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Nevin Manimala Statistics

Dual T-cell exhaustion and hyperactivation profiles identify patients with advanced HIV at high risk for fungal co-infections

BMC Infect Dis. 2026 Apr 3. doi: 10.1186/s12879-026-13223-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize immune alterations in PLWH across disease stages and identify laboratory indicators for diagnosing fungal co-infections.

METHODS: We conducted a comprehensive cross-sectional study comparing laboratory immunological parameters-including lymphocyte subsets, activation/exhaustion markers, and plasma cytokines-across patient groups stratified by co-infection type and CD4⁺ T cell count. Statistical significance was assessed using false discovery rate correction.

RESULTS: The most severe immunological compromise was observed in patients with advanced HIV disease (CD4⁺ ≤199 cells/µL) and co-infections, who exhibited profound pan-lymphopenia and a dissociated T cell profile featuring both hyperactivation (HLA-DR/CD38) and exhaustion (loss of CD28). Compared to patients with other opportunistic infections, those with fungal co-infections displayed a distinct immune phenotype characterized by significantly lower CD4⁺ T cell counts (51.32 ± 47.41 vs. 134.27 ± 130.12 cells/µL, q = 0.004) and B cell counts (65.74 ± 56.13 vs. 108.30 ± 101.10 cells/µL, q = 0.024), alongside elevated CD8⁺ T cell activation. Patients with localized Talaromyces marneffei infection had significantly higher CD4⁺ T, CD8⁺ T, and natural killer cell counts than those with disseminated disease, underscoring the importance of preserved cellular immunity in pathogen containment. No significant differences were observed across fungal pathogens or sites of cryptococcal disease. Correlation analysis revealed a strong positive association between HIV viral load and interleukin-10(R² = 0.587, r = 0.632, 95% CI: 0.473 to 0.755, P = 0.014).

CONCLUSION: Specific immunological parameters-particularly severe CD4⁺ and B cell lymphopenia with concurrent CD8⁺ T cell hyperactivation-provide an objective basis for identifying PLWH at high risk for fungal infections. These findings highlight the potential value of adjunctive immunomodulatory strategies alongside antiviral therapy in this patient population.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:41933298 | DOI:10.1186/s12879-026-13223-8

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Nevin Manimala Statistics

Unveiling the Th17/Treg imbalance: a key player in Clostridioides difficile-induced infection

Gut Microbes. 2026 Dec 31;18(1):2653290. doi: 10.1080/19490976.2026.2653290. Epub 2026 Apr 3.

ABSTRACT

Clostridioides difficile infection (CDI) can elicit varying degrees of intestinal inflammation. To investigate the association between CDI and Th17/Treg cell imbalance, fecal DNA was extracted for the specific detection of C. difficile toxins and combined with fecal bacterial culture to identify the presence of CDI. Peripheral blood samples were collected from CDI-positive and CDI-negative patients, and flow cytometry was performed to quantify the proportions of Th17 and Treg cells, as well as to measure the serum levels of IL-17A, IL-23, IL-6, and other cytokines. Moreover, peripheral blood mononuclear cell mRNA was isolated for reverse transcription and real-time PCR analysis to determine the relative expression levels of ROR-γt and Foxp3. Statistical analyses were conducted to evaluate the differences between CDI-positive and CDI-negative groups. The results revealed that CDI-positive patients exhibited an increased proportion of Th17 cells, along with elevated levels of Th17-related cytokines such as IL-23 and IL-17A. Additionally, these patients showed an upregulation in the expression of ROR-γt. a specific transcription factor (TF) for Th17 cells as well as an increased ratio of Th17 and Treg cells. These findings provide phenotypic evidence suggesting that CDI is potentially associated with a dynamic interplay between Th17 and Treg cells, a finding supported by measuring key TFs and proteins. Our experiments examining the effects of TcdA toxin-induced Th17 differentiation in peripheral blood also provide further evidence highlighting the importance of this CDI-triggered immune imbalance via Th17-mediated inflammatory responses.

PMID:41933277 | DOI:10.1080/19490976.2026.2653290

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MRI-based measurement of masseter muscle area: reliability and clinical relevance in acute neck infections

Eur Radiol. 2026 Apr 3. doi: 10.1007/s00330-026-12500-z. Online ahead of print.

ABSTRACT

OBJECTIVES: The role of low muscle mass in acute neck infections is underexplored. This study aimed to validate the reliability of MRI-based masseter muscle area (MMA) measurements, derive normative age-related data in a diverse patient cohort, and evaluate the association between MMA measurements and infection severity and clinical outcomes in patients with acute neck infections.

MATERIALS AND METHODS: In this retrospective single-center study, 526 patients with clinically confirmed acute neck infections who underwent emergency neck MRI had bilateral MMA measured on T2-weighted Dixon images at the mandibular foramen level. MMA was normalized to height squared (MMA/h2). Interobserver reliability of MMA was assessed between two readers using intraclass correlation coefficients (ICC). Among adults, associations with infection severity markers and clinical outcomes were examined using univariable and multivariable tests.

RESULTS: The interobserver agreement for MMA was excellent (ICC = 0.991). MMA/h2 declined significantly with age (r = -0.21, p < 0.01). In adults, MMA/h2 correlated negatively with age, maximal abscess diameter, and length of hospital stay (LOS; p < 0.01 for all); patients with abscesses had lower MMA/h2 than those without (p = 0.002). Multivariable analysis confirmed that MMA/h2 independently predicted abscess diameter after adjustment for age and C-reactive protein (CRP) (p = 0.001), but not LOS (p = 0.136).

CONCLUSION: Opportunistic MRI-based MMA measurements are highly reliable and associated with age, LOS, and abscess presence and size in acute neck infections. Our findings suggest a link between low masseter muscle mass and disease severity in patients with acute neck infections.

KEY POINTS: Question Low muscle mass associates with adverse outcomes in various diseases, yet its prognostic role in acute neck infections remains underexplored. Findings MRI-based masseter muscle area measurements showed excellent reliability, declined with age, and predicted larger abscess diameter and longer hospital stay in adult patients. Clinical relevance Opportunistic MRI measurement of masseter muscle area is reliable and clinically associated with abscess size and length of hospital stay in patients with acute neck infections, providing clinically relevant information and supporting early risk stratification.

PMID:41933254 | DOI:10.1007/s00330-026-12500-z

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Four new hydroxyl fatty acids, gambaoic acids A-C and gambaoic B methyl ester, from Shrimp Jeotgal-derived Bacillus sp. SNB-066

J Antibiot (Tokyo). 2026 Apr 3. doi: 10.1038/s41429-026-00914-2. Online ahead of print.

ABSTRACT

Four new hydroxyl fatty acids (HFAs), gambaoic acids A – C (1 – 3) and gambaoic B methyl ester (4), were isolated from Bacillus sp. SNB-066, a bacterium derived from shrimp jeotgal. The chemical structures of these HFAs were elucidated through extensive spectroscopic data analysis, including mass spectrometry (MS), ultraviolet (UV), and nuclear magnetic resonance (NMR) spectroscopy data. The relative configurations of compounds 2 and 3 were determined using quantum mechanics-based computational analysis with DP4+ statistical calculations. Further specific rotation analyses revealed the absolute configurations of both compounds 2 and 4 as 14 R and 15 R, while compound 3 was assigned as 14S and 15S. Antibacterial activity evaluated by the minimal inhibitory concentration (MIC) assay indicated that only compound 4 exhibited weak activity against the Gram-positive bacteria B. subtilis KCTC 1021 and K. rhizophila KCTC 1915, with MIC values of 64 μg/mL. Further, gambaoic acids B (2) and C (3) exhibited dose-dependent cytotoxicity toward Caco-2 cells, with gambaoic acid C (3) demonstrating a pronounced anti-invasive effect. These findings highlight the diverse bioactivities of the isolated hydroxyl fatty acids and reveal structural features underlying their antimicrobial and anticancer properties.

PMID:41933253 | DOI:10.1038/s41429-026-00914-2

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Gender Differences in Dietary Quality and Dietary Acculturation among Mexican Children of Immigrants

J Immigr Minor Health. 2026 Apr 3. doi: 10.1007/s10903-026-01914-y. Online ahead of print.

ABSTRACT

Childhood obesity-a risk factor for heart disease, type 2 diabetes, other non-communicable diseases and adverse psychosocial experiences-is especially high among children of Mexican immigrants, and among these children, boys have an obesity risk nearly twice as high as girls. Yet little research has examined whether there are also gender differences in the proximate determinants of obesity for this population. This study uses structural equation modeling and the 2003/4-2017/18 National Health and Nutrition Examination Survey to investigate gender differences in a key proximate determinant of obesity-diet-among adolescents with Mexican immigrant parents. We examine (1) whether there are gender differences in dietary quality and dietary acculturation, (2) whether gender differences in the settings in which adolescents eat explain gender differences in these outcomes, and (3) whether these patterns vary by parental acculturation (household language). We find that among adolescents in Spanish-speaking households, boys have significantly lower dietary quality and significantly higher dietary acculturation than girls and that gender differences in some meal settings outside the home contribute to these differences. We do not find statistically significant gender differences in the dietary outcomes or meal settings for adolescents in English-speaking households. Results highlight the importance of considering how gender and social contexts shape the health behaviors of children of Mexican immigrants.

PMID:41933227 | DOI:10.1007/s10903-026-01914-y

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HIF1A, ADRB3, and VEGFA gene expression in human cord blood across gestation: insights toward a pharmacological artificial placenta

Pediatr Res. 2026 Apr 3. doi: 10.1038/s41390-026-04879-8. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies have shown that from the 23rd week of gestation onward, the fetus becomes progressively more hypoxic, with oxygenation levels rising again after 33-34 weeks. The biological significance of this biphasic oxygenation pattern has remained unclear.

METHODS: Umbilical cord blood samples from 100 preterm and 100 full-term neonates were analyzed for blood gas parameters and for HIF1A, ADRB3 (β3-adrenoceptor), and VEGFA gene expression.

RESULTS: A progressive increase in mRNA expression of all three genes was observed with advancing gestational age, followed by a decline during the final weeks of pregnancy. This gene expression trend was inversely correlated with fetal oxygenation status.

CONCLUSION: This study demonstrates that β3-adrenoceptor expression progressively increases with gestational age, supporting the concept that this receptor plays a key role in fetal development and well-being. These findings strengthen the evidence from animal models showing that pharmacological activation of β3-adrenoceptors can reproduce, even after birth, some of the beneficial effects normally provided by the intrauterine environment. Collectively, this work supports the conceptual framework for developing a “pharmacological artificial placenta” aimed at mimicking intrauterine conditions to promote physiological neonatal adaptation.

IMPACT: Recent studies have shown that from the 23rd week of gestation onward, the fetus becomes progressively more hypoxic, with oxygenation levels rising again after 33-34 weeks. However, the biological significance of this biphasic oxygenation pattern had remained unclear. This study demonstrates for the first time that fetal oxygen fluctuations are accompanied by a synchronous and coordinated increase in the mRNA expression of HIF1A, ADRB3 (β3-adrenoceptor), and VEGFA genes. These findings support a mechanistic link between intrauterine hypoxia, β3-adrenergic signaling, and fetal maturation. This work contributes to ongoing research suggesting that pharmacological β3-adrenoceptor activation may help recreate intrauterine-like conditions, potentially promoting physiological fetal development in adverse environments.

PMID:41933214 | DOI:10.1038/s41390-026-04879-8

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Efficacy of the UV-LED treatment to inactivate phytoplankton in port waters: viable organisms, re-growth, and changes in the phytoplankton community

Mar Pollut Bull. 2026 Apr 2;229:119663. doi: 10.1016/j.marpolbul.2026.119663. Online ahead of print.

ABSTRACT

The ultraviolet C (UVC) treatment is used commonly as a Ballast Water Treatment System as a way for the ships to comply with the Ballast Water Management Convention (BWMC) D-2 standards. Developments in the Light Emitting Diodes (LEDs) technology in the range UVC suggest they may become a more sustainable alternative to the conventional UVC sources based on mercury lamps. The objective of this study is to compare the inactivation efficacy of UV treatment using LEDs emitting at 265 and 275 nm with a conventional low-pressure mercury vapor lamp emitting at 254 nm, employing a natural phytoplankton assemblage from the Algeciras (Spain) port-water as the target. Most Probable Number (MPN) indicated a reduction from 490 cell mL-1 into values in compliance with the BWMC D-2 standards by applying UV doses as of 100 mJ cm-2. The growth inhibition was greater than the 90% between 5 and 8 days after the treatment with UV doses as of 100 mJ cm-2; however, greater UV doses resulted effective for limiting the subsequent phytoplankton regrowth. The application of 202.1 ± 25.7 mJ cm-2 caused the reduction of the photosynthetic yield into 0.25, used as a reference for a safe ballast water discharge in indicative analyses. The metabarcoding analysis reported a significant reduction of the phytoplankton taxa with a UV doses as of 200 mJ cm-2. The statistical analyses indicated absence of significant differences between the three wavelengths used in this study, indicating that the UV LEDs are as effective as conventional UVC lamp.

PMID:41931909 | DOI:10.1016/j.marpolbul.2026.119663

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Coupling bayesian optimization and multi-paradigm ensemble learning to predict lead remediation in microbially induced carbonate precipitation: From model performance to crystalline control windows

J Hazard Mater. 2026 Mar 30;508:141918. doi: 10.1016/j.jhazmat.2026.141918. Online ahead of print.

ABSTRACT

Microbially Induced Carbonate Precipitation (MICP), recognized as a highly promising green remediation technology, exhibits lead (Pb) immobilization efficiency governed by the complex and nonlinear coupling of multiple biogeochemical factors. Consequently, achieving precise optimization through traditional experimental approaches remains a formidable challenge. To address this challenge, this study established a data driven framework coupling Bayesian Optimization (BO) with SHapley Additive exPlanations (SHAP). Based on a meticulously curated dataset of 168 high quality experimental records, we systematically evaluated six base models and four Stacking ensemble strategies, while comparing three hyperparameter optimization algorithms. The results indicate that, in small sample scenarios, a refined parameter optimization strategy outperforms complex model stacking. The Bayesian optimized Random Forest (BO-RF) model exhibited the superior generalization capability (R2=0.9035, RMSE=7.988). Furthermore, SHAP analysis successfully decoded the black box of the model, identifying pH, urea dosage, and initial lead concentration as the three dominant factors. The model, for the first time, quantitatively revealed the bell-shaped biphasic response of urea concentration, successfully reconstructing the underlying physicochemical logic of classical enzymatic kinetics (Michaelis Menten and Haldane mechanisms) and microenvironmental Pb speciation evolution (Biotic Ligand Model, BLM) within the algorithmic framework. More importantly, the identified global optimal thresholds (pH > 8.0, urea ≈ 20 g) precisely point to the formation boundary of thermodynamically stable calcite from statistical and thermodynamic perspectives, effectively averting the risks of explosive precipitation and metastable vaterite formation associated with excessive substrate concentrations. This study not only provides a high fidelity predictive tool (the MICP-Pb AI platform) but also elucidates the critical process windows for ensuring crystalline stability and acid resistance, thereby achieving the synergistic optimization of rapid Pb removal and long term secure sequestration.

PMID:41931893 | DOI:10.1016/j.jhazmat.2026.141918

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Evaluation of a vaginal and vestibular sampling technique and microbiological study of the vaginal and vestibular flora in female cats, healthy and with reproductive tract disorders

Theriogenology. 2026 Mar 31;260:117918. doi: 10.1016/j.theriogenology.2026.117918. Online ahead of print.

ABSTRACT

The vaginal bacterial flora plays a role in reproductive health in mammals; alterations of the vaginal microbiota are associated with urogenital diseases in several species. In cats, information on vaginal microbiota is limited, mainly due to anatomical constraints complicating uncontaminated sampling. This study evaluated a novel vaginal sampling method and compared vaginal and vestibular bacterial populations in queens of different breeds, ages, reproductive statuses, and health statuses. Vaginal and vestibular samples underwent bacteriological analysis. The proposed sampling method identified microbial populations at both sites that were not statistically different; however, descriptive analyses suggested that vestibular samples alone may poorly represent vaginal microbiota, potentially influenced by sex hormones (oestrogen, progesterone) but not by health status or sampling efficacy. Predominant bacterial species isolated from both sampling sites were Escherichia coli, Streptococcus canis, and Staphylococcus felis, regardless of oestrus stage or health status. The novel vaginal sampling technique detected 12 bacterial species at the vaginal level versus 9 at the vestibular level, suggesting it may better reflect the vaginal habitat. Compared with vestibular sampling, vaginal sampling showed high sensitivity and specificity for identifying the main bacterial species. Descriptive analyses indicated decreased bacterial positivity and species richness in cases of reproductive disorder, particularly at the vaginal level. Healthy status was significantly associated with the domestic shorthair breed (p < 0.001). Despite the limited sample size and the statistical results, the descriptive analysis supports the validity of this sampling method. Larger studies with quantitative analyses are needed to enhance the diagnosis and management of feline genital disorders.

PMID:41931884 | DOI:10.1016/j.theriogenology.2026.117918

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Variability in selective dorsal rhizotomy surgery: an analysis of the Cerebral Palsy Research Network registry

J Neurosurg Pediatr. 2026 Apr 3:1-9. doi: 10.3171/2025.11.PEDS25497. Online ahead of print.

ABSTRACT

OBJECTIVE: Selective dorsal rhizotomy (SDR) is a surgical procedure to reduce spasticity and improve function in children with cerebral palsy (CP). Randomized trials have shown that SDR is superior to physical therapy alone for reduction of spasticity and improvement in gait, but there is wide variation in surgical technique. The purpose of this study was to describe the scope of patient factors and surgical technique of SDR performed for the management of spasticity in children with CP.

METHODS: This study is a cross-sectional analysis of data included in the Cerebral Palsy Research Network (CPRN) registry from all subjects who underwent SDR at a CPRN member site. Data from consecutive cases were collected at each site and submitted to the CPRN registry. All cases of SDR submitted to the registry were included. Descriptive statistics were used to summarize data. When possible, results were compared across CPRN centers and patients using descriptive and inferential statistics.

RESULTS: A total of 564 patients underwent SDR and had data in the CPRN registry. Most (n = 356, 63%) children were male and White (n = 427, 76%). The Gross Motor Function Classification System (GMFCS) level was I in 63 (14%), II in 108 (23%), III in 134 (29%), IV in 81 (17%), and V in 76 (16%) children. Dystonia was present in 25 (6.2%) children. SDR was performed at the level of the conus medullaris or upper cauda equina in 193 (50%) children. Multilevel laminotomy was performed in 194 (50%) children. Intramuscular monitoring electrodes were placed in 486 (94%) children. The median number of nerve rootlets tested on each side was 27 (IQR 31-34, range 4-139). The median proportion of rootlets cut was 0.63 (IQR 0.52-0.67, range 0.21-1.0). The proportion of rootlets cut was associated with GMFCS level; patients who had a GMFCS level of V had a greater proportion of rootlets cut compared to those with levels of I (mean difference [MD] 0.079, p < 0.01), II (MD 0.129, p < 0.01), and III (MD 0.096, p < 0.01).

CONCLUSIONS: There are many variations in SDR technique for the management of spasticity in CP, including differences in approach to surgical site, number of rootlets tested, and proportion cut. Detailed outcome data are needed to compare variations and determine if an optimal technique is associated with ideal treatment results.

PMID:41931847 | DOI:10.3171/2025.11.PEDS25497