bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers and facilitators to cervical cancer screening for women from culturally and linguistically diverse backgrounds; a qualitative study of GPs
Authors: Chandrakumar Abira , Hoon Elizabeth , Benson Jill , Stocks Nigel 
Published: November 2022

ObjectiveTo explore general practitioners’ (GPs) perspectives on the barriers and facilitators to cervical cancer screening (CCS) for women from culturally and linguistically diverse (CALD) backgrounds.DesignQualitative descriptive study involving semi-structured interviews, with interview guide informed by the Theoretical Domains Framework.SettingAdelaide, South Australia.ParticipantsTwelve GPs with experience in providing CCS to women from CALD backgrounds participated.ResultsFour main themes emerged: ‘importance of clinician–patient relationship’, ‘patients’ cultural understanding regarding health care and CCS’, ‘communication and language’ and ‘health system related’. Each theme had several subthemes. GPs’ professional relationship with their patients and repeated advice from other clinicians, together with the provision of opportunistic CCS, were described as facilitators, and encompassed the theme of ‘importance of clinician–patient relationship’. This theme also raised the possibility of self-collection human papilloma virus tests. Lack of awareness and knowledge, lower priority for cancer screening and patients’ individual circumstances contributed to the theme of ‘patients’ cultural understanding regarding health care and CCS’, and often acted as barriers to CCS. ‘Communication and language’ consisted of language difficulties, interpreter use and use of appropriate resources. Language difficulties were a barrier to the provision of CCS, and GPs used interpreters and written handouts to help overcome this. The theme of ‘health system related’ involved the increased time needed for CCS consults for CALD women, access to appointments, funding, health promotion and effective use of practice management software.ConclusionsThis study highlights that multiple, inter-related barriers and facilitators influence CALD women’s engagement with CCS, and that GPs needed to manage all of these factors in order to encourage CCS participation. More efforts are needed to address the barriers to ensure that GPs have access to appropriate resources, and CALD patients have access to GPs they trust.
Trends of blood pressure, raised blood pressure, hypertension and its control among Italian adults: CUORE Project cross-sectional health examination surveys 1998/2008/2018
Authors: Donfrancesco Chiara , Di Lonardo Anna , Lo Noce Cinzia , Buttari Brigitta , Profumo Elisabetta , Vespasiano Francesca , Vannucchi Serena , Galletti Ferruccio , Onder Graziano , Gulizia Michele Massimo , Galeone Daniela , Bellisario Paolo , Palmieri Luigi 
Published: November 2022

ObjectivesTo assess in the Italian general adult population the trends of blood pressure (BP) and prevalence of raised BP (RBP), hypertension and its control in order to evaluate population health and care, and the achievement of an RBP 25% relative reduction as recommended by the WHO at population level.DesignResults comparison of health examination surveys, cross-sectional observational studies based on health examination of randomly selected age and sex stratified samples including residents aged 35–74 years. Data of the 2018/2019 survey were compared with the previous ones collected in 1998/2002 and 2008/2012.SettingHealth examination surveys conducted in Italy within the CUORE Project following standardised methodologies.Participants2985 men and 2955 women examined in 1998/2002, 2218 men and 2204 women examined in 2008/2012 and 1031 men and 1066 women examined in 2018/2019.Primary and secondary outcome measuresAge-standardised mean of BP, prevalence of RBP (systolic BP and/or diastolic BP ≥140/90 mm Hg), hypertension (presenting or being treated for RBP) and its awareness and control, according to sex, age class and educational level.ResultsIn 2018/2019, a significant reduction was observed in systolic BP and diastolic BP in men (1998/2002: 136/86 mm Hg; 2008/2012: 132/84 mm Hg; and 2018/2019: 132/78 mm Hg) and women (132/82 mm Hg, 126/78 mm Hg and 122/73 mm Hg), and in the prevalence of RBP (50%, 40% and 30% in men and 39%, 25% and 16% in women) and of hypertension (54%, 49% and 44% in men and 45%, 35% and 32% in women). Trends were consistent by age and education attainment. In 2018/2019, hypertensive men and women with controlled BP were only 27% and 41%, but a significant favourable trend was observed.ConclusionsData from 2018/2019 underlined that RBP is still commonly observed in the Italian population aged 35–74 years, however, the WHO RBP target at that time may be considered met.
Quality metrics for enhanced performance of an NGS panel using single-vial amplification technology
Authors: Barua Subit , Hsiao Susan , Clancy Emily , Freeman Christopher , Mansukhani Mahesh , Fernandes Helen 
Published: November 2022

AimsTargeted next-generation sequencing (NGS) panels, which identify genomic alterations, are the stronghold of molecular oncology laboratories. In spite of technological advances, the quantity and quality of DNA from formalin-fixed paraffin-embedded tissue and paucicellular specimens are barriers to successful sequencing. Here, we describe an NGS assay employing single tube stem-loop inhibition mediated amplification technology that delivers highly accurate results with low input DNA. Rigorous quality metrics, regular monitoring and in-depth validation make the test attractive for clinical laboratories.MethodsThe study used a customised NGS panel, targeting 48 genes across several solid tumour types. Validation, in accordance with guidelines from New York State, sequenced patient samples harbouring 136 known variants, including single-nucleotide variants (SNVs) and indels. Specimen types included formalin-fixed paraffin embedded blocks, core biopsies and cytology material. Neoplastic cellularity of the tumours ranged from 10% to 80%.ResultsThe assay was highly specific and sensitive with excellent accuracy, reproducibility and repeatability/precision. Concordant results for identification of SNVs and indels were obtained from specimens with DNA input of 2–3 ng, tissue with 10% neoplastic cellularity and variant allelic frequencies of 2.5%–3%. Over 99% of the target areas are shown to achieve at least 500X coverage when parsed through two bioinformatics pipelines. With over 2000 clinical specimens analysed, the success of the panel for reporting of results is 95.3%ConclusionsThe advanced technology enables accurate identification of clinically relevant variants with uniformity of coverage and an impressive turn-around-time. The overall workflow and cost-effectiveness provide added value.
Detection of cerebral aneurysms using artificial intelligence: a systematic review and meta-analysis
Authors: Din Munaib , Agarwal Siddharth , Grzeda Mariusz , Wood David A , Modat Marc , Booth Thomas C 
Published: November 2022

BackgroundSubarachnoid hemorrhage from cerebral aneurysm rupture is a major cause of morbidity and mortality. Early aneurysm identification, aided by automated systems, may improve patient outcomes. Therefore, a systematic review and meta-analysis of the diagnostic accuracy of artificial intelligence (AI) algorithms in detecting cerebral aneurysms using CT, MRI or DSA was performed.MethodsMEDLINE, Embase, Cochrane Library and Web of Science were searched until August 2021. Eligibility criteria included studies using fully automated algorithms to detect cerebral aneurysms using MRI, CT or DSA. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis: Diagnostic Test Accuracy (PRISMA-DTA), articles were assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis included a bivariate random-effect model to determine pooled sensitivity, specificity, and area under the receiver operator characteristic curve (ROC-AUC). PROSPERO: CRD42021278454.Results43 studies were included, and 41/43 (95%) were retrospective. 34/43 (79%) used AI as a standalone tool, while 9/43 (21%) used AI assisting a reader. 23/43 (53%) used deep learning. Most studies had high bias risk and applicability concerns, limiting conclusions. Six studies in the standalone AI meta-analysis gave (pooled) 91.2% (95% CI 82.2% to 95.8%) sensitivity; 16.5% (95% CI 9.4% to 27.1%) false-positive rate (1-specificity); 0.936 ROC-AUC. Five reader-assistive AI studies gave (pooled) 90.3% (95% CI 88.0% – 92.2%) sensitivity; 7.9% (95% CI 3.5% to 16.8%) false-positive rate; 0.910 ROC-AUC.ConclusionAI has the potential to support clinicians in detecting cerebral aneurysms. Interpretation is limited due to high risk of bias and poor generalizability. Multicenter, prospective studies are required to assess AI in clinical practice.
An Enhancer Demethylator Phenotype Converged to Immune Dysfunction and Resistance to Immune Checkpoint Inhibitors in Clear-Cell Renal Cell Carcinomas
Authors: Lu Xiaofan , Vano Yann , Helleux Alexandra , Su Xiaoping , Lindner Véronique , Davidson Guillaume , Mouawad Roger , Spano Jean-Philippe , Rouprêt Morgan , Elaidi Reza , Compérat Eva , Verkarre Virginie , Sun Chengming , Chevreau Christine , Bennamoun Mostefa , Lang Hervé , Tricard Thibault , Cheng Wenxuan , Xu Li , Davidson Irwin , Yan Fangrong , Fridman Wolf Herman , Sautes-Fridman Catherine , Oudard Stéphane , Malouf Gabriel G. 
Published: November 2022

AbstractPurpose:Immune checkpoint inhibitors (ICI) have revolutionized the treatment of patients with clear-cell renal cell carcinomas (ccRCC). Although analyses of transcriptome, genetic alterations, and the tumor microenvironment (TME) have shed light into mechanisms of response and resistance to these agents, the role of epigenetic alterations in this process remains fully unknown.Experimental Design:We investigated the methylome of six ccRCC cohorts as well as one cell line dataset. Of note, we took advantage of the BIONIKK trial aiming to tailor treatments according to Paris Descartes 4-gene expression subgroups, and performed Illumina EPIC profiling for 46 samples related to patients treated with ipilimumab plus nivolumab, and 17 samples related to patients treated with sunitinib.Results:A group of tumors associated with enhancer demethylation was discovered, namely TED. TED was associated with tumors with sarcomatoid differentiation and poor clinical outcome. TED harbored TET1 promoter demethylation, activated the gene expression signature of epithelial–mesenchymal transition and IL6/JAK/STAT3 pathways, and displayed a TME characterized by both immune activation and suppressive populations, fibroblast infiltration, and endothelial depletion. In addition, TED was a predictive factor of resistance to the combination of first-line ipilimumab-nivolumab in the BIONIKK clinical trial. Finally, TED was associated with activation of specific regulons, which we also found to be predictive of resistance to immunotherapy in an independent cohort.Conclusions:We report on the discovery of a novel epigenetic phenotype associated with resistance to ICIs that may pave the way to better personalizing patients’ treatments.See related commentary by Zhou and Kim, p. 1170
TBX20 Improves Contractility and Mitochondrial Function During Direct Human Cardiac Reprogramming
Authors: Tang Yawen , Aryal Sajesan , Geng Xiaoxiao , Zhou Xinyue , Fast Vladimir G. , Zhang Jianyi , Lu Rui , Zhou Yang 
Published: November 2022

Background:
Direct cardiac reprogramming of fibroblasts into cardiomyocytes has emerged as a promising strategy to remuscularize injured myocardium. However, it is insufficient to generate functional induced cardiomyocytes from human fibroblasts using conventional reprogramming cocktails, and the underlying molecular mechanisms are not well studied.

Methods:
To discover potential missing factors for human direct reprogramming, we performed transcriptomic comparison between human induced cardiomyocytes and functional cardiomyocytes.

Results:

We identified
TBX20
(T-box transcription factor 20) as the top cardiac gene that is unable to be activated by the MGT133 reprogramming cocktail (
MEF2C
,
GATA4
,
TBX5
, and
miR-133
). TBX20 is required for normal heart development and cardiac function in adult cardiomyocytes, yet its role in cardiac reprogramming remains undefined. We show that the addition of TBX20 to the MGT133 cocktail (MGT+TBX20) promotes cardiac reprogramming and activates genes associated with cardiac contractility, maturation, and ventricular heart. Human induced cardiomyocytes produced with MGT+TBX20 demonstrated more frequent beating, calcium oscillation, and higher energy metabolism as evidenced by increased mitochondria numbers and mitochondrial respiration. Mechanistically, comprehensive transcriptomic, chromatin occupancy, and epigenomic studies revealed that TBX20 colocalizes with MGT reprogramming factors at cardiac gene enhancers associated with heart contraction, promotes chromatin binding and co-occupancy of MGT factors at these loci, and synergizes with MGT for more robust activation of target gene transcription.

Conclusions:
TBX20 consolidates MGT cardiac reprogramming factors to activate cardiac enhancers to promote cardiac cell fate conversion. Human induced cardiomyocytes generated with TBX20 showed enhanced cardiac function in contractility and mitochondrial respiration.
Abstract P1048: Dual Myristic Acid And Trans Activator Of Transcription Conjugated Peptide Facilitates Delivery Of Protein Kinase C Beta II Peptide Inhibitor To Attenuate Myocardial Ischemia/Reperfusion Injury
Authors: Clair Logan , Ramsarran James , Augustin Taurai , Stinson Cameron , Dean Tameka , CHEN Qian , Barsotti Robert , Young Lindon 
Published: November 2022

Peptides conjugated to myristic acid (myr) or trans activator of transcription (tat) have long been used to increase cell permeability via simple diffusion and endocytosis, respectively. Previously myr-PKCβII inhibitor (myr-PKCβII-) exerted cardioprotective effects in myocardial ischemia/reperfusion (I/R) and inhibited superoxide (SO) release from rat leukocytes by 40% (20 μM). By contrast, dual conjugated myr-tat-PKCβII inhibitor (myr-tat-PKCβII-) inhibited SO release by 90% at the same concentration. The purpose of this study was to determine the potency of myr-tat-PKCβII- compared to myr-PKCβII- in mitigating infarct size and restoring cardiac function in an ex-vivo rat model of myocardial I/R injury.
Isolated hearts from male Sprague-Dawley rats (~300g) were subjected to global I(30-min)/R(50-min) . Left ventricular cardiac function was recorded using a pressure transducer. Treatments were infused during the first 5 min of R. After R, the hearts were sectioned (2 mm) from base to apex and stained with 1% triphenyltetrazolium chloride. Infarcted tissue was excised to determine infarct size (i.e. infarct tissue weight/ total tissue weight). Data were analyzed using ANOVA Fisher’s LSD analysis.
Compared to untreated controls (23.2±3.1%, n=17), myr-tat-PKCβII- exerted a significant and similar decrease in infarct size that was observed from 100 nM (9.7±0.59%, n=3, p<0.05), 1 nM (10.0±2.3%, n=5, p<0.05), to 100 pM (12.6±2.3%, n=5, p<0.05); but not at 10 nM (13.8±3.6%, n=5). Cardiac function for all treatment groups did not significantly improve from control. However, at 100pM (1070±170 mmHg/s), +dP/dt max was significantly improved compared to all other treatment groups (p<0.05).
The addition of myr to tat-conjugated peptides improved the cardioprotective effects ~200-fold compared to myr-PKCβII- and ~2000-fold compared to native peptide presumably by enhanced intracellular delivery of cargo. The ~50% reduction in infarct size suggests that myr-tat-PKCβII- is cardioprotective in I/R. Future studies will test our most effective dose determined in ex vivo hearts to restore post-reperfusion cardiac function combined with significant cardiac salvaging effect (reduced infarct size) in a porcine myocardial I/R model.
Abstract P2037: Activation Of A2A Adenosine Receptor Reduces Cardiac Dysfunction Resulting From Pulmonary Hypertension In Rats
Authors: Da Silva Jaqueline S , Rocha Bruna , Gomide Gabriel F , Nascimento-Carlos Bianca , Montagnoli Tadeu , Dematté Bruno E , Maia Rodolfo , Barreiro Eliezer J , Zapata-Sudo Gisele 
Published: November 2022

Pulmonary hypertension (PH) is characterized by extensive pulmonary vascular remodeling, leading to right ventricle (RV) hypertrophy and dysfunction. This work evaluates the hypothesis that the activation of adenosine A2A receptor (AR-A2) by LASBio-1900 could interfere with the cardiac and vascular dysfunction on monocrotaline (MCT)-induced PH in rats. After 14 days of PH induction using a single injection of MCT (60 mg/kg i.p.), twelve male Wistar rats were randomly divided in groups and treated orally either with vehicle or LASSBio-1900 (180 μmol/kg/day). Hemodynamic parameters were obtained using the echocardiography and summarized in table 1.

LASSBio-1900 reduced RV hypertrophy observed in PH because the Fulton index altered from 55.4 ± 2.3 to 35.3 ± 5.9% (p<0.05). HP increased RV systolic and diastolic pressure from 19.2 ± 2.0 and 4.7 ± 1.0 to 51.5 ± 5.2 and 11.9 ± 1.3 mmHg, respectively. Ventricular dysfunction was recovered with LASSBio-1900 treatment reducing pressures to 28.4 ± 4.0 and 6.5 ± 0.8 mmHg, indicating improvement of RV dysfunction. Pulmonary arteriole (PA) muscularization was evaluated by alpha- smooth muscle actin stained and vessel medial wall area was expressed as the percentage of the portion positively stained relative to total transversal area. The increase of the wall thickness of distal PA from 61.7 ± 1.1 to 83.24 ± 1.82 % was reduced by LASSBio-1900 (75.2 ± 3.4 %). Perivascular collagen in PA was evaluated through picrosirius red staining and interstitial fibrosis was measured by obtaining the total collagen area per arteriole area. PH increased the perivascular collagen deposition in 15.1 ± 1.3% however, treatment with LASSBio-1900 reduced to 8.7 ± 1.4% (p<0.05). Intense inflammation process on PH was confirmed with the increase of iNOS expression from 4.5 ± 0.3 (control) to 19.0 ± 0.9% (p<0.05) with reduction to 8.7 ± 1.4% when treated with LASSBio-1900.
In conclusion, the agonist of AR-A2, named LASSBio-1900 improved RV function and pulmonary structural alteration in PH, indicating a new alternative for treatment of PH-induced RV dysfunction.
Can We Accurately Quantify a Lateral Diffusivity from a Single Tracer Release?
Authors: Bisits Josef I. , Stanley Geoffrey J. , Zika Jan D. 
Published: November 2022

Abstract
Mixing along sloping isopycnals plays a key role in the transport and uptake of heat and carbon by the ocean. This mixing is quantified by a lateral diffusivity, which can be measured by tracking the lateral spreading of point release tracer patches. We present a definition for the area of a tracer patch, the time derivative of which provides the lateral diffusivity. To accurately estimate the diffusivity, an ensemble mean concentration field of many tracer release experiments is required. We use numerical experiments to quantify how accurately the “true” lateral diffusivity (obtained from the ensemble mean concentration field) can be estimated from a single tracer release experiment (one ensemble member). To simulate observational campaigns, we also estimate the diffusivity from a single tracer release that is spatially and/or temporally subsampled, quantifying how the error between the estimated diffusivity and the true diffusivity grows as this sampling resolution worsens. We perform these numerical experiments in a two-layer quasigeostrophic model of turbulent flow on a β plane, using an ensemble of 50 passive tracer release experiments, each initialized as a 2D Gaussian but with differing realizations of the turbulent flow. We find that the diffusivity estimates from the single tracer releases have a relative root-mean-square error (RMSE) of 1.43% from the true diffusivity. Subsampling a single tracer release experiment every 956 km increases the relative RMSE from the true diffusivity to 3.1%; also subsampling every 277 days raises this figure to 6.5%.
Effectiveness of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for incomplete spinal cord injury: A systematic review and meta-analysis of randomized controlled trials
Authors: Li Ran , Ding Mingfu , Wang Jiao , Pan Hongxia , Sun Xin , Huang Liyi , Fu Chenying , He Chengqi , Wei Quan 
Published: November 2022

Objective To determine the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for people with incomplete spinal cord injury. Methods PubMed, Embase, Web of Science, PEDro, CENTRAL and CINAHL were searched from inception until September 4, 2022. Randomized controlled trials that evaluated the effects of robotic-assisted gait training on cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury were selected. Mean differences (MD) with 95% confidence interval (CI) were calculated. The methodological quality was evaluated by the Cochrane Risk of Bias 2.0 tool. Subgroup analyses were conducted according to the time since injury. Results In total 19 studies involving 770 patients were eligible for analysis. Individuals with acute incomplete spinal cord injury in robotic-assisted gait training groups showed significantly greater improvements in 6-minute walking test (MD 53.32; 95% CI 33.49 to 73.15; P < 0.001), lower extremity motor scale (MD 5.22; 95% CI 3.63 to 6.80; P < 0.001) and walking index for spinal cord injury II (MD 3.18; 95% CI 1.34 to 5.02; P < 0.001). Robotic-assisted gait training improved peak oxygen consumption to a greater degree for chronic incomplete spinal cord injury patients (MD 4.90; 95% CI 0.96 to 8.84; P = 0.01). Conclusion Robot-assisted gait training may be a feasible and effective intervention in terms of cardiopulmonary fitness and exercise capacity for individuals with incomplete spinal cord injury.
Body mass index (BMI) does not predict responses to psilocybin
Authors: Spriggs Meg J , Giribaldi Bruna , Lyons Taylor , Rosas Fernando E , Kärtner Laura S , Buchborn Tobias , Douglass Hannah M , Roseman Leor , Timmermann Christopher , Erritzoe David , Nutt David J , Carhart-Harris Robin L 
Published: November 2022

Background: Psilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes. Method: Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis. Results: Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not. Conclusions: These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.