Tag: pubmed

Mol Biol Rep. 2025 Jun 4;52(1):548. doi: 10.1007/s11033-025-10631-y.

ABSTRACT

BACKGROUND: Recurrent pregnancy loss (RPL) is a multifactorial disorder, with unexplained causes in 50% of cases, and immune system involvement is suspected. The decidua, a maternal-fetal interface, requires immune cells such as B cells, NK cells, and dendritic cells for a healthy pregnancy. OX40L, expressed in these cells, plays a crucial immune regulatory role. Variations in OX40L (rs1234314 and rs844648) have not yet been studied in RPL patients.

OBJECTIVE: This study aims to investigate the association of these polymorphisms (rs1234314 and rs844648) with RPL in a Turkish population sample and is the first to do so in this regard.

METHODS: A genetic case-control study was conducted with 195 women who had a history of two or more miscarriages. Allele and genotype frequencies were compared between the RPL group and 135 control women.

RESULTS: No statistically significant differences were observed in allele frequencies for rs1234314 and rs844648 between the RPL and control populations. However, AA carriers of the rs844648 polymorphism were associated with a reduced risk of recurrent pregnancy loss in the recessive model (OR = 2.07, 95% CI = 1.11-3.89, p = 0.02).

CONCLUSION: This study is the first to examine the genetic association of rs1234314 and rs844648 SNPs of OX40L with RPL in a Turkish population. The significant association of the rs844648 AA genotype with a decreased risk of RPL suggests that this variant may play an important role as a protective factor against RPL, potentially through mechanisms related to immune regulation.

PMID:40465113 | DOI:10.1007/s11033-025-10631-y

Health Care Manag Sci. 2025 Jun 4. doi: 10.1007/s10729-025-09712-y. Online ahead of print.

ABSTRACT

Cardiovascular diseases (CVDs) are one of the primary reasons for death worldwide. These diseases often occur due to the occlusion of coronary arteries, thereby leading to insufficient blood and oxygen supply that damages cardiac muscle cells. Electrocardiogram (ECG) signals which reflect heart electrical activity are being used for diagnosing various cardiac diseases. Typically, a standard ECG consists of 12 channels referred to as leads which enable practitioners to monitor heartbeats through different channels where each heartbeat lasts approximately 600 ms. The majority of studies focus on the classification and early diagnosis of arrhythmias. Although the current studies on change-point methods have acquired massive accuracy in detecting potential shifts during a multi-channel process, they lack flexibility in manually assigning more weights to the channels, which are of more importance for experts. This could be addressed by implementing the weighted multivariate functional principal component analysis (WMFPCA). The objective of this study is to develop a novel change-point detection method to monitor long-term cardiovascular treatment. A third-order tensor structure was employed to represent the 12-lead ECG data in three dimensions (beats × samples × leads). Exploiting intra-beat, inter-beat, and inter-lead correlations along with channel significance in the third-order tensor, the WMFPCA is incorporated into Hotelling’s T 2 statistic to construct monitoring schemes. Simulation results show that the proposed approach outperforms the existing methods in monitoring multi-channel processes. Finally, applying the suggested model on a real-world dataset containing Myocardial Infarction (MI) subjects verifies the model.

PMID:40465102 | DOI:10.1007/s10729-025-09712-y

Clin Exp Nephrol. 2025 Jun 4. doi: 10.1007/s10157-025-02709-5. Online ahead of print.

ABSTRACT

BACKGROUND: Membranous lupus nephritis (MLN), a distinct subtype of lupus nephritis (LN), is generally associated with more favorable outcomes than proliferative LN (PLN). However, clinical data regarding pure MLN are limited. We investigated the prognosis of patients with pure MLN in Japan.

METHODS: We performed a sub-analysis of a previously reported nationwide retrospective cohort study of patients with LN in Japan. This study included patients who underwent renal biopsy between 2007 and 2012. Patients with pure MLN (Class V, n = 90) were compared to those with PLN (Class III/IV ± V, n = 362) over a median follow-up period of 5 years. The primary outcome was defined as a 50% increase in serum creatinine (S-Cr) levels.

RESULTS: The renal and patient outcomes of the pure MLN and PLN groups were as follows: A ≥ 50% increase in S-Cr occurred in 12.2 vs. 16.3% of patients. Doubling of S-Cr or progression to end-stage kidney disease (ESKD) occurred in 4.4 vs. 8.6%, ESKD alone in 2.2 vs. 3.0%, and all-cause mortality in 7.9 vs. 5.5%. After adjusting for age, sex, baseline renal function, proteinuria, and the use of mycophenolate mofetil or intravenous cyclophosphamide, no significant differences in renal outcomes were observed between groups (hazard ratio 0.564; 95% confidence interval 0.272-1.170; P = 0.124).

CONCLUSION: In this nationwide Japanese cohort, no statistically significant differences in renal outcomes were observed between pure MLN and PLN. Further research is needed to explore strategies to improve outcomes in pure MLN.

PMID:40465063 | DOI:10.1007/s10157-025-02709-5

J Neurol. 2025 Jun 4;272(6):445. doi: 10.1007/s00415-025-13189-8.

ABSTRACT

BACKGROUND: Disease-modifying therapies (DMTs) have significantly improved the management of multiple sclerosis (MS), but their potential nervous system adverse events (AEs) remain a critical concern. This study aims to evaluate the risk of nervous system AEs associated with 11 DMTs using the FDA Adverse Event Reporting System (FAERS) database, following the READUS-PV guidelines.

METHODS: We performed a disproportionality analysis on FAERS data from Q1 2004 to Q3 2024, focusing on nervous system AEs related to DMTs, such as Alemtuzumab (AL), Ofatumumab (OF), Ocrelizumab (OC), and Fingolimod (FI). Using disproportionality analysis and Bayesian methods, we identified signals of these AEs. We also conducted subgroup analyses across age, gender, weight, geographic regions, and outcomes to assess AE distribution. In addition, a sensitivity analysis was done to evaluate the consistency of the association between DMTs and nervous system AEs across severities. The time to onset and clinical characteristics of AEs were examined as well.

RESULTS: Among 245,469 nervous system AE reports, Siponimod (SI), Natalizumab (NA), FI, and Teriflunomide (TE) exhibited the highest signal values (ROR > 3.0), with SI showing the strongest association [ROR = 3.44, 95% CI (3.34-3.55)]. Females accounted for 76.0% of nervous system AEs, and severe AEs such as central nervous system lesions (mortality rate: 0.97%) and cognitive disorders (mortality rate: 0.94%) were detected. The median time to onset of AEs varied significantly across DMTs, ranging from 14 days for AL to 816 days for Interferon Beta-1a (IN). Subgroup analyses highlighted variations in AE reporting across different demographics and geographic regions. The sensitivity analysis further confirmed the robustness of our findings, indicating consistent associations between DMTs and severe nervous system AEs.

CONCLUSIONS: This study highlights significant differences in the nervous system AEs profiles of DMTs, with SI, NA, FI, and TE showing higher risks of nervous system AEs. These findings underscore the importance of vigilant monitoring and personalized treatment strategies to mitigate nervous system risks in MS patients. Further research is needed to confirm these associations and investigate the mechanisms that underlie them.

PMID:40465056 | DOI:10.1007/s00415-025-13189-8

Curr Mol Med. 2025 Jun 3. doi: 10.2174/0115665240361878250601074746. Online ahead of print.

ABSTRACT

BACKGROUND: Leukemia is marked by clonal hematopoietic stem cell expansion and metabolic reprogramming. The BNT162b2 mRNA COVID-19 vaccine has been proven effective, though questions remain about its broader physiological effects. This study investigates metabolomic alterations in leukemic bone marrow potentially associated with BNT162b2 vaccination.

OBJECTIVE: To compare the bone marrow metabolomic profiles of leukemia patients with and without BNT162b2 vaccination, and healthy unvaccinated controls, to explore potential metabolic differences.

METHODS: Bone marrow samples were obtained from three groups: vaccinated leukemia patients (n=7), unvaccinated leukemia patients without COVID-19 history (n=2), and unvaccinated healthy controls (n=7). Untargeted metabolomics was performed using LC-QTOF-MS. Data were analyzed using XCMS and MetaboAnalyst 5.0 to identify statistically significant metabolite differences and affected pathways. Fold change >1.5 and p<0.05 were considered significant.

RESULTS: Distinct metabolic profiles were observed between the leukemia and control groups. Increased glycolysis, pentose phosphate pathway activity, and altered tryptophan, lipid, and heme metabolism were noted in leukemia samples. Metabolic changes in vaccinated patients (ASL) were more similar to unvaccinated leukemia patients (LO) than to healthy controls, with minor vaccine-associated variations. Notable metabolites included 5-methoxyindoleacetate, phosphorylcholine, and tetrahydrofolic acid.

CONCLUSION: This preliminary study identified altered metabolic pathways in leukemia bone marrow and suggests metabolomic differences associated with BNT162b2 vaccination. While the findings do not support a causal link between mRNA vaccination and leukemia development, they highlight the need for further studies to understand vaccine-induced metabolic modulation in hematological contexts.

PMID:40464175 | DOI:10.2174/0115665240361878250601074746

Curr Med Imaging. 2025 Jun 3. doi: 10.2174/0115734056343395250526140343. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) complicated with interstitial lung abnormalities (ILAs) is often overlooked and can progress to severe diabetesinduced pulmonary fibrosis (DiPF). Therefore, early diagnosis of T2DM complicated with ILAs is crucial. Chest computed tomography (CT) is an important method for diagnosing T2DM complicated with ILAs. Quantitative computed tomography (QCT) is more objective and accurate than visual assessment on CT. However, there are currently limited studies on T2DM complicated with ILAs based on quantitative CT.

OBJECTIVE: This study aimed to explore the utility of quantitative computed tomography for early detection of lung injury in individuals with T2DM by examining CT-derived metrics in T2DM complicated with ILAs.

METHODS: We collected data from 135 T2DM complicated with ILAs on chest CT scans retrospectively, alongside 135 non-diabetic controls with normal CT findings. Employing digital lung software, chest CT images were processed to extract quantitative parameters: total lung volume (TLV), emphysema index (LAA-950%, the percentage of lung area with attenuation < -950 Hu to total lung volume), pulmonary fibrosis index (LAA-700~-200%, the percentage of lung area with attenuation from -700Hu to -200 Hu to the total lung volume), and pulmonary peripheral vascular index (ratio TAV/TNV, the number of blood vessels TNV, the cross-sectional area of blood vessels TAV). Statistical comparisons between groups utilized Mann-Whitney U or t-tests. Correlations between Hemoglobin A1c (HbA1c) levels and CT parameters were assessed via Pearson or Spearman correlations. Parameters showing statistical significance were further examined through receiver operating characteristic (ROC) analysis.

RESULTS: The T2DM-ILAs cohort displayed a significantly higher LAA-700~-200% compared to controls (Z = -7.639, P< 0.001), indicative of increased fibrotic changes. Conversely, TLV (Z =-3.120, P=0.002), TAV/TNV (Z = -9.564, P< 0.001), and LAA-950% (Z = -4.926, P < 0.001) were reduced in T2DM-ILAs patients. The correlation between HbA1c and various CT quantitative indicators was not significant, HbA1c and TLV (r=-0.043, P=0.618), HbA1c and TAV (r=0.143, P=0.099), HbA1c and TNV (r=0.064, P=0.461), HbA1c and LAA-700~-200% (r=0.102, P=0.239), HbA1c and LAA-950% (r=-0.170, P=0.049), HbA1c and TAV/TNV (r=0.175, P=0.043). The peripheral vascular marker, TAV/TNV, excelled in distinguishing T2DM-related lung changes (AUC=0.84, P<0.001), outperforming LAA-700~-200% (AUC=0.77,P<0.001). A composite index incorporating multiple quantitative parameters achieved the highest diagnostic accuracy (AUC = 0.91, P< 0.001).

CONCLUSION: Quantitative CT parameters distinguish T2DM complicated with ILAs from non-diabetic individuals, suggesting a distinct pattern of lung injury. Our findings imply a particular susceptibility of small pulmonary blood vessels to injury in T2DM.

PMID:40464171 | DOI:10.2174/0115734056343395250526140343

J Cachexia Sarcopenia Muscle. 2025 Jun;16(3):e13843. doi: 10.1002/jcsm.13843.

ABSTRACT

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance, accompanied by alterations in the peripheral skeletal muscle (SKM). We have recently shown that titin, a giant sarcomere protein, is hyperphosphorylated in HFpEF. MuRF1 is a muscle-specific ubiquitin E3-ligase that interacts with titin. Blocking this interaction via small molecules (MyoMed205) can improve muscle function and mitochondrial activity in HFpEF. This study aimed to investigate the impact of MyoMed205 on titin phosphorylation and its association with changes in muscle structure and function.

METHODS: Obese ZSF1 rats with established HFpEF received rat chow with (n = 15) or without (n = 15) MyoMed205 and were compared with lean littermates (n = 15), serving as controls. After 12 weeks, in vitro SKM force, atrophy and titin-as well as contractile protein expression-were evaluated (soleus and extensor digitorum longus [EDL]). Statistical analysis was performed via multiple unpaired t-test or one-way ANOVA.

RESULTS: In HFpEF, titin hyperphosphorylation by 13% in the EDL (p = 0.09) and 14% (p = 0.03) in the soleus muscle was evident. This hyperphosphorylation was driven in part by an increase in S11878 phosphorylation (EDL: +68%, p = 0.004; Sol: +23.8%, p = 0.03), which was linked to myofiber atrophy (r = -0.68, p = 0.006) and a decline in maximal specific muscle force (r = -0.54, p = 0.008). In the EDL, significant changes in protein expression related to atrophy (MuRF1 [+24.9%, p = 0.02], GDF8 [+20.6%, p = 0.09]) and calcium handling (slow troponin C [-46%, p = 0.02], fast troponin I [+35.8%, p = 0.02]) were found in HFpEF. All of the above-mentioned effects in HFpEF were almost completely abolished by MyoMed205 treatment, and significantly elevated titin expression was visible (+19.7%, p_con = 0.04, p_HFpEF = 0.01).

CONCLUSIONS: Titin hyperphosphorylation may negatively impact skeletal muscle integrity and function in HFpEF. MyoMed205 reduced titin hyperphosphorylation and was associated with preserved skeletal muscle function and mass. Further studies are necessary to confirm the direct role of titin hyperphosphorylation on muscle function and to evaluate the therapeutic potential of MyoMed205 in HFpEF.

PMID:40464169 | DOI:10.1002/jcsm.13843

J Diabetes. 2025 Jun;17(6):e70108. doi: 10.1111/1753-0407.70108.

ABSTRACT

AIMS: In patients with new onset type 2 diabetes, this study aimed to analyze glucose-lowering medication use patterns between 2014 and 2022.

MATERIALS AND METHODS: This retrospective study included adults with incident type 2 diabetes in the University of California Health System between 2014 and 2022. We determined medications used within 1 year of diagnosis and evaluated statistical evidence of use pattern changes via Mann-Kendall trend tests. Four categories of high-risk patients requiring cardio-kidney-metabolic protection were also evaluated in stratified analyses based on 2024 ADA guidelines.

RESULTS: Of 40 150 patients with incident type 2 diabetes, 38.5% initiated glucose-lowering medication within 1 year. Metformin remained the most used medication from 2014 to 2022. From 2014 to 2022, usage of GLP-1 receptor agonists and SGLT-2 inhibitors increased exponentially. GLP-1 receptor agonist use increased from below 2.5%-21%. While SGLT-2 inhibitor use increased from less than 2.5%-14%. This growth coincided with a decline in sulfonylurea usage. Among high-risk, insulin was most prevalent in those with heart failure or chronic kidney disease. However, usage of insulin declined overall in all groups. Utilization of SGLT-2 inhibitors was particularly high in patients with prior heart failure.

CONCLUSIONS: In adults with new onset type 2 diabetes, GLP-1 receptor agonist and SGLT-2 inhibitor utilization has markedly increased, coordinating with evolving guidelines that emphasize cardiovascular and chronic kidney disease management. However, overall adoption rates of these medications remain low based on indicated populations. Sulfonylurea use declined while metformin remains the most frequently initiated treatment.

PMID:40464139 | DOI:10.1111/1753-0407.70108

Emerg Med Australas. 2025 Jun;37(3):e70081. doi: 10.1111/1742-6723.70081.

ABSTRACT

INTRODUCTION: Emergency departments (ED) in Australia have experienced an increase in patient presentations. To address this demand, we introduced phlebotomists at ED triage seeking to reduce ED waiting and disposition times. We report the impact of this intervention.

METHOD: Using a quantitative retrospective comparative study design guided by the STROBE checklist, we investigated the impact on ED performance before and after the introduction of phlebotomists (the intervention). Data from two periods-T1 (January-June 2021) and T2 (January-June 2023) were obtained and analysed for all ED presentations.

RESULTS: A total of 90,020 patients were included (T1: 46,639; T2: 43,381). Post-intervention improvements included an increase in short stay unit-admissions from triage (3.1% vs. 5.9%, p < 0.001) and a decrease in the proportion of patients transferred to a cubicle from the waiting room (T1: 78.8%; T2: 76.4%). However, patients who left the ED before treatment was completed (known as ‘Did not Wait’) rose significantly (9.8% vs. 11.5%) as did waiting room times (80.02 vs. 112.91 min). Overall, ED length of stay (EDLOS) increased significantly (mean T1: 305.1 to T2: 319.4 min; p < 0.001). There were significant increases in blood tests (T1: 52.0% vs. T2: 59.9%) and ECGs (16.5% vs. 19.1%) performed.

CONCLUSION: The introduction of phlebotomists at triage failed to reduce waiting, treatment and disposition times and increased the number of investigations performed with an overall increase in EDLOS. We observed an increase in the number of patients directed from the waiting room to the short stay unit and fewer patients transferred from the waiting room to an ED cubicle.

PMID:40464127 | DOI:10.1111/1742-6723.70081

Am J Med Genet A. 2025 Jun 4:e64143. doi: 10.1002/ajmg.a.64143. Online ahead of print.

ABSTRACT

The main objective of this study is to establish normative craniocervical junction parameters in pediatric patients with achondroplasia and evaluate differences between patients with and without symptoms of foramen magnum stenosis (FMS) using static and dynamic MRI. A retrospective chart review identified 80 pediatric patients with achondroplasia evaluated at a single institution between 2007 and 2023. Patients were categorized into two groups based on clinical presentation: those with symptoms suggestive of FMS (FMSS group) and those who underwent imaging for unrelated indications (Non-FMSS group). Craniocervical MRI parameters, including minimal canal and cord diameters, atlanto-dental interval (ADI), clival-axial angle (CXA), and space available for the cord (SAC), were measured in neutral, flexion, and extension positions. Statistical comparisons were performed using t-tests, with p-values < 0.05 considered significant. A total of 80 neutral and 69 flexion-extension MRIs were analyzed. Patients in the FMSS group displayed significantly smaller minimal cord and canal diameters across all positions compared to the Non-FMSS group (p < 0.001). SAC measurements were also significantly smaller in the FMSS group. Changes in ADI between flexion and extension were modest and not clinically significant. Interobserver reliability was high across all measured parameters. This study provides preliminary normative data for craniocervical junction parameters in pediatric patients with achondroplasia, highlighting key differences between those with and without symptoms of foramen magnum stenosis. The findings suggest that SAC, minimal cord, and canal diameters may serve as valuable measurements for evaluating cervical stenosis in this population. Further research with larger cohorts and standardized protocols is necessary to validate these parameters.

PMID:40464123 | DOI:10.1002/ajmg.a.64143