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Humans: explore 2000 source-linked works published from 2026 to 2026, with original documents and citations.

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Sex-stratified mortality trends in preterm birth complications in Sierra Leone: progress, persistence, and equity implications.

BACKGROUND: Preterm birth complications remain a leading cause of neonatal mortality in Sierra Leone, despite recent health system gains. Evidence on long-term sex-specific disparities in mortality due to preterm birth complications is limited, constraining equitable neonatal care planning. OBJECTIVE: To examine two‑decade trends in sex‑stratified mortality from preterm birth complications using standardized equity indicators. METHODS: We conducted a retrospective longitudinal analysis of sex-disaggregated mortality estimates from the World Health Organization (WHO) Global Health Estimates (GHE), accessed through the WHO Health Equity Assessment Toolkit (HEAT), Built-in Database Edition (Version 6.0). Mortality rates per 100,000 population were extracted for 2001, 2006, 2011, 2016, and 2021. Inequality was assessed using absolute difference (D), relative ratio (R), population attributable risk (PAR), and population attributable fraction (PAF). RESULTS: Mortality declined substantially between 2001 and 2021 for both males (85.1-49.3 per 100,000) and females (71.2-39.9 per 100,000). Male mortality remained consistently higher across all years, with relative ratios indicating approximately 20-25% excess mortality among male neonates. Absolute inequalities narrowed modestly over time, whereas relative inequalities remained largely unchanged. PAR and PAF remained close to zero throughout the study period. Wider uncertainty intervals in earlier years reflected limited empirical data availability. CONCLUSION: Although preterm mortality declined over two decades, a persistent male disadvantage remained in Sierra Leone. These findings highlight the importance of integrating sex-disaggregated equity monitoring into neonatal policies and programmes. Future research should evaluate strategies to reduce the persistent excess mortality among male neonates while sustaining overall improvements in neonatal survival and progress toward Sustainable Development Goal 3.2.

Humans

The effect of metformin on the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in adults with tuberculosis.

Metformin is under investigation as adjunctive host-directed therapy for tuberculosis (TB), which might interact with first-line TB treatment. We used population pharmacokinetic modeling to assess whether metformin alters first-line TB-drug pharmacokinetics in HIV/TB-coinfected adults without diabetes. Rifampicin, isoniazid, and pyrazinamide pharmacokinetics were investigated in participants from a randomized clinical trial of adjunctive metformin (500 mg twice daily to week 12) in adults starting HIV-associated TB treatment. Antiretroviral therapy (ART)-na&#xef;ve participants initiated dolutegravir-based ART within 8 weeks. Intensive and semi-intensive sampling was conducted at week 5; concentration-time data were analyzed using non-linear mixed-effects modeling. Data from 78 individuals (43 receiving metformin, median weight 60.8 kg, 62.8% male, 79.5% on ART) were analyzed. Rifampicin and pyrazinamide were described by one-compartment models with linear elimination; typical clearances were 15.8 L/h (95% CI: 13.5-18.7) and 3.88 L/h (95% CI: 3.54-4.08), respectively. Isoniazid followed a two-compartment model with a mixture model for acetylator status; clearance was 10.5 L/h (95% CI: 9.44-11.9) in slow acetylators and 28.8 L/h (95% CI: 25.6-31.0) in fast/intermediate acetylators. Metformin reduced isoniazid bioavailability by 15.6% (95% CI: 4.45-26.4%, P < 0.009) and rifampicin bioavailability by 24.0% (95% CI: 7.83-36.3%, P < 0.007), decreasing the area under the curve from 0 to 24 h from 18.2 to 15.6 mg&#xb7;h/L and from 35.9 to 27.1 mg&#xb7;h/L, respectively. No significant effect on pyrazinamide was detected. We found that non-diabetic patients on metformin had lower isoniazid and rifampicin bioavailability. Lowered rifampicin exposure might be clinically relevant; simulations suggest that this could be offset by a single 150 mg rifampicin dose.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04930744.

Humans

Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 &#xb1; 2.3 vs 0.5 &#xb1; 1.7 mm; P = .002), as were lesion area (mean, 70 &#xb1; 16 vs 58 &#xb1; 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p&#x2009;<&#x2009;0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62&#xa0;min, 95% CI 0.18-7.06; p&#x2009;<&#x2009;0.05) and reduced mean power output (mean difference&#x2009;-&#x2009;19.97 W, 95% CI&#x2009;-&#x2009;36.87 to&#x2009;-&#x2009;3.06; p&#x2009;<&#x2009;0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans

Health-Related quality of life (HRQoL) and health state utility values (HSUV) in patients with head and neck Cancer: A systematic review and Meta-Analysis.

BACKGROUND: Head and neck cancer (HNC) and its treatment can substantially impair speech, swallowing, eating, appearance, and social functioning, resulting in persistent reductions in health-related quality of life (HRQoL). Although the EuroQol 5-Dimensions questionnaire (EQ-5D) is widely used to assess generic HRQoL and derive health state utility values (HSUVs), EQ-5D-based evidence in HNC has not been comprehensively synthesized. This study aimed to summarize EQ-5D-based HRQoL and HSUVs in HNC, estimate pooled utility and EQ-VAS scores, explore subgroup differences, and identify predictors of poorer HRQoL. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261307907). PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus were searched from inception to February 10, 2026. Studies reporting baseline EQ-5D utility values and/or EQ-VAS scores in patients with HNC were included. Random-effects meta-analyses using the DerSimonian-Laird (DL) estimator with the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment were performed to pool mean scores. Between-study variance (&#x3c4;2) and 95&#xa0;% prediction intervals (PI) were calculated to capture parameter dispersion. Subgroup analyses were conducted across clinical and methodological vectors. RESULTS: Twenty studies involving 7,403 patients were included. The pooled mean EQ-5D utility score was 0.79 (95&#xa0;% CI: 0.75-0.83; &#x3c4;2&#xa0;=&#xa0;0.0011; 95&#xa0;% PI: 0.72-0.86). The pooled mean EQ-VAS score was 69.36 (95&#xa0;% CI: 65.71-73.01; &#x3c4;2&#xa0;=&#xa0;38.4586; 95&#xa0;% PI: 55.11-83.61). Extreme heterogeneity was observed (I2&#xa0;=&#xa0;96.4&#xa0;% and 97.1&#xa0;%, respectively). Utility values were significantly higher in studies utilizing the EQ-5D-5&#xa0;L than the EQ-5D-3&#xa0;L version (0.82 vs. 0.76). By tumor subsite, nasopharyngeal cancer showed the highest utility value (0.85, exploratory), whereas oral cancer demonstrated the lowest (0.73). Adjusted multivariable models revealed that advanced stage, high treatment intensity, severe pharyngolaryngeal pain, dysphagia, malnutrition, and older age were robust predictors of poorer HRQoL. CONCLUSIONS: Patients with HNC experience substantial and persistent HRQoL impairment, with meaningful variations driven by tumor subsites and instrument versions. In light of the extreme heterogeneity, these pooled findings establish a macro-level, broad reference estimate rather than a fixed target. These parameters directly inform localized survivorship care planning, health technology evaluations, and cost-utility decision-making modeling in head and neck oncology.

Humans

METTL14-mediated m6A modification of CCNE1 accelerates progression of myelodysplastic syndromes via MAPK-ERK and PI3K-AKT signaling pathways.

BACKGROUND: N6-methyladenosine (m6A) is the most common RNA modification and plays a key role in the initiation, progression, and relapse of multiple cancers, including hematologic malignancies. However, the role of m6A and m6A regulatory genes in myelodysplastic syndromes (MDS) remains unclear. This study aims to elucidate the function and molecular mechanism of methyltransferase METTL14 in MDS. METHODS: RT-qPCR was used to assess the expression of multiple m6A regulators, focusing on METTL14 in MDS patients and cell lines. METTL14 overexpressing and knockdown cell lines were established, and CCK-8, EdU, and flow cytometry assays were performed to explore the biological functions of METTL14.Dot blot, MeRIP-Seq, MeRIP-qPCR, RT-qPCR, and Western blot were employed to investigate the underlying molecular mechanism. RESULTS: Dysregulation of multiple m6A regulators was observed in MDS, among which METTL14 was upregulated. Elevated METTL14 expression increases MDS risk and adverse prognosis, emerging as a biomarker for poor prognosis. METTL14 promoted proliferation and cell-cycle progression of MDS cells while inhibiting apoptosis; corresponding changes were observed in cell cycle and apoptosis markers. METTL14 regulated cellular m6A levels. Downstream targets of METTL14 were enriched in cell cycle-related pathways, with CCNE1 identified as a critical target. Knockdown of METTL14, actinomycin D, or S-adenosylhomocysteine treatment reduced CCNE1 mRNA and protein levels. Furthermore, METTL14 activated MAPK-ERK and PI3K-AKT signaling via CCNE1 in an m6A-dependent manner, thereby promoting proliferative MDS cells' capacity. CONCLUSIONS: This study delineates a METTL14/m6A/CCNE1 signaling axis in MDS progression and suggests that METTL14-mediated m6A modification may be a potential therapeutic target for MDS.

Humans

Response-optimised training improves learning of a complex motor task and closely related motor tasks.

Regular physical exercise is essential for promoting healthy aging and longevity. In older adults with varying physical and cognitive decline, optimising exercise interventions is crucial to maximise benefits. A promising approach to achieve this goal is by adjusting task demands to individual abilities in turn preventing over- or underloading their abilities. In the field of motor learning, it is currently unclear whether such an optimised training improves not only performance on the trained task but also transfers to untrained motor and cognitive tasks. We conducted a randomized, single-blinded, 6-week dynamic balance training (DBT) with healthy older adults (n&#xa0;=&#xa0;30). Training was tailored to individual balance ability. Participants were assigned to either suboptimal (high or low difficulty) or optimal (moderate difficulty) training groups. Transfer effects were assessed via cognitive tasks (memory and executive) and motor tasks (untrained DBT variations and other balance tasks) measured pre-, mid- and post-intervention. Multivariate longitudinal statistical analysis showed higher performance gains in the optimal training group in three out of six sessions compared to the suboptimal groups, especially under testing conditions with high task demands. The optimal group also showed greater improvements in near motor transfer tasks mid- and post-intervention, while no significant differences were observed in the cognitive tasks. Within-group DBT learning positively correlated with transfer gains, highlighting the role of training response in achieving transfer. In conclusion, optimised task difficulty in balance training enhances both task-specific performance and related motor skills, supporting the use of personalised interventions to maintain function and independence in older adults.

Humans

Effect of levothyroxine therapy on albuminuria and glomerular function in patients with type 2 diabetes and subclinical Hypothyroidism: a randomized controlled pilot trial.

AIMS: To evaluate the effect of levothyroxine therapy on renal outcomes in patients with type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SCH) with background SGLT2 inhibitor therapy. METHODS: In this hypothesis generating open-label, randomized controlled pilot trial, adults with T2DM and SCH were assigned (1:1) to levothyroxine or no levothyroxine therapy and followed for 6&#xa0;months. Primary outcomes were changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). RESULTS: Sixty participants were randomized (30 per group); 24 and 27 completed follow-up in the treatment and control groups respectively. UACR decreased with levothyroxine (-13.09&#xa0;mg/g) and increased in controls (31.84&#xa0;mg/g). The difference was significant in per-protocol (PP)(-44.93&#xa0;mg/g; 95% CI -77.6 to -12.26; p&#xa0;=&#xa0;0.008) but insignificant in intention to treat (ITT)(-35.61&#xa0;mg/g; 95% CI -77.31 to 6.08; p&#xa0;=&#xa0;0.092). eGFR changes were statistically insignificant in both ITT(4.65&#xa0;mL/min/1.73&#xa0;m2; 95% CI -8.3 to 17.6; p&#xa0;=&#xa0;0.472) and PP(7.35&#xa0;mL/min/1.73&#xa0;m2; 95% CI -1.68 to 16.37; p&#xa0;=&#xa0;0.108). Thyroid-stimulating hormone decreased significantly in treatment arm in comparison to control arm (p&#xa0;<&#xa0;0.001) in ITT and PP. No adverse event was reported. CONCLUSIONS: Levothyroxine treatment showed trend toward improving albuminuria and eGFR without reaching statistical significance, suggesting possible renoprotective effect warranting further studies. CLINICAL TRIAL REGISTRATION: This trial is registered with Clinical Trial Registry of India (CTRI/2025/06/089606).

Humans

Clinical Efficacy and Learning Curve of Far-Lateral Approach (FLA) in Uni-Portal Non-Coaxial Spinal Endoscopic Surgery (UNSES) in the Treatment of Lumbar Degenerative Diseases: A Prospective Study.

BACKGROUND: Uniportal non-coaxial spinal endoscopic surgery (UNSES) via far-lateral approach (FLA) is an innovative minimally invasive procedure for lumbar degenerative diseases, particularly far-lateral disc herniation and foraminal stenosis. However, complex lateral lumbar anatomy and strict endoscope-instrument coordination create a distinct learning curve that may compromise early surgical efficiency and safety. This study aimed to evaluate the efficacy and safety, quantify the learning curve, and to provide clinical guidance for the standardized promotion and application of this technology. METHODS: A total of 40 consecutive patients with lumbar degenerative diseases who underwent UNSES via FLA by a single surgeon between January 2025 and December 2025 were included. All data were analyzed using SPSS 26.0 statistical software (IBM, USA). Primary outcomes included operation time, blood loss, fluoroscopy frequency, and intraoperative complication rate. Secondary outcomes were VAS, ODI, and modified Macnab criteria at 1, 3, and 6&#x2009;months postoperatively. The learning curve and the inflection point of the learning curve was determined using cumulative sum (CUSUM) analysis. The differences in clinical indicators between early and proficient stage were compared. RESULT: Operation time, blood loss, and fluoroscopy times decreased significantly with case accumulation (p&#x2009;<&#x2009;0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3&#x2009;&#xb1;&#x2009;8.6) min, much shorter than the early phase (89.5&#x2009;&#xb1;&#x2009;10.3) min (p&#x2009;<&#x2009;0.001). Before the 16th case, the curve was in an upward trend; after the 16th case, the curve tended to be flat, indicating the proficiency stage. Postoperative VAS and ODI improved significantly than those before surgery at each follow-up time (p&#x2009;<&#x2009;0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p&#x2009;>&#x2009;0.05). The total complication rate was 12.5% (5/40), were cured by conservative treatment. The total excellent-good rate was 90.0% (36/40). L5/S1 and Bertolotti's syndrome were independent factors affecting the learning curve. CONCLUSION: UNSES via FLA is a safe and effective minimally invasive technique for treating complex lumbar degenerative diseases. It has a certain learning curve, and the inflection point is about the 16th case. After mastering the key techniques such as anatomical positioning, endoscopic manipulation and hemostasis, the surgeon can gradually reach the proficiency stage, with significantly improved surgical efficiency and clinical efficacy, and controllable complications. This study provides a theoretical basis for the clinical training and technology promotion of UNSES via FLA.

Humans

Factors Associated With Accelerated Fracture Healing in Patients With Traumatic Brain Injury and Extremity Comminuted Fractures: A Retrospective Case-Control Study.

OBJECTIVE: Although traumatic brain injury (TBI) has been clinically associated with accelerated bone healing, the factors that determine which patients experience this phenomenon remain poorly defined, and previous findings are conflicting. This study aimed to investigate the clinical factors associated with accelerated fracture healing in patients with TBI combined with comminuted fractures of the limbs, so as to provide an evidence-based foundation for elucidating the clinical phenomenon of TBI-promoted fracture healing. METHODS: A retrospective case-control study design was employed. Patients between January 2020 and April 2024 with concurrent diagnoses of TBI and comminuted fractures were included. Based on radiographic findings and RUST/mRUST scores, patients were divided into an accelerated healing group (AHG) and a normal/delayed healing group (NDHG). Clinical data including demographics (age, sex, BMI), TBI characteristics (injury site, GCS score), admission laboratory indices (blood count, coagulation function, inflammatory markers), and fracture site/local soft tissue conditions, as well as functional outcomes assessed by the Short Musculoskeletal Function Assessment (SMFA) questionnaire at final follow-up were collected. Univariate analysis and multivariate logistic regression analysis were used to identify independent factors influencing accelerated fracture healing. Receiver operating characteristic (ROC) curves were plotted to evaluate their predictive value. RESULTS: A total of 119 patients were included, with 69 in the AHG and 50 in the NDHG. Significant differences were observed between the two groups in terms of age, BMI, GCS score, and platelet count (p&#x2009;<&#x2009;0.05). Univariate analysis showed that age, BMI, GCS score, red blood cell count, and platelet count were associated with accelerated fracture healing (p&#x2009;<&#x2009;0.20). Multivariate logistic regression analysis indicated that younger age (OR&#x2009;=&#x2009;0.875, 95% CI: 0.821-0.934) and lower GCS score (indicating more severe TBI; OR&#x2009;=&#x2009;0.490, 95% CI: 0.339-0.707) were independent predictors of accelerated fracture healing. ROC curve analysis showed that the area under the curve (AUC) for age and GCS score in predicting accelerated healing were 0.893 and 0.851, respectively. CONCLUSIONS: In patients with TBI combined with comminuted fractures, younger age and greater TBI severity (lower GCS score) are independent predictors of accelerated fracture healing. These findings assist clinicians in the early identification of patients with high healing potential to optimize treatment strategies, facilitate the early identification of high-risk patients, and provide clinical clues for further exploration of the molecular mechanisms underlying neurohumoral regulation of bone regeneration.

Humans

Pharmacokinetics and Safety of Nerandomilast in Healthy Volunteers.

BACKGROUND AND OBJECTIVES: Nerandomilast, a preferential phosphodiesterase 4B inhibitor, is approved for idiopathic pulmonary fibrosis and progressive pulmonary fibrosis in some countries. The objective of this study was to evaluate the safety and pharmacokinetics of nerandomilast in healthy volunteers through single- and multiple-rising-dose studies, and a human mass balance study evaluating absorption, distribution, metabolism, and excretion. METHODS: Healthy participants received oral nerandomilast doses ranging from 0.02&#xa0;mg to 24&#xa0;mg in the single-rising-dose trial, 1&#xa0;mg or 6&#xa0;mg twice daily for 14 days in the multiple-rising-dose trial, and a single oral dose of 18&#xa0;mg [14C]-labeled nerandomilast in the mass balance trial. In each trial, pharmacokinetic blood samples were collected for determination of nerandomilast plasma concentrations. In the mass balance study, urine, feces, and blood samples were collected, and [14C]-radioactivity was quantified from these matrices. All pharmacokinetic parameters were calculated via noncompartmental analysis. RESULTS: Nerandomilast was rapidly absorbed postadministration, with peak plasma concentrations occurring between 0.5 and 1.25&#xa0;h postdose before declining in a multiphasic manner. Nerandomilast exposure increased dose proportionally following single- and multiple-dose administrations. Steady state was reached by day 7 after twice-daily dosing with up to 1.69-fold drug accumulation. Following a single oral dose administration of [14C]nerandomilast, 58.0% and 36.4% of radioactivity was excreted in feces and urine, respectively. Of the administered dose, 11.9% was excreted as unchanged parent compound in urine. Nerandomilast safety was acceptable across all three studies and nerandomilast was well tolerated in healthy participants. CONCLUSIONS: Nerandomilast exhibited rapid oral absorption, multiphasic elimination profile, dose-proportional exposure, and was excreted via urine and feces. TRIAL REGISTRATION: NCT01594515 (registered 2012-05-07), NCT01835899 (registered 2013-04-11), and NCT04771286 (registered 2021-02-23).

Humans

Online Social Anxiety in the Digital Age: Transitions, Predictors, and Mental Health Associations in Emerging Adulthood.

BACKGROUND: Online social anxiety (OSA), a multidimensional form of social evaluative anxiety in online social contexts, disproportionately affects emerging adults who constitute the largest active group of media users and face heightened psychological sensitivity due to growing pressures and immature sociocognitive regulation during the transition to adulthood. However, its heterogeneity, transitions, and longitudinal associations with mental health outcomes remain underexplored. METHODS: This study utilized data from two waves of a three-wave longitudinal survey, with 849 Chinese participants (Meanage = 21.6 years; 50.4 percent female) assessed at 4-month intervals. Individuals were classified using latent profile analysis and the stability and changes of profiles were assessed via latent transition analysis (LTA). Multinomial logistic regressions were conducted separately at baseline and follow-up to identify correlates of profile membership. Predictors of profile transitions were examined using manual three-step LTA models, and associations between latent transition patterns and follow-up mental health outcomes were examined using BCH-LTA distal outcome analyses controlling for the corresponding baseline symptom level. RESULTS: Four profiles of OSA were identified: low, privacy-sensitive, moderate-high, and high OSA. Extreme profiles (low/high OSA) showed high stability (80.4 percent and 79.1 percent), while privacy-sensitive OSA exhibited the lowest stability (55.1 percent). Profile memberships were influenced by social-cognitive biases and digital interaction, particularly fear of negative evaluation and online interpersonal trust, whereas profile transitions were mainly associated with anxiety. Transitions toward less severe OSA profiles were generally associated with better subsequent mental health, whereas transitions toward more severe profiles corresponded to poorer outcomes, particularly for offline social anxiety. CONCLUSION: OSA was heterogeneous in its manifestation, severity and transitions. Personalized and early interventions targeting profile-specific vulnerabilities are critical to prevent the worsening of OSA and mitigate its psychological burden.

Humans

Integrated morphologic, immunophenotypic, and molecular profiling of advanced upper tract urothelial carcinoma across tumor compartments supports biopsy-based testing.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with limited molecular characterization in advanced disease. FGFR3 alterations are well established in low-grade urothelial carcinoma, but their prevalence, stability, and biological significance in locally advanced and metastatic UTUC remain only partially defined. We performed an integrated morphologic, immunohistochemical, and molecular analysis of 24 locally advanced and/or metastatic UTUC from 20 patients. FGFR3 status was assessed by RT-PCR across multiple tumor compartments, including biopsies, primary tumors, lymph-node metastases, and distant metastatic sites. Immunohistochemistry included CK20, CK5, GATA3, p53, and mismatch repair proteins. Targeted next-generation sequencing (NGS) was used to characterize co-occurring genomic alterations and to assess concordance with p53 immunophenotype. FGFR3 alterations were identified in 50% of patients and in 54.2% of analyzed tumors. FGFR3 status showed high intra-patient stability, with concordance between primary tumors and distant metastases in 90% of cases, whereas concordance with lymph node metastases was lower (50%), suggesting site-specific clonal divergence. Despite advanced stage, 92.3% of FGFR3-altered tumors displayed papillary urothelial carcinoma morphology, and most showed a luminal immunophenotype (61.5% by CK20/CK5 and 69.2% by GATA3/CK5). Targeted NGS revealed additional pathogenic alterations in 75% of patients, most frequently involving RTK/RAS/MAPK signaling (70%), cell-cycle regulation (25%), and PI3K/AKT pathway components (10%). TP53 mutations co-occurred with FGFR3 alterations in 60% of FGFR3-mutated patients and showed 90.4% concordance with p53 immunohistochemistry. Finally, a few cases exhibited complex, multi-site FGFR3 mutational patterns, consistent with intratumoral clonal evolutions. In conclusion, FGFR3 alterations are frequent and remarkably stable in advanced UTUC, even in high-grade and metastatic disease. These findings support the reliability of FGFR3 testing on limited diagnostic material and reinforce its relevance for therapeutic stratification. UTUC emerges as a molecularly dynamic disease in which early oncogenic drivers such as FGFR3 continue to shape tumor biology and therapeutic vulnerability at advanced stages.

Humans

Diagnostic accuracy of nuclear STAT6 immunohistochemistry for solitary fibrous tumour: a systematic review and meta-analysis.

Nuclear STAT6 immunohistochemistry is the diagnostic surrogate for the NAB2::STAT6 fusion of solitary fibrous tumour (SFT); its sensitivity is established, but specificity varies for unexamined reasons. This review quantified pooled accuracy and tested whether antibody clone and nuclear threshold govern specificity. PubMed, Scopus and Web of Science were searched to 29 June 2026 for studies reporting nuclear STAT6 immunohistochemistry against a reference standard (NAB2::STAT6 confirmation and/or expert consensus) in SFT and comparators, with extractable two-by-two data. Two reviewers screened, extracted data and applied QUADAS-2. A bivariate generalised linear mixed model gave summary sensitivity and specificity, and exploratory subgroup analysis and meta-regression tested antibody clone, anatomical site and reference-standard type. Twenty-three studies (1216 SFT and 4715 comparators) were included. Summary sensitivity was 98.7% (95% confidence interval 96.7-99.5) and specificity 99.1% (97.8-99.6); the diagnostic odds ratio was approximately 8656. The monoclonal YE361 subgroup (8 studies) reached specificity 99.9% (99.3-100), with one false positive among 861 comparators, versus 98.1% (96.0-99.1) for polyclonal and other antibodies. False positives concentrated in dedifferentiated liposarcoma and prostatic stromal tumours. Estimates were stable after removing studies at higher risk of bias (98.9%/99.1%) and on leave-one-out analysis; the Deeks test was non-significant (p&#xa0;=&#xa0;0.08). Nuclear STAT6 immunohistochemistry is therefore highly sensitive and specific for SFT, and the residual specificity loss is structured and largely avoidable: the monoclonal YE361 read at a strict nuclear threshold is preferred, with MDM2 and CDK4 applied to exclude dedifferentiated liposarcoma when nuclear STAT6 is unexpectedly positive.

Humans

Glucocorticoids and placental 11&#x3b2;HSD2 - A systematic review of human studies and animal models.

CONTEXT: Elevated prenatal glucocorticoid (GC) exposure is linked to adverse offspring outcomes. The placental enzyme 11&#x3b2;-hydroxysteroid-dehydrogenase-type-2 (11&#x3b2;HSD2) protects the fetus by converting maternal derived cortisol to inactive cortisone. Although in vitro studies suggest GC mediated upregulation of 11&#x3b2;HSD2, in vivo evidence remains inconclusive. METHODS: PubMed, Embase, and PsycInfo were searched in October 2024 for human and mammalian animal studies on endogenous or exogenous GCs during pregnancy and associations with placental 11&#x3b2;HSD2 (mRNA, protein, activity, gene methylation). Narrative synthesis was conducted due to heterogeneity precluding meta-analysis. RESULTS: Eighteen studies (eight human, ten animal populations) met inclusion criteria. Exogenous GC exposure was associated with modifications in placental 11&#x3b2;HSD2 expression in animal models, with effects varying by substance, timing, and species. Dexamethasone trended towards increased expression in rodents, whereas betamethasone increased expression in non-human primates but not rodents. Human studies on endogenous GCs showed inconsistent associations with 11&#x3b2;HSD2 changes. In asthmatic pregnancies, moderate inhaled GC-use maintained enzyme activity compared to untreated patients. No convincing sex-specific trend emerged. CONCLUSIONS: GC exposure alters placental 11&#x3b2;HSD2 in a substance- and species-specific way; translational relevance remains limited based on current literature. Future studies should employ technological advances and include GC-sensitive biomarkers to clarify mechanisms of maternal-fetal stress transmission.

Female

Lower-limb electromyographic responses across four recumbent cycling configurations in healthy young men.

Recumbent cycling provides an adjustable configuration in which backrest angle and crank-axis height can alter lower-limb loading. Backrest angle changes the orientation of the active musculature relative to gravity, whereas crank-axis height modifies the foot-pedal interface and the ankle lever arm. Whether such positioning is associated with differences in lower-limb electromyographic (EMG) activation across both factors together has not been examined. Using a randomized crossover design, fifty-nine healthy young men cycled at 100&#xa0;W and 50&#xa0;rpm under four conditions combining two backrest angles (30&#xb0;, 75&#xb0;) and two crank-axis heights (Rh, high, 77&#xa0;cm; Rl, low, 45&#xa0;cm). Surface EMG from the rectus femoris (RF), biceps femoris (BF), and gastrocnemius medialis (GAS) was analyzed for root mean square (RMS) amplitude, absolute onset sequence, and relative recruitment timing (%Sequence, derived using Telescan software and referenced to RF). RMS amplitude did not differ across conditions for any muscle (all p&#xa0;&#x2265;&#xa0;0.356), and absolute onset sequence showed no condition effect (all p&#xa0;&#x2265;&#xa0;0.197). For GAS %Sequence, the Greenhouse-Geisser-corrected omnibus test was significant (F(1.32, 76.56)&#xa0;=&#xa0;28.45, p&#xa0;<&#xa0;0.001), driven by a within-30&#xb0; contrast in which %Sequence was lower under Rl than Rh (paired t(58)&#xa0;=&#xa0;10.39, Holm-adjusted p&#xa0;<&#xa0;0.0001; mean difference 22.0 percentage points, 95&#xa0;% CI [17.8, 26.3]; dz&#xa0;=&#xa0;1.35). Because %Sequence is referenced to RF, this exploratory shift should be interpreted cautiously. Lower-limb activation may be constrained by the closed-chain nature of pedaling, whereas distal recruitment timing may be sensitive to crank-axis height and the foot-pedal interface.

Humans

An expanded breakfast buffet increases daily energy and protein intakes in hospitalised patients: A prospective crossover quality improvement study.

BACKGROUND & AIMS: Inadequate dietary intake remains common during hospitalisation. Ordinary hospital meals are central to nutritional intake, but their contribution depends on what is offered and what patients are able and willing to eat. We evaluated whether a preference-informed, limited expansion of the hospital breakfast buffet could increase total daily energy and protein intakes. METHODS: This prospectively structured, ward-based crossover quality-improvement study was conducted in seven inpatient wards at a tertiary university hospital. Each ward was observed for four consecutive days and randomly allocated to begin with standard or expanded breakfast, after which conditions alternated daily. The expanded buffet consisted of standard breakfast supplemented with familiar energy- and protein-rich foods selected from previous patient-choice data. Twenty-four-hour intake was registered using component-level weighed food records during the day and nursing registration overnight. Primary outcomes were total daily energy and protein intakes. Linear mixed-effects models adjusted for observation day and ward-level starting sequence and accounted for repeated patient observations and ward-level clustering. Analyses used data from patients who consumed breakfast and contributed analysable observations under both breakfast conditions. RESULTS: The primary crossover population included 71 patients contributing 188 analysable patient-days. Compared with standard breakfast, the expanded breakfast increased total daily energy intake by +198 kcal/day (95% CI 44 to 352) and protein intake by +6.8 g/day (95% CI 1.0 to 12.5), without a statistically significant increase in total food weight. Daily energy and protein adequacy increased by +8.7 and + 6.8 percentage points, respectively. The increase was driven mainly by breakfast intake, with no measurable reduction in non-breakfast intake. CONCLUSIONS: A limited expansion of the ordinary hospital breakfast buffet increased total daily energy and protein intakes in the primary crossover population of hospitalised adults who consumed breakfast. This increase occurred without a statistically significant increase in total food weight or a measurable reduction in non-breakfast intake. Small, preference-informed additions of familiar energy- and protein-rich foods at breakfast may improve daily intake by increasing the nutrient yield of foods patients are able or willing to eat.

Humans

Comparison of the Effects of Spinal Versus General Anesthesia on the Perioperative Intraocular Pressure: A prospective, randomized clinical trial.

OBJECTIVES: To evaluate the effects of spinal and general anesthesia on the intraocular pressure (IOP) in patients, who had lumbar spine and lower extremity orthopedic surgeries. METHODS: Sixty adult were randomly classified into Group spinal anesthesia (SA) and Group general anesthesia (GA). The IOP, mean systemic arterial pressure, and heart rhythm were measured at 6 pre-determined timepoints (T0: Baseline, T1: Before spinal procedure or anesthesia induction, T2: After injection with intrathecal or anesthesia induction, T3: 5th minutes (min) after spinal procedure or tracheal intubation, T4: 30th min intraoperative, T5: At the end of surgery, T6: 5th min after surgery or tracheal extubation in the operation room. RESULTS: The baseline IOP and IOP1 measurements during were not significantly different between the groups (SA = 14.28 &#xb1; 0.8 mmHg; GA = 14.62 &#xb1; 0.9 mmHg, p = 0.923; and IOP1: SA = 15.83 &#xb1; 0.9 mmHg; GA = 15.88 &#xb1; 0.9 mmHg, p = 0.929). The most significant decrease in IOP in both groups was recorded at T2 (SA: 12.37 &#xb1; 0.6. GA: 12.24 &#xb1; 0.4, p < 0.001). The decrease in IOP2 was more significant in the GA group. The IOP3 was significantly higher in GA group after intubation (GA: 19.82 &#xb1; 1.2, SA: 12.86 &#xb1; 1.0)(p < 0.05). The IOP4 and IOP5 in the SA group were lower than those in the GA group. The IOP6 in both groups was higher (SA: 15.20 &#xb1; 0.8, GA: 16.50 &#xb1; 1.0) than the baseline IOP values, albeit not significant (p > 0.05). In prone position, IOP at the T4 and T5 timepoints were significantly higher than the initial values in both the SA and the GA groups; however, the increase in the GA group was more higher than that of the SA group. CONCLUSION: In intraoperative period, intraocular pressure may increase in both management of anesthesia, but this increase is higher in the general anesthesia group.

Humans
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Lower-limb electromyographic responses across four recumbent cycling configurations in healthy young men.2026-08-06PMID 42580165pubmed
An expanded breakfast buffet increases daily energy and protein intakes in hospitalised patients: A prospective crossover quality improvement study.2026-08-06PMID 42594842pubmed
Comparison of the Effects of Spinal Versus General Anesthesia on the Perioperative Intraocular Pressure: A prospective, randomized clinical trial.2026-08-06PMID 42598110pubmed

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