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Individual differences in brain dynamics across a social cognition network induced by cortico-cerebellar tDCS in adults with autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a neurodevelopmental condition with core diagnostic domains of social communication impairments, restricted interests and repetitive behaviors. Idiosyncratic brain organization is a potential hallmark of ASD. Previous transcranial direct current stimulation (tDCS) studies often targeted dorsolateral prefrontal cortex, with changes oin brain dynamics averaged across the cohort. We utilized a magnetoencephalographic (MEG) array to characterize individual differences in brain dynamics induced by cortico-cerebellar tDCS across nodes of a social cognition network. A randomized, sham-controlled, double-blind, within-subject clinical trial was conducted in a cohort of 24 young adults with ASD or high autistic traits. Two separate sessions of computerized social learning activities were combined with verum/sham tDCS, with anodal electrode over right temporoparietal junction (TPJ) and cathode on right deltoid. Following stimulation, theta- and alpha-band activity were evaluated within nodes of a social cognition network: bilateral TPJ, fusiform, medial prefrontal cortex and Crus I/II of cerebellum. Idiosyncratic participant-specific up- and down-regulation of theta- and alpha-band activity occurred across the network. Activity in right Crus I/II, a region inundated by the stimulation current, strongly correlated with the change of activity summed across all cerebral cortical nodes in theta- but not alpha-band. Intrinsic theta-band activity is believed to mediate input/output relationships in cerebellar cortex and to drive synaptic plasticity. These results suggest that theta-band stimulation of cerebellar cortex might be an effective therapy for individuals on the autism spectrum who present with cerebellar hyperactivity.

Humans

Routine methods misidentify Serratia spp.: Limitations of MALDI-TOF MS revealed by whole-genome sequencing.

Accurate species-level identification within the genus Serratia remains challenging due to extensive phenotypic overlap and high genomic relatedness among closely related and recently described taxa. This study presents an evaluation of routine and genome-based identification approaches applied to clinical Serratia isolates, integrating phenotypic assays, MALDI-TOF MS (Bruker Daltonics), 16S rRNA gene sequencing, and Whole-Genome Sequencing (WGS). A total of 103 isolates collected from a teaching hospital were analyzed. WGS was performed on a subset of isolates. Conventional biochemical methods classified all isolates as Serratia marcescens, whereas MALDI-TOF MS identified 60.1% as S. marcescens, 11.6% as S. ureilytica, and 28.1% just at the genus level. Peak analysis from MALDI-TOF MS revealed specific peaks associated with S. marcescens and S. ureilytica, but limited discriminatory power. WGS of six isolates initially identified as S. ureilytica by MALDI-TOF MS revealed reclassification as Serratia sarumanii (n = 5) and Serratia montpellierensis (n = 1), supported by Average Nucleotide Identity (ANI), Average Amino Acid Identity (AAI), and Digital DNA-DNA Hybridization (dDDH) thresholds. In contrast, 16S rRNA analysis showed limited species-level resolution. Phylogenomic and SNP-based analyses confirmed these classifications with strong support. Overall, this study underscores the critical role of high-resolution genomic approaches for precise species identification and highlights the need for continuous expansion and curation of MALDI-TOF MS reference databases to support reliable clinical diagnostics and epidemiological surveillance of emerging Serratia species.

Spectrometry, Mass, Matrix-Assisted Laser Desorpti

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145 particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI = 10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals

Physical therapy for urinary incontinence in older women: A systematic review.

BACKGROUND: Urinary incontinence is highly prevalent among older women, affecting more than one-third of this population and significantly impairing quality of life, independence, and healthcare utilization. Older women often present with complex needs that may require broader rehabilitation strategies. METHODS: This systematic review evaluated randomized controlled trials of physical therapy interventions for urinary incontinence in older women. PubMed, Embase, and Scopus were searched to October 2025. Eligible studies included women ≥60 years and assessed interventions such as Pelvic floor muscle training (PFMT), bladder training, Yoga, Pilates, general resistance training, electrical stimulation, or multimodal programs. Methodological quality was appraised using the PEDro scale, and random-effects meta-analysis was performed where appropriate. RESULTS: Twenty studies involving 2002 women across 13 countries were included. Eleven trials were rated as good quality and nine as fair. Meta-analysis demonstrated that PFMT significantly reduced urinary incontinence severity compared with usual care (SMD = -1.27, 95% CI: -2.18 to -0.36, p = 0.006). Multimodal programs combining PFMT with mobility, strength, or fall-prevention training also showed significant benefits (SMD = -0.98, 95% CI: -1.60 to -0.36, p = 0.002). Comparative studies indicated that PFMT was similarly effective to Yoga and Pilates, while adjuncts such as general resistance training or tibial nerve stimulation provided additional improvements. CONCLUSION: Physical therapy interventions, particularly PFMT and multimodal programs, are effective in reducing urinary incontinence severity and improving functional outcomes among older women. These findings support prioritizing physical therapy as an important management strategy, with multimodal approaches offering added value for enhancing functional independence and fall prevention.

Humans

Modulation of heart rate and heart rate variability during animal-assisted treatment of patients in a minimally conscious state: A randomized controlled crossover study.

BACKGROUND: Animal-assisted treatment (AATx) is a promising and increasingly used approach in neurorehabilitation, yet its psychophysiological effects remain largely unexplored. Patients in a minimally conscious state (MCS) show severely altered consciousness with minimal but definite behavioral signs of awareness. Because behavioral assessment in this population is limited, psychophysiological measures such as heart rate (HR) and heart rate variability (HRV) may offer valuable insights into autonomic regulation during therapy. AIM: The present study investigated whether AATx influences HR and HRV compared to treatment as usual (TAU). METHODS: A randomized controlled crossover design with repeated measures was conducted. HR and HRV data were recorded using an Empatica E4 wristband, and linear mixed-effects models were fitted for each outcome variable. The analytic sample included twenty-one patients with MCS who completed at least one of the four sessions. RESULTS: We found a significant decrease in mean HR (estimate = -12.75, p = .041) and a significant increase in the standard deviation of normal-to-normal intervals (SDNN) (estimate = 15.76, p = .020) during AATx compared to TAU from the pretreatment to the posttreatment phase, indicating enhanced parasympathetic activation and greater autonomic flexibility. Other HRV parameters revealed no significant effects of AATx, though trends were consistent with the hypotheses. CONCLUSIONS: These findings provide preliminary physiological evidence that AATx can modulate autonomic activity in MCS patients. Despite limitations related to sample size and recording quality, the results highlight the potential of AATx as an emotionally engaging intervention in early neurorehabilitation.

Humans

Dynamic lysine acetylation and succinylation of platelet proteins regulates platelet storage lesion: mechanistic insights from multi-omics.

OBJECTIVES: Platelet storage lesion (PSL) severely impairs platelet function during storage, presenting a major hurdle in transfusion medicine; however, the dynamic interplay between global proteomic changes and post-translational modifications (PTMs) underlying these functional deteriorations remains insufficiently characterized. Here, we report the first comprehensive multi-omics analysis integrating global proteomics, acetylomics, and succinylomics to dissect the molecular dynamics during platelet storage. METHODS: We performed quantification of global proteomics, acetylome and succinylome based on TMT-labeled LC-MS/MS analysis, combined with antibody-affinity enrichment and purification. Dynamic molecular changes and functional transformation of platelet were also characterized under proper conditions stored for 1, 3, 5, 7 days, respectively. RESULTS: We systematically characterized 3,609 proteins, 1,308 acetylation sites, and 1,947 succinylation sites across multiple storage time points (D1, D3, D5, D7). We distinct temporal patterns of post-translational modifications, with succinylation showing more extensive coverage than acetylation in platelets. Pathway enrichment analysis revealed extensive metabolic reprogramming involving complement activation, energy metabolism, and cellular detoxification processes. The identification of specific motif patterns provided mechanistic insights into the functional specificity of these modifications. Random forest machine learning identified 20 core regulatory proteins representing critical nodes in PSL development. Furthermore, we employed real - time quantitative polymerase chain reaction (RT - QPCR) to measure the expression levels of key genes related to platelet function and PTM - associated pathways. CONCLUSION: By mapping the interplay between proteomic abundance shifts and PTM dynamics, this study provides a multidimensional understanding of PSL, establishing a foundational framework for optimizing storage protocols and enhancing transfusion safety.

Blood Platelets

Evaluation of one-step amplicon-based targeted enrichment for SARS-CoV-2 whole-genome sequencing using the Midnight amplicon scheme.

Genomic surveillance proved invaluable during the COVID-19 pandemic for tracking SARS-CoV-2 variants and guiding outbreak responses, underscoring the ongoing need to reduce whole-genome sequencing (WGS) costs and improve workflow efficiency to ensure accessibility in resource limited settings. Here, we evaluated a one-step reverse transcription polymerase chain reaction (RT-PCR) approach using the Midnight V2 primer scheme for targeted amplification of the SARS-CoV-2 genome, assessed its compatibility with Illumina sequencing, and compared its performance to a well-established two-step method. Initially, we determined optimal RT-PCR reaction conditions using the Midnight V2 primer panel for the one-step RT-PCR kit and scaled reaction volumes for both RT-PCR and library preparation. Clinical specimens (n = 53) that had undergone routine WGS for surveillance purposes using the established two-step RT-PCR method were compared using the one-step RT-PCR assay. For samples with genome completeness greater than 70%, both methods gave comparable results with similar sequence coverage and 100% concordance for lineage assignment. Further investigation revealed a higher percentage of reads aligning to the SARS-CoV-2 genome with a greater depth of coverage using the one-step method compared to the two-step method. Finally, analysis of scaled one-step and library reaction volumes revealed significant cost savings for samples undergoing WGS. Overall, the results presented here verify the accuracy and reproducibility of one-step targeted amplification and offer an efficient and cost-effective workflow for routine SARS-CoV-2 genomic surveillance.

Humans

Littoral and wetland vegetation decrease carbon emissions from dry inland waters.

Lakes are recognized as active components of the inland water carbon (C) cycle, as organic matter is processed by microbial respiration, inducing large carbon dioxide (CO2) and methane (CH4) emissions. In the context of long-lasting drought periods, large uncertainties remain about: (1) the influence of wet-dry cycle on CO2 and CH4 fluxes in littoral zones and lacustrine wetlands; and (2) the contribution of emergent vegetation to C fluxes in dry inland waters. At the water-land interface of two shallow lakes, this study focuses on CO2 and CH4 fluxes from vegetated and bare dry inland waters in relation to hydrological fluctuations. Three seasonal campaigns were conducted to measure daytime CO2 and CH4 fluxes in pelagic, littoral and wetland surface waters, as well as in temporarily air-exposed sediments, using floating and static chambers, respectively. Our results reveal that wet-dry cycle in the littoral zone and wetlands strongly influence gaseous C fluxes through contrasting patterns, especially in late summer, when the biological processes are most active (primary production and respiration). In air-exposed littoral zones, organic-poor sandy sediments presented the lowest CO2 and CH4 emissions, whereas in air-exposed lacustrine wetlands, water-saturated sediments accumulated high amounts of plant-derived organic matter, promoting intense microbial activity and the highest C emissions. However, amphiphytes and helophytes vegetation in exposed littoral zones and wetlands reversed the direction of C fluxes, inducing the highest CO2 uptake due to high photosynthesis rates. This study underlines the relevance of considering vegetation in dry inland waters, particularly in lacustrine littoral zones and wetlands, to obtain comprehensive lake C budgets, especially under climate change scenarios.

Wetlands

Effects of acute resistance exercise on prefrontal oxygenation and task-switching performance: Considerations of loading strategies and blood flow restriction.

Although acute resistance exercise (RE) has been proposed to influence cognitive flexibility and underlying neural mechanisms, it remains unclear whether these effects vary across loading strategies and whether exercise-induced prefrontal hemodynamic responses translate into cognitive outcomes. The present study examined (1) prefrontal cortex (PFC) oxygenated hemoglobin (O2Hb) responses across exercise sets and conditions, (2) the effects of low-load (LL), LL with blood flow restriction (BFR), and high-load (HL) RE on task-switching performance, and (3) whether exercise-related PFC O2Hb responses were associated with pre- to post-exercise changes in task-switching performance. Thirty physically active adults completed three randomized, counterbalanced RE conditions consisting of four sets of barbell squats. LL was performed at 30% one-repetition maximum (1RM) with and without BFR, whereas HL was performed at 70% 1RM. Cognitive flexibility was assessed pre- and post-exercise using a modified Stroop task, indexed by switch-cost reaction time (RT) and accuracy. PFC O2Hb was assessed using functional near-infrared spectroscopy during exercise and expressed as changes from the resting baseline for each set (Sets 1-4). PFC O2Hb increased across sets, rising from Set 1 to Set 3 before plateauing, with no differences observed across conditions. Switch cost RT and accuracy did not improve from pre- to post-exercise, and no differences across conditions were detected. PFC O2Hb during the final set was not associated with changes in switch cost. These findings suggest that although acute RE elicits robust increases in prefrontal hemodynamic activity, such responses may not translate into acute improvements in cognitive flexibility.

Humans

Diversity and population connectivity of members of the family Eunicidae inhabiting deep-water corals in the North Atlantic.

Eunicid polychaetes are often found in association with Cold Water Corals (CWCs), even establishing symbiotic relationships, such as those described between Desmophyllum pertusum and Eunice norvegica. While genetic connectivity of CWCs across the North Atlantic has been widely studied, little is known about their associated fauna in this regard. Here, we present a study combining a focused analysis of the genetic and genomic connectivity of E. norvegica with a regional assessment of the distribution and evolutionary relationships of three CWC-associated eunicid species from the Cantabrian Sea and the North of the United Kingdom (190-1,230 m depth). An integrative approach using genetic (16S, COI and 18S), morphological and ecological data allowed the identification of the eunicids studied, with new records of Eunice cf. nicidioformis and Leodice cf. antarctica in the Cantabrian Sea, as well as previously undocumented associations with CWC species. In addition, RADseq data contributed to the delimitation of the closely related species E. norvegica and Eunice philocorallia. Moreover, the genetic connectivity of E. norvegica was studied trough a RADseq (1,067 neutral SNPs) approach. Our results indicate a single panmictic population across approximately 2,000 km, suggesting that oceanographic currents facilitate passive dispersal of E. norvegica lecithotrophic larvae, aided by coral host stepping-stones. The connectivity patterns observed for E. norvegica mirror those of D. pertusum, on which the worm is ecologically dependent. Our study highlights the importance of using integrated genetic, morphological and ecological data to characterise and delineate understudied CWC-associated species and improve our understanding of their dispersal capabilities and genetic connectivity to inform future conservation recommendations.

Animals

Effects of cinnamon supplementation combined with exercise training on anthropometric indices and reproductive hormones in overweight and obese women.

BACKGROUND: The prevalence of obesity and increased fat in the chest and abdomen in women and hormonal changes, can affect female fertility. The present study aims to investigate the effect of exercise training combined with cinnamon supplementation on chest and abdominal circumference, as well as sex hormones, in overweight and obese women. METHODS: Twenty-six inactive overweight and obese women were randomly allocated to an exercise (E; n = 13) and exercise plus cinnamon supplementation (E+S; n = 13) group. Both groups completed a 4-week exercise program three times weekly, while the E+S group additionally received cinnamon supplementation three times weekly. Chest and abdominal circumferences and serum concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were assessed before and after the intervention. RESULTS: Significant pre-to-post reductions in chest and abdominal circumference were observed in both groups (all p ≤ 0.005). Estradiol, progesterone, and FSH concentrations increased, whereas LH concentrations decreased significantly in both groups (all p ≤ 0.005). However, between-group comparisons revealed a significant difference only for chest circumference (p = 0.003), with no significant group differences in abdominal circumference or any reproductive hormone concentration (all p > 0.05). CONCLUSION: Both groups showed favorable changes in anthropometric and reproductive hormone measures following the 4-week study period. However, the significant between-group difference was limited to chest circumference, providing no clear evidence that cinnamon supplementation conferred additional benefits for abdominal circumference or reproductive hormone profiles beyond those observed with exercise. These findings highlight the potential relevance of exercise-based interventions while warranting confirmation in larger, adequately powered trials.

Humans

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged

Toward real-time quantification of driving risks: a systematic review and research agenda of risk field theory.

In complex traffic systems, driving risk often evolves in a continuous and progressive manner prior to crash occurrence. How to effectively represent and analyze such latent risk states remains a central challenge in traffic safety research. In recent years, risk field-based approaches have introduced spatial and spatiotemporal continuous modeling paradigms, providing new perspectives for characterizing the distribution of traffic risk and its dynamic evolution. Motivated by the rapid growth of this research area and the lack of a systematic synthesis, this paper presents a comprehensive review of studies applying risk field theory to driving safety and traffic risk analysis. Following the PRISMA guidelines, relevant literature was collected through multi-database searches and analyzed using a combination of bibliometric analysis and qualitative review. The review systematically summarizes the theoretical foundations, modeling elements, data sources, analytical methods, and application domains of risk field-related research. Particular attention is given to studies that conceptualize traffic risk as a continuous field, complemented by a broader review of traffic risk factor literature to identify key elements and analytical dimensions involved in risk field modeling. On this basis, the paper synthesizes research progress in major application areas, including traffic safety state representation, driving behavior analysis, traffic conflict assessment, and autonomous driving and human-machine cooperative systems. Differences and commonalities among existing studies are compared in terms of modeling strategies, data support, and application scenarios. Through this systematic review, the paper clarifies the main research themes and methodological trends of risk field-based studies, providing a structured framework for understanding the evolution and application of this approach and offering methodological insights for risk perception modeling and safety-oriented decision support in intelligent transportation systems (ITS).

Humans

Cerebrovascular involvement in Erdheim-Chester disease: a case report and systematic literature review.

BACKGROUND: Intracranial perivascular/vascular infiltrations and stenoses related to Erdheim-Chester disease (ECD), often associated with ischemic events, are rarely documented. This study aims to characterize intracranial perivascular/vascular infiltrations and stenoses. METHODS: We first report a new case of strokes revealing ECD with intracranial arterial involvement. We then searched all English- and French-language publications from database inception to November 2025 across 12 different search interfaces, including grey literature sources. Vascular involvement was defined by the presence of intracranial perivascular/vascular infiltrations and stenosis on imaging and/or histopathological evidence of small-vessel involvement. Cases with intracranial nodules or masses abutting vessels but without clear longitudinal perivascular infiltration were excluded. RESULTS: We present a case of recurrent strokes with intracranial vertebral and basilar artery wall stenosis, and aortitis. Initially diagnosed as giant cell arteritis, the patient was treated with corticosteroids, cyclophosphamide followed by methotrexate, but relapsed. The identification of tibial osteosclerosis led to the diagnosis of ECD, with a favorable response to anakinra. Twelve relevant articles were retrieved, in addition to our own case. Most patients exhibited focal cerebrovascular signs (11/13) and associated parenchymal involvement (11/13). Intracranial perivascular/vascular infiltrations and stenoses involved the carotid arteries (7/13), the vertebrobasilar arteries (1/13), or both territories (4/13). Aorta was involved in 8/12 cases. Among the nine patients with available follow-up data, five had poor overall or neurovascular outcomes. CONCLUSIONS: Intracranial perivascular/vascular infiltrations and stenoses, which leads to recurrent focal ischemic events, represents a likely underdiagnosed CNS pattern in ECD, referred to as "cerebrovascular ECD", which worsens overall prognosis. Vascular imaging should be included in brain MRI protocols for patients with ECD, given the overlap with parenchymal involvement.

Humans

Variability and ozone formation potential of ambient non-methane hydrocarbons in a tropical semi-arid atmosphere of northwest India.

We present first-time measurements of twenty-six ambient non-methane hydrocarbons (NMHCs; C2-C8), including isoprene (C5H8), at a semi-arid site in northwest India (Ajmer; 26.45&#xb0;N, 74.64&#xb0;E), during January 2022-December 2023. Ambient samples were analyzed using a thermal desorption gas chromatography system equipped with dual flame ionization detectors. Daily total NMHC levels ranged from 6 ppbV to >100 ppbV. Most NMHCs, except isoprene, toluene, ethylbenzene, m-xylene and o-xylene, exhibited the highest levels in winter and the lowest in the monsoon. In contrast, others were highest in the pre-monsoon and toluene was highest during monsoon. These variations reflect the combined influence of emissions, chemistry and meteorology. Toluene and o-xylene were the dominant NMHCs (25 %-67 %). Correlation analyses indicated major contributions from liquefied petroleum gas (LPG) and vehicular emissions, with additional influence from urban and oil and natural gas activities. Compared with other Indian sites, NMHCs levels at Ajmer were 2-5 times lower than Ahmedabad and Udaipur and 10 times lower than Delhi. The total ozone formation potential was highest in the monsoon (about 175 ppbV) and lowest in the post-monsoon (about 55 ppbV), with dominance of o-xylene (24 %-33 %) and toluene (8 %-37 %). Propylene-equivalent concentrations were highest in the pre-monsoon (30.23 ppb C) and lowest in the post-monsoon (7.28 ppb C). Similarly, OH reactivity was highest in the pre-monsoon (19.58 s&#x207b;&#xb9;) and lowest in the post-monsoon (4.71 s&#x207b;&#xb9;), dominated by benzene and toluene. These findings emphasize the importance of NMHC chemistry in a climatically sensitive region and highlight the need for their continuous monitoring.

India

Endovascular thrombectomy versus best medical therapy for acute vertebrobasilar artery occlusion in patients with low NIHSS scores: a&#xa0;meta-analysis.

OBJECTIVE: The efficacy of endovascular thrombectomy (EVT) for acute vertebrobasilar artery occlusion (VBAO) presenting with mild symptoms (National Institutes of Health Stroke Scale [NIHSS] score &#x2264;10) remains uncertain. This meta-analysis aimed to compare the effectiveness and safety of EVT versus best medical therapy (BMT) in this population. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 for comparative studies. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] score 0-1). Secondary outcomes included functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH), and all-cause mortality. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Seven observational studies involving 3,107 patients were included. In unadjusted analyses, EVT was associated with a higher rate of excellent functional outcome (OR 2.17; 95% CI 1.58-2.96) but not with functional independence (OR 1.58; 95% CI 0.90-2.77). After adjustment for confounders, EVT was associated with higher rate of excellent functional outcome (OR 2.86; 95% CI 1.89-4.31) and functional independence (OR 1.91; 95% CI 1.01-3.62). Safety outcomes including sICH and mortality did not differ significantly between groups. CONCLUSION: In patients with acute VBAO and mild symptoms, EVT may be associated with superior functional outcomes compared to BMT alone, without a significant increase in procedural risks. These findings suggest a potential role for EVT in selected patients with low NIHSS scores and underscore the need for confirmation in randomized trials.

Humans

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2&#xa0;with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p&#x2009;<&#x2009;0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43&#x2009;months, p&#x2009;<&#x2009;0.0001; 9.46 vs. 14.44&#x2009;months, p&#x2009;=&#x2009;0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 &#xd7; 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans