bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibroblast Growth Factor 21 Levels Exhibit the Association With Renal Outcomes in Subjects With Type 2 Diabetes Mellitus
Authors: Chang Li-Hsin , Chu Chia-Huei , Huang Chin-Chou , Lin Liang-Yu 
Published: April 2022

BackgroundWhether microalbuminuria predicts renal outcomes in patients with type 2 diabetes mellitus (T2DM) is argued. Fibroblast growth factor 21 (FGF-21) levels were elevated by the pathogenic process of diabetic kidney disease. The purpose of the study was to evaluate the associations of FGF-21 and renal outcomes in subjects with T2DM.MethodsChinese patients with T2DM were enrolled and then observed prospectively, and FGF-21 levels at baseline were measured. The associations of FGF-21 levels and renal composite events, defined by a drop &gt; 30% of eGFR or worsening category of albuminuria, were evaluated using Cox analysis. The appropriate cut-off value of FGF-21 was mapped by the receiver operating characteristic (ROC) curve.ResultsAmong 312 subjects, higher FGF-21 levels were associated with higher risks of renal events in Cox analysis. The area under the curve of FGF-21 levels in the ROC curve was optimal (0.67, p &lt; 0.001), and the cut-off value of 1.40 pg/dl exhibited the best sensitivity (76.2%) and specificity (53.5%). The frequency of renal composite events was higher in subjects with FGF-21 ≥ 1.40 pg/dl than in others (30% vs. 10%, p&lt;0.001 by the log-rank test). The worse renal outcomes predicted by FGF-21 ≥ 1.40 pg/dl were confirmed using the adjustments of Cox sequential models (hazard ratio 2.28, 95% confidence interval 1.23–4.24, p=0.009) and consistent across subjects with different status of baseline characteristics and renal risks.ConclusionFGF-21 levels were proportional to the risks of renal events in broad- spectrum Chinese T2DM subjects, making it a potential biomarker to predict the renal outcomes of T2DM.
High Follicle-Stimulating Hormone Level Associated With Risk of Rheumatoid Arthritis and Disease Activity
Authors: Zhang Xianhui , Qiao Pengyan , Guo Qianyu , Liang Zixie , Pan Jie , Wu Fengping , Wang Xuexue , Zhang Liyun 
Published: April 2022

BackgroundThe prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity.MethodsIn total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups.ResultsLower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p&lt;0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008).ConclusionHigh FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA.
Low Level of Serum Immunoglobulin G Is Beneficial to Clinical Cure Obtained With Pegylated Interferon Therapy in Inactive Surface Antigen Carriers
Authors: Li Hong , Lin Xiao , Liu Lili , Qin Ling , Zheng Yanhong , Liu Xiaohui , Wei Xinhuan , Liang Shan , Liu Yali , Zhang Jing , Chen Xinyue , Cao Zhenhuan 
Published: April 2022

PurposeOur recent study showed a high rate of HBsAg clearance in inactive HBsAg carriers (IHCs) treated with pegylated IFN (PEG-IFN). To better understand the immune-mediated component of HBsAg clearance, this study investigated the role of serum immunoglobulin G (IgG) and its subclasses in predicting HBsAg clearance in IHCs with PEG-IFN therapy.MethodsIn this study, IHCs received PEG-IFN for 96 weeks. Subjects who achieved clearance of HBsAg were considered responders (R group), and those in whom HBsAg was not cleared were considered non-responders (NR group). The HBsAg, ALT, and serum lgG subtypes (lgG1, IgG2, IgG3, lgG4) were tested at baseline, and at 12 and 24 weeks of treatment. To evaluate the factors in predicting HBsAg clearance, univariate and multivariate logistic regression analyses were performed. The receiver operator characteristic curves and the area under the receiver operator characteristic curve (AUROC) were used to evaluate prognostic values.ResultsOur results showed that 39 cases obtained HBsAg clearance (group R), while 21 cases did not (group NR). There was no significant difference in age, ALT, and AST levels between the two groups. The serum levels of IgG1, lgG2, lgG3 and lgG4 at baseline, and at 12 and 24 weeks were significantly lower in IHC with HBsAg clearance than in the NR group. Univariate logistic regression analysis showed that serum IgG1, IgG2, IgG3, and IgG4 levels at baseline, and at 12, and 24 weeks were all strong predictors of HBsAg clearance. In all indicators, lgG2 had the highest AUROC at baseline and lgG3 the highest AUROC at week 12. A multifactor logistic analysis was performed with y=33.933-0.001*BaselinelgG1-0.002*BaselinelgG2. The area under the curve was 0.941 with 100% sensitivity and 76.19% specificity.ConclusionTogether, our findings suggest that serum IgG has a higher predictive value compared to the convention predictors of HBsAg and ALT for HBsAg clearance and thus may be a better clinical predictor of HBsAg clearance in IHCs.
Comorbidities in the UK Primary Sjögren’s Syndrome Registry
Authors: Tarn Jessica , Lendrem Dennis , Barnes Michael , Casement John , Ng Wan-Fai 
Published: April 2022

IntroductionPrimary Sjögren’s Syndrome (PSS) is a chronic disease characterised by symptoms of oral and ocular dryness, pain, fatigue, anxiety and depression. PSS patients can be subclassified by the pattern of severity of these five key symptoms using the Newcastle Sjögren’s Stratification Tool (NSST). Although PSS is often associated with one or more comorbidities, the relationship between comorbidities, polypharmacy, and PSS symptom burden is unclear. Using data from the UK Primary Sjögren’s Syndrome Registry (UKPSSR) we describe the landscape of polypharmacy and comorbidities in PSS.MethodsThe UKPSSR is research biobank of clinically well-defined PSS patients where clinical, demographic, comorbidities and concomitant medications data are recorded. Patients were subclassified into the four NSST subgroups: Low Symptom Burden (LSB), High Symptom Burden (HSB), Dryness Dominated Fatigue (DDF) and Pain Dominated Fatigue (PDF). Group analyses of comorbid conditions and polypharmacy scores were performed. Comorbidity and Polypharmacy Scores (CPS) were modelled as a function of age, sex, symptom duration, body mass index (BMI), current immunosuppressant and hydroxychloroquine prescriptions and NSST subgroup.ResultsThere were marked differences in the number and the nature of comorbidities associated with the NSST subgroups. LSB and DDF patients were characterized by fewer comorbidities and medications. In contrast, HSB and PDF patients were associated with more comorbidities and were more likely to be prescribed multiple medications. Group analysis shows that HSB patients are more closely associated with peripheral vascular disease and infection whereas the PDF patients were associated with cardiovascular disease and gastrointestinal comorbidities. Comorbidity and polypharmacy scores increase with age and BMI regardless of symptom subgroup and symptom duration. In addition, the longer the reported symptom duration the higher the associated comorbidities and polypharmacy scores.ConclusionComorbid conditions are more prevalent in some subgroups of the PSS cohort but increase with age and BMI across the entire cohort. It is unclear from these data whether specific comorbid conditions are a consequence of PSS or represent shared aetiology or pathogenetic susceptibility. Regardless, these findings may have implications for disease management and clinical trial design.
Predicting Disease-Specific Survival for Patients With Primary Cholangiocarcinoma Undergoing Curative Resection by Using a Decision Tree Model
Authors: Quan Bing , Li Miao , Lu Shenxin , Li Jinghuan , Liu Wenfeng , Zhang Feng , Chen Rongxin , Ren Zhenggang , Yin Xin 
Published: April 2022

BackgroundThe aim of this study was to derive and validate a decision tree model to predict disease-specific survival after curative resection for primary cholangiocarcinoma (CCA).MethodTwenty-one clinical characteristics were collected from 482 patients after curative resection for primary CCA. A total of 289 patients were randomly allocated into a training cohort and 193 were randomly allocated into a validation cohort. We built three decision tree models based on 5, 12, and 21 variables, respectively. Area under curve (AUC), sensitivity, and specificity were used for comparison of the 0.5-, 1-, and 3-year decision tree models and regression models. AUC and decision curve analysis (DCA) were used to determine the predictive performances of the 0.5-, 1-, and 3-year decision tree models and AJCC TNM stage models.ResultsAccording to the fitting degree and the computational cost, the decision tree model derived from 12 variables displayed superior predictive efficacy to the other two models, with an accuracy of 0.938 in the training cohort and 0.751 in the validation cohort. Maximum tumor size, resection margin, lymph node status, histological differentiation, TB level, ALBI, AKP, AAPR, ALT, γ-GT, CA19-9, and Child-Pugh grade were involved in the model. The performances of 0.5-, 1-, and 3-year decision tree models were better than those of conventional models and AJCC TNM stage models.ConclusionWe developed a decision tree model to predict outcomes for CCA undergoing curative resection. The present decision tree model outperformed other clinical models, facilitating individual decision-making of adjuvant therapy after curative resection.
Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: A Meta-Analysis
Authors: Gómez-Llobell Marina , Peleteiro Raíndo Andrés , Climent Medina Jose , Gómez Centurión Ignacio , Mosquera Orgueira Adrián 
Published: April 2022

BackgroundExperience with immune checkpoint inhibitors (ICIs) in the treatment of acute myeloid leukemia (AML) is still limited and based on early clinical trials, with no reported randomized clinical data. In this study, we reviewed the available evidence on the use of ICIs, either in monotherapy or in combination with other treatments, in different AML settings, including newly diagnosed AML, relapsed or refractory (R/R) AML and maintenance treatment after allogeneic-HSCT (allo-HSCT).Materials and MethodsA systematic literature review was conducted using PubMed electronic database as primary source to identify the studies involving immune checkpoint inhibitors in first-line and R/R AML. We recorded Overall Response (ORR), Complete Response (CR) and Complete Response with incomplete count recovery (CRi) rates, overall survival (OS) and immune-related adverse events ≥ grade 3 (irAEs). Hereafter, we analyzed the overall profile of these ICIs by performing a meta-analysis of the reported outcomes.ResultsA total of 13 studies were identified where ICI was used in patients with AML. ORR across these studies was 42% (IC95%, 31% - 54%) and CR/CRi was 33% (IC95%, 22%-45%). Efficacy was also assessed considering the AML setting (first-line vs. relapsed/refractory) and results pointed to higher response rates in first-line, compared to R/R. Mean overall survival was 8.9 months [median 8 months, (IC95%, 3.9 - 15.5)]. Differences between first line and R/R settings were observed, since average overall survival in first line was 12.0 months, duplicating the OS in R/R which was 7.3 months. Additionally, the most specific adverse events (AEs) of these therapies are immune-related adverse events (irAEs), derived from their inflammatory effects. Grade ≥3 irAEs rate was low and similar among studies [12% (95%CI 8% - 16%)].ConclusionICIs in combination with intensive chemotherapy, hypomethylating agents or other targeted therapies are gaining interest in the management of hematological malignancies such as AML. However, results obtained from clinical trials are modest and limited by both, the type of design and the clinical trial phase. Hopefully, the prospective study of these therapies in late-stage development could help to identify patients who may benefit from ICI therapy.
Development of Diagnosis Model for Early Lung Nodules Based on a Seven Autoantibodies Panel and Imaging Features
Authors: Xu Leidi , Chang Ning , Yang Tingyi , Lang Yuxiang , Zhang Yong , Che Yinggang , Xi Hangtian , Zhang Weiqi , Song Qingtao , Zhou Ying , Yang Xuemin , Yang Juanli , Qu Shuoyao , Zhang Jian 
Published: April 2022

BackgroundThere is increasing incidence of pulmonary nodules due to the promotion and popularization of low-dose computed tomography (LDCT) screening for potential populations with suspected lung cancer. However, a high rate of false-positive and concern of radiation-related cancer risk of repeated CT scanning remains a major obstacle to its wide application. Here, we aimed to investigate the clinical value of a non-invasive and simple test, named the seven autoantibodies (7-AABs) assay (P53, PGP9.5, SOX2, GAGE7, GUB4-5, MAGEA1, and CAGE), in distinguishing malignant pulmonary diseases from benign ones in routine clinical practice, and construct a neural network diagnostic model with the development of machine learning methods.MethodA total of 933 patients with lung diseases and 744 with lung nodules were identified. The serum levels of the 7-AABs were tested by an enzyme-linked Immunosorbent assay (ELISA). The primary goal was to assess the sensitivity and specificity of the 7-AABs panel in the detection of lung cancer. ROC curves were used to estimate the diagnosis potential of the 7-AABs in different groups. Next, we constructed a machine learning model based on the 7-AABs and imaging features to evaluate the diagnostic efficacy in lung nodules.ResultsThe serum levels of all 7-AABs in the malignant lung diseases group were significantly higher than that in the benign group. The sensitivity and specificity of the 7-AABs panel test were 60.7% and 81.5% in the whole group, and 59.7% and 81.1% in cases with early lung nodules. Comparing to the 7-AABs panel test alone, the neural network model improved the AUC from 0.748 to 0.96 in patients with pulmonary nodules.ConclusionThe 7-AABs panel may be a promising method for early detection of lung cancer, and we constructed a new diagnostic model with better efficiency to distinguish malignant lung nodules from benign nodules which could be used in clinical practice.
Clinical Status and Outcome of Isolated Right Ventricular Hypoplasia: A Systematic Review and Pooled Analysis of Case Reports
Authors: Hirono Keiichi , Origasa Hideki , Tsuboi Kaori , Takarada Shinya , Oguri Masato , Okabe Mako , Miyao Nariaki , Nakaoka Hideyuki , Ibuki Keijiro , Ozawa Sayaka , Ichida Fukiko 
Published: April 2022

BackgroundIsolated right ventricular hypoplasia (IRVH), not associated with severe pulmonary or tricuspid valve malformation, is a rare congenital myocardial disease. This study aims to evaluate the clinical status and outcome of IRVH.MethodsA systematic search of keywords on IRVH was conducted. Studies were searched from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi (Ichushi) published between January 1950 and August 2021.ResultsThirty studies met the inclusion criteria. All of these studies were case reports and included 54 patients (25 males and 29 females). The median age of the patients was 2.5 years old (0–15.3 years). Of the 54 patients, 13 (24.1%) reported a family history of cardiomyopathy. Moreover, 50 (92.6%), 19 (35.2%), and 17 (31.5%) patients were diagnosed with cyanosis, finger clubbing, and dyspnea, respectively. Furthermore, 53 (98.2%) patients had a patent foramen ovale or an atrial septal defect (ASD). Z-score of the tricuspid valve diameter on echocardiogram was −2.16 ± 1.53, concomitant with small right ventricular end-diastolic volume. In addition, 29 (53.7%), 21 (38.9%), 7 (13.0%), and 2 (3.7%) patients underwent surgery, ASD closure, Glenn operation, and one and a half ventricular repair, respectively. Among them, nine (20.4%) patients expired, and the multivariable logistic regression analysis showed that infancy, heart failure, and higher right ventricular end-diastolic pressure were risk factors for death.ConclusionsIRVH was diagnosed early in children with cyanosis and was associated with high mortality. This systematic review and pooled analysis provided evidence to assess the of IRVH degree in order to evaluate the clinical status and outcome of IRVH.
Working Towards a Treat-to-Target Protocol in Juvenile Proliferative Lupus Nephritis – A Survey of Pediatric Rheumatologists and Nephrologists in Germany and Austria
Authors: Vollbach Kristina , Schuetz Catharina , Hedrich Christian M. , Speth Fabian , Mönkemöller Kirsten , Brunner Jürgen , Neudorf Ulrich , Rietschel Christoph , Hospach Anton , Kallinich Tilmann , Hinze Claas , Wagner Norbert , Tönshoff Burkhard , Weber Lutz T. , Latta Kay , Thumfart Julia , Bald Martin , Wiemann Dagobert , Zappel Hildegard , Tenbrock Klaus , Haffner Dieter 
Published: April 2022

BackgroundTo describe treatment practices for juvenile proliferative lupus nephritis (LN) class III and IV of pediatric rheumatologists and nephrologists in Germany and Austria in preparation for a treat-to-target treatment protocol in LN.MethodsSurvey study by members of the Society for Pediatric and Adolescent Rheumatology (GKJR) and the German Society for Pediatric Nephrology (GPN) on diagnostics and (concomitant) therapy of LN.ResultsFifty-eight physicians completed the survey. Overall, there was a considerable heterogeneity regarding the suggested diagnostics and management of juvenile proliferative LN. Increased urinary protein excretion, either assessed by 24 h urine collection or spot urine (protein-creatinine ratio), and reduced estimated glomerular filtration rate were specified as important parameters for indication of kidney biopsy to diagnose proliferative LN and monitoring of therapy. Corticosteroids were generally proposed for induction and maintenance therapy, most often in conjunction with either mycophenolate mofetil (MMF) or cyclophosphamide (CP) as steroid-sparing immunosuppressants. MMF was clearly preferred over CP for induction therapy of LN class III, whereas CP and MMF were equally proposed for LN class IV. MMF was most often recommended for maintenance therapy in conjunction with oral corticosteroids and continued for at least 3 years and 1 year, respectively, after remission. Hydroxychloroquine was widely accepted as a concomitant measure followed by renin-angiotensin system inhibitors in cases of arterial hypertension and/or proteinuria.ConclusionThe majority of pediatric rheumatologists and nephrologists in Germany and Austria propose the use of corticosteroids, most often in combination with either MMF or CP, for treatment of proliferative LN in children. The considerable heterogeneity of responses supports the need for a treat-to-target protocol for juvenile proliferative LN between pediatric rheumatologists and nephrologists.
Study on the Characteristics of Small-Molecule Kinase Inhibitors-Related Drug-Induced Liver Injury
Authors: Dong Huiqun , You Jia , Zhao Yu , Zheng Danhua , Zhong Yi , Li Gaozheng , Weng Zuquan , Luo Heng , Jiang Shan 
Published: April 2022

Background and Aim: More than half of the small-molecule kinase inhibitors (KIs) induced liver injury clinically. Meanwhile, studies have shown a close relationship between mitochondrial damage and drug-induced liver injury (DILI). We aimed to study KIs and the binding between drugs and mitochondrial proteins to find factors related to DILI occurrence.Methods: A total of 1,223 oral FDA-approved drugs were collected and analyzed, including 44 KIs. Fisher’s exact test was used to analyze DILI potential and risk of different factors. A total of 187 human mitochondrial proteins were further collected, and high-throughput molecular docking was performed between human mitochondrial proteins and drugs in the data set. The molecular dynamics simulation was used to optimize and evaluate the dynamic binding behavior of the selected mitochondrial protein/KI complexes.Results: The possibility of KIs to produce DILI is much higher than that of other types (OR = 46.89, p = 9.28E-13). A few DILI risk factors were identified, including molecular weight (MW) between 400 and 600, the defined daily dose (DDD) ≥ 100 mg/day, the octanol–water partition coefficient (LogP) ≥ 3, and the degree of liver metabolism (LM) more than 50%. Drugs that met this combination of rules were found to have a higher DILI risk than controls (OR = 8.28, p = 4.82E-05) and were more likely to cause severe DILI (OR = 8.26, p = 5.06E-04). The docking results showed that KIs had a significant higher affinity with human mitochondrial proteins (p = 4.19E-11) than other drug types. Furthermore, the five proteins with the lowest docking score were selected for molecular dynamics simulation, and the smallest fluctuation of the backbone RMSD curve was found in the protein 5FS8/KI complexes, which indicated the best stability of the protein 5FS8 bound to KIs.Conclusions: KIs were found to have the highest odds ratio of causing DILI. MW was significantly related to the production of DILI, and the average docking scores of KI drugs were found to be significantly different from other classes. Further analysis identified the top binding mitochondrial proteins for KIs, and specific binding sites were analyzed. The optimization of molecular docking results by molecular dynamics simulation may contribute to further studying the mechanism of DILI.
Case Report: Psychoacoustic Analysis of a Clarinet Performance With a Custom-Made Soft Lip Shield Worn to Prevent Mucosal Erosion of Lower Lip
Authors: Tanabe Gen , Hattori Mariko , Obata Satoshi , Takahashi Yuumi , Churei Hiroshi , Nishiyama Akira , Ueno Toshiaki , Sumita Yuka I. 
Published: April 2022

IntroductionWind instrument players sometimes suffer from erosion of the mucous membrane of the lip. This is caused by the action and pressure of the mouthpiece of the wind instrument against teeth. To address this problem, a lip shield is fitted over the dental arch to prevent direct contact between the lips and teeth. However, there are a few studies on the influence of the lip shield on the acoustics of wind instruments. The purpose of this study was to analyze the psychoacoustics of a clarinet performance with the player wearing a custom-made soft lip shield to prevent mucosal erosion of the lower lip.Case DescriptionA lip shield was custom-made with a soft thermoplastic material for a female clarinetist who complained of mucosal erosion and pain of the lower lip. The psychoacoustics of her musical performance played in different dynamics, fortissimo, mezzo forte and pianissimo were analyzed, including loudness and sharpness. A self-evaluation questionnaire with items rated on a 10-point scale was administered. After wearing the lip shield, the patient reported that the mucosal erosion and pain of her lower lip when playing clarinet resolved. The lip shield had little effect on the loudness. There was a slight decrease in sharpness when the lip shield was worn compared to when it was not, describing the reduction of high frequencies. Furthermore, fewer variations in sharpness between the tones were observed.ConclusionThe results suggest that lip shields made of soft materials can eliminate mucosal erosion and pain of the lower lip while having little effect on performance, although, a slight change in timbre is possible.