bluuebunny/crossref_metadata_2025 huggingface dataset:
Huddling as an Academic Quality Improvement Initiative
Authors: Schmitt Catherine , Lancaster Rachelle J. , Janquart Susan , Nevin Mary , Brickner Shanon
Published: May 2020

A huddle is described as a tight group gathered together to talk privately for the purpose of reviewing performance and engaging in future planning. Although huddles are described as an effective communication tool to enhance patient safety in hospital settings, little is known about their use in academe. This article describes a quality improvement initiative involving weekly huddles of faculty teaching medical/surgical nursing and provides preliminary findings after one year.
Integrating Videoconferencing into Primary Care to Address Alcohol Use Disorder
Authors: Palfai Tibor P.
Published: May 2020

This commentary on Leibowitz et al, “Video Consultation to Increase Treatment of Alcohol Use Disorder in Primary Care: A Pilot Feasibility Study” highlights the potential value of utilizing videoconferencing to address unhealthy drinking in primary care settings, the advantages of centralized expert consultants that may be accessed through technology, and the need for future implementation process and clinical care outcome research.
Altered Mental Status: A Case Report of Toxic Leukoencephalopathy Following Heroin Exposure
Authors: Weitzer Danielle , Shmuts Rachel , Khan Munaza
Published: May 2020

Toxic leukoencephalopathy is a rare illness that causes diffuse white matter destruction, and as a result may mimic psychiatric disorders. Multiple causes have been identified including nerve related injury from exposure to a toxin. When symptoms present, they typically improve after the offending agent is eliminated. However, the clinical presentation in this report is unique in that the syndrome got worse several weeks after the toxin was removed. Research indicates that supportive supplements and vitamins can be used to facilitate neurological recovery. This report outlines a case of toxic leukoencephalopathy following heroin overdose that was treated with vitamin supplementation.
Evaluation of the Pressure Injury Prevention Information System
Authors: Huang Hsiu-Yen , Lee Ting-Ting , Hsu Tzu-Chuan , Mills Mary Etta , Tzeng I-Shiang
Published: May 2020

Clinical decision support systems provide empirical guidance to improve the quality of nursing care. This study aimed to evaluate the outcomes of implementation of decision support functions into the preventive care system as regards nurses' acceptance of technology, documentation completeness, and incidence of hospital-acquired pressure injury. The researchers performed data collection in a regional hospital in northern Taiwan. The study used the Davis Science and Technology Acceptance Model scale to investigate nurses' technology acceptance before and after the introduction of a clinical decision support system and compared documentation compliance of preventive records with the incidence of hospital-acquired pressure injuries. Results showed that nurses' acceptance of the technology was significantly improved, and the completion rate of the pressure injury preventive care record significantly increased from 88.9% to 99.9%. Meanwhile, the incidence of hospital-acquired pressure injury decreased significantly from 0.057% to 0.021%. Therefore, it was concluded that the clinical decision support system provides evidenced-based support to nurses and is effective in identifying patient-specific prevention nursing plans of care.
Blunderbuss: Ocular and Orbital Injuries Due to Muzzle-Loading Firearms
Authors: De Niear Matthew A. , Law James J. , Breazzano Mark P. , Mawn Louise A.
Published: May 2020

Purpose:

Injury to the eye and/or orbital and adnexal structures associated with antiquated muzzle-loading firearms has not, to our knowledge, been characterized with the exception of a single case report.

Methods:

A retrospective chart review of 7 patients treated at Vanderbilt University Medical Center from 2003 to 2017 who sustained traumatic injuries to the ocular and/or orbital structures secondary to the discharge of muzzle-loading firearms. The study was approved by the Vanderbilt Institutional Review Board.

Results:

In 6/7 cases, injuries occurred secondary to the muzzle-loading firearm exploding due to dysfunction or misuse. Foreign material deriving from the firearm was retained in 3/7 patients. Initial examination of the orbit and adnexa revealed 5/7 individuals sustaining orbital fractures and 6/7 with facial lacerations (including 2 with eyelid lacerations); none had evidence of a lacrimal duct injury. Three patients suffered globe injuries (1 closed-globe and 2 open-globe). Visual acuity at last follow-up was ≥20/20 in 12/14 eyes examined. Surgical intervention was required in the treatment of 4/7 individuals (including 3/7 requiring intervention for sustained orbital fractures). No individuals were wearing eye protection at the time of injury. All individuals survived their injuries.

Conclusions:

The operation of muzzle-loading firearms poses a unique risk of injury to the operator. The resultant injuries in this case series were primarily due to the explosion of the firearm, which subsequently appear similar to orbital and ocular blast injuries caused by explosive weapons. Orbital injuries and more potentially more devastating ocular injuries may have been prevented by protective eyewear.
The Impact of Diabetes Status on Presenteeism in Japan
Authors: Mori Takahiro , Nagata Tomohisa , Nagata Masako , Otani Makoto , Fujino Yoshihisa , Mori Koji
Published: May 2020

Objective:

This study aimed to investigate the impact of diabetes status on presenteeism in companies in Japan.

Methods:

A cross-sectional study was conducted among workers aged 40 years or older. Using medical examination results and health insurance claims data, participants were classified as normal, borderline, or diabetic. The diabetic group was further classified as untreated or treated. The Quantity and Quality (QQ) method was used as an evaluation index of presenteeism. Logistic regression analysis was performed to predict presenteeism loss.

Results:

Data on 13,292 people were analyzed. Presenteeism loss was significantly higher in the diabetic group versus the normal group. The untreated group did not differ from the normal group, but presenteeism loss was significantly higher in the treated group.

Conclusions:

Presenteeism loss may occur among diabetic workers in Japan and can be caused by diabetes treatment.
The Good, the Bad, and the Ugly
Authors: Grace Kathleen
Published: May 2020

Lung injury associated with vaping has recently become a national concern and challenge, especially with our vulnerable youth population. This article offers a vaping primer: What is vaping? What are the effects of vaping and how does the lung injury present? How are vaping products marketed? What regulations are being considered or have been put into place? Lastly, a case study is reviewed, depicting a clinical scenario.
Distress Concealment and Depression Symptoms in a National Sample of Canadian Men
Authors: Cox Daniel W. , Ogrodniczuk John S. , Oliffe John L. , Kealy David , Rice Simon M. , Kahn Jeffrey H.
Published: May 2020

Men's tendency to conceal their distress has been linked with increased depressive symptoms. Although interpersonal connectedness has been associated with distress concealment and depression, it is unclear how connectedness mediates this association. The aim of the present study was to examine the mediating effects of feeling understood and loneliness—two facets of interpersonal connectedness—in the association between distress concealment and depressive symptoms in men. A sample of 530 Canadian men was selected based on age- and region-stratification that reflects the national population. Participants completed measures of depression symptoms, distress concealment, loneliness, and feeling understood. Mediation analyses were conducted. Results supported a sequential mediation model: concealing distress was associated with not feeling understood, not feeling understood was associated with loneliness, and loneliness was associated with depressive symptoms. These findings shed light on how distress concealment is associated with depressive symptoms among men. Implications for practice and theory are discussed.
Psychosocial Reactions to Plagues in the Cultural History of Medicine
Authors: Wigand Moritz E. , Becker Thomas , Steger Florian
Published: May 2020

The aim of this work is to elucidate psychosocial reactions to plagues by analyzing three landmark descriptions from different eras: Thucydides' description of the plague of Athens (430 bc) in The History of the Peloponnesian War, Giovanni Boccaccio's description of the plague in Florence (1348) in The Decameron, and Albert Camus' description in The Plague (1947). Using a narrative inquiry, we found psychosocial reactions to be complex and ambivalent and could discern several coping strategies. We propose that this knowledge can help psychiatrists and other healthcare professionals during the ongoing COVID-19 pandemic.
Properties of Ultraprocessed Foods That Can Drive Excess Intake
Authors: Rolls Barbara J. , Cunningham Paige M. , Diktas Hanim E.
Published: May 2020

Recent research suggests that ultraprocessed foods, particularly as defined by the NOVA system, facilitate overconsumption and may contribute to the development of obesity. Questions remain as to what properties of ultraprocessed foods are driving excess intake. Ultraprocessed foods tend to be high in energy density and low in volume, easy to eat rapidly, and highly palatable. Studies indicate that these properties are likely contributors to the overconsumption of ultraprocessed foods, rather than the processing per se. Indeed, processing can be used to modify food properties such as energy density and texture to help reduce overconsumption. For many people, ultraprocessed foods provide accessible and affordable sources of nutrients and energy when unprocessed foods are scarce. Future studies should focus on understanding how processing can be used to create widely available and affordable nutrient-rich foods that can help consumers manage energy intake.
US Department of Agriculture Summer Meals Program
Authors: Fleischhacker Sheila , Turner Lindsey , Mande Jerold R.
Published: May 2020

This article provides an overview of the US Department of Agriculture Summer Meals Program (SMP) and highlights opportunities to strengthen SMP's public health impacts. We also discuss initial SMP implications of 2 relevant policy provisions of the Families First Coronavirus Response Act (P.L. 116-127), signed into law on March 18, 2020. Ensuring access to summer meals among high-risk students can provide (1) supplemental nutrition assistance to families that helps address food insecurity during the summer months when there are no school meals, (2) healthy meals in structured settings that might help reduce obesity risk, and (3) support to other programs that offer other benefits such as education, physical activity, or job training.
COVID-19 and Food Safety
Authors: Pressman Peter , Naidu A. Satyanarayan , Clemens Roger
Published: May 2020

COVID-19, also known as the “novel coronavirus disease 2019,” is a respiratory illness, and the causative pathogen is officially named as “SARS-CoV-2.” Infections with SARS-CoV-2 have now been amplified to a global pandemic—as of April 3, 2020, nearly 1 018 000 cases have been confirmed in more than 195 countries, including more than 300 000 cases within the United States. Public safety guidelines are followed worldwide to stop the spread of COVID-19 and stay healthy. Despite COVID-19 is a respiratory illness with mode of invasion through the respiratory tract, not the gastrointestinal tract, an average food consumer is anxious and concerned about the food safety. Could an individual catch the deadly contagious COVID-19 from groceries brought home from the supermarket—or from the next restaurant takeout order? This brief review elucidates the epidemiology and pathobiological mechanism(s) of SARS-CoV-2 and its implications in food-borne infections, transmission via food surfaces, food processing, and food handling.
Poor Agreement but Good Predictive Value Between Automated and Manual QTc Intervals in Pediatric Emergency Department Electrocardiograms
Authors: Hoffman Robert J. , Alansari Khalid
Published: May 2020

Objectives

QTc interval is significant because prolongation may lead to ventricular dysrhythmia. Computerized electrocardiogram machines typically measure QT interval length and, using an algorithm assessment of multiple leads, calculate a QTc value. Manual measurement of the QT interval used to calculate the QTc value is more time-consuming but potentially more accurate. In this study, we compare the automated QTc calculation with the QTc value calculated using manual QT measurements.

Methods

We prospectively obtained 350 resting 12-lead electrocardiograms (ECGs) in children aged 2 to 14 years in an academic pediatric emergency department. Manual measurement of the QT interval was performed and the QTc was calculated using the 2 most commonly used correction methods, Bazzet and Fridericia formulas. The paired values were used to perform a Bland-Altman analysis and create a receiver operating characteristic curve.

Results

Bland-Altman analysis determined that QT-automated and QTc-Bazett had an average difference of 3.8 milliseconds, with a standard deviation of 86 milliseconds (95% confidence interval = −161 to 176). An automated QTc value of 455 milliseconds was sensitive to detect manual QTc values of greater than 480 milliseconds.

Conclusions

In children with resting ECGs, there is a poor agreement between the automated QTc produced by a computerized electrocardiogram and the QTc value obtained using manual QT measurement. Statistically and clinically relevant discrepancy between the automated QTc and QTc values calculated after manual QT measurement was present. Automated QTc values may be used as a screening tool to detect prolonged QTc, but for accurate determination of QTc, manual measurement is necessary.
A Bibliometric Analysis of Cirrhosis Nursing Research on Web of Science
Authors: Guo Lizhen , Lu Gendi , Tian Jun
Published: May 2020

The aims and objectives of this study were to (1) analyze the bibliometric characteristics of articles on Web of Science from 1986 to the present using literature mining and information visualization technologies developed by CiteSpace software, (2) reflect the current situation in this field as far as possible, and (3) provide evidence for improving research on nursing and clinical liver cirrhosis in Mainland China. No bibliometric analysis exists on Web of Science regarding cirrhosis nursing research. The status of current research, including hotspots and trends, has been assessed in this study through a bibliometric analysis. Literature related to cirrhosis and nursing was identified via Web of Science. Data were then analyzed using CiteSpace software. From 1986 to 2018, a total of 179 articles were published in 109 journals by 830 researchers in 36 countries/regions. The terms “cirrhosis,” “management,” and “quality of life” emerged most frequently and indicated the hotspots in liver cirrhosis nursing literature. Among all countries/regions, the United States contributed the most research overall; Asia also played an important role in the field of liver cirrhosis nursing research. The journal Gastroenterology Nursing published the greatest number of articles. Liver cirrhosis nursing research has attracted increasing amounts of attention around the world, although it remains less robust than other fields. Cirrhosis nursing research is still in its infancy in Mainland China, and there is an urgent need for additional support from government or research institutions to improve this research focus and promote international acceptance of the research outcomes.
Neurocognitive Impairment in Bipolar Disorder and Associated Factors: Using Population-based Norms and a Strict Criterion for Impairment Definition
Authors: Sarmento Stella Maria de Sá , Bittencourt Lorna , de Mendonça Filho Euclides José , Abreu Neander , Tavares de Lacerda Acioly Luiz , Miranda-Scippa Ângela
Published: May 2020

Background:

Cognitive impairment is often identified in individuals with bipolar disorder and is associated with their functional impairment. However, there is controversy surrounding potential classification methods for impairment in cognitive measures.

Objective:

To examine the proportion of cognitive measures indicating impairment of attention, processing speed, memory, visuoconstructional abilities, and executive functions in individuals with bipolar disorder type I (euthymic) and healthy controls, using a strict criterion for defining impairment.

Methods:

We gave 43 individuals with bipolar disorder type I and 17 healthy controls a comprehensive clinical and neuropsychological assessment. All scores were standardized using means and standard deviations according to age. Impaired performance in all cognitive measures was determined using a distribution-based threshold of z=±1645. The effects of the sociodemographic and clinical variables on cognitive performance were examined using multiple stepwise backward regression analyses.

Results:

Clinically significant cognitive impairment was observed more frequently in the bipolar disorder group, compared to controls, on all measures. From participant factors, we found that level of education and number of manic episodes predicted variation in more cognitive measure scores.

Discussion:

The use of population-based norms to standardize cognitive measures, and a strict criterion to define cognitive impairment, in individuals with bipolar disorder type 1 and healthy controls resulted in a prevalence of impairment in cognitive domains’ frequencies of deficits that fell within the ranges previously reported in meta-analyses.

Conclusions:

Clinically introducing population norms and a stringent cognitive impairment criterion can facilitate more accurate measures of cognitive impairment in individuals with bipolar disorder.
The Montreal Cognitive Assessment in Veteran Postacute Care: Implications of Cut Scores
Authors: Tolle Kathryn , Montgomery Valencia , Gradwohl Brian , Spencer Robert , Stelmokas Julija
Published: May 2020

Background:

The Montreal Cognitive Assessment (MoCA) is often used for cognitive screening across health care settings, especially in rehabilitation centers, where assessment and treatment of cognitive function is considered key for successful multidisciplinary treatment. Although the original MoCA validation study suggested a cut score of <26 to identify cognitive impairment, recent studies have suggested that lower cut scores should be applied.

Objectives:

To examine the percentage of positive screens for cognitive impairment using the MoCA in a veteran postacute care (PAC) rehabilitation setting and to identify the most accurate MoCA cut score based on criterion neuropsychological measures.

Methods:

We obtained data from 81 veterans with diverse medical diagnoses who had completed the MoCA during their admission to a PAC unit. A convenience subsample of 50 veterans had also completed four criterion neuropsychological measures.

Results:

Depending on the cut score used, the percentage of individuals classified as impaired based on MoCA performance varied widely, ranging from 6.2% to 92.6%. When predicting performance using a more comprehensive battery of criterion neuropsychological tests, we identified <22 as the most accurate MoCA cut score to identify a clinically relevant level of impairment and <24 to identify milder cognitive impairment.

Conclusions:

Our findings suggest that a MoCA cut score of <26 carries a risk of misdiagnosis of cognitive impairment, and scores in the range of <22 to <24 are more reliable for identifying cognitive impairment.
Seizure Detection: Interreader Agreement and Detection Algorithm Assessments Using a Large Dataset
Authors: Scheuer Mark L. , Wilson Scott B. , Antony Arun , Ghearing Gena , Urban Alexandra , Bagić Anto I.
Published: May 2020

Purpose:

To compare the seizure detection performance of three expert humans and two computer algorithms in a large set of epilepsy monitoring unit EEG recordings.

Methods:

One hundred twenty prolonged EEGs, 100 containing clinically reported EEG-evident seizures, were evaluated. Seizures were marked by the experts and algorithms. Pairwise sensitivity and false-positive rates were calculated for each human–human and algorithm–human pair. Differences in human pairwise performance were calculated and compared with the range of algorithm versus human performance differences as a type of statistical modified Turing test.

Results:

A total of 411 individual seizure events were marked by the experts in 2,805 hours of EEG. Mean, pairwise human sensitivities and false-positive rates were 84.9%, 73.7%, and 72.5%, and 1.0, 0.4, and 1.0/day, respectively. Only the Persyst 14 algorithm was comparable with humans—78.2% and 1.0/day. Evaluation of pairwise differences in sensitivity and false-positive rate demonstrated that Persyst 14 met statistical noninferiority criteria compared with the expert humans.

Conclusions:

Evaluating typical prolonged EEG recordings, human experts had a modest level of agreement in seizure marking and low false-positive rates. The Persyst 14 algorithm was statistically noninferior to the humans. For the first time, a seizure detection algorithm and human experts performed similarly.
Generalized mathematical model of cancer heterogeneity
Authors: Naito Motohiko
Published: May 2020

The number of reports on mathematical modeling related to oncology is increasing with advances in oncology. Even though the field of oncology has developed significantly over the years, oncology-related experiments remain limited in their ability to examine cancer. To overcome this limitation, in this study, a stochastic process was incorporated into conventional cancer growth properties to obtain a generalized mathematical model of cancer growth. Further, an expression for the violation of symmetry by cancer clones that leads to cancer heterogeneity was derived by solving a stochastic differential equation. Monte Carlo simulations of the solution to the derived equation validate the theories formulated in this study. These findings are expected to provide a deeper understanding of the mechanisms of cancer growth, with Monte Carlo simulation having the potential of being a useful tool for oncologists.
Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York
Authors: Rosenberg Eli S. , Tesoriero James M. , Rosenthal Elizabeth M. , Chung Rakkoo , Barranco Meredith A. , Styer Linda M. , Parker Monica M. , Leung Shu-Yin John , Morne Johanne E. , Greene Danielle , Holtgrave David R. , Hoefer Dina , Kumar Jessica , Udo Tomoko , Hutton Brad , Zucker Howard A.
Published: May 2020

Importance

New York State (NYS) is an epicenter of the United States’ COVID-19 epidemic. Reliable estimates of cumulative incidence of SARS-CoV-2 infection in the population are critical to tracking the extent of transmission and informing policies, but US data are lacking, in part because societal closure complicates study conduct.

Objective

To estimate the cumulative incidence of SARS-CoV-2 infection and percent of infections diagnosed in New York State, overall and by region, age, sex, and race and ethnicity.

Design

Statewide cross-sectional seroprevalence study, conducted April 19-28, 2020.

Setting

Grocery stores (n=99) located in 26 counties throughout NYS, which were essential businesses that remained open during a period of societal closure and attract a heterogenous clientele.

Participants

Convenience sample of patrons ≥18 years and residing in New York State, recruited consecutively upon entering stores and via an in-store flyer.

Exposures

Region (New York City, Westchester/Rockland, Long Island, Rest of New York State), age, sex, race and ethnicity.

Main Outcomes

Primary outcome: cumulative incidence of SARS-CoV-2 infection, based on dry-blood spot (DBS) SARS-CoV-2 antibody reactivity; secondary outcome: percent of infections diagnosed.

Results

Among 15,101 adults with suitable DBS specimens, 1,887 (12.5%) were reactive using a validated SARS-CoV-2 IgG microsphere immunoassay (sensitivity 87.9%, specificity 99.75%). Following post-stratification weighting on region, sex, age, and race and ethnicity and adjustment for assay characteristics, estimated cumulative incidence through March 29 was 14.0% (95% CI: 13.3-14.7%), corresponding to 2,139,300 (95% CI: 2,035,800-2,242,800) infection-experienced adults. Cumulative incidence was higher among Hispanic/Latino (29.2%, 95% CI: 27.2-31.2%), non-Hispanic black/African American (20.2% 95% CI, 18.1-22.3%), and non-Hispanic Asian (12.4%, 95% CI: 9.4-15.4%) adults than non-Hispanic white adults (8.1%, 95% CI: 7.4-8.7%, p<.0001). Cumulative incidence was highest in New York City (NYC) 22.7% (95% CI: 21.5%-24.0). Dividing diagnoses reported to NYS by estimated infection-experienced adults, an estimated 8.9% (95% CI: 8.4-9.3%) of infections were diagnosed, with those ≥55 years most likely to be diagnosed (11.3%, 95% CI: 10.4-12.2%).

Conclusions and Relevance

Over 2 million adults were infected through late March 2020, with substantial variations by subpopulations. As this remains below herd immunity thresholds, monitoring, testing, and contact tracing remain essential public health strategies.
HIV Diversity Considerations in the Application of the Intact Proviral DNA Assay (IPDA)
Authors: Kinloch Natalie N. , Ren Yanqin , Alberto Winiffer D. Conce , Dong Winnie , Khadka Pragya , Huang Szu Han , Mota Talia M. , Wilson Andrew , Shahid Aniqa , Kirkby Don , Harris Marianne , Kovacs Colin , Benko Erika , Ostrowski Mario A. , Del Rio Estrada Perla M. , Wimpelberg Avery , Cannon Christopher , Hardy W. David , MacLaren Lynsay , Goldstein Harris , Brumme Chanson J. , Lee Guinevere Q. , Lynch Rebecca M. , Brumme Zabrina L. , Jones R. Brad
Published: May 2020

Opening Paragraph (serves as abstract for submission) and Body

The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a precise and scalable method for intact HIV reservoir quantification1. This duplexed droplet digital PCR (ddPCR) assay simultaneously targets the HIV Packaging Signal (Ψ) and the Rev Responsive Element (RRE) within Envelope (env) to distinguish genomically intact proviruses against a large background of defective ones2. The IPDA requires less time, resources, and biological material than the gold standard for replication-competent HIV reservoir measurement, the Quantitative Viral Outgrowth Assay (QVOA)3, and is being adopted in research and clinical studies4–7. In our cohort of HIV-1 subtype B-infected individuals from North America however, the IPDA yielded a 28% failure rate due to HIV polymorphism. We further demonstrate that within-host HIV diversity can lead the IPDA to underestimate intact HIV reservoir size, which could negatively impact clinical trial results interpretation. While the IPDA represents an important methodological advance, HIV diversity should be addressed before its widespread adoption.
Observation of female-male mounting in the carrion crow
Authors: Wascher Claudia A.F. , Hillemann Friederike
Published: May 2020

In the biological sciences, sexual behaviours in non-human animals are traditionally investigated in the context of reproduction and direct fitness benefits. While the evolutionary functions of non-conceptive sexual behaviours (‘socio-sexual’) remain less well explored, these interactions and displays have been suggested to be important for shaping and maintaining social relationships. Here, we report an observation of a captive female carrion crow,Corvus corone corone, mounting her co-housed male partner. We highlight the importance of more systematic research and discussions of rarely observed behaviours in social evolution research, including considerations for behaviours that transcend binary or heteronormative frameworks, to provide a more comprehensive understanding of non-conceptive socio-sexual behaviours.
Tissue failure propagation as mediated by circulatory flow
Authors: Uppal G. , Bahcecioglu G. , Zorlutuna P. , Can Vural D.
Published: May 2020

Aging is driven by subcellular processes that are relatively well-understood. However the qualitative mechanisms and quantitative dynamics of how these micro-level failures cascade to a macro-level catastrophe in a tissue or organs remain largely unexplored. Here we experimentally and theoretically study how cell failure propagates in a synthetic tissue in the presence of advective flow. We argue that cells secrete cooperative factors, thereby forming a network of interdependence governed by diffusion and flow, which fails with a propagating front parallel to advective circulation.

SIGNIFICANCE

Mortality rates typically increase for complex organisms as they age. This leads us to suggest that aging depends on interactions between cells. As cells become damaged, the effect propagates to other cells, eventually leading to a systemic catastrophe. Yet it is unclear how this failure dynamically propagates. Here we present experiments with synthetic tissues and analogous analytical models to investigate the dynamics of failure propagation. Our main contribution is a detailed investigation of failure propagation when interactions are mediated by advective flow. We find analytical expressions for when a pronounced propagation occurs, its velocity, and acceleration in terms of system parameters.
Kinetic Membrane Model of Outer Hair Cells
Authors: Iwasa K. H.
Published: May 2020

The effectiveness of outer hair cells (OHCs) in amplifying the motion of the organ of Corti, and thereby contributing to the sensitivity of mammalian hearing, depends on the mechanical power output of these cells. Electromechanical coupling in OHCs, which enables these cells to convert electrical energy into mechanical energy, has been analyzed in detail using isolated cells using primarily static membrane models. In the preceding reports, mechanical output of OHC was evaluated by developing a kinetic theory based on a simplified onedimensional (1D) model for OHCs. Here such a kinetic description of OHCs is extended by using the membrane model, which has been used for analyzing in vitro experiments. The present theory predicts, for systems without inertial load, that elastic load enhances positive shift of voltage dependence of the membrane capacitance due to turgor pressure. For systems with inertia, mechanical power output also depends on turgor pressure. The maximal power output is, however, similar to the previous prediction of up to ∼10 fW based on the 1D model.

Statement of Significance

This paper is an attempt for developing a physical model to clarify the mechanism of outer hair cells in performing their role as an amplifier in mammalian hearing. Specifically, this paper extends a static model of these cells into a dynamic one to evaluate mechanical power production, which is essential for the function of these cells. It clarifies the assumptions essential for a previous phenomenological theory, a 1-D model. In addition, it describes the effect of turgor pressure on mechanical power generation.
Draft Genome of the Sea Cucumber Holothuria glaberrima, a model for the study of regeneration
Authors: Medina-Feliciano Joshua G. , Pirro Stacy , García-Arrarás Jose E. , Mashanov Vladimir , Ryan Joseph F.
Published: May 2020

Regeneration is one of the most fascinating and yet least understood processes of animals. Echinoderms, one of the closest related invertebrate groups to humans, can contribute to our understanding of the genetic basis of regenerative processes. Amongst echinoderms, sea cucumbers have the ability to grow back most of their body parts following injury, including the intestine and nervous tissue. The cellular and molecular events underlying these abilities in sea cucumbers have been most extensively studied in the speciesHolothuria glaberrima. However, research into the regenerative abilities of this species have been impeded due to the lack of adequate genomic resources. Here, we report the first draft genome assembly ofH. glaberrimaand demonstrate its value for future genetic studies. Using only short sequencing reads, we assembled the genome into 2,960,762 scaffolds totaling 1.5 gigabases with an N50 of 15 kilobases. Our BUSCO assessment of the genome resulted in 882 (90.2%) complete and partial genes from 978 genes queried. We incorporated transcriptomic data from several different life history stages to annotate 41,076 genes in our final assembly. To demonstrate the usefulness of the genome, we fully annotated the melanotransferrin (Mtf)gene family, which have a potential role in regeneration of the sea cucumber intestine. Using these same data, we extracted the mitochondrial genome, which showed high conservation to that of other holothuroids. Thus, these data will be a critical resource for ongoing studies of regeneration and other studies in sea cucumbers.
Molecular mechanisms underlying the extreme mechanical anisotropy of the flaviviral exoribonuclease-resistant RNAs (xrRNAs)
Authors: Niu Xiaolin , Liu Qiuhan , Xu Zhonghe , Chen Zhifeng , Xu Linghui , Xu Lilei , Li Jinghong , Fang Xianyang
Published: May 2020

Mechanical anisotropy is an essential property for many biomolecules to assume their structures, functions and applications, however, the mechanisms for their direction-dependent mechanical responses remain elusive. Herein, by using single-molecule nanopore sensing technique, we explore the mechanisms of directional mechanical stability of the xrRNA1 RNA from ZIKA virus (ZIKV), which forms a complex ring-like architecture. We reveal extreme mechanical anisotropy in ZIKV xrRNA1 which highly depends on Mg2+and the key tertiary interactions. The absence of Mg2+and disruption of the key tertiary interactions strongly affect the structural integrity and attenuate mechanical anisotropy. The significance of ring structure in RNA mechanical anisotropy is further supported by steered molecular dynamics simulations on ZIKV xrRNA1 and another two RNAs with ring structures, the HCV IRES and THF riboswitch. We anticipate the ring structures can be used as key elements to build RNA-based nanostructures with controllable mechanical anisotropy for biomaterial and biomedical applications.
Proteomic pipeline to identify age-related compositional and structural changes of the human dentin extracellular matrix
Authors: Reis Mariana , Lee Fred , Bedran-Russo Ana K. , Naba Alexandra
Published: May 2020

Objective

Devise a pipeline to investigate the protein composition of the human root dentin extracellular matrix (ECM) from single individuals of different age cohorts.

Design

Individual cervical root dentin of sound human molars from two age brackets, young (18-25 years old; n=3) and old (75-85 years old; n=3), were cut and pulverized. Protein extraction and fractionation were completed by sequential demineralization with EDTA buffer, chaotropic extraction with guanidine hydrochloride, and urea. The resulting protein extracts of differential solubility were digested into peptides and peptides were analyzed by mass spectrometry. Data generated for this study are available via ProteomeXchange, identifier PXD018320.

Results

We found that protein extracts of different solubilities present distinct biochemical compositions. We further define the matrisome of young (48 proteins) and old (50 proteins) human root dentin and report the identification of compositional and structural differences in ECM proteins from young and old teeth.

Conclusion

Our study provides a rigorous pipeline, from sample preparation to data analysis, to investigate the ECM composition – or matrisome – of the dentin. This pipeline has the potential to lead to the discovery of biomarkers of tooth aging and health.
Atoh7-independent specification of retinal ganglion cell identity
Authors: Brodie-Kommit Justin , Clark Brian S. , Shi Qing , Shiau Fion , Kim Dong Won , Langel Jennifer , Sheely Catherine , Schmidt Tiffany , Badea Tudor , Glaser Thomas , Zhao Haiqing , Singer Joshua , Blackshaw Seth , Hattar Samer
Published: May 2020

Retinal ganglion cells (RGCs), which relay visual information from the eye to the brain, are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factorAtoh7, which is expressed in multipotent early neurogenic retinal progenitor cells, leads to a selective and near complete loss of RGCs.Atoh7has thus been considered essential for conferring competence on progenitors to generate RGCs. However, when apoptosis is inhibited inAtoh7-deficient mice by loss of function ofBax, only a modest reduction in RGC number is observed. Single-cell RNA-Seq ofAtoh7;Bax-deficient retinas shows that RGC differentiation is delayed, but that RGC precursors are grossly normal.Atoh7;Bax-deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry, but exhibit severe axonal guidance defects. This study reveals an essential role forAtoh7in RGC survival, and demonstratesAtoh7-independent mechanisms for RGC specification.
Novel heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase
Authors: Gamiz-Arco Gloria , Gutierrez-Rus Luis I. , Risso Valeria A. , Ibarra-Molero Beatriz , Hoshino Yosuke , Petrović Dušan , Romero-Rivera Adrian , Seelig Burckhard , Gavira Jose A. , Kamerlin Shina C.L. , Gaucher Eric A. , Sanchez-Ruiz Jose M.
Published: May 2020

Glycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel fold with its modern descendants but displays large regions with greatly enhanced conformational flexibility. Yet, the barrel core remains comparatively rigid and the ancestral glycosidase activity is stable, with an optimum temperature within the experimental range for thermophilic family-1 glycosidases. None of the ~5500 reported crystallographic structures of ~1400 modern glycosidases show a bound porphyrin. Remarkably, the ancestral glycosidase binds heme tightly and stoichiometrically at a well-defined buried site. Heme binding rigidifies this TIM-barrel and allosterically enhances catalysis. Our work demonstrates the capability of ancestral protein reconstructions to reveal valuable but unexpected biomolecular features when sampling distant sequence space. The potential of the ancestral glycosidase as a scaffold for custom catalysis and biosensor engineering is discussed.
Making many out of few: deep generative models for single-cell RNA-sequencing data
Authors: Treppner Martin , Salas-Bastos Adrián , Hess Moritz , Lenz Stefan , Vogel Tanja , Binder Harald
Published: May 2020

Deep generative models, such as variational autoencoders (VAEs) or deep Boltzmann machines (DBM), can generate an arbitrary number of synthetic observations after being trained on an initial set of samples. This has mainly been investigated for imaging data but could also be useful for single-cell transcriptomics (scRNA-seq). A small pilot study could be used for planning a full-scale study by investigating planned analysis strategies on synthetic data with different sample sizes. It is unclear whether synthetic observations generated based on a small scRNA-seq dataset reflect the properties relevant for subsequent data analysis steps.

We specifically investigated two deep generative modeling approaches, VAEs and DBMs. First, we considered single-cell variational inference (scVI) in two variants, generating samples from the posterior distribution, the standard approach, or the prior distribution. Second, we propose single-cell deep Boltzmann machines (scDBM). When considering the similarity of clustering results on synthetic data to ground-truth clustering, we find that thescVIposteriorvariant resulted in high variability, most likely due to amplifying artifacts of small data sets. All approaches showed mixed results for cell types with different abundance by overrepresenting highly abundant cell types and missing less abundant cell types. With increasing pilot dataset sizes, the proportions of the cells in each cluster became more similar to that of ground-truth data. We also showed that all approaches learn the univariate distribution of most genes, but problems occurred with bimodality. Overall, the results showed that generative deep learning approaches might be valuable for supporting the design of scRNA-seq experiments.
Optimizing high-yield production of SARS-CoV-2 soluble spike trimers for serology assays
Authors: Esposito Dominic , Mehalko Jennifer , Drew Matthew , Snead Kelly , Wall Vanessa , Taylor Troy , Frank Peter , Denson John-Paul , Hong Min , Gulten Gulcin , Sadtler Kaitlyn , Messing Simon , Gillette William
Published: May 2020

The SARS-CoV-2 spike trimer is the primary antigen for several serology assays critical to determining the extent of SARS-CoV-2 exposure in the population. Until stable cell lines are developed to increase the titer of this secreted protein in mammalian cell culture, the low yield of spike protein produced from transient transfection of HEK293 cells will be a limiting factor for these assays. To improve the yield of spike protein and support the high demand for antigens in serology assays, we investigated several recombinant protein expression variables by altering the incubation temperature, harvest time, chromatography strategy, and final protein manipulation. Through this investigation, we developed a simplified and robust purification strategy that consistently yields 5 mg of protein per liter of expression culture for two commonly used forms of the SARS-CoV-2 spike protein. We show that these proteins form well-behaved stable trimers and are consistently functional in serology assays across multiple protein production lots.

Highlights

Improved yields of SARS-CoV-2 spike protein through modification of expression and purification parameters

Yields of greater than 5 mg/l obtained for VRC spike under optimal conditions

Spike protein quality was validated by QC methods to ensure utility in serology assays
Age separation dramatically reduces COVID-19 mortality rate in a computational model of a large population
Authors: Mizrahi Liron , Stern Shani
Published: May 2020

COVID-19 pandemic has caused a global lock down in many countries throughout the world. Faced with a new reality, and until a vaccine or efficient treatment is found, humanity must figure out ways to keep economy going on one hand, yet keep the population safe on the other hand, especially those that are susceptible to this virus. Here we use a network simulation, with parameters that were drawn from what is known about the virus, to explore 5 different scenarios of partial lock down release. We find that separating age groups by reducing interactions between age groups, protects the general population and reduces mortality rates. Furthermore, addition of new connections within the same age group to compensate for the lost connections outside the age group, still has a strong beneficial influence and reduces the total death toll by 66%. While complete isolation from society may be the most protective scenario for the elderly population, it would have an emotional and possibly cognitive impact that might outweigh its benefit. We therefore propose creating age-related social recommendations or even restrictions, thereby allowing social connections but still strong protection for the older population.
Renal function is preserved following Tenofovir Disoproxil Fumarate (TDF) initiation among Rwandan’s living with HIV
Authors: Rwibasira Gallican N. , Kim Hae-Young , Twizere Christella , Hoover Donald R , Shi Qiuhu , Adedimeji Adebola , Ross Jonathan , Murenzi Gad , Sinayobye Jean d’Amour , Anastos Kathryn
Published: May 2020

Background

Tenofovir disoproxil fumarate (TDF) is the antiretroviral drug most commonly associated with renal dysfunction. However, few studies have examined this association in sub-Saharan Africa despite recent scale-up of antiretroviral therapy (ART) to all people living with HIV (Treat All) in this region. We assessed estimated glomerular filtration rate (eGFR) change among HIV infected Rwandan adults following first line TDF-based therapy initiation.

Methods

This prospective, observational study was conducted in 10 Rwandan health centers. Participants were ART-naive adults (≥18 years) living with HIV who initiated TDF-based ART from 1st July 2016 through 30th July 2018. The primary outcome was eGFR change from pre-(within 12 months) to post-TDF initiation (within 6 months).

Results

Of 476 patients with pre- and post-TDF eGFR measurements, 264 (55.5%) were women and mean age was 35.9 years (SD 9.6). Mean pre-TDF eGFR was 92.4 (SD 24.0) and mean post-TDF was 96.0 (SD 21.0) mL/min/1.73m2. Mean pre-to post-TDF change thus increased 3.60 (SD, 26.6) mL/min/1.73m2 (p=0.001).

Conclusion

We detected a statistically significant clinically small renal function improvement within 6 months following TDF initiation among 476 ART-naïve patients. This supports continued TDF use for first-line treatment.
How did governmental interventions affect the spread of COVID-19 in European countries?
Authors: Post R.A.J. , Regis M. , Zhan Z. , van den Heuvel E.R.
Published: May 2020

Background

To reduce transmission of Coronavirus Disease 2019, European governments have implemented successive measures to encourage social distancing. However, it remained unclear how effectively measures reduced the spread of the virus, due to data complications. We examined how the effective-contact rate (ECR) among European citizens evolved over the period with implemented measures using a new data-oriented approach that is based on an extended Susceptible-Exposed-Infectious-Removed (SEIR) model.

Methods

Using the available data on the confirmed numbers of infections and hospitalizations, we first estimated the daily number of infectious-, exposed- and susceptible individuals and subsequently estimated the ECR with an iterative Poisson regression model, disregarding information on governmental measures. We then studied change points in the daily ECRs to the moments of the governmental measures.

Findings

The change points in the daily ECRs were found to align with the implementation of governmental interventions. At the end of the considered time-window, we found similar ECRs for Italy (0·29), Spain (0·24), and Germany (0·27), while the ECR in the Netherlands (0·34), Belgium (0·35) and the UK (0·37) were somewhat higher. The highest ECR was found for Sweden (0·45).

Interpretation

There seemed to be an immediate effect of banning events and closing schools, typically among the first measures taken by the governments. The effect of additionally closing bars and restaurants seemed limited. For most countries a somewhat delayed effect of the full lockdown was observed, and the ECR after a full lockdown was not necessarily lower than an ECR after (only) a gathering ban.