bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication Safety and the Accidental Death of a 9-Month-Old
Authors: Davis Laura
Published: September 2020

Since the turn of the century, there has been a 225% increase in the number of deaths of children under 5 years old caused by opioid poisoning because of accidental ingestion. One measure aimed at reducing this trend, currently being considered by the U.S. Food and Drug Administration, is increasing the safety of opioid use by requiring unit-dose packaging. Another classic measure is educational efforts around medication safety and children. Although medication safety education lacks standardization, stepped-up educational efforts by the Centers for Disease Control and Prevention, Safe Kids Worldwide, and others in response to the increase in accidental opioid poisoning in children appear to be making an impact. After the start of these programs' efforts, emergency room visits for children for accidental medicine poisoning have declined by 32%.
Operation After Radiologic Embolization for Blunt Liver Trauma
Authors: John Rebecca L. , Kabeer Mustafa H. , Guner Yigit S. , Gibbs David L.
Published: September 2020

Motor vehicle accidents and other blunt high-impact traumas occur with relative frequency in children and adolescents, potentially causing severe injury or death (Martin et al., 2017). A common consequence of blunt trauma is laceration to the solid organs such as liver, kidneys, or spleen. These injuries are typically managed nonoperatively, occasionally utilizing interventional radiology (IR) embolization (Arbra et al., 2017). This case report discusses a child with Grade V+ liver laceration, who underwent IR embolization and ultimately required laparoscopic evacuation of abdominal hemorrhage with peritoneal drain placement. As a complication of IR embolization, the patient developed an occlusive thrombus in his right common femoral artery. A systematic review of nonoperative management in pediatric trauma by the American Pediatric Surgical Association concluded that there is no need to put patients through the risks of an IR embolization procedure if the patient remains stable (Gates et al., 2019). Although the guidelines are useful, clinical judgment remains the best determinant for invasive intervention. From a trauma nursing perspective, these cases require serial abdominal examinations combined with excellent communication between nurses and physicians to highlight changes in physical examination findings. In addition, research on IR procedures in the context of hepatic injury needs further study.
Leadership After a Crisis
Authors: Owen Regina D. , Schimmels JoEllen
Published: September 2020

Nursing leaders have voiced concern about the health and well-being of nurses and other healthcare providers during the recovery phase of disaster response after the coronavirus pandemic. There is much that can be learned from the experiences of our military colleagues. Behavioral health military nurses serving on readiness teams have educated leaders on how to apply psychological first aid (PFA) within their units during the recovery phase of disasters. This article will describe how nursing leaders can use PFA to enhance psychological support and resilience in their staff.
The Effect of Nurse Practice Environment on Retention and Quality of Care via Burnout, Work Characteristics, and Resilience
Authors: Gensimore Mandy M. , Maduro Ralitsa S. , Morgan Merri K. , McGee Genemarie W. , Zimbro Kathie S.
Published: September 2020

OBJECTIVE

The aim of this study was to explore the influence of nurse work characteristics, resiliency, and burnout on retention, and patient quality and safety.

BACKGROUND

With an ongoing nursing shortage, maintaining qualified nursing staff is critical. We explored the direct and indirect effects of practice environment, nurse work characteristics, and burnout on retention, and perceived quality and safety.

METHODS

Responses from 507 RNs were collected via an anonymous online survey. Theorized relationships were explored via path analysis and invariance testing.

RESULTS

Positive practice environment and favorable work characteristics lowered burnout and improved outcomes. The indirect effects of work characteristics and burnout were dependent upon individual level of resilience. Social capital minimized the effects of burnout for participants reporting below-average resilience.

CONCLUSIONS

Leader support was critical in shaping positive perception of the practice environment. A nurse leader's visibility and actions impact intent to stay. Results of this study may inform healthcare systems struggling to retain a robust, engaged nursing workforce.
Impact of Teamwork and Communication Training Interventions on Safety Culture and Patient Safety in Emergency Departments: A Systematic Review
Authors: Alsabri Mohamed , Boudi Zoubir , Lauque Dominique , Dias Roger Daglius , Whelan Julia S. , Östlundh Linda , Alinier Guillaume , Onyeji Churchill , Michel Philippe , Liu Shan W. , Jr Camargo Carlos A. , Lindner Tobias , Slagman Anna , Bates David W. , Tazarourte Karim , Singer Sara J. , Toussi Anita , Grossman Shamai , Bellou Abdelouahab
Published: September 2020

Objectives

This study aimed to narratively summarize the literature reporting on the effect of teamwork and communication training interventions on culture and patient safety in emergency department (ED) settings.

Methods

We searched PubMed, EMBASE, Psych Info CINAHL, Cochrane, Science Citation Inc, the Web of Science, and Educational Resources Information Centre for peer-reviewed journal articles published from January 1, 1988, to June 8, 2018, that assessed teamwork and communication interventions focusing on how they influence patient safety in the ED. One additional search update was performed in July 2019.

Results

Sixteen studies were included from 8700 screened publications. The studies’ design, interventions, and evaluation methods varied widely. The most impactful ED training interventions were End-of-Course Critique, Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS), and crisis resource management (CRM)–based training. Crisis resource management and TeamSTEPPS CRM-based training curriculum were used in most of the studies. Multiple tools, including the Kirkpatrick evaluation model, the Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture, the TeamSTEPPS Teamwork Attitudes Questionnaire, the Safety Attitudes Questionnaire, and the Communication and Teamwork Skills Assessment, were used to assess the impact of such interventions. Improvements in one of the domains of safety culture and related domains were found in all studies. Four empirical studies established improvements in patient health outcomes that occurred after simulation CRM training (Kirkpatrick 4), but there was no effect on mortality.

Conclusions

Overall, teamwork and communication training interventions improve the safety culture in ED settings and may positively affect patient outcome. The implementation of safety culture programs may be considered to reduce incidence of medical errors and adverse events.
Lise Meitner, β-decay and non-radiative electromagnetic transitions
Authors: Mahnke Heinz-Eberhard
Published: September 2020

The current activities in detecting neutrinos as carriers of information from far out in our Universe prompt us to look back on the research activities a century ago that led to the discovery of these weakly interacting particles. One of the leading researchers was Lise Meitner, who observed electrons with well-defined energy, besides the continuous energy spectrum emitted in β decay. These
electron lines
are well understood as radiationless nuclear transitions competing with γ-ray emission. It is proposed to name the electrons resulting out of this so-called
internal conversion
process after Lise Meitner and Charles D. Ellis. The equivalent process within the electronic (atomic) shell is the
Auger effect
, competing with X-ray emission. In this context, the radioactive decay of UX1 or
234
Th, well studied a century ago by Lise Meitner and Charles Ellis, is re-visited, and the mono-energetic electrons are ascribed entirely to the internal conversion process.
Pseudokineococcus galaxeicola sp. nov., isolated from mucus of a stony coral
Authors: Li Qiqi , Zheng Yicong , Guo Anjie , Chen Yu , Zhang Si , Li Jie
Published: September 2020

A Gram-stain-positive, aerobic, motile, coccus-shaped bacterium, designated strain SCSIO 13315T, was isolated from mucus of the coralGalaxeasp. collected from Luhuitou fringing reef (Sanya, Hainan, PR China). Analysis of the 16S rRNA gene sequence showed that strain SCSIO 13315Texhibits 95.5 % 16S rRNA gene sequence similarity toPseudokineococcus basanitobsidensSKC1-2T, 95.8 % toPseudokineococcus lusitanusT2A-S27Tand 96.4 % toPseudokineococcus marinusKST3-3T. Results of phylogenetic analysis suggested that strain SCSIO 13315Twas a member of the genusPseudokineococcus. The DNA G+C content of strain SCSIO 13315Twas 73.5 %. Chemotaxonomic assessment of strain SCSIO 13315Tshowed that the menaquinones were MK-8(H4) and MK-9(H2). The main cellular fatty acids were anteiso-C15 : 0, C16 : 0and summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c). The polar lipids present were diphosphatidylglycerol, phosphatidylglycerol, two unknown phospholipids, four unidentified aminolipids and one unidentified lipid. Based on the phylogenetic and phenotypic analysis, it was evident that strain SCSIO 13315Trepresents a novel species of the genusPseudokineococcus, for which the namePseudokineococcus galaxeicolasp. nov. is proposed. The type strain is SCSIO 13315T(=NBRC 109944T=DSM 27812T).
In severe COVID-19, SARS-CoV-2 induces a chronic, TGF-β-dominated adaptive immune response
Authors: Ferreira-Gomes Marta , Kruglov Andrey , Durek Pawel , Heinrich Frederik , Tizian Caroline , Anne Heinz Gitta , Pascual-Reguant Anna , Du Weijie , Mothes Ronja , Fan Chaofan , Frischbutter Stefan , Habenicht Katharina , Budzinski Lisa , Ninnemann Justus , Jani Peter K. , Guerra Gabriela , Lehmann Katrin , Matz Mareen , Ostendorf Lennard , Heiberger Lukas , Chang Hyun-Dong , Bauherr Sandy , Maurer Marcus , Schönrich Günther , Raftery Martin , Kallinich Tilmann , Alexander Mall Marcus , Angermair Stefan , Treskatsch Sascha , Dörner Thomas , Max Corman Victor , Diefenbach Andreas , Volk Hans-Dieter , Elezkurtaj Sefer , Winkler Thomas H. , Dong Jun , Erika Hauser Anja , Radbruch Helena , Witkowski Mario , Melchers Fritz , Radbruch Andreas , Mashreghi Mir-Farzin
Published: September 2020

Here we have analyzed the dynamics of the adaptive immune response triggered by SARS-CoV-2 in severely affected COVID-19 patients, as reflected by activated B cells egressing into the blood, at the single cell level. Early on, before seroconversion in response to SARS-CoV-2 spike protein, activated peripheral B cells displayed a type 1 interferon-induced gene expression signature. After seroconversion, activated B cells lost this signature, expressed IL-21- and TGF-β-induced gene expression signatures, and mostly IgG1 and IgA1. In the sustained immune reaction of the COVID-19 patients, until day 59, activated peripheral B cells shifted to expression of IgA2, reflecting instruction by TGF-β. Despite the continued generation of activated B cells, those cells were not found in the lungs of deceased COVID-19 patients, nor did the IgA2 bind to dominant antigens of SARS-CoV-2. In severe COVID-19, SARS-CoV-2 thus triggers a chronic immune reaction distracted from itself and instructed by TGF-β.
Association of Opioid Use Disorder With 2016 Presidential Voting Patterns: A Cross-Sectional Study in New York State at Census Tract Level
Authors: Xiang Anthony , Rashidian Sina , Hou Wei , Rosenthal Richard N , Abell-Hart Kayley , Zhao Xia , Wang Fusheng
Published: September 2020

Background

Opioid overdose related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP) and opioid use disorder (OUD).

Objective

We aimed to discover geospatial patterns in problematic opioid use and its correlations with demographic features related to despair and economic hardship, most notably the US presidential voting patterns in 2016 at census tract level in New York State.

Methods

This cross-sectional analysis used data from New York Statewide Planning and Research Cooperative System claims data and the presidential voting results of 2016 in New York State from the Harvard Election Data Archive. We included 63,958 patients who had at least one opioid use disorder (OUD) diagnosis between 2010 and 2016, and 36,004 patients with at least one opioid poisoning (OP) diagnosis between 2012 and 2016. A logistic regression model was used to determine the associations between patient level characteristics (sex, age group, race, and payment type) and OUD and OP patient rates at census tract level.

Results

Several areas shared similar patterns of OUD rates and Republican vote: census tracts in Western New York, Central New York, and Suffolk County. The Spearman rank correlation between OUD rates and the Republican vote was 0.38 (P < 0.0001). A multiple regression model of census tract level demographic and socioeconomic factors explains 29% of the variance in OUD rates, with disability and republican vote the biggest predictors.

Conclusions

At the census tract level, opioid use disorder rates were positively correlated with Republican support in the 2016 presidential election, disability, unemployment, and unmarried status. Socioeconomic and demographic features explain a large portion of the association between the Republican vote and opioid use disorder. Together, these findings underscore the importance of socioeconomic interventions in combatting the opioid epidemic.
Frequency and accuracy of proactive testing for COVID-19
Authors: Bergstrom Ted , Bergstrom Carl T. , Li Haoran
Published: September 2020

September 5, 2020

The SARS-CoV-2 coronavirus has proven difficult to control not only because of its high transmissibility, but because those who are infected readily spread the virus before symptoms appear, and because some infected individuals, though contagious, never exhibit symptoms. Proactive testing of asymptomatic individuals is therefore a powerful, and probably necessary, tool for preventing widespread infection in many settings. This paper explores the effectiveness of alternative testing regimes, in which the frequency, the accuracy, and the delay between testing and results determine the time path of infection. For a simple model of disease transmission, we present analytic formulas that determine the effect of testing on the expected number of days of during which an infectious individual is exposed to the population at large. This allows us to estimate the frequency of testing that would be required to prevent uncontrolled outbreaks, and to explore the trade-offs between frequency, accuracy, and delay in achieving this objective. We conclude by discussing applications to outbreak control on college and university campuses.

Competing Interest Statement

Ted Bergstrom and Haoran Li have no competing interests. Carl Bergstrom consults for Color Genomics on COVID testing schedules.
Supporting the resilience and retention of frontline care workers in care homes for older people: A scoping review and thematic synthesis
Authors: Johnston Lucy , Malcolm Cari , Rambabu Lekaashree , Hockley Jo , Shenkin Susan D
Published: September 2020

The COVID-19 pandemic has reinforced the need to ensure that strategic and operational approaches to retain high quality, resilient frontline care home workers, who are not registered nurses, are informed by context specific, high quality evidence. We therefore conducted this scoping review to address the question: What is the current evidence for best practice to support the resilience and retention of frontline care workers in care homes for older people?

MEDLINE, PubMed, PsycINFO, Embase, MedRxiv, CINAHL, ASSIA, Social Science Premium were searched for literature published between 2010 and 2020. The search strategy employed combinations of search terms to target frontline care workers in care homes for older people and the key concepts relevant to resilience and retention were applied and adapted for each database.

Thirty studies were included. Evidence for best practice in supporting the resilience and retention specifically of frontline care workers in care homes is extremely limited, of variable quality and lacks generalisability. At present, it is dominated by cross-sectional studies mostly from out with the UK. The small number of intervention studies are inconclusive.

The review found that multiple factors are suggested as being associated with best practice in supporting resilience and retention, but few have been tested robustly. The thematic synthesis of these identified the analytical themes of – Culture of Care; Content of Work; Connectedness with Colleagues; Characteristics and Competencies of Care Home Leaders and Caring during a Crisis.

The evidence base must move from its current state of implicitness. Only then can it inform intervention development, implementation strategies and meaningful indicators of success. High quality, adequately powered, co-designed intervention studies, that address the fundamentally human and interpersonal nature of the resilience and retention of frontline care workers in care homes are required.
Relationships of total COVID-19 cases and deaths with ten demographic, economic and social indicators
Authors: Valev Dimitar
Published: September 2020

We have used data for 45 countries with a population of over 30 millions in which 85.8% of the world’s population lives. The statistical relationships of total COVID-19 Cases and Deaths per million populations in these countries with 10 demographic, economic and social indicators (indices) were studied. These indicators are Life Expectancy, Median Age, Growth Rate, Population Density, GDP PPP per capita, Human Development Index (HDI), Gini index of income equality, Intelligence Quotient (IQ), Corruption Perceptions Index (CPI) and Democracy Index. Statistically significant relationships were found with all indicators excluding Gini index and Population Density. We have found that the closest is the relationship of Deaths per million population and total Cases per million population with correlation coefficient R = 0.926. Therefore, it is clear statistically that the more are Cases per million in a country the more are Deaths per million. This confirms the correctness of the timely and effective introduction of the necessary pandemic restrictions in the countries.

It is interesting that the close correlations were found of Cases and Deaths per 1 million with a purely economic index like GDP PPP per capita, where R = 0.687 and R = 0.660, respectively. Even more close correlations were found of Cases and Deaths per 1 million with a composite index HDI, where the correlation coefficients reach 0.724 and 0.680, respectively. This paradoxical results show that the richest and well-being countries are most seriously affected by the COVID-19 pandemic. The most probable reason for this is the large percentage of aging population, comorbidity of population with severe chronic diseases and obesity in countries with high GDP and HDI. No less important reason appears the delayed and/or insufficiently effective pandemic restrictions in these countries, which have underestimated the danger of a pandemic in early stage.

Other indicators (excluding Gini index and Population Density) also show statistically significant correlations with Cases and Deaths per 1 million with correlation coefficients from 0.432 to 0.634. The countries that deviates the most from the regression lines were shown. Surprisingly, there was no statistically significant correlation between Cases and Deaths with Population Density. The statistical significance of the found correlations determined using Student’s t-test was p < 0.0001. The countries that deviate the most from both sides of the regression line were shown. It has been shown that the correlations of COVID-19 cases and Deaths with the studied indicators decrease with time.
Discrimination of melanoma cell lines with Fourier Transform Infrared (FTIR) spectroscopy
Authors: Shakya Bijay Ratna , Teppo Hanna-Riikka , Rieppo Lassi
Published: September 2020

Among skin cancers, melanoma is the lethal form and the leading cause of death in humans. Melanoma begins in melanocytes and is curable at early stages. Thus, early detection and evaluation of its metastatic potential are crucial for effective clinical intervention. Fourier transform infrared (FTIR) spectroscopy has gained considerable attention due to its versatility in detecting biochemical and biological features present in the samples. Changes in these features are used to differentiate between samples at different stages of the disease. Previously, FTIR spectroscopy has been mostly used to distinguish between healthy and diseased conditions. With this study, we aim to discriminate between different melanoma cell lines based on their FTIR spectra. Formalin-fixed paraffin embedded samples from three melanoma cell lines (IPC-298, SK-MEL-30 and COLO-800) were used. Statistically significant differences were observed in the prominent spectral bands of three cell lines along with shifts in peak positions. A partial least square discriminant analysis (PLS-DA) model built for the classification of three cell lines showed an overall accuracy of 92.6% with a sensitivity of 85%, 95.75%, 96.54%, and specificity of 97.80%, 92.14%, 98.64% for the differentiation of IPC-298, SK-MEL-30, and COLO-800, respectively. The results suggest that FTIR spectroscopy can differentiate between different melanoma cell lines and thus potentially characterize the metastatic potential of melanoma.

Sources of Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Characterization of ethylene-inducible pedicel-fruit abscission zone formation in non-climacteric sweet cherry (Prunus aviumL.)
Authors: Hewitt Seanna , Kilian Benjamin , Koepke Tyson , Abarca Jonathan , Whiting Matthew , Dhingra Amit
Published: September 2020

Harvesting of sweet cherry (Prunus aviumL.) fruit is a labor-intensive process. Mechanical harvesting of sweet cherry fruit is feasible; however, it is dependent on the formation of an abscission zone at the fruit-pedicel junction. The natural propensity for pedicel-fruit abscission zone (PFAZ) formation varies by cultivar, and the general molecular basis for PFAZ formation is not well characterized. In this study, ethylene-inducible change in pedicel fruit retention force (PFRF) was recorded in a developmental time course with a concomitant analysis of the PFAZ transcriptome from three sweet cherry cultivars. In ‘Skeena’, mean PFRF for both control and treatment fruit dropped below the 0.40kg-force (3.92N) threshold for mechanical harvesting and indicating the formation of a discrete PFAZ. In ‘Bing’, mean PFRF for both control and treatment groups decreased over time. However, a mean PFRF conducive to mechanical harvesting was achieved only in the ethylene-treated fruit. While in ‘Chelan’ the mean PFRF of the control and treatment groups did not meet the threshold required for efficient mechanical harvesting. Transcriptome analysis of the PFAZ followed by the functional annotation, differential expression analysis, and gene ontology (GO) enrichment analyses of the data facilitated the identification of phytohormone-responsive and abscission-related transcripts as well as processes that exhibited differential expression and enrichment in a cultivar-dependent manner over the developmental time-course. Additionally, read alignment-based variant calling revealed several short variants in differentially expressed genes, associated with enriched gene ontologies and associated metabolic processes, lending potential insight into the genetic basis for different abscission responses between the cultivars. These results provide genetic targets for induction or inhibition of PFAZ formation, depending on the desire to harvest the fruit with or without the stem attached. Understanding the genetic mechanisms underlying the development of the PFAZ will inform future cultivar development while laying a foundation for mechanized sweet cherry harvest.
Superspreaders and High Variance Infectious Diseases
Authors: Oz Yaron , Rubinstein Ittai , Safra Muli
Published: September 2020

(Dated: September 6, 2020)

A well-known characteristic of pandemics such as COVID-19 is the high level of transmission heterogeneity in the infection spread: not all infected individuals spread the disease at the same rate and some individuals (superspreaders) are responsible for most of the infections. To quantify this phenomenon requires the analysis of the effect of the variance and higher moments of the infection distribution. Working in the framework of stochastic branching processes, we derive an approximate analytical formula for the probability of an outbreak in the high variance regime of the infection distribution, verify it numerically and analyze its regime of validity in various examples. We show that it is possible for an outbreak not to occur in the high variance regime even when the basic reproduction number R0 is larger than one and discuss the implications of our results for COVID-19 and other pandemics.

PACS numbers: 87.10.+e
Covid-19 vs BCG Universal Immunization: Statistical Significance at Six Months of Exposure
Authors: Dolgikh Serge
Published: September 2020

With a time-adjusted dataset of Covid-19 statistical data by reporting jurisdiction at the time point of six months after the local epidemics landfall we perform a statistical analysis of the significance of the correlation hypothesis between universal BCG immunization and milder Covid-19 scenarios proposed in the earlier studies. With the data accumulated to date the statistical significance of the BCG immunization correlation hypothesis is evaluated both qualitatively and quantitatively with the conclusion that it has achieved a significant level of confidence. The conclusions of this research can be used in public policy as well as the rationale to investigate the nature and working of a potential broad immunity mechanism associated with an early-age BCG exposure.
Stretch Regulates Alveologenesis and Homeostasis Via Mesenchymal Gαq/11-Mediated TGFβ2 Activation
Authors: Goodwin Amanda T , John Alison E , Joseph Chitra , Habgood Anthony , Tatler Amanda L , Susztak Katalin , Palmer Matthew , Offermanns Stefan , Henderson Neil C , Jenkins R Gisli
Published: September 2020

Alveolar development and repair require tight spatiotemporal regulation of numerous signalling pathways that are influenced by chemical and mechanical stimuli. Mesenchymal cells play key roles in numerous developmental processes. Transforming growth factor-β (TGFβ) is essential for alveologenesis and lung repair, and the G protein α subunits Gαq and Gα11 (Gαq/11) transmit mechanical and chemical signals to activate TGFβ in epithelial cells. To understand the role of mesenchymal Gαq/11 in lung development, we generated constitutive (Pdgfrb-Cre+/−;Gnaqfl/fl;Gna11−/−) and inducible (Pdgfrb-Cre/ERT2+/−;Gnaqfl/fl;Gna11−/−) mesenchymal Gαq/11 deleted mice. Mice with constitutive Gαq/11 gene deletion exhibited abnormal alveolar development, with suppressed myofibroblast differentiation, altered mesenchymal cell synthetic function, and reduced lung TGFβ2 deposition, as well as kidney abnormalities. Tamoxifen-induced mesenchymal Gαq/11 gene deletion in adult mice resulted in emphysema associated with reduced TGFβ2 and elastin deposition. Cyclical mechanical stretch-induced TGFβ activation required Gαq/11 signalling and serine protease activity, but was independent of integrins, suggesting an isoform-specific role for TGFβ2. These data highlight a previously undescribed mechanism of cyclical stretch-induced Gαq/11-dependent TGFβ2 signalling in mesenchymal cells, which is imperative for normal alveologenesis and maintenance of lung homeostasis.

Summary statement

Mesenchymal cell Gαq/11 signalling regulates myofibroblast function and stretch-mediated TGFβ2 signalling, which are important for alveologenesis and organ homeostasis. These mechanisms are relevant to both developmental and adult lung disease.
Emergence of behavior in a self-organized living matter network
Authors: Fleig Philipp , Kramar Mirna , Wilczek Michael , Alim Karen
Published: September 2020

What is the origin of behavior? Although typically associated with a nervous system, simple life forms also show complex behavior – thus serving as a model to study how behaviors emerge. Among them, the slime moldPhysarum polycephalum, growing as a single giant cell, is renowned for its sophisticated behavior. Here, we show how locomotion and morphological adaptation behavior emerge from self-organized patterns of rhythmic contractions of the actomyosin lining of the tubes making up the network-shaped organism. We quantify the spatio-temporal contraction dynamics by decomposing experimentally recorded contraction patterns into spatial contraction modes. Surprisingly, we find a continuous spectrum of modes, as opposed to few dominant modes. Over time, activation of modes along this continuous spectrum is highly dynamic, resulting in contraction patterns of varying regularity. We show that regular patterns are associated with stereotyped behavior by triggering a behavioral response with a food stimulus. Furthermore, we demonstrate that the continuous spectrum of modes and the existence of irregular contraction patterns persist in specimens with a morphology as simple as a single tube. Our data suggests that the continuous spectrum of modes allows for dynamic transitions between a plethora of specific behaviors with transitions marked by highly irregular contraction states. By mapping specific behaviors to states of active contractions, we provide the basis to understand behavior’s complexity as a function of biomechanical dynamics. This perspective will likely stimulate bio-inspired design of soft robots with a similarly rich behavioral repertoire asP. polycephalum.
Balrog: A universal protein model for prokaryotic gene prediction
Authors: Sommer Markus J. , Salzberg Steven L.
Published: September 2020

Low-cost, high-throughput sequencing has led to an enormous increase in the number of sequenced microbial genomes, with well over 100,000 genomes in public archives today. Automatic genome annotation tools are integral to understanding these organisms, yet older gene finding methods must be retrained on each new genome. We have developed a universal model of prokaryotic genes by fitting a temporal convolutional network to amino-acid sequences from a large, diverse set of microbial genomes. We incorporated the new model into a gene finding system, Balrog (Bacterial Annotation by Learned Representation Of Genes), which does not require genome-specific training and which matches or outperforms other state-of-the-art gene finding tools. Balrog is freely available under the MIT license athttps://github.com/salzberg-lab/Balrog.

Author summary

Annotating the protein-coding genes in a newly sequenced prokaryotic genome is a critical part of describing their biological function. Relative to eukaryotic genomes, prokaryotic genomes are small and structurally simple, with 90% of their DNA typically devoted to protein-coding genes. Current computational gene finding tools are therefore able to achieve close to 99% sensitivity to known genes using species-specific gene models.

Though highly sensitive at finding known genes, all current prokaryotic gene finders also predict large numbers of additional genes, which are labelled as “hypothetical protein” in GenBank and other annotation databases. Many hypothetical gene predictions likely represent true protein-coding sequence, but it is not known how many of them represent false positives. Additionally, all current gene finding tools must be trained specifically for each genome as a preliminary step in order to achieve high sensitivity. This requirement limits their ability to detect genes in fragmented sequences commonly seen in metagenomic samples.

We took a data-driven approach to prokaryotic gene finding, relying on the large and diverse collection of already-sequenced genomes. By training a single, universal model of bacterial genes on protein sequences from many different species, we were able to match the sensitivity of current gene finders while reducing the overall number of gene predictions. Our model does not need to be refit on any new genome. Balrog (Bacterial Annotation by Learned Representation of Genes) represents a fundamentally different yet effective method for prokaryotic gene finding.
Lamin A/C functions independently from mechanical signaling during adipogenesis
Authors: Goelzer Matthew , Dudakovic Amel , Olcum Melis , Sen Buer , Ozcivici Engin , Rubin Janet , van Wijnen Andre J , Uzer Gunes
Published: September 2020

Mesenchymal stem cells (MSC) maintain the musculoskeletal system by differentiating into multiple cell types including osteocytes and adipocytes. Mechanical signals, including strain and low intensity vibration (LIV), are important regulators of MSC differentiation. Lamin A/C is a vital protein for nuclear architecture that supports chromatin organization, as well as mechanical integrity and mechano-sensitivity of the nucleus in MSCs. Here, we investigated whether Lamin A/C and mechano-responsiveness are functionally coupled during adipogenesis. Lamin depletion in MSCs using siRNA increased nuclear area, height and volume and decreased circularity and stiffness, while phosphorylation of focal adhesions and dynamic substrate strain in response to LIV remained intact. Lamin A/C depletion decelerates adipogenesis as reflected by delayed appearance of key biomarkers (e.g., adiponectin/ADIPOQ). Based on RNA-seq data, reduced Lamin A/C levels decrease the activation of the adipocyte transcriptome that is normally observed in response to adipogenic cues mediating differentiation of MSCs. Mechanical stimulation via daily LIV application reduced the expression levels of ADIPOQ in both control and Lamin A/C depleted cells. Yet, treatment with LIV did not induce major transcriptome changes in either control or Lamin A/C depleted MSCs, suggesting that the biological effects of LIV on adipogenesis may not occur at the transcriptional level. We conclude that while Lamin A/C activation is essential for normal adipogenesis, it is dispensible for activation of focal adhesions by dynamic vibration induced mechanical signals.
The ontogeny of multisensory peripersonal space in human infancy: From visual-tactile links to conscious expectations
Authors: Orioli Giulia , Parisi Irene , van Velzen José L. , Bremner Andrew J.
Published: September 2020

The influence of visual object motion on the processing of bodily events offers a marker for the development of human infants’ perception of themselves in peripersonal space. We presented 4- (n = 20) and 8-month-old (n = 20) infants with an unattended visual object moving towards or away from their body followed by a vibrotactile stimulus on their hands. The 4-month-olds’ somatosensory evoked potentials (SEPs) were modulated by approaching visual motion, demonstrating the early ontogeny of the cortical multisensory foundations of peripersonal space representations. We also observed rapid changes in these markers within the 8-month-old age group: as infants approach 9 months, salient SEP components were increasingly enhanced by (unexpected) tactile stimuli following receding visual motion. These findings provide important clues to the ontogeny of human self-awareness in the first year of life, and suggest important postnatal developments in infants’ expectations about interactions between the body and the external world.
Generating single-sex litters: development of CRISPR-Cas9 genetic tools to produce all-male offspring
Authors: Douglas Charlotte , Maciulyte Valdone , Zohren Jasmin , Snell Daniel M. , Ojarikre Obah A. , Ellis Peter J.I. , Turner James M.A.
Published: September 2020

Animals are extremely useful genetic tools in science and global resources in agriculture. However, a single sex is often required in surplus, and current genetic methods for producing all-female or all-male litters are inefficient. Using the mouse as a model, we developed a synthetic, two-part bicomponent strategy for generating all-male litters. We achieved this using CRISPR-Cas9 genome editing technology to generate large stable knock-ins on the autosomes and X chromosome. The bicomponent system functions via the sex-specific co-inheritance of a Cas9 transgene and an sgRNA transgene targeting the essentialTopoisomerase 1gene. This technology proved to be highly efficient in generating on-target mutations, resulting in embryonic lethality of the target sex. Our study is the first to successfully generate all-male mammalian litters using a CRISPR-Cas9 bicomponent system and provides great strides towards generating single-sex litters for laboratory or agricultural research.
The role of Anti-Mullerian hormone in predicting fertilization and pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI) cycles at a public fertility centre in Nigeria
Authors: Usman Safiyya Faruk , Ladipo Olubunmi Peter , Momoh J.A.F , Agboghoroma Chris Ovoroyeguono , Abubakar Nabila Datti
Published: September 2020

Objective

To determine the role of Anti-Mullerian Hormone (AMH) in predicting fertilization and pregnancy rates following in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI) treatment cycles.

Methods

This was a prospective cohort study of one hundred and fifty consecutive women undergoing IVF-ET/ICSI that were recruited from February 1, 2017 to October 31, 2018 at the Fertility centre of the National Hospital, Abuja, Nigeria. Participants’ plasma AMH were assayed and were followed up till achieving fertilization and pregnancy. Association between AMH levels, fertilization and pregnancy rates was assessed using univariable and multivariable logistic regression modelling to adjust for confounding variables.

Results

The mean age and mean AMH level of the participants were 36 ± 4.2 years and 1.74 ± 2.35ng/ml respectively. There was a statistically significant association between AMH level and age (P <0.001), duration of infertility (P =0.026), cause of infertility (P =0.035), number of oocytes retrieved (P =<0.001), number of embryos generated (P =<0.001) and type of treatment (P =<0.001). However, there was no significant difference in the fertilization rates (adjusted odds ratio [AdjOR] 0.36, 95% confidence interval [CI] 0.23–4.30; P =0.533) and pregnancy rates (AdjOR 0.26, 95% CI 0.04–2.00; P =0.210) at different plasma levels of AMH.

Conclusion

Plasma AMH level was not a predictor of fertilization and pregnancy rates among our cohort of patients who had IVF/ICSI treatment cycles.
Plasmodium falciparumguanylyl cyclase-alpha and the activity of its appended P4-ATPase domain are essential for cGMP synthesis and blood stage egress
Authors: Nofal Stephanie D. , Patel Avnish , Blackman Michael J. , Flueck Christian , Baker David A.
Published: September 2020

In malaria parasites, guanylyl cyclases (GCs), which synthesise cyclic GMP (cGMP), are associated with a P4-ATPase-like domain in a unique bifunctional configuration. P4-ATPases generate membrane bilayer lipid asymmetry by translocating phospholipids from the outer to the inner leaflet. Here we investigate the role ofPlasmodium falciparumguanylyl cyclase alpha (GCα) and its associated P4-ATPase module, showing that asexual blood stage parasites lacking both the cyclase and P4-ATPase domains are unable to egress from host erythrocytes. GCα-null parasites cannot synthesise cGMP, or mobilise calcium, a cGMP-dependent protein kinase (PKG)-driven requirement for egress. Using chemical complementation with a cGMP analogue and point mutagenesis of a crucial conserved residue within the P4-ATPase domain, we show that ATPase activity is up stream of and linked to cGMP synthesis. Collectively, our results demonstrate that GCα is a critical regulator of PKG and that its associated P4-ATPase domain plays a primary role in generating cGMP for merozoite egress.
The structural basis of the oncogenic mutant K-Ras4B homodimers
Authors: Kosoglu Kayra , Omur Meltem Eda , Jang Hyunbum , Nussinov Ruth , Keskin Ozlem , Gursoy Attila
Published: September 2020

Ras proteins activate their effectors through physical interactions in response to the various extracellular stimuli at the plasma membrane. Oncogenic Ras forms dimer and nanoclusters at the plasma membrane, boosting the downstream MAPK signal. It was reported that K-Ras4B can dimerize through two major interfaces: (i) the effector lobe interface, mapped to Switch I and effector binding regions; (ii) the allosteric lobe interface involving α3 and α4 helices. Recent experiments showed that constitutively active, oncogenic mutant K-Ras4BG12Ddimers are enriched in the plasma membrane. Here, we perform molecular dynamics simulations of K-Ras4BG12Dhomodimers aiming to quantify the two major interfaces in atomic level. To examine the effect of mutations on dimerization, two double mutations, K101D/R102E on the allosteric lobe and R41E/K42D on the effector lobe interfaces were added to the K-Ras4BG12Ddimer simulations. We observed that the effector lobe K-Ras4BG12Ddimer is stable, while the allosteric lobe dimer alters its helical interface during the simulations, presenting multiple conformations. The K101D/R102E mutations slightly weakens the allosteric lobe interface. However, the R41E/K42D mutations disrupt the effector lobe interface. Using the homo-oligomers prediction server, we obtained trimeric, tetrameric, and pentameric complexes with the allosteric lobe K-Ras4BG12Ddimers. However, the allosteric lobe dimer with the K101D/R102E mutations is not capable of generating multiple higher order structures. Our detailed interface analysis may help to develop inhibitor design targeting functional Ras dimerization and high order oligomerization at the membrane signaling platform.
Exploratory polarization facilitates mating partner selection inSaccharomyces cerevisiae
Authors: Clark-Cotton Manuella R. , Henderson Nicholas T. , Pablo Michael , Ghose Debraj , Elston Timothy C. , Lew Daniel J.
Published: September 2020

Yeast decode pheromone gradients to locate mating partners, providing a model for chemotropism. How yeast polarize toward a single partner in crowded environments is unclear. Initially, cells often polarize in unproductive directions, but then they relocate the polarity site until two partners’ polarity sites align, whereupon the cells “commit” to each other by stabilizing polarity to promote fusion. Here we address the role of the early mobile polarity sites. We found that commitment by either partner failed if just one partner was defective in generating, orienting, or stabilizing its mobile polarity sites. Mobile polarity sites were enriched for pheromone receptors and G proteins, and we suggest that such sites engage in an exploratory search of the local pheromone landscape, stabilizing only when they detect elevated pheromone levels. Mobile polarity sites were also enriched for pheromone secretion factors, and simulations suggest that only focal secretion at polarity sites would produce high pheromone concentrations at the partner’s polarity site, triggering commitment.
The SARS-CoV-2 multibasic cleavage site facilitates early serine protease-mediated entry into organoid-derived human airway cells
Authors: Mykytyn Anna Z. , Breugem Tim I. , Riesebosch Samra , Schipper Debby , van den Doel Petra B. , Rottier Robbert J. , Lamers Mart M. , Haagmans Bart L.
Published: September 2020

After the SARS-CoV outbreak in 2003, a second zoonotic coronavirus named SARS-CoV-2, emerged late 2019 in China and rapidly caused the COVID-19 pandemic leading to a public health crisis of an unprecedented scale. Despite the fact that SARS-CoV-2 uses the same receptor as SARS-CoV, transmission and pathogenesis of both viruses seem to be quite distinct. A remarkable feature of the SARS-CoV-2 spike is the presence of a multibasic cleavage site, which is absent in the SARS-CoV spike. The viral spike protein not only attaches to the entry receptor, but also mediates fusion after cleavage by host proteases. Here, we report that the SARS-CoV-2 spike multibasic cleavage site increases infectivity on differentiated organoid-derived human airway cells. Compared with SARS-CoV, SARS-CoV-2 entered faster into the lung cell line Calu-3, and more frequently formed syncytial cells in differentiated organoid-derived human airway cells. Moreover, the multibasic cleavage site increased entry speed and plasma membrane serine protease usage relative to endosomal entry using cathepsins. Blocking serine protease activity using the clinically approved drug camostat mesylate effectively inhibited SARS-CoV-2 entry and replication in differentiated organoid-derived human airway cells. Our findings provide novel information on how SARS-CoV-2 enters relevant airway cells and highlight serine proteases as an attractive antiviral target.

Significance Statement

Highly pathogenic coronaviruses have spilled from animals to humans three times in the past two decades. Late 2019, SARS-CoV-2 emerged in China and was declared a pandemic by March 2020. The other two highly pathogenic coronaviruses, SARS-CoV and MERS-CoV, emerged in 2002 and 2012, respectively, but did not attain sustained human-to-human transmission. Given the high diversity of coronaviruses in animals, urbanization and increased air travel, future coronavirus pandemics are likely to occur intermittently. Identifying which factors determine pandemic potential and pathogenicity are therefore of key importance to global health. Additionally, there is an urgent need to rapidly translate fundamental knowledge to the clinic, a process that is expedited through the use of relevant cell culture systems.
Vimentin intermediate filaments mediate cell shape on visco-elastic substrates
Authors: Swoger Maxx , Gupta Sarthak , Charrier Elisabeth E. , Bates Michael , Hehnly Heidi , Patteson Alison E.
Published: September 2020

The ability of cells to take and change shape is a fundamental feature underlying development, wound repair, and tissue maintenance. Central to this process is physical and signaling interactions between the three cytoskeletal polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). Vimentin is an IF protein that is essential to the mechanical resilience of cells and regulates cross-talk amongst the cytoskeleton, but its role in how cells sense and respond to the surrounding extracellular matrix is largely unclear. To investigate vimentin’s role in substrate sensing, we designed polyacrylamide hydrogels that mimic the elastic and viscoelastic nature of in vivo tissues. Using wild-type and vimentin-null mouse embryonic fibroblasts, we show that vimentin enhances cell spreading on viscoelastic substrates, even though it has little effect in the limit of purely elastic substrates. Our results provide compelling evidence that the vimentin cytoskeletal network is a physical modulator of how cells sense and respond to mechanical properties of their extracellular environment.