Tag: statistics

Nat Neurosci. 2026 May 21. doi: 10.1038/s41593-026-02302-3. Online ahead of print.

ABSTRACT

Multiple sclerosis (MS) is a chronic neuroinflammatory disease in which demyelinating white matter lesions accumulate and expand, driving irreversible disability. Here we identify a distinct population of foamy GPNMB⁺ microglia/macrophages associated with lesion expansion in secondary progressive MS. Using integrated lipidomic, transcriptomic, proteomic, chemical proteomic and histological analyses of human postmortem MS lesions, we show that lesions containing foamy microglia/macrophages exhibit disrupted lipid metabolism, lysosomal stress and markers associated with heightened phagocytosis and antigen presentation without classical pro-inflammatory signatures. These lesions are enriched for oxylipins, bismonoacylglycerolphosphates and cholesterol esters, and are associated with increased B cell infiltration and IgG1. Monoacylglycerol lipase (MAGL), a lipid-metabolizing enzyme enriched in lesions with foamy microglia/macrophages, emerged as a potential therapeutic target. Inhibition of MAGL promoted lesion recovery and reduced microgliosis in a mouse model of demyelination. Finally, oxylipins in cerebrospinal fluid correlate with the proportion of foamy lesions, suggesting potential biomarkers for progression. Our findings implicate disturbed lipid metabolism in chronic MS pathology and suggest that foamy microglia/macrophages are an interesting cell type to target for progressive disease.

PMID:42168651 | DOI:10.1038/s41593-026-02302-3

Eur J Nucl Med Mol Imaging. 2026 May 22. doi: 10.1007/s00259-026-07886-3. Online ahead of print.

ABSTRACT

PURPOSE: The 2024 Alzheimer’s Association Workgroup research framework designates tau proteinopathy (T₂) as a key element for Alzheimer’s disease (AD) staging, but optimal staging approaches have yet to be determined. Here, we compared visual and quantitative tau-PET-based Braak staging as candidate strategies to implement T₂ biological staging in vivo.

METHODS: We included 140 participants from the TRIAD cohort who underwent [¹⁸F]MK6240 tau-PET. Quantitative Braak staging (qBraak) was derived from regional SUVR thresholds, whereas visual Braak staging (vBraak) was independently performed by three nuclear medicine physicians using an adapted interpretation algorithm. Inter-rater and inter-method agreement were assessed using Cohen’s and Fleiss’ κ statistics. Associations with clinical severity, cortical thickness, plasma pTau217, and cortical tau extent were examined. Diagnostic performance for identifying amyloid-positive cognitively impaired individuals was evaluated.

RESULTS: vBraak demonstrated substantial to nearly perfect inter-rater agreement (κ = 0.65-0.93). Agreement between vBraak and qBraak was moderate when stages were treated categorically (κ = 0.51), but substantial when their ordinal nature was considered (weighted κ up to 0.73). Both strategies showed comparable associations with clinical severity and neurodegeneration. vBraak was more sensitive to amyloid-β-positive cognitive impairment and identified intermediate-stage involvement at lower global tau extent. Visual-quantitative discordant cases were primarily attributable to off-target binding or spatially heterogeneous tau patterns.

CONCLUSION: Both vBraak and qBraak staging provide complementary and largely concordant approaches for operationalizing T₂ staging. Quantitative methods enable scalable, group-level analyses, whereas visual assessment remains essential for identifying atypical tau patterns and informing clinically relevant decision-making.

PMID:42168643 | DOI:10.1007/s00259-026-07886-3

Rheumatol Int. 2026 May 21;46(6):95. doi: 10.1007/s00296-026-06134-z.

ABSTRACT

Hypermobile Ehlers-Danlos Syndrome (hEDS) is associated with joint hyperflexibility, pain, and connective tissue frailty. Patients are at high risk for fracture due to poor proprioception. This study reports on the mental and physical health, pain, physical activity, and kinesiophobia in patients with hEDS, and explores bone mineral density and fracture risk. This single-center, cross-sectional prospective study was approved by the IRB (HHC-2022-0143). Patients with diagnosed hEDS were consented and completed demographic forms, activity levels, PROMIS-10 Global Health Assessments, and the Tampa Kinesiophobia Scale, prior to DXA (Dual-energy X-ray absorptiometry) scans. Descriptive and inferential statistics were conducted including correlations and univariate regression analyses. All patients were female and pre-menopausal with a mean age of 36 (range: 19-55). Patients maintained an overall adequate bone mineral density (Spine: 1.16 ± 0.12 g/cm³, Femur: 0.961 ± 0.09 g/cm³ ) though three patients were identified as osteopenic and 50% had fractured as an adult. The PROMIS-10 mental health T-score and pain were strongly negatively correlated (r_s = -0.87, p < 0.001) as were the PROMIS-10 physical function T-score and pain (r_s = -0.78, p < 0.001). Kinesiophobia was negatively correlated with low mental health (r_s = -0.56, p = 0.03) and with physical function T-scores (r_s = -0.75, p < 0.001). This study illustrates the association of mental health, physical function, chronic pain, and kinesiophobia in this unique patient population. Patients had higher fracture incidence without a significant reduction in bone mineral density. Future interventions could be directed at exploring disease-specific rehabilitation programs.

PMID:42168630 | DOI:10.1007/s00296-026-06134-z

Surg Endosc. 2026 May 21. doi: 10.1007/s00464-026-12921-3. Online ahead of print.

ABSTRACT

BACKGROUND: Although endoscopic submucosal dissection (ESD) is widely accepted for early gastric cancer (EGC), its role in managing undifferentiated-type EGC (UD-EGC) is still debated. This multicenter study aimed to compare the short- and long-term outcomes of ESD and surgery in patients with UD-EGC.

METHODS: We retrospectively analyzed patients with UD-EGC who underwent ESD or surgery at 11 tertiary centers in Taiwan between 2007 and 2025. Inclusion criteria included intramucosal tumors ≤ 20 mm without ulceration or lymphovascular invasion. Demographic, endoscopic, and pathological data were collected, and long-term outcomes were compared.

RESULTS: A total of 37 ESD and 42 surgery patients were analyzed. En bloc resection was achieved in all cases. R0 resection rates were 86% for ESD and 98% for surgery in unadjusted analysis (P = 0.06), while propensity score-weighted analysis showed significantly higher R0 resection in the surgery group (85.8% vs. 98.7%, P = 0.017). The ESD group demonstrated significantly shorter procedure times (84.6 vs. 285.7 min, P < 0.001) and hospital stays (6.8 vs. 17.6 days, P < 0.001). Complication rates were comparable between groups (11% for ESD vs. 14% for surgery, P = 0.74). In unadjusted analyses, the cumulative incidence of recurrence was higher in the ESD group than in the surgery group (P = 0.03), whereas overall survival (OS) was similar between groups (5-year OS: 93% for ESD vs. 90% for surgery; log-rank P = 0.12). After propensity score overlap weighting, the difference in recurrence between groups was attenuated and no longer statistically significant (P = 0.22).

CONCLUSIONS: Although ESD is less invasive with shorter procedure time and hospital stay, its lower R0 resection rate and higher recurrence risk require careful patient selection and close surveillance. Similar OS supports the potential role of ESD in selected UD-EGC patients, although further validation is needed.

PMID:42168610 | DOI:10.1007/s00464-026-12921-3

Sci Rep. 2026 May 21. doi: 10.1038/s41598-026-51501-2. Online ahead of print.

ABSTRACT

Cell type markers have been instrumental to physiological and molecular investigation of the human brain and remain essential for annotating cell type clusters in single-cell expression data and for target validation studies. However, expression of canonical markers in the target cell type (which we termed as the expression ‘fidelity’) as well as expression in unrelated cell types (which we termed as the ‘background expression’) across cortical regions remains poorly characterized. Here, leveraging nearly 500,000 high-quality single-nucleus and single-cell profiles from 19 studies, we quantified marker fidelity, revealing substantial regional variability. We developed a statistical framework that aggregates annotated barcodes into pseudo-bulk profiles, applied rigorous performance metrics, and identified markers with high fidelity, low background, and consistent expression across regions. This approach extended the canonical marker set for six major brain cell types and yielded superior subtype-specific markers. The resulting marker lists, and a user-friendly analysis interface, provide a valuable resource for cell type annotation and validation in neuroscience research.

PMID:42168596 | DOI:10.1038/s41598-026-51501-2

Prev Vet Med. 2026 May 17;254:106916. doi: 10.1016/j.prevetmed.2026.106916. Online ahead of print.

ABSTRACT

INTRODUCTION: This review evaluates the effectiveness of culling and birth control interventions for managing free-roaming dogs (FRD) and cats (FRC) worldwide across key outcome domains-population metrics, zoonotic disease indicators, shelter indicators, public metrics, animal welfare, ecological externalities, and cost-effectiveness-and identifies contextual conditions determining intervention effectiveness.

METHODS: Following PRISMA, we conducted three separate systematic searches in PubMed, Web of Science, and Scopus (up to 16 October 2025) addressing culling, birth control, and modelling studies. Empirical evidence was synthesised using descriptive, stratified analyses. Modelling studies were synthesised to identify conditions associated with effectiveness.

RESULTS: Ninety-one empirical studies were included (33 culling; 58 birth control), alongside 18 modelling studies. Birth control interventions were more frequently classified as effective than culling, with statistically significant differences in effectiveness distributions between intervention types (p = 0.045). Culling effectiveness was context-dependent and largely confined to island systems, particularly for FRC, while FRD-targeted culling was rarely effective, especially for zoonotic disease indicators and public metrics. Birth control-particularly multi-component, long-term programmes-showed higher effectiveness across domains and in open mainland settings. Temporal analyses showed a decline in both the volume and reported effectiveness of culling studies since 2010, alongside increasing and geographically broader evidence for birth control. Modelling studies identified high population coverage, sustained implementation, and control of population inflow as key conditions for effectiveness.

CONCLUSIONS: Culling has limited, context-dependent effectiveness, whereas birth control within integrated strategies more consistently achieves sustained outcomes across domains. Effectiveness depends on coverage, duration, and addressing drivers of population inflow, including abandonment and uncontrolled breeding.

PMID:42166825 | DOI:10.1016/j.prevetmed.2026.106916

JMIR Res Protoc. 2026 May 21;15:e87165. doi: 10.2196/87165.

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are significant global health concerns, particularly prevalent in low- and middle-income countries (LMICs). In China, a significant number of international migrants from LMICs reside, many of whom are at high risk of HBV and HCV infection, while this group tends to engage in low HBV and HCV test use due to some adverse factors. Pay-it-forward (PIF) is a social innovation strategy that is based on the theories of upstream reciprocity and mutual aid. Previous studies have shown that the PIF strategy has proven effective in promoting sexually transmitted infections (STIs) testing in various populations.

OBJECTIVE: This study aims to evaluate the effectiveness of a PIF intervention in promoting HBV and HCV testing among international migrants from LMICs in China.

METHODS: A 2-arm cluster randomized controlled trial (RCT) will be conducted in Guangzhou, China. Participants will be recruited from a public hospital serving a large migrant community. A total of 100 eligible participants will be enrolled in blocks of 5 using a cluster randomization plan and randomly assigned to either the PIF intervention arm or the control arm in a 1:1 ratio. Participants in the intervention arm will watch a 2-minute video introducing the PIF concept and receive printed educational materials on HBV and HCV. Participants will then be offered free testing donated by previous participants, which they can accept or decline, and an opportunity to make a monetary donation to cover testing for a future participant. Control arm participants will receive standard medical services, with self-paid testing. The primary outcome is the proportion of participants tested for both HBV and HCV. Data will be collected through a self-administered questionnaire, and test information will be obtained from the hospital’s medical records without personally identifiable information. The survey data will be analyzed using generalized estimating equations to account for clustering effects.

RESULTS: This protocol was completed in August 2024, and implementation was conducted from September 2024 to February 2025. According to the baseline survey findings, 73.0% (73/100) of the 100 eligible participants recruited were male, 87.0% (87/100) were from African countries, and 85.0% (85/100) came to China for business purposes. About 40.0% (40/100) earned more than US $1100 per month, 62.0% (62/100) were married, and 6% (6/100) had both stable and casual sexual partners.

CONCLUSIONS: This study is innovative in targeting international migrants from LMICs in China and using the PIF strategy to promote HBV and HCV testing. The PIF intervention is expected to increase testing rates by addressing financial barriers and fostering community support. The findings will contribute to the understanding of HBV and HCV testing promotion among this understudied population, with potential implications for public health policy and practice.

PMID:42166794 | DOI:10.2196/87165

JMIR Mhealth Uhealth. 2026 May 21;14:e70188. doi: 10.2196/70188.

ABSTRACT

BACKGROUND: Dementia has an impact on the physical activities performed daily in a social context. Sleeping and resting, in general, are also affected by dementia. Monitoring techniques based on miniaturized wearable sensors and on sensorized environments allow for actigraphic recordings and location tracking. The availability of contemporaneous physical activities profile led to quantify, in the social actigraphy approach, the level of correlation between individuals living in the same environment.

OBJECTIVE: This study has two main objectives: (1) to define a methodology for actigraphic recordings, based on wearable accelerometers, and on location tracking, based on Bluetooth wearable technology, and to apply it in a well-defined social context, a long-term care residential unit for people with dementia; and (2) to quantify test-retest reliability of the indices obtained by the monitoring methodology.

METHODS: Persons with dementia living in the long-term care unit have been equipped with miniaturized wearable sensors, an accelerometer at their dominant wrist, and a Bluetooth beacon at their ankle for 7 days. The raw recordings allowed for computing indices related to physical activity intensities, to the occurrence of walking bouts, to the efficiency of sleep and waking phases, to social interactions between individuals, and to locations preferably occupied. The 7-day session was repeated at short (3 weeks) and long (3 months) terms in order to quantify the test-retest reliability of the indices.

RESULTS: Twenty-five persons with dementia were enrolled, 4 of them dropped out, and valid data were obtained, in the different sessions, from 19 to 21 individuals of the recruited group. Control data from 10 age-matched healthy participants were derived from published datasets. As a group, compared with age-matched healthy participants, persons with dementia showed a comparable duration of phases of no activity and of light activity (energy cost lower than 3 metabolic equivalents of tasks [METs]), a relevantly lower duration (-84.3%) of phases of moderate activity (energy cost ranging from 3 to 6 METs), and substantial absence (-100%) of phases of vigorous activity (larger than 6 METs); moreover, daytime and nighttime were characterized by comparable wake and sleep, respectively, efficiency; finally, as to the social interactions, persons with dementia showed a lower correlation of their motor activity profiles (-53.1%). The test-retest reliability was excellent for physical activity indices (intraclass correlation coefficients ranging from 0.76 to 0.98), good for social indices (0.65-0.67), excellent for sleep or wake efficiency (0.74-0.89), and fair for location tracking indices (0.37-0.78).

CONCLUSIONS: The considered methodology, particularly concerning accelerometry, proved to be feasible, informative, and with a good to excellent test-retest reliability. Interestingly, the methodology clearly identified behaviors, such as wandering, in a minority of individuals inside this study’s group of persons with dementia, thus supporting a possible clinical use of the methodology.

PMID:42166790 | DOI:10.2196/70188

J Med Internet Res. 2026 May 21;28:e83896. doi: 10.2196/83896.

ABSTRACT

BACKGROUND: Alcohol use disorder (AUD) profoundly affected ethnic minority young adults due to unique stressors, such as acculturation challenges and discrimination. Our prior studies found that experiential avoidance behavior and discrimination significantly contributed to AUD. These findings warranted third-wave interventions, such as acceptance and commitment therapy (ACT). Nonetheless, barriers to engagement with value-based activities may affect ACT efficacy. Behavioral activation (BA) may be an alternative for this shortcoming. Integrating these interventions has shown promise. However, no studies evaluated its effectiveness in this group. Therefore, evaluating the preliminary effectiveness and feasibility of this intervention was needed.

OBJECTIVE: This study aimed to evaluate the feasibility measures. The secondary objective aimed to examine its effectiveness on cumulative abstinence duration, drinking days, drinks per drinking day, heavy drinking days, alcohol abstinence self-efficacy, readiness to change, psychological flexibility (Acceptance and Action Questionnaire-version II), and everyday discrimination score.

METHODS: A pilot parallel randomized controlled trial was conducted. Forty young ethnic minorities who can speak English and have AUD based on DSM-5 (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) criteria were recruited and randomly assigned to either Acceptance and Commitment Therapy with Behavioral Activation (ACT-BA; n=20) or Treatment-as-Usual (TAU; n=20) using a computer-generated random number; assessors were blinded to group assignment. Outcomes were collected at baseline (T0) and postintervention (T1). The analysis included descriptive statistics, independent samples t test, chi-square test, and generalized estimating equations with multiple imputations. To further supplement findings, a qualitative interview was conducted.

RESULTS: A total of 148 ethnic minority young adults were screened, with an eligibility rate of 38.5% (57/148). Of these, 85.9% (49/57) consented, and among them, 81.6% (40/49) were randomized to either the ACT-BA or TAU. The retention rate was 82.5% (33/40), of which 75% (30/40) completed the postintervention assessment (ACT-BA: 16/20, 80%; TAU: 14/20, 70%). The adherence rate was 81.7% (4.9/6 sessions), and participants reported no adverse effects. Finally, 40 participants (20 for each group) were analyzed. The intervention group showed a promising improvement in drinking days (B=-4.12, 95% CI -8.10 to -0.13; P=.04, d=-0.57), drinks per drinking day (B=-1.56, 95% CI -3.06 to -0.07; P=.04, d=-1.89), alcohol abstinence self-efficacy (B=11.95, 95% CI 0.10-23.81; P=.048, d=0.81), and Acceptance and Action Questionnaire-version II (B=-6.41, 95% CI -12.77 to -0.06; P=.04, d=-0.65).

CONCLUSIONS: This study, unlike existing evidence, presents an innovative integration of ACT and BA delivered via an internet-based self-help format. The findings contribute to the field by providing preliminary evidence that this integrated intervention is feasible and promising for AUD. The main implication in the real world is to conduct a fully powered randomized controlled trial to further examine its effectiveness with longer follow-up to serve as a stand-alone treatment option for ethnic minorities.

PMID:42166789 | DOI:10.2196/83896

J Med Internet Res. 2026 May 21;28:e87216. doi: 10.2196/87216.

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that reduces quality of life and causes a heavy medical burden. Internet-based self-help interventions are flexible and scalable, showing potential for IBS symptom improvement, but relevant evidence is fragmented and lacks systematic review.

OBJECTIVE: This systematic review aimed to comprehensively evaluate the effects of internet-based self-help interventions on symptom severity, quality of life, and visceral sensitivity, as well as comorbid depressive and anxiety symptoms, in individuals with IBS.

METHODS: Only randomized controlled trials evaluating internet-based self-help interventions for individuals with IBS were included. A literature search was conducted across PubMed, Embase, Web of Science, CINAHL Complete, PsycINFO, the Cochrane Library, and 4 Chinese databases on June 25, 2025, with an updated search on March 9, 2026. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Meta-analyses were performed with the Hartung-Knapp-Sidik-Jonkman-adjusted random-effects model. Effect sizes were reported as standardized mean differences (SMDs) with 95% CIs, and evidence certainty was evaluated using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria.

RESULTS: A total of 17 randomized controlled trials from 7 countries were included, involving 2289 participants (predominantly female). Compared with control groups, internet-based self-help interventions were associated with a statistically significant improvement in IBS symptom severity (SMD -0.52, 95% CI -0.78 to -0.26, 95% prediction interval [PI] -1.46 to 0.42), quality of life (SMD 0.57, 95% CI 0.23 to 0.90, 95% PI -0.41 to 1.54), visceral sensitivity (SMD -0.55, 95% CI -0.89 to -0.21, 95% PI -1.43 to 0.33), and depressive symptoms (SMD -0.14, 95% CI -0.27 to -0.01, 95% PI -0.27 to -0.01). However, no statistically significant improvement was observed in anxiety symptoms (SMD -0.03, 95% CI -0.34 to 0.27, 95% PI -0.78 to 0.71). The certainty of evidence was rated as moderate to very low for all outcomes.

CONCLUSIONS: This review synthesizes the latest evidence on internet-based self-help interventions for individuals with IBS disease-specific and comorbid psychological symptoms. It stands out by encompassing a diverse range of such interventions and incorporating visceral sensitivity as a key outcome. In doing so, it establishes a more comprehensive multi-outcome evidence base for IBS digital interventions, advancing the field by clarifying the potential of these interventions as viable alternatives to conventional treatments. For real-world practice, these findings can inform targeted strategies for primary care and telemedicine platforms, especially in resource-limited regions. However, this review is limited by moderate bias risk, high heterogeneity, and moderate to very low GRADE evidence certainty. A wide 95% PI suggests that effect variability is linked to contextual and population factors, so findings should be interpreted cautiously. Future research should prioritize technical support, patients’ digital health literacy, and standardized intervention protocols to further validate clinical utility.

PMID:42166786 | DOI:10.2196/87216