Nevin Manimala

Eur J Med Res. 2025 Aug 21;30(1):783. doi: 10.1186/s40001-025-03038-9.

ABSTRACT

OBJECTIVES: Disruption of redox homeostasis and ferroptosis have been increasingly implicated in the pathogenesis of inflammatory lung injury. Glutathione peroxidase 4 (GPX4) and the ratio of reduced to oxidized glutathione (GSH/GSSG) are key regulators in this process. However, the clinical significance of ferroptotic factors in severe community-acquired pneumonia (CAP) is still lacking. This study investigated the prognostic value of serum glutathione peroxidase 4 (GPX4) and the GSH/GSSG ratio in severe CAP.

METHODS: A prospective cohort of 267 ICU-admitted severe CAP patients (2021-2023) was analyzed. Serum GPX4 and GSH/GSSG were measured within 24 h of admission. Patients were grouped by 30-day survival. Statistical analyses included comparative tests, Spearman correlation, ROC curves, Kaplan-Meier survival, and multivariate logistic regression.

RESULTS: Among 267 patients, 79 (29.6%) died within 90 days. Deceased patients had significantly lower GPX4 and GSH/GSSG (both P < 0.001). GPX4 was lower in COVID-19 cases (P = 0.022), while GSH/GSSG showed no such difference. GPX4 and GSH/GSSG were moderately correlated (r = 0.301, P < 0.001). ROC analysis showed good predictive accuracy for 30-day mortality, with an AUC of 0.778 for GPX4, 0.780 for GSH/GSSG, and 0.841 for their combination. Kaplan-Meier analysis indicated lower survival with reduced GPX4 or GSH/GSSG (P < 0.01). Multivariate analysis identified lower GPX4, GSH/GSSG, COVID-19, higher SOFA scores, prolonged ICU stay, and mechanical ventilation as independent mortality risk factors.

CONCLUSIONS: Lower serum GPX4 and GSH/GSSG ratios are associated with increased mortality in severe CAP.

PMID:40841690 | DOI:10.1186/s40001-025-03038-9

Cancer Imaging. 2025 Aug 21;25(1):105. doi: 10.1186/s40644-025-00928-3.

ABSTRACT

BACKGROUND: Accurate preoperative assessment of occult lymph node metastasis (OLNM) plays a crucial role in informing therapeutic decision-making for lung cancer patients. Computed tomography (CT) is the most widely used imaging modality for preoperative work-up. The aim of this study was to develop and validate a CT-based machine learning model integrating intra-and peri-tumoral features to predict OLNM in lung cancer patients.

METHODS: Eligible patients with peripheral lung cancer confirmed by radical surgical excision with systematic lymphadenectomy were retrospectively recruited from January 2019 to December 2021. 1688 radiomics features were obtained from each manually segmented VOI which was composed of gross tumor volume (GTV) covering the boundary of entire tumor and three peritumoral volumes (PTV3, PTV6 and PTV9) that capture the region outside the tumor. A clinical-radiomics model incorporating radiomics signature, independent clinical factors and CT semantic features was established via multivariable logistic regression analysis and presented as a nomogram. Model performance was evaluated by discrimination, calibration, and clinical utility.

RESULTS: Overall, 591 patients were recruited in the training cohort and 253 in the validation cohort. The radiomics signature of PTV9 showed superior diagnostic performance compared to PTV3 and PTV6 models. Integrating GPTV radiomics signature (incorporating Rad-score of GTV and PTV9) with clinical risk factor of serum CEA levels and CT imaging features of lobulation sign and tumor-pleura relationship demonstrated favorable accuracy in predicting OLNM in the training cohort (AUC, 0.819; 95% CI: 0.780-0.857) and validation cohort (AUC, 0.801; 95% CI: 0.741-0.860). The predictive performance of the clinical-radiomics model demonstrated statistically significant superiority over that of the clinical model in both cohorts (all p < 0.05).

CONCLUSIONS: The clinical-radiomics model was able to serve as a noninvasive preoperative prediction tool for personalized risk assessment of OLNM in peripheral lung cancer patients.

PMID:40841689 | DOI:10.1186/s40644-025-00928-3

BMC Pharmacol Toxicol. 2025 Aug 21;26(1):152. doi: 10.1186/s40360-025-00984-2.

ABSTRACT

BACKGROUND: Iron deficiency anemia (IDA) remains a prevalent global health issue. While oral iron therapy is the first-line treatment, the optimal dosing strategy-daily versus alternate-day-remains debated, especially for general population use. Therefore, this review aimed to compare the efficacy and tolerability of daily versus alternate-day oral iron supplementation for IDA in the general population.

METHODS: Searches were conducted across major databases through March 2025. Risk of bias was evaluated utilizing the Cochrane RoB 2 tool, and the certainty of evidence was graded using GRADE. The primary outcome was change in hemoglobin concentration; secondary outcomes included serum iron, ferritin, transferrin saturation, TIBC, MCV, and adverse events. R Studio software, version 4.2.3, and RevMan used for all analyses.

RESULTS: This SRMA (systematic review and meta-analysis) included 11 RCTs involving 1014 participants. The pooled analysis found a small, statistically non-significant increase in hemoglobin with daily dosing over alternate-day (MD: 0.28, 95% CI: -0.01 to 0.56, p = 0.06, z = 1.91). Secondary outcomes revealed no significant differences among groups for serum iron, ferritin, transferrin saturation, TIBC, and MCV. Adverse effects were similar between groups (RR: 1.07, 95% CI: 0.86 to 1.34), though metallic taste was more frequent with daily dosing. Risk of bias was low to moderate across studies. Certainty of evidence was rated very low for most outcomes due to heterogeneity and imprecision.

CONCLUSION: Both daily and alternate-day oral iron supplementation are comparably effective for treating IDA, with alternate-day dosing showing better tolerability. Due to low certainty in evidence, treatment decisions should be individualized pending further high-quality research.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40841680 | DOI:10.1186/s40360-025-00984-2

Int Breastfeed J. 2025 Aug 21;20(1):66. doi: 10.1186/s13006-025-00761-1.

ABSTRACT

BACKGROUND: Breast milk is widely recognized as the optimal source of infant nutrition, with the World Health Organization recommending exclusive breastfeeding for the first six months. However, breastfeeding rates remain suboptimal worldwide and in Taiwan. The six-month exclusive breastfeeding rate in Taiwan, defined as the percentage of infants aged six months who received only breast milk and no other foods or liquids in the previous 24 h, declined from 46.2% in 2018 to 37.9% in 2020. One barrier to continued breastfeeding is the discomfort or hesitation some mothers feel when breastfeeding in public. While qualitative research has indicated that conservative values may inhibit public breastfeeding, few quantitative studies have examined the simultaneous influence of traditionality and modernity. This study investigates how traditionality and modernity affect public breastfeeding behavior in Taiwan, using the Theory of Planned Behavior (TPB) as a framework.

METHODS: A cross-sectional online survey was conducted from 4 to 15 March 2024, recruiting 358 Taiwanese mothers with prior breastfeeding experience via social media. Validated instruments measured traditionality, modernity, TPB constructs (attitudes, subjective norms, perceived behavioral control, and intention), and frequency of public breastfeeding. Data were analyzed using descriptive statistics, bivariate correlations, and structural equation modeling.

RESULTS: Traditionality was negatively associated with attitudes (β = -0.30), perceived control (β = -0.11), intention (β = -0.14), and public breastfeeding behavior (β = -0.14). Modernity indirectly promoted public breastfeeding through positive links with attitudes (β = 0.12), subjective norms (β = 0.23), and perceived control (β = 0.26). Intention strongly predicted behavior (β = 0.60). The model explained 42% of the variance (CFI = 0.99, SRMR = 0.05).

CONCLUSIONS: The study confirms that traditionality may hinder public breastfeeding, while modernity enhances it by shaping attitudes, norms, and control beliefs. These findings have important implications for public health policy and practice. Since traditionality and modernity influence behavior through distinct psychological pathways, interventions should be culturally tailored. For mothers with high traditionality, mobilizing family and community support may reinforce positive norms. For those with strong modern values, strategies should focus on autonomy, self-efficacy, and informed decision-making to support breastfeeding in public spaces.

PMID:40841677 | DOI:10.1186/s13006-025-00761-1

Biopsychosoc Med. 2025 Aug 22;19(1):15. doi: 10.1186/s13030-025-00337-9.

ABSTRACT

BACKGROUND: Obesity is a chronic disease influenced by genetic, cultural, environmental, and psychosocial factors, making it difficult to manage through individual effort alone. Despite this complexity, obesity is often attributed to a lack of willpower and poor control over eating behaviors, contributing to stigma. However, research on this issue remains limited. This study quantified the extent to which multidimensional eating behaviors statistically explained the association between obesity and grit, which shared characteristics with self-control.

METHODS: We conducted a cross-sectional study involving Japanese adults across a wide range of age groups. Grit was measured using the 8-item Short Grit Scale. Multidimensional eating behaviors were measured using the Japanese version of the 21-item Three-Factor Eating Questionnaire-R21, including uncontrolled eating, emotional eating, and cognitive restraint. Obesity was defined as a body mass index ≥ 25.0 kg/m². A series of logistic regression models were created to analyze the association between grit and obesity with and without eating behaviors. Mediation analyses using the Karlson-Holm-Breen method were performed.

RESULTS: Of the 1,641 adults, 26.8% had obesity. Higher grit level was associated with a lower likelihood of obesity, less uncontrolled and emotional eating, and higher cognitive restraint. Grit was positively associated with cognitive restraint and negatively associated with uncontrolled and emotional eating; these multidimensional eating behaviors statistically accounted for the association between grit and obesity. Uncontrolled and emotional eating fully accounted for the association, whereas cognitive restraint partially accounted for it. These findings are consistent with the possibility of mediation through eating behavior in the relation between grit and obesity.

CONCLUSIONS: Our findings suggest that healthcare providers and policymakers should prioritize addressing multidimensional eating behaviors that explain the link between grit and obesity rather than on grit itself. Identifying and managing impairments in eating behavior rather than attributing obesity to an individual’s lack of willpower may help reduce stigma and support effective obesity prevention strategies.

PMID:40841668 | DOI:10.1186/s13030-025-00337-9

BMC Nurs. 2025 Aug 21;24(1):1095. doi: 10.1186/s12912-025-03765-8.

NO ABSTRACT

PMID:40841666 | DOI:10.1186/s12912-025-03765-8

Orphanet J Rare Dis. 2025 Aug 21;20(1):450. doi: 10.1186/s13023-025-03968-x.

ABSTRACT

BACKGROUND: Genetic counselling for adolescents necessitates an approach distinct from that used with adults. Developing best practices is crucial, considering the growing number of disabled adolescents worldwide and increasing use of genomic testing early in life. We investigated perceptions of adolescents (10-19 years) who had been diagnosed with a genetic disorder in terms of how they describe receiving, understanding, and living with a genetic condition. We undertook a cross-sectional, qualitatively oriented mixed methods study underpinned by the pragmatic paradigm. Adolescents completed two self-report measures – the psychological adaptation scale (PAS) and the illness identity questionnaire (IIQ)-and participated in semi-structured interviews. Demographic, PAS, and IIQ data were analyzed using descriptive statistics. We used phronetic iterative analysis to interrogate interview data. Qualitative and quantitative components were integrated through abduction.

RESULTS: Eighteen participants (median age: 15.5 years; 11/18 women/girls; 13/18 typical cognition; 8/18 de novo presentation) with a variety of genetic conditions participated. Participants had a mean PAS of 3.07 ± 0.84 indicating adequate adaptation. Their IIQ profiles indicated slightly better mean adaptive scores (3.10 ± 1.06) than mean maladaptive scores (2.85 ± 0.99). We developed a conceptual model that describes disability and genetic identity development and psychological adaptation among participants composed of three interacting components: internalizing processes; variability arising from contextual factors; and external factors associated with the processes. Adolescents generally moved among four internalizing processes (initiating, minimizing, exploring, and accepting). Movement across these processes took place frequently because of contextual factors like setting and disability type. Communication and engagement with caregivers, peers, and healthcare professionals, social interactions with others who have the same or a similar condition, and the impact of ableism constituted the main external factors with which adolescents engaged in the development of these identities.

CONCLUSIONS: Our findings present a foundation upon which to develop a care model optimized for the needs of adolescents with genetic conditions. Enhancing access to genetic counselling as a means of facilitating identity development is an important component of these care models.

PMID:40841658 | DOI:10.1186/s13023-025-03968-x

BMC Oral Health. 2025 Aug 21;25(1):1348. doi: 10.1186/s12903-025-06714-8.

ABSTRACT

OBJECTIVES: The aim of this retrospective cohort study was to compare the total duration of Class II malocclusion treatment with hybrid pendulum vs. buccal interradicular miniscrew supported distalization mechanics followed by fixed appliances. Molar distalization duration and end-of-the-treatment changes were also compared.

MATERIALS AND METHODS: The sample of this retrospective cohort study consisted of clinical records, pre-treatment (T1) and post-treatment (T2) dental models, and panoramic and lateral cephalometric radiographs of 80 skeletal Class I patients with bilateral Class II molar relation. Molar distalization was achieved with a hybrid pendulum in Group P (15 males, 25 females; mean age: 15.19 ± 0.32 years) and with buccal interradicular miniscrew-supported compressed sentalloy coil springs in Group B (15 males, 25 females; initial mean age: 15.65 ± 0.32 years). Following molar distalization, all patients in both groups received comprehensive fixed orthodontic treatment. Molar distalization and total treatment durations and changes in Peer Assessment Rating scores and 14 cephalometric measurements were evaluated.

RESULTS: Statistically significant molar distalization and distal tipping, mandibular incisor protrusion, and PAR reduction were achieved in both groups, with no difference between groups. There were no significant differences between groups for total treatment (24.58 ± 5.19 months in Group B and 24.81 ± 5.33 months in Group P) and molar distalization durations (7.01 ± 2.17 months in Group B and 7.03 ± 1.42 months in Group P) (p > 0.0167).

CONCLUSIONS: The total length of orthodontic treatment for Class II malocclusion which involved molar distalization by miniscrew supported appliances was not affected by whether the appliance was located palatally or buccally.

PMID:40841655 | DOI:10.1186/s12903-025-06714-8

JAMA Oncol. 2025 Aug 21. doi: 10.1001/jamaoncol.2025.2738. Online ahead of print.

ABSTRACT

IMPORTANCE: Obesity is associated with a higher risk of recurrence, mortality, comorbidities, treatment-related adverse effects, and poor quality of life in patients with breast cancer. Scalable interventions are needed to promote weight loss in this population.

OBJECTIVE: To evaluate the impact of a remotely delivered weight loss intervention (WLI) on weight change at 1 year in patients with breast cancer and obesity and to explore factors associated with weight change.

DESIGN, SETTING, AND PARTICIPANTS: The Breast Cancer Weight Loss trial is a phase 3, randomized clinical trial evaluating the impact of a telephone-based WLI on invasive disease-free survival and other outcomes in women with obesity and early breast cancer at 637 sites across the US and Canada. Participants were enrolled to the study between August 2016 and February 2021. Participants included women with stage II to III, ERBB2-negative breast cancer and a body mass index (BMI) of 27 or higher.

INTERVENTIONS: Participants were randomized to a 2-year, telephone-based WLI plus health education or health education alone control group.

MAIN OUTCOME AND MEASURES: The primary end point for this prespecified secondary analysis was weight change at 1 year. Weight was measured at baseline and 1 year, and changes in weight were compared between groups. Weight change was evaluated with a linear mixed-effects model including treatment group, weight over time, a time-by-group interaction, menopausal status, race and ethnicity, and hormone receptor status.

RESULTS: A total of 3180 women with breast cancer and BMI of 27 and higher were included in the study; 1591 were randomized to the WLI and 1589 to the control group. At baseline, the mean (SD) age of participants was 53.4 (10.6), and the mean (SD) BMI was 34.4 (5.6). The racial and ethnic breakdown included 406 (12.8%) Black, 231 (7.3%) Hispanic or Latino, 2906 (91.4%) non-Hispanic, and 2555 (80.3%) White participants. WLI participants lost a mean of 4.3 kg (95% CI 3.9-4.6 kg), or 4.7% (95% CI, 4.3%-5.0%) of baseline body weight at 1 year vs control participants, who gained 0.9 kg (95% CI, 0.5-1.3 kg), or 1.0% (95% CI 0.1%-1.4%) of baseline body weight (P < .001). Participants randomized to WLI experienced significant weight loss (vs control group participants) across demographic and tumor factors. WLI effect differed significantly by menopausal status, with postmenopausal participants having greater weight loss than premenopausal participants, and by race and ethnicity, with Black and Hispanic participants having less weight loss compared to other races and ethnicities.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, a telephone-based WLI induced significant weight loss in patients with breast cancer with overweight and obesity across demographic and treatment factors. Further follow-up of the Breast Cancer Weight Loss trial will evaluate whether the WLI improves disease outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02750826.

PMID:40839373 | DOI:10.1001/jamaoncol.2025.2738

JAMA. 2025 Aug 21. doi: 10.1001/jama.2025.13205. Online ahead of print.

ABSTRACT

IMPORTANCE: With the programmed cell death protein 1 (PD-1) blockade toripalimab, omitting highly toxic concurrent cisplatin may be feasible for nasopharyngeal carcinoma (NPC) without compromising survival.

OBJECTIVE: To evaluate the efficacy and safety of toripalimab incorporated into induction chemotherapy and radiotherapy, without concurrent cisplatin, for locoregionally advanced NPC.

DESIGN, SETTING, AND PARTICIPANTS: Open-label, multicenter, randomized phase 3 clinical trial conducted from August 2021 to July 2022 at 13 hospitals in China, enrolling 532 patients with T4N1M0 or T1-4N2-3M0 NPC; 400 (75.2%) completed the trial per protocol. The final date of follow-up was March 21, 2025.

INTERVENTIONS: Patients were randomly assigned to either the standard therapy group (n = 266), receiving toripalimab with gemcitabine-cisplatin induction chemotherapy and concurrent cisplatin-radiotherapy (100 mg/m2 triweekly for 2 cycles), or the concurrent cisplatin-sparing group (n = 266), receiving the same regimen without concurrent cisplatin. The 17 cycles of toripalimab (240 mg triweekly) were distributed across the induction, radiotherapy, and adjuvant phases as 3, 3, and 11 cycles, respectively.

MAIN OUTCOMES AND MEASURES: Coprimary end points were failure-free survival (noninferiority margin, 8%) and incidence of all-grade vomiting (superiority design). Secondary end points included overall survival, locoregional recurrence-free survival, distant metastasis-free survival, safety, tumor response, quality of life, and tolerability.

RESULTS: In the 532 patients in the intention-to-treat population (median [IQR] age, 47 [39-54] years; 25.2% women), after a median follow-up of 37.0 (range, 4.0-50.0) months, the concurrent cisplatin-sparing group had a 3-year failure-free survival rate of 88.3% vs 87.6% in the standard therapy group, a difference of 0.7% (lower limit of the 1-sided 95% CI, -3.9%; P = .002 for noninferiority; stratified hazard ratio, 0.92 [95% CI, 0.66-1.79]; log-rank P = .73). In the safety analysis, the incidence of all-grade vomiting was significantly lower in the concurrent cisplatin-sparing group vs the standard therapy group (26.2% [68/260] vs 59.8% [156/261]; difference, 33.6% [1-sided 95% CI, 26.9%-∞]; P < .001). Patient-reported quality of life (participation rate, 87.5%) and tolerability (participation rate, 94.7%) were better in the concurrent cisplatin-sparing group, primarily in gastrointestinal, functional, and global health status.

CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, among patients with locoregionally advanced NPC, toripalimab combination therapy without concurrent cisplatin was a feasible treatment with high efficacy in failure-free survival and low toxicity.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04907370.

PMID:40839372 | DOI:10.1001/jama.2025.13205