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Pre-treatment polyfunctionality percentage (PFA) of CD8+ T cells is associated with development of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs).

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have improved cancer survival, but immune-related adverse events (irAEs) occur frequently and can have devastating consequences. There are no validated methods to evaluate risk of irAEs prior to initiation of ICIs. MATERIALS AND METHODS: We conducted a pilot study evaluating the ability of blood-based, single-cell secretomic analysis to characterize irAEs. A total of 10 patients with thoracic malignancies who were scheduled to receive ICIs were enrolled. Each patient had a pre-ICI blood sample drawn as well as a sample at the time of irAE development or 12 weeks after ICI initiation, whichever came first. Utilizing IsoPlexis's IsoLight system, polyfunctionality percentages (PFAs) and strength indices (PSIs) were analyzed for CD4+ and CD8+ T cells. RESULTS: Five patients developed irAEs and 5 patients did not develop irAEs. Pre- and post-ICI CD8+ T cell PFA was significantly elevated in patients who developed irAEs compared with those who did not (p = 0.017 and p = 0.014, respectively). CONCLUSIONS: In this pilot study, pre-ICI CD8+ T cell PFA was associated with development of irAEs. While this is a pilot study, this is a first step toward developing a blood-based, streamlined assay to assess risk of irAEs prior to initiation of ICIs. Validation in larger cohorts is warranted.

Humans

Extended Venous Thromboembolism Prophylaxis After One-Anastomosis Gastric Bypass: A Three-Arm Randomized Trial of Enoxaparin Duration and Rivaroxaban.

BACKGROUND: Venous thromboembolism (VTE) is a serious but preventable complication after bariatric surgery, most of them after hospital discharge. The optimal regimen and duration of post-discharge prophylaxis, particularly the role of direct oral anticoagulants, remain uncertain. OBJECTIVES: To estimate 30-day VTE and bleeding event rates in high-risk patients undergoing one-anastomosis gastric bypass who received 15-day enoxaparin, 30-day enoxaparin, or 30-day rivaroxaban prophylaxis, and to perform exploratory comparisons among the regimens. METHODS: In this randomized, open-label, three-arm clinical trial, high-risk adults undergoing laparoscopic OAGB were randomized before discharge (1:1:1) to enoxaparin 40 mg subcutaneously twice daily for 15 days, enoxaparin 40 mg twice daily for 30 days, or rivaroxaban 10 mg orally once daily for 30 days, after standardized in-hospital enoxaparin and early ambulation. Participants underwent clinical assessment and duplex ultrasonography of the lower-limb and porto-mesenteric veins on postoperative days 15 and 30. The primary outcome was objectively confirmed VTE within 30 days. Bleeding was classified as International Society on Thrombosis and Haemostasis (ISTH) major bleeding or clinically relevant non-major bleeding (CRNMB). Because the expected event rate was low and no non-inferiority or equivalence margin was prespecified, comparisons were interpreted as exploratory. RESULTS: A total of 288 patients were randomized to 15-day enoxaparin (n = 97), 30-day enoxaparin (n = 97), or 30-day rivaroxaban (n = 94). One symptomatic lower-limb deep vein thrombosis occurred in the 15-day enoxaparin group (1.0%; 95% CI, 0.03%-5.6%); no VTE events occurred in the 30-day enoxaparin group (0%; 95% CI, 0%-3.7%) or the rivaroxaban group (0%; 95% CI, 0%-3.8%). Total bleeding occurred in 4/97 patients (4.1%) in each enoxaparin group and 8/94 patients (8.5%) in the rivaroxaban group. The absolute difference in total bleeding between rivaroxaban and 30-day enoxaparin was 4.4% points (95% CI, - 2.9 to 12.2), indicating substantial imprecision. No porto-mesenteric venous thrombosis was detected. CONCLUSION: Only one VTE event occurred, precluding reliable conclusions regarding comparative efficacy or prophylaxis duration. Bleeding estimates were also imprecise and do not establish comparative safety or equivalence between rivaroxaban and enoxaparin. The trial adds descriptive event-rate data from a standardized OAGB pathway, but larger multicenter studies with prespecified comparative hypotheses and assessment of adherence, oral tolerance, and drug exposure are required. The study was approved by the Research Ethics Committee and registered at ClinicalTrials.gov.

Humans

Driven toward care, avoiding the end: A systematic review and meta-analysis of the relationship between death anxiety and healthcare utilisation.

Both overuse and underuse of the healthcare system have been recognised as significant problems. Relatedly, growing research has recognised the key role of death anxiety in driving various health-relevant behaviours. However, the relationship between death anxiety and healthcare utilisation has not yet been systematically explored. The current systematic review and meta-analysis addressed this gap. In total, 987 papers were screened for inclusion, of which 63 were included in the final review (Ntotal = 21,271). This included 33 quantitative studies, 27 qualitative studies and 3 mixed-methods designs. In total, 17 studies contained sufficient data to be meta-analysed. Overall, the included studies highlighted a significant relationship between death anxiety and healthcare utilisation; in particular, positive associations with desire for life-prolonging treatments and contact with hospitals and medical professionals. By contrast, a negative association was found with other aspects of healthcare utilisation, including hospice use and end-of-life communication. The sample type emerged as a significant moderator, suggesting that the relationship between death anxiety and healthcare usage was strongest in non-medical samples. The current findings suggest that death anxiety plays a key role in utilisation of the healthcare system. The fear of death may need to be targeted in psychological interventions, in order to ensure maximal effectiveness of health services, and improve outcomes for healthcare users.

Humans

Effects of exercise snacking on neuromuscular performance in insufficiently active adults: A systematic review and meta-analysis.

OBJECTIVE: To examine the effects of exercise snacking (ES) on neuromuscular performance in insufficiently active adults. METHODS: Six databases were searched from inception to July 17, 2026. Randomized controlled trials and non-randomized studies of interventions involving insufficiently active adults undertaking ES interventions were included. Outcomes were functional performance, muscular strength, and muscular power. A three-level random-effects meta-analysis was performed. Risk of bias was assessed with RoB 2 or ROBINS-I, and certainty of evidence was evaluated using GRADE. RESULTS: Nine studies (13 reports) involving 313 participants were included. In the primary three-level model, ES showed a small positive overall effect on neuromuscular performance (g = 0.37, 95% CI 0.16-0.58, p = 0.001), which remained supported under trial-clustered robust inference with small-sample adjustment. Domain-specific estimates for muscular power/velocity, functional performance, and muscular strength were positive but imprecise and were not statistically supported after small-sample robust adjustment. Robust moderator tests provided no evidence of between-subgroup differences, and the certainty of evidence was low for all outcomes. CONCLUSION: Current low-certainty evidence suggests that ES may produce a small improvement in overall neuromuscular performance. However, domain-specific effects remain uncertain because of the limited number of independent trials, and the overall prediction interval crossed zero, indicating uncertainty across future populations and settings. Larger, preregistered randomized controlled trials are needed to confirm these preliminary findings.

Adult

Elucidating the evolution of meat quality, water distribution, microstructure, and protein structure during sous-vide and micro-pressure cooking.

This study investigated the evolution of eating quality (colour, texture and volatile flavour compounds), water status, microstructure and protein structure of pork meat under different cooking methods. The methods analysed included traditional cooking (TC: 10, 20, 30 and 40 min, 100 °C), sous-vide cooking (SV: 1, 2, 3 and 4 h, 60 °C) and micro-pressure cooking (MC: 10, 20, 30 and 40 min, 120 °C). Across the three cooking processes, as cooking time increased, cooking loss, lightness, yellowness, P23, β-sheet, random coil and surface hydrophobicity of the meat samples increased. By contrast, redness, P22, hydrogen proton density, esters content, α-helix, β-turn and sulfhydryl group content decreased. Moreover, the Warner-Bratzler shear force (WBSF), adhesiveness, hardness, springiness, gumminess, chewiness, alcohols, aldehydes, ketones and fluorescence intensity of the meat samples, initially increased and then decreased as cooking progressed. SV resulted in higher water-holding capacity (WHC), improved redness and increased alcohol and ester levels, whereas MC produced softer meat and greater water mobility. Furthermore, MC enhanced the degree of microstructural damage and protein structural unfolding in the meat. MC requires less time to achieve textures and flavours similar to those obtained using the TC and SV methods. Thus, MC is an efficient cooking method for the catering industry to obtain desired meat quality rapidly.

Cooking

Urban stormwater infrastructure as a microplastic superhighway: a critical review of transport dynamics, modelling, and mitigation across pavements and drainage networks.

This review examines the transport, fate, modelling, and mitigation of Microplastics (MPs) in urban stormwater infrastructure, with emphasis on pavements, runoff pathways, micro-drainage, and macro-drainage systems. Following a systematic review approach, more than 1000 records were screened and approximately 50 core studies were retained when they addressed urban stormwater or drainage-related MP transport with adequate methodological reporting; marine-only studies and biological-effect studies without direct relevance to transport processes were excluded. The evidence shows that stormwater systems function not merely as passive conduits but as dynamic reactive transport systems with temporary storage, where particle mobilisation, sedimentation, resuspension, and temporary retention regulate MP export. Road surfaces, especially high-traffic areas, are major reservoirs of tyre wear, road-marking, atmospheric, and litter-derived particles that are rapidly mobilised during rainfall. Conventional grab sampling may underestimate MP loads, which in some cases exceed treated wastewater effluent loads by up to six-fold. Drainage structures such as manholes can immobilise up to 17.3% of near-neutrally buoyant particles, while biofouling and aggregation may shift buoyant polymers from wash-load to bedload. Mitigation systems, including permeable pavements, bioretention, wetlands, and technical inserts, can achieve high removal of coarse MPs, but performance declines for fine particles below 100 µm. The review highlights the need for standardised flow-proportional sampling, physically informed modelling, and treatment-train strategies targeting both surface sources and in-network storage.

Microplastics

Tracking GAD-specific T-cell expansions in Type 1 diabetes by intradermal GAD-Alum challenge.

Identifying and monitoring autoreactive T cells that drive beta cell destruction remains a major obstacle to developing effective immunotherapies for type 1 diabetes (T1D). These cells are extremely rare in peripheral blood and cannot be accessed directly from the pancreas. We used intradermal injection of Glutamic Acid Decarboxylase (GAD)-Alum to recruit GAD-specific T cells to accessible sites in the skin and skin-draining lymph nodes (LNs), sampled by skin suction blisters and ultrasound-guided LN aspiration. Peripheral blood samples obtained before GAD injection were restimulated with GAD in vitro to detect reactive CD4+ T cells. Single-cell RNA sequencing (scRNAseq) followed by re-expression of selected T cell receptors (TCRs) confirmed antigen specificity. Up to 70% of T cells at the skin injection site were clonally-expanded and 4 of 14 (28%) re-expressed TCRs were GAD-reactive. In LNs 1 of 14 (4%) clonally-expanded TCRs was GAD-reactive, representing ~0.08% of all T-cells. GAD-reactive cells across compartments displayed Th1 and Th17-associated transcription signatures. These results demonstrate the intradermal autoantigen challenge and scRNAseq, enable direct identification and molecular profiling of autoreactive T cells in vivo. This minimally invasive approach provides a powerful platform for tracking antigen-specific T cells to monitor disease activity and evaluate immune interventions in T1D.

Autoimmunity

Avian egg incubation period: Revisiting existing allometric relationships via surface area-to-volume ratio of an egg.

The incubation period (I) for bird eggs varies among species and is used in establishing allometric relationships. Research on variations in I shed light on the evolutionary mechanisms that gave rise to the differentiation of embryonic development in distinct taxa of birds. Here, using a sampling of 444 images from 444 avian species, 89 families and 30 orders, we calculated their major geometric dimensions: volume (V) and surface area (S). An assessment of the relationship between I and the measured and calculated egg parameters demonstrated the closest and most significant correlation (R = -0.760) between I and the S/V ratio that was adopted as a conditional indicator and reflects the embryo's metabolic rate. Approximation of the values of these parameters made it possible to derive a power-law dependence for the prediction of I depending on the S/V value of a particular egg (R2 = 0.757). The prediction accuracy was higher (R2 = 0.783) if the eggs of the family Procellariiformes (petrels), whose I value is characterized by a longer time, were removed from the general sampling computation. We conclude that the value of the S/V ratio can characterize both the metabolism of an embryo and the conditional thermal conductivity of an egg, which aids in ensuring the temperature regime of egg incubation.

Animals

Quo vadis, BGA? A collaborative EDNAP exercise on the challenges and progress in forensic biogeographical ancestry inference.

There is a broad consensus that forensic tests for the prediction of externally visible characteristics (EVC) and analysis of biogeographic ancestry (BGA) of an individual are technically reliable. However, interpretation of the results and population-specific genotype distribution patterns remains challenging. EVC and BGA analyses provide valuable information for population genetics studies and as investigative leads for criminal cases, as well as for historical and contemporary identification tests. However, inaccurate or incorrect predictions, for example, from subjective bias in the interpretations made, have the potential to misdirect police investigations. The legal situation regarding EVC and BGA testing varies by country: ranging from countries where it is explicitly prohibited, to those without specific regulations on biogeographic ancestry prediction, and others that have already enacted laws governing its use. The reluctance to utilize these analyses is not only due to legal restrictions and data protection concerns, but also to initial limited sets of sufficiently comprehensive forensic DNA assays. Forensic BGA marker panels typically contain up to ∼300 SNPs. This relatively small number of genetic markers, along with limited reference population data, complicates the interpretation of results from donors of unknown origin. This paper presents the results of a collaborative EDNAP study, which, for the first time, evaluated the approach to reporting EVC and BGA data between international laboratories. For the study, DNA from nine individuals with self-reported ancestry was collected and analysed using various forensic panels differing in the number and composition of ancestry-informative markers genotyped, comprising: the Precision ID mtDNA Whole Genome Panel, the VISAGE Basic Tool and the VISAGE Enhanced Tool for Appearance and Ancestry Prediction, and the Ion AmpliSeq™ PhenoTrivium Panel. To ensure full data protection, all SNP genotypes and uniparental marker haplotypes obtained were not shared with third parties. Instead, the genetic data were analysed using a range of commonly used population analysis software packages. These analysis outcomes were then distributed to twelve European forensic laboratories (both academic and law enforcement institutions), who were asked to prepare reports based on their interpretation of the phenotypes and ancestry they inferred from the analysis data. A questionnaire sent alongside the genetic information, aimed to evaluate which difficulties were encountered by the participants in processing the BGA analysis data they were given.

Humans

Mitigating pH-induced instability in deruxtecan-based ADCs: an onboard-mixing icIEF approach for robust charge heterogeneity characterization.

Accurate charge variant analysis of antibody-drug conjugates (ADCs) is essential for understanding product heterogeneity and ensuring quality control. However, Deruxtecan (DXd)-based ADCs present a unique analytical challenge due to the intrinsic instability of the payload, where the lactone ring readily undergoes hydrolysis under alkaline conditions, resulting in time-dependent shifts in charge distribution during imaged capillary isoelectric focusing (icIEF). In this study, we describe the development of an onboard-mixing icIEF method designed to minimize pH-induced degradation during sample preparation. By separating ADC samples from carrier ampholytes (CAs) prior to injection and enabling real-time mixing within the instrument, this approach effectively suppresses premature lactone ring opening and stabilizes charge variant profiles. Comparative studies between conventional premixing and onboard-mixing approach demonstrated that the latter significantly enhances reproducibility, particularly for acidic variants that are highly sensitive to structural conversion. Comprehensive method validation confirmed excellent precision, linearity, and sensitivity, with consistent performance across run-to-run and intra-day analyses. The results underscore the importance of controlling microenvironmental pH exposure in the analysis of chemically instable ADCs. The proposed onboard-mixing strategy provides a robust and efficient solution for icIEF-based characterization, reducing analytical artifacts while simplifying method development. This approach is broadly applicable to ADCs and other biotherapeutics containing pH-sensitive functional groups.

Hydrogen-Ion Concentration

Development and validation of a comprehensive prognostic model for 28-day ICU mortality in non-traumatic subarachnoid hemorrhage: an analysis based on the MIMIC-IV database.

BACKGROUND: Due to the complex pathophysiology of non-traumatic subarachnoid hemorrhage (SAH), accurate risk prediction remains a challenge. Our aim is to develop and validate a comprehensive prognostic model that integrates demographic characteristics, vital signs, laboratory parameters, and more, to provide clinical decision-making support in real-world practice. METHODS: We conducted a retrospective cohort study of 785 Non-traumatic subarachnoid hemorrhage patients. The cohort was randomly divided into a training set (n = 549) and a validation set (n = 236). Feature selection was performed using LASSO regression, followed by backward stepwise Cox regression for optimization. A nomogram was constructed based on independent predictive factors, and model performance was assessed using discrimination, calibration, and decision curve analysis. To prevent immortal-time bias, all predictors were anchored to a fixed early (first-24-hour) measurement window, treatment variables were modelled as binary indicators rather than cumulative exposures, and a five-model sensitivity analysis with baseline-severity adjustment was performed. RESULTS: The development of our model followed a systematic approach: first, 15 potential predictive factors were selected via LASSO regression, which were then refined to 12 independent predictors using backward stepwise Cox regression. The final predictive factors included: Ventilation, AHT, Nimodipine 60 mg, Age, SAPS.II, Input amount, Calcium total, Platelet count, White blood cells, Anion gap, pH, and Chloride. The integrated model demonstrated excellent predictive ability for 7-day, 14-day, and 21-day mortality in both the training set (AUC: 0.972, 0.934, 0.898) and the validation set (AUC: 0.968, 0.948, 0.911). Calibration curves and decision curve analysis confirmed the model's reliability and clinical utility across different time points. We constructed a nomogram for individualized risk prediction. Univariate Kaplan-Meier survival analysis demonstrated significant stratification of survival outcomes by each predictor, while restricted cubic spline analysis revealed non-linear relationships between continuous variables and mortality risk. Random survival forest analysis identified the top three predictive factors (Nimodipine 60 mg, Ventilation, AHT) and compared them with our full 12-variable model, confirming superior performance of the integrated model at all time points. At the 28-day primary endpoint, the model achieved a time-dependent AUC of 0.898 (training) and 0.904 (validation); after restricting predictors to the early baseline window, the leakage-controlled model retained good discrimination (validation C-index 0.803). CONCLUSIONS: Our ICU 28-day mortality prognosis model demonstrated robust performance in predicting ICU 28-day mortality in non-traumatic subarachnoid hemorrhage. The model, through the nomogram, provides individualized risk assessment, aiding clinical decision-making and patient stratification.

Humans

Effectiveness of STK Spray® for semen stain localization on solid surfaces: A specificity and sensitivity study.

Semen identification is a crucial step in sexual assault cases. The aim of this study was to assess STK Spray®, a presumptive test for semen, under controlled conditions including, simulated crime scene stains detection. Easy to use, it can be sprayed directly onto different surfaces and visualized under UV light. Several tests were performed on five different substrates (ceramic tile, drywall, metal, wood, and faux leather). The spray was able to enhance semen fluorescence, especially in diluted samples, with characteristic "globular" spots. Although it showed good specificity, false positives could be obtained with 10% bleach. The fluorescence signals were quantified using ImageJ™ and showed a statistically significant substrate-dependent variability. Mixture analysis indicated that saliva did not interfere with detection of semen, while urine partially suppressed the signal and blood markedly affected its interpretation. Simulation tests with UV lamp comparisons confirmed the importance of choosing the right detection method and the utility of this presumptive test in combination with additional immunochromatographic tests. A preliminary signal retention test showed stable fluorescence for up to two years when stains were stored appropriately. Finally, complete DNA profiles (100% of alleles) were obtained from all samples (n = 24) after exposure to the reagent and UV light. Because of its ability to enhance semen signal, especially on specific surfaces, and its rapidity of use and detection, STK Spray® may represent a useful aid in the preliminary screening phase.

Humans

From bioactive compounds to volatile profiles: a multidimensional characterization of Indonesian stingless bee honeys.

BACKGROUND: Stingless bee honeys are drawing increasing attention as ingredients for functional foods and health-oriented products because of their distinctive sensory characteristics and bioactive potential. In this study, honeys collected from nine stingless bee species reared in West Sumatra, Indonesia, were comprehensively characterized using physicochemical indices, antioxidant assays [DPPH (i.e. 2,2-diphenyl-1-picrylhydrazyl) and ferric reducing antioxidant power], microbiological screening, volatile profiling [gas chromatography-mass spectrometry (GC-MS)] and Fourier transform infrared (FTIR) fingerprinting. RESULTS: Marked between-sample variability was observed across key quality attributes, including pH (2.80-3.68), Brix (49.83-61.25), viscosity (23.36-175.22 cP) and color parameters. FTIR spectra were consistent with carbohydrate-rich matrices and exhibited carbonyl-related bands. GC-MS profiling identified linalool oxide isomers and junenol among the predominant volatiles. To the best of our knowledge, junenol has not previously been reported in stingless bee honey and may represent a potential regional chemical marker for Indonesian stingless bee honeys. Lactic acid bacteria were detected in selected samples, whereas yeast and mold were not detected. Antioxidant activities were comparatively low, which may reflect local environmental and ecosystem-related factors. CONCLUSION: The results provide a multi-parameter baseline for stingless bee honeys produced within a shared ecosystem in West Sumatra and demonstrate the value of integrating conventional chemical indices with FTIR and volatile fingerprints for quality assessment. This combined approach may also support future authentication and origin-tracing frameworks for Indonesian stingless bee honeys. © 2026 Society of Chemical Industry.

Animals

Comparison of black carbon measurements using filter-specific reference transmittance to those using lab blanks or an average of unloaded filters.

Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). We analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial to assess the influence that different methods of I0 estimations have on eBC measures. We compared eBC measurements using filter-specific I0 values (Method 1) to those using three other methods of I0 estimation: the lab blank scan from a given session (Method 2), the average of all pre-sample filter scans (Method 3), and the average of all lab blank filter scans (Method 4). We assessed the agreement between Method 1 and the alternative methods using Bland-Altman analysis. We also assessed the relationship between Method 1 and the alternative methods across the complete measurement range and after stratifying exposure data into quartiles according to Method 1 eBC exposures. The mean (SD) personal eBC exposure for Method 1 was 7.8 μg/m3 (5.9), and exposures ranged from 1.3 to 46.8 μg/m3. Compared to Method 1, eBC using Methods 2, 3, and 4 were higher by 0.7 μg/m3, 0.1 μg/m3, and 0.7 μg/m3, respectively. The performances of linear regression models between Method 1 and all other methods were moderate to strong (R2 range: 0.42-0.93) in the second, third, and fourth quartiles; however, the models in the first quartile (eBC range: 1.3-2.9 μg/m3) performed poorly (R2 = 0.25-0.26), with error approximately 25% of the mean. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.Implications: Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). To assess the influence that different methods of I0 estimations have on eBC measures, we analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.

Soot

Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n = 45) and those with hEDS (n = 45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

Humans

Efficacy of a high-frequency repetitive transcranial magnetic stimulation for craving reduction in adolescents with gaming disorder: a 4-week randomized control trial with 24-week follow-up.

BACKGROUND: With the widespread popularity of online gaming, gaming addiction has come under scrutiny. While there is ongoing research on the diagnosis and treatment of gaming disorder among adolescents, the clinical robustness and reliability of intervention strategies remain uncertain. METHODS: A 4-week, double-blind, randomized, sham-controlled clinical trial was conducted to evaluate the efficacy of noninvasive, high-frequency repetitive transcranial magnetic stimulation (rTMS) in alleviating psychological craving in adolescents diagnosed with gaming disorder. Sham rTMS was administered to the control group using the tilted-coil method. Both groups of participants were treated with SSRI medications. A total of 80 adolescents with gaming disorder participated in this study, and 73 ultimately completed the 24-week follow-up. The primary outcome was the change in craving levels before and after the rTMS intervention, as assessed by the Visual Analogue Scale (VAS). Secondary outcomes included changes in anxiety and depression levels before and after the intervention, as assessed by the HAMA and HAMD. RESULTS: We assessed levels of psychological craving, anxiety, and depression among adolescents with gaming disorder at baseline, after completing a 4-week intervention, and at a 24-week follow-up post-intervention. Our repeated-measures MANOVA results, adjusted for course variables, revealed a significant main effect of rTMS intervention on psychological craving levels in adolescents addicted to online games (F(11, 781)&#x2009;=&#x2009;11.238, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.142), as well as significant main effects on time (F(11, 781)&#x2009;=&#x2009;6.809; P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.091) and group effects (F(1, 71)&#x2009;=&#x2009;26.707, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.282). In addition, repeated-measures ANOVA results showed significant time effects for anxiety (F(2, 142)&#x2009;=&#x2009;20.747, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.234) and depression levels (F(2, 142)&#x2009;=&#x2009;22.277, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.285) among adolescents with gaming disorder, with nonsignificant between-group effects and no intergroup interaction. In the active stimulation group, changes in psychological craving levels after 4 weeks of treatment were significantly and positively correlated with changes in anxiety levels after 4 weeks of treatment in adolescents addicted to online games (r&#x2009;=&#x2009;0.335, P&#x2009;<&#x2009;0.05). CONCLUSION: Our findings indicate that high-frequency rTMS targeting the left dorsolateral prefrontal cortex may be a promising approach for reducing psychological craving in adolescents with gaming disorder. TRIAL REGISTRATION: ChiCTR2500102979 in chictr.org.cn, registered on May 22, 2025.

Humans

The Effect of Mindfulness-Based Psychoeducation Program on Mindfulness, Self-Compassion, and Forgiveness Tendencies of Patients with Bipolar Disorder: A Randomized Controlled Trial.

This study examined the effects of a mindfulness-based psychoeducation program on mindfulness, self-compassion, and forgiveness in patients with bipolar disorder using a pretest-posttest randomized controlled experimental design. The study sample comprised of 40 patients (experimental group, n&#x2009;=&#x2009;20; control group, n&#x2009;=&#x2009;20). A mindfulness-based psychoeducation program was administered to the experimental group, while no intervention was administered to the control group. Data were collected using a personal information form, the Mindfulness Scale, the Self-Compassion Scale Short Form, and the Heartland Forgiveness Scale. The study revealed that the experimental group's mean scores on the mindfulness, self-compassion, and forgiveness scales following the intervention were significantly higher than those of the control group (p&#x2009;<&#x2009;.05). This study found that a mindfulness-based psychoeducation program increased mindfulness, self-compassion, and forgiveness in patients with bipolar disorder. The findings are limited to a small outpatient sample from a single CMHC and may not be generalizable to hospitalized patients with more severe clinical presentations. Mindfulness-based educational programs may enhance mental health, improve illness insight, support symptom management, and strengthen social functioning in individuals with bipolar disorder. The results emphasize the importance of integrating these programs into treatment processes and reveal the necessity for psychiatric nurses to actively implement mindfulness-based interventions. Psychiatric nurses should consider incorporating mindfulness-based techniques into their practice to improve the mental health of individuals with bipolar disorder, better understand the disorder, control symptoms, and improve social interactions.

Humans

A 4-year longitudinal wastewater surveillance of five gastroenteritis viruses and the correlation with clinical cases in Alberta, Canada.

Viruses are common causes of acute gastroenteritis worldwide. They are detected in large quantities in raw sewage making them amenable to wastewater-based surveillance (WBS). To monitor the prevalence of gastroenteritis viruses in wastewater and assess their correlation with clinical cases, wastewater samples collected between July 2020 and June 2024 from 12 wastewater treatment plants across Alberta, Canada were analyzed for norovirus (NoV) GI & GII, rotavirus (RoV), adenovirus (AdV), sapovirus (SaV) and astrovirus (AsV). Among the 5726 wastewater samples tested, AdV (80.5%) had the highest detection rate followed by NoV GII (75.6%), SaV (63.2%), NoV GI (59.4%), RoV (42.2%) and AsV (20.2%). Winter and spring seasonality was found for NoV and RoV in both wastewater and clinical disease. Public health interventions especially in the 1st year of the COVID-19 pandemic had a significant impact on their burden with marked reduction in wastewater detected viruses and clinical cases. NoV showed a strong correlation between its level in wastewater and the number of clinical cases, while moderate correlation was observed for the other four viruses. Cross-correlation analysis showed that changes of viral RNA concentration in wastewater lagged behind reported gastroenteritis cases by approximately 6&#xa0;days to 3&#xa0;weeks. To our knowledge, this is the longest multi-region WBS study monitoring multiple gastroenteritis viruses spanning both COVID-19 pandemic and post-pandemic periods. The data obtained from this study supported WBS as a complementary tool to track population-based circulation of gastroenteritis viruses, providing actionable public health data.

Clinical cases