Nevin Manimala

Genetics. 2025 Jun 12:iyaf112. doi: 10.1093/genetics/iyaf112. Online ahead of print.

ABSTRACT

Cellular diversification in processes from development to cancer progression and affinity maturation is often linked to the appearance of new mutations, generating genetic heterogeneity. Describing the underlying coupled genetic and growth processes that result in the observed diversity in cell populations is informative about the timing, drivers and outcomes of cell fates. Current approaches based on phylogenetic methods do not cover the entire range of evolutionary rates, often making artificial assumptions about the timing of events. We introduce CBA, a probabilistic method that infers the division, degradation and mutation rates from the observed genetic diversity in a population of cells. It uses a summarized backbone tree, intermediary between the true cell tree and the allelic tree representing the ancestral relationships between types, called a monogram, which allows for efficient sampling of possible phylogenies consistent with the observed mutational signatures. We demonstrate the accuracy of our method on simulated data and compare its performance to standard phylogenetic approaches.

PMID:40505111 | DOI:10.1093/genetics/iyaf112

Medwave. 2025 Jun 12;25(5):e2993. doi: 10.5867/medwave.2025.05.2993.

ABSTRACT

INTRODUCTION: According to the World Health Organization (WHO), 2.8 million mothers and newborns die each year from preventable causes, highlighting inequalities in access to quality healthcare services. The study describes the factors that limit institutional childbirth among Ashaninka mothers in the Peruvian Amazon.

METHODS: The research was descriptive, using a questionnaire administered to 152 Ashaninka mothers from five communities in Río Tambo.

RESULTS: Most Ashaninka mothers who gave birth at home were between 25 and 29 years old, lived with their partners, came from the Koterini Tarzo community, were Catholic, had incomplete secondary education, were housewives, and had a paternal income of less than or equal to 1000 PEN. They chose home birth for cultural reasons such as privacy, tradition, and economics, preferring traditional birth attendants because of their cultural acceptance and experience. Cultural practices included the burial of the placenta, the use of herbs such as “piri piri,” and vertical births. The perception of inadequate facilities and the prevalence of cesarean sections limit the acceptance of institutional childbirth. Added to this is a preference for female healthcare personnel, a lack of information about health procedures, and the prohibition of cultural practices.

CONCLUSIONS: There is a need to reform the maternal care model in Indigenous contexts, involving healthcare personnel, policymakers, and local authorities to create culturally relevant and accessible services. It is suggested that an intercultural approach be integrated into professional training and that traditional medicine be combined with the healthcare system. Future studies should evaluate the impact of these interventions on maternal and perinatal outcomes in Indigenous communities.

PMID:40505101 | DOI:10.5867/medwave.2025.05.2993

JMIR Infodemiology. 2025 Jun 12;5:e68469. doi: 10.2196/68469.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrinopathy among women that requires self-management to improve mental and physical health outcomes and reduce risk of comorbidity. Digital technology has rapidly emerged as a valuable self-management tool for people with chronic health conditions. However, little is known about the digital technology available for and used by women with PCOS. .

OBJECTIVE: The purpose of this scoping review was to identify what is known about digital technology currently available and used by women with PCOS for PCOS-specific knowledge, self-management, or social support.

METHODS: The databases PubMed, Embase, CINAHL, and Compendex were searched using Medical Subject Headings terms for PCOS, digital technology, health knowledge, self-management, and social support. Inclusion criteria were full-text, peer-reviewed publications of primary research from 2010 to 2025 in English about digital technology used for PCOS-specific knowledge, self-management, or social support by women aged 18 years and older with PCOS. Exclusion criteria were articles about pediatric populations and digital technology used for intervention recruitment or by health care providers to diagnose or treat patients.

RESULTS: In total, 34 full-text articles met the inclusion criteria. Given the scope of digital technology, eligible studies were grouped into 7 domains: mobile apps (n=14), internet-based programs (eg, Google; n=6), social media (n=6), SMS text message (n=2), machine learning (n=2), artificial intelligence (eg, ChatGPT [OpenAI]; n=3), and web-based intervention platforms (n=1). Findings highlighted participants’ varied perceptions of technology usefulness based on reliability of health care information, application features, accuracy of PCOS or fertility prediction, social group engagement, user-friendly interfaces, cultural sensitivity, and accessibility.

CONCLUSIONS: There is potential for digital technology to transform PCOS self-management, but further design and development are needed to optimize the technologies for women with PCOS. Future research should focus on including end users during the design phase of digital technology, refining predictive models, improving app inclusivity, conducting frequent reliability testing, and enhancing user engagement and support via additional features to promote more comprehensive self-management of PCOS. .

PMID:40505084 | DOI:10.2196/68469

Blood Adv. 2025 Jun 12:bloodadvances.2025016160. doi: 10.1182/bloodadvances.2025016160. Online ahead of print.

ABSTRACT

Pediatric patients with acute lymphoblastic leukemia and lymphoma (ALL/LL) and obesity are at increased risk for venous thromboembolism (VTE). The PREVAPIX-ALL trial was an open-label randomized controlled trial assessing the safety and efficacy of apixaban for VTE prevention in pediatric patients with ALL/LL. An a priori subgroup analysis of obese patients in PREVAPIX-ALL was planned due to increased VTE risk in this group. Obese patients, ages ≥ 2 to < 18 years, with a central venous catheter, and chemotherapy containing asparaginase were randomized to apixaban (prophylactic dose) versus standard of care (SOC-no anticoagulation) during induction chemotherapy (29 days). The primary efficacy endpoint was a composite of non-fatal symptomatic and asymptomatic VTE and VTE-related-death. The primary and secondary safety outcomes were major bleeding and a composite of major and clinically relevant non-major (CRNM) bleeding, respectively. Eighty-two PREVAPIX-ALL participants presented with obesity, of which 42 were randomized to apixaban. For the primary efficacy endpoint, a significant decrease in VTE events was present in the apixaban arm (1/42 [2.4%]) as compared to the SOC arm (10/40 [25%]), (Relative Risk (RR) 0.09; 95% confidence interval (CI), 0.01-0.97; P=0.007). There was a statistically significant treatment obesity interaction, P=0.03. No statistically significant difference was observed for the primary efficacy endpoint among the non-obese group (RR 0.85; 95% CI, 0.53-1.37; P=0.50). No significant difference was observed in major or CRNM bleeding among subgroups. Apixaban prophylaxis in obese ALL/LL patients resulted in a statistically significant VTE risk reduction with no increase in bleeding events. (NCT02369653).

PMID:40505060 | DOI:10.1182/bloodadvances.2025016160

JCO Oncol Pract. 2025 Jun 12:OP2500170. doi: 10.1200/OP-25-00170. Online ahead of print.

ABSTRACT

PURPOSE: To assess the impact and outcomes of a novel program for routine preemptive DPYD testing in fluoropyrimidine (FP)-naïve patients.

PATIENTS AND METHODS: This single-center, retrospective cohort study included adult patients who either received a systemic FP or had a DPYD test result between July 1, 2022, and June 30, 2023. Patients were categorized into preemptive or standard cohorts on the basis of the timing of their DPYD test relative to their initial FP dose. Primary outcomes measured were 90-day all-cause mortality, and FP-related hospitalizations and emergency department (ED) visits after the first FP dose. Secondary outcomes included the incidence of empiric dose reductions, FP avoidance, and dose escalation tolerability among patients with dihydropyrimidine dehydrogenase (DPD) deficiency.

RESULTS: Among 1,281 patients, 90-day all-cause mortality was 5.78% in the preemptive cohort versus 8.23% in the standard cohort (adjusted hazard ratio [HR], 0.69 [95% CI, 0.43 to 1.10]; P = .12), with a notable overrepresentation of patients treated with curative intent in the preemptive group (53.0% v 39.4%, P < .0001). Deaths attributed to DPD deficiency were one (0.18%) in the preemptive cohort and four (0.72%) in the standard cohort (not statistically significant with limited power). Hospitalizations and ED visits related to FP toxicity were paradoxically higher in the preemptive cohort (13.99% v 8.69%, adjusted HR, 1.67 [95% CI, 1.15 to 2.43]; P = .007). Among patients with DPD deficiency in the preemptive cohort, 84.6% received an empiric FP dose reduction, and dose escalation was attempted in 52.2% of these cases.

CONCLUSION: Preemptive DPYD testing did not significantly reduce treatment-related mortality, although a numerical decrease suggests potential benefits that may be substantiated with greater statistical power. Nearly half of the patients managed with a dose reduction did not undergo dose escalation.

PMID:40505058 | DOI:10.1200/OP-25-00170

Int J Surg. 2025 Jun 12. doi: 10.1097/JS9.0000000000002725. Online ahead of print.

ABSTRACT

BACKGROUND: By modulating inflammatory pathways and exerting sympatholytic effects, perioperative dexmedetomidine offers several benefits in non-transplant surgery. Its favorable impact on ischemia-reperfusion injury and perioperative renal function support the potential role of dexmedetomidine as an adjunct in transplant surgery. The evidence within various settings of kidney (KT) and liver transplantation (LT) is systematically reviewed.

METHODS: This systematic review evaluated randomized controlled trials investigating the efficacy of perioperative systemic dexmedetomidine in preventing allograft failure and/or kidney dysfunction in kidney and liver transplant recipients. Meta-analysis was performed using random or fixed effects model depending on the degree of statistical heterogeneity. Risk of bias and evidence quality were assessed.

RESULTS: Ten randomized controlled trials tested perioperative systemic dexmedetomidine in recipients of living (n = 3) or deceased donor (n = 1) kidney transplants and living (n = 5) or deceased donor (n = 1) liver transplants. With moderate to high certainty, cardiocirculatory, pulmonary or surgical complication rates did not differ between dexmedetomidine and control groups. Risk for delayed graft function was reduced with dexmedetomidine after deceased donor KT (risk ratio:0.52 [0.26-1.01]; p = 0.05) and living donor LT (risk ratio:0.35 [0.17-0.74]; p = 0.006), though this did not translate into improved long-term allograft survival within limited long-term follow-up. Rates of posttransplant acute kidney injury were decreased following these transplant modalities (risk ratio:0.40 [0.18-0.90]; p = 0.03 and 0.69 [0.50-0.95]; p = 0.02, respectively). Early postoperative serum creatinine was improved after KT and living donor LT. After living donor LT, serum parameters indicating allograft function improved with dexmedetomidine on postoperative days 1, 3, and 5. However, no such improvements were observed after deceased donor LT.

CONCLUSIONS: Current evidence suggests that perioperative dexmedetomidine may reduce delayed graft function in deceased donor KT and living donor LT while supporting overall renal recovery. However, due to limited data and moderate certainty of evidence, further large-scale multicenter trials are needed to confirm clinical applicability and assess long-term efficacy.

PMID:40505055 | DOI:10.1097/JS9.0000000000002725

Int J Surg. 2025 Jun 1;111(6):4056-4059. doi: 10.1097/JS9.0000000000002386. Epub 2025 Apr 3.

ABSTRACT

BACKGROUND: Large language models (LLMs) have demonstrated potential in medical diagnostics, but their accuracy in complex cases remains a subject of investigation. DeepSeek-R1, an open-source model with advanced reasoning capabilities, has gained global attention. This study evaluates the diagnostic performance of DeepSeek-R1 compared to GPT-4 in complex clinical cases.

MATERIALS AND METHODS: A historical control study was conducted using 100 clinicopathologic cases from the New England Journal of Medicine (NEJM), published between 18 August 2022, and 30 January 2025. Each case was processed using DeepSeek-R1 with a structured diagnostic prompt. The model’s performance was assessed based on final diagnosis accuracy, differential diagnosis inclusion rate, ranking of correct diagnoses, and differential quality scores. Results were statistically compared to previously published GPT-4 performance data using chi-square, Mann-Whitney U, and t-tests.

RESULTS: DeepSeek-R1 correctly matched the final diagnosis in 35% of cases (35/100), which was comparable to GPT-4’s accuracy (39%; P = 0.634). However, DeepSeek-R1 included the correct diagnosis in its differential list in 48% of cases, significantly lower than GPT-4 (64%; P = 0.036). DeepSeek-R1 generated longer differential diagnoses (11.9 ± 2.0 vs. 9.0 ± 1.4; P = 0.000004) but maintained a similar mean rank for correct diagnoses (1.8 ± 2.2 vs. 2.5 ± 2.5; P = 0.288566) and equivalent differential quality scores (4.2 ± 0.10 vs. 4.2 ± 1.3; P = 0.099667).

CONCLUSION: DeepSeek-R1 exhibits diagnostic accuracy comparable to GPT-4 while generating more diverse differential diagnoses. Its open-source nature and innovative reasoning strategies may enhance medical AI applications. Future studies should explore real-world clinical integration and refinement of differential diagnosis prioritization.

PMID:40505040 | DOI:10.1097/JS9.0000000000002386

Anesth Analg. 2025 Jun 12. doi: 10.1213/ANE.0000000000007582. Online ahead of print.

ABSTRACT

BACKGROUND: The right ventricle-pulmonary artery (RV-PA) coupling ratio provides an assessment of RV function indexed to PA afterload. A low preoperative RV-PA ratio has been associated with increased mortality after transcatheter procedures. In patients undergoing cardiac surgery, we hypothesized that a lower preoperative RV-PA ratio is independently associated with a higher risk of major morbidity and operative mortality (MMOM).

METHODS: We conducted a retrospective cohort study of adult patients who underwent coronary artery bypass graft and/or valve surgery (aortic, mitral, and tricuspid). The RV-PA ratio was calculated using the ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP). The primary outcome was MMOM as defined by the Society of Thoracic Surgeons (STS). The Youden index was used to determine the optimal cutoff to classify into low versus high TAPSE/PASP ratio groups. Multivariable analysis was performed to test the association of TAPSE/PASP ratio with MMOM and other clinical outcomes with P- value <0.05 used for statistical significance.

RESULTS: One hundred and twenty-four (14.3%) of the 868 patients who met inclusion criteria had the primary outcome of MMOM. Patients in the low TAPSE/PASP group were more likely to have MMOM (90 (22.0%) vs 34 (7.4%); P < .001) as well as longer intensive care unit length of stay (ICU-LOS), hospital LOS (H-LOS), and mechanical ventilation time (MVT). By multivariable analysis, TAPSE/PASP ratio <0.52 mm/mm Hg was associated with a significant increase in the risk of MMOM (odds ratio [OR] 1.77, 95% confidence interval [CI], 1.10-2.83, P = .018). In the analyses of secondary outcomes, for every 0.1 mm/mm Hg increase in TAPSE/PASP ratio, there was a 4% reduction in ICU-LOS and MVT, and a 3% reduction in H-LOS.

CONCLUSIONS: TAPSE/PASP ratio <0.52 mm/mm Hg was associated with a significant increase in the risk of MMOM. Low preoperative TAPSE/PASP ratio was also associated with longer ICU-LOS, H-LOS, and MVT, even when adjusting for STS risk score for MMOM and cardiopulmonary bypass time.

PMID:40505025 | DOI:10.1213/ANE.0000000000007582

Lab Med. 2025 Jun 12:lmaf015. doi: 10.1093/labmed/lmaf015. Online ahead of print.

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) is known to have an association with circular RNAs (circRNAs) and immune checkpoint factors. This study sought to examine the expression levels of hsa_circ_0000284 and hsa_circ_0004771 molecules and the programmed cell death 1 protein (PD-1) and ecto-5′-nucleotidase (CD73) immune checkpoints in the peripheral blood of patients with CRC as well as the ratios of circular to linear forms of homeodomain-interacting protein kinase 3 (HIPK3) and nuclear receptor interacting protein 1 (NRIP1).

METHODS: Real-time polymerase chain reaction (PCR) and flow cytometry were used to assess quantitatively the expression level of circRNAs, CD73, and PD-1 in blood samples from patients with CRC and healthy control individuals. The expression of CD73 and PD-1 molecules was analyzed using FlowJo software, and the expression levels of circRNAs, CD73, and PD-1 were calculated with real-time PCR analysis.

RESULTS: Real-time PCR analysis revealed a statistically significant increase in the linear form of hsa_circ_0004771 (linNRIP1) and PD-1 gene expression in patients’ blood compared with control individuals. In addition, the circHIPK3:linHIPK3 and circNRIP1:linNRIP1 ratios are statistically significantly higher in patients than in healthy control individuals. The flow cytometry assessment indicated a statistically significant increase in PD-1 on the surface of lymphocytes and monocytes and an increase in CD73 on the granulocytes of patients compared with the healthy control individual.

DISCUSSION: Based on these findings, hsa_circ_0000284, hsa_circ_0004771, PD-1, and CD73 were statistically significantly increased in our cancer group. If further research were done, these blood markers could potential be biomarkers for CRC progression.

PMID:40505000 | DOI:10.1093/labmed/lmaf015

Diabetes Care. 2025 Jun 12:dc250595. doi: 10.2337/dc25-0595. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the concordance of glycated albumin, fructosamine, 1,5-anhydroglucitol (1,5-AG), and hemoglobin A1c (HbA1c) with continuous glucose monitor (CGM) metrics of hyperglycemia and glycemic control in a diverse population of adults with type 2 diabetes.

RESEARCH DESIGN AND METHODS: This was a pooled cross-sectional analysis of 552 adults, ages 30 to 97 years old, with diabetes. Participants wore a CGM for up to 2 weeks, and we evaluated the agreement between blood biomarkers (glycated albumin, fructosamine, and 1,5-AG) with CGM-defined metrics of hyperglycemia and glycemic control.

RESULTS: Of the 552 participants (mean age 74 years, 53% women, 36% Black), the median of mean CGM glucose was 132 mg/dL, and participants spent on average 84% of their time in range (70-180 mg/dL). CGM mean glucose was strongly related to HbA1c (r = 0.72), glycated albumin (r = 0.64), and fructosamine (r = 0.64) but weakly related to 1,5-AG (r = 0.46). Results were similar for time above range (>180 mg/dL). Glycated albumin and fructosamine performed similarly to HbA1c in the detection of target time in and above range (c-statistics ranged from 0.85 to 0.94).

CONCLUSIONS: Glycated albumin and fructosamine had similar associations with CGM-defined metrics of hyperglycemia compared with HbA1c. These three biomarkers performed similarly in the detection of time above range and in range. Our results provide evidence for the utility of glycated albumin and fructosamine as alternate measures of hyperglycemia.

PMID:40504990 | DOI:10.2337/dc25-0595