bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health care professional recruitment of patients and family carers to palliative care randomised controlled trials: A qualitative multiple case study
Authors: Dunleavy Lesley , Preston Nancy , Walshe Catherine 
Published: September 2023

Background: Trial participant recruitment is an interactional process between health care professionals, patients and carers. Little is known about how clinicians carry out this role in palliative care trials and the reasons why they do or do not recruit participants. Aims: To explore how clinicians recruit to palliative care trials, why they choose to implement particular recruitment strategies, and the factors that influence their choices. Design: A qualitative multiple case study of three UK palliative care trials. Data collection included interviews and study documentation. Analysis involved developing and refining theoretical propositions, guided by the ‘6Ps’ of the ‘Social Marketing Mix Framework’ as an a priori framework (identifying participants, product, price, place, promotion and working with partners). Framework Analysis guided within and then cross-case analysis. Settings/participants: Study investigators and research staff ( n = 3, 9, 7) from trial coordinating centres and recruitment sites (hospice and hospital). Results: Cross-case analysis suggests the ‘Social Marketing Mix Framework’ is useful for understanding recruitment processes but wider contextual issues need to be incorporated. These include the ‘emotional labour’ of diagnosing dying and communicating palliative and end-of-life care to potential participants and how the recruitment process is influenced by the power relationships and hierarchies that exist among professional groups. These factors can lead to and support paternalistic practices. Conclusions: Those planning trials need to ensure that trial recruiters, depending on their experience and trial characteristics, have access to training and support to address the ‘emotional labour’ of recruitment. The type of training required requires further research.
Randomized placebo-controlled trial of CL2020, an allogenic muse cell–based product, in subacute ischemic stroke
Authors: Niizuma Kuniyasu , Osawa Shin-Ichiro , Endo Hidenori , Izumi Shin-Ichi , Ataka Kota , Hirakawa Akihiro , Iwano Masao , Tominaga Teiji 
Published: September 2023

Effective treatments for stroke after the acute phase remain elusive. Muse cells are endogenous, pluripotent, immune-privileged stem cells capable of selectively homing to damaged tissue after intravenous injection and replacing damaged/lost cells via differentiation. This randomized, double-blind, placebo-controlled trial enrolled ischemic stroke patients with modified Rankin Scale (mRS) ≥3. Randomized patients received a single intravenous injection of an allogenic Muse cell-based product, CL2020 (n = 25), or placebo (n = 10), without immunosuppressant, 14–28 days after stroke onset. Safety (primary endpoint: week 12) and efficacy (mRS, other stroke-specific measures) were assessed up to 52 weeks. Key efficacy endpoint was response rate (percentage of patients with mRS ≤2 at week 12). To week 12, 96% of patients in the CL2020 group experienced adverse events and 28% experienced adverse reactions (including one Grade 4 status epilepticus), compared with 100% and 10%, respectively, in the placebo group. Response rate was 40.0% (95% CI, 21.1–61.3) in the CL2020 group and 10.0% (0.3–44.5) in the placebo group; the lower CI in the CL2020 group exceeded the preset efficacy threshold (8.7% from registry data). This randomized placebo-controlled trial demonstrated CL2020 is a possible effective treatment for subacute ischemic stroke. Registry information: JAPIC Clinical Trials Information site (JapicCTI-184103, URL: https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-184103 ).
LI-RADS category 3, 4, and M observations: a multiple parameters diagnostic model for hepatocellular carcinoma
Authors: Chen Jianwei , Chen Huizhen , Zheng Dechun , Yan Chuan , Ye Rongping , Wen Liting , Li Yueming 
Published: September 2023

Background Hepatic lesions categorized as LR-3, LR-4, and LR-M are challenging to accurately assess and diagnose. Purpose To combine potential clinical and/or magnetic resonance imaging (MRI) features for a more comprehensive hepatocellular carcinoma (HCC) versus non-HCC diagnosis for patients with LR-3, LR-4, and LR-M graded lesions. Methods Data were consecutively retrieved from 82 at-risk patients with LR-3 (n = 43), LR-4 (n = 20), and LR-M (n = 23) lesions. Significant findings for the differentiation of HCC and non-HCC, including MRI features and clinical factors, were identified with univariable and multivariable analyses. The variables for a prediction model were selected through stepwise use of Akaike's Information Criterion (AIC) to build multivariable logistic regression model. Results Serum alpha-fetoprotein (AFP) >16.2 ng/mL (odds ratio [OR] = 22.4; P = 0.006), septum (OR = 52.1; P = 0.011), and hepatobiliary phase (HBP) hypointensity (OR = 40.2; P = 0.001) were confirmed as independent predictors of HCC. When combining the three predictors and mild-moderate T2 hyperintensity, the model (AIC = 50.91) showed good accuracy with a C-index of 0.948. Conclusion In at-risk patients with LR-3, LR-4, or LR-M lesions, integrating AFP, septum, HBP hypointensity, and mild-moderate T2 hyperintensity achieved high diagnostic performance for the diagnosis of HCC.
Comparison of paclitaxel liposomes combined with carboplatin versus paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer
Authors: Tan Xiangbin , Zou Shuangyou , Chen Hui , Chen Dachao 
Published: September 2023

Objective To compare the efficacy of paclitaxel liposomes combined with carboplatin and paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer and assess their effects on serum human epididymis protein 4 (HE4), CA125, CA199, matrix metalloproteinase-2 (MMP2), MMP-7, and MMP-9 levels. Methods In this observational study, 102 patients with advanced ovarian cancer were assigned to receive paclitaxel liposomes combined with carboplatin (Group A) or paclitaxel combined with carboplatin (Group B). Clinical efficacy; serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels; and the occurrence of adverse reactions were compared between the groups. Results The overall response rate was significantly higher in Group A than in Group B. After chemotherapy, serum HE4, CA125, CA199, MMP-2, MMP-7, and MMP-9 levels were lower in Group A than in Group B. The incidence of myalgia, dyspnea, nausea and vomiting, facial flushing, peripheral neuropathy, and skin rash was lower in Group A than in Group B. Conclusion Paclitaxel liposomes combined with carboplatin displayed better efficacy in the treatment of advanced ovarian cancer than paclitaxel combined with carboplatin, which might be attributable to reductions in serum marker levels and the occurrence of adverse events.
Lipid peroxidation and changes in major antioxidant markers in copper quinolate fungicide-exposed rats
Authors: Baali B , Kirane-Amrani L , Tichati L , Soual R , Ouali K 
Published: September 2023

The present study investigated the toxic effects of sub-chronic exposure to copper quinolate (CuQ) fungicide on liver and kidney function. Twenty-four adult male Wistar rats were equally divided into a control group, and three treated groups received, respectively, by oral gavage, three increasing doses of CuQ: 47; 67.1; and 94 mg/kg b.w corresponding, respectively, LD50/100, LD50/70, and LD50/50 daily for 8 weeks. CuQ resulted in a significant increase in the serum enzymatic activity of aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and the serum levels of urea, creatinine, uric acid, and malondialdehyde, along with a marked decrease in alanine aminotransferase (ALT) activity, and the contents of total protein and albumin compared to those of the control group. Furthermore, glutathione content and the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx) decreased significantly in a dose-dependent manner with respect to CuQ. The adverse effects of CuO were supported by the histopathological evaluations of liver and kidney tissues. Conclusively, sub-chronic CuQ exposure was shown to induce kidney and liver oxidative damage and dysfunction.
Moral distress thermometer: Swedish translation, cultural adaptation and validation
Authors: Grönlund Catarina Fischer , Isaksson Ulf , Brännström Margareta 
Published: September 2023

Background Moral distress is a problem and negative experience among health-care professionals. Various instruments have been developed to measure the level and underlying reasons for experienced moral distress. The moral distress thermometer (MDT) is a single-tool instrument to capture the level of moral distress experienced in real-time. Aim The aim of this study was to translate the MDT and adapt it to the Swedish cultural context. Research design The first part of this study concerns the translation of MDT to the Swedish context, and the second part the psychometric testing of the Swedish version. Participants and research context 89 healthcare professionals working at a hospital in northern Sweden participated. Convergent validity was tested between MDT and Measure of Moral Distress-Healthcare Professionals (MMD-HP), and construct validity was tested by comparing MDT scores among healthcare professionals. MDT was compared with responses to the final questions in MMD-HP. One-way ANOVA, Welch’s ANOVA, Games–Howell post-hoc test and Pearson’s correlation analysis were done. Ethical considerations The study was approved by the Swedish Ethics Review Authority (dnr 2020-04120) in accordance with Helsinki Declaration. Results The translated Swedish version of MDT was described as relevant to capture the experience of moral distress. The mean value for MDT was 2.26, with a median of 2 and a mode value of 0. The result showed moderate correlations between the MDT and MMD-HP total scores. There was a significant difference when comparing MDT and healthcare professionals who had never considered leaving their present position with those who had left and those who had considered leaving but had not done so, with the latter assessing significantly higher moral distress. Conclusion The MDT is an easily available instrument useful as an extension to MMD-HP to measure the real-time experience of moral distress among healthcare professionals in a Swedish context.
The Role Nurses Can Play in Addressing and Preventing the Prevalence of Missing or Murdered Indigenous Women and Girls (MMIWG)
Authors: Peters-Mosquera Autaquay , Bingham-Hendricks Chyla , Woods Cedric , Aronowitz Teri 
Published: September 2023

Introduction:In 2016, 5,712 American Indian/Alaskan Native (AI/AN) women and girls were reported missing in the United States. In Canada, 4% of the population is Indigenous, yet Indigenous females represent 50% of all sex trafficking victims. This systematic mixed-studies review examined the effects of Missing and Murdered Indigenous Women and Girls (MMIWG) to define a role for nurses.Methods:We used five databases with keywords, inclusion criteria, and the Mixed Methods Appraisal Tool.Results:Findings of 22 papers discuss: (a) demographic data; (b) factors that increase vulnerability of AI/AN women; and (c) how nurses can decrease the prevalence of MMIW.Discussion:Nurses are the first provider patients see when accessing care. Increasing knowledge about the impact of violence against AI/AN women and girls is the first step in identifying measures needed to address this public health concern.
Measuring disparities in virtual healthcare and outcomes in chronic obstructive pulmonary disease patients during the COVID-19 pandemic
Authors: Cherabuddi Medha R , Shadid Al Muthanna , Obeidat Liyan , Jesse Michelle , Bradley Patrick 
Published: September 2023

Introduction The use of virtual healthcare increased with the COVID-19 pandemic, even among chronic obstructive pulmonary disease (COPD) patients. We measured disparities in virtual compared to traditional healthcare and outcomes in COPD patients during the pandemic. Methods This study retrospectively identified adult patients with virtual or in-person primary care encounters at a large, Midwestern hospital system between March 1, 2020, and June 30, 2020. Data regarding age, sex, race, smoking, area deprivation index (ADI), COPD diagnosis, visit type (office, telephone, video, E-visit, virtual, or hybrid of office and virtual), and time to hospital admission in the following 12 months were collected. Analysis was performed using chi-square, analysis of variance, Kruskal-Wallis rank sum, and Cox proportional modeling. Results This study identified 86,715 patients. Of those, 4702 had COPD and were more likely to be 65 years or older, White, have higher ADI, use telephone or hybrid visits compared to the rest of the study population and majority had smoking history. Office, telephone, and hybrid visits were used frequently, consistently seen across sex, race, ADI, and smoking categories. Increasing age was associated with increased use of office and telephone visits, and decreased use of video visits. Higher ADI was associated with telephone visits, and lower ADI was associated with video visits. There were no significant differences in overall, COPD, or COVID-19 hospital admission rates across visit types. Discussion Complex disparities in utilizing traditional healthcare are also reflected in virtual healthcare in COPD patients, and do not significantly affect hospital admissions.
Impact of eConsults on Clinical Care in Primary Care: A Cross-Sectional Analysis of Primary Care Provider Behavior
Authors: Bifulco Lauren , Guidotti Olivia , Velez Idiana , Grzejszczak Lynsey , Angelocci Tracy , Okunade Lola , Anderson Daren 
Published: September 2023

Introduction/Objectives: Asynchronous electronic consultations (eConsults) support primary care providers (PCPs) by providing rapid specialist feedback and improve medically underserved patients’ access to care. Methods: This cross-sectional study assessed all eConsults requested over a one-year period at a multi-site federally qualified health center in Texas. We analyzed eConsult content and quality and conducted chart reviews for a randomly selected subsample (n = 100) to determine whether PCPs implemented specialists’ recommendations within 90 days. Semi-structured interviews with PCPs assessed their ability and willingness to follow recommendations. Results: There were 367 eConsults submitted by 25 PCPs across 15 adult medical and surgical specialties. Of the 100 charts reviewed n = 77 (77.0%) contained documentation indicating that the PCP had followed at least 1 of the specialist’s recommendations within 90 days. In two-thirds of the cases (n = 66, 66%) the reviewing specialist indicated that a face-to-face referral was not needed. PCPs were most likely to follow recommendations for new medications and least likely to document that they had obtained additional patient history. PCPs noted that they were sometimes unable to follow recommendations when patients could not afford or access treatment or did not return for follow up care, or when they felt that the specialist did not address their specific question. Conclusions: eConsults delivered to medically underserved patients in primary care help PCPs provide timely care for their patients. PCPs utilized a broad range of eConsult specialties and generally implemented eConsult specialists’ recommendations within 90 days.
Physiological functions of calcium signaling via Orai1 in cancer
Authors: Umemura Masanari , Nakakaji Rina , Ishikawa Yoshihiro 
Published: September 2023

AbstractIntracellular calcium (Ca2+) signaling regulates many cellular functions, including cell proliferation and migration, in both normal cells and cancer cells. Store-operated Ca2+ entry (SOCE) is a major mechanism by which Ca2+ is imported from the extracellular space to the intracellular space, especially in nonexcitable cells. Store-operated Ca2+ entry (SOCE) is also a receptor-regulated Ca2+ entry pathway that maintains Ca2+ homeostasis by sensing reduced Ca2+ levels in the endoplasmic reticulum (ER). In general, the activation of G protein-coupled receptors (GPCRs) or immunoreceptors, such as T-cell, B-cell and Fc receptors, results in the production of inositol 1,4,5-trisphosphate (IP3). IP3 binds to IP3 receptors located in the ER membrane. The, IP3 receptors in the ER membrane trigger a rapid and transient release of Ca2+ from the ER store. The resulting depletion of ER Ca2+ concentrations is sensed by the EF-hand motif of stromal interaction molecule (STIM), i.e., calcium sensor, which then translocates to the plasma membrane (PM). STIM interacts with Orai Ca2+ channel subunits (also known as CRACM1) on the PM, leading to Ca2+ influx from the extracellular space to increase intracellular Ca2+ concentrations. The physiological functions of Orai and STIM have been studied mainly with respect to their roles in the immune system. Based on numerous previous studies, Orai channels (Orai1, Orai2 and Orai3 channels) control Ca2+ release-activated Ca2+ (CRAC) currents and contribute to SOCE currents in other types of cells, including various cancer cells. There are many reports that Orai1 is involved in cell proliferation, migration, metastasis, apoptosis and epithelial–mesenchymal transition (EMT) in various cancers. We previously found that Orai1 plays important roles in cell apoptosis and migration in melanoma. Recently, we reported novel evidence of Orai1 in human oral squamous cell carcinoma (OSCC) cells and human cardiac fibroblasts (HCFs). In this review, we present multiple physiological functions of Orai1 in various cancer cells and cardiac fibroblasts, including our findings.
Fuzzy optimization for identifying antiviral targets for treating SARS-CoV-2 infection in the heart
Authors: Chu Sz-Wei , Wang Feng-Sheng 
Published: September 2023

AbstractIn this paper, a fuzzy hierarchical optimization framework is proposed for identifying potential antiviral targets for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the heart. The proposed framework comprises four objectives for evaluating the elimination of viral biomass growth and the minimization of side effects during treatment. In the application of the framework, Dulbecco’s modified eagle medium (DMEM) and Ham’s medium were used as uptake nutrients on an antiviral target discovery platform. The prediction results from the framework reveal that most of the antiviral enzymes in the aforementioned media are involved in fatty acid metabolism and amino acid metabolism. However, six enzymes involved in cholesterol biosynthesis in Ham’s medium and three enzymes involved in glycolysis in DMEM are unable to eliminate the growth of the SARS-CoV-2 biomass. Three enzymes involved in glycolysis, namely BPGM, GAPDH, and ENO1, in DMEM combine with the supplemental uptake of L-cysteine to increase the cell viability grade and metabolic deviation grade. Moreover, six enzymes involved in cholesterol biosynthesis reduce and fail to reduce viral biomass growth in a culture medium if a cholesterol uptake reaction does not occur and occurs in this medium, respectively.
A heterogeneous graph convolutional attention network method for classification of autism spectrum disorder
Authors: Shao Lizhen , Fu Cong , Chen Xunying 
Published: September 2023

Abstract
Background
Autism spectrum disorder (ASD) is a serious developmental disorder of the brain. Recently, various deep learning methods based on functional magnetic resonance imaging (fMRI) data have been developed for the classification of ASD. Among them, graph neural networks, which generalize deep neural network models to graph structured data, have shown great advantages. However, in graph neural methods, because the graphs constructed are homogeneous, the phenotype information of the subjects cannot be fully utilized. This affects the improvement of the classification performance.

Methods
To fully utilize the phenotype information, this paper proposes a heterogeneous graph convolutional attention network (HCAN) model to classify ASD. By combining an attention mechanism and a heterogeneous graph convolutional network, important aggregated features can be extracted in the HCAN. The model consists of a multilayer HCAN feature extractor and a multilayer perceptron (MLP) classifier. First, a heterogeneous population graph was constructed based on the fMRI and phenotypic data. Then, a multilayer HCAN is used to mine graph-based features from the heterogeneous graph. Finally, the extracted features are fed into an MLP for the final classification.

Results
The proposed method is assessed on the autism brain imaging data exchange (ABIDE) repository. In total, 871 subjects in the ABIDE I dataset are used for the classification task. The best classification accuracy of 82.9% is achieved. Compared to the other methods using exactly the same subjects in the literature, the proposed method achieves superior performance to the best reported result.

Conclusions
The proposed method can effectively integrate heterogeneous graph convolutional networks with a semantic attention mechanism so that the phenotype features of the subjects can be fully utilized. Moreover, it shows great potential in the diagnosis of brain functional disorders with fMRI data.
Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties
Authors: Das Nando D. , Chang Jen-Chien , Hon Chung-Chau , Kelly S. Thomas , Ito Shinsuke , Lizio Marina , Kaczkowski Bogumil , Watanabe Hisami , Katsushima Keisuke , Natsume Atsushi , Koseki Haruhiko , Kondo Yutaka , Minoda Aki , Umehara Takashi 
Published: September 2023

Abstract
Background
Super-enhancers (SEs), which activate genes involved in cell-type specificity, have mainly been defined as genomic regions with top-ranked enrichment(s) of histone H3 with acetylated K27 (H3K27ac) and/or transcription coactivator(s) including a bromodomain and extra-terminal domain (BET) family protein, BRD4. However, BRD4 preferentially binds to multi-acetylated histone H4, typically with acetylated K5 and K8 (H4K5acK8ac), leading us to hypothesize that SEs should be defined by high H4K5acK8ac enrichment at least as well as by that of H3K27ac.

Results
Here, we conducted genome-wide profiling of H4K5acK8ac and H3K27ac, BRD4 binding, and the transcriptome by using a BET inhibitor, JQ1, in three human glial cell lines. When SEs were defined as having the top ranks for H4K5acK8ac or H3K27ac signal, 43% of H4K5acK8ac-ranked SEs were distinct from H3K27ac-ranked SEs in a glioblastoma stem-like cell (GSC) line. CRISPR-Cas9–mediated deletion of the H4K5acK8ac-preferred SEs associated with MYCN and NFIC decreased the stem-like properties in GSCs.

Conclusions
Collectively, our data highlights H4K5acK8ac’s utility for identifying genes regulating cell-type specificity.