bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impulse control disorders and related behaviors in Parkinson's disease: risk factors, clinical and genetic aspects, and management
Authors: Faouzi Johann , Corvol Jean-Christophe , Mariani Louise-Laure 
Published: May 2021

Purpose of review
To review recent findings and research directions on impulse control disorders and related behaviors (ICDRBs) in Parkinson's disease (PD).

Recent findings
Longitudinal studies found that prevalence increases during PD progression, incident ICDRBs being around 10% per year in patients treated with dopaminergic therapies. Screening tools and severity scales already developed have been validated and are available in several countries and languages. The main clinical risk factors include young age, male gender, type, doses and duration of dopaminergic therapy, PD motor severity and dyskinesia, depression, anxiety, apathy, sleep disorders, and impulsivity traits. Genetic factors are suspected by a high estimated heritability, but individual genes and variants remain to be replicated. Management of ICDRBs is centered on dopamine agonist decrease, with the risk to develop withdrawal symptoms. Cognitive behavioral therapy and subthalamic nucleus deep brain stimulation also improve ICDRBs. In the perspective of precision medicine, new individual prediction models of these disorders have been proposed, but they need further independent replication.

Summary
Regular monitoring of ICDRB during the course of PD is needed, particularly in the subject at high risk of developing these complications. Precision medicine will require the appropriate use of machine learning to be reached in the clinical setting.
Clinical Validation of Saliency Maps for Understanding Deep Neural Networks in Ophthalmology
Authors: Ayhan Murat Seçkin , Kümmerle Louis Benedikt , Kühlewein Laura , Inhoffen Werner , Aliyeva Gulnar , Ziemssen Focke , Berens Philipp 
Published: May 2021

AbstractDeep neural networks (DNNs) have achieved physician-level accuracy on many imaging-based medical diagnostic tasks, for example classification of retinal images in ophthalmology. However, their decision mechanisms are often considered impenetrable leading to a lack of trust by clinicians and patients. To alle-viate this issue, a range of explanation methods have been proposed to expose the inner workings of DNNs leading to their decisions. For imaging-based tasks, this is often achieved via saliency maps. The quality of these maps are typically evaluated via perturbation analysis without experts involved. To facilitate the adoption and success of such automated systems, however, it is crucial to validate saliency maps against clinicians. In this study, we used three different network architectures and developed ensembles of DNNs to detect diabetic retinopathy and neovascular age-related macular degeneration from retinal fundus images and optical coherence tomography scans, respectively. We used a variety of explanation methods and obtained a comprehensive set of saliency maps for explaining the ensemble-based diagnostic decisions. Then, we systematically validated saliency maps against clinicians through two main analyses — a direct comparison of saliency maps with the expert annotations of disease-specific pathologies and perturbation analyses using also expert annotations as saliency maps. We found the choice of DNN architecture and explanation method to significantly influence the quality of saliency maps. Guided Backprop showed consistently good performance across disease scenarios and DNN architectures, suggesting that it provides a suitable starting point for explaining the decisions of DNNs on retinal images.
Estimating the Burden of Influenza on Daily Activity at Population Scale Using Commercial Wearable Sensors
Authors: Mezlini Aziz , Shapiro Allison , Daza Eric J. , Caddigan Eamon , Ramirez Ernesto , Althoff Tim , Foschini Luca 
Published: May 2021

ABSTRACTThe severity of viral infections can vary widely, from asymptomatic cases to complications leading to hospitalizations and death. Milder cases, despite being more prevalent, often go undocumented and their public health impact unaccounted for. We estimated the burden of influenza-like-illness (ILI) by leveraging the widespread use of commercial activity trackers. Analysing data from 15,382 US participants who reported ILI symptoms during the 2018–2019 flu season (before the COVID-19 pandemic) and who had high-density wearable sensor data at symptom onset, we estimated an overall nationwide reduction in mobility equivalent to 257 billion steps lost due to ILI symptoms. This finding reflects significant changes in routines, mobility, and employment and is equivalent to 15% of the active US population becoming completely immobilized for 1 day. Moreover, ∼60% of this impact occurred among individuals who sought no medical care, who would otherwise be invisible to healthcare and public health reporting systems. We validated our measure against self-reported measures of disease severity. We believe this method has applications for public health, healthcare, and clinical research, from estimating costs of lost productivity at population scale, to measuring effectiveness of anti-ILI treatments, to monitoring recovery after acute viral syndromes, such as during ‘long COVID’.
Estimated Spike Evolution and Impact of Emerging SARS-CoV-2 Variants
Authors: Lu Yong , Han Kun , Xue Gang , Zheng Ningbo , Jin Guangxu 
Published: May 2021

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been mutating and thus variants emerged. This suggests that SARS-CoV-2 could mutate at an unsteady pace. Supportive evidence comes from the accelerated evolution which was revealed by tracking mutation rates of the genomic location of Spike protein. This process is sponsored by a small portion of the virus population but not the largest viral clades. Moreover, it generally took one to six months for current variants that caused peaks of COVID-19 cases and deaths to survive selection pressure. Based on this statistic result and the above speedy Spike evolution, another upcoming peak would come around July 2021 and disastrously attack Africa, Asia, Europe, and North America. This is the prediction generated by a mathematical model on evolutionary spread. The reliability of this model and future trends out of it comes from the comprehensive consideration of factors mainly including mutation rate, selection course, and spreading speed. Notably, if the prophecy is true, then the new wave will be the first determined by accelerated Spike evolution.
Adaptation of the Person-Centered Maternity Care scale for people of color in the United States
Authors: Afulani Patience A. , Altman Molly R. , Castillo Esperanza , Bernal Nayeli , Jones Linda , Camara Tanefer , Carrasco Zoe , Williams Shanell , Sudhinaraset May , Kuppermann Miriam 
Published: May 2021

AbstractIntroductionMistreatment by healthcare providers disproportionately affects people of color in the United States (US). The goal of this study is to adapt the global Person-Centered Maternity Care (PCMC) scale to the experiences of people of color in the US using a community-engaged approach.MethodsWe conducted expert reviews to improve content validity and cognitive interviews with potential respondents were conducted to assess relevance, comprehension, and comprehensiveness. Surveys of 297 postpartum people, 82% of whom identified as Black, were used for psychometric analysis in which we assessed construct and criterion validity and reliability. The University of California, San Francisco, California Preterm Birth Initiative’s Community Advisory Board (CAB), which consists of community members, community-based health workers, and social service providers in Northern California, provided input during all stages of the project.ResultsThrough an iterative process of factor analysis, discussions with the CAB, and a prioritization survey, we eliminated items that performed poorly in psychometric analysis, yielding a 35-item PCMC-US scale with sub-scales for “dignity and respect,” “communication and autonomy,” and “responsive and supportive care.” The Cronbach’s alpha for the full scale is 0.95 and for the sub-scales is 0.87. Standardized summative scores range from 0 to 100, with higher scores indicating higher PCMC. Correlations with related measures indicated high criterion validity.ConclusionsThe 35-item PCMC-US scale and its sub-scales have high validity and reliability in a sample of predominantly Black women. This scale provides a tool to support efforts to reduce the disparities in birth outcomes among people of color.
Genetic variant in SPDL1 reveals novel mechanism linking pulmonary fibrosis risk and cancer protection
Authors: Koskela Jukka T. , Häppölä Paavo , Liu Aoxing ,   FinnGen, Partanen Juulia , Genovese Giulio , Artomov Mykyta , Myllymäki Mikko N.M. , Kanai Masahiro , Zhou Wei , Karjalainen Juha M. , Palviainen Teemu , Ronkainen Justiina , Sebert Sylvain , Tukiainen Taru , Palta Priit , Kaprio Jaakko , Kurki Mitja , Ganna Andrea , Palotie Aarno , Laitinen Tarja , Myllärniemi Marjukka , Daly Mark J. 
Published: May 2021

AbstractIdiopathic Pulmonary Fibrosis (IPF) is a rare disease with poor prognosis. By contrast, cancer is common in any elderly population and a leading killer, but is now often curable. Of note, whereas IPF is driven by cellular senescence, cancer is characterized by uncontrolled cell division.Using data available from two large biobank-based studies (Finnish FinnGen study and UK biobank), we conducted a comprehensive analysis of the shared genetic background of IPF and cancer. In a population sample of 218,792 Finns with complete longitudinal health histories, we estimated the effect of individual genetic variants to the lifetime risk of IPF and cancer. We extend the analysis from IPF-GWAS to pan-cancer meta-analysis over FinnGen and UK Biobank and finally to the identification of genetic drivers of somatic chromosomal alterations.We detected six loci (SPDL1, MAD1L1, MAP2K1, RTEL1-STMN3, TERC-ACTRT3, OBFC1) associated with both IPF and cancer, all closely related to cellular division. However, each individual signal is found with opposite effects over the two diseases, termed as antagonistic pleiotropy. Several of these loci (TERC-ACTRT3, RTEL1-STMN3, OBFC1) are among the strongest inherited factors for constitutive telomere length variation and consistently indicate that shorter telomere length would increase the risk for IPF but protect from malignancy. However, a Finnish enriched SPDL1 missense variant and a common MAD1L1 intronic variant had no effect on telomere length but were shown to protect individuals from accumulation of somatic mutations.The decreased risk of cancer in SPDL1 and MAD1L1 variant carriers might result from a lower number of chromosomal alterations accumulated over time, conversely leading to fibrosis in the lung due to cellular senescence-induced inflammation. We hypothesize that the SPDL1 missense variant functions as gain-of-function mutation, leading to cellular senescence, a barrier to cancer and a driver of fibrosis in IPF. If translated to therapy, these findings might not only be able to offer relief to individuals with IPF, but also to protect from onset of cancer.
Medication use and physical assaults in the psychiatric emergency room
Authors: Gao Y. Nina , Oberhardt Matthew , Vawdrey David , Lawrence Ryan E. , Dixon Lisa B. , Luo Sean X. 
Published: May 2021

AbstractObjectiveTo evaluate the relationship between medications used to treat acute agitation (antipsychotics, mood stabilizers and benzodiazepines) and subsequent assault incidence in the psychiatric emergency room.MethodsMedication orders and assault incident reports were obtained from electronic health records for 17,052 visits to an urban psychiatric emergency room from 2014-2019. Assault risk was modeled longitudinally using Poisson mixed-effect regression.ResultsAssaults were reported during 0.5% of visits. Intramuscular medications (IMs) were administered in 23.3% of visits overall, and predominately administered within the first 4-hours of a visit. IM administration was correlated with assault (IRR=24.2 [5.33, 110.0]), often because IM medication was administered immediately subsequent to reported assaults. Interacted with time, IMs were not significantly associated with reduction in future assaults (IRR=0.700 [0.467, 1.04]). Neither benzodiazepines nor mood stabilizers were associated with subsequent changes to the risk of reported assault. By contrast, antipsychotic medications were associated with decreased assault risk across time (IRR=0.583 [0.360, 0.942]).ConclusionsIM order rates are high relative to overall assault incident risk. Of the three major categories of medications administered commonly in the psychiatric emergency setting, only antipsychotic medications were associated with measurable decreases in subsequent assault risk. Careful weighing of the risks and benefits of medications is encouraged; antipsychotic medication can have a significant side effect burden, and other medications (IMs, benzodiazepines, mood stabilizers) were not associated with subsequent reduction in assault risk in this analysis.
A quantitative risk-benefit analysis of ChAdOx1 nCoV-19 vaccine among people under 60 in Italy
Authors: Palladino Raffaele , Ceriotti Daniele , De Ambrosi Damiano , De Vito Marta , Farsoni Marco , Seminara Giuseppina , Barone-Adesi Francesco 
Published: May 2021

AbstractChAdOx1 nCoV-19 is a vaccine against the COVID-19 infection that was granted a conditional marketing authorization by the European Commission in January 2021. However, following a report from the Pharmacovigilance Risk Assessment Committee (PRAC) of European Medicines Agency, which reported an association with thrombo-embolic events (TEE), in particular Disseminated intravascular coagulation (DIC) and Cerebral venous sinus thrombosis (CVST), many European countries either limited to individuals older than 55-60 years or suspended its use. We used publicly available data to carry out a quantitative risk-benefit analysis of the vaccine among people under 60 in Italy. Specifically, we used data from PRAC, Eudravigilance and ECDC to estimate the excess number of deaths for TEE, DIC and CVST expected in vaccine users, stratified by age groups. We then used data from the National Institute of Health to calculate age-specific COVID-19 mortality rates in Italy. Preventable deaths were calculated assuming a 72% vaccine efficacy over an 8-month period. Finally, benefit-risk ratio of ChAdOx1 nCoV-19 vaccination was calculated as the ratio between preventable COVID-19 deaths and vaccine-related deaths, using Monte-Carlo simulations. We found that among subjects aged 20-29 years the benefit-risk [B-R] ratio was not clearly favorable (0.70; 95% Uncertainty Interval [UI]: 0.27-2.11). However, in the other age groups the benefits of vaccination largely exceeded the risks (for age 30-49, B-R ratio: 22.9: 95%UI: 10.1-186.4). For age 50-59, B-R ratio: 1577.1: 95%UI: 1176.9-2121.5). Although many countries have limited the use of the ChAdOx1 nCoV-19 vaccine, the benefits of using this vaccine clearly outweigh the risks in people older than 30 years. The use of this vaccine should be a strategic and fundamental part of the immunization campaign considering its safety and efficacy in preventing COVID-19 and its complications.
Description of a University COVID-19 Outbreak and Interventions to Disrupt Transmission, Wisconsin, August – October 2020
Authors: Currie Dustin W. , Moreno Gage K. , Delahoy Miranda J. , Pray Ian W. , Jovaag Amanda , Braun Katarina M. , Cole Devlin , Shechter Todd , Fajardo Geroncio C. , Griggs Carol , Yandell Brian S. , Goldstein Steve , Bushman Dena , Segaloff Hannah E. , Kelly G. Patrick , Pitts Collin , Lee Christine , Grande Katarina M. , Kita-Yarbro Amanda , Grogan Brittany , Mader Sara , Baggott Jake , Bateman Allen C. , Westergaard Ryan P. , Tate Jacqueline E. , Friedrich Thomas C. , Kirking Hannah L. , O’Connor David H. , Killerby Marie E. 
Published: May 2021

AbstractUniversity settings have demonstrated potential for COVID-19 outbreaks, as they can combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin (UW)–Madison. During August – October 2020, 3,485 students tested positive, including 856/6,162 students living in residence halls. Case counts began rising during move-in week for on-campus students (August 25-31, 2020), then rose rapidly during September 1-11, 2020. UW-Madison initiated multiple prevention efforts, including quarantining two residence halls; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, where UW-Madison is located, did not find evidence of transmission from a large cluster of cases in the two residence halls quarantined during the outbreak. Coordinated implementation of prevention measures can effectively reduce SARS-CoV-2 spread in university settings and may limit spillover to the community surrounding the university.
Galectin-anchored indoleamine 2,3-dioxygenase suppresses local inflammation
Authors: Bracho-Sanchez Evelyn , Rocha Fernanda , Bedingfield Sean , Partain Brittany D. , Brusko Maigan A. , Colazo Juan M. , Fettis Margaret M. , Farhadi Shaheen A. , Helm Eric , Koenders Kevin , Kwiatkowski Alexander J. , Macias Sabrina L. , Restuccia Antonietta , Wanchoo Arun , Avram Dorina , Allen Kyle D. , Duvall Craig L. , Wallet Shannon M. , Hudalla Gregory A. , Keselowsky Benjamin G. 
Published: May 2021

Summary paragraphChronic inflammation underlies the onset, progression and associated pain of numerous diseases.(1) Current anti-inflammatory treatments administered systemically are associated with moderate-to-severe side effects, while locally administered drugs have short-lived efficacy, and neither approach successfully modifies the underlying causality of disease.(2) We report a new way to locally modulate inflammation by fusing the enzyme indoleamine 2,3-dioxygenase 1 (IDO) to galectin-3 (Gal3). A general regulator of inflammation(3), IDO is immunosuppressive(4), catabolizing the essential amino acid tryptophan into kynurenine.(5) Recently we demonstrated that extracellular exogenous IDO regulates innate immune cell function(6), and envisioned delivering IDO into specific tissues would provide control of inflammation. However, proteins problematically diffuse away from local injection sites. Addressing this, we recently established that fusion to Gal3 anchors enzymes to tissues(7) via binding to extracellular glycans. Fusion protein IDO-Gal3 was retained in injected tissues and joints for up to a week or more, where it suppressed local inflammation in rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis. Amelioration of local inflammation, disease progression and inflammatory pain were concomitant with homeostatic preservation of tissues without global immune suppression. Thus, IDO-Gal3 presents a new concept of anchoring immunomodulatory enzymes for robust control of focal inflammation in multiple disease settings.
Honeybee cognition as a tool for scientific engagement
Authors: Denton Jai A. , Koludarov Ivan , Thompson Michele , Bryk Jarosław , Velasque Mariana 
Published: May 2021

AbstractIn addition to the crowdsourcing of experimental data, citizen science, and scientific engagement more broadly, serve as a bridge between researchers and the wider community. This serves to foster a greater understanding of the scientific method and science-based solutions generally.Apis mellifera(honeybees) are a well-established model for the study of learning and cognition and can serve as an engaging outreach system for this wider community. Here, we developed and implemented a protocol using well established honeybee conditioning protocols to safely study the effects of caffeine and dopamine on learning performance. Using this protocol, a group of high-school aged students as part of the Ryukyu Girls program demonstrated that caffeine, but not dopamine, significantly reduced the number of trials required for a successful conditioning response. This allowed these students to explore the scientific method in a relatable and engaging way.Simple SummaryGlobal scientific literacy can be improved through widespread and effective community engagement by researchers. We proposeApis mellifera(honeybee) as an public engagement tool due to widespread awareness of colony collapse and the bees’ importance in food production. Moreover, their cognitive abilities make for engaging experiments. Their relative ease of cultivation means that studies can be performed cost-effectively, especially when partnering with local aperists. Using a proxy for honeybee learning, a group of non-specialist high-school-aged participants obtained data suggesting that caffeine, but not dopamine, improved learning. This hands-on experience facilitated student understanding of the scientific method, factors that shape learning and the importance of learning for hive health.
OPUS-X: An Open-Source Toolkit for Protein Torsion Angles, Secondary Structure, Solvent Accessibility, Contact Map Predictions, and 3D Folding
Authors: Xu Gang , Wang Qinghua , Ma Jianpeng 
Published: May 2021

AbstractIn this paper, we report an open-source toolkit for protein 3D structure modeling, named OPUS-X. It contains three modules: OPUS-TASS2, which predicts protein torsion angles, secondary structure and solvent accessibility; OPUS-Contact, which measures the distance and orientations information between different residue pairs; and OPUS-Fold2, which uses the constraints derived from the first two modules to guide folding. OPUS-TASS2 is an upgraded version of our previous method OPUSS-TASS (Bioinformatics2020,36(20), 5021-5026). OPUS-TASS2 integrates protein global structure information and significantly outperforms OPUS-TASS. OPUS-Contact combines multiple raw co-evolutionary features with protein 1D features predicted by OPUS-TASS2, and delivers better results than the open-source state-of-the-art method trRosetta. OPUS-Fold2 is a complementary version of our previous method OPUS-Fold (J. Chem. Theory Comput.2020,16(6), 3970-3976). OPUS-Fold2 is a gradient-based protein folding framework based on the differentiable energy terms in opposed to OPUS-Fold that is a sampling-based method used to deal with the non-differentiable terms. OPUS-Fold2 exhibits comparable performance to the Rosetta folding protocol in trRosetta when using identical inputs. OPUS-Fold2 is written in Python and TensorFlow2.4, which is user-friendly to any source-code level modification. The code and pre-trained models of OPUS-X can be downloaded fromhttps://github.com/OPUS-MaLab/opus_x.