bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of prediction models for short term outcome in COVID-19 patients in the emergency department: a retrospective study
Authors: van Dam Paul M.E.L. , Zelis Noortje , van Kuijk Sander M.J. , Linkens Aimée E.M.J.H. , Bruggemann Renée R.A.G. , Spaetgens Bart , van der Horst Iwan C.C. , Stassen Patricia M. 
Published: November 2020

AbstractIntroductionCoronavirus disease 2019 (COVID-19) has a high burden on the healthcare system and demands information on the outcome early after admission to the emergency department (ED). Previously developed prediction models may assist in triaging patients when allocating healthcare resources. We aimed to assess the value of several prediction models when applied to COVID-19 patients in the ED.MethodsAll consecutive COVID-19 patients who visited the ED of a combined secondary/tertiary care center were included. Prediction models were selected based on their feasibility. The primary outcome was 30-day mortality, secondary outcomes were 14-day mortality, and a composite outcome of 30-day mortality and admission to the medium care unit (MCU) or the intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC).ResultsA total of 403 ED patients were diagnosed with COVID-19. Within 30 days, 95 patients died (23.6%), 14-day mortality was 19.1%. Forty-eight patients (11.9%) were admitted to the MCU, 66 patients (16.4%) to the ICU and 152 patients (37.7%) met the composite endpoint. Eleven models were included: RISE UP score, 4C mortality score, CURB-65, MEWS, REMS, abbMEDS, SOFA, APACHE II, CALL score, ACP index and Host risk factor score. The RISE UP score and 4C mortality score showed a very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84 respectively, 95% CI 0.79-0.88 for both), for 14-day mortality (AUC 0.83, 95% CI: 0.79-0.88, for both) and for the composite outcome (AUC 0.79 and 0.77 respectively, 95% CI 0.75-0.84). The discriminatory performance of the RISE UP score and 4C mortality score was significantly higher compared to that of the other models.ConclusionThe RISE UP score and 4C mortality score have good discriminatory performance in predicting adverse outcome in ED patients with COVID-19. These prediction models can be used to recognize patients at high risk for short-term poor outcome and may assist in guiding clinical decision-making and allocating healthcare resources.
COVID-19 Growth in Rural versus Urban Counties with Major Universities at the Start of the 2020 Academic Year
Authors: Penuliar Mike , Clark Candice , Curti Debbie , Hudson Cathy , Philips Billy 
Published: November 2020

ABSTRACTUniversities play a central role in a rural or small town’s economy. They are often the main forms of enrichment to the lives of the longtime residents, the students, and the employees. Unfortunately, during a global pandemic, the migration and movement of young people in these communities can likely cause a rapid infection spike and drive spread easily, especially relative to larger urban areas. The current study investigates the relationship between COVID-19 case growth, university-county rurality, and time at the beginning of the Fall 2020 academic semester. Findings showed that small metro and non-metro counties with universities had a dramatic infection spike near the beginning of the semester and infection growth remained significantly higher than their large and medium metro counterparts for the duration of the study. Suggestions to slow the spread in rural communities are discussed.
Prevalence of Isolated Systolic Hypertension among People with Diabetes in Indonesia
Authors: Azam Mahalul , Hidayati Fetty Nur , Fibriana Arulita Ika , Bahrudin Udin , Aljunid Syed Mohamed 
Published: November 2020

AbstractThe present study aimed to explore the prevalence of isolated systolic hypertension (ISH) and its risk factors among diabetes mellitus (DM) subjects in the community setting study in Indonesia. This cross-sectional study extracted secondary data from basic health survey (Riset Kesehatan Dasar; RISKESDAS) conducted in 2018. DM subjects were defined based on fasting blood glucose level ≥ 126 mg/dL or 2 hours postprandial and random blood glucose level ≥ 200 mg/dL or previously had been diagnosed by a doctor; while ISH was determined based on systolic blood pressure ≥ 140 mmHg and diastolic blood pressure < 90 mmHg. We also observed the subject’s characteristics, such as demography, lipid profile, and subject’s compliance. Data were then analyzed using Chi-square and Binary logistic regression. Study involved 3,911 DM subjects, revealed the overall prevalence of ISH 17.5%. Age category of 35-44 years old (POR= 10.80; 95%CI: 2.595-44.957), 45-54 years old (POR=22.81; 95%CI: 5.616-92.677), 55-64 years old (POR=46.12; 95% CI: 11.393-186.720); 65-74 years old (POR= 81.82; 95% CI: 20.110-332.868); ≥75 years old (POR=109.64; 95% CI: 26.373-455.789), low HDL cholesterol (POR= 0,80; 95% CI: 0.653-0.972); duration of DM (POR= 1.73; 95% CI: 1.257-2.389) were associated with the ISH. The prevalence of ISH among DM subjects was 17.5%. Older DM subjects, low HDL cholesterol, and duration of DM were associated with the ISH, suggesting that modification lipid profile, especially the HDL cholesterol level, is an important measure to delay ISH in elderly and long-duration DM subjects.
A behavioral cascade of HIV seroadaptation among US men who have sex with men in the era of PrEP and U=U
Authors: Goodreau Steven M. , Maloney Kevin M. , Sanchez Travis H. , Morris Martina , Janulis Patrick , Jenness Samuel M. 
Published: November 2020

ABSTRACTSeroadaptive behaviors help to reduce HIV risk for some men who have sex with men (MSM), and have been well documented in a range of MSM populations. Advancements in biomedical prevention have changed the contexts in which seroadaptive behaviors occur. We thus sought to estimate and compare the prevalence of four stages of the “seroadaptive cascade” in the recent era: knowledge of own serostatus, knowledge of partner serostatus; serosorting (matching by status), and condomless anal intercourse. Serosorting overall appeared to remain common, especially with casual and one-time partners. Although PrEP use did not impact status discussion, it did impact serosorting and the likelihood of having condomless anal intercourse. For respondents not diagnosed with HIV and not on PrEP, condomless anal intercourse occurred in just over half of relationships with partners who were not on treatment. Biomedical prevention has intertwined with rather than supplanted seroadaptive behaviors, while contexts involving neither persist.
Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection
Authors: Bert Nina Le , Clapham Hannah E , Tan Anthony T , Chia Wan Ni , Tham Christine YL , Lim Jane M , Kunasegaran Kamini , Tan Linda , Dutertre Charles-Antoine , Shankar Nivedita , Lim Joey ME , Sun Louisa Jin , Zahari Marina , Tun Zaw Myo , Kumar Vishakha , Lim Beng Lee , Lim Siew Hoon , Chia Adeline , Tan Yee-Joo , Tambyah Paul Anantharajah , Kalimuddin Shirin , Lye David , Low Jenny GH , Wang Lin-Fa , Wan Wei Yee , Hsu Li Yang , Bertoletti Antonio , Tam Clarence C 
Published: November 2020

AbstractThe efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-γ, IL-4, IL-6, IL-1β, TNF-α and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-γ and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.
Data mining patented antibody sequences
Authors: Krawczyk Konrad , Buchanan Andrew , Marcatili Paolo 
Published: November 2020

AbstractPatent literature should be a reflection of thirty years of engineering efforts in developing monoclonal antibody therapeutics. Such information is potentially valuable for rational antibody design. Patents however are not designed to convey scientific knowledge, but rather legal protection. It is unclear whether antibody information from patent documents, such as antibody sequences could be useful for the therapeutic antibody sphere in conveying engineering know-how rather than act as legal reference only. To assess the utility of patent data for therapeutic antibody engineering, we quantified the amount of antibody sequences in patents destined for medicinal purposes and how well they reflect the primary sequences of therapeutic antibodies in clinical use. We identified 16,526 patent families from major jurisdictions (e.g. USPTO and WIPO) that contained antibody sequences. These families held 245,109 unique antibody chains (135,397 heavy chains and 109,712 light chains) that we compiled in our Patented Antibody Database (PAD, http://naturalantibody.com/pad). We find that antibodies make up a non-trivial proportion of all patent amino acid sequence depositions (e.g. 10.95% of USPTO Full Text database). Our analysis of the 16,526 families demonstrates that the volume of patent documents with antibody sequences is growing with the majority of documents classified as containing antibodies for medicinal purposes. We further studied the 245,109 antibody chains from patent literature to reveal that they very well reflect the primary sequences of antibody therapeutics in clinical use. This suggests that patent literature could serve as a reference of previous engineering efforts to improve rational antibody design.
Differential excitability of PV and SST neurons results in distinct functional roles in inhibition stabilization of Up-states
Authors: Romero-Sosa Juan L. , Motanis Helen , Buonomano Dean V. 
Published: November 2020

ABSTRACTUp-states are the best-studied example of an emergent neural dynamic regime. Computational models based on a single class of inhibitory neurons indicate that Up-states reflect bistable dynamical systems in which positive feedback is stabilized by strong inhibition and predict a paradoxical effect in which increased drive to inhibitory neurons results in decreased inhibitory activity. To date, however, computational models have not incorporated empirically defined properties of PV and SST neurons. Here we first, experimentally characterized the frequencycurrent (F-I) curves of pyramidal, PV, and SST neurons and confirmed a sharp difference between the threshold and slopes of PV and SST neurons. The empirically defined F-I curves were incorporated into a three-population computational model that simulated the empirically-derived firing rates of pyramidal, PV, and SST neurons. Simulations revealed that the intrinsic properties were sufficient to predict that PV neurons are primarily responsible for generating the nontrivial fixed points representing Up-states. Simulations and analytical methods demonstrated that while the paradoxical effect is not obligatory in a model with two classes of inhibitory neurons, it is present in most regimes. Finally, experimental tests validated predictions of the model that the Pyr↔PV inhibitory loop is stronger than the Pyr↔SST loop.SIGNIFICANCE STATEMENTMany cortical computations, such as working memory, rely on the local recurrent excitatory connections that define cortical circuit motifs. Up-states are among the simplest and best studied examples of neural dynamic regimes that rely on recurrent excitatory excitation. However, this positive feedback must be held in check by inhibition. To address the relative contribution of PV and SST neurons we characterized the intrinsic input-output differences between these classes of inhibitory neurons, and using experimental and theoretical methods show that the higher threshold and gain of PV leads to a dominant role in network stabilization.
1H, 15N and 13C sequence specific backbone assignment of the MAP Kinase Binding Domain of the Dual Specificity Phosphatase 1 and its interaction with the MAPK p38
Authors: Senthil Kumar Ganesan , Page Rebecca , Peti Wolfgang 
Published: November 2020

AbstractThe sequence-specific backbone assignment of the mitogen-activated protein kinase (MAPK) binding domain of the dual-specificity phosphatase 1 (DUSP1) has been accomplished using a uniformly [13C,15N]-labeled protein. These assignments will facilitate further studies of DUSP1 in the presence of inhibitors/ligands to target MAPK associated diseases and provide further insights into the function of dual-specificity phosphatase 1 in MAPK regulation.
Harnessing cytoplasmic particles movement of the human early embryo analysed by advanced imaging and artificial intelligence to predict development to blastocyst stage
Authors: Coticchio Giovanni , Fiorentino Giulia , Nicora Giovanna , Sciajno Raffaella , Cavalera Federica , Bellazzi Riccardo , Garagna Silvia , Borini Andrea , Zuccotti Maurizio 
Published: November 2020

AbstractResearch QuestionProgress in artificial intelligence (AI) and advanced image analysis offers unique opportunities to develop novel embryo assessment approaches. In this study, we tested the hypothesis that such technologies can extract and harness novel information derived from cytoplasmic movements of the early human embryo to predict development to blastocyst.DesignIn a proof-of principle study, an artificial neural network (ANN) approach was undertaken to assess retrospectively 230 human preimplantation embryos. After ICSI, embryos were subjected to time-lapse monitoring for 44 hours. For comparison as a standard embryo assessment methodology, a single senior embryologist assessed each embryo to predict development to blastocyst stage (BL) based on a single picture frame taken at 42 hours of development. In the experimental approach, in embryos that developed to blastocyst or destined to arrest (NoBL), cytoplasm movement velocity (CMV) was recorded by time-lapse monitoring during the first 44 hours of culture and analysed with a Particle Image Velocimetry (PIV) algorithm to extract quantitative information. Three main AI approaches, the k-Nearest Neighbor (k-NN), the Long-Short Term Memory Neural Network (LSTM-NN) and the hybrid ensemble classifier (HyEC) were employed to classify the two embryo classes.ResultsBlind operator assessment classified each embryo in terms of ability of development to blastocyst, reaching a 75.4% accuracy, 76.5% sensitivity, 74.3% specificity, 74.3% precision and 75.4% F1 score. After integration of results from AI models together with the blind operator classification, the performance metrics improved significantly, with a 82.6% accuracy, 79.4% sensitivity, 85.7% specificity, 84.4% precision and 81.8% F1 score.ConclusionsThe present study suggests the possibility to predict human blastocyst development at early cleavage stages by detection of CMV and AI analysis. This indicates the importance of the dynamics of the cytoplasm as a novel and valuable source of data to assess embryo viability.
A novel high-accuracy genome assembly method utilizing a high-throughput workflow
Authors: Zeng Qingdong , Cao Wenjin , Xing Liping , Qin Guowei , Wu Jianhui , Nagle Michael F. , Xiong Qin , Chen Jinhui , Yang Liming , Bajaj Prasad , Chitikineni Annapurna , Zhou Yan , Yu Yunxin , Xu Jiang , Nie Xiaojun , Huang Lin , Liu Shengjie , Šafář Jan , Šimková Hana , Song Weining , Guo Baozhu , Chen Shilin , Doležel Jaroslav , Hao Zhaodong , Cheng Qiang , Liang Jianguo , Tang Jiansong , Cao Aizhong , Wang Qiang , Lu Xiangqian , Yang Shouping , Ma Hongxiang , Liu Jiajie , Wang Xiaoting , Zhang Hong , Wang Zhonghua , Ji Wanquan , Wang Changfa , Yuan Fengping , Shi Jisen , Varshney Rajeev K. , Kang Zhensheng , Han Dejun , Xu Haibin 
Published: November 2020

AbstractAcross domains of biological research using genome sequence data, high-quality reference genome sequences are essential for characterizing genetic variation and understanding the genetic basis of phenotypes. However, the construction of genome assemblies for various species is often hampered by complexities of genome organization, especially repetitive and complex sequences, leading to mis-assembly and missing regions. Here, we describe a high-throughput gold standard genome assembly workflow using a large-scale bacterial artificial chromosome (BAC) library with a refined two-step pooling strategy and the Lamp assembler algorithm. This strategy minimizes the laborious processes of physical map construction and clone-by-clone sequencing, enabling inexpensive sequencing of several thousand BAC clones. By applying this strategy with a minimum tiling path BAC clone library for the short arm of chromosome 2D (2DS) of bread wheat, 98% of BAC sequences, covering 92.7% of the 2DS chromosome, were assembled correctly for this species with a highly complex and repetitive genome. We also identified 48 large mis-assemblies in the reference wheat genome assembly (IWGSC RefSeq v1.0) and corrected these large mis-assemblies in addition to filling 92.2% of the gaps in RefSeq v1.0. Our 2DS assembly represents a new benchmark for the assembly of complex genomes with both high accuracy and efficiency.
Pfcerli2, a duplicated gene in the malaria parasitePlasmodium falciparumessential for invasion of erythrocytes as revealed by phylogenetic and cell biological analysis
Authors: Liffner Benjamin , Balbin Juan Miguel , Shami Gerald J. , Strauss Jan , Frölich Sonja , Heinemann Gary K. , Alder Arne , Wichers Jan Stephan , Tilley Leann , Dixon Matthew W. A. , Gilberger Tim-Wolf , Wilson Danny W. 
Published: November 2020

ABSTRACTMerozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasitePlasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characteriseP. falciparumCytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show thatcerli2arose through an ancestral gene duplication ofcerli1, a related cytosolically exposed rhoptry bulb protein. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led to an inhibition of merozoite invasion after tight junction formation. PfCERLI2 knockdown was associated with inhibition of rhoptry antigen processing and a significant elongation of the rhoptries, suggesting that the inability of merozoites to invade is caused by aberrant rhoptry function due to PfCERLI2 deficiency. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.
Differential effects of amplitude-modulated transcranial focused ultrasound on excitatory and inhibitory neurons
Authors: Nguyen Duc T. , Berisha Destiny , Konofagou Elisa , Dmochowski Jacek P. 
Published: November 2020

AbstractAlthough stimulation with ultrasound has been shown to modulate brain activity at multiple scales, it remains unclear whether transcranial focused ultrasound stimulation (tFUS) exerts its influence on specific cell types. Here we propose a novel form of tFUS where a continuous waveform is amplitude modulated (AM) at a slow rate (i.e., 40 Hz) targeting the temporal range of electrophysiological activity: AM-tFUS. We stimulated the rat hippocampus while recording multi-unit activity (MUA) followed by classification of spike waveforms into putative excitatory pyramidal cells and inhibitory interneurons. At low acoustic intensity, AM-tFUS selectively reduced firing rates of inhibitory interneurons. On the other hand, higher intensity AM-tFUS increased firing of putative excitatory neurons with no effect on inhibitory firing. Interestingly, firing rate was unchanged during AM-tFUS at intermediate intensity. Consistent with the observed changes in firing rate, power in the theta band (3-10 Hz) of the local field potential (LFP) decreased at low-intensity, was unchanged at intermediate intensity, and increased at higher intensity. Temperature increases at the AM-tFUS target were limited to 0.2°C. Our findings indicate that inhibitory interneurons exhibit greater sensitivity to ultrasound, and that cell-type specific neuromodulation may be achieved by calibrating the intensity of AM-tFUS.
Egr2 induction in Drd1+ ensembles of the ventrolateral striatum supports the development of cocaine reward
Authors: Mukherjee Diptendu , Gonzales Ben Jerry , Ashwal-Fluss Reut , Turm Hagit , Groysman Maya , Citri Ami 
Published: November 2020

AbstractDrug addiction develops due to brain-wide plasticity within neuronal ensembles, mediated by dynamic gene expression. Though the most common approach to identify such ensembles relies on immediate early gene expression, little is known of how the activity of these genes is linked to modified behavior observed following repeated drug exposure. To address this gap, we present a broad-to-specific approach, beginning with a comprehensive investigation of brain-wide cocaine-driven gene expression, through the description of dynamic spatial patterns of gene induction in subregions of the striatum, and finally address functionality of region-specific gene induction in the development of cocaine preference. Our findings reveal differential cell-type specific dynamic transcriptional recruitment patterns within two subdomains of the dorsal striatum following repeated cocaine exposure. Furthermore, we demonstrate that induction of the IEG Egr2 in the ventrolateral striatum, as well as the cells within which it is expressed, are required for the development of cocaine seeking.Impact statementVLS ensembles are dynamically recruited by cocaine experiences to mediate cocaine reward.