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Nevin Manimala Statistics

Biomarker identification for Alzheimer’s disease through integration of comprehensive Mendelian randomization and proteomics data

J Transl Med. 2025 Mar 6;23(1):278. doi: 10.1186/s12967-025-06317-5.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) is the main cause of dementia with few effective therapies. We aimed to identify potential plasma biomarkers or drug targets for AD by investigating the causal association between plasma proteins and AD by integrating comprehensive Mendelian randomization (MR) and multi-omics data.

METHODS: Using two-sample MR, cis protein quantitative trait loci (cis-pQTLs) for 1,916 plasma proteins were used as an exposure to infer their causal effect on AD liability in individuals of European ancestry, with two large-scale AD genome-wide association study (GWAS) datasets as the outcome for discovery and replication. Significant causal relationships were validated by sensitivity analyses, reverse MR analysis, and Bayesian colocalization analysis. Additionally, we investigated the causal associations at the transcriptional level with cis gene expression quantitative trait loci (cis-eQTLs) data across brain tissues and blood in European ancestry populations, as well as causal plasma proteins in African ancestry populations.

RESULTS: In those of European ancestry, the genetically predicted levels of five plasma proteins (BLNK, CD2AP, GRN, PILRA, and PILRB) were causally associated with AD. Among these five proteins, GRN was protective against AD, while the rest were risk factors. Consistent causal effects were found in the brain for cis-eQTLs of GRN, BLNK, and CD2AP, while the same was true for PILRA in the blood. None of the plasma proteins were significantly associated with AD in persons of African ancestry.

CONCLUSIONS: Comprehensive MR analyses with multi-omics data identified five plasma proteins that had causal effects on AD, highlighting potential biomarkers or drug targets for better diagnosis and treatment for AD.

PMID:40050982 | DOI:10.1186/s12967-025-06317-5

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Impact of gastrointestinal and psychological symptoms on disease activity and functional impairment in patients with spondyloarthritis: a cross-sectional study

BMC Rheumatol. 2025 Mar 6;9(1):28. doi: 10.1186/s41927-025-00478-y.

ABSTRACT

INTRODUCTION: Spondyloarthritis (SpA) exhibits predominantly musculoskeletal symptoms but also significant gastrointestinal (GI) and psychological manifestations. Subclinical gut inflammation is common in SpA, with frequent symptoms such as abdominal pain and diarrhea. Psychological issues like depression and anxiety are also prevalent, with a negative impact on quality of life. This study aimed to evaluate the presence of GI and psychiatric symptoms in SpA patients without inflammatory bowel disease (IBD) and their association with disease characteristics.

METHODS: Cross-sectional study, which included SpA patients from two rheumatology outpatient clinics. Patients were assessed for GI, and depressive symptoms (PHQ-9), perceived stress (PSS-10), disease activity (ASDAS, BASDAI) and functionality (BASFI). Laboratory tests included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and Secretory IgA. Statistical analysis involved Spearman correlation, linear regression, and multiple correspondence discriminant analysis (MCDA).

RESULTS: Among 98 SpA patients, 79.6% had axial SpA. High disease activity and functional impairment were common. 65.3% reported ≥ 2 GI symptoms, predominantly abdominal pain and diarrhea. Depression (PHQ-9 ≥ 10) was observed in 46.7% of patients, being moderate to severe in 25.0%. Depression, perceived helplessness, and lack of self-efficacy were associated with high disease activity and GI symptoms. MCDA identified strong correlations between depression, GI symptoms, and disease activity.

CONCLUSION: This study highlights the association between GI and psychological symptoms with disease activity and functionality in SpA patients. Depression and perceived helplessness are prevalent and closely associated with high disease activity and GI symptoms, suggesting the need for interdisciplinary management from early stages to improve patient outcomes.

PMID:40050979 | DOI:10.1186/s41927-025-00478-y

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Effect of group-based nutritional education combined with individual standard care for outpatients with type 2 diabetes: study protocol for a randomized clinical trial {1}

Trials. 2025 Mar 6;26(1):78. doi: 10.1186/s13063-025-08720-1.

ABSTRACT

BACKGROUND: Diabetes remains a significant contributor to global morbidity and mortality in the twenty-first century. Lifestyle modification strategies are widely recommended for effective diabetes management. Research suggests that a person-centered approach, implemented in either group or individual settings, offers considerable potential for improving long-term disease outcomes. Nutritional counseling using the operative group model has been tested and shown to yield positive health outcomes across diverse populations affected by diabetes. This study aims to evaluate the impact of group-based nutritional education, combined with individual standard care, compared to individual standard care alone, on health outcomes among patients diagnosed with type 2 diabetes.

METHODS: This study is a 12-month, parallel-group, randomized superiority controlled trial. Individuals diagnosed with type 2 diabetes will be randomized in a 1:1 ratio into one of two treatment arms: (1) individual usual care alone or (2) usual care supplemented with group-based nutritional education. The group nutritional education will consist of three sessions addressing the following themes: “Let’s Go Shopping,” “Healthy Plate,” and “Hunger and Satiety.” The primary outcome will be the change in HbA1c levels. Secondary outcomes will include fasting glucose, lipid profile, body mass, dinapenic abdominal obesity, blood pressure, eating behavior, adherence to nutritional counseling, and diabetes-related complications. All outcomes will be assessed at baseline and at 4, 8, and 12 months, except diabetes-related complications that will be assessed at baseline and 12 months. Sample size calculations were based on an estimated mean difference of 0.59 ± 1.39% in HbA1c with the intervention (patient-centered group), using a type I error rate of 5% and a type II error rate of 20%. It was determined that 88 participants per group (1:1 randomization; n = 176) would provide sufficient statistical power. Accounting for an anticipated dropout rate of 30%, a total of 252 participants will be recruited to ensure the necessary sample size is maintained throughout the study period.

DISCUSSION: The American Diabetes Association recommends interventions for patients with diabetes lasting more than 10 h over a period of 6 to 12 months to optimize health outcomes. Therefore, this study hypothesizes that integrating group-based nutritional education into standard treatment within a nutrition-specialized outpatient clinic may lead to further improvements in health parameters among individuals diagnosed with type 2 diabetes mellitus. TRIAL REGISTRATION {2A AND 2B}: Clinicaltrials.gov identifier, NCT05598203. Registered on 13 October 2022.

PMID:40050966 | DOI:10.1186/s13063-025-08720-1

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Anatomical variability, morphofunctional characteristics, and clinical relevance of accessory ossicles of the back: implications for spinal pathophysiology and differential diagnosis

J Orthop Surg Res. 2025 Mar 6;20(1):240. doi: 10.1186/s13018-024-05407-2.

ABSTRACT

PURPOSE: This study explored the anatomical variations and clinical implications of accessory ossicles in the spine, which are often identified incidentally but can significantly impact the differential diagnosis of spinal disorders.

METHODS: A comprehensive review of the literature from MEDLINE, the Cochrane Library, ScienceDirect, and Google Scholar up to April 2024 was conducted. Statistical analyses emphasized distinct patterns in prevalence, location, and correlation with symptoms, reinforcing the importance of accurate identification and appropriate patient management.

RESULTS: Limbus Vertebra (LV) was observed in 2.5% of the cases, predominantly in the lumbar spine (70%). Ossicles of the nuchal ligament were identified in approximately 5.6% of cases, with a higher prevalence in males than in females.Correlation analysis indicated a weak positive correlation between LV and symptom severity (r = 0.25, p = 0.05) and a strong positive correlation between the ossicles of the nuchal ligament and male predominance (r = 0.75, p < 0.01). Additional accessory ossicles, including Oppenheimer’s ossicles, accessory ossicles of the atlas, persistent ossiculum terminale, and os odontoideum, exhibited lower prevalence rates (< 2%), emphasizing their infrequency.

CONCLUSIONS: Accessory ossicles of the spine exhibit varied prevalence and clinical significance, with some presenting minor associations with symptoms and others linked to specific syndromes or spinal disorders. The prevalence of different ossicles shows notable heterogeneity, highlighting the need for careful differential diagnosis to prevent the misinterpretation of fractures or other spinal pathologies.

PMID:40050963 | DOI:10.1186/s13018-024-05407-2

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Investigation of exercise-related leg pain, fear of pain, kinesiophobia, and injury anxiety in athletes

BMC Sports Sci Med Rehabil. 2025 Mar 6;17(1):40. doi: 10.1186/s13102-025-01079-5.

ABSTRACT

BACKGROUND: This study aimed to investigate the relationship between exercise-induced leg pain, fear of pain, kinesiophobia and injury anxiety in amateur and professional athletes. Secondarily, the present study also aimed to investigate the relationship between women or men athletes and individual or team sports.

METHODS: A cross-sectional study was conducted with a total of 304 athletes. Participants were categorized as amateur and professional athletes, male and female athletes, individual and team athletes. Participants were evaluated with Exercise Induced Leg Pain Questionnaire (EILP), Fear of Pain Questionnaire (FOPQ), Sports Injury Anxiety Scale (SIAS), and Tampa Scale of Kinesiophobia (TSK). Parametric tests were used for statistical analysis. A statistical significance level of 0.05 was chosen.

RESULTS: Fear of pain and anxiety about sports injury were significantly less in men (p < 0.05). Loss of social support for sports injury anxiety was less in women (p < 0.05). Anxiety about sports re-injury was less in professional athletes (p < 0.05). Anxiety about letting down important Others and loss of social support were greater in team sports (p < 0.05). Besides, there was a positive, moderate, and significant correlation between the Fear of Pain Questionnaire- III Total and Tampa scale for kinesiophobia (r = 0.411, p < 0.01). Finally, a positive, moderate and significant correlation was found between Sport Injury Anxiety Scale Total and Tampa scale for kinesiophobia (r = 0.579, p < 0.01).

CONCLUSION: Exercise and movement were associated with psychological parameters related to injury and pain in athletes. Female athletes were found to have more injury anxiety and fear of pain. In addition, amateur athletes have more injury anxiety. Besides, injury anxiety was found to be higher in individuals in team sports. Future studies may further investigate these groups who are more disadvantaged in terms of anxiety, fear of pain and kinesiophobia. In addition, clinicians should pay attention to the criteria for a biopsychosocial approach by choosing appropriate descriptive phrases to avoid exacerbating athletes’ anxiety.

PMID:40050954 | DOI:10.1186/s13102-025-01079-5

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Nutritional, functional, and microbial qualities of legume-based flour blends processed by SMEs in Zambia and Malawi compared to standard Corn-Soy Blend Plus (CSB +): a cross-sectional study

BMC Nutr. 2025 Mar 6;11(1):49. doi: 10.1186/s40795-025-01034-0.

ABSTRACT

BACKGROUND: Legumes enhance food security in developing countries, necessitating an understanding of their properties. This study examined the nutritional, functional, and microbial qualities of legume-based flour blends from Small and Medium Enterprises (SMEs) in Malawi and Zambia. SMEs were chosen for their key role in local food production, distribution, and complementary food supply.

METHOD: A total of 36 legume-based flour blend samples were collected using snowball sampling, consisting of 21 samples (7 sets of 3 similar samples) from SMEs in Zambia and 15 samples (5 sets of 3 similar samples) from SMEs in Malawi. Samples were analyzed for proximate composition, energy, iron, and zinc content. The nutritional contributions to the Recommended Dietary Allowances (RDA) for children aged 1-3 years were assessed. Additionally, functional properties such as water-holding and oil-holding capacities were measured. Microbial analysis was performed, and the data were statistically analyzed to determine significance (p ≤ 0.05).

RESULTS: Our findings revealed substantial variability in the nutritional content of these flour blends. Protein content ranged from 9.4% to 41.5%, carbohydrates from 8.1% to 71.3%, crude fat from 2.3% to 26.8%, and crude fiber from 6.2% to 35.2%. Iron and zinc levels also varied significantly, from 2.9 to 21.9 mg/100 g and 2.2 to 5.2 mg/100 g, respectively. These inconsistencies highlight a lack of standardization in nutrient content for blends intended for infant feeding. When prepared as 96 g porridge servings for children aged 1-3 years, the blends provided notable contributions to the Recommended Dietary Allowance (RDA). However, their nutrient levels were generally lower compared to the standard Corn-Soy Blend Plus (CSB +). The flour blends also showed variations in physico-functional properties, and some had microbial loads exceeding 250 cfu/g, reflecting inadequate hygiene practices during processing.

CONCLUSION: To enhance their products, SMEs should ensure that their flour blends meet both nutritional and safety standards while striving to match or surpass the nutrient content of CSB + to remain competitive in the market.

PMID:40050953 | DOI:10.1186/s40795-025-01034-0

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Efficacy of two doses of intra-articular ozone therapy for pain and functional mobility in knee osteoarthritis: a double-blind randomized trial

Adv Rheumatol. 2025 Mar 6;65(1):11. doi: 10.1186/s42358-025-00443-w.

ABSTRACT

AIM: This double-blind, trial sought to assess the effectiveness of intra-articular ozone therapy at concentrations of 20 µg/mL and 40 µg/mL in managing pain and enhancing functional mobility in patients with knee osteoarthritis (KOA).

METHOD: This parallel, three-arm randomized controlled trial, conducted between 2022 and 2023, included 59 knee osteoarthritis (KOA) patients randomly allocated to one of three groups: the first group received 40 µg/mL ozone therapy, the second group received 20 µg/mL ozone therapy, and the control group received oxygen. Functional mobility was assessed through the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee flexion range of motion (FROM), the Timed Up and Go (TUG) test, and the six-minute walk test (6MWT). Pain intensity was measured using the Visual Analog Scale (VAS) and the pain subscale of the WOMAC. Intra-articular injections were administered weekly for four consecutive weeks, with assessments conducted pre-treatment, and at two weeks, one month, and two months post-intervention. One-way ANOVA was employed for normally distributed quantitative data, while the Kruskal-Wallis test was utilized for non-normally distributed data. Qualitative variables were analyzed using the Chi-squared or Fisher’s exact test, as appropriate.

RESULTS: The groups receiving intra-articular ozone therapy exhibited notable reductions in mean VAS scores and improvement in functional mobility variables when compared to the control group (p < 0.05). However, post-hoc analysis indicated no statistically significant differences between the 40 µg/mL and 20 µg/mL ozone therapy groups regarding these parameters (VAS, FROM, TUG, 6MWT, or WOMAC scores) (p > 0.05).

CONCLUSION: Both 20 µg/mL and 40 µg/mL doses of intra-articular ozone therapy prove to be effective in reducing pain and enhancing functional mobility in patients with knee osteoarthritis (KOA). Nevertheless, there was no significant difference in the efficacy between the two ozone concentrations.

TRIAL REGISTRATION: The trial is registered on us ClinicalTrials.gov in 2024-05-01 with the following ID code NCT06088706.

PMID:40050950 | DOI:10.1186/s42358-025-00443-w

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Physical activity and lung cancer screening (PALS): feasibility randomised controlled trial of exercise and physical activity in lung cancer screening

Respir Res. 2025 Mar 6;26(1):89. doi: 10.1186/s12931-025-03158-0.

ABSTRACT

BACKGROUND: There is increasing evidence that screening provides a catalyst for behavioural change. Low physical activity (PA) levels are a potentially modifiable risk factor for developing lung cancer. This study aims to assess the feasibility and safety of a semi-supervised 8-week multi-modal exercise program to improve health-related quality of life and PA levels of participants of lung cancer screening.

METHODS: Participants without lung cancer from a single Australian International Lung Screen Trial (ILST; NCT02871856) site were invited to this feasibility randomised controlled trial. Enrolled participants were randomised to usual care, written material, or a home-based exercise program (in addition to written material). Assessments occurred at baseline, 9 weeks, and 6 months.

RESULTS: 75 participants were enrolled over a 3-month period in 2022 (consent rate of 67%). 43% of participants were female, median age 66 years old (IQR 62, 73). Of the 25 participants randomised to the home-based exercise program, 22 participants (88%) attended > 70% of weekly sessions. 99% (74/75) of study participants attended their 9-week and 6-month follow-up assessments.

CONCLUSIONS: This study confirms the feasibility and high compliance of delivering a semi-supervised 8-week multi-modal exercise program to participants of a lung cancer screening program. It was safe, with no adverse events.

CLINICAL TRIAL REGISTRATION: Australian Clinical Trials Register https://www.australianclinicaltrials.gov.au ACTRN12622001001785.

PMID:40050941 | DOI:10.1186/s12931-025-03158-0

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Effects of semaglutide in patients with chronic ankle instability: evidence from a prospective cohort

J Orthop Surg Res. 2025 Mar 6;20(1):243. doi: 10.1186/s13018-025-05664-9.

ABSTRACT

BACKGROUND: Whether patients with chronic ankle instability (CAI) can benefit from weight loss yielded by using glucagon-like peptide-1 receptor agonists (GLP1-RAs) has remained unclear.

METHODS: In this observational study, we recruited more than 2000 adults with CAI according to the selection criteria proposed by International Ankle Consortium with at least two-year follow up from three medical centers. The primary endpoint was the change from baseline of the Foot and Ankle Ability Measure (FAAM) sports subscale at the last follow up. Secondary endpoints included the change from baseline of Foot and Ankle Outcome Score (FAOS)/ Cumberland Ankle Instability Tool (CAIT)/ FAAM activities of daily living (ADL) subscale, number of ankle sprains during study period, incident ankle surgery in treatment of CAI.

RESULTS: In this study, 71 out of 2018 patients who received semaglutide in purpose of treating type 2 diabetes (T2DM) and/or weight loss during the study period. After controlling baseline characteristics, the adjusted mean difference in change from baseline was 16.3 for FAAM sports subscale and 9.3 for FAAM ADL subscale. Likewise, the adjusted analysis of five subscales of FAOS showed similar results, all consistently favoring semaglutide group. For CAIT, patients in the semaglutide group had achieved statistically significant improvement compared with control group. The association of semaglutide exposure with improvement in FAAM sports and ADL subscales was mediated by the weight loss measured by BMI (mediation proportion: FAAM sports subscale, 31.2% [22.2-41.2%]; FHSQ ADL subscale, 34.1% [24.4-44.8%]). We also observed statistically significant decreases in number of recurrent ankle sprains during study period. For incident ankle surgery, 1 out of 71 patients (1.4%) and 151 out of 1947 patients (7.8%) received ankle surgeries in semaglutide and control groups, respectively (P = 0.047).

CONCLUSIONS: Semaglutide may show potential benefits as a supplementary intervention in treatment of CAI by improving patient-reported outcomes and preventing recurrent ankle sprains. Further randomized trial is warranted by the current study to further confirm our findings.

TRIAL REGISTRATION: researchregistry10716.

PMID:40050929 | DOI:10.1186/s13018-025-05664-9

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Hesitancy towards COVID-19 booster vaccine among healthcare workers in Bangladesh

BMC Health Serv Res. 2025 Mar 6;25(1):346. doi: 10.1186/s12913-025-12482-6.

ABSTRACT

BACKGROUND: Despite completing the COVID-19 vaccination series, healthcare workers (HCWs) remain at an elevated risk of re-infection. Booster uptake, though essential for this group, remains poorly characterized among Bangladeshi HCWs. This study identified the prevalence and driving factors behind booster hesitancy among Bangladeshi HCWs, providing valuable insights for targeted interventions.

METHOD: From December 2022 to June 2023, we conducted a cross-sectional survey among 1772 HCWs enrolled from 20 healthcare facilities of all tiers purposively selected across four administrative divisions of Bangladesh. We collected information through face-to-face interviews regarding their sociodemographic, pre-existing, and currently existing medical conditions, COVID-19 vaccination status, and their intention, hesitancy, and willingness to receive future booster doses. We used a multivariable logistic regression model to analyze factors associated with booster hesitancy. Odd’s ratio with 95% confidence intervals (CIs) was calculated for each factor, with p < 0.05 considered statistically significant.

RESULT: Of the 1772 HCWs interviewed in our study, 49% (879) were nurses [median age 36 years (IQR: 30.0-46.0)]; 69% were female. Among the respondents, 94% (1667) were willing to take a booster, and 6% (105) showed hesitancy. Safety concerns, especially regarding potential side effects post-booster administration (86%), emerged as the leading cause of booster hesitancy among healthcare workers. Our multivariable logistic regression analysis revealed that support staff, compared to physicians, were the most hesitant to receive any additional booster dose (aOR 4.68, 95% CI: 1.56-9.03; p=0.006). Compared to rural residency, HCWs with an urban residency type were also more reluctant to receive booster doses (aOR 4.45, 95% CI: 2.03-9.73; p < 0.001).

CONCLUSION: Concerns about side effects following booster administration were the primary driver of hesitancy in our study. Targeted interventions focusing on education and addressing these anxieties-supported by evidence-based communication strategies-could play a crucial role in improving booster acceptance and safeguarding this vulnerable workforce.

PMID:40050921 | DOI:10.1186/s12913-025-12482-6