Tag: nevin manimala

Clin Cancer Res. 2025 Apr 21. doi: 10.1158/1078-0432.CCR-24-4105. Online ahead of print.

ABSTRACT

PURPOSE: Enabled by advancements in next-generation sequencing for hereditary cancer conditions, low allele frequency variants (LAFVs) are detected by testing laboratories. This study describes the frequency and clinical factors associated with LAFVs and reports results of follow-up testing when available.

PATIENTS AND METHODS: This retrospective study analyzed LAFV cases identified through multi-gene panel testing (MGPT) at a single high-volume germline genetic testing laboratory. LAFVs were defined as variant allele frequencies (VAF) between 10-30% as confirmed by Sanger sequencing. Comparative analyses were conducted between pathogenic variants (PVs) with a VAF of 30-60% (inferred heterozygous) and LAFV cohorts. Clinical characteristics were analyzed using descriptive statistics and logistic regression models. Ancillary testing was performed on alternative specimens or family members to determine if LAFVs were due to constitutional mosaicism.

RESULTS: Among 363,405 individuals undergoing MGPT, 965 (1.8%) had variants with VAF between 10-30%. Sanger sequencing confirmed 463 (0.1%) as LAFVs. Among the confirmed LAFVs, 262 (57.6%) were classified as PVs. The LAFV cohort compared to the control heterozygous cohort was significantly older, with a higher proportion of individuals > 50 years (84.1% vs. 54.9%; p<0.001). LAFVs were present in the following genes: TP53 (110;64.7%), NF1 (23;13.5%), CHEK2 (13;7.6%), ATM (12; 7.1%), and BRCA1 (4;2.4%). Ancillary testing performed on 62 cases with LAFVs confirmed 17.7% (11/62) as constitutional mosaicism.

CONCLUSION: LAFVs were infrequently detected in MGPT, representing 0.8% of the total variants and 0.1% of total tested. Ancillary testing is needed to understand the origins and clinical implications of LAFVs in patients and families.

PMID:40260637 | DOI:10.1158/1078-0432.CCR-24-4105

Mol Oncol. 2025 Apr 22. doi: 10.1002/1878-0261.70041. Online ahead of print.

ABSTRACT

Homologous recombination deficiency (HRD) leads to genomic instability, and patients with HRD can benefit from HRD-targeting therapies. Previous studies have primarily focused on identifying HRD biomarkers using data from a single technology. Here we integrated features from different genomic data types, including total copy number (CN), allele-specific copy number (ASCN) and single nucleotide variants (SNV). Using a semi-supervised method, we developed HRD classifiers from 1404 breast tumours across two datasets based on their BRCA1/2 status, demonstrating improved HRD identification when aggregating different data types. Notably, HRD-positive tumours in ER-negative disease showed improved survival post-adjuvant chemotherapy, while HRD status strongly correlated with neoadjuvant treatment response. Furthermore, our analysis of cell lines highlighted a sensitivity to PARP inhibitors, particularly rucaparib, among predicted HRD-positive lines. Exploring somatic mutations outside BRCA1/2, we confirmed variants in several genes associated with HRD. Our method for HRD classification can adapt to different data types or resolutions and can be used in various scenarios to help refine patient selection for HRD-targeting therapies that might lead to better clinical outcomes.

PMID:40260608 | DOI:10.1002/1878-0261.70041

Acta Paediatr. 2025 Apr 22. doi: 10.1111/apa.70102. Online ahead of print.

ABSTRACT

AIM: Adolescents predominantly suffer from headaches and sleep bruxism. Yet, the association between both conditions remains unclear. This study investigated the relationship between primary headaches and possible sleep bruxism in adolescents.

METHODS: A cross-sectional study was conducted from August 24 to October 13, 2022, with 567 adolescents (aged 14-19 years old) from public schools in Recife, Brazil. Data were collected via questionnaires on sociodemographic characteristics, self-medication and the Paediatric Migraine Disability Assessment. Possible sleep bruxism was diagnosed based on international consensus criteria. Pearson’s chi-square test and multivariate analysis were used for statistical evaluation (p < 0.05).

RESULTS: The sample comprised 567 students, predominantly female (54.1%) and aged 16-17 years old (65.1%). Most attended school full-time (61.6%), had employed guardians (57.5%) and had a family income around the minimum wage (44.3%). Possible sleep bruxism was identified in 10.6% of adolescents, while headaches affected 40.6%. Over-the-counter medication use was reported by 70.2%, with 68.8% specifically self-medicating for headaches. Headaches were associated with gender, guardian’s employment status, possible sleep bruxism and self-medication for headache (p < 0.05).

CONCLUSION: Primary headaches were associated with possible sleep bruxism. Female adolescents and those with possible sleep bruxism were nearly twice as likely to experience headaches.

PMID:40260584 | DOI:10.1111/apa.70102

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2025 Apr;41(4):339-347.

ABSTRACT

Objective To mine and analyze the routine blood test data of children with allergic rhinitis (AR), identify routine blood parameters related to childhood allergic rhinitis, establish an effective diagnostic model, and evaluate the performance of the model. Methods This study was a retrospective study of clinical cases. The experimental group comprised a total of 1110 children diagnosed with AR at the First Affiliated Hospital of Air Force Medical University during the period from December 12, 2020 to December 12, 2021, while the control group included 1109 children without a history of allergic rhinitis or other allergic diseases who underwent routine physical examinations during the same period. Information such as age, sex and routine blood test results was collected for all subjects. The levels of routine blood test indicators were compared between AR children and healthy children using comprehensive intelligent baseline analysis, with indicators of P≥0.05 excluded; variables were screened by Lasso regression. Binary Logistic regression was used to further evaluate the influence of multiple routine blood indexes on the results. Five kinds of machine model algorithms were used, namely extreme value gradient lift (XGBoost), logistic regression (LR), gradient lift decision tree (LGBMC), Random forest (RF) and adaptive lift algorithm (AdaBoost), to establish the diagnostic models. The receiver operating characteristic (ROC) curve was used to screen the optimal model. The best LightGBM algorithm was used to build an online patient risk assessment tool for clinical application. Results Statistically significant differences were observed between the AR group and the control group in the following routine blood test indicators: mean cellular hemoglobin concentration (MCHC), hemoglobin (HGB), absolute value of basophils (BASO), absolute value of eosinophils (EOS), large platelet ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), platelet count (PLT), absolute values of leukocyte neutrophil (W-LCC), leukocyte monocyte (W-MCC), leukocyte lymphocyte (W-SCC), and age. Lasso regression identified these variables as important predictors, and binary Logistic regression further analyzed the significant influence of these variables on the results. The optimal machine learning algorithm LightGBM was used to establish a multi-index joint detection model. The model showed robust prediction performance in the training set, with AUC values of 0.8512 and 0.8103 in the internal validation set. Conclusion The identified routine blood parameters can be used as potential biomarkers for early diagnosis and risk assessment of AR, which can improve the accuracy and efficiency of diagnosis. The established model provides scientific basis for more accurate diagnostic tools and personalized prevention strategies. Future studies should prospectively validate these findings and explore their applicability in other related diseases.

PMID:40260567

J Plast Surg Hand Surg. 2025 Apr 22;60:96-101. doi: 10.2340/jphs.v60.43375.

ABSTRACT

INTRODUCTION: Free flap reconstruction procedures are renowned for their duration and the requirement for many staff and large quantities of equipment. This single-centre cross-sectional study aimed to quantify the total emissions related to two such procedures carried out at a district general hospital.

METHODS: One deep inferior epigastric perforator (DIEP) free flap procedure and one anterolateral thigh (ALT) free flap procedure, both carried out in February 2024, were analysed. Data related to staff transport, anaesthetic duration, mass of disposable equipment, quantity of reusable surgical equipment and consumption of electricity and heating for the relevant theatre areas were collected. Emissions were calculated using UK government conversion factors and classified by scope and contributory element as per the Greenhouse Gas Protocol.

RESULTS: Total emissions were estimated at 385.5 kgCO2eq for the DIEP and 369.6 kgCO2eq for the ALT. Scope 1 emissions related to heating, atmospheric release of general anaesthetic and incineration of waste accounted for 33.7% of DIEP emissions and 35.6% of ALT emissions. Scope 2 emissions related to the use of grid electricity accounted for 44.8% of DIEP emissions and 46.7% of ALT emissions. Scope 3 emissions related to staff transport, cleaning of reusable equipment and the supply chain for disposable equipment accounted for 21.5% of DIEP emissions and 17.7% of ALT emissions.

CONCLUSION: Significant reductions in emissions may be achievable without significant infrastructural changes through initiatives to reduce staff transport by single-occupancy car, improving the energy efficiency of the theatre areas and reducing the use of single-use surgical equipment.

PMID:40260549 | DOI:10.2340/jphs.v60.43375

Palliat Support Care. 2025 Apr 22;23:e100. doi: 10.1017/S1478951525000318.

ABSTRACT

OBJECTIVES: This study aimed to examine the impact of perceived caregiver burden and associated factors on the anger levels and anger expression styles of family caregivers for patients receiving palliative care at home.

METHODS: This cross-sectional and exploratory correlational type study was conducted with 343 family caregivers. Data were collected face-to-face between March and September 2022 using a Caregiver and Care Recipient Information Form, the Burden Interview, and the Trait Anger and Anger Expression Scale.

RESULTS: There was a significant from very weak to weak correlation between the caregiver burden scores and trait anger, anger-in, anger-out, and anger control scores. The caregiver burden increased trait anger, anger-in, and anger-out while decreasing anger control. The caregiver burden, daily caregiving hours, presence of another dependent at home, presence of a separate room for the care recipient, income level, chronic illness of caregiver, duration of caregiving per month, and care recipient gender explained 17.2% of the total variation in anger control scores.

SIGNIFICANCE OF RESULTS: The caregiver burden levels and anger expression styles of family caregivers vary depending on the characteristics of both the caregiver and the care recipient. Family members may experience an increase in perceived caregiver burden, which can lead to elevated levels of trait anger, suppression of anger, and reduced anger control. Healthcare professionals should monitor the family caregivers’ caregiver burden and anger levels. Family caregivers should be encouraged and given opportunities to express their feelings and thoughts about caregiving. Strategies aimed at reducing the caregiver burden and coping with feelings of anger should be planned for the family members of patients receiving palliative care at home.

PMID:40260491 | DOI:10.1017/S1478951525000318

Palliat Support Care. 2025 Apr 22;23:e97. doi: 10.1017/S1478951525000252.

ABSTRACT

OBJECTIVES: To describe the frequency of prognostic awareness (PA) in a population of advanced cancer patients in a Latino community and to explore the relationship between accurate PA with emotional distress and other covariates.

METHODS: In this cross-sectional study performed in Puente Alto, Chile, advanced cancer patients in palliative care completed a survey that included a single question to assess PA (Do you believe your cancer is curable? yes/no). Patients reporting that their cancer was not curable were considered as having accurate PA. Demographics, emotional distress, quality of life, and patient perception of treatment goals were also assessed. Analyses to explore associations between PA and patient variables were adjusted.

RESULTS: A total of 201 patients were included in the analysis. Mean age was 65, 50% female. One hundred and three patients (51%) reported an accurate PA. In the univariate analysis, accurate PA was associated with not having a partner (p = 0.012), increased emotional distress (p = 0.013), depression (p = 0.003), and were less likely to report that the goal of the treatment was to get rid of the cancer (p < 0.001). In the multivariate analysis, patients with accurate PA had higher emotional distress or depression, were less likely to have a partner, and to report that the goal of the treatment was to get rid of the cancer.

SIGNIFICANCE OF RESULTS: Half of a population of Latino advanced cancer patients reported an accurate PA. Accurate PA was associated with increased emotional distress, which is similar to what has been reported in other countries. Weaknesses in prognostic disclosure by clinicians, local cultural factors, or higher motivation to seek prognostic information among distressed cancer patients could explain this association. Strategies to emotionally support patients when discussing prognostic information should be implemented.

PMID:40260487 | DOI:10.1017/S1478951525000252

Turk J Gastroenterol. 2025 Apr 21. doi: 10.5152/tjg.2025.24558. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is significantly influenced by the immune system, which plays a key role in its development, progression, treatment, and prognosis. While observational studies have revealed correlations between circulating immune traits and HCC, their genetic basis and causal links remain unclear. This study aims to investigate the genetic associations and bidirectional causal relationships between immune traits and HCC risk using Mendelian randomization (MR) approaches.

MATERIALS AND METHODS: Genome-wide association study summary statistics from the FinnGen cohort (R9, including 453 HCC cases and 287137 controls) were used to perform a bidirectional two-sample MR analysis. The causal effects of immune traits on HCC, as well as reverse causality, were assessed. Sensitivity analyses, including heterogeneity and pleiotropy tests, were used to ensure the robustness and validity of the results.

RESULTS: Thirty-nine immune traits were identified to be significantly associated with HCC risk. Elevated levels of 10 immune traits were positively associated with increased HCC risk, while the abundance of 29 immune traits was inversely correlated with HCC incidence. Furthermore, the reverse MR analysis revealed significant causal effects of HCC on 11 immune traits.

CONCLUSION: This study provides strong evidence of genetic links between systematic immune cell profiles and HCC, shedding light on the mechanisms underlying its onset and progression. These findings identify potential immune biomarkers for early diagnosis and immune-targeted therapies.

PMID:40260467 | DOI:10.5152/tjg.2025.24558

Eur J Anaesthesiol. 2025 Apr 22. doi: 10.1097/EJA.0000000000002180. Online ahead of print.

ABSTRACT

BACKGROUND: The use of lumbar epidural analgesia (LEA) during childbirth varies significantly among women. Factors influencing a woman’s choice of LEA and its possible effects on postpartum depression (PPD) remain underexplored.

OBJECTIVES: To investigate factors influencing the choice of LEA among women with intended vaginal deliveries. A secondary objective was to explore the association between LEA use and PPD.

STUDY DESIGN: A longitudinal cohort study.

SETTING: Uppsala University Hospital, Sweden, 2010 to 2019.

POPULATION: Women with an intended vaginal delivery.

EXCLUSIONS: Twins, elective caesarean section, induction of labour.

METHODS: Data were collected by web-based self-completed questionnaires at gestational weeks 17, 32 and at 6 weeks and 6 months postpartum. The exposures were sociodemographic, resilience-related, medical and obstetric characteristics of all participants from the BASIC (Biology, Affect, Stress, Imaging and Cognition) study. Information on the use of LEA was retrieved from medical records. PPD was assessed using either the Edinburgh Postnatal Depression Scale, or the Depression Self-Rating Scale, and/or the Mini-International Neuropsychiatric Interview at 6 to 8 weeks and 6 months postpartum. Bayesian models were applied to investigate the associations of multivariate factors with the choice for LEA, and the association between the use of LEA and PPD.

RESULTS: Among 4436 participants, 38% opted for LEA, while 62% did not. LEA users were younger, primiparous, reported higher rates of intimate partner violence (IPV) and had lower resilience. The adjusted model revealed primiparity, previous caesarean section, IPV, pregnancy length at least 280 days and fear of childbirth as independent predictors of LEA use. While LEA use was associated with higher odds of PPD in the crude regression model, it was no longer statistically significant after adjusting for possible confounders and mediators.

CONCLUSION: Social and psychological vulnerabilities influence a woman’s decision to opt for LEA during childbirth. LEA was not associated with PPD in adjusted models.

TRIAL REGISTRATION: This is a longitudinal study which was not registered back in 2010.

PMID:40260465 | DOI:10.1097/EJA.0000000000002180

J Trop Med. 2025 Apr 11;2025:5989447. doi: 10.1155/jotm/5989447. eCollection 2025.

ABSTRACT

Background: In the last two decades, Human immune deficiency virus has been a major health concern in sub-Saharan Africa particularly in Ethiopia. The objective of this study was to identify determinants associated with CD4 cell count and disclosure status among first-line antiretroviral therapy patients treated at Felege Hiwot Comprehensive Specialized Hospital, Ethiopia. Methods: This retrospective study was conducted at Felege Hiwot Comprehensive Specialized Hospital. Data analysis was conducted using Statistical System Analysis (SAS) software Version 9.4. In this study, quasi-Poisson mixed-effects model for CD4 cell count, a binary logistic regression model for disclosure status, and joint modeling were used. Result: Out of 300 adult participants, around 76% of the patients were discloses their disease status to their family members. The correlation between CD4 cell count and disclosure was positive (0.4607). The current study indicates that among the predictor variables, noneducators (β = -0.6185, p-value < 0.01), primary educators (β = -0.3687, p-value < 0.01), employed patients (β = 0.3888, p-value < 0.01), adherent patients (β = 0.2274, p-value < 0.01), and patients who did not had social support (β = -0.1148, p-value = 0.030) have a significant effect for CD4 cell count. Similarly, noneducators (AOR = 0.000145, p-value < 0.01), primary educators (AOR = 0.004413, p-value < 0.01), employed patients (AOR = 3.4562, p-value = 0.021), adherent patients (AOR = 1.564, p-value < 0.01), and patients who did not had social support (AOR = 0.075, p-value = 0.0078) had a significant effect for disclosure status. Conclusion: This study concluded that patients who had disclosed their disease status to near relatives or families have a positive correlation with CD4 cell count through time. This study also concluded that significant determinants affected both the variables of interest were educational level, occupation, adherence, and social support. Health professionals should give more attention to these important determinants to create good status of patients. In addition, health staff should conduct health-related studies for individuals to understand better ART follow-up. Patients should be adhere to their prescribed HIV medication properly on time and disclose their disease status without fearing stigma and discrimination to the community; this may help to increase their CD4 cell count. The family members should give social support to the infected patients, and the government should work on education; this may help to improve their CD4 cell count and increase the prevalence of disclosure of the disease status. The authors also recommended that further studies of this nature include other important variables that are not included in this study such as income of the patients and many other covariates.

PMID:40260411 | PMC:PMC12009679 | DOI:10.1155/jotm/5989447