bluuebunny/crossref_metadata_2025 huggingface dataset:
A Unique Clade of SARS-CoV-2 Viruses is Associated with Lower Viral Loads in Patient Upper Airways
Authors: Lorenzo-Redondo Ramon , Nam Hannah H. , Roberts Scott C. , Simons Lacy M. , Jennings Lawrence J. , Qi Chao , Achenbach Chad J. , Hauser Alan R. , Ison Michael G. , Hultquist Judd F. , Ozer Egon A.
Published: May 2020

Background

The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID- 19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we aimed to investigate the phylogenetic characteristics of SARS-CoV-2 infections in Chicago, Illinois and assess their relationship to clinical parameters.

Methods

We performed whole-genome sequencing of SARS-CoV-2 isolates collected from COVID-19 patients in a Chicago healthcare system in mid-March, 2020. Using these and other publicly available sequences, we performed phylogenetic, phylogeographic, and phylodynamic analyses. Patient data was assessed for correlations between demographic or clinical characteristics and virologic features.

Findings

The 88 SARS-CoV-2 genome sequences in our study separated into three distinct phylogenetic clades. Clade 1 was most closely related to viral sequences from New York, and showed evidence of rapid expansion across the US, while Clade 3 was most closely related to those in Washington state. Clade 2 was localized primarily to the Chicago area with limited evidence of expansion elsewhere. At the time of diagnosis, patients infected with Clade 1 viruses had significantly higher average viral loads in their upper airways relative to patients infected with Clade 2 viruses, independent of time to symptom onset and disease severity.

Interpretation

These results show that multiple variants of SARS-CoV-2 are circulating in the Chicago area that differ in their relative viral loads in patient upper airways. These data suggest that differences in virus genotype impact viral load and may in turn influence viral transmission and spread.

Funding

Dixon Family Translational Research Award, Northwestern University Clinical and Translational Sciences Institute (NUCATS), National Institute of Allergy and Infectious Diseases (NIAID)
Determinants of cardiac adverse events of chloroquine and hydroxychloroquine in 20 years of drug safety surveillance reports
Authors: Cohen Isaac V. , Makunts Tigran , Moumedjian Talar , Issa Masara , Abagyan Ruben
Published: May 2020

Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization’s List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to the risk of drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment.
SeSaMe: Metagenome Sequence Classification of Arbuscular Mycorrhizal Fungi Associated Microorganisms
Authors: Kang Jee Eun , Ciampi Antonio , Hijri Mohamed
Published: May 2020

Arbuscular mycorrhizal fungi (AMF) are plant root symbionts that play key roles in plant growth and soil fertility. They are obligate biotrophic fungi that form coenocytic multinucleated hyphae and spores. Numerous studies have shown that diverse microorganisms live on the surface and inside their mycelia, resulting in a metagenome when whole genome sequencing (WGS) data are obtained from sequencing AMF cultivatedin vivo.The metagenome contains not only the AMF sequences, but also those from associated microorganisms. In this article, we introduce a novel bioinformatics program, SeSaMe, designed for taxonomic classification of short sequences obtained by next-generation DNA sequencing. A genus-specific usage bias database was created based on amino acid usage and codon usage of three consecutive codon DNA 9-mers encoding for an amino acid trimer in a protein secondary structure. The program distinguishes between coding sequence (CDS) and non-CDS, and classifies a query sequence into a genus group out of 54 genera used as reference. The average correct prediction percentages of the CDS and the non-CDS test sets at the genus level were 71% and 50% for bacteria, 65% and 73% for fungi (excluding AMF), and 49% and 72% for AMF (Rhizophagus irregularis), respectively. The program provides a means for estimating not only taxonomic diversity and abundance but also the gene reservoir of the reference taxonomic groups associated with AMF. Therefore, the program enables users to study the symbiotic roles of associated microorganisms. SeSaMe can be applicable to other microorganisms as well as soil metagenomes. It is freely available atwww.journal.comandwww.fungalsesame.org.
Total and Stroke Related Imaging Utilization Patterns During the COVID-19 Pandemic
Authors: Tu Long Hoang , Sharma Richa , Malhotra Ajay , Schindler Joseph L , Forman Howard P
Published: May 2020

During the COVID-19 pandemic, radiology practices are reporting a decrease in imaging volumes. We review total imaging volume, CTA head and neck volume, critical results rate, and stroke intervention rates before and during the COVID-19 pandemic. Total imaging volume as well as CTA head and neck imaging fell approximately 60% since the beginning of the pandemic. Critical results fell 60-70% for total imaging as well as for CTA head and neck. Compared to the same time frame a year prior, the number of stroke codes at the early impact of the pandemic had decreased approximately 50%. Proportional reductions in total imaging volume, stroke-related imaging, and associated critical result reports during the COVID-19 pandemic raise concern for missed stroke diagnoses in our population.
Convalescent plasma therapy for the treatment of patients with COVID-19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels
Authors: Harvala Heli , Robb Matthew , Watkins Nicholas , Ijaz Samreen , Dicks Steven , Patel Mokika , Supasa Pyadai , Dejnirattisai Wanwisa , Liu Chang , Mongkolsapaya Juthathip , Brown Abbie , Bailey Daniel , Vipond Richard , Grayson Nicholas , Temperton Nigel , Bolton Jai , Fyfe Alex , Gopal Robin , Simmonds Peter , Screaton Gavin , Thompson Craig P , Brooks Tim , Zambon Maria , Miflin Gail , Roberts David
Published: May 2020

Introduction. The lack of approved specific therapeutic agents to treat COVID-19 associated with SARS coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation and/or randomised controlled trials of convalescent plasma therapy (CPT) in many countries including the UK. Effective CPT is likely to require high titres of neutralising antibody levels in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of large-scale collection and use of convalescent plasma. We assessed whether neutralising antibody titres correlated with reactivity in a range of ELISA assays targeting the spike (S) protein, the main target for human immune response.
Methods. Blood samples were collected from 52 individuals with a previous laboratory confirmed SARS-CoV-2 infection at least 28 days after symptom resolution. These were assayed for SARS-CoV-2 neutralising antibodies by microneutralisation and pseudotype assays, and for antibodies by four different ELISAs. ROC analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high neutralising antibody levels suitable for clinical use of convalescent plasma.
Results. All samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun IgG ELISA S/CO reactivity (Spearman Rho correlation co-efficient 0.88; p<0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22).
Discussion. Robust associations between virus neutralising antibody titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2 neutralising antibodies.
Association of trajectories of depressive symptoms with vascular risk, cognitive function and adverse brain outcomes: The Whitehall II MRI sub-study
Authors: Demnitz Naiara , Anatürk Melis , Allan Charlotte L , Filippini Nicola , Griffanti Ludovica , Mackay Clare E , Mahmood Abda , Sexton Claire E , Suri Sana , Topiwala Anya G , Zsoldos Eniko , Kivimäki Mika , Singh-Manoux Archana , Ebmeier Klaus P
Published: May 2020

Background: Trajectories of depressive symptoms over the lifespan vary between people, but it is unclear whether these differences exhibit distinct characteristics in brain structure and function. Methods: In order to compare indices of white matter microstructure and cognitive characteristics of groups with different trajectories of depressive symptoms, we examined 774 participants of the Whitehall II Imaging Sub-study, who had completed the depressive subscale of the General Health Questionnaire up to nine times over 25 years. Twenty-seven years after the first examination, participants underwent magnetic resonance imaging to characterize white matter hyperintensities (WMH) and microstructure and completed neuropsychological tests to assess cognition. Twenty-nine years after the first examination, participants completed a further cognitive screening test.
Results: Using K-means cluster modelling, we identified five trajectory groups of depressive symptoms: consistently low scorers ("low"; n=505, 62.5%), a subgroup with an early peak in depression scores ("early"; n=123, 15.9%), intermediate scorers ("middle"; n=89, 11.5%), a late symptom subgroup with an increase in symptoms towards the end of the follow-up period ("late"; n=29, 3.7%), and consistently high scorers ("high"; n=28, 3.6%). The late, but not the consistently high scorers, showed higher mean diffusivity, larger volumes of WMH and impaired executive function. In addition, the late subgroup had higher Framingham Stroke Risk scores throughout the follow-up period, indicating a higher load of vascular risk factors.
Conclusions: Our findings suggest that tracking depressive symptoms in the community over time may be a useful tool to identify phenotypes that show different etiologies and cognitive and brain outcomes.
Automated assessment of COVID-19 pulmonary disease severity on chest radiographs using convolutional Siamese neural networks
Authors: Li Matthew D. , Arun Nishanth Thumbavanam , Gidwani Mishka , Chang Ken , Deng Francis , Little Brent P. , Mendoza Dexter P. , Lang Min , Lee Susanna I. , O’Shea Aileen , Parakh Anushri , Singh Praveer , Kalpathy-Cramer Jayashree
Published: May 2020

Purpose

To develop an automated measure of COVID-19 pulmonary disease severity on chest radiographs (CXRs), for longitudinal disease evaluation and clinical risk stratification.

Materials and Methods

A convolutional Siamese neural network-based algorithm was trained to output a measure of pulmonary disease severity on anterior-posterior CXRs (pulmonary x-ray severity (PXS) score), using weakly-supervised pretraining on ~160,000 images from CheXpert and transfer learning on 314 CXRs from patients with COVID-19. The algorithm was evaluated on internal and external test sets from different hospitals, containing 154 and 113 CXRs respectively. The PXS score was correlated with a radiographic severity score independently assigned by two thoracic radiologists and one in-training radiologist. For 92 internal test set patients with follow-up CXRs, the change in PXS score was compared to radiologist assessments of change. The association between PXS score and subsequent intubation or death was assessed.

Results

The PXS score correlated with the radiographic pulmonary disease severity score assigned to CXRs in the COVID-19 internal and external test sets (ρ=0.84 and ρ=0.78 respectively). The direction of change in PXS score in follow-up CXRs agreed with radiologist assessment (ρ=0.74). In patients not intubated on the admission CXR, the PXS score predicted subsequent intubation or death within three days of hospital admission (area under the receiver operator characteristic curve=0.80 (95%CI 0.75-0.85)).

Conclusion

A Siamese neural network-based severity score automatically measures COVID-19 pulmonary disease severity in chest radiographs, which can be scaled and rapidly deployed for clinical triage and workflow optimization.

A convolutional Siamese neural network-based algorithm can calculate a continuous radiographic pulmonary disease severity score in COVID-19 patients, which can be used for longitudinal disease evaluation and clinical risk stratification.

KEY RESULTS

A Siamese neural network-based severity score correlates with radiologist-annotated pulmonary disease severity on chest radiographs from patients with COVID-19 (ρ=0.84 and ρ=0.78 in internal and external test sets respectively).

The direction of change in the severity score in follow-up radiographs is concordant with radiologist assessment (ρ=0.74).

The admission chest radiograph severity score can help predict subsequent intubation or death within three days of admission (receiver operator characteristic area under the curve=0.80).
The adaptability of H9N2 avian influenza A virus to humans: A comparative docking simulation study
Authors: Xu Hengyue , Qian Jiaqiang , Song Yifan , Ming Dengming
Published: May 2020

Influenza A virus, the H9N2 subtype, is an avian influenza virus that has long been circulating in the worldwide poultry industry and is occasionally found to be transmissible to humans. Evidence from genomic analysis suggests that H9N2 provides the genes for the H5N1 and H7N9 subtypes, which have been found to infect mammals and pose a threat to human health. However, due to the lack of a structural model of the interaction between H9N2 and host cells, the mechanism of the extensive adaptability and strong transformation capacity of H9N2 is not fully understood. In this paper, we collected 40 representative H9N2 virus samples reported recently, mainly in China and neighboring countries, and investigated the interactions between H9N2 hemagglutinin and the mammalian receptor, the polysaccharide α-2,6-linked lactoseries tetrasaccharide c, at the atomic level using docking simulation tools. We categorized the mutations of studied H9N2 hemagglutinin according to their effects on ligand-binding interactions and the phylogenetic analysis. The calculations indicated that all the studied H9N2 viruses can establish a tight binding with LSTc although the mutations caused a variety of perturbations to the local conformation of the binding pocket. Our calculations suggested that a marginal equilibrium is established between the conservative ligand-receptor interaction and the conformational dynamics of the binding pocket, and it might be this equilibrium that allows the virus to accommodate mutations to adapt to a variety of environments. Our results provided a way to understand the adaptive mechanisms of H9N2 viruses, which may help predict its propensity to spread in mammals.
Playing the piano with a robotic third thumb: Assessing constraints of human augmentation
Authors: Shafti Ali , Haar Shlomi , Mio Renato , Guilleminot Pierre , Faisal A. Aldo
Published: May 2020

Contemporary robotics gives us mechatronic capabilities for augmenting human bodies with extra limbs. However, how our motor control capabilities pose limits on such augmentation is an open question. We developed a Supernumerary Robotic 3rd Thumbs (SR3T) with two degrees-of-freedom controlled by the user’s body to endow them with an extra contralateral thumb on the hand. We demonstrate that a pianist can learn to play the piano with 11 fingers within an hour. We then evaluate 6 naïve and 6 experienced piano players in their prior motor coordination and their capability in piano playing with the robotic augmentation. We show that individuals’ augmented performance could be predicted by our new custom motor coordination assessment, the Human Augmentation Motor Coordination Assessment (HAMCA) performed pre-augmentation. Our work demonstrates how supernumerary robotics can augment humans in skilled tasks and that individual differences in their augmentation capability are predictable by their individual motor coordination abilities.
Automatic mapping of multiplexed social receptive fields by deep learning and GPU-accelerated 3D videography
Authors: Ebbesen Christian L. , Froemke Robert C.
Published: May 2020

Social interactions powerfully impact the brain and the body, but high-resolution descriptions of these important physical interactions are lacking. Currently, most studies rely on labor-intensive methods such as manual annotation. Scalable and objective tracking methods are required to understand the neural circuits underlying social behavior. Here we describe a hardware/software system and analysis pipeline that combines 3D videography, deep learning, physical modeling, and GPU-accelerated robust optimization, with automatic analysis of neuronal receptive fields recorded in interacting mice. Our system is capable of fully automatic multi-animal tracking with minimal errors (including in complete darkness) during complex, spontaneous social encounters, together with simultaneous electrophysiological recordings. We capture posture dynamics of multiple unmarked mice with high spatiotemporal precision (~2 mm, 60 frames/s). A generative model revealed the multiplexed ‘social receptive field’ of neurons in barrel cortex. This approach could be broadly useful for neurobehavioral studies of multiple animals interacting in complex low-light environments.
Multiplexed and extraction-free amplification for simplified SARS-CoV-2 RT-PCR tests
Authors: Byrnes Samantha A. , Gallagher Ryan , Steadman Amy , Bennett Crissa , Rivera Rafael , Ortega Corrie , Motley S. Timothy , Jain Paras , Weigl Bernhard H. , Connelly John T.
Published: May 2020

The rapid onset of the global COVID-19 pandemic has led to multiple challenges for accurately diagnosing the infection. One of the main bottlenecks for COVID-19 detection is reagent and material shortages for sample collection, preservation, and purification prior to testing. Currently, most authorized diagnostic tests require RNA extraction from patient samples and detection by reverse transcription polymerase chain reaction (RT-PCR). However, RNA purification is expensive, time consuming, and requires technical expertise to perform. Additionally, there have been reported shortages of the RNA purification kits needed for most tests. With these challenges in mind, we report on extraction-free amplification of SARS-CoV-2 RNA directly from patient samples. In addition, we have developed a multiplex RT-PCR using the CDC singleplex targets. This multiplex has a limit of detection of 2 copies/μL. We have demonstrated these improvements to the current diagnostic workflow, which reduce complexity and cost, minimize reagent usage, expedite time to results, and increase testing capacity.
Single cell RNA sequencing reveals regulation of fetal ovary development in the monkey (Macaca fascicularis)
Authors: Zhao Zheng-Hui , Li Chun-Yang , Meng Tie-Gang , Wang Yan , Liu Wen-Bo , Li Ang , Cai Yi-Jun , Hou Yi , Schatten Heide , Wang Zhen-Bo , Sun Qing-Yuan , Sun Qiang
Published: May 2020

Germ cells are vital for reproduction and heredity. However, the mechanisms underlying female germ cell development in primates, especially in late embryonic stages, remain elusive. Here, we performed single-cell RNA sequencing of 12471 cells from whole fetal ovaries, and explored the communications between germ cells and niche cells. We depicted the two waves of oogenesis at single cell resolution and demonstrated that progenitor theca cells exhibit similar characteristics to Leydig cells in fetal monkey ovaries. Notably, we found thatZGLP1displays differentially expressed patterns between mouse and monkey, which is not overlapped withNANOGin monkey germ cells, suggesting its role in meiosis entry but not in activating oogenic program in primates. Furthermore, the majority of germ cell clusters that highly expressedPRDM9andSPO11might undergo apoptosis after cyst breakdown, leading to germ cell attrition. Overall, our work provides new insights into the molecular and cellular basis of primate fetal ovary development at single-cell resolution.
A two-stage diffusion modeling approach to the compelled-response task
Authors: Diederich Adele , Colonius Hans
Published: May 2020

The issue of how perception and motor planning interact to generate a given choice between actions is a fundamental question in both psychology and neuroscience. Salinas and colleagues have developed a behavioral paradigm, the compelled-response task, where the signal that instructs the subject to make an eye movement is given before the cue that indicates which of two possible target choices is the correct one. When the cue is given rather late, the participant must guess and make an uninformed random choice. Perceptual performance can be tracked as a function of the amount of time during which sensory information is available. In Salina’s accelerated race-to-threshold model, two variables race against each other to a threshold, at which a saccade is initiated. The source of random variability is in the initial state of information buildup across trials. This implies that incorrect decisions are due to the inertia of the racing variables that have, at the start, sampled a constant buildup in the “wrong” direction. Here we suggest an alternative, non-time-homogeneous two-stage-diffusion model that is able to predict both response time distributions and choice probabilities with a few easy-to-interpret parameters and without assuming cross-trial parameter variability. It is falsifiable at the level of qualitative features already, e.g. predicting bimodal RT distributions for particular gap times. It connects the compelled-response paradigm with an approach to decision making that has been uniquely successful in describing both behavioral and neural data in a variety of experimental settings for the last 40 years.
Organizing Pneumonia of COVID-19: Time-dependent Evolution and Outcome in CT Findings
Authors: Wang Yan , Jin Chao , Wu Carol C. , Zhao Huifang , Liang Ting , liu Zhe , Jian Zhijie , Li Runqing , Wang Zekun , Li Fen , Zhou Jie , Cai Shubo , Liu Yang , Li Hao , Li Zhongyi , Liang Yukun , Zhou Heping , Wang Xibin , Ren Zhuanqin , Yang Jian
Published: May 2020

Objective

As a pandemic, a most-common pattern resembled organizing pneumonia (OP) has been identified by CT findings in novel coronavirus disease (COVID-19). We aimed to delineate the evolution of CT findings and outcome in OP of COVID-19.

Materials and Methods

106 COVID-19 patients with OP based on CT findings were retrospectively included and categorized into non-severe (mild/common) and severe (severe/critical) groups. CT features including lobar distribution, presence of ground glass opacities (GGO), consolidation, linear opacities and total severity CT score were evaluated at three time intervals from symptom-onset to CT scan (day 0-7, day 8-14, day>14). Discharge or adverse outcome (admission to ICU or death), and pulmonary sequelae (complete absorption or lesion residuals) on CT after discharge were analyzed based on the CT features at different time interval.

Results

79(74.5%) patients were non-severe and 103(97.2%) were discharged at median day 25 (range, day 8-50) after symptom-onset. Of 67 patients with revisit CT at 2-4 weeks after discharge, 20(29.9%) had complete absorption of lesions at median day 38 (range, day 30-53) after symptom-onset. Significant differences between complete absorption and residuals groups were found in percentages of consolidation (1.5% vs. 13.8%, P=0.010), number of involved lobe >3 (40.0% vs. 72.5%, P=0.030), CT score >4 (20.0% vs. 65.0%, P=0.010) at day 8-14.

Conclusions

Most OP cases had good prognosis. Approximately one-third of cases had complete absorption of lesions during 1-2 months after symptom-onset while those with increased frequency of consolidation, number of involved lobe>3, and CT score >4 at week 2 after symptom-onset may indicate lesion residuals on CT.
Estimation of the Final Size of the COVID-19 Epidemic in Balochistan, Pakistan
Authors: Arif Muhammad , Kakar Aftab , Larik Ehsan
Published: May 2020

COVID-19 is a new disease that is spreading very fast in Pakistan. Cases have been reported from all the provinces in Pakistan including Balochistan. The first two confirmed cases in Pakistan had travel history from Iran to Pakistan, The some of the initial cases were quarantine at Taftan boarder in Balochistan, hence SIR model is used to predict the magnitude of the disease in Balochistan from May 2020 on wards when lock down and other social distancing measures were loosen up by the government of Balochistan. Our Prediction model shows that about 30,00000 individuals in Balochistan will be infected by 5th of July 2020.Over all 25% of the total population of Balochistan will be affected by this disease with 98% (2940,000) recovery rate by the end of 15th July 2020.
A COVID-19 Reopening Readiness Index: The Key to Opening up the Economy
Authors: Suh Eunju , Alhaery Mahdi
Published: May 2020

With respect to reopening the economy as a result of the COVID-19 restrictions, governmental response and messaging have been inconsistent, and policies have varied by state as this is a uniquely polarizing topic. Considering the urgent need to return to normalcy, a method was devised to determine the degree of progress any state has made in containing the spread of COVID-19. Using various measures for each state including mortality, hospitalizations, testing capacity, number of infections and infection rate has allowed for the creation of a composite COVID -19 Reopening Readiness Index. This index can serve as a comprehensive reliable and simple-to-use metric to assess the level of containment in any state and to determine the level of risk in further opening. As states struggle to contain the outbreak and at the same time face great pressure in resuming economic activity, an index that provides a data-driven and objective insight is urgently needed.

Background

We are in the midst of a once-in-a-lifetime pandemic. All levels of society and governments are working together to “flatten the curve” of the infection and slow the spread of COVID-19. The universal goal is to mitigate its adverse effects on everyday life across the globe and to reduce the number of fatalities. While a vaccine is being developed, the aim is to limit the number of hospitalizations as not to overwhelm healthcare systems in any given city or country. It is well documented that certain regions and localities are more affected than others. It is imperative that containment efforts utilize state and local data at their disposal to understand the readiness of any given area prior to opening its economy, and the level of restrictions that are needed.
Evidence-Based Quality Scores for Rating Drug Products and Their Utility in Health Systems
Authors: Dabestani Arash , Bazil Carl W. , Costantino Ryan C. , Fox Erin , Graedon Joe , Lever Harry , Makuch Robert , White C. Michael
Published: May 2020

The quality of drug products in the United States, which are largely produced overseas, has been a matter of growing concern.1 Buyers and payers of pharmaceuticals, whether they are health-systems, insurers, PBMs, pharmacies, physicians, or patients, have little to no visibility into any quality metrics for the manufacturers of drug products or the products themselves. A system of “quality scores” is proposed to enable health-systems and other purchasers and payers of medication to differentiate among drug products according to evidence-based metrics. Metrics influencing the quality scores described herein include both broadly applicable regulatory information and more drug-specific, third-party chemical analysis information. The aggregation of these metrics through a proposed set of rules results in numerical values on a 0-100 scale that may be further simplified into a red/yellow/green designation. The simplicity of such scores enables seamless integration into existing healthcare systems and an integration scheme is proposed. Using real-world data from currently on-market valsartan drug products, this proposed system generated a variety of quality scores for six major manufacturers. These scores were further evaluated according to their current market price showing no significant correlation between quality score and price. The implementation of drug quality scores at healthcare institutions in the United States and their potential utilization by regulators, could create a much-needed, market-driven incentive for pharmaceutical manufacturers to produce quality medications that would reduce drug shortages and improve public health.
Flexible categorization in perceptual decision making
Authors: Prat-Ortega Genís , Wimmer Klaus , Roxin Alex , de la Rocha Jaime
Published: May 2020

Perceptual decisions require the brain to make categorical choices based on accumulated sensory evidence. The underlying computations have been studied using either phenomenological drift diffusion models or neurobiological network models exhibiting winner-take-all attractor dynamics. Although both classes of models can account for a large body of experimental data, it remains unclear to what extent their dynamics are qualitatively equivalent. Here we show that, unlike the drift diffusion model, the attractor model can operate in different integration regimes: an increase in the stimulus fluctuations or the stimulus duration promotes transitions between decision-states leading to a crossover between weighting mostly early evidence (primacy regime) to weighting late evidence (recency regime). Between these two limiting cases, we found a novel regime, which we nameflexible categorization, in which fluctuations are strong enough to reverse initial categorizations, but only if they are incorrect. This asymmetry in the reversing probability results in a non-monotonic psychometric curve, a novel and distinctive feature of the attractor model. Finally, we show psychophysical evidence for the crossover between integration regimes predicted by the attractor model and for the relevance of this new regime. Our findings point to correcting transitions as an important yet overlooked feature of perceptual decision making.
Excitatory and inhibitory modulation of septal and striatal neurons during hippocampal sharp-wave ripple events
Authors: Howe Andrew G. , Blair Hugh T.
Published: May 2020

Single-units were recorded in hippocampus, septum, and striatum while freely behaving rats (n=3) ran trials in a T-maze task, and rested in a holding bucket between trials. During periods of motor inactivity, SWRs triggered excitatory responses from 28% (64/226) and inhibitory responses from 14% (31/226) of septal neurons. By contrast, only 4% (14/378) of striatal neurons were excited and 6% (24/378) were inhibited during SWRs. In both structures, SWR-responsive neurons exhibited greater spike coherence with hippocampal theta rhythm than neurons that did not respond to SWRs. In septum, neurons that were excited by SWRs fired at late phases of the theta cycle, whereas neurons that were inhibited by SWRs fired at early phases of the theta cycle. By contrast, SWR-responsive striatal neurons did not show consistent phase preferences during the theta cycle. A subset of SWR-responsive neurons in septum (55/95) and striatum (26/38) behaved asspeed cells, with firing rates that were positively or negatively modulated by the rat’s running speed. In both structures, firing rates of most SWR-excited speed cells were positively modulated by running speed, whereas firing rates of most SWR-inhibited speed cells were negatively modulated by running speed. These findings are consistent with a growing body of evidence that SWRs can activate subcortical representations of motor actions in conjunction with hippocampal representations of places and states, which may be important for storing and retrieving values of state-action pairs during reinforcement learning and memory consolidation.
A rare coding mutation in the MAST2 gene causes venous thrombosis in a French family with unexplained thrombophilia: The Breizh MAST2 Arg89Gln variant
Authors: Morange Pierre-Emmanuel , Peiretti Franck , Gourhant Lenaick , Proust Carole , Sapirella GV , Pulcrano-Nicolas Anne-Sophie , Stefanucci Luca , Lacroix Romaric , Ibrahim-Kosta Manal , Lemarie Catherine , Frontini Mattia , Alessi Marie-Christine , Tregouet David-Alexandre , Couturaud Francis
Published: May 2020

Rare variants outside the classical coagulation cascade might cause rare inherited thrombosis. We aimed to identify the variant(s) causing venous thromboembolism (VTE) in a family with multiple relatives affected with unprovoked VTE and no thrombophilia defects. We identified by whole exome sequencing an extremely rare Arg to Gln variant (R89Q) in the Microtubule Associated Serine/Threonine Kinase 2 (MAST2) gene that segregates with VTE in the family. Free-tissue factor pathway inhibitor (f-TFPI) plasma levels were significantly decreased in affected family members compared to healthy relatives. Conversely, plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in affected members than in healthy relatives. RNA sequencing analysis of RNA interference experimental data conducted in endothelial cells revealed that, of the 13,387 detected expressed genes, 2,354 have their level of expression modified by MAST2 knockdown, including SERPINE1 coding for PAI-1 and TFPI. In HEK293 cells overexpressing the MAST2R289Q variant, TFPI and SERPINE1 promoter activities were respectively lower and higher than in cells overexpressing the MAST2 wild type allele. This study identifies a novel thrombophilia-causing R89Q variant in the MAST2 gene that is here proposed as a new molecular player in the etiology of VTE by interfering with hemostatic balance of endothelial cells.
Identifying Homeless Population Needs in the Emergency Department Using Community-Based Participatory Research
Authors: Franco, MD Andrew , Meldrum, MBBS Jonathan , Ngaruiya, MD, MSc Christine
Published: May 2020

Background: Annually 1.5 million Americans face housing insecurity, and compared to their domiciled counterparts are three times more likely to utilize the Emergency Department (ED). Community Based Participatory Research (CBPR) methods have been employed in underserved populations, but use in the ED has been limited. We employed CBPR with a primary goal of improved linkage to care, reduced ED recidivism, and improved homeless health care.
Methods: A needs analysis was performed using semi-structured individual interviews with participants experiencing homelessness as well as with stakeholders. Results were analyzed using principles of grounded theory. At the end of the interviews, respondents were invited to join the CBPR team. At CBPR team meetings, results from interviews were expounded upon and discussions on intervention development were conducted.
Results: Twenty-five stakeholders were interviewed including people experiencing housing insecurity, ED staff, inpatient staff, and community shelters and services. Three themes emerged from the interviews. First, the homeless population lack access to basic needs, thus management of medical needs must be managed alongside social ones. Second, specific challenges to address homeless needs in the ED include episodic care, inability to recognize housing insecurity, timely involvement of ancillary staff, and provider attitudes towards homeless patients affecting quality of care. Lastly, improved discharge planning and communication with outside resources is essential to improving homeless health and decreasing ED overutilization. A limitation of results is bias towards social networks influencing included stakeholders.
Conclusion: CBPR is a promising approach to address gaps in homeless health care as it provides a comprehensive view incorporating various critical perspectives. Key ED-based interventions addressing recidivism include improved identification of housing insecurity, reinforced relationships between ED and community resources, and better discharge planning.
On the COVID-19 Pandemic in Indian State of Maharashtra: Forecasting & Effect of different parameters
Authors: Avhad Arvind S. , Sutar Prasad P. , Mohite Onkar T. , Pawar Vaibhav S.
Published: May 2020

This work details the outbreak and factors affecting the spread of novel coronavirus (COVID-19) in the Indian state of Maharashtra, which is considered as one of the most massive and deadly pandemic outbreaks. Observational data collected between 14 March 2020 and 4 May 2020 is statistically analyzed to determine the nonlinear behavior of the epidemic. It is followed by validating predicted results with real-time data. Proposed model is further used to obtain statistical summaries in which Grubbs tests for outlier detection have justified high values of evaluation metrics. Outliers are found to be pilot elements in an outbreak under considered region. Statistically, a significant correlation has been observed between dependent and explanatory variables. Transmission pattern of this virus is very much different from the SARS-CoV-1 virus. Key findings of this work will be predominant in maintaining environment conditions at healthcare facilities to reduce transmission rates at these most vulnerable places.
Are we #Stayinghome to Flatten the Curve?
Authors: Sears James , Villas-Boas J. Miguel , Villas-Boas Vasco , Villas-Boas Sofia Berto
Published: May 2020

The recent spread of COVID-19 across the U.S. led to concerted efforts by states to flatten the curve through the adoption of stay-at-home mandates that encourage individuals to reduce travel and maintain social distance. Combining data on changes in travel activity with COVID-19 health outcomes and state policy adoption timing, we characterize nationwide changes in mobility patterns, isolate the portion attributable to statewide mandates, and link these reductions to changes in COVID-19 health outcomes. We find evidence of dramatic nationwide declines in mobility prior to adoption of any statewide mandates. Once states adopt a mandate, we estimate further mandate-induced declines between 2.1 and 7.0 percentage points relative to pre-COVID-19 baseline levels. Controlling for pre-treatment changes in mobility, we estimate mandate-induced declines of 0.13-0.17 fewer deaths and 5.6-6 fewer hospitalizations per 100,000 residents, equivalent to 23-30,000 averted deaths in adopting states for the months of March and April and death rates 42-54% lower than in the absence of policies. These estimates represent a likely lower bound on the health impacts of stay-at-home mandates, and our findings for the health impacts of early mobility reductions convey important policy implications for re-opening.
Containing the Spread of Coronavirus Disease 2019 (COVID-19): Meteorological Factors and Control Strategies
Authors: Lin Jun , Huang Weihao , Wen Muchen , Ma Shuyi , Hua Jiawen , Hu Hang , Li Dehong , Yin Shan , Qian Yanjun , Chen Peiling , Zhang Qiao , Yuan Ningbo , Sun Shaolong
Published: May 2020

The novel coronavirus disease 2019 (COVID-19) has spread globally and the meteorological factors vary greatly across the world. Understanding the effect of meteorological factors and control strategies on COVID-19 transmission is critical to contain the epidemic. Using individual-level data in mainland China, Hong Kong, and Singapore, and the number of confirmed cases in other regions, we explore the effect of temperature, relative humidity, and control measures on the spread of COVID-19. We found that high temperature mitigates the transmission of the disease. High relative humidity promotes COVID-19 transmission when temperature is low, but tends to reduce transmission when temperature is high. Implementing classical control measures can dramatically slow the spread of the disease. However, due to the occurrence of pre-symptomatic infections, the effect of the measures to shorten onset-to-isolation time is markedly reduced and the importance of contact tracing and quarantine and social distancing increases. The analytic results also highlight the importance of early intervention to contain the spread of COVID-19.
Coadaptation of the chemosensory system with voluntary exercise behavior in mice
Authors: Nguyen Quynh Anh Thi , Hillis David , Katada Sayako , Harris Timothy , Pontrello Crystal , Garland Theodore , Haga-Yamanaka Sachiko
Published: May 2020

Ethologically relevant chemical senses and behavioral habits are likely to coadapt in response to selection. As olfaction is involved in intrinsically motivated behaviors in mice, we hypothesized that selective breeding for a voluntary behavior would enable us to identify novel roles of the chemosensory system. Voluntary wheel running (VWR) is an intrinsically motivated and naturally rewarding behavior, and even wild mice run on a wheel placed in nature. We have established 4 independent, artificially evolved mouse lines by selectively breeding individuals showing high VWR activity (High Runners; HRs), together with 4 non-selected Control lines, over 88 generations. We found that several sensory receptors in specific receptor clusters were differentially expressed between the vomeronasal organ (VNO) of HRs and Controls. Moreover, one of those clusters contains multiple single-nucleotide polymorphism loci for which the allele frequencies were significantly divergent between the HR and Control lines, i.e., loci that were affected by the selective breeding protocol. These results indicate that the VNO has become genetically differentiated between HR and Control lines during the selective breeding process, strongly suggesting the chemosensory receptors as quantitative trait loci (QTL) for voluntary exercise in mice. We propose that olfaction may play an important role in motivation for voluntary exercise in mammals.
Comparison of Shoulder Functions Between Workers With and Without Shoulder Impingement Syndrome
Authors: Kim Jun-hee , Kwon Oh-yun , Yi Chung-hwi , Jeon Hye-seon , Choi Woo-chol Joseph , Weon Jong-hyuck
Published: May 2020

The occurrence of shoulder impingement syndrome (SIS) is associated with the frequent handling and lifting of heavy loads and excessive repetitive work above the shoulder level. Thus, assembly workers have a high prevalence of shoulder injuries, including SIS. The purpose of this study was to investigate differences in shoulder ROM, muscle strength, asymmetry ratio, function, productivity, and depression between workers with and without SIS.

Sixty-seven assembly line male workers (35 workers with SIS and 32 workers without SIS) participated in this study. The four shoulder ROMs and the five muscle strengths were measured using a Smart KEMA system. The asymmetry ratios were calculated using the asymmetry ratio formula; shoulder functions were measured using the shoulder pain and disability index (SPADI), disabilities of the arm, shoulder, and hand (DASH), and visual analogue scale (VAS); and Endicott work productivity scale (EWPS). Severity of depression was measured using the Beck depression inventory (BDI). Independent t-tests were performed for statistical analysis.

The SPADI, DASH, and VAS values of workers with SIS were significantly higher than those of workers without SIS. Also, workers with SIS had significantly smaller shoulder internal rotation and shoulder abduction compared to workers without SIS. In addition, workers with SIS exhibited significantly lower SIR muscle strength than workers without SIS. Workers with SIS had significantly higher asymmetry ratios in shoulder internal rotation, shoulder external rotation, and elbow flexion muscle strength than workers without SIS.

The SPADI and DASH scores, which indicate shoulder function, were higher, and the intensity of self-aware pain was higher in workers with SIS. Also, workers with SIS exhibited reduced SIR and SAB ROMs; decreased SIR muscle strength. Particularly, the asymmetry ratios of SIR, SER, EF muscle strength are good comparable factors for workers with and without SIS. In addition, the asymmetry ratios of shoulder muscle strengths could provide an important baseline comparison for the workers with SIS.
Pitting the Gumbel and logistic growth models against one another to model COVID-19 spread
Authors: Yoo Keunyoung , Arashi Mohammad , Bekker Andriette
Published: May 2020

In this paper, we investigate briefly the appropriateness of the widely used logistic growth curve modeling with focus on COVID-19 spread, from a data-driven perspective. Specifically, we suggest the Gumbel growth model for behaviour of COVID-19 cases in European countries in addition to the United States of America (US), for better detecting the growth and prediction. We provide a suitable fit and predict the growth of cases for some selected countries as illustration. Our contribution will stimulate the correct growth spread modeling for this pandemic outbreak.
1-C Nonlinear Covid-19 Epidemic Model and Application to the Epidemic Prediction in France
Authors: Quadrat J.-P.
Published: May 2020

We have shown in a previous paper that the standard time-invariant SIR model was not effective to predict the 2019-20 coronavirus pandemic propagation. We have proposed a new model predicting z the logarithm of the number of detected-contaminated people. It follows a linear dynamical system ż = b − az. We show here that we can improve this prediction using a non linear model ż = b − azr where r is an exponent that we have also to estimate from data. Some countries have an epidemic with a bell shaped form that we call unimodal epidemic. With this new model, we fit observed data of different countries having an unimodal epidemic with a surprising quality. We discuss also the prediction quality obtained with these models at the epidemic start in France. Finally, we evaluate the containment impact on the Covid French mortality in hospitals.