bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design Principles Underlying Robust Adaptation of Complex Biochemical Networks
Authors: Araujo Robyn P. , Liotta Lance A. 
Published: September 2020

AbstractBiochemical networks are often characterised by tremendous complexity – both in terms of the sheer number of interacting molecules (“nodes”) and in terms of the varied and incompletely understood interactions among these molecules (“interconnections” or “edges”). Strikingly, the vast and intricate networks of interacting proteins that exist within each living cell have the capacity to perform remarkably robustly, and reproducibly, despite significant variations in concentrations of the interacting components from one cell to the next, and despite mutability over time of biochemical parameters. Here we consider the ubiquitously observed and fundamentally important signalling response known as Robust Perfect Adaptation (RPA). We have recently shown that all RPA-capable networks, even the most complex ones, must satisfy an extremely rigid set of design principles, and are modular, being decomposable into just two types of network building-blocks – Opposer modules, and Balancer modules. Here we present an overview of the design principles that characterize all RPA-capable network topologies through a detailed examination of a collection of simple examples. We also introduce a diagrammatic method for studying the potential of a network to exhibit RPA, which may be applied without a detailed knowledge of the complex mathematical principles governing RPA.
TheClostridioides difficilespecies problem: global phylogenomic analysis uncovers three ancient, toxigenic, genomospecies
Authors: Knight Daniel R. , Imwattana Korakrit , Kullin Brian , Guerrero-Araya Enzo , Paredes-Sabja Daniel , Didelot Xavier , Dingle Kate E. , Eyre David W. , Rodríguez César , Riley Thomas V. 
Published: September 2020

AbstractClostridioides difficileinfection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen acrossC. difficileunderscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000C. difficilegenomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI-III. The emergence of these three novel genomospecies predates clades C1-5 by millions of years, rewriting the global population structure ofC. difficilespecifically and taxonomy of thePeptostreptococcaceaein general. These genomospecies all show unique and highly divergent toxin gene architecture, advancing our understanding of the evolution ofC. difficileand close relatives. Beyond the taxonomic ramifications, this work impacts the diagnosis of CDI worldwide.
Integrative taxonomy reveals hidden species within the western AtlanticCallichirus majors. l. (Decapoda, Axiidea, Callichiridae)
Authors: Hernáez Patricio , Miranda Marcel S. , Rio Juliana P. P. , Pinheiro Marcelo A.A. 
Published: September 2020

AbstractThe ghost shrimpCallichirus major(Say, 1818) is widely distributed in the Atlantic Ocean from ∼23°N to ∼26°S, and has also been reported from the tropical eastern Pacific. Evidence has been accumulating over many years thatC. majoris actually a species complex. Yet, the nameC. majoris widely and frequently used in many kinds of research. The current lack of clarity in the use of the nameC. majorhas resulted in nomenclatural instability, but also in unreliability and miscommunication of the available ecological and distributional information. Existing morphological and molecular evidence is reviewed and new evidence presented for the specimens from the southern localities previously assigned toC. majors. l. actually being a new species. That new species is herein described based on morphological and molecular evidence. Additionally, a neotype is selected forC. majorin order to settle the defining characters ofC. majors. str. and, therefore, ensuring the correct use of this name.
Influence of sensory modality and control dynamics on human path integration
Authors: Stavropoulos Akis , Lakshminarasimhan Kaushik J. , Laurens Jean , Pitkow Xaq , Angelaki Dora E. 
Published: September 2020

AbstractPath integration is a sensorimotor computation that can be used to infer latent dynamical states by integrating self-motion cues. We studied the influence of sensory observation (visual/vestibular) and latent control dynamics (velocity/acceleration) on human path integration using a novel motion-cueing algorithm. Sensory modality and control dynamics were both varied randomly across trials, as participants controlled a joystick to steer to a memorized target location in virtual reality. Visual and vestibular steering cues allowed comparable accuracies only when participants controlled their acceleration, suggesting that vestibular signals, on their own, fail to support accurate path integration in the absence of sustained acceleration. Nevertheless, performance in all conditions reflected a failure to fully adapt to changes in the underlying control dynamics, a result that was well explained by a bias in the dynamics estimation. This work demonstrates how an incorrect internal model of control dynamics affects navigation in volatile environments in spite of continuous sensory feedback.
At each site its diversity: DNA barcoding reveals remarkable earthworm diversity in neotropical rainforests of French Guiana
Authors: Maggia Marie-Eugénie , Decaëns Thibaud , Lapied Emmanuel , Dupont Lise , Roy Virginie , Schimann Heidy , Orivel Jérôme , Murienne Jérôme , Baraloto Christopher , Cottenie Karl , Steinke Dirk 
Published: September 2020

AbstractDespite their recognized essential role in soil, earthworms in tropical environments are still understudied. The aim of this study was to re-evaluate the diversity at the regional scale, as well as to investigate the environmental and spatial drivers of earthworm communities. We sampled earthworm communities across a range of habitats at six locations in French Guiana using three different sampling methods. We generated 1675 DNA barcodes and combined them with data from a previous study. Together, all sequences clustered into 119 MOTUs which were used as proxy to assess species richness. Only two MOTUs were common between the six locations and 20.2 % were singletons, showing very high regional species richness and a high number of rare species. A canonical redundancy analysis was used to identify key drivers of the earthworm community composition. The RDA results and beta-diversity calculations both show strong species turnover and a strong spatial effect, resulting from dispersal limitations that are responsible for the current community composition. Sampling in different microhabitats allowed the discovery of 23 MOTUs that are exclusively found in decaying trunks and epiphytes, highlighting hidden diversity of earthworms outside of soil.
Altered visual function in a larval zebrafish knockout of neurodevelopmental risk genepdzk1
Authors: Xie Jiaheng , Jusuf Patricia R. , Bui Bang V. , Dudczig Stefanie , Goodbourn Patrick T. 
Published: September 2020

AbstractThe humanPDZK1gene is located in a genomic susceptibility region for neurodevelopmental disorders. A genome-wide association study (GWAS) identified links betweenPDZK1polymorphisms and altered visual contrast sensitivity, an endophenotype for schizophrenia and autism spectrum disorder. The PDZK1 protein is implicated in neurological functioning, interacting with synaptic molecules including post-synaptic density 95 (PSD-95),N-methyl-D-aspartate receptors (NMDAR), corticotropin-releasing factor receptor 1 (CRFR1) and serotonin 2A receptors. To elucidate the role of PDZK1, we generatedpdzk1-knockout (pdzk1-KO)zebrafish using CRISPR/Cas-9 genome editing. Visual function of 7-day-old fish was assessed at behavioural and functional levels using the optomotor response (OMR) and scotopic electroretinogram (ERG). We also quantified retinal morphology and densities of PSD-95, NMDAR1, CRFR1 and serotonin in the synaptic inner plexiform layer at 7 days, 4 weeks and 8 weeks of age. Relative to wild-type,pdzk1-KO larvae showed spatial-frequency tuning functions with increased amplitude (likely due to abnormal gain control) and reduced ERGb-waves (suggestive of inner retinal dysfunction). However, these functional differences were not associated with gross synaptic or morphological retinal phenotypes. The findings corroborate a role forpdzk1in visual function, and our model system provides a platform for investigating other genes associated with abnormal visual behaviour.
Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution
Authors: Zhang Shuyuan , Qiao Shuyuan , Yu Jinfang , Zeng Jianwei , Shan Sisi , Lan Jun , Tian Long , Zhang Linqi , Wang Xinquan 
Published: September 2020

AbstractIn recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the “down” conformation, indicating they are more prone to adopt this receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. Through structure and sequence comparisons, we identified critical residues in the RBD that underlie the different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes and propose that N-linked glycans serve as conformational control elements of the RBD. These results collectively indicate that strong RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.
Heat Stress and PPE during COVID-19: Impact on health care workers’ performance, safety and well-being in NHS settings
Authors: Davey Sarah L , Lee Ben J , Robbins Timothy , Randeva Harpal , Thake C. Doug 
Published: September 2020

AbstractBackgroundThe impermeable nature of PPE worn by health care workers (HCWs) during the SARS-CoV-2 (COVID-19) pandemic can potentiate heat stress which may negatively impact the performance, safety and well-being of HCWs.AimThe aim of this study was to evaluate perceived levels of heat stress and its consequences in HCWs required to wear PPE during the COVID-19 pandemic in the UK.MethodAn anonymous online survey was distributed to HCWs required to wear Type 1 or 2 PPE in NHS settings to evaluate the perceived impact of PPE on: (1) physical and cognitive performance; (2) heat stress and heat-related symptoms; (3) frequency of removing PPE due to discomfort caused by heat stress; and (4) general working-life and well-being.ResultsThe survey received 224 responses from 192 (85.7%) women and 32 (14.3%) men. Even though 71.9% of respondents wore the less thermally challenging PPE (i.e. Type 2), a median of 3 (IQR: 2,5) heat-related symptoms were reported including syncope (7.7%). A median of 1 (IQR: 0-3) cognitive task was adversely affected with attentional focus being the most affected. To relieve discomfort, 32.6% reported removing PPE on five or more occasions in a shift. Ninety two percent reported PPE made their job more difficult and 76.2% advised that physical performance was impaired. Respondents also highlighted concerns of dermatitis and pressure sores in the facial region (22.3%) amongst other factors.ConclusionHeat stress experienced when PPE is worn negatively impacts the performance, safety and well-being of HCWs and patients. Therefore, modification to current working practices and current design of PPE is urgently required to improve HCWs’ resilience to pandemics of infectious diseases. Results suggest modifications to the design of the protective face mask and strict enforcement of specific work/rest ratios to limit the duration of PPE use would be immediate impactful interventions.
THE EFFECT OF DIOXIN ON LOW BIRTH WEIGHT IN SOUTHERN WEST VIRGINIA BETWEEN 1955 – 1969
Authors: Annie Frank H , Uejio Chris K , Embrey Sarah , Tager Alfred 
Published: September 2020

ABSTRACTObjectiveThe effect of low birth weight as a result of dioxin-based exposure has been investigated through the existing literature, but the debate on exact point source and production is still debated. The Monsanto factory located in Nitro, West Virginia produced Agent Orange from 1948 – 1969.MethodsThe vital statistics registry from the state of West Virginia of Kanawha county and Putnam county West Virginia. The production of dioxin and 2-4-5T was obtained from the legal files from (Civil Action No. 04-C-465) and the expert witness of Dr. Bruce Bell. In order to understand this relationship a time series analysis was conducted to compare 2-4-5T and dioxin and low-birthweight in Kanawha County and Putnam County, West Virginia.ResultsThe results suggest dioxin within Kanawha county had a suggestive relationship associated with dioxin production and low birthweight from 1948-1969 had a suggestive relationship of (p= 0.042). The comparison county of Putnam had no statistically significant relationship between low birthweight and dioxin production (p= 0.203). Agent Orange (2-4-5t) was also considered and measured within the counties of Kanawha and Putnam Counties, within these two counties no statistically significant relationship was observed.ConclusionsIn conclusion the association between dioxin and low birthweight still requires more research but this analysis illustrates that there appears to be a suggestive relationship that exists within Kanawha County, West Virginia as related to the production of and effect of the by-product of dioxin.
Self-applied ELCSA is valid for rapid tracking of household food insecurity among pregnant women during the COVID-19 pandemic
Authors: Agampodi Thilini C. , Hromi-Fiedler Amber , Agampodi Suneth B. , Amarasinghe Gayani S. , wickramasinghe Nuwan D. , Jayasinghe Imasha U. , Hettiarachchi Ayesh U. , Perez-Escamilla Rafael 
Published: September 2020

AbstractBackgroundRapid household food insecurity (HFI) tracking has been identified as a priority in the context of the COVID-19 pandemic and its aftermath. We report the validation of the Latin American and Caribbean Food Security Scale (Escala Latinoamericana y Caribena de Seguridad Alimentaria -ELCSA) among pregnant women in Sri Lanka.MethodsThe adult eight-items of the English version of ELCSA was translated into Sinhala and Tamil. Cognitive testing (on ten pregnant women and five local experts) and psychometric validation of the self-administered HFI tool was conducted among pregnant women (n=269) attending the Rajarata Pregnancy Cohort (RaPCo) special clinics in Anuradhapura in February 2020. We assessed psychometric properties and fit using a one parameter logistic model (Rasch analysis) using STATA version 14 and WINSTEP software version 4.3.4. Concurrent validity was tested using psychological distress.ResultsThe scale was internally consistent (Cronbach’s alpha = 0.79), had a good model fit (Rasch infit statistic range: 0.85 to 1.07). Item 8 (‘did not eat for the whole day’) was removed from the model fit analysis as it was not affirmed by anyone. Item severity scores ranged from -2.15 for ‘not eating a diverse diet’ to 4.43 for ‘not eating during the whole day’. Concurrent validity between HFI and psychological distress was confirmed (r=0.15, p<0.05).ConclusionsThe self-applied version of ELCSA-pregnancy in Sri Lanka (ELCSA-P-SL) is a valid and feasible tool to track HFI among pregnant women in similar contexts during the COVID-19 pandemic, where social distancing is a major concern and its aftermath.
Epidemiological characteristics of COVID-19 cases in non-Italian nationals notified to the Italian surveillance system
Authors: Fabiani Massimo , Mateo-Urdiales Alberto , Andrianou Xanthi , Bella Antonino , Del Manso Martina , Bellino Stefania , Rota Maria C. , Boros Stefano , Vescio Maria F. , D’Ancona Fortunato P. , Siddu Andrea , Punzo Ornella , Filia Antonietta , Brusaferro Silvio , Rezza Giovanni , Dente Maria G. , Declich Silvia , Pezzotti Patrizio , Riccardo Flavia ,   for the COVID-19 working group
Published: September 2020

AbstractBackgroundInternational literature suggests that disadvantaged groups are at higher risk of morbidity and mortality from SARS-CoV-2 infection due to poorer living/working conditions and barriers to healthcare access. Yet, to date, there is no evidence of this disproportionate impact on non-national individuals, including economic migrants, short-term travellers, and refugees.MethodsWe analysed data from the Italian surveillance system of all COVID-19 laboratory-confirmed cases tested positive from the beginning of the outbreak (20th of February) to the 19th of July 2020. We used multilevel negative-binomial regression models to compare the case-fatality rate and the rate of admission to hospital and intensive care unit (ICU) between Italian and non-Italian nationals. The analysis was adjusted for differences in demographic characteristics, pre-existing comorbidities, and period of diagnosis.ResultsWe analysed 213,180 COVID-19 cases, including 15,974 (7.5%) non-Italian nationals. We found that, compared to Italian cases, non-Italian cases were diagnosed at a later date and were more likely to be hospitalised [(adjusted relative risk (ARR)=1.39, 95% confidence interval (CI): 1.33-1.44)] and admitted to ICU (ARR=1.19, 95% CI: 1.07-1.32), with differences being more pronounced in those coming from countries with lower HDI. We also observed an increased risk of death in non-Italian cases from low-HDI countries (ARR=1.32, 95% CI: 1.01-1.75).ConclusionsA delayed diagnosis in non-Italian cases could explain their worse outcomes compared to Italian cases. Ensuring early access to diagnosis and treatment to non-Italians could facilitate the control of SARS-CoV-2 transmission and improve health outcomes in all people living in Italy, regardless of nationality.
The Association Between Obstructive Sleep Apnea Defined by 3 Percent Oxygen Desaturation or Arousal Definition and Self-Reported Cardiovascular Disease in the Sleep Heart Health Study
Authors: Quan Stuart F. , Budhiraja Rohit , Javaheri Sogol , Parthasarathy Sairam , Berry Richard B. 
Published: September 2020

AbstractBackgroundStudies have established that OSA defined using a hypopnea definition requiring a ≥4% oxygen desaturation (AHI4%) is associated with cardiovascular (CVD) or coronary heart (CHD) disease. This study determined whether OSA defined using a hypopnea definition characterized by a ≥3% oxygen desaturation or an arousal (AHI3%A) is associated with CVD/CHD.MethodsData were analyzed from 6307 Sleep Heart Health Study participants who had polysomnography. Self-reported CVD included angina, heart attack, heart failure, stroke or previous coronary bypass surgery or angioplasty. Self-reported CHD included the aforementioned conditions but not stroke or heart failure. The association between OSA and CVD/CHD was examined using logistic regression models with stepwise inclusion of demographic, anthropometric, social/behavioral and co-morbid medical conditions. A parsimonious model in which diabetes and hypertension were excluded because of their potential to be on the causal pathway between OSA and CVD/CHD also was constructed.ResultsFor CVD, the odds ratios and 95% confidence intervals for AHI3%A ≥30/hour were 1.39 (1.03-1.87) and 1.45 (1.09-1.94) in the fully adjusted and parsimonious models. Results for CHD were 1.29 (0.96-1.74) and 1.36 (0.99-1.85). In participants without OSA according to more stringent AHI4% criteria but with OSA using the AHI3%A definition, similar findings were observed.ConclusionOSA defined using an AHI3%A is associated with both CVD and CHD. Use of a more restrictive AHI4% definition will misidentify a large number of individuals with OSA who have CVD or CHD. These individuals may be denied access to therapy, potentially worsening their underlying CVD or CHD.
Development and clinical evaluation of non-viral genome specific targeted CAR T cells in relapsed/refractory B-cell non-Hodgkin lymphoma
Authors: Zhang Jiqin , Hu Yongxian , Yang Jiaxuan , Li Wei , Tian Yue , Wei Guoqing , Zhang Linjie , Zhao Kui , Qi Yalei , Tan Binghe , Zhang Mingming , Li Yi , Tian Qiliang , Fang Chunqian , Wu Yuxuan , Li Dali , Du Bing , Liu Mingyao , Huang He 
Published: September 2020

AbstractIn recent years, chimeric antigen receptor (CAR) T cell therapy has shown great promise in treating hematological malignancies. However, using virus in manufacture of CAR T cells brings about several problems. The application of CRISPR/Cas9 genome editing technology emerges in constructing novel CAR T cells by disrupting endogenous genes. Here we successfully develop a two-in-one approach to generate non-viral genome specific targeted CAR T cells through CRISPR/Cas9. By targeting a CAR in AAVS1 safe harbor locus, we demonstrated that these CAR T cells behave comparable to those conventionally produced by lentivirus. Furthermore, PD1-knockin anti-CD19 CAR T cells show a superior ability to eradicate tumor cells with high PD-L1 expression. In the adoptive therapy for relapsed/refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL), we observed durable responses without serious adverse events and complete remission (CR) in patients treated with these PD1 knockout CAR T cells. Collectively, our results prove the safety and feasibility of non-viral genome specific integrated CAR T cells, thus providing a new potential strategy for cancer treatment using these novel CAR T cells.
Single-cell multimodal omics and directly reprogrammed neurons to probe reduced penetrance in Frontotemporal Dementia
Authors: Natarajan Karthick , Eisfeldt Jesper , Hammond Maria , Patra Kalicharan , Laffita-Mesa José Miguel , Andrade-Talavera Yuniesky , Birtele Marcella , Öijerstedt Linn , Fisahn André , Parmar Malin , Graff Caroline 
Published: September 2020

Disclaimer“This manuscript has been withdrawn by the authors as it was submitted and made public without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.”
Pioglitazone improves deficits ofFmr1-KO mouse model of Fragile X syndrome by interfering with excessive diacylglycerol signaling
Authors: Geoffroy Andréa , Habbas Karima , Zambo Boglarka , Schramm Laetitia , Duchon Arnaud , Flatter Eric , Fouillen Laetitia , Zumsteg Julie , Heintz Dimitri , Mandel Jean-Louis , Hérault Yann , Moine Hervé 
Published: September 2020

AbstractFragile X syndrome (FXS), the leading cause of familial intellectual disability, is an uncured disease caused by the absence or loss of function of the FMRP protein. FMRP is an RNA binding protein that controls the translation of specific proteins in neurons. A main target of FMRP in neurons is diacylglycerol kinase kappa (DGKk) and the loss of FMRP leads to a loss of DGK activity causing a diacylglycerol excess in the brain. Excessive diacylglycerol signaling could be a significant contributor to the pathomechanism of FXS. Here we tested the contribution of DAG-signaling inFmr1-KO mouse model of FXS and we show that pioglitazone, a widely prescribed drug for type 2 diabetes, has ability to correct excessive DAG signaling in the brain and rescue behavioral alterations of theFmr1-KO mouse. This study highlights the role of lipid signaling homeostasis in FXS and provides arguments to support the testing of pioglitazone for treatment of FXS.