Category: Statistics

Bioinformatics. 2025 Jan 12:btaf017. doi: 10.1093/bioinformatics/btaf017. Online ahead of print.

ABSTRACT

MOTIVATION: Fine-mapping aims to prioritize causal variants underlying complex traits by accounting for the linkage disequilibrium of GWAS risk locus. The expanding resources of functional annotations serve as auxiliary evidence to improve the power of fine-mapping. However, existing fine-mapping methods tend to generate many false positive results when integrating a large number of annotations.

RESULTS: In this study, we propose a unified method to integrate high-dimensional functional annotations with fine-mapping (Funmap). Funmap can effectively improve the power of fine-mapping by borrowing information from hundreds of functional annotations. Meanwhile, it relates the annotation to the causal probability with a random effects model that avoids the over-fitting issue, thereby producing a well-controlled false positive rate. Paired with a fast algorithm, Funmap enables scalable integration of a large number of annotations to facilitate prioritizing multiple causal SNPs. Our comprehensive simulations across a wide range of annotation relevance settings demonstrate that Funmap is the only method that produces well-calibrated FDR under the setting of high-dimensional annotations while achieving better or comparable power gains as compared to existing methods. By integrating GWASs of 4 lipid traits with 187 functional annotations, Funmap consistently identified more variants that can be replicated in an independent cohort, achieving 15.5%-26.2% improvement over the runner-up in terms of replication rate.

AVAILABILITY: The Funmap software and all analysis code are available at https://github.com/LeeHITsz/Funmap.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39799513 | DOI:10.1093/bioinformatics/btaf017

Rheumatology (Oxford). 2025 Jan 12:keaf014. doi: 10.1093/rheumatology/keaf014. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the clinical profile and compare the long-term outcomes of patients with S-PAN treated with various treatment regimens at our centre in the last 2 decades.

METHODS: Data regarding clinical presentation, treatment allocation, relapses and outcomes of patients fulfilling American College of Rheumatology (ACR) 1990 criteria for PAN in the last 2 decades were recorded from electronic medical records. Relapse-free survival and predictors were analysed using KM survival statistics and regression analysis.

RESULTS: Altogether, 53 patients including 2 with hepatitis B infection were included. Cutaneous lesions and peripheral neuropathy were the commonest manifestations. Most patients (64.2%) presented with a five-factor score (FFS) of 0. Disease-attributable hypertension and peripheral gangrene were the most common manifestations of severe disease. During a median follow-up period of 53.5 months in 49 patients, 43 (87.8%) attained complete response while 3(6.1%) had a partial response. Nineteen (40.4%) patients relapsed at a median duration of 82 (IQR 36.3-127.7) months. The relapse-free survival in patients who received induction with mycophenolate (n = 26), was comparable to that with cyclophosphamide (n = 21) [adjusted HR : 0.68]. Smoking history was an independent predictor of relapse (HR = 6.28, p= 0.013) while age was protective (HR = 0.94, p= 0.015). FFS and BVAS at 3 months were among the predictors of mortality (total deaths = 5).

CONCLUSION: In our cohort of S-PAN, relapses were observed in 40.4% of patients. Mycophenolate was similar to cyclophosphamide in maintaining relapse-free survival. Only 10% fatality was recorded. FFS and BVAS at 3 months were predictors of mortality.

PMID:39799509 | DOI:10.1093/rheumatology/keaf014

QJM. 2025 Jan 12:hcaf008. doi: 10.1093/qjmed/hcaf008. Online ahead of print.

ABSTRACT

BACKGROUND: Falls are frequently reported within the HSE. The Irish Longitudinal Study on Ageing(TILDA) found that 40% of over 50 s experience a fall in a two year period, with 20% requiring hospital attendance (1). It has been estimated that the cost of injuries related to falls in older people will increase exponentially over the coming years (2). There is no national database in Ireland with statistics for nursing home(NH) residents presenting with falls to our Emergency Departments(ED).

AIM: To review the prevalence and risk factors for nursing home patients presenting to the Emergency Department with falls.

DESIGN: Retrospective chart review.

METHOD: Retrospective review of all NH presentations to the ED of a university hospital over one year.

RESULTS: There were 519 ED presentations by NH residents over one year. 48.17% (n = 250), presented with a fall. One third of ED visits presented during conventional working hours. Falls patients were more likely to be admitted when not reviewed by a G.P. prior to presentation. The average length of stay for falls admissions was 10.77 days(n = 132), vs 9.56(n = 153) for admissions with no documented fall. There was no statistical difference in the falls risk medications between groups. Patients presenting with falls were more likely to have bone protection reviewed during their stay(P=.011). Patients with falls were also more likely to use mobility aids(P < 0.001).

CONCLUSION: Rapid referral to falls prevention programmes and the use of standardised care pathways for high falls risk patients are essential for future prevention and management.

PMID:39799508 | DOI:10.1093/qjmed/hcaf008

Cell Mol Biol (Noisy-le-grand). 2025 Jan 12;70(12):73-80. doi: 10.14715/cmb/2024.70.12.10.

ABSTRACT

Today, methamphetamine (METH) is being used by adolescents and young adults. Our previous research demonstrated that intrauterine exposure to METH induces apoptosis in testicles and seminiferous tubes. However, based on available literature, the mechanism of this effect remains unidentified. This study aimed to investigate proteins involved in sperm growth and development pathways, such as testis-specific serine/threonine kinases (TSSK) and receptor-interacting protein kinases 2 (RIPK2), and to study the serine-threonine kinase pathway in the testes of rats whose mothers received intraperitoneal METH during pregnancy. In the present study, female rats during pregnancy received either 5 or 10 mg/kg of METH or normal saline for ten days. After reaching maturity, their testes were isolated and examined for histopathological and immunohistochemical mechanisms. Results were analyzed and reported using statistical software. Results revealed that following intrauterine exposure to METH, TSSK protein expression reduced from 52.68±2.4% in the control group to 48.04±2.29% in the 2 mg/kg/day group and 12.83±3.35% in the 5 mg/kg/day group with P=0.0029 and F=72.63. In addition, RIPK2 protein expression increased from 8.34±2.69% in the control group to 31.17±3.69% in the 2 mg/kg/day group and 98.49±4.66% in the 5 mg/kg/day group, with p=0.0037 and F=61.14. Histopathological findings indicated a reduction in the thickness of germ layers following intrauterine exposure to METH, with the seminiferous tubule’s thickness decreasing. Inflammatory cell populations increased, and the number of vessels decreased due to intrauterine exposure to METH. Our study suggests intrauterine exposure to METH increases the prevalence of inflammatory cell populations, enhances RIPK2 protein expression, reduces the number of vessels, reduces the diameter of seminiferous tubes, decreases TSSK protein expression, and reduces the thickness of germ layers in testicular tissue. Apoptosis of spermatid cells observed in our previous study may be related to the signaling pathways of TSSK and RIPK2 proteins.

PMID:39799494 | DOI:10.14715/cmb/2024.70.12.10

Cell Mol Biol (Noisy-le-grand). 2025 Jan 12;70(12):125-134. doi: 10.14715/cmb/2024.70.12.17.

ABSTRACT

Urinary tract infections (UTIs) are recognized as the second most common medical condition, following respiratory infections. Despite the availability of numerous efficacious antibiotics for the management of UTIs, the rising incidence of bacterial resistance presents significant challenges in the treatment of these infections. Bacteria are endowed with the ability to reproduce and develop resistance mechanisms against antibiotics. The current investigation aimed to evaluate the susceptibility of bacterial isolates from urinary tract infections (UTIs) to a variety of antibiotics, including ciprofloxacin, trimethoprim, amikacin, gentamicin, tetracycline, chloramphenicol, nalidixic acid, nitrofurantoin, meropenem, and novobiocin. Additionally, the study sought to quantify the levels of the inflammatory immune marker interleukin-6 (IL-6) in UTI patients. It also explored the correlation between IL-6 levels in UTI patients and healthy controls, as well as the relationship between IL-6 levels and blood parameters in both infected and healthy individuals. The present study involved the collection of 155 samples from patients diagnosed with urinary tract infections of both genders and varying age groups, ranging from 15 to 75 years, at Salah al-Din General Hospital. The findings revealed that 102 urine samples tested positive for bacterial growth, resulting in a prevalence rate of 68%. In contrast, 53 urine samples were negative for bacterial growth, reflecting a prevalence rate of 32%. The diagnostic outcomes for all isolates, following the application of laboratory diagnostic methodologies, revealed a diverse array of bacterial species, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Staphylococcus aureus, and Staphylococcus epidermidis. The immunological analysis revealed a statistically significant increase (p < 0.05) in IL-6 concentrations in the positive control group compared to the levels observed in the infected cohort. Our study concluded that significant antibiotic resistance in UTI pathogens, emphasizing the need for tailored treatments.

PMID:39799487 | DOI:10.14715/cmb/2024.70.12.17

Cell Mol Biol (Noisy-le-grand). 2025 Jan 12;70(12):135-141. doi: 10.14715/cmb/2024.70.12.18.

ABSTRACT

The rising global incidence of syphilis underscores the risk of transmission through blood transfusions. Treponema pallidum, the pathogen responsible for syphilis, represents a major public health challenge. Accurate detection is essential for controlling the disease, particularly in asymptomatic blood donors. This study aimed to evaluate the seroprevalence of specific antibodies against T. pallidum in blood donors, confirmed by DNA testing for seropositivity. The goal was to enhance our understanding of syphilis exposure and improve the safety of blood donations. A total of 1,260 HIV, HCV, and HBsAg-negative blood donors were screened for T. pallidum-specific antibodies using enzyme-linked immunosorbent assay (ELISA). Initially, reactive samples were re-evaluated, and those repeatedly reactive were classified as seropositive for syphilis. ELISA-positive samples were further tested for T. pallidum DNA using real-time polymerase chain reaction (RT-PCR). Data analysis was done using SPSS with a level of significance p< 0.05 Of 1,260 blood donors, the seroprevalence of anti-T. pallidum antibodies was 0.158%, with both positive cases confirmed by PCR. The prevalence was 0.2% in males and 0.00% in females, with no significant gender differences (P > 0.05). The highest prevalence was in the 31-40 age group (0.5%), but this was not statistically significant (P > 0.05). There were no significant differences by donation type or marital status. Significant associations were observed with educational level (P < 0.05), with higher prevalence among high school graduates Our results confirm syphilis in Iraqi blood donors, highlighting the need for routine T. pallidum ELISA screening at transfusion centers. Positive cases should be discarded and affected donors treated. ELISA is an effective primary screening method, consistent with WHO guidelines for low-prevalence settings, and is essential for preventing transfusion transmission.

PMID:39799486 | DOI:10.14715/cmb/2024.70.12.18

Cell Mol Biol (Noisy-le-grand). 2025 Jan 12;70(12):142-146. doi: 10.14715/cmb/2024.70.12.19.

ABSTRACT

Extensive research on COVID-19 has revealed a notable link between the disease and thyroid disorders, highlighting complex interactions between thyroid hormones, immunomodulatory signaling molecules within the thyroid gland, and viral infections. This study evaluated the relationship between thyroid function and COVID-19 in Iraqi patients at Adiwaniyah Teaching Hospital. The cohort for this investigation comprised all patients who were admitted to the isolation center at the Teaching Hospital during the timeframe extending from January 2024 to June 2024. Each participant included in this research underwent comprehensive evaluations of their thyroid function, which is composed of the measurement of thyroid-stimulating hormone (TSH), total triiodothyronine (T3), and serum total thyroxine (T4) levels. Results showed that the serum T4 levels in all participants included in the study were observed to range from 20 to 182 (ng/dl), with the average concentration recorded at 87.26 ± 38.29 (ng/dl); no statistically significant disparity was noted in the mean serum T4 levels relative to the severity of the disease (p = 0.291). The serum TSH levels across all enrolled individuals spanned from 0.03 to 82 (mU/L), with a mean concentration of 5.55 ± 12.36 (mU/L); similarly, there was no statistically significant difference in the mean serum TSH levels when assessed against the disease severity (p = 0.926). According to the serum thyroid hormone concentrations, the cohort was stratified into 17 (24.6%) individuals classified as hypothyroid, 34 (49.3%) categorized as euthyroid, and 18 (26.1%) identified as hyperthyroid. Furthermore, no significant correlation was identified between the disease’s severity and the participants’ thyroid status (p = 0.556). In conclusion, patients with COVID-19 are liable to develop thyroid function abnormalities that may explain several of the long-term symptoms associated with the disease.

PMID:39799485 | DOI:10.14715/cmb/2024.70.12.19

Health Econ. 2025 Jan 12. doi: 10.1002/hec.4933. Online ahead of print.

ABSTRACT

When judging the distributional impact of unhealthy food taxes, what matters is not just how much low income people would pay but how much the such taxes would benefit or harm them overall. In this paper, we assess the consumer welfare impact of a fat tax net of its expected benefits computed as savings from weight loss. Using Italian data, we estimate a censored Exact Affine Stone Index (EASI) incomplete demand system for food groups, simulating changes in purchases, calorie intake, consumer welfare, and the monetary value of short-run health benefits. While the Italian government has proposed a sugar tax, we show that there is no significant excess consumption of added sugars among Italian adults. Instead, excessive fat consumption is more prevalent, making a fat tax a more compelling and effective solution to address diet-related health risks. Our results suggest costs from fat taxation are larger than benefits at all income levels. As a fraction of income, the net impact would be slightly regressively distributed.

PMID:39799472 | DOI:10.1002/hec.4933

Psychooncology. 2025 Jan;34(1):e70079. doi: 10.1002/pon.70079.

ABSTRACT

BACKGROUND: Insomnia is the most common sleep disturbance among cancer patients undergoing active treatment. If untreated, it is associated with significant physical and psychological health consequences. Prior efforts to determine insomnia prevalence and correlates have primarily assessed patients in clinical trials, in limited disease groups, and excluding important patient subgroups. These findings are likely to be influenced by research participation effects, which could bias outcomes. We sought to address these limitations in a large, real-world sample.

METHODS: Between 2018 and 2021, all patients seen at our institution were offered an electronic patient-reported outcomes (PRO) questionnaire where they could self-report on a range of symptoms based on the National Cancer Institute’s PRO-CTCAE. Medical records were abstracted for demographics and cancer diagnosis/treatment. We evaluated N = 9350 patients for whom there was complete data.

RESULTS: During cancer treatment, 21% of patients reported insomnia symptoms. Demographically, prevalence was higher in patients who were female (22% vs. 19%), younger than 60 years of age (22% vs. 20%), non-White (24% vs. 20%), and on public insurance (22% vs. 20%). Medically, patients undergoing palliative treatment were more likely to report insomnia symptoms, irrespective of cancer site (23% vs. 19%). The prevalence of insomnia symptoms ranged from 18% (genitourinary) to 23% (gastrointestinal).

CONCLUSION: More than 1 in 5 cancer patients suffer from symptoms of insomnia. It is important that oncologists and cancer centers routinely assess insomnia severity in their patients. Leveraging the use of existing patient-reported outcomes at an institution may be important to help with the identification of insomnia symptoms.

PMID:39799462 | DOI:10.1002/pon.70079

J Periodontal Res. 2025 Jan 12. doi: 10.1111/jre.13376. Online ahead of print.

ABSTRACT

AIM: Ultrasonography (US) has shown accuracy in imaging healthy periodontium. This study aims to evaluate the feasibility and accuracy of US for estimating dimensions of inflamed periodontium induced by ligature and bacteria.

METHODS: Periodontal tissues of maxillary as well as mandibular premolars and molars in six female mini pigs were treated with ligature and three strains of bacteria for 4-10 weeks. Before euthanization, the periodontium was imaged with US. After euthanization, cone-beam computed tomography (CBCT) scans and histology were performed. Soft and hard tissue measurements by calibrated and masked examiners from US, CBCT, and histology were statistically compared.

RESULTS: Seventy-one histological samples with corresponding CBCT and US scans were available for analysis. Overall, there was a good to excellent agreement between histology and US (ICC: 0.77-0.96) for parameters such as Soft Tissue Thickness (STT), Gingival Recession, Crestal Bone Thickness (CBT), and the bone-to-cemento-enamel junction (B-CEJ) distance. However, discrepancies were observed for STT at 3 mm below the CEJ and Soft Tissue Height (STH) (ICC: 0.44 and 0.54, respectively). CBCT showed lower agreement with histology, particularly for thin CBT (< 1 mm), with an ICC of 0.20, compared to 0.90 for US vs. histology. CBCT failed to identify crestal bone in 14 cases when the crestal bone was thin. Notably, CBCT results differed more from histological measurements than US in assessing B-CEJ and thin CBT.

CONCLUSION: US demonstrated substantial potential as a transformative tool for periodontal diagnostics, exhibiting high agreement with histology in determining critical parameters. Compared to CBCT, US offered advantages, particularly in cases with thin crestal bone.

PMID:39799460 | DOI:10.1111/jre.13376