Tag: nevin manimala

J Biol Phys. 2026 Jan 29;52(1):6. doi: 10.1007/s10867-026-09701-4.

ABSTRACT

Regulatory T cells (Treg) and T helper 17 cells (Th17), both derived from naïve T cells, play pivotal roles in modulating immune responses, and their dynamic balance is critical for maintaining immune homeostasis. Existing studies predominantly focus on the regulatory mechanisms of individual cell types and lack a systematic analysis of how multiparametric interactions and stochastic perturbations jointly influence cell-fate equilibrium. In this study, we investigate the gene regulatory network of Treg and Th17 cells in two major aspects: (i) elucidating the dynamical features of the network and (ii) examining the regulatory effects of Gaussian white noise on the balance between the two lineages. By integrating systems dynamics, non-equilibrium mechanics, and stochastic process theory, we propose a unified modeling framework that incorporates Gaussian white noise to simulate stochastic perturbations in gene expression, thereby establishing a mapping between parameter sets and cellular phenotypes and quantifying the regulatory weights of key factors. Our results demonstrate that parameters such as extracellular TGF-β input, foxp3 mRNA synthesis rate, and Stat3 protein degradation rate significantly modulate the differentiation balance between Treg and Th17 cells. Furthermore, within a certain range, stronger Gaussian white noise promotes the differentiation of naïve T cells toward the Th17 lineage, thereby enhancing immune responsiveness. This finding aligns with prior experimental evidence demonstrating that stochastic noise can amplify immune response efficacy. This framework uniquely couples static and dynamic perturbations, revealing stochasticity’s role in cell-fate decisions and offering both a quantitative tool for studying Th17-Treg balance and a generalizable approach for other differentiation systems.

PMID:41606283 | DOI:10.1007/s10867-026-09701-4

Mamm Genome. 2026 Jan 28;37(1):27. doi: 10.1007/s00335-026-10193-9.

ABSTRACT

Indigenous cattle account for approximately 80% of Uganda’s cattle population. These animals are well adapted to the country’s ten agroecological zones and are mainly kept under pastoral and agropastoral systems. Unlike commercial breeds, they thrive on low-quality feeds, while tolerating major tropical diseases and parasites including tsetse flies, ticks, and vector-borne infections. Whole-genome sequence (WGS) analysis offers opportunities to uncover genomic regions underlying these adaptations and to trace the genetic footprints of long-term breeding decisions taken by cattle keepers. In this study, WGS data from 95 animals representing six indigenous cattle populations (Ankole, Karamojong, Nganda10, Nganda17, Nkedi, and Ntuku) were analyzed to identify genomic regions under putative selection. Two complementary approaches were applied: enumeration of the µ-statistic in RAiSD and runs of homozygosity (ROH) analysis. RAiSD identified population-level signals, while conserved ROH regions were defined using breed-specific SNP-incidence thresholds. The two methods identified 803 and 49 candidate genes respectively. The top genes identified included SLC37A1 (BTA1), CHCHD3 (BTA4), and RAB3GAP1 (BTA2) detected by RAiSD, and IL26 (BTA5), FBXL7 (BTA20), and HSPA9 (BTA7) contained in ROH. Furthermore, the regions harbored 107 novel genes (92 detected by RAiSD and 15 by ROH), corresponding to 255 quantitative trait loci. The identified genes under putative selection are associated with economically important traits including adaptation to tropical environments, resistance to parasites and diseases, and other farmer-preferred characteristics. These findings provide insights into the genetic basis of adaptation, selection and production in Ugandan indigenous cattle, supporting conservation and breeding strategies to enhance resilience and productivity.

PMID:41606260 | DOI:10.1007/s00335-026-10193-9

Eur Radiol. 2026 Jan 28. doi: 10.1007/s00330-026-12331-y. Online ahead of print.

ABSTRACT

OBJECTIVES: A new nomenclature and classification of the bicuspid aortic valve (BAV) was proposed. However, phenotyping using echocardiography remains limited in accuracy. This study aimed to evaluate the utility of cardiac CT for BAV phenotyping and its association with clinical relevance.

MATERIALS AND METHODS: Four hundred eighteen BAV patients who underwent both echocardiography and cardiac CT within 3 months were analyzed. BAV was classified as fused, 2-sinus, or partial-fusion type. We investigated the association between the CT-derived BAV phenotype and types of BAV dysfunction and aortopathy.

RESULTS: CT-derived BAV phenotypes showed 58.6% concordance with echocardiography-based phenotypes. Fifty patients (12.0%) had a partial-fusion type based on echocardiography, but 124 patients (29.7%) had this type based on CT. CT-derived fused and 2-sinus type had a higher incidence of significant aortic stenosis than the other CT-based phenotypes [adjusted odds ratio (aOR):1.21, 95% CI: 1.12-1.31, p < 0.001; aOR: 1.14, 95% CI: 1.05-1.23, p = 0.002, respectively]. Partial-fusion type was associated with a higher incidence of significant aortic regurgitation (aOR: 1.50, 95% CI: 1.38-1.63, p < 0.001) and lower incidence of ascending-type aortopathy (aOR:0.88, 95% CI: 0.80-0.97, p = 0.008). In the 2-sinus BAV subgroup, a latero-lateral opening was more significantly associated with all types of aortopathy than the antero-posterior opening type (aOR:1.23, 95% CI: 1.05-1.43, p = 0.011).

CONCLUSIONS: Cardiac CT provides accurate information for BAV phenotype using the new nomenclature system. CT-derived BAV phenotyping is associated with types of BAV dysfunction and aortopathy and may therefore be useful for risk prediction in patients with a BAV.

KEY POINTS: Question Echocardiographic phenotyping of BAV is limited in accuracy. This study evaluated the utility and clinical relevance of CT-based BAV phenotyping. Findings CT and echocardiography showed 58.6% agreement in BAV phenotyping. CT identified more partial-fusion types and was significantly associated with valve dysfunction and aortic disease. Clinical relevance Cardiac CT provides accurate BAV phenotyping using the new nomenclature. CT-derived phenotype correlates with BAV dysfunction and aortic disease, suggesting its potential role in risk stratification and personalized management of patients with BAV.

PMID:41606247 | DOI:10.1007/s00330-026-12331-y

Eur Radiol. 2026 Jan 28. doi: 10.1007/s00330-026-12324-x. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the diagnostic performance of semi-supervised learning models for aggressive prostate cancer detection on MRI compared to fully supervised models trained with additional expert annotations.

MATERIALS AND METHODS: We used 1500 MRI scans from the PI-CAI challenge training subset. Positive scans had 220 human and 205 AI-generated annotations. The mtU-Net (proposed teacher-student semi-supervised approach) was compared to supervised (trained using only 220 human annotations) and semi-supervised (trained on human and AI-generated annotations) nnU-Net. The 205 AI-annotated scans were manually annotated, and a fully supervised model was trained. External validation was performed on a newly annotated dataset from the PROMIS study (n = 574, 403 lesions) and the Prostate158 dataset (n = 158, 126 lesions). Patient-level performance was evaluated using the area under the curve (AUC) and lesion-level detection (overlap > 0.10) using average precision (AP), along with 95% confidence Intervals (in brackets), and the DeLong test to compare AUCs against the supervised and fully supervised models.

RESULTS: The fully supervised nnU-Net showed the highest performance on the internal PI-CAI test set (AUC = 0.89 [0.87-0.91], AP = 0.65 [0.60-0.70]) and external validation datasets PROMIS (AUC = 0.68 [0.64-0.72], AP = 0.24 [0.20-0.29]) and Prostate158 (AUC = 0.87 [0.82-0.92], AP = 0.64 [0.56-0.72]), significantly outperforming the supervised baseline (p < 0.0 5). The proposed semi-supervised mtU-Net demonstrated close external validation performance on PROMIS (AUC = 0.66 [0.62-0.71], AP = 0.20 [0.16-0.25]) and Prostate158 (AUC = 0.86 [0.81-0.92], AP = 0.58 [0.49-0.67]), significantly outperforming the supervised baseline on both datasets (p = 0.047 and p = 0.014, respectively), and showing no significant difference to the fully supervised model (p = 0.199 and p = 0.702, respectively).

CONCLUSION: In prostate MRI tumor detection, fully supervised learning performed best. However, in external validation, the semi-supervised methods demonstrated performance that approached that of the fully supervised model, proving a valuable approach when expert annotations are limited.

KEY POINTS: Question The need for extensive expert voxel-level annotations delays the development of AI-based prostate cancer diagnostic tools and their implementation in clinical practice. Findings The combination of pseudo-labeling with consistency regularization achieved performance comparable to that of fully supervised methods, demonstrating that data diversity matches the impact of expert annotation volume. Clinical relevance Semi-supervised learning reduces dependence on expert annotations while maintaining detection accuracy, enabling the development of scalable, automated diagnostic tools for prostate cancer amid growing clinical workflow demands.

PMID:41606246 | DOI:10.1007/s00330-026-12324-x

Ann Pharmacother. 2026 Jan 28:10600280251393677. doi: 10.1177/10600280251393677. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous fluids are commonly used in postcardiac surgery to maintain or increase intravascular volume. While volume expansion after cardiac surgery is often necessary, the optimal fluid type to use is not established.

OBJECTIVE: The objective of the study is to evaluate cost-savings and clinical outcomes of an albumin minimization protocol for postcardiac surgery fluid resuscitation at a surgical intensive care unit in a community teaching hospital.

METHODS: This was a single-center retrospective cohort study of patients who received fluid resuscitation after open heart coronary artery bypass surgery or valvular surgery while on cardiopulmonary bypass at a community teaching hospital between February 2021 and May 2022. Cohorts were split up prior to the implementation of an albumin minimization protocol that was implemented in September 2021. The primary outcome was the amount of albumin or crystalloid fluids received after surgery, and the overall cost of intravenous fluids after surgery. Secondary outcomes included 30-day mortality, acute kidney injury, hours on oxygen support, hours on vasopressors, multiple vasopressors used, perioperative blood product transfusions, and 72-hour surgery take back.

RESULTS: Of 434 total patients evaluated, 400 patients met criteria for inclusion. Baseline characteristics were balanced between the 2 groups. Average surgical time was shorter in the postprotocol arm. Per patient use of albumin decreased by 27.1 g (22.8-31.4) while crystalloid fluid use increased by 1 L (0.9-1.2) after implementation of the albumin minimization protocol. Average cost savings were approximately $178 per surgery. No statistically significant difference was seen in any of the secondary safety and efficacy outcomes.

CONCLUSION AND RELEVANCE: This study adds to the body of literature suggesting that the use of an albumin minimization protocol after open heart cardiac surgery was safe and effective. A significant reduction in cost and utilization of albumin was seen in the study without affecting patient outcomes.

PMID:41604250 | DOI:10.1177/10600280251393677

Plast Reconstr Surg. 2026 Jan 22. doi: 10.1097/PRS.0000000000012839. Online ahead of print.

ABSTRACT

BACKGROUND: Discrepancies between assigned and actual operative durations may distort time-based valuation of surgical procedures. This study evaluated the impact of operative time source on wRVU per minute and reimbursement per minute across commonly reimbursed reconstructive plastic surgery operations.

METHODS: Using 2023 National Surgical Quality Improvement Program (NSQIP) data, we compared actual operative times for 11 commonly reimbursed plastic surgery procedures to CMS-assigned times from the Physician Fee Schedule. Each CPT (15830, 19316, 19318, 19325, 19340, 19342, 19357, 19364, 19370, 19371, 19380) was linked to its CMS-assigned wRVU. wRVU per minute and reimbursement per minute were calculated using both NSQIP-observed and CMS-assigned operative times. Statistical analyses included Wilcoxon signed-rank tests, Kruskal-Wallis tests, Spearman correlations, and multivariable linear regression.

RESULTS: Among 6,537 single-CPT cases, CMS underestimated operative time in 5 of 11 procedures. The largest discrepancies were observed in immediate implant insertion (+93.5 min), free flap breast reconstruction (+60.5 min), and breast augmentation (+18.5 min), resulting in reduced wRVU/min and $/min. Time discrepancy correlated strongly with reduced wRVU/min (ρ=-0.84). NSQIP-modeled reimbursement showed 2,637 single-CPT cases (40.3%) as underpaid, totaling $751,149.18. Among 15,570 multi-CPT cases, 5,099 (32.7%) were under-reimbursed, with a cumulative modeled underpayment of $2,002,956.29.

CONCLUSIONS: CMS operative times frequently underestimated the duration of plastic surgery procedures. Time discrepancies were associated with substantial reductions in wRVU/min and $/min, particularly for complex or implant-based operations. These findings suggest that current CMS time assignments do not adequately capture operative complexity and may contribute to systematic underpayment in reconstructive surgery.

PMID:41604240 | DOI:10.1097/PRS.0000000000012839

Acta Ophthalmol. 2026 Jan 28. doi: 10.1111/aos.70063. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate changes in corneal tomography, pachymetry and endothelial cell density (ECD) following Paul Glaucoma Implant (PGI) surgery.

METHODS: Seventy-three patients were prospectively examined. Repeated measures anova was used to analyse corneal tomography, corneal thickness and ECD at baseline, 6 and 12 months.

RESULTS: PGI surgery was not associated with clinically meaningful changes in corneal tomography parameters. Simulated astigmatism and posterior astigmatism remained stable over 12 months. Simulated average keratometry showed a small but statistically significant flattening (≈0.3 diopters), whereas posterior average keratometry remained unchanged. Although some changes reached statistical significance, their magnitude was minimal and unlikely to be clinically relevant. Central corneal thickness remained stable, but pachymetry in the tube quadrant increased in the operated eyes, while adjusted pairwise comparisons were non-significant. Central ECD did not change significantly after surgery (p = 0.67). In contrast, paracentral (-2.9%) and peripheral (-4.7%) ECD values declined significantly over 12 months (p = 0.03 and p = 0.001, respectively) and study eyes consistently showed lower values than contralateral control eyes. However, PGI surgery did not accelerate the rate of cell loss, as the time × eye interaction was not significant.

CONCLUSIONS: PGI surgery did not induce progressive changes in corneal astigmatism or pachymetry during the first postoperative year. Central ECD remained stable, while paracentral and peripheral regions showed a moderate decline. PGI did not increase the rate of endothelial cell loss and the observed reduction was lower than previously reported for other glaucoma drainage implants.

PMID:41604236 | DOI:10.1111/aos.70063

J Magn Reson Imaging. 2026 Jan 28. doi: 10.1002/jmri.70204. Online ahead of print.

ABSTRACT

BACKGROUND: Skeletal muscle blood oxygen level dependent (BOLD) MRI is a technique for assessing vascular function in peripheral limbs. In patients, however, an increased frequency of atypical response patterns has been observed, warranting investigation into its underlying causes.

PURPOSE: To explore the dynamics of cuff-induced ischemia and reactive hyperemia with BOLD MRI, focusing on the occurrence, quantification, and interpretation of frequent atypical cuff-induced response patterns.

STUDY TYPE: Secondary assessment of prospectively collected datasets.

POPULATION: Seventeen peripheral artery disease (PAD) patients (age: 64-80 years, ankle-brachial index (ABI) range: 0.4-0.8), 8 age-matched controls (age: 64-82 years, ABI range: 1-1.2), and 14 young controls (age: 22-39 years). FIELD STRENGTH/SEQUENCE: $T_2^{*}$ -weighted multi-echo gradient-echo sequence with 11 equidistant echo-times at 3T.

ASSESSMENT: A transverse slice of the calf was imaged repeatedly during an upper-thigh cuff compression cycle consisting of 1-min baseline, 5-min arterial occlusion (cuff inflated) and 5-min reactive hyperemia (cuff deflated). $T_2^{*}$ -mapping with ROI-wise analysis of the soleus and gastrocnemius muscles produced $T_2^{*}$ -time curves and previously established metrics, including the hyperemic upslope ( ${\mathrm{HS}}_{\mathrm{up}}$ ) and time-to-peak (TTP) were assessed. The time-curves were surveyed to identify the frequency and type of deviations from expected. $T_2^{*}$ -time curves of soleus were further analyzed by fitting a parameterized function to derive additional metrics including depth of the undershoot on cuff release and deviation from a monotonic T2* decrease. Ankle-brachial index (ABI) served as a clinical reference for comparisons.

STATISTICAL TESTS: Non-parametric 2-tailed Wilcoxon rank-sum tests to assess differences between patients and age-matched controls. A p value < 0.05 was considered significant.

RESULTS: Atypical cuff-induced response patterns in PAD patients included a negative cuff-induced transient (42%, soleus) and non-monotonic declines in $T_2^{*}$ during cuffing (58%, soleus). While these contributed to increased variabilities in patients, $\text{there were significant differences in}{\mathrm{HS}}_{\mathrm{up}}$ (-0.63 ms/s) and TTP (62.8 s) between patients and age-matched controls.

DATA CONCLUSION: HS_up and TTP provided means to quantify calf muscle responses to cuffing. Specific cases of non-monotonous $T_2^{*}$ decrease during cuffing suggest the detection of venous valve leakages in inter-muscular veins. Insufficient cuff pressure produced curves with absent ischemic plateau and weak hyperemic responses, the recognition of which is important to prevent physiological misinterpretations of $T_2^{*}–\text{time}$ curves and derived metrics.

EVIDENCE LEVEL: 1.

TECHNICAL EFFICACY: 3.

PMID:41604213 | DOI:10.1002/jmri.70204

JAMA. 2026 Jan 28. doi: 10.1001/jama.2025.25686. Online ahead of print.

NO ABSTRACT

PMID:41604184 | DOI:10.1001/jama.2025.25686

JAMA Dermatol. 2026 Jan 28. doi: 10.1001/jamadermatol.2025.5662. Online ahead of print.

ABSTRACT

IMPORTANCE: Currently, there are no treatments approved by the US Food and Drug Administration for juvenile localized scleroderma (JLS), a rare disease. While methotrexate (MTX) is regularly used as a first-line therapy, emerging data from case series and applications in systemic sclerosis suggest that mycophenolate mofetil (MMF) may be clinically comparable, with potential benefits in tolerability and adherence.

OBJECTIVE: To compare clinical outcomes of patients with JLS treated with MTX and MMF using standardized clinical outcome measures.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with clinician-diagnosed JLS who were enrolled in the National Registry of Childhood Onset Scleroderma was conducted at UPMC Children’s Hospital of Pittsburgh. Data were from January 2010 to January 2023 and first analyzed in April 2023. All patients were evaluated and followed up by the same physician. Patients were included if they had disease onset before age 18 years and a localized scleroderma diagnosis and enrollment in the National Registry of Childhood Onset Scleroderma before age 21 years. Patients were required to be receiving MTX monotherapy, MMF monotherapy, or combination therapy (CT) of the 2 for their localized scleroderma.

EXPOSURES: Patients were treated with MTX, MMF, or CT as prescribed by the examining physician.

MAIN OUTCOMES AND MEASURES: This study measured comparative medication treatment response through associations with disease activity, as measured using the Localized Scleroderma Cutaneous Assessment Tool.

RESULTS: Of 114 patients, 77 (67.5%) were female, and the median (IQR) age at onset was 8.3 (5.4-11.2) years. The MTX, MMF, and CT groups included 68 (59.6%), 28 (24.6%), and 18 patients (15.8%), respectively. There were no significant differences in baseline demographic characteristics, disease subtype, or disease severity between groups, but patients in the MMF group had longer disease duration. Mixed-effects modeling showed statistically significant decreases in activity across all groups (β = -0.14; 95% CI, -0.62 to 0.33). A Kaplan-Meier analysis showed no significant difference in disease flare rate over the follow-up interval (hazard ratio, 0.85; 95% CI, 0.51-1.33). However, patients treated with MTX compared with those treated with MMF had significantly higher rates of fatigue (47% vs. 11%, P = .001) and nausea (60% vs. 7%; P = .001).

CONCLUSIONS AND RELEVANCE: The study results suggest that MMF demonstrated a similar response to treatment as MTX in reducing disease activity in JLS, with comparable flare rates and improved tolerability. These initial findings support MMF as a potential candidate for first-line treatment of JLS. Prospective, randomized, noninferiority trials are warranted to confirm these results and guide future treatment recommendations.

PMID:41604178 | DOI:10.1001/jamadermatol.2025.5662