bluuebunny/crossref_metadata_2025_split huggingface dataset:
ToxinPred2: an improved method for predicting toxicity of proteins
Authors: Sharma Neelam , Naorem Leimarembi Devi , Jain Shipra , Raghava Gajendra P S 
Published: April 2022

AbstractProteins/peptides have shown to be promising therapeutic agents for a variety of diseases. However, toxicity is one of the obstacles in protein/peptide-based therapy. The current study describes a web-based tool, ToxinPred2, developed for predicting the toxicity of proteins. This is an update of ToxinPred developed mainly for predicting toxicity of peptides and small proteins. The method has been trained, tested and evaluated on three datasets curated from the recent release of the SwissProt. To provide unbiased evaluation, we performed internal validation on 80% of the data and external validation on the remaining 20% of data. We have implemented the following techniques for predicting protein toxicity; (i) Basic Local Alignment Search Tool-based similarity, (ii) Motif-EmeRging and with Classes-Identification-based motif search and (iii) Prediction models. Similarity and motif-based techniques achieved a high probability of correct prediction with poor sensitivity/coverage, whereas models based on machine-learning techniques achieved balance sensitivity and specificity with reasonably high accuracy. Finally, we developed a hybrid method that combined all three approaches and achieved a maximum area under receiver operating characteristic curve around 0.99 with Matthews correlation coefficient 0.91 on the validation dataset. In addition, we developed models on alternate and realistic datasets. The best machine learning models have been implemented in the web server named ‘ToxinPred2’, which is available at https://webs.iiitd.edu.in/raghava/toxinpred2/ and a standalone version at https://github.com/raghavagps/toxinpred2. This is a general method developed for predicting the toxicity of proteins regardless of their source of origin.
Electrocardiographic biomarker based on machine learning for detecting overt hyperthyroidism
Authors: Choi Byungjin , Jang Jong Hwan , Son Minkook , Lee Min Sung , Jo Yong Yeon , Jeon Ja Young , Jin Uram , Soh Moonseung , Park Rae Woong , Kwon Joon myoung 
Published: April 2022

Abstract

Aims
Although overt hyperthyroidism adversely affects a patient’s prognosis, thyroid function tests (TFTs) are not routinely conducted. Furthermore, vague symptoms of hyperthyroidism often lead to hyperthyroidism being overlooked. An electrocardiogram (ECG) is a commonly used screening test, and the association between thyroid function and ECG is well known. However, it is difficult for clinicians to detect hyperthyroidism through subtle ECG changes. For early detection of hyperthyroidism, we aimed to develop and validate an electrocardiographic biomarker based on a deep learning model (DLM) for detecting hyperthyroidism.

Methods and results
This multicentre retrospective cohort study included patients who underwent ECG and TFTs within 24 h. For model development and internal validation, we obtained 174 331 ECGs from 113 194 patients. We extracted 48 648 ECGs from 33 478 patients from another hospital for external validation. Using 500 Hz raw ECG, we developed a DLM with 12-lead, 6-lead (limb leads, precordial leads), and single-lead (lead I) ECGs to detect overt hyperthyroidism. We calculated the model’s performance on the internal and external validation sets using the area under the receiver operating characteristic curve (AUC). The AUC of the DLM using a 12-lead ECG was 0.926 (0.913–0.94) for internal validation and 0.883(0.855–0.911) for external validation. The AUC of DLMs using six and a single-lead were in the range of 0.889–0.906 for internal validation and 0.847–0.882 for external validation.

Conclusion
We developed a DLM using ECG for non-invasive screening of overt hyperthyroidism. We expect this model to contribute to the early diagnosis of diseases and improve patient prognosis.
A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy
Authors: Cadrin-Tourigny Julia , Bosman Laurens P , Nozza Anna , Wang Weijia , Tadros Rafik , Bhonsale Aditya , Bourfiss Mimount , Fortier Annik , Lie Øyvind H , Saguner Ardan M , Svensson Anneli , Andorin Antoine , Tichnell Crystal , Murray Brittney , Zeppenfeld Katja , van den Berg Maarten P , Asselbergs Folkert W , Wilde Arthur A M , Krahn Andrew D , Talajic Mario , Rivard Lena , Chelko Stephen , Zimmerman Stefan L , Kamel Ihab R , Crosson Jane E , Judge Daniel P , Yap Sing Chien , van der Heijden Jeroen F , Tandri Harikrishna , Jongbloed Jan D H , Guertin Marie Claude , van Tintelen J Peter , Platonov Pyotr G , Duru Firat , Haugaa Kristina H , Khairy Paul , Hauer Richard N W , Calkins Hugh , te Riele Anneline S J M , James Cynthia A 
Published: April 2022

Abstract

Aims
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.

Methods and results
Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44–9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73–0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92–0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P &lt; 0.001).

Conclusion
Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
Cardiovascular risk factors in the elderly: a 10-year follow-up survival analysis
Authors: Vilela de Sousa Thaís , Cavalcante Agueda Maria Ruiz Zimmer , Lima Nathália Xavier , Souza Jennifer Siqueira , Sousa Ana Luiza Lima , Brasil Virginia Visconde , Vieira Flaviana Vely Mendonça , Guimarães Janaína Valadares , de Matos Marcos André , Silveira Erika Aparecida , Pagotto Valéria 
Published: April 2022

Abstract

Aims
Cardiovascular risk factors present a high prevalence and have an impact on the morbimortality of the elderly; however, studies evaluating the impact of cardiovascular risk factors in the elderly have had short follow-up times and have not allowed specific analyses of the effects of these factors in the aged population, including how they affect the survival of the elderly. This study aimed to analyse the survival of elderly individuals living in the community, considering the presence of cardiovascular risk factors.

Methods and results
A prospective 10-year follow-up was initiated in 2008 with a cohort of 418 elderly people living in a community in Central Brazil. The Kaplan–Meier method and the Cox proportional hazards model were used to examine the association between survival and cardiovascular risk factors. The mean age of the participants was 70.6 (±7.1) years; most participants were hypertensive (81.6%) and participated in irregular physical activity (44%), and 43.3% smoked. After a mean follow-up of 8.38 (±2.82) years, 59.3% had survived and 34.1% had died; among the deaths, 14.1% were due to cardiovascular causes. Age [hazard ratio (HR) 1.067, 95% confidence interval (CI) 1.027–1.109], hypertension (HR 3.178, 95% CI 1.144–8.826), and smoking (HR 2.235, 95% CI 1.253–3.987) were confirmed as risk factors for reduced survival, whereas physical activity was a protective factor (HR 0.456, 95% CI 0.206–1.007).

Conclusion
The results from this study highlight the need for educational policies towards hypertension and smoking prevention among elderly people, and participation in physical activity needs to be encouraged.
The influence of exercise and postural changes on ventricular repolarization in the long QT syndrome: a systematic scoping review
Authors: Harvey Audrey , Curnier Daniel , Dodin Philippe , Abadir Sylvia , Jacquemet Vincent , Caru Maxime 
Published: April 2022

Abstract
Current exercise recommendations make it difficult for long QT syndrome (LQTS) patients to adopt a physically active and/or athletic lifestyle. The purpose of this review is to summarize the current evidence, identify knowledge gaps, and discuss research perspectives in the field of exercise and LQTS. The first aim is to document the influence of exercise training, exercise stress, and postural change interventions on ventricular repolarization in LQTS patients, while the second aim is to describe electrophysiological measurements used to study the above. Studies examining the effects of exercise on congenital or acquired LQTS in human subjects of all ages were included. Systematic searches were performed on 1 October 2021, through PubMed (NLM), Ovid Medline, Ovid All EBM Reviews, Ovid Embase, and ISI Web of Science, and limited to articles written in English or French. A total of 1986 LQTS patients and 2560 controls were included in the 49 studies. Studies were mainly case–control studies (n = 41) and examined exercise stress and/or postural change interventions (n = 48). One study used a 3-month exercise training program. Results suggest that LQTS patients have subtype-specific repolarization responses to sympathetic stress. Measurement methods and quality were found to be very heterogeneous, which makes inter-study comparisons difficult. In the absence of randomized controlled trials, the current recommendations may have long-term risks for LQTS patients who are discouraged from performing physical activity, rendering its associated health benefits out of range. Future research should focus on discovering the most appropriate levels of exercise training that promote ventricular repolarization normalization in LQTS.
Genetic mapping and prediction of flowering time and plant height in a maize Stiff Stalk MAGIC population
Authors: Michel Kathryn J , Lima Dayane C , Hundley Hope , Singan Vasanth , Yoshinaga Yuko , Daum Chris , Barry Kerrie , Broman Karl W , Robin Buell C , de Leon Natalia , Kaeppler Shawn M 
Published: April 2022

Abstract
The Stiff Stalk heterotic pool is a foundation of US maize seed parent germplasm and has been heavily utilized by both public and private maize breeders since its inception in the 1930s. Flowering time and plant height are critical characteristics for both inbred parents and their test crossed hybrid progeny. To study these traits, a 6-parent multiparent advanced generation intercross population was developed including maize inbred lines B73, B84, PHB47 (B37 type), LH145 (B14 type), PHJ40 (novel early Stiff Stalk), and NKH8431 (B73/B14 type). A set of 779 doubled haploid lines were evaluated for flowering time and plant height in 2 field replicates in 2016 and 2017, and a subset of 689 and 561 doubled haploid lines were crossed to 2 testers, respectively, and evaluated as hybrids in 2 locations in 2018 and 2019 using an incomplete block design. Markers were derived from a practical haplotype graph built from the founder whole genome assemblies and genotype-by-sequencing and exome capture-based sequencing of the population. Genetic mapping utilizing an update to R/qtl2 revealed differing profiles of significant loci for both traits between 635 of the DH lines and 2 sets of 570 and 471 derived hybrids. Genomic prediction was used to test the feasibility of predicting hybrid phenotypes based on the per se data. Predictive abilities were highest on direct models trained using the data they would predict (0.55–0.63), and indirect models trained using per se data to predict hybrid traits had slightly lower predictive abilities (0.49–0.55). Overall, this finding is consistent with the overlapping and nonoverlapping significant quantitative trait loci found within the per se and hybrid populations and suggests that selections for phenology traits can be made effectively on doubled haploid lines before hybrid data is available.
Quality of Survey Responses at Older Ages Predicts Cognitive Decline and Mortality Risk
Authors: Schneider Stefan , Junghaenel Doerte U , Meijer Erik , Zelinski Elizabeth M , Jin Haomiao , Lee Pey-Jiuan , Stone Arthur A 
Published: April 2022

Abstract

Background and Objectives
It is widely recognized that survey satisficing, inattentive, or careless responding in questionnaires reduce the quality of self-report data. In this study, we propose that such low-quality responding (LQR) can carry substantive meaning at older ages. Completing questionnaires is a cognitively demanding task and LQR among older adults may reflect early signals of cognitive deficits and pathological aging. We hypothesized that older people displaying greater LQR would show faster cognitive decline and greater mortality risk.

Research Design and Methods
We analyzed data from 9, 288 adults 65 years or older in the Health and Retirement Study. Indicators of LQR were derived from participants’ response patterns in 102 psychosocial questionnaire items administered in 2006–2008. Latent growth models examined whether LQR predicted initial status and change in cognitive functioning, assessed with the modified Telephone Interview for Cognitive Status, over the subsequent 10 years. Discrete-time survival models examined whether LQR was associated with mortality risk over the 10 years. We also examined evidence for indirect (mediated) effects in which LQR predicts mortality via cognitive trajectories.

Results
After adjusting for age, gender, race, marital status, education, health conditions, smoking status, physical activity, and depressive symptoms, greater LQR was cross-sectionally associated with poorer cognitive functioning, and prospectively associated with faster cognitive decline over the follow-up period. Furthermore, greater LQR was associated with increased mortality risk during follow-up, and this effect was partially accounted for by the associations between LQR and cognitive functioning.

Discussion and Implications
Self-report questionnaires are not formally designed as cognitive tasks, but this study shows that LQR indicators derived from self-report measures provide objective, performance-based information about individuals’ cognitive functioning and survival. Self-report surveys are ubiquitous in social science, and indicators of LQR may be of broad relevance as predictors of cognitive and health trajectories in older people.
Ganciclovir and Valganciclovir Use Among Infants With Congenital Cytomegalovirus: Data From a Multicenter Electronic Health Record Dataset in the United States
Authors: Leung Jessica , Grosse Scott D , Yockey Bryan , Lanzieri Tatiana M 
Published: April 2022

Abstract
Among 342 US infants with congenital cytomegalovirus treated with antivirals, 114 (33%) received ganciclovir (with or without valganciclovir) and 228 (67%) received valganciclovir only, for a median of 8 and 171 days, starting at a median of 15 and 45 days of life, respectively, with neutropenia diagnosed in 25% and 17%.
Solidarity Work as Political Action: Advocating for Refugees and Asylum Seekers in the USA
Authors: Libal Kathryn , Harding Scott , Champagne Lukas 
Published: April 2022

AbstractVolunteers in the USA have long provided support for refugees being resettled through the UNHCR-based refugee resettlement program, as well as for asylum seekers and other undocumented migrants through local community or faith-based organizations. Individual and collective acts of solidarity on behalf of those seeking sanctuary, asylum seekers, and refugees have recently increased, reflecting public reaction to increasingly restrictive US immigration policies. Based on interviews with community volunteers and leaders, we analyse this activism in terms of whether it constitutes social solidarity, civic solidarity, and/or political solidarity. We find this solidarity action on behalf of forced migrants has been relatively ‘low-risk’ compared to other countries, where activists have faced imprisonment by engaging in ‘high-risk’ solidarity action. In the USA, these efforts have emphasized civic and social solidarity, with limited political solidarity actions even when volunteers have been confronted by explicitly racist and exclusionary policies. In addition, this response has yet to develop into a broader political movement in support of refugees, asylum seekers, and immigrants.
EDGE: The sensitivity of ultra-faint dwarfs to a metallicity-dependent initial mass function
Authors: Prgomet Mateo , Rey Martin P , Andersson Eric P , Segovia Otero Alvaro , Agertz Oscar , Renaud Florent , Pontzen Andrew , Read Justin I 
Published: April 2022

ABSTRACT
Motivated by the observed bottom-light initial mass function (IMF) in faint dwarfs, we study how a metallicity-dependent IMF affects the feedback budget and observables of an ultra-faint dwarf galaxy. We model the evolution of a low-mass ($\approx 8 \, \times \, 10^{8} \, \rm M_{\odot }$) dark matter halo with cosmological, zoomed hydrodynamical simulations capable of resolving individual supernovae explosions, which we complement with an empirically motivated subgrid prescription for systematic IMF variations. In this framework, at the low gas metallicities typical of faint dwarfs, the IMF of newborn stellar populations becomes top-heavy, increasing the efficiency of supernova and photoionization feedback in regulating star formation. This results in a 100-fold reduction of the final stellar mass of the dwarf compared to a canonical IMF, at fixed dynamical mass. The increase in the feedback budget is none the less met by increased metal production from more numerous massive stars, leading to nearly constant iron content at z = 0. A metallicity-dependent IMF therefore provides a mechanism to produce low-mass ($\rm M_{\star }\sim 10^3 \rm M_{\odot }$), yet enriched ($\rm [Fe/H]\approx -2$) field dwarf galaxies, thus opening a self-consistent avenue to populate the plateau in $\rm [Fe/H]$ at the faintest end of the mass–metallicity relation.
Search for gamma-ray emission from a galactic supernova with the anticoincidence system of SPI
Authors: Caixach M , Jean P , Isern J , Bravo E 
Published: April 2022

ABSTRACT
The detection of the very early gamma-emission of a Type Ia supernova (SNIa) could provide a deep insight on the explosion mechanism and nature of the progenitor. However, this has not been yet possible as a consequence of the expected low luminosity and the distance at which all the events have occurred up to now. An SNIa occurring in our Galaxy could provide a unique opportunity to perform such a measurement. The problem is that the optical flux would probably be so attenuated by interstellar extinction that it would prevent triggering the observations with gamma-spectrometers at the due time. In this paper, we analyse the possibility of using the anticoincidence system (ACS) of the spectrometer SPI on board of the INTEGRAL space observatory for detecting the early gamma-ray emission of an SNIa as a function of the explosion model and distance, as well as of pointing direction. Our results suggest that such detection is possible at about 6–12 d after the explosion, and at the same time, we can discard missing any hidden explosion during the lifetime of INTEGRAL.
Cryptococcus neoformans–Specific and Non–Cryptococcus neoformans–Specific Antibody Profiles in Organ Transplant Recipients With and Without Cryptococcosis
Authors: Yoon Hyunah , Nakouzi Antonio , Pappas Peter G , Hemmige Vagish S , Pirofski Liise anne 
Published: April 2022

Abstract
Antibody immunity has not been studied in organ transplant recipients (OTRs) with cryptococcosis. We determined serum antibody levels in OTRs: 23 cryptococcosis cases and 21 controls. Glucuronoxylomannan immunoglobulin M (IgM) and laminarin IgM were lower in cases than controls, were inversely associated with cryptococcosis status, and may hold promise as markers of cryptococcosis.
Textual Development
Authors: Kohn Livia 
Published: April 2022

Abstract
The Daode jing consists of five thousand words, eighty-one chapters, and two parts, focusing on Dao and de (virtue), respectively. Made up largely of aphorisms and sayings, its language and rhyme structure are like ancient Chinese poetry, suggesting a date around 500 bce. The text has survived in several manuscripts found in tombs. The bamboo slips discovered at Guodian (ca. 300 bce) contain about one third of the text; the silk manuscripts at Mawangdui (168 bce) present it entirely. The standard edition was probably edited at the Han court; it is associated with the Daoist immortal Heshang Gong, the Master on the River. The edition considered standard since the Tang, moreover, goes back to the philosopher Wang Bi, an intellectual and official of the early third century ce whose critical edition and in-depth understanding of the text has shaped its perception to the present day.
Later Developments
Authors: Kohn Livia 
Published: April 2022

Abstract
Under the Tang, Daode jing interpretation centered in Twofold Mystery, a school that understood it through Buddhist Mādhyamika and related it to advanced spiritual attainments. In the eighth century ce, Emperor Xuanzong elevated the text to sacred scripture, made it part of the imperial examination system, and used its teachings for governmental guidance. Under the Song, Emperor Huizong, who saw himself as an exiled immortal, applied its teachings in governance and society. It also featured in the meditation practice of internal alchemy, a refinement of bodily energies. Members of the school of Complete Perfection, dominant since the thirteenth century, moreover, emphasized the Daode jing notions of clarity and stillness, which were further codified in the formulaic Qingjing jing (Scripture of Clarity and Stillness), recited in daily Daoist services to the present day.
Animal ethics in a human world
Authors: Sebo Jeff 
Published: April 2022

Abstract
This chapter argues that we have a duty to reduce and repair human-caused harms to nonhuman animals. If we accept that we can have duties to members of other nations, generations, and species in general, then we should accept that we have a duty to help animals as much as reasonably possible and to harm them only when necessary for self-defense or other such purposes. For many consequentialists, we should accept this framework so that we can do the most good possible, given the increasing complexity of global harm. And for many nonconsequentialists, we should accept this framework so that we can reduce and repair human-caused harms, given our increasing complicity in global harm. Either way, consequentialists and nonconsequentialists alike should accept this framework in practice.