DAILY LITERATURE ARCHIVE

公共卫生文献雷达(2026-07-18)

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公共卫生文献雷达(2026-07-18)

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1. Ecological restructuring of the nonbacterial fecal microbiome in obesity across human cohorts.

主题:流行病学 / 可复现研究与开放科学
期刊:Gut microbes
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:同时命中多个关注主题;包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Obesity is a complex metabolic disorder increasingly linked to alterations in the gut microbiome. While most research has focused on bacterial communities, the contribution of nonbacterial components including viruses, archaea, and eukaryotic microorganisms remains insufficiently characterized. Here, we performed a multicohort analysis to investigate the role of the nonbacterial gut microbiome in obesity across three independent human cohorts. Using compositional analyses adjusted for key covariates and network based approaches, we identified consistent multikingdom alterations associated with obesity. Individuals without obesity showed a reproducible enrichment of methanogenic archaea, particularly Methanobrevibacter smithii and Methanobrevibacter millerae, whereas individuals with obesity were characterized by increased abundance of bacteriophages from the class Caudoviricetes. In an elderly cohort, eukaryotic taxa such as Blastocystis spp. were additionally associated with the without obesity group. These patterns were largely consistent across cohorts and robust to sex stratification. Beyond taxonomic differences, ecological network analyses revealed substantial reorganization of microbial interactions in obesity. The identity and composition of hub taxa differed significantly between obesity and without obesity networks across all cohorts, indicating a shift in the taxa occupying central ecological roles. Notably, these differences were observed even when similar microbial kingdoms were represented, underscoring the importance of species-level resolution. Collectively, our findings demonstrate that obesity is associated with coordinated compositional and ecological alterations across the nonbacterial gut microbiome. This multikingdom perspective expands current understanding of microbiome dysbiosis in metabolic disease and highlights the archaeome and virome as potential contributors to host metabolic health.

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2. Longitudinal modelling of microbiome subcommunities reveals parity-dependent dynamics during pregnancy and postpartum.

主题:临床研究与数据方法 / 流行病学
期刊:Gut microbes
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:同时命中多个关注主题;包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Dysregulation of maternal adaptations to pregnancy due to high pre-pregnancy BMI (pBMI) is associated with worsened health outcomes for mothers and children. The role of the gut microbiome in these adaptations remains unclear.

METHODS: Stool samples were collected from pregnant participants (n = 52) enrolled in the Be Healthy in Pregnancy study (NCT01689961) during first, second, and third trimesters, and 6-months postpartum, along with samples from their infants at 6 months of age. Following 16S rRNA gene sequencing, we implemented time-aligned LDA (TALDA) using a time-weighted sampling strategy with exponentially decaying weights to construct time-proximal cohorts, applied LDA to each cohort independently, and aligned resulting topics using the alto R package. Infant samples were analyzed using standard LDA.

RESULTS: Seven distinct subcommunities were identified, one of which represented perineal contamination and was excluded from further analysis. Remaining subcommunities had distinct taxonomic definitions which remained stable throughout pregnancy (mean cross-cohort stability 0.899) while subcommunity proportions within individuals varied. Multiparous individuals showed greater shifts in subcommunity proportions during early pregnancy, while primiparous individuals displayed progressively increasing shifts with the largest changes during the transition from pregnancy to postpartum. High pBMI was associated with reduced microbiome remodelling, particularly among multiparous individuals. In exploratory analyses, maternal SCFA-producing subcommunity abundance at late pregnancy was positively associated with infant Bifidobacterium-dominated subcommunity proportions at 6 months, while pBMI > 25 was independently associated with lower infant Bifidobacterium.

CONCLUSION: TALDA effectively distinguished between stable subcommunity definitions and dynamic subcommunity proportions, revealing that the microbiome maintains functional organization while subcommunity proportional contributions shift over the course of pregnancy and postpartum. These maternal dynamics may have intergenerational consequences through their influence on infant gut colonization. This work demonstrates that maternal factors modify microbiome trajectories and supports the existence of an ecological memory of pregnancy history within the maternal gut microbiome.

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3. Towards standardized gut microbiota diagnostics: normobiosis beyond geographical borders.

主题:流行病学 / 可复现研究与开放科学
期刊:Gut microbes
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:同时命中多个关注主题;包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Defining clinically meaningful reference states of the human gut microbiota remains a major barrier to the clinical translation of microbiome testing, largely due to variability across populations. We aimed at evaluating whether dysbiosis can be identified in a standardized, geography-independent manner, using a composite, system-level microbiome diagnostic framework. We performed a retrospective observational analysis of 831 adult stool samples collected from healthy individuals and patients with inflammatory bowel disease, irritable bowel syndrome, or other chronic inflammatory conditions across seven countries. In addition, U.S. National Institute of Standards Technology (NIST) human fecal reference materials were analyzed. Dysbiosis was assessed using a fixed microbial marker panel and composite distance metrics anchored to a clinically validated healthy Scandinavian reference population, using GA-map® Dysbiosis Test as an exemplar of this diagnostic framework. The diagnostic framework reproducibly identified normobiosis and dysbiosis across geographically distinct populations (USA, Canada, Germany, Italy, and the UK). Severe dysbiosis was detected with high specificity (93.6%) and positive predictive value (90.2%), independent of subjects’ country of origin. Healthy individuals showed highly comparable dysbiosis index distributions across regions. These findings demonstrate that clinically useful dysbiosis diagnostics do not require geographically tailored reference populations and support the feasibility of standardized, geography-independent microbiome diagnostics for clinical application.

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4. Accuracy and safety of C-TST for tuberculosis infection: A clinical trial in Brazil.

主题:生物统计与研究设计
期刊:Pulmonology
发表日期:2026-Dec
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Tuberculosis infection (TBI) diagnosis in BCG-vaccinated, high-burden settings remains challenging.

RESEARCH QUESTION: We aimed to assess the sensitivity, specificity, and safety of the C-tuberculin skin test (C-TST), compared with PPD RT-23, for tuberculosis infection in BCG-vaccinated adults.

STUDY DESIGN AND METHODS: Randomised, double-blind clinical trial in Brazil. Adults with pulmonary tuberculosis (PTB) and asymptomatic controls without known TB exposure or prior TB/TPT underwent C-TST, PPD RT-23, and QuantiFERON-TB Gold Plus (QFT-Plus). Skin tests were read by two strategies: (a) induration only or (b) induration or erythema, at a ≥5-mm cut-off. Sensitivity was assessed in PTB; specificity for C-TST and PPD RT-23 was estimated against QFT-Plus. Adverse events were monitored.

RESULTS: Among 446 participants (141 PTB; 305 controls), at the 5-mm cut-off, C-TST showed lower sensitivity but higher specificity than PPD RT-23. With strategy (a) and (b), C-TST sensitivity was 0.67 and 0.68, specificity was 0.92 and 0.9, compared to 0.74 sensitivity and 0.78 specificity for PPD RT-23. Adverse events were more frequent in PTB: 12.1% (C-TST) and 6.4% (PPD RT-23); none were serious.

CONCLUSION: In BCG‑vaccinated adults, C-TST showed a trade-off of higher specificity and lower sensitivity than PPD RT-23 at the 5-mm cut-off; and a favourable safety profile. Adding erythema to readings did not improve accuracy, suggesting that C-TST may be a useful alternative for programmatic TBI screening in high-burden settings.

TRIAL REGISTRATION: Trial registry number RBR-7tn2ysw (https://ensaiosclinicos.gov.br/ registered on 25 January 2021).

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5. Local governance and health equity: Practical reflections from Chinese crisis governance.

主题:卫生政策与真实世界证据
期刊:Global public health
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

This study examines mass testing in three Chinese cities since 2020 as a ‘stress test’ for local governance. It analyses the governance performance of Shenzhen, Nanjing and Wuxi in terms of efficiency, equity and community resilience. Using Melbourne’s pandemic lockdown as a reference case, it discusses the underlying mechanisms linking different governance approaches to health equity outcomes. The study adopts a nested governance framework to examine how governance capacities and policy logics operate across different local contexts. The results indicate that Chinese cities can efficiently complete mass testing within a few days, but face pressures related to health equity and community resilience. Melbourne’s lockdown governance emphasised participation and institutional transparency, but advanced policies at a relatively slower pace. This study recommends building a dynamic governance mechanism that better balances efficiency and equity.

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6. Rotation-traction manipulation versus cervical traction for axial neck pain caused by cervical degenerative disc disease: a multicenter randomized controlled trial.

主题:流行病学
期刊:The Libyan journal of medicine
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Axial neck pain is a common manifestation of cervical degenerative disc disease (CDD). Rotation-traction manipulation (RTM) is widely used in China, but its comparative effectiveness and safety versus cervical traction remain uncertain.

METHODS: In this prospective multicenter randomized controlled trial, 154 adults with CDD-related axial neck pain were randomized 1:1 to receive RTM (7 sessions over 2 weeks) or cervical traction (daily for 2 weeks). Outcomes were assessed at baseline, during treatment, and at 1 and 3 months after treatment. The primary outcome was pain intensity measured by the visual analogue scale (VAS); secondary outcomes were neck tenderness score (NTS) and cervical range of motion (ROM). Intention-to-treat analyses with multiple imputation were performed.

RESULTS: All 154 randomized participants were included in the analyses, and 151 completed follow-up. Both groups showed significant improvement over time in VAS and ROM (both P < 0.001). Confirmatory mixed-effects analyses did not demonstrate significant between-group differences in VAS or ROM after adjustment for multiple comparisons. Exploratory analyses suggested that RTM provided faster improvement during the treatment phase and a small cumulative advantage in pain reduction, whereas cumulative ROM improvement did not differ significantly between groups. RTM was also associated with a faster reduction in neck tenderness severity. Adverse events were mild and infrequent, and no treatment-related radiographic deterioration was observed.

CONCLUSIONS: Both RTM and cervical traction were associated with clinical improvement in patients with CDD-related axial neck pain. Confirmatory analyses did not demonstrate robust superiority of RTM for pain or cervical ROM, whereas exploratory analyses suggested faster early improvement and a small cumulative pain benefit with RTM. NTS findings should be interpreted cautiously because the tenderness score has not been formally validated. No serious adverse events were observed.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400082667. Registered retrospectively on 4 April 2024.

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7. Benralizumab effectiveness in a real-world Portuguese severe eosinophilic asthma population: BETREAT study.

主题:生物统计与研究设计
期刊:Pulmonology
发表日期:2026-Dec
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND AND OBJECTIVES: Severe eosinophilic asthma (SEA) is often inadequately controlled. The BETREAT study evaluated the real-world effectiveness of benralizumab, an anti-IL-5 receptor monoclonal antibody, in Portugal, focusing on treatment persistence, asthma control, exacerbation rates, and quality of life (QoL).

STUDY DESIGN AND METHODS: Retrospective, observational study including SEA adults who received benralizumab between July 2019 and October 2020 across 16 sites in Portugal. Data from electronic medical records were analysed over 24 months, with evaluations at 3, 6, 12, and 24 months after treatment initiation. Key outcomes included exacerbation rates, oral corticosteroid use, asthma and lung function, and QoL.

RESULTS: Of the 74 patients (mean ± SD age 56 ± 11 years and 73.0% female), 66.2% were biologic-naïve. After initiating benralizumab, median eosinophil counts decreased to 0 cells/µL after 3 months. Exacerbation rates decreased from a mean annual rate of 3.12 at baseline to 0.48 by 24 months. Patient-reported asthma control and QoL improved, with ACT and CARAT scores reaching well-controlled levels in most patients by 24 months. Notably, 20.0% of patients achieved clinical remission by the end of the study.

CONCLUSIONS: Benralizumab significantly improved SEA outcomes and contributed to clinical remission over a 24-month period, demonstrating potential for long-term disease control and QoL improvement.

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8. Brain iron deposition mediates cognitive impairment in COPD: A possible imaging marker linking systemic inflammation to neurodegeneration.

主题:流行病学
期刊:Pulmonology
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Cognitive impairment is a relatively prevalent comorbidity in chronic obstructive pulmonary disease (COPD), yet its neuropathological mechanism remains poorly understood.

METHODS: We enrolled 48 stable COPD patients, categorized into cognitively normal (CogN, n = 22) and impaired (Cog, n = 26) groups based on Montreal Cognitive Assessment (MoCA) scores, along with 34 matched healthy controls. All participants underwent 3T MRI with quantitative susceptibility mapping (QSM) to quantify regional brain iron content. Group comparisons of whole-brain and region-of-interest susceptibility were performed. Mediation analysis was then used to test whether specific brain iron deposition mediates the relationship of both COPD status and peripheral inflammatory markers with cognitive performance.

RESULTS: Cog patients showed increased total iron in the right cerebellum crus I, while CogN patients exhibited higher paramagnetic susceptibility (χpara) in the left orbitofrontal cortex (OFC), right precentral gyrus, and right brainstem. χpara in the left OFC and right brainstem were positively correlated with total MoCA, abstraction, and orientation scores. Mediation analysis demonstrated that χpara of the left OFC mediated the effects of both COPD status and systemic neutrophil counts on impaired abstraction. Additionally, right brainstem χpara mediated the relationship between COPD and deficits in orientation.

CONCLUSIONS: COPD patients with cognitive impairment exhibited distinct patterns of brain iron deposition. Importantly, deposition in several key regions served as a potential mediator, linking both COPD and systemic inflammation to specific cognitive deficits. These preliminary findings suggest a possible association between brain iron accumulation and cognitive impairment in COPD, offering candidate neuroimaging markers for early identification.  .

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9. The relationship between attentional bias and posttraumatic stress symptoms among bereaved parents: a three-year longitudinal study using linear mixed models.

主题:生物统计与研究设计
期刊:European journal of psychotraumatology
发表日期:2026-Dec
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Background: Attentional biases are often considered key mechanisms in the onset and maintenance of various emotional disorders. However, existing research has reported inconsistent findings regarding the relationship between attentional bias and posttraumatic stress symptoms.Objective: This study aimed to examine the predictive effects of attentional bias on posttraumatic stress symptoms among bereaved Chinese parents who have lost their only children, using a three-year longitudinal analysis with linear mixed models.Method: Attentional bias and posttraumatic stress symptoms of bereaved parents (N = 47, aged 52-72 years) were assessed annually over three consecutive years using a dot-probe task and the PTSD Checklist for DSM-5 (PCL-5).Results: We found that vigilance toward positive stimuli was a negative predictor of posttraumatic stress symptoms, whereas vigilance toward negative stimuli positively predicted posttraumatic stress symptoms. Additionally, difficulty disengaging from both positive and negative stimuli was positively associated with posttraumatic stress symptoms. These associations were particularly evident regarding intrusions and alterations in arousal and reactivity at specific stimulus presentation durations.Conclusions: These findings strengthen our understanding of the relationship between attentional bias and posttraumatic stress symptoms through a longitudinal study design and analytic approach that accounts for random individual and time-related effects. Specific attentional bias components at particular stimulus presentation durations predicted posttraumatic stress symptoms, especially intrusions and alterations in arousal and reactivity.

The current study examined the predictive effects of attentional bias on posttraumatic stress symptoms among bereaved Chinese parents who have lost their only children, using a three-year longitudinal analysis with linear mixed models.Vigilance toward positive stimuli was a negative predictor of posttraumatic stress symptoms, whereas vigilance toward negative stimuli positively predicted posttraumatic stress symptoms. Difficulty disengaging from both positive and negative stimuli was positively associated with posttraumatic stress symptoms.These associations were particularly evident regarding intrusions and alterations in arousal and reactivity at specific stimulus presentation durations.

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10. Ketone monoester ingestion and cognitive and physical performance during exercise-heat stress.

主题:流行病学
期刊:Journal of the International Society of Sports Nutrition
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Sustaining cognitive and physical performance under extreme environmental conditions is critical for special operation forces (SOF). Hyperthermia negatively impacts cognitive function due to reductions in cerebral blood flow, substrate availability, thermal tolerance, and increased cardiovascular strain. While ketone monoester have demonstrated beneficial effects on cognition, their efficacy during exercise-heat stress remains unexplored.

METHODS: Seventeen endurance-trained males (age = 23.8 ± 5.2 y; VO2max = 58.6 ± 3.2 ml·kg-1·min-1) completed a randomized, double-blind, counterbalanced, crossover study. Participants ingested 4 mg·kg-1 caffeine combined with either a ketone monoester (KET; (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate) or an energy-matched carbohydrate control (CHO; Cluster Dextrin™). Each experimental visit consisted of 90 minutes of loaded treadmill exercise in the heat (34 °C, 45% RH) followed by a high-intensity time-to-exhaustion (TTE) test. Cognitive performance (1-back, 2-back, Dynavision reaction time [RT], object hit and avoid [OHA]), blood metabolites, average heart rate, and core body temperature (CBT) were assessed before, during, and after exercise and analyzed using linear mixed-model ANCOVA. TTE duration and maximal heart rate during TTE were analyzed using paired-samples t tests.

RESULTS: For cognitive performance, KET demonstrated significantly greater 1-back total accuracy (+2.8%, p = 0.001) and target accuracy (8.9%, p < 0.001) relative to CHO across all timepoints, Additionally, KET increased overall target discrimination (d’: + 0.3, p = 0.001) irrespective of task condition and timepoint. For 2-back, no overall between-condition differences were observed in total or target accuracy across time points, although task difficulty remained higher than 1-back performance overall. No between-condition differences were observed for RT or OHA outcomes. For blood metabolites, KET significantly increased circulating BHB concentrations relative to CHO at mid- and post-exercise (+1.7 and + 3.5 mmol·L-1, respectively; both p < 0.001) and reduced blood glucose by 14.7 and 27.6 mg·dL-1 at the same time points (p = 0.002 and p < 0.001, respectively). For average heart rate, there was a main effect of time, with heart rate lower during the first 45-minutes exercise bout than the second (-7.7 beats·min-1, p = 0.01), but no effect of condition (p = 0.453). CBT increased over time in both conditions (p < 0.001) but did not differ between KET and CHO (p = 0.065). TTE duration was significantly longer following KET than CHO (8.9 ± 4.6 vs 7.0 ± 2.1 min; p = 0.04), whereas maximal heart rate during TTE did not differ between conditions (p = 0.112).

CONCLUSIONS: Ketone monoester ingestion combined with caffeine improved select aspects of working memory and resulted in a significantly longer time-to-exhaustion compared with carbohydrate control following prolonged, loaded exercise in the heat. However, these effects were not universal across all cognitive outcomes, as no between-condition differences were observed for 2-back, RT, or OHA. Notably, despite performance differences, average heart rate, maximal heart rate during TTE, and core temperature did not differ. Together, these findings suggest that ketone monoester and caffeine co-ingestion may support specific cognitive and physical aspects of performance during sustained exercise-heat stress without altering cardiovascular or thermal strain.

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11. Research interest in nursing undergraduate students: an exploration of research-linked courses.

主题:流行病学
期刊:Medical education online
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Among Hispanic undergraduate students, the association between research-related coursework and research interest remains largely underexplored. This exploratory study examined differences in research interest among undergraduate nursing students according to their exposure to research-related coursework, drawing on Social Cognitive Career Theory.

METHODS: A cross-sectional study was conducted with 106 nursing students from a Peruvian university. Participants completed the Interest in Research Questionnaire (IRQ), which demonstrated excellent internal consistency (α = 0.98). Research interest was compared across four academic-semester groupings reflecting proximal and distal exposure to research-related coursework using rank-based nonparametric methods.

RESULTS: Significant differences in research interest were observed across groups (Anderson-Darling test = 9.41, p = 0.001), indicating a curvilinear pattern. Students currently or recently exposed to research-related coursework (levels 2 and 4) reported significantly higher research interest than those with more distal exposure (level 3; p < 0.05; medium effect sizes). First-semester students showed research interest levels comparable to those of the proximally exposed groups.

CONCLUSION: Research interest may decline in the absence of sustained engagement in research activities, underscoring the importance of early and continuous integration of research experiences throughout undergraduate nursing curricula. The findings also provide initial evidence supporting the use of the IRQ in Spanish-speaking undergraduate contexts.

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12. Causal association and shared mechanisms between Graves’ disease and prostate cancer: insights from Mendelian randomization, machine learning, and comprehensive bioinformatics.

主题:流行病学
期刊:The aging male : the official journal of the International Society for the Study of the Aging Male
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Observational studies link hyperthyroidism to increased prostate cancer (PCa) risk, but causality and mechanisms remain unclear. Graves’ disease (GD), the primary cause of hyperthyroidism, involves chronic immune dysregulation that may influence PCa through shared immune pathways.

METHODS: We performed bidirectional two-sample Mendelian randomization (MR) using IEU Open GWAS data, then integrated differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning on Gene Expression Omnibus (GEO) datasets to identify shared gene, validated by ROC curves, and analyzed immune profilesusing ssGSEA.

RESULTS: MR analysis indicated that genetic predisposition to GD significantly reduced PCa risk (OR = 0.997, 95% CI = 0.996-0.999, p = 0.004), with consistentsensitivity and no reverse causality. Four key genes (BTG2, JUN, JUNB, FOS) were identified as robust shared genes with high predictive accuracy in external validation. Immune profiles analysis revealed disease-specific associations of these genes: BTG2 and JUNB correlated with memory CD8 T cells in GD, whereas all four genes correlated with dendritic cells, mast cells and NK cells in PCa.

CONCLUSION: This study provided novel insights into the protective effect of GD against PCa and identified shared genes and immune mechanisms, offering a deeper understanding of the common mechanisms between GD and PCa.

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13. Planning and implementation of a community-wide tuberculosis screening intervention: a case study from Naujaat, Nunavut, Canada.

主题:流行病学
期刊:International journal of circumpolar health
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

In Nunavut, public health management of tuberculosis (TB) remains a challenge due to social and economic inequities, geographic isolation, TB-related stigma, and distrust in healthcare linked to a history of colonialism. A TB outbreak was declared in Naujaat, Nunavut following an increase in reported cases starting in January 2023. In response to this outbreak, the Naujaat community-wide TB screening (CWS) clinic was held from April 15th to May 29th, 2024, with support from the Nunavut Tunavik Incorporated (NTI) leadership and community engagement teams. This article outlines the steps taken in the coordination and implementation of a large public health intervention in this remote, northern community. Despite significant logistical challenges, the CWS clinic screened 89.2% of the 1000-person target consisting of all previously unscreened individuals residing in the community. As a result, 31 individuals with latent TB infection and <5 active TB cases were diagnosed and offered treatment, representing nearly 4% of those undergoing 2-step testing. Although the screening outcomes suggested that community transmission was low at the time of community-wide screening, it nonetheless exceeded the WHO threshold of 0.5% prevalence for community-wide screening. Lessons learned through the Naujaat CWS can help inform future public health actions towards TB elimination in Nunavut and other circumpolar jurisdictions.

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14. xinguangA preliminary characterization of PI4K/PIPK alterations across solid tumors: an exploratory framework for prognostic and therapeutic stratification.

主题:流行病学
期刊:Cancer biology & therapy
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: This study aimed to systematically characterize the genomic alteration landscape of phosphatidylinositol 4-kinase (PI4K) and phosphatidylinositol phosphate kinase (PIPK) family genes in solid tumors, assess the correlation of these alterations with patient clinical outcomes and the tumor immune microenvironment, and explore their potential as novel biomarkers or therapeutic targets.

METHODS: A retrospective analysis was conducted on whole-exome sequencing data from a cohort of 2,144 Chinese patients encompassing 18 solid tumor types. Genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) pan-cancer project were integrated to perform survival analysis, correlating genomic alterations, gene expression levels, and patient overall survival. Associations between these gene alterations and tumor mutational burden (TMB), microsatellite instability (MSI), and levels of tumor-infiltrating immune cells were also evaluated.

RESULTS: We identified PI4K/PIPK alterations in 10.5% of 2,144 patients, with PIP4K2C amplification reaching 48%. While PI4K2B amplification and overexpression are consistently associated with poor prognosis in COAD, family-wide effects were highly heterogeneous across cancers. Alterations significantly correlated with higher TMB and MSI-H, and multi-omics analysis revealed tissue-specific immune landscapes, highlighting the family’s potential for risk stratification and immunotherapy.

CONCLUSIONS: This study provides the first systematic delineation of the genomic alteration landscape of PI4K and PIPK families at a pan-cancer scale within a Chinese population. It identifies PI4K2B as an amplification-driven prognostic biomarker in colorectal cancer, with potential clinical value analogous to HER2. These findings illuminate the significant roles of these kinases in cancer and provide novel insights for future precision oncology strategies.

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15. Canine brain imaging with a new low-field portable (0.05 T) MRI scanner: a pilot in vivo comparison to conventional 1.5 T.

主题:流行病学
期刊:The veterinary quarterly
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Prohibitive costs associated with high-field MRI systems have resulted in reduced access in resource-limited areas with consequential healthcare inequities. This has renewed interest in purposefully designed low-field (LF) systems that, despite inherently lower signal-to-noise ratios, have advantages in terms of cost, portability, and accessibility. This pilot study successfully translated a previously developed LF (0.05 T) MRI canine cadaver brain protocol for in vivo application and compared the acquired images with paired 1.5 T images from 21 different canine patients. The visibility of 15 anatomic features was ordinarily scored (scale 1-3) on transverse T1-weighted post-contrast (21/21 patients) and T2-weighted (17/21 patients) sequences. Lateral ventricles were easily visualized (89.3%-100% scored 3/3) across all sequence‒system combinations, with T2-weighted sequences also providing good identification of the mesencephalic aqueduct (56.3%-100%), fourth ventricle (77.1%-100%), and thalamus (68.8%-100%). Absolute visual grading characteristics (VGC) analysis confirmed comparable performance of the LF system to the 1.5 T MRI for these features, a particularly relevant finding given the system’s originally intended application for pediatric hydrocephalus neuroimaging in resource-limited areas. This study represents the first in vivo usage and evaluation of a 0.05 T MRI in a clinical veterinary context.

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16. Vaccination coverage and influencing factors of four non‑National Immunization Program vaccines: A cross‑sectional survey among children aged 1‒6 years in Beijing, China.

主题:流行病学
期刊:Human vaccines & immunotherapeutics
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

The pneumococcal conjugate vaccine (PCV), Haemophilus influenzae type b (Hib) vaccine, rotavirus vaccine (RV), and varicella vaccine (VarV) have been recommended by WHO for inclusion in National Immunization Program (NIP). However, their vaccination rate is low in China as self-funded vaccines. This study aimed to investigate the coverage of these four vaccines and to identify their influencing factors. Selected via multi-stage stratified sampling, 4,182 guardians participated in a February-March 2025 study. Guardians completed an online questionnaire capturing sociodemographic characteristics, attitudes toward vaccination, and indicators of immunization service accessibility. Individual-level vaccination histories for children were extracted from the Beijing Immunization Information System and linked to survey responses. The vaccination coverage of PCV, Hib vaccine, RV and VarV were 48.5%, 47.4%, 43.5% and 89.3%, respectively. Older age, residence outside urban areas (suburban, outer suburban), and greater number of children in the household were associated with lower coverage of PCV, Hib vaccine, and RV, with adjusted ORs ranging from 0.160 to 0.929 (all p values < .05). Conversely, higher household income (200,000-499,999 CNY and ≥500,000 CNY), guardians’ perceived vaccination necessity, and receipt of vaccination notifications were associated with higher coverage of PCV, Hib vaccine, and RV, with adjusted ORs ranging from 1.018 to 6.521 (all p values < .05). The results indicated the vaccination coverage of PCV, Hib vaccine, and RV remains suboptimal in Beijing, with evident regional disparities. Free vaccination policies for PCV, Hib vaccine, RV, and VarV, together with strengthened reminder systems and targeted health education interventions, may help improve vaccine coverage among children.

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17. Dose-response relationship between growth hormone treatment and the development of scoliosis in children with short stature.

主题:生物统计与研究设计
期刊:Annals of medicine
发表日期:2026-Dec
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: We sought to investigate whether growth hormone (GH) treatment increases the risk of scoliosis in children with short stature and analyse a dose-response relationship.

METHODS: A retrospective cross-sectional and cohort study design was used. The cross-sectional study included 1160 children with short stature (355 and 805 in the GH-exposed and non-exposed groups, respectively). The scoliosis prevalence was compared. A total of 313 short stature children without scoliosis at baseline were enrolled in the cohort study (158 and 155, respectively, in the GH and non-GH groups). The median follow-up time was approximately 4.5 years. The relationship between risk factors and GH dose and the occurrence of scoliosis was evaluated with the outcome of new-onset scoliosis.

RESULTS: The incidence of scoliosis in the GH exposure group was significantly higher than that in the non-exposure group (5.40% vs. 2.40%, p=0.008). The risk of scoliosis in the GH group was 2.726 times higher than that in the non-GH group (HR=2.726, 95%CI: 1.326-5.605, p=0.006). The total GH dose was positively correlated with scoliosis risk, and there was a dose-response relationship between the total GH dose and the risk (HR=1.002, 95%CI: 1.001-1.003, p<0.001). A dose-response relationship was confirmed, with the predicted probability of scoliosis increasing continuously with cumulative GH dose.

CONCLUSIONS: GH therapy is an independent risk factor for scoliosis in children with short stature, with a significant dose-response relationship. The cumulative GH dose can be used as a preliminary reference indicator for risk stratification and personalized monitoring.

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18. Rethinking vaccine mandates through the lens of penalties and incentives: A 7S framework approach.

主题:卫生政策与真实世界证据
期刊:Global public health
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Conceptually, current definitions of vaccine mandates involve two key elements: the requirement to be vaccinated and sanctions for non-compliance. However, during COVID-19, governments frequently introduced vaccine mandates in contexts where people were already denied access to work, travel, and social activities due to lockdowns and restrictions. This important context disrupts the standard operation of vaccine mandates. Accordingly, this paper explores COVID-19 vaccine mandates in New South Wales (Australia), France, Israel, Malaysia, Singapore, and Vietnam, where mandates primarily served as incentives to restore basic rights to travel, work, and access public spaces, that were restricted during the pandemic. Through document analysis and key informant interviews, the paper examines how governments employed this “removal and restoration” model and explores how mandate policy instruments create incentive structures. In discussing the implications of mandates in relation to lockdowns and restrictions, and the perception of mandates as “coercive offers”, the paper proposes a revised conception and a 7S vaccine mandate framework by adding synergy and sustainment to the existing 5S model. It concludes by outlining the significance of this revised conception and framework for vaccine mandate policy research, design, and communication.

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19. Effects of serotonergic pharmacological manipulation on exercise performance and central fatigue: a systematic review and three-level meta-analysis.

主题:临床研究与数据方法
期刊:Journal of the International Society of Sports Nutrition
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Exercise-induced fatigue is a complex, non-pathological state that acutely limits physical performance, and the serotonergic (5-HT) system has been proposed as an important modulator of its central components. This systematic review and meta-analysis aimed to clarify the effects of serotonergic pharmacological manipulation on exercise-related outcomes.

METHODS: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Web of Science, Cochrane Central, and SportDiscus from inception to August 2025. Randomized controlled trials examining the effects of serotonergic pharmacological manipulation on exercise-related outcomes in healthy adults were included. Study selection, data extraction, and risk-of-bias assessment using RoB 2.0 were conducted independently. Pooled effects were synthesized using three-level random-effects models, and the certainty and robustness of the evidence were examined in additional analyses.

RESULTS: Twenty-one randomized controlled trials involving 248 healthy adults were included in the systematic review, of which 19 studies involving 229 participants were included in the meta-analysis. In the primary models, serotonergic pharmacological manipulation was associated with small reductions in evoked motor response (Hedges’ g = -0.24, 95% CI -0.46 to -0.02), time-domain EMG (Hedges’ g = -0.18, 95% CI -0.33 to -0.02), heart rate (Hedges’ g = -0.17, 95% CI -0.34 to -0.01), and blood glucose (Hedges’ g = -0.50, 95% CI -0.89 to -0.11). Voluntary activation showed a borderline negative pooled estimate (Hedges’ g = -0.20, 95% CI -0.40 to 0), whereas ratings of perceived exertion showed a positive but statistically uncertain pooled estimate (Hedges’ g = 0.63, 95% CI -0.01 to 1.28). Resting twitch torque showed a small positive pooled effect (Hedges’ g = 0.12, 95% CI 0.04 to 0.19), whereas superimposed twitch torque, maximal voluntary contraction, prolactin, lactic acid, and time to task failure did not show clear overall effects.

CONCLUSIONS: Overall, this meta-analysis indicates that serotonergic pharmacological manipulation has outcome-specific effects on exercise-related fatigue rather than a single uniform influence across domains. The most consistent primary-model signals were found for evoked motor response, time-domain EMG, heart rate, and blood glucose, whereas overt performance and perceptual outcomes remained more variable. By integrating evidence across different serotonergic interventions and exercise paradigms, these findings improve our understanding of how 5-HT-related mechanisms may contribute to central fatigue during exercise.

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20. Efficacy and safety of doravirine/islatravir for HIV-1: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

主题:临床研究与数据方法
期刊:HIV research & clinical practice
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: The combination of doravirine and islatravir (DOR/ISL) is a novel two-drug regimen for HIV-1. Early development faced challenges due to dose-dependent immunological signals. We aimed to synthesize the evidence on the efficacy and safety of DOR/ISL across all treatment-experience categories, specifically evaluating the impact of islatravir dosage (0.25 mg vs 0.75 mg) on clinical and immunological outcomes.

METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, and Google Scholar from inception through April 2026. Primary outcomes were virological suppression (<50 copies/mL) and mean change in CD4+ T-cell count at week 48. Data were pooled using random-effects models. Islatravir dose was evaluated as a pre-specified moderator. Quality was assessed using Cochrane RoB 2.0 and certainty of evidence was graded using the GRADE approach.

RESULTS: Seven RCTs (n = 3,600 participants) were included. At Week 48, DOR/ISL showed non-inferior suppression rates (RR 1.01 [95% CI 0.99-1.02]; p = 0.516; moderate-certainty evidence) and a statistically significant reduction in virological failure risk (RR 0.55 [0.33-0.92]; p = 0.022) compared to active control. Overall CD4+ gain was lower with DOR/ISL (MD -34.55 cells/μL; low-certainty evidence); however, a profound moderator effect of dose was observed (p < 0.0001). The 0.75 mg dose was associated with significant CD4+ and lymphocyte declines, whereas the approved 0.25 mg dose was immunologically neutral. DOR/ISL was weight-neutral compared to bictegravir/emtricitabine/tenofovir alafenamide (MD -0.25 kg [-0.66 to 0.16]; low-certainty evidence).

CONCLUSION: DOR/ISL 100/0.25 mg once daily achieved virological suppression comparable to standard-of-care ART regimens and was associated with lower rates of virological failure compared with active comparators. The immunological safety concerns observed in early trials were successfully resolved by dose optimization. These findings support the use of DOR/ISL (IDVYNSO) as a potential treatment option for both treatment-naïve and virologically suppressed adults while emphasizing long-term safety surveillance.

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21. Professional identity formation among participants in a longitudinal pediatric program for final year medical students: a qualitative case study.

主题:生物统计与研究设计
期刊:Medical education online
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

OBJECTIVE: To explore aspects of professional identity formation in participants of a longitudinal pediatric program for final-year medical students in the US.

INTRODUCTION: Many institutions have specialty-specific courses focused on the transition to residency, typically at the end of medical school. This study examines professional identity formation among participants of a longitudinal fourth-year Pediatric Concentration.

METHODS: Authors used a case study design for this qualitative research study using semi-structured interview questions based on a conceptual model of professional identity formation. Authors used purposeful sampling to identify study participants who were randomly selected from former students who completed the program between 2019 and 2021. Three interviewers independently conducted interviews with individual program participants. Thematic analysis with coder reliability was utilized for data analysis; two investigators independently coded and performed inter-rater reliability (IRR) on three sets of questions from transcriptions. After ensuring acceptable IRR, investigators coded the remaining questions and subsequently identified themes and sub-themes.

FINDINGS: Eleven former students completed interviews. Following initial independent coding, IRR for three questions was 80%. After coding the 11 interviews, investigators determined that code saturation was achieved. They subsequently identified six main themes: career development, interpersonal connection, personal growth, positive role models, skill-building, and supportive learning environment. Two cross-cutting themes were recognized throughout the data: sense of belonging and gaining confidence toward starting residency.

CONCLUSIONS: Participants in a longitudinal specialty-specific program in the final year of medical school experienced professional identity formation through a supportive learning environment fostering connection and personal growth while building skills, surrounded by positive role models. This community of practice cultivated a sense of belonging and helped participants gain confidence toward their residency and career. This longitudinal, specialty-specific approach to the final year of medical school may enhance professional identity formation for students entering all specialties and could facilitate transition to internship.

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22. Effects of combined versus single supplementation of creatine and beta-alanine on aerobic and anerobic performance: a systematic review and network meta-analysis.

主题:临床研究与数据方法
期刊:Journal of the International Society of Sports Nutrition
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Creatine (Cr) and β-alanine (BA) are among the most studied ergogenic supplements, acting on distinct physiological pathways-Cr facilitates phosphocreatine resynthesis and rapid ATP turnover, while BA elevates intramuscular carnosine to enhance acid-base buffering. Although both compounds improve high-intensity performance independently, the ergogenic potential of their combined use remains uncertain.

OBJECTIVE: To systematically evaluate and compare the isolated and combined effects of Cr and BA supplementation on aerobic and anaerobic performance indices using a network meta-analytic approach.

METHODS: Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, and Web of Science (to August 2025) identified randomized controlled trials (RCTs) examining Cr, BA, or Cr + BA supplementation (≥2 weeks) in healthy adult athletes. Fifty-two RCTs (PEDro ≥ 6) met the inclusion criteria. Standardized mean differences (SMD) and 95% confidence intervals (CI) were computed within random effects models. Performance outcomes included sprint, jump, agility, upper- and lower-body muscular endurance (UME, LME), and repeated-sprint ability (RSA).

RESULTS: Cr supplementation significantly improved sprint performance (SMD = -0.64; p = 0.04), jump performance (SMD = 0.33; p = 0.002), RSA (SMD = -0.78; p = 0.01), and UME (SMD = 0.43; p = 0.01) versus placebo, with P scores ≥ 0.90 across these domains. In contrast, BA supplementation produced non-significant or context-specific effects, and combined Cr + BA showed no synergistic benefits. Agility and LME outcomes remained unaffected (p > 0.05). Heterogeneity ranged from low to moderate (I2 = 0-73%), with no global inconsistency or substantive publication bias.

CONCLUSION: Evidence indicates Cr supplementation alone yields the most consistent improvements in high-intensity and anaerobic performance by enhancing phosphocreatine recovery and neuromuscular output. BA’s buffering advantage appears task-specific and insufficient to augment Cr’s ergogenic efficacy. Co-supplementation of Cr and BA offers no additional advantage beyond Cr monotherapy. Standardized, long-term, multi-arm RCTs are warranted to further clarify potential interactive mechanisms and sex or sport-specific responses.

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23. Perinatal ampicillin exposure alters murine maternal fecal bile acid and acylcarnitine profiles.

主题:可复现研究与开放科学
期刊:Gut microbes
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Maternal intrapartum antibiotic prophylaxis (IAP) and postpartum maternal antibiotic usage are increasingly common and have been linked to altered growth and immune development in offspring. However, the mechanisms underlying these effects, particularly those arising from indirect early-life exposure to antibiotics, remain poorly understood. Here, using a preclinical murine model, we examined the impact of in vivo antepartum and postpartum maternal ampicillin administration on the maternal fecal microbiome and metabolome. Ampicillin treatment resulted in a significant depletion of bacterial species belonging to the Muribaculaceae family, including Muribaculum intestinale and Duncaniella dubosii, accompanied by a cohort-dependent enrichment of Enterococcus and Prevotella species. These microbial shifts coincided with substantial and reproducible metabolic remodeling, including elevated fecal acylcarnitines and altered bile acid profiles. Notably, we identified two previously uncharacterized trihydroxylated bile acids conjugated to a hexose moiety, which we annotated as cholic acid-galactose and taurocholic acid-galactose and synthesized. These metabolites were consistently associated with antibiotic exposure across public metabolomics data repositories. Finally, alterations in the maternal fecal microbiome and metabolome were associated with increased weight gain in offspring, suggesting potential pathways by which maternal antibiotic exposure may influence early developmental outcomes. These findings highlight microbial and metabolic signatures linked to perinatal antibiotic use and underscore the need to balance infection control with long-term infant health considerations.

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24. Effect of pasteurized Akkermansia muciniphila MucT on insulin sensitivity, body composition, and GLP-1 production in subjects with metabolic syndrome: impact of low baseline gut Akkermansia levels.

主题:临床研究与数据方法
期刊:Gut microbes
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Pasteurized Akkermansia muciniphila MucT was found to improve barrier function in preclinical models and a proof-of-concept study in obese and prediabetic adults. Here, we describe the results of a double-blind placebo-controlled multicenter (Ireland and Germany) trial in 142 adults with metabolic syndrome, with or without prediabetes. The primary endpoint of whole-body insulin sensitivity (Matsuda index) did not differ after 4-months of daily administration of capsules containing 30 billion cells of pasteurized A. muciniphila MucT compared to placebo in the intention-to-treat subjects. Subsequent exploratory analyses showed that 3-months intake of pasteurized A. muciniphila MucT already improved HOMA-based hepatic insulin sensitivity in prediabetic (12%; p = 0.05) and 63-y-or-older-age subgroups (p = 0.05) while increasing post-OGTT excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) over placebo (p < 0.01). Further analysis of the gut microbiota by deep metagenomic analysis showed minor effects of the intervention but revealed that the baseline microbial composition differed from that in matched healthy adults. We found that participants with low baseline Akkermansia gene counts experienced significant health improvements and GLP-1 excursion after 3-months of treatment with pasteurized A. muciniphila MucT over the placebo. These benefits included improved insulin sensitivity (as shown by Matsuda and HOMA-S indices) and GLP-1 excursion (post-OGTT) (p < 0.05), reductions in body weight (p = 0.06) and decreased trunk fat (p < 0.05). In conclusion, daily supplementation with pasteurized A. muciniphila MucT has the potential to improve health markers in overweight or obese normo- or dysglycemic adults with the most significant improvements in subjects with low baseline intestinal Akkermansia levels, who are apparently truly in need of this intervention. Clinical trial registration no.: NCT05114018 clinicaltrials.gov.

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25. Caffeine makes a splash: a systematic review and multilevel meta-analysis exploring the effects of caffeine intake on swimming performance.

主题:临床研究与数据方法
期刊:Journal of the International Society of Sports Nutrition
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Evidence for acute caffeine supplementation in swimming remains inconsistent across reviews, likely due to between-study heterogeneity and methodological differences.

METHODS: Five databases were searched for randomized placebo-controlled crossover trials exploring the effects of caffeine on swimming performance in competitive swimmers. Performance outcomes were pooled as standardized mean differences (SMD; Hedges’ g), with time outcomes sign-reversed so that positive values indicated improved performance. Dependence among multiple outcomes within studies was addressed using three-level random-effects models (REML). As a supplementary, interpretable metric, log ratios of means (lnRoM) were meta-analysed and expressed as percentage change. Post-exercise blood lactate (mmol/L) was pooled as mean differences (MD). Risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Prespecified exploratory moderator analyses examined potential effect modification (dose, timing, distance, administration form, stroke, gender, and athlete level).

RESULTS: Thirteen studies were included (144 men and 48 women), which contributed 28 performance effect sizes. Caffeine improved swimming performance (SMD = 0.57, 95% CI: 0.20 to 0.94; p = 0.005), corresponding to a +1.71% improvement in lnRoM (95% CI: +1.01% to +2.41%; p < 0.001). Heterogeneity was substantial (I²total = 64.7%) and primarily between studies. Eight studies contributed 24 blood lactate effect sizes. In the meta-analysis, caffeine increased post-test lactate (MD = 0.85 mmol/L, 95% CI: 0.22 to 1.49; p = 0.016) with high heterogeneity (I²total = 76.5%). Exploratory moderator analyses suggested a possible dose-related pattern for swimming performance, with larger pooled effects at ≥6 mg/kg (SMD = 0.95, 95% CI: 0.52 to 1.38) than at <6 mg/kg (SMD = 0.22, 95% CI: -0.15 to 0.60; p difference = 0.017). Other performance moderators did not show clear between-subgroup differences. For lactate, exploratory subgroup analyses suggested larger increases in freestyle and short-distance events, although these patterns were more sensitive to modelling assumptions and should be interpreted cautiously.

CONCLUSION: Acute caffeine ingestion confers a moderate ergogenic benefit for swimming performance (SMD = 0.57, 1.7% improvement) and is associated with higher post-test blood lactate (MD = 0.85 mmol/L). Dose (≥6 mg/kg) may be associated with larger performance benefits, whereas lactate responses appear more pronounced in freestyle and shorter events. However, these subgroup findings are hypothesis-generating and require exploration.

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26. Pooled analysis of 2 clinical trials of first-line chemoimmunotherapy for metastatic microsatellite stable colorectal cancer MEDITREME and METIMMOX studies.

主题:临床研究与数据方法
期刊:Oncoimmunology
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

BACKGROUND: Colorectal cancer with microsatellite stable (MSS) status is intrinsically resistant to immune checkpoint inhibitor monotherapy targeting PD-1 or PD-L1. However, emerging evidence suggests that chemotherapies may overcome this resistance when combined with immunotherapy.

METHODS: We conducted a pooled analysis of individual patient data from two phase II trials evaluating oxaliplatin-based chemotherapy combined with checkpoint inhibitors as first-line treatment for MSS metastatic colorectal cancer. The MEDITREME trial is a single-arm study assessing durvalumab and tremelimumab with oxaliplatin-based chemotherapy, while the METIMMOX trial is a randomized study comparing standard oxaliplatin-based chemotherapy with an alternating regimen of oxaliplatin-based chemotherapy and nivolumab. We compared overall survival (OS), progression-free survival (PFS), and response rates between patients treated with chemotherapy alone versus chemoimmunotherapy, and evaluated the association between these outcomes and transcriptomic and immunoscore data.

RESULTS: A total of 130 patients were included: 38 who received chemotherapy alone and 92 chemoimmunotherapy. The median OS was significantly improved in the chemoimmunotherapy group compared with chemotherapy alone (not reached vs. 15.3 months; HR = 0.58; 95% CI, 0.36-0.96; p = 0.03). The complete response rates were higher with chemoimmunotherapy (14% vs. 5%). No significant differences were observed in PFS. High baseline CD8+ T-cell infiltration was associated with improved outcomes in patients receiving chemoimmunotherapy but not in those treated with chemotherapy alone.

CONCLUSIONS: This pooled analysis provides compelling evidence supporting the clinical benefit of first-line chemoimmunotherapy in a subset of patients with MSS mCRC. Baseline CD8+ T-cell infiltration may serve as a predictive biomarker for identifying patients most likely to benefit from this treatment approach.

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27. Gut microbial markers of immunotherapy response in melanoma: a cross-cohort analysis including the first Russian dataset.

主题:可复现研究与开放科学
期刊:Gut microbes
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Melanoma is an aggressive malignancy with a significant risk of mortality. In recent years, treatment strategies have undergone a paradigm shift with the advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs). Despite notable clinical success, a substantial proportion of patients fail to respond or eventually develop resistance to ICIs. Emerging evidence highlights the gut microbiota as a critical modulator of host immune responses and is one of the potential determinants of immunotherapy efficacy. We performed a cross-cohort analysis of gut microbiome profiles from melanoma patients treated with ICIs. The study integrated the first Russian cohort (62 patients) with six previously published international datasets, comprising a total of 490 patients across seven cohorts. In all cases, metagenomic sequencing was performed using various Illumina platforms, and raw sequencing data were processed using a unified bioinformatic pipeline. Analysis revealed 527 metagenome-assembled genomes (MAGs) significantly associated with treatment outcome: 239 with response and 288 with non-response. Notably, the species Faecalibacterium sp900539945, Phocaeicola vulgatus, Bifidobacterium adolescentis, Faecalibacterium taiwanense, and Gemmiger qucibialis were consistently associated with response, while Enterobacter ludwigii was linked to non-response. Analysis of the Russian cohort revealed both conserved and population-specific microbial signatures, highlighting the coexistence of globally shared and region-dependent microbiome features. Our results also show that species-level annotations may obscure opposing response associations within the same taxa, highlighting the need for MAGs or strain profiling. Together, this study demonstrates that cross-cohort analysis enables the identification of robust and reproducible bacterial markers of immunotherapy response, providing a foundation for microbiome-based prediction and modulation strategies in melanoma.

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28. Real-world pegcetacoplan treatment of paroxysmal nocturnal hemoglobinuria patients with an unsatisfactory response to prior therapies.

主题:卫生政策与真实世界证据
期刊:Hematology (Amsterdam, Netherlands)
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

OBJECTIVES: Terminal complement inhibitors can control intravascular hemolysis in Paroxysmal Nocturnal Hemoglobinuria (PNH) patients, although the hematological response achieved may not persist, and it may become unsatisfactory. The proximal (C3) complement inhibitor Pegcetacoplan (PEG) improves this situation in clinical trials, yet real-world data on its efficacy and safety are scarce.

METHODS: This non-interventional, retrospective, multicenter study presents clinical and hematological data from the first PNH patients in Spain treated with PEG (n = 32, median 13 months, range 4-61).

RESULTS: PEG rapidly increases the patient’s hemoglobin (median increase of 2.65 g/dL in 4 weeks, > 2 g/dL increase in 56.3% of patients), reaching > 8, 10 and 12 g/dL in 93.7%, 87.5% and 46.9% of patients, respectively. Packed red blood cell transfusion requirements dropped from 62.5% to 15.6% of patients treated with PEG, and there was a fall in breakthrough hemolysis from 34.4% to 9.4% after 6 months of treatment. No thrombosis and only mild adverse events (n = 11 patients) were described with PEG therapy. Finally, physicians perceived important enhancements in patients’ health-related quality of life.

DISCUSSION: This real-world clinical data confirms that PEG produces significant and rapid improvements in hemoglobin and hemolytic parameters, with a favorable safety profile. The data extends that of earlier clinical trials and small real-world studies by offering a longitudinal (as opposed to cross-sectional) assessment of the patient responses across a large number of centers, following a variety of clinical practices.​​​​​.

CONCLUSION: PEG treatment of patients with PNH produces significant and rapid improvements in hemoglobin and hemolytic parameters, with a favorable safety profile.

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主题:可复现研究与开放科学
期刊:Autoimmunity
发表日期:2026-Dec-31
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with complex molecular mechanisms. Although transcriptomic studies have revealed prominent interferon signatures in SLE, robust prioritization of candidate genes across independent cohorts remains challenging. In this study, we performed a multi-cohort transcriptomic analysis using publicly available GEO datasets. Differential expression analysis was conducted independently within each cohort to minimize cross-study confounding. Machine learning models, including LASSO, support vector machine, and random forest, were applied for feature prioritization in a designated training cohort, followed by independent validation in separate datasets. Model interpretability was assessed using SHAP analysis. Immune cell composition was estimated descriptively using CIBERSORT. In addition, molecular docking and molecular dynamics simulations were performed as exploratory in silico analyses to evaluate potential protein-compound interactions. A set of consistently dysregulated genes across cohorts was identified, many of which are associated with interferon signaling. Among these, RSAD2 showed robust prioritization across multiple machine learning models. The predictive performance of the models was stable in independent validation datasets. SHAP analysis highlighted the contribution of interferon-stimulated genes to model predictions. Immune deconvolution suggested altered immune cell composition in SLE samples, consistent with previously reported immune activation patterns. Exploratory in silico analyses suggested a potential interaction between artemisinin and RSAD2. This study provides a robust, multi-cohort computational framework for prioritizing candidate genes associated with SLE. The findings highlight interferon-associated transcriptional features as reproducible molecular signatures of SLE and generate testable hypotheses for future experimental and clinical investigation.

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30. Worst Histology-Based Risk Stratification for Lymph Node Metastasis in Patients With T1b Colorectal Cancer: A Retrospective Pathology-based Study.

主题:可复现研究与开放科学
期刊:DEN open
发表日期:2027-Apr
内容状态:待评估
为什么值得看:包含可供初筛的摘要;仅作为选题线索,不代表证据质量结论。

OBJECTIVES: Histological subtype is an important pathological factor in risk stratification for lymph node metastasis (LNM) in T1 colorectal cancer (CRC); however, conventional predominant-type assessment may miss minor poorly differentiated components in T1b CRC. We aimed to develop a T1b-specific risk stratification framework incorporating a reproducible worst histology (WH) approach.

METHODS: We retrospectively analyzed 488 patients with pathologically confirmed pT1b CRC who underwent surgical resection with lymph node dissection. Histological evaluation was performed using three approaches: dominant histology (DH), WH, and WH focusing on poorly differentiated adenocarcinoma (WH-por). For each approach, independent risk factors for LNM were identified. Patients without these factors were defined as the low-risk subgroup, and LNM rates were compared with the conventional Japanese Society for Cancer of the Colon and Rectum (JSCCR) criteria.

RESULTS: In patients with T1b colon cancer, the WH-por approach demonstrated favorable performance for identifying LNM risk compared with the DH and WH approaches. In contrast, in rectal cancer, the WH approach performed better than the WH-por approach. In the colon cohort, the LNM rate in the low-risk subgroup was 1.7%, compared with 4.1% under the JSCCR criteria. In the rectal cohort, the corresponding rates were 8.0% and 8.6%, respectively.

CONCLUSIONS: A WH-based approach improves LNM risk stratification in T1b CRC and may help identify carefully selected patients at low risk of LNM, supporting more individualized clinical decision-making, including careful consideration of the necessity of additional surgical resection.Trial Registration: N/A.

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