bluuebunny/crossref_metadata_2025_split huggingface dataset:
A community-oriented survey on the association between androgenetic alopecia and metabolic syndrome in Chinese people
Authors: Zhu Hongliu , Guo Haijian , Gao Yihong , Wei Yuegang , Mao Tao , Yang Jianqiu 
Published: November 2022

BackgroundSeveral studies on Caucasians have revealed a positive relationship between androgenetic alopecia (AGA) and metabolic syndrome (MS). However, this correlation varies in different contexts. Currently, the association of AGA with MS is yet to be studied and elucidated in Chinese people.ObjectiveTo evaluate the association between AGA and MS in the Chinese population.MethodsThis study included information on components of MS along with other possible risk factors in a total of 3,703 subjects. The patients’ loss of hair was assessed using Hamilton-Norwood and Ludwig classification method.ResultsIn this study, 29.88% of male and 27.58% of female AGA patients were diagnosed with MS, while the rest were regarded as controls (29.95% of male and 27.89% of female control subjects) (P &gt; 0.05). The AGA males presented significantly higher systolic and diastolic blood pressure than the male control subjects (SP: P = 0.000; DP: P = 0.041). Among females with AGA, waist circumference, hip circumference, and waist-hip ratio elevated the loss of hair compared to that of the female controls (P = 0.000, P = 0.020, P = 0.001, respectively).ConclusionOur study indicated no direct association between AGA and MS in Chinese people. However, a close relationship was observed between AGA and systolic blood pressure.
Effects of tofacitinib therapy on arginine and methionine metabolites in association with vascular pathophysiology in rheumatoid arthritis: A metabolomic approach
Authors: Soós Boglárka , Hamar Attila , Pusztai Anita , Czókolyová Monika , Végh Edit , Szamosi Szilvia , Pethő Zsófia , Gulyás Katalin , Kerekes György , Szántó Sándor , Szűcs Gabriella , Christians Uwe , Klawitter Jelena , Seres Tamás , Szekanecz Zoltán 
Published: November 2022

IntroductionRheumatoid arthritis (RA) has been associated with changes in lipid, arginine and NO metabolism with increased cardiovascular (CV) risk. The aim of this study is to evaluate the effect of tofacitinib, a Janus kinase (JAK) inhibitor, on arginine and methionine metabolism in correlation with inflammation, functional and pathological vascular changes during one-year treatment of patients with RA.Materials and methodsThirty RA patients with active disease were treated with either 5 mg bid or 10 mg bid tofacitinib for 12 months. We determined DAS28, CRP, IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) levels. We assessed brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) by ultrasound at baseline and after 6 and 12 months. We also determined plasma L-arginine, L-citrulline, L-ornithine, inducible nitric oxide synthase (iNOS), asymmetric (ADMA) and symmetric dimethylarginine (SDMA), L-N-monomethyl-arginine (L-NMMA), cysteine, homocysteine, and methionine levels at these time points.ResultsTwenty-six patients (13 on each arm) completed the study. CRP, ESR and DAS28 decreased significantly during one-year treatment with tofacitinib. Arginine and ADMA showed a negative univariate correlation with CRP but not with FMD, PWV or IMT. Tofacitinib at 10 mg bid significantly increased L-arginine, L-ornithine, iNOS and methionine levels after 12 months. ADMA and SDMA levels did not change in our study. Methionine showed negative correlation with FMD at baseline and positive correlation with PWV after 12 months. No change was observed in FMD and PWV but a significant increase was measured in IMT at 6 and 12 months. Multivariate analysis indicated variable correlations of L-arginine, L-citrulline, ADMA, L-NMMA, homocysteine and methionine with DAS28, CRP, ESR and RF but not with anti-CCP after one-year treatment. With respect to vascular pathophysiology, only PWV and methionine correlated with each other.ConclusionOne-year tofacitinib treatment suppressed systemic inflammation and improved functional status in RA. FMD, PWV have not been affected by one-year tofacitinib treatment., while IMT increased further despite treatment. Increased arginine and methionine might contribute to the anti-inflammatory effects of tofacitinib. Increased arginine availability with no changing ADMA may protect FMD and PWV from deterioration. The increase of IMT in the anti-inflammatory environment cannot be explained by arginine or methionine metabolism in this study.
Neuro-vascular coupling and heart rate variability in patients with type II diabetes at different stages of diabetic retinopathy
Authors: Hommer Nikolaus , Kallab Martin , Schlatter Andreas , Janku Patrick , Werkmeister René M. , Howorka Kinga , Schmidl Doreen , Schmetterer Leopold , Garhöfer Gerhard 
Published: November 2022

Aims/HypothesisThere is evidence that diabetes is accompanied by a break-down of functional hyperemia, an intrinsic mechanism of neural tissues to adapt blood flow to changing metabolic demands. However, to what extent functional hyperemia is altered in different stages of diabetic retinopathy (DR) in patients with type II diabetes is largely unknown. The current study set out to investigate flicker-induced retinal blood flow changes in patients with type II diabetes at different stages of DR.Materials and methodsA total of 76 subjects were included in the present parallel-group study, of which 56 had diabetes with either no DR or different stages of non-proliferative DR (n = 29 no DR, 12 mild DR, 15 moderate to severe DR). In addition, 20 healthy subjects were included as controls. Retinal blood flow was assessed before and during visual stimulation using a combined measurement of retinal vessel calibers and blood velocity by the means of Doppler optical coherence tomography (OCT). To measure systemic autonomic nervous system function, heart rate variability (HRV) was assessed using a short-term orthostatic challenge test.ResultsIn healthy controls, retinal blood flow increased by 40.4 ± 27.2% during flicker stimulation. Flicker responses in patients with DR were significantly decreased depending on the stage of the disease (no DR 37.7 ± 26.0%, mild DR 26.2 ± 28.2%, moderate to severe DR 22.3 ± 13.9%; p = 0.035, ANOVA). When assessing systemic autonomous neural function using HRV, normalized low frequency (LF) spectral power showed a significantly different response to the orthostatic maneuver in diabetic patients compared to healthy controls (p &lt; 0.001).Conclusion/InterpretationOur study indicates that flicker induced hyperemia is reduced in patients with DR compared to healthy subjects. Further, this impairment is more pronounced with increasing severity of DR. Further studies are needed to elucidate mechanisms behind the reduced hyperemic response in patients with type II diabetes.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT03 552562].
Novel pathogenic variants in KIT gene in three Chinese piebaldism patients
Authors: Wang Chen , Zhang Yingzi , Hu Xuyun , Wang Lijuan , Xu Zhe , Xing Huan 
Published: November 2022

BackgroundPiebaldism is a rare autosomal dominant disease, and roughly 75% patients had KIT gene mutations. Up to date, approximately 90 KIT mutations causing piebaldism were reported.MethodsTo identify KIT gene mutations in three pediatric piebaldism patients from different families and explore the genotype-phenotype correlation, peripheral blood DNA were collected from probands and their parents. Whole-exome sequencing was performed to detect potential disease-causing variants in the three probands. Putative variants were validated by Sanger sequencing.ResultsHeterozygous variants of c.2469_2484del (p.Tyr823*), c.1994G &gt; C (p.Pro665Leu), and c.1982_1983insCAT (p.662_663insIle) in KIT gene were detected in three probands. These variants were all novel and classified as pathogenic/likely pathogenic variants according to the interpretation guidelines of American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The probands carrying variants located in tyrosine kinase domain exhibited a more severe phenotype.ConclusionThe piebaldism in three families was caused by novel heterozygous KIT variants. The severity of phenotypes is related with the types and locations of different mutations. Our results further provided evidence for genetic counseling for the three families.
Impact of parental rheumatoid arthritis on risk of autism spectrum disorders in offspring: A systematic review and meta-analysis
Authors: Sun Cheuk-Kwan , Cheng Yu-Shian , Chen I-Wen , Chiu Hsien-Jane , Chung Weilun , Tzang Ruu-Fen , Fan Hsin-Yi , Lee Chia-Wei , Hung Kuo-Chuan 
Published: November 2022

BackgroundTo investigate the association of risk of offspring autism spectrum disorder (ASD) with both maternal and paternal rheumatoid arthritis (RA).MethodsThe Embase, Medline, Cochrane Library databases were searched for studies that investigated the association of parental RA with risk of offspring ASD. The primary outcome was the associations of maternal/paternal RA with the risk of offspring ASD. Subgroup analyses were conducted based on the timing of maternal RA diagnosis (i.e., before/after childbirth) and geographical location (i.e., Western vs. Asian countries) of studies.ResultsTen studies published between 2005 and 2022 involving 6,177,650 participants were analyzed. Pooled results revealed a significant association between maternal RA and the risk of ASD (OR = 1.246, p &lt; 0.001, 10 studies), while there was no association of paternal RA with the risk of offspring ASD (OR = 1.104, p = 0.253, four studies). Subgroup analysis demonstrated no correlation between diagnosis of maternal RA before childbirth and the risk of offspring ASD (OR = 1.449, p = 0.192, four studies), while there was a significant association of maternal RA regardless of the timing of diagnosis with the risk of offspring ASD (OR = 1.227, p = 0.001, six studies). Subgroup analysis on geographical location showed a significant association of maternal RA with the risk of offspring ASD regardless of the study location (all p &lt; 0.05).ConclusionOur findings supported an association between maternal RA and an elevated risk of ASD in offspring. However, given the limited numbers of studies investigating the risk of offspring ASD in mothers diagnosed with RA before childbirth, further studies are warranted to elucidate this issue.Systematic review registration[www.crd.york.ac.uk/prospero/], identifier [CRD42022358470].
Urinary chemerin as a potential biomarker for inflammatory bowel disease
Authors: Gunawan Stefan , Elger Tanja , Loibl Johanna , Fererberger Tanja , Sommersberger Stefanie , Kandulski Arne , Müller Martina , Tews Hauke Christian , Buechler Christa 
Published: November 2022

PurposeSystemic levels of the adipokine chemerin are elevated in different inflammatory conditions such as inflammatory bowel disease (IBD). In IBD, chemerin protein expression in colon mucosa is induced and serum chemerin levels are increased. Aim of this study was to identify chemerin protein in human feces and/or urine and to evaluate a possible association with IBD activity.Materials and methodsFeces and urine of 40 patients with IBD and the respective sera of 34 patients were collected. Chemerin levels were analyzed by immunoblot in feces and urine samples. In addition, enzyme-linked immunosorbent assay (ELISA) was used to measure chemerin in all urine, feces and serum samples of the patients and in urine of 17 healthy controls.ResultsChemerin was not detectable in 80% of the human feces samples by ELISA. Chemerin in human urine was detected by immunoblot and ELISA. Compared to serum levels, urinary concentration was about 6,000-fold lower. Urinary chemerin did not differ between patients with ulcerative colitis (n = 15) and Crohn’s disease (n = 25). Urinary chemerin was not related to its serum levels, did not correlate with serum C-reactive protein level and negatively correlated with serum creatinine. Of note, urinary chemerin of patients with a fecal calprotectin &gt; 500 μg/g was significantly higher compared to patients with lower calprotectin levels and compared to healthy controls. Serum creatinine did not differ between the patient groups.ConclusionUrinary chemerin might present a novel non-invasive biomarker for monitoring IBD severity and clinical course.
Performance of leflunomide as a steroid-sparing agent in giant cell arteritis: A single-center, open-label study
Authors: Kramarič Jelka , Rotar Žiga , Tomšič Matija , Hočevar Alojzija 
Published: November 2022

BackgroundThe management of giant cell arteritis (GCA) remains challenging and many patients require prolonged glucocorticoid treatment due to high disease relapse rates. We aimed to evaluate the role of leflunomide as a steroid-sparing agent in GCA.MethodsThis prospective open-label study included patients diagnosed with GCA between July 2014 and August 2020 and followed them for 96 weeks. At the time of diagnosis all patients received treatment following a predefined glucocorticoid regimen. At week 12 of follow-up, 10 mg of leflunomide per day was recommended as an adjunctive therapy. The decision to start with leflunomide treatment was patient-dependent. Follow-up visits were performed adhering to a predetermined protocol. The number of relapses, the cumulative glucocorticoid dose and treatment-related adverse events were recorded and compared between glucocorticoid-only and leflunomide groups.ResultsOf the 215 GCA patients [67.6% female, median (IQR) age 74 (66–79) years], 151 (70.2%) received leflunomide at week 12 (leflunomide group); the others continued with glucocorticoids (glucocorticoid-only group). During the study 64/215 (29.8%) patients relapsed. Of the 51 patients who relapsed after 12 weeks, 22/151 patients (14.6%) and 29/64 patients (45.3%) were in the leflunomide and glucocorticoid-only group, respectively (p = 0.001; NNT 3.3 for leflunomide). Furthermore, 80/151 patients in the leflunomide group managed to stop glucocorticoids at week 48 [with relapses in 6/80 patients (7.5%)]. The cumulative glucocorticoid dose was lower in the leflunomide group (p = 0.009).ConclusionIn our cohort, leflunomide safely and effectively reduced the GCA relapse rate and demonstrated a steroid-sparing effect in over three quarters of patients.
Serum 4-hydroxynonenal associates with the recurrence of patients with primary cerebral infarction
Authors: Liu Xingliang , Bai Meiling , Fan Lei , Lou Zhan 
Published: November 2022

Background4-Hydroxynonenal (4-HNE), an α, β-unsaturated hydroxyalkenal, has been found to be associated with aspirin resistance, which is a risk factor for recurrent cerebral infarction. However, its effect on recurrent cerebral infarction is less defined. We designed this study to investigate the association between 4-HNE and increased risk of recurrent cerebral infarction.MethodsWe recruited 189 patients with primary cerebral infarction from 2017 to 2019. According to the recurrence of cerebral infarction during the 3-year follow-up period, they were divided into two groups, namely, the non-recurrence group (n = 93) and the recurrence group (n = 96). All patients were analyzed to explore the risk factors for the recurrence of primary cerebral infarction and the predictive value of serum 4-HNE for the recurrence of cerebral infarction.ResultsThe levels of serum 4-HNE in patients of the recurrence group were significantly higher than that in patients of the non-recurrence group. There was a positive correlation between serum 4-HNE levels and the serum levels of triglyceride (r = 0.448, p = 0.008) and low-density lipoprotein cholesterol (LDL-C; r = 0.442, p = 0.002) in primary cerebral infarction patients. Cox proportional hazards modeling showed that demographic and certain clinical parameters, such as age, serum triglyceride levels, the National Institutes of Health Stroke Scale (NIHSS) scores, and serum 4-HNE levels, were independent factors for the recurrence in patients. The results of the receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) value of serum 4-HNE in patients with cerebral infarction recurrence was 0.703, and when the cutoff value of serum 4-HNE was set at 42.34 ng/ml, the sensitivity and specificity values of serum 4-HNE in predicting recurrent cerebral infarction were 79.20 and 52.70%, respectively.ConclusionSerum 4-HNE is an independent risk factor for the recurrence of patients with primary cerebral infarction, and it may become a new intervention way to prevent the recurrence of patients with cerebral infarction.
Clinical features, radiological findings, and prognostic factors for primary intracranial chordoid meningioma
Authors: Jie Danyang , Liu Zhiyong , He Wenbo , Wang Shumin , Teng Haibo , Xu Jianguo 
Published: November 2022

ObjectivesChordoid meningioma (CM) is an infrequent histologic subtype of meningiomas. Owing to its low occurrence, this subtype has been rarely described. Our subject was to explore the clinical features, radiological characteristics, and prognostic factors of primary intracranial chordoid meningioma.MethodsWe reviewed the medical records and collected follow-up information of 34 cases who had been surgically treated and histologically diagnosed with CM at the Department of Neurosurgery, West-China Hospital of Sichuan University, from January 2009 to December 2021.ResultsAmong all 7,950 meningioma cases, the proportion of primary intracranial CM was 0.43% (34/7,950). The median diagnosis age was 47 (ranging from 12 to 74) and the gender ratio (male to female) was 2.1:1. For radiological features, heterogeneous enhancement, skull base, and ventricular localization, cystic degeneration and dural tail sign were common in CM cases. In treatment, gross total resection (GTR) was achieved in 22/34 cases (64.7%) and subtotal resection (STR) was achieved in 12/34 cases (35.3%). Further, 11/34 patients (32.4%) had received postoperative adjuvant radiotherapy (RT). The follow-up duration ranged from 4 to 157 months after operation. The progression rate was 20.7% (6/29) and the median of PFS was 38 months. By survival analysis, accepting adjuvant radiotherapy and achieving GTR were correlated with longer progression-free survival for prognosis.ConclusionCM is a rare subtype of meningiomas. In our series, it mainly involved adults and did not show a predilection for women compared with meningiomas in general. For a better prognosis, gross total resection and postoperative adjuvant radiotherapy are recommended. Nevertheless, due to the restriction of the series sample, patients lost for follow-up and inherent biases of a retrospective study, more cases and a shorter follow-up duration are needed for better management of chordoid meningioma.
Neuroform atlas stent-assisted coiling of tiny wide-necked intracranial aneurysms
Authors: Dong Linggen , Chen Xiheng , Wang Jiejun , Zhang Longhui , Zhao Zhiqiang , Peng Qichen , Liu Peng , Lv Ming 
Published: November 2022

ObjectiveTo investigate the safety and efficacy of Neuroform Atlas stent-assisted coiling for the treatment of tiny wide-necked intracranial aneurysms and evaluate risk factors associated with procedure-related complications.MethodsWe retrospectively examined 46 patients with 46 tiny wide-necked aneurysms who were treated using Atlas stent-assisted coiling at our institution from August 2020 to May 2022. Patient and aneurysm characteristics, procedural details, procedure-related complications, and angiographic and clinical outcomes were analyzed.ResultsA total of 10 patients presented with aneurysmal rupture. Atlas stent placement was successful in all patients. Angiography immediately after the procedure showed complete occlusion in 38 patients (82.6%), neck remnant in 7 (15.2%), and partial occlusion in 1 (2.2%). The mean angiographic follow-up was 8.4 months (range, 6–16). At the last follow-up, angiography showed complete occlusion in 41 patients (89.1%) and neck remnant in 5 (10.9%). No aneurysm recurrence or in-stent stenosis occurred. Incidence of procedure-related complications was 10.8% (intraprocedural aneurysm rupture, two cases; acute thrombosis, two cases; and coil migration, one case); only one patient (2.2%) experienced procedural neurological morbidity. The mean clinical follow-up was 9.7 months. A favorable outcome was achieved in 45 patients (97.8%). In univariate logistic regression analysis, aneurysm size (odds ratio, 4.538; P = 0.045) was significantly associated with procedure-related complications. However, multivariate analysis found no independent risk factors.ConclusionAtlas stent-assisted coiling of tiny wide-necked intracranial aneurysms is feasible and effective. Outcomes and occlusion rates are favorable and morbidity is low. The complication rate may be higher in larger tiny aneurysms.
The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: Findings from the ND0612 clinical development program
Authors: LeWitt Peter A. , Stocchi Fabrizio , Arkadir David , Caraco Yoseph , Adar Liat , Perlstein Itay , Case Ryan , Giladi Nir 
Published: November 2022

BackgroundWhile treatment with levodopa remains the cornerstone of Parkinson's disease (PD) management, chronic oral therapy is often associated with the development of motor complications, that correlate to fluctuating levodopa plasma concentrations, limiting its clinical utility. Continuous infusion is considered to be the optimal delivery route for treating PD patients with motor fluctuations, but current infusion systems require invasive surgery. Subcutaneous infusion of (SC) levodopa has the potential to provide a better tolerated and more convenient route of continuous levodopa delivery. ND0612 is in development as a combination product providing continuous levodopa/carbidopa via a minimally invasive, subcutaneous delivery system for PD patients experiencing motor response fluctuations. We present pharmacokinetic results from a series of studies that analyzed plasma concentrations after SC levodopa delivery with ND0612 to inform the clinical development program.MethodsWe performed a series of six Phase I and II studies to characterize the pharmacokinetics of levodopa and carbidopa derived from ND0612 infusion with/without adjunct oral therapy of the same ingredients. These studies were conducted in healthy volunteers and in PD patients experiencing motor response fluctuations while on their current levodopa therapy regimen.ResultsTaken together, the results demonstrate dose-proportionality dependent on rate of subcutaneous levodopa infusion leading to stable and sustained plasma concentrations of levodopa. Subcutaneous infusion of ND0612 administered with oral levodopa/carbidopa maintained near-constant, therapeutic levodopa plasma concentrations, thereby avoiding the troughs in levodopa plasma concentrations that are associated with OFF time in PD. The data generated in this series of studies also confirmed that a levodopa/carbidopa dose ratio of 8:1 would be the most reasonable choice for ND0612 development.ConclusionsThis series of clinical pharmacokinetic studies have demonstrated that ND0612, administered continuously with a levodopa concentration of 60 mg/ml combined with carbidopa 7.5 mg/ml, and complemented with oral levodopa/carbidopa, is suitable for 24 h continuous administration in patients with PD. The stable plasma concentrations of levodopa achieved predict utility of ND0612 as a parenteral formulation for achieving clinically useful delivery of levodopa for PD patients.