bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMC5 is Highly Expressed in Human Cancers and Corelates to Prognosis and Immune Cell Infiltration: A Comprehensive Bioinformatics Analysis
Authors: Zhang Hui , Zhang Xu , Xu Weiguo , Wang Jian 
Published: January 2022

Background: The oncological role of TMC5 in human cancers has only been revealed partially. We performed integrated bioinformatics analysis to provide a thorough and detailed insight of associations between TMC5 and tumorigenesis, cancer progression, and prognosis.Methods: With reference to the accessible online databases, the TMC5 expressions in tumor tissues and corresponding normal tissues, different pathological stages, and various cancer cells were analyzed, while the protein levels of TMC5 in different cancers were also inspected. Meanwhile, the prognostic value of TMC5 expression in multiple cancers as well as in advanced-stage patients was investigated. Furthermore, the mutational data of TMC5 and its correlation with cancer prognosis were assessed. Moreover, the association between the TMC5 level and immune cell infiltration was evaluated. Next, TMC5-related pathway alterations and drug responses were summarized. Finally, the TMC5 based protein network was generated, and relevant enrichment was performed.Results: In our study, the expression level of TMC5 was significantly higher in the tumor tissue than that of the normal tissues in most cancer types. Fluctuations of TMC5 levels were also observed among different pathological stages. In the meantime, the protein level elevated in the tumor tissue in the cancers enrolled. Moreover, the expression of TMC5 was not only prognostic for overall survival (OS) or recurrence free survival (RFS) in various types of cancers but also correlated to OS in patients with more advanced cancers. Additionally, the mutational status of TMC5 is also associated with prognosis in cancer patients. It is worth noting that the TMC5 level was closely related to immune cell infiltrations, especially in ESCA, TGCT, and USC. The TMC5 expression was also identified as an activator for pathways including PI3K/AKT, RAS/MAPK, and TSC/mTOR, proved to be associated with multiple drug responses and assessed to be interactive with the TMEM family.Conclusion: TMC5 might function as a potential marker for cancer survival and immune responses.
Awareness for People With Alzheimer’s Disease: Profiles and Weekly Trajectories
Authors: Mayelle Amandine , Hazebrouck Capucine , El Haj Mohamad , Mograbi Daniel C. , Antoine Pascal 
Published: January 2022

Objective: To understand awareness and fluctuations of awareness in Alzheimer’s disease (AD), it is fruitful to consider the objects of awareness, e.g., cognitive functioning or recognition of the disease, as well as the mechanisms and modes of expression underlying awareness. With a holistic and discourse-centered approach, we aimed to identify different awareness profiles and test whether these profiles were stable or whether transitions from one profile to another occurred over short time intervals.Methods: Twenty-eight residents of nursing homes with a diagnosis of AD participated in four semistructured interviews at biweekly intervals. These interviews were cluster analyzed to determine profiles of awareness. A Markov chain was applied to model their fluctuation.Results: Five awareness profiles were observed that differed in terms of objects and underlying processes. Awareness proved to be quite stable for four of the five profiles. Interindividual variability in awareness was also observed through numerous different trajectories that were identified.Discussion: Self-awareness and disease awareness are characterized by profiles that vary subtly between individuals. Fluctuations in awareness underscore the need to employ assessment intervals that closely reflect daily life in institutions.
Correlation Between Proprioceptive Impairment and Motor Deficits After Stroke: A Meta-Analysis Review
Authors: Yu Yifan , Chen Yufang , Lou Teng , Shen Xia 
Published: January 2022

Introduction: Proprioceptive impairment is a common symptom after stroke. Clarifying how proprioception correlates with motor function after stroke may be helpful in optimizing proprioception-augmented movement training. Previous studies have shown inconsistent findings. A meta-analysis is an optimal method to explore the correlation and identify the factors contributing to these inconsistencies.Objective: To explore the correlation between proprioception and motor function after stroke through a meta-analysis, taking into account characteristics of the measurements used in these studies.Methods: We searched multiple databases until November 2021 for eligible studies that measured both proprioception and motor functions in persons with stroke and reported their correlation or data for correlation analysis. A meta-analysis of the correlations was performed. The subgroup analysis and meta-regression were further conducted to investigate potential factors contributing to the heterogeneity of correlation strength, based on the participants' characteristics, proprioception, and motor function measures.Results: In total, 28 studies comprising of 1,829 participants with stroke were included in the meta-analysis. The overall correlation between proprioception and motor function was significant (r = 0.267, p &lt; 0.05), but there was heterogeneity across studies (I2 = 45%, p &lt; 0.05). The results of the subgroup analysis showed proprioception of the axial segment in weight-bearing conditions (r = 0.443, p &lt; 0.05) and upper limb without weight-bearing (r = 0.292, p &lt; 0.05) had a stronger correlation with motor function than proprioception of the lower limb without weight-bearing. The proprioception measured through ipsilateral matching (r = 0.412, p &lt; 0.05) showed a stronger correlation with motor function than through contralateral matching. The International Classification of Functioning, Disability, and Health (ICF) domains of motor function, movement function (r = 0.338, p &lt; 0.05), activity performance (r = 0.239, p &lt; 0.05), and independence (r = 0.319, p &lt; 0.05) showed a stronger correlation with proprioception than with other domains.Conclusion: There is a significant correlation between proprioception and motor dysfunction after stroke. The proprioception measured in the axial segment under weight-bearing conditions or measured with ipsilateral matching, and motor function, specifically in the ICF domains of movement function, activity performance, and independence showed a positive contribution to the association between proprioception and motor function. The correlation does not imply causation and might be underestimated by attributes of current tests for proprioception and motor function. Further studies are needed to clarify the cause-effect relationship.
Lower GDNF Serum Level Is a Possible Risk Factor for Constipation in Patients With Parkinson Disease: A Case–Control Study
Authors: Chen Gang , Du Yinzhen , Li Xue , Kambey Piniel Alphayo , Wang Li , Xia Ying , Tang Chuanxi , Shi Mingyu , Zai-li Li , Zai-e Xin , Xiao-ling Qin , Dian-shuai Gao 
Published: January 2022

Background: Constipation is a significant symptom of Parkinson's disease (PD). Glial-derived neurotrophic factor (GDNF) is important for the morphogenesis of the enteric nervous system and plays a critical role in the preservation of mucosal integrity under enteric glia surveillance. The aim of this work was to evaluate the serum levels of GDNF in patients with PD with and without constipation.Methods: This work included 128 patients with PD. The patients were classified into three groups: those with PD but no constipation (nCons-PD) (n = 49), those with prodromal stage constipation (Cons-Pro-PD) (n = 48), and those with clinical stage constipation (Cons-Clinic-PD) (n = 31). The association between serum GDNF concentration and constipation was explored using logical regression.Results: The nCons-PD group's mean GDNF levels were 528.44 pg/ml, which was higher than the Cons-Pro-PD group's 360.72 pg/ml and the Cons-Clinic-PD group's 331.36 pg/ml. The results of binary logistic regression indicated that GDNF was a protective factor in the prevention of constipation. Cons-Clinic-PD group had a higher score of MDS-UPDRS-II, MDS-UPDRS-III, MDS-UPDRS-IV, and a higher H-Y staging as compared with nCons-PD group. Relative to the nCons-PD group, Cons-Clinic-PD had higher NMSS scores, lower MoCA and PDSS scores, and were more likely to have RBD.Conclusions: GDNF serum levels are lower in patients with PD who are constipated. A low GDNF level is a potential risk factor for constipation in patients with PD.
Disrupted White Matter Functional Connectivity With the Cerebral Cortex in Migraine Patients
Authors: Qin Zhaoxia , Liang Huai-Bin , Li Muwei , Hu Yue , Wu Jing , Qiao Yuan , Liu Jian-Ren , Du Xiaoxia 
Published: January 2022

Background: In attempts to understand the migraine patients’ overall brain functional architecture, blood oxygenation level-dependent (BOLD) signals in the white matter (WM) and gray matter (GM) were considered in the current study. Migraine, a severe and multiphasic brain condition, is characterized by recurrent attacks of headaches. BOLD fluctuations in a resting state exhibit similar temporal and spectral profiles in both WM and GM. It is feasible to explore the functional interactions between WM tracts and GM regions in migraine.Methods: Forty-eight migraineurs without aura (MWoA) and 48 healthy controls underwent resting-state functional magnetic resonance imaging. Pearson’s correlations between the mean time courses of 48 white matter (WM) bundles and 82 gray matter (GM) regions were computed for each subject. Two-sample t-tests were performed on the Pearson’s correlation coefficients (CC) to compare the differences between the MWoA and healthy controls in the GM-averaged CC of each bundle and the WM-averaged CC of each GM region.Results: The MWoAs exhibited an overall decreased average temporal CC between BOLD signals in 82 GM regions and 48 WM bundles compared with healthy controls, while little was increased. In particular, WM bundles such as left anterior corona radiata, left external capsule and bilateral superior longitudinal fasciculus had significantly decreased mean CCs with GM in MWoA. On the other hand, 16 GM regions had significantly decreased mean CCs with WM in MWoA, including some areas that are parts of the somatosensory regions, auditory cortex, temporal areas, frontal areas, cingulate cortex, and parietal cortex.Conclusion: Decreased functional connections between WM bundles and GM regions might contribute to disrupted functional connectivity between the parts of the pain processing pathway in MWoAs, which indicated that functional and connectivity abnormalities in cortical regions may not be limited to GM regions but are instead associated with functional abnormalities in WM tracts.
The Role of MRI Pancreatic Protocol in Assessing Response to Neoadjuvant Therapy for Patients With Borderline Resectable Pancreatic Cancer
Authors: Hussien Nervana , Hussien Rasha S. , Saad Darine Helmy Amin , El Kassas Mohamed , Elkhatib Walid F. , Ezz El Din Mai 
Published: January 2022

BackgroundBorderline Resectable Pancreatic Cancer (BRPC) remains a unique entity that is difficult to categorize due to variance in definitions and the small number of patients. The ultimate goal is to achieve a free resection (R0) after a favorable response to neoadjuvant therapy that is somewhat difficult to assess by current radiological parameters.AimTo evaluate the role of Magnetic Resonance Imaging (MRI) pancreatic protocol, including Diffusion-Weighted Imaging (DWI), in patients with BRPC receiving neoadjuvant therapy, and further compare it to RECIST criteria and outcome.MethodsHistologically confirmed BRPC patients were prospectively included. DWI-MRI was performed pre- and post-therapy. Clinical characteristics with ensuing operability were recorded and correlated to radiological RECIST/apparent diffusion coefficient (ADC) change, preoperative therapy administrated, surgical resection status, and survival.ResultsOut of 30 BRPC cases, only 11 (36.7%) ultimately underwent pancreaticoduodenectomy. Attaining a stationary or stable disease via ADC/RECIST was achieved in the majority of cases (60%/53.3% respectively). Of the 12 patients (40%) who achieved a regression by ADC, 11 underwent surgery with an R0 status. These surgical cases showed variable RECIST responses (PR=5, SD=4, PD=3). Responders by ADC to neoadjuvant therapy were significantly associated to presenting with abdominal pain (p =0.07), a decline in post-therapy CA19-9 (p&lt;0.001), going through surgery (p&lt;0.001), and even achieving better survival (p&lt;0.001 vs. 0.66).ConclusionDWI-MRI ADC picked up patients most likely to undergo a successful operative procedure better than traditional RECIST criteria. An algorithm incorporating novel radiological advances with CA19-9 deserves further assessment in future studies.
Study Protocol of the Exercise Study: Unraveling Limitations for Physical Activity in Children With Chronic Diseases in Order to Target Them With Tailored Interventions—A Randomized Cross Over Trial
Authors: Scheffers Linda E. , Helbing Willem A. , Utens Elisabeth M. W. J. , Dieleman Gwen C. , Dulfer Karolijn , Noske Josefien , van den Broek Eline A. , Walet Sylvia , Olieman Joanne F. , Escher Johanna C. , Pijnenburg Marielle W. , van der Ploeg Ans T. , van den Berg Linda E. 
Published: January 2022

Introduction: Physical activity is associated with many physiological and psychological health benefits across the lifespan. Children with a chronic disease often have lower levels of daily physical activity, and a decreased exercise capacity compared to healthy peers. In order to learn more about limitations for physical activity, we investigate children with four different chronic diseases: children with a Fontan circulation, children with Broncho Pulmonary Dysplasia (BPD), Pompe disease and inflammatory bowel disease (IBD). Each of these diseases is likely to interfere with physical activity in a different way. Knowing the specific limitations for physical activity would make it possible to target these, and increase physical activity by a personalized intervention. The aim of this study is to first investigate limitations for physical activity in children with various chronic diseases. Secondly, to measure the effects of a tailored exercise intervention, possibly including a personalized dietary advice and/or psychological counseling, on exercise capacity, endurance, quality of life, fatigue, fear for exercise, safety, muscle strength, physical activity levels, energy balance, and body composition.Methods and Analysis: This randomized crossover trial will aim to include 72 children, aged 6–18 years, with one of the following diagnosis: a Fontan circulation, BPD, Pompe disease and IBD. Eligible patients will participate in the 12-week tailored exercise intervention and are either randomized to start with a control period or start with the intervention. The tailored 12-week exercise interventions, possibly including a personalized dietary advice and/or psychological counseling, will be designed based on the found limitations for physical activity in each disease group during baseline measurements by the Rotterdam Exercise Team. Effects of the tailored training interventions will be measured on the following endpoints: exercise capacity (measured by cardiopulmonary exercise test), endurance, physical activity levels, muscle strength, quality of life, fatigue, fear for exercise, disease activity, cardiac function (in children with a Fontan circulation), energy balance, and body composition.Ethics and Dissemination: Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval was obtained.Trial Registration Number: NL8181, https://www.trialregister.nl/trial/8181.
Screen Time, Age and Sunshine Duration Rather Than Outdoor Activity Time Are Related to Nutritional Vitamin D Status in Children With ASD
Authors: Shan Ling , Dong Hanyu , Wang Tiantian , Feng Junyan , Jia Feiyong 
Published: January 2022

Objective: This study aimed to investigate the possible association among vitamin D, screen time and other factors that might affect the concentration of vitamin D in children with autism spectrum disorder (ASD).Methods: In total, 306 children with ASD were recruited, and data, including their age, sex, height, weight, screen time, time of outdoor activity, ASD symptoms [including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Autism Diagnostic Observation Schedule–Second Edition (ADOS-2)] and vitamin D concentrations, were collected. A multiple linear regression model was used to analyze the factors related to the vitamin D concentration.Results: A multiple linear regression analysis showed that screen time (β = −0.122, P = 0.032), age (β = −0.233, P &lt; 0.001), and blood collection month (reflecting sunshine duration) (β = 0.177, P = 0.004) were statistically significant. The vitamin D concentration in the children with ASD was negatively correlated with screen time and age and positively correlated with sunshine duration.Conclusion: The vitamin D levels in children with ASD are related to electronic screen time, age and sunshine duration. Since age and season are uncontrollable, identifying the length of screen time in children with ASD could provide a basis for the clinical management of their vitamin D nutritional status.
Interaction of Serum Alkaline Phosphatase and Folic Acid Treatment on Chronic Kidney Disease Progression in Treated Hypertensive Adults
Authors: Zhang Yuanyuan , He Panpan , Wang Guobao , Liang Min , Xie Di , Nie Jing , Liu Chengzhang , Song Yun , Liu Lishun , Wang Binyan , Li Jianping , Zhang Yan , Wang Xiaobin , Huo Yong , Hou Fan Fan , Xu Xiping , Qin Xianhui 
Published: January 2022

The relation of alkaline phosphatase (ALP) with chronic kidney disease (CKD) is still uncertain. We aimed to examine the prospective association between serum ALP and CKD progression, and the modifying effect of serum ALP on folic acid in preventing CKD progression in treated hypertensive patients. This is a post-hoc analysis of 12,734 hypertensive adults with relevant measurements and without liver disease at baseline from the renal sub-study of the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid, or 10 mg enalapril alone. The primary outcome was CKD progression, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of &lt;60 ml/min/1.73 m2 if baseline eGFR was ≥60 ml/min/1.73 m2; or a decrease in eGFR of ≥50% if baseline eGFR was &lt;60 ml/min/1.73 m2; or end-stage renal disease. Over a median of 4.4 years, in the enalapril only group, participants with baseline serum ALP≥110IU/L (quartile 4) had a significantly higher risk of CKD progression (3.4% vs 2.3%; adjusted OR,1.61; 95%CI:1.11, 2.32), compared with those with ALP&lt;110IU/L. For those with enalapril and folic acid treatment, compared with the enalapril only treatment, the risk of CKD progression was reduced from 3.4 to 2.1% (adjusted OR, 0.53; 95%CI:0.34, 0.83) among participants with baseline ALP≥110IU/L, whereas there was no significant effect among those with ALP&lt;110IU/L. In hypertensive patients, higher serum ALP was associated with increased risk of CKD progression, and this risk was reduced by 47% with folic acid treatment.
Effects of Exogenous Hydrogen Sulfide in the Hypothalamic Paraventricular Nucleus on Gastric Function in Rats
Authors: Li Chenyu , Sun Hongzhao , Shi Yuan , Yu Yan , Ji Xiaofeng , Li Enguang , Zhou Xiaofan , Liu Xiaomeng , Xue Xikang , Sun Haiji 
Published: January 2022

Background: Hydrogen sulfide (H2S) is a new type of gas neurotransmitter discovered in recent years. It plays an important role in various physiological activities. The hypothalamus paraventricular nucleus (PVN) is an important nucleus that regulates gastric function. This study aimed to clarify the role of H2S in the paraventricular nucleus of the hypothalamus on the gastric function of rats.Methods: An immunofluorescence histochemistry double-labelling technique was used to determine whether cystathionine-beta-synthase (CBS) and c-Fos neurons are involved in PVN stress. Through microinjection of different concentrations of NaHS, physiological saline (PS), D-2-Amino-5-phosphonovaleric acid (D-AP5), and pyrrolidine dithiocarbamate (PDTC), we observed gastric motility and gastric acid secretion.Results: c-Fos and CBS co-expressed the most positive neurons after 1 h of restraint and immersion, followed by 3 h, and the least was at 0 h. After injection of different concentrations of NaHS into the PVN, gastric motility and gastric acid secretion in rats were significantly inhibited and promoted, respectively (p &lt; 0.01); however, injection of normal saline, D-AP5, and PDTC did not cause any significant change (p &gt; 0.05). The suppressive effect of NaHS on gastrointestinal motility and the promotional effect of NaHS on gastric acid secretion could be prevented by D-AP5, a specific N-methyl-D-aspartic acid (NMDA) receptor antagonist, and PDTC, an NF-κB inhibitor.Conclusion: There are neurons co-expressing CBS and c-Fos in the PVN, and the injection of NaHS into the PVN can inhibit gastric motility and promote gastric acid secretion in rats. This effect may be mediated by NMDA receptors and the NF-κB signalling pathway.
Discovery of the Potential Novel Pharmacodynamic Substances From Zhi-Zi-Hou-Po Decoction Based on the Concept of Co-Decoction Reaction and Analysis Strategy
Authors: Feng Xin , Bi Yuelin , Wang Jiaqi , Li Tianyi , Yu Gengyuan , Zhang Tonghua , Xu Haoran , Zhang Chenning , Sun Yikun 
Published: January 2022

Background: Zhi-Zi-Hou-Po Decoction (ZZHPD), a classic traditional Chinese medicine (TCM) formula, is clinically used to treat insomnia and depression. The analysis strategy based on the concept of co-decoction of TCM is helpful to analyse the effective substances of TCM formula in depth.Aim of the study: This manuscript intends to take ZZHPD as a model sample to explore the phenomenon of co-decoction of complex formula in the combination of liquid chromatography-mass spectrometry (LC-MS) technology, data analysis, and molecular docking.Materials and methods: In the current research, an innovative LC-MS method has been established to study the active ingredients in ZZHPD, and to identify the ingredients absorbed into the blood and brain tissues of mice. And molecular docking was used to study the binding pattern and affinities of known compounds of the brain tissue toward insomnia related proteins.Results: Based on new processing methods and analysis strategies, 106 chemical components were identified in ZZHPD, including 28 blood components and 18 brain components. Then, by comparing the different compounds in the co-decoction and single decoction, it was surprisingly found that 125 new ingredients were produced during the co-decoction, 2 of which were absorbed into the blood and 1 of which was absorbed into brain tissue. Ultimately, molecular docking studies showed that 18 brain components of ZZHPD had favourable binding conformation and affinity with GABA, serotonin and melatonin receptors. The docking results of GABRA1 with naringenin and hesperidin, HCRTR1 with naringenin-7-O-glucoside, poncirenin and genipin 1-gentiobioside, and luteolin with SLC6A4, GLO1, MAOB and MTNR1A may clarify the mechanism of action of ZZHPD in treating insomnia and depression.Conclusion: Our study may provide new ideas for further exploring the effective substances in ZZHPD.