bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Hemoglobin, in-vivo Alzheimer Pathologies, and Cognitive Impairment: A Cross-Sectional Study
Authors: Kim Jee Wook , Byun Min Soo , Yi Dahyun , Lee Jun Ho , Jeon So Yeon , Ko Kang , Joung Haejung , Jung Gijung , Lee Jun-Young , Sohn Chul-Ho , Lee Yun-Sang , Kim Yu Kyeong , Lee Dong Young 
Published: February 2021

Background: Despite known associations between low blood hemoglobin level and Alzheimer's disease (AD) or cognitive impairment, the underlying neuropathological links are poorly understood. We aimed to examine the relationships of blood hemoglobin levels with in vivo AD pathologies (i.e., cerebral beta-amyloid [Aβ] deposition, tau deposition, and AD-signature degeneration) and white matter hyperintensities (WMHs), which are a measure of cerebrovascular injury. We also investigated the association between hemoglobin level and cognitive performance, and then assessed whether such an association is mediated by brain pathologies.Methods: A total of 428 non-demented older adults underwent comprehensive clinical assessments, hemoglobin level measurement, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging. Episodic memory score and global cognition scores were also measured.Results: A lower hemoglobin level was significantly associated with reduced AD-signature cerebral glucose metabolism (AD-CM), but not Aβ deposition, tau deposition, or WMH volume. A lower hemoglobin level was also significantly associated with poorer episodic memory and global cognition scores, but such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a moderating effect.Conclusion: The present findings suggest that low blood hemoglobin in older adults is associated with cognitive decline via reduced brain metabolism, which seems to be independent of those aspects of AD-specific protein pathologies and cerebrovascular injury that are reflected in PET and MRI measures.
Case Report: Anti-NMDAR Encephalitis With Anti-MOG CNS Demyelination After Recurrent CNS Demyelination
Authors: Ren Bing-Yan , Guo Yi , Han Jing , Wang Qian , Li Zai-Wang 
Published: February 2021

Introduction: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a serious neurological autoimmune disorder caused by autoantibodies with diverse clinical manifestations, may simultaneously onset with antimyelin oligodendrocyte glycoprotein (MOG) demyelination after recurrent central nervous system (CNS) demyelination.Case Report: We present a case of anti-NMDAR encephalitis combining with anti-MOG CNS demyelination following recurrent CNS demyelination. A 38-year-old man admitted to hospital developed epileptic seizures following recurrent episodes of cross-sensory disturbance and dizziness. Magnetic resonance imaging (MRI) showed a demyelinating lesion in the right brainstem initially. Despite a good response to methylprednisolone pulse therapy at the beginning, the patient still had relapses and progression after corticosteroid reduction or withdrawal. Then brain MRI discovered new serpentine lesions involving extensive cerebral cortex on his second relapse. Repeat autoantibodies test indicated cerebrospinal fluid (CSF) NMDAR antibodies coexisted with MOG-Abs simultaneously, suggesting the diagnosis of anti-NMDAR encephalitis with anti-MOG CNS demyelination.Results: After a definite diagnosis, the patient was treated with mycophenolate mofetil (MMF) and corticosteroid. He was discharged after his symptoms ameliorated. No neurological sequels remained, and there were no effects on his activities of daily living after 6 months of immunoregulatory therapy of MMF and corticosteroid.Conclusion: For individuals with recurrent CNS demyelination, especially combining with cortical encephalitis, repeated detection of autoantibodies against AE, and demyelination in CSF/serum can be helpful to enable a definite early diagnosis. For patients who suffer from anti-NMDAR encephalitis combining with anti-MOG CNS demyelination, second-line immunotherapy is recommended when first-line treatment such as steroids, intravenous immunoglobulin G (IVIG) and plasma exchange has been proven ineffective to prevent the relapse of disease.
APOE-ε4 Carrier Status and Gut Microbiota Dysbiosis in Patients With Alzheimer Disease
Authors: Hou Min , Xu Gaolian , Ran Maosheng , Luo Wei , Wang Hui 
Published: February 2021

BackgroundAlternations in gut microbiota and a number of genes have been implicated as risk factors for the development of Alzheimer disease (AD). However, the interactions between the altered bacteria and risk genetic variants remain unclear.ObjectiveWe aimed to explore associations of the risk genetic variants with altered gut bacteria in the onset of AD.MethodsWe collected baseline data and stool and blood samples from 30 AD patients and 47 healthy controls in a case-control study. The rs42358/rs4512 (ApoE), rs3851179 (PICALM), rs744373 (BIN1), rs9331888 (CLU), rs670139 (MS4A4E), rs3764650 (ABCA7), rs3865444 (CD33), rs9349407 (CD2AP), rs11771145 (EPHA1), and rs3818361/rs6656401 (CR1) were sequenced, and microbiota composition was characterized using 16S rRNA gene sequencing. The associations of the altered gut bacteria with the risk genetics were analyzed.ResultsApolipoprotein ε4 allele and rs744373 were risk loci for the AD among 12 genetic variants. Phylum Proteobacteria; orders Enterobacteriales, Deltaproteobacteria, and Desulfovibrionales; families Enterobacteriaceae and Desulfovibrionaceae; and genera Escherichia–Shigella, Ruminococcaceae_UCG_002, Shuttleworthia, Anaerofustis, Morganelia, Finegoldia, and Anaerotruncus were increased in AD subjects, whereas family Enterococcaceae and genera Megamonas, Enterococcus, and Anaerostipes were more abundant in controls (P &lt; 0.05). Among the altered microbiota, APOE ε4 allele was positively associated with pathogens: Proteobacteria.ConclusionThe interaction of APOE ε4 gene and the AD-promoting pathogens might be an important factor requiring for the promotion of AD. Targeting to microbiota might be an effective therapeutic strategy for AD susceptible to APOE ε4 allele. This needs further investigation.
Identification of an Immune-Related Signature for Predicting Prognosis in Patients With Pancreatic Ductal Adenocarcinoma
Authors: Wang Weijia , Yan Liang , Guan Xiaoya , Dong Bin , Zhao Min , Wu Jianhui , Tian Xiuyun , Hao Chunyi 
Published: February 2021

PurposePancreatic ductal adenocarcinoma (PDAC) is one of the highest fatality rate cancers with poor survival rates. The tumor microenvironment (TME) is vital for tumor immune responses, leading to resistance to chemotherapy and poor prognosis of PDAC patients. This study aimed to provide a comprehensive evaluation of the immune genes and microenvironment in PDAC that might help in predicting prognosis and guiding clinical treatments.MethodsWe developed a prognosis-associated immune signature (i.e., PAIS) based on immune-associated genes to predict the overall survival of patients with PDAC. The clinical significance and immune landscapes of the signature were comprehensively analyzed.ResultsOwing to gene expression profiles from TCGA database, functional enrichment analysis revealed a significant difference in the immune response between PDAC and normal pancreas. Using transcriptome data analysis of a training set, we identified an immune signature represented by 5 genes (ESR2, IDO1, IL20RB, PPP3CA, and PLAU) related to the overall survival of patients with PDAC, significantly. This training set was well-validated in a test set. Our results indicated a clear association between a high-risk score and a very poor prognosis. Stratification analysis and multivariate Cox regression analysis revealed that PAIS was an important prognostic factor. We also found that the risk score was positively correlated with the inflammatory response, antigen-presenting process, and expression level of some immunosuppressive checkpoint molecules (e.g., CD73, PD-L1, CD80, and B7-H3). These results suggested that high-risk patients had a suppressed immune response. However, they could respond better to chemotherapy. In addition, PAIS was positively correlated with the infiltration of M2 macrophages in PDAC.ConclusionsThis study highlighted the relationship between the immune response and prognosis in PDAC and developed a clinically feasible signature that might serve as a powerful prognostic tool and help further optimize the cancer therapy paradigm.
The Outcome of Primary Hepatic Carcinoid Tumor: A Retrospective Study Based on Propensity Score Matched Survival Analysis
Authors: Jiang Shaotao , Wu Huijie , Fu Rongdang , Mai Jialuo , Yao Jiyou , Hua Xuefeng , Chen Huan , Liu Jie , Lu Minqiang , Li Ning 
Published: February 2021

BackgroundPrimary hepatic carcinoid tumor (PHCT) is rare and has unclear clinical characteristics and prognosis.MethodsA retrospective study using data from the SEER database for patients diagnosed with PHCT used univariate and multivariate Cox models to screen for independent prognostic factors. The outcomes of patients in the surgical and nonsurgical groups were compared, and Propensity Score Matching (PSM) analysis was used to reduce confounder bias.ResultsA total of 186 PHCT patients were identified and the median survival was 65 (95% CI [43.287, 86.713]) months. Tumor size(HR = 2.493, 95% CI[1.222,5.083], p = 0.012), male(HR = 1.690, 95% CI[1.144,2.497], p = 0.008), age(HR = 2.583, 95% CI[1.697,3.930], p &lt; 0.001), SEER stage(HR = 1.555, 95% CI[1.184,2.044], p = 0.002) and surgery(HR = 0.292, 95% CI[0.135,0.634], p = 0.002) were significantly correlated with patient prognosis. In multivariate analysis, sex(HR = 3.206, 95% CI[1.311,7.834], p = 0.011) and surgery(HR = 0.204, 95% CI[0.043,0.966], p = 0.0045) were independent predictors of patient prognosis. Females are potentially susceptible to PHCT but have a better prognosis. With consistent baseline data, surgical patients have a better prognosis.ConclusionsPHCT is uncommon and survival time is longer than that of other primary liver cancers. We found that none-surgery was potentially independent risk factors for poor prognosis.
Antagonizing αvβ3 Integrin Improves Ischemia-Mediated Vascular Normalization and Blood Perfusion by Altering Macrophages
Authors: Li Yongjie , Gao Qian , Shu Xin , Xiao Lamei , Yang Yan , Pang Ningbo , Luo Yulin , He Jing , Zhang Liping , Wu Jianbo 
Published: February 2021

Background: αVβ3 integrin has been implicated in the physiological processes and pathophysiology of important angiogenesis-related disorders; however, the preclinical and clinical data on integrin αVβ3 antagonists have not demonstrated improved outcomes. Our goal was to test the hypothesis that inhibition of αVβ3 integrin improves blood flow in a mouse hindlimb ischemia model.Methods: In this study, we examined the effect of cilengitide, an αVβ3/αVβ5 integrin-specific RGD-mimetic cyclic peptide, on blood perfusion and angiogenesis after hindlimb ischemia. Blood flow was measured using Laser Doppler Scanner. Vascular density, and macrophages infiltration were examined by immunofluorescence. Macrophage polarization was measured by quantitative real time PCR.Results: We found that low-dose, not high-dose, cilengitide increased blood flow perfusion, capillary formation, and pericyte coverage, accompanied by an accumulation of macrophages and increased expression of the chemokine (C-C motif) ligand 2 (CCL2) in ischemic muscles. Macrophage depletion using clodronate liposomes resulted in a reduction in low-dose cilengitide-induced blood flow perfusion, macrophage accumulation, pericyte coverage, and CCL2 expression. Finally, in vitro assays showed that low-dose, not high-dose, cilengitide increased macrophage migration.Conclusion: These studies identified a novel role of the inhibition of αVβ3 integrin in modulating ischemia-induced angiogenesis, possibly through effects on macrophage infiltration and polarization, and revealed αVβ3 integrin inhibition to be a promising therapeutic strategy for peripheral artery disease.
Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
Authors: Pacini Alessandra , Tomassoni Daniele , Trallori Elena , Micheli Laura , Amenta Francesco , Ghelardini Carla , Di Cesare Mannelli Lorenzo , Traini Enea 
Published: February 2021

Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system’s changes which followed loose-ligation-derived compression of sciatic nerve, the putative neuroprotective role of thioctic acid and the pain-alleviating effect on low-back pain suffering patients. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY). Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 15 days with 250 μmol·kg−1·die−1 of (+/−)-thioctic acid; 125 μmol·kg−1·die−1 of (+/−)-thioctic acid; 125 μmol·kg−1·die−1 of (+)-thioctic acid lysine salt; 125 μmol·kg−1·die−1 of (−)-thioctic acid; 300 μmol·kg−1·die−1 pregabalin. Control SHR and WKY rats received the same amounts of vehicle. The clinical trial NESTIORADE (Sensory-Motor Neuropathies of the Sciatic Nerve: Comparative evaluation of the effect of racemic and dextro-rotatory forms of thioctic acid) examined 100 patients (49 males and 51 females aged 53 ± 11 years) dividing them into two equal-numbered groups, each treated daily for 60 days with 600 mg of (+/−)-thioctic acid or (+)-thioctic acid, respectively. The trial was registered prior to patient enrollment at EudraCT website (OSSC Number: 2011-000964-81). In the preclinical study, (+)-thioctic acid was more active than (+/−)- or (−)-enantiomers in relieving pain and protecting peripheral nerve as well as in reducing oxidative stress and astrogliosis in the spinal cord. Main findings of NESTIORADE clinical trial showed a greater influence on painful symptomatology, a quicker recovery and a better impact on quality of life of (+)-thioctic acid vs. (+/−)-thioctic acid. These data may have a pharmacological and pharmacoeconomical relevance and suggest that thioctic acid, above all (+)-enantiomer, could be considered for treatment of low-back pain involving neuropathy.
The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment
Authors: Wu Lina , Xu Wenxiong , Li Xuejun , Liu Ying , Wang Lu , Zhu Shu , Yang Fangji , Xie Chan , Peng Liang 
Published: February 2021

Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this study to investigate whether the NTCP p.Ser267Phe variant exerts an additive anti-HBV effect in chronic hepatitis B (CHB) patients on mainstream NAs treatment. After propensity score matching (PSM), a total of 136 CHB patients were included, among whom 68 were heterozygous carriers and 68 were wild-type controls. Proportions of primary nonresponse, partial virological response, virological breakthrough and hepatitis B reactivation and the HBV DNA clearance rate at each time point were compared using the chi-square test. Kaplan-Meier analysis and matched t-tests were also performed to estimate the speed of viral clearance and serum HBV DNA reduction, respectively. The proportion of primary nonresponse was significantly lower in heterozygous carriers than in wild-type controls (p &lt; 0.001), especially in patients using entecavir (p = 0.013). Specifically, heterozygous carriers achieved HBV DNA clearance faster than wild-type controls (log-rank p = 0.0198). HBV DNA levels were reduced more in heterozygous carriers after 12 weeks (p &lt; 0.001) and 24 weeks (p = 0.006) of treatment, especially among patients using ETV. Here, our study demonstrated that heterozygous mutations in rs2296651 enhanced the antiviral response of first-line NAs and helped to explore the possibility of combining NAs and NTCP blockers for a better anti-HBV effect.
Effects of Apigenin Treatment on Random Skin Flap Survival in Rats
Authors: Ma Xinyi , Lin Yuting , Liu yingying , Li Wenjie , He Jibing , Fang Miaojie , Lin Dingsheng 
Published: February 2021

Random skin flaps are often used in plastic surgery, but the complications of marginal flap ischemia and necrosis often limit their wider clinical application. Apigenin (Api) is a flavonoid found in various fruits and vegetables. Api has been shown to promote angiogenesis, as well as reduce oxidative stress, membrane damage, and inflammation. In this study, we assessed the effects of Api treatment on random skin flap survival. Dorsal McFarlane skin flaps were transplanted into rats, which were randomly divided into three groups: control (normal saline), low-dose Api (20 mg/kg), and high-dose Api (50 mg/kg). Seven days after the surgery, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were measured. Histological analyses were performed to determine flap survival and tissue edema. H&amp;E staining was performed to assess the histopathological changes in skin flaps, and the levels of microvascular density (MVD) were determined. Laser doppler flowmetry was used to assess microcirculation blood flow. Flap angiography was performed by injection of lead oxide/gelatin. The expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interlukin-1β (IL-lβ) were evaluated by immunohistochemistry. Rats in the high-dose Api group exhibited higher average flap survival area, microcirculatory flow, increased SOD activity, and higher VEGF expression levels compared with the other two groups. Furthermore, the levels of MDA and pro-inflammatory cytokines were significantly decreased in rats treated with high-dose Api. Our findings suggest the potential usefulness of Api in preventing skin flap tissue necrosis.
Meaning in Life: A Major Predictive Factor for Loneliness Comparable to Health Status and Social Connectedness
Authors: Macià Dídac , Cattaneo Gabriele , Solana Javier , Tormos José M. , Pascual-Leone Alvaro , Bartrés-Faz David 
Published: February 2021

Objective: Loneliness is the subjective distress of feeling alone and has a strong impact on wellbeing and health. In addition to well-known predictors like isolation and poor health, a better understanding of the psychological determinants of loneliness would offer effective targets for future complementary interventions.Methods: In this cross-sectional observational study (N = 2,240), we compared the explanatory power of several important risk factors of loneliness with the affective, motivational, and cognitive aspects of the Meaning in Life (MiL) construct. Different nested linear models were compared including socio-demographic, lifestyles, social-connectedness, and self-rated health variables, to assess the overlapping and non-overlapping explanatory power of each of them.Results: Health status and MiL were found to be the most important predictors of loneliness, followed by social connectedness and, with a much lower weight, lifestyles, and socio-demographic factors. Within the MiL factor, the most cognitive component, sense of coherence, had a greater explanatory power than the more affective and motivational ones.Conclusion: Reduced MiL, the capacity of an individual to attach “value and significance” to life, is a crucial predictor to the feeling of loneliness. These results suggest that programs aiming to combat loneliness should go well beyond situational interventions and include more cognitive, value-centered interventions that enable individuals to define and pursue a meaningful vital plan.
Dancing With Health: Quality of Life and Physical Improvements From an EU Collaborative Dance Programme With Women Following Breast Cancer Treatment
Authors: Karkou Vicky , Dudley-Swarbrick Irene , Starkey Jennifer , Parsons Ailsa , Aithal Supritha , Omylinska-Thurston Joanna , Verkooijen Helena M. , van den Boogaard Rosalie , Dochevska Yoanna , Djobova Stefka , Zdravkov Ivaylo , Dimitrova Ivelina , Moceviciene Aldona , Bonifacino Adriana , Asumi Alexis Matua , Forgione Dolores , Ferrari Andrea , Grazioli Elisa , Cerulli Claudia , Tranchita Eliana , Sacchetti Massimo , Parisi Attilio 
Published: February 2021

Background:Women's health has received renewed attention in the last few years including health rehabilitation options for women affected by breast cancer. Dancing has often been regarded as one attractive option for supporting women's well-being and health, but research with women recovering from breast cancer is still in its infancy. Dancing with Health is multi-site pilot study that aimed to evaluate a dance programme for women in recovery from breast cancer across five European countries.Methods:A standardized 32 h dance protocol introduced a range of Latin American dances presented within a sports and exercise framework with influences from dance movement therapy. Fifty-four women (M age 53.51; SD 7.99) participated in the study who had a breast cancer diagnosis &lt;3 years, chemotherapy &gt;6 weeks, no indication of metastasis, or scheduled surgery/chemotherapy/radiation treatment for the duration of the intervention. Primary outcome data was collected for anthropometric and fitness measures next to cancer-related quality of life.T-tests and Wilcoxon signed ranked tests were used to establish differences pre and post intervention. Cohen's d was also calculated to determine the effect size of the intervention.Results:Statistically significant changes were found for: (i) weight, right and left forearm circumference and hip; (ii) 6 min walking, right and left handgrip, sit-to-stand and sit-and-reach; (iii) the EORTC-QLQ C30 summary score as well as the subscales of emotional and social functioning and symptoms. In all cases the direction of change was positive, while Cohen's d calculated showed that the effect of the intervention for these parameters ranged from intermediate to large.Conclusion:Changes on the above anthropometric, fitness and quality of life measures suggest that the intervention was of value to the participating women recovering from breast cancer. Results also advocate collaborative efforts across countries to further research.