bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of an Electronic Frailty Index for Predicting Mortality and Complications Analysis in Pulmonary Hypertension Using Random Survival Forest Model
Authors: Zhou Jiandong , Chou Oscar Hou In , Wong Ka Hei Gabriel , Lee Sharen , Leung Keith Sai Kit , Liu Tong , Cheung Bernard Man Yung , Wong Ian Chi Kei , Tse Gary , Zhang Qingpeng 
Published: July 2022

BackgroundThe long-term prognosis of the cardio-metabolic and renal complications, in addition to mortality in patients with newly diagnosed pulmonary hypertension, are unclear. This study aims to develop a scalable predictive model in the form of an electronic frailty index (eFI) to predict different adverse outcomes.MethodsThis was a population-based cohort study of patients diagnosed with pulmonary hypertension between January 1st, 2000 and December 31st, 2017, in Hong Kong public hospitals. The primary outcomes were mortality, cardiovascular complications, renal diseases, and diabetes mellitus. The univariable and multivariable Cox regression analyses were applied to identify the significant risk factors, which were fed into the non-parametric random survival forest (RSF) model to develop an eFI.ResultsA total of 2,560 patients with a mean age of 63.4 years old (interquartile range: 38.0–79.0) were included. Over a follow-up, 1,347 died and 1,878, 437, and 684 patients developed cardiovascular complications, diabetes mellitus, and renal disease, respectively. The RSF-model-identified age, average readmission, anti-hypertensive drugs, cumulative length of stay, and total bilirubin were among the most important risk factors for predicting mortality. Pair-wise interactions of factors including diagnosis age, average readmission interval, and cumulative hospital stay were also crucial for the mortality prediction. Patients who developed all-cause mortality had higher values of the eFI compared to those who survived (P &lt; 0.0001). An eFI ≥ 9.5 was associated with increased risks of mortality [hazard ratio (HR): 1.90; 95% confidence interval [CI]: 1.70–2.12; P &lt; 0.0001]. The cumulative hazards were higher among patients who were 65 years old or above with eFI ≥ 9.5. Using the same cut-off point, the eFI predicted a long-term mortality over 10 years (HR: 1.71; 95% CI: 1.53–1.90; P &lt; 0.0001). Compared to the multivariable Cox regression, the precision, recall, area under the curve (AUC), and C-index were significantly higher for RSF in the prediction of outcomes.ConclusionThe RSF models identified the novel risk factors and interactions for the development of complications and mortality. The eFI constructed by RSF accurately predicts the complications and mortality of patients with pulmonary hypertension, especially among the elderly.
Arterial Wave Reflection and Aortic Valve Stenosis: Diagnostic Challenges and Prognostic Significance
Authors: Pagoulatou Stamatia , Adamopoulos Dionysios , Rovas Georgios , Bikia Vasiliki , Müller Hajo , Giannakopoulos Georgios , Mauler-Wittwer Sarah , Licker Marc-Joseph , Stergiopulos Nikolaos , Noble Stéphane 
Published: July 2022

IntroductionArterial wave reflection is an important component of the left ventricular afterload, affecting both pressure and flow to the aorta. The aim of the present study was to evaluate the impact of wave reflection on transvalvular pressure gradients (TPG), a key parameter for the evaluation of aortic valve stenosis (AS), as well as its prognostic significance in patients with AS undergoing a transcatheter aortic valve replacement (TAVR).Materials and MethodsThe study population consisted of 351 patients with AS (mean age 84 ± 6 years, 43% males) who underwent a complete hemodynamic evaluation before the TAVR. The baseline assessment included right and left heart catheterization, transthoracic echocardiography, and a thorough evaluation of the left ventricular afterload by means of wave separation analysis. The cohort was divided into quartiles according to the transit time of the backward pressure wave (BWTT). Primary endpoint was all-cause mortality at 1 year.ResultsEarly arrival of the backward pressure wave was related to lower cardiac output (Q1: 3.7 ± 0.9 lt/min vs Q4: 4.4 ± 1.0 lt/min, p &lt; 0.001) and higher aortic systolic blood pressure (Q1: 132 ± 26 mmHg vs Q4: 117 ± 26 mmHg, p &lt; 0.001). TPG was significantly related to the BWTT, patients in the arrival group exhibiting the lowest TPG (mean TPG, Q1: 37.6 ± 12.7 mmHg vs Q4: 44.8 ± 14.7 mmHg, p = 0.005) for the same aortic valve area (AVA) (Q1: 0.58 ± 0.35 cm2 vs 0.61 ± 0.22 cm2, p = 0.303). In multivariate analysis, BWTT remained an independent determinant of mean TPG (beta 0.3, p = 0.002). Moreover, the prevalence of low-flow, low-gradient AS with preserved ejection fraction was higher in patients with early arterial reflection arrival (Q1: 33.3% vs Q4: 14.9%, p = 0.033). Finally, patients with early arrival of the reflected wave (Q1) exhibited higher all-cause mortality at 1 year after the TAVR (unadjusted HR: 2.33, 95% CI: 1.17–4.65, p = 0.016).ConclusionEarly reflected wave arrival to the aortic root is associated with poor prognosis and significant aortic hemodynamic alterations in patients undergoing a TAVR for AS. This is related to a significant decrease in TPG for a given AVA, leading to a possible underestimation of the AS severity.
A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype
Authors: Cárcel-Márquez Jara , Muiño Elena , Gallego-Fabrega Cristina , Cullell Natalia , Lledós Miquel , Llucià-Carol Laia , Sobrino Tomás , Campos Francisco , Castillo José , Freijo Marimar , Arenillas Juan Francisco , Obach Victor , Álvarez-Sabín José , Molina Carlos A. , Ribó Marc , Jiménez-Conde Jordi , Roquer Jaume , Muñoz-Narbona Lucia , Lopez-Cancio Elena , Millán Mònica , Diaz-Navarro Rosa , Vives-Bauza Cristòfol , Serrano-Heras Gemma , Segura Tomás , Ibañez Laura , Heitsch Laura , Delgado Pilar , Dhar Rajat , Krupinski Jerzy , Delgado-Mederos Raquel , Prats-Sánchez Luis , Camps-Renom Pol , Blay Natalia , Sumoy Lauro , de Cid Rafael , Montaner Joan , Cruchaga Carlos , Lee Jin-Moo , Martí-Fàbregas Joan , Férnandez-Cadenas Israel 
Published: July 2022

BackgroundOccult atrial fibrillation (AF) is one of the major causes of embolic stroke of undetermined source (ESUS). Knowing the underlying etiology of an ESUS will reduce stroke recurrence and/or unnecessary use of anticoagulants. Understanding cardioembolic strokes (CES), whose main cause is AF, will provide tools to select patients who would benefit from anticoagulants among those with ESUS or AF. We aimed to discover novel loci associated with CES and create a polygenetic risk score (PRS) for a more efficient CES risk stratification.MethodsMultitrait analysis of GWAS (MTAG) was performed with MEGASTROKE-CES cohort (n = 362,661) and AF cohort (n = 1,030,836). We considered significant variants and replicated those variants with MTAG p-value &lt; 5 × 10−8 influencing both traits (GWAS-pairwise) with a p-value &lt; 0.05 in the original GWAS and in an independent cohort (n = 9,105). The PRS was created with PRSice-2 and evaluated in the independent cohort.ResultsWe found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension.ConclusionThe loci found significantly associated with CES in the MTAG, together with the creation of a PRS that improves the predictive clinical models of CES, might help guide future clinical trials of anticoagulant therapy in patients with ESUS or AF.
Estimated Cumulative Incidence of Wisdom Tooth Extractions in Privately Insured US Patients
Authors: Schroeder Alan R. , Newman Thomas B. , Girod Sabine , Hashemi Sepehr , Häberle Astrid D. 
Published: July 2022

ObjectiveTo determine the cumulative incidence and predictors of third molar (3M, “wisdom teeth”) extractions in the United States.MethodsWe retrospectively analyzed a US private dental insurance claims database to create a Kaplan-Meier curve for the cumulative incidence of 3M extractions and used Cox proportional hazards to assess associations between sex, geographic region, and extractions.ResultsBetween 2007 and 2016, by age 25, ~80% of patients underwent ≥1 tooth extraction and an estimated 50% of patients underwent ≥1 3M extraction. Factors associated with 3M extractions included female sex (adjusted hazard ratio [aHR] 1.08, 95% CI 1.07–1.08) and residence in the West (aHR 1.82, 95% CI 1.81–1.85) or South (aHR 1.5, 95% CI 1.49–1.51) geographic regions as compared to the Northeast.Conclusion3M extractions are likely the most common surgery performed in US adolescents and young adults. Significant geographic variation suggests that elucidation of the indications for this common procedure is a public health priority.
Unraveling the Importance of the Yangtze River and Local Catchment on Water Level Variations of Poyang Lake (China) After the Three Gorges Dam Operation: Insights From Random Forest Modeling
Authors: Li Bing , Yang Guishan , Wan Rongrong , Wang Yanan , Xu Chen , Wang Dianchang , Mi Chuang 
Published: July 2022

Investigating the contributions of the factors influencing lake water level and their related changes with regard to hydraulic facilities is vital for understanding the driving mechanism of water level variations under the manifold pressures from anthropogenic activities and climate change. In this study, a random forest (RF) model was used to investigate the changes of the relationship between water level and discharge of the Yangtze River and local tributaries in Poyang Lake, China, based on daily hydrological data from 1980 to 2018. The results indicated that RF exhibited robust capability for water level prediction in Poyang Lake, with average R2 of 0.95, 0.88, 0.92, and 0.94 for the dry, rising, wet, and recession seasons, respectively. Predictor importance analysis showed that the discharge of the Yangtze River had greater influence on the water level than the discharge of local tributaries except for the dry season in Poyang Lake, where the influence on the water level was evident with discharge less than 5,000 m3/s. The influence of the Yangtze River also showed a clear attenuation pattern as the distance from the outlet of the lake increased, where the water level was constantly regulated by the Yangtze River. In addition, the partial dependence plots also indicated that the Yangtze River discharge changes after the TGD operation have resulted in remarkable water level decreases in the wet and recession seasons, especially for the recession period. Meanwhile, a slight increase in water level was predicted under identical discharge of local catchment in the dry season, which was only concentrated in the outlet of the lake. This study indicated the RF model as a robust technique for water level predictions and attribution analysis under multiple temporal and spatial scales. Moreover, this study confirmed the uneven influences of the Yangtze River and local tributaries on water level across different seasons, gauging stations, and phases.
Polyunsaturated Fatty Acids Level and Bone Mineral Density: A Two-Sample Mendelian Randomization Study
Authors: Wang Lin , Zhang Chao , Liang Hao , Zhou Nian , Huang Tianji , Zhao Zenghui , Luo Xiaoji 
Published: July 2022

BackgroundThis Mendelian randomization (MR) study aimed to explore the causal relationship between polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).MethodsWe conducted a two-sample MR analysis to figure out if there is any causal effect of PUFAs on BMD through the summary data from the genome-wide association study (GWAS). Relationships were evaluated through inverse variance weighted (IVW), MR-Egger, weighted median, and maximum likelihood methods. The MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test was performed to detect the horizontal pleiotropy.ResultsOur findings revealed that omega-6 fatty acids were negatively related to the TB-BMD (beta-estimate: −0.0515; 95% confidence interval [CI]: −0.0911 to −0.0119; standard error [SE]: 0.0201; p-value: 0.0106). The reverse direction MR analysis showed that TB-BMD was linked to the omega-6 FAs (beta-estimate: −0.0699; 95% CI: −0.1304 to −0.0095; SE: 0.0308; p-value: 0.0265). No statistically significant correlations between PUFAs and BMD were observed after adjusting the interactions between metabolites.ConclusionThis two-sample MR analyses produced strong and new genomic evidence that there was a causal relationship between omega-6 FAs and BMD. Further investigations are still required to elucidate the potential mechanism.
Association Between Globulin and Diabetic Nephropathy in Type2 Diabetes Mellitus Patients: A Cross-Sectional Study
Authors: Wang Jian , Liu Fang , Kong Rongzhen , Han Xiuxia 
Published: July 2022

BackgroundWith the development of economy, the living standard of people all over the world has been greatly improved, and the incidence of diabetes is also increasing. Many people with diabetes also develop other complications that reduce their quality of life. Diabetic nephropathy is a common complication of type2 diabetes. Understanding the related factors of diabetic nephropathy is greatly significant to control the occurrence of diabetic nephropathy and improve patient’s life quality.Data and MethodsData were collected from 2009 to 2018 in NHANES. Curve fitting graph was performed to investigate the association between globulin (GLB) and diabetic nephropathy(DN). Four logistic regression models were conducted to control the potential confounding factors. Subgroup analysis was carried out to assess the stability of results.ResultsGLB was positively correlated with the occurrence of DN after controlling for potential confounders. Higher GLB was associated with an increased risk of diabetic nephropathy [odds ratio(OR), 1.10; 95% confidence interval (CI), 1.07-1.13, P &lt; 0.001].ConclusionsIn this cross-sectional study, GLB was significant positively correlated with the occurrence of DN in patients with type2 diabetes mellitus.
Hounsfield Unit for Assessing Bone Mineral Density Distribution Within Cervical Vertebrae and Its Correlation With the Intervertebral Disc Degeneration
Authors: Liang Xiao , Liu Qingtao , Xu Jiaxin , Ding Wenyuan , Wang Hui 
Published: July 2022

Study DesignRetrospective radiological analysis.ObjectiveTo assess bone mineral mass distribution within cervical vertebrae based on Hounsfield unit (HU) measurement, and explore its correlation with intervertebral disc degeneration.MethodThree hundred and twenty-four patients with degenerative cervical spine disease were retrospectively reviewed and divided into six groups according to age. HU measurement of the whole vertebrae from C3 through C7 was obtained, then HU measurement within upper and lower part of the vertebrae on sagittal plane were obtained from C3 through C7. Disc degeneration on MRI was graded from I to V using the Pfirrmann classification.ResultsThere was a significant difference in the HU value from C3 to C7 among Group II to Group VI, the HU value presented consistently decreasing trend from young patients to old patients. In C6 and C7 vertebrae, there were significant differences in HU values between upper and lower parts of the vertebrae. More importantly. In all groups, HU values were highest in the upper part of the C4 vertebrae and then gradually decreased towards C3 and C7. HU value of both upper and lower vertebrae presented decreasing trend along with the aggravation of the disc degeneration.ConclusionHU values are not typically consistent throughout all levels of the cervical spine and the distribution within the vertebrae is not homogeneous. Decreased vertebral BMD and vertebral osteoporosis may trigger or exacerbate the adjacent intervertebral disc degeneration.
Unique Molecular Identifier-Based High-Resolution HLA Typing and Transcript Quantitation Using Long-Read Sequencing
Authors: Cornaby Caleb , Montgomery Maureen C. , Liu Chang , Weimer Eric T. 
Published: July 2022

HLA typing provides essential results for stem cell and solid organ transplants, as well as providing diagnostic benefits for various rheumatology, gastroenterology, neurology, and infectious diseases. It is becoming increasingly clear that understanding the expression of patient HLA transcripts can provide additional benefits for many of these same patient groups. Our study cohort was evaluated using a long-read RNA sequencing methodology to provide rapid HLA genotyping results and normalized HLA transcript expression. Our assay used NGSEngine to determine the HLA genotyping result and normalized mRNA transcript expression using Athlon2. The assay demonstrated an excellent concordance rate of 99.7%. Similar to previous studies, for the class I loci, patients demonstrated significantly lower expression of HLA-C than HLA-A and -B (Mann–Whitney U, p value = 0.0065 and p value = 0.0154, respectively). In general, the expression of class II transcripts was lower than that of class I transcripts. This study demonstrates a rapid high-resolution HLA typing assay using RNA-Seq that can provide accurate HLA genotyping and HLA allele-specific transcript expression in 7–8 h, a timeline short enough to perform the assay for deceased donors.
Perthes Disease in a Child With Osteogenesis Imperfecta From a Rare Genetic Variant: A Case Report
Authors: Hong Pan , Zhao Xiaolong , Liu Ruikang , Rai Saroj , Song Yingying , Xu Ruijing , Li Jin 
Published: July 2022

Background: Although certain genetic components have been reported as contributing factors for Perthes disease, its etiology remains unclear. We present a rare case of Perthes disease in a child with osteogenesis imperfecta (OI) caused by a mutation in the COL1A1 gene (NM_000088):exon25:c.1726C&gt;T, (p.Gln576X).Case presentations: A 7-year-old boy was initially treated at our medical facility in March 2016 with a history of chronic pain in right hip joint and limping for a year. He was diagnosed as Perthes disease in the right hip joint. He underwent acetabular osteotomy and ipsilateral proximal femoral varus osteotomy for better containment. During the follow-ups, the right hip demonstrated a normal range of motion without pain, and the pelvic X-ray demonstrated Stulberg Type II hip joint with a round femoral head. In the latest admission in 2022, he suffered from a right femoral shaft fracture after petty violence. After reviewing his medical history, he was suspected of having OI. The whole exome sequencing demonstrated a gene mutation in COL1A1 (OMIM 166200) and confirmed the diagnosis of OI. Telescopic nailing was used to treat the femoral shaft fracture. After the nailing of the right femur, the appearance of the lower extremity seemed normal and symmetrical.Conclusion: This study revealed that there might be an association between OI and Perthes disease. Our case report enriches the phenotypes of osteogenesis imperfecta and provides insight into the pathogenesis of LCPD.
Microbial Metabolites in the Maturation and Activation of Dendritic Cells and Their Relevance for Respiratory Immunity
Authors: Wilson Kayla R. , Gressier Elise , McConville Malcolm J. , Bedoui Sammy 
Published: July 2022

The respiratory tract is a gateway for viruses and bacteria from the external environment to invade the human body. Critical to the protection against these invaders are dendritic cells (DCs) - a group of highly specialized myeloid cells that monitors the lung microenvironment and relays contextual and antigenic information to T cells. Following the recognition of danger signals and/or pathogen molecular associated patterns in the lungs, DCs undergo activation. This process arms DCs with the unique ability to induce the proliferation and differentiation of T cells responding to matching antigen in complex with MHC molecules. Depending on how DCs interact with T cells, the ensuing T cell response can be tolerogenic or immunogenic and as such, the susceptibility and severity of respiratory infections is influenced by the signals DCs receive, integrate, and then convey to T cells. It is becoming increasingly clear that these facets of DC biology are heavily influenced by the cellular components and metabolites produced by the lung and gut microbiota. In this review, we discuss the roles of different DC subsets in respiratory infections and outline how microbial metabolites impact the development, propensity for activation and subsequent activation of DCs. In particular, we highlight these concepts in the context of respiratory immunity.
Microbiota-Derived Propionate Modulates Megakaryopoiesis and Platelet Function
Authors: Dürholz Kerstin , Schmid Eva , Frech Michael , Azizov Vugar , Otterbein Nadine , Lucas Sébastien , Rauh Manfred , Schett Georg , Bruns Heiko , Zaiss Mario M. 
Published: July 2022

Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across common autoimmune diseases was shown for RA, systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS). In this context, we evaluated the role of the microbial-derived short chain fatty acid (SCFA) propionate on hematopoietic progenitors in the collagen induced inflammatory arthritis model (CIA) as we recently showed attenuating effects of preventive propionate treatment on CIA severity. In vivo, propionate treatment starting 21 days post immunization (dpi) reduced the frequency of MEPs in the bone marrow of CIA and naïve mice. Megakaryocytes numbers were reduced but increased the expression of the maturation marker CD61. Consistent with this, functional analysis of platelets showed an upregulated reactivity state following propionate-treatment. This was confirmed by elevated histone 3 acetylation and propionylation as well as by RNAseq analysis in Meg-01 cells. Taken together, we identified a novel nutritional axis that skews platelet formation and function.
Efficacy and Safety of Drug-Eluting Beads Transarterial Chemoembolization Combining Immune Checkpoint Inhibitors in Unresectable Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis
Authors: Yang Xue-Gang , Sun Yan-Yuan , Li De-Shan , Xu Guo-Hui , Huang Xiao-Qi 
Published: July 2022

PurposeTo assess the effectiveness and safety of drug-eluting beads transarterial chemoembolization plus immune checkpoint inhibitors (DEB-TACE+ICIs) versus chemotherapy (gemcitabine+cisplatin) for patients with unresectable intrahepatic cholangiocarcinoma (iCCA).Materials and MethodsThis retrospective study included unresectable iCCA patients treated with DEB-TACE+ICIs or chemotherapy between May, 2019 and August, 2021. The differences in tumor responses, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the 2 groups. Patient baseline characteristics, PFS, and OS were compared among 2 groups before and after propensity score-matching (PSM). Factors affecting PFS and OS were analyzed by Cox’s proportional hazards regression model.ResultsThe study included 49 patients with unresectable iCCA patients, 20 in the DEB-TACE+ICIs group and 29 in the chemotherapy group. PSM analysis created 20 pairs of patients in 2 groups. The patients in the DEB-TACE+ICIs group had a higher objective response rate (55.0% vs. 20.0%, P=0.022), higher PFS (median, 7.2 vs. 5.7 months, P=0.036), and higher OS (median, 13.2 vs. 7.6 months, P=0.015) than those in the chemotherapy group. Multivariate analyses suggested that chemotherapy, tumor size &gt;5cm, and multiple tumors were the independent risk factors for PFS and OS. The incidence of TRAEs was similar between the 2 groups.ConclusionCompared to chemotherapy, DEB-TACE plus ICIs improved survival and was well-tolerated in patients with unresectable iCCA.