bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction and assembly of the DNA replication core proteins of Kaposi’s sarcoma-associated herpesvirus
Authors: Chen Lee-Wen , Wang Shie-Shan , Chen Li-Yu , Huang Hsiao-Yun , He Si-min , Hung Chien-Hui , Lin Chun-Liang , Chang Pey-Jium 
Published: October 2023

ABSTRACT
Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes six highly conserved core replication proteins essential for the viral lytic DNA synthesis, including ORF6 (single-stranded DNA-binding protein), ORF9 (DNA polymerase), ORF40/41 (primase-associated factor), ORF44 (helicase), ORF56 (primase), and ORF59 (polymerase processivity factor). Since the protein-protein interactions among KSHV core replication proteins are largely unknown, this study aimed to decipher their interrelationships. Herein, we propose a protein-protein interaction network of these six core replication proteins according to the results obtained from confocal fluorescence microscopy, coimmunoprecipitation, and mammalian two-hybrid (GAL4/VP16) reporter assays. In this interaction network, ORF40/41 plays a central role in the connection of different replication subcomplexes. In addition to the well-conserved helicase-primase subcomplex (consisting of ORF44, ORF56, and ORF40/41) and the replisome subcomplex (consisting of ORF9 and ORF59), our data also suggest that several discrete, stable subcomplexes exist in the cell nucleus. Among these replication subcomplexes in the nucleus, the tetrameric subcomplex composed of ORF44, ORF56, ORF40/41, and ORF6 exhibited the ability to trigger a DNA damage response. By using an established GAL4/VP16-based reporter system and confocal fluorescence microscopy, we additionally found that the heat shock protein 90 (Hsp90) inhibitor, radicicol, significantly inhibited the formation of both the helicase-primase subcomplex and the replisome subcomplex in a dose-dependent manner. Collectively, these data not only provide further insights into the interaction and assembly of KSHV-encoded core replication proteins but also suggest a critical role of Hsp90 in assisting the construction of the viral core replication machinery.

IMPORTANCE
Eukaryotic DNA replication is a highly regulated process that requires multiple replication enzymes assembled onto DNA replication origins. Due to the complexity of the cell’s DNA replication machinery, most of what we know about cellular DNA replication has come from the study of viral systems. Herein, we focus our study on the assembly of the Kaposi’s sarcoma-associated herpesvirus core replication complex and propose a pairwise protein-protein interaction network of six highly conserved viral core replication proteins. A detailed understanding of the interaction and assembly of the viral core replication proteins may provide opportunities to develop new strategies against viral propagation.
Procopius of Caesarea, Peter the Patrician, and the Outbreak of the Gothic War
Authors: Brodka✝ Dariusz 
Published: October 2023

Abstract
This article seeks to answer several questions about Procopius’ account of the causes for the Gothic war. The fundamental question is who was responsible for Amalasuintha’s death. Another issue under scrutiny relates to Procopius’ sources. The figure of Peter the Patrician sketched by Procopius is another point of interest. In the light of a comparative analysis of the sources, the accusation of Peter the Patrician and Theodora of complicity in the murder of Amalasuintha does not appear to have a firm basis. However, it is very likely that Procopius may indeed have had access to specific information about the secret negotiations—either directly from senator Alexander; or, more likely, via Marcellus. Contrary to what is generally assumed, it was probably not Peter the Patrician who provided Procopius with the most interesting details relating to the dramatic events in Italy in 534-536. The figure of Peter the Patrician fulfils an important literary function, serving primarily to explain the ‘real’ causes of the Gothic War.
Additional Evidence of Semantic and Syntactic Sensitivity in the Septuagint
Authors: Horton Tyler , Keenan Andrew , Lee Timothy , Walker Robert , Wright Travis , Dhont Marieke 
Published: October 2023

Abstract
In this article, a tribute to James Aitken by his students and postdoctoral collaborator, several case studies are presented that demonstrate how situating the Septuagint within its Post-classical Greek context can add significantly to our understanding of the textual-linguistic character of the Septuagint translations. They include a new approach to understanding parataxis with καί in the Greek Pentateuch, morphology and word formation in relation to presumed neologisms in Greek Jeremiah, lexical choice related to verbs of “pouring” in kaige, verbal periphrasis with ποιέω in Greek Genesis, the expression of motion in Greek Exodus, and the literary expression of “to die” in Greek Genesis. While we do not deny the existence of interference in the translations, we argue that its extent has been overstated. Through examples that showcase semantic and syntactic sensitivity on the part of the translators, we demonstrate various approaches to positioning the Septuagint within the history of Greek.
En attendant Godot (1952) de Samuel Beckett et Gerry (2002) de Gus Van Sant au prisme de Gilles Deleuze
Authors: Bénard Julie 
Published: October 2023

Résumé
Alors que la première représentation publique d’En attendant Godot s’inscrit dans un contexte d’après-guerre, Gerry de Gus Van Sant voyait le jour au tournant du XXe et XXIe siècles. Si les deux œuvres partagent les mêmes thématiques, c’est leur esthétique qui les rapproche en reposant sur un même principe : l’épuisement. Tout comme Gilles Deleuze qui déterminait dans son essai “L’Épuisé” (1992) trois sortes d’épuisements chez Beckett, Fabien Boully en identifie également trois chez le cinéaste. Cet article propose de faire dialoguer les deux œuvres à l’étude autour de l’épuisement du langage, de l’espace et de la représentation.
English headteacher perspectives on school responses to protect student and staff mental wellbeing in the later stages of the COVID-19 pandemic
Authors: McKay Gillian , Venner Georgia , Nguipdop-Djomo Patrick , Mangtani Punam , Sundaram Neisha , Lacey Andrea , Dawe Fiona , Jones Peter , Lelii Ffion , Ladhani Shamez , Bonell Chris 
Published: October 2023

Objective: The COVID-19 pandemic has had a significant impact on pupils and staff in English schools. This study aimed to provide an in-depth understanding of the challenges schools faced and the processes they implemented to protect the mental wellbeing of students and staff in the later stages of the pandemic, focusing on January–June 2022. Design: Qualitative study. Setting: Primary and secondary schools in England from April to September 2022. Method: Ten semi-structured interviews were conducted using Zoom with six primary and four secondary school headteachers (or other members of the senior leadership team) in England. Results: Mental wellbeing programming for students and staff was scaled up in both primary and secondary schools amid concerns that the COVID-19 pandemic would impact on mental health. Headteachers perceived changes in the behaviour of students, including increased dysregulation, and staff struggling with fatigue and a sense of being devalued as professionals. Schools scaled up the supports they offered to students and staff, but challenges remain in maintaining such increased support due to the perceived additional needs of staff and students within the context of funding constraints. Despite initial concerns that there would be tension between promoting mental wellbeing and academic catch-up among students, headteachers identified work addressing these two priorities as synergistic. Conclusion: Mental wellbeing impacts of the pandemic on pupils and staff required increased provision of support programmes. Ongoing efforts to monitor the wellbeing needs of students and staff is required. Formal and informal methods to enhance the mental health for pupils and staff should continue into the recovery period.
PerFSeeB: designing long high-weight single spaced seeds for full sensitivity alignment with a given number of mismatches
Authors: Titarenko Valeriy , Titarenko Sofya 
Published: October 2023

Abstract
Background
Technical progress in computational hardware allows researchers to use new approaches for sequence alignment problems. For a given sequence, we usually use smaller subsequences (anchors) to find possible candidate positions within a reference sequence. We may create pairs (“position”, “subsequence”) for the reference sequence and keep all such records without compression, even on a budget computer. As sequences for new and reference genomes differ, the goal is to find anchors, so we tolerate differences and keep the number of candidate positions with the same anchors to a minimum. Spaced seeds (masks ignoring symbols at specific locations) are a way to approach the task. An ideal (full sensitivity) spaced seed should enable us to find all such positions subject to a given maximum number of mismatches permitted.

Results
Several algorithms to assist seed generation are presented. The first one finds all permitted spaced seeds iteratively. We observe specific patterns for the seeds of the highest weight. There are often periodic seeds with a simple relation between block size, length of the seed and read. The second algorithm produces blocks for periodic seeds for blocks of up to 50 symbols and up to nine mismatches. The third algorithm uses those lists to find spaced seeds for reads of an arbitrary length. Finally, we apply seeds to a real dataset and compare results for other popular seeds.

Conclusions
PerFSeeB approach helps to significantly reduce the number of reads’ possible alignment positions for a known number of mismatches. Lists of long, high-weight spaced seeds are available in Additional file 1. The seeds are best in weight compared to seeds from other papers and can usually be applied to shorter reads. Codes for all algorithms and periodic blocks can be found at https://github.com/vtman/PerFSeeB.
Analysis and comparison of the trends in burden of rheumatic heart disease in China and worldwide from 1990 to 2019
Authors: Shi Lang , Bao Chenglu , Wen Ya , Liu Xuehui , You Guiying 
Published: October 2023

Abstract
Objectives
This study aimed to describe the temporal trends in age and gender burdens of rheumatic heart disease (RHD) in China from 1990 to 2019, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and to compare them with the global burden of the disease.

Methods
Using open data from the Global Burden of Disease (GBD) database from 1990 to 2019, this study analyzed the characteristics of RHD burden in China and worldwide, including changes in incidence, prevalence, mortality, and DALYs. Joinpoint was used to calculate the average annual percentage change (AAPC) and the corresponding 95% confidence interval (95% CI) to reflect the trends in the burden of RHD. A comprehensive comparative analysis of the differences in RHD burden between China and the rest of the world was conducted from multiple dimensions, including age, gender, and time periods.

Results
From 1990 to 2019, the age-standardized incidence rate (ASIR) of RHD in China decreased from 29.62/100,000 to 23.95/100,000, while the global ASIR increased from 32.69/100,000 to 37.40/100,000. The age-standardized prevalence rate (ASPR) in China decreased from 446.15/100,000 to 390.24/100,000, while the global ASPR increased from 451.56/100,000 to 513.68/100,000. The age-standardized rates of mortality (ASMR) in China decreased from 18.11/100,000 to 4.04/100,000, while the global ASMR decreased from 8.94/100,000 to 3.85/100,000. The age-standardized DALY rate (ASDR) in China decreased from 431.45/100,000 to 93.73/100,000, while the global ASDR decreased from 283.30/100,000 to 132.88/100,000. The AAPC of ASIR, ASPR, ASMR, and ASDR in China was − 0.73%, -0.47%, -5.10%, and − 5.21%, respectively, while the AAPC of the global burden of RHD was 0.48%, 0.45%, -2.87%, and − 2.58%, respectively. The effects of age and gender on the burden of RHD were different. ASIR generally decreased with increasing age, while ASPR increased first and then decreased. ASMR and ASDR increased with increasing age. Women had higher incidence and mortality rates of RHD than men.

Conclusion
From 1990 to 2019, the incidence, prevalence, mortality, and DALYs of RHD in China decreased, indicating a relative reduction in the burden of RHD in China. The burden of RHD is age-related, with a higher prevalence observed in the younger population, a peak incidence among young adults, and a higher mortality rate among the elderly population. Women are more susceptible to RHD and have a higher risk of mortality than men. Given China’s large population and aging population, RHD remains a significant public health challenge in China.
A comparative study on the effects of Mitchell and Benson relaxation techniques on quality of life of the old people in nursing homes: a quasi- experimental study
Authors: Jasour Aida , Afrasiabifar Ardashir , Zoladl Mohammad , Hosseini Nazafarin 
Published: October 2023

Abstract
Background
There is slight evidence on the effectiveness of relaxation techniques to improve quality of life of the old people, and no comparative studies have particularly investigated this population. Hence, the present study was conducted to examine the effect of Mitchell relaxation versus Benson relaxation technique to improve quality of life of the old people.

Methods
In the present quasi-experimental study, 96 eligible old people in a nursing home were selected by available sampling method. Afterwards, they were assigned to three groups: Mitchell’s Relaxation Technique, Benson Relaxation Technique, and control (each of 32 participants) using the random block sampling method. The intervention groups received relaxation for 8 weeks and 3 sessions of 20 min each week. However, the control group did not receive any relaxation. Data was gathered by questionnaires (SF-36) and (CASP-19) before (week 0) and after the intervention (week 8) and were analyzed using the SPSS software version 26.

Results
The results indicated that both Benson and Mitchell relaxation had improved the quality of life (SF-36) and (CASP-19) and their sub-scales in the participants compare to the control group (P < 0.001). Accordingly, the median (quartile 25, 75) of the specific quality of life of the participants before the intervention was 21 (18.25, 25.75) in the Benson group, 20.5 (16, 24) in the Michel group, and 21 (16.25, 24) in the control group. However, after the intervention they reached 35(26.25, 38.75), 34.5(26.75, 42.25), and 17 (14, 21) respectively. There was no statistically significant difference between the Benson and Michel relaxation groups.

Conclusions
Based on the results, Benson and Mitchell relaxation techniques improve the quality of life of the old people. If the results be confirmed in other studies, the education of each of them, especially for the old people living in nursing homes and their caregivers, is suggested as routine care.
Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19
Authors: Cosmi B. , Giannella M. , Fornaro G. , Cristini F. , Patacca A. , Castagna A. , Mazzaferri F. , Testa S. , Pan A. , Lupi M. , Brambilla P. , Montineri A. , Frattima S. , Bignami E. G. , Salvetti M. , De Stefano G. , Grandone E. , Di Perri G. , Rozzini R. , Stella A. , Romagnoli A. , Drago F. , Viale P. 
Published: October 2023

Abstract
Background
Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19.

Methods
A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45–60 kg, 80 mg for 61–100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4–0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm).

Results
Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8–16) vs 14 (11–21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups.

Conclusions
Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients.

Trial registration
The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.
A combined bioinformatics and experimental approach identifies RMI2 as a Wnt/β-catenin signaling target gene related to hepatocellular carcinoma
Authors: Tsai Hung-Wen , Cheng Shu-Wen , Chen Chou-Cheng , Chen I-Wen , Ho Chung-Liang 
Published: October 2023

Abstract
Background
The Wnt/β-catenin signaling pathway plays an important role in embryogenesis and tumorigenesis. In human cancer, abnormal activity of Wnt/β-catenin signaling pathway induces overexpressed of downstream genes, and initiate oncogene. There are several target genes known to be key players in tumorigenesis, such as c-myc, cyclin D1, MMPs or survivin. Therefore, identifying the target genes of Wnt/β-catenin signaling pathway is important to understanding Wnt/β-catenin-mediated carcinogenesis. In this study, we developed a combined bioinformatics and experimental approach to find potential target genes.

Methods
Luciferase reporter assay was used to analyze the promoter activity of RMI2. WST1 cell proliferation assays and transwell assays were performed to determine the proliferation and migration capacities of RMI2 overexpressing or knockdown stable hepatic cells. Finally, xenograft experiments were performed to measure the tumor formation capacity in vivo.

Results
The results showed that RMI2 mRNA was upregulated after LiCl treatment and Wnt3a-conditioned medium in a culture of SK-hep-1 cell lines. A chromatin immunoprecipitation (ChIP) assay showed that the β-catenin/T cell-specific factor (TCF) complex binds to the putative TCF binding site of the RMI2 promoter. We then found a TCF binding site at − 333/− 326 of the RMI2 promoter, which is crucial for β-catenin responsiveness in liver cell lines. RMI2 was overexpressed in hepatoma tissue and cell lines, and it promoted the migration and invasion of HCC cells. Moreover, RMI2 upregulated the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt3a/β-catenin-related genes, but silencing RMI2 had the opposite effects. Notably, the expression of RMI2 was positively correlated with the clinical data of HCC patients who had significantly shorter overall survival (OS) and disease-free survival (DFS) (Both: P < 0.05). In addition, a total of 373 HCC patients’ data from the Caner Genome Atlas project (TCGA) were used to validate our findings.

Conclusions
Taking all these findings together, we determined that RMI2 was a new target gene of the Wnt/β-catenin signaling pathway. We also found that RMI2 promotes EMT markers, HCC cell invasion, and metastasis, which indicated that RMI2 is a potential target for preventing or at least mitigating the progression of HCC.
Exploration and validation of a novel signature of seven necroptosis-related genes to improve the clinical outcome of hepatocellular carcinoma
Authors: Tao Qiqi , Lang Zhichao , Li Yifei , Gao Yuxiang , Lin Lifan , Yu Zhengping , Zheng Jianjian , Yu Suhui 
Published: October 2023

AbstractNecroptosis has been reported to be involved in cancer progression and associated with cancer prognosis. However, the prognostic values of necroptosis-related genes (NRGs) in hepatocellular carcinoma (HCC) remain largely unknown. This study aimed to build a signature on the basis of NRGs to evaluate the prognosis of HCC patients. In this study, using bioinformatic analyses of transcriptome sequencing data of HCC (n = 370) from The Cancer Genome Atlas (TCGA) database, 63 differentially expressed NRGs between HCC and adjacent normal tissues were determined. 24 differentially expressed NRGs were found to be related with overall survival (OS). Seven optimum NRGs, determined using Lasso regression and multivariate Cox regression analysis, were used to construct a new prognostic risk signature for predicting the prognosis of HCC patients. Then survival status scatter plots and survival curves demonstrated that the prognosis of patients with high-Riskscore was worse. The prognostic value of this 7-NRG signature was validated by the International Cancer Genome Consortium (ICGC) cohort and a local cohort (Wenzhou, China). Notably, Riskscore was defined as an independent risk factor for HCC prognosis using multivariate cox regression analysis. Immune infiltration analysis suggested that higher macrophage infiltration was found in patients in the high-risk group. Finally, enhanced 7 NRGs were found in HCC tissues by immunohistochemistry. In conclusion, a novel 7-NRG prognostic risk signature is generated, which contributes to the prediction in the prognosis of HCC patients for the clinicians.