bluuebunny/crossref_metadata_2025_split huggingface dataset:
A low cost electromechanical device injury model for hind limb murine muscles
Authors: Perez-Hernandez Daniel , Segura-Alegria Bertha , Garcia-Pelagio Karla 
Published: April 2020

In daily life, muscle injuries due to accidents, sports, traumatic events or pathological conditions are constantly occurring. Not knowing the forces involved or the torque or the angle at which the injury was caused represent a challenging clinical problem limiting appropriate treatment protocols. In here, we design, developed, built and validated a reproducible well‐characterized injury device for small species at low cost using Arduino platform. The device can perform two types of injuries while varying speed, angle and frequencies; the first one generated by eccentric contractions and the second one by doing torsions. Briefly, under anesthesia the animal is placed in a pre‐warmed bed, then one leg is secured to a foot plate attached to an electric steeper motor providing a torque of 48 N‐m controlled by Arduino. Two electrodes are placed in the rat’s gastrocnemius to generate the injury. For eccentric contraction type of injury, the foot plate moves backward and forward causing dorsi and plantarflexion intermittently at a certain angle and speed. As the bed can rotate 180° fibrillar and tendon ruptures can be determined. The torsion type of injury mimics an ankle sprain at controlled force and speed. This is intended to study joint and tendon damage by mechanical analysis. The instantaneous speed of the movement is measured with an electronic gyroscope attached to the axis of the bed. Torque, isometric and isotonic stimulation can be measured as well. With this, the mechanisms of hypertrophy and muscular strengthening can be studied by measuring their progress with the aim of generating adequate physiotherapy therapies. We are currently validating the device in small species animals. Results will be shown.Support or Funding InformationSupported partially by UNAM‐PAPIIT IA210320 and CONACyT AI‐S‐17636 to KPGP.
Regulator of G protein signaling 6 (RGS6) is a critical modulator of reward behavior and dopamine signaling in the mesolimbic circuit
Authors: Spicer Mackenzie Marie , Weber Matthew A. , Luo Zili , Yang Jianqi , Narayanan Kumar , Fisher Rory A. 
Published: April 2020

Alcohol (EtOH) is the most commonly abused drug worldwide and chronic EtOH consumption often leads to development of dependence and abuse. EtOH dependence is a progressive, neurological disorder characterized by an accumulation of neuroadaptations resulting from chronic EtOH exposure. The neurobiological mechanisms underlying EtOH‐seeking behavior and dependence are not fully understood. As a result, there are limited therapeutics designed to reduce alcohol cravings or withdrawal symptomology, and abstinence remains the only effective way to prevent alcohol use disorders (AUDs). Previously, we showed that RGS6 deficiency in mice leads to reduced EtOH seeking and reward behaviors. Reduced EtOH seeking in RGS6−/− mice was partially reversed by GABAB and D2 autoreceptor (D2R) antagonism and completely reversed by singular inhibition of DAT. These findings, together with the observed reduction in striatal DA content in RGS6−/− mice, led us to hypothesize that RGS6 functions to promote mesolimbic DA transmission by suppressing GPCR‐Gαi/o‐mediated upregulation of DAT. To investigate this possibility, we examined the effects of RGS6 loss on DAT expression in VTA cell bodies and synaptic terminals in the nucleus accumbens (NAcc). In addition, we examined the effects of RGS6 loss on mesolimbic DA transmission using optogenetic stimulated release of DA and c‐Fos staining in the NAcc. We observed robust expression of RGS6 in VTA cell bodies and terminals where its loss led to upregulated expression of DAT. These findings suggest that RGS6 functions to promote EtOH seeking and reward behavior by promoting DA neurotransmission in the mesolimbic circuit by suppressing GPCR‐Gαi/o‐DAT upregulation.Support or Funding InformationNational Institutes of Health [AA025919]; the Michael J. Fox Foundation [1151]; and University of Iowa Pharmacological Sciences Training Grant [T32GM067795].
Internal carotid artery blood flow response to cognitive task is similar between young and older adults
Authors: Asahara Ryota , Ishii Kei , Izaki Tsubasa , Iwaki Sunao , Komine Hidehiko 
Published: April 2020

Previous studies reported that the increase in the middle cerebral artery blood flow velocity during cognitive task was greater in older adults than in young adults, suggesting age‐related differences in cerebral blood flow responses to cognitive task. However, previous studies utilized transcranial Doppler ultrasound and thereby information regarding arterial diameter, blood volume flow, and vascular conductance was lacking. On the other hand, Doppler ultrasonography can assess blood volume flow in the internal carotid artery (ICA), which provides the blood supply to a large portion of the cerebral cortex. To date, it remains to be determined whether ICA blood flow response to cognitive task is different between young and older adults. The present study examined the ICA blood flow and blood pressure (BP) responses to 20 s of task switching in 6 young (30 ± 3 yr) and 6 older (66 ± 3 yr) subjects. The ICA blood flow and BP did not change significantly during task switching in young subjects. In older subjects, significant ICA blood flow response was not found, while BP increased (p<0.05) slightly and transiently during the first 10 s of the task. In both subjects, vascular conductance of the ICA was unaltered during task switching. Our present findings suggest that the ICA blood flow response to task switching was similar between young and older subjects.Support or Funding InformationGrant‐in‐Aid for Research Activity start‐up from the Japan Society for the Promotion of Science (19K24333)
Computational Modeling of Attentional Impairments in Disruptive Mood Dysregulation and Attention Deficit/Hyperactivity Disorder
Authors: Haller Simone P. , Stoddard Joel , Pagliaccio David , Bui Hong , MacGillivray Caroline , Joes Matt , Brotman Melissa A. 
Published: April 2020

AbstractObjectiveComputational models provide information about cognitive components underlying behavior. When applied to psychopathology-relevant processes, they offer additional insight to observed differences in behavioral performance. Drift diffusion models have been successfully applied to investigate processing efficiency during binary choice tasks. Using these, we examine the association between psychopathology (irritability and inattention) and processing efficiency under different attentional demands.Method187 youth with ADHD, DMDD, both disorders, or no major psychopathology (M age=13.09, SD=2.55; 34% female) completed an Eriksen Flanker task. Of these, 87 provided complete data on dimensional measures of the core symptom of DMDD, irritability, and those of ADHD, inattention and hyperactivity.ResultsIn a categorical analysis (n=187), we found a ADHD-by-DMDD-by task condition interaction on processing efficiency (b=−1.07, p=.01, 95%CI=[−1.89,−.24]), where increases in processing efficiency for non-conflict conditions were larger in youth without psychopathology relative to patients. Analysis of symptom severity (n=87) across diagnosis was consistent with the above analysis, revealing an interaction between symptom dimensions and task condition on processing efficiency (b=−0.10, p=.018, 95%CI[−.18, −.02]). Inattention, and its combined effect with irritability, predicted the magnitude of difference in processing efficiency between conflict and non-conflict conditions.DiscussionReduced processing efficiency may represent a shared cognitive endophenotype between ADHD and DMDD. Youth high in irritability or inattention may have difficulty adjusting processing efficiency to changing task demands possibly reflecting impairments in cognitive flexibility.
Trends and prediction in daily incidence and deaths of COVID-19 in the United States: a search-interest based model
Authors: Yuan Xiaoling , Xu Jie , Hussain Sabiha , Wang He , Gao Nan , Zhang Lanjing 
Published: April 2020

AbstractBackground and ObjectivesThe coronavirus disease 2019 (COVID-19) infected more than 586,000 patients in the U.S. However, its daily incidence and deaths in the U.S. are poorly understood. Internet search interest was found correlated with COVID-19 daily incidence in China, but not yet applied to the U.S. Therefore, we examined the association of internet search-interest with COVID-19 daily incidence and deaths in the U.S.MethodsWe extracted the COVDI-19 daily incidence and death data in the U.S. from two population-based datasets. The search interest of COVID-19 related terms was obtained using Google Trends. Pearson correlation test and general linear model were used to examine correlations and predict future trends, respectively.ResultsThere were 555,245 new cases and 22,019 deaths of COVID-19 reported in the U.S. from March 1 to April 12, 2020. The search interest of COVID, “COVID pneumonia,” and “COVID heart” were correlated with COVDI-19 daily incidence with ∼12-day of delay (Pearson’s r=0.978, 0.978 and 0.979, respectively) and deaths with 19-day of delay (Pearson’s r=0.963, 0.958 and 0.970, respectively). The COVID-19 daily incidence and deaths appeared to both peak on April 10. The 4-day follow-up with prospectively collected data showed moderate to good accuracies for predicting new cases (Pearson’s r=-0.641 to −0.833) and poor to good accuracies for daily new deaths (Pearson’s r=0.365 to 0.935).ConclusionsSearch terms related to COVID-19 are highly correlated with the trends in COVID-19 daily incidence and deaths in the U.S. The prediction-models based on the search interest trend reached moderate to good accuracies.
COVID-19 outbreak in Greece has passed its rising inflection point and stepping into its peak
Authors: Georgiou Harris V. 
Published: April 2020

Since the beginning of 2020, COVID-19 is the most urgent and challenging task for the international scientific community, in order to identify its behaviour, track its progress and plan effective mitigation policies. In this study, Greece is the main focus for assessing the national outbreak and estimating the general trends and outlook of it. Multiple data analytics procedures, spectral decomposition and curve-fitting formulations are developed based on the data available at hand. Standard SIEQRDP epidemic modelling is applied for Greece and for the general region around it, providing hints for the outbreak progression in the mid- and long-term, for various infections under-reporting rates. The overall short-term outlook for Greece seems to be towards positive, with a downward trend in infections rate daily increase (i.e., now beyond the exponential growth rate), a possible peak within a few days beyond April 14th, as well as the high availability level of ICU w.r.t. expected demand at peak. On the negative side, the fade-out period seems to be in the order of several months, with high probability of recurrent surges of the outbreak. The mitigation policies for the ‘next day’ should be focused on close tracking of the epidemic via large-scale tests, strict border checking in international travelling and an adaptive plan for selective activation of mitigation measures when deemed necessary.Significance StatementThis study focuses on the COVID-19 outbreak in Greece and provides data-driven epidemic modelling and experimental results regarding the current state. Based on these results, the overall short-term outlook for Greece seems to be towards positive, having recently passed the rising inflection point and approaching the peak of the infections, and most probably capable of covering the projected ICU demand peak by a large margin. On the downside, the fade-out period seems to be in the order of several months, with high probability of recurrent surges of the outbreak. The ‘next day’ mitigation policies need to be carefully planned, highly adaptive and based on close tracking of the outbreak via large-scale testing in the general population.
How deadly is COVID-19? A rigorous analysis of excess mortality and age-dependent fatality rates in Italy
Authors: Modi Chirag , Böhm Vanessa , Ferraro Simone , Stein George , Seljak Uroš 
Published: April 2020

ABSTRACTWe perform a counterfactual time series analysis on 2020 mortality data from towns in Italy using data from the previous five years as control. We find an excess mortality that is correlated in time with the official COVID-19 death rate, but exceeds it by a factor of at least 1.5. Our analysis suggests that there is a large population of predominantly older people that are missing from the official fatality statistics. We estimate that the number of cOvID-19 deaths in Italy is 49,000-53,000 as of May 9 2020, as compared to the official number of 33,000. The Population Fatality Rate (PFR) has reached 0.26% in the most affected region of Lombardia and 0.58% in the most affected province of Bergamo. These PFRs constitutes a lower bound to the Infection Fatality Rate (IFR). We combine the PFRs with the Test Positivity Ratio to derive the lower bound of 0.61% on the IFR for Lombardia. We further estimate the IFR as a function of age and find a steeper age dependence than previous studies: we find 17% of COVID-related deaths are attributed to the age group above 90, 7.5% to 80-89, declining to 0.04% for age 40-49 and 0.01% for age 30-39, the latter more than an order of magnitude lower than previous estimates. We observe that the IFR traces the Yearly Mortality Rate (YMR) above ages of 60 years, which can be used as a model to estimate the IFR for other populations and thus other regions in the world. We predict an IFR lower bound of 0.5% for NYC and that 27% of the total COVID-19 fatalities in NYC should arise from the population below 65 years. This is in agreement with the official NYC data and three times higher than the percentage observed in Lombardia. Combining the PFR with the Princess Diamond cruise ship IFR for ages above 70 we estimate the infection rates (IR) for regions in Italy. These peak in Lombardia at 26% (13%-47%, 95% c.l.), and for provinces in Bergamo at 69% (35%-100%, 95% c.I.). These estimates suggest that the number of infected people greatly exceeds the number of positive tests, e.g., by a factor of 35 in Lombardia.*
“Genomic and phenotypic characterization of Investigator Global Assessment (IGA) scale based endotypes in atopic dermatitis”
Authors: Smieszek Sandra P , Przychodzen Bartlomiej , Welsh Sarah E , Brzezynski Jennifer , Kaden Alyssa , Mohrman Michael , Wang Jingyuan , Xiao Changfu , Ständer Sonja , Birznieks Gunther , Polymeropoulos Christos , Polymeropoulos Mihael H 
Published: April 2020

ABTRACTBackgroundAtopic dermatitis (AD) is a heritable and heterogeneous inflammatory chronic skin disorder. Utilizing decision tree/supervised learning of extensive clinical, molecular and genetic data, we aimed to define distinct AD endotypes.MethodsDeep phenotyping and whole-genome sequencing was performed on samples obtained from participants of EPIONE, a randomized-controlled phase III study in AD patients with severe pruritus comprising mild (23%), moderate (64%) and severe (13%) AD as determined by AD Investigator Global Assessment scale. Three categories of analysis were performed: clinical associations, lab value associations (EOS, IgE, cytokines) and genetic analysis of whole-genome sequencing dataResultsBased on a decision tree, we found that five clinical features from the SCORing Atopic Dermatitis (SCORAD) Index can accurately differentiate between IGA severities. We observe a significant difference between severity and eosinophil counts (p<0.001), IgE (p<0.001) and Filaggrin (FLG) LOF frequency (OR 2.3, CI 1.6-3.2, p<0.0001) as well as interleukin pathway genes, specifically IL5RA variants differentiating the groups.ConclusionOur results suggest significant differences between severity groups across a number of features appear to constitute distinct endotypes with likely distinct causative factors. Differing underlying pathophysiology’s indicate endotype knowledge is critical to help guide therapeutic approaches to AD.Capsule summaryAD is a heritable and heterogeneous skin disorder that makes the ‘one size fits all’ therapeutic approach suboptimal for patients with AD.We attempted to define AD endotypes based on clinical, molecular, and genetic characteristics. Clinical, CBC, and genetic associations all tend to suggest existence of separate endotypes.
Rapid development of an inactivated vaccine for SARS-CoV-2
Authors: Gao Qiang , Bao Linlin , Mao Haiyan , Wang Lin , Xu Kangwei , Yang Minnan , Li Yajing , Zhu Ling , Wang Nan , Lv Zhe , Gao Hong , Ge Xiaoqin , Kan Biao , Hu Yaling , Liu Jiangning , Cai Fang , Jiang Deyu , Yin Yanhui , Qin Chengfeng , Li Jing , Gong Xuejie , Lou Xiuyu , Shi Wen , Wu Dongdong , Zhang Hengming , Zhu Lang , Deng Wei , Li Yurong , Lu Jinxing , Li Changgui , Wang Xiangxi , Yin Weidong , Zhang Yanjun , Qin Chuan 
Published: April 2020

AbstractThe COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans.One Sentence SummaryA purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology
The ΔF508 CFTR defect: molecular mechanism of suppressor mutation V510D and the contribution of transmembrane helix unraveling
Authors: Simon Kailene S. , Nagarajan Karthi , Mechin Ingrid , Duffy Caroline , Manavalan Partha , Altmann Steve , Majewski Aliza , Foley Joseph , Kaczmarek J. Stefan , Bercury Scott , Maderia Matthew , Hilbert Brendan , Batchelor Joseph D. , Ziegler Robin , Bajko Jeffrey , Kothe Michael , Scheule Ronald K. , Nair Anil , Hurlbut Gregory D. 
Published: April 2020

AbstractCystic fibrosis (CF) results from mutations within the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), a transmembrane chloride channel found on the apical surface of epithelial cells. The most common CF-causing mutation results in a deletion of phenylalanine 508 (ΔF508-CFTR), a residue normally found within the NBD1 domain. Loss of F508 causes NBD1 to be less thermodynamically stable and prevents proper tertiary folding of CFTR. As a result, CFTR is not properly trafficked to the cell surface. Recently, progress has been made towards the development of small molecule “correctors” that can restore CFTR tertiary structure and stabilize the channel to overcome the instability inherent in ΔF508-CFTR. However, the resultant improvement in channel activity has been modest, and the need for potent correctors remains. To fully inform such efforts, a better understanding of the molecular pathology associated with ΔF508-CFTR is required. Here we present a comprehensive study of the impact of F508 deletion on both purified NBD1 and full-length CFTR. Through the use of homology modeling, molecular dynamics simulations, mutational analysis, biochemical, biophysical and functional characterization studies, we obtained insight into how the ΔF508 mutation may lead to helical unraveling of transmembrane domains 10 and 11 (TM10, TM11), and how the known suppressor mutations V510D and R1070W, as well as novel second site suppressor mutations (SSSMs) identified in this work, may act to rescue ΔF508-CFTR maturation and trafficking.
Elucidating salespeople's market orientation, proactive service behavior and organizational culture in the B2B banking sector: a Malaysian perspective
Authors: Hamzah Muhammad Iskandar , Othman Abdul Kadir , Hassan Faridah 
Published: April 2020

PurposeConsidering that little is known on market orientation at the individual level, this study investigates the effects of individual market orientation on proactive service behavior, and subsequently, sales performance among business-to-business salespeople. Based on social cognitive theory and competing values framework, this paper also examines the interaction effects of organizational culture on the link between individual market orientation and proactive service behavior.Design/methodology/approachThe study sampled 539 business-to-business salespeople from 18 corporate banks in Kuala Lumpur by using a questionnaire survey.FindingsThe results of the study show that adhocracy culture strengthens the effects of information acquisition on proactive service behavior, while at the same time weakens the impact of coordination of strategic response on the same outcome. Meanwhile, rational culture displayed negative contingent effects of information dissemination on proactive service behavior.Practical implicationsGiven its link to sales performance and proactive service behavior, banks should motivate their employees to embrace market orientation as individual competencies. This research outcome will aid managers in developing strategies and inculcating the right culture to ensure the market-oriented behaviors are internalized and transpired into positive outcomes.Originality/valueThis paper contributes to the enrichment of the existing market orientation frameworks by offering underlying mechanisms (cultural environment and proactive service behavior) through which market-oriented behaviors contribute to the sales performance of business-to-business salespeople within the financial service industry. It is also among the earliest studies that examine the influence of individual market orientation and organizational culture on proactive service behavior.