bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Clinical Application of Nerve Injury Unit Mode in Patients with Moderate or Severe Traumatic Brain Injury
Authors: Zhou Bin , Dong Baizhuo , Fu Haitao , Yang Xiaolong , Sun Zhigang , Zhao Wei , Huang Shengming , Nie Honghua , Chen Guohui 
Published: September 2019

Objective:
To explore the efficacy of nerve injury unit mode and conventional management mode for the treatment of patients with moderate or severe traumatic brain injury (TBI).

Methods:
Eighty patients with TBI in our hospital from July 2016 to December 2017 were included as observation groups (Treated with injury unit mode). Eighty-three patients with TBI from January 2015 to June 2016 were included as control group (Treated with conventional management mode). The incidence of complications, satisfaction rate, Glasgow Coma Scale (GCS) scores, Barthel index (BI), National Institutes of Health Stroke Scale (NIHSS) scores and average length of hospital stay of 2 groups were compared.

Results:
Observation group achieved lower incidence of complications, higher satisfaction rate, higher GCS scores, higher GOS prognosis scores, higher BI, lower NIHSS scores, and shorter average length of hospital stay compared with control group (P < 0.05). There were no significant differences in the average hospitalization cost between 2 groups (P > 0.05).

Conclusion:
For patients with TBI, the nerve injury unit mode can reduce the incidence of complications, improve patient satisfaction rate, shorten the hospitalization time, enhance the daily living ability, improve the patient's neurological function, improve the ability to return to society and have a significant role in promoting the rehabilitation of patients.
Permanent Pancreatic Duct Occlusion With Neoprene-based Glue Injection After Pancreatoduodenectomy at High Risk of Pancreatic Fistula
Authors: Mazzaferro Vincenzo , Virdis Matteo , Sposito Carlo , Cotsoglou Christian , Droz Dit Busset Michele , Bongini Marco , Flores Maria , Prinzi Natalie , Coppa Jorgelina 
Published: September 2019

Objective:
The aim of this study was to assess safety and efficacy of pancreatic duct occlusion (PDO) with neoprene-based glue in selected patients undergoing pancreatoduodenectomy (PD) at high risk of postoperative pancreatic fistula (POPF).

Background Data:
PD is the reference standard approach for tumors of the pancreaticoduodenal region. POPF is the most relevant complication after PD. PDO has been proposed as an alternative to anastomosis to manage the pancreatic stump.

Methods:
A single-center, prospective, nonrandomized trial enrolled 100 consecutive PD for cancer. Patients at high risk for POPF according to Fistula Risk Score (FRS) >15% (≥6 points) were treated with PDO using neoprene glue (study cohort); patients with FRS ≤15% (≤5 points) received pancreaticojejunal anastomosis (PJA: control cohort). Primary endpoint was complication rate grade ≥3 according to Dindo–Clavien Classification (DCC). Other postoperative outcomes were monitored (ClinicalTrials.gov NCT03738787).

Results:
Fifty-one patients underwent PDO and 49 PJA. DCC ≥3, postoperative mortality, and POPF grade B-C were 25.5% versus 24.5% (P = 0.91), 5.9% versus 2% (P = 0.62), and 11.8% versus 16.3% (P = 0.51) in the study versus control cohort, respectively. At 1 and 3 years, new-onset diabetes was diagnosed in 13.7% and 36.7% of the study cohort versu 4.2% and 12.2% in controls (P = 0.007).

Conclusions:
PDO with neoprene-based glue is a safe technique that equalizes early outcome of selected patients at high risk of POPF to those at low risk undergoing PJA. Neoprene-based PDO, however, triples the risk of diabetes at 1 and 3 years.
Chronic circadian disruption modulates breast cancer cell stemness and their immune microenvironment to drive metastasis in mice
Authors: Hadadi Eva , Taylor William , Li Xiaomei , Aslan Yetki , Villote Marthe , Rivière Julie , Duvallet Gaelle , Auriau Charlotte , Dulong Sandrine , Letron Isabelle Raymond , Provot Sylvain , Bennaceur-Griscelli Annelise , Acloque Hervé 
Published: September 2019

AbstractBreast cancer is the most common type and one of the major causes of cancer death in woman worldwide. Epidemiological studies have established a link between night shift work and increased cancer risk, suggesting that circadian disruption may interfere with carcinogenesis. We aim to shed light on the effect of chronic jetlag on mammary tumour development. Therefore, we used a mouse model of spontaneous mammary tumorigenesis that we exposed to chronic circadian disruption. We observed that circadian disruption significantly increases cancer cell dissemination and metastasis. It also enhances the stemness and tumour–initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. We finally showed that all these defects can be corrected by the use of a CXCR2 inhibitor. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.
In-vivo crystals reveal protein interactions
Authors: Martin Eleanor R. , Barbieri Alessandro , Ford Robert C. , Robinson Robert C. 
Published: September 2019

AbstractCrystallisation of recombinant proteins has been fundamental to our understanding of protein function, dysfunction, and molecular recognition. However, this information has often been gleaned under non-physiological extremes of protein, salt, and H+ concentrations. Here, we describe the development of the robust iBox-PAK4cat system that spontaneously crystallises in several mammalian cell types. The developments described here allow the quantitation of in-vivo protein-protein interactions using a novel GFP-linked reporter system. Here, we have combined this assay with in-vitro X-ray crystallography and molecular dynamics studies characterise the molecular determinants of the interaction between NHERF1 PDZ2 and CFTR, a protein complex pertinent to the genetic disease cystic fibrosis. These studies have revealed the crystal structure of the extended PDZ domain of NHERF1, and indicated, contrary to previous reports, that residue selection at −1 and −3 PDZ-binding motif positions influence the affinity and specificity of the interaction. The results presented here demonstrate that the iBox-PAK4cat assay could easily be utilised to screen other protein-protein interactions.
Horizontal gene transfer to a defensive symbiont with a reduced genome amongst a multipartite beetle microbiome
Authors: Waterworth Samantha C. , Flórez Laura V. , Rees Evan R. , Hertweck Christian , Kaltenpoth Martin , Kwan Jason C. 
Published: September 2019

ABSTRACTThe loss of functions required for independent life when living within a host gives rise to reduced genomes in obligate bacterial symbionts. Although this phenomenon can be explained by existing evolutionary models, its initiation is not well understood. Here, we describe the microbiome associated with eggs of the beetleLagria villosa, containing multiple bacterial symbionts related toBurkholderia gladioliincluding a reduced-genome symbiont thought to produce the defensive compound lagriamide. We find that the putative lagriamide producer is the only symbiont undergoing genome reduction, and that it has already lost most primary metabolism and DNA repair pathways. The horizontal acquisition of the lagriamide biosynthetic gene cluster likely preceded genome reduction, and unexpectedly we found that the symbiont accepted additional genes horizontally during genome reduction, even though it lacks the capacity for homologous recombination. These horizontal gene transfers suggest that absolute genetic isolation is not a requirement for genome reduction.
Systematic profiling of full-length immunoglobulin and T-cell receptor repertoire diversity in rhesus macaque through long read transcriptome sequencing
Authors: Brochu Hayden N. , Tseng Elizabeth , Smith Elise , Thomas Matthew J. , Jones Aiden , Diveley Kayleigh , Law Lynn , Hansen Scott G. , Picker Louis J. , Gale Michael , Peng Xinxia 
Published: September 2019

AbstractThe diversity of immunoglobulin (Ig) and T-cell receptor (TCR) repertoires is a focal point of immunological studies. Rhesus macaques are key for modeling human immune responses, placing critical importance on the accurate annotation and quantification of their Ig and TCR repertoires. However, due to incomplete reference resources, the coverage and accuracy of the traditional targeted amplification strategies for profiling rhesus Ig and TCR repertoires are largely unknown. Here, using long read sequencing, we sequenced four Indian-origin rhesus macaque tissues and obtained high quality, full-length sequences for over 6,000 unique Ig and TCR transcripts, without the need for sequence assembly. We constructed the first complete reference set for the constant regions of all known isotypes and chain types of rhesus Ig and TCR repertoires. We show that sequence diversity exists across the entire variable regions of rhesus Ig and TCR transcripts. Consequently, existing strategies using targeted amplification of rearranged variable regions comprised of V(D)J gene segments miss a significant fraction (27% to 53% and 42% to 49%) of rhesus Ig/TCR diversity. To overcome these limitations, we designed new rhesus-specific assays that remove the need for primers conventionally targeting variable regions and allow single cell-level Ig and TCR repertoire analysis. Our improved approach will enable future studies to fully capture rhesus Ig and TCR repertoire diversity and is applicable for improving annotations in any model organism.
CIViCpy: a Python software development and analysis toolkit for the CIViC knowledgebase
Authors: Wagner Alex H. , Kiwala Susanna , Coffman Adam C. , McMichael Joshua F. , Cotto Kelsy C. , Mooney Thomas B. , Barnell Erica K. , Krysiak Kilannin , Danos Arpad M. , Griffith Obi L. , Griffith Malachi 
Published: September 2019

AbstractPurposePrecision oncology is dependent upon the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, open-access knowledgebase, providing a structured framework for evaluating genomic variants of various types (e.g., fusions, SNVs) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented API for accessing CIViC records: Assertions, Evidence, Variants, and Genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this API, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC web application.MethodsTo address this limitation, we developed CIViCpy (civicpy.org), a software development kit (SDK) for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples.ResultsWe used CIViCpy to evaluate variants from 59,437 sequenced tumors of the AACR Project GENIE dataset. We demonstrate that CIViCpy enables annotation of >1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors.ConclusionsThe clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, an SDK for downstream applications and rapid analysis. CIViCpy (civicpy.org) is fully documented, open-source, and freely available online.
Pathway engineering in yeast for synthesizing the complex polyketide bikaverin
Authors: Zhao Meng , Zhao Yu , Hu Qi , Iqbal Hala , Yao Mingdong , Liu Hong , Qiao Bin , Li Chun , Skovbjerg Christine A. S. , Nielsen Jens Christian , Nielsen Jens B. , Frandsen Rasmus J.N. , Yuan Yingjin , Boeke Jef D. 
Published: September 2019

AbstractFungal polyketides display remarkable structural diversity and bioactivity, and therefore the biosynthesis and engineering of this large class of molecules is therapeutically significant. Here, we successfully recoded, constructed and characterized the biosynthetic pathway of the formation of bikaverin, a tetracyclic polyketide with antibiotic, antifungal and anticancer properties, in S. cerevisiae. We used a green fluorescent protein (GFP) tagging strategy to identify the low expression of Bik1 (polyketide synthase) as the bottleneck step in the pathway, and a promoter exchange strategy to increase expression of Bik1 and bikaverin yield. To further increase product yield, we used an enzyme-fusion strategy to couple the monooxygenase (Bik2) and methyltransferase (Bik3) to efficiently channel intermediates between modifying enzymes, leading to a dramatic improvement of Bikaverin yield of nearly 60-fold. This study demonstrates that the biosynthesis of complex polyketides biosynthesis can be established and efficiently engineered in S. cerevisiae, highlighting the great potential for natural product synthesis and large-scale fermentation in yeast.
Temporal discounting correlates with directed exploration but not with random exploration
Authors: Sadeghiyeh Hashem , Wang Siyu , Alberhasky Maxwell R. , Kyllo Hannah M. , Shenhav Amitai , Wilson Robert C. 
Published: September 2019

AbstractThe explore-exploit dilemma describes the trade off that occurs any time we must choose between exploring unknown options and exploiting options we know well. Implicit in this trade off is how we value future rewards — exploiting is usually better in the short term, but in the longer term the benefits of exploration can be huge. Thus, in theory there should be a tight connection between how much people value future rewards, i.e. how much they discount future rewards relative to immediate rewards, and how likely they are to explore, with less ‘temporal discounting’ associated with more exploration. By measuring individual differences in temporal discounting and correlating them with explore-exploit behavior, we tested whether this theoretical prediction holds in practice. We used the 27-item Delay-Discounting Questionnaire to estimate temporal discounting and the Horizon Task to quantify two strategies of explore-exploit behavior: directed exploration, where information drives exploration by choice, and random exploration, where behavioral variability drives exploration by chance. We find a clear correlation between temporal discounting and directed exploration, with more temporal discounting leading to less directed exploration. Conversely, we find no relationship between temporal discounting and random exploration. Unexpectedly, we find that the relationship with directed exploration appears to be driven by a correlation between temporal discounting and uncertainty seeking at short time horizons, rather than information seeking at long horizons. Taken together our results suggest a nuanced relationship between temporal discounting and explore-exploit behavior that may be mediated by multiple factors.
No evidence for immune-gene specific signals of selection in termites
Authors: Meusemann Karen , Korb Judith , Schughart Maximilian , Staubach Fabian 
Published: September 2019

AbstractIt has been hypothesized that selection pressure from pathogens plays an important role in shaping social evolution. Social behaviour, in particular brood care, is associated with pathogen pressure in wood-dwelling “lower” termites. Yet, generally pathogen pressure is low in wood-dwelling termite species that never leave the nest except for the mating flight. In comparison, pathogen pressure is higher in species that leave the nest to forage, and thus constantly encounter a diversity of microbes from their environment. We hypothesized that such differences in pathogen pressure are also reflected by differences in the intensity of natural selection on immune genes. We tested this hypothesis in a phylogenetic framework, analyzing rates of non-synonymous and synonymous substitutions on single-copy immune genes. Therefore, we leveraged recent genomic and transcriptomic data from eight termite species, representing wood-dwelling and foraging species as well as 14 additional species spanning the winged insects (Pterygota). Our results provide no evidence for a role of pathogen pressure in selection intensity on single-copy immune genes. Instead, we found evidence for a genome-wide pattern of relaxed selection in termites.Life Science Identifiers (as available Zoobank)Ephemera danica:urn:lsid:zoobank.org:act:06633F75-4809-4BB3-BDCB-6270795368D5Coptotermes sp.urn:lsid:zoobank.org:pub:D6724B7F-F27A-47DC-A4FC-12859ECA0C71Blattella germanica:rn:lsid:zoobank.org:pub:1EA126BA-E9D2-4AA6-8202-26BA5B09B8ADLocusta migratoriaurn:lsid:zoobank.org:pub:D792A09E-844A-412A-BFCA-5293F8388F8CPeriplaneta americana (Blatta americana):urn:lsid:zoobank.org:act:95113A55-4C6D-4DC7-A0E5-620BACADFFE5Apis mellifera:urn:lsid:zoobank.org:act:9082C709-6347-4768-A0DC-27DC44400CB2Bombyx mori (Phalæna (Bombyx) mori)urn:lsid:zoobank.org:act:215466E3-E77F-46E9-8097-372837D7A375Drosophila melanogaster:urn:lsid:zoobank.org:act:5B39F0AA-270D-4AA8-B9A3-C36A3A265910
Computational reconstruction of the complete Piezo1 structure reveals a unique footprint and specific lipid interactions
Authors: Chong Jiehan , De Vecchis Dario , Hyman Adam J , Povstyan Oleksandr V , Shi Jian , Beech David J , Kalli Antreas C 
Published: September 2019

ABSTRACTPiezo1 is a critical mechanical sensor in many cells. It is activated by mechanical force thus allowing cells to sense the physical environment and respond to stress. Structural data have suggested that Piezo1 has a curved shape. Here, we use computational approaches to model, for the first time, the 3D structure of the full-length Piezo1 in an asymmetric membrane. A number of novel insights emerge: (i) Piezo1 creates a dome in the membrane with a trilobed topology that extends beyond the radius of the protein, (ii) Piezo1 changes the lipid environment in its vicinity via specific interactions with cholesterol and PIP2molecules, (iii) changes in cholesterol concentration that change the membrane stiffness result in changes in the depth of the dome created by Piezo1, and iv) modelling of the N-terminal region that is missing from current structures modifies Piezo1 membrane footprint, suggesting the importance of this region in Piezo1 function.
Microbiomes in the insectivorous bat species Mops condylurus rapidly converge in captivity
Authors: Edenborough Kathryn M , Mu Andre , Mühldorfer Kristin , Lechner Johanna , Lander Angelika , Bokelmann Marcel , Couacy-Hymann Emmanuel , Radonic Aleksandar , Kurth Andreas 
Published: September 2019

AbstractBats are well known reservoir hosts for RNA and DNA viruses. The use of captive bats in research has intensified over the past decade as researchers aim to examine the virus-reservoir host interface. In this study, we investigated the effects of captivity on the fecal bacterial microbiome of an insectivorous microbat, Mops condylurus, a bat species that roosts in close proximity to humans and has likely transmitted viral infections to humans. Using amplicon 16S rRNA gene sequencing, we characterized changes in fecal bacterial community composition for individual bats directly at the time of capture and again after six weeks in captivity. We found that microbial community richness by measure of the number of observed operational taxonomic units (OTUs) in bat feces does increase significantly in captivity. Importantly, we found the similarity of microbial community structures of fecal microbiomes between different bats to converge during captivity. We propose a six week-acclimatization period prior to carrying out infection studies or other research influenced by the microbiome composition, which may be advantageous to reduce variation in microbiome composition and minimize biological variation inherent to in vivo experimental studies.
KV1.2 channels inactivate through a mechanism similar to C-type inactivation
Authors: Suárez-Delgado Esteban , Rangel-Sandín Teriws G. , Ishida Itzel G. , Rangel-Yescas Gisela E. , Rosenbaum Tamara , Islas León D. 
Published: September 2019

AbstractC-type inactivation has been described in multiple voltage-gated K+ channels and in great detail in the Drosophila Shaker channel. As channels have moved into the structural era, atomic details of this and other gating mechanisms have started to be better understood. To date, the only voltage-gated channels whose structure has been solved are KvAP (X-ray diffraction), the KV1.2- KV2.1 “paddle” chimera (X-ray diffraction), KV1.2 (Cryo-EM); and ether-á-go-go (Cryo-EM) (Wang and MacKinnon, 2017), however, the characteristics and mechanisms of slow inactivation in these channels are unknown or poorly characterized. Here we present a detailed study of slow inactivation in the rat KV1.2 and show that it has some properties consistent with the C-type inactivation described in Shaker. We also study the effects of some mutations that are known to modulate C-type inactivation in Shaker and show that qualitative and quantitative differences exist in their functional effects, possibly underscoring subtle but important structural differences between the C-inactivated states in Shaker and KV1.2.
Human Rotavirus Diarrhea Is Associated with Altered Trafficking and Expression of Apical Membrane Transport Proteins
Authors: Zachos Nicholas C. , Baetz Nicholas W. , Gupta Akshita , Kapoor Anirudh , Cole Robert N. , Verkman Alan S. , Turner Jerrold R. , Estes Mary K. , Donowtiz Mark 
Published: September 2019

ABSTRACTBackgroundRotavirus (RV) is the 5th leading cause of death in children <5 years old but the leading cause of diarrhea related deaths in this age group. The mechanism of RV diarrhea involves decreased activity of Na+-dependent solute transporters with increased luminal secretion of Cl- in the absence of significant histologic damage. While our understanding of RV diarrhea has come from studies in animal models and cancer cell lines, the mechanism of the diarrhea and the transport proteins affected in human RV disease remains only partially understood. This understanding is likely to impact drug development therapy for RV diarrhea.MethodsFormalin-fixed paraffin-embedded small intestinal specimens from patients diagnosed with RV diarrhea (confirmed by anti-RV antibodies) were analyzed by immunofluorescence for changes in apical/basolateral ion/nutrient transporters/channels as well as tight junctional and cytoskeletal proteins. Proximal small intestinal enteroids generated from biopsies obtained from healthy human subjects were grown as monolayers, differentiated to resemble villus epithelial cells, and infected with human RV.ResultsRV diarrhea was associated with reduced expression and intracellular localization of transport proteins normally found in the brush border membranes, including SGLT1, NHE3, NHE2, the Na+-dependent amino acid transporter SLC6A19, and CFTR. In contrast, basolateral proteins, including Na+/K+-ATPase, NKCC1, and β-catenin, the brush border marker ezrin, as well as the tight junction protein, ZO-1, were expressed and localized normally. RV-induced mislocalization of NHE3, SGLT1, SLC6A19 and CFTR was also seen when human small intestinal enteroids were infected with RV.ConclusionsThese data demonstrate a new pathophysiologic mechanism of acute diarrhea in which expression of multiple apical transport proteins are reduced. This acute diarrhea is likely to be caused by an effect on a common apical trafficking pathway, as exemplified by RV diarrhea, and its contribution to other enteric pathogen-induced diarrheal diseases should be determined.