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The Impact of Upper Extremity Rehabilitation on Fatigue in Individuals With Multiple Sclerosis: A Systematic Review.

BACKGROUND: Although numerous interventions have been investigated to alleviate fatigue in people with multiple sclerosis (PwMS), evidence regarding the effects of upper extremity rehabilitation on fatigue remains limited. OBJECTIVE: The objective of this review was to evaluate and synthesize the available evidence on the effects of upper extremity rehabilitation interventions on fatigue in PwMS. METHODS: This review was conducted in accordance with the PRISMA guidelines and was prospectively registered in the PROSPERO database. A systematic search of PubMed, Web of Science, and Scopus was performed up to August 2026. Studies were eligible if they investigated the effects of upper extremity rehabilitation interventions on fatigue in PwMS. The risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 (RoB 2), and the certainty of the evidence was appraised using the GRADE methodology. RESULTS: Nine studies including 250 participants (136 intervention, 114 control) met the inclusion criteria. The included studies evaluated a range of technology-assisted, exercise-based, home-based, and task-oriented upper extremity rehabilitation approaches, with some interventions incorporating more than one therapeutic or technological component. Fatigue outcomes were measured using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Risk of bias was low in three randomized controlled trials, with some concerns in two and high in two; among the two crossover studies, one was rated as low risk and one as high risk. GRADE assessment showed low certainty of evidence for studies using the FSS and very low certainty for those using the MFIS, indicating an overall low certainty of the available evidence. CONCLUSIONS: The available evidence is insufficient to draw definitive conclusions regarding the effects of upper extremity rehabilitation on fatigue in PwMS. Further high-quality randomized controlled trials are required.

Humans

Sodium supplementation strategies in preterm infants: effects on growth, electrolyte balance, and exploratory evidence on neurodevelopment - a systematic review and meta-analysis.

This study evaluated the effects of sodium supplementation on growth, electrolyte balance, and neurodevelopmental outcomes in preterm infants. A systematic review and meta-analysis of published studies were conducted using data from PubMed, Embase, Scopus, and Google Scholar, including randomized controlled trials and observational studies involving infants born before 37 weeks of gestation. Twelve studies comprising more than 2,800 participants were analysed using random-effects models. Sodium supplementation was associated with improved weight gain and a significant reduction in the risk of hyponatremia (RR = 0.28, 95% CI: 0.08-0.96). Pooled incidence estimates indicated hypernatremia (32%) and intraventricular hemorrhage (29%) among supplemented cohorts; however, substantial heterogeneity was observed, and comparative risk estimates were limited. Only one study reported long-term neurodevelopmental follow-up, suggesting potential benefit; however, the available evidence remains limited and hypothesis-generating.These findings suggest that sodium supplementation may support growth and is associated with a lower risk of hyponatremia in preterm infants; however, hypernatremia and other morbidity estimates reported here are largely descriptive frequencies within supplemented cohorts rather than comparative treatment effects, and careful, individualized therapy with close monitoring is needed to minimize potential risks.

Growth outcomes

Effect of Smoking in Oropharyngeal Cancer Treated With TORS: Systematic Review and Meta-Analysis.

OBJECTIVE: While smoking has been implicated as a risk factor for recurrence in HPV-associated oropharyngeal squamous cell cancer (OPSCC) treated with definitive chemoradiation, its prognostic impact on surgically treated OPSCC is less clear. DATA SOURCES: MEDLINE, Embase, CENTRAL, and Scopus. REVIEW METHODS: Articles describing patients with HPV-associated OPSCC treated with transoral robotic surgery (TORS), which reported oncologic outcomes by smoking history, were included. RESULTS: 2079 patients were included across 12 studies. Median age was 58.5 years, and 1808 (87.0%) were male. HPV-associated disease was reported in 1681 (80.9%) patients. T stage was most commonly T2 in 831 (40.0%) and T1 in 764 (36.7%). N stage was N2 in 854 (41.1%), N1 in 544 (26.2%), and N0 in 307 (14.8%). 931 (44.8%) were considered individuals with a smoking history, while 1045 (50.3%) were considered without a smoking history. Median follow up was 33.7 months. Meta-analysis using a fixed effects model demonstrated an overall hazard ratio of 1.4 (95% confidence interval 1.0-2.0) for disease recurrence, 2.7 (95% confidence interval 1.5-4.8) for overall survival, and 1.4 (95% confidence interval 0.4-4.6) for disease specific survival. CONCLUSIONS: In this population of predominantly HPV-associated OPSCC treated with TORS, meta-analysis demonstrated no significant difference in recurrence-free survival or disease-specific survival between individuals with and without a smoking history. Individuals with a smoking history appeared to have worse overall survival, although only five studies reported on this outcome. Further research is required to clarify the prognostic influence of smoking on OPSCC treated with TORS.

Humans

Association Between 24-Hour Blood Pressure and Rates of Retinal Nerve Fiber Layer Progression in Glaucoma: The Vascular Imaging in Glaucoma Study.

PURPOSE: Low systemic blood pressure (BP) has been implicated as a risk factor for glaucoma progression. The purpose of this study was to investigate the association between 24-hour BP and rates of retinal nerve fiber layer (RNFL) loss in eyes with primary open-angle glaucoma. DESIGN: Prospective cohort study. PARTICIPANTS: Seventy-nine eyes from 42 subjects with glaucoma (mean age, 68.5 &#xb1; 7.6 years) enrolled in the Vascular Imaging in Glaucoma Study at the Bascom Palmer Eye Institute. METHODS: Participants underwent 24-hour ambulatory BP monitoring at baseline. Follow-up evaluations were conducted at 4-month intervals and included ophthalmic examination, BP measurement, and peripapillary RNFL thickness measurement with spectral-domain optical coherence tomography. The association between BP and RNFL loss over time was assessed using linear mixed-effects models adjusted for age, sex, race, baseline RNFL thickness, central corneal thickness, and intraocular pressure. MAIN OUTCOME MEASURES: The effect of baseline 24-hour mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) on the rate of average RNFL loss over time. RESULTS: Eyes underwent an average of 13 &#xb1; 3 optical coherence tomography exams over 43 &#xb1; 10 months of follow-up. The mean rate of RNFL loss was -0.34 &#xb1; 0.64 &#xb5;m/y (median: -0.32; interquartile range: -0.66 to -0.04 &#xb5;m/y). After adjusting for confounding factors, every 10 mm Hg lower in 24-hour minimum MAP, SBP, and DBP was associated with -0.542 &#xb5;m/y (P < .001), -0.360 &#xb5;m/y (P = .003), and -0.458 &#xb5;m/y (P = .008) faster RNFL loss, respectively. Eyes in the lowest quartile of average 24-hour MAP (81-90 mm Hg) and minimum 24-hour DBP (35-47 mm Hg) experienced significantly faster progression compared to those in the highest quartile, with differences of -0.68 &#xb5;m/y (P = .017) and -0.63 &#xb5;m/y (P = .030), respectively. CONCLUSIONS: Lower systemic BP, especially minimum MAP, SBP, and DBP measured by 24-hour ambulatory BP monitoring, is associated with faster rates of RNFL loss in primary open-angle glaucoma eyes. 24-hour BP monitoring may help predict glaucoma patients at greater risk of progression.

Humans

Ketoacidosis with SGLT2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case-control study.

BACKGROUND: SGLT2 inhibitors increase the risk of ketoacidosis, but data from routine clinical practice are scarce. We used nationwide registers with the aim of assessing the incidence, risk factors, and prognosis of ketoacidosis during SGLT2 inhibitor treatment in patients with type 2 diabetes. METHODS: In this cohort and nested case-control study we used data from three Scandinavian countries. In a cohort of SGLT2 inhibitor-treatment episodes among patients with type 2 diabetes aged at least 18 years in Sweden, Denmark, and Norway, we estimated ketoacidosis incidence. Using a nested case-control design (matched on age, sex, region of birth, calendar time, and time since treatment initiation), we assessed risk factors and precipitating or co-occurring events. Changes in diabetes medications were evaluated. FINDINGS: The study period was Jan 1, 2013, to Dec 31, 2021, in Denmark and Sweden, and Jan 1, 2013, to Dec 31, 2022, in Norway. We included 322&#x2008;597 treatment episodes among 282&#x2008;282 patients with type 2 diabetes (mean age 63 years, 116&#x2008;521 [36&#xb7;1%] of 322&#x2008;597 women). During a median (IQR) follow-up of 1&#xb7;3 (0&#xb7;7-2&#xb7;8) years, 1452 ketoacidosis events occurred (incidence 2&#xb7;43 per 1000 person-years). Although highest shortly after initiation, risk persisted throughout follow-up. Strong risk factors included high HbA1c (&#x2265;83 vs &#x2264;52 mmol/mol: odds ratio [OR] 15&#xb7;37 [95% CI 11&#xb7;50-20&#xb7;53]), malnutrition (OR 10&#xb7;54 [7&#xb7;32-15&#xb7;18]), previous ketoacidosis (OR 10&#xb7;40 [7&#xb7;09-15&#xb7;24]), low BMI (<20 kg/m2vs 20 to <25 kg/m2: OR 9&#xb7;98 [5&#xb7;68-17&#xb7;53]), and recent hypoglycaemia (OR 5&#xb7;22 [2&#xb7;60-10&#xb7;49]). Infection was the most common precipitating or co-occurring event (454 [31&#xb7;8%] of 1428 vs 862 [6&#xb7;1%] of 14&#x2008;233 for ketoacidosis cases vs controls; OR 7&#xb7;60 [6&#xb7;62-8&#xb7;71]). The strongest associations were observed for alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery, although associations for some transient exposures, particularly milder conditions, might have been overestimated because of under-registration among controls. Exploratory analyses suggested that the observed associations were largely general to patients with type 2 diabetes rather than specific to SGLT2 inhibitor use. At 1 year after ketoacidosis, 211 (25&#xb7;1%) of 842 remained on SGLT2 inhibitors and insulin use increased from 269 (31&#xb7;9%) of 842 to 615 (73&#xb7;0%) of 842. INTERPRETATION: Ketoacidosis risk with SGLT2 inhibitors varies greatly by patient characteristics and is not confined to early in treatment. Risk should be assessed throughout treatment, and patients should be instructed to pause treatment during acute illness and stress. FUNDING: Region Stockholm, Swedish Society of Medicine, Karolinska Institutet.

Journal Article

Distress Intolerance, Social Anxiety, and Depressive Symptoms in Adolescents: Evidence from Random-Intercept Cross-Lagged Panel and Cross-Lagged Panel Network Analyses.

Social anxiety and depressive symptoms frequently co-occur during adolescence, yet the mechanisms underlying their longitudinal associations remain insufficiently understood. Distress intolerance has been proposed as a transdiagnostic risk factor implicated across internalizing symptoms. However, it remains unclear whether distress intolerance is predicted by social anxiety and depressive symptoms, as well as the underlying mechanisms among these three constructs. The specific symptoms most centrally involved in these cross-domain associations remain poorly understood. The present study investigated the longitudinal associations among distress intolerance, social anxiety, and depressive symptoms using a dual-method framework combining random-intercept cross-lagged panel models (RI-CLPM) and cross-lagged panel network (CLPN) analyses. A total of 1,378 Chinese adolescents (Mage = 12.57, SDage = 0.63; 50.4% female) were assessed at three time points with six-month intervals between waves. The RI-CLPM analyses revealed that higher distress intolerance prospectively predicted subsequent increases in both social anxiety and depressive symptoms, whereas elevated social anxiety and depressive symptoms in turn predicted subsequent increases in distress intolerance. Moreover, distress intolerance mediated the longitudinal associations between social anxiety and depressive symptoms. Additionally, distress intolerance was also indirectly associated with its own subsequent levels through social anxiety and depressive symptoms. The CLPN analyses revealed that fear of negative evaluation and fatigue were the strongest predictors of other network nodes from T1 to T2 and from T2 to T3, respectively. In contrast, distress intolerance symptoms were predominantly predicted by other nodes in both cross-lagged networks. These findings extend prior views of distress intolerance as a unidirectional vulnerability by showing that distress intolerance is also predicted by social anxiety and depressive symptoms and accounts for part of their longitudinal associations across adolescence.

Humans

A narrative review of what cohorts have taught us and how they have laid the foundation for much of our understanding of type 2 diabetes.

This narrative review provides a historical perspective on how observational research on type 2 diabetes has been developed and consolidated over the last 50 years and how well-designed cohort studies will provide us with knowledge for research and practice in the future and aid guideline development. We have included data from a large number of cohorts from every continent that have been used to study the development and/or progression of type 2 diabetes, including cohorts that are general population-based, disease-based, intervention-based and registry-based. We have structured the results from the past 50 years based on the following themes: diagnosis and screening, complications, risk factors and pathophysiology. We also discuss the strengths and weaknesses of observational research when compared with other research designs. Finally, we discuss the emerging and future directions for type 2 diabetes research using cohorts, which include novel developments, such as artificial intelligence, precision health and the exposome. We conclude that cohort research has significantly advanced our understanding of type 2 diabetes and aided guideline development, and complements experimental work, such as human randomised controlled trials and animal studies. Both approaches are essential and complementary in our pursuit to provide a more comprehensive understanding of the development and progression of type 2 diabetes, and to change dogma, practice and policies for better outcomes.

Humans

Changes in sexual behavior among women in studies evaluating the dapivirine vaginal ring for HIV prevention.

BACKGROUND: Access to novel HIV prevention technologies often raise concerns of risk compensation. This analysis examined changes in the sexual behaviors of MTN 020/ASPIRE participants, a placebo controlled randomized control trial, who subsequently enrolled in MTN-025/HOPE, an open-label extension using the dapivirine vaginal ring. METHODS: Both studies enrolled healthy, sexually active, HIV-negative women from Malawi, South Africa, Uganda and Zimbabwe. Longitudinal data on participants' sexual behaviors, specifically sex with a nonprimary partner (past 3&#xa0;months), and use of male or female condoms at the last vaginal sex act were compared between ASPIRE and HOPE. Conditional and mixed ordinal logistic regression models evaluated associations between study and sexual behaviors at enrollment,&#xa0;and quarterly over the first 12&#xa0;months. RESULTS: Of the 2629 individuals enrolled in ASPIRE, 1456 (55%) participated in HOPE. At enrollment, the proportion of participants who reported sex with a nonprimary partner and condom use at last vaginal sex act did not differ by study. Across all quarterly follow-up visits, sex with a nonprimary partner was more common in HOPE (13.9-18.7%) than ASPIRE (10.7-12.6%); adjusted OR&#xa0;1.47, 95% CI 1.24-1.75, P&#xa0;<&#xa0;0.001. There was no difference in condom use at the last vaginal act across all quarterly follow-up visits between ASPIRE (36.5-42.7%) and HOPE (43.6-46.7%); adjusted OR&#xa0;1.05, 95% CI 0.94-1.18. CONCLUSION: More women reported sex with nonprimary partners in HOPE, with little change in condom use over time between the two studies. Understanding behavior changes during PrEP use allows for tailored, holistic reproductive health programming.

Humans

Incidence of silent cerebral lesions during pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is a first-line treatment for paroxysmal atrial fibrillation (PAF). Complications such as silent cerebral lesion (SCL) may occur during ablation. Pulsed field ablation (PFA) is a non-thermal method thatablates cardiac tissue via irreversible electroporation. Limited studies have reported the incidence of SCL during PFA, with highly variable results. However, randomized controlled trials (RCTs) remain scarce. The objective of this study was to compare perioperative SCL incidence between PFA and RFCA, and to identify risk factors for SCL during PFA. METHODS: In this prospective pilot RCT (ChiCTR2400088774), 62 patients with PAF were randomized 1:1 to undergo PFA or RFCA. Cerebral MRI (3.0 T) was performed preoperatively and 24-48h postoperatively. SCL was defined as a new acute brain lesion on MRI without neurological deficits. Baseline and surgical data of the patients were collected. RESULTS: SCL was detected post-procedure in 6.45% (2/31) in the RFCA group, 12.90% (4/31) in the PFA group. No statistically significant difference in the incidence of postoperative SCL was detected between the two groups (p&#x2009;=&#x2009;0.67). Left atrium dimension (LAD), left atrial operation time (LAOT), left ventricular end-diastolic dimension (LVEDD), and total operation time (TOT) were significantly higher in SCL group than those in no-SCL group (p&#x2009;<&#x2009;0.05) through univariate analyses. CONCLUSIONS: SCL incidence was 12.90% in the PFA group versus 6.45% in the RFCA group. While no statistically significant difference was detected between two groups, the numerically higher rate in the PFA group warrants larger studies to evaluate cerebral safety associated with PFA.

Humans

Uric Acid-to-HDL Cholesterol Ratio is Associated with Hepatic Steatosis but Not Fibrosis in Nonobese Adults: A NHANES 2017-2020 Study.

BACKGROUND: Although metabolic dysfunction-associated steatotic liver disease (MASLD) has traditionally been regarded as a disease closely related to obesity, its prevalence is gradually rising in nonobese populations. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel metabolic biomarker that has been shown to be associated with MASLD. However, its role in nonobese individuals remains unclear. This study aimed to investigate the association between UHR and nonobese MASLD. METHODS: Data from the 2017 to 2020 National Health and Nutrition Examination Survey (NHANES) were analyzed. UHR was calculated as the serum uric acid (UA) divided by the high-density lipoprotein cholesterol (HDL). Liver steatosis (using controlled attenuation parameters, CAP) and fibrosis (using liver stiffness measurement, LSM) were evaluated through vibration-controlled transient elastography (VCTE). Multivariate linear regression was employed to evaluate associations. Nonlinear relationships were examined using smoothed curve fitting. RESULTS: This analysis included 3573 participants (47.41% male; aged 20-80 years). Log2-UHR was positively associated with CAP (&#x3b2; = 9.96, 95% CI: 6.93-12.98, P < 0.001) and MASLD prevalence (OR = 1.64, 95% CI: 1.38-1.95, P < 0.001). Subgroup analyses revealed significant interactions by sex, age, ethnicity, and smoking status (all P for interaction < 0.05), with stronger associations in females, adults aged 40-59 years, individuals of other Hispanic ethnicity, and never-smokers. Moreover, the association between log2-UHR and CAP was linear and positive (P < 0.01). No significant association was found between log2-UHR and LSM (P > 0.05). CONCLUSIONS: UHR is independently associated with hepatic steatosis but not fibrosis in nonobese US adults, suggesting its potential utility as an early risk assessment to tool. Large scale prospective studies are needed in the future to further validate the conclusions of this study.

Humans

Factors Associated With Menopause Symptoms: A Systematic Review and Meta-Analysis.

BACKGROUND: Menopause, marked by hormonal decline and menstrual cessation, is associated with various symptoms. Socio-demographic and behavioural factors may influence symptom type and severity. Understanding these associations can inform better symptom management. OBJECTIVES: To identify factors associated with the presence and severity of menopausal symptoms through systematic review and meta-analysis. SEARCH STRATEGY: We searched Medline, Embase, CINAHL and Cochrane for studies on demographic, behavioural, or health factors linked to vasomotor, vaginal dryness and joint symptoms in women aged 40-60. SELECTION CRITERIA: Studies reporting odds ratios or raw numbers for symptom presence or severity were included. DATA COLLECTION AND ANALYSIS: Studies were combined for meta-analysis, reporting odds ratios and 95% confidence intervals. Quality assessment was performed to quantify the risk of bias. RESULTS: Of 9228 screened articles, 61 were meta-analysed. Compared with White women, Black women had higher odds of vasomotor symptom presence (OR 1.65, 1.41-1.94) and severity (OR 1.91, 1.10-3.29), and vaginal dryness presence (OR 1.27, 1.10-1.47), while Asian had lower vasomotor symptom presence and severity (OR 0.40, 0.22-0.72; OR 0.55, 0.53-0.56). Higher education (OR 1.31, 1.09-1.56), high income (OR 1.41, 1.01-1.97) and depression (OR 2.36, 1.51-3.70) were associated with increased presence of vasomotor symptoms. Smoking and obesity were associated with both presence (OR 1.63, 1.30-2.04 and 1.35, 1.02-1.78) and severity (OR 1.56, 1.07-2.27 and 1.42, 1.11-1.83) of vasomotor symptoms. CONCLUSION: Socio-demographic and behavioural factors, including ethnicity, education, income, smoking, obesity and depression, influence menopausal symptoms, highlighting the need for personalised care. TRIAL REGISTRATION: PROSPERO number: CRD42023459154.

Humans

Bone progression in multiple myeloma: Benefit of zoledronic acid for patients achieving at least Very Good Partial Response and prognostic value of bone turnover markers.

The Magnolia study demonstrated that continuation of zoledronic acid (ZOL) beyond 2&#x2009;years reduces the risk of progressive bone disease (PBD) in patients with multiple myeloma (MM). This follow-up study investigated the effects of ZOL in patients achieving very good partial response (VGPR) compared to patients who did not and whether bone turnover markers could identify patients at an increased risk of PBD following treatment cessation. Two Magnolia trial subgroups were analysed: patients with VGPR or better after 2&#x2009;years of ZOL, randomized to either continued treatment or observation, and patients randomized to observation in whom serial bone markers (C-terminal cross-linked telopeptide of type I collagen [CTX], procollagen type I N-terminal propeptide [P1NP], bone-specific alkaline phosphatase [BAP], tartrate-resistant acid phosphatase isoform 5b [TRAcP]) were measured for up to 4&#x2009;years. Continued monthly ZOL beyond 2&#x2009;years significantly reduced the risk of PBD (hazard ratio 0.40; 95% confidence interval [CI] 0.16-0.92) in patients with VGPR or better (subgroup 1). After ZOL discontinuation, bone markers increased gradually. Elevated CTX (&#x2265;0.30&#x2009;&#x3bc;g/L) and TRAcP (&#x2265;4&#x2009;U/L) levels were associated with increased 6-month PBD risk (29% and 15% respectively) (subgroup 2). Continuation of ZOL beyond 2&#x2009;years seems to reduce skeletal progression risk in patients achieving VGPR or better. Elevated CTX or TRAcP levels may help identify patients who could benefit from re-initiating ZOL.

Humans

Prenatal exposure to particulate matter (PM) and autism spectrum disorder (ASD) among children: a systematic review and meta-analysis.

The global surge in Autism Spectrum Disorder (ASD) cases, coupled with evidence linking prenatal Particulate Matter (PM) exposure to developmental disruption, demands a comprehensive review to design targeted health interventions. This systematic review and meta-analysis aim to evaluate the strength and consistency of evidence linking prenatal PM exposure to ASD across studies, quantifying this relation to identify actionable environmental risk thresholds. This study employed PRISMA protocols to systematically extract and evaluate evidence from PubMed, Web of Science, Scopus, and ScienceDirect (2010-2024), and screened 4,013 articles to identify qualified case-control and cohort studies (n=29). Data synthesis employed random-effects modeling, accompanied by comprehensive assessment through I2 statistics, Q-tests, funnel plots, Duval and Tweedie's trim-and-fill analysis, and Egger's regression, to ensure validity. A meta-analysis of 16&#xa0;case-control studies revealed a 34&#x202f;% increased risk of ASD associated with prenatal PM exposure (pooled OR=1.34; 95&#x202f;% CI: 1.13-1.54), despite substantial between-study heterogeneity (I2=94.02&#x202f;%, p<0.001). Publication bias was not significant (Egger's test p value=0.114). Critical trimester-specific analysis uncovered that third-trimester exposure significantly increased ASD risk (OR=1.17; 95&#x202f;% CI: 1.01-1.34), while first-trimester (OR=1.02; 95&#x202f;% CI: 0.92-1.11; I2=49.18&#x202f;%, p<0.10) and second-trimester exposures (OR=1.13; 95&#x202f;% CI: 0.88-1.38; I2=92.59&#x202f;%, p<0.001) showed non-significant associations. This review identified prenatal and early life exposure to PM as a risk factor for ASD, indicating a trimester-specific vulnerability. It highlighted the necessity of focused air quality interventions and targeted guidance to reduce prenatal PM exposure to alleviate ASD risk during the critical-window.

Child

Regional genomic analysis of lineage distribution and transferable multidrug resistance among chicken-associated Salmonella Kentucky isolates in China.

Salmonella enterica serovar Kentucky is an important multidrug-resistant foodborne pathogen in the poultry meat supply chain. Although recent broader genomic studies have elucidated the population structure and epidemiological significance of major lineages in China (e.g., ST198 and ST314), the regional dynamics within local poultry supply chains remain insufficiently characterized. In this study, 31 chicken meat-derived isolates from Shanghai and 39 publicly available genomes from China were analyzed using antimicrobial susceptibility testing, whole-genome sequencing, phylogenetic analysis, conjugation experiments, and complete sequencing of representative plasmids. This enabled a systematic characterization of the molecular epidemiological features of the population and the mechanisms underlying resistance dissemination. Population genomic analysis revealed a lineage composition markedly different from the global epidemiological pattern: ST314 was the predominant sequence type among the Shanghai chicken-derived isolates (74.2%), whereas the internationally recognized high-risk clone ST198 accounted for only 25.8% of the local isolates. However, risk stratification analysis indicated that although ST198 was detected less frequently, it carried a significantly greater burden of acquired resistance genes and therefore represented a higher-risk resistant lineage. Functional and structural validation further elucidated the molecular basis of resistance dissemination within this high-risk lineage. Conjugation experiments confirmed the co-transfer of a multidrug resistance module carrying blaTEM-1 and blaCTX-M-267 to the recipient strain Escherichia coli J53. Complete plasmid analysis revealed that these two &#x3b2;-lactam resistance genes were co-localized on a 242-kb transferable plasmid flanked by Tn1331, Tn3, and multiple transposase-associated elements, thereby providing a structural basis for their horizontal transfer. This study provides important molecular epidemiological evidence for lineage-specific surveillance and risk-stratified control of resistant Salmonella in the poultry meat supply chain and further underscores the need for continuous monitoring of mobile genetic elements within a One Health framework.

Animals

Global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD: a systematic review and meta-analysis.

BACKGROUND: The presence of diabetes increases the risk of adverse outcomes of patients with non-alcoholic fatty liver disease (NAFLD) even in those with lean or non-obese NAFLD. However, the epidemiological data regarding the prevalence of diabetes and prediabetes in lean or non-obese NAFLD populations remain limited. We assessed the global epidemiology of diabetes and prediabetes in lean or non-obese patients with NAFLD. METHODS: Published studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science databases from the inception of the databases to October 2024. The pooled global prevalence of diabetes or prediabetes in patients with NAFLD was evaluated using random-effects meta-analysis. Subgroup meta-analysis and meta-regression were used to investigate potential sources of heterogeneity. RESULTS: A total of 54 studies involving 146,714 patients with non-obese or lean NAFLD were included. The pooled global prevalence of diabetes among patients with lean or non-obese NAFLD was 15.6% (95% CI 10.8%-22.7%). Studies from South America reported the highest prevalence (41.3%, CI 39.1%-43.5%). Meta-regression models showed that geographic region and mean age (p&#x2009;<&#x2009;0.05) were associated with the were associated with the prevalence of diabetes, jointly accounting for 51.61% of the heterogeneity. The global prevalence of prediabetes among patients with lean or non-obese NAFLD was 22.9% (95% CI 12.5%-41.9%) with the highest prevalence reported in studies from Europe (34.4%, CI 23.0%-51.4%). Meta-regression models showed that geographic region and country (p&#x2009;<&#x2009;0.05) were associated with the prevalence of prediabetes, jointly accounting for 73.65% of the heterogeneity. CONCLUSION: The pooled global prevalence of diabetes and prediabetes were 15.6% and 22.9% in lean or non-obese patients with NAFLD, respectively. These findings suggest the importance of diabetes screening in these patients.

Humans

Dosimetric Parameters of the Heart and Its Substructures in Predicting Cardiac Events or Survival in Patients With Lung Cancer After Radiation Therapy: A Systematic Review and Meta-analysis.

The predictive value of radiation dose to the whole heart (WH) and cardiac substructures (CS) for cardiac events (CEs) and survival in patients with lung cancer remains uncertain. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between these associations. A systematic meta-analysis was performed following PRISMA guidelines. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. Outcomes were classified into major adverse cardiac events (MACE), arrhythmias, pericardial effusion, and survival. Depending on heterogeneity, random- or fixed-effects models were applied to calculate pooled hazard ratios (HRs) for univariable and multivariable analyses. A total of 80 studies, including 21,645 patients, were analyzed. Of these, 25 studies reported CEs, and 69 reported survival outcomes. Among 91 WH and 215 CS parameters evaluated, several showed significant associations. Key findings from our meta-analysis include: (1) left anterior descending (LAD) V15 was significantly associated with MACE. The mean heart dose (MHD), as well as ventricle and LAD doses, were significantly associated with ischemic events. (2) Multiple CS parameters were associated with different arrhythmia subtypes. (3) MHD, heart V5/V35/V55 and pericardial doses were significantly associated with pericardial effusion. (4) MHD was significantly associated with survival; CS parameters also showed predictive value, and especially, heart base dose being the most significant. (5) We also identified several thresholds with potential predictive values, such as LAD V15 <10% for MACE, left pulmonary vein (LPV) V55 <2%, and right pulmonary vein (RPV) V10 <54% for atrial fibrillation (AF), right atrium (RA) V60 <0.03 cc for non-AF supraventricular tachyarrhythmia, and left main artery (LMA) V10 &#x2265;1 cc for bradyarrhythmia. This study identified 130 WH and CS dosimetric parameters associated with CEs and 131 with survival outcomes. These findings enhance our understanding of radiation-induced heart injury mechanisms and provide guidance for potential protective and intervention strategies.

Humans

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy

Comparing the Efficacy of Mechanochemical Ablation Versus Radiofrequency Ablation for Treating Great Saphenous Vein Incompetence: A Meta-Analysis.

BACKGROUND: The objective of this meta-analysis was to compare the efficacy of mechanochemical ablation (MOCA) and radiofrequency ablation (RFA) in the treatment of great saphenous vein (GSV) incompetence. METHODS: Online databases including PubMed, Cochrane Library, Embase, and Web of Science were searched to collect randomized controlled trials (RCTs) and cohort studies comparing MOCA and RFA in the treatment of varicose veins in lower extremities from database inception to October 2025. Primary outcome was anatomic success. Secondary outcomes were visual analog scale (VAS), Aberdeen Varicose Vein Questionnaire score (AVVQ), and complications. Two reviewers independently screened the retrieved literature, extracted data, and assessed the risk of bias in the included studies. Subsequent analysis was performed using RevMan 5.3. RESULTS: A total of four RCTs, one cohort study and retrospective cross-sectional study involving 737 patients (380 MOCA patients and 357 RFA patients) were included. The meta-analysis results showed that the RFA group was significantly better than the MOCA group in short term and long term of anatomical success rate [(odds ratio [OR] = 0.38; 95% confidence interval [CI] (0.20, 0.71), P = 0.003), (OR = 0.17, 95% CI (0.06, 0.45), P = 0.0003)], but patients in the MOCA group had significantly lower perioperative period pain (mean difference [MD] = -4.48, 95% CI (-7.58, -1.37), P = 0.005] and required fewer days to return to normal activities (MD = -0.76, 95% CI, (-0.95, -0.57), P < 0.001). No significant differences were observed between the two groups in minor and major complications [(OR = 0.93, 95% CI (0.66, 1.33), P = 0.70), (OR = 1.30, 95% CI (0.32, 5.28), P = 0.72)] or quality of life scores (MD = -0.45, 95% CI (-2.53 to 1.63), P = 0.67). CONCLUSION: MOCA of GSV incompetence is an effective and safe method. Compared with RFA, it has lower postoperative pain score and faster recovery time. However, the anatomical success rates were significantly lower with MOCA than with RFA. Therefore, long-term follow-up to evaluate the impact on clinical results is required.

Humans