bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vici syndrome in Israel: Clinical and molecular insights
Authors: Chorin Odelia , Hirsch Yoel , Rock Rachel , Salzer Sheelo Liat , Goldberg Yael , Mandel Hanna , Hershkovitz Tova , Fleischer Nicole , Greenbaum Lior , Katz Uriel , Barel Ortal , Hamed Nasrin , Ben-Zeev Bruria , Greenberger Shoshana , Nasser Samra Nadra , Stern Zimmer Michal , Raas-Rothschild Annick , Pode-Shakked Ben 
Published: September 2022

Introduction: Vici Syndrome is a rare, severe, neurodevelopmental/neurodegenerative disorder with multi-systemic manifestations presenting in infancy. It is mainly characterized by global developmental delay, seizures, agenesis of the corpus callosum, hair and skin hypopigmentation, bilateral cataract, and varying degrees of immunodeficiency, among other features. Vici Syndrome is caused by biallelic pathogenic variants in EPG5, resulting in impaired autophagy. Thus far, the condition has been reported in less than a hundred individuals.Objective and Methods: We aimed to characterize the clinical and molecular findings in individuals harboring biallelic EPG5 variants, recruited from four medical centers in Israel. Furthermore, we aimed to utilize a machine learning-based tool to assess facial features of Vici syndrome.Results: Eleven cases of Vici Syndrome from five unrelated families, one of which was diagnosed prenatally with subsequent termination of pregnancy, were recruited. A total of five disease causing variants were detected in EPG5: two novel: c.2554-5A&gt;G and c.1461delC; and 3 previously reported: c.3447G&gt;A, c.5993C&gt;G, and c.1007A&gt;G, the latter previously identified in several patients of Ashkenazi-Jewish (AJ) descent. Amongst 140,491 individuals screened by the Dor Yeshorim Program, we show that the c.1007A&gt;G variant has an overall carrier frequency of 0.45% (1 in 224) among AJ individuals. Finally, based on two-dimensional facial photographs of individuals with Vici syndrome (n = 19), a composite facial mask was created using the DeepGestalt algorithm, illustrating facial features typical of this disorder.Conclusion: We report on ten children and one fetus from five unrelated families, affected with Vici syndrome, and describe prenatal and postnatal characteristics. Our findings contribute to the current knowledge regarding the molecular basis and phenotypic features of this rare syndrome. Additionally, the deep learning-based facial gestalt adds to the clinician’s diagnostic toolbox and may aid in facilitating identification of affected individuals.
Bidirectional causal link between inflammatory bowel disease and celiac disease: A two-sample mendelian randomization analysis
Authors: A Gu , Sun Caixia , Shan Yuezhan , Husile Husile , Bai Haihua 
Published: September 2022

Background: Observational research has shown a correlation between inflammatory bowel disease (IBD) [comprising ulcerative colitis (UC) and Crohn’s disease (CD)] and celiac disease. However, the relationship between these two diseases remains uncertain.Methods: We utilized two-sample Mendelian randomization (MR) to estimate the bidirectional causal relationships between IBD and celiac disease. This study utilized data on single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWASs). Heterogeneity, pleiotropy, and sensitivity analyses were also performed to evaluate the MR results.Results: There was a significant causal relationship between IBD and CD and celiac disease (e.g., IBD and celiac disease, inverse variance weighting (IVW) odds ratio (OR) = 1.0828, 95% CI = 1.0258–1.1428, p = 0.0039; CD and celiac disease, IVW OR = 1.0807, 95% CI = 1.0227–1.1420, p = 0.0058). However, in the reverse direction, we found only suggestive positive causality between celiac disease and CD (e.g., IVW OR = 1.0366, 95% CI = 1.0031–1.0711, p = 0.0319). No evidence of heterogeneity between genetic variants was found (e.g., IBD vs. celiac disease, MR-Egger Q = 47.4391, p = 0.6159). Horizontal pleiotropy hardly influenced causality (e.g., IBD vs. celiac disease, MR-Egger test: p = 0.4340). Leave-one-out analysis showed that individual SNPs did not influence the general results.Conclusion: Our MR analysis revealed a positive causal link between IBD and celiac disease in the European population. In addition, several recommendations for disease prevention and clinical management have been discussed.
Regulation of lipid droplet (LD) formation in hepatocytes via regulation of SREBP1c by non-coding RNAs
Authors: El Sobky Shereen A. , Aboud Nourhan K. , El Assaly Nihal M. , Fawzy Injie O. , El-Ekiaby Nada , Abdelaziz Ahmed I. 
Published: September 2022

IntroductionIncreased de novo lipogenesis (DNL) is one of the key factors contributing to fat accumulation and non-alcoholic fatty liver disease (NAFLD). Among the critical transcription factors (TFs) regulating DNL is mTOR and its downstream lipogenic TF, SREBP1c. In recent years, it has been established that non-coding RNAs (ncRNAs) play role in both biological processes and disease pathogenesis. Our group has previously characterized microRNAs that can target and regulate the expression of both mTOR and SREBP1c. Accordingly, this study aimed to broaden our understanding of the role of ncRNAs in regulating the mTOR/SREBP1c axis to elucidate the role of the non-coding transcriptome in DNL and lipid droplet (LD) formation. Hence, short ncRNA, miR-615-5p, and long non-coding RNA (lncRNA), H19, were chosen as they were previously proven to target mTOR by our group and in the published literature, respectively.MethodologyHuh-7 cells were treated with 800 μM oleic acid (OA) to promote LD formation. Transfection of miR-615-5p mimics or H19 over-expression vectors was performed, followed by the measurement of their downstream targets, mTOR and SREBP, on the mRNA level by quantitative real-time PCR (qRT-PCR), and on the protein level by Western blot. To determine the functional impact of miR-615-5p and H19 on LD formation and triglyceride (TG) accumulation, post-transfection LDs were stained, imaged, and characterized, and TGs were extracted and quantified.ResultsmiR-615-5p was able to reduce mTOR and SREBP1c significantly on both the mRNA and protein levels compared to control cells, while H19 caused a reduction of both targets on the protein level only. Both miR-615-5p and H19 were able to significantly reduce the LD count and total area, as well as TG levels compared to control cells.ConclusionTo conclude, this study shows, for the first time, the impact of miR-615-5p and H19 on the mTOR/SREBP1c axis, and thus, their functional impact on LDs and TG accumulation. These findings might pave the way for using ncRNAs as potential therapeutic targets in the management of fatty liver.
Determining the center of a keratoconus: Comparison of different tomographic parameters and impact of disease severity
Authors: Steinwender Gernot , Kollenc Alexander , Shajari Mehdi , Sommer Michael , Borenich Andrea , Horwath-Winter Jutta , Lindner Ewald , Woltsche Nora , List Wolfgang , Wedrich Andreas 
Published: September 2022

PurposeThere exists remarkable variation in definitions for the location of the center of a keratoconus. The objective of this study was to analyze deviations between locations obtained by different tomographic maps for that purpose. Furthermore, it was investigated whether these deviations are influenced by disease severity.MethodsIn 162 eyes with keratoconus, corneal tomographic maps derived by Scheimpflug technology were retrospectively analyzed to determine the cone location with 5 different methods: maximum axial curvature of the front surface (Kmax), maximum tangential curvature of the front surface (tKmax), minimum pachymetry (Pachymin), maximum elevation of the front surface (ELEF), and maximum elevation of the back surface (ELEB). Distances between the locations were calculated and tested for a correlation with keratoconus severity and distance between cone and corneal vertex.ResultsCone locations derived from the curvature maps (Kmax, tKmax) showed the lowest agreement with the locations determined by pachymetry or elevation maps. The largest distances were found between Kmax and Pachymin [Median and Interquartile range: 1.19 mm (0.87, 1.60)], Kmax and ELEB [1.12 mm (0.79, 1.41)], and Kmax and ELEF [0.97 mm (0.64, 1.27)]. Low distances (&lt;0.5 mm) were calculated between ELEB and ELEF, and ELEB and Pachymin. All of the calculated distances between the locations showed a significant negative correlation with keratoconus severity and most of them increased significantly with a more peripheral position of the cone (p &lt; 0.05).ConclusionsThere was low consistency between different methods for describing the location of a keratoconus. Curvature-based determinations of the cone center (Kmax, tKmax) showed the highest deviations and should not be used for that purpose. However, the discrepancies between different cone location methods diminished with increasing disease severity and more central position of the cone.
The hsp70 new functions as a regulator of reproduction both female and male in Ophraella communa
Authors: Zhang Yan , Ma Weihua , Ma Chao , Zhang Qinglu , Tian Zhenya , Tian Zhenqi , Chen Hongsong , Guo Jianying , Wan Fanghao , Zhou Zhongshi 
Published: September 2022

Heat shock proteins (Hsps) function as molecular chaperones that enable organisms to withstand stress and maintain normal life activities. In this study, we identified heat shock protein 70 (encoded by hsp70), which exhibits a higher expression in the mature male testis than in the unmature testis of Ophraella communa. Tissue expression profile revealed that Ochsp70 levels in males were highest in the testis, whereas those in females were highest in the head. Moreover, the expression of Ochsp70 was found to be significantly induced in female bursa copulatrix after mating. Double-stranded RNA dsOchsp70 was injected into males to performance RNA interference, which significantly decreased the male Ochsp70 expression levels within 20 d post-injection, whereas no effect was observed on the Ochsp70 expression level in the females after mating with dsOchsp70-injected males. However, significant downregulation of female fertility was marked simultaneously. Furthermore, knockdown of female Ochsp70 expression also led to a significant reduction in fertility. Finally, comparative transcriptomic analysis identified glucose dehydrogenase and insulin-like growth factor binding protein as putative downstream targets of Ochsp70. Overall, we deduced that Ochsp70 is an indispensable gene and a potential male mating factor in O. communa, which regulates reproduction.
Biosynthesis of silver nanoparticles using extract of Rumex nepalensis for bactericidal effect against food-borne pathogens and antioxidant activity
Authors: Geremew Addisie , Carson Laura , Woldesenbet Selamawit 
Published: September 2022

The evolution and incidence of multidrug-resistant food-borne pathogens still become a critical public health global issue. To avert this challenge there is great interest in medical applications of silver nanoparticles. Thus, this study aimed to synthesize silver nanoparticles (Rn-AgNPs) using aqueous leaf extract of Nepal Dock (Rumex nepalensis Spreng) and evaluate their antibacterial potential against food-borne pathogens and antioxidant activity. The Rn-AgNPs were characterized by UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Fourier Transform Infra-Red Spectroscopy (FTIR). The antibacterial activities of the Rn-AgNPs were evaluated using agar well diffusion (zone of inhibition, ZOI) and microdilution (minimum inhibitory concentration, MIC and minimum bactericidal concentration, MBC) methods. The antioxidant property of the Rn-AgNPs was investigated using radical scavenging (DPPH and hydroxyl) assays. The UV-Vis spectra of Rn-AgNPs elucidated the absorption maxima at 425 nm and FTIR detected numerous functional groups of biological compounds that are responsible for capping and stabilizing Rn-AgNPs. DLS analysis displayed monodispersed Rn-AgNPs of 86.7 nm size and highly negative zeta potential (-32.5 mV). Overall results showed that Escherichia coli was the most sensitive organism, whereas Staphylococcus aureus was the least sensitive against Rn-AgNPs. In the antioxidant tests, the AgNPs radical scavenging activity reached 95.44% at 100 μg/ml. This study indicates that Rn-AgNPs exhibit a strong antimicrobial on L. monocytogenes, S. aureus, S. typhimurium, and E. coli and antioxidant and thus might be developed as a new type of antimicrobial agent for the treatment of multidrug-resistant foodborne pathogens and extensible applications in nanomaterial food- and nanocomposite-based antimicrobial packaging and/or as an antioxidant.
Probiotic supplementation and systemic inflammation in relapsing-remitting multiple sclerosis: A randomized, double-blind, placebo-controlled trial
Authors: Rahimlou Mehran , Nematollahi Shima , Husain Durdana , Banaei-Jahromi Nasrin , Majdinasab Nastaran , Hosseini Seyed Ahmad 
Published: September 2022

BackgroundMultiple sclerosis (MS) is a complex inflammatory disease in which demyelination occurs in the central nervous system affecting approximately 2.5 million people worldwide. Intestinal microbiome changes play an important role in the etiology of chronic diseases.ObjectiveThis study aimed to investigate the effect of probiotic supplementation on systemic inflammation in patients with MS.MethodsA 12-week double-blind clinical trial study was designed and seventy patients with MS were randomly divided into two groups receiving probiotics and placebo. Patients in the intervention group received two capsules containing multi-strain probiotics daily and patients in the control group received the same amount of placebo. Factors associated with systemic inflammation were assessed at the beginning and end of the study.ResultsSixty-five patients were included in the final analysis. There was no significant difference between the two groups in terms of baseline variables except for the duration of the disease (P &gt; 0.05). At the end of the study, probiotic supplementation compared to the placebo caused a significant reduction in the serum levels of CRP (−0.93 ± 1.62 vs. 0.05 ± 1.74, P = 0.03), TNF-α (−2.09 ± 1.88 vs. 0.48 ± 2.53, P = 0.015) and IFN-γ (−13.18 ± 7.33 vs. −1.93 ± 5.99, P &lt; 0.001). Also, we found a significant increase in the FOXP3 and TGF-β levels in the intervention group (P &lt; 0.05).ConclusionThe results of our study showed that supplementation with probiotics can have beneficial effects on serum levels of some factors associated with systemic inflammation.Clinical trial registration[http://www.irct.ir], identifier [IRCT20181210041 918N1].
Plasma arginase-1 as a predictive marker for early transarterial chemoembolization refractoriness in unresectable hepatocellular carcinoma
Authors: Xia Wei-Li , Xu Shi-Jun , Guo Yuan , Zhao Xiao-Hui , Hu Hong-Tao , Zhao Yan , Yao Quan-Jun , Zheng Lin , Zhang Dong-Yang , Guo Chen-Yang , Fan Wei-Jun , Li Hai-Liang 
Published: September 2022

ObjectiveTo explore the relationship between plasma arginase-1 (ARG1) and early transarterial chemoembolization (TACE) refractoriness in patients with hepatocellular carcinoma (HCC) and develop nomograms for predicting early TACE refractoriness.MethodsA total of 200 patients with HCC, treated with TACE, were included in the study, including 120 in the training set and 80 in the validation set. Pre-treatment enzyme-linked immunosorbent assay was used to detected the plasma ARG1 levels of the patient, and independent predictors of early TACE refractoriness were determined using a multivariate logistic regression model, based on which a predictive model was developed using a nomogram.ResultsRisk of early TACE refractoriness was negatively correlated with plasma ARG1 levels, and multivariate logistic analysis showed tumour size (OR = 1.138, 95% CI = 1.006-1.288, P = 0.041), multiple tumors (OR=4.374, 95% CI = 1.189-16.089, P = 0.026), platelet count (OR = 0.990, 95% CI = 0.980-0.999, P = 0.036), and plasma ARG1 levels (OR = 0.209, 95% CI = 0.079-0.551, P = 0.002) to be independent prognostic factors for early TACE refractoriness.The AUC value for the nomogram of the training cohort was 0.786 (95% CI = 0.702–0.870), and the validation set AUC value was 0.833 (95% CI = 0.791-0.875).The decision curve analysis suggested that the nomogram had good clinical utility.ConclusionHigh plasma ARG1 expression was associated with a lower incidence of early TACE refractoriness. The nomogram constructed based on four independent prognostic factors could facilitate an individualised prediction of the incidence of early TACE refractoriness.
The burden of cervical cancer in China
Authors: Shen Xiu , Cheng Yiquan , Ren Fupeng , Shi Zhilong 
Published: September 2022

ObjectiveTrends in the incidence, disability-adjusted life-years (DALYs), and mortality rate of cervical cancer remain unknown.MethodsThe average annual percent changes (AAPCs) and relative risks (RR) in the incidence, DALYs, and mortality rate were determined using a joinpoint regression analysis; the net age, period, and cohort effects on above rates were evaluated.ResultsA significant increase in age-standardized incidence (AAPC, 0.9%; 95CI: 0.8, 1.1) but significant decreases in age-standardized DALYs (AAPC, -0.4%; 95%CI: -0.60, -0.20) and the mortality rate (AAPC, -0.4%; 95CI: -0.6, –0.3) were observed. As for age-specific rates, the incidence was higher in younger age groups, and the DALYs and mortality rate were lower in older age groups. The effects of age included a slight but significant increase in the RR with advancing age from 35 to 94 years; the period effect included a significant increase in the incidence over the 2005–2019 periods; and the cohort effect included a substantial increase in the incidence from earlier to later birth cohorts.ConclusionsThe incidence of cervical cancer increased from 1990 to 2019, particularly in younger age groups, and the DALYs and mortality rate decreased in the older age groups. Furthermore, the incidence increased with age, period, and cohort.
Relationship between bronchopulmonary dysplasia phenotypes with high-resolution computed tomography score in early preterm infants
Authors: Yao Qiong , Shen Quan-li , Huang Guo-ying , Hu Xi-hong 
Published: September 2022

ObjectiveTo assess the relationship between high-resolution computed tomography (HRCT) abnormalities and clinical phenotypes of bronchopulmonary dysplasia (BPD).MethodsA retrospective, single-center study was carried out at the Children’s Hospital of Fudan University between 2013 and 2020. Preterm infants born at ≤ 32 weeks’ gestation who were diagnosed with BPD and had HRCT between 40 and 50 weeks postmenstrual age (PMA)were included in the study. HRCT images from six pulmonary lobes were scored based on seven types of pulmonary lesions from two categories: hyperaeration lesions and parenchymal lesions. The hyperaeration score (HS) included scores of decreased attenuation, mosaic attenuation, and bulla/bleb, while the parenchymal score (PS) included those of linear lesion, consolidation, bronchial wall thickening, and bronchiectasis. All seven scores were summed up to create the total score (TS). One-way ANOVA testing or Kruskal-Wallis testing was adopted for the comparison of HRCT scores with BPD severity and clinical phenotypes. The correlation between HRCT scores and clinical phenotypes was evaluated by Spearman’s correlation analysis.ResultsA total of 81 cases were included in the study. Cases with more severe BPD had a higher TS (p = 0.01), HS (p = 0.02), PS (p = 0.02), mosaic attenuation score (p = 0.03), bulla/Bleb score (p = 0.03), and linear density score (p = 0.01). TS (r = 0.28), PS (r = 0.35), linear density (r = 0.34), and consolidation (r = 0.24) were correlated with pulmonary hypertension (PH). However, no HRCT score was significantly different between the patients with or without tracheobronchomalacia (TBM). BPD patients with a combination of lung parenchymal disease, PH, and TBM had the highest TS and HS.ConclusionHRCT scores correlated with BPD severity and PH in our study. HS might be a useful tool in the assessment of BPD severity while linear densities and consolidation might be helpful in predicting PH.
The median effective doses of propofol combined with two different doses of nalbuphine for adult patients during painless gastroscopy
Authors: Tang Lili , Ye Chenxuan , Wang Nan , Chen Chen , Chen Sirui , Gao Shan , Liu Xuesheng 
Published: September 2022

Objective: Propofol is the most widely administered intravenous anesthetic to induce deep sedation for gastroscopy procedures. Coadministration of nalbuphine can provide analgesia and sedation to patients experiencing visceral pain, thereby decreasing the amount of propofol needed and reducing the risk of propofol-induced adverse events. We carried out this study to determine the median effective dose (ED50) of propofol in combination with different dosages of nalbuphine and the optimal dosage of nalbuphine during painless gastroscopy.Methods: We recruited sixty-five patients aged 18–60 years who underwent elective painless gastroscopy. A total of sixty-one patients were allocated randomly to the N1 group (nalbuphine 0.1 mg/kg) or N2 group (nalbuphine 0.15 mg/kg). Three minutes after administration of nalbuphine, patients received a preset dose of propofol at 2.0 mg/kg with a dose gradient of 0.2 mg/kg according to Dixon’s “up-and-down” method. The primary outcome was the ED50 of propofol in combination with nalbuphine. Hemodynamic parameters, recovery time, pain score, and adverse events were recorded as secondary outcomes.Results: The ED50 of propofol in the N2 group was significantly lower than that observed in the N1 group (p &lt; 0.01). Using probit analysis, the ED50 and ED95 of propofol were 1.632 mg/kg and 2.759 mg/kg in the N1 group and 1.111 mg/kg and 2.243 mg/kg in the N2 group, respectively. The incidence of hypotension in the N2 group was lower than that in the N1 group (p &lt; 0.05), and the recovery time was shorter than that of the N1 group (p &lt; 0.05).Conclusion: In adult patients, 0.15 mg/kg nalbuphine led to a significant reduction in the ED50 and ED95 of propofol during gastroscopy. This dose of nalbuphine also reduced the incidence of hypotension and shortened the recovery time. Therefore, nalbuphine (0.15 mg/kg) combined with propofol is a safe option for enhancing recovery after painless gastroscopy in adult patients.Clinical Trial Registration: [https://www.chictr.org.cn/edit.aspx?pid=126699&amp;htm=4], identifier [ChiCTR2100053204].