bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patterns of large-vessel lesions are associated with treatment outcomes in large-vessel giant cell arteritis
Authors: Sugihara Takahiko , Uchida Haruhito A , Yoshifuji Hajime , Maejima Yasuhiro , Naniwa Taio , Katsumata Yasuhiro , Okazaki Takahiro , Ishizaki Jun , Murakawa Yohko , Ogawa Noriyoshi , Dobashi Hiroaki , Horita Tetsuya , Tanaka Yoshiya , Furuta Shunsuke , Takeuchi Tsutomu , Komagata Yoshinori , Nakaoka Yoshikazu , Harigai Masayoshi 
Published: October 2021

Abstract
ObjectiveTo evaluate whether the distribution of large-vessel lesions (LVLs) in giant cell arteritis (GCA) is associated with poor treatment outcomes.MethodsIn a retrospective, multi-centric, nationwide registry of GCA patients treated with glucocorticoids between 2007 and 2014, 68 newly-diagnosed patients with LVLs were identified by imaging. Non-achievement of clinical remission by week 24 and/or relapse within 104 weeks were primarily evaluated. Factors influencing the poor treatment outcome were analyzed using Cox proportional hazard modeling. Cumulative rates and median time to the first event were analyzed by the Kaplan-Meier method and log-rank testing.ResultsAortic lesions were detected in 72.1% of the 68 GCA patients with LVLs (defined as group 2). Patients without aortic lesions were classified as having large-vessel GCA with subclavian lesions (group 1) or atypical large-vessel GCA without subclavian lesions (group 3). The mean age and proportions of PMR in group 3 were higher than those in the other two groups. Cranial lesions were observed in 66.7%, 55.1%, and 80.0% of patients in groups 1, 2 and 3, respectively. In group 2, 73.5% had lesions in both the aorta and aortic branches. Group 1 had axillary lesions in 33.3%, and carotid lesions in 44.4%. Atypical LVLs in group 3 included pulmonary, hepatic or mesenteric lesions in addition to carotid lesions. Baseline doses of GCs were not different across the groups. Mean time to achievement of low-dose GC treatment (prednisolone ≤5 mg/day) was also not significantly different between the groups. The cumulative rate of poor treatment outcome over the two years was 11.1%, 55.3% and 88.0% in the groups 1, 2 and 3, respectively; mean time to the events was significantly different among the groups. Multivariable analysis showed that the risk of poor treatment outcome was significantly higher in the group 3.ConclusionsThe distribution of LVLs was associated with treatment outcomes in large-vessel GCA. In addition to subclavian arteries, lesions in aorta and aortic branches other than subclavian arteries should be evaluated by imaging for large-vessel GCA. The pattern of LVLs determined by imaging should be considered when determining treatment strategies for GCA.
Improving the Transglycosylation Activity of α-glucosidase From Xanthomonas Campestris Through Semi-rational Design for the Synthesis of Ethyl Vanillin-α-glucoside
Authors: Chen Luyi , Liu Yi , Zhou Yaoyao , Zhu Linjiang , Chen Xiaolong 
Published: October 2021

Abstract
The α-glucosidase (EC 3.2.1.20) Agl2 produced by Xanthomonas campestris shows high α-glucosyl transfer activity toward alcoholic and phenolic hydroxyl groups. Ethyl vanillin-α-glucoside, a precursor-aroma compound with improved water solubility and thermal stability, can be synthesized through the transglycosylation of ethyl vanillin by Agl2. However, its low ethyl vanillin-α-glucoside yield and ability to hydrolyze ethyl vanillin-α-glucoside limits for industrial applications. Rational design and site-directed mutagenesis were employed to generate three variants of X. campestris α-glucosidase: L145I, S272T and L145I/S272T, which displayed improved transglycosylation activity toward EV The ethyl vanillin-α-glucoside yield of L145I/S272T is the highest and is up to yield 52.41%. Besides, L145I/S272T also remarkably diminished the hydrolysis activity toward the transglycosylation product EVG compared to Agl2. Our rational design based the catalytic mechanism of the α-glucosidase reaction proved to be effective for producing mutants with improved the ratio of transglycosylation/hydrolysis of α-glucosidase, which provides an important theoretical basis for further research on the reaction mechanism of α-glucosidase.
Prognostic Analysis of Patients with Breast Cancer Based on Tumor Mutational Burden, DNA Damage Repair Genes, and Immune Infiltration
Authors: Yang Tianshu , Liu Jiaxiang , Wang Xin , Ma Tianyu , Yin Xin , Yang Yunkai , Yuan Baowen , Teng Xu , Yu Hefen , Wang Shuang , Huang Wei 
Published: October 2021

Abstract
Background
Breast cancer has a high tumor-specific death rate and poor prognosis. In this study, we aimed to provide a basis for the prognostic risk in patients with breast cancer using significant gene sets selected by analyzing tumor mutational burden (TMB) and DNA damage repair (DDR).
Methods
Breast cancer genomic and transcriptomic data were obtained from The Cancer Genome Atlas, and the breast tumor samples were grouped into high- and low-TMB groups based on the calculated TMB. The differentially expressed DDR genes between the two groups were used to construct the breast cancer prognosis model; they were also further analyzed, and 10 key prognostic genes were screened. Using least absolute shrinkage and selection operator (LASSO)-Cox regression analysis, seven genes were selected to construct a linear risk assessment model related to survival, and the patients were divided into high- and low-risk groups.
Results
The ability of the model to predict the 5-year and 10-year survival was assessed by time-dependent receiver operating characteristic (ROC) curves. The GSE26085 dataset was used to verify the prognostic risk model. Finally, immune cell abundance and infiltration between the high-and low-risk groups were compared.
Conclusions
We established a risk prognostic model based on the MDC1, PARP3, PSMB1, PSMB9, PSMD2, PSMD7, and PSMD14 genes, providing a basis for further exploration of a population-based prediction of prognosis and immunotherapy response in patients with breast cancer.
CREBRF p.Arg457Gln Promotes Obesity and Improves Insulin Sensitivity by Promoting Preadipocyte Differentiation and Reducing Oxidative Metabolism in Gene-modified Pig Models
Authors: Li Yingying , Wang Hai , Liao Yuan , Yan Quanmei , Ouyang Zhen , Zhao Yu , Zhang Quanjun , Lai Chengdan , Liu Zhaoming , Zhuang Zhenpeng , Li Hao , Zheng Shuwen , Wang Jiaowei , Li Chuan , Suo Yangyang , Lan Ting , Liu Yang , Ye Yinghua , Zou Qingjian , Dai Zhen , Nie Tao , Wu Donghai , Fan Nana , Lai Liangxue 
Published: October 2021

Abstract
Obesity is one of the most important risk factors for type 2 diabetes (T2DM). The CREBRF missense allele of rs373863828 (p.Arg457Gln) is associated with increased body mass index (BMI), yet reduced risk of T2DM in people with Pacific ancestry. To investigate the functional consequences of the CREBRF variant, we introduced the corresponding human mutation p.Arg457Gln into porcine genome by using a CRISPR/Cas9-mediated homologous recombination (HR)-dependent approach. The CREBRF p.Arg457Gln pig models displayed dramatically increased fat deposition, yet improved sensitivity to insulin. Transcriptome and metabolome analyses of subcutaneous white adipose tissues showed that the CREBRF p.Arg457Gln mutation promoted preadipocyte differentiation, which indicated that obesity was caused by increased number (hyperplasia) rather than size (hypertrophy) of adipocytes. In addition, the oxidative capacity decreased in the adipose tissue of pigs with CREBRF p.Arg457Gln variant. The pre-oxidative metabolite content (4-HNE and MDA) significantly decreased, while activity of antioxidant enzymes (GPX, SOD, and CAT) increased, thereby repressing oxidative metabolism of adipose tissue and reducing level of reactive oxygen species (ROS). The low reactive oxygen species could prevent insulin resistance and reduce risk of obesity-induced type 2 diabetes. This study provides further mechanistic insights into favourable adiposity resulting from CREBRF p.Arg457Gln.
SARS-CoV-2 Removal with a Polyurethane Foam Composite
Authors: Schoeler Guilherme Pereira , Afonso Thays França , Demarco Carolina Faccio , Barboza Victor dos Santos , Cadaval Tito Roberto Sant'anna , Igansi Andrei Valerão , Gelesky Marcos Alexandre , Giongo Janice Luehring , Voucher Rodrigo de Almeida , Delucis Rafael de Avila , Andreazza Robson 
Published: October 2021

Abstract
The pandemic of COVID-19 (SARS-CoV-2 disease) has been causing unprecedented health and economic impacts, alerting the world to the importance of basic sanitation and existing social inequalities. The risk of the spread and appearance of new diseases highlights the need for the removal of these pathogens through efficient techniques and materials. This study aimed to develop a polyurethane (PU) biofoam filled with dregs waste (leftover from the pulp and paper industry) for removal SARS-CoV-2 from the water. The biofoam was prepared by the free expansion method with the incorporation of 5wt% of dregs as a filler. For the removal assays, the all materials and its isolated phases were incubated for 24h with an inactivated SARS-CoV-2 viral suspension. Then, the RNA was extracted and the viral load was quantified using the quantitative reverse transcription (RT-qPCR) technique. The biofoam (polyurethane/dregs) reached a great removal percentage of 91.55%, whereas the isolated dregs waste was 99.03%, commercial activated carbon was 99.64%, commercial activated carbon/polyurethane was 99.30%, and neat PU foam reached was 99.96% for this same property and without statistical difference. Those new materials endowed with low cost and high removal efficiency of SARS-CoV-2 as alternatives to conventional adsorbents.
Application To Lipschitzian and Integral Systems Via Quadruple Coincidence Point in Fuzzy Metric Spaces
Authors: Hammad Hasanen A. , Sen Manuel De la 
Published: October 2021

Abstract

Without a partially ordered set, in this manuscript, we investigate quadruple coincidence point (QCP) results for commuting mapping in the setting of fuzzy metric spaces (FMSs). Furthermore, some relevant ndings are presented to generalize some of the previous results in this direction. Ultimately, non-trivial examples and applications to nd a unique solution for Lipschitzian and integral quadruple systems are provided to support and strengthen our theoretical results.
Fine Mapping the MAP2K5 Region Identified rs7175517 As a Causal Variant Associated With BMI in China And The UK Populations
Authors: Lu Ce , Wang Hai-Jun , Song Jie-Yun , Wang Shuo , Li Xue-Ying , Huang Tao , Wang Hui 
Published: October 2021

Abstract
Background: Genome-wide association studies (GWASs) have consistently identified MAP2K5 as the obesity susceptible gene. To deepen our understanding of the potential causal genetic variants of this region, a fine-mapping study of MAP2K5 was conducted. Results: First, a target single nucleotide polymorphisms (SNPs) sequencing of MAP2K5 was carried out in 2030 Chinese children and followed by a fine mapping with the UK biobank GWAS data in 264,838 adults to identify the leading SNPs within the MAP2K5 gene region. SNP rs7175517 (G>A) and rs4776970(T>A) were identified as the leading SNPs associated with BMI in both Chinese and the UK population. Second, colocalization of GWAS and expression quantitative trait loci (eQTL) analyses and bioinformatic functional annotations indicated that rs7175517 is the leading variants in MAP2K5 gene region functionally. Additionally, dual luciferase assay indicated that the G allele of rs7175517 reduced the mRNA expression of MAP2K5 in HEK293T cells. The possible mechanism was that the G allele of rs7175517 interacted with more RNA repressors from nuclei extracts, which was evidenced by electrophoretic mobility shift assays (EMSAs). Furthermore, the pathway enrichment analyses of the products from DNA pull-down and protein mass spectrometry demonstrated that the G allele of rs7175517 might interact with RNA catabolic or splicing transcription factors, which consequentially increased the adiposity deposition. Conclusions: SNP rs7175517 of MAP2K5 gene was the putative causal variant associated with BMI. More precisely designed in vitro or animal experiments are warranted to further delineate the function of MAP2K5 in the adipogenesis.
BarPlex v1.0: a multiplex PCR-based enrichment of genome-wide short segments that enable genetic studies in barley
Authors: Gao Guangqi , Yan Luxi , Cai Yu , Jiang Congcong , He Qiang , Tasnim Sarah , Feng Zongyun , Liu Jun , Zhang Jing , Yang Ping 
Published: October 2021

Abstract
Over the past 15 years sequencing methodologies have advanced greatly enabling high-throughput sequencing based genotyping of crop plants. In this study, we developed BarPlex v1.0, a robust and cost-efficient genotyping approach in barley (Hordeum vulgare L.). In this multiplex PCR-based amplification of five-hundred genome-wide segments, followed by high-throughput sequencing of barcoded PCR products, we obtained hundreds to thousands of polymorphic markers. Comparison of genotyping with BarPlex v1.0 to genotyping-by-sequencing (GBS) revealed a similar genetic diversity. The polymorphic markers revealed by BarPlex v1.0 were highly accurate, with an average sequencing depth >700x and a data missing rate <0.5%. By analyzing 1,068 genotypes of wild barley (brittle rachis; Hordeum vulgare ssp. spontaneum L.), Tibetan semi-wild barley (brittle rachis), landraces, cultivars, as well as an F2 population, this assay has been robust in studies of population diversity, variety pedigree, heterozygosity discrimination, linkage mapping, as well as genome-wide association study (GWAS). Notably, a diversity analysis in a population of Tibetan semi-wild barley suggested a close relationship with Chinese landraces, but a dramatic decrease in its genetic diversity, inferring that Tibet was not a center of domestication for the native wild barley.
Silencing of Mannitol Transporter Gene In Phelipanche Aegyptiaca Reduces The Parasite Development On The Host Root
Authors: Bari Vinay Kumar , Nassar Jackline Abu , Aly Radi 
Published: October 2021

Abstract
Parasitic weed Phelipanche aegyptiaca, is an obligate plant parasite which causes severe damage to host crops. Agriculture crops mainly belong to Brassicaceae, Leguminosae, Cruciferae and Solanaceae plant families affected by this parasitic weed which leads to devastating loss to crops yield and economic growth. This root specific parasitic plant is not able to complete its life-cycle without a suitable host and is totally dependent on the host plant for organic nutrients. Therefore, flow of organic solute molecules towards parasites is essential for the survival of the parasitic weed and disturbance in this network modulated host-parasitic interaction, which induces resistance in host against these parasitic weeds. To develop host resistance to this parasitic weed, we silenced selected prominent genes associated with P. aegyptiaca using virus-induced gene silencing (VIGS) methods. Our results demonstrated that the total number of parasite tubercle attached to root of the host plant Nicotiana benthamiana significantly reduced upon silencing of P. aegyptiaca specific gene which encodes mannitol transporter, however silencing of other gene(s), have no significant effects. Thus, our study indicates that mannitol transport plays an important role in host-parasite interaction and silencing of this gene causes development of host resistance against this parasite.
A Clinical Research of Ceritinib Treating Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer With Brain Metastasis
Authors: Cui Saiqiong , Liu Xin , Li Dan , Yang Dafu , Dai Zhaoxia 
Published: October 2021

Abstract
Objective

As a second-generation oral anaplastic lymphoma kinase (ALK) inhibitor, ceritinib was recommended as posterior line therapy in patients with crizotinib resistance or intolerance. While in the real world, the clinical efficacy and safety of ceritinib, 450mg/d, taken with a low-fat meal in crizotinib resistant patients, especially with brain metastases, are still to be further investigated.
Methods

This retrospective analysis was conducted on patients with ALK- positive advanced non-small cell lung cancer (NSCLC) between May 2017 and December 2020 in our hospital, who were crizotinib resistant or intolerant. The aim was to analyze the clinical efficacy and safety of ceritinib as posterior line therapy in patients, especially in those with brain metastases, and to further explore the efficacy against rare fusion of ALK and the option after ALK inhibitor resistance. RECIST (1.1) criteria were adopted, and for relevant statistical analysis, RStudio was used.
Results

Of the 13 cases treated with ceritinib, 8 were treated as second-line therapy, 5 as third-line or fourth-line treatment. Of the total, 12 had brain metastases, 3 had received brain radiotherapy previously, and 1 had received surgical treatment for brain metastases previously. There were 8 cases evaluated as partial remission (PR), 2 evaluated as stable disease (SD), and 3 unevaluable for the response. There were 1 case of PKNOX2-ALK fusion and 1 case of IGR-ALK fusion observed as rare ALK fusion, and intracranial lesions were evaluated as PR for both. There were 6 cases received subsequent targeted therapy after progression of ceritinib, including 5 with alectinib and 1 with ensartinib, all of which showed response. In 13 cases, by the terminal time of follow-up, median progression-free survival (PFS) was 7.4 m, disease control rate (DCR) was 76.92%, overall response rate (ORR) was 61.54%, and median overall survival (OS) was 25.4m. In 12 cases with brain metastasis, 9 were suitable for intracranial response evaluation, of which, 1 case achieved CR for intracranial lesions, 7 achieved PR and 1 SD was observed, ORR was 88.89%, and DCR was 100%. The adverse events rate of any grade was 91.67%, the common adverse events were diarrhea (46.15%), AST level increased (41.67%), ALT level increased (33.33%), increased GGT (33.33%), increased ALP (25.00%), nausea (16.67%), increased creatinine (16.67%). Other reported AEs were cough, vomiting, dizziness, arthralgia and fatigue, 1 case (8.33%) each.
Conclusion

Ceritinib 450mg taken with taken with low-fat meal showed good efficacy and safety in crizotinib resistant patients with central nervous system metastasis, and also, it is effective in some cases with rare fusion of ALK.
Glucose-Lowering and the Risk of Cardiovascular Events with Novel Antidiabetic Therapies: A Systematic Review and Additive-effects Network Meta-Analysis
Authors: de Carvalho Luiz Sergio Fernandes , Nogueira Ana Claudia Cavalcante , Cintra Riobaldo Marcelo Ribeiro , Bonilha Isabella , Luchiari Beatriz , Benchimol Alexander , Couri Carlos Eduardo Barra , Borges Jairo Lins , Barreto Joaquim , Sposito Andrei Carvalho 
Published: October 2021

Abstract
Background: Among individuals with type 2 diabetes mellitus (T2DM), RCTs designed to investigate the cardiovascular effects of achieving HbA1c ≤7.0% by using insulin and sulfonylureas were unable to prevent the incidence of major adverse cardiovascular events (MACE) defined as CV death, non-fatal myocardial infarction, and non-fatal stroke. Intense glucose-lowering with newer antidiabetic therapies (ADTs) including SGLT2i, GLP1-RA, pioglitazone and DPP4i show lower risk of hypoglycemia and could lead to additive effect in preventing MACE. In this context, this study was designed to assess the impact of the HbA1c levels achieved with newer ADTs on the risk of MACE. Methods. We searched MEDLINE/PubMed, Cochrane and ClinicalTrials.gov. RCTs published up to January/2021 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks, were selected. Data was extracted by four independent observers following PRISMA guidelines. We performed a systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression to assess the impact of achieved HbA1c on incident MACE. Results. A total of 122 RCTs were included with 139 treatment arms, 256,990 individuals, and 689,346 individuals-years who were randomized to an active treatment vs. control group. Therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo (HR 0.88 [95%CI 0.83, 0.94, p<0.001], 0.89 [95% CI 0.85, 0.94, p<0.0001], and 0.86 [95% CI 0.76, 0.98, p=0.025], respectively). The achievement of HbA1c≤7.0% in RCTs with SGLT2i, DPP4i, TZD, or GLP1-RA in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; p=0.039) compared with HbA1c>7.0%. All-cause mortality was not influenced by HbA1c thresholds.Conclusions: Achieving lower glucose levels with newer ADTs is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality. Targeting HbA1c between 6.5 and 7% with SGLT2i, GLP1A, pioglitazone or DPP4i brings cardiovascular benefits considering the available RCT evidence.Study registration: PROSPERO CRD42020200649
A Comprehensive Study On Soundness, Microstructure and Uniformity of 2024 Aluminum Cups Hydro-Mechanically Drawn at Elevated Temperatures
Authors: Yaghoubi Saeed , Fereshteh-Saniee Faramarz 
Published: October 2021

Abstract
In the present research work, the hydro-mechanical deep drawing (HMDD) process of 2024 aluminum alloy is performed experimentally and numerically for elevated temperatures. The main variables of the forming process include the fluid pressure, the pre-bulge pressure and the process temperature. The effects of these parameters on the thickness distribution and uniformity index of the final product have been investigated. Using the hardness test, the preferred crystallographic orientation, the energy dispersive spectroscopy and microstructure images obtained from an optical microscope and a scanning electron microscope, the relationship between the grain size, hardness and the effective plastic strain are studied and discussed. The findings imply that the HMDD process without the pre-bulge pressure reduces the uniformity of the final product and, on the other hand, excessive increase in this parameter causes tearing of the workpiece. The hardness distribution along the cup wall was in agreement with grain refinement and the Hall-Petch relationship, but it was not correspond to the expectations made via the texture analyses. The images gained from the energy dispersive spectroscopy for different areas of the 2024 Al sample demonstrated that the Al2Cu precipitations in the product wall were finer than the other areas and mainly dispersed at the grain boundaries. This type of precipitation distribution was the main origin for increasing the hardness of the cup wall in comparison with the cup corner and bottom. In other words, the precipitation hardening overwhelmed the influence of the preferred orientation of the grains in HMDD operation of Al 2024.