bluuebunny/crossref_metadata_2025_split huggingface dataset:
341 Observational multicentre study on effectiveness and tolerability of Alirocumab in real world, the OMERO study: interim data from the first 699 patients
Authors: Luigi Catapano Alberico , Maggioni Aldo Pietro , Rossi Francesco , Tirone Giampaolo , Notarianni Lucia , Agnelli Giancarlo , Cesaro Arturo 
Published: December 2021

Abstract

Aims
OMERO is a prospective study, aimed to assess the long-term effectiveness, tolerability, and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9-i), in the real life in Italy. The study is planned to include 800 patients, from 40 Italian sites, treated with alirocumab on top of standard lipid lowering therapy.

Methods and results
This analysis concerns 699 (out of 800) patients with all data available: 65.5% male; mean age 60.6 ± 11.09 years; 29.6% with HeFH in primary prevention; 70.4% in secondary prevention (with/without HeFH). Before ALI administration, 461 patients (66%) were treated with statins while 231 (33%) reported statin intolerance, that resulted in the statin discontinuation. Mean baseline LDL-C was 161.5 ± (53.07) mg/dl. Based on clinical judgement, ALI was initially prescribed at 75 mg Q2W dosing regimen in 60.80% of participants, whereas the remainder received 150 mg Q2W. At V1 57 patients (89.06%) switch from 75 mg Q2W to 150 mg Q2W and 7 patients (10.94%) from 150 mg Q2W to 75 mg Q2W. LDL-C level reduction from baseline (before ALI administration) to 6 months from the study enrolment (V1), was −45% (V1: mean LDL-C was 73.5 ± 45.70 mg/dl). LDL-C levels at V1 by participant category are shown in Figure 1. The rate of patients with at least one adverse event was 25.6% (of which SAE 7.4%); the rate of patients with at least one related adverse reaction to treatment was 3.8% none of them were serious.

Conclusions
OMERO confirmed in clinical practice the results observed in trials: a significant reduction of LDL-C was observed with ALI 75/150 mg Q2W in participants at high CV risk with or without HeFH. ALI was generally well tolerated.
809 Frequency and determinants of haemoglobin drop without overt bleeding in patients undergoing transcatheter aortic valve replacement
Authors: Carabetta Nicole , Sorrentino Sabato , Boccuto Fabiola , Bellantoni Antonio , Giordano Salvatore , Cacia Michele Antonio , Polimeni Alberto , Leo Isabella , Varano Ylenia , Augusto Florinda Maria , Mongiardo Annalisa , De Rosa Salvatore , Indolfi Ciro , Spaccarotella Carmen 
Published: December 2021

Abstract

Aims
Post-procedural bleedings have a significant impact on mortality in patients undergoing transcatheter aortic valve replacement (TAVR). Unfortunately, the source of these bleedings is often undetermined, causing difficulties in diagnosis and related treatment. Furthermore, the frequency and determinants of ‘non-overt’ bleeding are largely lacking in TAVR studies. Accordingly, in this analysis, we aimed to assess the frequency and determinants of haemoglobin drop without overt bleeding in patients undergoing TAVR.

Methods
Patients undergoing TAVR at Magna Graecia University in Catanzaro from September 2008 to November 2020 were included in this study. Post-procedural haemoglobin (Hb) drop was calculated subtracting the lowest value observed after the procedure to the one obtained at admission (Hb drop). The association between baseline clinical and procedural variables with Hb drop was investigated with a linear regression model.

Results
Out of 407 patients undergoing TAVR at our institution, 119 (29.2%) were excluded because experiencing overt bleeding, red blood cells transfusion, were treated with only balloon angioplasty, or for procedural unsuccess. Among the 288 patients included in the final analysis, 239 (83.0%) were older than 74 y.o., 148 (51.4%) were female, 94 (32.6%) were diabetics, and 69 (24.0%) had CKD. All the patients were deemed at intermediate/high operatory risk and treated using the transfemoral approach. After TAVR, Hb significantly decreased (12.6 ± 1.6 g/dL to 9.7 ± 1.3 g/dL, P &lt; 0.001), with an absolute mean reduction of 2.9 ± 1.23 g/dL 126 patients (43.8%) had Hb drop ≥ 3 g/dL, while 11 (3.8%) had Hb drop ≥ 5 g/dL. The table below summarizes the determinants of Hb drop. Among them, the new generation of self-expandable and balloon-expandable devices were associated with a lower post-procedural Hb drop compared to the previous generation of self-expandable devices, alongside, higher body mass index and hypertension.

Conclusions
Post-procedural reduction of Hb without overt bleeding or RBC transfusion is frequent, involving almost half of the patients undergoing TAVR. The introduction in clinical practice of new-generation valve devices is significantly associated with a reduction of this adverse event. However, further and thorough investigation should be accomplished to reclassify this large part of patients into a well-defined category.
817 Potent P2Y12 inhibitors in elderly population, insigth from praise registry
Authors: Elia Edoardo , D’Ascenzo Fabrizio , Breviario Susanna , Bruno Francesco , Marengo Giorgio , De Filippo Ovidio , Conrotto Federico , Maria De Ferrari Gaetano 
Published: December 2021

Abstract

Background
The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly patients with acute coronary syndrome (ACS) remains unclear.

Methods
All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3-5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones.

Results
4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16±3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63-1.52, p=0.94 and HR 0.38; 0.14-1.04, p=0,06), reduced risk of MACE and MI (HR 0.82; 0.23-0.91, p=0.03 and HR 0.43; 0.14-0.89, p=0.04) and increased risk of BARC 3-5 bleeding (HR 2.14; 1.19-3.85, p=0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22-0.95, p=0.04 and HR 2.36; 1.02-5.52, p=0.04, all 95%CI) with neutral effect on NACE and MACE.

Conclusions
In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older. 817 Figure 1
The recombination landscapes of spiny lizards (genusSceloporus)
Authors: Versoza Cyril J , Rivera Julio A , Rosenblum Erica Bree , Vital-García Cuauhcihuatl , Hews Diana K , Pfeifer Susanne P 
Published: December 2021

AbstractDespite playing a critical role in evolutionary processes and outcomes, relatively little is known about rates of recombination in the vast majority of species, including squamate reptiles—the second largest order of extant vertebrates, many species of which serve as important model organisms in evolutionary and ecological studies. This paucity of data has resulted in limited resolution on questions related to the causes and consequences of rate variation between species and populations, the determinants of within-genome rate variation, as well as the general tempo of recombination rate evolution on this branch of the tree of life. In order to address these questions, it is thus necessary to begin broadening our phylogenetic sampling. We here provide the first fine-scale recombination maps for two species of spiny lizards, Sceloporus jarrovii and Sceloporus megalepidurus, which diverged at least 12 Mya. As might be expected from similarities in karyotype, population-scaled recombination landscapes are largely conserved on the broad-scale. At the same time, considerable variation exists at the fine-scale, highlighting the importance of incorporating species-specific recombination maps in future population genomic studies.
Barcoded reciprocal hemizygosity analysis via sequencing illuminates the complex genetic basis of yeast thermotolerance
Authors: Abrams Melanie B , Chuong Julie N , AlZaben Faisal , Dubin Claire A , Skerker Jeffrey M , Brem Rachel B 
Published: December 2021

Abstract
Decades of successes in statistical genetics have revealed the molecular underpinnings of traits as they vary across individuals of a given species. But standard methods in the field cannot be applied to divergences between reproductively isolated taxa. Genome-wide reciprocal hemizygosity mapping (RH-seq), a mutagenesis screen in an interspecies hybrid background, holds promise as a method to accelerate the progress of interspecies genetics research. Here, we describe an improvement to RH-seq in which mutants harbor barcodes for cheap and straightforward sequencing after selection in a condition of interest. As a proof of concept for the new tool, we carried out genetic dissection of the difference in thermotolerance between two reproductively isolated budding yeast species. Experimental screening identified dozens of candidate loci at which variation between the species contributed to the thermotolerance trait. Hits were enriched for mitosis genes and other housekeeping factors, and among them were multiple loci with robust sequence signatures of positive selection. Together, these results shed new light on the mechanisms by which evolution solved the problems of cell survival and division at high temperature in the yeast clade, and they illustrate the power of the barcoded RH-seq approach.
Populations, Traits, and Their Spatial Structure in Humans
Authors: Sohail Mashaal , Izarraras-Gomez Alan , Ortega-Del Vecchyo Diego 
Published: December 2021

AbstractThe spatial distribution of genetic variants is jointly determined by geography, past demographic processes, natural selection, and its interplay with environmental variation. A fraction of these genetic variants are “causal alleles” that affect the manifestation of a complex trait. The effect exerted by these causal alleles on complex traits can be independent or dependent on the environment. Understanding the evolutionary processes that shape the spatial structure of causal alleles is key to comprehend the spatial distribution of complex traits. Natural selection, past population size changes, range expansions, consanguinity, assortative mating, archaic introgression, admixture, and the environment can alter the frequencies, effect sizes, and heterozygosities of causal alleles. This provides a genetic axis along which complex traits can vary. However, complex traits also vary along biogeographical and sociocultural axes which are often correlated with genetic axes in complex ways. The purpose of this review is to consider these genetic and environmental axes in concert and examine the ways they can help us decipher the variation in complex traits that is visible in humans today. This initiative necessarily implies a discussion of populations, traits, the ability to infer and interpret “genetic” components of complex traits, and how these have been impacted by adaptive events. In this review, we provide a history-aware discussion on these topics using both the recent and more distant past of our academic discipline and its relevant contexts.
Validation of the 3M™ Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) for the Detection of Shiga Toxin Gene (stx and eae) in Fresh Raw Beef Trim, Fresh Raw Ground Beef and Fresh Spinach: AOAC Performance Tested MethodSM 071902
Authors: Rosauer Micki L , Barnes Christina , Silbernagel Karen M , Koch Kateland M 
Published: December 2021

Abstract

Background
The 3M™ Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) method is based on gene amplification using real time loop-mediated isothermal amplification with the 3M Molecular Detection System for the rapid and specific detection of Shiga toxin gene (stx1 and/or stx2) and intimin gene (eae) from Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC) in enriched foods.

Objective
The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) method was evaluated for AOAC® Performance Tested MethodsSM certification.

Methods
Matrix studies, inclusivity/exclusivity, robustness, product stability, and lot-to-lot variability testing were conducted to assess the method’s performance.

Results
The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) demonstrated equivalent results to the US Department of Agriculture–Food Safety and Inspection Service Microbiology Laboratory Guidebook 5C.00 for fresh raw beef trim and fresh raw ground beef, and to the US Food and Drug Administration Bacteriological Analytical Manual Chapter 4A for fresh spinach. The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) detected 50 of 50 E. coli strains with stx1 and/or stx2 genes, and the eae gene, and detected zero of 40 strains from the exclusivity panel. Robustness testing indicated that small variations in critical test parameters did not adversely affect the assay’s performance. Product consistency and stability testing demonstrated no differences between the lots evaluated.

Conclusion
The data collected demonstrates that the 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) is a reliable method for the rapid and specific detection of STEC in raw beef trim, raw ground beef, and spinach.

Highlights
The 3M Molecular Detection Assay 2 - STEC Gene Screen (stx and eae) method is suitable for the rapid and specific detection of STECs in raw beef trim, raw ground beef, and spinach.
Radio Galaxy Zoo: giant radio galaxy classification using multidomain deep learning
Authors: Tang H , Scaife A M M , Wong O I , Shabala S S 
Published: December 2021

ABSTRACT
In this work we explore the potential of multidomain multibranch convolutional neural networks (CNNs) for identifying comparatively rare giant radio galaxies from large volumes of survey data, such as those expected for new generation radio telescopes like the SKA and its precursors. The approach presented here allows models to learn jointly from multiple survey inputs, in this case NVSS and FIRST, as well as incorporating numerical redshift information. We find that the inclusion of multiresolution survey data results in correction of 39 per cent of the misclassifications seen from equivalent single domain networks for the classification problem considered in this work. We also show that the inclusion of redshift information can moderately improve the classification of giant radio galaxies.
A new model for simulating circumstellar dynamics in young stellar clusters
Authors: Wiśniowski T , Rickman H , Wajer P 
Published: December 2021

ABSTRACT
Simulations of angular momentum transfer from a surrounding star cluster to distant planetesimals orbiting around a cluster member have been used since more than two decades to study the formation of small body populations in the outskirts of the Solar system (Oort Cloud and sednoids). We present a new model for these interactions, for the first time combining two features of earlier works: (1) a self-consistent treatment of cluster evolution based on N-body simulations, and (2) a treatment of circumstellar dynamics as resulting from a combination of a smooth tidal field representing the whole cluster and close encounters by individual cluster members. The model is expected to be both flexible, accurate, and efficient in terms of CPU time and hence a suitable tool when simulating large or long-lived clusters or when many independent runs are needed for statistical significance. We describe the model in detail and give examples of its outputs. These are of relevance not only for the perihelion extraction of small bodies but also for the stability properties of young or nascent planetary systems or protoplanetary discs.
Supervised learning with word embeddings derived from PubMed captures latent knowledge about protein kinases and cancer
Authors: Ravanmehr Vida , Blau Hannah , Cappelletti Luca , Fontana Tommaso , Carmody Leigh , Coleman Ben , George Joshy , Reese Justin , Joachimiak Marcin , Bocci Giovanni , Hansen Peter , Bult Carol , Rueter Jens , Casiraghi Elena , Valentini Giorgio , Mungall Christopher , Oprea Tudor I , Robinson Peter N 
Published: December 2021

Abstract
Inhibiting protein kinases (PKs) that cause cancers has been an important topic in cancer therapy for years. So far, almost 8% of &gt;530 PKs have been targeted by FDA-approved medications, and around 150 protein kinase inhibitors (PKIs) have been tested in clinical trials. We present an approach based on natural language processing and machine learning to investigate the relations between PKs and cancers, predicting PKs whose inhibition would be efficacious to treat a certain cancer. Our approach represents PKs and cancers as semantically meaningful 100-dimensional vectors based on word and concept neighborhoods in PubMed abstracts. We use information about phase I-IV trials in ClinicalTrials.gov to construct a training set for random forest classification. Our results with historical data show that associations between PKs and specific cancers can be predicted years in advance with good accuracy. Our tool can be used to predict the relevance of inhibiting PKs for specific cancers and to support the design of well-focused clinical trials to discover novel PKIs for cancer therapy.
A Rare Bird: Diagnosis of Psittacosis Meningitis by Clinical Metagenomic Next-Generation Sequencing
Authors: Davar K , Wilson M R , Miller S , Chiu C Y , Vijayan T 
Published: December 2021

Abstract
Psittacosis is a zoonotic infectious disease caused by the transmission of Chlamydia psittaci; it often presents as a pulmonary infection but rarely as disseminated disease. Because diagnoses of psittacosis are often underreported due to infrequent pathogen-specific testing, clinical metagenomic next-generation sequencing may be helpful to diagnose such an uncommon syndrome.
Circulation of Non-SARS-CoV-2 Respiratory Pathogens and Coinfection with SARS-CoV-2 Amid the COVID-19 Pandemic
Authors: Uhteg Katharine , Amadi Adannaya , Forman Michael , Mostafa Heba H 
Published: December 2021

Abstract

Background
Our understanding of the cocirculation of infrequently targeted respiratory pathogens and their contribution to symptoms during the coronavirus disease 2019 (COVID-19) pandemic is currently limited. This research aims at (1) understanding the epidemiology of respiratory pathogens since the start of the pandemic, (2) assessing the contribution of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/influenza/respiratory syncytial virus (RSV) respiratory pathogens to symptoms, and (3) evaluating coinfection rates in SARS-CoV-2-positive patients, both vaccinated and unvaccinated.

Methods
Retrospective analysis of respiratory pathogens identified by the Johns Hopkins Diagnostic Laboratory between December 2019 and October 2021 was performed. In addition, we assessed the contribution of respiratory pathogens other than SARS-CoV-2 to symptomatic disease by retesting 2 cohorts of specimens that were (1) collected from symptomatic patients and (2) received limited respiratory pathogen testing. The first cohort was patients who tested negative by the standard-of-care SARS-CoV-2/influenza/RSV testing. The second was a cohort of SARS-CoV-2-positive, symptomatic, fully COVID-19 immunized and unimmunized patients.

Results
Between December 2019 and October 2021, a total of 11 806, 62 829, and 579 666 specimens were tested for an extended respiratory panel, influenza/RSV with or without SARS-CoV-2 panel, or SARS-CoV-2, respectively. Positivity rates of different targets differed between different months and were impacted by the COVID-19 pandemic. The SARS-CoV-2-negative cohort had 8.5% positivity for other respiratory pathogens that included primarily enterovirus/rhinovirus (5.8%). In the SARS-CoV-2-positive cohort, no other respiratory pathogens were detected.

Conclusions
The COVID-19 pandemic impacted the circulation of certain respiratory pathogens. Other respiratory viral pathogens were associated with symptomatic infections; however, coinfections with SARS-CoV-2 were highly uncommon.
Low- Versus High-Dose Methylprednisolone in Adult Patients With Coronavirus Disease 2019: Less Is More
Authors: Joshi Seema , Smith Zachary , Soman Sana , Jain Saniya , Yako Atheel , Hojeij Marwa , Massoud Louis , Alsaadi Ayman , Williams Jonathan , Kenney Rachel , Miller Joseph , Alangaden George , Ramesh Mayur 
Published: December 2021

Abstract

Background
Corticosteroids use in severe coronavirus disease 2019 (COVID-19) improves survival; however, the optimal dose is not established. We aim to evaluate clinical outcomes in patients with severe COVID-19 receiving high-dose corticosteroids (HDC) versus low-dose corticosteroids (LDC).

Methods
This was a quasi-experimental study conducted at a large, quaternary care center in Michigan. A corticosteroid dose change was implemented in the standardized institutional treatment protocol on November 17, 2020. All patients admitted with severe COVID-19 that received corticosteroids were included. Consecutive patients in the HDC group (September 1 to November 15, 2020) were compared to the LDC group (November 30, 2020 to January 20, 2021). High-dose corticosteroids was defined as 80 mg of methylprednisolone daily in 2 divided doses, and LDC was defined as 32–40 mg of methylprednisolone daily in 2 divided doses. The primary outcome was all-cause 28-day mortality. Secondary outcomes included progression to mechanical ventilation, hospital length of stay (LOS), discharge on supplemental oxygen, and corticosteroid-associated adverse events.

Results
Four-hundred seventy patients were included: 218 (46%) and 252 (54%) in the HDC and LDC groups, respectively. No difference was observed in 28-day mortality (14.5% vs 13.5%, P = .712). This finding remained intact when controlling for additional variables (odds ratio, 0.947; confidence interval, 0.515–1.742; P = .861). Median hospital LOS was 6 and 5 days in the HDC and LDC groups, respectively (P &lt; .001). No differences were noted in any of the other secondary outcomes.

Conclusions
Low-dose methylprednisolone had comparable outcomes including mortality to high-dose methylprednisolone for the treatment of severe COVID-19.
“Es Como Que no los Conociera”: Reunification of Unaccompanied Migrant Youth with Their U.S. Families
Authors: Barros-Lane Liza , Brabeck Kalina , Berger Cardoso Jodi Arden 
Published: December 2021

Abstract
Family reunification following migration-related separations is often challenging for immigrant youth as they adjust to their new environment and reacquaint with their caregiver. Scant research has explored the experiences of family reunification specifically for unaccompanied immigrant youth. This study was a secondary analysis to explore the complexities of family reunification through the lens of attachment theory and family systems. Data were collected from 30 youth, six parents, and four school administrators via focus groups and semistructured interviews. Unaccompanied immigrant youth had arrived to the United States in the previous three years from Honduras, El Salvador, Guatemala, or Mexico. Data were analyzed using thematic analysis. Results showed that the youth struggled to reconnect with their parents due to prolonged separations, which contributed to loneliness and feelings of loss. Parent–child attachment disruptions contributed to problems related to relationships among family members, traditional family roles and hierarchies, and new family constellations (e.g., blended families). Results point to the importance of developing interventions to increase trust, empathy, and communication between unaccompanied immigrant youth and their parents.