bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Management of Atrial Fibrillation: A Century of Expert Opinions in Cecil Textbook of Medicine
Authors: Manu Peter , Rogozea Liliana M. , Dan Gheorghe-Andrei 
Published: January 2022

Background:
Advances in drug therapy for atrial fibrillation (AF) have had a significant impact on the quality of life of a substantial majority of affected persons, which has contributed to a remarkable decrease in the frequency and severity of thromboembolic complications, hospitalizations, and mortality.

Study Question:
What are the milestones of the changes in the expert approach to the pharmacological management of AF in the past century?

Study Design:
To determine the changes in the experts' approach to the management of AF, as presented in a widely used textbook in the United States.

Data Sources:
The chapters presenting the management of AF in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020.

Results:
AF was consistently described in Cecil Textbook of Medicine as the most common sustained arrhythmia in adults. The authors emphasized its thromboembolic complications and potential for hemodynamic deterioration. Rate control with digitalis and rhythm control with quinidine were the standard in 1927. The pharmacological advances have focused on atrioventricular nodal blocking for rate control, conversion to and maintenance of sinus rhythm, and preventive anticoagulation. The first new class of drugs for rate control was beta-adrenergic receptor blockers, starting with propranolol which was introduced in 1979, followed by the calcium channel blocker verapamil in 1988. Rhythm control with amiodarone, a potassium channel blocker, has been recommended since 2004, and the sodium channel blockers propafenone and flecainide became part of standard therapy in 2008. Anticoagulation with warfarin was recommended starting in 2000, followed by the introduction of direct thrombin inhibitor in 2012 and factor Xa inhibitors in 2016.

Conclusions:
The pharmacological management of AF was unchanged for more than 50 years (1927–1979), a period during which the devastating effects of thromboembolic complications were not addressed. The major therapeutic advance is represented by preventive anticoagulation with the newer, safer, and more user-friendly direct thrombin and factor Xa inhibitors.
Diagnosis and Follow‐up of Incidental Liver Lesions in Children
Authors: Karmazyn Boaz , Rao Girish S. , Johnstone Lindsey S. , Severance Tyler S. , Ferguson Michael J. , Marshalleck Francis E. , Molleston Jean P. 
Published: January 2022

ABSTRACTIncidental liver lesions are identified in children without underlying liver disease or increased risk of hepatic malignancy in childhood. Clinical and imaging evaluation of incidental liver lesions can be complex and may require a multidisciplinary approach. This review aims to summarize the diagnostic process and follow‐up of incidental liver lesions based on review of the literature, use of state‐of‐the‐art imaging, and our institutional experience. Age at presentation, gender, alpha fetoprotein levels, tumor size, and imaging characteristics should all be taken into consideration to optimize diagnosis process. Some lesions, such as simple liver cyst, infantile hemangioma, focal nodular hyperplasia (FNH), and focal fatty lesions, have specific imaging characteristics. Recently, contrast‐enhanced ultrasound (CEUS) was Food and Drug Administration (FDA)‐approved for the evaluation of pediatric liver lesions. CEUS is most specific in lesions smaller than 3 cm and is most useful in the diagnosis of infantile hemangioma, FNH, and focal fatty lesions. The use of hepatobiliary contrast in MRI increases specificity in the diagnosis of FNH. Recently, lesion characteristics in MRI were found to correlate with subtypes of hepatocellular adenomas and associated risk for hemorrhage and malignant transformation. Biopsy should be considered when there are no specific imaging characteristics of a benign lesion. Surveillance with imaging and alpha fetoprotein (AFP) should be performed to confirm the stability of lesions when the diagnosis cannot be determined, and whenever biopsy is not feasible.
Real‐life Performance of Multiplex Celiac Antibody Test in the Diagnosis of Pediatric Celiac Disease
Authors: Guz‐Mark Anat , Kori Michal , Topf‐Olivestone Chani , Weinberger Ronit , Morgenstern Sara , Ziv‐Sokolovskaya Nadya , Shamir Raanan 
Published: January 2022

ABSTRACTObjective:Tissue‐transglutaminase antibodies (TGA) may be used to diagnose celiac disease (CD) without biopsy in selected cases. We aimed to investigate real‐life performance of a CD serology automated analyzer (Bioplex2200), and to explore the correlation between TGA levels and intestinal biopsies in children.Methods:A retrospective review was performed in 2 pediatric gastroenterological centers, between November 1, 2018 and April 1, 2020 and included patients with both TGA serology testing and duodenal biopsies. Retrieved data included patients’ demographics, medical background, TGA levels, and biopsy results.Results:Overall, 538 children were evaluated, 256 with positive TGA (68.4% girls, median age 6.4 years), and 282 with negative TGA (53.9% girls, median age 13.4 years). Among patients with positive TGA, intestinal biopsies confirmed CD in 219 (85.5%). Overall, positive serology with normal histology was found in 14.5% of the cohort, with 52%; 21.6%; 21.1%; and 4.2% in TGA ranges of 1 to 3 times upper limit of normal (ULN); 3 to 5 ULN; 5 to 10 ULN; and above 10 times ULN, respectively, P < 0.001. Area under the receiver‐operating characteristic curve (AUC) was 0.963 (95% CI 0.947–0.980). Among patients with positive TGA, 216 (84.4%) had positive anti‐endomysial antibodies. In this sub‐group, the overall diagnostic performance was inferior, with AUC of 0.737 (95% CI 0.834–0.839).Conclusions:The Multiplex TGA assay had a very high diagnostic accuracy in real‐life. Among patients with positive TGA, adding EMA did not improve the diagnostic performance of the test. False‐positive rates differed between different ranges of TGA and were low with TGA above 10 times ULN.
Liver Transplantation in Recipients With Class III Obesity: Posttransplant Outcomes and Weight Gain
Authors: Soma Daiki , Park Yujin , Mihaylov Plamen , Ekser Burcin , Ghabril Marwan , Lacerda Marco , Chalasani Naga , Mangus Richard S. , Kubal Chandrashekhar A. 
Published: January 2022

Background.
There has been a dramatic increase in obesity in the United States. Several studies have reported conflicting results for the impact of obesity on outcomes of liver transplantation (LT). This study aims to assess the impact of obesity on LT and changes in body mass index (BMI) after transplantation.

Methods.
All adult LTs performed at Indiana University between 2001 and 2018 were reviewed. BMIs of recipients were subdivided into 6 categories. Survival outcomes were compared across the subgroup. BMI was followed up in a cohort of patients from 2008 to 2018.

Results.
Among 2024 patients, 25% were in class I obesity, 9.3% were in class II obesity, and 1.1% were in class III obesity. There was no significant difference in patient and graft survival at 10-y follow-up with respect to BMI. Among 1004 patients in the subgroup, BMI of all groups except the underweight group declined in the first 3 mo postoperatively; however, the BMI of all groups except the class III obesity group returned to the pre-LT level by 2 y and reached a plateau by 5 y. In the class III obesity group, there was a significant increase in body weight at 5 y.

Conclusions.
Class III obesity was not associated with higher mortality in our cohort. Because our cohort is small, it may be underpowered to detect a smaller difference in outcome. From our observation, obesity should not be considered a contraindication for LT. Post-LT interventions are required to prevent significant weight gain for the class III obesity group.
Intraoperative Verapamil Fails to Reduce Delayed Graft Function in Donation After Circulatory Death Renal Allografts
Authors: Lovett Jessica T. , Stern Jeffrey , Weldon Elaina P. , Lonze Bonnie E. , Stewart Zoe A. 
Published: January 2022

Background.
The shortage of transplantable organs has led to increased utilization of kidneys that may be particularly vulnerable to ischemia-reperfusion injury (IRI) and delayed graft function (DGF). Kidneys from donation after circulatory death (DCD) donors have additional IRI from donor procurement that results in increased risk of DGF. Verapamil may reduce IRI in kidney allografts when given at the time of organ reperfusion. This study sought to determine if intraoperative administration of verapamil (Ver) could reduce the risk of DGF in DCD kidney transplants.

Methods.
A single-center retrospective matched cohort study was performed of 93 Ver (–) kidney transplant recipients compared with 93 Ver (+) kidney transplant recipients, matched by donor age, Kidney Donor Profile Index, and DCD status. Covariates that could impact DGF risk were evaluated by univariate and multivariate logistic regression analyses.

Results.
The Ver (–) and Ver (+) matched cohorts did not have any significant differences in the demographic covariates. There was no difference in DGF rate between the Ver cohorts in either the overall study population or within the DCD subgroup. There was a trend toward reduced DGF in the Ver (+) cohort for cold ischemia time (CIT) ≤24 h, but this failed to achieve statistical significance. On multivariate analysis, only CIT was found to be independently associated with DGF.

Conclusions.
Intraoperative verapamil failed to reduce DGF risk in DCD kidney allografts. Limitations to this study include nonrandomization for the intraoperative administration of verapamil and the mean CIT >24 h in the study population. Only CIT was an independent prognosticator for DGF on multivariate analysis in a cohort matched for DCD status, consistent with prior studies.
The runaway evolution of SARS-CoV-2 leading to the highly evolved Delta strain
Authors: Ruan Yongsen , Hou Mei , Tang Xiaolu , He Xionglei , Lu Xuemei , Lu Jian , Wu Chung-I , Wen Haijun 
Published: January 2022

AbstractIn new epidemics after the host shift, the pathogens may experience accelerated evolution driven by novel selective pressures. When the accelerated evolution enters a positive feedback loop with the expanding epidemics, the pathogen’s runaway evolution may be triggered. To test this possibility in COVID-19, we analyze the extensive databases and identify 5 major waves of strains, one replacing the previous one in 2020 – 2021. The mutations differ entirely between waves and the number of mutations continues to increase, from 3-4 to 21-31. The latest wave is the Delta strain which accrues 31 new mutations to become highly prevalent. Interestingly, these new mutations in Delta strain emerge in multiple stages with each stage driven by 6 – 12 coding mutations that form a fitness group. In short, the evolution of SARS-CoV-2 from the oldest to the youngest wave, and from the earlier to the later stages of the Delta wave, is a process of acceleration with more and more mutations. The global increase in the viral population size (M(t), at time t) and the mutation accumulation (R(t)) may have indeed triggered the runaway evolution in late 2020, leading to the highly evolved Alpha and then Delta strain. To suppress the pandemic, it is crucial to break the positive feedback loop between M(t) and R(t), neither of which has yet to be effectively dampened by late 2021. New waves beyond Delta, hence, should not be surprising.
Safety and immunogenicity of anti-SARS CoV-2 conjugate vaccine SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults: Phase IIb Clinical Trial
Authors: Toledo-Romani María Eugenia , García-Carmenate Mayra , Verdecia-Sánchez Leslyhana , Pérez-Rodríguez Suzel , Rodriguez-González Meybis , Valenzuela-Silva Carmen , Paredes-Moreno Beatriz , Sanchez-Ramirez Belinda , González-Mugica Raúl , Hernández-Garcia Tays , Orosa-Vázquez Ivette , Díaz-Hernández Marianniz , Pérez-Guevara María Teresa , Enriquez-Puertas Juliet , Noa-Romero Enrique , Palenzuela-Diaz Ariel , Baro-Roman Gerardo , Mendoza-Hernández Ivis , Muñoz Yaima , Gómez-Maceo Yanet , Santos-Vega Bertha Leysi , Fernandez-Castillo Sonsire , Climent-Ruiz Yanet , Rodríguez-Noda Laura , Santana-Mederos Darielys , García-Vega Yanelda , Wu-Chen Guang , Doroud Delaram , Biglari Alireza , Boggiano-Ayo Tammy , Valdés-Balbín Yury , García-Rivera Daniel , García-Rivera Dagmar , Vérez-Bencomo Vicente ,   SOBERANA Research Group
Published: January 2022

AbstractBackgroundWe report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults in a phase IIb clinical trial.MethodThis phase IIb trial was designed as parallel, multicentre, adaptive, double blind, randomized and placebo-controlled. Subjects (N=810) aged 19-80 years were randomized to receive two doses of the recombinant SARS CoV-2 receptor binding domain (RBD) conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredient of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD IgG concentration. Secondary outcomes were safety, reactogenicity and neutralizing antibodies.ResultsSeroconversion rate in vaccinees was respectively 76.3 and 96.8% after two or three doses, compared with 7.3% in placebo group. Anti-RBD IgG increased significantly after first and second dose of SOBERANA 02 respect to placebo group; and the third dose with SOBERANA Plus boosts the response compared to the second dose. Neutralizing IgG antibodies were detected against D614G and VOCs α, β and δ. Specific and functional antibodies were detected at least until 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%); with only one serious AE consistent with vaccination. Local pain was the most frequent AE.ConclusionsTwo doses of SOBERANA 02 were well tolerated, safe an immunogenic in adults aged 19-80 years old. The heterologous combination with a third dose of SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after finishing the vaccination schedule.Trial registryhttps://rpcec.sld.cu/trials/RPCEC00000347
Seroresponse to third doses of SARS-CoV-2 vaccine among patients receiving maintenance dialysis
Authors: Hsu Caroline M. , Lacson Eduardo K. , Manley Harold J. , Aweh Gideon N. , Miskulin Dana , Johnson Doug , Weiner Daniel E. 
Published: January 2022

AbstractGiven the increased morbidity and mortality from COVID-19 among patients undergoing maintenance dialysis, we examined the seroresponse to an additional dose of SARS-CoV-2 mRNA vaccine, using a hypothesized protective anti-spike protein IgG antibody threshold of 7 based on prior work. Among 395 patients, 384 (97%) had seroresponse ≥7 following administration of the third dose. Among those with suboptimal (peak <7) and minimal (peak <1) seroresponse to an initial mRNA vaccine regimen, the rate of seroresponse ≥7 following a third dose was 97% (36 of 37) and 64% (14 of 22), respectively. Given ongoing high rates of COVID-19 and rapidly waning immunity after an initial vaccine series, we recommend a third mRNA vaccine dose be standard for all patients receiving maintenance dialysis.
The French Covid-19 vaccination policy did not solve vaccination inequities: a nationwide longitudinal study on 64.5 million individuals
Authors: Débarre F. , Lecoeur E. , Guimier L. , Jauffret-Roustide M. , Jannot A.-S. 
Published: January 2022

AbstractContextTo encourage Covid-19 vaccination, France introduced during the Summer 2021 a “Sanitary Pass,” which morphed into a “Vaccine Passe” in early 2022. While the Sanity Pass led to an increase in Covid-19 vaccination rates, spatial heterogeneities in vaccination rates remained. To identify potential determinants of these heterogeneities and evaluate the French Sanitary and Vaccine Pass’ efficacies in reducing them, we used a data-driven approach on exhaustive nationwide data, gathering 141 socio-economic, political and geographic indicators.MethodsWe considered the association between being a district above the median value of the first-dose vaccination rates and being above the median value of each indicator at different time points: just before the sanitary pass announcement (week 2021-W27), just before the sanitary pass came into force (week 2021-W31) and one month after (week 2021-W35), and the equivalent dates for the vaccine pass (weeks 2021-W49, 2022-W03, 2022-W07). We then considered the change over time of vaccination rates according to deciles of the three of the most associated indicators.ResultsThe indicators most associated with vaccination rates were the share of local income coming from unemployment benefits, the proportion of overcrowded households, the proportion of immigrants in the district, and vote for an “anti-establishment” candidate at the 2017 Presidential election. Vaccination rate also were also contrasted along a North-West – South East axis, with lower vaccination coverage in the South-East of France.ConclusionOur analysis reveals that, both before and after the introduction of the French sanitary and vaccination passes, factors with the largest impact are related to poverty, immigration, and trust in the government.
ifCNV: a novel isolation-forest-based package to detect copy number variations from various NGS datasets
Authors: Cabello-Aguilar Simon , Vendrell Julie A. , Van Goethem Charles , Brousse Mehdi , Gozé Catherine , Frantz Laurent , Solassol Jérôme 
Published: January 2022

AbstractCopy number variations (CNVs) are an essential component of genetic variation distributed across large parts of the human genome. CNV detection from next-generation sequencing data and artificial intelligence algorithms has progressed in recent years. However, only a few tools have taken advantage of machine learning algorithms for CNV detection, and none propose using artificial intelligence to automatically detect probable CNV-positive samples. Furthermore, in general, most CNV software that is developed for specific data types has sub-optimal reliability for routine practice. In addition, the most developed approach is to use a reference or normal dataset to compare with the samples of interest, and it is well known that selecting appropriate normal samples represents a challenging task which dramatically influences the precision of results in all CNV-detecting tools. With careful consideration of these issues, we propose here ifCNV, a new software based on isolation forests that creates its own reference, available in R and python with customisable parameters. ifCNV combines artificial intelligence using two isolation forests and a comprehensive scoring method to faithfully detect CNVs among various samples. It was validated using datasets from diverse origins (capture and amplicon, germline and somatic), and it exhibits high sensitivity, specificity and accuracy. ifCNV is a publicly available open-source software that allows the detection of CNVs in many clinical situations.Key pointsCopy number variation detectionMachine learningLocalisation scoringBenchmark on various clinical situations and on various datasetsEasy-to-use R and Python open-source Package
Structural and computational insights into the SARS-CoV-2 Omicron RBD-ACE2 interaction
Authors: Lan Jun , He Xinheng , Ren Yifei , Wang Ziyi , Zhou Huan , Fan Shilong , Zhu Chenyou , Liu Dongsheng , Shao Bin , Liu Tie-Yan , Wang Qisheng , Zhang Linqi , Ge Jiwan , Wang Tong , Wang Xinquan 
Published: January 2022

ABSTRACTSince SARS-CoV-2 Omicron variant (B.1.1.529) was reported in November 2021, it has quickly spread to many countries and outcompeted the globally dominant Delta variant in several countries. The Omicron variant contains the largest number of mutations to date, with 32 mutations located at spike (S) glycoprotein, which raised great concern for its enhanced viral fitness and immune escape[1–4]. In this study, we reported the crystal structure of the receptor binding domain (RBD) of Omicron variant S glycoprotein bound to human ACE2 at a resolution of 2.6 Å. Structural comparison, molecular dynamics simulation and binding free energy calculation collectively identified four key mutations (S477N, G496S, Q498R and N501Y) for the enhanced binding of ACE2 by the Omicron RBD compared to the WT RBD. Representative states of the WT and Omicron RBD-ACE2 systems were identified by Markov State Model, which provides a dynamic explanation for the enhanced binding of Omicron RBD. The effects of the mutations in the RBD for antibody recognition were analyzed, especially for the S371L/S373P/S375F substitutions significantly changing the local conformation of the residing loop to deactivate several class IV neutralizing antibodies.
Pathogens in exacerbations of chronic rhinosinusitis differ in sensitivity to silver nanoparticles
Authors: Szaleniec Joanna , Gibała Agnieszka , Stalińska Joanna , Oćwieja Magdalena , Żeliszewska Paulina , Drukała Justyna , Szaleniec Maciej , Gosiewski Tomasz 
Published: January 2022

AbstractPurposeThe significance of the microbiome in chronic rhinosinusitis (CRS) is not clear. Antimicrobials are recommended in acute exacerbations of the disease (AECRS). Increasing rates of antibiotic resistance stimulate research on alternative therapeutic options including silver nanoparticles (AgNPs), sometimes referred to as “colloidal silver”. However, there are concerns regarding the safety of silver administration and the emergence of silver resistance. The aim of this cross-sectional observational study was to assess the sensitivity of sinonasal pathogens to AgNPs and compare it with the toxicity of AgNPs for nasal epithelial cells.MethodsNegatively charged AgNPs (12±5 nm) were synthetized using tannic acid. The minimal inhibitory concentration (MIC) for pathogens isolated from patients with AECRS was approximated. Cytotoxicity of AgNPs was tested in vitro on human nasal epithelial cells line.Results48 clinical isolates and 4 reference strains were included in the study (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Acinetobacter baumanii, Serratia marcescens, Enterobacter cloacae). The MIC values differed between isolates, even within the same species. All the isolates (including antibiotic resistant) were sensitive to AgNPs in concentrations nontoxic to human cells during 24 h exposition. However, 48 h exposition to AgNPs increased toxicity to human cells, narrowing their therapeutic window and enabling 19% of pathogens to resist the AgNPs’ biocidal action.ConclusionsAgNPs are effective against most pathogens isolated from patients with AECRS, but sensitivity testing may be necessary before application. Results of sensitivity testing for reference strains cannot be extrapolated to other strains of the same species.
Discordant SARS-CoV-2 PCR and Rapid Antigen Test Results When Infectious: A December 2021 Occupational Case Series
Authors: Adamson Blythe , Sikka Robby , Wyllie Anne L. , Premsrirut Prem 
Published: January 2022

AbstractThe performance of Covid-19 diagnostic tests must continue to be reassessed with new variants of concern. The objective of this study was to describe the discordance in saliva SARS-CoV-2 PCR and nasal rapid antigen test results during the early infectious period. We identified a high-risk occupational case cohort of 30 individuals with daily testing during an Omicron outbreak in December 2021. Based on viral load and transmissions confirmed through epidemiological investigation, most Omicron cases were infectious for several days before being detectable by rapid antigen tests.