bluuebunny/crossref_metadata_2025_split huggingface dataset:
Curative Surgery and Ki-67 Value Rather Than Tumor Differentiation Predict the Survival of Patients With High-grade Neuroendocrine Neoplasms
Authors: Asano Daisuke , Kudo Atsushi , Akahoshi Keiichi , Maekawa Aya , Murase Yoshiki , Ogawa Kosuke , Ono Hiroaki , Ban Daisuke , Tanaka Shinji , Tanabe Minoru 
Published: September 2020

Objective:
To elucidate the role of surgery in patients with high-grade neuroendocrine neoplasms (hg-NENs) and Ki-67 more than 20%.

Background:
Although surgery is the first treatment choice in patients with low-grade NENs, whether it increases the survival of patients with hg-NENs is debatable.

Methods:
Between 2005 and 2018, 63 patients pathologically diagnosed with hg-NENs treated at our institution were retrospectively analyzed. The risk factors for overall survival (OS) and recurrence-free survival were analyzed, and OS was compared between each treatment group.

Results:
The median observation time was 21.2 months, and the median Ki-67 value was 52%. Patients with hg-NENs were classified into low Ki-67 (Ki-67 <52%) and high Ki-67 (Ki-67 ≥52%) groups. Multivariate analysis for OS identified surgery (P = 0.013) and low Ki-67 value (P = 0.007) as independent risk factors, whereas morphological differentiation defined by the WHO 2017 criteria showed no association with OS. Patients with low Ki-67 value subjected to R0/1, R2, and chemotherapy had a median survival time of 83.8, 16.6, and 28.1 months, respectively. The median survival time for R0/1 group was significantly longer than that for chemotherapy group (P = 0.001). However, no difference in survival was reported between patients from R0/1 and chemotherapy groups with high Ki-67. Ki-67 value could determine recurrence-free survival (P = 0.006) in patients who underwent R0/1 surgery for pancreatic hg-NENs.

Conclusions:
R0/1 surgery predicted prognoses in the low Ki-67 group. The indication of surgery for patients with hg-NENs did not depend on tumor differentiation.
Estimating Risk of Mechanical Ventilation and Mortality Among Adult COVID-19 patients Admitted to Mass General Brigham: The VICE and DICE Scores
Authors: Nicholson Christopher J. , Wooster Luke , Sigurslid Haakon H. , Li Rebecca F. , Jiang Wanlin , Tian Wenjie , Cardenas Christian L. Lino , Malhotra Rajeev 
Published: September 2020

AbstractBackgroundRisk stratification of COVID-19 patients upon hospital admission is key for their successful treatment and efficient utilization of hospital resources.ObjectiveTo evaluate the risk factors associated with ventilation need and mortality.Design, setting and participantsWe established a retrospective cohort of COVID-19 patients from Mass General Brigham hospitals. Demographic, clinical, and admission laboratory data were obtained from electronic medical records of patients admitted to hospital with laboratory-confirmed COVID-19 before May 19th, 2020. Using patients admitted to Massachusetts General Hospital (MGH, derivation cohort), multivariable logistic regression analyses were used to construct the Ventilation in COVID Estimator (VICE) and Death in COVID Estimator (DICE) risk scores.MeasurementsThe primary outcomes were ventilation status and death.ResultsThe entire cohort included 1042 patients (median age, 64 years; 56.8% male). The derivation and validation cohorts for the risk scores included 578 and 464 patients, respectively. We found seven factors to be independently predictive for ventilation requirement (diabetes mellitus, dyspnea, alanine aminotransferase, troponin, C-reactive protein, neutrophil-lymphocyte ratio, and lactate dehydrogenase), and 10 factors to be predictors of in-hospital mortality (age, sex, diabetes mellitus, chronic statin use, albumin, C-reactive protein, neutrophil-lymphocyte ratio, mean corpuscular volume, platelet count, and procalcitonin). Using these factors, we constructed the VICE and DICE risk scores, which performed with C-statistics of at least 0.8 in our cohorts. Importantly, the chronic use of a statin was associated with protection against death due to COVID-19. The VICE and DICE score calculators have been placed on an interactive website freely available to the public (https://covid-calculator.com/).LimitationsOne potential limitation is the modest sample sizes in both our derivation and validation cohorts.ConclusionThe risk scores developed in this study may help clinicians more appropriately determine which COVID-19 patients will need to be managed with greater intensity.
Exposure to stressors and antimicrobials induces cell-autonomous ultrastructural heterogeneity of an intracellular bacterial pathogen
Authors: Schulte Marc , Hensel Michael , Miskiewicz Katarzyna 
Published: September 2020

AbstractDespite being clonal, bacterial pathogens show a remarkable physiological heterogeneity during infection of host and within host cells. This diversity is reflected by distinct ultrastructural morphotypes in transmission electron microscopy (TEM). Gram-negative bacteria visualized at high resolution by TEM show a rather simple composition of cytoplasm with a centrally located nucleoid and large number of ribosomes. The cytoplasm is separated from the external environment by inner and outer membranes. In this study, we show that individual cells ofSalmonella entericaserovar Typhimurium (STM) are ultrastructural divergent in standard culture conditions, as well as during their intracellular lifestyle in mammalian host cells. STM can basically be discriminated into two morphotypes based on the criterion of cytoplasmic density. We identified environmental conditions which affect cytoplasmic densities. Using chemical treatments and defined mutant strains, we were able to link the occurrence of an electron-dense type to oxidative stress and other noxes. Furthermore, ultrastructural analyses of STM during infection and fluorescence reporter analyses for cell viability were combined in a correlative light and electron microscopy approach. We provide evidence that two newly characterized ultrastructural types with lucent or dense cytoplasm represent viable cells. Moreover, the presence of electron-dense types is stress related and can be experimentally induced only when amino acids are available in the environment. This study sheds more light on diversities between individual bacteria in populations and possible physiological meanings like a stress response to explain the diversities discussed.ImportanceBacterial pathogens show a remarkable resilience to adverse conditions during infection. Although being genetically identical, a clonal population may contain dead, dormant, slowly as well as rapidly proliferating cells. The physiological state of individual cells in a population may be analyzed by fluorescent probes or reporters. In contrast, reliable markers to interrogate single cells regarding viability, response to environmental cues, and exposure to antimicrobial compounds are sparse for ultrastructural approaches. For intracellularSalmonella entericawe observed distinct ultrastructural morphotypes. Using defined experimental conditions, these morphotypes were linked to reactions of bacteria to stressors or antimicrobials. The parameters defined here provide criteria for the interpretation of bacterial heterogeneity on the ultrastructural level.
Physcraper: a python package for continual update of evolutionary estimates using the Open Tree of Life
Authors: Reyes Luna L. Sanchez , Kandziora Martha , McTavish Emily Jane 
Published: September 2020

AbstractPhylogenies are a key part of research in many areas of biology. Tools that automate some parts of the process of phylogenetic reconstruction, mainly molecular character matrix assembly, have been developed for the advantage of both specialists in the field of phylogenetics and nonspecialists. However, interpretation of results, comparison with previously available phylogenetic hypotheses, and selection of one phylogeny for downstream analyses and discussion still impose difficulties to one that is not a specialist either on phylogenetic methods or on a particular group of study.Physcraper is a command-line Python program that automates the update of published phylogenies by adding public DNA sequences to underlying alignments of previously published phylogenies. It also provides a framework for straightforward comparison of published phylogenies with their updated versions, by leveraging upon tools from the Open Tree of Life project to link taxonomic information across databases.Physcraper can be used by the nonspecialist, as a tool to generate phylogenetic hypotheses based on publicly available expert phylogenetic knowledge. Phylogeneticists and taxonomic group specialists will find it useful as a tool to facilitate molecular dataset gathering and comparison of alternative phylogenetic hypotheses (topologies).The Physcraper workflow demonstrates the benefits of doing open science for phylogenetics, encour-aging researchers to strive for better sharing practices. Physcraper can be used with any OS and is released under an open-source license. Detailed instructions for installation and use are available athttps://physcraper.readthedocs.
CCP1, a tubulin deglutamylase, increases survival of rodent spinal cord neurons following glutamate-induced excitotoxicity
Authors: Ramadan Yasmin H. , Gu Amanda , Ross Nicole , McEwan Sara A. , Barr Maureen M. , Firestein Bonnie L. , O’Hagan Robert 
Published: September 2020

AbstractMicrotubules (MTs) are cytoskeletal elements that provide structural support, establish morphology, and act as roadways for intracellular transport in cells. Neurons extend and must maintain long axons and dendrites to transmit information through the nervous system. Therefore, in neurons, the ability to independently regulate cytoskeletal stability and MT-based transport in different cellular compartments is essential. Post-translational modification of MTs is one mechanism by which neurons can regulate the cytoskeleton.The carboxypeptidase CCP1 negatively regulates post-translational glutamylation of MTs. We previously demonstrated that the CCP1 homolog inC. elegansis important for maintenance of cilia. In mammals, loss of CCP1, and the resulting hyperglutamylation of MTs, causes neurodegeneration. It has long been known that CCP1 expression is activated by neuronal injury; however, whether CCP1 plays a neuroprotective role after injury is unknown. Furthermore, it not yet clear whether CCP1 acts on ciliary MTs in spinal cord neurons.Using anin vitromodel of excitotoxic neuronal injury coupled with shRNA-mediated knockdown of CCP1, we demonstrate that CCP1 protects neurons from excitotoxic death. Unexpectedly, excitotoxic injury reduced CCP1 expression in our system, and knockdown of CCP1 did not result in loss or shortening of cilia in cultured spinal cord neurons. Our results suggest that CCP1 acts on axonal and dendritic MTs to promote cytoskeletal rearrangements that support neuroregeneration and that enzymes responsible for glutamylation of MTs might be therapeutically targeted to prevent excitotoxic death after spinal cord injuries.
Cerebrospinal fluids from healthy pregnant women does not harbor a detectable microbial community
Authors: Kang Yongyong , Ji Xinchao , Guo Li , Xia Han , Yang Xiaofei , Xie Zhen , Shi Xiaodan , Wu Rui , Feng Dongyun , Wang Chen , Chen Min , Zhang Wenliang , Wei Hong , Guan Yuanlin , Ye Kai , Zhao Gang 
Published: September 2020

ABSTRACTCerebrospinal fluids circulating human central nervous system have long been considered aseptic in healthy individuals, because normally the blood-brain barrier protects against microbial invasions. However, this dogma has been questioned by several reports that microbes were identified in human brains, raising the question whether a microbial community is present in cerebrospinal fluids of healthy individuals without neurological diseases. Here, we collected and analyzed metagenomic and metatranscriptomic sequencing data of cerebrospinal fluid specimens from a cohort of 23 pregnant women aged between 23 and 40 and one-to-one matched contamination controls. From data analysis of 116 specimens of eight different types, we detected 619 nonredundant microbial taxa which were dominated by bacteria (75%) and viruses (24%). In cerebrospinal fluids metagenomic samples, a total of 76 redundant species were detected including four (one nonredundant) eukaryota taxa, eleven (four nonredundant) bacteria, and 61 (21 nonredundant) viruses that were mostly bacteriophages. Metagenomic data analysis found no significant difference between cerebrospinal fluid specimens and negative controls in terms of microbial species diversity. In addition, no active or viable microbiome were present in the cerebrospinal fluid samples after subtracting microbes detected in contamination controls. In conclusion, we found no strong evidence that colonized microbial community exist in the cerebrospinal fluids of healthy individuals.IMPORTANCEMicrobiome are prevalent throughout human bodies with profound health implications. However, it remains unclear whether a microbiome is present and active in human cerebrospinal fluids that are long considered aseptic given the blood-brain barrier. Here, we applied unbiased metagenomic and metatranscriptomic sequencing to detect microbiome in cerebrospinal fluids collected from a cohort of 23 pregnant women with matched controls. By analyzing 116 specimens of eight types, no strong evidence was found to support a presence of colonized microbiome in the cerebrospinal fluids. Our findings have profound implications to human immunity against neurological infections and disorders, providing a guide for disease diagnostics, prevention and therapeutics in clinical settings.
Reaction Pathway Sampling and Free Energy Analyses for Multimeric Protein Complex Disassembly with Employing Hybrid Configuration Bias Monte Carlo/Molecular Dynamics Simulation
Authors: Kurisaki Ikuo , Tanaka Shigenori 
Published: September 2020

AbstractPhysicochemical characterization of multimeric biomacromolecule assembly and disassembly processes is a milestone to understand the mechanisms for biological phenomena at molecular level. Mass spectroscopy (MS) and structural bioinformatics (SB) approaches have become feasible to identify subcomplexes involved in assembly and disassembly, while they cannot provide atomic information sufficient for free energy calculation to characterize transition mechanism between two different sets of subcomplexes. To combine observations derived from MS and SB approaches with conventional free energy calculation protocols, we here designed a new reaction pathway sampling method with employing hybrid configuration bias Monte Carlo/Molecular Dynamics (hcbMC/MD) scheme and applied it to simulate disassembly process of serum amyloid P component (SAP) pentamer. The results we obtained are consistent with those of the earlier MS and SB studies with respect to SAP subcomplex species and the initial stage of SAP disassembly processes. Furthermore, we observed a novel dissociation event, ring-opening reaction of SAP pentamer. Employing free energy calculation combined with the hcbMC/MD reaction pathway trajectories, we moreover obtained experimentally testable observations on (1) reaction time of the ring-opening reaction and (2) importance of Asp42 and Lys117 for stable formation of SAP oligomer.
A non-canonical lipid droplet metabolism regulates the conversion of alpha-Synuclein to proteolytic resistant forms in neurons of aDrosophilamodel of Parkinson disease
Authors: Girard Victor , Jollivet Florence , Knittelfelder Oskar , Arsac Jean-Noel , Chatelain Gilles , Van den Brink Daan M. , Baron Thierry , Shevchenko Andrej , Davoust Nathalie , Mollereau Bertrand 
Published: September 2020

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by alpha-synuclein (αSyn) aggregation and associated with abnormalities in lipid metabolism. The accumulation of lipids in cytoplasmic organelles called lipid droplets (LDs) was observed in cellular models of PD. To investigate the pathophysiological consequences of interactions between αSyn and proteins that regulate the homeostasis of LDs, we used a transgenicDrosophilamodel of PD, in which human αSyn is specifically expressed in photoreceptor neurons. We first found that overexpression of the LD-coating proteins perilipin 1 or 2 (dPlin1/2), which limit the access of lipases to LDs, markedly increased triacylglyclerol (TG) loaded LDs in neurons. However, dPlin-induced-LDs in neurons are independent of lipid anabolic (diacylglycerol acyltransferase 1/Midway, fatty acid transport protein/dFatp) and catabolic (lipase Brummer) enzymes, indicating that non-canonical mechanisms regulate neuronal LD homeostasis. Interestingly, the accumulation of LDs induced by several distinct LD proteins (dPlin1, dPlin2, CG7900 or KlarsichtLD-BD) was synergistically amplified by the co-expression of αSyn, which was found at the surface of LDs both in photoreceptors neurons ofDrosophilaand in human neuroblastoma cells. Finally, the accumulation of LDs increased the resistance of αSyn to proteolytic digestion, a phenomenon associated with αSyn aggregation in human neurons. We thus propose that αSyn cooperates with LD proteins to inhibit lipolysis and that binding of αSyn to LDs contributes to the pathogenic misfolding and aggregation of αSyn in neurons.
Structure Model Analysis Of Phosphorylation Dependent Binding And Sequestration Of SARS-COV-2 Encoded Nucleocapsid Protein By Protein 14-3-3
Authors: Limtung Pierre , Tung H.Y. Lim 
Published: September 2020

AbstractPhosphorylation of serines 197 and 206 of SARS-COV-2 Nucleocapsid protein (NCp) enhanced the stability and binding efficiency and sequestration of NCp to Protein 14-3-3 by increasing the Stability Energy (ΔGstability energy) and Binding Energy (ΔΔGbinding energy) from ~545 Kcal/mol to ~616 Kcal/mol, and from 108 Kcal/mol to ~228 Kcal/mol respectively. The calculated Binding Energy Difference (ΔΔGbinding energy difference) between dephospho-NCp-14-3-3 complex and phospho-NCp-13-3-3 complex was ~72 Kcal/mol. Phosphorylations of serines 186, 197, 202 and 206, and threonines 198 and 205 NCp also caused an increase in the Stability Energy (ΔGstability energy) and Binding Energy (ΔΔGbinding energy) from ~545 Kcal/mol to ~617, 616, 583, 580, 574, 564 and 566 Kcal/mol and from ~108 Kcal/mol to ~228, 216, 184, 188, 184, 174 and 112 Kcal/mol respectively. Phosphorylation of NCp on serines 197 and 206 caused a decrease in Stability Energy and Binding Energy from ~698 Kcal/mol to 688 Kcal/mol, and from ~91 Kcal/mol to ~82 Kcal/mol for the dimerization of NCp. These results support the existence of a phosphorylation dependent cellular mechanism to bind and sequester NCp.
Embryotoxic and teratogenic effects of polyethylene microbeads found in facial wash products in Zebrafish (Danio rerio)using the Fish Embryo Acute Toxicity Test
Authors: De Guzman Margaret C. , Chua Patricia Anne P. , Sedano Franceska S. 
Published: September 2020

AbstractUse of polyethylene beads in facial cleansers has been continuously questioned by scientific communities for they adversely affect aquatic organisms once these beads find their way into their habitats. This study specifically aims to determineDanio reriomortality rate using lethal endpoints and to evaluate sublethal teratogenic effects inDanio reriodue to polyethylene microbead exposure.Danio rerio,a model organism for ecotoxicology, was subjected to the Fish Embryo Acute Toxicity Test. Embryos were exposed to polyethylene microbead suspensions (PE-MBS) of varying concentrations (i.e., 20 μg/L, 200 μg/L, 2000 μg/L). They were also exposed to 5% ethanol (positive control), reconstituted water (negative control), 0.01% Tween 80 (emulsifier control), and 1% DMSO (solvent control). Toxicological endpoints (i.e., egg coagulation, lack of somite formation, non-detachment of tail, and lack of heartbeat) were observed every 24 hours until the 96th hour exposure. Hatching was observed from 48 hpf while teratogenicity was observed at 144 hpf. Significant differences between means and variances were observed for all treatment groups in relation to the negative control. For all groups, 0.01% Tween 80, 1% DMSO and 20 μg/L PE-MBS did not significantly differ with the negative control due to negligible concentration but 5% ethanol and higher concentrations of PE-MBS did. This indicated that high concentrations of PE-MBS exposure may induce early hatching, mortality, increased malformation, and increased heart rate. Tukey Kramerpost hocTest substantiated that PE-MBS toxicity is dose dependent since embryotoxicity and teratogenicity increases at higher concentrations. LC50obtained using probit analysis based on experimental data was 2455.096 μg/L, and was higher than the concentrations used in this study. Further studies should be conducted to know more about the adverse effects of polyethylene microbeads to the biota.Author SummaryMargaret De Guzman, MSc, Patricia Chua, and Franceska Sedano have all equally contributed to this work in conceptualization, formal analysis, funding acquisition, and investigation. All authors have also equally headed project administration, procurement of resources and writing.
INFLUENCE OF A 30-DAY SPACEFLIGHT ON THE STRUCTURE OF MOTONEURONS OF THE TROCHLEAR NERVE NUCLEUS IN MICE
Authors: Pavlik Lyubov , Mikheeva Irina , Shtanchaev Rashid , Mikhailova Gulnara , Arkhipov Vladimir 
Published: September 2020

AbstractDuring spaceflight and immediately after it, adaptive neuroplastic changes occur in the sensorimotor structures of the central nervous system, which are associated with changes of mainly vestibular and visual signals. It is known that the movement of the eyeball in the vertical direction is carried out by muscles that are innervated by the trochlear nerve (CN IV) and the oculomotor nerve (CN III). To elucidate the cellular processes underlying the atypical vertical nystagmus that occurs under microgravity conditions, it seems necessary to study the state of these nuclei in animals in more detail after prolonged space flights. In this work, we carried out a qualitative and quantitative light-optical and ultrastructural analysis of the nuclei of the trochlear nerve in mice after a 30-day flight on the Bion-M1 biosatellite and followed by a stay for 13-14 hours under the influence of the Earth’s gravity after landing. As a result, it was shown that the motoneurons in the nucleus of the trochlear nerve changed their morphology under the influence of microgravity. Cell nuclei of the motoneurons had a more simplified rounded shape than in the control. In addition, the dendrites of these motoneurons significantly reorganized geometry and orientation under microgravity conditions; the number of dendritic branches has been increased to enhance the reduced signal flow. Apparently, to ensure such plastic changes, the number and size of mitochondria in the soma of motoneurons and in axons coming from the vestibular structures increased. In addition, the experimental animals showed an increase in the size of the cisterns of the rough and smooth endoplasmic reticulum in comparison with the control group of animals left on Earth, for which the environmental conditions in the spacecraft were reproduced. Thus, the main role in the adaptation of the trochlear nucleus to microgravity conditions, apparently, belongs to the dendrites of motoneurons, which rearrange their structure and function to enhance the flow of sensory information. These results are useful for the development of new, more effective means to facilitate the stay and work of space travelers in a long spaceflight.