bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Anti-SARS-CoV-2 Convalescent Plasma in Patients Admitted for COVID-19: A Randomized Phase II Clinical Trial
Authors: Balcells María Elvira , Rojas Luis , Le Corre Nicole , Martínez-Valdebenito Constanza , Ceballos María Elena , Ferrés Marcela , Chang Mayling , Vizcaya Cecilia , Mondaca Sebastián , Huete Álvaro , Castro Ricardo , Sarmiento Mauricio , Villarroel Luis , Pizarro Alejandra , Ross Patricio , Santander Jaime , Lara Barbara , Ferrada Marcela , Vargas-Salas Sergio , Beltrán-Pavez Carolina , Soto-Rifo Ricardo , Valiente-Echeverría Fernando , Caglevic Christian , Mahave Mauricio , Selman Carolina , Gazitúa Raimundo , Briones José Luis , Villarroel-Espindola Franz , Balmaceda Carlos , Espinoza Manuel A. , Pereira Jaime , Nervi Bruno 
Published: September 2020

AbstractBackgroundConvalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression.MethodsOpen-label, single-center, randomized clinical trial performed in an academic center in Santiago, Chile from May 10, 2020, to July 18, 2020, with final follow-up August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptoms onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted in immediate CP (early plasma group) versus no CP unless developing pre-specified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days or death. Key secondary outcomes included: time to respiratory failure, days of mechanical ventilation, hospital length-of-stay, mortality at 30 days, and SARS-CoV-2 RT-PCR clearance rate.ResultsOf 58 randomized patients (mean age, 65.8 years, 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We found no benefit in the primary outcome (32.1% vs 33.3%, OR 0.95, 95% CI 0.32-2.84, p>0.99) in the early versus deferred CP group. In-hospital mortality rate was 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), mechanical ventilation 17.9% vs 6.7% (OR 3.04, 95% CI 0.54-17.2, p=0.25), and prolonged hospitalization 21.4% vs 30% (OR 0.64, 95%CI, 0.19-2.1, p=0.55) in early versus deferred CP group, respectively. Viral clearance rate on day 3 (26% vs 8%, p=0.20) and day 7 (38% vs 19%, p=0.37) did not differ between groups. Two patients experienced serious adverse events within 6 or less hours after plasma transfusion.ConclusionImmediate addition of CP therapy in early stages of COVID-19 -compared to its use only in case of patient deterioration-did not confer benefits in mortality, length of hospitalization or mechanical ventilation requirement.Clinical Trials RegistrationNCT04375098
The epidemiological characteristics of COVID-19 in Libya during the ongoing-armed conflict
Authors: Daw Mohamed Ali , El-Bouzedi Abdallah Hussean , Ahmed Mohamed Omar , Alejenef Ali Ali 
Published: September 2020

AbstractIntroductionCOVID-19 can have even more dire consequences in countries with ongoing armed conflict. Libya, the second largest African country, has been involved in a major conflict since 2011. This study analyzed the epidemiological situation of the COVID-19 pandemic in Libya, examined the impact of the armed conflict in Libya on the spread of the pandemic, and proposes strategies for dealing with the pandemic during this conflict.MethodsWe collected the available information on all COVID-19 cases in the different regions of Libya, covering the period from March 25 to May 25, 2020. The cumulative number of cases and the daily new cases are presented in a way to illustrate the patterns and trends of COVID-19 and the effect of the ongoing armed conflict was assessed regionally.ResultsA total of 698 cases of COVID-19 were reported in Libya during a period of three months. The number of cases varied from one region to another and was affected by the fighting. The largest number of cases was reported in the southern part of the country, which has been severely affected by the conflict in comparison to the eastern and western parts of the country.ConclusionThis study describes the epidemiological pattern of COVID-19 in Libya and how it has been affected by the ongoing armed conflict. This conflict seems to have hindered access to populations and thereby masked the true dimensions of the pandemic. Hence, efforts should be combined to combat these consequences.
Aerosol emission of child voices during speaking, singing and shouting
Authors: Mürbe Dirk , Kriegel Martin , Lange Julia , Schumann Lukas , Hartmann Anne , Fleischer Mario 
Published: September 2020

AbstractSince the outbreak of the COVID-19 pandemic, singing activities for children and young people have been strictly regulated with far-reaching consequences for music education in schools and ensemble and choir singing in some places. This is also due to the fact, that there has been no reliable data available on aerosol emissions from children’s speaking, singing, and shouting. By utilizing a laser particle counter in cleanroom conditions we show, that children emit fewer aerosols during singing than what has been known so far for adults. In our data, the emission rates ranged from 16 P/s to 267 P/s for speaking, 141 P/s to 1240 P/s for singing, and 683 P/s to 4332 P/s for shouting. The data advocate an adaptation of existing risk management strategies and rules of conduct for groups of singing children, like gatherings in an educational context, e.g. singing lessons or choir rehearsals.
Ductal Carcinoma In Situ with Diffuse Growth Distribution: A Potentially Lethal Subtype of “Preinvasive” Disease
Authors: O’Keefe Thomas J , Harismendy Olivier , Wallace Anne M 
Published: September 2020

AbstractPURPOSEThe current trend in ductal carcinoma in situ (DCIS) research is towards treatment de-escalation. Problematically, prognostic indicators for patients at high risk of breast cancer mortality (BCM), rather than recurrence, have not been identified. We aim to identify prognostic factors for the development of metastatic disease and mortality.EXPERIMENTAL DESIGNPatients diagnosed with DCIS in a local cancer registry as well as in the National Cancer Database (NCDB) and the Surveillance, Epidemiology and End Results (SEER) program were assessed for factors prognostic of metastatic disease, overall, and breast-cancer specific survival. Cox and competing risks regressions were developed.RESULTSAmong 5 patients who developed distant metastatic disease in the cancer registry, 3 had identifiable growth distribution; all 3 were diffuse type. None had in-breast invasive or DCIS recurrences before metastasis. In NCDB and SEER, cumulative incidence of any cause mortality (ACM) and BCM at 10 years was 12%/5.0% for diffuse lesions; 8%/3.6% for patients with microinvasive disease, 7.4%/2.3% for lesions >5 cm, 5.6%/1.4% for lesions 2-5 cm and 5.5%/1.5% for lesions <2 cm. Multivariate hazard ratios for ACM in NCDB and BCM in SEER were 2.0 and 5.3 (p=0.03 and 0.02, respectively). Among patients with diffuse lesions, cumulative incidence ACM at 10 years was 15.0% among those undergoing unilateral mastectomy vs. 2.5% among those undergoing bilateral mastectomy (p=0.11).CONCLUSIONDiffuse DCIS represents an uncommon but deadly subtype for whom treatment escalation, rather than de-escalation, is likely necessary. Further studies elucidating the mechanism of metastasis and best treatment course are needed.
In-concert immune dynamics during natural influenza virus infection and recovery in acute hospitalized patients
Authors: Nguyen Thi H.O. , Koutsakos Marios , van de Sandt Carolien E. , Crawford Jeremy Chase , Loh Liyen , Sant Sneha , Grzelak Ludivine , Allen Emma K. , Brahm Tim , Clemens E. Bridie , Auladell Maria , Hensen Luca , Wang Zhongfang , Nüssing Simone , Jia Xiaoxiao , Günther Patrick , Wheatley Adam K. , Kent Stephen J. , Aban Malet , Deng Yi-Mo , Laurie Karen L. , Hurt Aeron C. , Gras Stephanie , Rossjohn Jamie , Crowe Jane , Xu Jianqing , Jackson David , Brown Lorena E. , Gruta Nicole La , Chen Weisan , Doherty Peter C. , Turner Stephen J. , Kotsimbos Tom C. , Thomas Paul G. , Cheng Allen C. , Kedzierska Katherine 
Published: September 2020

AbstractWe report in-concert dynamics of 18 key immune parameters, related to clinical, genetic and virological factors, in patients hospitalized with influenza across different severity levels. Influenza disease was associated with correlated increases in IL6/IL-8/MIP-1α/β cytokines and lower antibody responses. Robust activation of circulating T follicular helper cells (cTfhs) correlated with peak antibody-secreting cells (ASC) and influenza heamaglutinin-specific memory B-cell numbers, which phenotypically differed from vaccination-induced B-cell responses. Influenza-specific CD8+/CD4+T-cells increased early in disease and remained activated during patient recovery. Here, we describe the broadest to-date immune cellular networks underlying recovery from influenza infection, highly relevant to other infectious diseases.
WASP: A software package for correctly characterizing the topological development of ribbon structures
Authors: Sierzega Zachary , Wereszczynski Jeff , Prior Chris 
Published: September 2020

ABSTRACTWe introduce the Writhe Application Software Package (WASP) which can be used to characterise the topology of ribbon structures, the underlying mathematical model of DNA, Biopolymers, superfluid vorticies, elastic ropes and magnetic flux ropes. This characterisation is achieved by the general twist-writhe decomposition of both open and closed ribbons, in particular through a quantity termed the polar writhe. We demonstrate how this decomposition is far more natural and straightforward than artificial closure methods commonly utilized in DNA modelling. In particular, we demonstrate how the decomposition of the polar writhe in local and non-local components distinctly characterizes local helical structure and knotting/linking of the ribbon. This decomposition provides additional information not given by alternative approaches. As an example application, the WASP routines are used to characterise the evolving topology (writhe) of DNA minicircle and open ended plectoneme formation magnetic/optical tweezer simulations. Finally it is demonstrated that a number of well known alternative writhe expressions are actually simplifications of the polar writhe measure.
Deorphanisation of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning
Authors: Morud Julia , Hardege Iris , Liu He , Wu Taihong , Basu Swaraj , Zhang Yun , Schafer William R 
Published: September 2020

SummaryPentameric ligand-gated ion channels (LGCs) play conserved, critical roles in fast synaptic transmission, and changes in LGC expression and localisation are thought to underlie many forms of learning and memory. TheC. elegansgenome encodes a large number of LGCs without a known ligand or function. Here, we deorphanize five members of a family of Cys-loop LGCs by characterizing their diverse functional properties that are activated by biogenic amine neurotransmitters. To analyse the neuronal function of these LGCs, we show that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning.lgc-50mutants show a specific defect in learned olfactory avoidance of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the expression of LGC-50 in neuronal processes is enhanced by olfactory conditioning; thus, the regulated expression of these receptors at synapses appears to represent a molecular cornerstone of the learning mechanism.
High-sensitivity vision restoration via ectopic expression of chimeric rhodopsin in mice
Authors: Katada Yusaku , Yoshida Kazuho , Serizawa Naho , Kobayashi Kenta , Neghisi Kazuno , Okano Hideyuki , Kandori Hideki , Tsubota Kazuo , Kurihara Toshihide 
Published: September 2020

AbstractPhotoreception requires amplification by mammalian rhodopsin through G protein activation, which requires a visual cycle. To achieve this in retinal gene therapy, we incorporated human rhodopsin cytoplasmic loops intoGloeobacterrhodopsin, thereby generatingGloeobacterand human chimeric rhodopsin (GHCR). In a murine model of inherited retinal degeneration, we induced retinal GHCR expression by intravitreal injection of a recombinant adeno-associated virus vector. Retinal explant and visual thalamus electrophysiological recordings, behavioral tests, and histological analysis showed that GHCR restored dim-environment vision and prevented the progression of retinal degeneration. Thus, GHCR may be a potent clinical tool for the treatment of retinal disorders.One Sentence SummaryOptogenetic therapy with Gloeobacter and human chimeric rhodopsin resulted in highly sensitive visual restoration and protection effects.
DNA Methylation Reprogramming during Sex Determination and Transition in Zebrafish
Authors: Wang Xinxin , Ma Xin , Wei Gaobo , Ma Weirui , Zhang Zhen , Chen Xuepeng , Gao Lei , Liu Zhenbo , Yuan Yue , Yi Lizhi , Wang Jun , Tokumoto Toshinobu , Huang Junjiu , Chen Dahua , Zhang Jian , Liu Jiang 
Published: September 2020

AbstractIt is a mystery about sex determination and sexual plasticity in species without sex chromosomes. DNA methylation is a prevalent epigenetic modification in vertebrates, which has been shown to involve in the regulation of gene expression and embryo development. However, it remains unclear about how DNA methylation regulates sexual development. To elucidate it, we used zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We revealed that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germline development and set to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When blocking DNMTs activity in juveniles after 9 dpf, the zebrafish preferably develops into females. We also show thatTet3involves in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMTs activity can prevent the female-to-male sex transition, suggesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germline development and sexual plasticity.
Conserved Arginine Residues in Synaptotagmin 1 Regulate Fusion Pore Expansion Through Membrane Contact
Authors: Nyenhuis Sarah B. , Karandikar Nakul , Kiessling Volker , Kreutzberger Alex , Thapa Anusa , Liang Binyong , Tamm Lukas , Cafiso David S. 
Published: September 2020

AbstractSynaptotagmin 1 is a vesicle-anchored membrane protein that functions as the Ca2+sensor for synchronous neurotransmitter release. In this work, an arginine containing region in the second C2 domain of synaptotagmin 1 (C2B) is shown to control the expansion of the fusion pore and thereby the concentration of neurotransmitter released. This arginine apex, which is opposite the Ca2+binding sites, interacts with membranes or membrane reconstituted SNAREs; however, only the membrane interactions occur under the conditions in which fusion takes place. Other regions of C2B influence the probably and kinetics of fusion but do not control the expansion of the fusion pore. These data indicate that the C2B domain has at least two distinct molecular roles in the fusion event, and the data are consistent with a novel model where the arginine apex of C2B positions the domain at the curved membrane surface of the expanding fusion pore.
Including intraspecific trait variability to avoid distortion of functional diversity and ecological inference: lessons from natural assemblages
Authors: Wong Mark K. L. , Carmona Carlos P. 
Published: September 2020

ABSTRACTFunctional diversity assessments are crucial and increasingly used for understanding ecological processes and managing ecosystems. The functional diversity of a community is assessed by sampling traits at one or more scales (individuals, populations, species) and calculating a summary index of the variation in trait values. However, it remains unclear how the scale at which traits are sampled and the indices used to estimate functional diversity may alter the patterns observed and inferences about ecological processes.For 40 plant and 61 ant communities, we assess functional diversity using six methods – encompassing various mean-based and probabilistic methods – chosen to reflect common scenarios where different levels of detail are available in trait data. We test whether including trait variability at different scales (from individuals to species) alter functional diversity values calculated using volume-based and dissimilarity-based indices, Functional Richness (FRic) and Rao, respectively. We further test whether such effects alter the functional diversity patterns observed across communities and their relationships with environmental drivers such as abiotic gradients and occurrences of invasive species.Intraspecific trait variability strongly determined FRic and Rao. Methods using only species’ mean trait values to calculate FRic (convex hulls) and Rao (Gower-based dissimilarity) distorted the patterns observed when intraspecific trait variability was considered. These distortions generated Type I and Type II errors for the effects of environmental factors structuring the plant and ant communities.The high sensitivity of FRic to individuals with extreme trait values was revealed in comparisons of different probabilistic methods including among-individual and among-population trait variability in functional diversity. By contrast, values and ecological patterns in Rao were consistent among methods including different scales of intraspecific trait variability.Decisions about where traits are sampled and how trait variability is included in functional diversity can drastically change the patterns observed and conclusions about ecological processes. We recommend sampling the traits of multiple individuals per species and capturing their intraspecific trait variability using probabilistic methods. We discuss how intraspecific trait variability can be reasonably estimated and included in functional diversity in the common circumstance where only limited trait data are available.
Release of insulin granules by simultaneous, high-speed correlative SICM-FCM
Authors: Bednarska Joanna , Novak Pavel , Korchev Yuri , Rorsman Patrik , Tarasov Andrei I. , Shevchuk Andrew 
Published: September 2020

SummaryExocytosis of peptides and steroids stored in a dense core vesicular (DCV) form is the final step of every secretory pathway, indispensable for the function of nervous, endocrine and immune systems. The lack of live imaging techniques capable of direct, label-free visualisation of DCV release makes many aspects of the exocytotic process inaccessible to investigation. We describe the application of correlative scanning ion conductance and fluorescence confocal microscopy (SICM-FCM) to study the exocytosis of individual granules of insulin from the top, non-adherent, surface of pancreatic β-cells. Using SICM-FCM, we were first to directly follow the topographical changes associated with physiologically-induced release of insulin DCVs. This allowed us to report the kinetics of the full fusion of the insulin vesicle as well as the subsequent solubilisation of the released insulin crystal.
Identification and Characterization of a Residual Host Cell Protein Hexosaminidase B Associated with N-glycan Degradation During the Stability Study of a Therapeutic Recombinant Monoclonal Antibody Product
Authors: Li Xuanwen , An Yan , Liao Jing , Xiao Li , Swanson Michael , Martinez-Fonts Kirby , Pavon Jorge Alexander , Sherer Edward C. , Jawa Vibha , Gao Xinliu , Letarte Simon , Richardson Douglas D. 
Published: September 2020

AbstractHost cell proteins (HCPs) are process-related impurities derived from host organisms, which need to be controlled to ensure adequate product quality and safety. In this study, product quality attributes were tracked for several mAbs under the intended storage and accelerated stability conditions. One product quality attribute not expected to be stability indicating is the N-glycan heterogeneity profile. However, significant N-glycan degradation was observed for one mAbs under accelerated and stressed stability conditions. The root cause for this instability was attributed to Hexosaminidase B (HEXB), an enzyme known to remove terminal N-acetylglucosamine (GlcNAc). HEXB was identified by liquid chromatography–mass spectrometry (LC-MS) based proteomics approach to be enriched in the impacted stability batches from mAb-1. Subsequently, enzymatic and targeted multiple reaction monitoring (MRM) MS assays were developed to support process and product characterization. A potential interaction between HEXB and mAb-1 was initially observed from the analysis of process intermediates by proteomics among several mAbs and later supported by computational modeling. An improved bioprocess was developed to significantly reduce HEXB levels in the final drug substance. A risk assessment was conducted by evaluating thein silicoimmunogenicity risk and the impact on product quality. To the best of our knowledge, HEXB is the first residual HCP reported to have impact on the glycan profile of a formulated drug product. The combination of different analytical tools, mass spectrometry and computational modeling provide a general strategy on how to study residual HCP for biotherapeutics development.