bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Machine Learning to Predict Obesity Based on Genome-Wide and Epigenome-Wide Gene–Gene and Gene–Diet Interactions
Authors: Lee Yu-Chi , Christensen Jacob J. , Parnell Laurence D. , Smith Caren E. , Shao Jonathan , McKeown Nicola M. , Ordovás José M. , Lai Chao-Qiang 
Published: January 2022

Obesity is associated with many chronic diseases that impair healthy aging and is governed by genetic, epigenetic, and environmental factors and their complex interactions. This study aimed to develop a model that predicts an individual’s risk of obesity by better characterizing these complex relations and interactions focusing on dietary factors. For this purpose, we conducted a combined genome-wide and epigenome-wide scan for body mass index (BMI) and up to three-way interactions among 402,793 single nucleotide polymorphisms (SNPs), 415,202 DNA methylation sites (DMSs), and 397 dietary and lifestyle factors using the generalized multifactor dimensionality reduction (GMDR) method. The training set consisted of 1,573 participants in exam 8 of the Framingham Offspring Study (FOS) cohort. After identifying genetic, epigenetic, and dietary factors that passed statistical significance, we applied machine learning (ML) algorithms to predict participants’ obesity status in the test set, taken as a subset of independent samples (n = 394) from the same cohort. The quality and accuracy of prediction models were evaluated using the area under the receiver operating characteristic curve (ROC-AUC). GMDR identified 213 SNPs, 530 DMSs, and 49 dietary and lifestyle factors as significant predictors of obesity. Comparing several ML algorithms, we found that the stochastic gradient boosting model provided the best prediction accuracy for obesity with an overall accuracy of 70%, with ROC-AUC of 0.72 in test set samples. Top predictors of the best-fit model were 21 SNPs, 230 DMSs in genes such as CPT1A, ABCG1, SLC7A11, RNF145, and SREBF1, and 26 dietary factors, including processed meat, diet soda, French fries, high-fat dairy, artificial sweeteners, alcohol intake, and specific nutrients and food components, such as calcium and flavonols. In conclusion, we developed an integrated approach with ML to predict obesity using omics and dietary data. This extends our knowledge of the drivers of obesity, which can inform precision nutrition strategies for the prevention and treatment of obesity.Clinical Trial Registration: [www.ClinicalTrials.gov], the Framingham Heart Study (FHS), [NCT00005121].
Insights Into Comparative Analyses and Phylogenomic Implications of Acer (Sapindaceae) Inferred From Complete Chloroplast Genomes
Authors: Yu Tao , Gao Jian , Liao Pei-Chun , Li Jun-Qing , Ma Wen-Bao 
Published: January 2022

Acer L. (Sapindaceae) is one of the most diverse and widespread plant genera in the Northern Hemisphere. It comprises 124–156 recognized species, with approximately half being native to Asia. Owing to its numerous morphological features and hybridization, this genus is taxonomically and phylogenetically ranked as one of the most challenging plant taxa. Here, we report the complete chloroplast genome sequences of five Acer species and compare them with those of 43 published Acer species. The chloroplast genomes were 149,103–158,458 bp in length. We conducted a sliding window analysis to find three relatively highly variable regions (psbN-rps14, rpl32-trnL, and ycf1) with a high potential for developing practical genetic markers. A total of 76–103 SSR loci were identified in 48 Acer species. The positive selection analysis of Acer species chloroplast genes showed that two genes (psaI and psbK) were positively selected, implying that light level is a selection pressure for Acer species. Using Bayes empirical Bayes methods, we also identified that 20 cp gene sites have undergone positive selection, which might result from adaptation to specific ecological niches. In phylogenetic analysis, we have reconfirmed that Acer pictum subsp. mono and A. truncatum as sister species. Our results strongly support the sister relationships between sections Platanoidea and Macrantha and between sections Trifoliata and Pentaphylla. Moreover, series Glabra and Arguta are proposed to promote to the section level. The chloroplast genomic resources provided in this study assist taxonomic and phylogenomic resolution within Acer and the Sapindaceae family.
Multi-Omics Analysis for Transcriptional Regulation of Immune-Related Targets Using Epigenetic Data: A New Research Direction
Authors: Huang Chenshen , Zhang Na , Xiong Hao , Wang Ning , Chen Zhizhong , Ni Zhizhan , Liu Xiaohong , Lin Boxu , Ge Bujun , Du Bing , Huang Qi 
Published: January 2022

BackgroundCurrently, a comprehensive method for exploration of transcriptional regulation has not been well established. We explored a novel pipeline to analyze transcriptional regulation using co-analysis of RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq).MethodsThe G protein-coupled receptors (GPCRs) possibly associated with macrophages were further filtered using a reduced-Cox regression model. ATAC-seq profiles were used to map the chromatin accessibility of the GPRC5B promoter region. Pearson analysis was performed to identify the transcription factor (TF) whose expression was correlated with open chromatin regions of GPRC5B promoter. ChIP-seq profiles were obtained to confirm the physical binding of GATA4 and its predicted binding regions. For verification, quantitative polymerase chain reaction (qPCR) and multidimensional database validations were performed.ResultsThe reduced-Cox regression model revealed the prognostic value of GPRC5B. A novel pipeline for TF exploration was proposed. With our novel pipeline, we first identified chr16:19884686-19885185 as a reproducible open chromatin region in the GPRC5B promoter. Thereafter, we confirmed the correlation between GATA4 expression and the accessibility of this region, confirmed its physical binding, and proved in vitro how its overexpression could regulate GPRC5B. GPRC5B was significantly downregulated in colon adenocarcinoma (COAD) as seen in 28 patient samples. The correlation between GPRC5B and macrophages in COAD was validated using multiple databases.ConclusionGPRC5B, correlated with macrophages, was a key GPCR affecting COAD prognosis. Further, with our novel pipeline, TF GATA4 was identified as a direct upstream of GPRC5B. This study proposed a novel pipeline for TF exploration and provided a theoretical basis for COAD therapy.
Persistence of Anti-SARS-CoV-2 Antibodies in Long Term Care Residents Over Seven Months After Two COVID-19 Outbreaks
Authors: Tanunliong Guadalein , Liu Aaron , Vijh Rohit , Pidduck Tamara , Kustra Jesse , Márquez Ana Citlali , Choi Alexandra , McLennan Meghan , Hayden Althea , Kearney Christy , Gantt Soren , Krajden Mel , Morshed Muhammad , Jassem Agatha N. , Sekirov Inna 
Published: January 2022

BackgroundAs part of the public health outbreak investigations, serological surveys were carried out following two COVID-19 outbreaks in April 2020 and October 2020 in one long term care facility (LTCF) in British Columbia, Canada. This study describes the serostatus of the LTCF residents and monitors changes in their humoral response to SARS-CoV-2 and other human coronaviruses (HCoV) over seven months.MethodsA total of 132 serum samples were collected from all 106 consenting residents (aged 54-102) post-first outbreak (N=87) and post-second outbreak (N=45) in one LTCF; 26/106 participants provided their serum following both COVID-19 outbreaks, permitting longitudinal comparisons between surveys. Health-Canada approved commercial serologic tests and a pan-coronavirus multiplexed immunoassay were used to evaluate antibody levels against the spike protein, nucleocapsid, and receptor binding domain (RBD) of SARS-CoV-2, as well as the spike proteins of HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43. Statistical analyses were performed to describe the humoral response to SARS-CoV-2 among residents longitudinally.FindingsSurvey findings demonstrated that among the 26 individuals that participated in both surveys, all 10 individuals seropositive after the first outbreak continued to be seropositive following the second outbreak, with no reinfections identified among them. SARS-CoV-2 attack rate in the second outbreak was lower (28.6%) than in the first outbreak (40.2%), though not statistically significant (P&gt;0.05). Gradual waning of anti-nucleocapsid antibodies to SARS-CoV-2 was observed on commercial (median Δ=-3.7, P=0.0098) and multiplexed immunoassay (median Δ=-169579, P=0.014) platforms; however, anti-spike and anti-receptor binding domain (RBD) antibodies did not exhibit a statistically significant decline over 7 months. Elevated antibody levels for beta-HCoVs OC43 (P&lt;0.0001) and HKU1 (P=0.0027) were observed among individuals seropositive for SARS-CoV-2 compared to seronegative individuals.ConclusionOur study utilized well-validated serological platforms to demonstrate that humoral responses to SARS-CoV-2 persisted for at least 7 months. Elevated OC43 and HKU1 antibodies among SARS-CoV-2 seropositive individuals may be attributed to cross reaction and/or boosting of humoral response.
O-Acetyl-GD2 as a Therapeutic Target for Breast Cancer Stem Cells
Authors: Cheng Jing-Yan , Hung Jung-Tung , Lin Juway , Lo Fei-Yun , Huang Jing-Rong , Chiou Shih-Pin , Wang Ya-Hui , Lin Ruey-Jen , Wu Jen-Chine , Yu John , Yu Alice L. 
Published: January 2022

SynopsisA sugar-lipid molecule called OAcGD2 is a novel marker for breast cancer stem cells. Treatment with anti-OAcGD2 mAb8B6 may have superior anticancer efficacy by targeting cancer stem cells, thereby reducing metastasis and recurrence of cancer.BackgroundCancer stem cells (CSCs) that drive tumor progression and disease recurrence are rare subsets of tumor cells. CSCs are relatively resistant to conventional chemotherapy and radiotherapy. Eradication of CSCs is thus essential to achieve durable responses. GD2 was reported to be a CSC marker in human triple-negative breast cancer, and anti-GD2 immunotherapy showed reduced tumor growth in cell lines. Using a specific anti-OAcGD2 antibody, mAb8D6, we set out to determine whether OAcGD2+ cells exhibit stem cell properties and mAb8D6 can inhibit tumor growth by targeting OAcGD2+CSCs.MethodOAcGD2 expression in patient-derived xenografts (PDXs) of breast cancer was determined by flow cytometric analyses using mAb8D6. The stemness of OAcGD2+ cells isolated by sorting and the effects of mAb8B6 were assessed by CSC growth and mammosphere formation in vitro and tumor growth in vivo using PDX models.ResultWe found that the OAcGD2 expression levels in six PDXs of various molecular subtypes of breast cancer highly correlated with their previously defined CSC markers in these PDXs. The sorted OAcGD2+ cells displayed a greater capacity for mammosphere formation in vitro and tumor initiation in vivo than OAcGD2− cells. In addition, the majority of OAcGD2+ cells were aldehyde dehydrogenase (ALDH+) or CD44hiCD24lo, the known CSC markers in breast cancer. Treatment of PDXs-bearing mice with mAb8B6, but not doxorubicin, suppressed the tumor growth, along with reduced CSCs as assessed by CSC markers and in vivo tumorigenicity. In vitro, mAb8B6 suppressed proliferation and mammosphere formation and induced apoptosis of OAcGD2+ breast cancer cells harvested from PDXs, in a dose-dependent manner. Finally, administration of mAb8B6 in vivo dramatically suppressed tumor growth of OAcGD2+ breast CSCs (BCSCs) with complete tumor abrogation in 3/6 mice.ConclusionOAcGD2 is a novel marker for CSC in various subtypes of breast cancer. Anti-OAcGD2 mAb8B6 directly eradicated OAcGD2+ cells and reduced tumor growth in PDX model. Our data demonstrate the potential of mAb8B6 as a promising immunotherapeutic agent to target BCSCs.
Derlin-1, as a Potential Early Predictive Biomarker for Nonresponse to Infliximab Treatment in Rheumatoid Arthritis, Is Related to Autophagy
Authors: Cai Yongsong , Xu Ke , Aihaiti Yirixiati , Li Zhijin , Yuan Qiling , Xu Jing , Zheng Haishi , Yang Mingyi , Wang Bo , Yang Yanni , Yang Yin , Xu Peng 
Published: January 2022

BackgroundThe goal of this study was to identify potential predictive biomarkers for the therapeutic effect of infliximab (IFX) in Rheumatoid arthritis (RA) and explore the potential molecular mechanism of nonresponse to IFX treatment to achieve individualized treatment of RA.MethodsDifferential gene expression between IFX responders and nonresponders in the GSE58795 and GSE78068 datasets was identified. Coexpression analysis was used to identify the modules associated with nonresponse to IFX therapy for RA, and enrichment analysis was conducted on module genes. Least absolute shrink and selection operator (LASSO) regression was used to develop a gene signature for predicting the therapeutic effect of IFX in RA, and the area under the receiver operating characteristic curve (AUC) was used to evaluate the predictive value of the signature. Correlation analysis and single-sample gene set enrichment analysis (ssGSEA) were used to explore the potential role of the hub genes. Experimental validation was conducted in synovial tissue and RA fibroblast-like synoviocytes (RA-FLSs).ResultsA total of 46 common genes were obtained among the two datasets. The yellow-green module was identified as the key module associated with nonresponse to IFX therapy for RA. We identified a 25-gene signature in GSE78068, and the AUC for the signature was 0.831 in the internal validation set and 0.924 in the GSE58795 dataset(external validation set). Derlin-1 (DERL1) was identified as the hub gene and demonstrated to be involved in the immune response and autophagy regulation. DERL1 expression was increased in RA synovial tissue compared with OA synovial tissue, and DERL1-siRNA partially inhibited autophagosome formation in RA-FLSs.ConclusionThe 25-gene signature may have potential predictive value for the therapeutic effect of IFX in RA at the beginning of IFX treatment, and autophagy may be involved in nonresponse to IFX treatment. In particular, DERL1 may be associated with the regulation of autophagy.
Immune Checkpoint Inhibitor-Induced Cerebral Pseudoprogression: Patterns and Categorization
Authors: Urban Hans , Steidl Eike , Hattingen Elke , Filipski Katharina , Meissner Markus , Sebastian Martin , Koch Agnes , Strzelczyk Adam , Forster Marie-Thérèse , Baumgarten Peter , Ronellenfitsch Michael W. , Steinbach Joachim P. , Voss Martin 
Published: January 2022

BackgroundThe inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.MethodsWe screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria.ResultsWe identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblastoma (n=1), hepatocellular carcinoma (n=1) or lymphoma (n=1) when cerebral pseudoprogression was detected. Median time from the start of ICI treatment to pseudoprogression was 5 months. All but one patient developed neurological symptoms. Three different patterns of cerebral pseudoprogression could be distinguished: new or increasing contrast-enhancing lesions, new or increasing T2 predominant lesions and cerebral vasculitis type pattern.ConclusionCerebral pseudoprogression followed three distinct patterns and was detectable in 3.2% of all patients during ICI treatment and in 9.75% of the patients with sufficient brain imaging follow up. The fact that all but one of the affected patients developed neurological symptoms, which would be classified as progressive disease according to iRANO criteria, mandates vigilance in the diagnosis and treatment of ICI-induced cerebral lesions.
Clinical Characteristics of 10 Pregnant and Postpartum Women With Extracorporeal Membrane Oxygenation: A Retrospective Study
Authors: Gu Qiao , Peng Weihua , Zhu Ying , Xi Shaosong , Diao Mengyuan , Hu Wei , Zeng Xiaokang 
Published: January 2022

Background: The aim of study was to summarize the clinical characteristics and experience of extracorporeal membrane oxygenation (ECMO) in pregnant and postpartum patients.Methods and Results: We retrospectively reviewed 131 consecutive ECMO patients at our center from May 2015 to May 2021. A total of 10 Chinese patients were pregnant or postpartum at the time of ECMO initiation. Patients ranged in age from 25 to 36 years (median age 30.5 years). The ECMO duration ranged from 3 to 31 days (median duration 8 days). There was a stabilizing trend of acid-base balance and decreasing lactic acid over the 3 days following ECMO initiation. Seven (70%) patients survived at least 48 h after weaning from ECMO. Four (40%) patients survived until discharge, and four (40%) fetuses survived until discharge.Conclusion: ECMO provides a suitable temporary cardiopulmonary support for pregnant and postpartum patients. ECMO shows a favorable effect on short-term stability in critical obstetric patients.
Prostate-Specific Antigen Velocity Predicts Surgical Outcome of Thulium Laser Enucleation of the Prostate
Authors: Chen Po-You , Chen Shao-Ming , Juang Horng-Heng , Hou Chen-Pang , Lin Yu-Hsiang , Yang Pei-Shan , Chen Chien-Lun , Chang Phei-Lang , Lin Kuo-Yen , Tsui Ke-Hung 
Published: January 2022

Background: We determined the effect of prostate-specific antigen velocity (PSAV) on the surgical outcome of thulium laser enucleation of the prostate (ThuLEP) in patients with benign prostatic hyperplasia (BPH).Methods: A retrospective review was performed of prospectively collected data of patients with BPH who underwent ThuLEP at any time from 2017 to 2019. Patients who had undergone BPH surgery or had prostate cancer previously were excluded, and patients with prostate-specific antigen (PSA) &gt; 4 ng/ml were examined through transrectal ultrasound-guided prostate biopsy to rule out prostatic malignancy. Furthermore, patients were excluded if prostatic malignancy was diagnosed during postsurgery follow-up.Results: The PSA level, International Prostate Symptom Score (IPSS), and quality of life (QoL) of 27 male patients at 3 and 15 months postsurgery differed significantly from those at presurgery; the maximum flow rate (Qmax) and postvoid residual (PVR) significantly differed between 3 months postsurgery and presurgery; and 22 and 5 patients had good to excellent and fair to poor outcomes, respectively, at 15 months postsurgery. Patients were divided into two groups (fair and poor vs. good and excellent outcomes at 15 months postsurgery), which significantly differed with respect to PSAV at 3 months postsurgery (P = 0.04), IPSS presurgery (P &lt; 0.02), surgical length (P = 0.01), and hospitalization duration (P = 0.04). In a receiver operating characteristic (ROC) analysis, the optimal cutoff value of PSAV of −0.52 ng/ml characterized effectiveness at 15 months after ThuLEP, and the area under the curve (AUC), sensitivity, and specificity were 0.82 (P &lt; 0.02), 0.80, and 0.82, respectively. For PSAV &lt; -0.52 and ≥-0.52 ng/ml, the percentages of reduction for IPSS, QoL, Qmax, and PVR were −78.6 and −71.4%, −33.3 and 0.0%, 94.4 and 40.0%, and −85.1 and −38.7%, respectively.Conclusions: Postsurgical PSAV was positively correlated with surgical success, and the PSAV cutoff was −0.52 ng/ml. PSAV can, thus, be used to guide the postsurgical follow-up treatment at 3 months after BPH surgery.
Experimental Characterization of the Hepatitis B Virus Capsid Dynamics by Solid-State NMR
Authors: Malär Alexander A. , Callon Morgane , Smith Albert A. , Wang Shishan , Lecoq Lauriane , Pérez-Segura Carolina , Hadden-Perilla Jodi A. , Böckmann Anja , Meier Beat H. 
Published: January 2022

Protein plasticity and dynamics are important aspects of their function. Here we use solid-state NMR to experimentally characterize the dynamics of the 3.5 MDa hepatitis B virus (HBV) capsid, assembled from  240 copies of the Cp149 core protein. We measure both T1 and T1ρ relaxation times, which we use to establish detectors on the nanosecond and microsecond timescale. We compare our results to those from a 1 microsecond all-atom Molecular Dynamics (MD) simulation trajectory for the capsid. We show that, for the constituent residues, nanosecond dynamics are faithfully captured by the MD simulation. The calculated values can be used in good approximation for the NMR-non-detected residues, as well as to extrapolate into the range between the nanosecond and microsecond dynamics, where NMR has a blind spot at the current state of technology. Slower motions on the microsecond timescale are difficult to characterize by all-atom MD simulations owing to computational expense, but are readily accessed by NMR. The two methods are, thus, complementary, and a combination thereof can reliably characterize motions covering correlation times up to a few microseconds.
MRI Volumetric Analysis of the Thalamus and Hypothalamus in Amyotrophic Lateral Sclerosis
Authors: Ye Shan , Luo Yishan , Jin Pingping , Wang Yajun , Zhang Nan , Zhang Gan , Chen Lu , Shi Lin , Fan Dongsheng 
Published: January 2022

Background: Increasing evidence has shown that amyotrophic lateral sclerosis (ALS) can result in abnormal energy metabolism and sleep disorders, even before motor dysfunction. Although the hypothalamus and thalamus are important structures in these processes, few ALS studies have reported abnormal MRI structural findings in the hypothalamus and thalamus.Purpose: We aimed to investigate volumetric changes in the thalamus and hypothalamus by using the automatic brain structure volumetry tool AccuBrain®.Methods: 3D T1-weighted magnetization-prepared gradient echo imaging (MPRAGE) scans were acquired from 16 patients with ALS with normal cognitive scores and 16 age-, sex- and education-matched healthy controls. Brain tissue and structure volumes were automatically calculated using AccuBrain®.Results: There were no significant differences in bilateral thalamic (F = 1.31, p = 0.287) or hypothalamic volumes (F = 1.65, p = 0.213) between the ALS and control groups by multivariate analysis of covariance (MANCOVA). Left and right hypothalamic volumes were correlated with whole-brain volume in patients with ALS (t = 3.19, p = 0.036; t = 3.03, p = 0.044), while the correlation between age and bilateral thalamic volumes tended to be significant after Bonferroni correction (t = 2.76, p = 0.068; t = 2.83, p = 0.06). In the control group, left and right thalamic volumes were correlated with whole-brain volume (t = 4.26, p = 0.004; t = 4.52, p = 0.004).Conclusion: Thalamic and hypothalamic volumes did not show differences between patients with normal frontotemporal function ALS and healthy controls, but further studies are still needed.