bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nomogram Based on Clinical and Ultrasound Characteristics to Predict Central Lymph Node Metastasis of Papillary Thyroid Carcinoma
Authors: Feng Jia-Wei , Hong Li-Zhao , Wang Fei , Wu Wan-Xiao , Hu Jun , Liu Sheng-Yong , Jiang Yong , Ye Jing 
Published: April 2021

BackgroundThe status of lymph nodes in the central compartment is crucial to determining the surgical strategies for papillary thyroid carcinoma (PTC). We aimed to develop a nomogram for predicting central lymph node metastasis (CLNM).MethodsA total of 886 PTC patients who underwent total thyroidectomy or lobectomy with central neck dissection (CND) from July 2019 to June 2020 were retrospectively retrieved. Clinical and ultrasound features were collected. Univariate and multivariate analysis were performed to determine risk factors of CLNM. A nomogram for predicting CLNM was developed, internal and external calibration was performed for the established model.ResultsVariables (sex, chronic lymphocytic thyroiditis, tumor size, the number of foci, tumor location, margin) significantly associated with CLNM were included in the nomogram. The nomogram showed excellent calibration in the training group and validation group, with area under curves of 0.806 (95% CI, 0.771 to 0.825), and 0.799 (95% CI, 0.778–0.813) respectively.ConclusionThrough this accurate and easy-to-use nomogram, the possibility of CLNM can be objectively quantified preoperatively. Clinicians can use this nomogram to evaluate the status of lymph nodes in PTC patients and consider prophylactic CND for those with high scores.
High Levels of Common Cold Coronavirus Antibodies in Convalescent Plasma Are Associated With Improved Survival in COVID-19 Patients
Authors: Greenbaum Uri , Klein Kimberly , Martinez Fernando , Song Juhee , Thall Peter F. , Ramdial Jeremy L. , Knape Cristina , Aung Fleur M. , Scroggins Jamie , Knopfelmacher Adriana , Mulanovich Victor , Borjan Jovan , Adachi Javier , Muthu Mayoora , Leung Cerena , Medina Mayrin Correa , Champlin Richard , Olson Amanda , Alousi Amin , Rezvani Katayoun , Shpall Elizabeth J. 
Published: April 2021

BackgroundCOVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.Patients and MethodsPatients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.ResultsCCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.ConclusionsCommon cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.
Diagnostic, Therapeutic, and Prognostic Value of the Thrombospondin Family in Gastric Cancer
Authors: Lu Yi , Kong Xianhe , Zhong Weijie , Hu Minhui , Li Chujun 
Published: April 2021

Background: Gastric cancer (GC) is the fifth leading cancer in the world. The dysregulated expressions of the thrombospondin (THBS) family were reported to associate with GC, but their relations with tumor stage, prognosis, and correlations with tumor immunity have not been systematically reported.Methods: We used versatile public databases such as Oncomine, GEPIA, UALCAN, Kaplan–Meier Plotter, LinkedOmics, STRING, cBioPortal, TIMER, and TISIDB to analyze the expression and mutations of different THBSs in GC, along with their functional networks, survival analysis, and tumor–immune interactions.Results: The mRNA levels of THBS2, THBS4, and COMP were significantly higher in the tumor tissues; the expression levels of THBS1, THBS2, and THBS4 were higher in stages 2–4 than that of stage 1; patients with high expression of THBS1, THBS2, THBS4, and COMP had poor OS; the genes correlated with THBSs were enriched in focal adhesion, glycosaminoglycan biosynthesis, ECM-receptor interaction, and hedgehog signaling pathway; THBS1 and THBS4 expression had significant correlations with tumor purity, and all the THBSs expression correlated with macrophage and dendritic cells infiltration.Conclusions: THBS2, THBS4, and COMP were potentially diagnostic markers for GC; THBS1, THBS2, THBS4, and COMP were potentially prognostic markers for GC; investigating the relations of THBSs and tumor immunology might help in immunotherapy of GC, while more studies are needed to confirm these results.
Identification of a Potential miRNA–mRNA Regulatory Network Associated With the Prognosis of HBV-ACLF
Authors: Ma Shanshan , Xie Zhongyang , Zhang Lingjian , Yang Ya , Jiang He , Ouyang Xiaoxi , Zhao Yalei , Liu Qiuhong , Xu Xiaowei , Li Lanjuan 
Published: April 2021

BackgroundHepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening disease with a high mortality rate; the systemic inflammatory response plays a vital role in disease progression. We aimed to determine if a miRNA–mRNA co-regulatory network exists in the peripheral blood mononuclear cells (PBMCs) of HBV-ACLF patients, which might be important for prognosis.MethodsTranscriptome-wide microRNA (miRNA) and mRNA microarrays were used to define the miRNA and mRNA expression profiles of the PBMCs of HBV-ACLF patients in a discovery cohort. The targets of the miRNAs were predicted. We built a miRNA-mRNA regulatory network through bioinformatics analysis, and used quantitative real-time polymerase chain reaction (qRT-PCR) to assess the importance of candidate miRNAs and mRNAs. We also assessed the direct and transcriptional regulatory effects of miRNAs on target mRNAs using a dual-luciferase reporter assay.ResultsThe miRNA/mRNA PBMC expression profiles of the discovery cohort, of whom eight survived and eight died, revealed a prognostic interactive network involving 38 miRNAs and 313 mRNAs; this was constructed by identifying the target genes of the miRNAs. We validated the expression data in another cohort, of whom 43 survived and 35 died; miR-6840-3p, miR-6861-3p, JADE2, and NR3C2 were of particular interest. The levels of miR-6840-3p and miR-6861-3p were significantly increased in the PBMCs of the patients who died, and thus predicted prognosis (areas under the curve values = 0.665 and 0.700, respectively). The dual-luciferase reporter assay indicated that miR-6840-3p directly targeted JADE2.ConclusionWe identified a prognostic miRNA-mRNA co-regulatory network in the PBMCs of HBV-ACLF patients. miR-6840-3p-JADE2 is a potential miRNA–mRNA pair contributing to a poor prognosis.
Valproic Acid Induces Autism-Like Synaptic and Behavioral Deficits by Disrupting Histone Acetylation of Prefrontal Cortex ALDH1A1 in Rats
Authors: Liu Huan , Tan Mei , Cheng Boli , Wang Si , Xiao Lu , Zhu Jiang , Wu Qionghui , Lai Xi , Zhang Qian , Chen Jie , Li Tingyu 
Published: April 2021

ObjectivesThis study aimed to investigate the impact of valproic acid (VPA) on the histone acetylation of acetaldehyde dehydrogenase 1A1 (ALDH1A1) and the mechanism underlying VPA-induced autism-like behavior.MethodsFemale Sprague-Dawley rats were intraperitoneally injected with VPA during gestation to establish an autism model in their offspring. Some offspring prenatally exposed to VPA were randomly treated with MS-275, one histone deacetylase (HDAC) inhibitor, or retinoic acid (RA) after birth. Behavioral tests were conducted on the offspring 6 weeks after birth. Electrophysiological experiments were performed to investigate long-term potentiation (LTP) in the prefrontal cortex (PFC). The expression levels of AMPA receptors (GluA1 and 2), NMDA receptors (GluN1 and 2), synapsin 1 (SYN1), HDAC, acetylated histone 3 (AcH3), RA receptor alpha (RARα), and ALDH1A1 in the PFC were measured by Western blotting and quantitative polymerase chain reaction. ALDH enzyme activity in PFC tissue was detected using a Micro ALDH Assay Kit. The RA level in the PFC was measured using ultrahigh-performance liquid chromatography/tandem mass spectrometry. A chromatin immunoprecipitation (ChIP) experiment explored the interaction between the ALDH1A1 gene and AcH3.ResultsOffspring prenatally exposed to VPA showed autism-like behavior, upregulated the levels of LTP and GluN2A, GluA1, and SYN1 proteins relevant to synaptic plasticity in the PFC. The expression levels of HDAC3 mRNA and protein were increased. On the other hand, there was a significant reduction in the levels of AcH3, RARα, RA, ALDH1A1 mRNA and protein, the level of ALDH activity and AcH3 enrichment in the ALDH1A1 promoter region in VPA-induced offspring. Administration of MS-275 in VPA offspring significantly elevated the levels of AcH3, ALDH1A1 mRNA and protein, ALDH activity, RA, the level of RARα protein and the binding of AcH3 to the ALDH1A1 promoter. In addition, the GluA1 protein level and LTP were reduced, and most behavioral deficits were reversed. After RA supplementation in the VPA-treated offspring, the RA and RARα protein levels were significantly upregulated, GluA1 protein and LTP were downregulated, and most autism-like behavioral deficits were effectively reversed.ConclusionThese findings suggest that VPA impairs histoneacetylation of ALDH1A1 and downregulates the RA-RARα pathway. Such epigenetic modification of ALDH1A1 by VPA leads to autism-like synaptic and behavioral deficits.
Individualized Prediction of Colorectal Cancer Metastasis Using a Radiogenomics Approach
Authors: Liu Qin , Li Jie , Xu Lin , Wang Jiasi , Zeng Zhaoping , Fu Jiangping , Huang Xuan , Chu Yanpeng , Wang Jing , Zhang Hong-Yu , Zeng Fanxin 
Published: April 2021

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis.Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram.Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892–0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570–0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953–1.000), the validation cohort (AUC = 0.822, 95% CI 0.635–1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608–0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model.Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients.
Review of Prognostic Expression Markers for Clear Cell Renal Cell Carcinoma
Authors: Petitprez Florent , Ayadi Mira , de Reyniès Aurélien , Fridman Wolf H. , Sautès-Fridman Catherine , Job Sylvie 
Published: April 2021

Context:The number of prognostic markers for clear cell renal cell carcinoma (ccRCC) has been increasing regularly over the last 15 years, without being integrated and compared.Objective:Our goal was to perform a review of prognostic markers for ccRCC to lay the ground for their use in the clinics.Evidence Acquisition:PubMed database was searched to identify RNA and protein markers whose expression level was reported as associated with survival of ccRCC patients. Relevant studies were selected through cross-reading by two readers.Evidence Synthesis:We selected 249 studies reporting an association with prognostic of either single markers or multiple-marker models. Altogether, these studies were based on a total of 341 distinct markers and 13 multiple-marker models. Twenty percent of these markers were involved in four biological pathways altered in ccRCC: cell cycle, angiogenesis, hypoxia, and immune response. The main genes (VHL, PBRM1, BAP1, andSETD2) involved in ccRCC carcinogenesis are not the most relevant for assessing survival.Conclusion:Among single markers, the most validated markers wereKI67, BIRC5, TP53, CXCR4, andCA9. Of the multiple-marker models, the most famous model, ClearCode34, has been highly validated on several independent datasets, but its clinical utility has not yet been investigated.Patient Summary:Over the years, the prognosis studies have evolved from single markers to multiple-marker models. Our review highlights the highly validated prognostic markers and multiple-marker models and discusses their clinical utility for better therapeutic care.
Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate Depot Formulation With Tamoxifen for Postoperative Premenopausal Estrogen Suppression in Hormone Receptor-Positive Breast Cancer
Authors: Wu Zhen-Yu , Lee Young-jin , Kim Heejeong , Lee Jongwon , Chung Il Yong , Kim Jisun , Lee Saebyeol , Son Byung-Ho , Kim Sung-Bae , Jeong Jae Ho , Gong Gyungyub , Ahn Sei-Hyun , Ko BeomSeok 
Published: April 2021

BackgroundIn patients with hormone receptor-positive (HR+)/premenopausal breast cancer, luteinizing hormone-releasing hormone analogs (LHRHas) are used as standard endocrine treatment. Based on previous clinical studies, 1-month formulations are recommended in most breast cancer treatment guidelines, but long-acting formulations facilitate reductions in side effects and patient discomfort caused by frequent administration. However, few efficacy studies have been conducted on 6-month formulations. Therefore, this study aimed to evaluate the efficacy of 6-month formulations of LHRHas.MethodsThis retrospective study was conducted from January 2018 to December 2019 and involved premenopausal patients with HR+ breast cancer administered 6-month LHRHas as adjuvant treatment after surgery, and those previously administered chemotherapy or other LHRHa types were excluded. Patients’ estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured before surgery, and their E2 levels were also measured at 3, 6, 12, 18, and 24 months at periodic postsurgical examinations.ResultsA total of 228 patients were included, and the median patient age was 44 (range, 25–54) years. The mean serum E2 and FSH levels before surgery were 69.7 (range, 4–683) pg/mL and 7.3 (range, 0.4–88.9) mIU/mL, respectively, whereas the mean serum E2 level monitored at intervals during the 6-month LHRHa administration was 5.5 (range, 4.0–52) pg/mL. No women menstruated during the follow-up period after the LHRHas administration, and the E2 levels were less than 30 pg/mL in all patients except one.ConclusionsThe 6-month LHRHa formulation adequately suppressed ovarian function in premenopausal patients with HR+ breast cancer. This indicates that long-acting LHRHas can be effectively used for patient convenience and that there is high compliance with long-term use.
Precise Species Detection in Traditional Herbal Patent Medicine, Qingguo Wan, Using Shotgun Metabarcoding
Authors: Liu Jinxin , Shi Mengmeng , Zhao Qing , Kong Weijun , Mu Weishan , Xie Hongbo , Li Zhongsi , Li Baoli , Shi Linchun 
Published: April 2021

As one of the high-incidence diseases in the world, pharyngitis seriously affects the lives of those with the condition. Qingguo Wan is a herbal medicine used for treating pharyngitis, and its quality evaluation is currently only accomplished via traditional identification. However, precise identification becomes challenging with fake products on the market or fungal contamination during the production process. This study used the Illumina NovaSeq platform for targeting the ITS2, psbA-trnH, matK, and rbcL sequences to survey the species composition of lab-made and commercial samples. The results showed that a total of 34.56 Gb of raw data that was obtained represented more than 0.23 billion reads. After assembly, annotation, and operational taxonomic unit clustering, 103, 12, 10, and 12 OTUs were obtained, which belonged to the ITS2, psbA-trnH, matK, and rbcL sequences of the mock lab-made and commercial samples. The analytical results indicated that the sequences of all the prescription ingredients were successfully obtained in the two lab-made samples. The positive control medicinal Panax quinquefolius L. sequence was obtained in HSZY175, while Scutellaria baicalensis Georgi, Lonicera japonica Thunb. Menispermum dauricum DC. and Paeonia lactiflora Pall. were detected in the three commercial samples. The detection results of the other four herbs in different fragments were not all the same. In addition, a total of 28 fungi OTUs, representing 19 families and 20 genera, were obtained from both the commercial and mock lab-made samples. Aspergillus, Cladosporium, and Penicillium dominated among the 20 genera. This study demonstrated that the shotgun metabarcoding method is a powerful tool for the molecular identification of the biological ingredients in Qingguo Wan. It can be used to effectively supplement traditional methods while providing a new technique for the quality evaluation of Qingguo Wan.
A Comparison of Four Caries Risk Assessment Methods
Authors: Featherstone John D. B. , Crystal Yasmi O. , Alston Pamela , Chaffee Benjamin W. , Doméjean Sophie , Rechmann Peter , Zhan Ling , Ramos-Gomez Francisco 
Published: April 2021

Introduction: Caries risk assessment (CRA) is essential as the basis for successful management of dental caries. Of the many published CRA tools, four well-known ones are CAMBRA, Cariogram, American Dental Association (ADA), and American Academy of Pediatric Dentistry (AAPD) CRAs. The predictive accuracy of CAMBRA and Cariogram CRA tools have been examined in clinical outcomes studies in thousands of patients and the tools are widely used all over the world. The purpose of the present paper is three-fold, namely (1) to briefly review, compare and contrast these four CRA methods, (2) to provide a concise method for CRA introducing a quantitative component to the CAMBRA forms (CAMBRA 123), and (3) to guide the choice of CRA methods that will support caries management decisions.Comparison of Caries Risk Assessment Methods: In the present evaluation, the above-mentioned four CRA methods for ages 0–6 years and 6 years-adult were compared using 26 hypothetical patients (13 per age group). Comparison results show that Cariogram and CAMBRA categorized patients into identical risk categories. Each of the ADA and AAPD tools gave different results than CAMBRA and Cariogram in several comparison examples. CAMBRA 123 gave the same caries risk level results as the Cariogram and the CAMBRA methods for all hypothetical patients for both age groups.Conclusions: Both the Cariogram and the CAMBRA CRA methods are equally useful for identifying the future risk of dental caries. CAMBRA 123 shows promise as an easy-to-use quantitative method for CRA in clinical practice. The health care providers will be the ones to decide which CRA method will allow them to establish individualized, successful caries management therapies and how to combine these for the best care of their patients.
Vascular Access Perspectives in Patients After Kidney Transplantation
Authors: Letachowicz Krzysztof , Banasik Mirosław , Królicka Anna , Mazanowska Oktawia , Gołębiowski Tomasz , Augustyniak-Bartosik Hanna , Zmonarski Sławomir , Kamińska Dorota , Kuriata-Kordek Magdalena , Krajewska Magdalena 
Published: April 2021

Introduction: More attention has been paid to the influence of arteriovenous fistula (AVF) on the cardiovascular system. In renal transplant recipients, some beneficial effect of an elective vascular access (VA) ligation was observed in patients with a high AVF flow. However, this strategy is not widely accepted and is in contradiction to the rule of vasculature preservation for possible future access. The aim of our study is to elucidate the vascular access function and VA perspective in the kidney transplantation (KTx) population.Materials and Methods: KTx patients with a stable graft function were recruited to participate in this single center observational study (NCT04478968). The measurement of VA flow and vessel mapping for future vascular access was performed by a color Doppler ultrasound. The study group included 99 (63%) males and 58 (37%) females; the median age was 57 (IQR 48–64) years. The median time from the transplantation to the baseline visit was 94 (IQR 61–149) months. Median serum creatinine concentration was 1.36 (IQR 1.13–1.67) mg/dl.Results: Functioning VA was found in 83 out of 157 (52.9%) patients. The sites were as follows: snuffbox in six (7.2%), wrist in 41 (49.4%), distal forearm in 18 (21.7%), middle or proximal forearm in eight (9.6%), upper-arm AV graft in one (1.2%), and upper-arm AVFs in nine (10.8%) patients, respectively. Blood flow ranged from 248 to 7,830 ml/min; the median was 1,134 ml/min. From the transplantation to the study visit, 66 (44.6%) patients experienced access loss. Spontaneous thrombosis was the most common, and it occurred in 60 (90.9%) patients. The surgical closure of VA was performed only in six (4%) patients of the study group with a functioning VA at the time of transplantation. Access loss occurred within the 1st year after KTx in 33 (50%) patients. Majority (50 out of 83, 60.2%) of the patients with an active VA had options to create a snuffbox or wrist AVF on the contralateral extremity. In a group of 74 patients without a functioning VA, the creation of a snuffbox or wrist AVF on the non-dominant and dominant extremity was possible in seven (9.2%) and 40 (52.6%) patients, respectively. In 10 (13.1%) patients, the possibilities were limited only to the upper-arm or proximal forearm VA on both sides. Access ligation was considered by 15 out of 83 (18.1%) patients with a patent VA.Conclusions: In the majority of the patients, vascular access blood flow was below the threshold of the negative cardiovascular effect of vascular access. Creation of a distal AVF is a protective measure to avoid a high flow and preserve the vessels for future access. The approach to VA should be individualized and adjusted to the patient's profile.