bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prevalence, Popular Trends, and Associated and Predictive Factors of Non-Obese Fatty Liver Disease
Authors: Deng Jiang , Zhang Yonghong , Bu Limei , Shi Haitao , Tang Hailing , Wang Shenhao , Wang Qian , Dang Shuangsuo , Li Ming , Han Zhiyi , Lu Xiaolan 
Published: September 2021

Background and AimsThere are few studies on non-obese fatty liver disease, the aims of this study was to analyze its prevalence, popular trends, and associated and predictive factors, so as to provide reference for its prevention and treatment.MethodsIndividuals with complete data of body mass index, sex, age, and abdominal ultrasound in Karamay Central Hospital from 2009 to 2016 were selected to analyze the prevalence and popular trends of non-obese fatty liver disease (body mass index &lt;24 kg/m2), and associated and predictive factors.ResultsBetween 2009 and 2016, a total of 191,555 medical check-ups were included. The prevalence of non-obese fatty liver disease increased from 1.9% to 5.1% among general medical examinants (P&lt;0.001), increased from 4.6% to 11.7% in non-obese individuals (P&lt;0.001). Compared with the non-obese control group, the levels of age, body mass index, blood pressure, fasting blood glucose, triglycerides, total cholesterol and uric acid in the non-obese fatty liver group were higher (P&lt;0. 05). Even among non-obese subjects, elevated body mass index was associated with a 0.63-fold increased risk for non-obese fatty liver disease (P&lt;0.001, odds ratio=1.63, 95% confidence interval 1.54-1.72) for every one-unit increase in body mass index. The most common abnormal indicator of non-obese fatty liver disease was elevated triglycerides (44.2%), which was also the best predictor of non-obese fatty liver disease (area under the curve =0.795) in non-obese physical examinators.ConclusionsThe prevalence of non-obese fatty liver disease was high and increasing rapidly in Karamay. Triglycerides is the best predictor of non-obese fatty liver in non-obese physical examinators.
Peripheral B-Cell Immunophenotyping Identifies Heterogeneity in IgG4-Related Disease
Authors: Li Jieqiong , Liu Zheng , Zhang Panpan , Lin Wei , Lu Hui , Peng Yu , Peng Linyi , Zhou Jiaxin , Wang Mu , Chen Hua , Zhao Lidan , Wang Li , Qin Chenman , Hu Chaojun , Zeng Xiaofeng , Zhao Yan , Fei Yunyun , Zhang Wen 
Published: September 2021

ObjectivesTo elucidate heterogeneity of IgG4-related disease (IgG4-RD) based on B cell immunophenotyping.MethodsImmunophenotyping of 4 B-cell subsets in peripheral blood from patients with active IgG4-RD (aIgG4-RD, n=105) was performed using flow cytometry to get preliminary B-cell heterogeneity spectrum. Then 10 B-cell subsets were characterized in aIgG4-RD (n = 49), remissive IgG4-RD (rIgG4-RD, n = 49), and healthy controls (HCs, n = 47), followed by principal components analysis (PCA) and cluster analysis to distinguish B-cell immunophenotypes and classify IgG4-RD patients into subgroups.ResultsCluster analysis identified two endotypes in 105 aIgG4-RD patients based on 4 B-cell subsets: Group1 with higher Breg and naive B cells (n = 48), and Group2 with higher plasmablasts and memory B cells (MBCs) (n = 57). PCA indicated that aIgG4-RD consisted of plasmablast-naive B cell and MBCs-Breg axes abnormalities. There was a negative relationship between naive B cells and disease activity. Both plasmablasts and MBCs were positively associated with serological biomarkers. Cluster analysis stratified aIgG4-RD patients into 3 subgroups based on 10 B-cell subsets: subgroup1 with low MBCs and normal Breg, subgroup2 with high MBCs and low Breg, and subgroup3 with high plasmablasts and low naive B cells. Patients in subroup2 and subgroup3 were more likely to be resistant to treatment.ConclusionPatients with aIgG4-RD can be divided into 3 subgroups based on B cell heterogeneity. The B cell immunophenotyping could help elucidate the pathogenesis of IgG4-RD, identify patients with potential refractory IgG4-RD, and provide important information for the development of new therapies.
Cerebral Aneurysm Occlusion at 12-Month Follow-Up After Flow-Diverter Treatment: Statistical Modeling for V&V With Real-World Data
Authors: Narata Ana Paula , Obradó Laura , Moyano Raquel Kalé , Macho Juan M. , Blasco Jordi , Rueda Antonio López , Roman Luis San , Remollo Sebastian , Marinelli Claudia , Cepeda Rosana , Fernández Héctor , Larrabide Ignacio 
Published: September 2021

Background: Flow-Diverter (FD) porosity has been pointed as a critical factor in the occlusion of cerebral aneurysms after treatment.Objective: Verification and Validation of computational models in terms of predictive capacity, relating FD porosity and occlusion after cerebral aneurysms treatment.Methods: Sixty-four aneurysms, with pre-treatment and follow-up images, were considered. Patient demographics and aneurysm morphological information were collected. The computational simulation provided by ANKYRAS provided FD porosity, expansion, and mesh angle. FD occlusion was assessed and recorded from follow-up images. Multiple regression Logit and analysis of covariance (ANCOVA) models were used to model the data with both categorical and continuous models.Results: Occlusion of the aneurysm after 12 months was affected by aneurysm morphology but not by FD mesh morphology. A Time-To-Occlusion (TTO) of 6.92 months on average was observed with an SE of 0.24 months in the aneurysm population surveyed. TTO was estimated with statistical significance from the resulting model for the data examined and was capable of explaining 92% of the data variation.Conclusions: Porosity was found to have the most correction power when assessing TTO, proving its importance in the process of aneurysm occlusion. Still, further Verification and Validation (V&amp;V) of treatment simulation in more extensive, multi-center, and randomized databases is required.
High Throughput Transcriptome Data Analysis and Computational Verification Reveal Immunotherapy Biomarkers of Compound Kushen Injection for Treating Triple-Negative Breast Cancer
Authors: Liu Xinkui , Wu Yang , Zhang Yingying , Bu Dechao , Wu Chao , Lu Shan , Huang Zhihong , Song Yurong , Zhao Yi , Guo Fengying , Ye Peizhi , Fu Changgeng , Shen Liangliang , Zhang Jingyuan , Wang Haojia , Duan Xianchun , Wu Jiarui 
Published: September 2021

BackgroundAlthough notable therapeutic and prognostic benefits of compound kushen injection (CKI) have been found when it was used alone or in combination with chemotherapy or radiotherapy for triple-negative breast cancer (TNBC) treatment, the effects of CKI on TNBC microenvironment remain largely unclear. This study aims to construct and validate a predictive immunotherapy signature of CKI on TNBC.MethodsThe UPLC-Q-TOF-MS technology was firstly used to investigate major constituents of CKI. RNA sequencing data of CKI-perturbed TNBC cells were analyzed to detect differential expression genes (DEGs), and the GSVA algorithm was applied to explore significantly changed pathways regulated by CKI. Additionally, the ssGSEA algorithm was used to quantify immune cell abundance in TNBC patients, and these patients were classified into distinct immune infiltration subgroups by unsupervised clustering. Then, prognosis-related genes were screened from DEGs among these subgroups and were further overlapped with the DEGs regulated by CKI. Finally, a predictive immunotherapy signature of CKI on TNBC was constructed based on the LASSO regression algorithm to predict mortality risks of TNBC patients, and the signature was also validated in another TNBC cohort.ResultsTwenty-three chemical components in CKI were identified by UPLC-Q-TOF-MS analysis. A total of 3692 DEGs were detected in CKI-treated versus control groups, and CKI significantly activated biological processes associated with activation of T, natural killer and natural killer T cells. Three immune cell infiltration subgroups with 1593 DEGs were identified in TNBC patients. Then, two genes that can be down-regulated by CKI with hazard ratio (HR) &gt; 1 and 26 genes that can be up-regulated by CKI with HR &lt; 1 were selected as key immune- and prognosis-related genes regulated by CKI. Lastly, a five-gene prognostic signature comprising two risky genes (MARVELD2 and DYNC2I2) that can be down-regulated by CKI and three protective genes (RASSF2, FERMT3 and RASSF5) that can be up-regulated by CKI was developed, and it showed a good performance in both training and test sets.ConclusionsThis study proposes a predictive immunotherapy signature of CKI on TNBC, which would provide more evidence for survival prediction and treatment guidance in TNBC as well as a paradigm for exploring immunotherapy biomarkers in compound medicines.
Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies
Authors: Sharif Najam A. 
Published: September 2021

Damage to the optic nerve and the death of associated retinal ganglion cells (RGCs) by elevated intraocular pressure (IOP), also known as glaucoma, is responsible for visual impairment and blindness in millions of people worldwide. The ocular hypertension (OHT) and the deleterious mechanical forces it exerts at the back of the eye, at the level of the optic nerve head/optic disc and lamina cribosa, is the only modifiable risk factor associated with glaucoma that can be treated. The elevated IOP occurs due to the inability of accumulated aqueous humor (AQH) to egress from the anterior chamber of the eye due to occlusion of the major outflow pathway, the trabecular meshwork (TM) and Schlemm’s canal (SC). Several different classes of pharmaceutical agents, surgical techniques and implantable devices have been developed to lower and control IOP. First-line drugs to promote AQH outflow via the uveoscleral outflow pathway include FP-receptor prostaglandin (PG) agonists (e.g., latanoprost, travoprost and tafluprost) and a novel non-PG EP2-receptor agonist (omidenepag isopropyl, Eybelis®). TM/SC outflow enhancing drugs are also effective ocular hypotensive agents (e.g., rho kinase inhibitors like ripasudil and netarsudil; and latanoprostene bunod, a conjugate of a nitric oxide donor and latanoprost). One of the most effective anterior chamber AQH microshunt devices is the Preserflo® microshunt which can lower IOP down to 10–13 mmHg. Other IOP-lowering drugs and devices on the horizon will be also discussed. Additionally, since elevated IOP is only one of many risk factors for development of glaucomatous optic neuropathy, a treatise of the role of inflammatory neurodegeneration of the optic nerve and retinal ganglion cells and appropriate neuroprotective strategies to mitigate this disease will also be reviewed and discussed.
Pithecellobium clypearia: Amelioration Effect on Imiquimod-Induced Psoriasis in Mice Based on a Tissue Metabonomic Analysis
Authors: Li Ying , Zong Jiaxin , Ye Wenjun , Fu Yuanfeng , Gu Xinyi , Pan Weisong , Yang Li , Zhang Ting , Zhou Mingmei 
Published: September 2021

Pithecellobium clypearia Benth. (accepted name: Archidendron clypearia (Jack) I.C.Nielsen; Mimosaceae), a popular traditional Chinese medicine, has a significant anti-inflammatory effect. The crude water extract of the aerial part of P. clypearia has been clinically applied to treat upper respiratory tract infections, acute gastroenteritis, laryngitis, and pharyngitis. However, the therapeutic mechanism of ethanol fraction of water extract (ESW) of P. clypearia to treat psoriasis should be complemented. The aim of our research was to clarify the protective effects of ESW from P. clypearia against psoriasis-like skin inflammation induced by imiquimod (IMQ) in mice with efficacy indexes and target tissue (spleen and serum) metabolomics. The ingredient of ESW was analyzed by ultrahigh-performance liquid chromatography combined with tandem mass spectrometry (UHPLC-MS/MS) method. The imiquimod-induced psoriatic mouse model was employed to investigate the effect of ESW against psoriasis, where the treatment method was implemented for 6 days both topically (Gel at 5%) and orally (at 2.4 g/kg p.o.). Traditional pharmacodynamic indicators (phenotypic characteristics, psoriasis area and severity index (PASI) score, H&amp;E staining, immunohistochemical staining, the thickness of epidermis, body weight change, and spleen index) were conducted to appraise the efficacy of ESW. Furthermore, a gas chromatography-mass spectrometer (GC-MS) coupled with multivariate analysis was integrated and applied to obtain serum and spleen metabolic profiles for clarifying metabolic regulatory mechanisms of ESW. The current study illustrated that ESW is composed mainly of gallic acid, ethyl gallate, quercitin, 7-O-galloyltricetiflavan, quercetin, and myricetin by UHPLC-MS/MS analysis. ESW could distinctly improve IMQ-induced psoriasis in mouse through reducing PASI score, alleviating tissue damage, restoring spleen index, and inhibiting proliferating cell nuclear antigen (PCNA) expression in psoriasis-like skin tissue. From the metabolomics study, 23 markers with significant changes are involved in eight main pathways in spleen and serum samples, including linoleic acid metabolism and glycine, serine, and threonine metabolism. The current study showed that ESW had obvious antipsoriasis effects on IMQ-induced psoriasis in mice, which might be attributed to regulating the dysfunction of differential biomarkers and related pathways. In summary, ESW of P. clypearia showed a favourable therapeutic effect on IMQ-induced psoriasis, and metabolomics provided insights into the mechanisms of ESW to the treatment of psoriasis.
Effect of Cold Stress on Neurobehavioral and Physiological Parameters in Rats
Authors: El Marzouki Hajar , Aboussaleh Youssef , Najimi Mohamed , Chigr Fatiha , Ahami Ahmed 
Published: September 2021

Objective: Cold stress is an important current issue and implementing control strategies to limit its sometimes harmful effects is crucial. Cold is a common stressor that can occur in our work and our occupational or leisure time activities every day. There are substantial studies on the effects of chronic stress on memory and behavior, although, the cognitive changes and anxiety disorders that can occur after exposure to chronic intermittent cold stress are not completely characterized. Therefore, the present study was undertaken with an aim to investigate the effects of chronic intermittent cold stress on body weight, food intake and working memory, and to elucidate cold stress related anxiety disorders using cognitive and behavioral test batteries.Methods: We generated a cold stress model by exposing rats to chronic intermittent cold stress for 5 consecutive days and in order to test for the potential presence of sex differences, a comparable number of male and female rats were tested in the current study. Then, we measured the body weights, food intake and the adrenal glands weight. Working memory and recognition memory were assessed using the Y maze and the Novel Object Recognition (NOR) tasks. While, sex differences in the effects of chronic stress on behavior were evaluated by the elevated plus maze (EPM), open field maze (OF), and Marble burying (MB) tests.Results: We found that 2 h exposure to cold (4°C) resulted in an increase in the relative weight of the adrenal glands in male rats. Given the same chronic stress 5 days of cold exposure (2 h per day), increased weight gain in male rats, while females showed decreased food intake and no change in body weight. Both sexes successfully performed the Y maze and object recognition (OR) tasks, indicating intact spatial working memory performance and object recognition abilities in both male and female rats. In addition, we have shown that stress caused an increase in the level of anxiety in male rats. In contrast, the behavior of the female rats was not affected by cold exposure.Conclusion: Overall, the current results provide preliminary evidence that chronic intermittent cold stress model may not be an efficient stressor to female rats. Females exhibit resilience to cold exposure that causes an increase in the level of anxiety in male rats, which demonstrates that they are affected differently by stress and the gender is an important consideration in experimental design.
Utilization of Intravenous Ribavirin Among Reproductive Age Adults in 2010–2017: A Population-Based Study in the Yinzhou District, Ningbo City of China
Authors: Li Hailong , Zhao Houyu , Lin Hongbo , Shen Peng , Liu Cuili , Zhan Siyan 
Published: September 2021

Background: Intravenous (IV) ribavirin is not approved in US and European Union, but it is authorized in China. Significant teratogenic and embryocidal effects of ribavirin have been found in almost all animal studies, it is critical to investigate the prevalence and trends of the utilization of IV ribavirin among reproductive age population.Objective: To evaluate the prevalence and trends of IV ribavirin use among reproductive-age population in 2010–2017.Methods: The study design of our study is retrospective cross-sectional study based on healthcare database. We identified and extracted the data of residents aged 18–44 years by using Yinzhou healthcare information database at 21 January, 2018. A cohort of IV ribavirin users were identified through outpatient prescription records in 3 general hospitals and 24 community health centers from 2010 to 2017. We reported the number, proportion, and prevalence of the exposure to IV ribavirin stratified by sex, age, marital status, education level, occupation, hospital level, calendar year, diagnosis, and dosage. The overall trends of IV ribavirin use, and the trends in different levels of hospital and common diagnoses were further analyzed and described.Result: During the study period, the prevalence of IV ribavirin use among reproductive-age adults was 6.02% (48,287/801,667). Relatively higher prevalence were found in adults aged 40–44 (8.04%, 95% CI: 7.90–8.17), unmarried patients (8.91%, 95% CI: 8.74–9.08), and who had more than 9 years of education (6.82%, 95% CI: 6.74–6.90). Compared to secondary and tertiary hospitals, IV ribavirin was more likely to be dispensed in primary hospitals (19.44%, 95% CI: 19.28–19.61). The most common diagnoses were acute upper respiratory infections (AURIs), accounting for 80% of the patients exposed to IV ribavirin. For patients with AURIs, the prevalence of IV ribavirin was nearly 30%. Overall, the prevalence of IV ribavirin use decreased from 1.72% in 2010 to 0.24% in 2017.Conclusion: We found IV ribavirin was mainly used for AURIs which suggested that a large amount of IV ribavirin use was probably inappropriate. The prevalence was decreasing by 87% over the past 8 years, and we encourage clinicians and pharmacists to continually avoid inappropriate use of IV ribavirin.
Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan
Authors: Hsu Wei-Hao , Sue Shu-Ping , Liang Hsiu-Ling , Tseng Chin-Wei , Lin Hsiu-Chu , Wen Wei-Lun , Lee Mei-Yueh 
Published: September 2021

Introduction: Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are incretin-based oral antidiabetic drugs. Previous studies have shown an association between increased plasma activity of DPP-4 and chronic hepatitis C virus (HCV) infection. Dipeptidyl peptidase 4 inhibitors may be associated with preventing the development of chronic HCV infection. The aim of this study was to investigate whether the use of DPP-4 inhibitors is associated with a decreased risk of hepatocellular carcinoma (HCC) in patients with diabetes mellitus (DM) and chronic HCV infection.Methods: In this retrospective cohort study, we enrolled patients with type 2 diabetes and chronic HCV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The patients were divided into two groups (DPP-4 inhibitor cohort and non-DPP-4 inhibitor cohort) according to whether or not they received DPP-4 inhibitor treatment.Results: Multivariate Cox proportional hazard regression analysis showed a significantly lower risk of HCC in the patients who took DPP-4 inhibitors compared to those who did not. Kaplan-Meier survival analysis demonstrated a significantly higher HCC-free rate in the DPP-4 inhibitor cohort than in the non-DPP-4 inhibitor cohort.Conclusion: The use of DPP-4 inhibitors was associated with a lower risk of HCC in patients with type 2 DM and chronic HCV infection.
Intraoperative Indocyanine Green Retention Test of Left Hemiliver in Decision-Making for Patients With Hepatocellular Carcinoma Undergoing Right Hepatectomy
Authors: Yu Tingdong , Ye Xinping , Wen Zhang , Zhu Guangzhi , Su Hao , Han Chuangye , Huang Ketuan , Qin Wei , Liao Xiwen , Yang Chengkun , Liu Zhen , Wang Xiangkun , Xu Banghao , Su Ming , Lv Zili , Lau Wan Yee , Peng Tao 
Published: September 2021

Introduction: The aim of this study was to select qualified patients with hepatocellular carcinoma (HCC) who underwent right hepatectomy (RH) via intraoperative indocyanine green retention test at 15 min (ICG-R15) of the left hemiliver, which prevents severe posthepatectomy liver failure (PHLF).Methods: Twenty HCC patients who were preoperatively planned to undergo RH were enrolled. Intraoperative ICG-R15 of left hemiliver was measured after the right Glissonean pedicle was completely blocked. Patients then underwent RH if intraoperative ICG-R15 was ≤ 10%. Otherwise, patients underwent staged RH (SRH), either associating liver partitioning and portal vein ligation for staged hepatectomy (ALPPS) or portal vein ligation (PVL), followed by stage-2 RH. The comparison group consisted of patients with a ratio of standard left liver volume (SLLV) of &gt; 40% and preoperative ICG-R15 ≤ 10% who underwent RH. The clinical outcomes of these two groups were compared.Results: Of the 20 patients, six underwent stage-1 RH, six underwent ALPPS, five underwent PVL followed by stage-2 RH, and three failed to proceed to stage-2 RH after PVL. No significant differences were found among the 17 patients who underwent stage-1 or stage-2 RH in the study group, the 19 patients in the comparison group, the 11 patients in the stage-2 RH group, and the six patients in the stage-1 RH group in incidences of PHLF, postoperative complications, hospital stay, and HCC recurrence within 1 year after RH. Compared with the stage-1 ALPPS group, the mean operative time and blood loss of the stage-1 PVL group were significantly less (p &lt;0.001 and p = 0.022, respectively). The stage-1 PVL group had a significantly longer waiting-time (43.4 vs. 14.0 days, p = 0.016) than the stage-1 ALPPS group to proceed to stage-2 RH. After stage-2 RH, tumor recurrence within 1 year was 20% (1/5) in patients after PVL and 50% (3/6) after stage-1 ALPPS.Conclusions: Intraoperative ICG-R15 ≤ 10% of left hemiliver was valuable in intraoperative decision-making for patients who were planned to undergo RH. There is a possibility that stage-1 PVL might help to select patients with more favorable biological behavior to undergo stage-2 RH.