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Nevin Manimala Statistics

mcRigor: A Statistical Software Package for Evaluating and Optimizing Metacell Partitioning in Single-Cell Data Analysis

J Comput Biol. 2025 Oct 9. doi: 10.1177/15578666251383561. Online ahead of print.

ABSTRACT

Metacell partitioning is a common preprocessing step in single-cell data analysis, used to reduce sparsity by aggregating similar cells. However, existing metacell partitioning algorithms may inadvertently group heterogeneous cells, potentially biasing downstream analyses. The resulting metacell partitions can vary substantially with different hyperparameter settings, leaving users uncertain about which result to trust. The mcRigor R package offers a statistical method for evaluating and optimizing metacell partitioning in single-cell data analysis. This article provides instructions for installing and using mcRigor to support more rigorous and interpretable metacell-based workflows.

PMID:41066085 | DOI:10.1177/15578666251383561

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Nevin Manimala Statistics

Adaptive Biomarker-Based Design for Early Phase Clinical Trials

Stat Med. 2025 Oct;44(23-24):e70275. doi: 10.1002/sim.70275.

ABSTRACT

Identifying and quantifying predictive biomarkers is a critical issue of Precision Medicine approaches and patient-centric clinical development strategies. Early phase adaptive designs can improve trial efficiency by allowing for adaptations during the course of the trial. In this work, we are interested in adaptations based on interim analysis permitting a refinement of the existing study population according to their predictive biomarkers. At an early stage, the goal is not to precisely define the target population, but to not miss an efficacy signal that might be limited to a biomarker subgroup. In this work, we propose a one-arm two-stage early phase biomarker-guided design in the setting of an oncology trial where at the time of the interim analysis, several decisions can be made regarding stopping the entire trial early or continuing to recruit patients from the full or a selected patient population. Via simulations, we show that, although the sample size is limited, the proposed design leads to better decision-making compared to a classical design that does not consider an enrichment expansion.

PMID:41066076 | DOI:10.1002/sim.70275

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Nevin Manimala Statistics

Exploring the Definitions of Physician-Delivered Palliative Care in Canada: A Narrative Review

J Palliat Med. 2025 Oct 9. doi: 10.1177/10966218251386947. Online ahead of print.

ABSTRACT

Background: Palliative care is essential yet underutilized in Canada. Inconsistent definitions and fee codes across provinces/territories hinder effective comparative analysis. Aim: Explore palliative care definitions and fee codes in Canada by examining the provincial/territorial schedules of benefits. Design: We conducted a narrative review of provincial/territorial schedules of benefits, focusing on palliative care definitions and fee codes. Qualitative comparative analysis was performed on the definitions, and descriptive statistical analysis was conducted on the fee codes. Setting/Participants: The study reviewed schedules of benefits from 11 Canadian provinces and territories, excluding Quebec and Nunavut. Results: About 7/11 (64%) provinces/territories published definitions for palliative care, typically characterizing it as terminal, focusing on comfort, and providing a time-based prognosis. The number of specific palliative care fee codes varied from 4 to 32. Conclusions: There is substantial variability in the definition and fee codes used for physician-delivered palliative care across Canada. A standardized national framework for palliative care definitions and fee codes could improve access and care delivery.

PMID:41066074 | DOI:10.1177/10966218251386947

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Nevin Manimala Statistics

Module-Based Teaching Versus Conventional Lectures in Undergraduate Teaching in Pediatrics: A Quasi-Experimental Study

Indian Pediatr. 2025 Oct 9. doi: 10.1007/s13312-025-00192-5. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare module-based versus conventional lectures for undergraduate teaching in pediatrics.

METHODS: This quasi-experimental study was conducted among phase III part II MBBS students during their pediatric posting at a tertiary care teaching center in Southern India. Fifty students each in the experimental and control group were taught using module-based and conventional lectures, respectively. The learning outcome was evaluated by pre-, and post-test scores and analyzed by ‘paired t test’, ‘unpaired t test’ and ‘repeated measure ANOVA’. Perception was assessed using five-point Likert scale.

RESULTS: The gain of marks for module-based teaching was statistically significant compared to conventional lecture (P < 0.001). Regarding perception, 72% of students ‘strongly agreed’ (40%) and ‘agreed’ (32%) to the different characteristics of modular teaching whereas in conventional lecture, 34% were neutral, 32% disagreed, and 12% strongly disagreed.

CONCLUSION: The knowledge outcome and perception level in module-based teaching are superior to that of conventional lectures.

PMID:41066067 | DOI:10.1007/s13312-025-00192-5

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Nevin Manimala Statistics

Reduction in anastomotic leakage by fluorescent laparoscopic resection for ultra-low rectal cancer: a propensity-matched analysis with BMI stratification

Updates Surg. 2025 Oct 9. doi: 10.1007/s13304-025-02352-5. Online ahead of print.

ABSTRACT

Anastomotic leakage (AL) is a serious complication in colorectal surgery, particularly after laparoscopic intersphincteric resection (LsISR) for ultra-low rectal cancer. This study evaluates the effectiveness of ICG fluorescence laparoscopic (FL) resection in reducing AL and improving recovery, especially in high-BMI patients. A retrospective cohort study was conducted on patients undergoing LsISR for ultra-low rectal adenocarcinoma from January 2012 to July 2023, comparing FL (n = 133) and non-FL groups (n = 266). The primary endpoint was the incidence of anastomotic leakage, including symptomatic AL. Secondary endpoints included intraoperative blood loss, lymph node yield, and short-term recovery parameters such as bowel function recovery, soft diet initiation, and hospital stay.Propensity score matching (PSM) was used to reduce baseline differences. In the PSM cohort, the FL group had a significantly lower AL rate (3.0%) compared to the non-FL group (9.4%) (P = 0.035). Severe symptomatic anastomotic leaks (SSAL) were also reduced in the FL group (0.8% vs. 5.6%, P = 0.045). Subgroup analysis showed that FL significantly reduced AL in normal BMI patients (2.4% vs. 8.5%, P = 0.041). In high-BMI patients, FL reduced AL (3.9% vs. 10.8%, P = 0.063), but the difference was not statistically significant. FL also reduced blood loss, improved lymph node yield, and accelerated recovery, including earlier return of bowel function, quicker soft diet initiation, and shorter hospital stays. ICG FL reduces AL and enhances recovery, particularly in normal BMI patients, with a potential benefit for high-BMI patients. Further studies are needed to confirm its effect in this group.

PMID:41066064 | DOI:10.1007/s13304-025-02352-5

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Nevin Manimala Statistics

Some novel causes and clinical characteristics of reversible splenial lesion syndrome- found in children

Neurol Sci. 2025 Oct 9. doi: 10.1007/s10072-025-08554-4. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe causes, clinical manifestations, imaging features and prognosis of reversible splenial lesion syndrome (RESLES) in children.

METHODS: A total of 36 patients with RESLES hospitalized in Children’s Hospital of Chongqing Medical University between January 1, 2017 and Mar 31, 2024 were included. The clinical features including the causes, clinical manifestations and prognosis were statistically analyzed.

RESULTS: The patients’ ages ranged from 16 to 170 months with a median age of 49 months. Of the 36 patients, 24 patients were RESLES type-1 (the lesions were limited to SCC) and 12 patients were RESLES type-2(the lesions spread to other parts of the corpus callosum, extensive brain white matter, or both). The participating causes included infection, chemotherapy, immunoglobulin A vasculitis, autoimmune glial fibrillary acidic protein astrocytopathy, hypertension and hypoparathyroidism. The common neurological symptoms were seizures(n = 27), headache(n = 10), dizziness(n = 6), altered consciousness(n = 8), and psychologico-behavioral abnormalities(n = 14). Most patients had a good prognosis except 1 patient remained in a state of minimal consciousness during the follow-up.

CONCLUSION: This research demonstrates some possible causes of RESLES. Patients with RESLES present with a variety of nonspecific symptoms and most of them had a good prognosis.

SIGNIFICANCE: These findings are groundbreaking to a deeper understanding of RESLES.

PMID:41066056 | DOI:10.1007/s10072-025-08554-4

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Nevin Manimala Statistics

Risk of dementia in patients treated with anticholinergics for overactive bladder syndrome: a systematic review and meta-analysis

Neurol Sci. 2025 Oct 9. doi: 10.1007/s10072-025-08546-4. Online ahead of print.

ABSTRACT

BACKGROUND: Urinary anticholinergic (AC) medications are commonly prescribed for Overactive Bladder (OAB) syndrome. Although recent studies suggest a potential link between their use and an increased risk of dementia, this association remains debated.

METHODS: We conducted a systematic review and meta-analysis to evaluate the risk of dementia in patients receiving AC treatment for OAB syndrome. A comprehensive search of PubMed, Embase, and Cochrane databases was performed. Outcomes of interest included dementia risk and its association with age, sex distribution, treatment duration, and follow-up length. Two subgroup analyses were assessed: (1) AC vs. no drug therapy and (2) AC vs. mirabegron, a beta-3 agonist and current standard of care for OAB syndrome. Relative risk (RR) with p-value < 0.05 was considered statistically significant.

RESULTS: Eight studies were included, comprising a total of 3,656,686 patients diagnosed with OAB syndrome, of whom 44.7% were exposed to urinary AC. The comparison between AC and no drug therapy showed a statistically significant higher risk of dementia in the exposed group (RR 1.2, 95% CI [1.09-1.32], I²=96%, p < 0.01). When the AC group was compared to patients who received Mirabegron, the AC use also presented a statistically significant increase in dementia risk (RR 1.28; 95% CI [1.03-1.58], I²=98%, p = 0.02).

CONCLUSIONS: Patients who received urinary AC therapy for OAB syndrome were associated with an increased risk of dementia compared to both no drug therapy and medical therapy with mirabegron. These findings suggest that, for the long-term treatment of adult patients with OAB syndrome, alternative therapeutic options to AC should be considered, with Mirabegron emerging as a valid choice in clinical decision-making.

PMID:41066055 | DOI:10.1007/s10072-025-08546-4

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Nevin Manimala Statistics

Bayesian joint models for longitudinal, recurrent, and terminal event data

Lifetime Data Anal. 2025 Oct 9. doi: 10.1007/s10985-025-09673-y. Online ahead of print.

ABSTRACT

Many methods exist to jointly model either recurrent and related terminal survival events or longitudinal outcome measures and related terminal survival event. However, few methods exist which can account for the dependency between all three outcomes of interest, and none allow for the modeling of all three outcomes without strong correlation assumptions. We propose a joint model which uses subject-specific random effects to connect the survival model (terminal and recurrent events) with a longitudinal outcome model. In the proposed method, proportional hazards models with shared frailties are used to model dependence between the recurrent and terminal events, while a separate (but correlated) set of random effects are utilized in a generalized linear mixed model to model dependence with longitudinal outcome measures. All random effects are related based on an assumed multivariate normal distribution. The proposed joint modeling approach allows for flexible models, particularly for unique longitudinal trajectories, that can be utilized in a wide range of health applications. We evaluate the model through simulation studies as well as through an application to data from the Atherosclerosis Risk in Communities (ARIC) study.

PMID:41066052 | DOI:10.1007/s10985-025-09673-y

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Nevin Manimala Statistics

Effects of iodine supplementation on thyroid function in children with mild congenital hypothyroidism and non-autoimmune subclinical hypothyroidism

J Endocrinol Invest. 2025 Oct 9. doi: 10.1007/s40618-025-02718-x. Online ahead of print.

ABSTRACT

PURPOSE: The role of iodine treatment in congenital and acquired non-autoimmune subclinical hypothyroidism (SH) remains unclear, although it has been demonstrated that iodine can improve thyroid function in some dyshormonogenetic defects. We aimed to evaluate the effect of iodine administration in children with congenital hypothyroidism (CH) with gland in situ (GIS) and non-autoimmune SH diagnosed during childhood.

PATIENTS AND METHODS: 13 children with CH and GIS and 19 with non-autoimmune SH (7 females, 25 males; median age 10 years) were given iodine for 9 months at increasing doses from 50 µg/day to 150 µg/day, after stopping levothyroxine (LT4), when taken. 4 children had DUOX2 mutations, whereas the etiology was unknown in the remaining cases. Thyroid hormones, anti-thyroid antibodies and ultrasound were evaluated every 3 months for 12 months and then after 1 year.

RESULTS: At increasing of the daily iodine dose, there was in both groups a slight progressive increase in TSH, that became statistically significant only after 150 µg/day, both in the SH group (p 0.044) and in the whole group (p 0.015). The other parameters did not change with treatment. No children developed thyroid autoimmunity, even one year after iodine withdrawal, and iodine treatment did not modify the course of disease as shown by follow-up data.

CONCLUSION: This study shows a failure of physiological doses of iodine to improve mild CH with GIS and idiopathic SH. The increase of serum TSH during treatment may reflect the spontaneous course of the disease in children rather than a detrimental effect of iodine.

PMID:41066039 | DOI:10.1007/s40618-025-02718-x

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Nevin Manimala Statistics

Electrochemical Characterization of Site-Specifically Metal-Modified DNA Films on Gold Electrode Surfaces

Chempluschem. 2025 Oct 9:e202500494. doi: 10.1002/cplu.202500494. Online ahead of print.

ABSTRACT

The electrochemical characterization of DNA films with different base mismatches or with CuII– or AgI-mediated pairs was carried out to assess possible immobilization and interaction effects. Toward this end, 3-hydroxy-2-methylpyridin-4(1H)-one (H), imidazole-4-carboxylate (K), purine-6-carboxylate (P), and 7-deaza-6-pyrazolylpurine (D) were used as artificial metal-binding nucleobases. Cyclic voltammetry and square-wave voltammetry confirmed the immobilization of suitably modified oligonucleotides on Au electrodes. The incorporation of the metal ions into the base mismatches to form metal-mediated base pairs showed a negligible effect on the peak potentials. Ambiguous electrochemical impedance spectroscopy results were obtained for DNA with metal-mediated base pairs, as some duplexes showed no effect of metal ion addition, while others showed variable charge transfer resistance (RCT) with no discernible pattern. Notably, the formation of AgI-mediated base pairs induced larger relative changes in RCT compared to CuII-mediated base pairs. Amongst the latter, only strands containing the artificial nucleobase H showed statistically relevant sequence- and distance-dependent charge transfer changes upon metalation. The data indicate that neither nucleobase charge nor nucleobase size directly correlates with the charge transfer resistance, but suggest that changes in DNA film stiffness and hence permeability outweigh other effects.

PMID:41066038 | DOI:10.1002/cplu.202500494