bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causality of genetically determined metabolites and metabolic pathways on joint diseases: a two-sample mendelian randomization study
Authors: Zhang Binbin , Lu Chuan , Dou Bin , Yan Qi , Zhaxi Dawa , Wei Shuqing , Luo Xiang , Gu Wenzuo , Li Kewen 
Published: August 2024

Abstract

OBJECTIVE: Infectious arthropathies, inflammatory polyarthropathy, osteoarthropathies, and many other joint diseases are now prevalent worldwide. A large number of studies have suggested an association between metabolites and joint diseases, but due to the limitations of routine observational studies, its significance is not clear. In this paper, we used Mendelian randomization to assess potential causal associations between metabolites and a variety of joint diseases.
METHODS: By screening publicly available data from non-overlapping genome-wide association studies with 1400 metabolites as exposure data and 11 joint diseases as outcome data, the inverse-variance weighted (IVW) method was used as the study to assess the causal effect, MR-Egger, weighted median, weighted mode, and simple mode were used as supplementary methods, and Cochran's Q, MR-Egger- intercept, and MR-PRESSO for sensitivity analysis.
RESULTS: Positive correlations were found between N-formyl anthranilic acid levels and Arthropathies (PFDR=0.019) after FDR correction. Glycine levels (PFDR=0.016), N-acetylglycine levels (PFDR=0.010), Glycine to serine ratio (PFDR=0.018), Propionylcarnitine (c3) levels (PFDR=0.015) were positively correlated with Gonarthrosis. Cystine levels (PFDR=0.017), N-acetylglycine levels (PFDR<0.001), Glycine to serine ratio (PFDR<0.001), and X-24757 levels (PFDR=0.021) were positively associated with Gonarthrosis, primary, with knee surgery. Correlation.
There was a negative correlation between Taurine to cysteine ratio and Arthropathies (PFDR=0.035) and a negative correlation between Docosatrienoate (22:3n3) levels and Rheumatoid arthritis (PFDR=0.013). There was a negative correlation between taurine to cysteine ratio and Other joint disorders (PFDR=0.011). Cysteinylglycine to taurine ratio (PFDR=0.005), Adenosine 3',5'-cyclic monophosphate (cAMP) to adenosine 5'-monophosphate (AMP) ratio (PFDR=0.034) were negatively correlated with Other arthrosis. adenosine 5'-monophosphate (AMP) to histidine ratio (PFDR=0.024), and Glycohyocholate levels (PFDR=0.011) were negatively associated with Gonarthrosis, primarily, with knee surgery. Sensitivity analyses did not reveal the presence of heterogeneity as well as level pleiotropy (P>0.05), suggesting that the findings were not biased, and the leave-one-out method also suggested robust results. Six significant metabolic pathways were identified by metabolic pathway analysis.
CONCLUSION: This study provides new evidence of a causal relationship between metabolites and a variety of joint diseases. Metabolites are important markers in the progression of joint diseases, which is clinically important for the prevention and treatment of joint diseases.
Analysis of Factors Affecting the Population Growth Rate in Rural Areas of Khorasan Razavi Province Based on a MGWR Model
Authors: Aghajani Hossein , Sarkari Farnaz 
Published: August 2024

Abstract

Rural abandonment is a critical demographic issue that has impacted various countries across the world, including Iran, and specifically Khorasan Razavi Province. This research aims to pinpoint factors affecting rural population growth rates within this region. To overcome the limitations of the GWR model, its advanced form, known as Multiscale Geographically Weighted Regression, has been introduced. In this study, the average rural population growth rate of the province's districts between 2006 to 2016 was used as the dependent variable, and 38 variables across socio-demographic, environmental, and infrastructural sectors as independent variables. Results indicate a significant spatial autocorrelation within the rural population growth, suggesting that local regression models are more apt for examining spatial variable relationships. In analyzing local growth factors through MGWR, influencing variables included literacy rates, the average population of villages per district, and the percentage of rural health houses have had a positive impact, while variables included the percentage of the working-age population, the percentage of villages with fewer than 100 residents per district and distance from Wells have had a negative impact on rural population growth rate in the province.
Cellular angiofibroma of the female pelvic cavity: a case report
Authors: Chen Li , Zhang Gumuyang , Sun Hao 
Published: August 2024

Abstract

Background:
Cellular angiofibroma is a rare benign mesenchymal tumor that mostly occurs in the genital area. Its occurrence outside this region, particularly in the pelvis, is extremely rare. To our knowledge, this study reports the first case of cellular angiofibroma occurring in the pelvic cavity, except for one case reported in the retroperitoneum.
Case presentation:
A 25-year-old female patient with chronic, intermittent, dull pain in the lower abdomen that lasted for several months was referred to our clinic. Imaging studies revealed a tumor in the pelvic cavity anterior to the bladder. The radiographic characteristics of this tumor indicated a hypervascular nature, suggesting the possibility of a pheochromocytoma or a neuroendocrine tumor. The patient underwent surgical excision of the lesion. To date, no recurrence has been observed three months after excision.
Conclusions:
Cellular angiofibroma, although rare in the pelvic cavity, should be considered in the differential diagnosis of hypervascular pelvic space-occupying lesions. Immunohistochemical staining can help confirm the diagnosis of this condition. Treatment is generally straightforward, involving local excision of the tumor followed by postoperative monitoring.
Causal Relationship Among Intestinal Microbiota, Lipid Metabolites, and Cholangiocarcinoma: A Mendelian Randomization Study
Authors: Xu Sicheng , He Xing , Liu Liqiang , Ren Junkai , Zhou Qixian , Ye Huilin , Li Wenbin , Wang Haikuo 
Published: August 2024

Abstract

Background:
Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis. Numerous animal experiments and clinical studies have indicated an association between the gut microbiota (GM) and the incidence of CCA. Additionally, patients with CCA often exhibit metabolic disorders, but there is a lack of evidence regarding causality. Therefore, elucidating the causal relationships among GM, plasma metabolites, and CCA is crucial and can provide insights for the prevention and treatment of CCA.
Objective:
We utilized summary statistics from the largest available genome-wide association studies, including gut microbiota (GM) data from the MiBioGen consortium (n = 18,340), plasma metabolites from four distinct human metabolomics studies, and cholangiocarcinoma (CCA) patient data from the UK Biobank (cases n = 832 and controls n = 475,259). We conducted bidirectional Mendelian randomization analyses to explore the causal relationship between GM and CCA. Additionally, we performed two mediation analyses and a two-step Mendelian randomization (MR) to identify potential mediating metabolites, offering guidance for the clinical early detection and intervention of CCA.
Results:
In our analysis, we identified that two types of gut microbes (Enterobacteriaceae and Enterobacteriales) increase the risk of cholangiocarcinoma (CCA), while eight types of gut microbes, including Lachnospiraceae and Eggerthella, have protective effects. Additionally, we identified 31 plasma metabolites significantly associated with CCA, with lipid metabolism disorders being a key factor. Notably, four plasma metabolites, such as Intermediate-Density Lipoprotein Triglycerides (IDL_TG), mediate the relationship between gut microbiota and CCA, highlighting the role of plasma metabolites as intermediaries. These findings underscore the potential of targeting gut microbiota and plasma metabolites for the prevention and treatment of CCA.
Conclusion:
Our research demonstrates that plasma metabolites play a pivotal role in the pathogenesis of CCA induced by gut microbiota. This finding deepens our understanding of how gut microbiota dysbiosis contributes to the development of CCA by influencing plasma metabolites.
Empowering Alzheimer's Caregivers with Conversational AI: A Novel Approach for Enhanced Communication and Personalized Support
Authors: Hasan Wordh Ul , Zaman Kimia Tuz , Wang Xin , Li Juan , Xie Bo , Tao Cui 
Published: August 2024

Abstract

Alzheimer's disease and related dementias (ADRD) significantly impact patients and their caregivers, causing emotional stress, lack of training, and financial strain for the latter. Addressing the need for effective support, this research developed and validated ADQueryAid, a conversational AI system designed to empower ADRD caregivers. Built on a Large Language Model (LLM) and enriched with authoritative ADRD information through a knowledge graph, ADQueryAid uses Retrieval Augmented Generation (RAG) techniques to retrieve relevant information from both structured and unstructured data sources. Prompt engineering and conversation policies ensure the delivery of informative, empathetic, and personalized responses. Evaluated via a Blind Within-Subjects Design study with 20 ADRD caregivers interacting with both ADQueryAid and a baseline model (ChatGPT 3.5) in fictional caregiving scenarios, the system's usability was assessed using the Chatbot Usability Questionnaire (CUQ). Results showed ADQueryAid significantly outperformed the baseline model across all CUQ metrics, offering more contextually relevant information, accurate guidance, and emotional support, which enhanced the caregiving experience. This study highlights the potential of AI to support ADRD caregivers by providing personalized assistance, with future research focusing on expanding the knowledge base, refining conversational strategies, and exploring the long-term impact on caregiver well-being and patient outcomes.
Plasma mutation profile of precursor lesions and colorectal cancer using the Oncomine Colon cfDNA Assay
Authors: Reis Mariana Bisarro dos , Santos Wellington dos , de Carvalho Ana Carolina , Lima Adhara Brandão , Reis Monise Tadin , Santos Florinda , Reis Rui Manuel , Guimarães Denise Peixoto 
Published: August 2024

Abstract

Background
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening.
Aim
To assess the presence of genetic variants in plasma cell-free tumor DNA from patients with precursor lesions and colorectal cancer using the commercial Oncomine Colon cfDNA Assay.
Material and Methods
Cell-free DNA (cfDNA) samples from the blood plasma of 52 Brazilian patients were analyzed. Eight patients did not have any significant lesions (five normal colonoscopies and three hyperplastic polyps), 24 exhibited precursor lesions (13 nonadvanced adenomas, ten advanced adenomas, and one sessile serrated lesion), and 20 patients with cancer (CRC). The mutation profile of 14 CRC-associated genes were determined by next-generation sequencing (NGS) using the Oncomine Colon cfDNA Assay in the Ion Torrent PGM/S5 sequencer.
Results
Thirty-three variants were detected in eight genes (TP53, PIK3CA, FBXW7, APC, BRAF, GNAS, KRAS, and SMAD4). No variants were detected in the AKT1, CTNNB1, EGFR, ERBB2, MAP2K1 and NRAS genes. All variants were considered pathogenic and classified as missense or truncating. The TP53 gene harbored the most variants (48.48%), followed by the KRAS gene (15.15%) and the APC gene (9.09%). It was possible to detect the presence of at least one variant in cfDNA in 60% of CRC patients (12/20) and 25% of precursor lesions (6/24), which included variants in three patients with nonadvanced adenoma (3/13–23.08%) and three with advanced adenomas (3/10–30%). No variants were detected in the eight patients with normal findings during colonoscopy. The detection of mutations showed a sensitivity of 60% and a specificity of 100% for detecting CRC and a sensitivity of 50% and a specificity of 100% for detecting advanced lesions.
Conclusion
The detection of plasma NGS-identified mutations could assist in early screening and diagnostic of CRC in a noninvasive manner.
Development and Validation of Newly Biopsy-Free Nomograms for Predicting Clinically Significant Prostate Cancer in Men with PI-RADS ≥4 Lesions
Authors: Wang Junxin , Chen Mingzhe , Xu Yong , Guo Shanqi , Jiang Xingkang 
Published: August 2024

Abstract

To develop and validate biopsy-free nomograms to more accurately predict clinically significant prostate cancer (csPCa) in biopsy-naïve men with Prostate Imaging Reporting and Data System (PI-RADS) ≥ 4 lesions. A cohort of 931 patients with PI-RADS ≥ 4 lesions, undergoing prostate biopsies or radical prostatectomy from January 2020 to August 2023, was analyzed. Various clinical variables, including age, prostate-specific antigen (PSA) levels, prostate volume (PV), PSA density (PSAD), prostate health index (PHI), and maximum standardized uptake values (SUVmax) from PSMA PET-CT imaging, were assessed for predicting csPCa. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), calibration plots, and decision-curve analyses, with internal validation. The foundational model (nomogram 1) encompassed the entire cohort, accurately predicting csPCa by incorporating variables such as age, PSAD, PV, PSA ratio variations, suspicious lesion location, and history of acute urinary retention (AUR). The AUC for csPCa prediction achieved by the foundational model was 0.918, with internal validation confirming reliability (AUC: 0.908). Advanced models (nomogram 2 and 3), incorporating PHI and PHI + PSMA SUVmax, achieved AUCs of 0.908 and 0.955 in the training set and 0.847 and 0.949 in the validation set, respectively. Decision analysis indicated enhanced biopsy outcome predictions with the advanced models. Nomogram 3 could potentially reduce biopsies by 92.41%, while missing only 1.53% of csPCa cases. In conclusion, the newly biopsy-free approaches for patients with PI-RADS ≥ 4 lesions represent a significant advancement in csPCa diagnosis in this high-risk population.
Posaconazole enteric-coated tablets on the efficacy and tolerability of secondary antifungal prophylaxis in haploidentical allogeneic stem cell transplantation
Authors: wang xiaoning , Sun Chunhong , wang yuqi , Liu Ruimin , Ren juan , zhu huachao , He pengcheng 
Published: August 2024

Abstract

Background:
There are limited researches about posaconazole enteric-coated tablets on the efficacy and tolerability of secondary antifungal prophylaxis(SAP)for invasive fungal disease (IFD) in haploidentical allogeneic hematopoietic stem cell transplantation༈allo-HSCT༉.
Objective:
To investigate the plasma concentration of posaconazole enteric-coated tablets on the efficacy and tolerability of SAP and drug-drug interactions between posaconazole, cyclosporine A (CsA) and mycophenolate mofetil (MMF) in haploidentical allo-HSCT.
Methods:
We conducted a single-arm, open-label, prospective trial (ChiCTR2200059472, Date of Registration 30th April, 2022) to assess efficacy and tolerability of posaconazole enteric-coated tablets as SAP in haploidentical allo-HSCT patients. Plasma concentrations of posaconazole and mycophenolic acid (MPA,active metabolites of MMF) as well as CsA were monitored within 30 days post-transplantation. Additionally, the incidence of IFD was observed.
Results
Fourty-six patients previously with IFD were enrolled in the trial. The incidence of IFD was 4.35% at 100 days and 10.86% at 6 months. The primary cause of prophylaxis failure was gastrointestinal intolerance. The mean plasma concentrations of posaconazole were 0.48 ± 0.06ug/ml at week 1, 0.54 ± 0.07ug/ml at week 2, 0.75 ± 0.08ug/ml at week 3 and 0.90 ± 0.08ug/ml at week 4. The mean plasma concentrations of CsA were 133.04 ± 0.13ng/ml at week 1, 179.53 ± 11.19ng/ml at week 2, 225.02 ± 13.80ng/ml at week 3 and 278.61 ± 13.61ng/ml at week 4. The mean plasma concentrations of MPA during week 2, 3 and 4 were 0.41 ± 0.06mg/L, 0.84 ± 0.08mg/L and 1.08 ± 0.13mg/L, respectively. Posaconazole reached steady state concentrations by week 2 and MPA reached target concentrations at week 3.
Conclusion
Posaconazole enteric-coated tablets appears to be effective and tolerability for SAP of IFD after haploidentical allo-HSCT. When cyclosporine, MMF, and posaconazole are used in combination, the dosage of MMF does not need to be adjusted. The dosage of CsA needs to be personalized and adjusted based on therapeutic drug monitoring.
Alpha-Adrenergic Antagonists and Iris Dynamics: Challenges and Solutions in Cataract Surgery
Authors: Kaushik Jaya , Sharma Rishi , Goyal Sumit , Dangi Meenu , Jha Rakesh Kumar , Singh Ankita 
Published: August 2024

Abstract

Background: Alpha-1 adrenergic receptor antagonists (α1-ARAs) are frequently used in treatment of Hypertension and symptomatic benign prostatic hypertrophy (BPH). Numerous studies have demonstrated the association between α1-ARAs like Tamsulosin and increased surgical risks for patients undergoing cataract surgery. This study aims to identify and study the effects of α1-ARAs on iris parameters and the subsequent operative challenges encountered during cataract surgery.
Methods: A cross-sectional, prospective study involving 30 patients on α1-ARAs planned for cataract surgery and equal number of age and sex matched controls were subjected to evaluation of changes on iris parameters and subsequent challenges in cataract surgery.
Results: The study group had statistically significant lesser pupil diameter. Iris thickness at sphincter muscle region (SMR) was similar between groups (P = 0.53). Significantly lower values of iris thickness at dilator muscle region (DMR) found in treated subjects (P = <0.001). There was statistically significant difference between DMR/SMR ratio of two groups (P<0.001). Multiple regression analysis revealed longer duration of α1-ARAs treatment correlated with reduced DMR/SMR ratio (P = 0.001; r = 0.47).
Conclusion: α1-ARAs have implications for pupil size regulation and surgical procedures involving the eye. Tamsulosin is more potent than alfuzosin in inducing IFIS. Systemic α1-ARAs lower values of DMR thickness, DMR/SMR ratio and reduces pupillary diameter. Therefore, ophthalmologists, primary care physicians, urologists, and patients should be aware of the potential difficulties that these drugs pose for cataract surgery.
Screening and management of obstructive sleep apnea (OSA) and daytime sleepiness in professional drivers in Tunisia: A protocol study using machine learning
Authors: MSAAD Sameh , GARGOURI Rahma , KAMMOUN Nesrine , KHEMEKHEM Rim , ABID Narjes , FEHRI Sonia , KALLEL Kaouther , KAMMOUN Rim , GHARBI Leila DOUIK EL , Maalej Sonia , Bouhamed Heni , Abdelghani Ahmed , Aichaouia Chiraz , Turki Mohamed , KAMMOUN Samy 
Published: August 2024

Abstract

Background
Professional drivers have high rates of Obstructive Sleep Apnea (OSA). This study aims to determine the prevalence of OSA and Excessive Daytime Sleepiness (EDS) and identify their risk factors among a large representative sample of professional drivers in Tunisia. We will also evaluate the risk of accidents associated with OSA and EDS before and after treatment.
Methods
This will be a population-based and prospective study about 3000 professional drivers. Participants will receive a structured questionnaire to evaluate five main outcomes: the likelihood of OSA, EDS, drowsy driving, related sleepiness near misses and accidents, as well as work productivity. Validated self-report measures will be used to evaluate these outcomes.
Participants suspected of having OSA and/or EDS will undergo sleep laboratory investigations, including sleep study. Participants who have moderate-to-severe OSA combined with EDS will be recommended CPAP treatment. After one year of follow-up, all participants will be re-evaluated with self-report questionnaires. For those treated with CPAP, they will undergo the Maintenance of Wakefulness Test (MWT) and adherence, tolerance, and consistency of CPAP usage will be recorded.
We will also use machine learning models. Among the models we will evaluate: Random Forests (RF), XGBoost, and Deep Neural Networks (DNN). The data will be split into two sets: a training set and a test set. The training set will be used to train the machine learning models. The test set will be used to evaluate the models' performances. We will compare the performances of the different machine learning models using standard evaluation metrics such as accuracy, recall, and F1-score.
Conclusion
Our results will pave the way for the creation of a clinical screening instrument that can identify sleep-wake disturbances in professional drivers. This is likely to have a significant impact on the legal regulations concerning driving fitness and road safety.
Early thrombocytopenia at hospital admission predicts mortality in patients with non-isolated severe traumatic brain injury
Authors: Piñeiro Patricia , Calvo Alberto , Perez-Díaz Maria Dolores , Ramos Silvia , García-Ramos Sergio , Power Mercedes , Solchaga Isabel , Rey Cristina , Hortal Javier , Turégano Fernando , Garutti Ignacio 
Published: August 2024

Abstract

Background
Patients with severe traumatic brain injury (STBI) often experience an abnormal hemostasis that contributes to mortality and unfavorable neurological outcomes. We aimed to analyze epidemiologic, clinical and laboratory factors associated with mortality in patients with severe traumatic brain injury during the first 48 hours after in-hospital admission.
Methods
We performed an observational retrospective study of STBI patients with associated extracranial trauma [defined as Injury Severity Score (ISS) ≥ 16 with an Abbreviated Injury Scale (AIS) head and neck ≥ 3 and Glasgow Coma Scale (GCS) ≤ 8], admitted to a Level II trauma center over 7 years (2015–2021). Patients were divided in 2 groups: survivors and dead. We assessed differences regarding demographics, trauma severity, hemodynamics, disability, need of surgery, length of stay, transfusions, need of massive transfusion protocol and hemostatic laboratory parameters at different time points.
Results
134 STBI patients were included. Patients who died were older, mostly men and showed higher trauma severity and disability. Hemoglobin, platelets and clotting parameters deteriorated after admission to the emergency department (ED) with significant differences between groups within the first 24h after admission. Platelet count < 150 × 103/µL at ED arrival, Glasgow coma scale and age were independent risk factors for mortality.
Conclusions
Older age, Glasgow coma scale and platelet count at ED arrival were independent risk factors for mortality in STBI patients with associated extracranial trauma. Early thrombocytopenia < 150 × 103/µL at ED arrival may be used as a simple prognostic tool to early predict mortality between non-isolated STBI.