Tag: nevin manimala

J Am Med Inform Assoc. 2025 Feb 18:ocaf035. doi: 10.1093/jamia/ocaf035. Online ahead of print.

ABSTRACT

OBJECTIVE: This study addresses the significant challenges posed by emerging SARS-CoV-2 variants, particularly in developing diagnostics and therapeutics. Drug repurposing is investigated by identifying critical regulatory proteins impacted by the virus, providing rapid and effective therapeutic solutions for better disease management.

MATERIALS AND METHODS: We employed a comprehensive approach combining mathematical modeling and efficient parameter estimation to study the transient responses of regulatory proteins in both normal and virus-infected cells. Proportional-integral-derivative (PID) controllers were used to pinpoint specific protein targets for therapeutic intervention. Additionally, advanced deep learning models and molecular docking techniques were applied to analyze drug-target and drug-drug interactions, ensuring both efficacy and safety of the proposed treatments. This approach was applied to a case study focused on the cytokine storm in COVID-19, centering on Angiotensin-converting enzyme 2 (ACE2), which plays a key role in SARS-CoV-2 infection.

RESULTS: Our findings suggest that activating ACE2 presents a promising therapeutic strategy, whereas inhibiting AT1R seems less effective. Deep learning models, combined with molecular docking, identified Lomefloxacin and Fostamatinib as stable drugs with no significant thermodynamic interactions, suggesting their safe concurrent use in managing COVID-19-induced cytokine storms.

DISCUSSION: The results highlight the potential of ACE2 activation in mitigating lung injury and severe inflammation caused by SARS-CoV-2. This integrated approach accelerates the identification of safe and effective treatment options for emerging viral variants.

CONCLUSION: This framework provides an efficient method for identifying critical regulatory proteins and advancing drug repurposing, contributing to the rapid development of therapeutic strategies for COVID-19 and future global pandemics.

PMID:39965087 | DOI:10.1093/jamia/ocaf035

Endosc Int Open. 2025 Jan 29;13:a24094916. doi: 10.1055/a-2409-4916. eCollection 2025.

ABSTRACT

BACKGROUND AND STUDY AIMS: Post-polypectomy surveillance colonoscopy (SC) plays an integral role in efforts to reduce colorectal cancer risk, but its effectiveness is invariably dependent on patient compliance. This study aimed to evaluate patient adherence to SC after endoscopic resection (ER) of polyps ≥ 20 mm and identify potential barriers associated with loss to follow-up.

PATIENTS AND METHODS: This was a single-center retrospective study evaluating adherence to SC after ER of polyps ≥ 20 mm between April 2018 to December 2021. Adherence to SC was defined as the proportion of patients who underwent follow-up colonoscopy. Multivariate logistic regression was performed to identify factors associated with loss to follow-up.

RESULTS: A total of 959 patients (mean age 67 years; 47.9% women) underwent endoscopic resection of colorectal polyps ≥ 20 mm (mean size 33.2 ± 13.7 mm). Nearly half of the patients (n = 478; 49.8%) were lost to follow-up. On multivariate analysis, factors associated with a higher likelihood of SC non-adherence were: lack of a primary care physician (odds ratio [OR] 1.7;95% confidence interval [CI] 1.3- 2.3; P < 0.05), American Society of Anesthesiologists grade 3 or 4 (OR 1.4; 95% CI 1.1-1.9; P < 0.05), residence > 60 miles from the endoscopy suite (OR 1.6; 95% CI 1.2-2.3; P = 0.02), being referred by a physician outside of our healthcare system (OR 1.4; 95% CI 1.1-1.8; P = 0.01), and lack of written follow-up recommendations on the colonoscopy report (OR 3.6; 95% CI 1.4-10.2; P = 0.01).

CONCLUSIONS: Nearly half of patients undergoing ER of colorectal polyps ≥ 20 mm are lost to follow-up. We identified several patient- and healthcare-related factors as barriers to SC adherence. Strategies to address these issues and targeting of high-risk populations are urgently needed to enhance SC programs.

PMID:39965041 | PMC:PMC11827743 | DOI:10.1055/a-2409-4916

PLoS Comput Biol. 2025 Feb 18;21(2):e1012717. doi: 10.1371/journal.pcbi.1012717. Online ahead of print.

ABSTRACT

We propose, implement, and evaluate a method for nowcasting the daily number of new COVID-19 hospitalizations, at the level of individual US states, based on de-identified, aggregated medical insurance claims data. Our analysis proceeds under a hypothetical scenario in which, during the Delta wave, states only report data on the first day of each month, and on this day, report COVID-19 hospitalization counts for each day in the previous month. In this hypothetical scenario (just as in reality), medical insurance claims data continues to be available daily. At the beginning of each month, we train a regression model, using all data available thus far, to predict hospitalization counts from medical insurance claims. We then use this model to nowcast the (unseen) values of COVID-19 hospitalization counts from medical insurance claims, at each day in the following month. Our analysis uses properly-versioned data, which would have been available in real-time at the time predictions are produced (instead of using data that would have only been available in hindsight). In spite of the difficulties inherent to real-time estimation (e.g., latency and backfill) and the complex dynamics behind COVID-19 hospitalizations themselves, we find altogether that medical insurance claims can be an accurate predictor of hospitalization reports, with mean absolute errors typically around 0.4 hospitalizations per 100,000 people, i.e., proportion of variance explained around 75%. Perhaps more importantly, we find that nowcasts made using medical insurance claims are able to qualitatively capture the dynamics (upswings and downswings) of hospitalization waves, which are key features that inform public health decision-making.

PMID:39965031 | DOI:10.1371/journal.pcbi.1012717

JMIR Rehabil Assist Technol. 2025 Feb 18;12:e65358. doi: 10.2196/65358.

ABSTRACT

BACKGROUND: Children with neurodevelopmental disorders, such as cerebral palsy (CP), often experience motor impairments in manual dexterity, which hinder daily tasks and social interactions. Traditional rehabilitation methods require repetitive task practice, which can be difficult for children to sustain due to low engagement. Game-based rehabilitation devices and robots offer a promising alternative by combining therapy with digital play, improving motivation and compliance. However, many systems fail to incorporate actual object manipulation, which is essential for motor learning through sensory feedback. To address this limitation, a low-cost, easy-to-use robotic manipulandum device (RMD) was developed. The RMD enables real-time object manipulation during gameplay while providing assistive force, allowing the practice of a wide range of manual dexterity skills beyond gross reaching. This system offers an engaging and effective rehabilitation approach to enhance hand function in children with CP.

OBJECTIVE: This study aimed to provide evidence for the feasibility and therapeutic value of the RMD game-based exercise program for children with CP.

METHODS: In total, 34 children with CP, aged 4 to 10 years, were randomly assigned to the experimental group (XG) or the control group (CG). The XG received a computer game-based exercise program using the RMD, focusing on object manipulation tasks, while the CG received task-specific training similar to constraint-induced movement therapy. Both groups received their respective therapy programs 3 times per week for 8 weeks. Semistructured interviews with parents and children, along with qualitative analysis, were conducted to evaluate their experiences with the exercise program. The following outcome measures were used: (1) the Peabody Developmental Motor Scale-2 (PDMS-2) grasping and visual-motor integration subtests and (2) the computer game-based upper extremity (CUE) assessment of manual dexterity.

RESULTS: No dropouts occurred during the 8-week program. Both groups showed significant improvements in the PDMS-2 subtests (P<.001) and the CUE assessment of manual dexterity, including success rates (tennis ball: P=.001; cone: P<.001; medicine ball: P=.001; and peanut ball: P<.001) and movement errors (tennis ball: P=.01; cone: P<.001; medicine ball: P=.04; and peanut ball: P<.001). The XG outperformed the CG, showing greater improvements in PDMS-2 grasping (P=.002) and visual-motor integration (P=.01). In the CUE assessment, the XG demonstrated higher success rates (medicine ball: P=.001 and peanut ball: P=.02) and fewer movement errors (cone: P<.001). Parents reported an increase in the children’s independence in daily tasks.

CONCLUSIONS: This study demonstrates the feasibility, acceptability, and positive outcomes of the RMD game-based exercise program for improving hand function in children with CP. The findings support further research and development of computer game-assisted rehabilitation technologies.

TRIAL REGISTRATION: Clinical Trials Registry – India CTRI/2021/07/034903; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NTc4ODU.

PMID:39964707 | DOI:10.2196/65358

Anticancer Drugs. 2025 Feb 18. doi: 10.1097/CAD.0000000000001706. Online ahead of print.

ABSTRACT

The objective of this study is to explore the effect of adjuvant chemotherapy with toad venom injection in patients with intermediate and advanced colon cancer, in order to provide new reference drugs for clinical treatment. Prospectively, 148 patients with mid-stage to late-stage colon cancer in our hospital from January 2021 to May 2023 were selected for the study and randomly divided into two groups of 74 cases each. The control group was treated with FOLFOX4 chemotherapy, and the observation group was treated with four consecutive chemotherapy cycles based on the control group combined with toad venom injection. The treatment effects, adverse reactions, quality of life improvement rate, prognosis and cellular immune indexes [natural killer (NK) cells, CD4+/CD8+, CD4+, CD3+], phosphatase tensin gene (PTEN), phosphatidylinositol-3-kinase (PI3k), and serine threonine protein kinase (pAKT) protein expression before and after treatment were counted in the two groups. The total effective rate of treatment in the observation group was 58.11% (43/74) after four cycles of chemotherapy, which was higher than that in the control group of 41.89% (31/74) (P < 0.05). After two cycles of chemotherapy and four cycles of chemotherapy, PTEN, CD4+/CD8+, CD4+, CD3+, and NK cells in peripheral blood were higher in the observation group than in the control group, and PI3k and pAKT were lower than in the control group (P < 0.05). There was no statistically significant difference in the rate of adverse reactions in the observation group compared with the control group (P > 0.05); the improvement rate of quality of life in the observation group was better than that in the control group after four chemotherapy cycles of treatment (P < 0.05); the survival rate was 75.00% (54/72) in the observation group compared with 54.29% (38/70) in the control group at 1-year follow-up. Toad venom injection adjuvant chemotherapy is effective in treating patients with intermediate and advanced colon cancer, which can upregulate PTEN level, inhibit PI3k and AKT expression, and improve immune function and quality of life of patients, thus improving prognosis.

PMID:39964699 | DOI:10.1097/CAD.0000000000001706

Chaos. 2025 Feb 1;35(2):023142. doi: 10.1063/5.0242061.

ABSTRACT

Forecasting complex systems is important for understanding and predicting phenomena. Due to the complexity and error sensitivity inherent in these predictive models, forecasting proves challenging. This paper presents a novel approach to assimilate system observations into predictive models. The approach makes use of a recursive partitioning algorithm to facilitate the computation of local sets of model corrections as well as provide a data structure to traverse the model space. These local sets of corrections act as a sample from a piecewise stochastic process. Appending these corrections to the predictive model incorporates hidden residual dynamics, resulting in improved forecasting performance. Numerical experiments demonstrate that this approach results in improved forecasting for the Lorenz 1963 model. In addition, comparisons are made between two types of corrections: Vector Difference and Gaussian. Vector Difference corrections provide the best computational efficiency and forecasting performance. To further justify the effectiveness of this approach it is successfully applied to more complex systems such as Lorenz for various chaotic parameterizations, coupled Lorenz, and cubic Lorenz.

PMID:39964695 | DOI:10.1063/5.0242061

JAMA Netw Open. 2025 Feb 3;8(2):e2460460. doi: 10.1001/jamanetworkopen.2024.60460.

NO ABSTRACT

PMID:39964687 | DOI:10.1001/jamanetworkopen.2024.60460

JAMA Netw Open. 2025 Feb 3;8(2):e2460087. doi: 10.1001/jamanetworkopen.2024.60087.

ABSTRACT

IMPORTANCE: Foot ulcers are a common and feared complication for people with diabetes because 20% of foot ulcers become infected and lead to a lower extremity amputation.

OBJECTIVE: To evaluate the effect of daily foot care using chlorhexidine wipes vs soap-and-water wipes for 1 year on the risk of developing new foot complications in veterans with diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, phase 2b randomized clinical trial was conducted at the Baltimore Veterans Affairs (VA) Medical Center between January 2019 to January 2023. Veterans were eligible if they had a diabetes diagnosis, were at high risk for diabetic foot complications, were ambulatory, had both feet, and did not have a current foot infection. Participants were randomly assigned 1:1 to receive either soap-and-water wipes (control group) or 2% chlorhexidine wipes (chlorhexidine group). Intention-to-treat data analysis was conducted from October 5, 2023, to April 24, 2024.

INTERVENTION: Daily use of a 2% chlorhexidine wipe or a soap-and-water wipe on the feet for 1 year. Wipes were nearly identical in color, size, shape, thickness, feel, and scent. Both chlorhexidine and control groups received the same lotion for application on the feet after wipe use and education on foot self-care.

MAIN OUTCOMES AND MEASURES: The primary outcome was time in days from randomization to new foot complication, including chronic foot ulcer, foot infection, or foot amputation.

RESULTS: A total of 175 participants (170 males [97%]; mean [SD] age at enrollment, 68 [9] years; 1 Asian [1%], 117 Black or African American [67%], 53 White [30%] individuals) were randomly assigned to the chlorhexidine group (n = 88) or the control group (n = 87). Twelve participants (14%) in the chlorhexidine group and 14 participants (16%) in the control group developed a new foot complication within 1 year. Median (IQR) time from randomization to development of a new foot complication was 232 (115-315) days. The reduction in hazard of new foot complications in the chlorhexidine group compared with the control group was not significant (hazard ratio, 0.83; 95% CI, 0.39-1.80). The intervention was well tolerated, with 145 participants (83%) continuing it over the study period. Sixty adverse events occurred, but none was related to the study products or procedures.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that daily use of chlorhexidine wipes for foot washing for 1 year did not lead to a significant reduction in the risk of new foot complications compared with daily use of soap-and-water wipes. The intervention was well tolerated, and the trial provides important lessons for future studies on diabetic foot ulcer prevention.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03503370.

PMID:39964684 | DOI:10.1001/jamanetworkopen.2024.60087

JAMA Netw Open. 2025 Feb 3;8(2):e2460312. doi: 10.1001/jamanetworkopen.2024.60312.

ABSTRACT

IMPORTANCE: Metaplastic breast cancer (MpBC) is a rare, heterogeneous disease often associated with inferior outcomes. A growing body of literature describes the clinical and molecular features of MpBC, yet limited data describe the pathogenic germline variants (PGVs) in breast cancer susceptibility genes among affected individuals.

OBJECTIVE: To examine the frequency and types of PGVs in breast cancer genes among patients with MpBC.

DESIGN, SETTING, AND PARTICIPANTS: This is a descriptive retrospective cohort study of patients who received a diagnosis of MpBC at the University of Pennsylvania between January 2010 and May 2023. Electronic medical records were reviewed for demographic, clinicopathologic, and germline genetic testing information. Germline variant status was independently confirmed by a licensed genetic counselor and a physician with expertise in genetics. MpBC diagnosis and subtype were confirmed by a breast pathologist. Participants were identified via query of an institutional pathology database for reports signed between January 2010 and May 2023 including the term metaplastic. Among 320 initially obtained reports, 272 individuals had confirmed MpBC and were included in the study.

EXPOSURE: Germline genetic testing to investigate the presence of PGVs in breast cancer susceptibility genes.

MAIN OUTCOMES AND MEASURES: The primary outcome measurement was the prevalence of PGVs in breast cancer susceptibility genes among participants. The hypothesis that individuals with MpBC have an enrichment of PGVs in genes associated with inherited breast cancer risk was formulated before data collection.

RESULTS: The total sample size was 272 women, and the median age at diagnosis was 58 years (range, 20-102 years); all were biological female patients; 143 of 272 (52.6%) had documentation of germline genetic testing; and participants with testing were significantly younger than those without (median age, 53 years [range, 20-79 years] vs 63 years [range, 29-102 years]; P < .001). Of the 143 patients, 24 (16.8%) had a PGV in a breast cancer susceptibility gene (BRCA1, n = 17; BRCA2, n = 5; PALB2, n = 1; CHEK2, n = 1). Patients with PGV-associated MpBC received a diagnosis at a younger age than those with sporadic disease, but there were no significant differences in hormone receptor positivity, ERBB2 status, or metaplastic subtype.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with MpBC, a substantial proportion of clinically tested patients had a PGV in a breast cancer susceptibility gene, most commonly BRCA1. Germline testing was high yield in patients with MpBC, many of whom would be included in current germline testing eligibility criteria.

PMID:39964682 | DOI:10.1001/jamanetworkopen.2024.60312

JAMA Netw Open. 2025 Feb 3;8(2):e2460315. doi: 10.1001/jamanetworkopen.2024.60315.

ABSTRACT

IMPORTANCE: Acute pulmonary embolism (PE) is a major cause of morbidity and mortality in patients with cancer in the US and worldwide.

OBJECTIVES: To assess the trends in PE-related mortality from 2011 to 2020 among US patients with cancer across age, sex, ethnic and racial groups, urbanicity, and regionality.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system to determine national trends in age-adjusted mortality rates (AAMRs) due to acute PE among US patients with cancer aged 15 years or older from January 2011 to December 2020. Concomitant trends in cancer mortality and incidence that may have contributed to PE-related mortality were obtained from US Cancer Statistics. Data were analyzed from September to November 2024.

EXPOSURE: PE-related mortality.

MAIN OUTCOMES AND MEASURES: The primary outcome was PE-related deaths among individuals with cancer. AAMRs and cancer incidence were assessed using joinpoint regression modeling, expressed as an average annual percentage change (AAPC) with relative 95% CIs.

RESULTS: From 2011 to 2020, a total of 27 280 194 individuals aged 15 years or older (13 897 519 male [50.9%]; 13 382 675 female [49.1%]) died in the US. The AAMR for PE-related mortality in patients with cancer increased during this time period (AAPC, 2.5%; 95% CI, 1.4% to 3.6%; P = .001), without differences between sexes (P for parallelism = .38). The AAMR increased among those aged 15 to 64 years (AAPC, 3.2%; 95% CI, 1.9% to 4.6%; P = .001), non-Hispanic and non-Latinx White individuals (AAPC, 2.7%; 95% CI, 1.52% to 3.94%; P = .001), non-Hispanic and non-Latinx Black or African American individuals (AAPC, 2.2%; 95% CI, 0.7% to 3.7%; P = .001), Hispanic and Latinx individuals (AAPC, 2.6%; 95% CI, 0.7% to 4.5%; P = .006), and among individuals residing in the Southern US (AAPC, 3.7%; 95% CI, 1.3% to 6.2%; P = .003). During the same period, age-adjusted cancer incidence and cancer-related mortality decreased while the absolute number of new cancer diagnoses and cancer-related deaths increased.

CONCLUSIONS AND RELEVANCE: This cohort study found that despite decreases in cancer-related mortality rates, age-adjusted PE-related mortality in US patients with cancer increased over the last decade; concerning trends included rising PE-related mortality in younger individuals aged 15 to 64 years, particular ethnic and racial groups, and the Southern region of the US. Recognition of such patterns may inform further research into thromboprophylaxis and treatment of PE as a complication of cancer and cancer-directed therapy.

PMID:39964681 | DOI:10.1001/jamanetworkopen.2024.60315