bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stroke Risk Stratification in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting
Authors: Taha Amar , Nielsen Susanne J. , Franzén Stefan , Rezk Mary , Ahlsson Anders , Friberg Leif , Björck Staffan , Jeppsson Anders , Bergfeldt Lennart 
Published: May 2022

Background

The CHA
2
DS
2
‐VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long‐term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new‐onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA
2
DS
2
‐VASc scoring system for estimating the 1‐year ischemic stroke risk in patients with new‐onset postoperative atrial fibrillation after coronary artery bypass grafting.

Methods and Results

All patients with new‐onset postoperative atrial fibrillation and without oral anticoagulation after first‐time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry‐based observational cohort study. The 1‐year ischemic stroke rate at each step of the CHA
2
DS
2
‐VASc score was estimated using a Kaplan‐Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow‐up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA
2
DS
2
‐VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results.

Conclusions

Patients with new‐onset atrial fibrillation after coronary artery bypass grafting and a CHA
2
DS
2
‐VASc score <3 have such a low 1‐year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.
Feasibility, Safety, and Short‐Term Outcomes of Transcatheter Patent Ductus Arteriosus Closure in Premature Infants on High‐Frequency Jet Ventilation
Authors: Shibbani Kamel , Mohammad Nijres Bassel , McLennan Daniel , Bischoff Adrianne Rahde , Giesinger Regan , McNamara Patrick J. , Klein Jonathan , Windsor Jimmy , Aldoss Osamah 
Published: May 2022

Background
Prolonged exposure to a hemodynamically significant patent ductus arteriosus (PDA) is associated with major morbidity, particularly in infants born at <27 weeks’ gestation. High‐frequency jet ventilation (HFJV) is a standard of care at our center. There are no data about transcatheter PDA closure while on HFJV. The aim of this study was to assess the feasibility, safety, and outcomes of HFJV during transcatheter PDA closure.

Methods and Results

This is a retrospective cohort study of premature infants undergoing transcatheter device closure on HFJV. The primary outcome was successful device placement. Secondary outcomes included procedure time, fluoroscopy time and dose, time off unit, device complications, need for escalation in respiratory support, and 7‐day survival. Subgroup comparative evaluation of patients managed with HFJV versus a small cohort of patients managed with conventional mechanical ventilation was performed. Thirty‐eight patients were included in the study. Median age and median weight at PDA device closure for the HFJV cohort were 32 days (interquartile range, 25.25–42.0 days) and 1115 g (interquartile range, 885–1310 g), respectively. There was successful device placement in 100% of patients. There were no device complications noted. The time off unit and the procedure time were not significantly different between the HFJV group and the conventional ventilation group. Infants managed by HFJV had shorter median fluoroscopy times (4.5 versus 6.1 minutes;
P
<0.05) and no increased risk of adverse respiratory outcomes.

Conclusions
Transcatheter PDA closure in premature infants on HFJV is a safe and effective approach that does not compromise device placement success rate and does not lead to secondary complications.
The Effects of Transit Systems on International Trade
Authors: Carballo Jerónimo , Graziano Alejandro G. , Schaur Georg , Volpe Martincus Christian 
Published: May 2022

Abstract
In this paper, we estimate the trade effects of a transit system upgrading that streamlines border processing in developing countries. Our empirical approach combines transaction-level export data from El Salvador with unique data that distinguishes export flows that were processed on the transit system. Our results indicate that the new transit system lowered regulatory border costs and raised exports. At the low end, our back-of-the-envelope estimate of the return to investment is US$ 3-to-1. This evidence informs a policy covered by the 2013 WTO Agreement of Trade Facilitation.
Testing the Presence of Implicit Hiring Quotas with Application to German Universities
Authors: Janys Lena 
Published: May 2022

Abstract
Women are underrepresented in academia in general and economics in particular. I introduce a test to detect an underresearched form of hiring bias: implicit quotas. I derive a test under the null hypothesis of gender-blind hiring that requires no additional information about individual hires and can be used to analyze hiring bias in a variety of other hiring settings. I derive its asymptotic distribution and propose a parametric bootstrap procedure that resamples from the exact distribution. I analyze the distribution of female professors at German universities and find an implicit quota of one or two women on the department level.
Random Assignment with Nonrandom Peers: A Structural Approach to Counterfactual Treatment Assessment
Authors: Griffith Alan 
Published: May 2022

Abstract
Efforts to leverage peer effects by changing assignment have often fallen short due to endogenous peer choice. To address this, I build a two-part model: agents form networks via continuous linking decisions; conditional on realized networks, outcomes are determined. I provide results on identification of both parts of the model. Using data from a randomized study in India, I estimate the model, assess its performance in out-of-sample prediction, and simulate outcomes under preferential assignment rules. This paper contributes new methodology for identifying effects of alternative assignments in the presence of network endogeneity, as well as identification of network formation models.
Congressional Elections and Union Officer Prosecutions
Authors: Downey Mitch 
Published: May 2022

Abstract
Politicizing the investigation of politically active groups is harmful for both the justice system and democratic accountability. I test whether members of the U.S. Congress affect the investigation and prosecution of politically active labor unions. Union officers are 1.5 percentage points more likely to be prosecuted when their supported candidate barely loses instead of barely wins (compared to the 3% base rate). Anecdotal evidence and a novel decomposition suggest a role for both union-supported winners protecting allies and union-opposed winners pushing for aggressive prosecution of their opponents. I show that prosecutions undermine unions' strength, and I calculate implications for the incumbency advantage.
The Targeting and Impact of Partisan Gerrymandering: Evidence from a Legislative Discontinuity
Authors: Jeong Dahyeon , Shenoy Ajay 
Published: May 2022

Abstract
A party’s influence over redistricting increases discontinuously when its seat share in the state legislature exceeds 50%. We apply bunching tests to show that, in the election before redistricting, parties systematically win narrow majorities in legislatures of states where they have lost recent U.S. House races. This trend of losses is reversed after redistricting despite no change in overall House vote shares in states near the cutoff. The pre-to-post-redistricting change in regression discontinuity estimates implies that the party that controls redistricting engineers an 11 percentage point increase in its probability of winning a House race.
How I approach smoldering multiple myeloma
Authors: Vaxman Iuliana , Gertz Morie A. 
Published: May 2022

Abstract
The current standard of care in smoldering multiple myeloma (SMM) is close surveillance, outside of clinical trials. Efforts are being made to understand the pathobiologic process that leads to the progression of SMM to active MM. This review provides a critical description of available data, including risk factors and risk models of progression, as well as clinical trials investigating interventions for this patient population. We describe 2 cases in which patients were seen before the concept of a myeloma-defining event was established. Today, based on the International Myeloma Working Group criteria, both patients would have been identified as experiencing myeloma-defining events, and therapy would have been initiated. These cases show that occasionally, patients can undergo observation only, even when they exceed criteria for high-risk SMM.
A phase 1 dose escalation study of the pyruvate kinase activator mitapivat (AG-348) in sickle cell disease
Authors: Xu Julia Z. , Conrey Anna , Frey Ingrid , Gwaabe Eveline , Menapace Laurel A. , Tumburu Laxminath , Lundt Maureen , Lequang Timothy , Li Quan , Glass Kristen , Dunkelberger Emily B. , Iyer Varsha , Mangus Heidi , Kung Charles , Dang Lenny , Kosinski Penelope A. , Hawkins Peter , Jeffries Neal , Eaton William A. , Lay Thein Swee 
Published: May 2022

Abstract
Polymerization of deoxygenated hemoglobin S underlies the pathophysiology of sickle cell disease (SCD). In activating red blood cell pyruvate kinase and glycolysis, mitapivat (AG-348) increases adenosine triphosphate (ATP) levels and decreases the 2,3-diphosphoglycerate (2,3-DPG) concentration, an upstream precursor in glycolysis. Both changes have therapeutic potential for patients with SCD. Here, we evaluated the safety and tolerability of multiple ascending doses of mitapivat in adults with SCD with no recent blood transfusions or changes in hydroxyurea or l-glutamine therapy. Seventeen subjects were enrolled; 1 subject was withdrawn shortly after starting the study. Sixteen subjects completed 3 ascending dose levels of mitapivat (5, 20, and 50 mg, twice daily [BID]) for 2 weeks each; following a protocol amendment, the dose was escalated to 100 mg BID in 9 subjects. Mitapivat was well tolerated at all dose levels, with the most common treatment-emergent adverse events (AEs) being insomnia, headache, and hypertension. Six serious AEs (SAEs) included 4 vaso-occlusive crises (VOCs), non–VOC-related shoulder pain, and a preexisting pulmonary embolism. Two VOCs occurred during drug taper and were possibly drug related; no other SAEs were drug related. Mean hemoglobin increase at the 50 mg BID dose level was 1.2 g/dL, with 9 of 16 (56.3%) patients achieving a hemoglobin response of a ≥1 g/dL increase compared with baseline. Mean reductions in hemolytic markers and dose-dependent decreases in 2,3-DPG and increases in ATP were also observed. This study provides proof of concept that mitapivat has disease-modifying potential in patients with SCD. This trial was registered at www.clinicaltrials.gov as #NCT04000165.
Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm
Authors: Yang Huan , George Sam J. , Thompson Dane A. , Silverman Harold A. , Tsaava Téa , Tynan Aisling , Pavlov Valentin A. , Chang Eric H. , Andersson Ulf , Brines Michael , Chavan Sangeeta S. , Tracey Kevin J. 
Published: May 2022

AbstractBackgroundSevere COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease, attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine released by mast cells. Here we hypothesized that famotidine activates the inflammatory reflex, a brain-integrated vagus nerve mechanism which inhibits inflammation via alpha 7 nicotinic acetylcholine receptor (α7nAChR) signal transduction, to prevent cytokine storm.MethodsThe potential anti-inflammatory effects of famotidine and other H2R antagonists were assessed in mice exposed to lipopolysaccharide (LPS)-induced cytokine storm. As the inflammatory reflex is integrated and can be stimulated in the brain, and H2R antagonists penetrate the blood brain barrier poorly, famotidine was administered by intracerebroventricular (ICV) or intraperitoneal (IP) routes.ResultsFamotidine administered IP significantly reduced serum and splenic LPS-stimulated tumor necrosis factor (TNF) and IL-6 concentrations, significantly improving survival. The effects of ICV famotidine were significantly more potent as compared to the peripheral route. Mice lacking mast cells by genetic deletion also responded to famotidine, indicating the anti-inflammatory effects are not mast cell-dependent. Either bilateral sub-diaphragmatic vagotomy or genetic knock-out of α7nAChR abolished the anti-inflammatory effects of famotidine, indicating the inflammatory reflex as famotidine’s mechanism of action. While the structurally similar H2R antagonist tiotidine displayed equivalent anti-inflammatory activity, the H2R antagonists cimetidine or ranitidine were ineffective even at very high dosages.ConclusionsThese observations reveal a previously unidentified vagus nerve-dependent anti-inflammatory effect of famotidine in the setting of cytokine storm which is not replicated by high dosages of other H2R antagonists in clinical use. Because famotidine is more potent when administered intrathecally, these findings are also consistent with a primarily central nervous system mechanism of action.
Identification and validation of an eight-lncRNA signature that predicts prognosis in patients with esophageal squamous cell carcinoma
Authors: Zhang Jinfeng , Ling Xiaodong , Fang Chengyuan , Ma Jianqun 
Published: May 2022

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is correlated with worse clinical prognosis and lacks available targeted therapy. Thus, identification of reliable biomarkers is required for the diagnosis and treatment of ESCC.

Methods
We downloaded the GSE53625 dataset as a training dataset to screen differentially expressed RNAs (DERs) with the criterion of false discovery rate (FDR) < 0.05 and |log2fold change (FC)| > 1. A support vector machine classifier was used to find the optimal feature gene set that could conclusively distinguish different samples. An eight-lncRNA signature was identified by random survival forest algorithm and multivariate Cox regression analysis. The RNA sequencing data from The Cancer Genome Atlas (TCGA) database were used for external validation. The predictive value of the signature was assessed using Kaplan–Meier test, time-dependent receiver operating characteristic (ROC) curves, and dynamic area under the curve (AUC). Furthermore, a nomogram to predict patients’ 3-year and 5-year prognosis was constructed. CCK-8 assay, flow cytometry, and transwell assay were conducted in ESCC cells.

Results
A total of 1136 DERs, including 689 downregulated mRNAs, 318 upregulated mRNAs, 74 downregulated lncRNAs and 55 upregulated lncRNAs, were obtained in the GES53625 dataset. From the training dataset, we identified an eight-lncRNA signature, (ADAMTS9-AS1, DLX6-AS1, LINC00470, LINC00520, LINC01497, LINC01749, MAMDC2-AS1, and SSTR5-AS1). A nomogram based on the eight-lncRNA signature, age, and pathologic stage was developed and showed good accuracy for predicting 3-year and 5-year survival probability of patients with ESCC. Functionally, knockdown of LINC00470 significantly suppressed cell proliferation, G1/S transition, and migration in two ESCC cell lines (EC9706 and TE-9). Moreover, knockdown of LINC00470 downregulated the protein levels of PCNA, CDK4, and N-cadherin, while upregulating E-cadherin protein level in EC9706 and TE-9 cells.

Conclusion
Our eight-lncRNA signature and nomogram can provide theoretical guidance for further research on the molecular mechanism of ESCC and the screening of molecular markers.
Mechanism-aware imputation: a two-step approach in handling missing values in metabolomics
Authors: Dekermanjian Jonathan P. , Shaddox Elin , Nandy Debmalya , Ghosh Debashis , Kechris Katerina 
Published: May 2022

AbstractWhen analyzing large datasets from high-throughput technologies, researchers often encounter missing quantitative measurements, which are particularly frequent in metabolomics datasets. Metabolomics, the comprehensive profiling of metabolite abundances, are typically measured using mass spectrometry technologies that often introduce missingness via multiple mechanisms: (1) the metabolite signal may be smaller than the instrument limit of detection; (2) the conditions under which the data are collected and processed may lead to missing values; (3) missing values can be introduced randomly. Missingness resulting from mechanism (1) would be classified as Missing Not At Random (MNAR), that from mechanism (2) would be Missing At Random (MAR), and that from mechanism (3) would be classified as Missing Completely At Random (MCAR). Two common approaches for handling missing data are the following: (1) omit missing data from the analysis; (2) impute the missing values. Both approaches may introduce bias and reduce statistical power in downstream analyses such as testing metabolite associations with clinical variables. Further, standard imputation methods in metabolomics often ignore the mechanisms causing missingness and inaccurately estimate missing values within a data set. We propose a mechanism-aware imputation algorithm that leverages a two-step approach in imputing missing values. First, we use a random forest classifier to classify the missing mechanism for each missing value in the data set. Second, we impute each missing value using imputation algorithms that are specific to the predicted missingness mechanism (i.e., MAR/MCAR or MNAR). Using complete data, we conducted simulations, where we imposed different missingness patterns within the data and tested the performance of combinations of imputation algorithms. Our proposed algorithm provided imputations closer to the original data than those using only one imputation algorithm for all the missing values. Consequently, our two-step approach was able to reduce bias for improved downstream analyses.
Molecular docking analysis reveals the functional inhibitory effect of Genistein and Quercetin on TMPRSS2: SARS-COV-2 cell entry facilitator spike protein
Authors: Manjunathan Reji , Periyaswami Vijayalakshmi , Mitra Kartik , Rosita Arokiaraj Sherlin , Pandya Medha , Selvaraj Jayaraman , Ravi Lokesh , Devarajan Nalini , Doble Mukesh 
Published: May 2022

Abstract
Background
The Transmembrane Serine Protease 2 (TMPRSS2) of human cell plays a significant role in proteolytic cleavage of SARS-Cov-2 coronavirus spike protein and subsequent priming to the receptor ACE2. Approaching TMPRSS2 as a therapeutic target for the inhibition of SARS-Cov-2 infection is highly promising. Hence, in the present study, we docked the binding efficacy of ten naturally available phyto compounds with known anti-viral potential with TMPRSS2. The aim is to identify the best phyto compound with a high functional affinity towards the active site of the TMPRSS2 with the aid of two different docking software. Molecular Dynamic Simulations were performed to analyse the conformational space of the binding pocket of the target protein with selected molecules.

Results
Docking analysis using PyRx version 0.8 along with AutoDockVina reveals that among the screened phyto compounds, Genistein shows the maximum binding affinity towards the hydrophobic substrate-binding site of TMPRSS2 with three hydrogen bonds interaction ( − 7.5 kcal/mol). On the other hand, molecular docking analysis using Schrodinger identified Quercetin as the most potent phyto compound with a maximum binding affinity towards the hydrophilic catalytic site of TMPRSS2 ( − 7.847 kcal/mol) with three hydrogen bonds interaction. The molecular dynamics simulation reveals that the Quercetin-TMPRSS complex is stable until 50 ns and forms stable interaction with the protein ( − 22.37 kcal/mol of MM-PBSA binding free energy). Genistein creates a weak interaction with the loop residues and hence has an unstable binding and exits from the binding pocket.

Conclusion

The compounds, Quercetin and Genistein, can inhibit the TMPRSS2 guided priming of the spike protein. The compounds could reduce the interaction of the host cell with the type I transmembrane glycoprotein to prevent the entry of the virus. The critical finding is that compared to Genistein, Quercetin exhibits higher binding affinity with the catalytic unit of TMPRSS2 and forms a stable complex with the target. Thus, enhancing our innate immunity by consuming foods rich in Quercetin and Genistein or developing a novel drug in the combination of Quercetin and Genistein could be the brilliant choices to prevent SARS-Cov-2 infection when we consider the present chaos associated with vaccines and anti-viral medicines.
Transcriptomic and genomic analysis provides new insights in molecular and genetic processes involved in zucchini ZYMV tolerance
Authors: Amoroso C. G. , Andolfo G. , Capuozzo C. , Di Donato A. , Martinez C. , Tomassoli L. , Ercolano M. R. 
Published: May 2022

AbstractBackgroundCucurbita pepois highly susceptible to Zucchini yellow mosaic virus (ZYMV) and the resistance found in several wild species cannot be considered as complete or broad-spectrum resistance. In this study, a source of tolerance introgressed inC. pepo(381e) fromC. moschata,in True French (TF) background, was investigated 12 days post-inoculation (DPI) at transcriptomic and genomic levels.ResultsThe comparative RNA-sequencing (RNA-Seq) of TF (susceptible to ZYMV) and 381e (tolerant to ZYMV) allowed the evaluation of about 33,000 expressed transcripts and the identification of 146 differentially expressed genes (DEGs) in 381e, mainly involved in photosynthesis, transcription, cytoskeleton organization and callose synthesis. By contrast, the susceptible cultivar TF triggered oxidative processes related to response to biotic stimulus and activated key regulators of plant virus intercellular movement. In addition, the discovery of variants located in transcripts allowed the identification of two chromosome regions rich in Single Nucleotide Polymorphisms (SNPs), putatively introgressed fromC. moschata,containing genes exclusively expressed in 381e.Conclusion381e transcriptome analysis confirmed a global improvement of plant fitness by reducing the virus titer and movement. Furthermore, genes implicated in ZYMV tolerance inC. moschataintrogressed regions were detected. Our work provides new insight into the plant virus recovery process and a better understanding of the molecular basis of 381e tolerance.