bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-cancer analysis of UBE2T with a focus on prognostic and immunological roles in lung adenocarcinoma
Authors: Cao Kui , Ling Xiaodong , Jiang Xiangyu , Ma Jianqun , Zhu Jinhong 
Published: November 2022

Abstract
Background
Ubiquitin-conjugating enzyme E2 T (UBE2T) is a potential oncogene. However, Pan-cancer analyses of the functional, prognostic and predictive implications of this gene are lacking.

Methods
We first analyzed UBE2T across 33 tumor types in The Cancer Genome Atlas (TCGA) project. We investigated the expression level of UBE2T and its effect on prognosis using the TCGA database. The correlation between UBE2T and cell cycle in pan-cancer was investigated using the single-cell sequencing data in Cancer Single-cell State Atlas (CancerSEA) database. The Weighted Gene Co-expression Network analysis (WGCNA), Univariate Cox and Least absolute shrinkage and selection operator (LASSO) Cox regression models, and receiver operating characteristic (ROC) were applied to assess the prognostic impact of UBE2T-related cell cycle genes (UrCCGs). Furthermore, the consensus clustering (CC) method was adopted to divide TCGA-lung adenocarcinoma (LUAD) patients into subgroups based on UrCCGs. Prognosis, molecular characteristics, and the immune panorama of subgroups were analyzed using Single-sample Gene Set Enrichment Analysis (ssGSEA). Results derived from TCGA-LUAD patients were validated in International Cancer Genome Consortium (ICGC)-LUAD data.

Results
UBE2T is highly expressed and is a prognostic risk factor in most tumors. CancerSEA database analysis revealed that UBE2T was positively associated with the cell cycle in various cancers(r > 0.60, p < 0.001). The risk signature of UrCCGs can reliably predict the prognosis of LUAD (AUC1 year = 0.720, AUC3 year = 0.700, AUC5 year = 0.630). The CC method classified the TCGA-LUAD cohort into 4 UrCCG subtypes (G1–G4). Kaplan–Meier survival analysis demonstrated that G2 and G4 subtypes had worse survival than G3 (Log-rank test PTCGA training set < 0.001, PICGC validation set < 0.001). A comprehensive analysis of immune infiltrates, immune checkpoints, and immunogenic cell death modulators unveiled different immune landscapes for the four subtypes. High immunophenoscore in G3 and G4 tumors suggested that these two subtypes were immunologically “hot,” tending to respond to immunotherapy compared to G2 subtypes (p < 0.001).

Conclusions
UBE2T is a critical oncogene in many cancers. Moreover, UrCCG classified the LUAD cohort into four subgroups with significantly different survival, molecular features, immune infiltrates, and immunotherapy responses. UBE2T may be a therapeutic target and predictor of prognosis and immunotherapy sensitivity.
Acceptability of pre-referral rectal artesunate for severe malaria in children under 5 years by health workers and caregivers in the Democratic Republic of the Congo, Nigeria and Uganda
Authors: Awor Phyllis , Kimera Joseph , Athieno Proscovia , Tumukunde Gloria , Okitawutshu Jean , Tshefu Antoinette , Omoluabi Elizabeth , Signorell Aita , Brunner Nina , Kalenga Jean-Claude , Akano Babatunde , Ayodeji Kazeem , Okon Charles , Yusuf Ocheche , Delvento Giulia , Lee Tristan , Burri Christian , Lengeler Christian , Hetzel Manuel W. 
Published: November 2022

Abstract
Background
For children below 6 years with suspected severe malaria attending a health care provider unable to provide parenteral malaria treatment, pre-referral rectal artesunate (RAS) is recommended by the World Health Organization to prevent death and disability. A number of African countries are in the process of rolling out quality-assured RAS for pre-referral treatment of severe malaria at community-level. The success of RAS depends, among other factors, on the acceptability of RAS in the communities where it is being rolled-out. Yet to date, there is limited literature on RAS acceptability. This study aimed to determine the acceptability of RAS by health care providers and child caregivers in communities where quality assured RAS was rolled out. This study was nested within the comprehensive multi-country observational research project Community Access to Rectal Artesunate for Malaria (CARAMAL), implemented in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Data from three different sources were analysed to understand RAS acceptability: interviews with health workers during three health care provider surveys (N = 341 community health workers and 467 primary health facility workers), with caregivers of children < 5 years of age during three household surveys (N = 9332 caregivers), and with caregivers of children < 5 years of age who were treated with RAS and enrolled in the CARAMAL Patient Surveillance System (N = 3645 caregivers).

Results
RAS acceptability was high among all interviewed stakeholders in the three countries. After the roll-out of RAS, 97–100% heath care providers in DRC, 98–100% in Nigeria and 93–100% in Uganda considered RAS as very good or good. Majority of caregivers whose children had received RAS for pre-referral management of severe malaria indicated that they would want to get the medication again, if their child had the same illness (99.8% of caregivers in DRC, 100% in Nigeria and 99.9% in Uganda). In three household surveys, 67–80% of caregivers whose children had not previously received RAS considered the medication as useful.

Conclusion
RAS was well accepted by health workers and child caregivers in DRC, Nigeria and Uganda. Acceptability is unlikely to be an obstacle to the large-scale roll-out of RAS in the studied settings.
Poor semen parameters are associated with abnormal methylation of imprinted genes in sperm DNA
Authors: Song Bing , Chen Yujie , Wang Chao , Li Guanjian , Wei Zhaolian , He Xiaojin , Cao Yunxia 
Published: November 2022

AbstractBackgroundAltered sperm DNA methylation patterns of imprinted genes as well as certain spermatogenesis-related genes has been proposed as a possible mechanism of male subfertility. Some reports suggest that there is an elevated risk of congenital diseases, associated with imprinted genes, in children conceived via intra-cytoplasmic sperm injection, due to the involvement of spermatozoa with aberrant imprinted genes obtained from infertile men.MethodsIn this study, the DNA methylation status of the promoter regions of six imprinted genes, namely potassium voltage-gated channel subfamily Q member 1 (KCNQ1), maternally expressed gene 3 (MEG3), insulin-like growth factor 2 (IGF-2), KCNQ1 overlapping transcript 1 (KCNQ1OT1), mesoderm specific transcript (MEST), and paternally expressed gene 3 (PEG3), were detected by a next generation sequencing-based multiple methylation-specific polymerase chain reaction analysis of sperm samples obtained from 166 men who sought fertility evaluation in our Reproductive Medicine Center. Thereafter, the semen samples were classified into subgroups according to sperm motility and DNA integrity status.ResultsAs compared to the normozoospermic group, the samples of the asthenospermic group exhibited significant hypermethylation in two CpG sites ofIGF-2and significant hypomethylation in one CpG site ofKCNQ1as well as three CpG sites ofMEST(P < 0.05). However, we did not observe any significant differences in the overall methylation levels of these six imprinted genes (P > 0.05). Additionally, we found that 111 of 323 CpG sites were hypomethylated in the group with DNA fragmentation index (DFI) ≥ 30% as compared to the group with DFI < 30% (P < 0.05). In this case, there were significant differences in the overall methylation levels ofMEG3,IGF-2,MEST, andPEG3(P < 0.05), but not in that ofKCNQ1OT1andKCNQ1(P > 0.05). Hence, aberrant methylation patterns of imprinted genes were more prevalent in males with poor sperm quality, especially in those with severe sperm DNA damage.ConclusionIn conclusion, abnormal DNA methylation of some CpG sites of imprinted genes are associated with poor sperm quality, including asthenospermia and severe sperm DNA impairment.
Reach-to-grasp kinematics and kinetics with and without visual feedback in early-stage Alzheimer’s disease
Authors: Zhang Jianhong , Xiao Yunling , Li Zong-Ming , Wei Na , Lin Leitong , Li Ke 
Published: November 2022

AbstractThis study aimed to investigate the effects of early-stage Alzheimer’s disease (AD) on the reach-to-grasp kinematics and kinetics with and without visual supervision of the grasping arm and hand. Seventeen patients who had been diagnosed with early-stage AD and 17 age- and gender-matched, cognitive normal (CN) adults participated in the experiment. A mirror operating system was designed to block the visual feedback of their grasping hand and forearms but to virtually show grasped targets. The target for reach-to-grasp kinematics was a reflective marker installed on a base; and the target for reach-to-grasp kinetics was a custom-made apparatus installed with two six-component force/torque transducers. Kinematics and kinetic parameters were used to quantify the reach-to-grasp performances. Results showed that the early-stage AD remarkably decreased the reaching speed, reduced the grasping accuracy and increased the transportation variability for reach-to-grasp kinematics. For kinetic analysis, early-stage AD extended the preload duration, disturbed the grip and lift forces coordination, and increased the feedforward proportion in the grasping force control. The AD-related changes in the reach-to-grasp kinematic and kinetic parameters depended on visual feedback and were associated with nervous system function according to correlation analyses with the neuropsychological testing. These results suggest that the abnormal kinematic and kinetic characteristics may correlate with the neuropsychological status of early-stage AD, and that the reach-to-grasp kinematic and kinetic maneuver could potentially be used as a novel tool for non-invasive screening or evaluation of early-stage AD.
Zishen Pill alleviates diabetes in Db/db mice via activation of PI3K/AKT pathway in the liver
Authors: Wu You , Sun Boju , Guo Xiaoyuan , Wu Lili , Hu Yaomu , Qin Lingling , Yang Tao , Li Mei , Qin Tianyu , Jiang Miao , Liu Tonghua 
Published: November 2022

Abstract
Background
The rising global incidence of type 2 diabetes mellitus (T2DM) highlights a need for new therapies. The Zishen Pill (ZSP) is a traditional Chinese herbal decoction that has previously shown hypoglycemic effects in C57BL/KsJ-db/db mice, although the therapeutic mechanism remains unknown. This study aims to explore the underlying mechanisms of ZSP’s hypoglycemic effects using db/db mice.

Methods
Db/db mice were divided into two groups: model group and ZSP group, while wt/wt mice were used as a normal control. ZSP was given to mice by gavage for 40 days. During treatment, blood glucose level and body weight were monitored continuously. Oral glucose tolerance test (OGTT) was performed at day 35. Blood and tissue samples were collected at the end of treatment for further analyses. Mice liver samples were analyzed with mRNA transcriptomics using functional annotation and pathway enrichment to identify potential mechanisms that were then explored with qPCR and Western Blot techniques.

Results
ZSP treatment significantly reduced weight gain and glycemic severity in db/db mice. ZSP also partially restored the glucose homeostasis in db/db mice and increased the hepatic glycogen content. Transcriptomic analyses showed ZSP increased expression of genes involved in glycolysis including Hk2, Hk3, Gck and Pfkb1, and decreased expression of G6pase. Additionally, the gene and protein expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and Csf1 and Flt3 mRNA expression were significantly upregulated in ZSP group.

Conclusion
ZSP treatment reduced the severity of diabetic symptoms in db/db mice. ZSP increased expression of genes associated with glycogen synthesis and glycolysis, and decreased gluconeogenesis via the enhancement of the PI3K/AKT signaling in the liver.
Scaffold Generator: a Java library implementing molecular scaffold functionalities in the Chemistry Development Kit (CDK)
Authors: Schaub Jonas , Zander Julian , Zielesny Achim , Steinbeck Christoph 
Published: November 2022

AbstractThe concept of molecular scaffolds as defining core structures of organic molecules is utilised in many areas of chemistry and cheminformatics, e.g. drug design, chemical classification, or the analysis of high-throughput screening data. Here, we present Scaffold Generator, a comprehensive open library for the generation, handling, and display of molecular scaffolds, scaffold trees and networks. The new library is based on the Chemistry Development Kit (CDK) and highly customisable through multiple settings, e.g. five different structural framework definitions are available. For display of scaffold hierarchies, the open GraphStream Java library is utilised. Performance snapshots with natural products (NP) from the COCONUT (COlleCtion of Open Natural prodUcTs) database and drug molecules from DrugBank are reported. The generation of a scaffold network from more than 450,000 NP can be achieved within a single day.
Reinforcement learning empowered multi-AGV offloading scheduling in edge-cloud IIoT
Authors: Liu Peng , Liu Zhe , Wang Ji , Wu Zifu , Li Peng , Lu Huijuan 
Published: November 2022

AbstractThe edge-cloud computing architecture has been introduced to industrial circles to ensure the time constraints for industrial computing tasks. Besides the central cloud, various numbers of edge servers (ESes) are deployed in a distributed manner. In the meantime, most large factories currently use auto guided vehicles (AGVs). They usually travel along a given route and can help offload tasks to ESes. An ES maybe accessed by multiple AGVs, thus incurring offloading and processing delays due to resource competition. In this paper, we investigate the offloading scheduling issue for cyclical tasks and put forth the Multi-AGV Cyclical Offloading Optimization (MCOO) algorithm to reduce conflicts. The solution divides the offloading optimization problem into two parts. Firstly, the load balancing algorithm and greedy algorithm are utilized to find the optimal allocation of tasks for a single AGV under limited conditions. Then, multiple AGVs are asynchronously trained by applying the Reinforcement Learning-based A3C algorithm to optimize the offloading scheme. The simulation results show that the MCOO algorithm improves the global offloading performance both in task volume and adaptability compared with the baseline algorithms.
Gryllus bimaculatus extract protects against palmitate-induced β-cell death by inhibiting ceramide synthesis
Authors: Park Ie Byung , Kim Min Hee , Han Jung-Soon , Park Woo-Jae 
Published: November 2022

AbstractType I diabetes mellitus is an autoimmune disease characterized by the destruction of β-cells, leading to severe insulin deficiency. Environmental factors and genetic predisposition are implicated in β-cell destruction, which is the final step in a cascade of complex events. Possible triggers of β-cell destruction are activation of Fas, activation of perforin, increased generation of reactive oxygen species, increased production of inflammatory cytokines, and endoplasmic reticulum (ER) stress. In this study, we examined whether Gryllus bimaculatus (GB) extract could prevent palmitate-induced β-cell apoptosis. Exposure to GB extract prevented palmitate-induced death of MIN6 cells, a mouse pancreatic β-cell line. Palmitate increased total ceramide levels with the elevation of ceramide synthase (CerS)1, CerS4, and CerS6 expressions. Treatment with GB extract decreased the levels and expressions of ceramides related to insulin resistance. CerS4 and CerS6 overexpression, but not CerS1 overexpression, increased palmitate-induced MIN6 cell death by increasing ceramide synthesis. Oppositely, inhibition of ceramide synthesis by fumonisin B1 treatment partially recovered palmitate-induced MIN6 cell death. Furthermore, GB extract reduced ER stress (phosphorylation of PERK and eIF2α), NF-κB–iNOS signaling, and the phosphorylation of MAP kinase (JNK, p38). GB extract reduced pro-apoptotic Bax protein expression but increased anti-apoptotic Bcl2 expression. In addition, CerS4 and CerS6 overexpression aggravated impairment of insulin secretion by palmitate, but GB extract recovered it. In conclusion, GB could be a functional food that improves palmitate-induced β-cell death and insulin secretion.
Cross-generational bacterial strain transfer to an infant after fecal microbiota transplantation to a pregnant patient: a case report
Authors: Wei Shaodong , Jespersen Marie Louise , Baunwall Simon Mark Dahl , Myers Pernille Neve , Smith Emilie Milton , Dahlerup Jens Frederik , Rasmussen Simon , Nielsen Henrik Bjørn , Licht Tine Rask , Bahl Martin Iain , Hvas Christian Lodberg 
Published: November 2022

Abstract
Background
Fecal microbiota transplantation (FMT) effectively prevents the recurrence of Clostridioides difficile infection (CDI). Long-term engraftment of donor-specific microbial consortia may occur in the recipient, but potential further transfer to other sites, including the vertical transmission of donor-specific strains to future generations, has not been investigated. Here, we report, for the first time, the cross-generational transmission of specific bacterial strains from an FMT donor to a pregnant patient with CDI and further to her child, born at term, 26 weeks after the FMT treatment.

Methods
A pregnant woman (gestation week 12 + 5) with CDI was treated with FMT via colonoscopy. She gave vaginal birth at term to a healthy baby. Fecal samples were collected from the feces donor, the mother (before FMT, and 1, 8, 15, 22, 26, and 50 weeks after FMT), and the infant (meconium at birth and 3 and 6 months after birth). Fecal samples were profiled by deep metagenomic sequencing for strain-level analysis. The microbial transfer was monitored using single nucleotide variants in metagenomes and further compared to a collection of metagenomic samples from 651 healthy infants and 58 healthy adults.

Results
The single FMT procedure led to an uneventful and sustained clinical resolution in the patient, who experienced no further CDI-related symptoms up to 50 weeks after treatment. The gut microbiota of the patient with CDI differed considerably from the healthy donor and was characterized as low in alpha diversity and enriched for several potential pathogens. The FMT successfully normalized the patient’s gut microbiota, likely by donor microbiota transfer and engraftment. Importantly, our analysis revealed that some specific strains were transferred from the donor to the patient and then further to the infant, thus demonstrating cross-generational microbial transfer.

Conclusions
The evidence for cross-generational strain transfer following FMT provides novel insights into the dynamics and engraftment of bacterial strains from healthy donors. The data suggests FMT treatment of pregnant women as a potential strategy to introduce beneficial strains or even bacterial consortia to infants, i.e., neonatal seeding.
Phosphoproteomics revealed cellular signals immediately responding to disruption of cancer amino acid homeostasis induced by inhibition of l-type amino acid transporter 1
Authors: Okanishi Hiroki , Ohgaki Ryuichi , Xu Minhui , Endou Hitoshi , Kanai Yoshikatsu 
Published: November 2022

Abstract
Background
Cancer-upregulated l-type amino acid transporter 1 (LAT1; SLC7A5) supplies essential amino acids to cancer cells. LAT1 substrates are not only needed for cancer rapid growth, but involved in cellular signaling. LAT1 has been proposed as a potential target for cancer treatment—its inhibitor, JPH203, is currently in clinical trials and targets biliary tract cancer (BTC). Here, we revealed to what extent LAT1 inhibitor affects intracellular amino acid content and what kind of cellular signals are directly triggered by LAT1 inhibition.

Methods
Liquid chromatography assay combined with o-phthalaldehyde- and 9-fluorenyl-methylchloroformate-based derivatization revealed changes in intracellular amino acid levels induced by LAT1 inhibition with JPH203 treatment in three BTC cell lines. Tandem mass tag-based quantitative phosphoproteomics characterized the effect of JPH203 treatment on BTC cells, and suggested key regulators in LAT1-inhibited cells. We further studied one of the key regulators, CK2 protein kinase, by using Western blot, enzymatic activity assay, and co-immunoprecipitation. We evaluated anticancer effects of combination of JPH203 with CK2 inhibitor using cell growth and would healing assay.

Results
JPH203 treatment decreased intracellular levels of LAT1 substrates including essential amino acids of three BTC cell lines, immediately and drastically. We also found levels of some of these amino acids were partially recovered after longer-time treatment. Therefore, we performed phosphoproteomics with short-time JPH203 treatment prior to the cellular compensatory response, and revealed hundreds of differentially phosphorylated sites. Commonly downregulated phosphorylation sites were found on proteins involved in the cell cycle and RNA splicing. Our phosphoproteomics also suggested key regulators immediately responding to LAT1 inhibition. Focusing on one of these regulators, protein kinase CK2, we revealed LAT1 inhibition decreased phosphorylation of CK2 substrate without changing CK2 enzymatic activity. Furthermore, LAT1 inhibition abolished interaction between CK2 and its regulatory protein NOLC1, which suggests regulatory mechanism of CK2 substrate protein specificity controlled by LAT1 inhibition. Moreover, we revealed that the combination of JPH203 with CK2 inhibitor resulted in the enhanced inhibition of proliferation and migration of BTC cells.

Conclusion
This study provides new perspectives on LAT1-dependent cellular processes and a rationale for therapeutics targeting reprogrammed cancer metabolism.
Bullying victimization and its associated factors among adolescents in Illu Abba Bor Zone, Southwest Ethiopia: a cross-sectional study
Authors: Tarafa Hunde , Alemayehu Yadeta , Bete Tilahun , Tarecha Debela 
Published: November 2022

AbstractBackgroundBullying victimization is a repetitive exposure to negative actions from one or more students over time. Bullying victim adolescents have higher levels of mental health problems, worse mental health outcomes, and lowered social status than non-victim adolescents. Literature on bullying among adolescents in Ethiopia is limited. This study aimed to assess the magnitude of bullying victimization and its associated factors among adolescents.MethodsA community-based cross-sectional study was carried out among 847 adolescents in Mettu town. A Stratified sampling technique was used to select eligible Study participants from September, 1 to 30, 2020. Linear regression analysis model was used; first bivariate analysis was performed to see the association of each independent variable with bullying victimization. Variables with (P < 0.25) in bivariate analysis were entered into a multivariate linear regression model to identify the association of each independent variable with bullying victimization. The statistical significance was considered atPvalue < 0.05.ResultsFrom the total of 847 adolescents 819 were voluntarily involved in the study giving the response rate of 96.7%. The prevalence of bullying victimization in this study was 30.4%. Being male (β = 1.135,p = 0.001), physical abuse (β = 0.622,p ≤ 0.001), emotional abuse (β = 0.512,p ≤ 0.001), current substance use (β = 1.153,p = 0.005), psychological distress (β = 0.406,p ≤ 0.001) and having medical illness (β = 3.500,p ≤ 0.001) were significantly associated with bullying victimization.ConclusionsBullying victimization is quite common among adolescents and has both short- and long-term consequences. Bullying prevention treatments should focus on male adolescents and those who report being bullied. Anti-bullying policies in schools are critical for educating teachers, parents, and students about bullying.