bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hubungan Lama Penggunaan Kontrasepsi Hormonal terhadap Skor Inner Scan Body Composition Monitor pada Wanita Usia Subur
Authors: Saleng Hasriani , Rahayu Eryanti K  , Sudirman Jumrah 
Published: December 2021

Osteoporosis merupakan masalah kesehatan dunia dimana saat ini diderita oleh kelompok usia yang lebih muda. Kepadatan mineral tulang merupakan salah satu jenis parameter dalam mengukur status osteoporosis. Semakin rendah kepadatan mineral tulang maka semakin besar risiko osteoporosis. Salah satu faktor risiko rendahnya kepadatan mineral tulang adalah jenis dan lama penggunaan kontrasepsi hormonal. Penelitian ini bertujuan untuk mengetahui hubungan penggunaan kontrasepsi hormonal dengan skor Inner Scan Body Composition Monitor dalam kepadatan tulang wanita usia subur. Metode penelitian yang digunakan adalah kuantitatif dengan desain cross sectional study, sampel penelitian 46 akseptor dengan teknik sampling yaitu Purposive sampling. Analisis data menggunakan Mann Whitney. Hasil penelitian didapatkanhasil untuk Skor Inner Scan Body Composition Monitor pada akseptor baru dengan nilai mean±SD yaitu 2.1429 ± 0.45779 dan nilai min-max adalah 1.40 – 3.00. Sementara pada akseptor lama dengan nilai mean±SD yaitu 2.3840 ± 0.38479 dan nilai min-max adalah 1.50 - 3.20. Pada analisis Bivariat didapatkannilai p= 0.086> 0,05, hal ini menunjukkan tidak Ada hubungan antara lama penggunaan kontrasepsi hormonal dengan skor inner scan bodyatau kepadatan tulang pada akseptor kontrasepsi hormonal. Kesimpulan, lama penggunaan kontrasepsi hormonal tidak mempengaruhi skor Inner Scan Body Composition Monitor pada kepadatan tulang akseptor di Wilayah Kota Makassar
Bamboo Shark as a Small Animal Model for Single Domain Antibody Production
Authors: Wei Likun , Wang Meiniang , Xiang Haitao , Jiang Yuan , Gong Jinhua , Su Dan , Al Azad M. A. R. , Dong Hongming , Feng Limin , Wu Jiajun , Chan Leo Lai , Yang Naibo , Shi Jiahai 
Published: December 2021

The development of shark single domain antibodies (sdAbs) is hindered by the high cost and tediousness of large-sized shark farming. Here, we demonstrated white-spotted bamboo sharks (Chiloscyllium plagiosum) being cultivated commercially as a promising small animal model to produce sdAbs. We found that immunoglobulin new antigen receptor (IgNAR) presented in bamboo shark genome, transcriptome, and plasma. Four complete IgNAR clusters including variable domains (vNARs) were discovered in the germline, and the Variable–Joining pair from IgNAR1 cluster was dominant from immune repertoires in blood. Bamboo sharks developed effective immune responses upon green fluorescent protein (GFP), near-infrared fluorescent protein iRFP713, and Freund’s adjuvant immunization revealed by elevated lymphocyte counts and antigen specific IgNAR. Before and after immunization, the complementarity determining region 3 (CDR3) of IgNAR were the major determinant of IgNAR diversity revealed by 400-bp deep sequencing. To prove that bamboo sharks could produce high-affinity IgNAR, we isolated anti-GFP and anti-iRFP713 vNARs with up to 0.3 and 3.8 nM affinities, respectively, from immunized sharks. Moreover, we constructed biparatopic vNARs with the highest known affinities (20.7 pM) to GFP and validated the functions of anti-GFP vNARs as intrabodies in mammalian cells. Taken together, our study will accelerate the discovery and development of bamboo shark sdAbs for biomedical industry at low cost and easy operation.
Vascular Access Site Complications Do Not Correlate With Large Sheath Diameter in TAVI Procedures With New Generation Devices
Authors: Gonska Birgid , Reuter Christopher , Mörike Johannes , Rottbauer Wolfgang , Buckert Dominik 
Published: December 2021

Background: Vascular complications after transfemoral transcatheter aortic valve implantation (TAVI) are associated with morbidity and mortality. However, consistent predictors have not been identified yet. The size of the implantation sheath seems to play a role, though especially with new generation TAVI devices and their improved sheaths and delivery systems this remains uncertain.Objectives: This study aimed to determine the incidence and predictors of access site-related vascular complications (VC) in the era of new generation TAVI devices.Methods and Results: Four hundred consecutive patients receiving TAVI in an experienced tertiary care center were analyzed. VC occurred in 89 patients (22.25%) with the majority being minor VC (21%) and only 1.25% major VC. Possible predictors for VC were tested, and only peri-interventional dual antiplatelet therapy (DAPT) showed to be predictive for VC [OR 2.11 (95% CI 1.10–4.06, p = 0.025)]. The female gender [OR 0.75 (95% CI 0.44–1.3), p = 0.31], sheath to femoral artery ratio &gt;1.05 [OR 1.18 (95% CI 0.66–2.08, p = 0.58)], calcification of the access site vessel [OR 0.83 (95% CI 0.48–1.42, p = 0.48)], known peripheral artery disease [OR 0.95 (95% CI 0.4–2.25, p = 0.9)], and BMI ≥ 25 kg/m2 [OR 0.69 (95% CI 0.41–1.19, p = 0–19)] were not predictive of VC. The larger sheath with 20 French even showed less VC than the smaller sheath with 16 French [OR 0.43 (95% CI 0.25–0.74, p = 0.002)].Conclusions: Overall, the rate of major and minor VC was low in this study population (for major VC: rate of 1.25%). Predefined risk factors were not associated with the occurrence of VC, except for peri-interventional treatment with DAPT. Especially, larger sheath size could not be identified as a predictor for VC in the setting of TAVI procedures performed with contemporary devices.
Established Tumour Biomarkers Predict Cardiovascular Events and Mortality in the General Population
Authors: Bracun Valentina , Suthahar Navin , Shi Canxia , de Wit Sanne , Meijers Wouter C. , Klip IJsbrand T. , de Boer Rudolf A. , Aboumsallem Joseph Pierre 
Published: December 2021

Introduction: Several lines of evidence reveal that cardiovascular disease (CVD) and cancer share similar common pathological milieus. The prevalence of the two diseases is growing as the population ages and the burden of shared risk factors increases. In this respect, we hypothesise that tumour biomarkers can be potential predictors of CVD outcomes in the general population.Methods: We measured six tumour biomarkers (AFP, CA125, CA15-3, CA19-9, CEA and CYFRA 21-1) and determined their predictive value for CVD in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. A total of 8,592 subjects were enrolled in the study.Results: The levels of CEA significantly predicted CV morbidity and mortality, with hazard ratios (HRs) of HR 1.28 (95% CI 1.08–1.53), respectively. Two biomarkers (CA15-3 and CEA) showed statistical significance in predicting all-cause mortality, with HRs 1.58 (95% CI 1.18–2.12) and HR 1.60 (95% CI 1.30–1.96), when adjusted for shared risk factors and prevalent CVD. Furthermore, biomarkers seem to be sex specific. CYFRA 21-1 presented as an independent predictor of CV morbidity and mortality in female, but not in male gender, with HR 1.82 (95% CI 1.40–2.35). When it comes to all-cause mortality, both CYFRA and CEA show statistical significance in male gender, with HR 1.64 (95% CI 1.28–3.12) and HR 1.55 (95% CI 1.18–2.02), while only CEA showed statistical significance in female gender, with HR 1.64 (95% CI 1.20–2.24). Lastly, CA15-3 and CEA strongly predicted CV mortality with HR 3.01 (95% CI 1.70–5.32) and HR 1.82 (95% CI 1.30–2.56). On another hand, CA 15-3 also presented as an independent predictor of heart failure (HF) with HR 1.67 (95% CI 1.15–2.42).Conclusion: Several tumour biomarkers demonstrated independent prognostic value for CV events and all-cause mortality in a large cohort from the general population. These findings support the notion that CVD and cancer are associated with similar pathological milieus.
A Novel Gene Prognostic Signature Based on Differential DNA Methylation in Breast Cancer
Authors: Zhu Chunmei , Zhang Shuyuan , Liu Di , Wang Qingqing , Yang Ningning , Zheng Zhewen , Wu Qiuji , Zhou Yunfeng 
Published: December 2021

Background: DNA methylation played essential roles in regulating gene expression. The impact of DNA methylation status on the occurrence and development of cancers has been well demonstrated. However, little is known about its prognostic role in breast cancer (BC).Materials: The Illumina Human Methylation450 array (450k array) data of BC was downloaded from the UCSC xena database. Transcriptomic data of BC was downloaded from the Cancer Genome Atlas (TCGA) database. Firstly, we used univariate and multivariate Cox regression analysis to screen out independent prognostic CpGs, and then we identified methylation-associated prognosis subgroups by consensus clustering. Next, a methylation prognostic model was developed using multivariate Cox analysis and was validated with the Illumina Human Methylation27 array (27k array) dataset of BC. We then screened out differentially expressed genes (DEGs) between methylation high-risk and low-risk groups and constructed a methylation-based gene prognostic signature. Further, we validated the gene signature with three subgroups of the TCGA-BRCA dataset and an external dataset GSE146558 from the Gene Expression Omnibus (GEO) database.Results: We established a methylation prognostic signature and a methylation-based gene prognostic signature, and there was a close positive correlation between them. The gene prognostic signature involved six genes: IRF2, KCNJ11, ZDHHC9, LRP11, PCMT1, and TMEM70. We verified their expression in mRNA and protein levels in BC. Both methylation and methylation-based gene prognostic signatures showed good prognostic stratification ability. The AUC values of 3-years, 5-years overall survival (OS) were 0.737, 0.744 in the methylation signature and 0.725, 0.715 in the gene signature, respectively. In the validation groups, high-risk patients were confirmed to have poorer OS. The AUC values of 3 years were 0.757, 0.735, 0.733 in the three subgroups of TCGA dataset and 0.635 in GSE146558 dataset.Conclusion: This study revealed the DNA methylation landscape and established promising methylation and methylation-based gene prognostic signatures that could serve as potential prognostic biomarkers and therapeutic targets.
Glycolysis Changes the Microenvironment and Therapeutic Response Under the Driver of Gene Mutation in Esophageal Adenocarcinoma
Authors: Zhu Lei , Yang Fugui , Li Xinrui , Li Qinchuan , Zhong Chunlong 
Published: December 2021

Background: Esophageal cancer is one of the most leading and lethal malignancies. Glycolysis and the tumor microenvironment (TME) are responsible for cancer progressions. We aimed to study the relationships between glycolysis, TME, and therapeutic response in esophageal adenocarcinoma (EAC).Materials and Methods: We used the ESTIMATE algorithm to divide EAC patients into ESTIMATE high and ESTIMATE low groups based on the gene expression data downloaded from TCGA. Weighted gene co-expression network analysis (WGCNA) and Gene Set Enrichment Analysis (GSEA) were performed to identify different glycolytic genes in the TME between the two groups. The prognostic gene signature for overall survival (OS) was established through Cox regression analysis. Impacts of glycolytic genes on immune cells were assessed and validated. Next, we conducted the glycolytic gene mutation analysis and drug therapeutic response analysis between the two groups. Finally, the GEO database was employed to validate the impact of glycolysis on TME in patients with EAC.Results: A total of 78 EAC patients with gene expression profiles and clinical information were included for analysis. Functional enrichment results showed that the genes between ESTIMATE high and ESTIMATE low groups (N = 39, respectively) were strongly related with glycolytic and ATP/ADP metabolic pathways. Patients in the low-risk group had probabilities to survive longer than those in the high-risk group (p &lt; 0.001). Glycolytic genes had significant impacts on the components of immune cells in TME, especially on the T-cells and dendritic cells. In the high-risk group, the most common mutant genes were TP53 and TTN, and the most frequent mutation type was missense mutation. Glycolysis significantly influenced drug sensitivity, and high tumor mutation burden (TMB) was associated with better immunotherapeutic response. GEO results confirmed that glycolysis had significant impacts on immune cell contents in TME.Conclusion: We performed a comprehensive study of glycolysis and TME and demonstrated that glycolysis could influence the microenvironment and drug therapeutic response in EAC. Evaluation of the glycolysis pattern could help identify the individualized therapeutic regime.
The Assessment of the Innovativeness of a New Medicine in Italy
Authors: Fortinguerra Filomena , Perna Serena , Marini Roberto , Dell'Utri Alessandra , Trapanese Maurizio , Trotta Francesco ,   Scientific & Technical Committee (Commissione Tecnico-Scientifica, CTS) of Italian Medicines Agency-AIFA
Published: December 2021

Objectives: Starting from April 2017, the Italian Medicine Agency (AIFA) has approved new criteria for defining any new medicinal product with an innovative indication. The purpose of the study is to analyze the activity of innovativeness evaluation according to the new approach, to estimate the weight of each criterion considered for innovativeness definition, and to evaluate how the new approach works in terms of consistency and reproducibility.Methods: A retrospective analysis was performed on the final reports evaluating the drug innovativeness assessment published on the AIFA's website between April 2017 and January 2021. Descriptive statistics, chi-square test, whether the conditions were respected, or Fisher's exact test was used to explore the association between characteristics of drugs and the innovativeness status and the association between the three criteria. Profiles of the decision process and their relationship with innovativeness response were described. In order to evaluate the weight of each criterion in predicting the innovativeness status, a Classification Tree (CT) algorithm was applied.Results: Overall, of the 109 published drugs reports, 37 (33.9%) were recognized as fully innovative, 29 (26.6%) were considered conditionally innovative, while for 43 (39.4%) reports innovativeness was not recognized. Considering the three criteria of the decision process, the added therapeutic value was the only criterion statistically associated with a drug's degree of innovation (p &lt; 0.001). The therapeutic need and the quality of clinical evidence were statistically associated (p = 0.008) even if only a mild association was observed. The added therapeutic value was the most important variable in predicting the innovativeness status according to the classification tree (CT) model applied, achieving an accuracy of 89.4%. No difference was found between orphans and non-orphan drugs or oncological and non-oncological drugs.Discussion: The added therapeutic value is the most important criterion of the multidimensional approach for the innovativeness status definition of a new medical product. A mild association was found between the therapeutic need and the quality of evidence. Overall, similar decision profiles bring the same evaluation of innovativeness status, indicating a good consistency and reproducibility between decisions.
Subcortical Volume Changes in Early Menopausal Women and Correlation With Neuropsychological Tests
Authors: Zhang Si , Fan Weijie , Hu Hao , Wen Li , Gong Mingfu , Liu Bo , Hu Junhao , Li Guanghui , Zhang Dong 
Published: December 2021

Background: The aging process and declining estradiol levels are two important factors that cause structural brain alterations. Many prior studies have investigated these two elements and revealed controversial results in menopausal women. Here, a cross-sectional study was designed to individually evaluate estradiol-related structural changes in the brain.Methods: A total of 45 early menopausal women and 54 age-matched premenopausal controls were enrolled and subjected to magnetic resonance imaging (MRI) scans, blood biochemistry tests, and neuropsychological tests. MRI structural images were analyzed using FreeSurfer to detect changes in subcortical and cortical volumes as well as cortical thickness. Finally, structural brain data as well as clinical and neuropsychological data were used for Pearson’s correlation analyses to individually determine estradiol-related structural and functional changes in the brains of early menopausal women.Results: Compared with the premenopausal controls, the early menopausal women showed significant subcortical volumetric loss in the left amygdala and right amygdala, higher serum follicle-stimulating hormone (FSH) levels, more recognizable climacteric and depressive symptoms, decreased quality of sleep, and decreased working memory and executive functions. Simultaneously, FSH levels were related to lower working memory accuracy and longer working memory reaction time. Decreased subcortical volume in the bilateral amygdala was also related to lower working memory accuracy and longer executive reaction time in early menopausal women.Conclusion: The data suggest that estradiol deficiency in early menopausal women can lead to subcortical volume and functional brain changes, which may contribute to further understanding the neurobiological role of declined estradiol levels in early menopausal women.
Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study
Authors: Lampignano Luisa , Donghia Rossella , Griseta Chiara , Lagravinese Gianvito , Sciarra Sabrina , Zupo Roberta , Castellana Fabio , Bortone Ilaria , Guerra Vito , Tirelli Sarah , De Nucci Sara , Tatoli Rossella , Lozupone Madia , Sborgia Giancarlo , Leo Antonio , De Pergola Giovanni , Giannelli Gianluigi , Panza Francesco , Sardone Rodolfo 
Published: December 2021

Objectives: Non-alcoholic fatty liver disease (NAFLD) currently affects a quarter of the global population. Systemic inflammation, metabolic syndrome, and coronary artery disease, all conditions associated with NAFLD, have also been related to cognitive dysfunction in older age. The present study aimed to investigate the relationship between NAFLD risk and a dementia diagnosis in a large population-based sample aged &gt; 65 years.Methods: We selected 1,542 participants (723 men) from the Salus in Apulia Study. To assess the risk of fat distribution in the liver, we used the Fatty Liver Index (FLI). Dementia was diagnosed according to the American Psychiatric Association criteria (DSM-5).Results: The overall prevalence of dementia was 8.5% [95% confidence interval (CI): 7–10%]. Subjects with dementia were older [effect size (ES): −0.89, 95% CI: −1.07 to −0.70], had a lower level of education (ES:0.88, 95% CI:0.69–1.06), higher levels of gamma-glutamyl transferase (ES: −0.21, 95% CI: −0.39 to −0.03), lower levels of total cholesterol (ES: −0.24, 95% CI: −0.42 to −0.06) and low-density lipoprotein cholesterol (ES: −0.20, 95% CI: −0.38 to 0.02), and a higher FLI (ES: −0.22, 95% CI: −0.39 to −0.04). In the logistic regression model adjusted for age, sex, education, hypertension, diabetes mellitus, alcohol consumption, smoking habits, stroke, cholesterol, and Apo-E, a dementia diagnosis was positively associated with FLI &gt; 60 [odds ratio (OR):1.81; standard error (SE): 0.53; 95% CI: 1.02–3.21].Conclusion: Our findings suggested that an increased NAFLD risk may be associated to dementia and cognitive decline in older age. Considering the high NAFLD prevalence, the possible adverse disease effects on cognitive performance pose a health problem with significant social and economic implications.
Standard-Dose Atorvastatin Treatment in Patients With Symptomatic Middle Cerebral Artery Atherosclerotic Stenosis: A Vessel Wall Magnetic Resonance Imaging Study
Authors: Wu Yejun , Li Fangbing , Wang Yilin , Hu Tianxiang , Gao Honghua 
Published: December 2021

Background and Purpose: Ischemic stroke can be caused by atherosclerotic lesions of the middle cerebral artery (MCA). Some studies have described the effects of statin treatment on carotid artery plaques, but little is known about the effects of statin treatment on MCA plaques. The purpose of this study was to validate the efficacy of standard-dose atorvastatin (20 mg/day) in patients with symptomatic MCA atherosclerotic stenosis (SMAS) in northern China.Materials and Methods: This study is a prospective, single-arm, single-center, 12-month follow-up observational study monitoring imaging, and clinical outcomes of standard-dose atorvastatin treatment among patients with SMAS. The primary outcomes were changes in vessel wall magnetic resonance imaging (VWMRI) and serum lipid profiles before and after (1, 3, 6, and 12 months) statin treatment.Results: A total of 46 patients were recruited for this study, and 24 patients completed the follow-up. During the follow-up period, serum non-high-density lipoprotein cholesterol concentrations gradually decreased in the patients. Fourteen patients (54.33%) had a reversal of MCA plaques and 10 patients (41.67%) had no significant progression of MCA plaques and remained stable at the follow-up endpoint. At the 12 months follow-up time-point, the treatment did not reverse vascular remodeling or change the shape and distribution of plaques. Altered serum low-density lipoprotein cholesterol (LDL-C) concentrations in patients were strongly associated with plaque reversal.Conclusion: Vessel wall magnetic resonance imaging could accurately characterize changes in MCA plaques after lipid-lowering therapy. Standard-dose atorvastatin treatment could stabilize and reverse plaques in northern Chinese patients with SMAS.
Accelerated Long-Term Hearing Loss Progression After Recovery From Idiopathic Sudden Sensorineural Hearing Loss
Authors: Early Samuel , van der Valk Jens C. , Frijns Johan H. M. , Stankovic Konstantina M. 
Published: December 2021

Background and Introduction: Idiopathic sudden sensorineural hearing loss (ISSNHL) is characterized by rapid onset, typically unilateral presentation, and variable recovery. This case-control observational study aimed to improve patient counseling by objectively characterizing long-term hearing loss progression following ISSNHL, using sequential audiometry in the largest-to-date cohort of patients with ISSNHL.Methods: Patients diagnosed with ISSNHL at a tertiary referral hospital from 1994 through 2018 with sequential audiometry were studied. Case controls with sensorineural hearing loss (SNHL) were matched by age, sex, baseline hearing status, and frequency of sequential audiometry. Hearing loss progression was quantified using Kaplan–Meier (K–M) analysis to account for variable follow-up duration. A subgroup analysis was performed by age, sex, preexisting comorbidities, ISSNHL-associated symptoms, ISSNHL treatment, and degree of post-ISSNHL hearing recovery.Results: A total of 660 patients were identified with ISSNHL. In patients with post-ISSNHL recovery to good hearing [pure tone average (PTA) &lt;30 dB and word recognition score (WRS) &gt; 70%], median time to progression to non-serviceable (PTA &gt; 50 dB or WRS &lt;50%) SNHL was 16.4 years. In patients with incomplete post-ISSNHL hearing recovery, contralateral ears were also at significantly higher risk of SNHL progression over the following 12-year period. Male sex was associated with increased risk of SNHL progression [odds ratio (OR) 3.45 male vs. female] at 5-year follow up. No other subgroup factors influenced the likelihood of SNHL progression.Discussion and Conclusion: Patients should be counseled on continued risk to long-term hearing after stabilization of hearing post-ISSNHL, with particular emphasis on greater risk to the contralateral ear in those with incomplete ipsilateral recovery.