bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.
Authors: Matsuoka Hiroshi , Hayashi Takahiro , Takigami Karen , Imaizumi Kazuyoshi , Shiroki Ryoichi , Ohmiya Naoki , Sugiura Kazumitsu , Kawada Kenji , Sawaki Akira , Maeda Koutarou , Ando Yousuke , Uyama Ihiro 
Published: June 2020

Abstract
Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are used for the treatment of various cancer types. However, immune-related adverse events (irAEs) occur in patients treated with ICIs. Several small-scale studies have reported the onset of irAEs and therapeutic effects of ICIs. Here we report a large-scale retrospective study covering a wide range of cancers. We evaluated irAEs and the therapeutic effects of ICIs and determined whether irAEs could be predicted.Methods: This study included patients treated with the anti-PD-1 antibodies nivolumab or pembrolizumab at Fujita Health University Hospital between December 2015 and March 2019. We retrospectively reviewed the electronic medical records for age, cancer type, pre-treatment blood test data, presence or absence of irAE onset, type and severity of irAEs, outcome of irAE treatment, response rate, progression-free survival and overall survival.Results: Two hundred-eighty patients received ICIs. The overall incidence of irAEs was 41.1% (115 patients), and the incidence of severe irAEs of grade 3 and higher was 2.8% (eight patients). The most common irAEs were skin disorders, thyroid disorders and interstitial pneumonia. Patients with irAEs were significantly older than those without irAEs (69.7 versus 66.0 years, P=0.02). The objective response rate (ORR) in patients with irAEs was 30.4%, which was significantly higher than in patients without irAEs (12.7%; P<0.01). Both the median overall and progression-free survival were significantly longer in patients with irAEs. Based on the blood test data obtained before ICI therapy, hypothyroidism, thyroid-stimulating hormone levels and thyroglobulin antibody levels were associated with the onset of irAEs. In many patients with irAEs of Common Terminology Criteria for Adverse Events Grade 3 or higher, re-administration of ICIs was difficult, and their outcomes were poor. In contrast, many patients with irAEs of a lower grade were able to resume ICI therapy.Conclusion: Although the onset of irAEs was difficult to be predicted based on pre-treatment tests. It appeared that the continuation of ICI therapy, along with early detection and adequate control of irAEs, might contribute to the improved prognosis of patients.
Is Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Indicated in Hepatobiliary Malignancies?
Authors: Leigh Natasha , Solomon Daniel , Pletcher Eric , Labow Daniel M. , Magge Deepa R. , Sarpel Umut , Golas Benjamin J. 
Published: June 2020

Abstract
Background: Hepatopancreaticobiliary malignancies with peritoneal carcinomatosis exhibit poor survival with current therapies; hepatocellular carcinoma 11 months with sorafenib, pancreaticobiliary 9-14 months with systemic chemotherapy. However, limited data exist on the utility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. Methods: We retrospectively reviewed our institutional hepatopancreaticobiliary malignancies with peritoneal carcinomatosis which underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 2007-2017 and analyzed perioperative and oncologic outcomes. Results: 17 patients were included; 9 hepatocellular carcinoma, 8 pancreaticobiliary (4 cholangiocarcinoma, 3 gallbladder, 1 pancreatic). PCI, number of organs resected, completeness of cytoreduction and 30-day morbidity were equivalent. Hepatocellular carcinoma received significantly less neoadjuvant therapy (11%, p=0.008), though adjuvant therapy rates were similar. At a median follow-up of 15 months, progression-free survival was similar amongst all cohorts. However, overall survival was longer in hepatocellular carcinoma (42 months vs. cholangiocarcinoma 19 months, gallbladder 8 months, pancreatic 15 months, p=0.206) with 59% 3-year overall survival (vs. 0% cholangiogarcinoma, 0% gallbladder, 0% pancreatic).Conclusions: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may offer a survival benefit in select hepatocellular carcinoma patients with peritoneal carcinomatosis, though has dubious utility in pancreaticobiliary malignancies.
The establishment of a rheumatoid arthritis primate model in Macaca fascicularis
Authors: Na Hyun Sik , Lee Seon-young , Min Hong Ki , Park Wan-je , Lee Jung-hwan , Cho Ka-hee , Hong Shin-hee , Kim Dae-hoon , Jhun Jooyeon , Choi Jeong-Won , Kim Sung-Min , Kwok Seung-Ki , Cho Mi-La , Park Sung-Hwan 
Published: June 2020

Abstract
Background: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies.Methods: We used a collagen-induced arthritis (CIA) model in Macaca fascicularis. CIA was induced by the immunization of chicken type II collagen. Swelling was measured as the longitudinal and transverse axes of 16 proximal interphalangeal joints. Results: A new system for visual evaluation was created, with a perfect score of 16. Individual behavioral analysis was also conducted. Serum was collected once a week after the first immunization. Blood chemistry and inflammatory cytokine parameters were higher in the CIA group than in the wild type group. Conclusion: In conclusion, we established CIA in M. fascicularis, and the results can be used for drug evaluation models.
The protective effects of liguzinediol on congestive heart failure induced by myocardial infarction and its relative mechanism
Authors: Chen Qi , Zhang Dini , Bi Yunhui , Zhang Weiwei , Zhang Yuhan , Meng Qinghai , Li Yu , Bian Huimin 
Published: June 2020

Abstract
Background: Heart failure (HF) is one of the most common causes of cardiovascular diseases in the world. Currently, the drugs used to treat HF in the clinic may cause serious side effects. Liguzinediol, 2, 5-dimethyl-3, 6-dimethyl-pyrazine, is a compound synthesized after the structural modification of ligustrazine (one active ingredient of Szechwan Lovage Rhizome). We aimed to observe the effects of liguzinediol on preventing HF and explore the related mechanisms.Methods: The ligation of left anterior descending coronary artery was operated to established the myocardial infarction (MI) model in Sprague–Dawley rats. Cardiac functions were recorded by echocardiography and hemodynamics. The changes in the Renin-Angiotensin-Aldosterone System (RAAS), inflammation, and oxidative stress were detected by radioimmunoassay and Elisa kits. Western blot and real-time PCR were applied to determine the expressions of the TGF-β1/Smads pathway.Results: Firstly, liguzinediol enhanced the systolic and diastolic functions of the heart in MI rats. Liguzinediol improved ventricular remodeling by reducing myocardial cell necrosis, as well as reducing collagen deposition and myocardial fibrosis. Then, liguzinediol suppressed the activation of RAAS, inhibited the synthesis of pro-inflammation factors, and reduced oxidative stress. In the end, liguzinediol also down-regulated the expressions of the TGF-β1/Smads pathway.Conclusions: Liguzinediol could alleviate HF caused by MI in rats, and the protective effect was associated with the regulation of the TGF-β1/Smads pathway.
FRET-based Tau seeding assay does not represent prion-like templated assembly of Tau filaments
Authors: Kaniyappan Senthilvelrajan , Tepper Katharina , Biernat Jacek , Chandupatla RamReddy , Hübschmann Sabrina , Irsen Stephan , Bicher Sandra , Klatt Christoph , Mandelkow Eva-Maria , Mandelkow Eckhard 
Published: June 2020

Abstract
Tau aggregation into amyloid fibers based on the cross-beta structure is a hallmark of several Tauopathies, including Alzheimer Disease (AD). Trans-cellular propagation of Tau with pathological conformation has been suggested as a key disease mechanism. This is thought to cause the spreading of Tau pathology in AD by templated conversion of naive Tau in recipient cells into a pathological state, followed by assembly of pathological Tau fibers, similar to the mechanism of nucleated polymerization proposed for prion pathogenesis. In cell cultures, the process is often monitored by a FRET assay where the recipient cell expresses the Tau repeat domain (TauRD) with a pro-aggregant mutation, fused to GFP-based FRET pairs. Since the size of the reporter GFP (barrel of ~3nm x 4nm) is ~7 times larger than the β-strand distance (0.47nm), this points to a potential steric clash. Hence, we investigated the influence of the GFP tag on Tau or TauRD aggregation. Using biophysical methods (light scattering, atomic force microscopy (AFM), and scanning-transmission electron microscopy (STEM)), we found that the assembly of TauRD-GFP was severely inhibited and incompatible with that of Alzheimer filaments. These observations argue against the hypothesis that the propagation of Tau pathology in AD is caused by the prion-like templated aggregation of Tau protein, transmitted via cell-to-cell spreading of Tau. Thus, even though the observed local increase of FRET in recipient cells may be a valid hallmark of a pathological reaction, our data argue that it is caused a process distinct from assembly of TauRD filaments.
The Mental Impact of COVID-19 Outbreak: A Population-Based Survey in Iran
Authors: Shahriarirad Reza , Erfani Amirhossein , Ranjbar Keivan , Bazrafshan Amir , Mirahmadizadeh Alireza 
Published: June 2020

Abstract
Objective: Disease outbreak not only carries the risk of death to the public due to the infection, it also endures an unbearable psychological impact on the mental health of the individuals. This study aims to explore and evaluate the burden of psychological problems on the Iranian general population during the outbreak of COVID-19.Method: A cross-sectional web-based survey was conducted among the general population of Iran age 15 and above. Demographic variables, depression, and anxiety symptoms were evaluated using the Patient Health Questionnaire-9 and General Anxiety Disorder-7 questionnaires.Results: Among the 8591 participants, the mean age was 34.37 (±11.25) years and 66.4% were female while 33.6% were male. Based on our results, 1295 (15.07%) and 1733 (20.17%) of the general population had depression and anxiety respectively. Based on the demographic variables, Among the risk factors for both anxiety and depression, one could name female gender, whereas getting information about the disease from medical journals and articles, being older and being married were considered as protective factors. In terms of depression, being a non-healthcare worker was a risk factor. On the other hand, for anxiety, having higher education was a protective factor while a higher number of individuals in a household was considered as a risk factor.Conclusions: This study identified a major mental health problem in the Iranian population during the time of the COVID-19 outbreak. Therefore, establishing a targeted mental health support program during the time of public emergencies, such as the disease outbreak, is advised.
Evaluation and utility of mitochondrial ribosomal genes for molecular systematics of parasitic nematodes
Authors: Chan Abigail Hui En , Chaisiri Kittipong , Morand Serge , Saralamba Naowarat , Thaenkham Urusa 
Published: June 2020

Abstract
Background Molecular advances have accelerated our understanding of nematode systematics and taxonomy. However, comparative analyzes between various genetic markers have led to discrepancies in nematode phylogenies. This study aimed to evaluate the suitability of using mitochondrial 12S and 16S ribosomal RNA genes for nematode molecular systematics. Methods To study the suitability of mitochondrial 12S and 16S ribosomal RNA genes as genetic markers for nematode molecular systematics, we compared them with the other commonly used genetic markers, nuclear internal transcribed spacer 1 and 2 regions, nuclear 18S and 28S ribosomal RNA genes, and mitochondrial cytochrome c oxidase subunit 1 gene. After that, phylum-wide primers for mitochondrial 12S and 16S ribosomal RNA genes were designed, and parasitic nematodes of humans and animals from 75 taxa with 21 representative species were inferred through phylogenetic analyzes. Phylogenetic analyzes were carried out using maximum likelihood and Bayesian inference algorithms. Results The phylogenetic relationships of nematodes based on the mitochondrial 12S rRNA gene supported the monophyly of nematodes in clades I, IV, and V, reinforcing the potential of this gene as a genetic marker for nematode systematics. In contrast, the mitochondrial 16S rRNA gene only supported the monophyly of clades I and V, providing evidence that the 12S rRNA gene is more suitable for nematode molecular systematics. In this study, subclades of clade III containing various nematode families were not monophyletic when the 16S or 12S rRNA gene was used as the genetic marker. This is similar to the phylogenetic relationship revealed by previous studies using whole mitochondrial genomes as genetic markers. Conclusions This study supports the use of the 12S rRNA gene as a genetic marker for studying the molecular systematics of nematodes to understand intra-phyla relationships. Phylum-wide primers for nematodes using mitochondrial ribosomal genes were prepared, which may enhance future studies. Furthermore, sufficient genetic variation in the mitochondrial 12S and 16S rRNA genes between species also allowed for accurate taxonomy to species level, revealing the potential of these two genes as genetic markers for DNA barcoding.
WITHDRAWN: IL-10-producing B cells regulated 1,3-β-glucan induced Th responses in coordinated with Treg
Authors: Liu Fangwei , Lu Yiping , Zeng Xinning , Chen Jie 
Published: June 2020

Abstract
Background: Repeated exposure to fungi contaminated dust can lead to multiple adverse effect on lung, such as hypersensitivity pneumonitis, granuloma even irreversible fibrosis. 1,3-β-glucan, as the major cell wall component of fungi, was considered as its exposure biomarker. Existing studies showed that series of Th response were involved in 1,3-β-glucan induced hypersensitivity pneumonitis, in which macrophages, regulatory T cells (Treg) and IL-10 producing B cells were reported to participate. The reciprocal interaction among those critical immune cells in 1,3-β-glucan induced inflammation were not investigated yet.Results: To clarify the regulatory mechanism of IL-10 producing B cells on Th and Treg, current study set up a primary cell co-culture system. Anti-CD22 antibody was injected intraperitoneally to generate IL-10 producing B cells deficiency mouse model. Cells were isolated and purified from different groups’ mice. Flow cytometry was used to check the phenotype of different cell subtypes. CBA assay and realtime PCR were used to examine the levels of multiple cytokines. Our results indicated that IL-10 producing B cells were involved in modulating 1,3-β-glucan induced inflammatory response. The modulation of IL-10 producing B cells on Th response after 1,3-β-glucan treatment was independent on cell-cell contact. What’s more, the modulation pattern of IL-10 producing B cells might be impaired without Treg response.Conclusions: IL-10-producing B cells regulated 1,3-β-glucan induced Th responses in coordinated with Treg.
Health services utilization and out-of-pocket (OOP) expenditures in public and private facilities in Pakistan: An empirical analysis of 2013-14 OOP Health Expenditure Survey
Authors: Khalid Faraz , Raza Wajeeha , Hotchkiss David R. , Soelaeman Rieza H. 
Published: June 2020

Abstract
Background As low- and middle-income countries (LMICs) progress towards achieving Universal Health Coverage (UHC), there is an increasing focus on measuring both out-of-pocket (OOP) expenditure and health services utilization within countries. While there have been several reforms to improve health services coverage and financial protection in Pakistan, there is limited empirical research comparing OOP expenditure and health services utilization between public and private facilities and exploring their determinants. In this paper, we have addressed this gap by using the 2013-2014 OOP Expenditure Survey Methods Our study is based on data from nationally representative household survey that includes 7,969 encounters from 4,293 households. In our analysis, we examined factors associated with two outcome variables; the sector where care was sought (public or private) and OOP expenditures. To investigate factors associated with the sector where care was sought, we fitted multivariate models stratified by type of care (i.e., inpatient and outpatient). Next, we fitted multivariate linear regression models to identify determinants of OOP expenditures stratified by type of care.Results  Our bivariate analysis shows that most encounters (82.5%) were in the private sector, and 85% of encounters were for outpatient visits. Expenditures on medicines and vaccines account for the largest proportion of OOP expenditures, followed by diagnostic tests and transportation. We found that the probability of seeking outpatient care in the private sector was higher for men, richer individuals, residents of Punjab and Sindh provinces, and households of smaller sizes. For inpatient care, we found that rural households and females with reproductive health concerns were more likely to seek private sector care. Importantly, our study found no significant difference in OOP expenditures between public and private facilities for both inpatient and outpatient visits. However, there were differences in OOP expenditures by sociodemographic factors. Conclusions This is the first study that has comprehensively investigated how healthcare utilization and OOP expenditures vary by sector, type of care, and socio-economic characteristics in Pakistan. Its findings will be useful for federal and provincial health ministries in planning and monitoring the impact of the next phase of their social health protection programs and supply side reforms.
Comparison of Clinical Characteristics According to the Existence of Secondary appendicitis in Pediatric Acute Gastroenteritis: A Retrospective Single Center study
Authors: Choi Soyoon 
Published: June 2020

Abstract
Background

In patients with acute gastroenteritis, radiologic findings are sometimes accompanied by secondary inflammation of the appendix. The purpose of this study was to evaluate the clinical features of acute gastroenteritis with secondary inflammation of the appendix.
Methods

Medical records from patients who underwent abdominal ultrasonography or computed tomography among those admitted for acute gastroenteritis at Haeundae Paik Hospital from June 2017 to May 2019 were retrospectively reviewed. Clinical features were compared by distinguishing patients with inflammation of the appendix from those without, based on their symptoms and laboratory findings.
Results

Of the 165 patients, 12 (7.3%) had secondary inflammation of the appendix on ultrasonography and/or computed tomography. Patients with secondary inflammation of the appendix were significantly older than those without (11.7 vs 6.1 years, p = 0.011) and more frequently had fever (83.3% vs 49.0%, p = 0.033), and high values of C-reactive protein (5.38 vs 0.32 mg/dl, p < 0.001). The proportion of viral pathogens was higher in patients without secondary appendicitis (0% vs 40.7%, p = 0.012), and the proportion of bacterial pathogens was higher in patients with secondary inflammation of the appendix (60% vs 15.1%, p = 0.004).
Conclusions

Patients with acute gastroenteritis accompanied by secondary appendicitis more commonly have fever, higher C-reactive protein levels, higher bacterial pathogen detection rates, and longer hospital stays. Treatment equivalent to that of bacterial infection is required for patients with secondary appendicitis, and that their symptoms should be closely and continuously monitored and followed-up.
Microbial diversity in rhizosphere soil of soybean grass under different cultivation methods in an alpine region
Authors: Zhang Ying , Liu Wenhui , Li Xilai , Zhang Zhiying , Su Beibei , Dao Ri-na , Wang Yan 
Published: June 2020

Abstract
Background

A large number of studies have shown that soybean grass with mixed seeding cultivation can significantly improve the yield and quality of forage grass compared with clean culture cultivation.This study explores the differences in the characteristics of the composition and diversity of the microbial community in the rhizosphere of soybean grasses between clean culture and mixed seeding methods in an alpine region. We used high-throughput sequencing technology to determine the microbial diversity and analytical methods to determine the physicochemical characteristics of plant rhizosphere soil of Avena sativa L. and Vicia sativa L.
Results

There were no significant differences in pH, total nitrogen, total phosphorus, and total potassium in the rhizosphere soil samples of soybean grasses under the clean culture and mixed seeding methods, while there were significant differences in the available nitrogen, available phosphorus, available potassium, and organic matter content (P < 0.05). The bacterial diversity of the rhizosphere soil of Avena sativa L. was the highest under the clean culture method, and the fungal diversity of the rhizosphere soil of Vicia sativa L. was the highest under the clean culture method. Furthermore, the microbial diversity of the rhizosphere was significantly different under the different cultivation methods (P < 0.05). The differences between the microbial species in the rhizosphere of the treated soil were at three class level. The abundance of Alphaproteobacteria and Actinobacteria in the rhizosphere of Avena sativa L. and Vicia sativa L. under the mixed seeding method was conspicuously higher than that of Avena sativa L. and Vicia sativa L. under the clean culture method, while the abundance of Gemmatimonadetes, Nitrospira, and Acidimicrobiia were significantly lower than that obtained under the clean culture method. Regarding fungal predominance, Mortierellomycetes was the most abundant (32.66%) under the mixed seeding method, while the abundance of Sordariomycetes and Leotiomycetes were significantly lower than that under clean culture. The distribution of bacterial and fungal community species in the rhizosphere differed significantly between the treatments. The Kyoto Encyclopedia of Genes and Genomes metabolism analysis showed that the metabolic pathways of functional genes in the soil microbial communities were similar.
Conclusions

Mixed sowing changed the diversity of plant rhizosphere microbial community structure and promoted plant yield.