Nevin Manimala

Asian Pac J Cancer Prev. 2025 Aug 1;26(8):2909-2917. doi: 10.31557/APJCP.2025.26.8.2909.

ABSTRACT

BACKGROUND: Gastrointestinal (GI) cancer constitute a major global health problem influenced by genetic and environmental factors. Genetic variations within base excision repair (BER and) nucleotide exchange repair (NER) pathway genes can impact DNA repair capacity. Investigating the combined effects of BER and NER pathway genes offers a promising avenue for understanding their impact on cancer susceptibility. This study was aimed to address combined effects of genetic variants in BER and NER on the risk of developing GI cancer.

METHODS: Genetic polymorphisms within BER and NER genes were examined in two hundred histologically confirmed GI cancer cases, along with equal number of controls by the PCR-RFLP technique. Odds ratios (OR) with 95% CI and associated p-values were computed to assess an extent of association of these polymorphisms with GI cancer susceptibility, with statistical significance established at p ≤0.005.

RESULTS: Regression analysis revealed compelling evidence of synergistic effects between specific variant genotypes. Notably, combinations involving variants of XPG (rs17655) and XRCC1 (rs1799782) (OR=2.20; 95% CI: 1.02-4.72; p=0.042) and XRCC1 (rs25487) (OR=2.56; 95% CI: 1.39-4.72; p=0.002) as well as XPD (rs238406) and XRCC1 (rs1799782) (OR=3.02; 95% CI: 1.60-5.70; p=0.0006) and XCC1 (rs25487) (OR=6.63; 95% CI: 3.63-12.10; p=0.0001) exhibited significant associations with increased GI cancer risk within the study population.

CONCLUSION: These findings suggested combined influence of SNPs within XRCC1, XRCC3, and APE1, in combination with polymorphisms of XPC and XPD, on the development of GI cancer. Nonetheless, further investigations on larger scale are warranted to validate and expand upon these observations.

PMID:40849707 | DOI:10.31557/APJCP.2025.26.8.2909

Asian Pac J Cancer Prev. 2025 Aug 1;26(8):2803-2810. doi: 10.31557/APJCP.2025.26.8.2803.

ABSTRACT

INTRODUCTION: The oral cavity includes the lips, buccal mucosa, teeth, gingiva, anterior two third of the tongue, the floor of the mouth, and hard palate. Comprehensive data on the burden of oral cancer are lacking at the national and state levels. Therefore, analysing the changing trend in oral cancer in India over the last three decades fills a significant gap.

METHODS: In this study, the number of new cancer cases, the population at risk, and the crude incidence rate were extracted from the GBD 2019 data. We used the Joinpoint regression to assess the trends in age-adjusted incidence rates per 100,000 population for lip ad oral cancer among men in India from 1990 to 2019 and we used the cancer registry data for the projection of the cancer incidence for all the states, union territories, and India every five years from 2026 to 2036 for lip and oral cancer among men.

RESULTS: The estimate of lip and oral cancer cases among Indian men will be 131,414 in 2026, will increase to 147,488 during 2031, and will increase to 163,224 during 2036.

CONCLUSION: The present study estimates the lip and oral cancer cases, which will help for planning purpose of cancer screening facilities for early detection, awareness of cancer, modifying lifestyle, reduction in tobacco use, and establishment of adequate treatment guidelines that can effectively be carried out at different levels (district hospitals, teaching hospitals, specialized hospitals, etc.) would also help in the reduction of mortality due to oral cancer as well as the burden of oral cancer.

PMID:40849696 | DOI:10.31557/APJCP.2025.26.8.2803

Asian Pac J Cancer Prev. 2025 Aug 1;26(8):2793-2802. doi: 10.31557/APJCP.2025.26.8.2793.

ABSTRACT

INTRODUCTION: This systematic review and meta-analysis assessed the efficacy and safety of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared to CCRT alone in locally advanced cervical cancer (LACC).

METHODS: We systematically searched PubMed, ScienceDirect, Cochrane Library, EBSCOHost, ProQuest, and grey literature (Google Scholar, OpenGrey, WorldCat) up to April 26, 2024 (PROSPERO: [CRD42024540599]). Seven studies were included (stages IB2-IVA, FIGO 2018), involving 446 participants. Outcomes included complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse effects.

RESULTS: Seven studies were included (n = 1,638), with 825 patients receiving NACT+CCRT and 813 receiving CCRT alone. The NACT+CCRT group showed higher CR rates (77% vs. 70.9%), but the difference was not statistically significant (OR 1.23, 95% CI 0.40-3.83). No significant differences were found in PFS (HR 0.94, 95% CI 0.53-1.69) or OS (HR 1.07, 95% CI 0.56-2.03). Adverse effects, including anemia, neutropenia, thrombocytopenia, nausea, vomiting, fatigue, and creatinine elevation, showed no significant differences between the groups.

CONCLUSION: In patients with locally advanced cervical cancer, NACT followed by CCRT is associated with comparable survival outcomes and a similar safety profile to standard CCRT, with a non-significant trend toward improved CR.

PMID:40849695 | DOI:10.31557/APJCP.2025.26.8.2793

Asian Pac J Cancer Prev. 2025 Aug 1;26(8):2785-2792. doi: 10.31557/APJCP.2025.26.8.2785.

ABSTRACT

OBJECTIVE: To compare the clinical outcomes of thyroid artery embolization (TAE) in the treatment of thyroid nodules.

METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Relevant studies published between 1973 and 2023 were identified through PubMed, Cochrane Central, Web of Science, and Google Scholar. Eligible studies included randomized controlled trials and observational studies that evaluated TAE in patients with thyroid nodules. Data were extracted on hormonal levels (FT4, TSH), nodule volume, complications, quality of life, and surgical outcomes. Statistical analyses were performed using Review Manager 5.4.1 with fixed or random-effect models, and results were expressed with pooled mean differences or odds ratios with 95% confidence intervals (CIs).

RESULTS: Ten studies with a total of 347 patients were included. TAE significantly reduced nodule volume (mean difference: -51.95 mL, 95% CI: -78.58 to -25.33, p = 0.0001), increased TSH levels (mean difference: -0.63 µIU/mL, 95% CI: -1.10 to -0.16, p = 0.009), and reduced surgical blood loss and operative time. The odds ratio for minor versus major complications was 42.60 (95% CI: 17.51 to 103.64, p < 0.00001), indicating a favorable safety profile. Quality of life showed a trend toward improvement, although not statistically significant (OR: 27.72, 95% CI: 0.47 to 1648.47, p = 0.11).

CONCLUSION: TAE appears to be a safe and potentially effective procedure for reducing thyroid nodule volume and improving surgical outcomes. However, conclusions should be interpreted cautiously due to high heterogeneity and the observational nature of the included studies.

PMID:40849694 | DOI:10.31557/APJCP.2025.26.8.2785

Biophys J. 2025 Aug 22:S0006-3495(25)00532-6. doi: 10.1016/j.bpj.2025.08.020. Online ahead of print.

ABSTRACT

To gain molecular and mechanistic insights into initiation of the RAS-RAF signaling cascade we developed and used a combination of multiscale simulation and experimental approaches. The influence and impact of the membrane on RAS and RAF proteins is a factor we are just beginning to understand and appreciate in more detail. Molecular simulation is an ideal methodology to further study this complicated relationship between the membrane and associated proteins. Our previous work using MuMMI (Multiscale Machine-learned Modeling Infrastructure) investigated different lipid compositions solely around the KRAS4b protein and the interplay between protein behavior and these membrane environments. MuMMI uses machine learning to couple adjacent simulation scales and has been efficiently scaled across some of the world’s largest high-performance computers. Recently, we have expanded this multi-resolution framework to include the all-atom simulation scale, and to incorporate the RAF RBDCRD domains. Here we present the overall analysis results from this new simulation campaign comprising a mixture of RAS and RAF RBDCRD proteins. Approximately 35,000 coarse-grained, and 10,000 all-atom molecular dynamics simulations were completed, sampled from a variety of protein/lipid composition configurations that were generated from a micron-scale continuum simulation containing hundreds of copies of the proteins. Our studies suggest that orientations of the RAS-RBDCRD complex on the membrane occupy distinct configurational states and the spatial patterns of lipid arrangements around these different protein states are unique to each state. The extent, and size of lipid ‘fingerprints’ imposed on the membrane by the RAS-RBDCRD protein complex is significantly larger than observed for just the RAS protein on its own. These protein complexes strongly associate but we do not observe statistically significant preferred protein-protein orientations. These observations indicate that spatial co-localization of RAS-RBDCRD proteins in the same vicinity may be assisted by specific membrane environments, acting to increase the probability of signaling complex formation.

PMID:40849684 | DOI:10.1016/j.bpj.2025.08.020

Med Sci Monit. 2025 Aug 24;31:e948936. doi: 10.12659/MSM.948936.

ABSTRACT

BACKGROUND At great heights, reduced oxygen levels and barometric pressure can cause retinal damage, leading to high-altitude retinopathy. Military pilots additionally experience gravitational forces from rapid changes in speed and direction, which can impair vision due to short-term retinal ischemia. This study evaluated the association between flight duration and altitude with retinal and choroidal changes on optical coherence tomography (OCT) in 44 Polish military pilots. MATERIAL AND METHODS This study enrolled 88 adult men – 44 pilots from military bases in Poland and 44 controls recruited from among male ground staff in these bases. Data regarding the pilots’ individual work experience was obtained from their official records on site. The average age of the pilots was 39.7 years (SD=6.9; range: 27-50), while the average age of the comparison group was 41.2 years (SD=6.3; range: 28-53). RESULTS Retinal thickness in the foveal and parafoveal region, along with the mean retinal nerve fibers layer (RNFL) thickness and total ganglion cells complex (GCC) thickness, did not differ significantly between study groups. There was also no statistically significant difference in terms of choroidal thickness between the military pilots and controls. However, after splitting the pilots into groups based on their overall hours spent flying, a very significant correlation was revealed in reduction of subfoveal choroidal thickness (SCT) (P=0.0010) proportionally to total flight time. CONCLUSIONS The results of our study suggest that retinal parameters remain stable in military pilots, but the cumulative changes are expressed in choroidal thinning.

PMID:40849679 | DOI:10.12659/MSM.948936

Orthop Surg. 2025 Aug 23. doi: 10.1111/os.70155. Online ahead of print.

ABSTRACT

OBJECTIVE: Given the limitations of conventional anterior and lateral approaches, such as variable success rates and risks of neurovascular injury, there is a critical need to evaluate alternative techniques that enhance procedural safety and efficiency. This study aimed to investigate the safety and precision of the anterolateral approach for hip joint puncture and compare its clinical efficacy with those of the anterior and lateral approaches.

METHODS: A single-center, prospective, randomized Williams crossover trial was conducted from March 2023 to June 2023 involving 30 patients with hip pain. Each patient underwent three hip joint punctures within 3 weeks, all conducted using anatomical landmark-guided blind puncture. The punctures were administered in different sequences of anterior, anterolateral, and lateral approaches, with one-week intervals between punctures. Thirty patients were randomly assigned to six groups (n = 5), following different sequences of the three approaches. The primary outcomes were the success rate and accuracy, and the secondary outcomes were post-puncture pain assessed using the Visual Analogue Scale (VAS), procedure time, puncture depth, and complications.

RESULTS: The anterolateral approach achieved a higher success rate (96.7%) compared to the anterior (86.7%) and lateral (83.3%) approaches; although statistical significance was not reached (p = 0.328). Besides, it significantly shortened procedure duration (72.87 s, SD 9.66) compared to anterior (87.20 s, SD 20.57) and lateral (92.80 s, SD 39.02) approaches (p = 0.006). The puncture path length was shorter with the anterolateral approach (57.77 mm, SD 1.295) than with the lateral approach (63.33 mm, SD 1.295) (p = 0.004). The anterolateral approach achieved lower VAS pain scores (1.77, SD 0.94) compared to the lateral approach (2.90, SD 2.17). During the anterior approach injection, one patient experienced numbness in the lateral thigh of the surgical side.

CONCLUSION: This preliminary randomized crossover trial demonstrates that the anterolateral approach offers significant advantages in procedural efficiency (reduced time, shorter path length) and suggests a trend toward higher success rates compared to standard anterior and lateral approaches for hip joint puncture. These findings, particularly the improvements in efficiency and patient comfort (lower VAS), support the anterolateral approach as an effective technique.

LEVEL OF EVIDENCE: I, Randomized controlled trial.

TRIAL REGISTRATION: chictr.org.cn: ChiCTR2300074174.

PMID:40849673 | DOI:10.1111/os.70155

Cardiovasc Diabetol. 2025 Aug 23;24(1):347. doi: 10.1186/s12933-025-02866-7.

ABSTRACT

BACKGROUND: The objective of this study was to examine the degree to which conventional cardiovascular (CV) risk factor changes induced by once-weekly exenatide (EQW) might explain the placebo-controlled differences in CV outcomes observed in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

METHODS: We entered participant-level risk factor values over time into a validated type 2 diabetes-specific clinical outcomes model to estimate event rates, and compared simulated with observed relative risk changes in EXSCEL. We performed simulations for each participant to minimize uncertainty and to optimize confidence interval precision around risk point estimates. Six outcomes were examined: major adverse CV event (MACE), all-cause mortality (ACM), CV death, fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and hospitalization for heart failure (hHF). We also performed a mediation analysis using Cox regression models to evaluate potential key mediators for ACM.

RESULTS: Model simulations explained only modest proportions of the observed relative risk reductions for MACE (29%), ACM (15%), CV death (18%), and stroke (29%), but greater proportions for hHF (67%) and MI (200%). Mediation analysis suggested that baseline-to-6 or 12-month changes in HbA_1c, blood pressure, heart rate, low-density lipoprotein cholesterol, triglycerides, and weight did not mediate the EQW effect on ACM.

CONCLUSIONS: These model simulations explain only a modest proportion of the impact of observed EQW-induced changes in conventional CV risk factors on EXSCEL outcomes, apart from hHF and MI. Up to 1-year changes in conventional risk factors did not mediate the observed ACM risk reduction.

PMID:40849664 | DOI:10.1186/s12933-025-02866-7

Eur J Med Res. 2025 Aug 23;30(1):794. doi: 10.1186/s40001-025-03080-7.

ABSTRACT

BACKGROUND: Hypoxia can impair cell and organ function, and cause apoptosis and various diseases. At present, there are many studies on pulmonary hypoxia but few studies on bronchial injury. The study aimed to research the impact of hypoxia on the barrier function of human bronchial epithelial cells and the expression level of tight junction proteins.

METHODS: Primary human bronchial epithelial cells were allocated into four groups: (1) control group, (2) intermittent hypoxia group, (3) sustained hypoxia group, and (4) cigarette smoke exposure group. Apoptosis in each group was assessed by flow cytometric analysis. The expression levels of ZO-1, occludin, and claudin-1 were evaluated via Western blotting. Furthermore, trans-epithelial electrical resistance (TEER) was measured using an epithelial voltohmmeter to assess barrier function.

RESULTS: (1) Compared with the control group, the intermittent hypoxia group exhibited no significant differences in apoptosis rate, TEER, or the expression of tight junction proteins ZO-1, occludin, and claudin-1 (P > 0.05). In contrast, both the sustained hypoxia and cigarette smoke groups demonstrated significantly elevated apoptosis rates (P < 0.05). Claudin-1 expression was significantly reduced in the sustained hypoxia group (P < 0.05), while the increase in ZO-1 expression was not statistically significant (P > 0.05). In the cigarette smoke group, expression levels of ZO-1, occludin, and claudin-1 were all markedly decreased (P < 0.05). (2) Compared with the control group, TEER values were significantly reduced in both the sustained hypoxia and cigarette smoke groups (P < 0.05). (3) A significant difference in ZO-1 expression was observed between the sustained hypoxia and cigarette smoke groups (P < 0.05).

CONCLUSIONS: Hypoxia modulates the expression of tight junction proteins in human bronchial epithelial cells, disrupts intercellular junctional integrity, increases epithelial permeability, and ultimately impairs barrier function.

PMID:40849658 | DOI:10.1186/s40001-025-03080-7

BMC Health Serv Res. 2025 Aug 23;25(1):1122. doi: 10.1186/s12913-025-13162-1.

ABSTRACT

BACKGROUND: Globally, maternal and child health outcomes were negatively affected during the COVID-19 pandemic. There is limited qualitative evidence focused on access to maternal health services during the COVID-19 pandemic in rural sub-Saharan African populations. This study aims to fill this gap by exploring key community perspectives on access to maternal health services during the COVID-19 pandemic in rural western Kenya.

METHODS: We conducted five focus group discussions and sixty one in-depth interviews. Participants were mothers who delivered in 2020 during the acute phase of the COVID-19 pandemic and rural community health workers (CHWs) in Siaya and Kisii counties. The three-delay model framework helped to guide discussions around access to maternal health services during the COVID-19 pandemic in rural western Kenya. We transcribed the data and conducted a thematic content analysis.

RESULTS: According to CHWs and expectant mothers, fear and misconceptions about COVID-19 were associated with delays in making the decision to seek maternal health care. Lockdowns, movement restrictions, and curfews made it challenging to physically reach health facilities. The shortage of drugs and supplies and an insufficient number of healthcare workers in health facilities were barriers to care seeking. The quality of maternal health services was perceived to have declined during the COVID-19 pandemic. Mothers reported the Linda Mama health insurance program helped them pay for maternal health services during the COVID-19 pandemic; however, out-of-pocket expenses were common. As reported by mothers, CHWs when engaged and active, helped alleviate access challenges by serving as a link to the health system. There were significant socio-economic difficulties experienced by community members because of closed businesses and schools.

CONCLUSIONS: Community perspectives revealed significant challenges with accessing maternal health services during the COVID-19 pandemic in rural western Kenya. The pandemic amplified each of three delays in accessing care leading to poorer access to maternal health services. The overriding perception among mothers was that CHWs helped mitigate challenges around access to health services. CHWs should be included in future pandemic preparedness and response efforts.

PMID:40849655 | DOI:10.1186/s12913-025-13162-1