bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mismatch repair endonuclease MutLα tethers duplex regions of DNA together and relieves DNA torsional tension
Authors: Witte Scott J , Rosa Isabella M , Collingwood Bryce W , Piscitelli Jonathan M , Manhart Carol M 
Published: February 2023

AbstractIn eukaryotic mismatch repair, MutS homologs recognize mismatches and recruit the MutLα endonuclease which introduces a nick in the newly replicated, error-containing DNA strand. The nick occurs in response to the mismatch, but at a site up to several hundred base pairs away. The MutLα nick promotes mismatch excision by an exonuclease (Exo1) or removal by the strand displacement activity of a DNA polymerase which may work in conjunction with a flap endonuclease. Models have suggested that MutL homolog endonucleases form oligomeric complexes which facilitate and are activated by strand capture mechanisms, although such models have never been explicitly tested. We present evidence that the mismatch repair MutLα endonuclease is activated by DNA–DNA associations and that it can use this property to overcome DNA torsional barriers. Using DNA ligation and pull-down experiments, we determined that the MutLα endonuclease associates two DNA duplexes. Using nuclease assays, we determined that this activity stimulates MutLα’s endonuclease function. We also observe that MutLα enhances a topoisomerase without nicking the DNA itself. Our data provide a mechanistic explanation for how MutL proteins interact with DNA during mismatch repair, and how MutL homologs participate in other processes, such as recombination and trinucleotide repeat expansions.
Clinical, histological, and molecular features of gliomas in adults with neurofibromatosis type 1
Authors: Romo Carlos G , Piotrowski Anna F , Campian Jian L , Diarte Jose , Rodriguez Fausto J , Bale Tejus A , Dahiya Sonika , Gutmann David H , Lucas Calixto-Hope G , Prichett Laura , Mellinghoff Ingo , Blakeley Jaishri O 
Published: February 2023

AbstractBackgroundPeople with NF1 have an increased prevalence of central nervous system malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research.MethodsAdults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990 and 2020 were identified. Retrospective data were collated, and pathology was reviewed centrally.ResultsForty-five patients, comprising 23 females (51%), met eligibility criteria, with a median of age 37 (18–68 years) and performance status of 80% (30%–100%). Tissue was available for 35 patients. Diagnoses included infiltrating (low-grade) astrocytoma (9), glioblastoma (7), high-grade astrocytoma with piloid features (4), pilocytic astrocytoma (4), high-grade astrocytoma (3), WHO diagnosis not reached (4) and one each of gliosarcoma, ganglioglioma, embryonal tumor, and diffuse midline glioma. Seventy-one percent of tumors were midline and underwent biopsy only. All 27 tumors evaluated were IDH1-wild-type, independent of histology. In the 10 cases with molecular testing, the most common genetic variants were NF1, EGFR, ATRX, CDKN2A/B, TP53, TERT, and MSH2/3 mutation. While the treatments provided varied, the median overall survival was 24 months [2–267 months] across all ages, and 38.5 [18–109] months in individuals with grade 1–2 gliomas.ConclusionsNon-OPGs in adults with NF1, including low-grade tumors, often have an aggressive clinical course, indicating a need to better understand the pathobiology of these NF1-associated gliomas.
Green carbon science: fundamental aspects
Authors: He Mingyuan , Zhang Kun , Guan Yejun , Sun Yuhan , Han Buxing 
Published: February 2023

Abstract
Carbon energy has contributed to the creation of human civilization, and it can be considered that the configuration of the carbon energy system is one of the important laws that govern the operation of everything in the universe. The core of the carbon energy system is the opposition and unity of two aspects: oxidation and reduction. The operation of oxidation and reduction is based on the ternary elemental system composed of the three elements of carbon, hydrogen and oxygen. Its operation produces numerous reactions and reaction products. Ancient Chinese philosophy helps us to understand in depth the essence of green carbon science, to explore its scientific basis, and to identify the related platforms for technology development.
Workup of difficult-to-treat asthma: implications from treatable traits
Authors: Zhang Qing , Wu Wen Wen , Li Lei , McDonald Vanessa M , Chen Yu Cheng , Wang Gang , Gibson Peter G 
Published: February 2023

Abstract
Traditional stepwise approach usually adjusts the treatment regimen based on changes in asthma symptoms and severity to achieve good asthma control. However, due to the generalized heterogeneity and complexity of asthma, its therapeutic efficacy in difficult-to-treat asthma is limited. Recently, a precision medicine approach based on the identification and intervention of treatable traits of chronic airway disease has been proposed and appears to be of greater benefit to asthmatics. We reported a 71-year-old male with uncontrolled asthma and multiple exacerbations over the past year. He complained of persistent dyspnea despite high-dose of inhaled corticosteroids plus other controllers. Does this patient have some potential treatable traits contributing to difficult-to-treat asthma? Through a multidimensional assessment of three domains including pulmonary, extrapulmonary, and behavioral/risk factors, 15 treatable traits were identified in the patient, mainly including airflow limitation, eosinophilic airway inflammation, small airway dysfunction, exacerbation prone, dilated cardiomyopathy, diabetes mellitus, inhaler device polypharmacy, smoking, and the absence of an asthma action plan. After targeted treatment for these treatable traits, the patient experienced significant improvement in dyspnea and he could maintain good asthma control with low-dose inhaled corticosteroids and long-acting β2-agonist. This study shows that, in response to the limitation of a stepwise approach to therapy, treatable traits is a new strategy where patients are individually assessed for a specified set of treatable problems, and an individualized treatment program is developed and implemented based on this multidimensional assessment, especially for difficult-to-treat asthma.
Police Recognition of Gender Issues in Relation to Intimate Partner Domestic Violence and Abuse in Greece
Authors: Kravvariti Vasiliki , Browne Kevin 
Published: February 2023

AbstractThe aim of the research was to understand the perceptions and beliefs of police officers who work and support victims of intimate partner domestic violence and abuse (DVA) and evaluate the way it is recorded. A sample was collected from eight police departments in Greece. The head of each police department was approached by the researcher and asked to distribute a structured questionnaire to front-line police officers who work with DVA victims. In total 358 police officers completed the questionnaire. Overall, nearly twice as many police officers referred to female victims (n = 170) compared to male victims (n = 83) of DVA. The police officers indicated that female victims usually suffered from severe physical violence/GBH (43%) and psychological abuse (27%), whereas male victims were most likely to disclose minor physical injuries and verbal abuse (49%) and less psychological violence (10%). An arrest was the most common response for both female and male victims (51% and 60%, respectively). Police participants indicated that offenders against males were more likely to be charged (28%) but less likely to be convicted (4%), whereas the opposite was reported for offenders of female victims (14% and 13%, respectively). If the offender was known to the police, the opinion was they were less likely to be prosecuted. Police respondents reported no significant differences for female and male victims as to causal factors and reasons for NOT reporting DVA. These were discrimination (31%), few DVA services (23%), intimidation (15%), shame and stigma of media reports (14%), lack of community support (6%), and personal reasons (9%).
Malnutrition and sarcopenia worsen short- and long-term outcomes in internal medicine inpatients
Authors: Carretero Gómez Juana , Galeano Fernández Tomás F , Vidal Ríos Antonio S , Pérez Palacios María R , García García Gema M , García Carrasco Carolina , Romero Requena Jorge M , Fernández Recio José M , Nevado López-Alegría Leticia , Pijierro Amador Agustín , Arévalo Lorido José C 
Published: February 2023

AbstractPurposeThis work aims to describe patients hospitalized in internal medicine wards in terms of nutrition and sarcopenia. It also seeks to evaluate short- and long-term mortality related to malnutrition and sarcopenia.MethodsThis cross-sectional study collected data on consecutive patients admitted to a single center’s internal medicine ward. Patients were recruited in May and October 2021. Malnutrition was determined by the Mini-Nutritional Assessment-Short Form (MNA-SF) and sarcopenia by the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls questionnaire (SARC-F scale) and handgrip strength test. Patients who were hospitalized for &gt;48 hours were excluded.ResultsThe sample included 619 patients with a mean ± SD age of 76.0 ± 14.8 years of which 50.6% were women. Patients were classified into three groups based on malnutrition: group 1 (MNA-SF 12–14 points) (no risk) included 158 patients, group 2 (MNA-SF 8–12 points) (high risk) included 233 patients, and group 3 (MNA-SF 0–7 points) (malnourished) included 228 patients. Malnourished patients had more dysphagia, significantly lower protein and albumin levels, and significantly higher inflammatory marker levels and pressure ulcers. In-hospital mortality was significantly higher in groups 2 and 3 (p &lt; .00001). The worst outcome (mortality and readmissions or mortality) was more common among malnourished patients (p = .0001). Inflammation, comorbidity, and sarcopenia were most closely associated with negative outcomes.ConclusionMalnutrition upon admission is associated with worse short- and long-term outcomes in internal medicine inpatients. Sarcopenia, multimorbidity, and inflammation—measured by albumin, C-reactive protein, or their ratios—are key risk factors. Early identification of malnutrition and sarcopenia through active screening is important in caring for internal medicine patients.
Predictors of self-reported research self-efficacy and perception of research amongst medical students in the United Kingdom: a national cross-sectional survey
Authors: Osunronbi Temidayo , Adeboye William , Faluyi David , Sofela Jasmine , Shoker Serena , O'Riordan Marguerite , Mitoko Christine A , Mberu Valentine K , Mandangu Chenai , Madume Rachael , Kolawole Adebola I , Jones Robert I , Inyang Deborah , Ibrahim Ummulkhulsum , Ibeanusi Ikenna M , Fofanah Isata J , Corriero Anna C , Chimba Chimba , Akhionbare Izieduwa , Ahmad Zain , Adamu-Biu Fatima , Abraha Semhar , Abankwa Efua , Sofela Agbolahan ,   REMED-UK collaborators, Abdelhafiz Dima , Adebayo Ayanfe , Afolabi Oluwafemi , Awow Fatima , Crankson Akua , Exley Henry , Frame Lauren , Johnson Ola , Kufuor Risata A , Madu William , McCutcheon Calum , Mohamed Suaad , Munyebvu Samantha R , Nelson-Rowe Ellen , Shah Max , Stewart Oonagh , Watts Alice 
Published: February 2023

Abstract

Purpose
There has been a decline in the number of academic clinicians in the UK, and there are ethnic/gender disparities in the academic workforce. Higher research self-efficacy (RSE) and a positive perception of research (PoR) amongst students are associated with a higher motivation to engage in academic medicine. Hence, this study aimed to determine the factors that influence RSE and PoR amongst UK medical students.

Methods
This is a multicentre cross-sectional survey of medical students in 36 UK medical schools in the 2020/21 academic year. Multiple linear regression was used to investigate the association between students’ demographics and RSE/PoR. P-values less than a Bonferroni-corrected significance level of .05/28 = .0018 were considered statistically significant.

Results
In total, 1573 individuals participated from 36 medical schools. There were no ethnic differences in PoR or RSE scores. Although there were no gender differences in PoR, female students had lower RSE scores than male students (adjusted β = −1.75; 95% CI: −2.62, −0.89). Research experience before medical school (adjusted β = 3.02; 95% CI: 2.11, 3.93), being in the clinical training phase (adjusted β = 1.99; 95% CI: 1.09, 2.90), and completing a degree before medical school (adjusted β = 3.66; 95% CI: 2.23, 5.09) were associated with higher RSE.

Conclusion
There were no associations between the predictor variables and PoR. Female students had lower self-reported RSE scores. Future studies should investigate the role of targeted research mentorship in improving RSE amongst female medical students.
Role of denosumab in bone erosions in rheumatoid arthritis
Authors: Stefania Silvia , Rotondo Cinzia , Mele Angiola , Trotta Antonello , Cantatore Francesco Paolo , Corrado Addolorata 
Published: February 2023

Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and synovitis which evolve into joint destruction and deformity. Bone abnormalities are represented by marginal bone erosions and iuxta-articular and generalized osteoporosis. Overactivation of osteoclasts along with dysregulation of osteoblasts are the key events. Bone resorption is mediated by the receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANK-L), responsible for the differentiation, proliferation, and activation of osteoclasts. RANK-L binds its receptor RANK, localized on the surface of preosteoclasts and mature osteoclasts promoting osteoclastogenesis. High levels of RANK-L were demonstrated in active RA patients. Denosumab, a fully human monoclonal antibody, binds RANK-L and suppresses the RANK–RANK-L signaling pathway leading to the inhibition of osteoclastogenesis. A retrospective analysis of published studies such as clinical trials evidenced the efficacy of denosumab in preventing bone erosion progression in RA patients.
Key messages Key questions to answer in future include the following: Could denosumab be associated with other biologic therapies in RA patients? Could denosumab block the progression of bone damage in RA? Could denosumab be used for the prevention of bone erosion in RA?
Visual Hallucinations in Psychosis: The Curious Absence of the Primary Visual Cortex
Authors: van Ommen Marouska M , van Laar Teus , Renken Remco , Cornelissen Frans W , Bruggeman Richard 
Published: February 2023

AbstractBackground and HypothesisApproximately one-third of patients with a psychotic disorder experience visual hallucinations (VH). While new, more targeted treatment options are warranted, the pathophysiology of VH remains largely unknown. Previous studies hypothesized that VH result from impaired functioning of the vision-related networks and impaired interaction between those networks, including a possible functional disconnection between the primary visual cortex (V1) and higher-order visual processing regions. Testing these hypotheses requires sufficient data on brain activation during actual VH, but such data are extremely scarce.Study DesignWe therefore recruited seven participants with a psychotic disorder who were scanned in a 3 T fMRI scanner while indicating the occurrence of VH by pressing a button. Following the scan session, we interviewed participants about the VH experienced during scanning. We then used the fMRI scans to identify regions with increased or decreased activity during VH periods versus baseline (no VH).Study ResultsIn six participants, V1 was not activated during VH, and in one participant V1 showed decreased activation. All participants reported complex VH such as human-like beings, objects and/or animals, during which higher-order visual areas and regions belonging to the vision-related networks on attention and memory were activated.DiscussionThese results indicate that VH are associated with diffuse involvement of the vision-related networks, with the exception of V1. We therefore propose a model for the pathophysiology of psychotic VH in which a dissociation of higher-order visual processing areas from V1 biases conscious perception away from reality and towards internally generated percepts.
Converting donation to transaction: how platform capitalism exploits relational labor in non-profit fundraising
Authors: Zheng Wenjuan 
Published: February 2023

Abstract
Viewing platforms as a new kind of factory and playground, scholars have investigated how the platform economy transforms work and entertainment. As dominant platforms continue to encroach on new markets and sectors, including the non-profit sector, few have examined the ramifications when they serve as a plaza for civic action. Despite the civic orientation of these platform activities, platforms can reconfigure the charity event and mediate civic interaction through the permissive power they possess to extract surplus value from users’ online interactions invisibly. Drawing from the ethnographic fieldwork of the two non-governmental organizations (NGOs) participating in a crowdfunding event in China, I show how the platform company creates a competition-based civic event to mobilize thousands of NGOs to crowdfund on their social media platform. In particular, the platform induced NGO workers working for those organizations to mobilize their networks for fundraising. Performing relational labor to persuade friends, families and acquaintances to give donations as a job responsibility deviated from the norms of reciprocity, which incurred workers’ emotional, social and even financial costs. Invisibly, the platform extracts social capital from workers’ relational labor.
The Feasibility and Acceptability of a Needs-Oriented Psychoeducational Intervention Among Caregivers of Adolescent and Young Adult Cancer Patients
Authors: Cheng Qinqin , Ng Marques S. N. , Chen Yongyi , Li Xuying , Liu Gaoming , Zhang Mengyue , So Winnie K. W. 
Published: February 2023

Background
Little is known about the psychoeducational interventions for caregivers of adolescent and young adult (AYA) cancer patients.

Objective
To evaluate the feasibility and acceptability of a needs-oriented psychoeducational intervention among caregivers of AYA cancer patients.

Methods
In this 2-arm (parallel-group), pilot randomized controlled trial, participants were randomized to the intervention or control group. Participants in the control group received usual care, whereas those in the intervention group received a needs-oriented psychoeducational intervention via WeChat as well as the usual care. Feasibility was evaluated on recruitment, attrition, and adherence rates and the data collection process. Acceptability was assessed based on participants’ satisfaction with and perceived usefulness of the intervention, collected using a questionnaire. In addition, a semistructured interview was conducted to explore their experiences.

Results
Twenty-four caregivers of AYA cancer patients were recruited, with a consent rate of 61.5%. The attrition and response rates 5 weeks after baseline were 8.3% and 91.7%. Among the 12 participants in the intervention group, 10 (83.3%) completed all of the 5 weekly sessions. Most of the participants were satisfied with the program and perceived its usefulness. The semistructured interviews revealed 3 major categories: facilitators of participation, perception of the intervention, and perceived benefits.

Conclusions
The needs-oriented psychoeducational intervention delivered through WeChat is feasible for and acceptable to caregivers of AYA cancer patients. A full-scale study is warranted to examine the effects of this intervention on caregivers’ health outcomes.

Implications for Practice
The WeChat-based, needs-oriented psychoeducational intervention may be beneficial to improve caregivers’ health outcomes.
Vitamin C and Transferrin Reduce RNA Methylation in Mouse Embryonic Stem Cells
Authors: Brandt Gabrielle , Sedivy Laura J. , Mitchell Matthew , Phiel Christopher J. 
Published: February 2023

AbstractMethylation of mRNA on adenosine bases (referred to as m6A) is the most common internal modification of mRNA in eukaryotic cells. Recent work has revealed a detailed view of the biological significance of m6A-modified mRNA, with a role in mRNA splicing, control of mRNA stability, and mRNA translation efficiency. Importantly, m6A is a reversible modification, and the primary enzymes responsible for methylating (Mettl3/Mettl14) and demethylating RNA (FTO/Alkbh5) have been identified. Given this reversibility, we are interested in understanding how m6A addition/removal is regulated. Recently, we identified glycogen synthase kinase-3 (Gsk-3) activity as a mediator of m6A regulation via controlling the levels of the FTO demethylase in mouse embryonic stem cells (ESCs), with Gsk-3 inhibitors and Gsk-3 knockout both leading to increased FTO protein and decreased m6A mRNA levels. To our knowledge, this remains one of the only mechanisms identified for the regulation of m6A modifications in ESCs. Several small molecules that have been shown to promote the retention of pluripotency of ESCs, and interestingly, many have connections to the regulation of FTO and m6A. Here we show that the combination of Vitamin C and transferrin potently reduces levels of m6A and promotes retention of pluripotency in mouse ESCs. Combining Vitamin C and transferrin should prove to be valuable in growing and maintaining pluripotent mouse ESCs.
Antibody landscape of C57BL/6 mice cured of B78 melanoma via immunotherapy
Authors: Hoefges A , McIlwain SJ , Erbe AK , Mathers N , Xu A , Melby D , Tetreault K , Le T , Kim K , Pinapati RS , Garcia B , Patel J , Heck M , Feils AS , Tsarovsky N , Hank JA , Morris ZS , Ong IM , Sondel PM 
Published: February 2023

1AbstractAntibodies can play an important role in innate and adaptive immune responses against cancer, and in preventing infectious disease. Flow cytometry analysis of sera of immune mice that were previously cured of their melanoma through a combined immunotherapy regimen with long-term memory showed strong antibody-binding against melanoma tumor cell lines. Using a high-density whole-proteome peptide array, we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by 2 or more of these 6 mice and exhibited strong antibody binding only by immune, not naive sera. Confirmatory studies were done to validate these results using 2 separate ELISA-based systems. To the best of our knowledge, this is the first study of the “immunome” of protein-based epitopes that are recognized by immune sera from mice cured of cancer via immunotherapy.summaryHoefges et al. utilized a whole-proteome peptide array approach to show that C57BL/6 mice develop a large repertoire of antibodies against linear peptide sequences of their melanoma after receiving a curative immunotherapy regimen consisting of radiation and an immunocytokine.