bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness analysis with direct-acting antivirals in a cohort of HCV-infected inmates in Italy
Authors: Ravasio Roberto , Lucania Luciano , Ranieri Roberto , Dominguez Raquel 
Published: January 2021

Objective: To evaluate the cost-effectiveness of a strategy based on direct-acting antivirals (DAAs) versus no drug strategy in HCV-infected inmates, from the perspective of the Italian National Health System (iNHS).
Methods: A previous Markov model was adapted to the Italian setting to evaluate the direct medical costs and health outcomes (quality-adjusted life years, QALY) throughout the life of HCV-infected inmates. Epidemiological data, patient characteristics (genotype, METAVIR classification), DAAs sustained virological response (SVR), annual likelihood of transition, treatment costs and utilities were gathered from the literature. The DAAs strategy included the administration of elbasvir/grazoprevir or sofosbuvir/velpatasvir or glecaprevir/pibrentasvir. Direct medical costs and QALYs were discounted at a 3.0% annual rate. Cost-effectiveness was evaluated as incremental cost-effectiveness ratio (€, 2019) per QALY gained. A deterministic sensitivity analysis (DSA) was performed.
Results: Over a lifetime horizon, the DAAs strategy showed higher health costs per patient compared to no drugs strategy in the base-case analysis (€ 42,571 vs. € 26,119). However, it was associated with an increase of QALYs gained (21.14 vs. 15.67), showing an incremental cost-effectiveness ratio of € 3,010 per QALY. The sensitivity analysis confirmed the base-case results.
Conclusions: Extending the DAAs treatment to HCV-infected inmates was estimated to be cost effective from the perspective of the Italian NHS, regardless genotype and METAVIR classification.
MICAL-L2 Is Essential for c-Myc Deubiquitination and Stability in Non-small Cell Lung Cancer Cells
Authors: Min Pengxiang , Zhang Lin , Wang Yueyuan , Qi Chenxiang , Song Yixuan , Bibi Maria , Zhang Yujie , Ma Yadong , Zhao Xuyang , Yu Minjie , Du Jun 
Published: January 2021

Objectives: MICAL-L2, a member of the molecules interacting with the CasL (MICAL) family, was reported to be highly expressed in several types of cancers, however, the roles of MICAL-L2 in NSCLC pathogenesis remain to be explored. This study is designed to clarify the mechanisms by which MICAL-L2 participates in NSCLC cell proliferation.Materials and Methods: The expression levels of MICAL-L2 in human lung cancer samples were assessed by immunohistochemical staining. Cells were transfected with siRNA or plasmids to regulate MICAL-L2 expression. Cell proliferation was measured by EdU staining and CCK-8 assays. MICAL-L2 and phosphorylated/total c-Myc expression were examined by Western blotting analysis. Interaction between MICAL-L2 and c-Myc was assessed by immunofluorescence staining, Western blotting and co-immunoprecipitation assays. Western blotting, polyubiquitylation detection and protein stability assays were used to assess whether MICAL-L2 exerts its oncogenic effect via c-Myc.Results: We found that MICAL-L2 was highly expressed in human NSCLC. While overexpressing MICAL-L2 increased NSCLC cell proliferation, MICAL-L2 depletion decreased the proliferation of NSCLC cells, an effect that was linked to cell cycle arrest. MICAL-L2 physically interacted with the c-Myc protein and functioned to maintain nuclear c-Myc levels and prolonged its half-life. Knockdown of MICAL-L2 expression led to decreased c-Myc protein stability through accelerating polyubiquitylation of c-Myc and gave rise to c-Myc degradation. We further found that MICAL-L2 deubiquitinated c-Myc and blocked its degradation, presumably by inhibiting c-Myc phosphorylation at threonine residue 58.Conclusions: These results indicate that MICAL-L2 is a key regulator of c-Myc deubiquitination and stability in the nucleus, and this activity may be involved in promoting NSCLC cell proliferation.
Comparison of the Gut Microbiota Disturbance in Rat Models of Irritable Bowel Syndrome Induced by Maternal Separation and Multiple Early-Life Adversity
Authors: Enqi Wu , Jingzhu Song , Lingpeng Pei , Yaqin Ling 
Published: January 2021

BackgroundThe study aimed to identify the effects of modeling procedures on bacterial communities and to investigate whether different modeling procedures lead to consistent patterns of gut microbiome compositions.MethodsTwo irritable bowel syndrome (IBS) rat models maternal separation (MS) alone and multiple-early-adversity modeling (MAM) were established and the gut microbiome were analyzed using 16S-rRNA-based high-throughput sequencing methods.ResultsRats from both models exhibited visceral hypersensitivity and the two model groups exhibited differences in the extent of visceral sensitivity and fecal water content. The microbial community structure of the two models exhibited significant differences compared to the controls, while the two model groups also exhibited significant differences between them. Furthermore, microbial community functional predictions suggested that the two models exhibited different abundances of metabolisms and pathways. Several common and distinct characteristic differences were also observed between the two model groups. Alloprevotella were more abundant in both model groups, while Butyricicoccus, Turicibacter, Ruminococcus, and Clostridium_sensu_stricto along with the family it belongs to were less abundant relative to controls. In addition, the abundance of Clostridium_IV, Corynebacterium, Rothia, Elusimicrobium, Romboutsia, Allobaculum, Parasutterella, and their related taxa were specifically associated with MS group, whereas Butyricimonas and Vampirovibrio along with its related taxa were specifically associated with MAM group. Among those, Butyricimonas, Butyricicoccus and Corynebacterium were found to partially mediate early adversity exposure-induced visceral hypersensitivity.ConclusionsOur results highlight the importance in evaluating gut microbiota characteristics in IBS research while also systematically considering potential modeling procedural differences. The microbial compositional/functional differences identified in this study were suggestive to further investigation of mechanisms of early adversity induced IBS.
Comparison of Experimental Rat Models in Donation After Circulatory Death (DCD): in-situ vs. ex-situ Ischemia
Authors: Arnold Maria , Méndez-Carmona Natalia , Wyss Rahel K. , Joachimbauer Anna , Casoni Daniela , Carrel Thierry , Longnus Sarah 
Published: January 2021

Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. However, warm ischemia prior to procurement is of particular concern for cardiac graft quality. We describe a rat model of DCD with in-situ ischemia in order to characterize the physiologic changes during the withdrawal period before graft procurement, to determine effects of cardioplegic graft storage, and to evaluate the post-ischemic cardiac recovery in comparison with an established ex-situ ischemia model.Methods: Following general anesthesia in male, Wistar rats (404 ± 24 g, n = 25), withdrawal of life-sustaining therapy was simulated by diaphragm transection. Hearts underwent no ischemia or 27 min in-situ ischemia and were explanted. Ex situ, hearts were subjected to a cardioplegic flush and 15 min cold storage or not, and 60 min reperfusion. Cardiac recovery was determined and compared to published results of an entirely ex-situ ischemia model (n = 18).Results: In donors, hearts were subjected to hypoxia and hemodynamic changes, as well as increased levels of circulating catecholamines and free fatty acids prior to circulatory arrest. Post-ischemic contractile recovery was significantly lower in the in-situ ischemia model compared to the ex-situ model, and the addition of cardioplegic storage improved developed pressure-heart rate product, but not cardiac output.Conclusion: The in-situ model provides insight into conditions to which the heart is exposed before procurement. Compared to an entirely ex-situ ischemia model, hearts of the in-situ model demonstrated a lower post-ischemic functional recovery, potentially due to systemic changes prior to ischemia, which are partially abrogated by cardioplegic graft storage.
Seafloor Pressure Change Excited at the Northwest Corner of the Shikoku Basin by the Formation of the Kuroshio Large-Meander in September 2017
Authors: Nagano Akira , Yamashita Yusuke , Ariyoshi Keisuke , Hasegawa Takuya , Matsumoto Hiroyuki , Shinohara Masanao 
Published: January 2021

The Kuroshio takes a greatly southward displaced path called a large-meander (LM) path off the southern coast of Japan on interannual to decadal time scales. The transition of the current path from a non-large-meander path to an LM path is the most salient ocean current variation south of Japan. The change in pressure on the seafloor due to the formation of the LM path in September 2017 is of critical importance to understand the dynamics of the LM path and to distinguish the change due to the Kuroshio path variation from changes due to crustal deformation. Hence, we examined the seafloor pressure across the continental slope off the eastern coast of Kyushu for the period March 2014 to April 2019. The pressure and its cross-slope gradient over the continental slope shallower than 3,000 m beneath near the Kuroshio are invariable. As a mesoscale current path disturbance, called a small meander, passed over the observation stations, the pressure decreased by approximately 0.1 dbar on the continental slope deeper than 3000 m and was kept low until the end of the observation period (April 2019). The pressure decrease is consistent with the changes in sea surface height and subsurface water density and is caused by the baroclinic enhancement of the Shikoku Basin local recirculation. This seafloor pressure change implies a strengthening of the deep southwestward current, possibly as a part of a deep cyclonic circulation in the Shikoku Basin. The present study demonstrated that, in addition to altimetric sea surface height data, hydrographic data are useful to distinguish the ocean variation in seafloor pressure from the variation due to crustal deformation, and vice versa.
Earthquake Analysis Suggests Dyke Intrusion in 2019 Near Tarawera Volcano, New Zealand
Authors: Benson Thomas W. , Illsley-Kemp Finnigan , Elms Hannah C. , Hamling Ian J. , Savage Martha K. , Wilson Colin J. N. , Mestel Eleanor R. H. , Barker Simon J. 
Published: January 2021

Tarawera volcano (New Zealand) is volumetrically dominated by rhyolitic lavas and pyroclastic deposits, but the most recent event in AD 1886 was a basaltic Plinian fissure eruption. In March 2019 a swarm of at least 64 earthquakes occurred to the NE of Tarawera volcano, as recorded by the New Zealand Geohazard Monitoring Network (GeoNet). We use seismological analysis to show that this swarm was most likely caused by a dyke that intruded into the brittle crust between depths of 8–10 km and propagated toward Tarawera volcano for 2 km at a rate of 0.3–0.6 m s−1. We infer that this was a dyke of basaltic composition that was stress-guided toward Tarawera volcano by the topographic load of the volcanic edifice. Dyke intrusions of this nature are most likely a common occurrence but a similar process may have occurred during the 1886 eruption with a dyke sourced from some lateral distance away from the volcano. The 2019 intrusion was not detected by InSAR geodesy and we use synthetic models to show that geodetic monitoring could only detect a ≥6 m wide dyke at these depths. Improvements to geodetic monitoring, combined with detailed seismological analysis, could better detect future magmatic intrusions in the region and serve to help assess ongoing changes in the magmatic system and the associated possibilities of a volcanic event.
Extracellular Vesicles in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Functions and Applications
Authors: Zhang Bo , Zhao Ming , Lu Qianjin 
Published: January 2021

In the last two decades, extracellular vesicles (EVs) have aroused wide interest among researchers in basic and clinical research. EVs, small membrane vesicles are released by almost all kinds of cells into the extracellular environment. According to many recent studies, EVs participate in immunomodulation and play an important role in the pathogenesis of autoimmune diseases. In addition, EVs have great potential in the diagnosis and therapy of autoimmune diseases. Here, we reviewed the latest research advances on the functions and mechanisms of EVs and their roles in the pathogenesis, diagnosis, and treatment of rheumatoid arthritis and systemic lupus erythematosus.
Vagus Nerve Stimulation Decreases Pancreatitis Severity in Mice
Authors: Zhang Luyao , Wu Zhiyang , Tong Zhihui , Yao Qi , Wang Ziyu , Li Weiqin 
Published: January 2021

BackgroundVagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP).MethodsTwo independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-α levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of α7nAChR+ macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned α7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS.ResultsVNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-α and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of α7nAChR+ macrophages in pancreas and spleen. Adoptive transfer of VNS-treated α7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS.ConclusionsVNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to α7nAChR on macrophage.
The Role of Heat Shock Proteins in Type 1 Diabetes
Authors: Moin Abu Saleh Md , Nandakumar Manjula , Diane Abdoulaye , Dehbi Mohammed , Butler Alexandra E. 
Published: January 2021

Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease characterized by recognition of pancreatic β-cell proteins as self-antigens, called autoantigens (AAgs), followed by loss of pancreatic β-cells. (Pre-)proinsulin ([P]PI), glutamic acid decarboxylase (GAD), tyrosine phosphatase IA-2, and the zinc transporter ZnT8 are key molecules in T1D pathogenesis and are recognized by autoantibodies detected in routine clinical laboratory assays. However, generation of new autoantigens (neoantigens) from β-cells has also been reported, against which the autoreactive T cells show activity. Heat shock proteins (HSPs) were originally described as “cellular stress responders” for their role as chaperones that regulate the conformation and function of a large number of cellular proteins to protect the body from stress. HSPs participate in key cellular functions under both physiological and stressful conditions, including suppression of protein aggregation, assisting folding and stability of nascent and damaged proteins, translocation of proteins into cellular compartments and targeting irreversibly damaged proteins for degradation. Low HSP expression impacts many pathological conditions associated with diabetes and could play a role in diabetic complications. HSPs have beneficial effects in preventing insulin resistance and hyperglycemia in type 2 diabetes (T2D). HSPs are, however, additionally involved in antigen presentation, presenting immunogenic peptides to class I and class II major histocompatibility molecules; thus, an opportunity exists for HSPs to be employed as modulators of immunologic responses in T1D and other autoimmune disorders. In this review, we discuss the multifaceted roles of HSPs in the pathogenesis of T1D and in autoantigen-specific immune protection against T1D development.
Hot Stamping of a B-Pillar Reinforced Panel With 7075 Aluminum Alloy and the Feasibility Study of Short-Time Aging
Authors: Liu Yong , Li Jiahao , Wang Liang , Wang Kai , Zhu Bin , Zhang Yisheng 
Published: January 2021

The hot stamping of a B-pillar reinforced panel with 7075 aluminum alloy was carried out in an industrial production line. The effect of blank holding force (BHF) on the formability of the B-pillar reinforced panel and the effect of solution heat treatment (SHT) time on the mechanical properties were studied. Additionally, the forming precisions of a formed part before and after standard aging were detected further. Finally, both standard aging and short-time aging processes were carried out to investigate the feasibility of short-time aging for real parts. The stamping results demonstrated that lower BHF or no blank holding should be used during hot stamping to avoid cracking and wrinkling. The detection of forming precisions indicated that the great majority of measured points on the part were within ±1 mm of nominal. The mechanical property testing showed that the strength of the formed parts after a short-time aging was up to more than 90% of the as-received T6 state and more than 93% of the time can be reduced if the 90% of strength can be accepted.
The Comorbid Relationship Between Migraine and Asthma: A Systematic Review and Meta-Analysis of Population-Based Studies
Authors: Wang Long , Deng Zi-Ru , Zu Mei-Dan , Zhang Juan , Wang Yu 
Published: January 2021

Objective: Recent studies have indicated a pathophysiologic link between migraine and asthma. This meta-analysis aimed to comprehensively estimate the risk ratio for migraine in asthma as well as that of asthma in migraine based on available evidence.Method: We systematically searched the electronic databases including PubMed, Web of Science, and SCOPUS for population-based studies that measured either the odds or the risk of asthma in subjects with migraine as well as that of migraine in subjects with asthma. The titles and abstracts were screened by two independent reviewers to identify eligible studies, and this was followed by full-text review of the included studies. Newcastle–Ottawa Scale (NOS) was used to assess the risk of bias of included literature. A meta-analysis was conducted with Review Manager 5.3 Software to calculate the odds ratio (OR) for case-control and cross-sectional studies and either relative ratio (RR) or hazard ratio (HR) for cohort studies, and the source of heterogeneity was assessed. Subgroup and sensitivity analyses were conducted, and the I2 test were used to assess the source of heterogeneity. The funnel plot, Galbraith plot, and Egger's test were used to evaluate publication bias.Results: Fifteen published studies covering a total of 1,188,780 individuals were identified. Pooled analysis indicated that migraine was associated with increased odds (OR = 1.54; 95% CI: 1.34~1.77) and risk for asthma (HR = 1.42; 95% CI: 1.26~1.60), and asthma associated with increased odds (OR = 1.45; 95% CI: 1.22~1.72) and risk for migraine (HR = 1.47; 95% CI: 1.41~1.52).Conclusion: Migraine is a potential risk indicator for asthma, and vice versa, asthma is a potential risk indicator for migraine. However, future prospective cohort studies are warranted to provide more evidence concerning the detailed association between migraine and asthma.
Dermoscopic Patterns in Juvenile Xanthogranuloma Based on the Histological Classification
Authors: Xu Jiaosheng , Ma Lin 
Published: January 2021

Background: Several dermoscopic features of juvenile xanthogranuloma (JXG) have been previously described in single cases or small case series and need to be further verified in a large sample.Objective: We aimed to investigate the dermoscopic patterns of JXG in a large case series and the correlations of these with clinical features of different histopathological subtypes of JXG.Methods: Patients who underwent dermoscopic evaluation and had a histopathological diagnosis of JXG were recruited. Histological findings, including stage and Ki67 proliferative index and the dermoscopic features of each lesion were recorded.Results: Forty-one patients with JXG were included. The male to female ratio was 1.28: 1 and the median age of onset was 11 months (range: 0–95 months). Fourteen lesions were histologically categorized in the early stage, 17 in the developed stage, and 10 in the late stage. The “setting sun” pattern was observed in 35 lesions (85.4%) and “clouds” of paler yellow areas in 26 lesions (63.4%). The frequency of the “setting sun” pattern was higher in the early and developed stages (30/31) than in the late stage (5/10) (P = 0.002), while that of “clouds” of paler yellow areas was not significantly different between each stage. Branched linear vessels were detected in the early (11/14) and developed stage (6/17), but not in the late stage. The mean Ki67 index of the lesions with linear vessels was 11.8% (range: 2–40%), which was higher than that of lesions without linear vessels (mean index: 5%, range: 1–30%) (P = 0.005). The pigment network and whitish areas were only detected in 6 and 5 lesions in the late stage, respectively. The whitish areas presented either as streak or stellate shape. The pigment network exhibited either in a centric or a peripheral pattern.Conclusions: The “setting sun” pattern is the characteristic dermoscopic features of JXG in the early and developed stages, while whitish areas and pigment network are the characteristic patterns in the late stage. Linear vessels present as branched patterns and mostly occur in the early stage with a high proliferative index, indicating rapid growth. The whitish areas and pigment network may present in various patterns. Dermoscopy is a useful adjunctive tool in the diagnosis and staging of JXG.