Tag: nevin manimala

Am J Respir Cell Mol Biol. 2025 Mar 19. doi: 10.1165/rcmb.2024-0459OC. Online ahead of print.

ABSTRACT

Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the precapillary pulmonary arteries. Genomic variation within the T-box 4 (TBX4) transcription factor is the second most common genetic cause of PAH, and can also cause severe lung developmental disorders with neonatal PH. Currently, the effect of TBX4 loss-of-function on later stages of lung development and predisposition to lung disease, including PH, is not well understood. Therefore, we have generated Tbx4 conditional knockout (Tbx4-CKO) mice in which Cre recombinase deletes exon 5 of Tbx4 within the embryonic lung mesenchyme to create a null allele. We harvested lungs from these mice at various timepoints to examine alveologenesis, vascularization, vascular remodeling, lung cellular composition, and disruption of transcriptional activity compared with control lungs. Right ventricular systolic pressure (RVSP) was measured in six-month-old mice to evaluate for PH. Tbx4-CKO lungs show enlargement of airspaces, as confirmed by an increase in mean linear intercept at P14 (24.9%), P36 (31.5%), and P180 (49.6%). These lungs also show a 39.3% decrease in von Willebrand Factor-positive vessels and a 14.2% increase in vessel wall thickness. Consistent with these results, Tbx4-CKO mice show a statistically significant increase of 15.7% in RVSP and 16.3% in the Fulton index. Bulk-RNA sequencing analysis revealed enrichment of pathways and genes relevant to lung alveologenesis, angiogenesis, and PH. Our results show that disruption of Tbx4 expression during early lung development is sufficient to disrupt postnatal lung development and circulation.

PMID:40106779 | DOI:10.1165/rcmb.2024-0459OC

PLoS One. 2025 Mar 19;20(3):e0320487. doi: 10.1371/journal.pone.0320487. eCollection 2025.

ABSTRACT

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are associated with lymph node metastasis and prognosis in breast cancer. Therefore, we explored the value of TILs in predicting sentinel lymph node metastasis (SLNM) in patients with early-stage (cT1-2N0) breast cancer and provided a new method for preoperative assessment of SLNM status.

METHODS: This study included 337 patients with early-stage breast cancer who underwent surgery at our hospital from January 2022 to December 2023. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 in the patients was assessed using immunohistochemistry (IHC). TILs in the core needle biopsy samples were evaluated histopathologically, and patients were divided into high and low TILs groups based on the density of TILs. Statistical analysis was conducted, and a predictive model was established.

RESULTS: The study found that patients with high TILs had a significantly lower rate of SLNM compared to those with low TILs (P < 0.001). The cT stage and the level of TILs were identified as independent predictive factors for SLNM. The ROC curve analysis indicated that the density of TILs has good predictive efficacy for SLNM. Based on the results of the multivariate regression analysis, a nomogram predictive model for SLNM was constructed.

CONCLUSIONS: Our study showed that the density of TILs and cT stage are independent predictive factors for SLNM in early-stage (cT1-2N0) breast cancer, and the predictive effect of TILs density on SLNM is significant in Luminal and triple-negative breast cancers.

PMID:40106761 | DOI:10.1371/journal.pone.0320487

Retina. 2025 Mar 10. doi: 10.1097/IAE.0000000000004467. Online ahead of print.

ABSTRACT

PURPOSE: Investigate the relationship between Bilateral Macular Telangiectasia Type II (MacTel) and Asteroid Hyalosis (AH) and identify the factors that influence this correlation.

METHODS: A retrospective review utilizing the Retina Consultants of Alabama database from January 2016 to February 28, 2024 was conducted. The charts of 321 patients with retinal telangiectasias were assessed, and 143 were excluded. They were further partitioned into those with AH+MacTel (n=16) versus MacTel only (n=162). The incidence was determined and compared to population-based AH studies with similar patient demographics. Demographic and ocular data were collected and compared between the AH+MacTel and MacTel only groups.

RESULTS: AH was more prevalent in our MacTel cohort (9.88%) compared to Beaver Dam (1.20%, p<.001), Blue Mountains (1.01%, p<0.001), UCLA Autopsy (1.96%, p<.001), and Gutenberg Health studies (0.477%, p<0.001). An inverse link was found between AH+MacTel patients and posterior vitreous detachments (p<0.045 univariate, p<0.025 multivariate). AH+MacTel patients presented fewer ocular conditions (1.79±1.12) than MacTel only patients (2.31±1.11) and significantly lower OCT Central Subfield Thickness (224±43.0 μm) versus MacTel alone (249±49.6 μm; unadjusted mean difference: -25 μm, 95% CI: -45.3 to -4.76).

CONCLUSION: There was a statistically significantly higher prevalence of patients with AH who also had a diagnosis of MacTel compared to the general population.

PMID:40106717 | DOI:10.1097/IAE.0000000000004467

Bioinformatics. 2025 Mar 19:btaf125. doi: 10.1093/bioinformatics/btaf125. Online ahead of print.

ABSTRACT

MOTIVATION: Whole Genome and Proteome Alignments, represented by the Multiple Alignment File (MAF) format, have become a standard approach in comparative genomics and proteomics. These often require identifying conserved motifs, which is crucial for understanding functional and evolutionary relationships. However, current approaches lack a direct method for motif detection within MAF files. We present MAFin, a novel tool that enables efficient motif detection and conservation analysis in MAF files to address this gap, streamlining genomic and proteomic research.

RESULTS: We developed MAFin, the first motif detection tool for Multiple Alignment Format files. MAFin enables the multithreaded search of conserved motifs using three approaches: 1) using user-specified k-mers to search the sequences. 2) with regular expressions, in which case one or more patterns are searched, and 3) with predefined Position Weight Matrices. Once the motif has been found, MAFin detects the motif instances and calculates the conservation across the aligned sequences. MAFin also calculates a conservation percentage, which provides information about the conservation levels of each motif across the aligned sequences, based on the number of matches relative to the length of the motif. A set of statistics enables the interpretation of each motif’s conservation level, and the detected motifs are exported in JSON and CSV files for downstream analyses.

AVAILABILITY: MAFin is offered as a Python package under the GPL license as a multi-platform application and is available at: https://github.com/Georgakopoulos-Soares-lab/MAFin.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40106711 | DOI:10.1093/bioinformatics/btaf125

J AOAC Int. 2025 Mar 19:qsaf025. doi: 10.1093/jaoacint/qsaf025. Online ahead of print.

ABSTRACT

BACKGROUND: Dendrobium nobile is an edible orchid with diverse therapeutic properties. In north-eastern Himalayan states of India, the extract of this flower is consumed by tribal populations for the treatment of diabetes, cancer, and cardiovascular diseases. However, the profile of biologically active compounds in the colored varieties of D. nobile orchid flowers cultivated in the north-eastern Himalayan region is not well-established, necessitating a thorough investigation.

OBJECTIVE: This study aims to establish and compare the metabolite profile of three types of D. nobile flowers (white, light-pink, and dark pink) using liquid chromatography-high resolution mass spectrometry (LC-HRMS).

METHODS: The homogenized and cryoground flower samples were extracted with aqueous methanol. After LC-MS data acquisition through full-scan (untargeted) and MS/MS (targeted) modes, data processing involved peak alignment, adduct identification, and integration. Results were compared by multivariate statistics using Independent Component Analysis.

RESULTS: A total of 73 metabolites was identified, each with mass error of less than 5 ppm for both precursor and fragment ions. From anthocyanin classes, the chemometric analysis revealed 11 distinguishing biomarker metabolites, with variable influence on projection values above 1. Across the test accessions, three compounds, viz. cyanidin-3-diglucoside, delphinidin-3-sophoroside, and delphinidin-3-gentiobioside revealed their discriminatory presence.

CONCLUSION: The study identified the therapeutically important anthocyanins for metabolomic discrimination of three different D. nobile flower accessions. The study will be useful for authenticating D. nobile accessions, derived products, and selecting candidate traits for future breeding programs for varietal improvements.

HIGHLIGHTS: This study identified and profiled the bioactive anthocyanin compounds in D. nobile orchid flowers grown in the north-eastern Himalayan region of India, based on color variations using a non-target metabolomics approach.

PMID:40106708 | DOI:10.1093/jaoacint/qsaf025

Sci Adv. 2025 Mar 21;11(12):eadq9461. doi: 10.1126/sciadv.adq9461. Epub 2025 Mar 19.

ABSTRACT

Whether the rapid warming of the Arctic, particularly the Barents-Kara Sea (BKS), substantially affects the Eurasian winter climate has been debated for over a decade. Here, we use an extended dynamical adjustment method to separate the effects of internal dynamics and thermodynamically forced BKS warming on atmospheric circulation, relying solely on observations. Evidence shows that the observed link between BKS warming and Eurasian cooling is influenced by both atmospheric internal variability and forced BKS warming. Internal variability, particularly the Arctic Oscillation, predominantly contributed to the observed Eurasian cooling from 1991 to 2012. While BKS warming has a weaker impact on Eurasian cooling on interannual to interdecadal timescales, it notably affects multidecadal scales, contributing to the observed “warming hole” in central Eurasia during 1980-2022. Our findings suggest a weak but non-negligible Eurasian cooling response to BKS warming on multidecadal timescales. These findings advance the understanding of the complex causal relationships between Arctic and mid-latitude climates.

PMID:40106553 | DOI:10.1126/sciadv.adq9461

PLoS One. 2025 Mar 19;20(3):e0319685. doi: 10.1371/journal.pone.0319685. eCollection 2025.

ABSTRACT

Crohn’s disease (CD) is a long-term inflammatory gastrointestinal disorder, often adversely affecting physical, emotional, and psychological well-being. Pharmaceutical management is habitually adopted; although medicinal therapies require continuous administration, and are often associated with significant side effects and low adherence rates. Whole body vibration (WBV) represents a non-invasive technique, that provides vibration stimulation to the entire body. As WBV appears to target the physiological pathways and symptoms pertinent to CD epidemiology, it may have significant potential as a novel non-pharmaceutical intervention therapy in CD. This paper presents the study protocol for a randomised controlled trial investigating the impact of WBV on health outcomes in individuals with CD. This 6-week, parallel randomised controlled trial will recruit 168 individuals, assigned to receive WBV and lifestyle education 3 times per week compared to control, receiving lifestyle education only. The primary outcome of the trial will be the difference from baseline to post-intervention in health-related quality of life between the groups, assessed with the Inflammatory Bowel Disease Quality of Life Questionnaire. Secondary outcomes will include between-group differences in other questionnaires assessing fatigue, anxiety and pain, measures of physical fitness, and biological markers for disease activity and inflammation. Statistical analyses will follow an intention-to-treat approach, using linear mixed-effects models to compare changes between time points and both trial groups. Ethical approval was granted by the Nottingham Research Ethics Committee (REC: 24/EM/0106) and the study has been registered prospectively as a clinical trial (NTC06211400).

PMID:40106525 | DOI:10.1371/journal.pone.0319685

PLoS One. 2025 Mar 19;20(3):e0314661. doi: 10.1371/journal.pone.0314661. eCollection 2025.

ABSTRACT

INTRODUCTION: Gallstone disease (GD) is a prevalent condition frequently encountered in surgical units worldwide. The objective of this comprehensive systematic review and meta-analysis study was to examine the relationship between gallstones and the risk of cardiovascular diseases (CVDs).

METHODS: To conduct our study, we performed a systematic review and meta-analysis. We gathered relevant studies from reputable databases, including Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase. The quality of the articles was assessed using the Newcastle-Ottawa Scale checklist. To assess heterogeneity among the studies, we utilized statistical tests such as the Chi-square test, I² statistic, and forest plots. Meta-regression analysis considered variables such as the year of the study, study design, sample size, study quality assessment score, geographical region, average age of subjects, and follow-up duration. Additionally, we evaluated publication bias using Begg’s and Egger’s tests.

RESULTS: Data from 22 studies conducted between 1985 and 2023 were analyzed. The combined number of participants across these studies was 7,496,303. The meta-analysis results revealed that individuals with GD had a higher risk of CVDs (Risk Ratio (RR): 1.29; 95% CI: 1.22-1.36; P < 0.001). Subgroup analysis showed consistent results across good quality studies (RR: 1.20, 95% CI: 11.12-1.28; P < 0.001), moderate quality studies (RR: 1.41, 95% CI: 1.15-1.74; P < 0.001), and low-quality studies (RR: 1.22, 95% CI: 1.15-1.30; P < 0.001). In the meta-regression analysis, none of the variables had a significant relationship with the observed heterogeneity (P-value > 0.10). In a sensitivity analysis, the estimated RR remained consistent, confirming the robustness of the meta-analysis results.

CONCLUSION: Our findings suggest an association between gallstone disease and an increased risk of CVDs. It seems that one of the important factors of this relationship is having common causes for the formation of gallstones and cardiovascular diseases. However, gallstones can be considered an important sign of increased risk of cardiovascular diseases.

PMID:40106516 | DOI:10.1371/journal.pone.0314661

J Am Nutr Assoc. 2025 Mar 19:1-7. doi: 10.1080/27697061.2025.2475879. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the compatibility between the Mini Nutritional Assessment (MNA), a validated tool for screening for malnutrition among older adults, and the Healthy Diet Indicator-2015 (HDI-2015), a diet quality index, to investigate their relationship in assessing nutritional status.

METHOD: This cross-sectional study included 6094 community-dwelling older adults aged 65 and older. The MNA was administered to assess the nutritional status, and the adherence to the World Health Organization’s HDI-2015 was determined based on 24-hour dietary recalls.

RESULTS: According to the MNA, 70.4% of older adults had a normal nutritional status, 27.6% had a risk of malnutrition, and 2.0% were malnourished. Advanced age, female sex, poor appetite, difficulty chewing and swallowing, consistently skipping meals, and not exercising regularly were significantly associated with the rate of malnutrition in older adults (p < 0.001). Only 3.8% of older adults demonstrated high adherence to the HDI-2015, whereas 27.0% demonstrated moderate adherence and 69.2% demonstrated low adherence. The rate of malnutrition was higher in older adults who demonstrated low adherence to the HDI-2015 (p < 0.001). A weak positive correlation was found between the MNA and the HDI-2015 (r = 0.119; p < 0.01).

CONCLUSIONS: Even if older adults living in the community have a normal nutritional status according to the MNA, periodically obtaining dietary recalls to assess diet quality, such as using HDI-2015, is important for developing personalized nutrition plans.

PMID:40106508 | DOI:10.1080/27697061.2025.2475879

PLoS One. 2025 Mar 19;20(3):e0319396. doi: 10.1371/journal.pone.0319396. eCollection 2025.

ABSTRACT

INTRODUCTION: Autistic people experience higher risk of suicidal ideation (SI) and suicide attempts (SA) compared to non-autistic people, yet there is limited understanding of complex, multilevel factors that drive this disparity. Further, determinants of mental health service receipt among this population are unknown. This study will identify socioecological factors associated with increased risk of SI and SA for autistic people and evaluate determinants of mental health care receipt.

METHODS: This study will link information for individuals aged 12-64 years in healthcare claims data (IBM® MarketScan® Research Database and CMS Medicaid) to publicly available databases containing community and policy factors, thereby creating a unique, multilevel dataset that includes health, demographic, community, and policy information. Machine learning data reduction methods will be applied to reduce the dimensionality prior to nested, multilevel empirical estimation. These techniques will allow for robust identification of clusters of socioecological factors associated with 1) risk of SI and SA and 2) receipt of mental health services (type, dose, delivery modality). Throughout, the research team will partner with an established group of autistic partners to promote community relevance, as well as receive input and guidance from a council of policy and practice advisors.

DISCUSSION: We hypothesize that nested individual (co-occurring conditions, age, sex), community (healthcare availability, social vulnerabilities), and policy factors (state mental health legislation, state Medicaid expansion) will be associated with heightened risk of SI and SA, and that receipt, dose, and delivery of mental health services will be associated with interdependent factors at all three levels. The approach will lead to identification of multilevel clusters of risk and factors that facilitate or impede mental health service delivery. The study team will then engage the community partners, and policy and practice advisors to inform development of recommendations to reduce risk and improve mental health for the autistic population.

PMID:40106500 | DOI:10.1371/journal.pone.0319396