bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB
Authors: Plaza-G.A. Ismael , Lemishko Kateryna M , Crespo Rodrigo , Truong Thinh Q , Kaguni Laurie S , Cao-García Francisco J , Ciesielski Grzegorz L , Ibarra Borja 
Published: February 2023

AbstractMany replicative DNA polymerases couple DNA replication and unwinding activities to perform strand displacement DNA synthesis, a critical ability for DNA metabolism. Strand displacement is tightly regulated by partner proteins, such as single-stranded DNA (ssDNA) binding proteins (SSBs) by a poorly understood mechanism. Here, we use single-molecule optical tweezers and biochemical assays to elucidate the molecular mechanism of strand displacement DNA synthesis by the human mitochondrial DNA polymerase, Polγ, and its modulation by cognate and noncognate SSBs. We show that Polγ exhibits a robust DNA unwinding mechanism, which entails lowering the energy barrier for unwinding of the first base pair of the DNA fork junction, by ∼55%. However, the polymerase cannot prevent the reannealing of the parental strands efficiently, which limits by ∼30-fold its strand displacement activity. We demonstrate that SSBs stimulate the Polγ strand displacement activity through several mechanisms. SSB binding energy to ssDNA additionally increases the destabilization energy at the DNA junction, by ∼25%. Furthermore, SSB interactions with the displaced ssDNA reduce the DNA fork reannealing pressure on Polγ, in turn promoting the productive polymerization state by ∼3-fold. These stimulatory effects are enhanced by species-specific functional interactions and have significant implications in the replication of the human mitochondrial DNA.
LINE-1 retrotransposon expression in cancerous, epithelial and neuronal cells revealed by 5′ single-cell RNA-Seq
Authors: McKerrow Wilson , Kagermazova Larisa , Doudican Nicole , Frazzette Nicholas , Kaparos Efiyenia Ismini , Evans Shane A , Rocha Azucena , Sedivy John M , Neretti Nicola , Carucci John , Boeke Jef D , Fenyö David 
Published: February 2023

AbstractLINE-1 retrotransposons are sequences capable of copying themselves to new genomic loci via an RNA intermediate. New studies implicate LINE-1 in a range of diseases, especially in the context of aging, but without an accurate understanding of where and when LINE-1 is expressed, a full accounting of its role in health and disease is not possible. We therefore developed a method—5′ scL1seq—that makes use of a widely available library preparation method (10x Genomics 5′ single cell RNA-seq) to measure LINE-1 expression in tens of thousands of single cells. We recapitulated the known pattern of LINE-1 expression in tumors—present in cancer cells, absent from immune cells—and identified hitherto undescribed LINE-1 expression in human epithelial cells and mouse hippocampal neurons. In both cases, we saw a modest increase with age, supporting recent research connecting LINE-1 to age related diseases.
Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy
Authors: Anand Jay , Chiou Lilly , Sciandra Carly , Zhang Xingyuan , Hong Jiyong , Wu Di , Zhou Pei , Vaziri Cyrus 
Published: February 2023

Abstract
DNA damage tolerance and mutagenesis are hallmarks and enabling characteristics of neoplastic cells that drive tumorigenesis and allow cancer cells to resist therapy. The ‘Y-family’ trans-lesion synthesis (TLS) DNA polymerases enable cells to replicate damaged genomes, thereby conferring DNA damage tolerance. Moreover, Y-family DNA polymerases are inherently error-prone and cause mutations. Therefore, TLS DNA polymerases are potential mediators of important tumorigenic phenotypes. The skin cancer-propensity syndrome xeroderma pigmentosum-variant (XPV) results from defects in the Y-family DNA Polymerase Pol eta (Polη) and compensatory deployment of alternative inappropriate DNA polymerases. However, the extent to which dysregulated TLS contributes to the underlying etiology of other human cancers is unclear. Here we consider the broad impact of TLS polymerases on tumorigenesis and cancer therapy. We survey the ways in which TLS DNA polymerases are pathologically altered in cancer. We summarize evidence that TLS polymerases shape cancer genomes, and review studies implicating dysregulated TLS as a driver of carcinogenesis. Because many cancer treatment regimens comprise DNA-damaging agents, pharmacological inhibition of TLS is an attractive strategy for sensitizing tumors to genotoxic therapies. Therefore, we discuss the pharmacological tractability of the TLS pathway and summarize recent progress on development of TLS inhibitors for therapeutic purposes.
APE2: catalytic function and synthetic lethality draw attention as a cancer therapy target
Authors: McMahon Anne , Zhao Jianjun , Yan Shan 
Published: February 2023

Abstract
AP endonuclease 2 (APE2, APEX2 or APN2) is an emerging critical protein involved in genome and epigenome integrity. Whereas its catalytic function as a nuclease in DNA repair is widely accepted, recent studies have elucidated the function and mechanism of APE2 in the immune response and DNA damage response. Several genome-wide screens have identified APE2 as a synthetic lethal target for deficiencies of BRCA1, BRCA2 or TDP1 in cancer cells. Due to its overexpression in several cancer types, APE2 is proposed as an oncogene and could serve as prognostic marker of overall survival of cancer treatment. However, it remains to be discovered whether and how APE2 catalytic function and synthetic lethality can be modulated and manipulated as a cancer therapy target. In this review, we provide a current understanding of alterations and expression of APE2 in cancer, the function of APE2 in the immune response, and mechanisms of APE2 in ATR/Chk1 DNA damage response. We also summarize the role of APE2 in DNA repair pathways in the removal of heterogenous and complexed 3’-termini and MMEJ. Finally, we provide an updated perspective on how APE2 may be targeted for cancer therapy and future directions of APE2 studies in cancer biology.
Hand–arm vibration: Swedish carpenters’ perceptions of health and safety management
Authors: Fisk K , Nordander C , Ek Å 
Published: February 2023

AbstractBackgroundWorkers in the construction industry are highly exposed to vibration from handheld equipment, which can have negative effects on the nerves and blood vessels in the hands. Employers in this industry often fail to comply with legislation regarding vibration exposure.AimsTo assess carpenters’ perceptions of proactive health and safety (H&S) management regarding hand–arm vibration exposure at construction sites in Sweden.MethodsThe carpenters answered a questionnaire on their perception of the implementation of H&S management, on symptoms indicating injury and on the use of vibrating equipment.ResultsOne hundred and ninety-four carpenters from 4 construction companies and 18 construction sites completed the questionnaire. Attitudes to H&S management were generally positive. However, 36% of the carpenters reported that the H&S regulations and routines did not function in practice, and 40% claimed they did not receive necessary information on the exposure and effects of vibration. Most respondents (74%) perceived a high risk of injury in general in their work. Younger carpenters, carpenters employed at smaller companies and carpenters with symptoms indicating injury or with higher vibration exposure reported more negative perceptions.ConclusionsIn general, the carpenters were positive about management’s commitment to H&S management. However, the results indicate deficiencies in the way in which this commitment is applied in practice at the workplace. This highlights the importance of raising awareness concerning vibration exposure and possible injuries, and strengthening proactive H&S programmes, especially in smaller companies.
Cognitive mechanisms and resilience in UK-based general practitioners: cross-sectional findings
Authors: Kaleta F O , Kristensen C B , Duncan M , Crutchley P , Kerr P , Hirsch C R 
Published: February 2023

AbstractBackgroundBeing a general practitioner (GP) is a stressful occupation, and the strain GPs are under can have negative effects on their psychological well-being, as well as on the patients’ experience of healthcare. Resilience can help buffer against this and is a dynamic process by which one can cope with adversity and stress.AimsThis study aimed to identify modifiable cognitive mechanisms related to resilience in GPs, specifically interpretation bias and cognitive reappraisal.MethodsOne hundred and fourteen GPs completed an online cross-sectional correlational study. This comprised questionnaires assessing resilience, emotional distress, work environment and cognitive mechanisms (emotion regulation), as well as a task assessing interpretation bias.ResultsResilience of GPs was negatively correlated with measures of emotional distress. Furthermore, resilience was positively correlated with positive interpretation bias (r = 0.60, ρ = 0.60, P &lt; 0.01) and cognitive reappraisal (r = 0.39, ρ = 0.40, P &lt; 0.01). In a hierarchical regression, positive interpretation bias (B = 0.25, SE B = 0.06, β = 0.39, P &lt; 0.01) was a significant independent predictor of resilience when controlling for depression, anxiety and stress.ConclusionsThis is the first study to establish an association between resilience and positive interpretation bias and cognitive reappraisal in GPs. Future research should use longitudinal designs to determine if they have a causal role in promoting resilience, and importantly whether interventions focusing on these processes may foster resilience in less resilient GPs.
The potential role of descriptive and dynamic norms in promoting climate change advocacy
Authors: Campbell Eryn , Kotcher John E , Myers Teresa , Munson Sammi , Borth Amanda C , Rosenthal Seth A , Leiserowitz Anthony , Maibach Edward 
Published: February 2023

AbstractPolitical advocacy is arguably the most powerful form of action that citizens concerned about climate change can take. One motivator for political advocacy is the perception that there is a social norm (i.e. inherently understood social rules and standards that serve to guide social behaviors) for doing so. Using nationally representative survey data (N = 1303), we examined the association of three types of social norms—descriptive norms (i.e. perceptions about how many other people perform a behavior), retrospective and prospective dynamic norms (i.e. perceptions that a behavior has become more or less common in the past or will in the future)—with intentions to engage in political advocacy in the upcoming year and past advocacy. We found that descriptive norms and prospective dynamic norms were positively related to advocacy intentions, while only prospective dynamic norms were positively related to past advocacy (retrospective dynamic norms were negatively related to both outcomes, contrary to our theorized direction). Furthermore, we examined whether the relationship between norms and intentions/behaviors differed based on political party identification and four potential mediators of this relationship: identification with climate activists; collective efficacy (i.e. the belief that people can engage in climate advocacy and that it will make a difference); collective response efficacy (i.e. beliefs about the results of advocacy); and injunctive norms (i.e. perceptions of others’ approval of advocacy). In the moderated mediation models, we found that party identification moderated the relationships between descriptive norms and prospective dynamic norms and advocacy intention, while retrospective dynamic norms were not related as theorized. These relationships were mediated by identification with climate activists and collective efficacy as well as by injunctive norms in the case of descriptive norms. Party identification also moderated the relationship between descriptive norms and past advocacy; this relationship was mediated by identification with climate activists and injunctive norms. Taken together, these findings underscore the potential importance of perceived descriptive norms and prospective dynamic norms on political advocacy to address climate change, extending both well-established and emerging research and providing insights useful for academics and practitioners alike.
PET vascular activity score for predicting new angiographic lesions in patients with Takayasu arteritis: a Chinese cohort study
Authors: Ma Lingying , Wu Bing , Sun Ying , Ding Zhenqi , Dai Xiaomin , Wang Li , Dai Xiaojuan , Zhang Lijuan , Chen Huiyong , Ma Lili , Lv Peng , Shi Hongcheng , Jiang Lindi 
Published: February 2023

Abstract

Objective
To investigate the ability of 18F-fluorodeoxyglucose PET/CT to predict new lesions in Takayasu arteritis.

Methods
Eighty-two Chinese patients with newly diagnosed Takayasu arteritis were recruited. Their clinical characteristics, serum biomarkers and imaging results were recorded at baseline and every visit. They were followed up for at least 2 years. New angiographic lesions were evaluated by magnetic resonance angiography. Baseline PET vascular activity scores (PETVAS) for predicting new lesions were evaluated.

Results
At baseline, a moderate correlation was observed between PETVAS and ESR (r = 0.74, P &lt; 0.01) and CRP level (r = 0.69, P &lt; 0.01). Overall, 18 (22%) patients showed new lesions on imaging during a median follow-up time of 36 months. The median time to the first occurrence of new lesions was 18 months. Compared with patients without new lesions, the patients with new lesions included more female patients (67.2% vs 94.4%, P = 0.03), patients with higher ESR values (20 vs 49, P = 0.02) and patients with active disease (62.5% vs 94.4%, P &lt; 0.01). Multivariate Cox regression analysis revealed PETVAS was an independent risk factor for new angiographic lesions (PETVAS ≥8, hazard ratio = 7.56; 95% CI 2.20, 26.01, P &lt; 0.01) with adjustment of age, sex, chest pain, ESR and Physician Global Assessment. Furthermore, patients with PETVAS ≥8 at baseline were more likely to experience adverse events including arterial ischaemic events during the follow-up.

Conclusion
PETVAS showed good performance in predicting new lesions in Takayasu arteritis.
Sexual dysfunction in male childhood cancer survivors and adolescent and young adult survivors of hematologic malignancies
Authors: Crist Nikos , Egert Melissa C , Bernie Helen L 
Published: February 2023

AbstractSexual Health is an important aspect of overall health and quality of life (QoL) among adolescent and young adult (AYA) as well as childhood cancer survivors (CCS). Sexual health encompasses psychosocial, physical, developmental, emotional and relationship factors that impact sexual function. Cancer and its associated treatments are associated with negative effects on sexual health, body image, relationships, as well as overall physical and mental health. Data shows that CCS are known to experience diminished QoL compared to their peers. However, limited information is available to guide the assessment and treatment of sexual dysfunction in AYA and CCS. Further, exploration into specific cancer types, treatment methods and their resultant effects on sexual function within these populations is far more limited. We conducted an extensive review of the literature that focused on sexual dysfunction in male survivors of hematologic malignancies (HM). Our review identified an increased incidence of sexual dysfunction within male AYA and CCS of HM, and the negative impact this has on overall QoL. Our results show the degree to which survivors of HM experience increased sexual dysfunction, and the therapies and pathophysiologic mechanisms that may contribute to the development of sexual dysfunction within this population. These findings highlight the lack of research on this topic and need for further exploration into AYA and CCS sexual health to improve patient care and close the knowledge gaps to better assess and treat sexual dysfunction in this patient population.
Sequences and Genome-Wide Analysis of mRNA and microRNA Expression in Tea (Camellia sinensis) Leaves in Response to Epicoccum sorghinum Infection
Authors: Huang Hongke , Jiang Xinyue , Huang Chen , Xia Zhongqiu , Yang Yuqin , Yin Jiayu , Zhao Hong , Mo Bin , Zhao Yongtian , Wang Delu , Chen Zhuo 
Published: February 2023

Due to our lack of understanding of the host-pathogen epidemiology and the absence of effective control measures, tea leaf spot, caused by the fungus Epicoccum sorghinum, continues to reduce the productivity and quality of tea leaves in plantations in Guizhou Province, southwestern China. Here, samples of tea ( Camellia sinensis [L.] O Kuntze) leaves either infected or uninfected by E. sorghinum were used as the study model. The mRNA and microRNA (miRNA) sequences in tea leaves from the two treatments were determined using the Illumina NovaSeq 6000 and the Illumina HiSeq 2500 platforms, respectively. In total, 33,932 genes or transcripts from tea leaves were annotated. In response to infection by E. sorghinum, 1,068 or 467 of the differentially expressed mRNAs (DEmRNAs) were up- or downregulated, respectively, and the DEmRNAs containing peroxidase 21 and LRR receptor-like serine/threonine-protein kinase ERECTA were enriched in terms of defense response. Meanwhile, 1,889 miRNAs were identified from infected or uninfected leaves. Nine or seven of the differentially expressed miRNAs (DEmiRNAs) were up- or downregulated, respectively. The DEmiRNAs MIR5303j-p5, MIR6173-p5, miR858-3p, and novel-miR0377-3p were predicted to bind to DEmRNAs. Fifteen DEmRNAs annotated into transcription factor proteins enriched with respect to the plant-pathogen interaction pathway were predicted to be bound by the DEmiRNA miR858-3p. The sequences and abundances of the mRNAs and miRNAs from tea leaves infected by E. nigrum, and the prediction of the interaction between DEmiRNAs and DEmRNAs could contribute to our understanding of this plant-pathogen interaction. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Effect of Tomato Cultivar on Pythium Root Rot and Efficacy of Biopesticides
Authors: DeGenring Liza , Poleatewich Anissa 
Published: February 2023

Barriers to broad commercial use of biopesticides include inconsistent efficacy, which can be influenced by plant species, soil type, and production system. Few studies have evaluated the effect of plant cultivar on the efficacy of commercial biopesticides to suppress disease under greenhouse production conditions. The objective of this study was to evaluate the effect of tomato cultivar on Pythium root rot and the efficacy of commercially available microbial biopesticides (Rootshield WP and Cease). Under low to moderate disease, plants treated with Rootshield had lower Pythium root rot severity compared with the control, and this efficacy was influenced by cultivar. The tomato cultivars ‘Ailsa Craig’, ‘Glamour’, and ‘Maxifort’ had up to 75% less disease when treated with Rootshield compared with the water control. This effect was not observed on cultivar ‘Trust’, a scion cultivar used in greenhouse vegetable production. Cease had no effect on Pythium root rot severity. The aboveground dried biomass of plants treated with Rootshield was lower for tomato cultivars Trust and Glamour. This research suggests that cultivar can explain some of the variability of biopesticide efficacy in reducing root rot disease. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Pediatric trauma center vs. adult trauma center: which is better?
Authors: Russell Katie , Biswas Subarna 
Published: February 2023

Purpose of Review
Pediatric trauma centers (PTCs) have been championed as multidisciplinary facilities specializing in the care of pediatric trauma, the leading cause of childhood mortality in the United States.1 However, the vast majority of pediatric trauma is still seen in trauma centers focused on treating adults. This article reviews the latest evidence comparing the relative strengths of PTCs and adult trauma centers (ATCs) in treating childhood injury.

Recent findings
Recent multicenter studies comparing outcomes of pediatric injury in PTCs and ATCs have found no differences in mortality or hospital length of stay, contradicting earlier findings. However, fewer invasive procedures and CT scans were performed at PTCs, and more children were discharged back to their homes.

Summary
It is difficult to demonstrate a difference in outcomes for children treated at PTCs vs. ATCs. However, PTCs do offer a multidisciplinary, nuanced approach to pediatric trauma care, which may result in long term benefits and offer opportunities for regional collaboration.
Entering a new era of molecular classification of brain tumors: An update of 2021 World Health Organization classification in adult gliomas
Authors: Wang Ching-Ying , Lin Shih-Chieh , Chen Ming-Teh , Lee Yi-Yen 
Published: February 2023

Abstract
Glioma is the most common primary central nervous system tumor. The World Health Organization (WHO) 2021 classification of gliomas extended from WHO 2016 in the integration of molecular and histological classifications. WHO 2021 aims to establish a specific diagnosis that could reflect the biological and clinical features of the tumors, and further transform into more specific clinical studies or trials and therapeutics. Major updates of WHO 2021 classification focusing on glioma were reviewed in this article.
EGF receptor modulates HEV entry in human hepatocytes
Authors: Schrader Jil A. , Burkard Thomas L. , Brüggemann Yannick , Gömer André , Meister Toni L. , Fu Rebecca M. , Mehnert Ann-Kathrin , Dao Thi Viet L. , Behrendt Patrick , Durantel David , Broering Ruth , Vondran Florian W. R. , Todt Daniel , Kinast Volker , Steinmann Eike 
Published: February 2023

Background and Aims:
Being the most common cause of acute viral hepatitis with >20 million cases per year and 70,000 deaths annually, HEV presents a long-neglected and underinvestigated health burden. Although the entry process of viral particles is an attractive target for pharmacological intervention, druggable host factors to restrict HEV entry have not been identified so far.

Approach and Results:
Here we identify the EGF receptor (EGFR) as a novel host factor for HEV and reveal the significance of EGFR for the HEV entry process. By utilizing RNAi, chemical modulation with Food and Drug Administration–approved drugs, and ectopic expression of EGFR, we revealed that EGFR is critical for HEV infection without affecting HEV RNA replication or assembly of progeny virus. We further unveiled that EGFR itself and its ligand-binding domain, rather than its signaling function, is responsible for the proviral effect. Modulation of EGF expression in HepaRG cells and primary human hepatocytes affected HEV infection.

Conclusions:
Taken together, our study provides novel insights into the life cycle of HEV and identified EGFR as a possible target for future antiviral strategies against HEV.