Nevin Manimala

Bioinform Adv. 2024 Dec 24;5(1):vbae207. doi: 10.1093/bioadv/vbae207. eCollection 2025.

ABSTRACT

MOTIVATION: The expansion of genetic association data from genome-wide association studies has increased the importance of methodologies like Polygenic Risk Scores (PRS) and Mendelian Randomization (MR) in genetic epidemiology. However, their application is often impeded by complex, multi-step workflows requiring specialized expertise and the use of disparate tools with varying data formatting requirements. Existing solutions are frequently standalone packages or command-line based-largely due to dependencies on tools like PLINK-limiting accessibility for researchers without computational experience. Given Python’s popularity and ease of use, there is a need for an integrated, user-friendly Python toolkit to streamline PRS and MR analyses.

RESULTS: We introduce Genal, a Python package that consolidates SNP-level data handling, cleaning, clumping, PRS computation, and MR analyses into a single, cohesive toolkit. By eliminating the need for multiple R packages and for command-line interaction by wrapping around PLINK, Genal lowers the barrier for medical scientists to perform complex genetic epidemiology studies. Genal draws on concepts from several well-established tools, ensuring that users have access to rigorous statistical techniques in the intuitive Python environment. Additionally, Genal leverages parallel processing for MR methods, including MR-PRESSO, significantly reducing the computational time required for these analyses.

AVAILABILITY AND IMPLEMENTATION: The package is available on Pypi (https://pypi.org/project/genal-python/), the code is openly available on Github with a tutorial: https://github.com/CypRiv/genal, and the documentation can be found on readthedocs: https://genal.rtfd.io.

PMID:39776894 | PMC:PMC11706532 | DOI:10.1093/bioadv/vbae207

Exp Ther Med. 2024 Dec 18;29(2):34. doi: 10.3892/etm.2024.12784. eCollection 2025 Feb.

ABSTRACT

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with an annual incidence of ~2 cases per million worldwide. The hereditary form is more likely to present in younger patients. To date, PPGL is considered a complex pathology that is difficult to diagnose. The present study aimed to improve the molecular diagnosis and other driver mutations related to PPGLs using TruSight One clinical exome panel (Illumina, Inc.). The clinical protocol used involved examining 28 patients with suspicion of genetic alterations as the cause of PPGLs. The variants of genes commonly associated with PPGLs (RET, FH, VHL, SDHA, SDHB, SDHC, SDHD, NF1, MAX, HIF2A, TMEM127 and TP53) were filtered across the panel. The libraries were sequenced on a MiSeq instrument (Illumina, Inc.) and the result was ≥20X coverage on 95% of the target regions in the panel, calculated by averaging the mean coverage for each exon. The results of sequencing detected 7% of pathogenic variants in the 18-40 years age subgroup and 11% in the 41-59 years age subgroup, whereas no pathogenic/likely pathogenic variants were identified in patients ≥60 years old. The identification of a germline mutation in patients with apparently sporadic PPGLs could lead to an early diagnosis of multiple or more aggressive tumors, or other neoplastic syndromes, in patients. Furthermore, this information may improve the development of targeted primary and secondary prevention programs tailored to these high-risk groups.

PMID:39776888 | PMC:PMC11705218 | DOI:10.3892/etm.2024.12784

J Gen Fam Med. 2024 Dec 10;26(1):73-78. doi: 10.1002/jgf2.740. eCollection 2025 Jan.

ABSTRACT

BACKGROUND: Our goal was to identify, and risk stratify primary care patients with microscopic hematuria (MH), describe the diagnostic evaluations they received, and determine whether the evaluations were consistent with the recommendations of the 2020 AUA/SUFU microscopic hematuria guidelines.

METHODS: A retrospective review of patients presenting to primary care clinics with a diagnosis of MH was performed. The patient risk category was determined based on the 2020 AUA/SUFU guidelines. Diagnostic strategies were recorded, and guideline concordance was determined. Descriptive statistics were generated to describe outcomes.

RESULTS: A total of 368 patients had a diagnosis of MH; 267/368 (72.6%) patients had all pertinent data available for risk stratification. One-hundred and fifty-six (58.4) patients were high-risk and 55 (35.3%) had a urologic visit. Forty-one of the 55 (75%) were diagnostically evaluated of which 13 (31.7%) were in-line with guideline recommendations. Eighty-two (30.7%) patients were at intermediate risk of which 33 (40.2%) had a urology visit. Of these 33 intermediate-risk patients, 27 (81.8%) were diagnostically evaluated, five (18.5%) of which were in-line with guideline recommendations. Twenty-nine patients were low risk of which 4 (13.8%) had a urology visit. Three of the four patients seen by urology (75%) were evaluated with imaging studies and none received a cystoscopy.

CONCLUSION: Almost 60% of the patients in our cohort were high-risk according to the AUA/SUFU 2020 guidelines. Across all strata, the majority of patients lacked a urology visit and diagnostic evaluation consistent with guideline recommendations. Future efforts should ensure appropriate urologic referral and optimize initial diagnostic strategies for patients with MH.

PMID:39776878 | PMC:PMC11702366 | DOI:10.1002/jgf2.740

Front Cardiovasc Med. 2024 Dec 24;11:1434265. doi: 10.3389/fcvm.2024.1434265. eCollection 2024.

ABSTRACT

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Various factors can exacerbate disease progression in patients with HF and negatively impact treatment outcomes. This study aims to evaluate the pooled prevalence and contributing factors associated with poor heart failure treatment outcomes in Ethiopia.

METHODS: A systematic review and meta-analysis were conducted using five databases: Google Scholar, ScienceDirect, Hinari, PubMed, and Scopus. In total, 12 studies met the eligibility criteria for inclusion in this analysis. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Data extraction was performed using a Microsoft Excel spreadsheet, and statistical analysis was conducted with STATA 14. The Joanna Briggs Institute Meta-analysis of Statistics Assessment and Review Instrument was utilized for quality assessment. Heterogeneity among the studies was evaluated using the I ² statistic and the Cochrane Q test. Publication bias was assessed using Begg’s test, Egger’s weighted regression, and funnel plots.

RESULTS: The pooled prevalence of poor HF treatment outcomes was found to be 16.67% [95% confidence interval (CI): 10.67-22.67]. No significant heterogeneity was observed across the included studies (I ² = 0.0%, p = 0.962). Significant predictors of a poor treatment outcome were smoking cigarettes [adjusted odds ratio (AOR) = 10.74; 95% CI: 3.24-35.63] and medication-related problems (AOR = 3.99; 95% CI: 1.90-8.37).

CONCLUSION: The prevalence of poor HF treatment outcomes in Ethiopia was found to be high. Smoking cigarettes and medication-related problems are significant predictors of these adverse outcomes. Comprehensive health education and improved clinical pharmacy services are essential for addressing these issues.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023437397, PROSPERO (CRD42023437397).

PMID:39776867 | PMC:PMC11703969 | DOI:10.3389/fcvm.2024.1434265

Front Cardiovasc Med. 2024 Dec 24;11:1442957. doi: 10.3389/fcvm.2024.1442957. eCollection 2024.

ABSTRACT

BACKGROUND: Poor nutritional status may affect outcomes after coronary revascularization, but the association between nutritional status and outcomes in patients undergoing coronary revascularization has not been fully evaluated. This study was based on the MIMIC-IV database to analyze the impact of baseline nutritional status on poor outcomes in patients with coronary revascularization.

METHODS: Patients with coronary revascularization were screened from the MIMIC-IV database. A geriatric nutritional risk index (GNRI) was calculated and used to divide patients into 4 groups: no malnutrition (Q4: ≥96.79), mild malnutrition (Q3: 90.85-96.78), moderate malnutrition (Q2: 86.37-90.84), and severe malnutrition (Q1: 86.37). The primary outcome measure was 28-day mortality, and the secondary outcome measures were AKI and length of hospital stay. Cox proportional hazards model, Kaplan-Meier survival analysis, restricted cubic spline (RCS), and multiple linear regression model were used for statistical analysis, respectively, to ensure the robustness of study results.

RESULTS: A total of 1,168 patients with coronary revascularization were included. The GNRI demonstrated a significant association with 28-day mortality in patients undergoing coronary revascularization. As a continuous variable, the GNRI exhibited a notable inverse correlation with mortality across unadjusted, partially adjusted, and fully adjusted Cox regression models [hazard ratios (HRs): 0.93, 0.94, 0.96, respectively; all P < 0.001]. When considered as a categorical variable, a low GNRI (first quartile, Q1) was significantly associated with elevated mortality risks (HRs: 2.64, 2.30, 1.82 in the unadjusted, partially adjusted, and fully adjusted models, respectively; all P < 0.05). Subgroup analysis revealed a more pronounced association in patients under 65 years of age (P for interaction = 0.014). Furthermore, reduced GNRI levels were also associated with an increased incidence of AKI and extended hospital lengths of stay.

CONCLUSION: GNRI is associated with prognosis in patients with coronary revascularization. Patients with lower GNRI had higher 28-day mortality, greater risk of AKI, and longer hospital stays.

PMID:39776862 | PMC:PMC11703724 | DOI:10.3389/fcvm.2024.1442957

Patterns (N Y). 2024 Dec 6;5(12):101115. doi: 10.1016/j.patter.2024.101115. eCollection 2024 Dec 13.

ABSTRACT

Guidelines in statistical modeling for genomics hold that simpler models have advantages over more complex ones. Potential advantages include cost, interpretability, and improved generalization across datasets or biological contexts. We directly tested the assumption that small gene signatures generalize better by examining the generalization of mutation status prediction models across datasets (from cell lines to human tumors and vice versa) and biological contexts (holding out entire cancer types from pan-cancer data). We compared model selection between solely cross-validation performance and combining cross-validation performance with regularization strength. We did not observe that more regularized signatures generalized better. This result held across both generalization problems and for both linear models (LASSO logistic regression) and non-linear ones (neural networks). When the goal of an analysis is to produce generalizable predictive models, we recommend choosing the ones that perform best on held-out data or in cross-validation instead of those that are smaller or more regularized.

PMID:39776849 | PMC:PMC11701843 | DOI:10.1016/j.patter.2024.101115

Patterns (N Y). 2024 Nov 19;5(12):101097. doi: 10.1016/j.patter.2024.101097. eCollection 2024 Dec 13.

ABSTRACT

The placenta is vital to maternal and child health but often overlooked in pregnancy studies. Addressing the need for a more accessible and cost-effective method of placental assessment, our study introduces a computational tool designed for the analysis of placental photographs. Leveraging images and pathology reports collected from sites in the United States and Uganda over a 12-year period, we developed a cross-modal contrastive learning algorithm consisting of pre-alignment, distillation, and retrieval modules. Moreover, the proposed robustness evaluation protocol enables statistical assessment of performance improvements, provides deeper insight into the impact of different features on predictions, and offers practical guidance for its application in a variety of settings. Through extensive experimentation, our tool demonstrates an average area under the receiver operating characteristic curve score of over 82% in both internal and external validations, which underscores the potential of our tool to enhance clinical care across diverse environments.

PMID:39776848 | PMC:PMC11701861 | DOI:10.1016/j.patter.2024.101097

J Avian Med Surg. 2025 Jan;38(4):188-196. doi: 10.1647/AVIANMS-D-23-00050.

ABSTRACT

Viscoelastic testing evaluates the formation and lysis of a clot over time, allowing more complete assessment of patient hemostasis in real time, whereas traditional tests, such as prothrombin time and partial thromboplastin time, only measure coagulation factor function. Patient-side viscoelastic coagulation monitors are easy to use, portable, and provide faster turnaround time than commercial laboratories. Viscoelastic testing requires only 0.2 mL of blood and is useful in diagnosing and treating hemostatic disorders. Currently, there is no standardized coagulation testing method across bird species. In this cross-sectional study, a viscoelastic coagulation device, the Entegrion Viscoelastic Coagulation Monitor-Vet (VCM-Vet), was evaluated. Blood samples were obtained from 26 Hispaniolan Amazon parrots (HAPs) (Amazona ventralis) under manual restraint. Results were recorded on the device as graphical output with quantitative viscoelastic measurements. Results were reported using standard rotational thromboelastometry terminology, including clotting time, clot formation time, alpha angle, maximum clot firmness, clot firmness amplitude at 10 and 20 minutes after clot formation, and clot lysis at 30 and 45 minutes. The median clotting time was 463 seconds (reference interval: 56-1635 seconds), the mean clot formation time was 704.7 seconds (reference interval: 172-1697 seconds), the mean alpha angle was 27.3 (reference interval: 7-60), and the mean maximum clot firmness was 15.4 (reference interval: 7-25). Statistical analysis found that all parameters were normally distributed aside from clotting time in seconds. There was no appreciable breakdown of the clot during the 60-minute device runtime, and there was no significant difference in any parameter based on sex. The VCM-Vet produced clotting times for this population of HAPs and enabled the creation of reference intervals. Based on our findings, the VCM-Vet can be used to assess clot potential in HAPs and possibly other avian species.

PMID:39772379 | DOI:10.1647/AVIANMS-D-23-00050

J Perianesth Nurs. 2025 Jan 6:S1089-9472(24)00450-7. doi: 10.1016/j.jopan.2024.08.022. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of the project was to reduce the occurrence of nonclinical delays resulting in increased postanesthesia care unit length of stay for carpal tunnel release patients in an ambulatory orthopedic surgery center through the implementation of new workflow processes in both the preoperative and postoperative phases of care.

DESIGN: Pre-post design, with data being analyzed both before and after implementation of evidence-based quality improvement measures to assess for effectiveness of project interventions.

METHODS: At the ambulatory orthopedic surgery center, preintervention data were gathered for 6 months on carpal tunnel release patients (n = 185) to determine the root causes of discharge delays (January to June 2023). Subsequently, the following evidence-based workflow processes were implemented: the provision of preoperative discharge instructions to the patient, clearly delineated expectations for family members during their stay, early presence of family to the bedside during phase 1 of recovery, and extensive staff education. Postintervention data (n = 189) were collected on a biweekly basis throughout the 6 months of project implementation (September 2023 to February 2024) and were analyzed using the paired t test for statistical significance.

FINDINGS: The average length of stay decreased from 44.45 to 37.07 minutes with an increase in the percentage of patients meeting discharge goals from 13.5% to 35.4%. This is a statistically significant improvement in length of stay (P < .0001).

CONCLUSIONS: Interventions to maintain efficiency such as preoperative discharge teaching, early family presence at bedside, and clear expectations for family member participation can collectively contribute to a decrease in non-anesthesia-related delays and subsequently reduce postanesthesia care unit length of stay.

PMID:39772372 | DOI:10.1016/j.jopan.2024.08.022

J Am Coll Cardiol. 2024 Nov 28:S0735-1097(24)10316-6. doi: 10.1016/j.jacc.2024.10.104. Online ahead of print.

ABSTRACT

BACKGROUND: The results of ablation of sustained monomorphic ventricular tachycardia (SMVT) are suboptimal. For many patients with implantable cardioverter-defibrillators (ICDs), ICD electrograms (ICD-EGs) provide the only available information on SMVT. ICD-EGs have the ability to distinguish morphologically distinct SMVT and can be used for pace mapping.

OBJECTIVES: This study aimed to evaluate whether using ICD-EG information during an ablation procedure influences outcomes.

METHODS: Patients with structural heart disease and SMVT documented by an ICD-EG, undergoing ablation, were randomly assigned in a 1:1 ratio to either an ablation incorporating ICD-EG data during the procedure (intervention group) or to conventional ablation. The ICD-EG obtained during induced SMVT and pace mapping was compared to ICD-EG from spontaneous SMVT to target the “clinical” SMVT for ablation. Ablation could be performed during SMVT (if tolerated), during sinus rhythm (“substrate ablation”), or both.

RESULTS: A total of 15 centers randomized 260 patients. Characterization of induced SMVT as clinical/nonclinical and pace mapping were more frequent in the intervention group. Most patients underwent pure substrate ablation (65%), with complementary ablation during SMVT in 26%, showing no significant difference between groups. No differences were found in acute efficacy. In the intention-to-treat analysis, the primary endpoint of SMVT recurrence within 6 months postablation occurred in 46 (36%) patients in the intervention group and 59 (46%) in the conventional group (HR: 0.73; 95% CI: 0.49-1.07; P = 0.11). In the per-protocol analysis, SMVT recurrence at 6 months postablation reached statistical significance (HR: 0.66; 95% CI: 0.44-0.99; P = 0.045). During the entire follow-up period (44 ± 29 months), SMVT recurrence occurred in 67% and 76% (HR: 0.80; 95% CI: 0.60-1.08; P = 0.14). The number of SMVT episodes was significantly lower in the intervention group (HR: 0.45; 95% CI: 0.24-0.84; P = 0.013), as was the rate of electrical storm (23% vs 41%; HR: 0.54; 95% CI: 0.34-0.85; P = 0.007). There were no differences in ICD shocks.

CONCLUSIONS: In patients with structural heart disease and ICD-documented SMVT, using ICD-EG information during the ablation procedure to focalize ablation toward the clinical ventricular tachycardia is associated with a nonsignificant decrease in SMVT recurrence rate, a significant reduction in the number of ventricular tachycardia episodes, and a lower rate of arrhythmic storm.

PMID:39772368 | DOI:10.1016/j.jacc.2024.10.104