bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of human ACE2 to membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins
Authors: Anand Sai Priya , Chen Yaozong , Prévost Jérémie , Gasser Romain , Beaudoin-Bussières Guillaume , Abrams Cameron F. , Pazgier Marzena , Finzi Andrés 
Published: September 2020

AbstractA novel severe acute respiratory (SARS)-like coronavirus (SARS-CoV-2) is responsible for the current global coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The viral entry of SARS-CoV-2 depends on an interaction between the receptor binding domain of its trimeric Spike glycoprotein and the human angiotensin converting enzyme 2 (ACE2) receptor. A better understanding of the Spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. We show that there exist differential inter-protomer conformational transitions between both Spike trimers. Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restrains. Our findings can be of importance in the development of therapeutics that block the Spike/ACE2 interaction.
Adjusting for reporting lags in remote regions to improve malaria surveillance: Guyana as a case study
Authors: Menkir Tigist F. , Cox Horace , Poirier Canelle , Saul Melanie , Jones-Weekes Sharon , Clementson Collette , de Salazar Pablo M. , Santillana Mauricio , Buckee Caroline O. 
Published: September 2020

AbstractTime lags in reporting to national surveillance systems represent a major barrier for the control of infectious diseases, preventing timely decision making and resource allocation. This issue is particularly acute for infectious diseases like malaria, which often impact rural and remote communities the hardest. In Guyana, a country located in South America, poor connectivity among remote malaria-endemic regions hampers surveillance efforts, making reporting delays a key challenge for elimination. Here, we analyze 13 years of malaria surveillance data, identifying key correlates of time lags between clinical cases occurring and being added to the central data system. We develop nowcasting methods that use historical patterns of reporting delays to estimate occurred-but-not-reported monthly malaria cases. To assess their performance, we implemented them retrospectively, using only information that would have been available at the time of estimation, and found that they substantially enhanced the estimates of malaria cases. Specifically, we found that the best performing models achieved up to two- to four-fold improvements in accuracy (or error reduction) over known cases in selected regions. Our approach provides a simple, generalizable tool to improve malaria surveillance in endemic countries.
Towards molecular stratification of pediatric T-cell lymphoblastic lymphomas based on Minimal Disseminated Disease andNOTCH1/FBXW7mutational status: the French EURO-LB02 experience
Authors: Trinquand Amélie , Plesa Adriana , Abdo Chrystelle , Aladjidi Nathalie , Rigaud Charlotte , Touzart Aurore , Lhermitte Ludovic , Petit Arnaud , Michaux Katell , Jung Charlotte , Chassagne-Clement Catherine , Asnafi Vahid , Bertrand Yves , Garnier Nathalie , Macintyre Elizabeth 
Published: September 2020

AbstractWhile outcome for pediatric T lymphoblastic lymphoma (T-LBL) has improved with Acute Leukemia-type therapy, survival after relapse remains rare. Few prognostic markers have been identified and the value of Minimal Residual Disease (MRD) is less clear than in T-ALL. Mutations ofNOTCH1and/orFBXW7(N/F) identify good prognosis T-LBL and both MRD and high-level Minimal Disseminated Disease (MDD) are reported to be of poor prognosis. We evaluated MDD status by 8-color flow cytometry (MFC) and/or digital droplet PCR (ddPCR) in 86 French pediatric T-LBL, of whichN/Fstatus was known for 65 (61 treated on the Euro-LB02 protocol). Both techniques gave identical results for MDD/MRD values above 0.1%, allowing compilation. While an MDD threshold of 1% had no prognostic significance, the 54% (44/82) of protocol-treated patients with MDD ≥0.1% had a relatively favorable outcome (overall survival/OS; p = 0.026). MDD 0.1% status had no prognostic significance in the 68% of patients withN/Fmutations, whereas low/negative MDD status (9/61) identifiedN/Fgermline patients at a high risk of relapse (5-year OS of 44.4% vs 90% for MDD ≥ 0.1%,p = 0.014; and a 5-year DFS of 50% vs 90.9% respectively, p = 0.041). Combining oncogenetic and MDD status allows identification of 85% of patients with an excellent outcome (5-year OS 91.9% and DFS 95%) and 15% ofN/Fgermline/MDD< 0.1% patients who clearly require early alternative treatment (5-year OS 44.4%; p< 0.0001 and DFS 50%; p = 0.0001).
The structure, function, and evolution of a complete human chromosome 8
Authors: Logsdon Glennis A. , Vollger Mitchell R. , Hsieh PingHsun , Mao Yafei , Liskovykh Mikhail A. , Koren Sergey , Nurk Sergey , Mercuri Ludovica , Dishuck Philip C. , Rhie Arang , de Lima Leonardo G. , Porubsky David , Bzikadze Andrey V. , Kremitzki Milinn , Graves-Lindsay Tina A. , Jain Chirag , Hoekzema Kendra , Murali Shwetha C. , Munson Katherine M. , Baker Carl , Sorensen Melanie , Lewis Alexandra M. , Surti Urvashi , Gerton Jennifer L. , Larionov Vladimir , Ventura Mario , Miga Karen H. , Phillippy Adam M. , Eichler Evan E. 
Published: September 2020

ABSTRACTThe complete assembly of each human chromosome is essential for understanding human biology and evolution. Using complementary long-read sequencing technologies, we complete the first linear assembly of a human autosome, chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.08 Mbp centromeric α-satellite array, a 644 kbp defensin copy number polymorphism important for disease risk, and an 863 kbp variable number tandem repeat at chromosome 8q21.2 that can function as a neocentromere. We show that the centromeric α-satellite array is generally methylated except for a 73 kbp hypomethylated region of diverse higher-order α-satellite enriched with CENP-A nucleosomes, consistent with the location of the kinetochore. Using a dual long-read sequencing approach, we complete the assembly of the orthologous chromosome 8 centromeric regions in chimpanzee, orangutan, and macaque for the first time to reconstruct its evolutionary history. Comparative and phylogenetic analyses show that the higher-order α-satellite structure evolved specifically in the great ape ancestor, and the centromeric region evolved with a layered symmetry, with more ancient higher-order repeats located at the periphery adjacent to monomeric α-satellites. We estimate that the mutation rate of centromeric satellite DNA is accelerated at least 2.2-fold, and this acceleration extends beyond the higher-order α-satellite into the flanking sequence.
Microglial signalling pathway deficits associated with the R47H TREM2 variant linked to AD indicate inability to activate inflammasome
Authors: Cosker Katharina , Mallach Anna , Limaye Janhavi , Piers Thomas M , Staddon James , Neame Stephen J , Hardy John , Pocock Jennifer M 
Published: September 2020

AbstractThe R47H variant of the microglial membrane receptor TREM2 is linked to increased risk of late onset Alzheimer’s disease. Human induced pluripotent stem cell derived microglia (iPS-Mg) from patient iPSC lines expressing the AD-linked R47HhetTREM2 variant, common variant (Cv) or an R47HhomCRISPR edited line and its isogeneic control, demonstrated that R47H-expressing iPS-Mg expressed a deficit in signal transduction in response to the TREM2 endogenous ligand phosphatidylserine with reduced pSYK-pERK1/2 signalling and a reduced NLRP3 inflammasome response, (including ASC speck formation, Caspase-1 activation and IL-1beta secretion). Apoptotic cell phagocytosis and soluble TREM2 shedding were unaltered, suggesting a disjoint between these pathways and the signalling cascades downstream of TREM2 in R47H-expressing iPS-Mg, whilst metabolic deficits in glycolytic capacity and maximum respiration were reversed when R47H expressing iPS-Mg were exposed to PS+ expressing cells. These findings suggest that R47H-expressing microglia are unable to respond fully to cell damage signals such as phosphatidylserine, which may contribute to the progression of neurodegeneration in late-onset AD.
Forward genetics inWolbachia: Regulation ofWolbachiaproliferation by the amplification and deletion of an addictive genomic island
Authors: Duarte Elves H , Carvalho Ana , López-Madrigal Sergio , Costa João , Teixeira Luís 
Published: September 2020

AbstractWolbachiais one of the most prevalent bacterial endosymbionts, infecting approximately 40% of terrestrial arthropod species.Wolbachiais often a reproductive parasite but can also provide fitness benefits to its host, as, for example, protection against viral pathogens. This protective effect is currently being applied to fight arboviruses transmission by releasingWolbachia-transinfected mosquitoes. Titre regulation is a crucial aspect ofWolbachiabiology. Higher titres can lead to stronger phenotypes and fidelity of transmission but can have a higher cost to the host. SinceWolbachia is maternally transmitted, its fitness depends on host fitness, and, therefore, its cost to the host may be under selection. Understanding howWolbachiatitres are regulated and other aspects ofWolbachia biology has been hampered by the lack of genetic tools. Here we developed a forward genetic screen to identify newWolbachiaover-proliferative mutant variants. We characterized in detail two new mutants,wMelPop2 andwMelOctoless, and show that the amplification or loss of the Octomom genomic region lead to over-proliferation. These results confirm previous data and expand on the complex role of this genomic region in the control ofWolbachiaproliferation. Both new mutants shorten the host lifespan and increase antiviral protection. Moreover, we show thatWolbachiaproliferation rate inDrosophila melanogasterdepends on the interaction between Octomom copy number, the host developmental stage, and temperature. Our analysis also suggests that the life shortening and antiviral protection phenotypes ofWolbachiaare dependent on different, but related, properties of the endosymbiont; the rate of proliferation and the titres near the time of infection, respectively. Altogether, we demonstrate the feasibility of a novel and unbiased experimental approach to studyWolbachiabiology, which can be further adapted to characterize other genetically intractable bacterial endosymbionts.
Contributions of h- and Na+/K+pump currents to the generation of episodic and continuous rhythmic activities
Authors: Sharples Simon A. , Parker Jessica , Vargas Alex , Lognon Adam P. , Cheng Ning , Young Leanne , Shonak Anchita , Cymbalyuk Gennady S. , Whelan Patrick J. 
Published: September 2020

AbstractDeveloping spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and their transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-centre oscillator (HCO). Following predictions of our computational model, we tested the contributions of key properties to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model recapitulates the diverse state-dependent rhythms evoked by dopamine. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with Na+/K+ATPase pump (IPump) and hyperpolarization-activated currents (Ih) playing key roles. Modulation of either IPumpMaxor Ihproduced transitions between episodic and continuous rhythms and silence. As IPumpincreased, the episode duration and period increased along with a reduction in interepisode interval. Increasing Ihincreased the episode period along with an increase in episode duration. Pharmacological manipulations of Ihwith ZD7288 and IPumpwith ouabain or monensin in isolated spinal cords produced findings consistent with the model. Our modelling and experimental results highlight key roles of Ihand IPumpin producing episodic rhythms and provide insight into mechanisms that permit a single CPG to produce multiple patterns of rhythmicity.Significance statementThe ability of a single CPG to produce and transition between multiple rhythmic patterns of activity is poorly understood. We deployed a complementary computational half-centre oscillator model and an isolated spinal cord experimental preparation to identify key currents whose interaction produced episodic and continuous rhythmic activity. Together, our experimental and modelling approaches suggest mechanisms in spinal networks that govern diverse rhythms and transitions between them. This work sheds light on the ability of a single CPG to produce episodic bouts observed in behavioural and pathological contexts.
Non-obese population with the rs7903146 T allele exhibits higher sugar and more dyslipidaemia in subjects with Type-2-diabetes
Authors: Shaibu Sarah , Longdet Ishaya Yohanna , Luka Carrol Domkat , Fanen Ortswen Jesse , Eneọjọ-Abah Gloria Eleọjọ , Oguche Joel Iko-Ojo , Salami Tijani , Akor Shedrack Egbunu , Abah Samuel Eneọjọ 
Published: September 2020

ABSTRACTType 2 diabetes (T2D), the most prevalent type of diabetes has been associated with Transcription-Factor-7-Like-2 gene Single Nucleotide Polymorphisms (SNPs), rs12255372 and rs7903146 as risk factors, thought to be modulated by obesity status. In sub-Saharan Africa, the onset of T2D in the non-obese is rarely suspected. This study looks into the genetics and the biochemical parameters in non-obese population, with and without T2D and living in Jos, Nigeria. A total of 68 subjects, 40 diabetic patients and 28 healthy control group, all with closely matched age, height, nutrition, family history, Body Mass Index and socioeconomic status, recruited from within the same population were studied. SNPs Genotyping were performed using Polymerase Chain Reaction and Sangers Sequencing. Lipid profiles, Fasting Blood Sugar and C-peptide levels were measured and analysed alongside with demographic data from questionnaire. Odd-ratio at 95% confidence interval at a conventional level of alpha, <0.05 and Product Moment Correlation Coefficient Analysis were used to analyse the data in both groups. The entire population showed the GG genotype for the rs12255372. However, different genotype combination, CC, CT and TT were observed with the rs7903146. Though no significant association was observed between the genotypes and the odd of T2D, healthy subjects with the T allele showed a higher level of two hours postprandial plasma glucose level than those with CC genotype. Patients with T allele shows a more abnormal level of diabetes metabolic syndrome indicators such as Fasting Blood Sugar; two hours postprandial plasma glucose level; C-peptide; Low Density Lipoprotein, High Density Lipoprotein and Total Cholesterol. The study suggests that lower sugar metabolism and more dyslipidaemia are observed in subject with T allele. Hence, this could constitute poorer prognosis and a risk factor for non-obese population, particularly with high carbohydrate intake.
Passive surveillance assesses compliance with COVID-19 behavioral restrictions in a rural US county
Authors: Faust Christina L , Lambert Brian , Kochenour Cale , Robinson Anthony C. , Bharti Nita 
Published: September 2020

SummaryFollowing the emergence of SARS-CoV-2, early outbreak response relied on behavioral interventions. In the United States, local governments implemented restrictions aimed at reducing movements and contacts to limit viral transmission. In Pennsylvania, restrictions closed schools and businesses in the spring of 2020 and interventions eased later through the summer. In a rural Pennsylvania county, we use passive monitoring of vehicular traffic volume and mobile device derived visits to points of interest as proxies for movements and contacts. Rural areas have limited health care resources, which magnifies the importance of disease prevention. These data show the lowest levels of movement occurred during the strictest phase of restrictions, indicating high levels of compliance with behavioral intervention. We find that increases in movement correlated with increases in SARS-CoV-2 cases 9-18 days later. The methodology used in this study can be adapted to inform outbreak management strategies for other locations and future outbreaks that use behavioral interventions to reduce pathogen transmission.
Airborne contamination of COVID-19 in hospitals: a scoping review of the current evidence
Authors: Birgand Gabriel , Peiffer-Smadja Nathan , Fournier Sandra , Kerneis Solen , Lescure François-Xavier , Lucet Jean-Christophe 
Published: September 2020

ABSTRACTIntroductionA controversy remains worldwide regarding the transmission routes of SARS-CoV-2 in hospital settings. We reviewed the current evidence on the air contamination with SARS-CoV-2 in hospital settings, and the factors associated to the contamination including the viral load and the particles size.MethodsThe MEDLINE, Embase, Web of Science databases were systematically interrogated for original English-language articles detailing COVID-19 air contamination in hospital settings between 1 December 2019 and 21 July 2020. This study was conducted in accordance with the PRISMA-ScR guidelines. The positivity rate of SARS-CoV-2 viral RNA and culture were described and compared according to the setting, clinical context, air ventilation system, and distance from patient. The SARS-CoV-2 RNA concentrations in copies per m3 of air were pooled and their distribution were described by hospital areas. Particle sizes and SARS-CoV-2 RNA concentrations in copies or TCID50 per m3 were analysed after categorization of sizes in < 1 µm, 1–4 µm, and > 4 µm.ResultsAmong 2,034 records identified, 17 articles were included in the review. Overall, 27.5% (68/247) of air sampled from close patients’ environment were positive for SARS-CoV-2 RNA, without difference according to the setting (ICU: 27/97, 27.8%; non-ICU: 41/150, 27.3%; p = 0.93), the distance from patients (< 1 meter: 1/64, 1.5%; 1–5 meters: 4/67, 6%; p = 0.4). In other areas, the positivity rate was 23.8% (5/21) in toilets, 9.5% (20/221) in clinical areas, 12.4% (15/121) in staff areas, and 34.1% (14/41) in public areas. A total of 78 viral cultures were performed in three studies, and 3 (4%) were positive, all from close patients’ environment. The median SARS-CoV-2 RNA concentrations varied from 1.103 copies per m3 (IQR: 0.4.103-9.103) in clinical areas to 9.7.103 (5.1.103-14.3.103) in the air of toilets or bathrooms. The protective equipment removal and patients’ rooms had high concentrations/titre of SARS-CoV-2 with aerosol size distributions that showed peaks in the < 1 µm region, and staff offices in the > 4µm region.ConclusionIn hospital, the air near and away from COVID-19 patients is frequently contaminated with SARSCoV-2 RNA, with however, rare proofs of their viability. High viral loads found in toilet/bathrooms, staff and public hallways suggests to carefully consider these areas.
China’s outward foreign direct investment and exports diversification: an asymmetric analysis
Authors: Rehman Faheem Ur , Ding Yibing , Noman Abul Ala , Khan Muhammad Asif 
Published: September 2020

PurposeOver the past two decades, China’s outward foreign direct investment (OFDI) has risen remarkably. Whether such an increase affects the Chinese export diversification (ED) is a significant issue that has surprisingly remained unaddressed. This study aims to explain this issue that how OFDI plays a vital role in symmetric and asymmetric effects on its ED.Design/methodology/approachThe authors introduce a robust nonlinear autoregressive distributed lag (NARDL) model. Ironically, the purpose of this study is to analyze the symmetric and asymmetric effect of OFDI on ED.FindingsThe authors propose that growing OFDI would be more advantageous to China, rather than the policies of contraction. Therefore, the study provides valuable policy insights to consider the long-run asymmetric momentum given to ED by China’s OFDI.Originality/valueThe results of this study may seem to be an important newsletter for further policy discussion on how China can catch up on the benefits of ED through OFDI.
Integrated thinking: measuring the unobservable
Authors: Malafronte Irma , Pereira John 
Published: September 2020

PurposeThe purpose of this paper is to add to the growing literature on integrated thinking and reporting by exploring the challenges of measuring integrated thinking in academic research. It provides a review of previous studies, presents a proxy measure to quantify the level of integrated thinking and investigates companies’ approach towards integrated thinking in practice.Design/methodology/approachFirstly, this study proposes a measure to quantify the level of integrating thinking. Secondly, this study implements factor analysis to identify a parsimonious representation and explore the relevance of each variable in explaining the proposed measure of integrated thinking. Thirdly, this study implements cluster analysis to determine the natural grouping of firms with a certain level of integrated thinking and to identify the existence of distinctive companies’ approaches.FindingsThe findings suggest that the proposed measure of integrated thinking could be reduced into two main principal components that explain the current practices and the future direction. Firms’ integrated thinking practices can be clustered into groups denoting various practices among firms, and exhibit routine over time. Across clusters, firms reveal significantly different characteristics highlighting the existence of systematic demographic differences.Research limitations/implicationsThis research does not endeavour to overcome all the measurement issues related to integrated thinking. It attempts to measure the level and companies’ approaches towards integrated thinking that can inspire further empirical studies in this field.Originality/valueThis study answers the call for an empirical investigation of the internal aspects of integration. This paper provides academics, companies, and policymakers with a proxy measure of integrated thinking that can inspire empirical studies and advance the understanding of integrated thinking practices.