bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Immune Checkpoint Inhibitors in Advanced Cancer patients with Autoimmune Disease: a Meta-Analysis
Authors: Cai Qi , Huo Geng-wei , Zhu Fu-yi , Yue Ping , Yuan Dong-qi , Chen Peng 
Published: May 2022

Abstract
Background: Cancer patients with autoimmune disease (AID) are usually excluded from clinical trials involving immune checkpoint inhibitors (ICIs); their safety and effectiveness remain uncertainty. Methods: The available electronic databases were systematically searched. We recorded the incidence of immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS) of included studies. Results: This meta-analysis included 11 studies comprising 5489 participants. The pooled risk ratio (RR) for any grade and grade ≥3 irAEs was 1.79 (95% confidence interval [CI]: 1.31-2.45) and 1.58 (95% CI: 1.06-2.36), respectively. The irAEs in the same system as the AID were referred to as AID-homogeneous irAEs, otherwise known as AID-heterogeneous irAEs. Subgroup analysis found that the higher risk of AID-homogeneous irAEs contributed to the higher risk of overall irAEs among patients with AID. The pooled hazard ratio (HR) for PFS and OS was 1.09 (95% CI: 0.96–1.25) and 1.10 (95% CI: 0.68–1.77), respectively. The results of PFS and OS subgroup analyses matched the overall results. Conclusion: patients with AID had a significantly higher risk of developing any grade and ≥3 grade irAEs under ICI therapy, specifically AID-homogeneous irAEs; however, AID-heterogeneous irAEs were higher among patients with AID than in those without. No statistically significant differences in PFS and OS were observed between two groups.
Metabolomic and transcriptomic exploration of the Biosynthetic Pathways of Uric Acid-reducing flavonoids in the fruit of Actinidia arguta Sieb. Zucc.
Authors: Wang Yubo , Dong Kuiling , Zhang Minghui , Yin Xiaojuan , Hao Chunhui , Irfan Muhammad , Chen Li-jing , Wang Yong 
Published: May 2022

Abstract
Extensive targeted metabolomic and transcriptomic analyses were used to determine the types of flavonoids present in the fruit of two varieties of Actinidia arguta Sieb. Zucc. cultivated in Northern China. Fractionation and preparative liquid chromatography were used to isolate and purify the potentially biologically active flavonoids chrysin (flavone1), rutin (flavone2), and daidzein (flavone3) from the fruit of Actinidia arguta Sieb. Zucc. The structures of these flavonoids were appraised using mass spectroscopy/high-performance liquid chromatography (MS-HPLC). Serum levels of uric acid (UA), urea nitrogen (BUN), creatinine (Cr), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and liver glycogen were measured in male Kunming mice treated with each flavonoid to determine biological effects of the flavonoids on the measured parameters. The three flavonoids were found to be mainly distributed within three metabolic pathways, namely the flavonoids and flavonol biosynthesis pathway(BP), the flavonoid BP, and the secondary metabolite BP. Through a correlation analysis of the transcriptome and metabolome, regulatory genes were screened for activity in the BPs of the three flavonoids. This is the first study to explore the UA-lowering activity of flavonoids in the fruit of Actinidia arguta Sieb., the main variety cultivated in Northern China. These data provide valuable information for understanding the biosynthetic mechanisms and regulatory pathways of flavonoids in Actinidia arguta Sieb. and contribute to its development as a food and drug homologous functional food.
Overexpressed C1q-TNF-related protein-9 in hypothalamic paraventricular nucleus ameliorates hypertension through modulating cytokines and attenuating oxidative stress in spontaneously hypertensive rats
Authors: Miao Yu-Wang 
Published: May 2022

Abstract
The adipocytokine C1q/TNF-related protein 9 (CTRP9) was recently reported to have multiple protective effects on cardiac and cardiovascular function. However, the exact role of CTRP9 in the progression of hypertension remains unclear. This study was designed to determine whether overexpressed CTRP9 in hypothalamic paraventricular nucleus (PVN) attenuates hypertension through modulating pro-inflammatorycytokines and attenuating oxidative stress in spontaneously hypertensive rats (SHRs). Our data on enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction showed that CTRP9 mRNA and protein content were markedly downregulated in SHRs. SHRs had higher mean arterial pressure (MAP) and plasma norepinephrine (NE). These rats also had higher levels of tumor necrosis factor alpha (TNF)-α, interleukin-1beta (IL-1β), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and higher gp91phox, gp47phox (subunits of NAD (P)H oxidase) expression and superoxide production in PVN. Bilateral PVN microinjection of adeno-associated virus (AAV)-CTRP9 significantly attenuated MAP and NE, also reduced the expressions of TNF-α, IL-1β, IL-6, MCP-1, gp91phox and gp47phox in PVN of SHRs, but not in WKY rats. The mRNA expression of TNF-α, IL-1β, IL-6, MCP-1, gp91phox and gp47phox are in accordance with their protein expression. In conclusion, CTRP9 in PVN ameliorated hypertension may through modulating cytokines and attenuating oxidative stress in spontaneously hypertensive rats.
The Clinical Significance of Integrin Subunit Alpha V in Cancers: From Small Cell Lung Carcinoma to Pan-cancer
Authors: Tang Yu-Lu , Li Guo-Sheng , Li Dong-Ming , Tang Deng , Huang Jie-Zhuang , Feng Hao , He Rong-Quan , Huang Zhi-Guang , Dang Yi-Wu , Kong Jin-Liang , Gan Ting-Qing , Zhou Hua-Fu , Zeng Jing-Jing , Chen Gang 
Published: May 2022

Abstract
Background: Little is known about the relationship between integrin subunit alpha V (ITGAV) and cancers. Materials & Methods: Using large sample size from multiple sources, the clinical roles of ITGAV expression in pan-cancer were explored. Results: Upregulated ITGAV mRNA expression was revealed in multiple cancers (p < .05). Decreased mRNA (SMD = −1.05) and increased protein levels of ITGAV were detected in small cell lung cancer (SCLC) (n = 865). ITGAV expression made it feasible to distinguish cancers from non-cancers (e.g., for SCLC and non-SCLC, AUC = 0.88, sensitivity = 0.78, specificity = 0.84), and represented a risk role in cancers’ prognosis (p < .05). Conclusion: ITGAV served as a potential marker for prognosis and identification of cancers including SCLC.
Gene signature of m6A-related targets to predict prognosis and immunotherapy response in ovarian cancer
Authors: Tan Wei , Liu Shiyi , Deng Zhimin , Dai Fangfang , Yuan Mengqin , Hu Wei , Cheng Yanxiang 
Published: May 2022

Abstract
Purpose: The aim of the study was to construct a risk score model based on m6A-related targets to predict overall survival and immunotherapy response in ovarian cancer.Methods: The gene expression profiles of 24 m6A regulators were extracted. Survival analysis screened 9 prognostic m6A regulators. Next, consensus clustering analysis was applied to identify clusters of ovarian cancer patients. Furthermore, 47 phenotype-related differentially expressed genes, strongly correlated with 9 prognostic m6A regulators, were screened and subjected to univariate and the least absolute shrinkage and selection operator (LASSO) cox regression. Ultimately, a nomogram was constructed which presented a strong ability to predict overall survival in ovarian cancer.Results: CBLL1, FTO, HNRNPC, METTL3, METTL14, WTAP, ZC3H13, RBM15B and YTHDC2 were associated with worse overall survival (OS) in ovarian cancer. Three m6A clusters were identified, which were highly consistent with the three immune phenotypes. What’s more, a risk model based on seven m6A-related targets was constructed with distinct prognosis. And the low-risk group are the best candidate population for immunotherapy. Conclusions: We comprehensively analyzed the m6A modification landscape of ovarian cancer and detected seven m6A-related targets as an independent prognostic biomarker for predicting survival. Furthermore, we divided patients into high- and low- risk groups with distinct prognosis and select the optimum population which may benefit from immunotherapy and constructed a nomogram to precisely predict ovarian cancer patients’ survival time and visualize the prediction results.
Fabrication of a novel eco-friendly hybrid biocomosite based on carboxymethyl chitosan /polypropylene glycol /activated carbon for the highly efficient removal of Cr (III) from the aquatic medium: Adsorption, kinetic and antimicrobial evaluations
Authors: Mohamed Eslam A. , Altalhi Amal A. , Negm Nabel. A. 
Published: May 2022

Abstract
Different nonionic biocomposite frameworks were prepared by supporting carboxymethylated chitosan polypropylene glycol on active carbon and characterized using sufficient characterization techniques. The prepared biocomposites comprised different modified chitosan to active carbon ratios. The biocomposites were achieved during remediation of chromium (III) ions from an aqueous medium. The influences of pH, chromium (III) ions concentration, time, and weight used in the remediation process were extensively studied to point out the optimized process conditions. The assigned optimum conditions of chromium (III) ions remediation were: 25 oC, using 0.6 g sorbents, and 100 ppm of ions concentration for 300 minutes at semi-neutral to neutral pH range of 6–7 to attain removal efficiency of 98.7%. The process was followed Freundlich adsorption isotherm and pseudo-second-order kinetics. The accumulation of ions onto biocomposites was regulated according to the intraparticle diffusion model, and the rate-determining step was the diffusion step. Increasing the active carbon-modified chitosan ratio in the biocomposites from 1:4 to 4:1, enhanced the remediation effectiveness of carboxymethylated chitosan in terms of equilibrium adsorption capacities increase from 67.93 mg/g to 70.25 mg/g. An opposing attitude was achieved by increasing the incorporated active carbon in the biocomposites during their antimicrobial efficacies assessments. The study presents a low-cost, eco-friendly, highly effective eliminator for highly contaminated aqueous media with Cr3+ ions. Furthermore, the prepared adsorbents exhibited high elimination efficiency in the presence of a high abundance of Cr3+ in the medium.
Scutellarin acts via MAPKs pathway to promote M2 polarization of microglial cells
Authors: Chen Haolun , Yang Li , Zhang Xiaolina , Jia Qiuye , Li Juanjuan , Zheng Liyang , Liu Tengteng , Qi Zhi , Yuan Yun , Wu Chunyun 
Published: May 2022

Abstract
Scutellarin, an herbal agent, is known to possess anti-oxidant and anti-inflammatory properties. In activated microglia, it has been reported that this is achieved through acting on the MAPKs, a key pathway that regulates microglia activation. This study sought to determine if scutellarin would affect the commonly described microglia phenotypes, namely, M1 and M2, thought to contribute to pro- and anti-inflammatory roles, respectively. This is in consideration of its potential effect on the polarization of microglia phenotypes that are featured prominently in cerebral ischemia. For this purpose, we have used an experimentally induced cerebral ischemia rat model and LPS-stimulated BV-2 cell model. Thus, by Western blot and immunofluorescence, we show here a noticeable increase in expression of M2 microglia markers, namely, CD206, Arg1, YM1/2, IL-4 and IL-10 in activated microglia both in vivo and in vitro. Remarkably, scutellarin treatment markedly augmented the increased expression of the respective markers in activated microglia. It is therefore suggested scutellarin can exert the polarization of activated microglia from M1 to M2 phenotype. Because M1 microglia are commonly known to be proinflammatory, while M2 microglia are anti-inflammatory and neuroprotective effect, it stands to reason therefore that with the increase of M2 microglia which became predominant by scutellarin, the local inflammatory response is ameliorated. More importantly, we have found that scutellarin promotes the M2 polarization through inhibiting the JNK and p38 signaling pathways, and concomitantly augmenting the ERK1/2 signaling pathway. This lends its strongly support from observations in LPS activated BV-2 microglia treated with p38 and JNK inhibitors in which expression of M2 markers was increased; on the other hand, in cells subjected to ERK1/2 inhibitor treatment, the expression was suppressed. In light of the above, MAPKs pathway is deemed to be a potential target of scutellarin in mitigating microglia mediated neuroinflammation in activated microglia.
Imaginary Powers of (K,1)-generalized Harmonic Oscillator
Authors: Teng Wentao 
Published: May 2022

Abstract
See Manuscript PDF file for complete Abstract.In this paper we will define and investigate the imaginary powers of the (k,1)-generalized harmonic oscillator −4 k, 1 = −kxk4 k + kxk and prove the Lp-boundedness (1 < p < ∞) and weak L1-boundedness of such operators. It is a parallel result to the Lp-boundedness (1 < p < ∞) and weak L1-boundedness of the imaginary powers of the Dunkl harmonic oscillator −4 k + kxk2. To prove this result, we develop the Calder´on–Zygmund theory adapted to the (k,1)-generalized setting by constructing the metric space of homogeneous type corresponding to the (k,1)-generalized setting, and show that are singular integral operators satisfying the corresponding H¨ormander type condition.
Documenting manifestations and impacts of recessive ataxia to develop patient-reported outcome.
Authors: Tremblay Marjolaine , Girard-Côté Laura , Brais Bernard , Gagnon Cynthia 
Published: May 2022

Abstract
Background. Autosomal recessive cerebellar ataxias (ARCA) are a group of rare inherited disorders characterized by degeneration or abnormal development of cerebellum. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is the second most prevalent in Europe. Objectives. The aim of this study is to provide a better understanding of manifestations and impacts of ARSACS. Methods. A systematic review of literature has been conducted followed by a qualitative study using semi-structured interviews and discussion groups to get the experience of people affected. Results. According to the PROMIS framework, results show manifestations and impacts in three components of health: physical, mental, and social. Fatigue and struggles with balance and dexterity are the are the physical manifestations of the disease most often cited by participants. Negative affects like frustration and depression are among the mental health impacts with some loss in cognitive abilities. Social health is the least documented component; nonetheless, people with the disease report significant impacts in terms of social relationships, activities and work. Conclusions. These findings shed a new light on the experience of people with recessive ataxia and identify key aspects to assess to improve their overall health.
The efficacy of platelet rich plasma in pelvic organ prolapse surgery : A protocol for scoping review
Authors: Saputra Akbar Novan Dwi , Rizal Dicky Moch , Pangastuti Nuring , Ayuandari Sarrah 
Published: May 2022

Abstract
Background : Platelet-rich plasma (PRP) is an autologous, self-blood product, anticoagulated blood product generated by centrifugation method of whole blood that primarily contains platelets at amounts up to 5 times those found in physiologic platelet concentrations. PRP contains multiple growth factors such as transforming growth factor (TGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and insulin-like growth factor-1 within the alpha granules of platelets (IGF-1). Platelets also contain antibacterial and fungicidal proteins, metalloproteinases, coagulation factors, and membrane glycoproteins, which can regulate inflammation by promoting the production of various integrins, interleukins, and chemokines. Pelvic organ prolapse occurs when the genitalia organ, bladder, rectum, and intestine protrude into the vaginal canal or even out of it due to the weakening of ligaments and muscles that serve as suspensors for the pelvic organs. Surgery is one of the treatment options for pelvic organ prolapse. The use of platelet rich plasma in pelvic organ prolapse surgery is becoming much more common. The goal of this procedure is to reconstruct the anatomical components of the pelvic supporting tissues and increase the healing process. To determine the efficacy of PRP on pelvic organ prolapse surgery, we will synthesize the available research on the use of platelet rich plasma for pelvic organ prolapse surgery. The goal of this study is to conduct a scoping study of the published research on the efficacy of platelet rich plasma for the surgery procedure of female pelvic organ prolapse. Methods/design : This review was conducted on research articles in PubMed, Proquest, EBSCO, ScienceDirect databases published between January 2010 – Desember 2021 regarding the use of platelet rich plasma for pelvic organ prolapse surgery. All primary research in human, case reports and case series will be included to evaluate the outcome of platelet rich plasma as an adjunct to conventional surgery in the treatment of pelvic organ prolapse. Discussion : This review will offer actual evidence of PRP's efficacy for pelvic organ prolapse surgery. This is a new approach, and the findings of this study are expected to inform clinical practice and ongoing research focused on improving outcome of pelvic organ prolapse surgery. Trial registration number : osf.io/gyr72
Parameters for drilling a stepped microhole of nitride ceramics using Taguchi-based grey relational analysis method
Authors: Chang Dar-Yuan , Lin Chien-Hung , Chien Hsiang-Cheng 
Published: May 2022

Abstract
Microdrilling is an essential process in the semiconductor industry to produce microholes for wafer testing instruments such as a wafer probe card. The microholes are laid on an insulating ceramic plate in an array form for piloting microprobes to their specified positions, which are commonly machined by a peck-drilling process. This study investigated the parameters of cutting speed, feed rate, and depth in the peck-drilling process for making a stepped microhole of nitride ceramic plates. A two-level microdrilling experiment was first carried out to investigate the thrust force in drilling a 310-µm-diameter through microhole for checking the interactivity between the drilling parameters. After clarifying parametric interactions, Taguchi’s three-level fractional-factorial experiment of a stepped microhole was performed to derive “preferred factorial level set” for minimizing the thrust force and improving hole characteristics. Furthermore, Grey Relational Analysis (GRA) model was built to infer “optimal parameters level design” for considering the multi-characteristic problem of the microhole drilled. Experimental validations were implemented to confirm the analytical results. Experimental data provide useful references for drilling a stepped microhole of nitride ceramic plates.
Activation of NF-κB signaling by dense granule protein GRA15 of a newly discovered type 1 Toxoplasma gondii strain
Authors: Guo Guanghao , Cui Jianmin , Song Lindong , Tang Lvqing , Fan Sijie , Zhao Junlong , Hu Min , Shen Bang , Fang Rui , Zhou Yanqin 
Published: May 2022

Abstract
Background
It has been reported that the NF-κB pathway, an important component of host defense system against pathogens infections, can be modulated by GRA15 of type 2 Toxoplasma gondii strains. A newly reported Toxoplasma strain (T.gHB1) belonging to type 1 showed polymorphic phenotypes comparable to the classic type 1 parasite, such as virulence determinant mechanisms. Therefore, it is worth investigating whether the novel type 1 Toxoplasma strain (T.gHB1) has an effect on host NF-κB signaling pathway.
Methods
The effects of T.gHB1 on host NF-κB pathway was investigated in HEK293T cells. The GRA15 gene product was analysed by bioinformatics method and its effect on NF-κB was examined by detection of the levels of phosphorylation and nuclear translocation of p65 by Western blotting (WB) and indirect fluorescence assay (IFA). Functional domain of GRA15 was mapped by using the luciferase reporter assay and its effects on p65 nuclear translocation and IκBα phosphorylation were examined by IFA and WB, respectively.
Results
We demonstrated that the NF-κB pathway signaling can be activated by the newly identified type 1 T.gHB1 strain of Toxoplasma, while other known type 1 RH parasites exerted an inhibitory effect. T.gHB1 GRA15 possesses only one transmembrane region with an extended C terminal region, which is distinct from other known GRA15 from type 2 parasites. T.gHB1 GRA15 could clearly induce IκBα phosphorylation and p65 nuclear translocation. Dual luciferase assays in HEK293T cells revealed a requirement for 194–518 aa of T.gHB1 GRA15 to effectively activate NF-κB.
Conclusions
The overall results indicated that the newly discovered type 1 isolate T.gHB1 and its GRA15 gene product can activate NF-κB through a classical pathway in mammalian cells. These results provide new sights for our understanding of the interaction between Toxoplasma parasites and its host.
Highly efficient CRISPR–Cpf1 genome editing toolkit development for Corynebacterium glutamicum and its application for vitamin production
Authors: Su Rui , Wang Ting , Bo Taidong , Cai Ningyun , Yuan Meng , Wu Chen , Jiang Hao , Peng Huadong , Chen Ning , Li Yanjun 
Published: May 2022

Abstract
Corynebacterium glutamicum has industrial track records for producing a variety of valuable products such as amino acids. Although CRISPR-based genome editing technologies have undergone immense developments in recent years, the suicide-plasmid-based approaches are still predominant for C. glutamicum genome manipulation. In this study, we developed a RecombinAtion Prior to Induced Double-strand-break (RAPID) genome editing technology for C. glutamicum, as Cpf1 cleavage was found to disrupt RecET-mediated homologous recombination (HR) of the donor template into the genome. The RAPID toolbox enabled highly efficient gene deletion and insertion, and notably, a linear DNA template was sufficient for gene deletion. Due to the simplified procedures and iterative operation property, this methodology could be widely applied in C. glutamicum genetic manipulations. As a proof of concept, a high-yield D-pantothenic acid (vitamin B5)-producing strain was constructed, which, to the best of our knowledge, achieved the highest reported titer of 18.62 g/L from glucose only.
QTL Analysis and Development of HRM Markers Associated with Fruit Shape in Interspecific Pears (Pyrus pyrifolia × P. bretschneideri)
Authors: Cho Sun-Heum , Oh Sewon , Han Hyeondae , Kim Keumsun , Jeong Hae Won , Kim Daeil 
Published: May 2022

Abstract
Fruit shape is one of the important quantitative traits in pear (Pyrus spp.) breeding program, thus genetic study related to fruit shape could be beneficial to pear breeding. Quantitative trait loci (QTL) analysis was carried out using ‘Whangkeumbae’ (P. pyrifolia, round) × ‘Yali’ (P. bretschneideri, pyriform) and high-resolution melting (HRM) markers were developed. The genetic linkage map of ‘Whangkeumbae’ × ‘Yali’ was constructed using single nucleotide polymorphisms (SNPs) derived from Axiom Pear 70K Genotyping Array and simple sequence repeats. The integrated genetic linkage map of ‘Whangkeumbae’ × ‘Yali’ showed ~90% of genome coverage, a total genetic distance of 998.2 cM, and a marker density of 1.6 cM. F1 progenies of ‘Whangkeumbae’ × ‘Yali’ showed normal distribution of fruit length (L), diameter (D), and L/D ratio. Three QTLs located in linkage group (LG) 6, 7, and 12 were identified with LOD thresholds of 2.8 to 3.0. Six HRM markers were developed using array-SNPs anchored in the QTLs and predicted fruit shape with 28.6 to 65.3% accuracy. Notably, accuracy was increased by ~90% using an HRM marker combination consisting of CBp06sn02, CBp07sn01, and CBp12sn03. These results could provide a better understanding of the genetic mechanism of fruit shape development and reducing pear breeding period.