bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling rare form of adult-onset NIID by characteristic brain MRI features: A single-center retrospective review
Authors: Li Fan , Wang Qi , Zhu Ying , Xiao Jiangxi , Gu Muliang , Yu Jiaxi , Deng Jianwen , Sun Wei , Wang Zhaoxia 
Published: December 2022

Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with high clinical heterogeneity. Previous studies indicated that the high-intensity signals in the corticomedullary junction on diffusion-weighted imaging (DWI) on brain MRI, known as the “ribbon sign,” could serve as a strong diagnostic clue. Here we used the explorative approach to study the undiagnosed rate of adult-onset NIID in a single center in China via searching for the ribbon sign in picture archive and communication system (PACS) and report the clinical and radiological features of initially undiagnosed NIID patients.Consecutive brain MRI of 21,563 adult individuals (≥18 years) in the PACS database in 2019 from a tertiary hospital were reviewed. Of them, 4,130 were screened out using the keywords “leukoencephalopathy” and “white matter demyelination.” Next, all 4,130 images were read by four neurologists. The images with the suspected ribbon sign were reanalyzed by two neuroradiologists. Those with the ribbon sign but without previously diagnosed NIID were invited for skin biopsy and/or genetic testing for diagnostic confirmation. The clinical features of all NIID patients were retrospectively reviewed.Five patients with high-intensity in the corticomedullary junction on DWI were enrolled. Three patients were previously diagnosed with NIID confirmed by genetic or pathological findings and presented with episodic encephalopathy or cognitive impairment. The other two patients were initially diagnosed with limb-girdle muscular dystrophy (LGMD) with rimmed vacuoles (RVs) and normal pressure hydrocephalus (NPH) in one each. Genetic analysis demonstrated GGC repeat expansion in the NOTCH2NLC gene of both, and skin biopsy of the first patient showed the presence of intranuclear hyaline inclusion bodies. Thus, five of the 21,563 adult patients (≥18 years) were diagnosed with NIID. The distinctive subcortical high-intensity signal on DWI was distributed extensively throughout the lobes, corpus callosum, basal ganglia, and brainstem. In addition, T2-weighted imaging revealed white matter hyperintensity of Fazekas grade 2 or 3, atrophy, and ventricular dilation. Distinctive DWI hyperintensity in the junction between the gray and white matter can help identify atypical NIID cases. Our findings highly suggest that neurologists and radiologists should recognize the characteristic neuroimaging pattern of NIID.
Lipid storage myopathy due to late-onset multiple Acyl-CoA dehydrogenase deficiency with novel mutations in ETFDH: A case report
Authors: Tian Huihong , Zhong Yi , Liu Zhihua , Wei Liping , Yuan Yanbo , Zhang Yuhu , Wang Limin 
Published: December 2022

BackgroundLipid storage myopathy (LSM) is an autosomal recessive inherited lipid and amino metabolic disorder with great clinical heterogeneity. Variations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene cause multiple acyl-CoA dehydrogenase deficiency (MADD), and have a manifestation of LSM. Muscle biopsy helps clarify the diagnosis of LSM, and next-generation sequencing (NGS) can be useful in identifying genomic mutation sites. The diagnosis of MADD contributes to targeted therapy.Case presentationWe report on a teenager who appeared to have muscle weakness and exercise intolerance at the onset. Before the referral to our hospital, he was unsuccessfully treated with glucocorticoid for suspected polymyositis. The next-generation sequencing of the proband and his parents revealed heterozygous variations, c.365G&gt;A (p.G122D) inherited from the father, c.176-194_176-193del, and c.832-316C&gt;T inherited from the mother in the ETFDH gene. The tandem mass spectrometry identified the mutations to be pathogenic. However, his parents and his younger sister who were detected with a mutation of c.365G&gt;A presented no clinical symptoms. This indicates that the combination of the three compound heterozygous mutations in ETFDH is significant. After MADD was diagnosed, a dramatic clinical recovery and biochemical improvement presented as riboflavin was given to the patient across a week, which further confirmed the diagnosis of MADD.ConclusionOur observations extend the spectrum of ETFDH variants in Chinese the population and reinforce the role of NGS in diagnosis of MADD. Early diagnosis and appropriate treatment of LSM lead to great clinical efficacy and avoid some lethal complications.
Prognostic significance of sarcopenia and systemic inflammation for patients with renal cell carcinoma following nephrectomy
Authors: Liu Qiuchen , Yang Jiajian , Chen Xin , Yang Jiakang , Zhao Xiaojun , Huang Yuhua , Lin Yuxin , Pu Jinxian 
Published: December 2022

BackgroundTo clarify the prognostic effect of preoperative sarcopenia and systemic inflammation, and to develop a nomogram for predicting overall survival (OS) of patients with renal cell carcinoma (RCC) following partial or radical nephrectomy.MethodsPatients with RCC following nephrectomy from the First Affiliated Hospital of Soochow University during January 2018 to September 2020 were included in this study. The relationship between sarcopenia and inflammatory markers was identified by logistic regression analysis. Then univariable Cox regression analysis, LASSO regression analysis and multivariable Cox regression analysis were analyzed sequentially to select the independent prognostic factors. Kaplan-Meier survival curves were applied to ascertain the prognostic value. Finally, the identified independent predictors were incorporated in a nomogram, which was internally validated and compared with other methods.ResultsA total of 276 patients were enrolled, and 96 (34.8%) were diagnosed with sarcopenia, which was significantly associated with neutrophil-to-lymphocyte ratio (NLR). Sarcopenia and elevated inflammation markers, i.e., NLR, platelet-to-lymphocyte ratio (PLR) and the modified Glasgow Prognostic Score (mGPS), were independent factors for determining the OS. The model had good discrimination with Concordance index of 0.907 (95% CI: 0.882–0.931), and the calibration plots performed well. Both net reclassification index (NRI) and integrated discriminant improvement (IDI) exhibited better performance of the nomogram compared with clinical stage-based, sarcopenia-based and integrated “NLR+PLR+mGPS” methods. Moreover, decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 20%.ConclusionsPreoperative sarcopenia was significantly associated with NLR. A novel nomogram with well validation was developed for risk stratification, prognosis tracking and personalized therapeutics of RCC patients.
Construction and validation of a clinical predictive nomogram for intraductal carcinoma of the prostate based on Chinese multicenter clinical data
Authors: Yang YunKai , Zhang Wei , Wan LiJun , Tang ZhiLing , Zhang Qi , Bai YuChen , Zhang DaHong 
Published: December 2022

IntroductionIntraductal carcinoma of the prostate (IDC-P) is a special pathological type of prostate cancer that is highly aggressive with poor prognostic outcomes.ObjectiveTo establish an effective predictive model for predicting IDC-P.MethodsData for 3185 patients diagnosed with prostate cancer at three medical centers in China from October 2012 to April 2022 were retrospectively analyzed. One cohort (G cohort) consisting of 2384 patients from Zhejiang Provincial People’s Hospital was selected for construction (Ga cohort) and internal validate (Gb cohort)of the model. Another cohort (I cohort) with 344 patients from Quzhou People’s Hospital and 430 patients from Jiaxing Second People’s Hospital was used for external validation. Univariate and multivariate binary logistic regression analyses were performed to identify the independent predictors. Then, the selected predictors were then used to establish the predictive nomogram. The apparent performance of the model was evaluated via externally validated. Decision curve analysis was also performed to assess the clinical utility of the developed model.ResultsUnivariate and multivariate logistic regression analyses showed that alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase were independent predictors of IDC-P. Therefore, a predictive nomogram of IDC-P was constructed. The nomogram had a good discriminatory power (AUC = 0.794). Internal validation (AUC = 0.819)and external validation (AUC = 0.903) also revealed a good predictive ability. Calibration curves showed good agreement between the predicted and observed incidences of IDC-P.ConclusionWe developed a clinical predictive model composed of alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase (LDH) with a high precision and universality. This model provides a novel calculator for predicting the diagnosis of IDC-P and different treatment options for patients at an early stage.
The integrative bioinformatics approaches to predict the xanthohumol as anti-breast cancer molecule: Targeting cancer cells signaling PI3K and AKT kinase pathway
Authors: Gupta Kartikey Kumar , Sharma Kamal Kant , Chandra Harish , Panwar Himalaya , Bhardwaj Nitin , Altwaijry Najla A. , Alsfouk Aisha A. , Dlamini Zodwa , Afzal Obaid , Altamimi Abdulmalik S. A. , Khan Shahanavaj , Mishra Abhay Prakash 
Published: December 2022

BackgroundBreast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage.MethodsThe current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through in silico analysis.ResultsThe result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of −7.5, −7.9, and −7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound’s absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski’s rule of five.ConclusionsThe finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.
Pharmacokinetics, metabolite profiling, safety, and tolerability of inhalation aerosol of 101BHG-D01, a novel, long-acting and selective muscarinic receptor antagonist, in healthy Chinese subjects
Authors: Gao Huaye , Li Jintong , Chen Xiaoping , Sun Zhanguo , Cui Gang , Cheng Minlu , Ding Li 
Published: December 2022

101BHG-D01 is a novel, long-acting, selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD). A single-site, randomized, double-blind, placebo-controlled and dose-escalation study of 101BHG-D01 inhalation aerosol was conducted to evaluate its pharmacokinetics, metabolite profiling, safety and tolerability following the single inhaled doses ranged from 20 to 900 μg in healthy Chinese subjects. After inhalation, 101BHG-D01 was absorbed rapidly into plasma with the time to maximum concentration about 5 min, and eliminated slowly with the terminal phase half-life about 30 h. The cumulative excretion rates of 101BHG-D01 in feces and urine were about 30% and 2%, respectively, which showed the study drug was mainly excreted in feces. The maximum drug concentration and area under the plasma concentration-time curve increased with dose escalation in the range of 20–600 μg, but their values increased out of proportion to the whole studied doses. The main metabolic pathways were loss of phenyl group and hydroxylation. No metabolite that presented at greater than 10 percent of total drug-related exposure was observed. 101BHG-D01 was safe and well tolerated after administration. The study results indicate that 101BHG-D01 is a good candidate for the treatment of COPD and enable further clinical development in subsequent studies in patients.Clinical Trial Registration:http://www.chinadrugtrials.org.cn; Identifier: CTR20192058.
Pharmacological effects of Bufei Jianpi granule on chronic obstructive pulmonary disease and its metabolism in rats
Authors: Yang Xin-Xin , Wang Shuai , Cui Lin-Lin , Li Tian-Jiao , Bai Gang , Bao Yong-Rui , Meng Xian-Sheng 
Published: December 2022

This work was performed to determine the pharmacological effects of Bufei Jianpi granules on chronic obstructive pulmonary disease and its metabolism in rats.Chronic obstructive pulmonary disease (COPD), ranked as the third leading cause of death worldwide, is seriously endangering human health. At present, the pathogenesis of COPD is complex and unclear, and the drug treatment mainly aims to alleviate and improve symptoms; however, they cannot achieve the purpose of eradicating the disease. Bufei Jianpi granule (BJG) is a Chinese medicine developed by the First Affiliated Hospital of Henan University of Traditional Chinese Medicine for treating COPD. This study focuses on the pharmacological effects of BJG on COPD and its metabolism in rats, aiming to provide a scientific basis for developing BJG against COPD. A total of 72 Sprague–Dawley (SD) rats were divided into the blank group, model group, positive control group, and BJG groups (2.36, 1.18, and 0.59 g/kg). Except for the blank group, rats in other groups were administered lipopolysaccharide (LPS) combined with smoking for 6 weeks to establish the COPD model. After another 6 weeks of treatment, the therapeutic effect of BJG on COPD rats was evaluated. In the BJG (2.36 g/kg) group, the cough condition of rats was significantly relieved and the body weight was close to that of the blank group. Compared with the mortality of 16.7% in the model group, no deaths occurred in the BJG (2.36 g/kg) and (1.18 g/kg) groups. The lung tissue damage in the BJG groups was less than that in the COPD group. Compared with the model group, MV, PIF, PEF, and EF50 in the BJG groups were observably increased in a dose-dependent manner, while sRaw, Raw, and FRC were obviously decreased. Also, the contents of IL-6, IL-8, TNF-α, PGE2, MMP-9, and NO in the serum and BALF were lowered dramatically in all BJG groups. All indicators present an obvious dose–effect relationship. On this basis, the UPLC-QTOF-MS/MS technology was used to analyze characteristic metabolites in rats under physiological and pathological conditions. A total of 17 prototype and 7 metabolite components were detected, and the concentration of most components was increased in the COPD pathologic state. It is suggested that BJG has a pharmacological effect in the treatment of COPD and the absorption and metabolism of chemical components of BJG in rats exhibited significant differences under physiological and pathological conditions.
Non-alcoholic fatty liver disease—A pilot study investigating early inflammatory and fibrotic biomarkers of NAFLD with alcoholic liver disease
Authors: Watt Joanne , Kurth Mary Jo , Reid Cherith N. , Lamont John V. , Fitzgerald Peter , Ruddock Mark W. 
Published: December 2022

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a condition where excess fat accumulates in the liver (hepatic steatosis) and there is no history of alcohol abuse or other secondary causes of chronic liver disease. NAFLD is a very common disorder, occurring in 25% of the global population. NAFLD is now the most common chronic liver disorder in Western countries. Liver biopsy is the gold standard for NAFLD diagnosis and staging; however, this is invasive, costly and not without risk. Biomarkers that could diagnose and stage disease would reduce the need for biopsy and allow stratification of patients at risk of progression to non-alcoholic steatohepatitis (NASH).Methods: One hundred and thirty-five patients were involved in the study [N = 135: n = 34 controls; n = 26 simple steatosis; n = 61 NAFLD/NASH, and n = 14 alcoholic liver disease (ALD)]. Clinically diagnosed (ICD-10) patient serum samples were obtained from Discovery Life Sciences (US) along with clinical history. Samples were run in duplicate using high-sensitivity cytokine array I, immunoassays and ELISAs. In total, n = 20 individual biomarkers were investigated in this pilot study.Results: Thirteen/20 (65%) biomarkers were identified as significantly different between groups; IFNγ, EGF, IL-1β, IL-6, IL-8, IL-10, TNFα, FABP-1, PIIINP, ST2/IL-33R, albumin, AST and ALT. Five/20 (25%) biomarker candidates were identified for further investigation; namely, three biomarkers of inflammation, IL-6, IL-8, and TNFα, and two biomarkers of fibrosis, PIIINP and ST2/IL-33R.Discussion: Single biomarkers are unlikely to be diagnostic or predictive at staging NAFLD due to the complex heterogeneity of the disease. However, biomarker combinations may help stratify risk and stage disease where patients are averse to biopsy. Further studies comparing the 5 biomarkers identified in this study with current diagnostic tests and fibrotic deposition in liver tissue are warranted.
Modeling personality antecedents and second language self-efficacy constructs with emerging adults in Japan: Domain-specific matching for assessing global competence in applied contexts
Authors: Kabir Russell Sarwar , Kramer Brandon , Koike Mayu , Sponseller Aaron C. 
Published: December 2022

IntroductionResearch on self–efficacy in intercultural communication (SEIC) provided validity evidence for second language (L2) self-efficacy domains. However, it lacked (1) an analysis of individual differences in personality as antecedents, (2) divergent validity from anxiety variables (i.e., foreign language classroom anxiety; FLCA), and (3) disambiguation from speaking (S-SE) and listening (L-SE) skill-specific self-efficacy types.MethodsWe conducted structural equation modeling of L2 self-efficacy and anxiety as response variables predicted by the Big Five model of personality in the context of Japanese undergraduate students at three university sites (n = 373), and a geographically diverse online survey of emerging adults (n = 1,326) throughout Japan.ResultsThe final model for the nationally representative sample showed that SEIC was predicted by all identified personality factors. Differentially supported paths were observed linking L-SE with Conscientiousness (β = 0.24) and Extraversion (β = 0.16), and S-SE with Extraversion (β = 0.24) and Neuroticism (β = −0.12). The fear of failure factor of FLCA was predicted positively by Neuroticism (β = 0.25) and, surprisingly, Conscientiousness (β = 0.10), and negatively by Extraversion (β = −0.13). Relationships to Openness to Experience were only supported for SEIC (β = 0.17) and S-SE (β = 0.12).DiscussionThese findings provide specificity matching for personality and L2 self-efficacy domains as empirical advances for assessing global competence within the context of Japan. Implications for cultural influences on self-efficacy and applied educational practices in language and intercultural learning are discussed.
Psychogenic non-epileptic seizures in youth: Individual and family psychiatric characteristics
Authors: Doss Julia 
Published: December 2022

IntroductionYouth with psychogenic non-epileptic seizures (PNES) are an understudied group associated with significant medical and psychiatric morbidity. Several studies have examined characteristics associated with youth's development of this disorder, though the exploration of family factors including psychiatric illness, has been lacking. This study sought to establish the need for a more comprehensive future study.MethodsA retrospective chart review was conducted on patients who had been admitted and diagnosed with PNES at the epilepsy monitoring unit at Children's Hospitals and Clinics of Minnesota. A total of 62 patients were included. All patients were evaluated by an epileptologist and psychologist during their diagnostic admission. “Spells” in question were captured via video EEG monitoring. PNES youth and family risk factors were assessed.ResultsMean age of PNES symptom onset was 13.9 years. Patients (73%) were diagnosed within 6 months of onset of symptoms. Histories of other impairing somatic complaints were present in the youth (54%), with 67% having prior psychiatric diagnoses. Experiencing suicidal ideation or thoughts of self-harm occurred in 47% of this sample. Family members were unaware of the history of these symptoms with 12% of the parent's reporting awareness. Family history of psychiatric disorders (first-degree relatives of patient) was present in 54% of the sample, with anxiety, depression and conversion disorder being the most commonly endorsed diagnoses.ConclusionsYouth with PNES present with comorbid psychiatric disorders, though prior assessment and treatment for these disorders was not common. Youth with PNES have history of suicidal ideation and thoughts of self-harm, though parental awareness of these co-occurring symptoms is limited. Family risk factors, such as history of psychiatric disorder in first degree relatives, was high. The impact of these family risk factors is understudied and should be further evaluated to better understand the impact on development and maintenance of this disorder in youth.
Multi-band network fusion for Alzheimer’s disease identification with functional MRI
Authors: Guo Lingyun , Zhang Yangyang , Liu Qinghua , Guo Kaiyu , Wang Zhengxia 
Published: December 2022

IntroductionThe analysis of functional brain networks (FBNs) has become a promising and powerful tool for auxiliary diagnosis of brain diseases, such as Alzheimer’s disease (AD) and its prodromal stage. Previous studies usually estimate FBNs using full band Blood Oxygen Level Dependent (BOLD) signal. However, a single band is not sufficient to capture the diagnostic and prognostic information contained in multiple frequency bands.MethodTo address this issue, we propose a novel multi-band network fusion framework (MBNF) to combine the various information (e.g., the diversification of structural features) of multi-band FBNs. We first decompose the BOLD signal adaptively into two frequency bands named high-frequency band and low-frequency band by the ensemble empirical mode decomposition (EEMD). Then the similarity network fusion (SNF) is performed to blend two networks constructed by two frequency bands together into a multi-band fusion network. In addition, we extract the features of the fused network towards a better classification performance.ResultTo verify the validity of the scheme, we conduct our MBNF method on the public ADNI database for identifying subjects with AD/MCI from normal controls.DiscussionExperimental results demonstrate that the proposed scheme extracts rich multi-band network features and biomarker information, and also achieves better classification accuracy.