bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC1-3 inhibition reduces CCR2 expression and immunosuppressive function of myeloid-derived suppressor cells
Authors: Xie Zhiqi , Okada Yoshiaki , Okuzaki Daisuke , Okada Naoki , Tachibana Masashi 
Published: June 2023

AbstractMyeloid-derived suppressor cells (MDSCs) play a critical role in cancer progression and resistance, making them significant targets for cancer immunotherapy. Although epigenetic regulation by histone deacetylases (HDACs) regulates cell fate and function, the specific roles of HDACs in modulating MDSCs remain poorly understood. We aimed to examine the effects and underlying mechanisms of HDAC on MDSCs using various HDAC inhibitors. HDAC1-3 inhibitors were found to reduce the expression of CCR2, a chemokine receptor that mediates the migration of monocytic (M-)MDSCs to tumors and attenuated the immunosuppressive activity of MDSCs. In an orthotopic hepatocellular carcinoma (HCC) murine model, HDAC1-3 inhibitors reduced the infiltration of M-MDSCs, increased the number of natural killer cells in tumors, and suppressed tumor growth. Our results also suggest that HDAC1-3 inhibitors potentiate the antitumor effects of anti-programmed cell death protein 1 antibodies. To elucidate the molecular mechanisms underlying the inhibition of MDSCs by HDAC1-3 inhibitors, ATAC-seq and RNA-seq analyses were performed. We identified 115 genes that were epigenetically upregulated by HDAC1-3 inhibitors, related to transcriptional regulation and ubiquitination. HDAC1-3 inhibitors further reduced CCR2 protein expression by enhancing ubiquitination-mediated degradation. Our findings reveal a novel mechanism of action of HDAC1-3 inhibitors in MDSCs and suggest a potential combination strategy with immunotherapy for the clinical translation of HCC.
Validity of observation tools for patients hospitalized with osteoporotic vertebral fractures
Authors: Yoshimi Youhei , Matsuura Takanori , Miyazato Kazuaki , Takahashi Shiho , Tanaka Nami , Morinaga Hanae , Hayata Asuka , Onishi Minami , Nagano Yousuke , Ohnishi Hideo 
Published: June 2023

AbstractOsteoporotic vertebral fractures in older patients impair activities of daily living because of low back pain and abnormal posture. Assessing pain using self-reported assessment tools is difficult, especially in patients with moderate-to-severe cognitive impairment. In recent years, observational assessment tools have been used when self-reported assessment tools were difficult to implement. However, no reports have investigated the usefulness of observational assessment tools in patients with acute-phase orthopedic disorders without comorbidities. This study examined the validity of observational tools for pain assessment in patients with lumbar vertebral fractures. Patients admitted to our hospital with acute-phase vertebral fractures were enrolled in this prospective study. Pain was assessed using Japanese versions of the Abbey Pain Scale and Doloplus-2 observational assessment tools, in addition to the Numerical Rating Scale, a self-reported assessment tool. To verify the validity of each pain assessment tool, we examined whether each tool correlated with the activities of daily living and ambulatory status. Activities of daily livings were assessed using the Barthel Index. Ambulatory status was assessed using the Functional Ambulation Categories and the 10-m walking test. Similar to the Numerical Rating Scale scores, assessments with the Abbey Pain Scale and Doloplus-2 showed significant decreases in scores over time. In addition, a significant positive correlation was observed between the self-reported and observational assessment tools. Each pain assessment tool was significantly negatively correlated with activities of daily livings and ambulatory status. Our results indicated when self-reported assessment with the Numerical Rating Scale was difficult for patients with cognitive impairment, pain could be estimated using the Abbey Pain Scale and Doloplus-2 observational assessment tools.
Environment-Wide Association Studies of Anemia in the National Health and Nutrition Examination Surveys
Authors: Zhou Jiayan , Palmiero Nicole , Passero Kristin , McGuigan John R , Zarzar Tomás González , Sandeep Prabhu K. , Hall Molly A. 
Published: June 2023

AbstractBackgroundAnemia is a global health problem that can lead to chronic illness in adults and may be fatal in children and the elderly. While some dietary factors and heavy metals are known risk factors for anemia, there are no environment-wide studies of anemia.ObjectivesOur goal was to identify environment-wide risk factors for anemia.MethodsWe evaluated general anemia in children and adults and further classified anemia as a) iron, vitamin B12, or folate deficiency anemia; b) anemia in general chronic diseases; and c) anemia in chronic kidney disease. As well as quantitative measures including level of hemoglobin, serum vitamin B12, red blood cell (RBC) folate, and serum iron. Environment-wide association studies (EWAS) were performed to identify novel environmental risk factors of anemia in discovery and replication subsets of the National Health and Nutrition Examination Surveys (NHANES).ResultsWe identified and replicated 106 potential environmental risk factors for anemia. As expected, serum iron was the top exposure associated with general anemia for adults. Cadmium was associated with adult hemoglobin levels, as were vitamin Bs, micronutrients, smoking, and alcohol consumption. Further, decreased levels of multiple vitamins, including vitamin A, vitamin Es and multiple vitamin Bs, were associated with general anemia in adults. Use of tobacco and alcohol was also found to be associated with red blood cell folate and serum iron levels. In children, serum iron level was associated with folic acid supplements and vitamin A supplements.DiscussionThis is the first EWAS of anemia, providing insights into the environmental etiology of anemia risk in children and adults. These results may lead to the development of public health recommendations to mitigate anemia risk factors.
Risk of tuberculosis and uptake rates of latent tuberculosis infection screening among clinical risk groups in South Korea: A nationwide population-based cohort study
Authors: Kim Hyung Woo , Min Jinsoo , Choi Joon Young , Shin Ah Young , Myong Jun-Pyo , Lee Yunhee , Yim Hyeon Woo , Jeong Hyunsuk , Bae Sanghyuk , Hoyong Choi , In Hyekyung , Park Ahyoung , Jang Miri , Koo Hyeon-Kyoung , Lee Sung-Soon , Park Jae Seuk , Kim Ju Sang 
Published: June 2023

AbstractBackgroundThis study aimed to investigate actual tuberculosis (TB) risk and uptake rates of latent tuberculosis infection (LTBI) screening among eight clinical risk groups specified in Korean guidelines. Proportions of potentially preventable TB in these groups were also calculated.Methods and FindingsPatients enrolled before January 1st, 2018, were classified into a prevalence cohort whereas those enrolled thereafter were classified into an incidence cohort. Both cohorts were followed up until December 31st, 2020. Sex, age, and calendar year-adjusted standardized incidence ratio (SIR) of tuberculosis was calculated with total population in South Korea as a reference group. The number of TB patients notified in 2018 was investigated for both prevalence and incidence cohorts. SIR of TB in each incidence cohort was higher than that in each corresponding prevalence cohort. Among all incidence cohorts, SIR in people living with human immunodeficiency virus (PLHIV) was the highest (17.41, (95% CI: 14.14-21.43)). Although classified as moderate TB risk diseases in current guideline, end-stage renal disease (ESRD) (8.05, (7.02-9.23)) and uncontrolled diabetes mellitus (DM) (6.31, (5.78-6.99)) showed high SIRs comparable to other high-risk diseases. Among total TB cases notified in 2018, each cohort accounted for less than 1.5% except for patients with DM. The uptake rate of LTBI test was the highest among patients using TNF inhibitors (92.7%), followed by those who underwent organ transplantation (60.4%) and PLHIV (41.3%).ConclusionsLTBI screening should be reinforced for certain clinical risk groups such as ESRD or uncontrolled DM. Beyond the current guideline, additional high-risk groups should be identified.
Early Psychosis Informatics into Care [EPICare]: A co-designed protocol for implementing and evaluating a national integrated digital registry and clinical decision support system within early intervention in psychosis services
Authors: Lowri Griffiths Siân , Murray Graham K. , Logeswaran Yanakan , Ainsworth John , Allan Sophie M. , Campbell Niyah , Drake Richard , Katshu Mohammad Zia , Machin Matthew , Pope Megan A. , Sullivan Sarah A. , Waring Justin , Bogatsu Tumelo , Kane Julie , Weetman Tyler , Johnson Sonia , Kirkbride James B. , Upthegrove Rachel 
Published: June 2023

ABSTRACTIntroductionEarly Intervention in Psychosis services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems have revolutionised delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care and prognosis. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. Here, we provide details of a co-designed protocol to produce an evidence-based, stakeholder-informed framework for the build, implementation, and evaluation of a national integrated digital registry and clinical decision support system for psychosis, known as EPICare (Early Psychosis Informatics for Care).Methods and AnalysisUsing a participatory co-design framework, we engaged key stakeholders (N∼40-50) across four meetings to establish the parameters and essential features of EPICare and identify factors likely to influence adoption and implementation into routine practice. Stakeholders consisted of organisational, clinical, academic, and patient and public contributors. In collaboration with National Health Service (NHS) informatics teams, we identified how to retrieve key data items from Electronic Health Records and subsequently design the software architecture and data model to create an infrastructure plan for future implementation. Guided by Normalisation Process Theory, data synthesised from observations of stakeholder meetings and individual interviews (n=10) were subject to interpretative qualitative analysis. Finally, a co-designed set of guides were produced to allow for the build, implementation, and evaluation of EPICare in a larger, future study. An inclusive, representative stakeholder group, fully engaged with the future co-development of EPICare, was also established.
Cost components of school-based oral health-promoting programs: a systematic review protocol
Authors: Matoso Bárbara da Silva Mourthé , Gomes Viviane Elisângela , Marcenes Wagner , Micaela de Souza Noronha Kênya Valéria , Lima Camilla Aparecida Silva de Oliveira , Ferreira Raquel Conceição 
Published: June 2023

AbstractIntroductionOral health-promoting school programs play a crucial role in achieving universal coverage of oral health care by addressing oral diseases and promoting the well-being and quality of life of children and adolescents. However, a lack of studies has evaluated the costs associated with implementing these programs, which hinders decision-makers in adopting them on a large scale. This review aims to assess the cost components involved in school-based oral health-promoting programs.MethodsThis review will include studies that have conducted either partial or full economic evaluations, focusing on describing the cost components of oral health-promoting programs implemented in primary schools involving students aged 6 to 14. A systematic search was conducted across multiple databases: MEDLINE, The Cochrane Library, the Virtual Health Library, the NHS Economic Evaluation Database, Web of Science, Scopus, and EMBASE. Additionally, gray literature was searched using the Health Technology Assessment Database. Two independent reviewers will screen the titles and abstracts, followed by a full-text review based on predefined inclusion criteria. Data extraction and critical appraisal evaluation will also be carried out independently by two reviewers. In case of disagreements, the reviewer team will resolve them through discussion.DiscussionThe systematic review resulting from this protocol aims to provide evidence regarding the cost components and necessary resources for implementing and maintaining oral health-promoting school programs. This information can assist decision-makers in adopting these programs on a larger scale and effectively addressing oral diseases among children and adolescents.Protocol registrationCRD42022363743.
Bone Morphogenetic Protein-9 Controls Pulmonary Vascular Growth and Remodeling
Authors: Berrebeh Nihel , Mbouamboua Yvon , Thuillet Raphaël , Ottaviani Mina , Chelgham Mustapha Kamel , Magnone Virginie , Desroches-Castan Agnès , Ricard Nicolas , Anegon Ignacio , Remy Séverine , Schermuly Ralph Theo , Lebrigand Kevin , Kojonazarov Baktybek , Savale Laurent , Humbert Marc , Bailly Sabine , Barbry Pascal , Tu Ly , Guignabert Christophe 
Published: June 2023

AbstractBackgroundPulmonary arterial hypertension (PAH), a life-limiting condition characterized by dysfunction of pulmonary microvascular endothelium, is predisposed by mutations in several genes that are critical for the proper activation of specific bone morphogenetic protein (BMP) receptor complexes that phosphorylate intracellular Smad1/5/8 in endothelial cells. However, the functional importance of BMP-9 (GDF2), one of the high affinity ligands for ALK1 (ACVRL1) and BMPR-II (BMPR2), for the pulmonary microvasculature remains imperfectly understood.ObjectiveThe aim of this study was first to determine thein vivoimpact of BMP-9 deficiency on pulmonary vascular growth and remodeling, then to assess whether ALK1 expression can alter BMP-9 transcriptional signatures in human pulmonary microvascular endothelial cells (PMECs).MethodsCRISPR-Cas9gene editing was used to createGdf2knockout rats inSprague Dawleybackground. Computed micro-tomography (Micro-Ct) scan after Microfil perfusion was performed to generate high-resolution 3D-images of the pulmonary arterial tree. The influence of ALK1 abundance on the transcriptional signatures of BMP-9 responses in human PMECs was assessed by single cell (sc)-RNAseq. Functional studies were performed using human PMECs exposed to BMP-9, the ALK1/2 inhibitor ML347, and ALK1-Fc fusion protein that neutralizes BMP9/10 and two animal models of severe pulmonary hypertension (PH).ResultsMicro-Ct angiography revealed structural and functional remodeling along the pulmonary vascular tree in BMP-9 deficient rats, resulting in vasodilation and increase in vascular density. scRNA-seq experiments identified distinct transcriptional signatures in human PMECs in response to BMP-9 responses. ALK1 expression had a direct impact on both proangiogenic capacities and transcriptional responses of PMECs to BMP-9. Functional studies performed in human PMECs confirmed that abundance of BMP-9 and ALK1 acted as modulators of PMEC tube formation, migration and proliferation, and also of vascular endothelial growth factor (VEGF)/VEGFR activities. The structural and functional remodeling observed inGdf2knockout rats coincided with a lower susceptibility to develop severe PH induced by monocrotaline (MCT) and SU5416+hypoxia (SuHx).ConclusionBMP-9 and ALK1 are critical modulators of pulmonary vascular growth and remodeling. Our results provide potential mechanisms explaining why BMP-9 deficient animals are less susceptible to the rise in pulmonary vascular resistance in experimental models of PH.
dsRID: Editing-free in silico identification of dsRNA region using long-read RNA-seq data
Authors: Yamamoto Ryo , Liu Zhiheng , Choudhury Mudra , Xiao Xinshu 
Published: June 2023

AbstractDouble-stranded RNAs (dsRNAs) are potent triggers of innate immune responses upon recognition by cytosolic dsRNA sensor proteins. Identification of endogenous dsRNAs helps to better understand the dsRNAome and its relevance to innate immunity related to human diseases. Here, we report dsRID (double-stranded RNA identifier), a machine learning-based method to predict dsRNA regionsin silico, leveraging the power of long-read RNA-sequencing (RNA-seq) and molecular traits of dsRNAs. Using models trained with PacBio long-read RNA-seq data derived from Alzheimer’s disease (AD) brain, we show that our approach is highly accurate in predicting dsRNA regions in multiple datasets. Applied to an AD cohort sequenced by the ENCODE consortium, we characterize the global dsRNA profile with potentially distinct expression patterns between AD and controls. Together, we show that dsRID provides an effective approach to capture global dsRNA profiles using long-read RNA-seq data.
Age-dependent increase in tau phosphorylation at serine 396 in Huntington’s disease pre-frontal cortex
Authors: Petrozziello Tiziana , Huntress Sommer S. , Castillo-Torres Ayleen L. , Quinn James P. , Connors Theresa R. , Auger Corinne A. , Mills Alexandra N. , Kim Spencer E. , Liu Sophia , Mahmood Farah , Boudi Adel , Wu Muzhou , Sapp Ellen , Kivisäkk Pia , Sunderesh Shekar R. , Pouladi Mahmoud A. , Arnold Steven E. , Hyman Bradley T. , Rosas H. Diana , DiFiglia Marian , Pinto Ricardo Mouro , Kegel-Gleason Kimberly , Sadri-Vakili Ghazaleh 
Published: June 2023

AbstractBackgroundTo date, it is still controversial whether tau phosphorylation plays a role in Huntington’s disease (HD), as previous studies demonstrated either no alterations or increases in phosphorylated tau (pTau) in HD post-mortem brain and mouse models.ObjectivesThe goal of this study was to determine whether total tau and pTau levels are altered in HD.MethodsImmunohistochemistry, cellular fractionations, and western blots were used to measure tau and pTau levels in a large cohort of HD and control post-mortem prefrontal cortex (PFC). Furthermore, western blots were performed to assess tau, and pTau levels in HD and control isogenic embryonic stem cell (ESC)-derived cortical neurons and neuronal stem cells (NSCs). Similarly, western blots were used to assess tau and pTau inHttQ111and transgenic R6/2 mice. Lastly, total tau levels were assessed in HD and healthy control plasma using Quanterix Simoa assay.ResultsOur results revealed that, while there was no difference in tau or pTau levels in HD PFC compared to controls, tau phosphorylated at S396 levels were increased in PFC samples from HD patients 60 years or older at time of death. Additionally, tau and pTau levels were not changed in HD ESC-derived cortical neurons and NSCs. Similarly, tau or pTau levels were not altered inHttQ111and transgenic R6/2 mice compared to wild-type littermates. Lastly, tau levels were not changed in plasma from a small cohort of HD patients compared to controls.ConclusionTogether these findings demonstrate that pTau-S396 levels increase significantly with age in HD PFC.
Complexity of baseline cognitive and psychological status in haematology patients planned for chimeric antigen receptor T-cell therapy
Authors: Kuznetsova Valeriya , Rosenfeld Hannah , Sales Carmela , van der Linde Samantha , Roos Izanne , Roberts Stefanie , D’Aprano Fiore , Loi Samantha M , Dowling Mark , Dickinson Michael , Kalincik Tomas , Harrison Simon J , Anderson Mary Ann , Malpas Charles B 
Published: June 2023

AbstractBackgroundImmune effector cell-associated neurotoxicity syndrome (ICANS) is a relatively common consequence of chimeric antigen receptor T-cell (CAR-T) therapy, with a wide range of possible cognitive presentations. The aim of this study was to characterise a real-word cognitive and psychological status of patients with advanced haematologic and solid organ malignancies planned for CAR-T. We also aimed to examine utility of two cognitive screening approaches.MethodsPatients underwent specialist cognitive assessment, including a self-report questionnaire of psychopathology and subjective cognitive function. A subset of individuals also completed the Montreal Cognitive Assessment (MoCA).ResultsOf 60 patients included, 15-16 (25%-27%) presented with evidence of cognitive impairment, with six unique patterns of dysfunction. Impaired patients were more likely to have B-cell acute lymphoblastic leukaemia (BF10=9.30), be younger (BF10=7.76), have bone marrow involvement (BF10=5.18), report history of anxiety (BF10=4.85), or have evidence of psychopathology (BF10=31.30). Analyses did not support the utility of cognitive screening. Of those patients who completed a self-report measure of psychopathology, nine (15.8%) were elevated on at least one symptom domain.ConclusionsThe findings demonstrate a broad spectrum of dysfunction and psychopathology in this cohort, emphasising the importance of baseline evaluation for detecting cognitive neurotoxicity symptoms that might arise after CAR-T infusion.
Associations of social media use with tobacco smoking and e-cigarettes: a national longitudinal study
Authors: Hopkinson Nicholas S. , Vrinten Charlotte , Parnham Jennie C. , Radó Márta K. , Filippidis Filippos T. , Vamos Eszter , Laverty Anthony A. 
Published: June 2023

ABSTRACTBackgroundSocial media may influence children and young people’s health behaviour, including smoking and e-cigarette use.MethodsWe analysed data from participants aged 10-25 in the UK Household Longitudinal Study 2015-2022. The amount of social media use reported on a normal weekday, was related to current tobacco smoking and e-cigarette use. Generalised Estimating Equation (GEE) logistic regression models investigated associations of social media use with tobacco and e-cigarette use. Models controlled for possible confounders including age, sex, country of UK, ethnicity, household income and use of tobacco/e-cigarettes by others within the home.ResultsAmong 10,808 participants with 27,962 observations, current tobacco smoking was reported by 2,237(20.7%) at least one time point, and current e-cigarette use by 1,013 participants (9.4%). In adjusted GEE models, increasing use of social media was associated with greater odds of current smoking and this was particularly apparent at higher levels of use (AOR 3.11, CI 2.41-4.03 for ≥7hours/day vs no use). Associations were similar for e-cigarettes, e.g. OR=3.04, CI 2.11-4.40 for ≥7hours social media use versus none).ConclusionsSocial media use is associated with an increased risk of e-cigarette and tobacco use, reinforcing the need for policies to address this as an avenue for marketing to children and young people.