Nevin Manimala

Proc Natl Acad Sci U S A. 2025 Nov 18;122(46):e2423469122. doi: 10.1073/pnas.2423469122. Epub 2025 Nov 11.

ABSTRACT

Histological images offer a wealth of data. Mining these data holds significant potential for enhancing disease diagnosis and prognosis, though challenges remain, especially in noncancer contexts. In this study, we developed a statistical framework that links raw histological images and their derived features to the genotype, transcriptome, and chronological age of the samples. We first demonstrated an association between image features and genotypes, identifying 906 image quantitative trait loci (imageQTLs) significantly associated with image features. Next, we identified differentially expressed (DE) genes by stratifying samples into image-similar groups based on image features and performing DE comparisons between groups. Additionally, we developed a deep-learning model that accurately predicts gene expression in specific tissues from raw images and their features, highlighting gene sets associated with observed morphological changes. Finally, we constructed another deep-learning model to predict chronological age directly from raw images and their features, revealing relationships between age and tissue morphology, especially aspects derived from nucleus features. Both models are supported by a computational approach that greatly compresses gigapixel whole-slide images and extracts interpretable nucleus features, integrating both large-scale tissue morphology and smaller local structures. We have made all interpretable nucleus features, imageQTLs, DE genes, and deep-learning models available as online resources for further research.

PMID:41218125 | DOI:10.1073/pnas.2423469122

Eur Heart J Cardiovasc Imaging. 2025 Nov 11:jeaf305. doi: 10.1093/ehjci/jeaf305. Online ahead of print.

ABSTRACT

AIMS: This study aimed to investigate the prognostic and incremental value of epicardial adipose tissue (EAT) parameters, including volume index (EATVI) and regional fat thickness, assessed by cardiac magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM).

METHODS AND RESULTS: In this retrospective cohort of 457 HCM patients who underwent CMR between 2018 and 2024, EATVI and regional fat thickness at key cardiac grooves were quantified along with conventional clinical and imaging risk factors. Over a median follow-up of 27.5 months (IQR 15.6-47.6), major adverse cardiovascular events (MACE) occurred in 18.1% of patients. Significantly higher EATVI (72.21±14.21 vs. 56.71±10.36 ml/m², P<.001) and increased regional fat thickness (all P<0.05) were observed in patients with MACE. In multivariable Cox regression, EATVI remained an independent predictor of MACE (HR 1.03, 95% CI 1.01-1.05, P<.001). Incorporating EATVI into the clinical-CMR model improved discrimination (C-statistic 0.82 to 0.84; P=0.002), enhanced calibration, and provided greater net clinical benefit on decision-curve analysis. When appended to the 2014 ESC HCM Risk-SCD model, EATVI further improved discrimination (C-statistic 0.80 vs 0.71; P<.001) and calibration. Kaplan-Meier analyses using quartiles and the 62.5 ml/m² cutoff showed progressively worse event-free survival with higher EATVI; within the ESC-defined low-risk subgroup, curves also separated significantly (log-rank P<0.05). Time-dependent Receiver Operating Characteristic analyses confirmed stable predictive performance of these parameters.

CONCLUSION: EATVI and regional fat thickness derived from CMR independently predict adverse outcomes in HCM and improve risk stratification. Comprehensive EAT assessment may serve as a promising imaging biomarker for personalized management.

PMID:41218064 | DOI:10.1093/ehjci/jeaf305

PLoS One. 2025 Nov 11;20(11):e0336666. doi: 10.1371/journal.pone.0336666. eCollection 2025.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global health concern associated with complications that significantly impact patients’ quality of life and place significant burdens on healthcare systems. While the prevalence of T2DM is rising in Ethiopia, the scope and factors contributing to its complications remain understudied. Hence, this study aimed to assess the burden and identify associated factors of chronic complications among Type 2 diabetes mellitus patients attending Wolaita Sodo University Comprehensive Specialized Hospital in Southern Ethiopia.

METHODS: A facility-based cross-sectional quantitative study was conducted from July 1 to August 30, 2024, involving 404 systematically sampled T2DM patients. Data on sociodemographic characteristics, clinical profiles, self-care practices, and chronic complications were collected through structured interviews and medical record reviews. Descriptive statistics summarized patient characteristics, while multivariable logistic regression identified factors associated with chronic complications. Results were reported as Adjusted Odds Ratios (AORs) with 95% Confidence Intervals (CIs), and a p-value < 0.05 was considered statistically significant.

RESULTS: A total of 404 type 2 Diabetes mellitus patients participated in the study, with a response rate of 97.58%. The mean age of participants was 44.80 ± 14.10 years, 41.09% had diabetes for more than 5 years, and 64.85% had suboptimal glycemic control. Among participants, 45.54% (95% CI: 40.61-50.54) had at least one chronic complication, and one in five had multimorbidity. The most common microvascular complications were peripheral neuropathy (14.85%) and nephropathy (9.65%), while macrovascular complications included congestive heart failure (14.11%) and cerebrovascular disorders (11.39%). Multivariable logistic regression identified older age (AOR = 2.74; 95% CI: 1.73, 4.37; p < 0.000), female sex (AOR = 2.14; 95% CI: 1.12, 4.16; p = 0.039), longer diabetes duration (AOR = 2.98; 95% CI: 1.41, 6.54; p = 0.007), poor glycemic control (AOR = 2.02; 95% CI: 1.33, 3.09; p = 0.001), hypertriglyceridemia (AOR = 2.00; 95% CI: 1.06, 3.80; p = 0.038), high salt intake (AOR = 1.57; 95% CI: 1.06, 2.32; p = 0.024), and physical inactivity (AOR = 1.75; 95% CI: 1.16, 2.64; p = 0.008) as significant factors associated with chronic complications.

CONCLUSION: Nearly half of patients with Type 2 diabetes in Southern Ethiopia experienced chronic complications, emphasizing the need for improved prevention and management strategies. Strengthening diabetes care should include routine lipid and blood pressure screening, HbA1c testing where feasible, and nurse-led foot assessment. Community-based interventions promoting physical activity and dietary modification, along with patient education on glycemic control, should be scaled up. Implementing these feasible, low-cost measures within Ethiopia’s existing chronic care framework can help reduce the burden and improve health outcomes.

PMID:41218056 | DOI:10.1371/journal.pone.0336666

PLoS One. 2025 Nov 11;20(11):e0335902. doi: 10.1371/journal.pone.0335902. eCollection 2025.

ABSTRACT

BACKGROUND: Previous studies have demonstrated that cognitive decline is related to meteorological conditions, but most of them focus on air pollutants rather than thermal inversion (TI). The impact of TI on cognitive function remains unclear. Therefore, this study aims to explore the role of TI in the changes of cognitive function trajectories.

METHODS: This study included 5,762 participants aged 45 years and older from China Health and Retirement Longitudinal Study (CHARLS) between 2011-2015. The latent class trajectory model (LCTM) was used to fit population trajectories of cognitive development. The TI data were obtained from NASA’s MERRA-2 dataset, which were totaled by comparing temperatures of atmosphere. The multinomial logistic regression model and restricted cubic spline (RCS) were used to assess the relationship between TI and cognition, the primary outcome was class membership in cognitive trajectories estimated by LCTM.

RESULTS: There were three trajectories of cognitive development in 5,762 participants, which were categorized into three trajectories: U-shaped (decline then improvement), Slowly decline and N-shaped (improvement then decline). In the Slowly decline class, the proportion of individuals exposed to moderate and high levels of TI was the highest. After adjusting for covariates, at medium TI exposure, the odds of being classified into the Slowly decline trajectory versus the U-shaped trajectory were 26.9% higher (OR=1.269, 95% CI = 1.054 ~ 1.528, P = 0.012), at high exposure, 47.8% higher (OR=1.478, 95% CI = 1.152 ~ 1.895, P = 0.002).

CONCLUSION: Higher TI exposure was associated with trajectory membership patterns indicative of worse cognition, strategies that reduce TI exposure may support healthier cognitive trajectories.

PMID:41218051 | DOI:10.1371/journal.pone.0335902

PLoS One. 2025 Nov 11;20(11):e0334957. doi: 10.1371/journal.pone.0334957. eCollection 2025.

ABSTRACT

BACKGROUND: Human granulocytotropic anaplasmosis (HGA), caused by Anaplasma phagocytophilum, and human monocytotropic ehrlichiosis (HME), caused by Ehrlichia chaffeensis, are tick-borne zoonoses. The vast majority of Anaplasma phagocytophilum infections reported worldwide are from the United States. Ehrlichia chaffeensis infections are reported exclusively from North America, with the majority reported from the United States. We have recently summarized the available data on HGA and HME in the form of two systematic reviews. We compared data from these two systematic reviews to objectify differences in epidemiological and clinical presentation between the two diseases in the United States.

METHODS: From our recently published systematic reviews on HGA and HME, «best evidence data» were extracted and comparatively analyzed. Cases were included if (i) they had a high level of diagnostic certainty (i.e., diagnosed by PCR, culture, immunostaining of tissue, or paired IgG IFA serology), (ii) individual clinical data were available, (iii) no concomitantly present coinfection(s) were reported, and (iv) the infection was acquired in the United States.

RESULTS: HME cases were statistically more frequent immunocompromised and younger and had gastrointestinal symptoms, hepatosplenomegaly and elevated liver function tests (LFT) levels. HGA cases were statistically more frequent presenting with pulmonary symptoms and encephalitis. Hospitalization and a fatal outcome was more frequent in HME. No differences in fatal outcome were observed between immunocompetent and immunocompromised HME cases.

CONCLUSION: Although HGA and HME show similarities, there are statistically significant differences in terms of their clinical patterns and outcomes and a not yet described difference in the affected age pattern.

PMID:41218048 | DOI:10.1371/journal.pone.0334957

PLoS One. 2025 Nov 11;20(11):e0335187. doi: 10.1371/journal.pone.0335187. eCollection 2025.

ABSTRACT

INTRODUCTION: Hereditary Spastic Paraplegias (HSP) are a group of genetic disorders leading to the degeneration of long motor and sensory tracts in a progressive course. Clinician-reported outcomes (ClinROs) are the most commonly used endpoints for monitoring these diseases, but they have low sensitivity to detect progression. Therefore, identifying new monitoring biomarkers with higher sensitivity to change is crucial. Our objective was to compare the progression of Somatosensory Evoked Potential (SSEP) latencies over time with ClinROs in HSP.

METHODS: A longitudinal study was conducted on 22 individuals with a genetic diagnosis (13 SPG4, 3 SPG5, 3 SPG7, 2 SPG10, and 1 cerebrotendinous xanthomatosis), with two evaluations over a 4-year interval of upper limb (UL) and lower limb (LL) SSEPs and the Spastic Paraplegia Rating Scale (SPRS) total score and motor items only (mSPRS).

RESULTS: In the follow-up time analysis, progression after 4 years was observed only for SPRS and mSPRS, with an annual progression of 1.12 points and 1.02 points, respectively. No statistically significant progression was observed for SSEPs. Disease progression modeled according to disease duration showed worsening in all outcomes. For each additional year of disease, the SPRS worsened by 0.834 points (95% CI 0.62 to 1.04, p < 0.001), mSPRS by 0.758 points (95% CI 0.55 to 0.96, p < 0.001), SSEP-UL latency by 0.164 ms (95% CI 0.03 to 0.3, p < 0.001), and SSEP-LL latency by 1.343 ms (95% CI 0.74 to 1.93, p < 0.001). Results for the SPG4 subgroup were similar to those for the overall HSP group.

CONCLUSION: The neurophysiological progression of sensory long tract dysfunction is even slower than the progression of motor findings measured by COAs in HSP. The low sensitivity to change of SSEPs identified suggests that they should not be used as primary endpoints in future clinical trials for disease-modifying drugs.

PMID:41218046 | DOI:10.1371/journal.pone.0335187

PLoS One. 2025 Nov 11;20(11):e0336700. doi: 10.1371/journal.pone.0336700. eCollection 2025.

ABSTRACT

Pale shrimp disease is an emerging threat in Thailand, characterized by pale body coloration in Pacific white shrimp (Litopenaeus vannamei). Although the etiology had been identified as Photobacterium damselae subsp. damselae, the disease effects on gut microbiome remain poorly understood. This study investigated changes in the gut microbiota of Pacific white shrimp suffering from pale shrimp disease (diseased group) compared to disease-free shrimp (healthy group) collected from Surat Thani Province, Thailand. DNA extracted from the intestinal samples was subjected to 16S rRNA metagenomic sequencing, followed by taxonomic identification, diversity analyses, and functional prediction of the metabolic pathways. Despite a limited number of biological replicates, the occurrence of pale shrimp disease was able to reveal alterations in intestinal microbial composition, diversities, and functional features compared to the healthy shrimp. In most cases, the intestinal microbiota of the diseased shrimp were dominated by only 2 genera of bacteria, i.e., Photobacterium (54.63-70.53%) and Vibrio (24.94-26.12%), which together accounted for 79.58-95.47% of the total bacterial community. α-diversity, as indicated by the observed features, Shannon, and Simpson indices, was significantly decreased, and dominance was significantly increased in the diseased shrimp compared to healthy shrimp. Likewise, β-diversity was significantly different between groups; PCoA of un-weighted and weighted UniFrac clearly distinguished intestinal microbiota of the shrimp into 2 clusters, and ANOSIM of these data revealed statistical differences between groups, suggesting different microbiota communities between healthy and diseased shrimp. Moreover, diseased shrimp had significantly higher predicted functional features associated with bacterial virulence factors and antibacterial resistance. These exploratory findings suggest an association among pale shrimp disease, gut microbiota dysbiosis, and the proliferation of opportunistic taxa, particularly Photobacterium.

PMID:41218045 | DOI:10.1371/journal.pone.0336700

Interv Neuroradiol. 2025 Nov 11:15910199251394570. doi: 10.1177/15910199251394570. Online ahead of print.

ABSTRACT

BackgroundFlow diversion for intracranial aneurysms is indicated for wide-necked aneurysms in non-perforator-rich segments. However, devices are challenging to deploy in distal/tortuous vasculature. LVIS^TM EVO^TM is a braided intermediate-density stent offering greater flexibility and navigability than flow diverters with higher metal-to-surface ratios. We investigated its off-label use as an independent flow diverter for small, complex intracranial aneurysms.MethodsWe retrospectively reviewed patients at a single center who underwent independent stenting with LVIS^TM EVO^TM from December 2023 to September 2024. Demographics, procedural details, and angiographic outcomes were analyzed. Follow-up computed tomography angiography was performed from May 2024 to October 2025. Descriptive statistics were used; non-parametric tests compared aneurysm and parent vessel diameters.ResultsNine patients (median age 59; 89% female) with off-label intracranial aneurysms (median diameter 5 mm) were treated using LVIS^TM EVO^TM (median diameter 3 mm, length 18 mm). Deployment was technically successful in 100% of cases with no peri-procedural complications. One patient experienced delayed hemorrhage with full neurological recovery. At follow-up (available for 6 patients), 83.3% showed complete aneurysm occlusion (Raymond-Roy Occlusion Classification [RROC] class I). All patients demonstrated 100% stent patency and no new neurological deficits.ConclusionLVIS^TM EVO^TM demonstrated technical feasibility and acceptable initial safety as an off-label flow-diverting device for small (as low as 2.5 mm), distal aneurysms in this limited single-center experience. Its favorable deliverability, safety profile, and occlusion rates suggest it as a possible alternative to currently marketed flow diverters in anatomically challenging patients. These findings warrant validation in larger, multicenter studies with extended follow-up.

PMID:41217987 | DOI:10.1177/15910199251394570

Braz J Cardiovasc Surg. 2025 Nov 1;40(6). doi: 10.21470/1678-9741-2024-0446.

ABSTRACT

OBJECTIVE: This study aimed to investigate the frequency of persistent left superior vena cava (PLSVC) and its impact on outcomes in children undergoing congenital heart surgery.

METHODS: The study was conducted retrospectively in cases diagnosed with congenital heart disease who were operated on under the age of 16 years between October 1st, 2021, and October 1st, 2024, at two major tertiary centers. The frequency of PLSVC and its possible impact on surgical outcomes were evaluated in these cases. The results were analyzed statistically.

RESULTS: There were 4,000 cases during the study period, with 52% being male. The median weight was 5.2 kg (interquartile range 4.5 – 6 kg). PLSVC was detected in a total of 260 cases (6.5%). Of these cases, 92.3% (240/260) drained into the coronary sinus, while 7.7% (20/260) drained directly into the left atrium. In 251 (96.5%) of the patients with PLSVC, there was a right SVC, while nine (3.5%) did not have a right SVC. Of the 251 patients with double SVC, 105 (42%) had a normal innominate vein. PLSVC was primarily associated with heterotaxy syndrome, atrioventricular septal defect, and vascular ring defects.

CONCLUSION: There is an increased frequency of PLSVC among certain congenital heart disease groups, and raising awareness during echocardiographic examination can facilitate the diagnosis of PLSVC. Preoperative diagnosis of PLSVC can help in managing complications more effectively.

PMID:41217972 | DOI:10.21470/1678-9741-2024-0446

Sci Prog. 2025 Oct-Dec;108(4):368504251396066. doi: 10.1177/00368504251396066. Epub 2025 Nov 11.

ABSTRACT

ObjectiveTo improve the S.T.O.N.E. nephrolithometry scoring system by applying a factor weighting method derived from odds ratios (ORs) in logistic regression analysis for a more scientific prediction of stone-free rate (SFR) after percutaneous nephrolithotomy (PCNL).MethodsWe conducted a retrospective cohort study of 283 patients undergoing PCNL. The SFR was the primary outcome. Binary logistic regression identified independent predictors among the S.T.O.N.E. components. Statistically significant factors were assigned weighted points based on their ORs. The improved system’s performance was compared to the traditional S.T.O.N.E. score using receiver operating characteristic analysis, Net Reclassification Improvement (NRI), and risk stratification based on Youden index-optimized cutoffs.ResultsStone size, obstruction, and stone density were independent predictors of SFR (all p < .05) and were assigned weighted scores of 2, 3, and 3, respectively, creating a revised score (range 0-11). The improved system demonstrated comparable discriminative ability to the traditional system (AUC: 0.804 vs 0.814, p > .05) but provided significantly superior risk reclassification (NRI = 0.233, p = .007). Using the Youden index-derived cutoff of 5.5, the improved system stratified patients into low-risk (scores 0-5, n = 123) and high-risk (scores 6-11, n = 160) groups. The SFR was 91.9% in the low-risk group versus 51.9% in the high-risk group (p < .001). This low-risk group had a significantly higher SFR than the low-risk group defined by the traditional system (91.9% vs 81.4%, p = .011).ConclusionThe factor-weighted S.T.O.N.E. scoring system provides enhanced clinical risk stratification for PCNL outcomes. It effectively identifies a distinct cohort of low-risk patients with a > 90% probability of stone-free success, offering improved utility for preoperative patient counseling and surgical planning.

PMID:41217967 | DOI:10.1177/00368504251396066