bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cox regression is robust to inaccurate EHR-extracted event time: an application to EHR-based GWAS
Authors: Irlmeier Rebecca , Hughey Jacob J , Bastarache Lisa , Denny Joshua C , Chen Qingxia 
Published: February 2022

AbstractMotivationLogistic regression models are used in genomic studies to analyze the genetic data linked to electronic health records (EHRs), and do not take full usage of the time-to-event information available in EHRs. Previous work has shown that Cox regression, which can account for left truncation and right censoring in EHRs, increased the power to detect genotype–phenotype associations compared to logistic regression. We extend this to evaluate the relative performance of Cox regression and various logistic regression models in the presence of positive errors in event time (delayed event time), relating to recorded event time accuracy.ResultsOne Cox model and three logistic regression models were considered under different scenarios of delayed event time. Extensive simulations and a genomic study application were used to evaluate the impact of delayed event time. While logistic regression does not model the time-to-event directly, various logistic regression models used in the literature were more sensitive to delayed event time than Cox regression. Results highlighted the importance to identify and exclude the patients diagnosed before entry time. Cox regression had similar or modest improvement in statistical power over various logistic regression models at controlled type I error. This was supported by the empirical data, where the Cox models steadily had the highest sensitivity to detect known genotype–phenotype associations under all scenarios of delayed event time.Availability and implementationAccess to individual-level EHR and genotype data is restricted by the IRB. Simulation code and R script for data process are at: https://github.com/QingxiaCindyChen/CoxRobustEHR.gitSupplementary informationSupplementary data are available at Bioinformatics online.
riboviz 2: a flexible and robust ribosome profiling data analysis and visualization workflow
Authors: Cope Alexander L , Anderson Felicity , Favate John , Jackson Michael , Mok Amanda , Kurowska Anna , Liu Junchen , MacKenzie Emma , Shivakumar Vikram , Tilton Peter , Winterbourne Sophie M , Xue Siyin , Kavoussanakis Kostas , Lareau Liana F , Shah Premal , Wallace Edward W J 
Published: February 2022

Abstract

Motivation
Ribosome profiling, or Ribo-seq, is the state-of-the-art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses.

Results
We present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system for end-to-end processing of Ribo-seq data. riboviz 2 has been extensively tested on diverse species and library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline.

Availability and implementation
riboviz 2 is freely available at github.com/riboviz/riboviz.
Irx3 promotes gap junction communication between uterine stromal cells to regulate vascularization during embryo implantation
Authors: Brown Ryan M , Wang Linda , Fu Anqi , Kannan Athilakshmi , Mussar Michael , Bagchi Indrani C , Jorgensen Joan S 
Published: February 2022

Abstract
Appropriate embryo-uterine interactions are essential for implantation. Besides oocyte abnormalities, implantation failure is a major contributor to early pregnancy loss. Previously, we demonstrated that two members of the Iroquois homeobox transcription factor family, IRX3 and IRX5, exhibited distinct and dynamic expression profiles in the developing ovary to promote oocyte and follicle survival. Elimination of each gene independently caused subfertility, but with different breeding pattern outcomes. Irx3 KO (Irx3LacZ/LacZ) females produced fewer pups throughout their reproductive lifespan which could only be partially explained by poor oocyte quality. Thus, we hypothesized that IRX3 is also expressed in the uterus where it acts to support pregnancy. To test this hypothesis, we harvested pregnant uteri from control and Irx3 KO females to evaluate IRX3 expression profiles and the integrity of embryo implantation sites. Our results indicate that IRX3 is expressed in the endometrial stromal cells at day 4 of pregnancy (D4) with peak expression at D5–D6, and then greatly diminishes by D7. Further, studies showed that while embryos were able to attach to the uterus, implantation sites in Irx3 KO pregnant mice exhibited impaired vascularization and abnormal expression of decidualization markers. Finally, we also observed an impaired response of the Irx3 KO uteri to an artificial deciduogenic stimulus, indicating a critical role of this factor in regulating the decidualization program. Together, these data established that IRX3 promotes female fertility via at least two different mechanisms: (1) promoting competent oocytes and (2) facilitating functional embryo–uterine interactions during implantation.
Making the ‘Local’ Visible in Social Work Education: Insights from Nigeria and Scotland on (Re)balancing and Contextualising Indigenous and International Knowledge
Authors: Levy Susan , Okoye Uzoma O , Ingram Richard 
Published: February 2022

AbstractSocial work in the twenty-first century is maturing as a global profession. This comparative study offers an original contribution to the evolving discussion in the field of international social work. The paper makes visible the socio-spatial dimensions and contested interpretations of international and indigenous knowledge through the experiences of social work students in the Global South and Global North. Drawing on findings from an online survey completed by undergraduate and postgraduate Nigerian and Scottish social work students (n = 142), the paper provides insights into the students’ experiences, expectations and perceived challenges. The Nigerian students critiqued the international (Western) knowledge informing their learning and practice, questioned the absence of indigenous knowledge and were aware of the importance, and challenges, of working with cultural diversity. The Scottish students showed little criticality of the Western (local) knowledge underpinning their learning and practice, did not prioritise learning about international social work and highlighted tensions between working with a culture of neoliberalism and social work values and social justice. We call for raising awareness of the epistemological foundations of what is included/excluded in curriculum and why, making the ‘local’ visible through re-balancing and contextualising the use of international and indigenous knowledge within social work.
Lower Rates of Emergency Department Visits and Hospitalizations Among Patients With Chronic Hepatitis C With Sustained Virological Response to Interferon-Free Direct-Acting Antiviral Therapy (2014–2018)
Authors: Gordon Stuart C , Teshale Eyasu H , Spradling Philip R , Moorman Anne C , Boscarino Joseph A , Schmidt Mark A , Daida Yihe G , Rupp Loralee B , Trudeau Sheri , Zhang Jiaqi , Lu Mei ,   CHeCS Investigators, Teshale Eyasu H , Spradling Philip R , Moorman Anne C , Xing Jian , Zhong Yuna , Gordon Stuart C , Rupp Loralee B , Trudeau Sheri , Lu Mei , Li Jia , Akkerman Nonna , Zhou Yueren , Boscarino Joseph A , Daar Zahra S , Smith Robert E , Daida Yihe G , Trinacty Connie Mah , Lai Jonathan W , Nie Sixiang , Wong Carmen P , Schmidt Mark A , Donald Judy L 
Published: February 2022

Abstract
We compared rates of emergency department visits and hospitalizations between patients with hepatitis C virus who achieved sustained virological response after direct-acting antiviral therapy (case patients) and matched controls. Among 3049 pairs, case patients demonstrated lower rates of liver-related emergency department visits (P = .01) than controls; all-cause and liver-related hospitalization rates and number of hospitalized days were also lower in case patients (P &lt; .001).
AmBisome Monotherapy and Combination AmBisome–Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial
Authors: Burza Sakib , Mahajan Raman , Kazmi Shahwar , Alexander Neal , Kumar Deepak , Kumar Vikash , Lasry Estrella , Harshana Amit , de Lima Pereira Alan , Das Pradeep , Verma Neena , Das Vidya Nand Ravi , Lal Chandra Shekhar , Rewari Bharat , Goyal Vishal , Rijal Suman , Alves Fabiana , Gill Naresh , Pandey Krishna 
Published: February 2022

Abstract

Background
Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent.

Methods
This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations.

Results
Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77–100%) in the monotherapy arm, and 96%, (72/75; 90–100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82–100%) in the monotherapy and 97% (59/61; 91–100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm.

Conclusions
Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations.

Clinical Trials Registration
Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r).
Theory of Mind and Alexithymia in Deaf and Hard-of-Hearing Young Adults
Authors: Blose Brittany A , Schenkel Lindsay S 
Published: February 2022

AbstractThe aim of the current study was to examine theory of mind (ToM), the ability to infer the mental states of others, in young adults who are deaf and hard-of-hearing (DHH), and to explore the influence of alexithymia, an inability to understand emotions of the self and others, on ToM performance in this group. Compared to participants with typical hearing, DHH participants displayed significantly lower affective ToM skills and greater alexithymia. After accounting for verbal intelligence quotient, hearing status and alexithymia significantly contributed to poorer ToM performance, accounting for over 14% of the variance. Having a parent who is deaf and being part of the Deaf community were associated with better emotion processing and appear to be important protective factors. Findings provide support that ToM difficulties may linger into young adulthood among DHH individuals and that alexithymia may be a contributing factor. Early intervention programs emphasizing emotional understanding, perspective-taking, and communication skills are warranted for DHH children as well as their caregivers.
Suggested modification of the recommendations for echocardiography in patients with clinical suspicion of infective endocarditis
Authors: Damlin A , Eriksson MJE 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Infective endocarditis (IE) is a serious condition that requires prompt diagnosis and treatment. Transthoracic echocardiography (TTE) is usually the initial imaging modality, however transoesophageal echocardiography (TOE) is often necessary because of its higher sensitivity for IE compared with TTE. Yet, TOE has an increased risk of complications. The European Society of Cardiology (ESC) has established guidelines for the management of IE with recommendations for the use of TOE in patients with clinical suspicion of IE.

Purpose
This project aims to evaluate the ESC recommendations for the use of TOE in patients with clinical suspicion of IE. The purpose of the study is further to examine whether the ESC recommendations for TOE among patients with clinical suspicion of IE result in an unnecessarily large number of negative TOE examinations.

Methods
All TOE examinations performed due to referrals of patients with clinical suspicion of IE between 1 May 2019 and 30 April 2020 at a university hospital in our city were analysed. The variables included for analysis were age; sex; cardiac comorbidities; prosthetic valves; blood culture results; results from TTE and TOE; number of TOEs during the inclusion period; Duke criteria. The TOE and TTE results were compared in relation to the ESC guidelines.

Results
In total 195 TOE examinations from 160 patients were included, of which 61 (31%) TOEs were positive for IE. All examinations were of patients with clinical suspicion of IE, of which 37 (19%) had negative TTE. Of the 37 patients with negative TTE, 13 had prosthetic valve or intracardiac device of which 5 had positive TOE. All the 24 (12%) examinations with negative TTE and no prosthetic valve or intracardiac device had negative TOE.

Conclusions
The ESC recommendations for TOE in patients with clinical suspicion of IE are probably broad enough not to miss patients with IE, but there might be an unnecessarily large number of patients that get referred for TOE with negative results. To avoid this, we propose a modification of the recommendations for TOE in patients with clinical suspicion of IE. Negative TTE examination with good image quality and no indications for TOE according to Fig 1, could result in avoiding unnecessary TOE examinations without jeopardizing the IE diagnosis. Abstract Figure. Fig 1
Atrial mechanics in anthracycline chemotherapy: insights into a prospective study
Authors: Vahabi S , Kharati-Koopaei E , Norouzi M , Maddox J , Humphreys A , Hancock H , Zaman A , Austin D 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public hospital(s). Main funding source(s): South Tees Research and Development Fund
Background
In cancer treatment, detection of anthracycline induced cardiotoxicity (AIC) has been dependent on serial cardiac imaging to identify a reduction in left ventricular ejection fraction (LVEF) and more recently LV global longitudinal strain (GLS). However, studies have failed to assess the adverse effects of these agents on other cardiac chambers such as the left (LA) and right atria (RA).
Purpose
The PROACT PLUS study is an observational, prospective, cohort study investigating the effects of anthracyclines on the left and right atrial mechanics using 2 dimensional speckle tracking echocardiography (STE). We hypothesize that anthracyclines can affect the heart as a whole rather than solely affecting the LV.
Methods
From October 2018 to March 2020, patients with a new diagnosis of lymphoma or breast cancer receiving anthracycline chemotherapy were recruited into this study. Echocardiography was performed pre-chemotherapy (V1) and 1 month post-chemotherapy (V2). LA and RA volumes, LA (4-chamber)- and RA GLS, reservoir strains (RS), conduit strains (CS), contractile strains (CoS), peak-systolic (PS) strain-rates, early-diastolic (ED) strain-rates, and late-diastolic (LD) strain-rates were measured offline using vendor-independent software. This study was ethically approved by the Health Research Association (REC reference 18/EM/0177).
Results
A total number of 62 patients were recruited into this study. Unfortunately, 7 patients passed away during their treatment and 5 failed to attend their follow-up appointment at V2. From V1 to V2, there was a significant deterioration in the LA CS (-18.1% vs. -14.5%, p = 0.02) and LA ED strain-rate (-1.24 1/s vs. -0.86 1/s, p = 0.001). There was no other statistical significant change in the LA volume or other strain parameters. Additionally, there was a statistically significant decline in RA GLS (34.9% vs. 30.8%, p = 0.029), RA RS (41.1% vs. 37.1%, p = 0.03), RA CS (-23.8 vs. -20.6, p = 0.05), and RA ED strain-rate (-1.17 vs. -0.99, p = 0.02) with no significant change in the RA volume and other measures of RA strain.

Conclusion
These findings support our hypothesis that anthracyclines exert their cardiotoxic effects on all cardiac chambers including the atria. Whether these changes lead to subsequent permanent structural abnormalities in the atria hence increasing the future risk of atrial arrhythmias, or whether these changes predate subsequent cardiac dysfunction and poor prognosis, remains unknown. Long-term follow up and assessment of atrial mechanics is crucial in better understanding of AIC to help guide the future monitoring and management of patients undergoing cancer treatment.
Automated left atrial strain after electrical cardioversion for atrial fibrillation
Authors: Orphanou N , Zamfir T , Siama A , Michelinakis N , Tsoukas A 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Evidence shows that atrial dysfunction and stunning occur, after successful cardioversion from persistent atrial fibrillation (AF) to sinus rhythm (SR). Electrical and mechanical recovery of the left atrium (LA), do not seem to coincide. Traditional Doppler parameters show reduced atrial contractility immediately after cardioversion, while mechanical improvement in atrial function mainly occurs within the first 4 weeks after sinus rhythm restoration.

Purpose
This study aimed to determine whether automated left atrial strain (auto-LA strain) could be used to measure global LA function and the time required for mechanical improvement to be seen in LA after cardioversion.

Methods
Auto-LA strain was measured via transthoracic echocardiography in 20 patients with persistent AF who had been cardioverted to SR and followed up for 3 months, and in a cohort of 20 healthy individuals. Conventional measures of atrial function derived from transmitral pulsed Doppler and tissue Doppler imaging of lateral mitral annulus were included, such as transmitral A wave velocity, A wave velocity-time integral, atrial fraction, A" wave velocity, and A" velocity-time integral.

Results
Immediately after cardioversion auto-LA strain was significantly lower than in control subjects. Atrial function improved over time with maximal change observed at 1 month after cardioversion. Doppler tissue imaging parameters were also normalised after 1 month of restoration to SR. Despite this initial improvement in LA function, the values of auto-LA strain remained stable for the following 3 months.

Conclusion
Although the electrical function of LA is immediately restored after successful cardioversion in AF patients, there remains a persistent degree of atrial dysfunction for at least 3 months. This difference could explain the increased propensity for these patients to develop recurrent atrial fibrillation. Additionally, this dysfunction could indicate longer-term use of anti-arrhythmic and antithrombotic medications in the AF cohort. Abstract Figure.
Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial efficiency four months after infection
Authors: Katogiannis K , Ikonomidis I , Thymis J , Mitrakou A , Kountouri A , Stamoulis K , Korakas E , Varlamos C , Andreadou I , Tsoumani M , Bamias A , Thomas K , Antoniadou A , Dimopoulos MA , Lambadiari V 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Aims
SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We
investigated alterations of arterial stiffness, endothelial coronary and myocardial
function markers four months after COVID-19 infection.

Methods
In a case-control prospective study, we included 100 patients four months after COVID-19 infection, 50 age- and sex-matched healthy individuals. We measured a) pulse wave velocity (PWV), b) flow-mediated dilation (FMD) of brachial artery, c) coronary Flow Reserve (CFR) by Doppler echocardiography d) left ventricular (LV) global longitudinal strain (GLS), e) left ventricular myocardial work index, constructive work, wasted work and work efficiency and e) von-Willenbrand factor and thrombomodulin as endothelial biomarkers.

Results
COVID-19 patients had lower CFR and FMD values than controls (2.39 ± 0.39 vs 3.31 ± 0.59, p = 0.0122, 5.12 ± 2.95% vs 8.12 ± 2.23%, p = 0.006 respectively). Compared to controls, COVID-19 patients had higher PWV (PWVc-f 12.32 ± 2.44 vs 10.11 ± 1.85 m/sec, p = 0.033) and impaired LV GLS (-19.11 ± 2.14% vs -20.41 ± 1.61%, p = 0.001). Compared to controls, COVID-19 patients had higher myocardial work index, and wasted work (2067.7 ± 325.9 mmHg% vs 1929.4 ± 312.7 mmHg%, p = 0.026, 104.6 ± 58.9 mmHg% vs 75.1 ± 52.6 mmHg%, p = 0.008, respectively), while myocardial efficiency was lower (94.8 ± 2.5% vs 96.06 ± 2.3%, p = 0.008). and thrombomodulin were higher in COVID-19 patients than controls (3716.63 ± 188.36 vs 2590.02 ± 156.51pg/ml, p &lt; 0.001). MDA was higher in COVID-19 patients than controls (10.55 ± 2.45 vs 1.01 ± 0.50 nmole/L, p = 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress markers. Myocardial work efficiency was related with PWV (F=-0.309, p = 0.016) and vWillenbrand (F=-0.541, p = 0.037). Myocardial wasted work was related with PWV (F = 0.255, p = 0.047) and vWillenbrand (F = 0.610, p = 0.016).

Conclusions
SARS-CoV-2 may cause vascular dysfunction, followed by a waste of cardiac work, in order to compensate for increased arterial stiffness 4 months after infection.