Category: Nevin Manimala

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

Ren Fail. 2026 Dec;48(1):2694246. doi: 10.1080/0886022X.2026.2694246. Epub 2026 Jul 2.

ABSTRACT

BACKGROUND: Patients with advanced chronic kidney disease (CKD) and dyslipidemia are at high risk of kidney failure and cardiovascular events, yet many do not receive lipid-lowering therapy. Pentoxifylline (PTX) has anti-inflammatory and antifibrotic properties, but its association with hard cardiorenal outcomes remains uncertain.

METHODS: We conducted a retrospective cohort study of adults with stage 3b-5 CKD and dyslipidemia enrolled in a pre-end-stage renal disease program from 2007 to 2018. Patients receiving lipid-lowering therapy were excluded. PTX initiators were matched 1:1 to nonusers using propensity score matching. The primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes included major adverse cardiovascular events (MACE), 50% estimated glomerular filtration rate decline within 2 years, and doubling of serum creatinine. Sensitivity analyses included time-varying exposure, lag, and landmark analyses.

RESULTS: Among 3,542 eligible patients, 2,776 were included in the matched cohort. PTX use was associated with lower risks of ESKD (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.75-0.96) and MACE (HR, 0.80; 95% CI, 0.65-0.98). No significant associations were observed for short-term kidney function decline or creatinine doubling. Time-related sensitivity analyses attenuated estimates toward the null but did not suggest harm.

CONCLUSION: In patients with advanced CKD and untreated dyslipidemia, PTX use was associated with lower risks of kidney failure in propensity score-matched analyses, whereas the association with cardiovascular events was less robust after sensitivity analyses. These findings require cautious interpretation and further validation.

PMID:42393494 | DOI:10.1080/0886022X.2026.2694246

Ren Fail. 2026 Dec;48(1):2678061. doi: 10.1080/0886022X.2026.2678061. Epub 2026 Jul 2.

ABSTRACT

BACKGROUND: Urological complications remain a significant source of morbidity following kidney transplantation, often leading to re-intervention and graft dysfunction. Although advances in surgical technique and perioperative care have reduced incidence rates, controversy persists regarding risk predictors and the prophylactic role of double-J ureteral stenting.

METHODS: We retrospectively analyzed 425 adult kidney transplant recipients at a single tertiary center between January 2008 and December 2023. Patient demographics, donor characteristics, surgical variables, and postoperative outcomes were reviewed. Complications were defined as urinary leak, ureteral stricture, or anastomotic obstruction requiring intervention within 12 months. Data were compared across three eras (2008-2012, 2013-2017, 2018-2023). Multivariable logistic regression identified independent risk factors.

RESULTS: Overall, 11.1% (n = 47) of patients developed urological complications. Ureteral stricture was the most frequent (57%), followed by urinary leak (28%) and anastomotic obstruction (15%). Older recipient age (OR 1.04, 95% CI 1.01-1.07, p = 0.012), re-transplantation (OR 2.95, 95% CI 1.12-7.77, p = 0.028), and deceased donor grafts (OR 2.17, 95% CI 1.12-4.19, p = 0.021) were independent predictors. Prophylactic double-J ureteral stenting demonstrated a non-significant protective trend (OR 0.71, 95% CI 0.44-1.15, p = 0.091). Routine stenting in Era 3 coincided with a non-significant reduction in leak and stricture rates.

CONCLUSION: Older age, re-transplantation, and deceased donor grafts independently predicted complications, while prophylactic stenting showed a non-significant protective effect. Further multicenter studies are needed to validate these findings and optimize stent protocols.

PMID:42393492 | DOI:10.1080/0886022X.2026.2678061

Shock. 2026 Jul 2. doi: 10.1097/SHK.0000000000002891. Online ahead of print.

ABSTRACT

INTRODUCTION: Smoke inhalation injury alone or combined with burns and other traumas remains a serious threat for military members as well as the civilian population. It causes acute respiratory distress syndrome requiring life-saving interventions (LSI), including various respiratory support e.g., oxygen supplementation, intubation, and non-invasive or invasive mechanical ventilation. While potentially scarce in austere environments and/or during mass casualties, LSI require trained personnel, equipment, and resources. In this study, we tested the hypothesis that nebulized epinephrine can delay the need for LSI using the clinically relevant ovine model of smoke inhalation.

METHODS: Adult Merino female sheep were surgically instrumented with multiple catheters five to seven days prior to the study. After recovery from surgery, sheep were subjected to smoke inhalation (48 breaths of cooled cotton smoke inhalation below 40°C) under anesthesia and analgesia. Then, sheep were randomly allocated to two groups. Sheep in the control group were injured and treated with saline nebulization (n=6). Sheep in the treatment group were injured and treated with epinephrine nebulization (n=6). Nebulization was started immediately following injury and repeated every 4 hours.After the smoke inhalation injury, sheep were allowed to spontaneously breath room-air via a mechanical ventilator set with PEEP=0 and pressure support (PS)=0, which is equal to no mechanical support. An arterial blood gas analysis was determined every hour to adjust respiratory support, if needed. The changes in FiO2, PaO2/FiO2 ratio, PEEP, and P support were recorded every hour from the onset of smoke injury.The primary outcomes were variables comparing of oxygen demand, PaO2/FiO2 ratio, PEEP, and P support as representatives of the LSI. The secondary outcomes were comparison of systemic hemodynamics, bloodless lung wet-to-dry weight ratio, and histological analysis. Statistical significance was set at P<0.05.

RESULTS: The time from the onset of smoke injury until the FiO2 increased over 25% in the treatment group was significantly longer than in the control group (p=0.0406). The time until the FiO2 increased over 30% in the treatment group was significantly longer (p=0.0474). The time until the PaO2/FiO2 ratio decreased below 300 in the treatment group was significantly longer than in the control group (p=0.0195). The time for the increase in PEEP over 5 cmH2O in the treatment group was significantly delayed compared to the control group (p=0.0050). One animal in the control group required positive pressure mechanical ventilation vs. zero in the treatment group.

CONCLUSIONS: The present data indicate that nebulized epinephrine delays the need for LSI following smoke inhalation injury in ovine model. If it is also effective in humans, nebulized epinephrine may be immediately used at the injury site as an effective resuscitation tool for smoke inhalation victims until they are admitted to the hospital for more progressive care.

PMID:42393491 | DOI:10.1097/SHK.0000000000002891

Dig Dis Sci. 2026 Jul 2. doi: 10.1007/s10620-026-10086-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Rapid gastric emptying (RGE) is conventionally defined as ≥ 70% emptying of a standardized solid meal at 1 h using gastric emptying scintigraphy (GES). However, this threshold is not universally adopted, and variability exists in how accelerated gastric emptying is defined in practice. We aimed to better characterize patients with conventionally defined RGE as well as those with accelerated emptying not meeting this threshold, and to evaluate what clinical differences exist across varying degrees of accelerated gastric emptying.

METHODS: We identified a cohort of 258 adult patients (≥ 18 years old) with increased gastric emptying (≥ 30% emptied at 1 h) at a tertiary medical center. Patients with a history of esophageal, gastric or thoracic surgery were excluded. Patients were stratified into three cohorts based on 1-h gastric emptying percentages: 30-49%, 50-69%, and ≥ 70%. Manual chart review was performed to extract data on demographics, medications, laboratory values, GES indications, and management changes resulting from GES findings.

RESULTS: The majority of patients (n = 205, 79.4%) were in the 30-49% emptying cohort. Only 10 patients (3.9%) met the conventional threshold of ≥ 70% emptying at 1 h. The most common indications for GES were nausea (39.1%), vomiting (33.7%), and abdominal pain (25.6%), with no statistically significant differences in indications across the 3 cohorts. Furthermore, there were no differences in age, sex, BMI, comorbidities, medications, or management changes between the cohorts.

CONCLUSIONS: RGE that meets current consensus criteria is uncommon in clinical practice. Clinical characteristics and interventions were similar among cohorts with different degrees of accelerated emptying. The current cutoff of ≥ 70% emptying at 1 h may not represent a clinically distinct phenotype, emphasizing the need for better criteria to guide diagnosis and management.

PMID:42393488 | DOI:10.1007/s10620-026-10086-6