bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Tranexamic Acid in Reducing Blood Loss in Patients Undergoing Coronary Artery Bypass Surgery: A Systematic Review
Authors: Chitneni Ahish , Dalal Suhani
Published: July 2020

Tranexamic acid is a medication typically used to prevent excessive blood loss in the setting of trauma, surgery, and menstrual cycles. Administration of tranexamic acid within the first three hours of trauma has been shown to reduce blood loss and mortality in patients. [1] Tranexamic acid is also commonly used during heavy menstrual bleeding or postpartum hemorrhage cases in which administration has been shown to reduce bleeding in patients. [2] Although there have been studies conducted on the effects of tranexamic acid on blood loss during various surgeries, this systematic review aims to understand the effects specifically on patients undergoing coronary artery bypass grafting (CABG), a common procedure known to have significant blood loss. A systematic review using the PubMed database on the use of tranexamic acid in blood loss for patients undergoing CABG was conducted with the hypothesis that tranexamic acid administration reduces perioperative and postoperative blood loss. This systematic review includes 8 papers from the years 1997-2018 which report on a total of 712 patients. Although significant large, randomized, control studies on the topic are still pending, this systematic review of studies conducted thus far can conclude that tranexamic acid has a positive effect on reducing blood loss in patients undergoing CABG.
Impact of SARS-CoV-2 pandemic among health care workers in a secondary teaching hospital in Spain
Authors: Fernandez Javier Garralda , Vilches Ignacio Molero , Rodríguez Alfredo Bermejo , Torres Isabel Cano , Colino Romay Elda I. , García Arata Isabel , Aroca Jerónimo Jaqueti , Lillo Rosa , Lacomba Daniel Lopez , Mazón Luis , Esteban Laura Molina , Morales García Luis J , Monzo Laura Moratilla , Nieto-Borrajo Elva , Delgado Maria Pacheco , Menchero Santiago Prieto , Hernández Cristina Sánchez , Testillano Eva Sánchez , García-Martínez Jesús
Published: July 2020

Background

The COVID-19 pandemic has posed a huge challenge to healthcare systems and their personnel worldwide. The study of the impact of SARS-CoV-2 infection among healthcare workers, through prevalence studies, will let us know viral expansion, individuals at most risk and the most exposed areas. The aim of this study is to gauge the impact of SARS-CoV-2 pandemic in our hospital workforce and identify groups and areas at increased risk.

Methods and Findings

This is a cross-sectional and longitudinal study carried out on healthcare workers based on molecular and serological diagnosis of SARS-CoV-2 infection. Of the 3013 HCW invited to participate, finally 2439 (80.9%) were recruited, including 674 (22.4%) who had previously consulted at the OHS for confirmed exposure and/or presenting symptoms suggestive of COVID-19. A total of 411 (16.9%) and 264 (10.8%) healthcare workers were SARS-CoV-2 IgG and rRT-PCR positive, respectively. The cumulative prevalence considering all studies (IgG positive HCW and/or rRT-PCR positive detection) has been 485 (19.9%). SARS-CoV-2 IgG-positive patients in whom the virus was not detected were 221 (9.1%); up to 151 of them (68.3%) did not report any compatible symptoms nor consult at the OHS for this reason. Men became more infected than women (25% vs 18.5%, p=0.0009), including when data were also classified by age. COVID-19 cumulative prevalence among the HCW assigned to medical departments was higher (25.2%) than others, as well as among medical staff (25.4%) compared with other professional categories (p<0.01).

Conclusions

Global impact of the COVID-19 pandemic on HCW of our centre has been 19.9%. Doctors and medical services personnel have had the highest prevalence of SARS-CoV-2 infection, but many of them have not presented compatible symptoms. This emphasizes the performance of continuous surveillance methods of the most exposed health personnel and not only based on the appearance of symptoms.
Predicting PPE use, post-traumatic stress, and physical symptoms during the early weeks of COVID-19 lockdowns in the USA
Authors: O’Brien William H. , Wang Shan , Varga Aniko Viktoria , Xu Huanzhen , Sims Tracy E. , Horan Kristin A. , Lim Chung Xiann
Published: July 2020

The COVID-19 pandemic combined with inconsistent governmental and public health recommendations, media communications emphasizing threat, and widespread lockdowns created a complex psychological environment for Americans. In this study, 450 MTurk workers completed measures of (a) risk for COVID-19, (b) perceived vulnerability to disease, (c) intolerance of uncertainty, (d) mindfulness, (e) COVID-19 preventive health behaviors, (f) post-Trauma symptoms, and (g) stress related physical symptoms. The surveys were completed between April 9, 2020 and April 18, 2020 which is a period that corresponded to the first 2-3 weeks of lockdown for most participants.

A substantial number of participants reported a reduction employment status and 69% were in self-isolation. The participants reported a high degree of perceived vulnerability with 68% indicating they felt there was a 50/50 chance or greater they would contract COVID-19. Mask wearing was variable: 16% “not at all,” 20% “some of the time,” 42% “a good part of the time,” and 26% “most of the time.” Using clinical cutoff on the post-trauma scale, 70% of the sample would be considered to have symptoms consistent with PTSD. The mean level of physical symptoms was significantly (p < .001) and substantially higher (d = 1.46) than norms.

PPE use was positively associated with level of education and mindfulness nonreactivity and negatively associated with age, having a current medical condition, and mindfulness nonjudgment. Post trauma and physical health symptoms were strongly predicted by susceptibility variables and intolerance of uncertainty.

Highlights

COVID-19 created a complex psychological environment for Americans due to threat exposure combined with contradictory communications from government and media.

In a survey of 450 Americans, 68% reported that there was a 50/50 chance of greater they would contract COVID-19 and 70% of participants reported symptoms that met criteria for PTSD.

Mask wearing was variable with only 26% reporting use “most of the time.”

Participants who reported: older age, having one or mode medical conditions, less educational attainment, and less judgmental attitudes about their own thinking reported lower PPE use.

Intolerance of uncertainty and perceived susceptibility were associated with higher PTSD symptoms.

Mindfulness awareness and being judgmental attitudes about thinking were associated with lower PTSD symptoms.
Computer-aided medical microbiology monitoring tool: a strategy to adapt to the SARS-CoV-2 epidemic and that highlights RT-PCR consistency
Authors: Mueller Linda , Scherz Valentin , Greub Gilbert , Jaton Katia , Opota Onya
Published: July 2020

Since the beginning of the COVID-19 pandemic, important health and regulatory decisions relied on SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) results. Our diagnostic laboratory faced a rapid increase in the number of SARS-CoV-2 RT-PCR, with up to 1,007 tests per day. To maintain a rapid turnaround time to support patient management and public health authorities’ decisions, we moved from a case-by-case validation of RT-PCR to an automated validation and immediate transmission of the results to clinicians. To maintain high quality and to track possible aberrant results, we developed a quality-monitoring tool based on a homemade algorithm coded in R.

We present the results of this quality-monitoring tool applied to 35,137 RT-PCR results corresponding to 30,198 patients. Patients tested several times led to 4,939 pairwise comparisons; 88% concordant and 12% discrepant. Among the 573 discrepancies, 428 were automatically solved by the algorithm. The most likely explanation for these 573 discrepancies was related for 44.9% of the situations to “Clinical evolution”, 27.9% to “Preanalytical” problems, and 25.3% to “Stochastic”. Finally, 11 discrepant results could not be explained, including 8 received from external partners for which clinical data were not available.

The implemented quality-monitoring strategy allowed to: i) assist the investigation of discrepant results ii) focus the attention of medical microbiologists onto results requiring a specific expertise and iii) maintain an acceptable TAT. This work highlighted the high RT-PCR consistency for the detection of SARS-CoV-2 and the importance of automated processes to handle a huge number of samples while preserving quality.
SARS-CoV-2 antibody responses determine disease severity in COVID-19 infected individuals
Authors: Hansen Cecilie Bo , Jarlhelt Ida , Pérez-Alós Laura , Hummelshøj Landsy Lone , Loftager Mette , Rosbjerg Anne , Helgstrand Charlotte , Bjelke Jais Rose , Egebjerg Thomas , Jardine Joseph G. , Sværke Jørgensen Charlotte , Iversen Kasper , Bayarri-Olmos Rafael , Garred Peter , Skjoedt Mikkel-Ole
Published: July 2020

Globally, the COVID-19 pandemic has had extreme consequences for the healthcare system and calls for diagnostic tools to monitor and understand the transmission, pathogenesis and epidemiology, as well as to evaluate future vaccination strategies. Here we have developed novel flexible ELISA-based assays for specific detection of SARS-CoV-2 antibodies against the receptor-binding domain (RBD): An antigen sandwich-ELISA relevant for large population screening and three isotype-specific assays for in-depth diagnostics. Their performance was evaluated in a cohort of 350 convalescent participants with previous COVID-19 infection, ranging from asymptomatic to critical cases. We mapped the antibody responses to different areas on protein N and S and showed that the IgM, A and G antibody responses against RBD are significantly correlated to the disease severity. These assays—and the data generated from them—are highly relevant for diagnostics and prognostics and contribute to the understanding of long-term COVID-19 immunity.
The Pandemics in Artificial Society Agent-Based Model to Reflect Strategies on COVID-19
Authors: Situngkir Hokky , Lumbantobing Andhika Bernad
Published: July 2020

Various social policies and strategies have been deliberated and used within many countries to handle the COVID-19 pandemic. Some of those basic ideas are strongly related to the understanding of human social interactions and the nature of disease transmission and spread. In this paper, we present an agent-based approach to model epidemiological phenomena as well as the interventions upon it. We elaborate on micro-social structures such as social-psychological factors and distributed ruling behaviors to grow an artificial society where the interactions among agents may exhibit the spreading of the virus. Capturing policies and strategies during the pandemic, four types of intervention are also applied in society. Emerged macro-properties of epidemics are delivered from sets of simulations, lead to comparisons between each policy/strategy,s effectivity.
Mental Health of Medical Workers During the COVID-19 Pandemic in Russia: Results of a Cross-Sectional Study
Authors: Bachilo E.V. , Barylnik J.B. , Shuldyakov A.A. , Efremov A.A. , Novikov D.E.
Published: July 2020

This is the first study in Russia regarding the mental health of medical workers during a pandemic. In this survey, the study of medical workers during pandemic COVID-19 in Russia reported high rates of symptoms of depression and anxiety. There is a higher risk of developing symptoms of anxiety and depression among young employees working directly in high-risk areas of the infection. Protecting medical workers is an important component of public health measures for addressing the COVID-19 pandemic. Special measures to improve the mental health of medical workers should be based on their needs. Special attention needs to be paid to young medical workers working in areas with a high risk of infection.

Highlights

medical workers are at high risk of developing mental disorders during a pandemic COVID-19;

the overall prevalence of GAD (5 or more points on the GTD-7 scale) and depressive symptoms (5 or more points on the PHQ-9 scale) among medical workers in Russia during the pandemic period was 48.77% and 57.63% respectively;

there is a higher risk of developing symptoms of anxiety and depression among young employees working directly in high-risk areas of the infection;

the provision of personal protective equipment (69.2%), the optimization of the work and rest regime during the shift (58%), the support of management (52.7%) and relatives (51.1%) are the main areas that reduce the psycho-emotional stress of medical workers during a pandemic.
Examining side effect variation in antipsychotic treatment and schizophrenia spectrum disorders
Authors: Neumeier Maria S. , Homan Stephanie , Vetter Stefan , Seifritz Erich , Kane John M. , Huhn Maximilian , Leucht Stefan , Homan Philipp
Published: July 2020

Background

Side effects of antipsychotic drugs play a key role in non-adherence and discontinuation of treatment in schizophrenia spectrum disorders (SSD). Precision medicine aims to minimize such side effects by selecting the right treatment for the right patient. However, to determine the extent of precision medicine that is required, we need to (1) show that there is indeed variation in side effects and (2) estimate the amount of variation in those side effects between patients. While clinical impression suggests that such variation is considerable, analyzing how side effect variation differs between treatment and control can address this question more formally. Here, we hypothesized to find larger side effect variation in treatment compared with control in patients treated with second generation antipsychotics.

Methods

We included double-blind, placebo-controlled, randomized controlled trials of adults with a diagnosis of SSD and prescription for licensed antipsychotic drugs. Standard deviations of the pre-post treatment differences of weight gain, prolactin levels, and corrected QT (QTc) times were extracted. Data quality and validity were ensured by following the PRISMA guidelines. The outcome measure was the overall variability ratio of treatment to control across randomized controlled trials (RCTs). Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model.

Results

We included N = 16578 patients for weight gain, N = 16633 patients for prolactin levels, and N = 10384 patients for QTc time. Variability ratios (VR) were significantly increased for weight gain (VR = 1.08; 95% CI: 1.02 - 1.14; P = 0.004) and prolactin levels (VR = 1.38; 95% CI: 1.17 - 1.62; P < 0.001) but did not reach significance for QTc time (VR = 1.05; 95% CI: 0.98 - 1.12; P = 0.135).

Conclusion

We found increased variability in major side effects in patients with SSD under treatment with second generation antipsychotics, suggesting that subgroups of patients or even individual patients may benefit from improved treatment allocation through stratified or personalized medicine, respectively.
A multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort
Authors: Müller Stephanie J. , Schurz Haiko , Tromp Gerard , van der Spuy Gian D. , Hoal Eileen G. , van Helden Paul D. , Owusu-Dabo Ellis , Meyer Christian G. , Thye Thorsten , Niemann Stefan , Warren Robin M. , Streicher Elizabeth , Möller Marlo , Kinnear Craig
Published: July 2020

Despite decades of research and advancements in diagnostics and treatment, tuberculosis remains a major public health concern, particularly in low- and middle-income countries. New bioinformatics and computational methods are needed to interrogate the intersection of host- and bacterial genomes and identify novel targets for anti-tuberculosis drugs. Host genotype datum and paired infecting bacterial isolate information were analysed for associations using a multinomial logistic regression framework implemented in SNPTest. Two geographically distinct cohorts were evaluated: a cohort of 947 participants self-identifying as belonging to a five-way admixed South African population and a Ghanaian cohort consisting of 3 311 participants. We report potential associations between host genetic variants and multiple members of the Mycobacterium tuberculosis complex (MTBC). Although none of the variants analyzed in the South African cohort passed the GWAS cut-off for significance, 32 single nucleotide polymorphisms were identified in the Ghanaian cohort as being statistically significantly associated with risk for infection with strains of different members of the MTBC. Further analysis revealed that two of these SNPs were directly genotyped, and the rest were imputed using the 1000 Genomes Phase 3 reference panel. The availability of paired host-pathogen data is imperative for investigating strain-specific interactions between MTBC and its host. As demonstrated by this study, the implementation of a multinomial logistic regression using paired host-pathogen data may prove valuable for further research investigating the complex relationships driving infectious disease.
Metabolomics differentiate cancer from non-cancer pleural effusions based on steroid lipids and acyl carnitines
Authors: Love Katie , da Costa Ricardo MF , Beckmann Manfred , Morley Anna , Bhatnagar Rahul , Maskell Nick , Mur Luis AJ , Lewis Keir E
Published: July 2020

Objective

To identify and detect metabolomic markers to differentiate cancer related from other pleural effusions.

Material and methods

Un-targeted flow infusion electrospray mass spectrometry was used on a cohort of 100 samples from benign and malignant pleural effusions (12 primary lung cancers, 14 mesotheliomas, 24 other cancers, 25 congestive cardiac failure, 22 parapneumonic effusion, 3 empyema). Standard metabolomic statistical models for analysis were performed.

Results

Five novel markers were identified using univariate and multivariate receiving operator curve analyses using five discriminant features yielding a diagnostic accuracy of above 0.91 (95% CI: 0.839-0.976) with a sensitivity of 0.97 (95% CI 0.952-0.979) and specificity 0.87 (95% CI 0.852-0.894).

Conclusion

Individual biomarkers with the highest accuracy (>0.84) were all raised in cancer and are involved in metabolism of sterol-lipids and acyl carnitines linked to β-oxidation. Our markers performed better than those previously published. Further, these published markers failed to achieve their stated accuracies in our data.
Whence the next pandemic? The intersecting global geography of the animal-human interface, poor health systems and air transit centrality reveals conduits for high-impact spillover
Authors: Walsh Michael G. , Sawleshwarkar Shailendra , Hossain Shah , Mor Siobhan M.
Published: July 2020

The health and economic impacts of infectious disease pandemics are catastrophic as most recently manifested by coronavirus disease 2019 (COVID-19). The emerging infections that lead to substantive epidemics or pandemics are typically zoonoses that cross species boundaries at vulnerable points of animal-human interface. The sharing of space between wildlife and humans, and their domesticated animals, has dramatically increased in recent decades and is a key driver of pathogen spillover. Increasing animal-human interface has also occurred in concert with both increasing globalisation and failing health systems, resulting in a trifecta with dire implications for human and animal health. Nevertheless, to date we lack a geographical description of this trifecta that can be applied strategically to pandemic prevention. This investigation provides the first geographical quantification of the intersection of animal-human interfaces, poor human health system performance and global connectivity via the network of air travel. In so doing, this work provides a systematic, data-driven approach to classifying spillover hazard based on the distribution of animal-human interfaces while simultaneously identifying globally connected cities that are adjacent to these interfaces and which may facilitate global pathogen dissemination. We present this geography of high-impact spillover as a tool for developing targeted surveillance systems and improved health infrastructure in vulnerable areas that may present conduits for future pandemics.
TASK-3 Two-Pore Potassium Channels drive neuronal excitability of the circadian clock and entrainment to challenging light environments
Authors: Steponenaite Aiste , Lalic Tatjana , Atkinson Lynsey , Wei Liting , Mathie Alistair , Cader M. Zameel , Lall Gurprit S.
Published: July 2020

The suprachiasmatic nucleus (SCN), the mammalian circadian clock, is a heterogenous structure made of several neuron types that generate a circadian electrical activity profile. However, it is unclear how such regulation in endogenous neuronal excitability is maintained. Background two-pore domain potassium channels (K2P), such as TASK-3, play an important role in inhibiting neuronal activity. Here, we utilize a TASK-3 KO mouse model to unravel the role played by this channel in SCN circadian neuronal regulation and behavioral photoentrainment. Our results reveal that TASK-3 is needed to adapt to challenging lighting conditions, such as those experienced through seasonal changes and jet lag. From our investigations this appears to be very distinct from pathways that drive acute, ‘one-off’ adjustments in clock phase, in response to single pulses of light. These findings provide crucial information on the intricate pathways linking clock output to behavioral adaptation to light-dark cycles.
Single cell visualisation ofmir-9aandSenselessco-expression duringDrosophila melanogasterembryonic and larval peripheral nervous system development
Authors: Gallicchio Lorenzo , Griffiths-Jones Sam , Ronshaugen Matthew
Published: July 2020

TheDrosophila melanogasterperipheral nervous system (PNS) comprises the sensory organs that allow the fly to detect environmental factors such as temperature and pressure. PNS development is a highly specified process where each sensilla originates from a single sensory organ precursor (SOP) cell. One of the major genetic orchestrators of PNS development isSenseless, which encodes a zinc finger transcription factor (Sens). Sens is both necessary and sufficient for SOP differentiation.Senselessexpression and SOP number are regulated by the microRNAmiR-9a. However, the reciprocal dynamics ofSenselessandmiR-9aare still obscure. By coupling smFISH with immunofluorescence, we are able to visualize transcription of themir-9alocus and expression of Sens simultaneously. During embryogenesis, we show that the expression ofmir-9ain SOP cells is rapidly lost asSenselessexpression increases. However, this mutually exclusive expression pattern is not observed in the third instar imaginal wing disc, where someSenseless-expressing cells show active sites ofmir-9atranscription. These data challenge and extend previous models ofSenselessregulation, and show complex co-expression dynamics betweenmir-9aandSenseless. The differences in this dynamic relationship between embryonic and larval PNS development suggest a possible switch inmiR-9afunction. Our work brings single-cell resolution to the understanding of dynamic regulation of PNS development bySenselessandmiR-9a.
Effects of constitutive and acute Connexin 36 deficiency on brain-wide susceptibility to PTZ-induced neuronal hyperactivity
Authors: Brunal Alyssa A. , Clark Kareem C. , Ma Manxiu , Pan Y. Albert
Published: July 2020

Connexins are transmembrane proteins that form hemichannels allowing the exchange of molecules between the extracellular space and cell interior. Two hemichannels from adjacent cells dock and form a continuous gap junction pore, thereby permitting direct intercellular communication. Connexin 36 (Cx36), expressed primarily in neurons, is involved in the synchronous activity of neurons and may play a role in aberrant synchronous firing, as seen in seizures. To understand the reciprocal interactions between Cx36 and seizure-like neural activity, we examined three questions: a) does Cx36 deficiency affect seizure susceptibility, b) does seizure-like activity affect Cx36 expression patterns, and c) does acute blockade of Cx36 conductance increase seizure susceptibility. We utilize the zebrafish pentylenetetrazol (PTZ; a GABA(A) receptor antagonist) induced seizure model, taking advantage of the compact size and optical translucency of the larval zebrafish brain to assess how PTZ affects brain-wide neuronal activity and Cx36 protein expression. We exposed wild-type and genetic Cx36-deficient (cx35.5- /-) zebrafish larvae to PTZ and subsequently mapped neuronal activity across the whole brain, using phosphorylated extracellular-signal-regulated kinase (pERK) as a proxy for neuronal activity. We found thatcx35.5-/-fish exhibited region-specific susceptibility and resistance to PTZ-induced hyperactivity compared to wild-type controls, suggesting that genetic Cx36 deficiency may affect seizure susceptibility in a region-specific manner. Regions that showed increased PTZ sensitivity include the dorsal telencephalon, which is implicated in human epilepsy, and the lateral hypothalamus, which has been underexplored. We also found that PTZ-induced neuronal hyperactivity resulted in a rapid reduction of Cx36 protein levels. 30 minutes and one-hour exposure to 20 mM PTZ significantly reduced the expression of Cx36. This Cx36 reduction persists after one-hour of recovery but recovered after 3-6 hours. This acute downregulation of Cx36 by PTZ is likely maladaptive, as acute pharmacological blockade of Cx36 by mefloquine results in increased susceptibility to PTZ-induced neuronal hyperactivity. Together, these results demonstrate a reciprocal relationship between Cx36 and seizure-associated neuronal hyperactivity: Cx36 deficiency contributes region-specific susceptibility to neuronal hyperactivity, while neuronal hyperactivity-induced downregulation of Cx36 may increase the risk of future epileptic events.
Automated prediction and annotation of small proteins in microbial genomes
Authors: Durrant Matthew G. , Bhatt Ami S.
Published: July 2020

Recent work performed by Sberro et al. (2019) revealed a vast unexplored space of small proteins existing within the human microbiome. At present, these small open reading frames (smORFs) are unannotated in existing reference genomes and standard genome annotation tools are not able to accurately predict them. In this study, we introduce an annotation tool namedSmORFinderthat predicts small proteins based on those identified by Sberro et al. This tool combines profile Hidden Markov models (pHMMs) of each small protein family and deep learning models that may better generalize to smORF families not seen in the training set. We find that combining predictions of both pHMM and deep learning models leads to more precise smORF predictions and that these predicted smORFs are enriched for Ribo-Seq or MetaRibo-Seq translation signals. Feature importance analysis reveals that the deep learning models learned to identify Shine-Dalgarno sequences, deprioritize the wobble position in each codon, and group codons in a way that strongly corresponds to the codon synonyms found in the codon table. We perform a core genome analysis of 26 bacterial species and identify many core smORFs of unknown function. We pre-compute small protein annotations for thousands of RefSeq isolate genomes and HMP metagenomes, and we make these data available through a web portal along with other useful tools for small protein annotation and analysis. The systematic identification and annotation of those important small proteins will help researchers to expand our understanding of this exciting field of biology.
Antibodies that potently inhibit or enhance SARS-CoV-2 spike protein-ACE2 interaction isolated from synthetic single-chain antibody libraries
Authors: Beasley Matthew D. , Aracic Sanja , Gracey Fiona M. , Kannan Ruban , Masarati Avisa , Premaratne S. R. , Udawela Madhara , Wood Rebecca E. , Jabar Shereen , Church Nicole L. , Le Thien-Kim , Makris Dahna , McColl Bradley K. , Kiefel Ben R.
Published: July 2020

Antibodies with high affinity against the receptor binding domain (RBD) of the SARS-CoV-2 S1 ectodomain were identified from screens using the Retained Display™ (ReD) platform employing a 1 × 1011clone single-chain antibody (scFv) library. Numerous unique scFv clones capable of inhibiting binding of the viral S1 ectodomain to the ACE2 receptorin vitrowere characterized. To maximize avidity, selected clones were reformatted as bivalent diabodies and monoclonal antibodies (mAb). The highest affinity mAb completely neutralized live SARS-CoV-2 virus in cell culture for four days at a concentration of 6.7 nM, suggesting potential therapeutic and/or prophylactic use. Furthermore, scFvs were identified that greatly increased the interaction of the viral S1 trimer with the ACE2 receptor, with potential implications for vaccine development.
Neural synchrony predicts children’s learning of novel words
Authors: Piazza Elise A. , Cohen Ariella , Trach Juliana , Lew-Williams Casey
Published: July 2020

Social interactions have a well-studied influence on early development and language learning. Recent work has begun to investigate the neural mechanisms that underlie shared representations of input, documenting neural synchrony or coupling (measured using intersubject temporal correlations of neural activity) between individuals exposed to the same stimulus. Neural synchrony has been found to predict the quality of engagement with a stimulus and with communicative cues, but studies have yet to address how neural synchrony among children may relate to real-time learning. Using functional near-infrared spectroscopy (fNIRS), we recorded the neural activity of 45 children (3.5-4.5 years) during joint book reading with an adult experimenter. The custom children’s book contained four novel words and objects embedded in an unfolding story, as well as a range of narrative details about object functions and character roles. We observed synchronized neural activity between child participants during book reading and found a positive correlation between learning and intersubject neural synchronization in parietal cortex, an area implicated in narrative-level processing in adult research. Our findings suggest that children’s learning is facilitated by active neural engagement with the dynamics of natural social input.
Cortical Silent Period reflects individual differences in action stopping performance
Authors: Paci Mario , Di Cosmo Giulio , Perrucci Mauro Gianni , Ferri Francesca , Costantini Marcello
Published: July 2020

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate of motor inhibition within the primary motor cortex (M1), such as the Cortical Silent period (CSP). CSP’s length is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, we here explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the length of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s length and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.
How scars shape the neural landscape: key molecular mediators of TGF-β1’s anti-neuritogenic effects
Authors: Jeon Kye-Im , Huxlin Krystel R.
Published: July 2020

Following injury to the peripheral and central nervous systems, tissue levels of transforming growth factor (TGF)-β1 often increase, which is key for wound healing and scarring. However, active wound regions and scars appear to inhibit process outgrowth by regenerating neurons. We recently showed that corneal wound myofibroblasts block corneal nerve regenerationin vivo, and sensory neurite outgrowthin vitroin a manner that relies critically on TGF-β1. In turn, delayed, abnormal re-innervation contributes to long-term sensory dysfunctions of the ocular surface. Here, we exposed morphologically and biochemically-differentiated sensory neurons from the ND7/23 cell line to TGF-β1 to identify the intracellular signals regulating these anti-neuritogenic effects, contrasting them with those of Semaphorin(Sema)3A, a known inhibitor of neurite outgrowth. Neuronal morphology was quantified using phase-contrast imaging. Western blotting and specific inhibitors were then used to identify key molecular mediators. Differentiated ND7/23 cells expressed neuron-specific markers, including those involved in neurite extension and polarization. TGF-β1 increased phosphorylation of collapsin response mediator protein-2 (CRMP2), a molecule that is key for neurite extension. We now show that both glycogen synthase kinase (GSK)-3β and Smad3 modulate phosphorylation of CRMP2 after treatment with TGF-β1. GSK-3β appeared to exert a particularly strong effect, which could be explained by its ability to phosphorylate not only CRMP2, but also Smad3. In conclusion, TGF-β1’s inhibition of neurite outgrowth in sensory neurons appears to be regulated through a highly-conserved signaling pathway, which involves the GSK-3β/CRMP-2 loop via both canonical and non-canonical mechanisms. It is hoped that by defining the signaling pathways that control neurite outgrowth in wound environments, it will become possible to identify optimal molecular targets to promote re-innervation following injury.
Serial co-expression analysis of host factors from SARS-CoV viruses highly converges with former high-throughput screenings and proposes key regulators and co-option of cellular pathways
Authors: Pérez-Pulido Antonio J. , Asencio-Cortés Gualberto , Brokate-Llanos Ana M. , Brea-Calvo Gloria , Rodríguez-Griñolo Rosario , Garzón Andrés , Muñoz Manuel J.
Published: July 2020

The current genomics era is bringing an unprecedented growth in the amount of gene expression data, only comparable to the exponential growth of sequences in databases during the last decades. This data now allows the design of secondary analyses that take advantage of this information to create new knowledge through specific computational approaches. One of these feasible analyses is the evaluation of the expression level for a gene through a series of different conditions or cell types. Based on this idea, we have developed ASACO, Automatic and Serial Analysis of CO-expression, which performs expression profiles for a given gene along hundreds of normalized and heterogeneous transcriptomics experiments and discover other genes that show either a similar or an inverse behavior. It might help to discover co-regulated genes, and even common transcriptional regulators in any biological model, including human diseases or microbial infections. The present SARS-CoV-2 pandemic is an opportunity to test this novel approach due to the wealth of data that is being generated, which could be used for validating results. In addition, new cell mechanisms identified could become new therapeutic targets. Thus, we have identified 35 host factors in the literature putatively involved in the infectious cycle of SARS-CoV and/or SARS-CoV-2 and searched for genes tightly co-expressed with them. We have found around 1900 co-expressed genes whose assigned functions are strongly related to viral cycles. Moreover, this set of genes heavily overlap with those identified by former laboratory high-throughput screenings (with p-value near 0). Some of these genes aim to cellular structures such as the stress granules, which could be essential for the virus replication and thereby could constitute potential targets in the current fight against the virus. Additionally, our results reveal a series of common transcription regulators, involved in immune and inflammatory responses, that might be key virus targets to induce the coordinated expression of SARS-CoV-2 host factors. All of this proves that ASACO can discover gene co-regulation networks with potential for proposing new genes, pathways and regulators participating in particular biological systems.

Highlights

ASACO identifies regulatory associations of genes using public transcriptomics data.

ASACO highlights new cell functions likely involved in the infection of coronavirus.

Comparison with high-throughput screenings validates candidates proposed by ASACO.

Genes co-expressed with host’s genes used by SARS-CoV-2 are related to stress granules.
3D MAPs discovers the morphological sequence chondrocytes undergo in the growth plate and the regulatory role of GDF5 in this process
Authors: Rubin Sarah , Agrawal Ankit , Stegmaier Johannes , Svorai Jonathan , Addadi Yoseph , Villoutreix Paul , Stern Tomer , Zelzer Elazar
Published: July 2020

The activity of the epiphyseal growth plates, which drive longitudinal growth of long bones, is dependent on the ability of chondrocytes to change their shape and size extensively as they differentiate. However, organ size, extracellular matrix density and cell number have hindered the study of chondrocyte morphology. Here, we describe a new pipeline called 3D Morphometric Analysis for Phenotypic significance (3D MAPs), which overcomes these obstacles. By using 3D MAPs, we have created an image database of hundreds of thousands of cells from orthologous long bones. Analysis of this database revealed the growth strategies that chondrocytes use during differentiation. We found that chondrocytes employed both allometric and isometric growth, and that allometric growth is achieved by changes either in volume or surface area along a specific cell axis in a zone-specific manner. Additionally, we discovered a new organization of chondrocytes within the growth plate, where cells are orientated such that their longest axis always aligns with the dorsal-ventral axis of the bone. To demonstrate the ability of 3D MAPs to explore mechanisms of growth plate regulation, we studied the abnormally short tibiae ofGdf5-null mice. 3D MAPs identified aberrant cellular growth behaviors which resulted in a 3-fold reduction in volumetric cell growth, as well as affected cell morphology and orientation, highlighting GDF5 as a new regulator of growth plate activity. Overall, our findings provide new insight into the morphological sequence that chondrocytes undergo during differentiation and highlight the ability of 3D MAPs to uncover molecular and cellular mechanisms regulating this process. More broadly, this work provides a new framework for studying growth plate biology.
ADAR-deficiency perturbs the global splicing landscape in mouse tissues
Authors: Kapoor Utkarsh , Licht Konstantin , Amman Fabian , Jakobi Tobias , Martin David , Dieterich Christoph , Jantsch Michael F.
Published: July 2020

Adenosine-to-inosine RNA editing and pre-mRNA splicing largely occur cotranscriptionally and influence each other. Here, we use mice deficient in either one of the two editing enzymes ADAR (ADAR1) or ADARB1 (ADAR2) to determine the transcriptome-wide impact of RNA editing on splicing across different tissues. We find that ADAR has a 100× higher impact on splicing than ADARB1, although both enzymes target a similar number of substrates with a large common overlap. Consistently, differentially spliced regions frequently harbor ADAR editing sites. Moreover, catalytically dead ADAR also impacts splicing, demonstrating that RNA binding of ADAR affects splicing. In contrast, ADARB1 editing sites are found enriched 5′ of differentially spliced regions. Several of these ADARB1-mediated editing events change splice consensus sequences, therefore strongly influencing splicing of some mRNAs. A significant overlap between differentially edited and differentially spliced sites suggests evolutionary selection toward splicing being regulated by editing in a tissue-specific manner.
Interest articulation, social stability and public governance
Authors: Gui Lin , Yin Zhendong , Nie Huihua
Published: July 2020

Purpose

The stability maintenance system has played an essential role in maintaining social stability although it also has brought about social problems worthy of attention. Admittedly compensation-based stability maintenance policy can address the appeals of citizens whose rights are infringed and the dissolving effect in the provision of compensation can save the cost of stability maintenance but such stability maintenance system lacks equilibrium.

Design/methodology/approach

The establishment of a strict assessment system for stability maintenance performance can encourage the stability maintenance authorities to eliminate the “fuse effect” as much as possible and ensure the effective implementation of the stability maintenance system. However, the rigorous stability maintenance performance assessment also provides the possibility for profit-driven petitions.

Findings

Due to the continuous accumulation of social dissatisfaction and the lack of stability maintenance equilibrium in the implementation of the compensation-based stability maintenance policy, public governance will fall into a stability maintenance paradox of “greater instability resulting from stability maintenance”.

Originality/value

The provision of sufficient means for the people to protect their interest by implementing measures such as strengthening the rule of law mechanisms is the key to achieve long-term social stability.
Nonfinancial employment commitment among Muslims and Jews in Israel: examination of the core–periphery model on majority and minority groups
Authors: Sharabi Moshe , Shdema Ilan , Abboud-Armaly Oriana
Published: July 2020

Purpose

The Nonfinancial employment commitment (NFEC) of Muslims in general, and of Arab Muslims in particular, has not yet been studied. Accordingly, the purpose of this study is to fill this gap by exploring the NFEC among Arab Muslims in Israel and comparing it to that of Jews in Israel.

Design/methodology/approach

The most common indicator of NFEC is the classic “Lottery Question,” which asked whether an individual would continue or stop working if they won a lottery or inherited a large sum of money. The sample included 215 Muslims and 898 Jews representing the Israeli labor force.

Findings

The findings reveal higher NFEC among Arab Muslims, particularly among women, compared to Jews. Muslims and Jews in urban areas have a lower NFEC then those who live in smaller localities. Among both Jews and Muslims, NFEC significantly increases with education level and income.

Social implications

NFEC is an important measure of the work ethic. A high NFEC of Arab Muslims, especially among women, reflects a high nonactualized potential for Western societies integrating Arab Muslim immigrants and refugees into the labor market.

Originality/value

The authors adapted the core–periphery model and found that it could explain the authors’ findings regarding NFEC differences among ethnoreligious groups in different residential areas. As the authors indicated before, it is the first time that NFEC of Arab Muslims has been studied.
Impact of supply risk management on firm performance: a case of the Indian electronics industry
Authors: KT Ramesh , Sarmah Sarada Prasad
Published: July 2020

Purpose

The purpose of this research is to study and examine the influence of systematic supply risk management (SRM) on the buyer's firm performance, mainly focussing on the Indian electronics industry.

Design/methodology/approach

The study has framed a set of hypotheses on the risk management model. A thorough literature review and experts' opinion were considered in framing constructs and hypothesis for the model. We adopted self-administration questionnaires mainly focusing on the Indian electronics industry. The derived hypothesis is tested using partial least squares (PLS) method from 140 survey data pertaining to small, medium and large scale industries.

Findings

Study justify that constructs with high loadings for risk identification, risk assessment, risk reduction, and risk monitoring supports all hypothesized relation to better risk management. The model captures superior risk identification, risk control and risk monitoring for overall firm performance, but fails to justify with organization supply risk assessment process on overall firm performance.

Research limitations/implications

The study mainly focused on SRM process on firm performance. Study mainly focused on single survey responses and expert's perceptions on SRM practices in Indian electronics industry.

Practical implications

Research empirically justifies the effects of SRM process on organization performance. Furthermore, effective SRM practices assist decision makers framing corrective strategies to mitigate risk occurrences and their negative impact.

Originality/value

This empirical work provides a deep understanding of SRM process on the Indian electronics industry and their perception towards firm performance. Moreover, this is one of the few empirical studies addressing SRM practices in the Indian electronics industry.
Risk analysis for lot-sizing and maintenance optimization problem under energy constraint with subcontractor solution
Authors: Kammoun Mohamed Ali , Hajej Zied , Rezg Nidhal
Published: July 2020

Purpose

The main contribution of this manuscript is to suggest new approaches in order to deal with dynamic lot-sizing and maintenance problem under aspect energetic and risk analysis. The authors introduce a new maintenance strategy based on the centroid approach to determine a common preventive maintenance plan for all machines to minimize the total maintenance cost. Thereafter, the authors suggest a risk analysis study further to unforeseen disruption of availability machines with the aim of helping the production stakeholders to achieve the obtained forecasting lot-size plan.

Design/methodology/approach

The authors tackle the dynamic lot-sizing problem using an efficient hybrid approach based on random exploration and branch and bound method to generate possible solutions. Indeed, the feasible solutions of random exploration method are used as input for branch and bound to determine the near-optimal solution of lot-size plan. In addition, our contribution to the maintenance part is to determine the optimal common maintenance plan for M machines based on a new algorithm called preventive maintenance (PM) periods means.

Findings

First, the authors have funded the optimal lot-size plan that should satisfy the random demand under service level requirement and energy constraint while minimizing the costs of production and inventory. Indeed, establishing a best lot-size plan is to determine the appropriate number of available machines and manufactured units per period. Second, for risk analysis study, the solution of subcontracting is proposed by specifying a maximum cost of subcontractor in the context of a calling of tenders.

Originality/value

For maintenance problem, the originality consists in regrouping the maintenance plans of M machines into only one plan. This approach lets us to minimize the total maintenance cost and reduces the frequent breaks of production. As a second part, this paper contributed to the development of a new risk analysis study further to unforeseen disruption of availability machines. This risk analysis developed a decision-making system, for production stakeholders, in order to achieve the forecasting lot-size plan and keeps its profitability, by specifying the unit cost threshold of subcontractor in the context of a calling of tender.