Nevin Manimala

Mol Med Rep. 2026 May;33(5):156. doi: 10.3892/mmr.2026.13866. Epub 2026 Apr 3.

ABSTRACT

Lung cancer is an aggressive malignancy associated with a rapid progression and poor prognosis, for which immunotherapy only exhibits modest efficacy in most patients. In lung cancer, high lactate is associated with a low immunotherapy response and shortened survival; however, causal lactylation‑related genes remain to be elucidated. In the present study, candidate genes were screened using Mendelian randomization (MR) analysis, with expression quantitative trait loci data and genome‑wide association study summary statistics used as analytical resources. A total of 46 lactylation‑related genes were included in the MR analysis, and multiple testing correction was performed using the false discovery rate (FDR) and Bonferroni methods to control the false‑positive risk. MR identified three core genes [platelet‑type phosphofructokinase; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; and stathmin 1 (STMN1)]. Among these genes, only STMN1 was significantly associated with increased lung cancer risk (inverse variance weighting original P=0.005, FDR‑corrected P=0.014995, Bonferroni‑corrected P=0.014995, odds ratio=1.741, 95% confidence interval: 1.182‑2.564), with robust results confirmed by heterogeneity/pleiotropy/sensitivity analyses. Subsequently, transcriptomic analysis was conducted to assess STMN1 expression in lung cancer tissues and its association with patient survival. In vitro (cell proliferation, migration, invasion and apoptosis assays) and in vivo experiments (murine tumor models) were also conducted to explore the function of STMN1. STMN1 exhibited upregulation in lung cancer tissues, and was associated with a shorter survival, reduced antitumor immune cell infiltration and an immunosuppressive tumor microenvironment (TME) phenotype. STMN1 knockdown inhibited lung cancer malignancy both in vitro and in vivo, and modulated key markers, whereas its overexpression exhibited the opposite effects. Additionally, STMN1 promoted global histone lactylation and histone H3 lysine 18 lactylation in lung cancer cells, establishing a direct functional link between STMN1 and the lactylation pathway. In conclusion, STMN1 is a lactylation‑related causal oncogene in lung cancer, driving progression via malignant phenotypes, and its high expression is associated with an immunosuppressive TME that may synergistically facilitate tumor progression. Therefore, STMN1 may be considered a novel target for lung cancer therapy.

PMID:41930463 | DOI:10.3892/mmr.2026.13866

Pacing Clin Electrophysiol. 2026 Apr 3. doi: 10.1111/pace.70228. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac implantable electronic device (CIED) related complications occur frequently. Given the uncertainties, a comprehensive investigation of predictive factors is crucial. This study aimed to identify the determinants influencing the occurrence of CIED-related complications and to evaluate their predictive capability for the onset of CIED-related complications.

METHODS: This retrospective cohort study recruited 870 patients who underwent CIED implantation. The primary outcome was overall complications, and the secondary was pocket hematomas (PH). Logistic regression model was used to estimate the odds ratio (OR) with the 95% confidence interval (CI), and to establish the prediction models for all complications and PH.

RESULTS: 43 cases (4.95%) developed complications during follow-up, including 24 (2.8%) PH and 19 others. After adjusted for potential confounders, body mass index (BMI), having diabetes and chronic kidney disease (CKD), usage of anticoagulants and antiplatelets, device type, device replacement, and device electrode quantities were all associated with the risk of both the complications and PH. The prediction model with these variables displayed a good performance in predicting the complications occurrence, with AUC and C-statistic being 0.886 and 0.886 in training dataset, and 0.780 and 0.761 in the test dataset. Similar good performance in predicting PH onset were also observed.

CONCLUSION: The results indicate that BMI, diabetes, CKD, anticoagulants, antiplatelets, device types, device replacement, and device electrode quantities are critical risk factors, which can help predict the onset of the complications and PH.

PMID:41930459 | DOI:10.1111/pace.70228

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2026 Mar;42(3):230-236.

ABSTRACT

Objective To investigate the concordance of programmed death ligand-1 (PD-L1) expression between primary non-small cell lung cancer (NSCLC) and paired brain metastasis, analyze its relationship with clinicopathological characteristics, and evaluate the feasibility of using primary tumor PD-L1 status to predict brain metastasis status. Methods Thirty-two paired primary NSCLC and brain metastasis samples, pathologically diagnosed between January 1, 2017 and July 1, 2022, were collected. PD-L1 expression was detected by immunohistochemistry and interpreted using the Tumor Proportion Score (TPS), with cut-off values set at 1% and 50%. The Chi-square test was used to analyze the relationship between PD-L1 expression and clinicopathological features. Paired Chi-square and Kappa consistency tests were employed to assess the concordance of PD-L1 expression between primary and metastatic sites. Results PD-L1 expression showed no significant correlation with patient gender, age, treatment history, or histologic type. At the 1% cut-off, the overall PD-L1 expression showed moderate concordance between primary and metastatic sites (Kappa=0.624). Subgroup analysis revealed high concordance in untreated patients (Kappa=0.761, P=0.001), whereas the treated group showed weak concordance without statistical significance (Kappa=0.324, P=0.205). At the 50% cut-off, both the treatment group and the untreated group showed weak concordance without statistical significance. Although the chemotherapy subgroup showed perfect agreement (Kappa=1.000) at the 50% cut-off, the high-expression concordance rate was only 20.00%, indicating limited clinical reference value. Conclusion The strong concordance of PD-L1 expression in the untreated group patients supports the use of primary tumor PD-L1 status to guide clinical decision-making when brain metastasis tissue is unavailable. Treatment status (mainly including chemotherapy) may be an important factor affecting the consistency of high PD-L1 expression between primary NSCLC and brain metastasis.

PMID:41930444

J Cosmet Laser Ther. 2026 Apr 3:1-8. doi: 10.1080/14764172.2026.2652488. Online ahead of print.

ABSTRACT

This study aimed to evaluate pain levels, patient satisfaction, and preferences for different anesthetic techniques during the cosmetic application of botulinum toxin A in the upper third of the face. A randomized, double-blind, split-face clinical trial was conducted with 100 women undergoing esthetic procedures for facial wrinkle reduction. Patients were assigned to three groups: vibratory anesthesia versus placebo (Group I), topical anesthesia versus placebo (Group II), and vibratory anesthesia versus topical anesthesia (Group III). Pain levels were assessed using the visual analog scale (VAS). Patients identified the side with better pain control, expressed satisfaction, and provided recommendations for each technique. Group I (vibration 5.02 ± 2.56 vs. placebo 6.00 ± 2.75, p = .034), Group II (topical anesthetic 4.69 ± 2.45 vs. placebo 5.50 ± 2.38, p = .039), and Group III (topical anesthetic 4.89 ± 2.29 vs. vibration 6.06 ± 2.22, p = .048). While satisfaction levels showed no statistically significant differences between techniques, topical anesthesia in Group III received the highest recommendations (p = .010). This study suggests that topical anesthesia and vibratory stimulation both offer small-to-medium analgesic benefits over placebo during BoNT-A injections. Despite comparable satisfaction scores, patients preferred topical anesthesia for future use.

PMID:41930421 | DOI:10.1080/14764172.2026.2652488

Monaldi Arch Chest Dis. 2026 Apr 2. doi: 10.4081/monaldi.2026.3644. Online ahead of print.

ABSTRACT

Interstitial lung diseases (ILDs) comprise a heterogeneous group of disorders characterized by varying degrees of inflammation and fibrosis, necessitating precise epidemiological characterization. This ambispective observational study evaluated the clinical spectrum and diagnostic distribution of 1201 patients at a tertiary center in North India, utilizing a multidisciplinary discussion (MDD) framework for final diagnostic consensus. The mean age of the cohort was 52.7 (±13.04) years, with a female predominance of 55.6%. Idiopathic interstitial pneumonia (IIP) was the most prevalent diagnosis (48.8%), followed by connective tissue disease-associated ILD (CTD-ILD; 19.8%) and hypersensitivity pneumonitis (14.6%). Within the IIP subgroup, idiopathic pulmonary fibrosis predominated (49.7%), followed by nonspecific interstitial pneumonia (39.2%). Statistical analysis identified tobacco use as a significant driver for IIP phenotypes (odds ratio: 3.36; 95% confidence interval: 2.37-4.75; p<0.01). Physiological assessment revealed a restrictive ventilatory defect in 83.9% of the cohort. Patients with sarcoidosis (13.4%) exhibited significantly higher functional reserve (mean forced vital capacity %: 74.1±17.9%) compared to more fibrotic subtypes (p<0.01), and demonstrated superior exercise capacity (mean 6-minute walk distance: 392.4±85.6 m vs. 347.7±90.1 m in CTD-ILD; p<0.01). These findings establish that fibrotic IIPs constitute the primary disease burden in North India, highlighting the clinical necessity of standardized, MDD-based pathways to ensure accurate phenotype differentiation and timely initiation of targeted therapies in a region characterized by complex environmental triggers.

PMID:41930418 | DOI:10.4081/monaldi.2026.3644

Worldviews Evid Based Nurs. 2026 Apr;23(2):e70137. doi: 10.1111/wvn.70137.

ABSTRACT

BACKGROUND: Chronic diseases require sustained medication adherence, yet nonadherence remains common, leading to poor outcomes and increased healthcare costs. Digital self-management technologies such as mobile health (mHealth) apps, SMS reminders, and web-based platforms offer scalable ways to support adherence, but evidence on their overall effectiveness across diverse contexts is fragmented.

AIM: To systematically review and meta-analyze the effectiveness of self-management technologies in improving medication adherence among adults with chronic diseases and to examine potential moderators of intervention impact.

METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, CINAHL, and JMIR for peer-reviewed studies (January 2010-June 2025) evaluating digital self-management interventions with adherence outcomes and comparator groups. Eligible designs included RCTs, quasi-experimental, and controlled before-after studies in adults with chronic disease. Random-effects meta-analysis estimated pooled effect sizes (Cohen’s d). Heterogeneity (I²), subgroup analyses, and publication bias (Egger’s, Begg’s, trim-and-fill) were assessed.

RESULTS: Fifty-two studies were included, spanning 2015-2025. Early interventions (2015-2019) focused on feasibility, using SMS and basic web tools; later years (2021-2025) showed technological maturity, dominated by mHealth apps integrating monitoring, reminders, and education. The pooled random-effects effect size was d = 0.268 (95% CI 0.123-0.414, p = 0.0003), indicating a small-to-moderate benefit. Heterogeneity was high (I² = 89%). Medium-duration (10.8-24 weeks) interventions had the largest effect (d = 0.50), and effects varied markedly by country (e.g., Iran d = 2.29; Taiwan d = -0.94). Begg’s test suggested possible publication bias; trim-and-fill adjustment increased the pooled effect to d = 0.366.

LINKING EVIDENCE TO ACTION: Digital self-management technologies yield a statistically significant, small-to-moderate improvement in medication adherence across chronic diseases, with potential underestimation due to selective reporting. Effectiveness is moderated by temporal trends, geography, intervention duration, and study design, underscoring the need for context-specific adaptation and methodological rigor. Future research should prioritize large, well-controlled trials, pre-registration, and exploration of cultural and systemic determinants to optimize intervention impact.

PMID:41930416 | DOI:10.1111/wvn.70137

Health Soc Care Deliv Res. 2026 Apr 1:1-26. doi: 10.3310/TNFT6414. Online ahead of print.

ABSTRACT

BACKGROUND: Domestic abuse and suicidal ideation are highly prevalent in the United Kingdom, often co-occurring. Numerous practical and psychosocial barriers inhibit help-seeking. This study explored whether community pharmacy could offer an accessible setting for a domestic abuse and suicidal ideation response service.

METHODS: The design was a randomised cluster feasibility trial. Twelve pharmacies were recruited from one pharmacy organisation, randomised into eight intervention pharmacies and four controls. Thirty-seven pharmacy staff were trained to deliver the Lifeguard Pharmacy intervention, which involved providing a consultation and structured referral or signposting to customers identified as experiencing domestic abuse and/or suicidal ideation. Staff learning from the training was evaluated using the validated Continuing Professional Development reaction questionnaire, analysed using a paired t-test. The intervention ran from January to July 2023 and was accompanied by a nested process evaluation consisting of staff focus groups and a multistakeholder final evaluation workshop with a mix of lay, pharmacy staff and representatives from referral organisations. Data were collected on number and category of client contacts from intervention and control pharmacies; descriptive analyses were performed.

RESULTS: After intervention training, pharmacy staff showed statistically significant improvements in their levels of perceived ability, ease and confidence in responding to and referring people in need of help for domestic abuse and suicidal ideation with increased confidence in the ability of other pharmacy staff to support domestic abuse and suicidal ideation. During the intervention period, staff responded to 24 cases in intervention pharmacies: 8 for suicidal ideation, 9 for domestic abuse and 7 for both domestic abuse and suicidal ideation. Of these, 22 were staff-initiated and 2 were client-initiated. Two cases (one suicidal ideation and one domestic abuse) were identified in control pharmacies. Staff participants had a positive perception of the service and its impact on them and their clients. The multistakeholder workshop findings confirmed the feasibility of a staff-initiated response service for both domestic abuse and suicidal ideation in a community pharmacy setting. However, there were challenges marketing and delivering a client-initiated service, and the study was not able to collect all of the information required to inform a future trial.

LIMITATIONS: There were challenges to collecting data and obtaining informed consent from Lifeguard Pharmacy clients, especially when distressed or time-pressured. Consequently, full data sets were only collected from 4 of the 24 people who used the service. All 12 participating pharmacies were located in 1 region of England, hence a future study would need to test implementation across a broader range of settings.

CONCLUSIONS: It is feasible to implement a staff-initiated response service for domestic abuse and/or suicidal ideation in selected pharmacies. The combination of staff training, consultation guide, referral tool and client support resources and organisational support empowered staff to proactively identify people experiencing domestic abuse and/or suicidal ideation.

FUTURE WORK: Further development work would be needed before a client-initiated service could be delivered, and a future implementation study is contingent on finding ways to safely consent and collect data from clients. Some preliminary health economic work was conducted but a full health economic analysis would be needed as part of a future study.

FUNDING: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR133132.

PMID:41930409 | DOI:10.3310/TNFT6414

Inquiry. 2026 Jan-Dec;63:469580261427422. doi: 10.1177/00469580261427422. Epub 2026 Apr 3.

ABSTRACT

Improving medication adherence can reduce the burden of cardiovascular disease (CVD) in Saudi Arabia and its related healthcare expenses. This study aimed to assess physicians’ awareness and knowledge of barriers to medication adherence in cardiovascular patients in Saudi Arabia and to evaluate the strategies they employ in clinical practice to enhance adherence. A sample of Saudi Arabian licensed physicians specializing in CVD participated in an observational cross-sectional investigation. Participants were recruited using convenience sampling method through in-person visits conducted at various healthcare facilities. Using a standardized, peer-reviewed questionnaire spanning areas of knowledge, awareness, and practice, data were gathered. SPSS version 27 was used for statistical analysis; multivariate linear regression was utilized to identify independent factors. A total of 265 physicians participated. Among physicians, 44.9% always asked about medication habits, 26.8% about missed doses, 28.3% discussed illness severity, and 19.2% explained consequences of nonadherence. None consistently addressed side effects, though 46.4% did so frequently. Over half (58.1%) reported that 36% to 65% of patients failed to start therapy after the first prescription. Univariate analysis identified age as associated factors for knowledge, and sex, age, and training for practice. Regression analysis identified age and private work significant independent predictor for knowledge (β = -.05, -.68; P = .01, and .03; respectively), and only training remained a significant independent predictor for practice (β = 8.03, P < .001). Physicians showed modest knowledge with major gaps in practice especially educating patients about side effects and consequences of nonadherence. Knowledge was lower among older physicians and those in private practice, while training was the strongest predictor of better clinical practice, highlighting the need for targeted education and training to improve adherence-related practices.

PMID:41930408 | DOI:10.1177/00469580261427422

Int J Dent Hyg. 2026 Apr 3. doi: 10.1111/idh.70055. Online ahead of print.

ABSTRACT

BACKGROUND: This study assessed the impact of toothbrushing and exposure to cherry juice on the discoloration of various restorative materials commonly used in paediatric dentistry.

METHODS: Forty specimens of each of the three types of restorative material (compomer, resin-modified glass ionomer cement and composite) were prepared. The specimens were immersed in cherry juice and distilled water for 10 days, forming two subgroups (brushed and unbrushed) within each material group (n = 10). The brushed samples were treated every 8 h for 1 min daily over 10 days. The colour change was measured at baseline and after 10 days, and the data were analysed using three-way ANOVA and Tamhane’s T2 post hoc test.

RESULTS: After 10 days, the brushed, cherry juice-soaked resin-modified glass ionomer cement exhibited the highest ΔE00 value (13.91 ± 2.9), while the lowest value was observed in the unbrushed, distilled water-soaked microhybrid composite (0.90 ± 0.46). Statistically significant differences were found between materials (p < 0.001), brushed and unbrushed (p = 0.005), and cherry juice- and distilled water-soaked (p < 0.001).

CONCLUSION: Brushing and the consumption of colouring negatively influence the colour stability of restorative materials. The composites demonstrate greater resistance to discoloration from brushing and exposure to coloured beverages.

PMID:41930404 | DOI:10.1111/idh.70055

J Forensic Sci. 2026 Apr 3. doi: 10.1111/1556-4029.70322. Online ahead of print.

ABSTRACT

Soft tissue removal is a fundamental step in forensic anthropology, allowing for the detailed analysis of bone morphology and trauma. Among the available maceration techniques, hot water maceration is widely used due to its efficiency and ease of application. However, its effects on internal bone structure remain poorly documented. This study assessed the impact of simmering water maceration (85°C, 6 days) on cortical bone density using computed tomography (CT). Twelve paired femora and humeri from six human donors were scanned before and after maceration. Cortical bone density was measured in Hounsfield units (HU) at the proximal and distal diaphyses. Results showed no statistically significant changes in bone density post-maceration (p > 0.05). Femora demonstrated higher density than humeri, and male donors exhibited greater values than females. Intra- and inter-observer reproducibility was excellent, validating the reliability of the imaging protocol. These findings tend to support the idea that hot water maceration preserves bone mineral integrity and supports its continued use in forensic settings. The study also demonstrates the utility of CT-based densitometry as a precise, non-invasive method for postmortem bone analysis, contributing to the standardization of forensic protocols.

PMID:41930402 | DOI:10.1111/1556-4029.70322