bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Methylation as a Marker of Body Shape in Premenopausal Women
Authors: Divoux Adeline , Eroshkin Alexey , Erdos Edina , Sandor Katalin , Osborne Timothy F. , Smith Steven R. 
Published: July 2021

Preferential accumulation of fat in the gluteo-femoral (GF) depot (pear shape) rather than in the abdominal (A) depot (apple shape), protects against the development of metabolic diseases but the underlying molecular mechanism is still unknown. Recent data, including our work, suggest that differential epigenetic marking is associated with regulation of genes attributed to distinct fat distribution. Here, we aimed to compare the genomic DNA methylation signatures between apple and pear-shaped premenopausal women. To investigate the contribution of upper and lower body fat, we used paired samples of A-FAT and GF-FAT, analyzed on the BeadChip Methylation Array and quantified the differentially methylated sites between the 2 groups of women. We found unique DNA methylation patterns within both fat depots that are significantly different depending on the body fat distribution. Around 60% of the body shape specific DNA methylation sites identified in adipose tissue are maintained ex vivo in cultured preadipocytes. As it has been reported before in other cell types, we found only a hand full of genes showing coordinated differential methylation and expression levels. Finally, we determined that more than 50% of the body shape specific DNA methylation sites could also be detected in whole blood derived DNA. These data reveal a strong DNA methylation program associated with adipose tissue distribution with the possibility that a simple blood test could be used as a predictive diagnostic indicator of young women who are at increased risk for progressing to the apple body shape with a higher risk of developing obesity related complications.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02728635 and https://clinicaltrials.gov/ct2/show/NCT02226640, identifiers NCT02728635 and NCT02226640.
Association Between Insulin Resistance and Remote Diffusion-Weighted Imaging Lesions in Primary Intracerebral Hemorrhage
Authors: Ye Xiang-hua , Zhang Jian-li , Jin Yu-jia , Shen Dan , Hao Xiao-di , Li Jia-wen , Zhong Jia-wei , Jin Lu-hang , Tong Lu-sha , Gao Feng 
Published: July 2021

BackgroundAbnormal glucose metabolism was shown to be associated with the occurrence of remote diffusion-weighted imaging lesions (R-DWILs) after primary intracerebral hemorrhage (ICH) onset. Insulin resistance is a metabolic disorder that was regarded as an indicator of chronic systemic inflammation. In this study, we aimed to determine the effect of insulin resistance on the occurrence of R-DWILs in ICH.MethodsPatients with primary ICH within 14 days after onset were prospectively enrolled from November 2017 to October 2019. R-DWILs was defined as remote focal hyperintensity from the hematoma in DWI, with corresponding hypointensity in apparent diffusion coefficient. The homeostasis model assessment of insulin resistance (HOMA-IR) was used for insulin resistance estimation and calculated as fasting insulin (μU/ml) × fasting glucose (mmol/L)/22.5. Patients in our cohort were divided into four groups according to HOMA-IR index quartiles. Logistic regression analysis and smoothing plots were used to evaluate the association of HOMA-IR with R-DWIL occurrence. Sensitivity analysis was performed in non-diabetic patients, non-obese patients, hypertensive ICH patients, and patients 60 years and older separately. The association between HOMA-IR and systemic inflammatory immune indices neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) was examined with multiple linear regression analysis.ResultsAmong the 345 patients, 54 (15.7%) had R-DWILs. Both the third and fourth quartiles of HOMA-IR index were robustly associated with an increased risk of R-DWIL occurrence (adjusted OR 3.58, 95% CI 1.33-9.65; adjusted OR 3.91, 95%CI 1.47-10.41) when compared with the first quartile. The association was consistent in non-diabetic, non-obese, hypertensive ICH patients, as well as in patients 60 years and older. Furthermore, both NLR and MLR were independently associated with HOMA-IR.ConclusionsOur study suggested that insulin resistance evaluated with HOMA-IR index was independently associated with the presence of R-DWILs in patients with acute and subacute primary ICH. It may provide new insights into the metabolism-related brain injury after ICH ictus.
Characterization of Spacesuit Associated Microbial Communities and Their Implications for NASA Missions
Authors: Danko David , Malli Mohan Ganesh Babu , Sierra Maria A. , Rucker Michelle , Singh Nitin K. , Regberg Aaron B. , Bell Mary S. , O’Hara Niamh B. , Ounit Rachid , Mason Christopher E. , Venkateswaran Kasthuri 
Published: July 2021

BackgroundCrewed National Aeronautics and Space Administration (NASA) missions to other solar system bodies are currently being planned. One high-profile scientific focus during such expeditions would be life detection, specifically the discovery of past or present microbial life, if they exist. However, both humans and associated objects typically carry a high microbial burden. Thus, it is essential to distinguish between microbes brought with the expedition and those present on the exploring planets. Modern spacesuits are unique, customized spacecraft which provide protection, mobility and life support to crew during spacewalks, yet they vent, and the mobility of microbes through spacesuits has not been studied.ResultsTo evaluate the microbial colonization of spacesuits, NASA used an Extravehicular Activity swab kit to examine viable microbial populations of 48 samples from spacesuits using both traditional microbiological methods and molecular sequencing methods. The cultivable microbial population ranged from below the detection limit to 9 × 102 colony forming units per 25 cm2 of sample and also significantly varied by the location. The cultivable microbial diversity was dominated by members of Bacillus, Arthrobacter, and Ascomycota. However, 16S rRNA-based viable bacterial burden ranged from 105 to 106 copies per 25 cm2 of sample. Shotgun metagenome sequencing revealed the presence of a diverse microbial population on the spacesuit surfaces, including Curtobacterium and Methylobacterium from across all sets of spacesuits in high abundance. Among bacterial species identified, higher abundance of Cutibacterium acnes, Methylobacterium oryzae, and M. phyllosphaerae reads were documented.ConclusionThe results of this study provide evidence that identical microbial strains may live on the wrist joint, inner gauntlet, and outer gauntlet of spacesuits. This raises the possibility, but does not confirm that microbial contaminants on the outside of the suits could contaminate planetary science operations unless additional measures are taken. Overall, these data provide the first estimate of microbial distribution associated with spacesuit surfaces, which will help future mission planners develop effective planetary protection strategies.
Peer Support to Enhance Social and Emotional Self-Management Following Acquired Brain Injury Rehabilitation: Design of a Pre–post Study With Process Evaluation
Authors: Baumgartner-Dupuits Milou , Sep Simone J. S. , Verbunt Jeanine , Bosma Hans , van Eijk Jacques 
Published: July 2021

Background: Specialized rehabilitation following acquired brain injury provides intensive multidisciplinary treatment to individuals with complex disabilities for optimizing recovery and supporting a safe transition to the community. Post-specialist rehabilitation, patients and caregivers have reported a need for support. We present the design of an implementation study to evaluate a new self-management support service for individuals with acquired brain injury and their caregivers.Methods: This is a pre–post intervention study with a mixed-method design. The study population comprises individuals aged ≥18 years with acquired brain injury living independently following specialized rehabilitation in the Southern part of the Netherlands. All participants receive a post-rehabilitation support service. The support service consists of several house visits by a peer support volunteer in the first weeks after specialized rehabilitation treatment. The peer support volunteers are trained according to an adapted version of the previously developed Self-Management Support (SMS) program. The SMS program is directed at improving social and emotional self-management. Patient outcomes are assessed by questionnaire pre-, directly post-, and 6 months post-intervention. The primary patient outcome measure is self-efficacy. Secondary outcomes are perceived autonomy, quality of life, and psychological well-being. A process evaluation will be performed to gain insight into barriers and facilitators for the implementation of peer-led SMS by combining both quantitative, questionnaire data and qualitative data derived from focus groups with peer supporters and patients. In a workshop with relevant stakeholders, possibilities for dissemination and sustainability will be explored.Discussion: This paper describes the design of a practice-based study on feasibility, barriers, and facilitators to the implementation of a home-based, peer-led self-management support intervention for patients with acquired brain injury. We will quantitatively and qualitatively evaluate the change in relevant patient outcomes pre- and post-intervention and the barriers and facilitators related to the implementation of the intervention. Following a positive evaluation, the final stage of the study aims to facilitate deployment and utilization of the intervention.
Cognitive Impairment After COVID-19—A Review on Objective Test Data
Authors: Daroische Rania , Hemminghyth Mathilde S. , Eilertsen Thomas H. , Breitve Monica H. , Chwiszczuk Luiza J. 
Published: July 2021

Objective: The aim was to conduct a review on the literature on objective cognitive impairment in patients after COVID-19.Methods: We performed a literature review and searched Ovid Medline in February 2021 based on a PECO scheme.Results: Twelve articles met all inclusion criteria. Total patient sample was &lt;1,000. All studies on global cognitive function found impairment, ranging from 15 to 80% of the sampled patients. Seven studies on attention and executive functions reported impairment, with varying results depending on sub-domain and different tests. Three out of four studies reported memory difficulties, with two studies reporting short-term memory deficits. Although results indicate possible language impairment, only one study used domain-specific language tasks. Two out of four studies on visuospatial function did not report any impairment.Conclusion: Patients with recent SARS-CoV-2 infection appear to experience global cognitive impairment, impairment in memory, attention and executive function, and in particular verbal fluency. Based on the current results, we recommend clinicians to evaluate the need for cognitive assessment of patients with a recent COVID-19 infection, regardless of the severity of the disease, treatment methods and length of ICU stay. We need studies with larger sample and control group.
Neutrophil-to-Lymphocyte Ratio as a Predictive Biomarker for Stroke Severity and Short-Term Prognosis in Acute Ischemic Stroke With Intracranial Atherosclerotic Stenosis
Authors: Ying Yuanlin , Yu Fang , Luo Yunfang , Feng Xianjing , Liao Di , Wei Minping , Li Xi , Huang Qin , Liu Zeyu , Zhang Lin , Zhao Tingting , Tu Ruxin , Xia Jian 
Published: July 2021

Background: Neutrophil-to-lymphocyte ratio (NLR) is an indicator of poor prognosis in acute ischemic stroke (AIS), but associations between NLR with stroke severity and prognosis of intracranial atherosclerotic stenosis (ICAS)-related ischemic events have not been well-elucidated; therefore, we aimed to evaluate whether admission NLR levels correlate with the early stroke severity and short-term functional prognosis in patients with symptomatic intracranial atherosclerotic stenosis (sICAS).Methods: This retrospective study enrolled 899 consecutive patients with AIS attributed to ICAS at Xiangya Hospital stroke center between May 2016 and September 2020. The initial stroke severity was rated by the admission National Institutes of Health Stroke Scale (NIHSS) scores, and the short-term prognosis was evaluated using the 14-day modified Rankin Scale (mRS) scores after stroke onset. A severe stroke was defined as NIHSS &gt;8; an unfavorable functional outcome was defined as mRS scores of 3–6. Admission NLR was determined based on circulating neutrophil and lymphocyte counts.Results: The median admission NLR of all patients was 2.80 [interquartile range (IQR), 2.00–4.00]. In univariate analysis, admission NLR was significantly elevated in patients with severe stroke and poor short-term prognosis. After multivariate adjustment, admission NLR levels were significantly correlated with severe stroke [odds ratio (OR), 1.132; 95% confidence interval (95% CI), 1.038–1.234; P = 0.005] and unfavorable short-term prognosis (OR, 1.102; 95% CI, 1.017–1.195; P = 0.018) in Model 1. In Model 2, the highest NLR tertile (≥3.533) remained an independent predictor of severe stroke (OR, 2.736; 95% CI, 1.590–4.708; P &lt; 0.001) and unfavorable functional outcome (OR, 2.165; 95% CI, 1.416–3.311; P &lt; 0.001) compared with the lowest NLR tertile (&lt;2.231). The receiver operating characteristic (ROC) curves showed the predictability of NLR regarding the stroke severity [area under the curve (AUC), 0.659; 95% CI, 0.615–0.703; P &lt; 0.001] and short-term prognosis (AUC, 0.613; 95% CI, 0.575–0.650; P &lt; 0.001). The nomograms were constructed to create the predictive models of the severity and short-term outcome of sICAS.Conclusions: Elevated admission NLR levels were independently associated with the initial stroke severity and could be an early predictor of severity and poor short-term prognosis in AIS patients with ICAS, which might help us identify a target group timely for preventive therapies.
Targeted Next-Generation Sequencing of Circulating Tumor DNA, Bone Marrow, and Peripheral Blood Mononuclear Cells in Pediatric AML
Authors: Ruan Min , Liu Lipeng , Qi Benquan , Chen Xiaoyan , Chang Lixian , Zhang Aoli , Liu Fang , Wang Shuchun , Liu Xiaoming , Chen Xiaojuan , Zhang Li , Guo Ye , Zou Yao , Zhang Yingchi , Chen Yumei , Liu LiXia , Cao Shanbo , Lou Feng , Wang Chengcheng , Zhu Xiaofan 
Published: July 2021

BackgroundThe aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia (AML).MethodsBone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel.ResultsAmong 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R2 = 0.895).ConclusionThis study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.
Exploring the Pharmacological Mechanism of Radix Salvia Miltiorrhizae in the Treatment of Radiation Pneumonia by Using Network Pharmacology
Authors: Li Peng , Xia Xiaochun , Zhou Jundong , Wu Jinchang 
Published: July 2021

BackgroundRadiation pneumonia (RP) is the most common complication of radiotherapy to the thorax and seriously affects the survival rate and quality of life of patients. Radix Salviae Miltiorrhizae (RSM) is an ancient Chinese medicine, whose main pharmacological effect is to promote blood circulation and remove stasis. A growing number of studies have proved that RSM has a good effect on RP. However, the underlying mechanism is still unclear and needs to be fully elucidated.MethodsThe effective components and predictive targets of RSM were analyzed by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the related targets of RP were predicted by GeneCards database. The common targets of the two targets mentioned above were analyzed by protein-protein interaction on the STRING website, GO and KEGG analysis on the DAVID website, visualization by CytoScape3.7.0, and screening for Hubber gene by cytoHubber plug-in.ResultsA search of the TCMSP database revealed that RSM contains 65 chemical constituents and 165 potential protein targets. A total of 2,162 protein targets were found to be associated with RP. The top 10 hub genes were obtained by MCC algorithm for 70 common genes, including TP53, CASP3, MAPK1, JUN, VEGFA, STAT3, PTGS2, IL6, AKT1, and FOS. By analyzing the Gene Ontology, The anti-radiation pneumonia effect of RSM is that it performs molecular functions (protein homodimerization activity) in the nucleus through three biological processes (positive regulation of transcription from RNA polymerase II promoter,Extrinsic apoptotic signaling pathway in absence of ligand and lipopolysaccharide-mediated signaling pathway). Through KEGG analysis, the mechanism of RSM treatment of radiation pneumonia may be through PI3K-Akt, HIF-1, TNF signaling pathways.ConclusionsThrough network pharmacology analysis, we found the possible target genes of RSM on RP and revealed the most likely signaling pathway, providing theoretical basis for further elucidating the potential mechanism of RSM on RP.
Involvement and Targeted Intervention of Mortalin-Regulated Proteome Phosphorylated-Modification in Hepatocellular Carcinoma
Authors: Yang Ye , Jin Ming , Dai Yi , Shan Wenqi , Chen Shuai , Cai Rong , Yang Haojun , Tang Liming , Li Lei 
Published: July 2021

ObjectivesTo reveal the mechanisms of the effects of mortalin in hepatocellular carcinoma (HCC) and to identify potential novel chemical inhibitors of mortalin.Materials and MethodsFor the experiments, three HCC cell lines (HepG2 cells, Hep3B cells, and sorafenib-resistant HuH7 cells) and xenografted nude mice were used. For the clinical analysis, cohorts of 126 patients with HCC and 34 patients with advanced recurrent HCC receiving sorafenib therapy were examined.ResultsMortalin regulated the phosphorylation-modification of cancer-associated proteins and also regulated angiogenesis-related secretome to cause angiogenesis and sorafenib resistance in HCC cells. Two molecular mechanisms were identified. In one, via phosphatidylinositol 3-kinase (PI3K)/Akt signaling, mortalin regulated nuclear factor (NF)-κB and then activated vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to neovascularization. In the other, mortalin regulated PI3K/Akt/β-catenin and then regulated Bcl-XL and Bcl-2, leading to the antiapoptosis effect of HCC. Treatment of the sorafenib-resistant xenografts with sorafenib in combination with mortalin knockdown facilitated the sorafenib-mediated inhibition of tumor growth and angiogenesis and increased apoptosis. Mortalin was a potential risk factor for HCC, predicting poor prognosis and sorafenib resistance. Finally, we showed that caffeic acid (C9H8O4) could bind to and induce the ubiquitination-mediated degradation of mortalin, which in turn blocked the abovementioned signaling pathways, leading to the inhibition of angiogenesis and the reversal of sorafenib resistance.ConclusionsMortalin, which regulates the phosphorylation of cancer-associated proteins, caused angiogenesis and sorafenib resistance, and was a competitive risk factor for HCC. Caffeic acid can therefore be considered a novel chemical inhibitor that targets the action of mortalin and a potential treatment for HCC.
Beyond BRCA Status: Clinical Biomarkers May Predict Therapeutic Effects of Olaparib in Platinum-Sensitive Ovarian Cancer Recurrence
Authors: Nakanishi Kazuho , Yamada Takashi , Ishikawa Gen , Suzuki Shunji 
Published: July 2021

The purpose of this study was to investigate the predictors of the effect of olaparib on platinum-sensitive recurrent ovarian cancer with unknown germline BRCA mutations. We retrospectively examined 20 patients with platinum-sensitive ovarian cancer who were treated at the Nippon Medical School Chiba Hokusoh Hospital, Japan, from 2018 to 2020. We found that the median progression-free survival was 11.4 months (95% Confidence interval (CI): 3.8–Not Available (NA)) in the group with NLPN score [recurrent neutrophil-lymphocyte ratio (rNLR) × number of previous regimens] &gt;7.51, and median progression-free survival was not reached in the group with NLPN score &lt;7.51 (95% CI: 21.8–NA) (p = 0.0185). There was a clear correlation between the degree of dose reduction of olaparib and recurrence (p = 0.00249). Our results show that NLPN scores lower than 7.51 are associated with a favorable outcome of olaparib treatment for platinum-sensitive recurrent ovarian cancer. In cases with a high rNLR, it may be necessary to start olaparib treatment as early as possible to obtain low NLPN scores. Our results imply that the effectiveness of olaparib can be determined after recurrence and before platinum treatment begins. As newer drugs for ovarian cancer are developed, the measurement of biomarker levels at the start of treatment for recurrent ovarian cancer, as shown in our study, may provide strong support for cancer treatment protocols.