Category: Nevin Manimala

CPT Pharmacometrics Syst Pharmacol. 2026 Apr;15(4):e70232. doi: 10.1002/psp4.70232.

ABSTRACT

This work aimed to assess the correctness of covariate clinical relevance (CCR) assessment using SCM+, FFEM, and FREM within a high-dimensional covariate framework with varying effect sizes and correlations. A clinical trial simulation inspired by the dupilumab case study was conducted (200 datasets of 300 patients each), using a 2-compartment PK model with 12 covariates having small, medium, or high effect size. Covariate analysis was based on a 70 covariate-parameter relationships predefined set including 12 continuous and 7 binary covariates sampled from the NHANES database, spanning high to low correlations. The simulated reference model (RM) was fitted for comparison. Parameter estimation was performed in NONMEM/PsN using FOCEi (SCM+, FFEM) or IMPMAP (FREM), with SE derived from the S matrix. CCR assessment followed a forest plot-inspired approach: 90% confidence intervals with a [0.8-1.25] reference area for clinical relevance; 5% type I error for statistical significance. Parameter estimates and SE were always obtained, allowing full CCR evaluation. For covariates with simulated effects, all methods were consistent with RM. SCM+ missed up to 9% of small-effect covariates, whereas FFEM/FREM more often indicated insufficient information to conclude across all effect sizes. For covariates without any effect, SCM+ mostly did not select them, while FFEM/FREM was more informative by classifying them as non-relevant or with insufficient information. As non-selection may reflect a lack of power rather than no effect, robust CCR assessment should begin with FFEM/FREM for a comprehensive exploration, followed by SCM+ to build a parsimonious predictive model.

PMID:41944131 | DOI:10.1002/psp4.70232

Microrna. 2026 Apr 6. doi: 10.2174/0122115366434903260330072807. Online ahead of print.

ABSTRACT

BACKGROUND: About 80-90% of all oral cancers worldwide are Oral Squamous Cell Carcinomas (OSCCs), making them the most common type of oral malignancy. Due to its propensity for lymph node metastasis, lack of accurate prognostic indicators, and delayed diagnosis, OSCC remains linked to high morbidity and mortality despite advancements in surgical and therapeutic approaches. A mucin-type transmembrane glycoprotein, Podoplanin (PDPN), is well known as a lymphatic endothelial marker and plays roles in metastasis, Epithelial-Mesenchymal Transition (EMT), and tumor progression and growth. The goal of the current study was to determine whether podoplanin’s immunohistochemistry expression in OSCC and its association with other clinicopathological parameters could serve as a biomarker for the course and outcome of the disease.

METHODS: This observational study was conducted over one year in the Department of Pathology in collaboration with the Department of Surgical Oncology, King George’s Medical University, Lucknow. A total of 110 histopathologically confirmed, treatment-naïve cases of OSCC were included. Detailed clinical and demographic data were collected. Tumour specimens were processed and evaluated as per the College of American Pathologists (CAP) guidelines. Immunohistochemistry was performed using anti-podoplanin (D2-40 clone) monoclonal antibody. The expression of podoplanin was assessed semi-quantitatively using the German Immunoreactive Score (IRS), which combines staining intensity and percentage of positive tumour cells.

RESULTS: The age of patients ranged from 23 to 75 years, with a mean of 45.3 years; the predominant age group was 31-40 years (35.5%). Males constituted 83.6% of the study population, and 89.1% had a history of tobacco, smoking, or alcohol use. The most commonly affected sites were the buccal mucosa (33.6%) and anterior tongue (30.9%). Most tumours were larger than 2.5 cm (58.2%) and exhibited a depth of invasion exceeding 10 mm (54.5%). Advanced pathological stage (Stage III-IV) was observed in 79.1% of cases, and 64.5% had nodal metastasis. Welldifferentiated tumours were most common (48.2%). Podoplanin expression ranged from weak (IRS 0-6) in 35.5% to strong (IRS >6) in 64.5%. Strong podoplanin expression correlated positively with larger tumour size, moderate to well-differentiated tumours, and nodal metastasis (N1-N3), although no significant association was found with early vs. late pathological stage. Interestingly, T4-stage and poorly differentiated tumours showed a tendency toward weak expression.

DISCUSSION: The study confirms that strong podoplanin expression correlates with parameters indicative of tumour aggressiveness, including size, differentiation, and nodal involvement. These findings align with several prior studies, though the lack of significant association with pathological stage or overall survival underscores the complexity of podoplanin’s role in tumour biology. The expression pattern-predominantly peripheral and membranous-suggests podoplanin may be involved in tumour invasion fronts and early carcinogenic events.

CONCLUSION: The study findings suggest that podoplanin overexpression is significantly associated with tumour size, differentiation, and lymph node metastasis in OSCC, indicating its potential utility as a prognostic biomarker. Although the survival analysis did not demonstrate a statistically significant correlation with podoplanin expression, the trend toward higher mortality in patients with strong expression warrants further exploration. This study adds to the growing body of evidence supporting podoplanin’s role in tumour progression and highlights its promise as a diagnostic and prognostic adjunct in oral cancer. Multicentric studies with larger cohorts and long-term follow-up are recommended to validate these observations.

PMID:41944122 | DOI:10.2174/0122115366434903260330072807

Popul Health Manag. 2026 Apr 7:19427891261437477. doi: 10.1177/19427891261437477. Online ahead of print.

ABSTRACT

In 2015, the Centers for Medicare and Medicaid Services started reimbursing chronic care management (CCM) services for patients with multiple chronic conditions. This study used 2015-2020 Medicare claims data from Illinois, Iowa, Minnesota, and Wisconsin and conducted a retrospective cohort study of 885,132 beneficiaries with an evaluation and management visit, following a diabetes diagnosis with other co-occurring chronic conditions. A competing-risk model was estimated to analyze factors associated with patients’ receipt of their first CCM services and a Cox proportional hazard model was estimated to assess the risk of death post-CCM initiation. Diabetic patients with multiple chronic conditions had mean age of 70 years (SD = 10.3), 50.7% were female, and 81.3% were white. 1.0% (9,075 beneficiaries) had CCM claims. Excluding chronic conditions, variables associated with a higher likelihood of CCM initiation included age (sub-distribution hazard ratios [SHR] = 1.003 for each additional year, 95% CI:1.00-1.01), female (SHR = 1.10, 95%CI:1.05-1.15), Black (SHR = 1.27, 95% CI:1.19-1.36) or Hispanic (SHR = 1.40, 95% CI:1.23-1.58), receiving care at home (SHR = 5.00, 95% CI:4.55-5.51) or skilled nursing facilities (SHR = 1.60, 95% CI:1.48-1.73), being a non-Iowa resident, and getting a diabetes diagnosis post-2015. However, patients in non-urban areas were less likely to receive such services. No statistical difference was found in the likelihood of mortality with CCM initiation vs. non-CCM. After accounting for CCM initiation, variables associated with a higher likelihood of death included age, American Indian/Alaska Native, residing in non-urban areas, getting a diabetes diagnosis in 2020, and receiving care in non-outpatient settings. CCM remains largely underutilized among Medicare beneficiaries. Addressing barriers, including improving access in non-urban areas and managing chronic condition earlier, may enhance adoption and decrease the risk of death for patients with multimorbidity.

PMID:41944097 | DOI:10.1177/19427891261437477

Physiother Res Int. 2026 Apr;31(2):e70208. doi: 10.1002/pri.70208.

ABSTRACT

BACKGROUND AND PURPOSE: Patellofemoral pain (PFP) is a common condition in women and is associated with high recurrence rates. Kinematic alterations are among the factors that may persist even after muscle strengthening programs. Given the multifactorial nature of PFP, non-mechanical factors, such as kinesiophobia, may be related to the movement patterns adopted by this population. This study aimed to investigate the associations between kinesiophobia, pain-related factors, and lower limb kinematics during uphill walking and treadmill running in women with PFP.

METHODS: This was a cross-sectional study. Data were collected from 22 young women (24.0 ± 5.87 years) with PFP. Anthropometric data were collected, and participants completed the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, and the Numerical Rating Scale for pain. Subsequently, kinematics of the affected lower limb was analyzed during uphill walking and treadmill running. The angles of knee flexion, hip flexion, ankle dorsiflexion, knee valgus, and pelvic tilt were calculated. Pearson’s correlation coefficient was used for statistical analysis, with the significance level set at p < 0.05.

RESULTS: Significant negative correlations were observed between knee flexion angle and kinesiophobia (r = -0.381, p = 0.040) as well as pain catastrophizing (r = -0.482, p = 0.023) during uphill walking. During treadmill running, stronger negative correlations were found between knee flexion angle and both kinesiophobia (r = -0.694, p = 0.008) and pain catastrophizing (r = -0.972, p = 0.008). No significant correlations were observed for the other joint angles analyzed.

DISCUSSION: The findings of this study indicate that higher levels of kinesiophobia and pain catastrophizing are associated with reduced knee flexion during uphill walking and treadmill running in women with PFP. Rather than suggesting a causal effect, these results highlight a meaningful relationship between psychological factors and movement patterns during functional activities. Reduced knee flexion may reflect a protective or avoidance strategy commonly observed in individuals with elevated fear of movement or maladaptive pain-related beliefs. Clinically, these associations underscore the importance of considering psychological factors during assessment and rehabilitation, as they may be related to altered movement strategies and functional performance in individuals with knee pain.

PMID:41944085 | DOI:10.1002/pri.70208

Cyberpsychol Behav Soc Netw. 2026 Apr 7:21522715261439452. doi: 10.1177/21522715261439452. Online ahead of print.

ABSTRACT

As generative artificial intelligence (AI) becomes increasingly integrated into news production, concerns about the credibility of synthetic news content are intensifying. While some studies report that audiences find AI-generated news less credible than human-written content, others reveal mixed or even reversed findings. This meta-analysis synthesizes findings across 31 studies (41 effect sizes) to assess how the source label (AI vs. human) influences news users’ evaluations of source credibility and message credibility. Results show a small but statistically significant penalty for AI-labeled (vs. human-labeled) news on both credibility measures. To better understand variability across studies, we put forth three moderators: (1) the value-ladenness of the topic, (2) participants’ source orientation, and (3) actual authorship of the text. Although the first two moderators showed descriptive trends consistent with expectations, only the third reached statistical significance, with effects being more pronounced when the news articles were actually written by human only (vs. AI). These findings contribute to ongoing debates about the role of automation in journalism by clarifying when and why audiences mind the source.

PMID:41944061 | DOI:10.1177/21522715261439452

J Neurotrauma. 2026 Apr 7:8977151251412889. doi: 10.1177/08977151251412889. Online ahead of print.

ABSTRACT

Post-traumatic headache (PTH) is one of the most disabling sequelae of mild traumatic brain injury (mTBI); however, its clinical determinants and long-term trajectories remain poorly defined. We conducted a large, multicenter, prospective follow-up study to characterize the phenotypic spectrum of persistent PTH, identify predictors of persistence, and explore the role of pre-existing migraine in shaping headache outcomes after mTBI. A total of 478 adults (52.1% male, mean age 40.5 ± 18.7 years) with mTBI were recruited and evaluated by experienced neurologists at two time points: immediately after mTBI and at 6 months post injury. Demographic data and detailed headache features were collected using clinical examination and standardized questionnaires, administered face-to-face during the first visit and either face-to-face or by phone at the 6-month follow-up by physicians. Headache-related disability, depression, and insomnia were assessed using the Headache Impact Test (HIT-6), Beck Depression Inventory (BDI), and Insomnia Severity Index (ISI), respectively. Statistical analyses included classification tree analysis to identify predictors of persistent PTH and K-means clustering to delineate phenotypic subgroups. Overall, 22.6% of patients developed persistent PTH at 6 months. Pre-existing headache (PH) was reported in 31.4% of participants, predominantly migraine (57.3%). Patients with pre-existing migraine more frequently exhibited migraine-like PTH features (throbbing quality, unilateral localization, longer headache attack duration, and associated symptoms such as nausea, photophobia, and phonophobia) and scored significantly higher on the HIT-6, numeric rating scale (NRS) for headache severity, ISI, and BDI, indicating greater disability, pain severity, insomnia, and depressive symptoms (p < 0.01 for all). Classification tree analysis revealed two robust predictors of persistent PTH: acute PTH lasting more than 30 consecutive days and an initial HIT-6 score greater than 45. Furthermore, cluster analysis of patients with persistent PTH identified two phenotypic groups. Cluster 1 (n = 47) comprised patients with ≥ 180 days of continuous headache, high disability, and poor sleep quality, whereas Cluster 2 (n = 60) included patients with shorter headache duration following mTBI (<180 days), lower disability, and infrequent, shorter headache attacks. This study demonstrates that nearly one in four patients with mTBI experiences persistent PTH. Early indicators of persistence, particularly prolonged continuous headache and higher disability, may help identify high-risk individuals who warrant early aggressive, targeted interventions. Recognition of distinct PTH clusters reflects the heterogeneity of this frequent but under-investigated disorder with high burden and highlights the need for early and tailored management strategies.

PMID:41944049 | DOI:10.1177/08977151251412889

J Chem Theory Comput. 2026 Apr 7. doi: 10.1021/acs.jctc.6c00116. Online ahead of print.

ABSTRACT

StochasticGW is a code for computing accurate quasi-particle (QP) energies of molecules and material systems in the GW approximation. StochasticGW utilizes the stochastic Resolution of the Identity (sROI) technique to enable a massively parallel implementation with computational costs that scale semilinearly with system size, allowing the method to access systems with tens of thousands of electrons. We introduce a new implementation, StochasticGW-GPU, for which the main bottleneck steps have been ported to GPUs and give substantial performance improvements over previous versions of the code. We showcase the new code by computing band gaps of hydrogenated silicon clusters (Si_xH_y) containing up to 10,001 atoms and 35,144 electrons, and we obtain individual QP energies with a statistical precision of better than ±0.03 eV with times-to-solution of less than 1 h.

PMID:41944047 | DOI:10.1021/acs.jctc.6c00116

Gut Liver. 2026 Apr 7. doi: 10.5009/gnl250140. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Weight loss following gastric cancer (GC) surgery is a prevalent and significant long-term complication that impacts the patient’s oncologic prognosis and quality of life. The impact of lifestyle changes after surgery with regard to regular exercise, smoking, and alcohol consumption on weight loss have not been fully explored. We studied the factors associated with underweight (body mass index <18.5 kg/m²) after gastrectomy, focusing on variation across sex and age groups.

METHODS: We utilized a population-based cohort provided by the Korean National Health Insurance Service, which included cancer screening data. In total, 27,854 patients who underwent GC surgery between 2010 and 2016 were included.

RESULTS: Among the 27,854 patients in the study cohort, 3,064 (11.0%) were underweight. Female sex (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.55 to 1.96; p<0.001) was a significant risk factor for becoming underweight postoperatively. Engaging in regular exercise (OR, 0.73; 95% CI, 0.60 to 0.89; p=0.002) and ceasing smoking (OR, 0.31; 95% CI, 0.13 to 0.78; p<0.001) emerged as substantial preventive factors against becoming underweight, particularly in female patients. Exercise (OR, 0.76; 95% CI, 0.65 to 0.89; p=0.001) proved more beneficial for patients aged <65 years.

CONCLUSIONS: Smoking cessation and regular exercise are associated with a reduced risk of postoperative underweight in GC patients following gastrectomy.

PMID:41944028 | DOI:10.5009/gnl250140

Sci Prog. 2026 Apr;109(2):368504261441363. doi: 10.1177/00368504261441363. Epub 2026 Apr 7.

ABSTRACT

ObjectivePeripheral arterial disease (PAD) is a prevalent cardiovascular disorder that significantly impairs functional capacity and quality of life. Vascular inflammation is recognized as a key pathophysiological component of PAD. This cross-sectional study aimed to investigate the associations between a panel of novel, readily available hematological inflammatory indices and the presence of PAD in a nationally representative sample.MethodsThis is a cross-sectional study. This investigation utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 cycles. PAD diagnosis was rigorously defined according to American Heart Association guidelines, with ankle-brachial index (ABI) values ≤0.9 obtained through standardized bilateral lower extremity doppler measurements and repeated verification protocols. Our analytical approach incorporated advanced statistical methodologies to elucidate complex relationships: Survey-weighted multivariable logistic regression analyses were conducted with sequential adjustment for demographic characteristics, clinical covariates, and traditional cardiovascular risk factors. The inflammatory biomarker panel included both composite indices – Systemic Inflammation Response Index (SIRI), Aggregate Index of Systemic Inflammation (AISI), Systemic Immune-Inflammation Index (SII), Neutrophil-to-HDL ratio (NHR), Monocyte-to-HDL ratio (MHR), Lymphocyte-to-HDL ratio (LHR), Platelet-to-HDL ratio (PHR) and Neutrophil-to-Lymphocyte ratio (NLR).ResultsAmong 5,954 eligible participants, higher levels of SIRI, MHR, and NHR were significantly associated with an increased odds of prevalent PAD in fully adjusted models. Threshold analysis revealed nonlinear associations for MHR with PAD, with positive associations observed below identified inflection points. In comparative receiver operating characteristic (ROC) curve analysis, SIRI demonstrated modest discriminatory ability for PAD presence, though its predictive utility, like that of the other indices, was limited.ConclusionIn this large, population-based cross-sectional study, several novel hematological inflammatory indices, particularly SIRI, MHR, and NHR, showed significant associations with prevalent PAD. These findings contribute to the understanding of the inflammatory landscape in PAD. However, their utility for clinical discrimination in a cross-sectional setting appears constrained, highlighting the need for further investigation into their potential roles.

PMID:41944010 | DOI:10.1177/00368504261441363

J Child Lang. 2026 Apr 7:1-24. doi: 10.1017/S0305000926100610. Online ahead of print.

ABSTRACT

This study is concerned with Albanian children speaking a nonstandard dialect who learn Standard Albanian (SA) in primary school. Our main research question is whether the phonetic characteristics of these children’s first dialect are influenced by their learning of SA. We followed longitudinally 48 children in 1st, 2nd, and 5th grades (24 girls, 24 boys, 6-11 years old), some of whom grew up in a village, the others in a city. A picture-naming task was used to record four vowel features of interest, which were analyzed acoustically, then statistically with distributional regression models and generalized additive models. We found evidence that the children’s first dialect was affected by SA, suggesting that by 5th grade, they were not fully proficient at distinguishing between the two systems. The four analyzed features followed different developmental trajectories, similar to adults acquiring a second dialect, and similar to feature selectivity observed in language change.

PMID:41943983 | DOI:10.1017/S0305000926100610