bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinfection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients Undergoing Serial Laboratory Testing
Authors: Qureshi Adnan I , Baskett William I , Huang Wei , Lobanova Iryna , Hasan Naqvi S , Shyu Chi-Ren 
Published: April 2021

Abstract

Background
A better understanding of reinfection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become one of the healthcare priorities in the current pandemic. We determined the rate of reinfection, associated factors, and mortality during follow-up in a cohort of patients with SARS-CoV-2 infection.

Methods
We analyzed 9119 patients with SARS-CoV-2 infection who received serial tests in total of 62 healthcare facilities in the United States between 1 December 2019 and 13 November 2020. Reinfection was defined by 2 positive tests separated by interval of &gt;90 days and resolution of first infection was confirmed by 2 or more consecutive negative tests. We performed logistic regression analysis to identify demographic and clinical characteristics associated with reinfection.

Results
Reinfection was identified in 0.7% (n = 63, 95% confidence interval [CI]: .5%–.9%) during follow-up of 9119 patients with SARS-CoV-2 infection. The mean period (±standard deviation [SD]) between 2 positive tests was 116 ± 21 days. A logistic regression analysis identified that asthma (odds ratio [OR] 1.9, 95% CI: 1.1–3.2) and nicotine dependence/tobacco use (OR 2.7, 95% CI: 1.6–4.5) were associated with reinfection. There was a significantly lower rate of pneumonia, heart failure, and acute kidney injury observed with reinfection compared with primary infection among the 63 patients with reinfection There were 2 deaths (3.2%) associated with reinfection.

Conclusions
We identified a low rate of reinfection confirmed by laboratory tests in a large cohort of patients with SARS-CoV-2 infection. Although reinfection appeared to be milder than primary infection, there was associated mortality.
Comparative 1-Year Outcomes of Invasive Staphylococcus aureus Infections Among Persons With and Without Drug Use: An Observational Cohort Study
Authors: Appa Ayesha , Adamo Meredith , Le Stephenie , Davis Jennifer , Winston Lisa , Doernberg Sarah B , Chambers Henry , Martin Marlene , Hills Nancy K , Coffin Phillip O , Jain Vivek 
Published: April 2021

Abstract

Background
Persons who use drugs (PWUD) face substantial risk of Staphylococcus aureus infections. Limited data exist describing clinical and substance use characteristics of PWUD with invasive S. aureus infections or comparing treatment and mortality outcomes in PWUD vs non-PWUD. These are needed to inform optimal care for this marginalized population.

Methods
We identified adults hospitalized from 2013 to 2018 at 2 medical centers in San Francisco with S. aureus bacteremia or International Classification of Diseases–coded diagnoses of endocarditis, epidural abscess, or vertebral osteomyelitis with compatible culture. In addition to demographic and clinical characteristic comparison, we constructed multivariate Cox proportional hazards models for 1-year infection-related readmission and mortality, adjusted for age, race/ethnicity, housing, comorbidities, and methicillin-resistant S. aureus (MRSA).

Results
Of 963 hospitalizations for S. aureus infections in 946 patients, 372 of 963 (39%) occurred in PWUD. Among PWUD, heroin (198/372 [53%]) and methamphetamine use (185/372 [50%]) were common. Among 214 individuals using opioids, 98 of 214 (46%) did not receive methadone or buprenorphine. PWUD had lower antibiotic completion than non-PWUD (70% vs 87%; P &lt; .001). While drug use was not associated with increased mortality, 1-year readmission for ongoing or recurrent infection was double in PWUD vs non-PWUD (28% vs 14%; adjusted hazard ratio [aHR], 2.0 [95% confidence interval {CI}: 1.3–2.9]). MRSA was independently associated with 1-year readmission for infection (aHR, 1.5 [95% CI: 1.1–2.2]).

Conclusions
Compared to non-PWUD, PWUD with invasive S. aureus infections had lower rates of antibiotic completion and twice the risk of infection persistence/recurrence at 1 year. Among PWUD, both opioid and stimulant use were common. Models for combined treatment of substance use disorders and infections, particularly MRSA, are needed.
Local Hyperthermia at 44°C Is Effective in Clearing Cervical High-Risk Human Papillomaviruses: A Proof-of-Concept, Randomized Controlled Clinical Trial
Authors: Yang Yang , Zhang Lan , Zhang Yuqing , Huo Wei , Qi Ruiqun , Guo Hao , Li Xiaodong , Wu Xin , Bai Feng , Liu Kuiran , Qiao Youlin , Piguet Vincent , Croitoru David , Chen Hong-Duo , Gao Xing-Hua 
Published: April 2021

Abstract

Background
Persistent infection by high-risk human papillomavirus (HPV) is the leading cause of cervical intraepithelial neoplasia and cervical carcinoma. Local hyperthermia at 44ºC has been proven efficacious to clear cutaneous or anogenital warts caused by HPV infection. This study aims to assess the effect of hyperthermia at 44ºC on the clearance of high-risk HPV.

Methods
A randomized, patient-blind, sham treatment–controlled trial was conducted in 4 medical centers. We enrolled patients with positive high-risk HPVs and normal or insignificant cytological findings (negative/atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion). Participants were randomly assigned (1:1) to receive either hyperthermia at 44ºC or 37ºC, for 30 minutes in each session. Patients in both groups received treatment once a day for 3 consecutive days, plus 2 more sessions 10 ± 3 days later. The primary outcome was clearance rate of HPV 3 months after treatment.

Results
After a 3-month follow-up, hyperthermia treatment at 44ºC and 37ºC achieved HPV clearance rates of 85.19% (23/27) and 50% (13/26), respectively (P = .014). There was no significant difference of treatment response between patients with single and multiple type of HPV by 44ºC hyperthermia treatment. There were no significant adverse events recorded during the treatment period in both groups.

Conclusions
Local hyperthermia at 44ºC safely and significantly aids in clearing cervical high-risk HPVs, the effect of which helps halt the progression of cervical transformation and transmission of the virus.

Clinical Trials Registration
NCT03436251.
Vaccinated and Convalescent Donor–Derived Severe Acute Respiratory Syndrome Coronavirus 2–Specific T Cells as Adoptive Immunotherapy for High-Risk Coronavirus Disease 2019 Patients
Authors: Papayanni Penelope-Georgia , Chasiotis Dimitrios , Koukoulias Kiriakos , Georgakopoulou Aphrodite , Iatrou Anastasia , Gavriilaki Eleni , Giannaki Chrysavgi , Bitzani Militsa , Geka Eleni , Tasioudis Polychronis , Chloros Diamantis , Fylaktou Asimina , Kioumis Ioannis , Triantafyllidou Maria , Dimou-Besikli Sotiria , Karavalakis Georgios , Boutou Afroditi K , Siotou Eleni , Anagnostopoulos Achilles , Papadopoulou Anastasia , Yannaki Evangelia 
Published: April 2021

Abstract

Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19).

Methods
We first tested SARS-CoV-2–specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19–infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)–positive subjects, vaccinated individuals, non–intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment.

Results
We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2–specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2–specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity.

Conclusions
Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an “off-the shelf” T-cell immunotherapy for high-risk patients.
The music of Iannis Xenakis’ estrangedKassandra
Authors: Pillinger Emily 
Published: April 2021

AbstractIannis Xenakis (1922–2001) was a radically innovative composer. Violently persecuted for his leftist activism in the Greek Civil War that followed the Second World War, he fled Greece to live the rest of his life in Paris. One of the most explicit expressions of his resultant feelings of trauma, guilt, and displacement can be found in the vocal piece he called Kassandra (1987). This demanding work requires its two performers to enact and explore the alienation experienced by the prophet Cassandra in Aeschylus’ Agamemnon. Xenakis’ Kassandra is defined by a symbiotic relationship between percussionist and vocalist, by a simultaneously controlled and improvisatory score based on extracts from Aeschylus’ Agamemnon, and by a striking use of the baritone singer’s falsetto as well as his chest voice. These features of the piece mark out Cassandra as ‘other’ in her origins, her sex, and her language, while also hinting that her characteristics are not entirely foreign, but are in fact understood or even shared by the very communities that initially seemed to exclude her.
Perioperative Venous Thromboembolism in Ulcerative Colitis: A Multicenter Prospective Study in Japan
Authors: Itabashi Michio , Ikeuchi Hiroki , Kimura Hideaki , Fukushima Kohei , Fujii Hisao , Nezu Riichiro , Futami Kitaro , Sugita Akira , Suzuki Yasuo , Hisamatsu Tadakazu 
Published: April 2021

Abstract

Background
Recently, the prevalence of venous thromboembolism (VTE) in Asian patients with inflammatory bowel disease (IBD) is gradually increasing. IBD surgery is a well-recognized risk factor for VTE. However, there are no prospective studies about VTE after surgery for ulcerative colitis (UC) in Asia. This multicenter prospective study aimed to clarify the prevalence and risk factors for perioperative VTE in UC surgery in Japan.

Methods
A total of 134 patients with UC were included from January 1, 2013 to December 31, 2014. Preoperative screening was performed in all patients. In the perioperative period, standard VTE prophylaxis based on risk assessment was administered. The prevalence of pre- and postoperative VTE, its risk factors, and mortality rates were investigated.

Results
Perioperative deep vein thrombosis and pulmonary embolism were diagnosed in 15 (11.1%) and 1 patient (0.7%), respectively. All patients were asymptomatic. No surgery-related deaths were found (mortality rate 0%). Seven patients (5.2%) were diagnosed, and 8 (6.4%) during postoperative follow-up by ultrasonography or computed tomography. Forty-seven percent of VTE cases was developed preoperatively. A preoperative hospital length stay of over 5 days was a significant risk factor [P = 0.04; odds ratio: 8.26 (1.06–64.60)] for preoperative VTE. Postoperative deep vein thrombosis occurred in 8 of the 127 patients (6.4%). Six out of these 8 (75.0%) occurred after postoperative day 14. Perioperative blood transfusion was a significant risk factor [P = 0.04; odds ratio: 8.26 (1.06–64.60)] for postoperative VTE.

Conclusion
A VTE-conscious perioperative management is as necessary in Asia as in Western countries.
Optimizing indices of atrial fibrillation susceptibility and burden to evaluate atrial fibrillation severity, risk and outcomes
Authors: Boriani Giuseppe , Vitolo Marco , Diemberger Igor , Proietti Marco , Valenti Anna Chiara , Malavasi Vincenzo Livio , Lip Gregory Y H 
Published: April 2021

Abstract
Atrial fibrillation (AF) has heterogeneous patterns of presentation concerning symptoms, duration of episodes, AF burden, and the tendency to progress towards the terminal step of permanent AF. AF is associated with a risk of stroke/thromboembolism traditionally considered dependent on patient-level risk factors rather than AF type, AF burden, or other characterizations. However, the time spent in AF appears related to an incremental risk of stroke, as suggested by the higher risk of stroke in patients with clinical AF vs. subclinical episodes and in patients with non-paroxysmal AF vs. paroxysmal AF. In patients with device-detected atrial tachyarrhythmias, AF burden is a dynamic process with potential transitions from a lower to a higher maximum daily arrhythmia burden, thus justifying monitoring its temporal evolution. In clinical terms, the appearance of the first episode of AF, the characterization of the arrhythmia in a specific AF type, the progression of AF, and the response to rhythm control therapies, as well as the clinical outcomes, are all conditioned by underlying heart disease, risk factors, and comorbidities. Improved understanding is needed on how to monitor and modulate the effect of factors that condition AF susceptibility and modulate AF-associated outcomes. The increasing use of wearables and apps in practice and clinical research may be useful to predict and quantify AF burden and assess AF susceptibility at the individual patient level. This may help us reveal why AF stops and starts again, or why AF episodes, or burden, cluster. Additionally, whether the distribution of burden is associated with variations in the propensity to thrombosis or other clinical adverse events. Combining the improved methods for data analysis, clinical and translational science could be the basis for the early identification of the subset of patients at risk of progressing to a longer duration/higher burden of AF and the associated adverse outcomes.
Human IRES Atlas: an integrative platform for studying IRES-driven translational regulation in humans
Authors: Yang Tzu-Hsien , Wang Chung-Yu , Tsai Hsiu-Chun , Liu Cheng-Tse 
Published: April 2021

Abstract
It is now known that cap-independent translation initiation facilitated by internal ribosome entry sites (IRESs) is vital in selective cellular protein synthesis under stress and different physiological conditions. However, three problems make it hard to understand transcriptome-wide cellular IRES-mediated translation initiation mechanisms: (i) complex interplay between IRESs and other translation initiation–related information, (ii) reliability issue of in silico cellular IRES investigation and (iii) labor-intensive in vivo IRES identification. In this research, we constructed the Human IRES Atlas database for a comprehensive understanding of cellular IRESs in humans. First, currently available and suitable IRES prediction tools (IRESfinder, PatSearch and IRESpy) were used to obtain transcriptome-wide human IRESs. Then, we collected eight genres of translation initiation–related features to help study the potential molecular mechanisms of each of the putative IRESs. Three functional tests (conservation, structural RNA–protein scores and conditional translation efficiency) were devised to evaluate the functionality of the identified putative IRESs. Moreover, an easy-to-use interface and an IRES–translation initiation interaction map for each gene transcript were implemented to help understand the interactions between IRESs and translation initiation–related features. Researchers can easily search/browse an IRES of interest using the web interface and deduce testable mechanism hypotheses of human IRES-driven translation initiation based on the integrated results. In summary, Human IRES Atlas integrates putative IRES elements and translation initiation–related experiments for better usage of these data and deduction of mechanism hypotheses.
Database URL: http://cobishss0.im.nuk.edu.tw/Human_IRES_Atlas/
The 12-lead electrocardiogram as a biomarker of biological age
Authors: Ladejobi Adetola O , Medina-Inojosa Jose R , Shelly Cohen Michal , Attia Zachi I , Scott Christopher G , LeBrasseur Nathan K , Gersh Bernard J , Noseworthy Peter A , Friedman Paul A , Kapa Suraj , Lopez-Jimenez Francisco 
Published: April 2021

Abstract

Background
We have demonstrated that a neural network is able to predict a person’s age from the electrocardiogram (ECG) [artificial intelligence (AI) ECG age]. However, some discrepancies were observed between ECG-derived and chronological ages. We assessed whether the difference between AI ECG and chronological age (Age-Gap) represents biological ageing and predicts long-term outcomes.

Methods and results
We previously developed a convolutional neural network to predict chronological age from ECGs. In this study, we used the network to analyse standard digital 12-lead ECGs in a cohort of 25 144 subjects ≥30 years who had primary care outpatient visits from 1997 to 2003. Subjects with coronary artery disease, stroke, and atrial fibrillation were excluded. We tested whether Age-Gap was correlated with total and cardiovascular mortality. Of 25 144 subjects tested (54% females, 95% Caucasian) followed for 12.4 ± 5.3 years, the mean chronological age was 53.7 ± 11.6 years and ECG-derived age was 54.6 ± 11 years (R2 = 0.79, P &lt; 0.0001). The mean Age-Gap was small at 0.88 ± 7.4 years. Compared to those whose ECG-derived age was within 1 standard deviation (SD) of their chronological age, patients with Age-Gap ≥1 SD had higher all-cause and cardiovascular disease (CVD) mortality. Conversely, subjects whose Age-Gap was ≤1 SD had lower all-cause and CVD mortality. Results were unchanged after adjusting for CVD risk factors and other survival influencing factors.

Conclusion
The difference between AI ECG and chronological age is an independent predictor of all-cause and cardiovascular mortality. Discrepancies between these possibly reflect disease independent biological ageing.
Daily rhythms of both host and parasite affect antimalarial drug efficacy
Authors: Owolabi Alíz T Y , Reece Sarah E , Schneider Petra 
Published: April 2021

ABSTRACT

Background and objectives
Circadian rhythms contribute to treatment efficacy in several non-communicable diseases. However, chronotherapy (administering drugs at a particular time-of-day) against infectious diseases has been overlooked. Yet, the daily rhythms of both hosts and disease-causing agents can impact the efficacy of drug treatment. We use the rodent malaria parasite Plasmodium chabaudi, to test whether the daily rhythms of hosts, parasites and their interactions affect sensitivity to the key antimalarial, artemisinin.

Methodology
Asexual malaria parasites develop rhythmically in the host’s blood, in a manner timed to coordinate with host daily rhythms. Our experiments coupled or decoupled the timing of parasite and host rhythms, and we administered artemisinin at different times of day to coincide with when parasites were either at an early (ring) or later (trophozoite) developmental stage. We quantified the impacts of parasite developmental stage, and alignment of parasite and host rhythms, on drug sensitivity.

Results
We find that rings were less sensitive to artemisinin than trophozoites, and this difference was exacerbated when parasite and host rhythms were misaligned, with little direct contribution of host time-of-day on its own. Furthermore, the blood concentration of haem at the point of treatment correlated positively with artemisinin efficacy but only when parasite and host rhythms were aligned.

Conclusions and implications
Parasite rhythms influence drug sensitivity in vivo. The hitherto unknown modulation by alignment between parasite and host daily rhythms suggests that disrupting the timing of parasite development could be a novel chronotherapeutic approach.

Lay Summary
We reveal that chronotherapy (providing medicines at a particular time-of-day) could improve treatment for malaria infections. Specifically, parasites’ developmental stage at the time of treatment and the coordination of timing between parasite and host both affect how well antimalarial drug treatment works.
Underperformance of clinical risk scores in identifying vascular ultrasound-based high cardiovascular risk in systemic lupus erythematosus
Authors: Drosos George C , Konstantonis George , Sfikakis Petros P , Tektonidou Maria G 
Published: April 2021

Abstract

Aims
The aim of this study was to assess the performance of eight clinical risk prediction scores to identify individuals with systemic lupus erythematosus (SLE) at high cardiovascular disease (CVD) risk, as defined by the presence of atherosclerotic plaques.

Methods
CVD risk was estimated in 210 eligible SLE patients without prior CVD or diabetes mellitus (female: 93.3%, mean age: 44.8 ± 12 years) using five generic (Systematic Coronary Risk Evaluation (SCORE), Framingham Risk Score (FRS), Pooled Cohort Risk Equations (ASCVD), Globorisk, Prospective Cardiovascular Münster Study risk calculator (PROCAM)) and three ‘SLE-adapted’ (modified-SCORE, modified-FRS, QRESEARCH risk estimator, version 3 (QRISK3)) CVD risk scores, as well as ultrasound examination of the carotid and femoral arteries. Calibration, discrimination and classification measures to identify high CVD risk based on the presence of atherosclerotic plaques were assessed for all risk models. CVD risk reclassification was applied for all scores by incorporating ultrasound results.

Results
Moderate calibration (p-value range from 0.38 to 0.63) and discrimination (area under the curve 0.73–0.84), and low-to-moderate sensitivity (8.3–71.4%) and classification ability (Matthews correlation coefficient (MCC) 0.25–0.47) were observed for all risk models to identify patients with plaques at any arterial site as high-risk. MCC was improved for modified-FRS versus FRS (0.43 vs 0.36), but not for modified-SCORE versus SCORE (0.25 vs 0.25). Based on plaque presence, CVD risk was upgraded to high-risk in 10%, 16.1%, 20.5%, 21.5%, 24%, 28.2% and 28.6% of cases classified as non-high-risk by QRISK3, modified-FRS, Globorisk, FRS/PROCAM, ASCVD, modified-SCORE and SCORE, respectively.

Conclusions
Most of the five generic and three ‘SLE-adapted’ clinical risk scores underestimated high CVD risk defined by atherosclerotic plaque presence in patients with SLE.