bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race, sex and age disparities in echocardiography among Medicare beneficiaries in an integrated healthcare system
Authors: Hyland Patrick M , Xu Jiaman , Shen Changyu , Markson Lawrence J , Manning Warren J , Strom Jordan B. 
Published: October 2021

ObjectiveTo identify potential race, sex and age disparities in performance of transthoracic echocardiography (TTE) over several decades.MethodsTTE reports from five academic and community sites within a single integrated healthcare system were linked to 100% Medicare fee-for-service claims from 1 January 2005 to 31 December 2017. Multivariable Poisson regression was used to estimate adjusted rates of TTE utilisation after the index TTE according to baseline age, sex, race and comorbidities among individuals with ≥2 TTEs. Non-white race was defined as black, Asian, North American Native, Hispanic or other categories using Medicare-assigned race categories.ResultsA total of 15 870 individuals (50.1% female, mean 72.2±12.7 years) underwent a total of 63 535 TTEs (range 2–55/person) over a median (IQR) follow-up time of 4.9 (2.4–8.5) years. After the index TTE, the median TTE use was 0.72 TTEs/person/year (IQR 0.43–1.33; range 0.12–26.76). TTE use was lower in older individuals (relative risk (RR) for 10-year increase in age, 0.91, 95% CI 0.89 to 0.92, p<0.001), women (RR 0.97, 95% CI 0.95 to 0.99, p<0.001) and non-white individuals (RR 0.95, 95% CI 0.93 to 0.97, p<0.001). Black women in particular had the lowest relative use of TTE (RR 0.92, 95% CI 0.88 to 0.95, p<0.001). The only clinical conditions associated with increased TTE use after multivariable adjustment were heart failure (RR 1.04, 95% CI 1.00 to 1.08, p=0.04) and chronic obstructive pulmonary disease (RR 1.05, 95% CI 1.00 to 1.10, p=0.04).ConclusionsAmong Medicare beneficiaries with multiple TTEs in a single large healthcare system, the median TTE use after the index TTE was 0.72 TTEs/person/year, although this varied widely. Adjusted for comorbidities, female sex, non-white race and advancing age were associated with decreased TTE utilisation.
Biallelic variants in ZFP36L2 cause female infertility characterised by recurrent preimplantation embryo arrest
Authors: Zheng Wei , Sha Qian-Qian , Hu Huiling , Meng Fei , Zhou Qinwei , Chen Xueqin , Zhang Shuoping , Gu Yifan , Yan Xian , Zhao Lei , Zong Yurong , Hu Liang , Gong Fei , Lu Guangxiu , Fan Heng-Yu , Lin Ge 
Published: October 2021

BackgroundRecurrent preimplantation embryo developmental arrest (RPEA) is the most common cause of assisted reproductive technology treatment failure associated with identified genetic abnormalities. Variants in known maternal genes can only account for 20%–30% of these cases. The underlying genetic causes for the other affected individuals remain unknown.MethodsWhole exome sequencing was performed for 100 independent infertile females that experienced RPEA. Functional characterisations of the identified candidate disease-causative variants were validated by Sanger sequencing, bioinformatics and in vitro functional analyses, and single-cell RNA sequencing of zygotes.ResultsBiallelic variants in ZFP36L2 were associated with RPEA and the recurrent variant (p.Ser308_Ser310del) prevented maternal mRNA decay in zygotes and HeLa cells.ConclusionThese findings emphasise the relevance of the relationship between maternal mRNA decay and human preimplantation embryo development and highlight a novel gene potentially responsible for RPEA, which may facilitate genetic diagnoses.
The status and future of tidal marshes in New Jersey faced with sea level rise
Authors: Weis Judith S. , Watson Elizabeth Burke , Ravit Beth , Harman Charles , Yepsen Metthea 
Published: October 2021

Abstract
Salt marshes are key coastal ecosystems that provide habitats for wildlife, including invertebrates, fishes, and birds. They provide ecosystem services such as protection from storm surges and waves, attenuation of flooding, sequestration of pollutants (e.g., blue carbon), and nutrient removal. They are currently under great threat from sea level rise (SLR). We collected information about trends in the horizontal extent (acreage) of New Jersey salt marshes and recent elevation changes compared with the current local rate of SLR in New Jersey, which is between 5 and 6 mm year−1. We found pervasive, although variable, rates of marsh loss that resulted from both anthropogenic disturbance as well as edge erosion and interior ponding expected from SLR. Elevation trends suggest that the current rates of SLR exceed most marsh elevation gains, although some Phragmites-dominated marshes keep pace with SLR. Four potential remedies to address current coastal trends of marsh loss were described in the context of New Jersey’s regulatory and management environment: protection of marsh inland migration pathways, altered management of Phragmites, thin layer sediment placement, and living shoreline installations. Proactive steps are necessary if coastal wetland ecosystems are to be maintained over the next few decades.
The protein tyrosine kinase inhibitor genistein suppresses hypoxia-induced atrial natriuretic peptide secretion mediated by the PI3K/Akt-HIF-1α pathway in isolated beating rat atria
Authors: Zhang Qiu-li , Li Ping , Hong Lan , Li Rui-zhuang , Wang Jia-qi , Cui Xun 
Published: October 2021

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, has been shown to play pivotal roles in the signal transduction pathways of hypoxic disorders. In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced atrial natriuretic peptide (ANP) secretion. Radioimmunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor 1α (HIF-1α), and GATA4 in the atrial tissue. The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 μM). By Western blotting analysis, we found that hypoxia-induced increase in phosphorylation of Akt and transcriptional factors, including HIF-1α, were also reversed by genistein. The perfused HIF-1α inhibitors rotenone (0.5 μM) or CAY10585 (10 μM) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist insulin-like growth factor 1 (30 μM) also abolished ANP secretion induced by genistein and inhibited expression of HIF-1α. In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the phosphoinositide-3 kinase (PI3K)/HIF-1α dependent pathway.
The evolutions of the innermost stable circular orbits in dynamical spacetimes
Authors: Song Yong 
Published: October 2021

AbstractIn this paper, we studied the evolutions of the innermost stable circular orbits (ISCOs) in dynamical spacetimes. At first, we reviewed the method to obtain the ISCO in Schwarzschild spacetime by varying its conserved orbital angular momentum. Then, we demonstrated this method is equivalent to the effective potential method in general static and stationary spacetimes. Unlike the effective potential method, which depends on the presence of the conserved orbital energy, this method requires the existence of conserved orbital angular momentum in spacetime. So it can be easily generalized to the dynamical spacetimes where there exists conserved orbital angular momentum. From this generalization, we studied the evolutions of the ISCOs in Vaidya spacetime, Vaidya-AdS spacetime and the slow rotation limit of Kerr–Vaidya spacetime. The results given by these examples are all reasonable and can be compared with the evolutions of the photon spheres in dynamical spacetimes.
Performance of a geometric deep learning pipeline for HL-LHC particle tracking
Authors: Ju Xiangyang , Murnane Daniel , Calafiura Paolo , Choma Nicholas , Conlon Sean , Farrell Steven , Xu Yaoyuan , Spiropulu Maria , Vlimant Jean-Roch , Aurisano Adam , Hewes Jeremy , Cerati Giuseppe , Gray Lindsey , Klijnsma Thomas , Kowalkowski Jim , Atkinson Markus , Neubauer Mark , DeZoort Gage , Thais Savannah , Chauhan Aditi , Schuy Alex , Hsu Shih-Chieh , Ballow Alex , Lazar Alina 
Published: October 2021

AbstractThe Exa.TrkX project has applied geometric learning concepts such as metric learning and graph neural networks to HEP particle tracking. Exa.TrkX’s tracking pipeline groups detector measurements to form track candidates and filters them. The pipeline, originally developed using the TrackML dataset (a simulation of an LHC-inspired tracking detector), has been demonstrated on other detectors, including DUNE Liquid Argon TPC and CMS High-Granularity Calorimeter. This paper documents new developments needed to study the physics and computing performance of the Exa.TrkX pipeline on the full TrackML dataset, a first step towards validating the pipeline using ATLAS and CMS data. The pipeline achieves tracking efficiency and purity similar to production tracking algorithms. Crucially for future HEP applications, the pipeline benefits significantly from GPU acceleration, and its computational requirements scale close to linearly with the number of particles in the event.
Efficacy of Qingfei Paidu Decoction on Patients with COVID-19 Pneumonia in Wuhan, China: A Propensity Score Matching Study
Authors: Liu Zhen , Du Shan , Shao Fei , Li Haibin , Xu Shuang , Ma Xuedi , Xu Zhouming , Cui Hao , Yu Changxiao , Wu Yang , Wang Feng , Li Liyan , Chen Rui , Qiu Hui , Tang Ziren , Sun Peng 
Published: October 2021

Background. In view of the global efforts to develop effective treatments for the current worldwide coronavirus 2019 (COVID-19) pandemic, Qingfei Paidu decoction (QPD), a novel traditional Chinese medicine (TCM) prescription, was formulated as an optimized combination of constituents of classic prescriptions used to treat numerous febrile and respiratory-related diseases. This prescription has been used to treat patients with COVID-19 pneumonia in Wuhan, China. Hypothesis/Purpose. We hypothesized that QPD would have beneficial effects on patients with COVID-19. We aimed to prove this hypothesis by evaluating the efficacy of QPD in patients with COVID-19 pneumonia. Methods. In this single-center, retrospective, observational study, we identified eligible participants who received a laboratory diagnosis of COVID-19 between January 15 and March 15, 2020, in the west campus of Union Hospital in Wuhan, China. QPD was supplied as an oral liquid packaged in 200-mL containers, and patients were orally administered one package twice daily 40 minutes after a meal. The primary outcome was death, which was compared between patients who did and did not receive QPD (QPD and NoQPD groups, respectively). Propensity score matching (PSM) was used to identify cohorts. Results. In total, 239 and 522 participants were enrolled in the QPD and NoQPD groups, respectively. After PSM at a 1 : 1 ratio, 446 patients meeting the criteria were included in the analysis with 223 in each arm. In the QPD and NoQPD groups, 7 (3.2%) and 29 (13.0%) patients died, and those in the QPD group had a significantly lower risk of death (hazard ratio (HR) 0.29, 95% CI: 0.13–0.67) than those in the NoQPD group (

p

= 0.004). Furthermore, the survival time was significantly longer in the QPD group than in the NoQPD group (

p

< 0.001). Conclusion. The use of QPD may reduce the risk of death in patients with COVID-19 pneumonia.
Mucin Expression and Splicing Determine Novel Subtypes and Patient Mortality in Pancreatic Ductal Adenocarcinoma
Authors: Thompson Christopher M. , Cannon Andrew , West Sean , Ghersi Dario , Atri Pranita , Bhatia Rakesh , Smith Lynette , Rachagani Satyayanarayana , Wichman Christopher , Kumar Sushil , Batra Surinder K. 
Published: October 2021

Abstract

Purpose:
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy demonstrating aberrant and progressive expression of mucins. The contribution of individual mucins has been extensively investigated in PDAC; however, comprehensive mucin profiling including splice variants in PDAC tumors has not been reported.

Experimental Design:
Using publicly available RNA sequencing (RNA-seq) datasets, we assess the expression of mucin family members and their splice variants (SV) in PDAC tumor samples for the first time. Mucin SVs that are correlated with PDAC patient survival are validated in a cohort of patient tumor samples. Further, we use computational methods to derive novel pancreatic tumor subtypes using mucin expression signatures and their associated activated pathways.

Results:
Principal component analysis identified four novel mucin-based PDAC subtypes. Pathway analysis implicated specific biological signatures for each subtype, labeled (i) immune activated, (ii) progressive, (iii) pancreatitis-initiated, and (iv) anti-inflammatory/PanIN-initiated. Assessing mucin SVs, significantly longer survival is observed with higher expression of 4 MUC1 and 1 MUC13 SVs, whereas patients expressing 2 MUC4 and 1 MUC16 SVs had shorter survival. Using a whole-transcriptome correlation, a three-gene panel, including ESRP2, PTK6, and MAGEH1, is designated to assess PDAC tumor sample cellularity by PCR. One MUC4 SV and one MUC13 SV are quantified in a separate PDAC patient cohort, and their effects on survival are experimentally validated.

Conclusions:
Altogether, we demonstrate the unique expression pattern of mucins, four mucin-based PDAC subtypes, and the contribution of MUC1, MUC4, and MUC16 SVs in PDAC patient survival.
Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations: Results from a Multi-institutional European Retrospective Study
Authors: Vincenzi Bruno , Napolitano Andrea , Fiocco Marta , Mir Olivier , Rutkowski Piotr , Blay Jean-Yves , Reichardt Peter , Joensuu Heikki , Fumagalli Elena , Gennatas Spyridon , Hindi Nadia , Nannini Margherita , Spalato Ceruso Mariella , Italiano Antoine , Grignani Giovanni , Brunello Antonella , Gasperoni Silvia , De Pas Tommaso , Badalamenti Giuseppe , Pantaleo Maria A. , van Houdt Winan J. , IJzerman Nikki S. , Steeghs Neeltje , Gelderblom Hans , Desar Ingrid M.E. , Falkenhorst Johanna , Silletta Marianna , Sbaraglia Marta , Tonini Giuseppe , Martin-Broto Javier , Hohenberger Peter , Le Cesne Axel , Jones Robin L. , Dei Tos Angelo P. , Gronchi Alessandro , Bauer Sebastian , Casali Paolo G. 
Published: October 2021

AbstractPurpose:The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9–mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.Experimental Design:Data from 185 patients were retrospectively collected in 23 European GIST reference centers. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Univariate and multivariate unweighted and weighted Cox proportional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival.Results:Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79–1.94; mRFS: HR, 1.69; 95% CI, 0.92–3.10; IFFS: HR, 1.35; 95% CI, 0.79–2.28]. The variables consistently associated with worse survival outcomes were high mitotic index and nongastric tumor location.Conclusions:In this retrospective series of patients with KIT exon 9–mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.
Myocardial Perfusion in Hypoplastic Left Heart Syndrome
Authors: Rickers Carsten , Wegner Philip , Silberbach Michael , Madriago Erin , Gabbert Dominik Daniel , Kheradvar Arash , Voges Inga , Scheewe Jens , Attmann Tim , Jerosch-Herold Michael , Kramer Hans-Heiner 
Published: October 2021

Background:
The status of the systemic right ventricular coronary microcirculation in hypoplastic left heart syndrome (HLHS) is largely unknown. It is presumed that the systemic right ventricle’s coronary microcirculation exhibits unique pathophysiological characteristics of HLHS in Fontan circulation. The present study sought to quantify myocardial blood flow by cardiac magnetic resonance imaging and evaluate the determinants of microvascular coronary dysfunction and myocardial ischemia in HLHS.

Methods:
One hundred nineteen HLHS patients (median age, 4.80 years) and 34 healthy volunteers (median age, 5.50 years) underwent follow-up cardiac magnetic resonance imaging ≈1.8 years after total cavopulmonary connection. Right ventricle volumes and function, myocardial perfusion, diffuse fibrosis, and late gadolinium enhancement were assessed in 4 anatomic HLHS subtypes. Myocardial blood flow (MBF) was quantified at rest and during adenosine-induced hyperemia. Coronary conductance was estimated from MBF at rest and catheter-based measurements of mean aortic pressure (n=99).

Results:

Hyperemic MBF in the systemic ventricle was lower in HLHS compared with controls (1.89±0.57 versus 2.70±0.84 mL/g per min;
P
<0.001), while MBF at rest normalized by the rate-pressure product, was similar (1.25±0.36 versus 1.19±0.33;
P
=0.446). Independent risk factors for a reduced hyperemic MBF were an HLHS subtype with mitral stenosis and aortic atresia (
P
=0.017), late gadolinium enhancement (
P
=0.042), right ventricular diastolic dysfunction (
P
=0.005), and increasing age at total cavopulmonary connection (
P
=0.022). The coronary conductance correlated negatively with systemic blood oxygen saturation (r, −0.29;
P
=0.02). The frequency of late gadolinium enhancement increased with age at total cavopulmonary connection (
P
=0.014).

Conclusions:
The coronary microcirculation of the systemic ventricle in young HLHS patients shows significant differences compared with controls. These hypothesis-generating findings on HLHS-specific risk factors for microvascular dysfunction suggest a potential benefit from early relief of frank cyanosis by total cavopulmonary connection.
Matricellular Protein Cilp1 Promotes Myocardial Fibrosis in Response to Myocardial Infarction
Authors: Zhang Qing-Jun , He Yu , Li Yongnan , Shen Huali , Lin Ling , Zhu Min , Wang Zhaoning , Luo Xiang , Hill Joseph A. , Cao Dian , Luo Richard L. , Zou Raymond , McAnally John , Liao Jun , Bajona Pietro , Zang Qun S. , Yu Yonghao , Liu Zhi-Ping 
Published: October 2021

Rationale:
Cilp1 (cartilage intermediate layer protein 1) is a secreted extracellular matrix protein normally associated with bone and cartilage development. Its function and mechanism of action in adult heart disease remain elusive.

Objective:
To establish the function and mechanism of action of Cilp1 in postmyocardial infarction (MI) cardiac remodeling.

Methods and Results:

We investigated the expression of Cilp1 in mouse models of pathological cardiac remodeling and human heart failure patients. Cilp1 was expressed predominantly in cardiac fibroblasts and upregulated in response to cardiac injury and in the heart and blood of patients with heart failure. We generated
Cilp1
knock out (KO) and transgenic (Tg) mice with NCilp1 (N-terminal half of the protein) overexpressed in myofibroblasts.
Cilp1
KO mice had better cardiac function, reduced number of immune cells and myofibroblasts, and enhanced microvascular survival after MI compared with wild-type littermates. Conversely, NCilp1-transgenic mice had augmented loss of cardiac function, increased number of myofibroblasts and infarct size after the MI injury. RNA-seq and gene ontology analysis indicated that cell proliferation and mTORC1 (mammalian Target of Rapamycin Complex 1) signaling were downregulated in KO hearts compared with wild-type hearts. In vivo BrdU labeling and immunofluorescence staining showed that myofibroblast proliferation in the
Cilp1
KO heart was downregulated. Biaxial mechanical testing and extracellular matrix gene expression analysis indicated that while MI caused significant stiffness in wild-type hearts it had little effect on KO hearts. Upregulation of collagen expression after MI injury was attenuated in KO hearts. Recombinant CILP1 protein or NCilp1-conditioned medium promoted proliferation of neonatal rat ventricular cardiac fibroblasts via the mTORC1 signaling pathway.

Conclusions:
Our studies established a pathological role of Cilp1 in promoting post-MI remodeling, identified a novel function of Cilp1 in promoting myofibroblast proliferation, and suggested that Cilp1 may serve as a potential biomarker for pathological cardiac remodeling and target for fibrotic heart disease.
Assessment of an ECG‐Based System for Localizing Ventricular Arrhythmias in Patients With Structural Heart Disease
Authors: Zhou Shijie , AbdelWahab Amir , Sapp John L. , Sung Eric , Aronis Konstantinos N. , Warren James W. , MacInnis Paul J. , Shah Rushil , Horáček B. Milan , Berger Ronald , Tandri Harikrishna , Trayanova Natalia A. , Chrispin Jonathan 
Published: October 2021

Background
We have previously developed an intraprocedural automatic arrhythmia‐origin localization (AAOL) system to identify idiopathic ventricular arrhythmia origins in real time using a 3‐lead ECG. The objective was to assess the localization accuracy of ventricular tachycardia (VT) exit and premature ventricular contraction (PVC) origin sites in patients with structural heart disease using the AAOL system.

Methods and Results

In retrospective and prospective case series studies, a total of 42 patients who underwent VT/PVC ablation in the setting of structural heart disease were recruited at 2 different centers. The AAOL system combines 120‐ms QRS integrals of 3 leads (III, V2, V6) with pace mapping to predict VT exit/PVC origin site and projects that site onto the patient‐specific electroanatomic mapping surface. VT exit/PVC origin sites were clinically identified by activation mapping and/or pace mapping. The localization error of the VT exit/PVC origin site was assessed by the distance between the clinically identified site and the estimated site. In the retrospective study of 19 patients with structural heart disease, the AAOL system achieved a mean localization accuracy of 6.5±2.6 mm for 25 induced VTs. In the prospective study with 23 patients, mean localization accuracy was 5.9±2.6 mm for 26 VT exit and PVC origin sites. There was no difference in mean localization error in epicardial sites compared with endocardial sites using the AAOL system (6.0 versus 5.8 mm,
P
=0.895).

Conclusions
The AAOL system achieved accurate localization of VT exit/PVC origin sites in patients with structural heart disease; its performance is superior to current systems, and thus, it promises to have potential clinical utility.