bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza-Negative Influenza-Like Illness (fnILI) Z-Score as a Proxy for Incidence and Mortality of COVID-19
Authors: Mirza Fatima N. , Malik Amyn A. , Omer Saad B. 
Published: April 2020

AbstractThough ideal for determining the burden of disease, SARS-CoV2 test shortages preclude its implementation as a robust surveillance system in the US. We correlated the use of the derivative influenza-negative influenza-like illness (fnILI) z-score from the CDC as a proxy for incident cases and disease-specific deaths. For every unit increase of fnILI z-score, the number of cases increased by 70.2 (95%CI[5.1,135.3]) and number of deaths increased by 2.1 (95%CI[1.0,3.2]). FnILI data may serve as an accurate outcome measurement to track the spread of the and allow for informed and timely decision-making on public health interventions.
Dynamical SPQEIR model assesses the effectiveness of non-pharmaceutical interventions against COVID-19 epidemic outbreaks
Authors: Proverbio Daniele , Kemp Françoise , Magni Stefano , Husch Andreas , Aalto Atte , Mombaerts Laurent , Skupin Alexander , Gonçalves Jorge , Ameijeiras-Alonso Jose , Ley Christophe 
Published: April 2020

AbstractAgainst the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to suppress it, but the efficacy of distinct measures is not yet well quantified. In this paper, we propose a novel tool to achieve this quantification. In fact, this paper develops a new extended epidemic SEIR model, informed by a socio-political classification of different interventions, to assess the value of several suppression approaches. First, we inquire the conceptual effect of suppression parameters on the infection curve. Then, we illustrate the potential of our model on data from a number of countries, to perform cross-country comparisons. This gives information on the best synergies of interventions to control epidemic outbreaks while minimising impact on socio-economic needs. For instance, our results suggest that, while rapid and strong lock-down is an effective pandemic suppression measure, a combination of social distancing and contact tracing can achieve similar suppression synergistically. This quantitative understanding will support the establishment of mid- and long-term interventions, to prepare containment strategies against further outbreaks. This paper also provides an online tool that allows researchers and decision makers to interactively simulate diverse scenarios with our model.
Characterizing clinical progression of COVID-19 among patients in Shenzhen, China: an observational cohort study
Authors: Bi Qifang , Hong Chengcheng , Meng Juan , Wu Zhenke , Zhou Pengzheng , Ye Chenfei , Sun Binbin , Kucirka Lauren M. , Azman Andrew S. , Wang Tong , Chen Jiancong , Wang Zhaoqin , Liu Lei , Lessler Justin , Edwards Jessie K. , Ma Ting , Zhang Guoliang 
Published: April 2020

AbstractBackgroundUnderstanding clinical progression of COVID-19 is a key public health priority that informs resource allocation during an emergency. We characterized clinical progression of COVID-19 and determined important predictors for faster clinical progression to key clinical events and longer use of medical resources.Methods and FindingsThe study is a single-center, observational study with prospectively collected data from all 420 patients diagnosed with COVID-19 and hospitalized in Shenzhen between January 11th and March 10th, 2020 regardless of clinical severity. Using competing risk regressions according to the methods of Fine and Gray, we found that males had faster clinical progression than females in the older age group and the difference could not be explained by difference in baseline conditions or smoking history. We estimated the proportion of cases in each severity stage over 80 days following symptom onset using a nonparametric method built upon estimated cumulative incidence of key clinical events. Based on random survival forest models, we stratified cases into risk sets with very different clinical trajectories. Those who progressed to the severe stage (22%,93/420), developed acute respiratory distress syndrome (9%,39/420), and were admitted to the intensive care unit (5%,19/420) progressed on average 9.5 days (95%CI 8.7,10.3), 11.0 days (95%CI 9.7,12.3), and 10.5 days (95%CI 8.2,13.3), respectively, after symptom onset. We estimated that patients who were admitted to ICUs remained there for an average of 34.4 days (95%CI 24.1,43.2). The median length of hospital stay was 21.3 days (95%CI, 20.5,22.2) for cases who did not progress to the severe stage, but increased to 52.1 days (95%CI, 43.3,59.5) for those who required critical care.ConclusionsOur analyses provide insights into clinical progression of cases starting early in the course of infection. Patient characteristics near symptom onset both with and without lab parameters have tremendous potential for predicting clinical progression and informing strategic response.
Conformational Tuning of Amylin by Charged Styrene-maleic-acid Copolymers
Authors: Sahoo Bikash R. , Souders Christopher L. , Nakayama Takahiro W. , Deng Zhou , Linton Hunter , Suladze Saba , Ivanova Magdalena I. , Reif Bernd , Ando Toshio , Martyniuk Christopher J. , Ramamoorthy Ayyalusamy 
Published: April 2020

ABSTRACTHuman amylin forms structurally heterogeneous amyloids that have been linked to type-2 diabetes. Thus, understanding the molecular interactions governing amylin aggregation can provide mechanistic insights in its pathogenic formation. Here, we demonstrate that fibril formation of amylin is altered by synthetic amphipathic copolymer derivatives of the styrene- maleic-acid (SMAQA and SMAEA). High-speed AFM is used to follow the real-time aggregation of amylin by observing the rapid formation ofde novoglobular oligomers and arrestment of fibrillation by the positively-charged SMAQA. We also observed an accelerated fibril formation in the presence of the negatively-charged SMAEA. These findings were further validated by fluorescence, SOFAST-HMQC, DOSY and STD NMR experiments. Conformational analysis by CD and FT-IR revealed that the SMA copolymers modulate the conformation of amylin aggregates. While the species formed with SMAQA are α-helical, the ones formed with SMAEA are rich in β-sheet structure. The interacting interfaces between SMAEA or SMAQA and amylin are mapped by NMR and microseconds all-atom MD simulation. SMAEA displayed π-π interaction with Phe23, electrostatic π-cation interaction with His18 and hydrophobic packing with Ala13 and Val17; whereas SMAQA showed a selective interaction with amylin’s C-terminus (residues 31-37) that belongs to one of the two β-sheet regions (residues 14-19 and 31-36) involved in amylin fibrillation. Toxicity analysis showed both SMA copolymers to be non-toxicin vitroand the amylin species formed with the copolymers showed minimal deformity to zebrafish embryos. Together, this study demonstrates that chemical tools, such as copolymers, can be used to modulate amylin aggregation, alter the conformation of species.
COVID-19 serial interval estimates based on confirmed cases in public reports from 86 Chinese cities
Authors: Du Zhanwei , Xu Xiaoke , Wu Ye , Wang Lin , Cowling Benjamin J. , Meyers Lauren Ancel 
Published: April 2020

AbstractAs a novel coronavirus (COVID-19) continues to spread widely and claim lives worldwide, its transmission characteristics remain uncertain. Here, we present and analyze the serial intervals–the time period between the onset of symptoms in an index (infector) case and the onset of symptoms in a secondary (infectee) case–of 339 confirmed cases of COVID-19 identified from 264 cities in mainland China prior to February 19, 2020. Here, we provide the complete dataset in both English and Chinese to support further COVID-19 research and modeling efforts.
Value of SiPM PET in myocardial perfusion imaging using Rubidium-82
Authors: Koenders S.S. , van Dalen J.A. , Jager P.L. , Knollema S. , Timmer JR , Mouden M. , Slump C.H. , van Dijk J.D. 
Published: April 2020

AbstractBackgroundPET scanners using silicon photomultipliers with digital readout (SiPM PET) have an improved temporal and spatial resolution compared to PET scanners using conventional photomultiplier tubes (PMT PET). However, the effect on image quality and visibility of perfusion defects in myocardial perfusion imaging (MPI) is unknown. Our aim was to determine the value of a SiPM PET scanner in MPI.MethodsWe prospectively included 30 patients who underwent rest and regadenoson-induced stress Rubidium-82 (Rb-82) MPI on the D690 PMT PET (GE Healthcare) and within three weeks on the Vereos SiPM PET (Philips Healthcare). Two expert readers scored the image quality and assessed the existence of possible defects. In addition, interpreter’s confidence, myocardial blood flow (MBF) and myocardial flow reserve (MFR) values were compared.ResultsImage quality improved (p=0.03) using the Vereos as compared to the D690. Image quality of the Vereos and the D690 was graded fair in 20% and 10%, good in 60% and 50%, and excellent in 20% and 40%, respectively. Defect interpretation and interpreter’s confidence did not differ between the D690 and the Vereos (p>0.50). There were no significant differences in rest MBF (p≥0.29), stress MBF (p≥0.11) and MFR (p≥0.51).ConclusionSiPM PET provides an improved image quality in comparison to PMT PET. Defect interpretation, interpreter’s confidence and absolute blood flow measurements were comparable between both systems. SiPM PET is therefore a reliable technique for MPI using Rb-82.
In-silico studies of Riparin B in the design of drugs: Physicochemical, pharmacokinetic and pharmacodynamic parameters
Authors: Rodrigues Aldenora Maria Ximenes , Costa Rayla Kelly Magalhães , Machado Ranyelison Silva , Gutierrez Stanley Juan Chavez , das Chagas Alves Lima Francisco , de Oliveira Aldeídia Pereira 
Published: April 2020

AbstractThe process involved in the research, discovery and development of drugs is characterized by high extensive and complex cost linked to scientific and technological innovations, and it is necessary to study and verify the progress of research carried out in the field that results in patent applications.Aniba riparia (Nees) Mezis a plant species often used for therapeutic purposes, where its pharmacological properties are associated to the presence of alkaloids called riparins. 5 synthetic analog compounds (riparins A, B, C, D, E and F) were developed from natural riparins. These molecules, natural and synthetic, showed several pharmacological activities in tests performedin vitro and in vivo, highlighting the Central Nervous System (CNS). The objective of this work was to evaluate the physical-chemical, pharmacokinetic parameters (absorption, distribution, metabolism, excretion and toxicity) and pharmacodynamic parameters (bioactivity and adverse reactions) of Riparin B by means ofin silicocomputational prediction.Online softwaresuch asPre-ADMET, SwissADME, Molinspirationand PASSon linewere used for the analysis. Riparin B fits the characteristics ofdruglikeness, pharmacokinetic properties appropriate to the predicted patterns and activities within the scope for the treatment of AD, demonstrating a possible potential in the inhibition of AChE. Therefore, in silico results allow us to conclude that riparin B is predicted to be a potential future drug candidate, especially via oral administration, due to its relevant Drug-likeness profile, bioavailability, excellent liposolubility and adequate pharmacokinetics, including at the level of CNS, penetrating the blood-brain barrier.
Synaptic processes and immune-related pathways implicated in Tourette Syndrome
Authors: Tsetsos Fotis , Yu Dongmei , Sul Jae Hoon , Huang Alden Y. , Illmann Cornelia , Osiecki Lisa , Darrow Sabrina M. , Hirschtritt Matthew E. , Greenberg Erica , Muller-Vahl Kirsten R. , Stuhrmann Manfred , Dion Yves , Rouleau Guy A. , Aschauer Harald , Stamenkovic Mara , Schlögelhofer Monika , Sandor Paul , Barr Cathy L. , Grados Marco A. , Singer Harvey S. , Nöthen Markus M. , Hebebrand Johannes , Hinney Anke , King Robert A. , Fernandez Thomas V. , Barta Csaba , Tarnok Zsanett , Nagy Peter , Depienne Christel , Worbe Yulia , Hartmann Andreas , Budman Cathy L. , Rizzo Renata , Lyon Gholson J. , McMahon William M. , Batterson James R. , Cath Danielle C. , Malaty Irene A. , Okun Michael S. , Berlin Cheston , Woods Douglas W. , Lee Paul C. , Jankovic Joseph , Robertson Mary M. , Gilbert Donald L. , Brown Lawrence W. , Coffey Barbara J. , Dietrich Andrea , Hoekstra Pieter J. , Kuperman Samuel , Zinner Samuel H. , Wagner Michael , Knowles James A , Willsey A. Jeremy , Tischfield Jay A. , Heiman Gary A. , Cox Nancy J. , Freimer Nelson B. , Neale Benjamin M. , Davis Lea K. , Coppola Giovanni , Mathews Carol A. , Scharf Jeremiah M. , Paschou Peristera 
Published: April 2020

AbstractTourette Syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with Tourette Syndrome (TS) and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating Ligand-gated Ion Channel Signaling, Lymphocytic, and Cell Adhesion and Trans-synaptic Signaling processes. MAGMA analysis further supported the involvement of the Cell Adhesion and Trans-synaptic Signaling gene set. The Lympho-cytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of Ligand-gated Ion Channel Signaling reinforce the role of GABA in TS, while the association of Cell Adhesion and Trans-synaptic Signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders.
COVID-19 in Iran: A Deeper Look Into The Future
Authors: Kafieh Rahele , Arian Roya , Saeedizadeh Narges , Minaee Shervin , Amini Zahra , Yadav Sunil Kumar , Vaezi Atefeh , Rezaei Nima , Javanmard Shaghayegh Haghjooy 
Published: April 2020

ABSTRACTThe novel corona-virus (COVID-19) has led to a pandemic, affecting almost all countries and regions in a few weeks, and therefore a global plan is needed to overcome this battle. Iran has been among the first few countries that has been affected severely, after China, which forced the government to put some restriction and enforce social distancing in majority of the country. In less than 2 months, Iran has more than 80,000 confirmed cases, and more than 5,000 death. Based on the official statistics from Iran’s government, the number of daily cases has started to go down recently, but many people believe if the lockdown is lifted without proper social distancing enforcement, there is a possibility for a second wave of COVID-19 cases. In this work, we analyze at the data for the number cases in Iran in the past few weeks, and train a predictive model to estimate the possible future trends for the number of cases in Iran, depending on the government policy in the coming weeks and months. Our analysis may help political leaders and health officials to take proper action toward handling COVID-19 in the coming months.
Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood
Authors: Skead Kimberly , Houle Armande Ang , Abelson Sagi , Agbessi Mawusse , Bruat Vanessa , Lin Boxi , Soave David , Shlush Liran , Wright Stephen , Dick John , Morris Quaid , Awadalla Philip 
Published: April 2020

AbstractA small population of self-renewing, hematopoietic stem cells continuously reconstitutes our immune system. As we age, these cells, or their pluripotent descendants, accumulate somatic mutations; some of these mutations provide selection advantages and increase in frequency in the peripheral blood cell population. This process of positive selection, deemed age-related clonal hematopoiesis (ARCH), is associated with increased risk for cardiac disease and blood malignancies, like acute myeloid leukemia (AML). However, it remains unclear why some people with ARCH do not progress to AML, even when their blood cells harbor well-known AML driver mutations. Here, we examine whether negative selection can play a role in determining AML progression by modelling the complex interplay of positive and negative selective processes. Using a novel approach combining deep learning and population genetic models, we detect pervasive negative selection in targeted sequence data from the blood of 92 pre-AML individuals and 385 healthy controls. We find that the relative proportion of passenger to driver mutations is critical in determining if the selective advantage conferred to a cell by a known driver mutation is able to overwhelm negative selection acting on passenger mutations and allow clones harbouring disease-predisposing mutations to rise to dominance. We find that a subset of non-driver genes is enriched for mildly damaging mutations in healthy individuals fitting purifying models of evolution suggesting that mutations in these genes might confer a protective role against disease-predisposing clonal expansions. Through exploring non drivercentric models of evolution, we show how different classes of evolution act to shape hematopoietic dynamics and subsequent health outcome which may better inform disease prediction and unveil novel therapeutic targets. We anticipate that our results and modelling techniques can be broadly applied to identify both driver mutations and those mildly damaging passenger mutations, as well as help understand the early evolution of cancer in other cells and tissues.
Detection of epistasis between ACTN3 and SNAP-25 with an insight towards gymnastic aptitude identification
Authors: Płóciennik Łukasz , Zaucha Jan , Zaucha Jan Maciej , Łukaszuk Krzysztof , Jóźwicki Marek , Płóciennik Magdalena , Cięszczyk Paweł 
Published: April 2020

AbstractIn this study, we performed an analysis of the impact of performance enhancing polymorphisms (PEPs) on gymnastic aptitude while considering epistatic effects. Seven PEPs (rs1815739, rs8192678, rs4253778, rs6265, rs5443, rs1076560, rs362584) were considered in a case (gymnasts) – control (sedentary individuals) setting. The study sample comprised of two athletes’ sets: 27 elite (aged 24.8 ± 2.1 years) and 46 sub-elite (aged 19.7 ± 2.4 years) sportsmen as well as a control group of 245 sedentary individuals (aged 22.5 ± 2.1 years). The DNA was derived from saliva and PEP alleles were determined by PCR, RT-PCR. Following Multifactor Dimensionality Reduction, logistic regression models were built. The synergistic effect for rs1815739 × rs362584 reached 5.43%. The rs1815739 × rs362584 epistatic regression model exhibited a good fit to the data (Chi-squared = 33.758, p ≈ 0) achieving a significant improvement in sportsmen identification over naïve guessing. The area under the receiver operating characteristic curve was 0.715 (Z-score = 38.917, p ≈ 0). In contrast, the additive ACTN3 – SNAP-25 logistic regression model has been verified as non-significant.We demonstrate that a gene involved in the differentiation of muscle architecture – ACTN3 and a gene, which plays an important role in the nervous system – SNAP-25 interact. From the perspective originally established by the Berlin Academy of Science in 1751, the matter of communication between the brain and muscles via nerves adopts molecular manifestations. Further in-vitro investigations are required to explain the molecular details of the rs1815739 – rs362584 interaction.
Targeting Thymidine Phosphorylase with Tipiracil Hydrochloride is a Safe and Effective Antithrombotic Therapy
Authors: Zulfiker Abu Hasanat Md , Belcher Adam , Li Oliver Qiyue , Yue Hong , Gupta Anirban Sen , Wei Li 
Published: April 2020

AbstractRationaleMost of the current anti-platelet drugs inhibit platelet function permanently and have systemic side effects, including thrombocytopenia and hemorrhage. We previously found that thymidine phosphorylase (TYMP), a platelet cytoplasmic protein, facilitates multiple agonist induced platelet activation and enhances thrombosis. A specific TYMP inhibitor, namely, tipiracil hydrochloride (TPI), has been approved by the U.S. Food and Drug Administration for clinical use as an auxiliary drug making it possible to be repositioned as an anti-platelet medicine.ObjectiveWe aimed to test the hypothesis that TPI is a novel and safe anti-platelet drug by examining its role in platelet activation and thrombosis using both in vitro and in vivo studies.Methods and ResultsBy co-expression of TYMP and Lyn or Lyn-SH3 domain tagged with glutathione S-transferase, we showed the direct evidence that TYMP binds to the SH3 domain in its partners. TYMP haplodeficiency is sufficient to inhibit thrombosis in vivo regardless of gender. TPI treatment rapidly inhibited collagen- and ADP-induced platelet aggregation, which copied the phenotype of TYMP deficient platelets. Under both normal and hyperlipidemic conditions, treating wild type (WT) mice with TPI via intraperitoneal injection, intravenous injection, or gavage feeding dramatically inhibited thrombosis without inducing significant bleeding. Even administered above the effective dose, TPI has a lower bleeding side effect compared to aspirin and clopidogrel. Most importantly, intravenously delivery of TPI alone or combined with tissue plasminogen activator dramatically inhibited the growth of developing thrombi. Dual administration of very low dose of aspirin and TPI also dramatically inhibited thrombosis without disturbing hemostasis.ConclusionThis pharmacological study demonstrated that TYMP participates in multiple signaling pathways in platelet and plays a mechanistic role in regulating platelet activation and thrombosis. TPI, a specific TYMP inhibitor, would be a novel safe anti-platelet and anti-thrombosis medicine.