discussing the highest-priority practice, panelists stressed that follow-up should be arranged in a way that accounts for patient preferences regarding modality and timing, rather than blindly assigning patients to whatever clinic slots happen to be open. This nuance separates the endorsed practice from the downgraded one: the problem was never with follow-up itself, which the panel rated valid and highly important, but with rigid, one-size-fits-all mandates about when and in what format it must occur. The heterogeneity of sepsis presentations—ranging from patients discharged after brief resuscitation to those with prolonged organ dysfunction—makes uniform timing rules difficult to defend.

For quality improvement leaders, the framework offers a defensible starting point for resource allocation decisions that have until now lacked empirical grounding. Because the panel explicitly scored resource intensity alongside importance, the results can be mapped directly onto implementation planning: the five high-importance, moderate-resource practices represent the clearest near-term targets, while the valid but resource-intensive practices, such as pre-discharge physical therapy evaluation, may warrant adoption where institutional capacity permits. The authors intend the ratings to inform management, quality improvement efforts, and resource allocation, and the methodology—transparent scales, statistical assessment of disagreement, and documented deliberation—allows other institutions to adapt the framework to their own constraints. As evidence from future trials accumulates, the panel’s judgments can be revisited, with uncertain practices either earning validation or fading from recommended practice.

Subject of Research: Best Practices for Optimizing Recovery from Sepsis; Results of an Expert Panel

Article Title: Best Practices for Optimizing Recovery from Sepsis; Results of an Expert Panel

Article References: Sussman, J. B., Hogan, C. K., Whittington, T., Akgün, K. M., Anderson, M. L., Duseja, R., Eaton, T. L., Falvey, J. R., Ganz, D. A., McPeake, J., Taylor, S. P., Pawlikowski, S., Piazza, K. M., Sullivan, S. C., Bernstein, S. J., & Prescott, H. C. (2026). Best Practices for Optimizing Recovery from Sepsis; Results of an Expert Panel. Journal of General Internal Medicine. https://doi.org/10.1007/s11606-026-10926-1

Image Credits: AI Generated

DOI: 10.1007/s11606-026-10926-1

Keywords: Best, Practices, Optimizing, Recovery, Sepsis, Results, Expert, Panel, scientific research

The authors, a team from the National Laboratory of the Rockies Biosciences Center led by Carolyn E. Lubner, focus on the cyanobacterium Synechocystis sp. PCC 6803, a workhorse organism for photosynthesis research. Their central claim is that the interplay between primary light capture, the conversion of photons into high-energy electrons, and the downstream sinks that consume those electrons forms a feedback loop. When engineers redirect electrons toward a desired product, the organism compensates by altering the light capture and conversion machinery in ways that can profoundly affect photosynthetic efficiency and product yield.

The perspective highlights four components where this plasticity is emerging. Phycobilisomes, the large light-harvesting antennae of cyanobacteria, exist in two major forms that differentially associate with specific configurations of the reaction centers. Photosystem I, the reaction center that converts photons into high-energy electrons, can be found predominantly as a trimer or, under dynamic environmental conditions, as a monomer. The [NiFe]-hydrogenase complex known as HOX consists of five subunits catalyzing reversible oxidation of molecular hydrogen linked to NAD(P)H and ferredoxin reactivity, as well as a three-subunit subcomplex with diaphorase activity. Finally, four distinct flavodiiron enzymes can form homo- or heterodimer pairs that link oxidation of photosynthetic carrier pools to the reduction of oxygen to water.

Phycobilisomes are supramolecular protein complexes ranging from 3 to 18 megadaltons, containing thousands of covalently bound linear tetrapyrrole chromophores called bilins. These absorb light between roughly 500 and 600 nanometers and give the isolated complexes their brilliant blue color. Excitation energy transfer through the phycobilisome is nearly quantum efficient, proceeding via both Förster and coherent mechanisms. The precise orientation of the highly conjugated bilin pi-systems underlies all phycobilisome architecture, with large uninterrupted rows of these pi-systems funneling light energy down the antennae toward the reaction centers. The rods, made of multimeric disks of phycobiliproteins such as phycocyanin and phycoerythrin, are assembled via rod-specific linkers and either link directly to the thylakoid membrane through the CpcL linker or arrange into fanned supramolecular rods emanating from cores of allophycocyanin via CpcG-type linkers.

Both CpcL single-rod phycobilisomes and the massive CpcG complexes with fanned rods associate with Photosystem I and Photosystem II to form the largest categorizable molecular superstructures in nature, deemed mega- or super-complexes. Within minutes of altered incident light, cyanobacteria undergo so-called state transitions, adjusting excitation energy transfer from phycobilisomes to Photosystem I, Photosystem II, or both. Fluorescence studies have shown preferential transfer to Photosystem II during state 1 and to Photosystem I during state 2, but exactly how this redistribution occurs remains under debate. Do state transitions arise primarily from phycobilisome rearrangement between super-complexes, or does excess energy migrate via emergent transfer funnels in response to over-reduced Photosystem II within fixed supercomplexes? Recent kinetic modeling of time-resolved fluorescence spectra suggests that phycobilisome structural changes dictate state transitions within supercomplexes, and the authors’ own laboratory found evidence of structural alterations in both Photosystem I and CpcL-phycobilisomes caused by knocking out a flavodiiron gene, begging the question of what role single-rod phycobilisomes play in cyanobacterial state transitions.

Photosystem I itself displays marked plasticity. Under continuous light conditions, it exists in a uniform and packed state, but under light-dark periods it becomes more dispersed throughout the thylakoid membrane. Under times of high and fluctuating light stress, Photosystem I shifts from predominantly trimeric to increased monomeric forms in a mutant background where a downstream electron utilization pathway involving flavodiiron proteins is absent. In addition to changes in oligomeric state, Photosystem I displays changes in photooxidation capacity, spectral properties, pigment composition and an altered PsaL subunit environment. The authors contend that multiple mechanisms regulate overexcitation in Photosystem I, including chemical modifications, carotenoid biosynthesis and conversion, non-photochemical quenching, and changes to supramolecular organization and architecture.

The thylakoid membrane itself may play a role in this regulation through the lateral segregation of lipids. Trimeric Photosystem I isolated from Thermosynechococcus elongatus using styrene maleic acid copolymers, rather than detergents, retains an annulus of nearly 1,300 native thylakoid lipids. Lipidomic analysis of these nanodiscs shows a distinct profile in the proximal environment of Photosystem I, highly enriched in the negatively charged glycerolipid sulfoquinovosyldiacylglycerol, which accounts for 62 percent of the lipid annulus despite being a minor constituent of the bulk membrane. Sulfoquinovosyldiacylglycerol was found to spontaneously self-associate into microdomains within Langmuir monolayers, and these microdomains allow faster migration and deeper insertion of the copolymer compared to any other thylakoid lipid. The authors suggest that the thylakoid lipids may exhibit lateral segregation and the formation of microdomains that only allow the copolymer to insert in the region of trimeric Photosystem I, raising the question of whether the lipid environment is altered when the oligomeric state of Photosystem I changes and vice versa.

Flavodiiron enzymes are metallo-enzymes comprising a pair of core domains that bind a flavin mononucleotide and a non-heme diiron cofactor to catalyze the reduction of either nitric oxide to nitrous oxide or oxygen to water. Synechocystis encodes four flavodiiron proteins and Anabaena encodes six, which are differentially regulated and proposed to have distinct physiological roles. Kinetic studies of Flv1 and Flv3 homodimers show turnover numbers of 10 to 100 per second, with structural models predicting a head-to-tail orientation of monomers and electron transfer likely occurring across the dimer interface. How electron transfer in flavodiiron proteins is controlled to achieve selective four-electron reduction of oxygen to water remains a key question. Cellular studies suggest that flavodiiron proteins can function as heterodimers, with indirect evidence suggesting they may couple to ferredoxins or, in the case of Flv2 and Flv4, to the Q(B) site of Photosystem II. Strains lacking either Flv1 or Flv3, or both, show distinct differences in growth rate, pigment composition and susceptibility to high-light or low carbon dioxide conditions, and microarray analysis of a Flv3 knockout mutant reveals significant changes among proteins functioning in stress responses, metal homeostasis and electron flow, including downregulation of Photosystem I subunits B, C, D, E, J and L, increases in orange carotenoid protein, and only minimal effects on Photosystem II expression.

The cyanobacterial HoxEFUYH [NiFe]-hydrogenase complex comprises diaphorase and hydrogenase subcomplexes that can associate to form the full hydrogenase, catalyzing the interconversion of ferredoxins, flavodoxins and pyridine nucleotides with molecular hydrogen. The bidirectional nature of the hydrogenase affords the ability to store excess electrons in the form of hydrogen or to uptake electrons from hydrogen under oxidizing conditions. The HoxEFU diaphorase subcomplex has been shown to function independently from HoxYH, catalyzing the interconversion of ferredoxins and flavodoxins with NAD(P)(H), and the HoxEFU subunits share primary sequence homology to Complex I subunits containing multiple iron-sulfur clusters and a flavin cofactor. Through complementary electron paramagnetic resonance and electrochemical measurements, the authors identified a quaternary structure dependent shift in the reduction potential of a [2Fe-2S] cluster in the HoxE subunit, which is adjacent to a proposed ferredoxin binding site and within electron transfer distance to the NAD(P)H flavin binding site. This observation underscores the dynamic structural nature of the complex, and the authors hypothesize that conformational gating plays a role in the allosteric control of reactivity based on the presence of substrates, with cooperative reaction kinetics between ferredoxin and NAD(P)+ suggesting a possible functional role for higher-ordered complexes in managing photosynthetic electron flow.

Collectively, the work highlighted in this perspective has profound implications for the design and re-engineering of photosynthetic organisms for biotechnology applications. The authors argue that until the mechanistic diversity of these intertwined pathways is well understood and factored into an engineering strategy, the organism may simply override the desired metabolic outcome by adapting in another manner. Expanding understanding of the natural variation of reaction centers is expected to support novel approaches for engineering natural systems and designing synthetic and biohybrid energy-converting complexes. The authors conclude that photosynthesis is wonderfully complex in ways that are currently not fully understood, and that more research will only lead to more successful efforts in redirecting function to meet applied goals.

Subject of Research: Photosynthesis

Article Title: Influence of cellular redox reactions on the structure and function of light harvesting and photosystems

Article References: Laughlin, A. L., Brady, N. G., Kisgeropoulos, E. C., Stroeva-Dahl, E. M., Dawson, M. E., Mulder, D. W., King, P. W., & Lubner, C. E. (2026). Influence of cellular redox reactions on the structure and function of light harvesting and photosystems. Frontiers in Photobiology, 4, Article 1835508. https://doi.org/10.3389/fphbi.2026.1835508

Image Credits: AI Generated

DOI: 10.3389/fphbi.2026.1835508

Keywords: Influence, cellular, redox, reactions, structure, function, light, harvesting, photosystems, scientific research