Category: Nevin Manimala

Front Cell Dev Biol. 2026 Jun 18;14:1840498. doi: 10.3389/fcell.2026.1840498. eCollection 2026.

ABSTRACT

BACKGROUND: Maternal recognition of pregnancy (MRP) in the mare requires coordinated adaptations of both the conceptus and the endometrium during the peri-recognition interval; however, integrated transcriptomic analyses of both compartments within the same biological window remain limited. Here, we analyzed conceptus RNA-seq data across embryonic age (Days 8 and 12 post ovulation) and endometrial RNA-seq data across pregnancy status (pregnant versus non-pregnant mares sampled between Days 8 and 12 post ovulation). In pregnant mares, conceptus recovery and endometrial biopsy collection were performed within the same gestation, allowing biological integration of embryo and maternal transcriptomes while preserving tissue-specific statistical contrasts.

RESULTS: RNA-seq analysis followed by TMM normalization and voom-limma modeling identified differential expression in both compartments. Differential expression was defined by an adjusted P-value (FDR threshold <0.001). The B-statistic (log-odds of differential expression) was used to prioritize high-confidence candidates for interpretation and downstream modeling, considering genes with a Bayesian posterior probability >1. Gene-level interpretation was restricted to transcripts with a Bayesian posterior probability of differential expression (B > 1). In the conceptus, high-confidence upregulated genes from day 8 to 12 included steroidogenic enzymes (CYP19A1, CYP17A1), extracellular matrix components (COL4A1, COL4A2, COL4A5, SPON1, DSG2), protease regulators (SERPINE1, TMPRSS2, LGMN), and selective transporters (AQP5, SLC2A5, ATP1B3). In the endometrium, downregulated genes in pregnant mares included immediate-early transcriptional regulators (EGR1, FOS, DUSP1) and oxidative stress-associated genes (GSTA4), while upregulated genes in pregnant mares included signaling and regulatory components (HRAS, PUM3, U2AF1L4, COPS6), complement regulator C4BPA, and mitochondrial sulfide metabolism gene SQOR. Functional enrichment analysis supported coordinated extracellular matrix organization and signaling modulation without enrichment of inflammatory pathways.

CONCLUSION: Matched transcriptomic profiling reveals coordinated but compartment-specific gene regulation at the onset of early equine pregnancy. The conceptus exhibits endocrine and interface specialization, whereas the endometrium demonstrates attenuation of immediate-early transcriptional programs and selective signaling recalibration. These data define a high-confidence systems-level framework for early embryo-maternal communication that precedes the classical maternal recognition phase and is consistent with early embryo-maternal communication associated with the transition toward maternal recognition.

PMID:42396560 | PMC:PMC13325742 | DOI:10.3389/fcell.2026.1840498

PCN Rep. 2026 Jul 2;5(3):e70355. doi: 10.1002/pcn5.70355. eCollection 2026 Sep.

ABSTRACT

AIM: Anorexia nervosa (AN) is a severe psychiatric disorder causing life-threatening physical conditions. Management strategies differ between the restricting subtype (ANR) and the binge-eating/purging subtype (ANBP), with underreported binge-eating/purging behaviors. Objective biomarkers are needed to detect these behaviors for improved treatment. This study explored fingertip autofluorescence (FAF) Advanced Glycation End Products (AGEs), reflecting carbonyl stress, to assess their potential in reflecting binge-eating/purging behavior in AN.

METHODS: This cross-sectional study involved 26 female patients with AN and 27 healthy control (HC) participants. Participants completed the Eating Disorder Examination Questionnaire 6.0 (EDE-Q 6.0) and underwent percutaneous fluorescence measurement of AGE levels. Statistical analysis included one-way anova with Tukey’s Honestly Significant Difference (HSD) test, Pearson correlation, and multiple linear regression to determine if EDE-Q items predicted fingertip AGE levels in patients with ANBP.

RESULTS: Fingertip AGE levels and all EDE-Q 6.0 subscale scores significantly differed among groups (p < 0.05). Post hoc analyses indicated that participants with ANBP had significantly higher fingertip AGE levels than those with ANR. Correlation analysis showed that the frequency of binge-eating and vomiting significantly positively correlated with fingertip AGE levels. Stepwise regression analysis suggested that the frequency of vomiting significantly predicted fingertip AGE levels.

CONCLUSION: Fingertip AGE levels were higher in patients with ANBP than in those with ANR. Purging behavior, which was significantly correlated with binge-eating behavior in the ANBP group, was suggested to be a primary determinant of elevated AGE levels. Fingertip AGE levels may serve as objective biomarkers for detecting these behaviors and facilitating improved treatment strategies.

PMID:42396552 | PMC:PMC13324242 | DOI:10.1002/pcn5.70355

Open Mind (Camb). 2026 Jun 17;10:808-826. doi: 10.1162/OPMI.a.358. eCollection 2026.

ABSTRACT

This study examined visual statistical learning using EEG-based steady-state visual evoked potentials (SSVEP). Fifty-one adults were exposed to image sequences organized into triplets across three conditions (n = 17 per condition) in which the alignment of category-level and exemplar-level information was manipulated. Neural entrainment at the triplet frequency (1.11 Hz) differed significantly across conditions (η _p ² = .13), with stronger responses in the Single-Category and No-Category conditions than in the Mixed-Category condition. There were no differences at the image frequency (3.33 Hz; η _p ² = .05). Behavioral reaction times mirrored this pattern, showing faster responses to the last exemplar in the triplet in the Single-Category (η _p ² = .71) and No-Category (η _p ² = .22) conditions, but not in the Mixed-Category (η _p ² = .10) condition. Both signal-to-noise ratio (SNR) and inter-trial coherence (ITC) captured neural entrainment across fronto-central and parietal-occipital electrode clusters. These findings validate SSVEP as an online measure of visual statistical learning and demonstrate that category-exemplar mismatch interfered with statistical learning.

PMID:42396548 | PMC:PMC13327787 | DOI:10.1162/OPMI.a.358

Int J Nurs Stud Adv. 2026 Jun 15;11:100600. doi: 10.1016/j.ijnsa.2026.100600. eCollection 2026 Dec.

ABSTRACT

BACKGROUND: Healthcare workers are frequently exposed to workplace violence (including threats and physical aggression), which may increase the risk of burnout complaints through maladaptive coping behaviours such as harmful alcohol use. Leadership climate may buffer these adverse effects by fostering psychological safety and supportive supervisor-employee interactions. This study examined whether leadership climate moderates the association between violence and harmful alcohol use, whether the indirect association between violence and subsequent burnout via harmful alcohol use depends on leadership climate, and whether these pathways differ between physicians and nurses.

METHODS: Two-wave panel data were drawn from the Longitudinal Occupational Health Survey in Healthcare Sweden (LOHHCS). The sample included 2446 healthcare workers. Violence, harmful alcohol use, and leadership climate were assessed at Time 1, while burnout was measured at Time 2. Moderated mediation analyses were conducted using the PROCESS macro.

RESULTS: Violence was positively associated with harmful alcohol use, with this association weakened under stronger leadership climate. The conditional indirect prospective association between violence and later burnout through harmful alcohol use was evident primarily under weaker leadership conditions (b = 0.007, 95% CI [0.001, 0.016]) and nonsignificant under moderate or strong leadership. Formal tests did not indicate statistically significant differences between professional groups.

CONCLUSIONS: A supportive leadership climate may play a modest protective role in the associations between violence and harmful alcohol use and subsequent burnout. Despite small effect sizes and limited causal inference, consistency with theory suggests that leadership climate may play a meaningful protective role in violence-exposed healthcare environments.

REGISTRATION: Swedish Occupational and Education Registries.

PMID:42396545 | PMC:PMC13324672 | DOI:10.1016/j.ijnsa.2026.100600

Res Sq [Preprint]. 2026 Jun 23:rs.3.rs-9798756. doi: 10.21203/rs.3.rs-9798756/v1.

ABSTRACT

INTRODUCTION Background : Depression and suicidality are prevalent among individuals with chronic illnesses. Data on their prevalence in children and adolescents with sickle cell anaemia in Uganda is limited. This study aimed to determine the prevalence and associated factors of depression and suicidality among children with SCA in Eastern Uganda. Methods :We consecutively enrolled children with SCA between 9 and 17 years, at Mbale Regional Referral Hospital between 01/02/2024 and 05/06/2024. Depression and suicidality were measured using the MINI KID. Data were collected using an interviewer administered questionnaire and entered into KoboToolbox for electronic data management. Analysis was performed using Stata 17. Bivariate and multivariable logistic regression analyses were done to examine factors associated with depression and suicidality.Statistical significance was assessed at the 0.05. Results :421 participants were enrolled, the prevalence of depression was 31.8%, while suicidality was 19.0%. The Factors associated with depression, were secondary level of education (AOR: 3.5, 95% CI: 1.965-12.756; p = 0.049), Children with formally employed parents or guardians (AOR: 3.3, 95% CI:1.399-7.675, P = 0.006), Household income over 150,000 Uganda Shillings monthly (AOR: 0.3, 95% CI: 0.126-0.937, p = 0.037), 5-10 past year admissions (AOR:3.1, 95% CI: 1.651-5.749, p < 0.001). For suicidality,being aged 13-17 years (AOR:2.3, 95% CI:1.398-3.809, p = 0.001), Medication side effects (AOR:1.6, 95% CI:1.105-6.121; p = 0.039). Conclusion :1 in 3 children aged 9-17 years were depressed. Older children and adolescents living with SCA had a higher risk of depression and suicidality. Findings highlight the magnitude of mental health challenges,and underline the need for integrated mental health screening within chronic disease management.

PMID:42396527 | PMC:PMC13321266 | DOI:10.21203/rs.3.rs-9798756/v1

Res Sq [Preprint]. 2026 Jun 28:rs.3.rs-9977950. doi: 10.21203/rs.3.rs-9977950/v1.

ABSTRACT

Background Mobile populations in malaria-endemic regions are at increased risk of Plasmodium falciparum infection and may contribute to the spread of antimalarial drug resistance across borders. However, evidence on infection prevalence, molecular resistance markers, and associated risk factors in these populations remains limited. This systematic review and meta-analysis synthesized available evidence to inform mobility-responsive malaria surveillance and control strategies. Methods A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Studies published between January 2000 and October 2025 reporting P. falciparum infection and resistance-associated mutations in PfK13, PfCRT, PfMDR1, PfDHFR, and PfDHPS among mobile populations were included. PubMed, EMBASE, Global Health, and Scopus were searched. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Pooled prevalence estimates were generated using random-effects models in Stata 17, with subgroup analyses by WHO region and population type. Heterogeneity was assessed using I² statistics. Results Twenty-six studies involving 7,217 participants from 10 countries were included. Populations studied comprised refugees, migrant workers, travellers, forest-goers, gold miners, and nomadic groups. The pooled prevalence of P. falciparum infection was 18% (95% CI: 15-21%), with higher prevalence in Africa (36%) and lower prevalence in South-East Asia (6%). Refugees had the highest pooled prevalence (38%), whereas short-term travellers had lower prevalence (8%). Resistance markers were widely reported, although prevalence varied across settings and time periods. PfK13 mutations were generally infrequent but heterogeneous; validated mutations such as C580Y were repeatedly detected in Myanmar and neighbouring areas of Cambodia and Vietnam, indicating artemisinin resistance hotspots. PfCRT K76T remained common in older studies. PfMDR1 mutations, especially N86Y and Y184F, were frequently reported and reached up to 68% in African refugee populations, although declining trends were noted in recent African studies. PfDHFR and PfDHPS mutations were widely distributed. Infection risk was associated with mobility patterns, occupational exposure, and parasite origin. Substantial heterogeneity was observed (I² = 97.8%). Conclusion Mobile populations bear a substantial burden of P. falciparum infection and frequently harbor antimalarial drug-resistance markers. Integrating these populations into genomic and cross-border surveillance systems may improve early detection of resistance and strengthen malaria elimination efforts.

PMID:42396518 | PMC:PMC13321344 | DOI:10.21203/rs.3.rs-9977950/v1

Res Sq [Preprint]. 2026 Jun 23:rs.3.rs-9944700. doi: 10.21203/rs.3.rs-9944700/v1.

ABSTRACT

Purpose To investigate the diagnostic utility of the ganglion cell layer (GCL) to inner plexiform layer (IPL) thickness ratio, in differentiating branch retinal vein occlusion (BRVO) from primary open-angle glaucoma (POAG) exhibiting hemifield defects. Given the impact of POAG on the ganglion cell complex (GCC), we hypothesized that POAG wound show disproportionately greater thinning in the GCL and tested if the GCL:IPL ratio could differentiate between these two conditions. Methods We conducted a retrospective case series of macular OCT images (Spectralis [Heidelberg Engineering, Heidelberg, Germany]) from patients with old BRVO/HRVO and POAG. Inclusion criteria were 1) BRVO/HRVO Diagnosis at least 6 months, without macular edema at the time of imaging, and 2) POAG with an arcuate or altitudinal hemifield defect on Humphrey Visual Field (Carl Zeiss Meditec, Inc., Dublin, CA). Exclusion criteria were the presence of poor-quality OCT scans, history of pan-retinal photocoagulation (PRP), corneal, retinal or neuroophthalmological conditions. Using the Heidelberg automated segmentation analysis of the macular cube, a 20-degree PMB grid was centered over the foveal pit and utilized to generate a 6×10 grid to provide a comprehensive assessment of the retinal layers in the macular region. The GCL:IPL ratio was calculated by dividing the GCL by the corresponding IPL thickness. Calculation of the inner retina:total retina ratio was done in an identical manner, and the average thicknesses and ratios were then compared using the Wilcoxon rank-sum test (MedCalc Statistical Software, Ostend Belgium). Results Final analysis included 60 eyes of 60 patients (mean age 67 ± 13 years; 57% female; 42% African American, 28% Hispanic, 12% White, 18% as others) diagnosed with old BRVO/HRVO (n = 30) or POAG (n = 30). Patients with POAG had an average visual field mean deviation of -16.22dB ± 5.02. The GCL:IPL ratio was significantly lower in patients with POAG was 0.91 (95% CI [0.85, 0.94]) compared to RVO with 1.14 (95% CI [1.09, 1.17], ( P < 0.0001). By adopting the GCL:IPL ratio of less than 1 as a diagnostic marker for POAG, the area under the curve (AUC) was 0.83, with a sensitivity of 90.0% and a specificity of 76.7%. Conclusions There was disproportionately greater thinning in the GCL compared to the IPL in patients with POAG compared to those with RVO as evidenced by the observed differences in GCL:IPL ratios. Our findings characterized by high AUC and sensitivity suggest that the GCL:IPL ratio has potential to be a marker for distinguishing between old BRVO and POAG with hemifield defects.

PMID:42396514 | PMC:PMC13321245 | DOI:10.21203/rs.3.rs-9944700/v1

Res Sq [Preprint]. 2026 Jun 25:rs.3.rs-8524201. doi: 10.21203/rs.3.rs-8524201/v1.

ABSTRACT

Correlation matrices are fundamental summaries of functional brain networks, yet standard analyses often treat entries independently, ignoring the curved geometry of correlation space. Existing geometric methods frequently lack closed-form operations or depend on arbitrary region ordering, limiting scalability.We introduce a scalable geometric framework with two components: (i) the Off-log metric, a smooth transformation mapping correlation matrices to symmetric zero-diagonal matrices. This enables closed-form expressions for distances, Fréchet means, and linear models, allowing standard statistical modeling without complex manifold optimization. (ii) Grassmannian subspace discrimination, which compares subjects via principal-angle distances between eigenvector subspaces, resolving inherent sign and basis ambiguities.Both components integrate into standard machine-learning workflows for inference, regression, and classification. Validated across two clinical cohorts (Parkinson’s and psychosis) and three ageing fMRI datasets, the Off–log metric increased sensitivity in permutation tests and matched or exceeded Riemannian and Euclidean baselines in classification. Brain-age prediction performance was comparable, with Riemannian metrics excelling in two of three cohorts. The Grassmannian method consistently outperformed Euclidean baselines, highlighting disease-relevant networks. Overall, geometry-aware representations improve sensitivity and predictive performance while remaining straightforward to deploy at scale.

PMID:42396505 | PMC:PMC13321239 | DOI:10.21203/rs.3.rs-8524201/v1

Res Sq [Preprint]. 2026 Jun 22:rs.3.rs-10093844. doi: 10.21203/rs.3.rs-10093844/v1.

ABSTRACT

BACKGROUND: The claim that Monte Carlo is the most accurate method is a case of misattributed credit. This claim is based on experience with advanced systems MC- NPX, Geant4 and EGS. These systems achieve remarkable performance because they use most accurate physics, not because they use random numbers. The latter simpli es algorithms, but contaminates the solution with random noise. Currently prevalent fast Monte Carlo algorithms retain this worst part while achieving high computing speed at the expense of the best part – accurate physics. We employ an opposite strategy. We develop a Boltzmann solver for protons that retains unchanged the physics of most ad- vanced Monte Carlo systems. We eliminate random noise, because our solution method is deterministic. Our method is also applicable to heavier ions, helium and carbon, for example.

PURPOSE: To develop a fast and accurate deterministic Boltzmann solver for protons. It calculates dose distributions and uence spectra. The spectra are needed for biolog- ical modelling. The main application is treatment planning of proton beam therapy.

METHODS: We solve the Boltzmann transport equation using an iterative procedure. Our algorithm accounts for Coulomb scattering and nuclear reactions. It uses the same physical models, as do the most rigorous Monte Carlo systems. Thereby it achieves the same low level of systematic errors. Our solver does not involve random sampling. The solution is not contaminated by statistical noise. This means that the overall un- certainties of our solver are lower than those realistically achievable with Monte Carlo. Furthermore, our solver is orders of magnitude faster. Its another advantage is that it calculates uence spectra. They are needed for calculation of relative biological e ec- tiveness, especially when advanced radiobiological models are used that may present a challenge for other algorithms.

RESULTS: We have developed a novel Boltzmann equation solver, have written pro- totype software, and completed its testing for calculations in water. For 40-220 MeV protons we calculated uence spectra, depth doses, three-dimensional dose distribu- tions for narrow Gaussian beams. The CPU time was 5-11 ms for depth doses and uence spectra at multiple depths. Gaussian beam calculations took 31-78 ms. All the calculations were run on a single Intel i7 2.9 GHz CPU. Comparison of our solver with Geant4 showed good agreement for all energies and depths. For the 1%/1 mm -test the pass rate was 0.95-0.99. In this test, 1% was the di erence between our and Geant4 doses at the same point. The test included low dose regions down to 1% of the maximum dose.

CONCLUSIONS: Results of the study provide a foundation for achieving a high comput- ing speed with uncompromised accuracy in proton treatment planning systems.

PMID:42396489 | PMC:PMC13321288 | DOI:10.21203/rs.3.rs-10093844/v1

Front Immunol. 2026 Jun 18;17:1844666. doi: 10.3389/fimmu.2026.1844666. eCollection 2026.

ABSTRACT

We conducted a retrospective review of adult kidney transplant recipients (KTRs) who received belatacept in addition to calcineurin inhibitors, antimetabolites, and corticosteroids for recurrent or refractory rejection or for persistent donor-specific antibodies (DSAs) unresponsive to standard therapy. Fifteen recipients were included. Kidney function remained stable on follow-up; median eGFR was 52 mL/min (R 23-91) at baseline and 54 mL/min (R 25-105) at 6 months (p = 0.15) after belatacept initiation. The DSA intensity declined significantly from a median of 4,990 mean fluorescence intensity (MFI) (R 0-23,305) at baseline to 1,644 MFI (R 0-6,903) at 3-6 months (p = 0.03). There was also a small reduction in biopsy-proven rejections from 85.7% to 63.6%. Infections occurred in most recipients (73.3%), with a majority arising more than 6 months after therapy initiation. Two patients developed post-transplant lymphoproliferative disorder (PTLD), each with either substantial prior exposure to lymphocyte-depleting agents or prolonged immunosuppression. Two deaths occurred, one related to PTLD and one to septic shock. These findings suggest that belatacept-based quadruple immunosuppression may reduce DSA and stabilize kidney function in patients with persistent alloimmunity, but without a statistically significant reduction in rejections. There is also a significant burden of infections and PTLD, highlighting the need for careful patient selection and caution before adopting this approach.

PMID:42396448 | PMC:PMC13322944 | DOI:10.3389/fimmu.2026.1844666