bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study
Authors: Otomo Nao , Khanshour Anas M. , Koido Masaru , Takeda Kazuki , Momozawa Yukihide , Kubo Michiaki , Kamatani Yoichiro , Herring John A. , Ogura Yoji , Takahashi Yohei , Minami Shohei , Uno Koki , Kawakami Noriaki , Ito Manabu , Sato Tatsuya , Watanabe Kei , Kaito Takashi , Yanagida Haruhisa , Taneichi Hiroshi , Harimaya Katsumi , Taniguchi Yuki , Shigematsu Hideki , Iida Takahiro , Demura Satoru , Sugawara Ryo , Fujita Nobuyuki , Yagi Mitsuru , Okada Eijiro , Hosogane Naobumi , Kono Katsuki , Nakamura Masaya , Chiba Kazuhiro , Kotani Toshiaki , Sakuma Tsuyoshi , Akazawa Tsutomu , Suzuki Teppei , Nishida Kotaro , Kakutani Kenichiro , Tsuji Taichi , Sudo Hideki , Iwata Akira , Inami Satoshi , Wise Carol A. , Kochi Yuta , Matsumoto Morio , Ikegawa Shiro , Watanabe Kota , Terao Chikashi 
Published: June 2023

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.
Total serum FGF-21 levels positively relate to visceral adiposity differently from its functional intact form
Authors: Crudele Lucilla , Garcia-Irigoyen Oihane , Cariello Marica , Piglionica Marilidia , Scialpi Natasha , Florio Marilina , Piazzolla Giuseppina , Suppressa Patrizia , Sabbà Carlo , Gadaleta Raffaella Maria , Moschetta Antonio 
Published: June 2023

ObjectiveIncreased Fibroblast Growth Factor-21 (FGF-21) circulating levels have been described in obesity. In this observational study, we analysed a group of subjects with metabolic disorders to unravel the putative link between visceral adiposity and FGF-21 serum levels.MethodsTotal and intact serum FGF-21 concentration was measured with an ELISA assay respectively in 51 and 46 subjects, comparing FGF-21 levels in dysmetabolic conditions. We also tested Spearman’s correlations between FGF-21 serum levels and biochemical and clinical metabolic parameters.ResultsFGF-21 was not significantly increased in high-risk conditions such as visceral obesity, Metabolic Syndrome, diabetes, smoking, and atherosclerosis. Waist Circumference (WC), but not BMI, positively correlated with total FGF-21 levels (r=0.31, p &lt;0.05), while HDL-cholesterol (r=-0.29, p &lt;0.05) and 25-OH Vitamin D (r=-0.32, p &lt;0.05) showed a significant negative correlation with total FGF-21. ROC analysis of FGF-21 in prediction of increased WC, showed that patients with total FGF-21 level over cut-off value of 161.47 pg/mL presented with impaired FPG. Conversely, serum levels of the intact form of FGF-21 did not correlate with WC and other metabolic biomarkers.ConclusionOur newly calculated cut-off for total FGF-21 according to visceral adiposity identified subjects with fasting hyperglycemia. However, waist circumference correlates with total FGF-21 serum levels but does not correlate with intact FGF-21, suggesting that functional FGF-21 does not necessarily relate with obesity and metabolic features.
Azathioprine as an adjuvant therapy in severe Graves’ disease: a randomized controlled open-label clinical trial
Authors: Allam Magdy Mohamed , El-Zawawy Hanaa Tarek , Kader Okda Amr Abdel , Ali Alshaikh Ayoub , Ghazy Ramy Mohamed 
Published: June 2023

IntroductionAzathioprine (AZA) interferes with the activation of T and B lymphocytes, which are the main cells involved in the pathogenesis of Graves’ disease (GD). The aim of this study was to investigate the effectiveness of AZA as an adjuvant therapy to antithyroid drugs (ATDs) for moderate and severe GD. In addition, we conducted an incremental cost-effectiveness analysis of AZA to determine its cost-effectiveness.MethodsWe conducted a randomized, open-label, and parallel-group clinical trial. We randomized untreated hyperthyroid patients with severe GD into three groups. All patients received 45-mg carbimazole (CM) as the starting dose and propranolol 40–120 mg daily. The first group (AZA1) received an additional 1 mg/kg/day AZA, the second group (AZA2) received an additional 2 mg/kg/day AZA, and the third group (control group) received only CM and propranolol. We measured thyroid-stimulating hormone (TSH) and TSH-receptor antibody (TRAb) levels at baseline and every 3 months, while free triiodothyronine (FT3) and free thyroxine (FT4) levels were measured at the time of diagnosis, 1 month after initiation of therapy, and every 3 months thereafter until 2 years after remission. Thyroid volume (TV) was assessed by ultrasound at baseline and 1 year after remission.ResultsA total of 270 patients were included in this trial. By the end of follow-up, there was higher remission rate in the AZA1 and AZA2 groups compared with controls (87.5% and 87.5% vs. 33.4%, p = 0.002). Throughout the course of follow-up, FT3, FT4, TSH, and TRAb were significantly different between the AZA groups and the control group, but there was no significant difference regarding TV. The decline in the concentrations of FT4, FT3, and TRAb was significantly faster in the AZA2 group than in the AZA1 group. The relapse rate during the 12-month follow-up was insignificantly higher in the control group than in either the AZA1 or AZA2 group (10, 4.4, and 4.4%, p = 0.05, respectively). The median relapse time was 18 months for the control group and 24 months for the AZA1 and AZA2 groups. The incremental cost-effectiveness ratio for the AZA group compared with the conventional group was 27,220.4 Egyptian pounds per remission reduction for patients using AZA as an adjuvant for ATDs.ConclusionAZA could be a novel, affordable, cost-effective, and safe drug offering hope for patients with GD to achieve early and long-lasting medical remission.Trial registryThe trial is registered at the Pan African Clinical Trial Registry (Registration number: PACTR201912487382180).
Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of responders
Authors: Sordi Valeria , Monti Paolo , Lampasona Vito , Melzi Raffaella , Pellegrini Silvia , Keymeulen Bart , Gillard Pieter , Linn Thomas , Bosi Emanuele , Rose Ludger , Pozzilli Paolo , Giorgino Francesco , Cossu Efisio , Piemonti Lorenzo 
Published: June 2023

AimIn a recent randomized, multicenter trial (NCT02814838) a short-term anti-inflammatory treatment with ladarixin (LDX; an inhibitor of the CXCR1/2 chemokine receptors) did not show benefit on preserving residual beta cell function in new-onset type 1 diabetes. We present a post hoc analysis of trial patients in the predefined subgroup analysis developed according to baseline daily insulin requirement (DIR) tertiles.MethodA double-blind, randomized (2:1), placebo-controlled study was conducted in 45 men and 31 women (aged 18–46 years) within 100 days of the first insulin administration. Patients received LDX (400 mg twice daily) for three cycles of 14 days on/14 days off, or placebo. The primary endpoint was the area under the curve for C-peptide [AUC (0–120 min)] in response to a 2-h mixed meal tolerance test (MMTT) at week 13 ± 1. Seventy-five patients completed the week 13 MMTT and were divided into three groups according to the DIR tertiles: lower, ≤ 0.23U/kg/die (n = 25); middle, 0.24–0.40 U/kg/die (n = 24); upper, ≥ 0.41 U/kg/die (n = 26).ResultsWhen considering the patients in the upper tertile (HIGH-DIR), C-peptide AUC (0–120 min) at 13 weeks was higher in the LDX group (n = 16) than in the placebo (n = 10) group [difference: 0.72 nmol/L (95% CI 0.9–1.34), p = 0.027]. This difference reduced over time (0.71 nmol/L at 26 weeks, p = 0.04; 0.42 nmol/L at 52 weeks, p = 0.29), while it has never been significant at any time in patients in the lower and/or middle tertile (LOW-DIR). We characterized at baseline the HIGH-DIR and found that endo-metabolic (HOMA-B, adiponectin, and glucagon-to-C-peptide ratio) and immunologic (chemokine (C-C motif) ligand 2 (CCL2)/monocyte chemoattractant protein 1 (MCP1) and Vascular Endothelial Growth Factor (VEGF)) features distinguished this group from LOW-DIR.ConclusionWhile LDX did not prevent the progressive loss of beta-cell function in the majority of treated subjects, the post hoc analysis suggests that it could work in subjects with HIGH-DIR at baseline. As we found differences in endo-metabolic and immunologic parameters within this subgroup, this generates the hypothesis that the interactions between host factors and drug action can contribute to its efficacy. Further research is needed to evaluate this hypothesis.
m6A-related lncRNAs predict prognosis and indicate cell cycle in gastric cancer
Authors: Wan Dong , He Lingnan , Guo Cheng , Zhong Zishao , Yan Xiaohan , Cao Jia , Xu Qinwei , Zhang Haibin , Duan Bensong 
Published: June 2023

Background: N6-methyladenosine (m6A) modification is a common epigenetic methylation modification of RNA, which plays an important role in gastric carcinogenesis and progression by regulating long non-coding RNA (lncRNA). This study is aimed to investigate the potential prognostic signatures of m6A -related lncRNAs in STAD.Methods: The m6A-related lncRNAs with the most significant impact on gastric cancer prognosis in the TCGA database were identified by bioinformatics and machine learning methods. The m6A-related lncRNA prognostic model (m6A-LPS) and nomogram was constructed by Cox regression analysis with the minimum absolute contraction and selection operator (LASSO) algorithm. The functional enrichment analysis of m6A-related lncRNAs was also investigated. The miRTarBase, miRDB and TargetScan databases were utilized to establish a prognosis-related network of competing endogenous RNA (ceRNA) by bioinformatics methods. The correlation of AL391152.1 expressions and cell cycle were experimentally testified by qRT-PCR and flow cytometry.Results: In total, 697 lncRNAs that were identified as m6A-related lncRNAs in GC samples. The survival analysis showed that 18 lncRNAs demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of GC patients. Cox regression analysis and ROC curve indicated that this lncRNA prediction model was an independent risk factor for survival rates. Functional enrichment analysis and ceRNA network revealed that the nomogram was notably associated with cell cycle. qRT-PCR and flow cytometry revealed that downregulation of GC m6A-related lncRNA AL391152.1 could decrease cyclins expression in SGC7901 cells.Conclusion: A m6A-related lncRNAs prognostic model was established in this study, which can be applied to predict prognosis and cell cycle in gastric cancer.
Incidence, persistence, and clearance of anogenital human papillomavirus among men who have sex with men in Taiwan: a community cohort study
Authors: Zhou Xinyi , Tian Tian , Lu Zhen , Yu Yi-Fang , Li Yuwei , Zhou Yiguo , Lin Yi-Fan , Strong Carol , Zou Huachun 
Published: June 2023

BackgroundMen who have sex with men (MSM) have an increased risk of human papillomavirus (HPV) infection. This study aimed to assess the incidence, persistence, and clearance of anogenital HPV infections among MSM and the correlates in a 3-year community cohort study.MethodsFrom 2015 to 2019, MSM were recruited and followed up at 6, 12, 24, and 36 months in Taiwan. Questionnaires and anogenital swabs were collected at baseline and each follow-up visit. Thirty-seven HPV genotypes were tested and genotyped using the linear array HPV genotyping test. The incidence, persistence, and clearance rates of anogenital HPV infection and 95% confidence intervals (CIs) were estimated through Poisson regression. Correlates of the incidence and clearance rates were examined using a generalized estimating equations (GEE) model.ResultsA total of 201 MSM were retained in the cohort study with a median age of 27 years (interquartile range [IQR]: 24–32) at baseline. The incidence, persistence, and clearance rates of any anal HPV infection among MSM were 43.6 (95% CI: 33.7–55.6), 23.4 (17.7–30.2), and 58.3 (45.1–74.1) per 1,000 person months (pms), respectively. The incidence, persistence, and clearance rates of any penile HPV infection among MSM were 26.8 (20.1–34.9), 13.4 (8.0–20.9), and 51.5 (37.8–68.5) pms, respectively. MSM who did not consistently use a condom in receptive sex (adjusted odds ratio [AOR]: 2.06, 95% CIs: 1.14–3.72) were more likely to acquire any anal HPV infection. Age at recruitment (1.05, 1.01–1.09) was positively associated with any penile HPV incidence. MSM with over one sex partner in receptive anal sex (0.53, 0.30–0.94) were less likely to clear any anal HPV infection. MSM who were unemployed/students (0.55, 0.30–0.98) were less likely to clear any penile HPV infection.ConclusionHigh incidence and low clearance of anogenital HPV infection among MSM in the study serve as a reminder that this population needs to be targeted for HPV vaccination. It is essential for MSM to scale up HPV screening and adhere to safe sex.
Skin-infiltrating T cells display distinct inflammatory signatures in lichen planus, bullous pemphigoid and pemphigus vulgaris
Authors: Schinner Jona , Cunha Tomas , Mayer Johannes U. , Hörster Stefan , Kind Peter , Didona Dario , Keber Corinna , Hertl Michael , Worzfeld Thomas , Juratli Hazem A. 
Published: June 2023

IntroductionWe here thought to dissect the inflammatory signature in lesions of three skin disorders, which show a common adaptive immune response against autoantigens of the skin but are characterized by diverging clinical phenotypes. Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are type-2-dependent, IgG autoantibody-driven blistering disorders of mucous membranes and skin, which target desmoglein (Dsg)3 and bullous pemphigoid (BP)180, respectively. In contrast, lichen planus (LP) is a common chronic inflammatory disease of the skin and mucous membranes with a pronounced dermal T cell infiltrate. We previously identified peripheral type 1 and 17 T cell responses against Dsg3 and BP180 in a cohort of LP patients strongly suggesting that the underlying inflammatory T cell signature may drive the evolving phenotype.MethodsParaffin-embedded skin biopsies from well-characterized patients with LP (n=31), BP (n=19), PV (n=9), and pemphigus foliaceus (PF) (n=2) were analysed. Areas with the most prominent inflammatory infiltrate were excised with punch biopsies and tissue microarrays (TMA) containing multiple biopsies were created. Using multicolor immunofluorescence, the inflammatory infiltrate was stained with antibodies against multiple cellular markers, i. e. CD3ϵ, CD4, CD15, TCR-δ, the cytokine IL-17A, and the transcription factors, T-bet and GATA-3.ResultsIn LP, there was a higher number of CD4+ T cells expressing T-bet compared to GATA-3. In contrast, CD4+ T cells in PV and BP skin lesions more frequently expressed GATA-3 than T-bet. IL-17A+ cells and IL-17A+ T cells were found to a similar extent in all the three disorders. IL-17A+ granulocytes were more predominant in BP than in LP or PV. Of note, the majority of IL-17A+ cells in LP were neither T cells nor granulocytes.DiscussionOur findings in inflammatory skin infiltrates clearly show a predominant type 1 signature in LP in contrast to a preponderance of type 2 T cells in PV and BP. In contrast to LP, granulocytes and to a much lesser extent CD3+ T cells were a cellular source of IL-17A in BP and PV. These data strongly suggest that different inflammatory cell signatures drive evolving clinically diverse phenotypes of LP, PV and BP despite common target antigens of the skin.
Nano drug delivery platform based on thermosensitive PEG-PCL hydrogel encapsulated in silver-bearing micelles and its antifungal activity investigation against vaginal candidiasis
Authors: Hosseinzadeh Fatemeh , Tabesh Hadi , Farzaneh Farah 
Published: June 2023

Introduction: Vaginal candidiasis is a genital mucosal disease. Polymeric micelles (PMs) utilization due to improved solubility and low bioavailability of hydrophobic drugs e.g. clotrimazole is of interest. Silver nanoparticles could be applied to enhance antifungal properties. Loading PMs in injectable thermosensitive hydrogels by rapid distribution across vaginal walls improves the bioavailability of the drug and provides suitable therapeutic efficiency for drug delivery systems.Method: PCL-PEG-PCL (LGL) and PEG-PCL-PEG (GLG) copolymers were characterized by FTIR, HNMR, and GPC. Zeta potential and Size of synthesized PMs were determined by EMSA and DLS technics and morphological examination of PMs was conducted by FESEM and TEM. Silver-bearing polymeric micelles (PM-Ag) were characterized by DLS and LDE technics. EDX and UV-VIS spectroscopy confirmed silver nanoparticles' binding to PMs. Thermosensitive GLG hydrogel was considered a carrier for PM-Ag.Results: Encapsulation efficiency and drug loading content of micelles were calculated 64.53% and 14.6% respectively. The diameter and zeta potential of PMs were measured 166 ± 1.73 nm±SD and −6.26 ± 0.3 mV±SD and after silver-bearing it reached 197 ± 2.29 nm±SD and −5.38 ± 0.45 mV±SD respectively.Discussion: The biocompatibility of samples was investigated by MTT assay and the results indicated that up to a concentration of 125 µg/mL, the relative cell viability percentage exceeded 80%. Therefore, by considering the acceptable antifungal activity of the samples against C. Albicans, the designed drug delivery system is capable of sustained drug release over a specified period.
In vitro activities of antimicrobial combinations against planktonic and biofilm forms of Stenotrophomonas maltophilia
Authors: Su Bo-An , Chen Chi-Chung , Chen Hung-Jui , Lai Hsin-Yu , Tsai Chia-Hung , Lai Chih-Cheng , Tang Hung-Jen , Chao Chien-Ming 
Published: June 2023

ObjectivesTo investigate the in vitro activity of antibiotic combinations against Stenotrophomonas maltophilia isolates and their associated biofilms.MethodsThirty-two S. maltophilia clinical isolates with at least twenty-five different pulsotypes were tested. The antibacterial activity of various antibiotic combinations against seven randomly selected planktonic and biofilm-embedded S. maltophilia strains with strong biofilm formation was assessed using broth methods. Extraction of bacterial genomic DNA and PCR detection of antibiotic resistance and biofilm-related genes were also performed.ResultsThe susceptibility rates of levofloxacin (LVX), fosfomycin (FOS), tigecycline (TGC) and sulfamethoxazole-trimethoprim (SXT) against 32 S. maltophilia isolates were 56.3, 71.9, 71.9 and 90.6%, respectively. Twenty-eight isolates were detected with strong biofilm formation. Antibiotic combinations, including aztreonam-clavulanic (ATM-CLA) with LVX, ceftazidime-avibactam (CZA) with LVX and SXT with TGC, exhibited potent inhibitory activity against these isolates with strong biofilm formation. The antibiotic resistance phenotype might not be fully caused by the common antibiotic-resistance or biofilm-formation gene.ConclusionS. maltophilia remained resistant to most antibiotics, including LVX and β-lactam/β-lactamases; however, TGC, FOS and SXT still exhibited potent activity. Although all tested S. maltophilia isolates exhibited moderate-to-strong biofilm formation, combination therapies, especially ATM-CLA with LVX, CZA with LVX and SXT with TGC, exhibited a higher inhibitory activity for these isolates.
Association between delirium and statin use in patients with congestive heart failure: a retrospective propensity score-weighted analysis
Authors: Xia Jiangling , Wang Leilei , Zhang Nannan , Xu Hongyu 
Published: June 2023

BackgroundThe relationship between statin use and delirium remains controversial; therefore, we aimed to study the association between statin exposure and delirium and in-hospital mortality in patients with congestive heart failure.MethodsIn this retrospective study, patients with congestive heart failure were identified from the Medical Information Mart for Intensive Care database. The primary exposure variable was statin use 3 days after admission to the intensive care unit, and the primary outcome measure was the presence of delirium. The secondary outcome measure was in-hospital mortality. Since the cohort study was retrospective, we used inverse probability weighting derived from the propensity score to balance various variables.ResultsOf 8,396 patients, 5,446 (65%) were statin users. Before matching, the prevalence of delirium was 12.5% and that of in-hospital mortality was 11.8% in patients with congestive heart failure. Statin use was significantly negatively correlated with delirium, with an odds ratio of 0.76 (95% confidence interval: [0.66–0.87]; P &lt; 0.001) in the inverse probability weighting cohort and in-hospital mortality of 0.66 (95% confidence interval: [0.58–0.75]; P &lt; 0.001).ConclusionStatins administered in the intensive care unit can significantly reduce the incidence of delirium and in-hospital mortality in patients with congestive heart failure.