bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Expression of Plasma Extracellular HSP90α is Associated With the Poor Efficacy of Chemotherapy and Prognosis in Small Cell Lung Cancer
Authors: Huang Baoyue , Pan Jinmiao , Liu Haizhou , Tang Yamei , Li Shirong , Bian Yingzhen , Ning Shufang , Li Jilin , Zhang Litu 
Published: July 2022

Purpose: eHSP90α is closely related to tumor progression and prognosis. This study aimed to investigate the significance of eHSP90α in the response evaluation and prediction of small cell lung cancer.Methods: We analyzed the relationship between eHSP90α expression and clinicopathological features in 105 patients with small cell lung cancer. Univariate and multivariate analyses were used to determine the association of parameters and ratios with response assessment, progression-free survival (PFS), and overall survival (OS).Results: In SCLC patients, eHSP90α and NSE were positively correlated. The cutoff values of eHSP90α in OS, PFS, and response evaluation were 61.2 ng/ml, 48.7 ng/ml, and 48.7 ng/ml, respectively. eHSP90α could better predict OS, PFS, and response evaluation (AUC OS 0.791, PFS 0.662, 0.685). Radiotherapy and eHSP90α were independent variables for effective chemotherapy through univariate and multivariate analysis. In contrast, radiotherapy, eHSP90α, NSE, and M stage were independent variables for OS. eHSP90α, and M stage were independent variables for PFS. Kaplan-Meier analysis showed that higher eHSP90α expression predicted poorer OS and earlier progression in patients.Conclusions: This study aims to provide new evidence for the efficacy response and prognostic assessment of SCLC. eHSP90α may be a better biomarker for SCLC.
Cryo-EM Structure of an Atypical Proton-Coupled Peptide Transporter: Di- and Tripeptide Permease C
Authors: Killer Maxime , Finocchio Giada , Mertens Haydyn D. T. , Svergun Dmitri I. , Pardon Els , Steyaert Jan , Löw Christian 
Published: July 2022

Proton-coupled Oligopeptide Transporters (POTs) of the Major Facilitator Superfamily (MFS) mediate the uptake of short di- and tripeptides in all phyla of life. POTs are thought to constitute the most promiscuous class of MFS transporters, with the potential to transport more than 8400 unique substrates. Over the past two decades, transport assays and biophysical studies have shown that various orthologues and paralogues display differences in substrate selectivity. The E. coli genome codes for four different POTs, known as Di- and tripeptide permeases A-D (DtpA-D). DtpC was shown previously to favor positively charged peptides as substrates. In this study, we describe, how we determined the structure of the 53 kDa DtpC by cryogenic electron microscopy (cryo-EM), and provide structural insights into the ligand specificity of this atypical POT. We collected and analyzed data on the transporter fused to split superfolder GFP (split sfGFP), in complex with a 52 kDa Pro-macrobody and with a 13 kDa nanobody. The latter sample was more stable, rigid and a significant fraction dimeric, allowing us to reconstruct a 3D volume of DtpC at a resolution of 2.7 Å. This work provides a molecular explanation for the selectivity of DtpC, and highlights the value of small and rigid fiducial markers such as nanobodies for structure determination of low molecular weight integral membrane proteins lacking soluble domains.
Sleepiness in Cognitively Unimpaired Older Adults Is Associated With CSF Biomarkers of Inflammation and Axonal Integrity
Authors: Carvalho Diego Z. , St. Louis Erik K. , Przybelski Scott A. , Morgenthaler Timothy I. , Machulda Mary M. , Boeve Bradley F. , Petersen Ronald C. , Jack Clifford R. , Graff-Radford Jonathan , Vemuri Prashanthi , Mielke Michelle M. 
Published: July 2022

IntroductionSleepiness has been associated with cognitive decline and dementia in the elderly. Older adults with excessive daytime sleepiness appear to be more vulnerable to longitudinal amyloid PET accumulation before the onset of the dementia. However, it remains unclear whether sleepiness is similarly associated with other biomarkers of Alzheimer’s disease (AD), axonal integrity, and inflammation, which may also contribute to neurodegeneration and cognitive decline.MethodsIn this cross-sectional analysis, we identified 260 cognitively unimpaired adults (&gt;60 years) from the Mayo Clinic Study of Aging, a population-based cohort from Olmsted County (MN), who underwent CSF quantification of AD biomarkers (Aβ42, p-tau, p-tau/Aβ42) in addition to at least one of the following biomarkers [neurofilament light chain (NfL) interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α)]. We fit linear regression models to assess associations between sleepiness, as measured by the Epworth Sleepiness Scale (ESS), and CSF biomarkers, controlling for age, sex, APOε4 status, body mass index, hypertension, dyslipidemia, and prior diagnosis of obstructive sleep apnea.ResultsHigher ESS scores were associated with higher CSF IL-6 and NfL, but not with the other CSF biomarkers. For every ESS score point increase, there was a 0.009 ([95% CI 0.001–0.016], p = 0.033) increase in the log of IL-6 and 0.01 ([95% CI 0.002–0.018], p = 0.016) increase in the log of NfL. A sensitivity analysis showed an association between ESS scores and log of p-tau/Aβ42 only in participants with an abnormal ratio (&gt;0.023), highly predictive of amyloid positivity. For every ESS score point increase, there was a 0.006 ([95% CI 0.001–0.012], p = 0.021) increase in the log of CSF p-tau/Aβ42.ConclusionSleepiness was associated with greater CSF IL-6 and NfL levels, which could contribute to neurodegeneration or alternatively cause sleepiness. Higher NfL levels may result from sleep disruption and/or contribute to sleepiness via disturbed connectivity or damage to wake-promoting centers. Associations between sleepiness and p-tau/Aβ42 in participants with abnormal ratio suggest that amyloid positivity contributes to vulnerability to sleep disturbance, which may further amyloid accumulation in a feed-forward loop process. Prospective studies of these markers are needed to determine cause-effect relationships between these associations.
Expanding the Phenotypic and Genetic Spectrum of Neuromuscular Diseases Caused by DYNC1H1 Mutations
Authors: Li Jia-Tong , Dong Si-Qi , Zhu Dong-Qing , Yang Wen-Bo , Qian Ting , Liu Xiao-Ni , Chen Xiang-Jun 
Published: July 2022

ObjectivesSpinal muscular atrophy with lower extremity predominance 1 (SMALED1) and Charcot–Marie-Tooth diseasetype 2O (CMT2O) are two kinds of hereditary neuromuscular diseases caused by DYNC1H1 mutations. In this study, we reported two patients with SMALED1 caused by DYNC1H1 mutations. The genotype–phenotype correlations were further analyzed by systematically reviewing previous relevant publications.Materials and MethodsTwo patients' with SMALED1 and their parents' clinical data were collected, and detailed clinical examinations were performed. WES was then applied, which was confirmed by Sanger sequencing. PubMed, Web of Science, CNKI, and Wanfang Data were searched, and all publications that met the inclusion criteria were carefully screened. Any individual patient without a detailed description of clinical phenotypes was excluded.ResultsThe two patients manifested delayed motor milestones and muscle wasting of both lower extremities. The diagnosis was further confirmed as SMALED1. Genetic testing revealed heterozygous DYNC1H1 mutations c.1792C&gt;T and c.790C&gt;G; the latter is a novel dominant mutation. Genotype–phenotype analysis of DYNC1H1 variants and neuromuscular diseases revealed that mutations in the DYN1 region of DYNC1H1 protein were associated with a more severe phenotype, more complicated symptoms, and more CNS involvement than the DHC_N1 region.ConclusionOur study potentially expanded the knowledge of the phenotypic and genetic spectrum of neuromuscular diseases caused by DYNC1H1 mutations. The genotype–phenotype correlation may reflect the pathogenesis underlying the dyneinopathy caused by DYNC1H1 mutations.
Maternal Mental Health in Late Pregnancy and Longitudinal Changes in Postpartum Serum Vitamin B-12, Homocysteine, and Milk B-12 Concentration Among Brazilian Women
Authors: Batalha Mônica Araujo , dos Reis Costa Paula Normando , Ferreira Ana Lorena Lima , Freitas-Costa Nathalia C. , Figueiredo Amanda C. Cunha , Shahab-Ferdows Setareh , Hampel Daniela , Allen Lindsay H. , Pérez-Escamilla Rafael , Kac Gilberto 
Published: July 2022

BackgroundLittle is known regarding the association between mental health distress during pregnancy and postpartum maternal serum biomarkers of vitamin B-12 status and milk B-12 concentration.ObjectiveTo evaluate the association between depressive and anxiety symptoms in the third trimester of pregnancy and changes in postpartum serum B-12, homocysteine, and B-12 milk concentration.MethodsA total of 101 women (18–40 years) were studied in a prospective cohort with data at the third trimester of pregnancy (baseline) and three postpartum time-points (TPs): 2–8 days (TP1), 28–50 days (TP2), and 88-119 days (TP3) postpartum. B-12 concentrations in milk were measured by competitive chemiluminescent enzyme immunoassay at TP1, TP2, and TP3. Serum B-12 and homocysteine concentrations were evaluated at baseline, TP1, TP2, and TP3 by chemiluminescent immunoassays. Depressive and anxiety symptoms were measured with the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory at baseline. Spearman's correlation test and multiple linear mixed-effect models were performed.ResultsThe prevalence of depressive and anxiety state symptoms was 35.6 and 39.6% at baseline. High prevalence of low milk B-12 concentration (&lt;310 pmol/L) were observed at TP1 (53.2%), TP2 (71.4%), and TP3 (71.1%). Women with anxiety symptoms at baseline presented higher median concentrations of serum homocysteine at TP1 and lower concentrations of serum and milk B-12 at TP2 compared with women without anxiety symptoms [8 (7; 9) vs. 6 (5; 8) and 266 (188; 369) vs. 332 (272; 413)]. Milk B-12 concentrations were positively and significantly correlated with maternal serum B-12 concentrations at different TP. Women with anxiety symptoms at baseline exhibited a decrease in daily postpartum homocysteine concentrations compared to women without anxiety symptoms (β = −0.002, SE = 0.001, p = 0.024).ConclusionAnxiety symptoms at the end of pregnancy were associated with longitudinal changes in maternal serum homocysteine concentrations during the first 3 months postpartum.
Association Between Serum Iron Status and Muscle Mass in Adults: Results From NHANES 2015–2018
Authors: Chen Zhi , Chen Jing , Song Chenyang , Sun Jun , Liu Wenge 
Published: July 2022

BackgroundIron deficiency or overload may contribute to complications associated with diseases, but the link between iron status and skeletal muscle disorder is poorly understood. This study aimed to investigate the relationship between serum iron status, reflected by serum ferritin concentration, and muscle mass in U.S. adults.MethodsWe utilized data from National Health and Nutrition Examination Survey (NHANES) 2015-2018 for analysis. Data on serum ferritin, appendicular skeletal muscle mass (ASM), body mass index (BMI) and confounding factors were extracted and analyzed. Multivariate linear regression analyses and smooth curve fittings were employed to investigate the association between serum ferritin and muscle mass. Subgroup analysis based on iron status, age, gender and race were performed.ResultsA total of 2,078 participants were included, and divided into iron deficiency (n = 225), normal iron status (n = 1,366), and iron overload (n = 487) groups. Participants with iron overload had significantly lower ASM and appendicular skeletal muscle index (ASMI) (ASM: 19.329 ± 4.879, ASMI: 0.709 ± 0.138) compared to those with iron deficiency (ASM: 22.660 ± 6.789, ASMI: 0.803 ± 0.206) and normal iron status (ASM: 22.235 ± 6.167, ASMI: 0.807 ± 0.201). The serum ferritin was negatively linked with muscle mass after adjusting for potential confounders (β = −0.0001, 95% CI: −0.0001, −0.0000). When stratified by iron status, the trend test between them remained significant (P for trend: 0.008). Furthermore, subgroup analysis identified a stronger association in men (β = −0.0001, 95% CI: −0.0002, −0.0001), age ≥ 40 years (β = −0.0001, 95% CI: −0.0002, −0.0000), non-Hispanic black (β = −0.0002, 95% CI: −0.0003, −0.0001) and other races (β = −0.0002, 95% CI: −0.0003, −0.0000).ConclusionsOur study revealed an inverse relationship between serum iron status and muscle mass in adults. This finding improves our understanding of the impact of serum iron status on muscle mass, and sheds new light on the prevention and treatment of muscle loss.
Evaluation of Epidermal Growth Factor Receptor 2 Status in Gastric Cancer by CT-Based Deep Learning Radiomics Nomogram
Authors: Guan Xiao , Lu Na , Zhang Jianping 
Published: July 2022

PurposeTo explore the role of computed tomography (CT)-based deep learning and radiomics in preoperative evaluation of epidermal growth factor receptor 2 (HER2) status in gastric cancer.Materials and methodsThe clinical data on gastric cancer patients were evaluated retrospectively, and 357 patients were chosen for this study (training cohort: 249; test cohort: 108). The preprocessed enhanced CT arterial phase images were selected for lesion segmentation, radiomics and deep learning feature extraction. We integrated deep learning features and radiomic features (Inte). Four methods were used for feature selection. We constructed models with support vector machine (SVM) or random forest (RF), respectively. The area under the receiver operating characteristics curve (AUC) was used to assess the performance of these models. We also constructed a nomogram including Inte-feature scores and clinical factors.ResultsThe radiomics-SVM model showed good classification performance (AUC, training cohort: 0.8069; test cohort: 0.7869). The AUC of the ResNet50-SVM model and the Inte-SVM model in the test cohort were 0.8955 and 0.9055. The nomogram also showed excellent discrimination achieving greater AUC (training cohort, 0.9207; test cohort, 0.9224).ConclusionCT-based deep learning radiomics nomogram can accurately and effectively assess the HER2 status in patients with gastric cancer before surgery and it is expected to assist physicians in clinical decision-making and facilitates individualized treatment planning.
Differentiation of Benign From Malignant Parotid Gland Tumors Using Conventional MRI Based on Radiomics Nomogram
Authors: Qi Jinbo , Gao Ankang , Ma Xiaoyue , Song Yang , zhao Guohua , Bai Jie , Gao Eryuan , Zhao Kai , Wen Baohong , Zhang Yong , Cheng Jingliang 
Published: July 2022

ObjectivesWe aimed to develop and validate radiomic nomograms to allow preoperative differentiation between benign- and malignant parotid gland tumors (BPGT and MPGT, respectively), as well as between pleomorphic adenomas (PAs) and Warthin tumors (WTs).Materials and MethodsThis retrospective study enrolled 183 parotid gland tumors (68 PAs, 62 WTs, and 53 MPGTs) and divided them into training (n = 128) and testing (n = 55) cohorts. In total, 2553 radiomics features were extracted from fat-saturated T2-weighted images, apparent diffusion coefficient maps, and contrast-enhanced T1-weighted images to construct single-, double-, and multi-sequence combined radiomics models, respectively. The radiomics score (Rad-score) was calculated using the best radiomics model and clinical features to develop the radiomics nomogram. The receiver operating characteristic curve and area under the curve (AUC) were used to assess these models, and their performances were compared using DeLong’s test. Calibration curves and decision curve analysis were used to assess the clinical usefulness of these models.ResultsThe multi-sequence combined radiomics model exhibited better differentiation performance (BPGT vs. MPGT, AUC=0.863; PA vs. MPGT, AUC=0.929; WT vs. MPGT, AUC=0.825; PA vs. WT, AUC=0.927) than the single- and double sequence radiomics models. The nomogram based on the multi-sequence combined radiomics model and clinical features attained an improved classification performance (BPGT vs. MPGT, AUC=0.907; PA vs. MPGT, AUC=0.961; WT vs. MPGT, AUC=0.879; PA vs. WT, AUC=0.967).ConclusionsRadiomics nomogram yielded excellent diagnostic performance in differentiating BPGT from MPGT, PA from MPGT, and PA from WT.
Association Between Metformin Use and the Risk, Prognosis of Gynecologic Cancer
Authors: Yao Kui , Zheng Heng , Li Tao 
Published: July 2022

BackgroundFor gynecological cancer patients, the beneficial effect of metformin use remains controversial due to inconsistent results of published articles. By conducting a meta-analysis, we aimed to evaluate the effect of metformin in reducing the risk and improving the survival of gynecological cancer among women with diabetes mellitus (DM).MethodsArticles exploring association between metformin use and the risk, as well as prognosis of gynecologic cancer in DM, were searched in the databases: PubMed, Web of Science, SCOPUS, EMBASE, EBSCO, and PROQUEST. Articles were published before May 2022. All the studies were conducted using STATA 12.0 software.ResultsThe meta-analysis showed no significant association between metformin use and risk of gynecologic cancer in DM with a random effects model [odds ratio (ORs)/relative risk (RR) = 0.91, 95% confidence intervals (CI) 0.77 to 1.08, I2 = 84.2%, p &lt; 0.001]. Metformin use was associated with reduced overall survival (OS) and progression-free survival (PFS) of gynecologic cancer in DM with random effects models [OS: hazard ratio (HR) = 0.60, 95% CI 0.49–0.74, I2 = 55.2%, p = 0.002; PFS: HR = 0.55, 95% CI 0.33–0.91, I2 = 69.1%, p = 0.006], whereas no significant association was showed between metformin use and recurrence-free survival (RFS), as well as cancer-specific survival (CSS) of gynecologic cancer in DM with random effects models (RFS: HR = 0.60, 95% CI 0.30–1.18, I2 = 73.7%, p = 0.010; CSS: HR = 0.78, 95% CI 0.43–1.41, I2 = 72.4%, p = 0.013).ConclusionsIn conclusion, this meta-analysis indicated that metformin may be a useful adjuvant agent for gynecological cancer with DM, especially for patients with ovarian cancer and endometrial cancer.
Performance of Imaging Techniques in Non-invasive Diagnosis of Non-alcoholic Fatty Liver Disease in Children: A Systematic Review and Meta-Analysis
Authors: Yu Qun , Liu Yiwei , Hu Peipei , Gao Feng , Huang Guoqing 
Published: July 2022

Background and AimNon-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. With the continuous emergence of various non-invasive diagnostic methods, imaging techniques have always been considered as potential alternative methods to liver biopsy. This study aimed to evaluate the diagnostic performance of imaging techniques so as to search for the most promising technology.MethodsWe searched English and Chinese databases. English databases included Cochran library, Embase, PubMed, and Web of Science, while Chinese databases included the Wanfang database and China National Knowledge Internet.ResultsFinally, 11 articles were included (12 studies, one of which included studies on both fibrosis and steatosis). Further, 26.2% of the participants had mild steatosis, 34.1% had moderate steatosis, and 34.9% had severe steatosis. Also, 64.0% had any fibrosis, 29.1% had significant fibrosis, 13.8% had advanced fibrosis, and 2.8% had cirrhosis. Irrespective of the grade of fibrosis, transient elastography (TE) had higher sensitivity (97–100%), whereas magnetic resonance elastography (MRE) had the lowest sensitivity (58–63%). The pooled sensitivity and specificity of imaging techniques in diagnosing steatosis were 89% (95% CI, 71–96) and 89% (95% CI, 72–96), and AUROC 0.95 (95% CI, 93–97), multifrequency magnetic resonance elastography-hepatic fat fraction (mMRE-HFF) had the highest sensitivity (87%, 95% CI 77–97), ultrasonography (US) had the lowest specificity (96%, 95% CI 92–98%).ConclusionImaging techniques have a good diagnostic performance for children with NAFLD, especially the diagnosis of liver fibrosis based on ultrasound or magnetic resonance elastography. Compared with different imaging techniques, TE has the best performance in diagnosing significant fibrosis. Liver stiffness measurement (LSM) is expected to become a biological indicator for routine screening, dynamic monitoring of disease changes, and prognostic evaluation.
In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease
Authors: Wu Yichuang , Su Xiangdong , Lu Jielang , Wu Meifang , Yang Seo Young , Mai Yang , Deng Wenbin , Xue Yongbo 
Published: July 2022

Current studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer’s disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are considered as an important resource for screening natural products to against AD. In this study, thirty-four compounds (1–34) were isolated from Fallopia dentatoalata (Fr. Schm.) Holub, and their inhibitory effects against AChE and BuChE were assessed. Compounds of the phenylpropanoid sucrose ester class emerged as the most promising members of the group, with 31–33 displaying moderate AChE inhibition (IC50 values ranging from 30.6 ± 4.7 to 56.0 ± 2.4 µM) and 30–34 showing potential inhibitory effects against BuChE (IC50 values ranging from 2.7 ± 1.7 to 17.1 ± 3.4 µM). Tacrine was used as a positive control (IC50: 126.7 ± 1.1 in AChE and 5.5 ± 1.7 nM in BuChE). Kinetic analysis highlighted compounds 31 and 32 as non-competitive inhibitors of AChE with Ki values of ∼30.0 and ∼34.4 µM, whilst 30–34 were revealed to competitively inhibit BuChE with Ki values ranging from ∼1.8 to ∼17.5 µM. Molecular binding studies demonstrated that 30–34 bound to the catalytic sites of BuChE with negative binding energies. The strong agreement between both in vitro and in silico studies highlights the phenylpropanoid sucrose esters 30–34 as promising candidates for use in future anti-cholinesterase therapeutics against Alzheimer’s disease.