bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneously administered antibiotics: a review
Authors: Jumpertz Marie , Guilhaumou Romain , Million Matthieu , Parola Philippe , Lagier Jean-Christophe , Brouqui Philippe , Cassir Nadim 
Published: November 2022

Abstract

Background
Subcutaneous (SC) administration of antibiotics represents an attractive alternative to the intravenous (IV) route.

Methods
We performed a systematic electronic search of PubMed and the Cochrane Library for all articles published prior to April 2022, using the key terms and MeSH terms ‘subcutaneous’, ‘antibiotic’ and the international non-proprietary name of antibiotics.

Results
A total of 30 studies were selected including data on the efficacy and tolerability of antibiotics, and seven studies that were conducted in healthy subjects, for relevant information regarding the safety and tolerability of antibiotics. Comparative studies have shown that efficacy is similar for the SC and IV routes for ceftriaxone, teicoplanin and ertapenem. The SC use of other antibiotics such as ampicillin, ceftazidime, cefepime, piperacillin/tazobactam, metronidazole and fosfomycin has also been described. These results have largely been corroborated by pharmacokinetic/pharmacodynamic analyses, especially for time-dependent antibiotics. Complications of SC treatment are rarely severe, with no reports of bacteraemia or other invasive infection related to this route of administration. Therapeutic drug monitoring has been proposed to adapt the dose and avoid toxicity.

Discussion
The rationale for using SC administration of ceftriaxone, ertapenem and teicoplanin is strong in patients with non-severe infections. It is already commonly practised in some countries, particularly in France. Other antibiotics could be administered subcutaneously, but further studies are needed to validate their use in clinical practice. Further research is needed to safely generalize and optimize this route of administration whenever possible. This would reduce the risk of catheter-related infections and their complications, together with the length of hospital stay.
Gastrointestinal dynamics, immune response, and nutrient digestibility of weanling pigs fed diets supplemented with enzymatically treated yeast
Authors: Alagbe Emmanuel O , Aderibigbe Ayodeji S , Schulze Hagen , Ajuwon Kolapo M , Adeola Olayiwola 
Published: November 2022

Abstract
The objective of this trial was to investigate the effect of enzymatically treated yeast (ETY) on the growth performance, nutrient digestibility, immune response, and gut health of weanling pigs. A total of 192 weanling pigs (6.0 ± 1.04 kg) were allocated to 4 corn and soybean-based diets with increasing concentrations of ETY (0, 1, 2, or 4 g/kg) for a 43-d trial. There were 8 replicate pens (4 replicate pens per sex) and 6 pigs per replicate. The experiment was set up as a randomized complete block design with body weight used as a blocking factor. Pigs had ad libitum access to water and diets for the duration of the study. There was no effect of ETY supplementation on the growth performance indices of weanling pigs. At day 14, there was a quadratic decrease (P &lt; 0.05) in the apparent total tract digestibility (ATTD) of acid detergent fiber (ADF). At day 28, there was a linear increase (P &lt; 0.05) in the ATTD of neutral detergent fiber and a quadratic decrease (P &lt; 0.05) in the ATTD of ADF. On day 14, there was a linear increase (P &lt; 0.05) in serum catalase activity with ETY supplementation. There was a linear increase (P &lt; 0.01) in the gene expression of glutathione peroxidase-4 in the ileal mucosa of pigs. Increasing dietary ETY supplementation linearly decreased (P &lt; 0.05) the gene expression of ileal peptide transporter 1. There was a tendency for a quadratic effect (P = 0.07) in the ileal villus height to crypt depth ratio with ETY supplementation. In addition, there was a tendency for a linear increase (P = 0.06) in ileal digesta butyrate with ETY supplementation. In conclusion, the current study demonstrated that dietary ETY supplementation could partly ameliorate the deleterious effects of post-weaning stress by enhancing the antioxidative status of weanling pigs. However, prolonged supplementation of ETY may be needed to see its effect on growth performance.
A comparative study of fatigue behavior between S-shaped and involute POM gears
Authors: Wu Ruo , Wei Peitang , Lu Zehua , Liu Huaiju , Zorko Damijan , Xie Huaijie 
Published: November 2022

Abstract
Applications of polymer gears have been gradually expanding from motion transmission to power transmission fields. Design of new gear teeth profiles plays a crucial role in meeting the requirement of replacing metallic gears with polymer ones. This work develops a computational framework consisting of tooth profile generation and fatigue life prediction of S-shaped and involute POM gears. The contact and bending fatigue performances of S-shaped and involute POM gears under oil lubrication are comparatively studied. It is found that the S-shaped profile reduces the tooth root stress by 25% and significantly improves the bending fatigue life by 10 times compared with the involute profile, especially under medium or high loading levels. Furthermore, the S-shaped gear with a single circular-filleted root curve benefits a 20% reduction of tooth root stress and a 30% increase in bending fatigue life compared to a double circular-filleted root curve S-shaped gear.
Additional evidence that Fomalhaut b might be a non-exoplanet
Authors: Del Vecchio Alexa , Stone Jonathon Rick 
Published: November 2022

ABSTRACT
Fomalhaut b is an extrasolar object that was imaged directly in 2008. Its status since has changed from exoplanet – including super-Earth and low-mass candidates – to neutron star to dust cloud, generating contention, controversy, and confusion. We contribute to the discussion by reporting additional evidence that, given a set containing celestial objects classified as exoplanets, Fomalhaut b might be a non-member. We conducted a principal component (PC) analysis on a data set containing 425 extrasolar objects and 7 variables and found a single isolated point in PC space representing Fomalhaut b. Whatever its existential status, Fomalhaut b is characterized by properties very different from those characterizing exoplanets.
NPInter v5.0: ncRNA interaction database in a new era
Authors: Zheng Yu , Luo Huaxia , Teng Xueyi , Hao Xinpei , Yan Xiaoyu , Tang Yiheng , Zhang Wanyu , Wang Yuanxin , Zhang Peng , Li Yanyan , Zhao Yi , Chen Runsheng , He Shunmin 
Published: November 2022

Abstract
Noncoding RNAs (ncRNAs) play key regulatory roles in biological processes by interacting with other biomolecules. With the development of high-throughput sequencing and experimental technologies, extensive ncRNA interactions have been accumulated. Therefore, we updated the NPInter database to a fifth version to document these interactions. ncRNA interaction entries were doubled from 1 100 618 to 2 596 695 by manual literature mining and high-throughput data processing. We integrated global RNA–DNA interactions from iMARGI, ChAR-seq and GRID-seq, greatly expanding the number of RNA–DNA interactions (from 888 915 to 8 329 382). In addition, we collected different types of RNA interaction between SARS-CoV-2 virus and its host from recently published studies. Long noncoding RNA (lncRNA) expression specificity in different cell types from tumor single cell RNA-seq (scRNA-seq) data were also integrated to provide a cell-type level view of interactions. A new module named RBP was built to display the interactions of RNA-binding proteins with annotations of localization, binding domains and functions. In conclusion, NPInter v5.0 (http://bigdata.ibp.ac.cn/npinter5/) provides informative and valuable ncRNA interactions for biological researchers.
Mod(mdg4) variants repress telomeric retrotransposon HeT-A by blocking subtelomeric enhancers
Authors: Takeuchi Chikara , Yokoshi Moe , Kondo Shu , Shibuya Aoi , Saito Kuniaki , Fukaya Takashi , Siomi Haruhiko , Iwasaki Yuka W 
Published: November 2022

Abstract
Telomeres in Drosophila are composed of sequential non-LTR retrotransposons HeT-A, TART and TAHRE. Although they are repressed by the PIWI-piRNA pathway or heterochromatin in the germline, the regulation of these retrotransposons in somatic cells is poorly understood. In this study, we demonstrated that specific splice variants of Mod(mdg4) repress HeT-A by blocking subtelomeric enhancers in ovarian somatic cells. Among the variants, we found that the Mod(mdg4)-N variant represses HeT-A expression the most efficiently. Subtelomeric sequences bound by Mod(mdg4)-N block enhancer activity within subtelomeric TAS-R repeats. This enhancer-blocking activity is increased by the tandem association of Mod(mdg4)-N to repetitive subtelomeric sequences. In addition, the association of Mod(mdg4)-N couples with the recruitment of RNA polymerase II to the subtelomeres, which reinforces its enhancer-blocking function. Our findings provide novel insights into how telomeric retrotransposons are regulated by the specific variants of insulator proteins associated with subtelomeric sequences.
Incorporating cell hierarchy to decipher the functional diversity of single cells
Authors: Chen Lingxi , Li Shuai Cheng 
Published: November 2022

Abstract
Cells possess functional diversity hierarchically. However, most single-cell analyses neglect the nested structures while detecting and visualizing the functional diversity. Here, we incorporate cell hierarchy to study functional diversity at subpopulation, club (i.e., sub-subpopulation), and cell layers. Accordingly, we implement a package, SEAT, to construct cell hierarchies utilizing structure entropy by minimizing the global uncertainty in cell–cell graphs. With cell hierarchies, SEAT deciphers functional diversity in 36 datasets covering scRNA, scDNA, scATAC, and scRNA-scATAC multiome. First, SEAT finds optimal cell subpopulations with high clustering accuracy. It identifies cell types or fates from omics profiles and boosts accuracy from 0.34 to 1. Second, SEAT detects insightful functional diversity among cell clubs. The hierarchy of breast cancer cells reveals that the specific tumor cell club drives AREG-EGFT signaling. We identify a dense co-accessibility network of cis-regulatory elements specified by one cell club in GM12878. Third, the cell order from the hierarchy infers periodic pseudo-time of cells, improving accuracy from 0.79 to 0.89. Moreover, we incorporate cell hierarchy layers as prior knowledge to refine nonlinear dimension reduction, enabling us to visualize hierarchical cell layouts in low-dimensional space.
CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase
Authors: Krysiak Kilannin , Danos Arpad M , Saliba Jason , McMichael Joshua F , Coffman Adam C , Kiwala Susanna , Barnell Erica K , Sheta Lana , Grisdale Cameron J , Kujan Lynzey , Pema Shahil , Lever Jake , Ridd Sarah , Spies Nicholas C , Andric Veronica , Chiorean Andreea , Rieke Damian T , Clark Kaitlin A , Reisle Caralyn , Venigalla Ajay C , Evans Mark , Jani Payal , Takahashi Hideaki , Suda Avila , Horak Peter , Ritter Deborah I , Zhou Xin , Ainscough Benjamin J , Delong Sean , Kesserwan Chimene , Lamping Mario , Shen Haolin , Marr Alex R , Hoang My H , Singhal Kartik , Khanfar Mariam , Li Brian V , Lin Wan-Hsin , Terraf Panieh , Corson Laura B , Salama Yasser , Campbell Katie M , Farncombe Kirsten M , Ji Jianling , Zhao Xiaonan , Xu Xinjie , Kanagal-Shamanna Rashmi , King Ian , Cotto Kelsy C , Skidmore Zachary L , Walker Jason R , Zhang Jinghui , Milosavljevic Aleksandar , Patel Ronak Y , Giles Rachel H , Kim Raymond H , Schriml Lynn M , Mardis Elaine R , Jones Steven J M , Raca Gordana , Rao Shruti , Madhavan Subha , Wagner Alex H , Griffith Malachi , Griffith Obi L 
Published: November 2022

Abstract
CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC’s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing &gt;3200 variants in &gt;470 genes from &gt;3100 publications.
ANGI-02. EPIGENETIC REGULATION OF GLIOMA INVASION BY CHITINASE-3-LIKE PROTEIN 1 (CHI3L1) CPG PROMOTER METHYLATION
Authors: Schreiner Sophie , Cialini Camille , Salcedo Uxue , Mittelbronn Michel , Hau Ann-Christin , Müller Tanja 
Published: November 2022

Abstract
Epigenetically controlled processes play an important role in development but also in the formation and progression of many common diseases. Molecular signatures are increasingly incorporated into cancer classifications and DNA methylation-based analyses of brain tumors including glioma is currently the gold standard. Glioblastoma (GBM), CNS WHO grade 4, is characterized by a very diffuse infiltrative growth into the adjacent brain parenchyma. Due to these highly invasive but also genetically heterogeneous and plastic cellular phenotypes, standard treatment, including maximum resection, radio- and chemotherapy, has limited efficacy. It can be assumed that intertumoral or molecular heterogeneity of gliomas at the transcriptome level is caused by altered epigenetic changes within the individual tumor cells. Considering this, we hypothesize that tumor cell invasion being one of the major hallmarks of highly malignant gliomas can be associated with altered DNA methylation and therefore transcript expression. To analyze this, we isolated fractions of glioma cells with increased invasive properties and performed Illumina® array-based methylation profiling as well as RNA sequencing analysis to identify methylation-driven, invasion-promoting genes. Among other, we focused on Chitinase-3-like protein 1 (CHI3L1) as a candidate gene with significantly decreased promoter methylation in invasive cell fractions and overall strong transcript expression in high-grade gliomas. Differential expression and methylation correlation of TCGA data combined with our own dataset revealed that CHI3L1 expression is dependent on the methylation status of at least three CpG sites within the gene promoter region. We validated these findings using several in vitro experimental settings and propose an upstream regulatory mechanism in which single CpG DNA demethylation within the CHI3L1 promoter facilitates transcription factor binding resulting in gene expression.
ANGI-04. DEPLETION OF CHITINASE-3-LIKE PROTEIN 1 (CHI3L1) IN HUMAN U87-MG GLIOMA CELLS AFFECTS TUMOUR GROWTH AND NEOVASCULATURE IN INTRACRANIAL MOUSE MODEL
Authors: Cyranowski Salwador , Zawadzka Malgorzata , Wojtas Bartosz , Swatler Julian , Kaminska Bozena 
Published: November 2022

Abstract
Chitinase-3-like protein 1 (CHI3L1) plays multiple roles in inflammation, tissue remodelling, and wound healing. It is a new, potentially druggable target for the treatment of cancer due to its association with both extracellular matrix (ECM) modifications and potential involvement in neoangiogenesis. Expression of CHI3L1 is upregulated in glioblastoma (GBM), the most common and aggressive primary brain tumour. The role of CHI3L1 in GBM progression is not fully understood and calls for further research. We generated a knockout (KO) of CHI3L1 in human glioblastoma U87-MG cells. To evaluate the effects of CHI3L1 KO on tumour growth, wild-type (WT) or CHI3L1 KO cells were intracranially implanted into athymic mice and tumour volume was assessed with magnetic resonance imaging. We have measured the serum level of CHI3L1 in both groups and correlated it with the tumour burden. Immunofluorescent staining against endothelium marker – von Willebrand factor (vWF), and perivascular water channel – aquaporin 4 (AQP4) were employed to evaluate the tumour vasculature in both groups. We found that CHI3L1 KO in glioblastoma cells significantly reduced volume of established tumors. Blood serum level of CHI3L1 positively correlated with tumour burden of experimental animals, which corroborates its role as a biomarker. Immunostaining for vWF revealed that in CHI3L1 KO gliomas there were more non-capillary blood vessels than in controls. We observed a higher level of AQP4 in CHI3L1 KO tumours, which suggests a difference in the structure of perivascular space, and thus vasculature functionality, in CHI3L1 depleted gliomas. In conclusion, we demonstrated the involvement of glioma-derived CHI3L1 in the growth and neovasculature of experimental human gliomas. Our findings suggest that the depletion of CHI3L1 in glioma cells results in a higher number and possibly different structure of non-capillary blood vessels in the tumour. Studies supported by the grant N 2020/39/B/NZ4/02683 from the National Science Center.
BIOM-06. IDENTIFICATION OF AN INFLAMMATORY BIOMARKER SIGNATURE IN PLASMA-DERIVED EXTRACELLULAR VESICLES OF GLIOBLASTOMA PATIENTS
Authors: Giamas Georgios , Cilibrasi Chiara , Simon Thomas , Stewart Nicolas , Critchley Giles , Eravci Murat 
Published: November 2022

Abstract
Diagnosis of Glioblastoma (GBM) remains a clinical challenge, currently relying on symptomatic presentation of the tumour, brain imaging and invasive biopsy. Description of effective biomarkers in biofluids could prove invaluable in GBM diagnosis. Extracellular vesicles (EVs) are essential to intercellular crosstalk in the tumour bulk and circulating EVs have been described as a potential reservoir of GBM biomarkers. Our work focuses on the: (i) isolation of EVs from blood liquid biopsies of GBM patients. (ii) Characterisation of their transcriptomic and proteomic cargoes to identify/validate novel candidate GBM biomarkers that could improve GBM diagnosis/prognosis. (iii) For cases where the original GBM tumour tissues are available, we will examine the expression of the identified biomarker signatures (derived from blood-EVs) to see if the content of EVs mirrors the transcriptomic/proteomic profile of the original tissue. Similar comparisons will be performed in GBM cohorts available in TCGA. Ultimately, in future studies, transcriptomic/proteomic analyses will be assessed during patients’ follow-ups to correlate the observed biomarker profiles with MRI data,treatment,recurrence, including molecular and clinical features.Our preliminary data comparing the proteomic cargoes of EVs derived from GBM patients (n=15) and those from healthy volunteers (n=10) indicated the presence of a GBM inflammatory biomarker signature comprising members of the complement and regulators of inflammation and coagulation. Bioinformatic analysis highlighted that all potential markers exclusively identified in patient samples have been linked with either GBM diagnosis,prognosis or associated signalling, suggesting that sEVs protein cargo could mirror the landscape of the original tumour and that selective circulating sEV-derived proteins might be used as hallmarks for GBM patients.Overall, this study is a step forward in the development of a non-invasive liquid biopsy approach for the identification of valuable biomarkers that could significantly improve GBM diagnosis and, consequently, patients’ prognosis and quality of life.
BIOM-07. LOW EXPRESSION OF HLA-A AS A NOVEL PROGNOSTIC FACTOR IN GLIOBLASTOMA TREATED WITH TUMOR FUSED DENDRITIC CELL VACCINES
Authors: Takei Jun , Akasaki Yasuharu , Tanaka Toshihide , Fukasawa Nei , Gomisawa Kazutaka , Satake Mari , Mori Ryosuke , Yamamoto Yohei , Oda Ayaka , Kamata Yuko , Murahashi Mutsunori , Fukuda Takahiro , Shimoda Masayuki , Murayama Yuichi 
Published: November 2022

Abstract
Although immunotherapy has become an attractive approach to cancer treatment in patients with broad types of aggressive tumors, phase III clinical trials of immunotherapy for glioblastoma (GBM) have not achieved extended survival of patients. Dendritic cells perform an essential role in the immune system as antigen-presenting cells and tumor fused dendritic cells (TFDCs) can induce tumor-specific cytotoxic T cells as a cancer vaccine. We have previously described the safety and mechanisms of TFDCs therapy, as well as immunological and clinical responses of patients with GBM, however, there were little known about predictive and prognostic biomarkers specific to TFDCs therapy. In the present study, we investigated the whole transcriptome sequencing of tumor cells, and novel prognostic factors were identified through molecular profiling GBM treated with TFDCs immunotherapy. Fifty-three patients were eligible in this study and 28 samples from patients with newly diagnosed GBM IDH wild-type were included. Of these 28 samples, 15 high-quality RNA samples successfully extracted from tumors were analysed. The samples were divided into two groups based on the median patient's overall survival. Differential expression analyses and enrichment analysis between the two groups were carried out using CLC Genomics Workbench (QIAGEN), and Gene Ontologies (GO) were assigned. A total of 473 differentially expressed genes were detected including 327 enriched GO terms. Fifteen GO terms out of 327 GO terms represented the highest enrichment scores, revealed that five GO terms were associated with the major histocompatibility complex (MHC). The relationship among the MHC, immune-related genes, and clinical outcomes was investigated using the Cox regression model and Kaplan–Meier log-rank test. Low expression of HLA-A in the tumors turned out to be a significantly favorable prognostic impact (p = 0.01). The decreased expression of HLA-A might be a novel prognostic factor in GBM patients treated with TFDCs immunotherapy.