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Nevin Manimala Statistics

Age-appropriate needs-based care in an onco-primary care survivorship program for survivors of childhood, adolescent and young adult, and adult cancers

J Cancer Surviv. 2025 Nov 20. doi: 10.1007/s11764-025-01919-w. Online ahead of print.

ABSTRACT

PURPOSE: Routine assessment of cancer survivors’ needs is inconsistently performed in both primary care and oncology. Age influences survivorship needs, with younger survivors facing prolonged symptom burden and late effects, and older survivors experiencing compounded aging-related issues. We describe age-appropriate needs-based care in a university onco-primary care survivorship clinic serving adult survivors of childhood and adult cancers.

METHODS: Between November 1, 2022, and May 31, 2023, the clinic administered age-appropriate assessments during routine visits (ages ≤ 39 years: Adolescent and Young Adult Psycho-Oncology Screening Tool for Survivorship [AYA-SPOST]; ≥ 40 years: NCCN Distress Thermometer and Problem List [NCCN DTPL]). Survivors prioritized their top three concerns, and clinicians addressed them in the visit. Descriptive statistics were used to summarize priority concerns.

RESULTS: Two hundred and twenty-eight patients (100%) completed age-appropriate assessments (AYA-SPOST: 112; NCCN DTPL: 116) and prioritized their concerns at their clinic visit. Leukemia (21%) and lymphoma (18%) were the most common diagnoses. Survivors ≤ 39 years old prioritized anxiety/fear (21%), sleep disturbances (14%), and worry about long-term effects (12%), while those ≥ 40 years old prioritized pain (40%), fatigue (28%), and worry/anxiety (23%). Clinicians discussed survivors’ concerns with them and made 74 referrals to supportive services.

CONCLUSIONS: We implemented age-appropriate needs-based care in an onco-primary care clinic as part of standard care. Patients’ priority concerns helped drive clinical visits to ensure patient-centered care.

IMPLICATIONS FOR CANCER SURVIVORS: Routine use of age-appropriate assessments for different stages of adulthood, with opportunities for survivors to prioritize their concerns, allows clinicians to take immediate action to help address those concerns.

PMID:41264205 | DOI:10.1007/s11764-025-01919-w

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Clinical application value of modified overlap anastomosis for Siewert type II and III adenocarcinoma of esophagogastric junction

J Cancer Res Clin Oncol. 2025 Nov 20;151(12):327. doi: 10.1007/s00432-025-06379-4.

ABSTRACT

AIM: To explore the clinical application value of modified overlap anastomosis for Siewert type II and III adenocarcinoma of esophagogastric junction, and to further evaluate its feasibility and safety.

METHODS: We retrospectively analyzed clinical data from 222 patients with Siewert type II and III adenocarcinoma of the esophagogastric junction admitted to our hospital between January 2017 to October 2023. All patients underwent laparoscopic total gastrectomy with D2 lymph node dissection. 64 patients underwent esophagojejunostomy with modified overlap anastomosis, and 158 patients were operated using the circular stapled anastomosis. Variables that are statistically different were compared between groups using propensity score matching (PSM). The differences in surgical-related indicators and clinical outcomes for the two groups were compared. Finally, we analyzed the risk factors associated with esophagojejunostomy (EJ)-related complications.

RESULTS: There was no statistically significant difference between the two groups of patients in terms of BMI, gender, age, and tumor-related information (P value > 0.05). However, there was then a difference in preoperative hemoglobin between the two groups. To eliminate heterogeneity, we combined patients with PSM. In terms of intraoperative conditions and postoperative recovery after PSM, compared with the circular stapled anastomosis group, the modified overlap group showed the shorter total operation time, shorter the length of the auxiliary incision, shorter time to the soft diet intake, milder postoperative pain. In terms of postoperative complications and overall survival after PSM, the modified overlap group can reduce the probability of abdominal infection and there was no difference in overall survival (OS) and postoperative late complications between the two groups. Multivariate analysis showed that the Siewert type [odds ratio (OR), 0.355; 95% confidence interval (CI) 0.189-0.639, P value = 0.005] was independent risk factors of EJ-related complications.

CONCLUSION: Although the modified overlap group had slightly lower total protein after surgery, it had advantages in operation time, the length of the auxiliary incision, the soft diet intake time, postoperative pain, abdominal infection. General surgeons should exercise heightened vigilance in preventing EJ-related complications for patients classified as Siewert type II. In summary, modified Overlap anastomosis is safe and reliable. It has clinical application value.

PMID:41264122 | DOI:10.1007/s00432-025-06379-4

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A novel integrating quantitative and qualitative approaches for comprehensive assessment of wastewater: combined water quality and community attitudes

Environ Geochem Health. 2025 Nov 20;48(1):8. doi: 10.1007/s10653-025-02860-8.

ABSTRACT

The rapid urbanization and industrialization in Pakistan have significantly escalated wastewater generation, much of which remains untreated and is discharged into rivers and canals. This study presents an innovative framework that integrates quantitative analysis of wastewater quality with qualitative insights from community attitudes, focusing on Abbottabad and Lahore City. Comprehensive evaluations of physico-chemical parameters like potential of hydrogen, chemical oxygen demand, total dissolved solids, turbidity, and electrical conductivity alongside microbial indicators such as coliform and E.coli, reveal critical insights into wastewater characteristics and treatment efficiency. Comparisons with World Health Organization standards expose substantial site-to-site variations, with several parameters exceeding permissible limits. Secondary treatment processes effectively mitigate TDS, EC, turbidity, and COD to compliant levels. While initial treatments reduce bacterial loads, regrowth during storage raises concerns about long-term microbial safety. Multivariate statistical analyses, including principal component analysis and Pearson correlation matrices, uncover strong interdependencies among parameters, such as inverse correlations between pH and both TDS and turbidity, and a perfect positive correlation between EC and TDS. Community surveys amplify the study’s scope, revealing widespread dissatisfaction with water and wastewater management, as 74% of respondents associate health issues such as diarrhea, kidney ailments, and vomiting with inadequate treatment systems. This study introduces the novel Enhanced Wastewater Quality Index (EWWQI), integrating both wastewater quality parameters and community perceptions. The Adjusted EWWQI score of 17.0 (poor) highlights the need for improved treatment processes and greater public trust in wastewater management. By integrating scientific evaluation with community perspectives, this study underscores the urgent need for enhanced treatment processes and sustainable management practices. The findings provide actionable insights for policymakers, paving the way for improved wastewater management and addressing critical environmental and public health challenges effectively.

PMID:41264103 | DOI:10.1007/s10653-025-02860-8

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Genetic variation in anti-diabetic drug targets and risk of atrial fibrillation: a drug-target mendelian randomization study

Int J Clin Pharm. 2025 Nov 20. doi: 10.1007/s11096-025-02034-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF) is a common cardiac arrhythmia with limited options for upstream prevention. While several anti-diabetic drugs have shown cardiovascular benefits, their potential role in modifying AF risk remains unclear.

AIM: This study aimed to evaluate the causal relationship between genetically proxied antidiabetic drug targets and the risk of AF using a drug-target Mendelian randomization (MR) approach.

METHOD: A two-sample MR analysis was conducted to investigate the association between genetic variants related to antidiabetic drug targets and AF. Thirty-eight FDA-approved glucose-lowering agents were identified, and their targets were extracted from the ChEMBL (Chemical Biology Database and Information System) database. Protein quantitative trait loci (pQTL) data from a large plasma proteome GWAS (Genome-Wide Association Study) were used to construct instrumental variables. Positive control testing was conducted to confirm that the selected drug targets were significantly associated with diabetes, using summary statistics from the UK Biobank, FinnGen, and other GWAS datasets. Causal effects on AF were evaluated using multiple independent GWAS cohorts for replication. MR methods included inverse-variance weighted (IVW), MR-Egger, and weighted median approaches with sensitivity analyses for pleiotropy and heterogeneity.

RESULTS: The alpha-glucosidase inhibitor miglitol was causally associated with a reduced risk of AF. Specifically, miglitol was shown to inhibit lactase (LCT), a protein whose elevated levels were associated with increased AF risk (IVW, OR = 1.013; 95%CI, 1.007-1.018; P = 2.37 × 10⁻5). This association was confirmed using MR-Egger and weighted median methods and validated across multiple datasets. Sensitivity analyses did not reveal evidence of pleiotropy or confounding factors, supporting the robustness of the findings.

CONCLUSION: This study provides novel genetic evidence suggesting that miglitol may reduce AF risk through lactase inhibition. These findings highlight a potential opportunity for drug repurposing for cardiovascular prevention, particularly for clinical pharmacists managing patients with higher risks in cardiovascular outcomes meanwhile with type 2 diabetes. Further mechanistic and clinical studies are warranted to confirm these observations and explore their translational value in practice.

PMID:41264079 | DOI:10.1007/s11096-025-02034-7

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Inherited immune traits and cisplatin-induced ototoxicity in cancer patients: a Mendelian randomization study

Int J Clin Pharm. 2025 Nov 20. doi: 10.1007/s11096-025-02038-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Cisplatin is a cornerstone chemotherapeutic agent frequently associated with dose-limiting ototoxicity. Increasing evidence suggests that immune-mediated mechanisms may influence interindividual susceptibility to this adverse effect; however, the role of inherited immune traits remains poorly understood.

AIM: This study aimed to evaluate the causal relationship between 33 inherited immune traits and cisplatin-induced ototoxicity using Mendelian randomization (MR), and to identify age-stratified susceptibility markers in pediatric and adult cancer survivors.

METHOD: MR was used to assess the causal effects of genetically predicted immune traits on cisplatin-induced ototoxicity. Single-nucleotide polymorphisms associated with immune traits were selected from large-scale genome-wide association study datasets. The primary analysis used the inverse variance weighted method with MR-Egger, weighted median, weighted mode, and MR-PRESSO as the sensitivity approaches. Bidirectional MR and sensitivity analyses were conducted to assess robustness and rule out reverse causation. Bonferroni correction was employed to minimize potential false-positive findings (P < 0.05/165 ≈ 0.0003).

RESULTS: Transforming Growth Factor-beta principal component analysis (TGF-β PCA) showed an age-stratified effect: it was associated with increased risk of hearing loss in pediatric patients (OR (95% CI): 1.0 × 101 (1.6 × 100-6.6 × 101), P = 0.014) but conferred strong protection against Speech Recognition Threshold (SRT) impairment (OR (95% CI): 2.8 × 10⁻1 (1.4 × 10⁻1-5.3 × 10⁻1), P = 0.00012) and hearing loss (OR (95% CI): 4.7 × 10⁻1 (2.7 × 10⁻1-8.1 × 10⁻1), P = 0.006) in adults. Additional protective associations have been identified for T Central Memory (TCM) cells and Programmed Cell Death Protein-1 (PD-1) in adults. Reverse MR analysis excluded significant reverse causation. Following Bonferroni correction, the association between TGF-β PCA and SRT remained statistically significant (P < 0.0003) in the adult cohort. However, all other associations in adults and the entire pediatric cohort demonstrated only nominal significance (0.0003 ≤ P < 0.05).

CONCLUSION: Inherited immune traits, particularly TGF-β PCA, PD-1, and TCM cells, exhibit age-stratified causal effects on cisplatin-induced ototoxicity. These findings suggest the use of immunogenetic profiling for risk prediction and personalized strategies in oncology pharmacy practice.

PMID:41264078 | DOI:10.1007/s11096-025-02038-3

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Identification of candidate susceptibility genes for cutaneous malignant melanoma through integrated multi-method analysis

Discov Oncol. 2025 Nov 20. doi: 10.1007/s12672-025-04006-9. Online ahead of print.

ABSTRACT

BACKGROUND: Cutaneous malignant melanoma (CMM) is a deadly skin cancer with genetic basis. Although genome-wide association studies (GWAS) have identified various risk loci, their functional consequences remain largely undefined. This study aims to uncover novel CMM-associated genes and investigate their potential biological mechanisms by integrating large-scale genetic and transcriptomic datasets.

METHODS: We combined CMM GWAS summary statistics with gene expression data from GTEx v8 and conducted transcriptome-wide association studies (TWAS) across multiple tissues. Key genes were further examined using MAGMA-based gene-level analysis, Bayesian fine-mapping, Mendelian randomization (MR), and colocalization to infer potential causality. Functional associations were explored via GeneMANIA network analysis.

RESULTS: Two genes, TMEM184B and MAFF, were repeatedly identified across analytical approaches. TMEM184B emerged as a novel gene associated with melanoma risk. Both MR (P < 0.05) and colocalization (PP.H4 > 0.8) provided consistent evidence of causal links between gene expression and CMM susceptibility. Functional network analysis implicated TMEM184B in transmembrane ion transport and MAPK signaling pathways, while MAFF was linked to oxidative stress response pathways.

CONCLUSION: This study identifies TMEM184B as a previously unreported risk gene for CMM and reaffirms the relevance of MAFF in disease predisposition. These findings advance our understanding of melanoma’s genetic architecture and highlight specific, high-priority genes and pathways for future experimental investigation, suggesting they may serve as potential therapeutic targets.

PMID:41264070 | DOI:10.1007/s12672-025-04006-9

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Ex ante evaluation of risk adjustment models for prospective provider payment: a conceptual framework and empirical application

Eur J Health Econ. 2025 Nov 20. doi: 10.1007/s10198-025-01871-7. Online ahead of print.

ABSTRACT

Alternative payment models (APMs) aim to improve efficiency and fairness in healthcare by shifting financial responsibility from payers to providers. Given their prospective nature, APMs require effective risk adjustment (RA) to prevent risk-selection incentives. RA design comes with complex trade-offs between risk selection, cost control and gaming. In the light of these trade-offs, thorough ex-ante evaluation of RA models is crucial. Traditionally, RA-model evaluation in the context of APMs has heavily relied on statistical metrics like R-squared. While useful for assessing model fit, these metrics often fail to capture the full spectrum of relevant incentives. This study therefore addresses the question: “What do meaningful incentive metrics for ex-ante evaluation of RA models look like in the context of prospective APMs for healthcare providers?” We conducted a literature review and consulted experts to synthesize existing work on RA evaluation. This informed the development of a conceptual framework for defining incentive metrics, distinguishing among risk-selection, cost-control, and gaming incentives. We applied our framework in a simulation of prospective payments to primary care practices (PCPs) in the Netherlands, using 2019 claims data from 346 PCPs (N = 1.4 M patients). The analysis focused on selection incentives, comparing traditional statistical metrics with metrics derived from our framework. Results show that statistical metrics like R-squared fall short in assessing selection incentives compared to our incentive metrics. This highlights the need for tailored incentive metrics for the ex-ante evaluation of RA models that are grounded in a thorough understanding of relevant provider behaviors in the light of APM goals.

PMID:41264066 | DOI:10.1007/s10198-025-01871-7

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Toll-like receptor 3 (TLR 3) polymorphisms predisposition to schizophrenia and bipolar disorder

Mol Biol Rep. 2025 Nov 20;53(1):104. doi: 10.1007/s11033-025-11278-5.

ABSTRACT

BACKGROUND: Toll-like receptor 3 (TLR 3) abnormal inflammatory response was described as one of the possible mechanisms implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). However, the genetic predisposition of TLR 3 to these disorders’ onset is still unclear. Therefore, the predisposition of TLR 3 functional variants L412F (rs3775291) and F459L (rs3775290) was examined in both disorders.

METHODS AND RESULTS: In a case-control study, 260 controls, 260 SCZ, and 130 BD patients were recruited and genotyped by PCR-RFLP. Genotypes, alleles, and haplotypes frequencies were compared between controls and patients based on clinical features. Statistical analyses were adjusted by gender and age and validated by Bonferroni correction. In the dominant model, our results showed significantly higher L412F AA + GA frequency in controls compared to BD patients (padjusted=0.004; ORadjusted=0.5) and type I BD patients (padjusted=0.009; ORadjusted=0.5). Moreover, BD BPRS scores were significantly lower in L412F AA + GA carriers compared to GG carriers (p = 0.001) before treatment. Otherwise, F459L TT + CT and minor allele frequencies were significantly elevated in the paranoid subgroup compared to controls (p = 0.004; OR = 2.1, p = 0.002; OR = 1.8, respectively). After antipsychotic treatment, SCZ SANS scores decreased significantly in F459L TT + CT and CC carriers (p < 10– 4) and in TT + CT carriers compared to CC carriers (p = 0.001).

CONCLUSIONS: The present study suggests that L412F could be a protective genetic factor from BD onset. However, F459L could be a genetic risk factor for the paranoid subtype and a potential genetic predictor of SCZ negative symptoms treatment improvement.

PMID:41264056 | DOI:10.1007/s11033-025-11278-5

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A preliminary study on the prevalence of mental health symptoms in current and former elite kickboxers and their possible association with severe musculoskeletal injuries and concussions

Discov Ment Health. 2025 Nov 20;5(1):181. doi: 10.1007/s44192-025-00328-w.

ABSTRACT

AIM(S): This study aimed to explore the prevalence of mental health symptoms in current and former elite kickboxers and to establish whether these mental health symptoms were associated with severe musculoskeletal injuries and/or concussions.

METHODS: A cross-sectional study was conducted by utilizing an electronic questionnaire among current and former elite kickboxers from the highest and second highest international level. Validated screening questionnaires from the International Olympic Committee Sport Mental Health Assessment Tool 1 (SMHAT-1) were used to asses mental health symptoms.

RESULTS: The most prevalent mental health symptoms among current elite kickboxers (N = 45) were psychological distress (57%) and disordered eating (63%). Among former elite kickboxers (N = 29), the most prevalent mental health symptoms were 36% for psychological distress and 43% for alcohol misuse. Additionally, no statistically significant associations were found between mental health symptoms and severe musculoskeletal injuries and/or concussions among current and former elite kickboxers.

CONCLUSIONS: The substantial prevalence rates of mental health symptoms among current and former elite kickboxers emphasize the need for increased attention in this area. No associations were found between the potential contributing factors and mental health symptoms among current and former elite kickboxers. While further research is needed, raising awareness as well as developing preventive and supportive measures to assist elite kickboxers with personal and career development should be prioritized, both inside and outside the ring.

PMID:41264054 | DOI:10.1007/s44192-025-00328-w

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Association of LAMA3 expression with perineural invasion and chemoresistance in pancreatic ductal adenocarcinoma

Discov Oncol. 2025 Nov 20. doi: 10.1007/s12672-025-03971-5. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common type of malignant tumor of the pancreas with high aggressiveness and low prognosis. Due to the insidious early symptoms of pancreatic adenocarcinoma, patients are mostly diagnosed at advanced stages with a high incidence of nerve invasion. With the rapid development of precision medicine, studying the molecular mechanisms behind PDAC can help its diagnosis and treatment, which is conducive to improving the prognosis of PDAC patients.

OBJECTIVE: To explore the correlation between LAMA3 expression and nerve invasion in pancreatic ductal adenocarcinoma tissues.

METHODS: Ninety-four patients with pathologically confirmed diagnosis of PDAC in the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Anhui Medical University were retrospectively collected from January 2023 to December 2023, and the patients’ clinicopathological data were collected and followed up for 5 months. Immunohistochemical staining was applied to detect the expression level of LAMA3 in cancer tissues, and paraneoplastic tissues were used as controls to compare the differences in the expression level of LAMA3. The Kaplan-Meier method was used to draw the survival curves, and the Cox proportional risk regression model was set up to analyze the correlation between the expression of LAMA3 and the nerve invasion.

RESULTS: Immunohistochemical staining results showed that LAMA3 was mainly expressed in the cytoplasm and appeared as yellow to brown granules.The positive expression rate of LAMA3 in PDAC cancer tissues was 63.83% (60/94), which was significantly higher than that in paracancerous tissues (12.77%, 12/84), and the difference between the two groups was statistically significant (x2 = 51.862, P < 0.001). Patients were categorized into nerve invasion negative (n = 30) and nerve invasion positive (n = 64) according to the presence or absence of nerve invasion.Cox proportional analysis regression results showed that the LAMA3 expression level was an independent risk factor affecting the occurrence of nerve invasion in PDAC patients. Survival analysis showed that median OS was significantly lower in patients with high LAMA3 expression and development of vascular invasion than in patients with low LAMA3 expression and no vascular invasion (P < 0.001); in TNM staging, median OS was significantly lower in patients with stage II than in patients with stage I (P < 0.001).

CONCLUSION: LAMA3 expression level is an independent risk factor for the occurrence of neuroinvasion in PDAC patients; LAMA3 expression level, TNM staging and prognosis of PDAC patients are correlated; LAMA3 expression level may serve as a valuable biomarker for the occurrence, development, and prediction of prognosis of patients with PDAC, and also as a potential therapeutic target for PDAC patients.

PMID:41264049 | DOI:10.1007/s12672-025-03971-5