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Spatio-temporal dynamics of total mercury contamination in diving birds as bioindicators of tropical wetlands in India

EZH2 as regulator of stemness signature and driver of esophageal squamous cell carcinomas

Load-resilient shingled photovoltaic module for field-scale thermoelectric coupling

Abstract Photovoltaic (PV) solar cells generate waste heat during field operations, which reduces their overall power output. One potential solution for future solar power technology is to integrate solar cells with thermoelectric generators (TEGs) to enable waste heat reclamation, thereby enhancing power output. However, the high TEG resistance ( R TEG ) increases the series resistance of these devices, leading to significant power loss. Here, we demonstrated that PV operation at low current and high voltage sufficiently reduces the impact of R TEG , facilitating field-scale PV–TEG coupling. Furthermore, to achieve low-current, high-voltage operation, a shingled PV module configuration proved effective. This module comprises narrow strip-shaped solar cells connected in series; hence, the current is divided, and the voltage output across the strips is increased. Consequently, lower current and higher voltage than those of an uncut cell of the same size are achieved. Particularly, for a 14-strip shingled module, a load-resilient shingled PV module was realized for a field-scale PV–TEG (170 cm 2 ) that delivers 3.27 W with a P loss of only 0.043%. This shingled configuration is versatile and can be applied to any solar cell type, including organic, perovskite, and state-of-the-art tandem solar cells. Our study provides potential solutions to the problem of high R TEG and new directions for achieving load-resilient PV modules for reliable field-scale PV–TEG coupling.

Longitudinal evidence for the principle of allocation in Japanese university decathletes

Decision processes in 3D structural MRI schizophrenia classification evaluated with saliency maps

Abstract Clinical decision support systems for psychiatric disorders such as schizophrenia can benefit from machine learning models based on neuroimaging data for objective diagnosis, prognosis, and effective treatment selection. Deep learning (DL) models promise to be suitable for this task since they can detect complex patterns in images without the need for prior information about candidate regions. Their downside, however, is the lack of transparency about the decision process. Explainable AI methods address this problem and might be helpful in the clinical translation of DL applications as well as potential biomarker indication. The current study qualitatively and quantitatively evaluates seven DL architectures frequently employed in medical image analyses with gradient-weighted class activation mapping (Grad-CAM) for plausibility and finds that only two of the seven models base their decisions in a schizophrenia classification task on plausible structural brain information, despite similar classification performance. Furthermore, we develop an approach to translate the saliency maps from the Grad-CAM into universally interpretable anatomical markers of schizophrenia and find candidate regions corresponding to known markers of schizophrenia. To conclude, this study demonstrates the necessity of using explainable methods alongside DL approaches and the feasibility to derive biomarkers with such methods.

SPP1-positive myeloid cell subpopulations associated with resistance to PD-1/L1 immunotherapy in lung adenocarcinoma

Phonological awareness in Urdu language speaking children with down syndrome (DS)

Introduction Phonological awareness (PA) is a vital part of literacy development. With dearth of evidence on phonological processing among Urdu-speaking children with down syndrome (DS), current study was conducted to determine the association between response time on rapid naming tasks and phonological awareness performance in children with Down syndrome. Methods A quasi-experimental study that used cross-sectional design was carried out with 48 children with DS and who are Urdu speaking children (4–12 years) at three rehabilitation centers in Lahore, Pakistan. Rapid automatized naming and phoneme identification tasks were measured with the help of the Urdu Phonological Tele-Assessment (U-PASS) tool. Simple linear regression and partial correlation were analyzed. Results The results revealed that the mean response time and phonological awareness had no significant relationship (R2 = 0.006, p = 0.587). The phoneme recognition (M = 9.42) at the beginning was much higher than the phoneme recognition (M = 5.42) at the end. There was moderate positive correlation existing between initial and final phoneme awareness (r = 0.423, p = 0.004) that did not depend on response time. Conclusion Processing speed processing and phonological accuracy are two different cognitive constructs in children with DS. The clinicians are encouraged to emphasize the accuracy-based testing and adopt specific interventions addressing the end phoneme awareness.

Structure-based pharmacophore modeling, high-throughput screening, and molecular dynamics identify a novel DrugBank-derived HIV-1 protease inhibitor

HIV-1 protease (PR) is required for viral maturation and is a major antiretroviral target. In this study, a structure-based pharmacophore modeling, drug repurposing, docking, and molecular dynamics (MD) was applied to discover new PR inhibitors. A pharmacophore model was generated from the HIV-1 PR–3TL complex (PDB 3KFP) and used to screen the DrugBank library and hit identification. The identified hit and reference 3TL were docked into PR, and each complex was simulated for 100 ns. Key metrics, including binding energy, RMSD, RMSF, SASA, hydrogen bonds, salt bridges, PCA were analyzed and compared. Through the screening, one hit, HONH-BENZYLMALONYL-L-ALANYLGLYCINE-P-NITROANILIDE (DrugBank Accession Number: DB07434) (BAN), was identified. Docking predicted BAN’s binding energy (–7.51 kcal/mol) slightly better than 3TL (–7.05 kcal/mol). MD showed BAN established a dense H-bond network, including Asp25, and a highly favorable total interaction energy (–69 kJ/mol). However, BAN binding significantly increased protease flexibility. BAN-bound PR had higher backbone RMSD (0.34 nm) and RMSF (0.215 nm) than 3TL-bound (0.22 nm, 0.121 nm), and disrupted salt bridges that remained stable with 3TL. PCA revealed BAN-bound PR sampled a larger conformational space. SASA changes were minor in all systems. BAN binds HIV-1 PR with affinity comparable to 3TL but via a distinct mechanism, stronger polar interactions accompanied by greater protein flexibility. These results, supported by recent literature, suggest BAN as a novel scaffold for PR inhibition. Experimental validation of BAN’s inhibitory activity is warranted.

Using mixed reality to support component restoration of Chinese traditional dwellings: A case study of column bases in Yanling House

Due to limited surveying, mapping, and image data, as well as technological constraints, current efforts to restore missing components in traditional Chinese dwellings often result in mismatches with the original appearance. This study employed a mixed-methods approach to evaluate the effectiveness of using mixed reality (MR) to address these challenges. Using an MR system built with Microsoft HoloLens 2 and Trimble Connect, we conducted an on-site experiment with twelve participants focused on column base restoration in the main hall of Yanling House, a typical traditional Chinese dwelling in Jintong Village, Youxi County, Fujian Province. Quantitative questionnaire ratings were utilized to illustrate the effects of MR in this on-site experiment, while qualitative semi-structured interviews provided further elucidation and validation of these effects. The results demonstrate that MR can help participants restore the components in a way that conforms to their original appearance through immersive perceptions, accurate adjustments, and convenient communications, thus providing effective technical support for preserving the unique historical and cultural value of traditional Chinese dwellings.

Trends in recorded deaths involving antipsychotics: The role of deprivation, ethnicity, and regional disparities

Objective The relationship between antipsychotic use and mortality remains uncertain, with evidence suggesting both potential risks and benefits. This study aimed to examine trends in recorded deaths involving antipsychotics in England and to explore regional, socioeconomic, and ethnic variation in these patterns. Methods A population-level analysis of NHS prescription data (2015–2023) across seven regions of NHS England used linear regression and generalised additive models (GAMs) to explore associations between recorded deaths involving antipsychotics and deprivation, ethnic density, and regional variation. Results Recorded deaths involving antipsychotics increased from 10.33 to 13.85 deaths per million prescription items between 2015 and 2023 (p < 0.01), with an annual increase of 3.56%. Regional analysis showed significant disparities, with the highest increase observed in London (9.99%, 95%CI: 9.50–10.48) and a decrease was observed in the Midlands (−2.06%, 95%CI: −2.71 – −1.41). Deprivation was significantly associated with increased mortality (p < 0.01), while regions with higher Asian density exhibited lower mortality rates (p = 0.01). Conclusions Recorded deaths involving antipsychotics have increased over the past decade, with considerable regional disparities. Deprivation remains a key driver of mortality risk. While antipsychotics have well‑established clinical benefits in the management of severe mental illness, these findings highlight the need for strengthened prescribing safety, improved monitoring, and equity‑focused interventions to reduce preventable deaths.

Altered brain–behavior coupling during inhibitory control in ankylosing spondylitis: ERP evidence from NoGo-P3 component

Background Cognitive dysfunction has increasingly been recognized in Ankylosing Spondylitis (AS), yet the neural mechanisms underlying inhibitory control in this population remain insufficiently characterized. Rather than reflecting a simple global deficit, cognitive alterations in AS may involve task-dependent changes in the coupling between neural activity and behavioral performance. This study examined executive control in AS using a Go/NoGo paradigm and focus on brain-behavior coupling during inhibitory processing. Methods 16 male patients and 23 age-matched healthy controls completed a Go/NoGo task while undergoing 32-channel EEG recording. ERP analyses focused on N2 (200–300ms) and the late positive component in the NoGo condition (hereafter termed NoGo-P3; 400–600ms). Mean amplitudes were extracted at fronto-parietal midline electrodes. To directly test group differences in brain–behavior coupling, linear regression models including the ERP × Group interaction term were fitted. Theta-band (4–7 Hz) power within the 400–600 ms window was additionally analyzed using FFT-based spectral estimation. Results Behaviorally, AS patients showed lower Go accuracy and longer Go reaction times, together with a tendency toward higher NoGo accuracy. In AS patients, NoGo accuracy positively correlated with NoGo-P3 amplitude at FCz (r = .64, p = .009) and Cz (r = .55, p = .035), whereas these associations were not significant in controls. Direct group comparison showed a significant ERP × Group interaction at FCz (b = 0.084, p = 0.033), indicating that the relationship between NoGo-P3 amplitude and inhibitory accuracy differed between AS patients and healthy controls, while Cz (b = 0.051, p = 0.106) showed a similar but non-significant trend. Complementary theta analyses revealed enhanced post-stimulus theta power in centro-parietal regions during NoGo processing in AS. Conclusions The findings suggest altered brain–behavior coupling during inhibitory control in AS, with the most robust evidence emerging from the NoGo-P3 component at FCz. This pattern is consistent with greater reliance on effortful control-related neural recruitment during successful inhibition and may represent a candidate electrophysiological marker of altered executive processing in AS.

Unraveling Puerarin’s impact on MRI hepatic lipid deposition and serum lipids in IUGR offspring rats

Intrauterine growth restriction (IUGR) is associated with long-term metabolic programming effects, including hepatic structural alterations and later-life susceptibility to metabolic disease, potentially involving dysregulation of peroxisome proliferator-activated receptor alpha (PPARα), a key regulator of hepatic fatty acid oxidation. Given its established antioxidant and lipid-modulating properties in adult models of metabolic syndrome, puerarin, a natural isoflavone, was evaluated as an early-life intervention to mitigate hepatic injury in IUGR offspring. An IUGR rat model was established via gestational protein restriction. Male offspring were randomized into Control, IUGR, and IUGR plus puerarin groups. Separate cohorts (n = 6 per group per time point) were assessed at weeks 3, 8, and 12. Puerarin (50 mg/kg/day) was administered intraperitoneally from postnatal days 7–21. Hepatic tissue characteristics were evaluated using T1 mapping and intravoxel incoherent motion (IVIM) MRI. Serum lipid profiles and hepatic PPARα mRNA expression were also measured. Data were analyzed using two-way ANOVA followed by Tukey’s post hoc test. IUGR offspring exhibited significantly elevated hepatic T1 relaxation times from week 3 onward ( P  < 0.0001), indicating early and persistent hepatic microstructural alterations. Serum lipid parameters remained largely comparable across all groups, with no significant intergroup differences in TG, TC, LDL-C, or HDL-C at individual time points. Puerarin treatment significantly reduced T1 values and improved diffusion-related parameter (D) across all time points ( P  < 0.05), indicating improved hepatic water mobility and microstructural integrity. ADC showed early improvement at week 3, whereas perfusion-related IVIM parameters (D* and F) showed no consistent or significant intergroup differences. Serum TG levels were significantly reduced by puerarin at week 12 compared with untreated IUGR offspring ( P  < 0.05), while TC and LDL-C remained unchanged. Hepatic PPARα expression was markedly suppressed in IUGR offspring across all time points ( P  < 0.0001) and was significantly increased by puerarin only at week 12 ( P  < 0.01), although overall expression remained below control levels. These findings suggest that IUGR primarily induces early hepatic microstructural alterations detectable by quantitative MRI before overt systemic dyslipidemia. Early-life puerarin intervention partially ameliorates hepatic diffusion abnormalities and improves selected metabolic markers, potentially through delayed activation of lipid oxidation pathways including PPARα. However, further studies incorporating direct hepatic lipid quantification and functional metabolic assessments are required to validate these findings.

Comparison of self-collected vaginal swabs and first-void urine for detection of human papillomavirus in sexually active girls and women in three South Asian countries

Background As more countries plan and launch human papillomavirus (HPV) vaccination campaigns, a variety of self-sampling methods and assays have been used for detecting high-risk HPV (HR-HPV) types. This study compared HR-HPV detection in self-collected vaginal swabs (SCVS) and first-void urine (FVU) among sexually active girls and women aged 15–25 years in diverse settings (Bangladesh, Nepal, and Pakistan) using harmonized methods for each step. Methods Within the Global Burden Estimation of HPV (GLOBE-HPV) project, which aims to estimate HPV prevalence and incidence across eight low- and middle-income countries in South Asia and Sub-Saharan Africa, we analyzed paired SCVS and FVU samples from 753 participants in Bangladesh, Pakistan, and Nepal using standardized protocols. DNA was extracted using the QIAamp DNA Mini Kit, and HPV testing was performed with the Allplex HPV28 Detection PCR assay. We evaluated HPV detection and type-specific concordance using Cohen’s Kappa, McNemar’s test, and a 3 × 3 agreement table, along with accuracy and positive/negative agreement metrics. Results The overall prevalence of 14 HR-HPV types was 8.6% in SCVS and 7.2% in FVU samples. Detection rates for 7 HR-HPV vaccine types were similar (5.3% in SCVS versus 5.0% in FVU), with nearly identical HPV 16/18 rates (2.3% in SCVS and 2.4% in FVU). Bi-directional type-specific discordance was noted, with each sample type detecting unique types. SCVS demonstrated higher sensitivity for detecting HPV types beyond the 9 vaccine types with McNemar p-values of 0.013 and <0.001 for 14 and 28 types, respectively, while overall concordance remained high (Kappa >0.7). Samples with lower viral load (indicated by higher real-time PCR cycle threshold values) were more likely to yield discordant results. Conclusion SCVS and FVU yielded similar HR-HPV results, including those targeted by the 9-valent HPV vaccine, in sexually active young women. Both non-invasive self-sampling methods have potential for use in large-scale HPV surveillance programs in resource-limited settings.

Sodium Bicarbonate for Critically Ill Adults with Metabolic Acidosis and Shock

HPA-UNet-LSNet: An LSNet-based U-Net with hybrid pooling attention for accurate segmentation of Haloxylon ammodendron crowns from UAV RGB imagery

Accurate segmentation of Haloxylon ammodendron crowns from UAV RGB imagery remains challenging in desert environments because of sparse crown distribution, weak crown–background contrast, and interference from sandy soil and co-occurring shrubs. To address this problem, this study developed HPA-UNet-LSNet , an enhanced U-Net framework that replaces the original encoder with LSNet and introduces hybrid pooling attention (HPA) for feature fusion. On the independent test set, HPA-UNet-LSNet achieved a Precision of 0.8890, a Recall of 0.9198, an F1-score of 0.9041, and an mIoU of 0.8456. Compared with the baseline U-Net, it reduced false positives from 454 ± 53 to 267 ± 18 and false negatives from 224 ± 11 to 185 ± 10. The improvement was especially evident for small crowns, where the F1-score increased from 0.7318 ± 0.0179 to 0.7611 ± 0.0102, and the mIoU increased from 0.6498 ± 0.0045 to 0.6929 ± 0.0089. Grad-CAM results further showed more concentrated responses over crown regions and relatively reduced activation in irrelevant background areas. Overall, HPA-UNet-LSNet provides an effective and practical RGB-based solution for Haloxylon ammodendron crown segmentation in desert environments.

Lonvoguran Ziclumeran — In Vivo CRISPR Gene Editing in Hereditary Angioedema

“Picking the right person … can make or break the whole deal”: Development of a layperson injector selection tool for administration of home-based long-acting injectable antiretroviral therapies

Background Clinic-based administration of long-acting injectable antiretroviral therapy (LAI-ART) is resource-intensive and may exacerbate disparities in access to care. Home-based administration by trained layperson injectors, or treatment buddies (TBYs), could expand access to LAI-ART; however, maintaining high-quality clinical care requires selecting suitable TBYs for its implementation. This paper describes the development of the TBY Selection Tool to support people with HIV (PWH) in identifying appropriate TBYs. Methods The tool development process consisted of 5 phases. In Phase 1, semi-structured interviews were conducted with 19 clinicians, 16 PWH, and 15 candidate TBYs. Transcripts were thematically coded to identify domains influencing TBY suitability. In Phase 2, draft items were developed and refined into a structured survey. In Phase 3, 7 PWH completed the tool during a 2-month pilot. In Phase 4, a Community Advisory Panel (CAP) (n = 10) reviewed items for clarity, relevance, and comprehensiveness. In Phase 5, feedback was incorporated to finalize the tool. Results Clinicians emphasized the reliability of TBYs, the confidentiality of home-based injections, and the importance of adhering to injection schedules. PWH prioritized trust in the TBYs, TBY availability, and comfort with bodily intimacy. TBYs highlighted emotional steadiness, willingness to learn, and responsibility for continuity of care. These domains were operationalized into a survey assessing relationship history, reliability, confidentiality, availability, proximity, and comfort with injections. Pilot testing showed 100% completion without difficulties. CAP feedback led to refined wording, expanded response options, and clearer phrasing, which were used to finalize a 12-item survey. Conclusions The TBY Selection Tool provides a structured framework to support PWH in identifying appropriate TBYs for home-based LAI-ART. By integrating clinical, individual, and community perspectives, the tool addresses factors important for the safe, acceptable, and feasible implementation of home-based LAI-ART. Psychometric assessment, scoring, and further validation in larger, more diverse populations is needed.

Drug-induced gastric motility disorders: A disproportionality analysis from the FAERS and CVARD databases

Background Delayed gastric emptying and gastroesophageal reflux represent critical yet frequently underrecognized complications in hospitalized patients, particularly in the context of polypharmacy. While multiple medication classes have been implicated in disrupting gastrointestinal motility, the comprehensive risk spectrum of individual drugs remains poorly characterized. This study aimed to conduct a comprehensive disproportionality analysis to identify drugs associated with delayed gastric emptying and reflux using large-scale pharmacovigilance data. Methods We analyzed adverse event reports from the FDA Adverse Event Reporting System (FAERS; 2004–2025; n > 58 million) and validated findings against the Canada Vigilance Adverse Reaction Online Database (CVARD). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN). Weibull time-to-onset analysis was conducted to characterize temporal patterns of adverse event onset. Results Among the top 50 drugs screened, 20 demonstrated positive signals across all three algorithms. Glucagon-like peptide-1 (GLP-1) receptor agonists exhibited the strongest associations with gastric motility disorders, with semaglutide showing the highest ROR for impaired gastric emptying (ROR: 80.27; 95% CI: 76.39–84.34), validated in CVARD (ROR: 54.17). Insulin formulations, particularly insulin degludec (ROR: 18.90), bisphosphonates, angiotensin receptor blockers, and trofinetide also demonstrated significant signals. Weibull analysis revealed divergent temporal patterns, ranging from early-onset (trofinetide: median 6.6 days) to late-onset (immunoglobulin G: median 535.1 days). Conclusion This study identifies a broad spectrum of drug-associated gastric motility disorders with distinct temporal profiles. These findings provide evidence-based priorities for enhanced pharmacovigilance and inform clinical decision-making to mitigate this preventable cause of morbidity.

Correction: Efficacy and safety of the ayurvedic formulation ‘Trikatu’ as an add-on to standard care in dyslipidemia: Study protocol for a randomized, double-blind, placebo-controlled trial evaluating lipid parameters, and gut microbiota

Dynamic analysis of critical maternal complications in tertiary hospitals in Wuxi: A study based on four years of monitoring data

Background Severe maternal morbidity (SMM) is a significant public health concern. This study analyzed the incidence, trends, causes, and pregnancy outcomes of SMM in Wuxi to inform future clinical and public health strategies. Methods A retrospective analysis was conducted on 315 critical maternal cases identified from 156,435 deliveries in Wuxi between October 1, 2020, and September 30, 2024. Data were extracted from a citywide near-miss maternal surveillance system. Statistical analyses were performed using SPSS 25.0, employing chi-square tests and Cochran-Armitage trend tests to evaluate trends, and chi-square tests for comparisons between groups. Results The overall incidence of SMM was 0.20%. Initially, this rate remained stable at 0.19% across the first three cycles (P > 0.05); however, it significantly increased to 0.24% during the cycle from October 2023 to September 2024 (χ² = 5.24, P = 0.02). This increase was closely associated with a rise in the proportion of women of advanced maternal age (≥35 years), which reached 26.03% (χ² = 11.76, P = 0.001). Over time, the distribution of risk levels shifted. Initially, the high-risk group was dominant (63.29%), but in recent cycles, the moderate-risk group became more prominent (64.44%). The moderate-risk group was associated with a higher rate of adverse outcomes (25.00–25.71%) compared to the high-risk group (17.11–20.69%; χ² = 10.83, P = 0.01). Direct obstetric factors were the primary causes, accounting for 79.05% of cases, with obstetric hemorrhage being the most prevalent (53.97%). In contrast, the proportion of cases attributable to indirect obstetric factors increased from 17.81% to 26.67%, primarily due to heart disease and infectious diseases. Conclusion Improving maternal safety involves dynamic risk assessments, tiered referrals for moderate-risk pregnancies, better multidisciplinary management of complications, optimized emergency responses in primary care, and refined regional referral systems to reduce preventable SMM and mortality.