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Nevin Manimala Statistics

CRAK-Velo: chromatin accessibility kinetics integration improves RNA velocity estimation

Genome Biol. 2026 May 5. doi: 10.1186/s13059-026-04086-y. Online ahead of print.

ABSTRACT

RNA velocity has recently emerged as a key tool in the analysis of single-cell transcriptomic data, yet connecting RNA velocity analyses to underlying regulatory processes has proved challenging. Here, we propose CRAK-Velo, a semi-mechanistic model that integrates chromatin accessibility data in the estimation of RNA velocities. CRAK-Velo provides biologically consistent estimates of developmental flows and enables accurate cell-type deconvolution, while additionally shining light on regulatory processes at the level of interactions between genes and chromatin regions.

PMID:42087173 | DOI:10.1186/s13059-026-04086-y

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Patient characteristics and interventions at a trauma stabilization point in Gaza- a retrospective analysis

Confl Health. 2026 May 5. doi: 10.1186/s13031-026-00795-0. Online ahead of print.

ABSTRACT

BACKGROUND: Timely prehospital care is essential in preventing trauma‑related deaths in conflict settings, yet civilian systems often lack the capacity for rapid stabilization and evacuation. Trauma Stabilization Points (TSPs), adapted from military models, have been introduced in Gaza to provide forward‑deployed triage and stabilization. This study describes patient characteristics, clinical presentations, interventions, and outcomes at a TSP operating in Khan Younis, Gaza, in 2024 during the ongoing war.

METHODS: We conducted a retrospective cross‑sectional analysis of routinely collected patient‑level data from a TSP operated by the Palestinian Red Crescent Society with support from the WHO and an international emergency medical team. All patients presenting between 12 February and 28 April 2024 were included. Descriptive statistics and logistic regression assessed associations between patient characteristics, injury severity, interventions, and referral outcomes.

RESULTS: 1,928 patients were entered into the dataset. Non‑traumatic conditions accounted for 53% of attendances, while 47% were trauma‑related. Most patients (94.8%) were stable, as defined by the Interagency Integrated Triage Tool (IITT) on arrival. A total of 3482 interventions were recorded, dominated by basic care (86%). Overall, 80.6% of patients were discharged, 19.3% referred to still-functioning hospitals, and 0.1% died at the TSP. Clinical instability, fractures, and penetrating injuries were significantly associated with referral, while basic interventions (e.g., wound suturing, antipyretics) predicted discharge.

CONCLUSIONS: Despite operating in a high‑intensity conflict, the TSP primarily functioned as a triage and primary‑care access point rather than a trauma‑focused facility. The dominance of on-site treatment and same-day discharge suggest the TSP offloaded some non-urgent patients from overwhelmed hospitals and likely contributed to reducing consumption of limited ambulance resources.

PMID:42087157 | DOI:10.1186/s13031-026-00795-0

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Association between intraoperative irrigation volume and postoperative abdominal abscess in perforated peptic ulcer

BMC Surg. 2026 May 6. doi: 10.1186/s12893-026-03813-3. Online ahead of print.

ABSTRACT

BACKGROUND: Perforated peptic ulcer is a critical emergency disease requiring surgery, and postoperative intra-abdominal abscess (IAA), an organ/space surgical site infection (SSI), is a common complication. Intraoperative irrigation is a common IAA prevention approach; however, scientific evidence supporting its effectiveness is lacking. We aimed to investigate the association between intraoperative irrigation volume and IAA using multicentre data.

METHODS: This multicentre retrospective cohort study was conducted between January 2011 and December 2023. The study included patients aged ≥ 18 years who underwent laparotomy or laparoscopy for perforated peptic ulcer, defined as perforation of a gastric or duodenal ulcer. The primary and secondary outcomes were IAA incidence and superficial incisional SSI, respectively, and their association with the intraoperative irrigation volume was determined through multivariable logistic regression analyses.

RESULTS: The study included 478 patients with a median age of 66 years (interquartile range [IQR]: 54-75 years), 344 (72.0%) of whom were males. The median irrigation volume was 7.0 (IQR: 5-10) L. Among the 478 patients, IAA and superficial incisional SSI occurred in 52 (10.9%) and 71 (14.9%), respectively. The irrigation volume and the outcomes exhibited no significant association (for IAA: adjusted odds ratio [AOR] = 1.04, 95% confidence interval [CI] = 0.97-1.11, p = 0.25; for superficial incisional SSI: AOR = 1.07, 95% CI = 1.00-1.14, p = 0.053).

CONCLUSIONS: There was no statistically significant association between increased intraoperative irrigation volume and a decreased incidence of postoperative IAA formation. These findings suggest that alternative strategies, rather than uncontrolled high-volume irrigation, are required for IAA prevention.

PMID:42087153 | DOI:10.1186/s12893-026-03813-3

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Long-term effect of early-life arsenic exposure on morning plasma cortisol in adults from Antofagasta, Chile

Environ Health. 2026 May 6. doi: 10.1186/s12940-026-01304-9. Online ahead of print.

ABSTRACT

Over 100,000 people were exposed to arsenic-contaminated drinking water in Antofagasta, Chile from 1958-1970. Individuals born during this high exposure period have elevated rates of cancer, lung and cardiovascular disease, and hypertension. However, the mechanisms of long-term arsenic toxicity remain unclear. We investigated whether early-life arsenic exposure was associated with altered glucocorticoid levels in adulthood. This study included 114 individuals born in Antofagasta during the high exposure period and 118 individuals born in other Chilean cities with lower exposure. Arsenic exposure metrics were constructed based on residential histories and included: concentration at birth, peak and highest 5-year average between ages 0-10 years, and highest lifetime 5-year average, and lifetime cumulative exposure. Morning plasma cortisol concentrations were measured using a cell-based bioassay. Individuals in the highest quartile of highest lifetime 5-year average of arsenic exposure had approximately 11% lower mean log cortisol levels than those in the lowest quartile of exposure (β = -0.116; 95% CI: -0.229, -0.003). In sex-stratified analyses, associations were stronger among female participants. For example, female participants in the highest quartile of cumulative exposure had 22.0% lower cortisol levels compared to those in the lowest quartile (β = -0.248; 95% CI: -0.444, -0.053) and the test for interaction by sex was statistically significant (p = 0.036). This study is the first to show that early-life arsenic exposure may suppress HPA axis activity decades after exposure has ceased. These findings support endocrine disruption as a potential mechanism underlying long-term health effects of arsenic and highlight early development as a critical exposure window.

PMID:42087152 | DOI:10.1186/s12940-026-01304-9

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Geographic disparities and methodological quality of type 2 diabetes prediction models: a systematic review and meta-analysis of 97 models

BMC Endocr Disord. 2026 May 6. doi: 10.1186/s12902-026-02301-2. Online ahead of print.

ABSTRACT

IMPORTANCE: Accurate risk prediction is essential for targeted prevention of type 2 diabetes mellitus (T2DM). However, the global applicability and methodological rigor of existing prediction models remain uncertain.

OBJECTIVE: To systematically review and meta-analyze the geographic distribution, methodological quality, and predictive performance of all published T2DM risk prediction models.

DATA SOURCES: PubMed, Embase, Web of Science, Cochrane Library, CNKI, WanFang, and VIP were searched from inception to December 2025 (eAppendix S1 in the Supplement).

STUDY SELECTION: Studies that developed or validated a multivariable prediction model for incident T2DM in general adult populations and reported at least one performance measure.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias using the PROBAST tool. A random-effects meta-analysis was used to pool C-statistics. Heterogeneity was explored via subgroup analyses and meta-regression. The study followed TRIPOD-SRMA and PRISMA reporting guidelines.

MAIN OUTCOMES AND MEASURES: The primary outcome was the geographic origin of models. Secondary outcomes included pooled measures of discrimination (C-statistic/AUC) stratified by region and an overall assessment of methodological quality (PROBAST).

RESULTS: A total of 65 studies comprising 97 distinct prediction models were included (eTable 1). Geographic distribution was highly skewed, with 70.1% of models developed in Asian populations (China: 47.4%; Japan: 13.4%; South Korea: 9.3%), while only 7.2% originated from the US and 4.1% from Europe. Logistic regression was used in 97.9% of models. External validation was performed for only 21 models (21.6%). According to PROBAST, 91.8% of models were at high risk of bias (eTable 2), primarily due to inadequate handling of missing data, lack of external validation, and poor calibration reporting. Meta-analysis revealed wide variation in discrimination by geographic region (eTable 7). US-based models achieved the highest pooled AUC (0.97; 95% CI, 0.94-0.99), but this finding is likely influenced by overfitting, small sample bias, and publication bias (see Discussion). European models showed a pooled AUC of 0.84 (0.81-0.87), while Chinese models showed the lowest performance (AUC, 0.79; 0.76-0.82). Due to very high heterogeneity (I² > 80% in most regions), these pooled estimates should be interpreted as descriptive summaries rather than precise estimates of true regional performance. Performance was lowest in prediabetic cohorts (AUC, 0.72; 0.68-0.76); however, this finding is preliminary due to the limited number of models and high heterogeneity. Funnel plot asymmetry suggested potential publication bias (Egger’s test p=0.03); The most frequently included predictors were age (69.1%), body mass index (64.9%), family history of diabetes (44.3%), and waist circumference (39.2%) (eFigure 4 and eTable 3).

CONCLUSIONS AND RELEVANCE: T2DM prediction models exhibit striking geographic inequity and poor methodological quality, with over 90% at high risk of bias. The substantial variation in performance by region and the lack of external validation critically limit their global clinical utility. These findings underscore an urgent need for rigorous external validation in diverse populations and de novo model development in under-represented regions, guided by PROBAST and TRIPOD standards.

TRIAL REGISTRATION: Not applicable.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:42087146 | DOI:10.1186/s12902-026-02301-2

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Metabolic profile in Prader-Willi syndrome patients followed at a single expert center of rare endocrine diseases

BMC Endocr Disord. 2026 May 5. doi: 10.1186/s12902-026-02302-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Prader-Willi syndrome (PWS) is a rare imprinting disorder characterized by typical dysmorphic features, lack of satiety, infantile hypotonia, and later morbid obesity with complications, short stature, hypogonadotropic hypogonadism, skeletal and psychiatric problems. From the literature, it is well known that patients with PWS have a more favorable metabolic pattern than healthy controls.

AIM: The aim of the study is to assess the metabolic profile of PWS patients followed at an Expert Center for Rare Endocrine Diseases compared with healthy controls and to look for relations between components of the metabolic syndrome (MetS), adipokines, and the compartments of body composition (BC-lean and fat mass).

PATIENTS AND METHODS: The current study is a cross-sectional evaluation of 25 patients with Prader-Willi syndrome (mean age 11.3 ± 8.2 years), with a total of 183.6 patient-years of regular follow-up (from the first visit to the center to the data collection cutoff date), compared with 24 age-, sex-, and BMI-matched healthy controls (mean age 11.3 ± 3.9 years). Each participant underwent anthropometric measurements, physical examination, biochemical and hormonal blood sampling, and whole-body DXA scan. Statistical analysis (SPSS 15.0 statistical package, Chicago, IL, USA) was performed to assess the relations between the metrics in the PWS group compared with controls.

RESULTS: Patients with PWS showed a better profile of glucose homeostasis with significantly lower serum insulin concentration and calculated HOMA-IR index compared with the controls (p < 0.05). Taking into consideration age, sex, and body mass index (BMI) in the PWS group, the analysis showed strong positive correlations between waist circumference (WC) and systolic blood pressure (SBP) (r = 0.864, p < 0.001), and WC and diastolic blood pressure (DBP) (r = 0.534, p = 0.033). Partial correlation analysis with respect to age, sex, and pubertal development found significant positive WC correlations with insulin (r = 0.796, p = 0.006), HOMA-IR (r = 0.697, p = 0.025), LDL-cholesterol (r = 0.735, p = 0.002), uric acid (r = 0.735, p = 0.002), CRP (r = 0.600, p = 0.023), and leptin (r = 0.730, p = 0.005). Strong negative correlations existed between WC and SHBG (r = -0.772, p = 0.002) and HMW adiponectin (r = -0.998, p = 0.044). Additionally, a negative correlation of HMW adiponectin and SBP was demonstrated. 88% of the patients were treated with recombinant human growth hormone (rhGH). Bone mineral density adjusted for height (BMD/height) was significantly lower in patients with PWS (p < 0.05) compared with healthy controls. The analysis did not reveal significant relationships between BC compartments and metabolic and auxological parameters in the PWS group.

CONCLUSION: Our study confirms that patients with PWS have a favorable metabolic profile compared with healthy controls matched by age, sex, and BMI. Syndromic participants who manifest greater accumulation of abdominal adipose tissue have a higher risk of hemodynamic changes and metabolic disturbances predictive of the development of cardiovascular diseases (CVD) in adulthood. WC could serve as a predictive marker for detecting higher metabolic risk in this syndromic group of patients, and both WC and HMW adiponectin for hypertension. In the future, on this basis, we could possibly implement both of these metrics in clinical practice.

PMID:42087144 | DOI:10.1186/s12902-026-02302-1

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Short-term clinical and micromorphological comparison of injectable and paste composites in occlusal cavities

BMC Oral Health. 2026 May 5. doi: 10.1186/s12903-026-08472-7. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this clinical trial was to evaluate and compare the 12-month performance of a contemporary injectable and a conventional paste-type resin composite in Class I cavities using the modified USPHS criteria, supported by SEM analysis.

METHODS: A total of 72 teeth from 34 volunteers were included. Each participant received at least two restorations (one per material); in cases where more eligible cavities were present, additional restorations were performed accordingly. All restorations were performed under rubber dam isolation following conservative Class I cavity preparation, using selective enamel etching and a universal adhesive. All procedures were carried out by the same clinician using a paste-type resin composite (Filtek Z250 Universal Restorative) and an injectable resin composite (G-ænial Universal Injectable). Two calibrated investigators evaluated restorations at baseline, 6, and 12 months using modified USPHS criteria. SEM analysis was conducted on a total of 66 epoxy replicas obtained at baseline, 6, and 12 months from 11 randomly selected participants. Statistical analysis was performed using SPSS (Version 23.0, IBM, NY) with Pearson’s chi-square and Cochran’s Q tests.

RESULTS: Both materials demonstrated comparable and clinically acceptable performance over the 12-month evaluation period according to the modified USPHS criteria, with no statistically significant differences observed at any time point across all criteria, although minor changes were observed in marginal adaptation and color match in a few restorations (p > 0.05). All participants attended the follow-up visits, resulting in a 100% recall and retention rate.

CONCLUSION: The injectable (G-ænial Universal Injectable) and paste-type (Filtek Z250) resin-composites demonstrated comparable and clinically acceptable short-term performance in Class I occlusal restorations, although longer-term follow-up is needed to confirm these findings.

TRIAL REGISTRATION: As trial registration took place after the first participant was enrolled, the study was retrospectively registered at ClinicalTrials.gov on December 21, 2023, with ID: NCT06192667. https://register.

CLINICALTRIALS: gov/prs/beta/studies/S000DTX600000072/recordSummary/.

PMID:42087142 | DOI:10.1186/s12903-026-08472-7

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Investigation of copper and oxidative stress levels in oral contraceptive users

BMC Womens Health. 2026 May 5. doi: 10.1186/s12905-026-04519-7. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the relationship between oxidative stress parameters [total oxidant status (TOS), total antioxidant status (TAS), thiol/disulfide homeostasis, ischemia-modified albumin (IMA)] and serum copper levels in women who use oral contraceptives (OCs) compared to those who do not.

METHODS: This single-center, prospective case-control study included a total of 154 women aged 18 to 45 years (72 OC users and 82 non-users) who presented to the gynecology outpatient clinic of a tertiary care training and research hospital. After obtaining written informed consent, demographic data and information regarding OC use were collected. Venous blood samples were drawn and serum samples were stored at -80 °C until analysis. Serum levels of TOS, TAS, total thiol, native thiol, disulfide, IMA and copper were measured. A p-value of < 0.05 was considered statistically significant.

RESULTS: In OC users, serum levels of copper, TOS, oxidative stress index (OSI), disulfide and IMA were significantly elevated, whereas TAS and native thiol levels were significantly reduced compared to non-users (p < 0.05). Serum copper levels showed a positive correlation with oxidative stress markers and a negative correlation with antioxidant capacity indicators.

CONCLUSIONS: OC use is associated with increased serum copper levels, which in turn have a significant impact on oxidative stress biomarkers. These findings suggest that OC use elevates systemic oxidative stress while compromising antioxidant defense mechanisms. Moreover, elevated copper levels may independently contribute to oxidative stress regardless of OC use.

PMID:42087140 | DOI:10.1186/s12905-026-04519-7

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Plasmodium vivax infection in Duffy-negative populations in Sudan: a systematic review and meta-analysis of host-parasite genetic adaptation

Malar J. 2026 May 5. doi: 10.1186/s12936-026-05923-y. Online ahead of print.

ABSTRACT

BACKGROUND: Sudan is one of the few African countries reporting increasing Plasmodium vivax infections despite the high prevalence of the Duffy-negative phenotype, historically considered protective against this parasite. Emerging molecular evidence challenges this paradigm. The objective of this systematic review and meta-analysis was to synthesize evidence on the prevalence and geographic distribution of P. vivax infection, Duffy antigen polymorphisms, parasite genetic adaptations, and diagnostic limitations in Sudan.

METHODS: This review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and was registered in PROSPERO (CRD42025127714). The reports of P. vivax infection in Sudan focusing on host Duffy status and the parasite genetic variability from 2005 to 2025 were identified through systematic searches of PubMed, Web of Science, Scopus, and EMBASE with predefined Boolean search operators. To determine the risk of bias, the Joanna Briggs Institute prevalence study checklist was employed. To obtain a pooled prevalence estimate in Duffy-negative individuals, a random-effects meta-analysis (DerSimonian-Laird estimator) was conducted. Heterogeneity was assessed using Cochran’s Q test and the I2 statistic, while publication bias was evaluated using funnel plots and Egger’s regression test.

RESULTS: A total of sixteen studies conducted between 2005 and 2025, including 5,753 participants from various regions of Sudan, were included. P. vivax infection was reported in both Duffy-positive and Duffy-negative individuals. Meta-analysis of five studies reporting host Duffy antigen status showed a pooled prevalence of P. vivax infection of 11.7% (95% CI 7.2-17.3%) among Duffy-negative individuals. The studies showed moderate heterogeneity (I2 = 56%). Substantial genetic diversity was observed in the P. vivax Duffy Binding Protein (PvDBP), including multiple haplotypes and both Malagasy-type and Cambodian-type gene duplications. Most studies were assessed as having low to moderate risk of bias, and funnel plot inspection did not suggest substantial publication bias, although interpretation is limited by the small number of studies.

CONCLUSIONS: This systematic review and meta-analysis provide evidence that P. vivax infection occurs among Duffy-negative individuals in Sudan, challenging the long-standing assumption of complete Duffy-mediated protection. The observed parasite genetic diversity highlights adaptive mechanisms that may facilitate infection in Duffy-negative hosts. Strengthening molecular surveillance and integrating host-parasite genomic data into national malaria control programs will be critical to inform malaria elimination strategies and vaccine development in Africa.

PMID:42087123 | DOI:10.1186/s12936-026-05923-y

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Accuracy of Zygomatic Implant Placement Using Completely Versus Partially Guided

BMC Oral Health. 2026 May 6. doi: 10.1186/s12903-026-08436-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Zygomatic implant placement is a challenging surgical procedure, as the implants are inserted with limited accessibility and visibility. The aim of this study was to compare the accuracy of completely limiting versus partially limiting computer-generated 3D surgical guides for zygomatic implant placement in patients with atrophic maxillae.

MATERIALS AND METHODS: This prospective randomized controlled study included participants with atrophic posterior maxilla indicated for zygomatic implant (ZI) placement. The participants were randomly allocated to one of two groups. Group I received ZI using completely limiting 3D computer-guided surgical templates, while Group II underwent ZI placement using partially limiting 3D computer-guided surgical templates. The primary outcome variable was the accuracy of implant placement, which was assessed by measuring linear deviations at the implant coronal and apical points, as well as angular deviations. The secondary outcome was the duration of the operative time.

RESULTS: This study evaluated 12 zygomatic implants (6 per group) in 6 patients (mean age: 56.9 ± 7.57 years). Baseline demographics and clinical features were well-balanced between groups, with comparable age and sex distributions. There were no statistically significant differences in linear or angular deviations between the groups, except for a statistically significant greater apical deviation in the midsagittal plane for Group II (p = 0.015). Group II had a significantly shorter mean operative time (21.17 ± 2.14 min) than Group I (27 ± 2.37 min) (p = 0.01). No dropouts or postoperative complications (e.g., infection, peri-implantitis, or sinus-related issues) have occurred.

CONCLUSIONS: Within the limitations of the sample size of this study, the partially limiting surgical guide could provide a successful and less invasive treatment modality for zygomatic implant placement, as it significantly reduces the surgical time with comparable overall accuracy. However, the completely limiting guide demonstrates superior control at the critical apical implant position.

TRIAL REGISTRATION: ClinicalTrials.org (NCT06227351) 2024-02-05.

PMID:42087122 | DOI:10.1186/s12903-026-08436-x