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Nevin Manimala Statistics

PFKM Promotes the Progression of Gastric Cancer by Up-regulating CNTN1 Expression Through H3K18la Modification

Appl Biochem Biotechnol. 2025 Jul 3. doi: 10.1007/s12010-025-05319-9. Online ahead of print.

ABSTRACT

Gastric cancer (GC) stands as one of the most common malignancies globally, characterized by significant incidence rates. Phosphofructokinase muscle isoform (PFKM), a critical rate-limiting enzyme in glycolysis, has its expression modulated by lactate production in tumor cells. The objective of this study is to elucidate the underlying molecular mechanisms by which PFKM contributes to the pathogenesis of GC. The viability, migration, and invasion of GC cells were analyzed by CCK-8 and transwell assays. Each condition was repeated three times. The regulation of H3K18la on transcription activity of CNTNl was evaluated by·dua-luciferase reporter assay. Animal experiment was performed using nude mice with six mice in each group, and tumor growth was evaluated. Statistical analysis was performed using GraphPad Prism software with t-test, one-way or two-way ANOVA. We found that PFKM was over-expressed in GC. Downregulated PFKM restrained the viability, migration, invasion, glucose uptake, and lactate production of GC cells. Mechanically, PFKM interacted with CNTN1 and facilitated the enrichment of H3K18la at the CNTN1 promoter region. Overexpression of CNTN1 reversed the inhibitory effects of PFKM knockdown on GC progression. Our research showed that increasing PFKM levels accelerated GC development by regulating CNTN1 expression through mechanisms involving histone lactylation, which could potentially contribute to novel approaches in diagnosing and treating GC.

PMID:40608258 | DOI:10.1007/s12010-025-05319-9

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Effectiveness of centralized hospitalization treatment on transmission in household contacts of pulmonary tuberculosis patients: a contact-traced study

Eur J Clin Microbiol Infect Dis. 2025 Jul 3. doi: 10.1007/s10096-025-05170-0. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary tuberculosis (PTB) is a respiratory infectious disease that seriously endangers people’s health and incurs high treatment costs, which quickly leads to catastrophic expenditure for patients and their families. A centralized hospitalization treatment (CHT) strategy can be implemented to mitigate the transmission of PTB. This study evaluates the effectiveness of a CHT approach in reducing the magnitude of Mycobacterium tuberculosis (MTB) transmission in household contacts (HHCs) of confirmed PTB cases and explores potential risk factors for PTB.

METHODS: This retrospective cohort study used PTB cases from Guizhou, China, between January 2022 and October 2023. The HHCs of PTB cases diagnosed etiologically and treated with non-CHT were designated as the exposed group, and the HHCs of those treated with CHT were the non-exposed group. The ratio of the HHCs to index cases was 1:1-3. Face-to-face interviews were conducted for the participants by medical staff at home. R software was used for data analysis. Continuous variables were cut to create new categorical variables and were analyzed using the Chi-square test or Fisher test according to the nature of the data. The risk factors of PTB/LTBI and covariates were analyzed using a multivariate logistic regression model evaluated by the Akaike information criterion (AIC) and elucidated by a Directed Acyclic Graph (DAG). The alpha (α) test level of all statistical tests was 0.05.

RESULTS: 1007 participants were investigated, including 559 HHCs of PTB index cases from CHT settings and 448 HHCs of PTB index cases from non-CHT sites (treated at home). Of the two groups, 46 HHCs tested positive for PTB/LTBI (latent TB infections), with a 3.4% positive detection rate (19 cases) in the HHCs of PTB index cases treated with CHT and 6.0% (27 cases) in the HHCs of those treated with non-CHT, with positive detection of LTBI [17(3.0%) vs. 26(5.8%)] and [3(0.5%) vs. 5(1.1%)] of PTB in the former than that in the latter. A statistically significant difference was found between the two LTBI groups. In the univariate analysis, family caregivers, age, marital status, CHT, eating the same food with the patient, sleeping in the same room with the patient, and caring for the patient for more than or equal to 2 months were risk factors for PTB/LTBI among HHCs. The treatment of PTB families with non-CHT was an independent factor of PTB/LTBI in the HHCs through multivariate analysis and AIC evaluation.

CONCLUSIONS: The transmission of PTB/LTBI to HHCs is lower in the HHCs of CHT patients than in the HHCs of those treated with non-CHT after controlling for the other factors including older age, abnormal marriage, and staying with PTB patients equal to or more than two months.

PMID:40608256 | DOI:10.1007/s10096-025-05170-0

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Nevin Manimala Statistics

ΔBSIJ: a quantitative marker for early detection of medication-related osteonecrosis of the jaw in patients with prostate cancer receiving bone-modifying agents

Ann Nucl Med. 2025 Jul 3. doi: 10.1007/s12149-025-02078-9. Online ahead of print.

ABSTRACT

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bone-modifying agent (BMA) therapy in patients with prostate cancer and bone metastasis. This study aimed to assess the effectiveness of the temporal changes in jaw-specific bone scan index (ΔBSIJ) as quantitative markers for early prediction of MRONJ in patients with prostate cancer receiving BMA therapy.

METHODS: This retrospective study included 33 patients with prostate cancer with bone metastases who underwent bone scintigraphy before and after BMA initiation. BSIJ was measured using BONENAVI software, and the difference between pre- and post-BMA BSIJ values was considered ΔBSIJ. Statistical analyses, including paired t-test, receiver operating characteristic (ROC) curve analysis, and Kaplan-Meier survival estimate, were employed to assess the predictive value of ΔBSIJ for MRONJ.

RESULTS: Of the 33 patients, 10 developed MRONJ during a median follow-up period of 29 months. ΔBSIJ was significantly higher in the MRONJ group than in the non-MRONJ group (0.05 vs. – 0.04, p = 0.002). ROC analysis revealed the highest area under the curve (AUC = 0.823) for ΔBSIJ compared with the pre- and post-BMA BSIJ values. A ΔBSIJ cutoff of 0.039 predicted MRONJ with 60% sensitivity and 91% specificity. Patients with ΔBSIJ ≥ 0.039 exhibited significantly shorter MRONJ-free survival than those with ΔBSIJ < 0.039 (median: 18.4 months vs. not reached, p < 0.001).

CONCLUSION: ΔBSIJ is a novel and clinically useful quantitative marker for the early detection of MRONJ in patients with prostate cancer receiving BMA therapy. This study highlights the potential of leveraging functional imaging and temporal changes in BSIJ to improve MRONJ management.

PMID:40608250 | DOI:10.1007/s12149-025-02078-9

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Progressive Collapsing Foot Deformity: Multi-bone Modeling and Joint Level Measurements

Ann Biomed Eng. 2025 Jul 3. doi: 10.1007/s10439-025-03775-2. Online ahead of print.

ABSTRACT

PURPOSE: The objective of this study was to characterize joint level morphology and alignment differences across stages of progressive collapsing foot deformity (PCFD) within the talocrural, subtalar, talonavicular, and calcaneocuboid joints using multi-bone statistical shape modeling (SSM) and joint distance measurements from weightbearing computed tomography (WBCT) scans. This was achieved by employing multi-bone SSM in conjunction with precise joint measurement analysis, utilizing WBCT scans to investigate the intricate changes within the talocrural, subtalar, talonavicular, and calcaneocuboid joints.

METHODS: A retrospective analysis was conducted on patients with PCFD who failed conservative treatment. Two groups of 20 feet each were formed for flexible PCFD and rigid PCFD, with 27 additional feet identified as asymptomatic controls. All 67 participants underwent a WBCT scan, and 3D models were created as inputs for multi-bone SSM and joint distance measures.

RESULTS: The first principal component analysis mode contained 45.8% of the variation in the population while the second mode contained 13.3% of the variation and the third mode contained 6.4% of variation accounting for 65.6% of the overall variation in the multi-bone model. Joint space distance measurement differences were observed between all three groups for all articulations. The primary difference between flexible PCFD and rigid PCFD multi-bone SSM was a statistically significant medial shift of alignment of the talar neck, resulting in worsened peritalar subluxation.

CONCLUSION: PCFD is quantifiably variable across a clinical population when evaluating joint level measurements as well as morphologic and alignment variations. Talonavicular joint malalignment severity may be a clinical key in distinguishing between stages of PCFD.

PMID:40608241 | DOI:10.1007/s10439-025-03775-2

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The Effect of Opioid Agonist Treatment on Injection-Related Sequelae: A Population-Based Observational Study

Drug Saf. 2025 Jul 3. doi: 10.1007/s40264-025-01574-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Opioid agonist treatment (OAT) reduces drug-related poisonings and injection-related infections among people with opioid use disorder (OUD). Despite buprenorphine-naloxone (BNX) and methadone (MET) both being first-line OAT options in Canada, their comparative effectiveness in preventing recurrent injection-related infections and poisonings remains unclear.

OBJECTIVES: This study compared the effectiveness of buprenorphine-naloxone and methadone in reducing recurrent risks of injection-related bacterial infections and opioid-related poisoning among people on OAT.

METHODS: We used administrative health data from Québec, Canada to create our cohort of adult patients (aged 18-65 years) on OAT maintenance between 2014 and 2019. We applied a time-dependent Cox proportional hazards model for our time-varying exposure definition to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the recurrent risks of injection-related bacterial infections and opioid-related poisoning, adjusting for age, sex, socio-demographic, and clinical factors. We also compared the effectiveness of buprenorphine-naloxone and methadone during the OAT induction phase (i.e., first 30 days of treatment).

RESULTS: The study population included 2010 patients (mean age: 41.21 years, 67.41% male). Compared to methadone, buprenorphine-naloxone was associated with 45% lower recurrent risk of opioid-related poisoning (HR: 0.55; 95% CI 0.35-0.86). Overall, the association between buprenorphine-naloxone and recurrent risk of injection-related bacterial infections suggested a weak protective effect (HR: 0.80; 95% CI 0.59-1.09). During the induction phase, there was limited evidence of differences between buprenorphine-naloxone and methadone for the recurrent risks of injection-related bacterial infections (HR: 0.91; 95% CI 0.51-1.60) and opioid-related poisoning (HR: 1.07; 95% CI 0.51-2.24).

CONCLUSION: Among patients in OAT maintenance, buprenorphine-naloxone was associated with lower risk of recurrent opioid-related poisoning compared to methadone, but not for injection-related infections. This advantage was not observed during induction, suggesting the need for improved treatment retention early in OAT.

PMID:40608239 | DOI:10.1007/s40264-025-01574-1

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Psychometric testing of two respiratory bolt-on items to EQ-5D-5L in patients with obstructive airway diseases

Qual Life Res. 2025 Jul 3. doi: 10.1007/s11136-025-04016-8. Online ahead of print.

ABSTRACT

OBJECTIVES: Two recently developed respiratory bolt-ons were shown to improve the construct validity of EQ-5D-5L among community-treated patients with obstructive airway disease (OAD). We evaluated their psychometric properties, including responsiveness and reliability in a specialist-managed OAD cohort.

METHODS: We performed in-depth interviews with ten OAD patients and ten clinicians to assess their content validity. We administered the Saint George’s Respiratory Questionnaire (SGRQ), EQ-5D-5L and two respiratory bolt-on items, (physical impediment, R1 & symptoms, R2) in adult OAD patients at baseline and follow-up visits. We used the baseline data to compare among four EQ-5D versions, EQ-5D-5L, + R1, + R2 & + R1R2: (1) ceiling using individual item responses; and (2) Spearman’s rho correlations (Rs) with SGRQ, (3) association with clinical characteristics using C-statistics from receiver operating characteristic (ROC) analyses, and (4) coefficient of determination from regression modelling using index/level sum scores. We used the follow-up data to compare intra-class correlation coefficients (ICCs)/Cohen’s Kappas (κ) of “stable” patients; and standardized effect sizes/C-statistics of “better” patients using SGRQ and clinical criteria, across the four versions.

RESULTS: Psychometric properties of the respiratory bolt-ons proved to be acceptable. We included 184 patients with a mean age of 54 (standard deviation, 18) years at baseline, and 120 at follow-up at 2.8 (standard deviation, 1.7) months. The ceilings were nullified in + R1, + R2 and + R1R2. Construct validity and responsiveness were consistently higher in + R2 and + R1R2 compared to EQ-5D-5L, while reliability remained comparable among the four versions.

CONCLUSIONS: Respiratory bolt-ons demonstrated good content validity and enhanced the psychometric properties of EQ-5D-5L in OAD.

PMID:40608236 | DOI:10.1007/s11136-025-04016-8

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Using Social Media to Combat Influenza Vaccine Misinformation and Improve Uptake: A Social Media Campaign and Repeated Cross-sectional Survey Analysis

Mayo Clin Proc Digit Health. 2025 May 23;3(3):100229. doi: 10.1016/j.mcpdig.2025.100229. eCollection 2025 Sep.

ABSTRACT

OBJECTIVE: To combat influenza (flu)-vaccine misinformation and improve vaccine uptake using social media.

PATIENTS AND METHODS: Unbiased Science used an online survey to identify flu vaccine-hesitant demographic groups and their specific objections to vaccination. Targeted educational content was then created and deployed through a variety of media formats, including podcasts, newsletters, reels, and infographics. A postcampaign survey determined the proportion of individuals who changed their minds about vaccination as a result of the educational content. The study was conducted between October 28, 2022 and February 7, 2023.

RESULTS: In 3626 precampaign surveys, 187 individuals (5.1%) reported being unvaccinated and not planning to get the flu vaccine (the unvaccinated group). Multivariable analysis showed that geographic region (Northeast and Southeast), gender identity (male and other), race-ethnicity (non-Hispanic Black, and non-Hispanic other), and education level (high-school or less and some college) were independently associated with being unvaccinated. The main reasons were needlephobia, dismissal of flu severity, and concerns about vaccine components, multiple vaccines, and side effects. In 838 postcampaign surveys, 39 individuals (4.7%) indicated changing their mind about vaccination: of these, 27 (69.2%) said they were more likely to get vaccinated and 22 (56.4%) had gotten vaccinated. Twenty individuals (51.3%) said they changed their mind at least in part because of the targeted educational content.

CONCLUSION: Social media has the potential to change attitudes and behaviors around vaccination. When science messaging is deployed across several platforms and targeted to key demographic characteristics, it has the ability to combat misinformation and influence vaccine uptake.

PMID:40607109 | PMC:PMC12213263 | DOI:10.1016/j.mcpdig.2025.100229

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Nevin Manimala Statistics

Development of Powerly, unguided mobile app intervention preventing postpartum depression and anxiety & study protocol of randomized clinical trial

Internet Interv. 2025 Jun 16;41:100843. doi: 10.1016/j.invent.2025.100843. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: Up to 30 % of pregnant individuals experience high levels of stress. At the same time, 15-20 % of new mothers develop postpartum depression, and 25-35 % experience postpartum anxiety. Mobile applications have the potential to provide an accessible, scalable solution to these mental health challenges. However, previous evidence indicates that none of the commercially available apps for perinatal depression and anxiety have been rigorously evaluated through randomized clinical trials (RCTs), and the quality of these apps remains moderate. In response to this gap, we aim to develop and empirically evaluate Powerly, a mobile app intervention designed to prevent postpartum depression and anxiety.

METHODS: We will conduct a two-arm RCT with 140 healthy pregnant participants to assess the impact of Powerly use compared to care as usual (CAU). Powerly is based on cognitive behavioral therapy techniques and developed in consultation with stakeholders, including healthcare professionals and pregnant individuals. It will offer personalized psychological support tailored to users’ needs for four weeks. Self-reported mental health assessments will be collected at baseline, after four weeks of app use, and six weeks postpartum.

DISCUSSION: We anticipate that participants using Powerly will demonstrate significant improvements in mental health outcomes, including reduced rates of postpartum depression, compared to the CAU group. Additionally, we expect positive changes in emotion regulation, resilience, and mother and child outcomes, such as enhanced maternal bonding and a more positive birth experience. If proved effective, Powerly can offer a scalable, publicly accessible solution for pregnant individuals in need.

TRIAL REGISTRATION: NCT06610552.

PMID:40607107 | PMC:PMC12213272 | DOI:10.1016/j.invent.2025.100843

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Morula complementation restores male germline in NANOS2 null sheep

PNAS Nexus. 2025 Jun 14;4(7):pgaf200. doi: 10.1093/pnasnexus/pgaf200. eCollection 2025 Jul.

ABSTRACT

Current livestock breeding is slow to respond to rapidly mounting environmental pressures that threaten sustainable animal protein production. New approaches can accelerate genetic improvement by multiplying valuable embryonic, rather than adult genotypes. Chimeras, derived from complementing a sterile host with a fertile donor embryo, provide a pathway to multiply and exclusively transmit elite male germlines. We established genetically sterile hosts and optimized embryo complementation conditions to achieve absolute germline transmission in sheep. The spermatogonia-specific gene NANOS2 was disrupted in male (NANOS2+/- , NANOS2-/- ) and female (NANOS2-/- ) ovine fetal fibroblasts via gRNA-Cas9-mediated homology-directed repair. Targeted cell strains and wild-type controls were used to produce cloned offspring for breeding and phenotyping. Male homozygous knockout clones lacked detectable germ cells, while the somatic compartment of the testis remained intact. By contrast, male monoallelic and female biallelic targeting of NANOS2 did not affect germline development, resulting in fertile animals capable of producing fertile offspring with normal reproductive performance. The germ cell niche in NANOS2-/- hosts was most efficiently complemented by aggregating compacted morulae, rather than earlier cleavage stages, resulting in 97% blastocyst chimerization. Embryo-complemented cloned lambs from two different donor cell lines showed variable chimerism across tissues from each germ layer, including various degrees of germline colonization. A subset of germline chimeras contained normal numbers of prospermatogonia, indicating that the germline was fully restored for absolute transmission of the donor cell genotype.

PMID:40607105 | PMC:PMC12218192 | DOI:10.1093/pnasnexus/pgaf200

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Frequency of Fals and Degree of Diability in Stroke Patients

Mater Sociomed. 2025;37(2):164-168. doi: 10.5455/msm.2025.37.164-168.

ABSTRACT

BACKGROUND: Stroke patients have significant disability and an increased risk of falling.

OBJECTIVE: To determine the incidence of falls and the degree of disability in stroke patients and to determine the correlation of falls with the degree of disability.

METHODS: This is a prospective study of 100 stroke patients confirmed by computed tomography and magnetic resonance imaging of the brain. We used a demographic questionnaire together with the Glasgow Coma Scale, Stroke Assessment Scale, Rankin Scale and Morse Scale to collect data and analyzed them using SPSS 17, including statistical measures, including Pearson correlation.

RESULTS: Hemorrhagic stroke patients had a higher incidence of falls (p = 0.06). There was no difference in the incidence of falls according to the gender of the patients (p = 0.07). Older people had a higher frequency of falls, and women and patients with hemorrhagic stroke had a higher risk of falling (p = 0.2). Patients with a stroke in the area of the anterior circulation were statistically significantly more disabled (p < 0.05). A weak positive correlation was calculated between the frequency of falls of patients after stroke and the degree of disability (r = 0.08, n = 94, p = 0.4). Stroke patients who also had atrial fibrillation as a comorbidity had a statistically significantly higher frequency of falls compared to patients with other comorbidities (p = 0.02).

CONCLUSION: Patients with hemorrhagic stroke have a higher frequency of falls. Women, elderly people, patients with a stroke in the area of the anterior circulation and with atrial fibrillation as a comorbidity are statistically significantly more disabled after a stroke. There is a positive correlation between the frequency of falls in patients after a stroke and the degree of disability.

PMID:40607099 | PMC:PMC12212237 | DOI:10.5455/msm.2025.37.164-168