bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal performance of marine diatoms under contrasting nitrate availability
Authors: Aranguren-Gassis María , Litchman Elena 
Published: October 2020

Abstract
Environmental factors that interact with increasing temperature under the ongoing global warming are an urgent issue determining marine phytoplankton’s performance. Previous studies showed that nutrient limitation alters phytoplankton responses to temperature and may lower their temperature optima (Topt), making them more susceptible to high temperatures. The generality of this relationship is unknown, as very few species were tested. Here we investigated how growth rate depended on temperature at two contrasting nitrogen concentrations in six marine diatoms isolated from different thermal environments, including the tropics. Low nitrate had a significant effect on thermal performance in five of the six species. The effect size was larger around the optimum temperature for growth, resulting in flattened thermal performance curves but no shift in Topt. While that trend is independent of the thermal regime from which each species was isolated, the implications for the phytoplankton response to global warming may be region dependent.
Post-Partition Citizenship Policies: Lessons from Post-Yugoslav Federal States
Authors: Džankić Jelena , Keil Soeren 
Published: October 2020

AbstractCitizenship policies are important tools of inclusion and exclusion in a post-partition context. In most cases, they reflect the unitary and mono-ethnic character of newly established states. Their function in countries and territories where an ethnonational break-up resulted in further ethnically diverse societies is far more complex. Citizenship in multilevel states created through state disintegration is a counterintuitive combination of (1) the legacies of the old citizenship tradition and replications of the old federal structure, and (2) processes of ethnic engineering and designing group-centric citizenship regimes. Legacies of the old structure are framed by the modalities of break-up and initial determination of citizenry (e.g., the absence of zero solution), but strongly mirror elements of the previous multilevel construction of citizenship, including bottom-up derivation, ethno-national determination of membership, voting rights and representation. Discontinuities in citizenship policies reflect wider tensions between nation- and state-building (and destruction), and how these processes have been molded through different international influences. We undertake a case-study of two post-Yugoslav multilevel states, Bosnia and Herzegovina and the Federal Republic of Yugoslavia/the State Union of Serbia and Montenegro, with the intent of drawing broader conclusions on how citizenship policies can keep states together or break them apart.
Tuberculosis risk with biologics by screening-guided preventive strategy in rheumatoid arthritis under intermediate tuberculosis burden
Authors: Shin Anna , Lee Yun Jong , Lee Eun Bong , Song Yeong Wook , Kim Seoyoung C , Kang Eun Ha 
Published: October 2020

Abstract

Objectives
We aimed to compare tuberculosis (TB) risk during biologics treatment between patients with RA who did (prophylaxis) and did not (non-prophylaxis) undergo chemoprophylaxis following pre-biologic latent TB screening in Korea of an intermediate TB burden.

Methods
Using the 2002–16 Korea National Health Insurance database, we conducted a cohort study examining TB risk, defined by International Classification of Diseases Tenth Revision codes plus anti-TB drugs, among RA patients initiating a biologic drug with and without chemoprophylaxis after screening triage for latent TB. To control baseline confounding, we used propensity score-based fine stratification (PSS) and weighting. Cox proportional hazards models estimated hazard ratios and 95% CIs comparing TB risk between the prophylaxis vs non-prophylaxis groups.

Results
The PSS-weighted study cohort (mean age 57.0 years; 81.3% female) included 2249 and 7225 RA patients in the prophylaxis and non-prophylaxis groups, respectively. During 2.42 years of biologics treatment, 118 patients developed TB with the incidence rate per 100 person-years of 0.33 in the prophylaxis and 0.63 in the non-prophylaxis groups. The PSS-weighted hazard ratio (95% CI) for TB associated with the prophylaxis was 0.52 (0.32, 0.86). During the follow-up time, the incidence rate of TB remained consistently low in the prophylaxis group but it was highest in the first year, then time-dependently declined in the non-prophylaxis group.

Conclusion
This population-based cohort study warns that the current screening-based preventive strategy generates a substantially higher TB risk after biologics initiation among screening-negative patients compared with screening-positive patients receiving chemoprophylaxis, when the background TB burden is not low.
Morning brain: real-world neural evidence that high school class times matter
Authors: Dikker Suzanne , Haegens Saskia , Bevilacqua Dana , Davidesco Ido , Wan Lu , Kaggen Lisa , McClintock James , Chaloner Kim , Ding Mingzhou , West Tessa , Poeppel David 
Published: October 2020

Abstract
Researchers, parents and educators consistently observe a stark mismatch between biologically preferred and socially imposed sleep–wake hours in adolescents, fueling debate about high school start times. We contribute neural evidence to this debate with electroencephalogram data collected from high school students during their regular morning, mid-morning and afternoon classes. Overall, student alpha power was lower when class content was taught via videos than through lectures. Students’ resting state alpha brain activity decreased as the day progressed, consistent with adolescents being least attentive early in the morning. During the lessons, students showed consistently worse performance and higher alpha power for early morning classes than for mid-morning classes, while afternoon quiz scores and alpha levels varied. Together, our findings demonstrate that both class activity and class time are reflected in adolescents’ brain states in a real-world setting, and corroborate educational research suggesting that mid-morning may be the best time to learn.
Spatial Expression Pattern of ZNF391 Gene in the Brains of Patients With Schizophrenia, Bipolar Disorders or Major Depressive Disorder Identifies New Cross-Disorder Biotypes: A Trans-Diagnostic, Top-Down Approach
Authors: Ren Hongyan , Meng Yajing , Zhang Yamin , Wang Qiang , Deng Wei , Ma Xiaohong , Zhao Liansheng , Li Xiaojing , Wang Yingcheng , Sham Pak , Li Tao 
Published: October 2020

Abstract
The results generated from large psychiatric genomic consortia show us some new vantage points to understand the pathophysiology of psychiatric disorders. We explored the potential of integrating the transcription output of the core gene underlying the commonality of psychiatric disorders with a clustering algorithm to redefine psychiatric disorders. Our results showed that an extended MHC region was associated with the common factor of schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) at the level of genomic significance, with rs7746199 (P = 4.905e-08), a cis-eQTL to the gene ZNF391, pinpointed as a potential causal variant driving the signals in the region. Gene expression pattern of ZNF391 in the brain led to the emergence of 3 biotypes, independent of disorder. The 3 biotypes performed significantly differently in working memory and demonstrated different gray matter volumes in the right inferior frontal orbital gyrus (RIFOG), with a partial causal pathway arising from ZNF391 to RIFOG to working memory. Our study illustrates the potential of a trans-diagnostic, top-down approach in understanding the commonality of psychiatric disorders.
In silico design and automated learning to boost next-generation smart biomanufacturing
Authors: Carbonell Pablo , Le Feuvre Rosalind , Takano Eriko , Scrutton Nigel S 
Published: October 2020

Abstract
The increasing demand for bio-based compounds produced from waste or sustainable sources is driving biofoundries to deliver a new generation of prototyping biomanufacturing platforms. Integration and automation of the design, build, test and learn (DBTL) steps in centers like SYNBIOCHEM in Manchester and across the globe (Global Biofoundries Alliance) are helping to reduce the delivery time from initial strain screening and prototyping towards industrial production. Notably, a portfolio of producer strains for a suite of material monomers was recently developed, some approaching industrial titers, in a tour de force by the Manchester Centre that was achieved in less than 90 days. New in silico design tools are providing significant contributions to the front end of the DBTL pipelines. At the same time, the far-reaching initiatives of modern biofoundries are generating a large amount of high-dimensional data and knowledge that can be integrated through automated learning to expedite the DBTL cycle. In this Perspective, the new design tools and the role of the learning component as an enabling technology for the next generation of automated biofoundries are discussed. Future biofoundries will operate under completely automated DBTL cycles driven by in silico optimal experimental planning, full biomanufacturing devices connectivity, virtualization platforms and cloud-based design. The automated generation of robotic build worklists and the integration of machine-learning algorithms will collectively allow high levels of adaptability and rapid design changes toward fully automated smart biomanufacturing.
Cohabitation des intérêts des créanciers et des actionnaires de la société anonyme dans la protection du capital social: quid de la législation burundaise et de l’espace OHADA?
Authors: Nzohabonayo Anaclet 
Published: October 2020

Abstract
Les intérêts des actionnaires et des créanciers sont moins antagonistes qu’ils le paraissent en dépit des différences les caractérisant. Les premiers n’existent pas sans les seconds et vice versa. Dès lors, seule une protection concurrente de ces intérêts constitue le soubassement de la confiance de ces partenaires et le garant de la continuité de l’exploitation de la société. Cette réflexion est organisée autour de l’analyse des aménagements mis en place dans le code burundais des sociétés privées et à participation publique et dans l’acte uniforme de l’OHADA portant droit des sociétés commerciales et groupement d’intérêt économique pour assurer une cohabitation fructueuse des intérêts des partenaires suscités dans la protection du capital social. La forme juridique qui sert de cadre d’analyse est la société anonyme.
En explicitant les mécanismes de protection des intérêts des actionnaires et des créanciers, cette analyse met en lumière les principes de protection du capital social et des intérêts de ceux qui participent à sa formation. L’étude se veut un ingrédient indispensable pour maintenir la performance financière de la société. Étant par essence comparative, cette réflexion expose les textes commentés et est par conséquent susceptible de susciter les commentaires pouvant provoquer leur relecture par les décideurs.
De l’ensemble de l’analyse, il s’avère que les principes qui protègent les intérêts des actionnaires préservent aussi par ricochet les intérêts des créanciers et vice versa. Il y a donc une interdépendance entre ces principes qui converge vers la protection du capital, centre d’intérêt des partenaires de la SA.
Additional analyses exploring the hypothesized transdifferentiation of plasmablasts to developing neutrophils in severe COVID-19
Authors: Wilk Aaron J. , Rustagi Arjun , Zhao Nancy Q. , Martin Beth A. , Rogers Angela J. , Blish Catherine A. 
Published: October 2020

AbstractWe thank Alquicira-Hernandez et al. for their reanalysis of our single-cell transcriptomic dataset profiling peripheral immune responses to severe COVID-19. We agree that careful analysis of single-cell sequencing data is important for generating cogent hypotheses but find several aspects of their criticism of our analysis to be problematic. Here we respond briefly to misunderstandings and inaccuracies in their commentary that may have led to misinformed interpretation of our results.
Deep-learning based fully automatic segmentation of the globus pallidus interna and externa using ultra-high 7 Tesla MRI
Authors: Solomon Oren , Palnitkar Tara , Patriat Remi , Braun Henry , Aman Joshua , Park Michael C. , Vitek Jerry , Sapiro Guillermo , Harel Noam 
Published: October 2020

AbstractDeep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson’s disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this work, we present a deep-learning based neural network, which we term GP-net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP-net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP-net performs 3D inference in a patient-specific manner, alleviating the need for atlas-based segmentation. GP-net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state-of-the-art atlas-based segmentations. We also demonstrate a post-operative lead location assessment with respect to a segmented globus pallidus obtained by GP-net.
Multivalency transforms SARS-CoV-2 antibodies into broad and ultrapotent neutralizers
Authors: Rujas Edurne , Kucharska Iga , Tan Yong Zi , Benlekbir Samir , Cui Hong , Zhao Tiantian , Wasney Gregory A. , Budylowski Patrick , Guvenc Furkan , Newton Jocelyn C. , Sicard Taylor , Semesi Anthony , Muthuraman Krithika , Nouanesengsy Amy , Prieto Katherine , Bueler Stephanie A. , Youssef Sawsan , Liao-Chan Sindy , Glanville Jacob , Christie-Holmes Natasha , Mubareka Samira , Gray-Owen Scott D. , Rubinstein John L. , Treanor Bebhinn , Julien Jean-Philippe 
Published: October 2020

AbstractThe novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19), has caused a global pandemic. Antibodies are powerful biotherapeutics to fight viral infections; however, discovery of the most potent and broadly acting clones can be lengthy. Here, we used the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC50) values as low as 9 × 10−14M were achieved as a result of up to 10,000-fold potency enhancements. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and Ig-likein vivobioavailability. This MULTi-specific, multi-Affinity antiBODY (Multabody; or MB) platform contributes a new class of medical countermeasures against COVID-19 and an efficient approach to rapidly deploy potent and broadly-acting therapeutics against infectious diseases of global health importance.One Sentence Summarymultimerization platform transforms antibodies emerging from discovery screens into potent neutralizers that can overcome SARS-CoV-2 sequence diversity.
Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score
Authors: Sen S. , Sanders E.C. , Gabriel K.N. , Miller B.M. , Isoda H.M. , Salcedo G.S. , Garrido J.E. , Dyer R.P. , Nakajima R. , Jain A. , Caldaruse A.-M. , Santos A.M. , Bhuvan K. , Tifrea D.F. , Ricks-Oddie J.L. , Felgner P.L. , Edwards R.A. , Majumdar S. , Weiss G.A. 
Published: October 2020

AbstractEffective methods for predicting COVID-19 disease trajectories are urgently needed. Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the ICU, requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within six days post-symptom onset and sometimes within one day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 Likelihood Ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention.Significance statementThe COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.
Functional spreading of hyperexcitability induced by human and synthetic intracellular Aβ oligomers
Authors: Fernandez-Perez Eduardo J. , Muñoz Braulio , Bascuñan Denisse A. , Peters Christian , Riffo-Lepe Nicolas O. , Espinoza Maria P. , Morgan Peter J. , Filippi Caroline , Bourboulou Romain , Sengupta Urmi , Kayed Rakez , Epsztein Jérôme , Aguayo Luis G. 
Published: October 2020

AbstractBackgroundIntracellular amyloid-beta oligomers (iAβo) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimer’s disease (AD). However, to date, no mechanism linking them has been reported.MethodsHere, the effects of human AD brain-derived (h-iAβo) and synthetic (iAβo) peptides on synaptic currents and action potential (AP) firing were investigated in hippocampal neuronsin vitro, ex vivoandin vivo.ResultsStarting from 500 pM, iAβo rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-related fluorescence changes indicated that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iAβo, indicating that iAβo can increase network excitability at a distance. Current-clamp recordings suggested that iAβo increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties.ConclusionThese results strongly indicate that iAβo causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offer an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.
Highly efficient CRISPR-Cas9-mediated gene knockout in primary human B cells for functional genetic studies of Epstein-Barr virus infection
Authors: Akidil Ezgi , Albanese Manuel , Buschle Alexander , Ruhle Adrian , Keppler Oliver T. , Hammerschmidt Wolfgang 
Published: October 2020

AbstractGene editing is now routine in all prokaryotic and metazoan cells but has not received much attention in immune cells when the CRISPR-Cas9 technology was introduced in the field of mammalian cell biology less than ten years ago. This versatile technology has been successfully adapted for gene modifications in human myeloid cells and T cells, among others, but applications to human primary B cells have been scarce and limited to activated B cells. This limitation has precluded conclusive studies into cell activation, differentiation or cell cycle control in this cell type. We report on highly efficient, simple and rapid genome engineering in primary resting human B cells using nucleofection of Cas9 ribonucleoprotein complexes. We provide proof-of-principle of gene editing in quiescent human B cells using two model genes:CD46andCDKN2A. The latter encodes the cell cycle regulator p16INK4awhich is an important target of Epstein-Barr virus (EBV). Infection of B cells carrying a knockout ofCDKN2Awith wildtype and EBNA3 oncoprotein mutant strains of EBV allowed us to conclude that EBNA3C controlsCDKN2A, the only barrier to B cell proliferation in EBV infected cells. Together, this approach enables efficient targeting of specific gene loci in quiescent human B cells supporting basic research as well as immunotherapeutic strategies.Author summaryHuman hematopoietic stem cells and their derivatives of the myeloid and lymphoid lineages are important targets for gene correction or modifications using the CRISPR-Cas9 technology. Among others, this approach can support site-specific insertion of chimeric antigen receptors (CARs) or T cell receptors (TCRs) into primary T cells. Their subsequent adoptive transfer to patient donors is a promising immunotherapeutic concept that may control chronic infection or certain types of cancer. Human B cells have a similar potential but, in contrast to T cells, they are very sensitive, difficult to handle, and short-livedex vivoprecluding their genetic modification. Here, we provide means to manipulate primary human B cells genetically usingin vitroassembled Cas9 ribonucleoprotein complexes and electroporation for their delivery. Our study demonstrates near-to-complete loss of a model target gene and provides examples to evaluate a cellular gene with a critical role during infection with Epstein-Barr virus (EBV).