bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of ‘never use’ abbreviations (Error Prone Abbreviations-EPA’s) list on incidence of EPAs in inpatient medical prescriptions in apex tertiary care public hospital in India
Authors: Thachaparambil Arif , Kausar Mohammad , Mahesh R , Sharma DK 
Published: October 2020

AbstractBackgroundAbbreviations are commonly used in medical records to save time and space but use in prescriptions can be a reason for communication failures and preventable harm during healthcare delivery. Nearly 5% of medication errors can be attributable to abbreviation use. Prescriptions need to be clear so that nurses and pharmacists can correctly interpret intentions of doctors. For patient safety, hospitals should implement a process for uniform use of approved abbreviations, such as through use of an approved list or never-use list of abbreviations and symbols.Local ProblemIn the hospital under study, there was no system of avoiding error prone abbreviations while prescribing to prevent medical errors. Hence, an interventional study was done to quantify and reduce incidence of error prone abbreviations.MethodsThe study design was pre-post interventional / quasi-experimental design to assess the impact of never use list and standardized abbreviations. The study was conducted after ethical approval from Institute Ethics Committee. Pre intervention data was collected by a retrospective closed in-patient medical record review. Post interventional incidence of error prone abbreviations was determined and the effectiveness of the same was assessed by using statistical analysis.InterventionAn approved ‘Never use’ list and standardized abbreviations were developed and poster copies were affixed in inpatient wards, doctors were educated and poster pamphlets were also distributed.ResultsIncidence of error abbreviations in inpatient prescription were 47.5% and ‘Never Use’ list of abbreviation led to a statistically significant reduction of error-prone abbreviation by 8.2% from 47.5% to 43.6% (P\0.006)Conclusion‘Never Use’ lists are effective in reducing incidence of common error-prone abbreviations and discipline wise variation is observed. Adoption of such lists is highly recommended. The lists should be comprehensive, regularly updated and educational interventions should be comprehensive and integration into patient medical charts and pocket friendly flash cards may be provided for better outcomes. Enforcing a policy to prohibit the use of EPAs while prescribing will also be helpful.
In-silico, interactomic and clinical validation based approach for screening and identification of miR biomarkers involved in Oral submucous fibrosis to Oral squamous cell carcinoma transition
Authors: Ukey Shweta , Vishnoi Jeewan Ram , Choudhury Chinmayee , Purohit Purvi , Dwivedi Shailendra , jain Ankit , Chugh Ankita , Elhence Poonam , Pareek Puneet , Misra Sanjeev , Sharma Praveen 
Published: October 2020

ABSTRACTOral Squamous Cell Carcinoma (OSCC) is common preventable disease when diagnosed early, but mostly its progression follows transition from oral potentially malignant disorders (OPMDs) like Oral Submucous Fibrosis (OSF). However, it is difficult to predict possibilities of progression in these premalignant lesions hence, identification of molecular biomarkers would have major clinical impact in early diagnosis and better prognosis. In this context microRNA’s(miR’s) provide better opportunities in malignancy prediction and demarcation in OSF to OSCC transition as they perform key regulatory roles in many tumorigenic processes. Here, we computationally screened differentially expressed miR’s of OSCC and OSF from public databases followed by construction of protein interaction networks and enrichment analyses. The relevant miR’s were validated using qPCR of total 93 samplesincluding 34 OSCC, 30 OSF and 29 control blood and tissue samples. We identified significant down regulation of miR-133a-3p in OSCC compared to controls and interesting up-regulation compared to OSCC and control. miR-9-5p was up-regulated in OSF as well as OSCC and down-regulated in OSF compared to OSCC. Therefore, these two miR’s may serve as risk stratification biomarkers with validation in larger categorical datasets.
Small molecule targeting r(UGGAA)ndisrupts RNA foci and alleviates disease phenotype inDrosophilamodel
Authors: Shibata Tomonori , Nagano Konami , Ueyama Morio , Ninomiya Kensuke , Hirose Tetsuro , Nagai Yoshitaka , Ishikawa Kinya , Kawai Gota , Nakatani Kazuhiko 
Published: October 2020

AbstractSynthetic small molecules modulating RNA structure and function have therapeutic potential for RNA diseases. Here we report our discovery that naphthyridine carbamate dimer (NCD) targets disease-causing r(UGGAA)nrepeat RNAs in spinocerebellar ataxia type 31 (SCA31). Structural analysis of the NCD-UGGAA/UGGAA complex by nuclear magnetic resonance (NMR) spectroscopy clarified the mode of binding that recognizes four guanines in UGGAA/UGGAA pentad by hydrogen bonding with four naphthyridine moieties of two NCD molecules. Biological studies show that NCD disrupts naturally occurring RNA foci built on r(UGGAA)nrepeat RNA known as nuclear stress bodies (nSBs) by interfering with RNA-protein interactions resulting in the suppression of nSBs-mediated splicing event. Feeding NCD to larvae of theDrosophilamodel of SCA31 alleviates disease phenotype induced by toxic r(UGGAA)nrepeat RNA. These studies demonstrated that small molecules targeting toxic repeat RNAs are a promising chemical tool for studies on repeat expansion diseases.
Genome analysis ofSalmonella entericaserovar Typhimurium bacteriophage L, indicator for StySA (StyLT2III) restriction-modification system action
Authors: Zaworski Julie , McClung Colleen , Ruse Cristian , Weigele Peter R. , Hendrix Roger W. , Ko Ching-Chung , Edgar Robert , Hatfull Graham F. , Casjens Sherwood R. , Raleigh Elisabeth A. 
Published: October 2020

ABSTRACTBacteriophage L, a P22-like phage ofSalmonella entericasv Typhimurium LT2, was important for definition of mosaic organization of the lambdoid phage family and for characterization of restriction-modification systems ofSalmonella. We report the complete genome sequences of bacteriophage LcI−4013−am43 and LcII−101; the deduced sequence of wildtype L is 40,633 bp long with a 47.5% GC content. We compare this sequence with those of P22 and ST64T, and predict 71 Coding Sequences, 2 tRNA genes and 14 intergenic rho-independent transcription terminators. The overall genome organization of L agrees with earlier genetic and physical evidence; for example, no secondary immunity region (ImmI:ant,arc) or genes for superinfection exclusion (sieAandsieB) are present. Proteomic analysis confirmed identification of virion proteins, along with low levels of assembly intermediates and host cell envelope proteins. The genome of L is 99.9% identical at the nucleotide level to that reported for phage ST64T, despite isolation on different continents ~35 years apart. DNA modification by the epigenetic regulator Dam is generally incomplete. Dam modification is also selectively missing in one location, corresponding to the P22 phase-variation-sensitive promoter region of the serotype-convertinggtrABCoperon. The number of sites for SenLTIII (StySA) action may account for stronger restriction of L (13 sites) than of P22 (3 sites).
Metabolomic profiling identifies complex lipid species associated with response to weight loss interventions
Authors: Bihlmeyer Nathan A. , Kwee Lydia Coulter , Clish Clary B. , Deik Amy Anderson , Gerszten Robert E. , Pagidipati Neha J. , Laferrère Blandine , Svetkey Laura P. , Newgard Christopher B. , Kraus William E. , Shah Svati H. 
Published: October 2020

AbstractObesity is an epidemic internationally. While weight loss interventions are efficacious, they are compounded by heterogeneity with regards to clinically relevant metabolic responses. Thus, we sought to identify metabolic pathways and biomarkers that distinguish individuals with obesity who would most benefit from a given type of intervention. Liquid chromatography mass spectrometry-based profiling was used to measure 765 metabolites in baseline plasma from three different weight loss studies: WLM (behavioral intervention, N=443), STRRIDE-PD (exercise trial, N=163), and CBD (surgical cohort, N=125). The primary outcome was percent change in insulin resistance (as measured by the Homeostatic Model Assessment of Insulin Resistance [%ΔHOMA-IR]) over the intervention. Overall, 92 individual metabolites were associated with %ΔHOMA-IR after adjustment for multiple comparisons. Concordantly, the most significant metabolites were triacylglycerols (TAGs; p=2.3e-5) and diacylglycerols (DAGs; p=1.6e-4), with higher TAG and DAG levels associated with a greater improvement in HOMA-IR. In tests of heterogeneity, 50 metabolites changed differently between weight loss interventions; we found amino acids, peptides, and their analogues to be most significant (4.7e-3) in this category. Our results highlight novel metabolic pathways associated with heterogeneity in response to weight loss interventions, and related biomarkers which could be used in future studies of personalized approaches to weight loss interventions.
Glyoxal fixation facilitates transcriptome analysis after antigen staining and cell sorting by flow cytometry
Authors: Channathodiyil Prasanna , Houseley Jonathan 
Published: October 2020

AbstractA simple method for extraction of high quality RNA from cells that have been fixed, stained and sorted by flow cytometry would allow routine transcriptome analysis of highly purified cell populations and single cells. However, formaldehyde fixation impairs RNA extraction and inhibits RNA amplification. Here we show that good quality RNA can be readily extracted from stained and sorted mammalian cells if formaldehyde is replaced by glyoxal - a well-characterised fixative that is widely compatible with immunofluorescent staining methods. Although both formaldehyde and glyoxal efficiently form protein-protein crosslinks, glyoxal does not crosslink RNA to proteins nor form stable RNA adducts, ensuring that RNA remains accessible and amenable to enzymatic manipulation after glyoxal fixation. We find that RNA integrity is maintained through glyoxal fixation, permeabilisation with methanol or saponin, indirect immunofluorescent staining and flow sorting. RNA can then be extracted by standard methods and processed into RNA-seq libraries using commercial kits; mRNA abundances measured by poly(A)+ RNA-seq correlate well between freshly harvested cells and fixed, stained and sorted cells. We validate the applicability of this approach to flow cytometry by staining MCF-7 cells for the intracellular G2/M-specific antigen cyclin B1 (CCNB1), and show strong enrichment for G2/M-phase cells based on transcriptomic data. Switching to glyoxal fixation with RNA-compatible staining methods requires only minor adjustments of most existing staining and sorting protocols, and should facilitate routine transcriptomic analysis of sorted cells.
Effects of heat-killedEnterococcus faecalisT-110 supplementation on gut immunity, gut flora, and intestinal infection in normal aged hamsters
Authors: Inatomi Takio , Otomaru Konosuke 
Published: October 2020

AbstractInfectious diseases are a threat to elderly people, whose immune systems become depressed with age. Among the various infectious diseases,Clostridium difficileinfections in particular lead to significant mortality in elderly humans and are a serious problem worldwide, especially because of the increasing infection rates. Probiotics have been proposed as an effective countermeasure againstC. difficileinfection. The aim of this study was to evaluate the effects of heat-killedEnterococcus faecalisT-110 on intestinal immunity, intestinal flora, and intestinal infections, especiallyC. difficileinfections, in naturally ageing animals, for extrapolation to elderly human subjects. Twenty female hamsters were randomly distributed into two groups. Group 1 was fed a basal diet, and group 2 was fed a basal diet supplemented with heat-killedE. faecalisfor 7 days. Heat-killedE. faecalisT-110 improved gut immunity and microflora, especiallyClostridium perfringensandC. difficile, of the normal aged hamsters. Heat-killedE. faecalisT-110 may, therefore, be a countermeasure against age-related immune dysfunction and intestinal infections, especiallyC. difficileinfection, in elderly humans. However, further investigation in humans is needed.
Lipid anchoring and electrostatic interactions target the phospholipase NOT-LIKE-DAD to pollen endo-plasma membrane
Authors: Gilles Laurine M. , La Padula Veronica , Jacquier Nathanaël M.A. , Martinant Jean-Pierre , Rogowsky Peter M. , Widiez Thomas 
Published: October 2020

AbstractPhospholipases are ubiquitous enzymes that cleave phospholipids, one major constituent of membranes. They are thus essential for many developmental processes, including male gamete development. In flowering plants, mutation of phospholipase NOT-LIKE-DAD (NLD) leads to peculiar defects in sexual reproduction. Indeed, pollination of a wild-type female with mutant pollen generates haploid embryos containing solely maternal genetic information. Contrary to previous reports NLD does not localize to cytosol and plasma membrane (PM) of sperm cells but to the pollen endo-plasma membrane (endo-PM), a specific membrane derived from the PM of the pollen vegetative cell that encircles the two sperm cells. Pharmacological approaches coupled with targeted mutagenesis revealed that lipid anchoring together with electrostatic interactions between membrane and NLD are involved in the attachment of NLD to this atypical endo-PM. Membrane surface-charge and anionic lipid bio-sensors indicated that phosphatidylinositol-4,5-bisphosphate (PIP(4,5)P2) is enriched in the endo-PM as compared to the PM. Our results uncover a unique example of how membrane electrostatic properties can specify a unique polar domain (i.e. endo-PM), which is critical for plant reproduction and gamete formation.
Composition and stage dynamics of mitochondrial complexes inPlasmodium falciparum
Authors: Evers Felix , Cabrera-Orefice Alfredo , Elurbe Dei M. , Lindert Mariska Kea-te , Boltryk Sylwia D. , Voss Till S. , Huynen Martijn A. , Brandt Ulrich , Kooij Taco W.A. 
Published: October 2020

AbstractOur current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages ofPlasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.
Metformin alleviates aging-associated cellular senescence of human adipose stem cells and derived adipocytes
Authors: Mantecon Matthieu , Le Pelletier Laura , Gorwood Jennifer , Auclair Martine , Atlan Michael , Fève Bruno , Capeau Jacqueline , Lagathu Claire , Béréziat Véronique 
Published: October 2020

SUMMARYAging is associated with central fat redistribution, and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived-stemcells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25y) or older women (>60y).Aged-donor ASCs showed more intense features of aging (senescence, mitochondrial dysfunction, and oxidative stress) than young-donor ASCs. Oxidative stress and mitochondrial dysfunction occurred earlier in adipocytes derived from aged-donor than from young-donor ASCs, leading to insulin resistance and impaired adipogenesis.When aged-donor ASCs were treated with metformin, senescence, oxidative stress and mitochondrial dysfunction returned to the levels observed in young-donor ASCs. Furthermore, metformin’s prevention of senescence and dysfunction during ASC proliferation restored the cells’ adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated-protein-kinase.We show here that targeting senescent ASCs from aged women with metformin may alleviate age-related dysfunction, insulin resistance, and impaired adipogenesis.
NAP-CNB: Bioinformatic pipeline to predict MHC-I-restricted T cell epitopes in mice
Authors: Wert-Carvajal Carlos , Sánchez-García Rubén , Macías José R , Sanz-Pamplona Rebeca , Pérez Almudena Méndez , Alemany Ramon , Veiga Esteban , Sorzano Carlos Óscar S. , Muñoz-Barrutia Arrate 
Published: October 2020

AbstractLack of a dedicated integrated pipeline for neoantigen discovery in mice hinders cancer immunotherapy research. Novel sequential approaches through recurrent neural networks can improve the accuracy of T-cell epitope immunogenicity predictions in mice, and a simplified variant selection process can reduce operational requirements. We have developed a web server tool (NAP-CNB) for a full and automatic pipeline based on recurrent neural networks, to predict putative neoantigens from tumoral RNA sequencing reads. The developed software can estimate H-2 peptide ligands, with an AUC of 0.95, directly from tumor samples. As a proof-of-concept, we used the B16 melanoma model to test the system’s predictive capabilities, and we report its putative neoantigens. NAP-CNB web server is freely available at http://biocomp.cnb.csic.es/NeoantigensApp/ with scripts and datasets accessible through the download section.
Representational drift in the mouse visual cortex
Authors: Deitch Daniel , Rubin Alon , Ziv Yaniv 
Published: October 2020

AbstractNeuronal representations in the hippocampus and related structures gradually change over time despite no changes in the environment or behavior. The extent to which such ‘representational drift’ occurs in sensory cortical areas and whether the hierarchy of information flow across areas affects neural-code stability have remained elusive. Here, we address these questions by analyzing large-scale optical and electrophysiological recordings from six visual cortical areas in behaving mice that were repeatedly presented with the same natural movies. We found representational drift over timescales spanning minutes to days across multiple visual areas. The drift was driven mostly by changes in individual cells’ activity rates, while their tuning changed to a lesser extent. Despite these changes, the structure of relationships between the population activity patterns remained stable and stereotypic, allowing robust maintenance of information over time. Such population-level organization may underlie stable visual perception in the face of continuous changes in neuronal responses.
PapRIV, a BV-2 microglial cell activating quorum sensing peptide
Authors: Janssens Yorick , Debunne Nathan , De Spiegeleer Anton , Wynendaele Evelien , Planas Marta , Feliu Lidia , Quarta Alessandra , Claes Christel , Van Dam Debby , De Deyn Peter Paul , Ponsaerts Peter , Blurton-Jones Matthew , De Spiegeleer Bart 
Published: October 2020

AbstractBackgroundQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced byBacillus cereusspecies.MethodsGastro-intestinal transport of the peptide is investigated using thein vitroCaco-2 model while transport over the blood-brain barrier is investigated in mice using multiple time regression experiments. Microglial activation is assessed using ELISA, fluorometry, immunoblotting, qPCR and phase-contrast microscopy.In vivoplasma detection andex vivometabolization experiments are performed using UHPLC-MS2and UHPLC-UV/MS, respectively.ResultsPapRIV showedin vitroactivating properties of BV-2 microglia cells and was able to cross thein vitroCaco-2 cell model and pass the blood-brain barrierin vivo.In vivopeptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite (DLPFEH) still remained active.ConclusionsPapRIV is thus able to cross the gastro-intestinal tract and the blood-brain barrier and showsin vitroactivating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.
A polarity pathway for exocyst-dependent intracellular tube extension
Authors: Abrams Joshua , Nance Jeremy 
Published: October 2020

ABSTRACTLumen extension in intracellular tubes can occur by the directed fusion of vesicles with an invading apical membrane domain. Within theC. elegansexcretory cell, which contains an intracellular tube, the exocyst vesicle-tethering complex is enriched at the lumenal membrane domain and is required for tube formation, suggesting that it targets vesicles needed for lumen extension. Here, we identify a polarity pathway that promotes intracellular tube formation by enriching the exocyst at the lumenal membrane. We show that the PAR polarity proteins PAR-6 and PKC-3/aPKC localize to the lumenal membrane domain and function within the excretory cell to promote lumen extension, similar to exocyst component SEC-5 and exocyst regulator RAL-1. Using acute protein depletion, we find that PAR-6 is required to recruit the exocyst to the lumenal membrane domain, whereas PAR-3, which functions as an exocyst receptor in mammalian cells, appears to be dispensable for exocyst localization and lumen extension. Finally, we show that the Rho GTPase CDC-42 and the RhoGEF EXC-5/FGD act as upstream regulators of lumen formation by recruiting PAR-6 and PKC-3 to the lumenal membrane. Our findings reveal a molecular pathway that connects Rho GTPase signaling, cell polarity, and vesicle-tethering proteins to promote lumen extension in intracellular tubes.