bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracarotid Transplantation of Skin-Derived Precursor Schwann Cells Promotes Functional Recovery After Acute Ischemic Stroke in Rats
Authors: Liang Jingjing , Cui Ronghui , Wang Jinglei , Shen Jiabing , Chen Ying , Cao Maosheng , Ke Kaifu 
Published: February 2021

Purpose: Skin-derived Precursor Schwann cells (SKP-SCs) have been reported to provide neuroprotection for the injured and dysmyelinated nervous system. However, little is known about SKP-SCs on acute ischemic stroke (AIS). We aimed to explore the efficacy and the potential mechanism of action of SKP-SCs on AIS in a rat ischemic stroke model.Methods: Adult male Sprague–Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) for 1.5 h on Day 0 and subsequently received an intracarotid injection of 2 × 106 green fluorescent protein (GFP) -labeled SKP-SCs or phosphate buffered saline (PBS) during reperfusion. Neurological function was assessed by behavioral tests on Days 1, 4, 7, 14, and 28. In a satellite cohort, rat brains were harvested and infarct volume was measured with 2,3,5-triphenyltetrazolium chloride (TTC) staining on Days 1 and 7, and migration and survival of SKP-SCs in the brain were traced by monitoring green fluorescence at 6 and12 h on Day 0, and on Days 1, 4, 7, 14, and 28. Histopathology and immunofluorescence staining were used to analyze the morphology, survival and apoptosis of neurons. Additionally, in an in vitro SKP-SC co-culture model using fetal rat primary cortical neurons underwent oxygen glucose deprivation/reoxygenation (OGD/R), Western blot was used to detect the expression of apoptosis indicators including activated caspase-3, Bax, and Bcl-2. TUNEL staining was used to count apoptotic cells.Results: Intracarotid transplantation of SKP-SCs effectively migrated to the periinfarct area and survived for at least 4 weeks. Transplanted SKP-SCs inhibited neuronal apoptosis, reduced infarct volume, and improved neurological recovery in the MCAO rats. Moreover, in vitro data showed that SKP-SCs treatment inhibited OGD/R-induced neuronal apoptosis and promoted survival of the cultured primary cortical neurons.Conclusions: Intracarotid transplantation of SKP-SCs promoted functional recovery in the rat AIS model and possesses the potential to be further developed as a novel therapy to treat ischemic stroke in humans.
Clinical Presentation and Disease Course of 37 Consecutive Cases of Progressive Multifocal Leukoencephalopathy (PML) at a German Tertiary-Care Hospital: A Retrospective Observational Study
Authors: Graf Lisa M. , Rosenkranz Sina C. , Hölzemer Angelique , Hagel Christian , Goebell Einar , Jordan Sabine , Friese Manuel A. , Addo Marylyn M. , Schulze zur Wiesch Julian , Beisel Claudia 
Published: February 2021

Background: Progressive multifocal leukoencephalopathy (PML) caused by JCV is a rare but frequently fatal disease of the central nervous system, usually affecting immunocompromised individuals. Our study aims to expand the data on patient characteristics, diagnosis, clinical course, possible PML-directed treatment, and outcome of patients with PML at a German tertiary-care hospital.Methods:In this single-center observational cohort study, 37 consecutive patients with a confirmed diagnosis of PML seen at the University Medical Center Hamburg-Eppendorf from 2013 until 2019 were retrospectively analyzed by chart review with a special focus on demographics, risk factors, and clinical aspects as well as PML-directed treatment and survival.Results:We identified 37 patients with definite, probable, and possible PML diagnosis. 36 patients (97%) had underlying immunosuppressive disorders such as HIV/AIDS (n = 17; 46%), previous treatment with monoclonal antibodies (n = 6; 16%), hematological or oncological malignancies (n = 6; 16%), sarcoidosis (n = 5; 14%), solid organ transplantation (n = 1; 3%), and diagnosis of mixed connective tissue disease (n = 1; 3%). In only one patient no evident immunocompromised condition was detected (n = 1; 3%). Treatment attempts to improve the outcome of PML were reported in 13 patients (n = 13; 35%). Twenty seven percent of patients were lost to follow-up (n = 10). Twenty four-month survival rate after diagnosis of PML was 56% (n = 15).Conclusion: This interdisciplinary retrospective study describes epidemiology, risk factors, clinical course, and treatment trials in patients with PML at a German tertiary-care hospital. Acquired immunosuppression due to HIV-1 constituted the leading cause of PML in this monocenter cohort.
Revisiting the L-Dopa Response as a Predictor of Motor Outcomes After Deep Brain Stimulation in Parkinson’s Disease
Authors: Lin Zhengyu , Zhang Xiaoxiao , Wang Linbin , Zhang Yingying , Zhou Haiyan , Sun Qingfang , Sun Bomin , Huang Peng , Li Dianyou 
Published: February 2021

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson’s disease (PD).Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively.Results: Pearson’s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R2 = 0.283, p = 0.016) but not on the non-tremor total score (R2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R2′ = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R2 = 0.290, p = 0.021), but not on the total score (R2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R2′ = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor.Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.
Neurobiological Mechanisms of Transcranial Direct Current Stimulation for Psychiatric Disorders; Neurophysiological, Chemical, and Anatomical Considerations
Authors: Yamada Yuji , Sumiyoshi Tomiki 
Published: February 2021

Backgrounds: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique for the treatment of several psychiatric disorders, e.g., mood disorders and schizophrenia. Therapeutic effects of tDCS are suggested to be produced by bi-directional changes in cortical activities, i.e., increased/decreased cortical excitability via anodal/cathodal stimulation. Although tDCS provides a promising approach for the treatment of psychiatric disorders, its neurobiological mechanisms remain to be explored.Objectives: To review recent findings from neurophysiological, chemical, and brain-network studies, and consider how tDCS ameliorates psychiatric conditions.Findings: Enhancement of excitatory synaptic transmissions through anodal tDCS stimulation is likely to facilitate glutamate transmission and suppress gamma-aminobutyric acid transmission in the cortex. On the other hand, it positively or negatively modulates the activities of dopamine, serotonin, and acetylcholine transmissions in the central nervous system. These neural events by tDCS may change the balance between excitatory and inhibitory inputs. Specifically, multi-session tDCS is thought to promote/regulate information processing efficiency in the cerebral cortical circuit, which induces long-term potentiation (LTP) by synthesizing various proteins.Conclusions: This review will help understand putative mechanisms underlying the clinical benefits of tDCS from the perspective of neurotransmitters, network dynamics, intracellular events, and related modalities of the brain function.
Glucose Control Has an Impact on Cerebral Blood Flow Alterations in Chronic Tinnitus Patients
Authors: Xia Wenqing , Cui Jinluan , Luo Yong , Xu Jin-Jing , Chen Huiyou , Yin Xindao , Ma Jianhua , Wu Yuanqing 
Published: February 2021

PurposeBoth tinnitus and type 2 diabetes mellitus (T2DM) are linked with cognitive decline and brain dysfunction. This study used arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to examine the abnormal cerebral blood flow (CBF) patterns existed in tinnitus patients and potential relationships between the abnormal CBF and cognitive performance. The impact of T2DM on CBF alterations in tinnitus patients was further explored.MethodsSixty tinnitus patients and 40 non-tinnitus subjects were recruited. CBF images were collected and analyzed using ASL perfusion fMRI. Brain regions with CBF alterations between tinnitus patients and non-tinnitus controls were identified by one-way analysis of variance. Interaction effects between tinnitus and T2DM for CBF changes were also selected. Then, correlation analyses were calculated to specify the link between CBF changes and cognitive performance and between CBF changes and diabetic characteristics.ResultsTinnitus patients showed decreased CBF, primarily in the auditory area and default mode network (DMN), compared with non-tinnitus controls. Decreased CBF in these regions was correlated with executive function and attention. The interaction effect between tinnitus and T2DM was significant in the right medial prefrontal gyrus. Additionally, CBF in the right medial prefrontal gyrus was correlated with tinnitus distress and cognitive performance. In tinnitus patients, Hemoglobin A1c was associated with CBF in the right medial prefrontal gyrus.ConclusionTinnitus affects brain perfusion in the auditory area and DMN. T2DM and uncontrolled glucose levels may aggravate a CBF decrease in tinnitus patients. These new findings implied that tinnitus patients may benefit from blood glucose control in terms of their cognitive function and tinnitus distress.
Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma
Authors: Ge Jingjing , Li Cheng , Xue Fengjun , Qi Shaopei , Gao Zhimeng , Yu Chunjiang , Zhang Junping 
Published: February 2021

BackgroundTreatment for recurrent glioblastoma is poor, and there is a need for better therapies. Here we retrospectively assessed the efficacy and toxicity of temozolomide plus apatinib, an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 in recurrent glioblastoma.Materials and MethodsA retrospective analysis of patients with recurrent glioblastoma who underwent apatinib plus temozolomide treatment was performed. Apatinib was given at 500 mg once daily. Temozolomide was administered at 200 mg/m2/d on days 1–5 or 50 mg/m2/d continuous daily according to whether they had experienced temozolomide maintenance treatment before. The main clinical data collected included tumor characteristics, status of MGMT promoter, and IDH mutation, number of relapse, response, survival, adverse reactions, and salvage therapies.ResultsFrom April 2016 to August 2019, thirty-one patients were identified. The objective response rate was 26.3%, and the disease control rate was 84.2%. The progression-free survival (PFS) at 6 months and overall survival (OS) at 12 months were 44.6 and 30.2%. The median PFS and OS were 4.9 and 8.2 months, respectively. Two patients achieved long PFS of 30.9 and 38.7+ months. The median survival time after progression of the patients with or without salvage bevacizumab was 5.1 versus 1.2 months. The most common grade 3 or 4 toxicities were hypertension (5.8%), decreased appetite (5.8%), and thrombocytopenia (4.3%), most of which were resolved after symptomatic treatment or dose reduction.ConclusionApatinib plus temozolomide is an effective salvage regimen with manageable toxicities for recurrent glioblastoma and could not reduce the sensitivity to bevacizumab.
Prognostic and Therapeutic Potentials of OncomiRs Modulating mTOR Pathways in Virus-Associated Hepatocellular Carcinoma
Authors: Nadda Neeti , Paul Shashi Bala , Yadav Dawesh P. , Kumar Sonu , Sreenivas Vishnubhatla , Saraya Anoop , Gamanagatti Shivanand , Acharya Subrat Kumar , Shalimar  , Nayak Baibaswata 
Published: February 2021

BackgroundDysregulated oncomiRs are attributed to hepatocellular carcinoma (HCC) through targeting mTOR signaling pathway responsible for cell growth and proliferation. The potential of these oncomiRs as biomarker for tumor response or as target for therapy needs to be evaluated.AIMTumor response assessment by OncomiR changes following locoregional therapy (LRT) and targeting of these oncomiRs modulating pathwayMethodsAll consecutive viral-HCC patients of BCLC stage-A/B undergoing LRT were included. OncomiRs (miR-21, -221, and -16) change in circulation and AFP-ratio at 1-month post-LRT to baseline was estimated to differentiate various categories of response as per mRECIST criteria. OncomiR modulating mTOR pathway was studied by generating miR-21 and miR-221 overexpressing Huh7 stable cell lines.ResultsPost-LRT tumor response was assessed in 90 viral-HCC patients (CR, 40%; PR, 31%, and PD, 29%). Significant increase of miRNA-21 and -221 expression was observed in PD (p = 0.040, 0.047) and PR patients (miR-21, p = 0.045). Fold changes of miR-21 can differentiate response in group (CR from PR+PD) at AUROC 0.718 (95% CI, 0.572–0.799) and CR from PD at AUROC 0.734 (95% CI, 0.595–0.873). Overexpression of miR-21 in hepatoma cell line had shown increased phosphorylation p70S6K, the downstream regulator of cell proliferation in mTOR pathway. Upregulation of AKT, mTOR, and RPS6KB1 genes were found significant (P &lt; 0.005) and anti-miR-21 specifically reduced mTOR gene (P = 0.02) expression.ConclusionsThe miR-21 fold change correlates well with imaging in predicting tumor response. Overexpression of miR-21 has a role in HCC through mTOR pathway activation and can be targeted.
Clinical Pharmacology of Clazosentan, a Selective Endothelin A Receptor Antagonist for the Prevention and Treatment of aSAH-Related Cerebral Vasospasm
Authors: Juif Pierre-Eric , Dingemanse Jasper , Ufer Mike 
Published: February 2021

Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm and is associated with significant morbidity and mortality. It represents a major unmet medical need due to few treatment options with limited efficacy. The role of endothelin-1 (ET-1) and its receptor ETA in the pathogenesis of aSAH-induced vasospasm suggests antagonism of this receptor as promising asset for pharmacological treatment. Clazosentan is a potent ETA receptor antagonist for intravenous use currently under development for the prevention of aSAH-induced cerebral vasospasm. The pharmacokinetics of clazosentan are characterized by an intermediate clearance, a volume of distribution similar to that of the extracellular fluid volume, dose-proportional exposure, an elimination independent of drug-metabolizing enzymes, and a disposition mainly dependent on the hepatic uptake transporter organic anion transport polypeptide 1B1/1B3. In healthy subjects, clazosentan leads to an increase in ET-1 concentration and prevents the cardiac and renal effects mediated by infusion of ET-1. In patients, it significantly reduced the incidence of moderate or severe vasospasm as well as post-aSAH vasospasm-related morbidity and mortality. Clazosentan is well tolerated up to the expected therapeutic dose of 15 mg/h and, in aSAH patients, lung complications, hypotension, and anemia were adverse events more commonly reported following clazosentan than placebo. In summary, clazosentan has a pharmacokinetic, pharmacodynamic, and safety profile suitable to become a valuable asset in the armamentarium of therapeutic modalities to prevent aSAH-induced cerebral vasospasm.
Heart Slices to Model Cardiac Physiology
Authors: Meki Moustafa H. , Miller Jessica M. , Mohamed Tamer M. A. 
Published: February 2021

Translational research in the cardiovascular field is hampered by the unavailability of cardiac models that can recapitulate organ-level physiology of the myocardium. Outside the body, cardiac tissue undergoes rapid dedifferentiation and maladaptation in culture. There is an ever-growing demand for preclinical platforms that allow for accurate, standardized, long-term, and rapid drug testing. Heart slices is an emerging technology that solves many of the problems with conventional myocardial culture systems. Heart slices are thin (&lt;400 µm) slices of heart tissue from the adult ventricle. Several recent studies using heart slices have shown their ability to maintain the adult phenotype for prolonged periods in a multi cell-type environment. Here, we review the current status of cardiac culture systems and highlight the unique advantages offered by heart slices in the light of recent efforts in developing physiologically relevant heart slice culture systems.
Training and Racing Behavior of Recreational Runners by Race Distance—Results From the NURMI Study (Step 1)
Authors: Knechtle Beat , Tanous Derrick R. , Wirnitzer Gerold , Leitzmann Claus , Rosemann Thomas , Scheer Volker , Wirnitzer Katharina 
Published: February 2021

The present study investigated pre-race preparation of a large sample of recreational runners competing in different race distances (e.g., shorter than half-marathon, half-marathon, marathon and ultra-marathon). An online questionnaire was used and a total of 3,835 participants completed the survey. Of those participants, 2,864 (75%) met the inclusion criteria and 1,628 (57%) women and 1,236 (43%) men remained after data clearance. Participants were categorized according to race distance in half-marathon (HM), and marathon/ultra-marathon (M/UM). Marathon and ultra-marathon data were pooled since the marathon distance is included in an ultra-marathon. The most important findings were (i) marathon and ultra-marathon runners were more likely to seek advice from a professional trainer, and (ii) spring was most commonly reported across all subgroups as the planned season for racing, (iii) training volume increased with increasing race distance, and (iv) male runners invested more time in training compared to female runners. In summary, runners competing in different race distances prepare differently for their planned race.Clinical Trial Registration:www.ClinicalTrials.gov, identifier ISRCTN73074080. Retrospectively registered 12th June 2015.
CA125 test result, test-to-diagnosis interval, and stage in ovarian cancer at diagnosis: a retrospective cohort study using electronic health records
Authors: Funston Garth , Mounce Luke TA , Price Sarah , Rous Brian , Crosbie Emma J , Hamilton Willie , Walter Fiona M 
Published: February 2021

BackgroundIn the UK, the cancer antigen 125 (CA125) test is recommended as a first-line investigation in women with symptoms of possible ovarian cancer.AimTo compare time between initial primary care CA125 test and diagnosis, tumour morphology, and stage in women with normal (<35 U/ml) and abnormal (≥35 U/ml) CA125 levels prior to ovarian cancer diagnosis.Design and settingRetrospective cohort study using English primary care and cancer registry data.MethodAssociations between CA125 test results and test-to-diagnosis interval, stage, and ovarian cancer morphology were examined.ResultsIn total, 456 women were diagnosed with ovarian cancer in the 12 months after having a CA125 test. Of these, 351 (77%) had an abnormal, and 105 (23%) had a normal, CA125 test result. The median test-to-diagnosis interval was 35 days (interquartile range [IQR] 21–53) for those with abnormal CA125 levels, and 64 days (IQR 42–127) for normal CA125 levels. Tumour morphology differed by CA125 result: indolent borderline tumours were less common in those with abnormal CA125 levels (n = 47, 13%) than those with normal CA125 levels (n = 51, 49%) (P<0.001). Staging data were available for 304 women with abnormal, and 77 with normal, CA125 levels. Of those with abnormal CA125 levels, 35% (n = 106) were diagnosed at an early stage, compared to 86% (n = 66) of women with normal levels. The odds of being diagnosed with early-stage disease were higher in women with normal as opposed to abnormal CA125 levels (odds ratio 12.2, 95% confidence interval = 5.8 to 25.1, P<0.001).ConclusionDespite longer intervals between testing and diagnosis, women with normal, compared with abnormal, CA125 levels more frequently had indolent tumours and were more commonly diagnosed at an early stage in the course of the disease. Although testing approaches that have greater sensitivity might expedite diagnosis for some women, it is not known if this would translate to earlier-stage diagnosis.
PENERAPAN TRANSPARANSI , AKUNTABILITAS, SERTA KESESUAIANNYA PADA LAPORAN KEUANGAN UMKM DI KOTA SEMARANG
Authors: Tyas Dheasey Amboning 
Published: February 2021

Usaha Mikro Kecil dan Menengah (UMKM) merupakan salah satu aspek penting dari perekonomian suatu negara ataupun daerah tidak terkecuali di Indonesia. UMKM mampu menyerap tenaga kerja yang cukup besar, sehingga memberi peluang bagi UMKM untuk dapat berkembang dan bersaing. UMKM memiliki peranan cukup besar di dalam pembangunan ekonomi nasional,hal ini terlihat dari kontribusinya terhadap Produk Domestik Bruto (PDB) Indonesia. UMKM seringkali mengabaikan pencatatan dan pelaporan keuangan mereka, dikarenakan lebih fokus pada kegiatan operasional semata. Laporan keuangan berperan sangat penting, disamping sebagai acuan bagi pemilik usaha dalam pengambilan keputusan, juga terutama untuk memperoleh gambaran kondisi kinerja keuangan perusahaan, untung atau rugi, sehingga pelaku usaha dapat membuat rencana kedepannya agar usahanya lebih berkembang.Penelitian ini dilakukan untuk mengetahui bagaimana pemahaman, penerapan serta model implementasi penulisan laporan keuangan yang sesuai dengan Transparansi dan Akuntabilitas. Pengambilan data menggunakan metode purposive sampling yang kemudian data diuji dengan alat analisis SEM. Dari penelitian yang telah dilakukan, terdapat kesesuaian yang diharapkan di UMKM.