bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simulation-based nursing education of psychological first aid for adolescents exposed to hazardous chemical disasters
Authors: Kim Hye-won , Choi Yun-Jung 
Published: February 2022

Abstract
Background
Simulation-based education facilitates a learner-centered experience, which has been found to be effective in improving clinical performance, problem-solving ability, and self-confidence in nursing practice. The objective of this study was to develop and test a psychological first aid simulation-based education program for nurses caring for adolescents exposed to hazardous chemical disasters.

Methods
This study employed a nonequivalent pre and post-control group research design. The simulation-based education program was developed, and the participants were 30 nurses working in a medical center who were randomly assigned to the experimental, comparison, and control groups. The collected data were statistically analyzed using IBM SPSS Statistics for Windows, Ver. 22.0.

Results
The nurses who participated in the simulation-based education program showed statistically significantly improved psychological first aid performance knowledge, competence, and self-efficacy compared to those in the other groups.

Conclusions
Nursing simulation programs could help to improve nurses’ performance in mental health care and psychological support for adolescents suffering from hazardous chemical disasters.
Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment
Authors: Chen Ruyin , Li Qiong , Xu Shuaishuai , Ye Chanqi , Tian Tian , Jiang Qi , Shan Jianzhen , Ruan Jian 
Published: February 2022

AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Tyrosine kinase inhibitors (TKIs) remain the backbone of systematic therapy for advanced hepatocellular carcinoma. Sorafenib and lenvatinib are currently approved as first-line therapeutic drugs, and regorafenib and cabozantinib are applied as second-line treatments. With inhibition of angiogenesis as the main target, TKIs exert a profound effect on the tumour microenvironment (TME). The TME is a complex mixture of cellular and noncellular components surrounding the tumour mass, and is associated with tumour progression partially through the epithelial–mesenchymal transition. Specifically, the TME of HCC is characterized by profound extracellular matrix remodelling and an immunosuppressive microenvironment. The purpose of this review is to provide a summary of TME remodelling mediated by four Food and Drug Administration approved TKIs in HCC and thus summarize the rationale and potential targets for combination therapy. The modulatory effect of TKIs on the TME of HCC was reported to enhance the antitumour effect of TKIs through pyroptosis of macrophages and subsequent natural killer cell activation, T cell activation, regulatory T cell reduction in HCC. Meanwhile, TKIs also induce drug resistance via M2 polarization and accumulation, recruitment of tumour-associated neutrophils, and induction of the epithelial–mesenchymal transition. In conclusion, the effect of TKIs on TME can enhance its antitumour effect, but might also partially contribute to the drug resistance that hinders the progression of TKIs as treatment for HCC. Additionally, the effect of TKIs also provides the rationale for combination therapy, including combining TKIs with immune checkpoint inhibitors, to facilitate increased drug efficacy of TKIs.
SGLT2 inhibition restrains thyroid cancer growth via G1/S phase transition arrest and apoptosis mediated by DNA damage response signaling pathways
Authors: Wang Yan , Yang Longyan , Mao Lin , Zhang Lijie , Zhu Yingjun , Xu Yongsong , Cheng Yanan , Sun Rongxin , Zhang Yuanyuan , Ke Jing , Zhao Dong 
Published: February 2022

AbstractBackgroundAlthough the prognosis for most patients with papillary thyroid cancer (PTC) is good, the present treatment is ineffective for 5–10% patients. Several studies found sodium–glucose cotransporter 2 (SGLT2) inhibitors may inhibit the growth of tumors. However, whether SGLT2 inhibitors have therapeutic effect on thyroid cancer remains unclear.Materials and methodsThe levels of SGLT2 in PTC and normal thyroid tissue were assessed by immunohistochemistry and clinical dataset analysis. Cell growth was detected by the CCK-8 and colony formation. Glucose uptake into thyroid cancer cell was evaluated by 2-DG uptake assay. Glycolysis were analyzed by Seahorse XF Extracellular Flux Analysis. RNA-seq were used to screen differentially expressed genes of cells treated with/without canagliflozin (a SGLT2 inhibitor). Furthermore, flow cytometry, western blot, and gene set enrichment analysis were employed to elucidate cell cycle, apoptosis and the underlying mechanism of the anticancer effect of canagliflozin. The effect of canagliflozin on thyroid cancer growth was further confirmed in vivo through xenograft formation assay.ResultsSGLT2 inhibition attenuated the growth of thyroid cancer cells in vitro and in vivo. Canagliflozin inhibited glucose uptake, glycolysis and AKT/mTOR signaling activation, and increased AMPK activation in thyroid cancer cell. Furthermore, canagliflozin inhibited G1/S phase transition and cyclin D1, cyclin D3, cyclin E1, cyclin E2, and E2F1 expression levels in thyroid cancer cell. In addition, canagliflozin increased apoptosis of thyroid cancer cell. Further investigation revealed that canagliflozin could increase γ-H2AX expression levels and DNA damage response signaling ATM/CHK2 activation. In thyroid cancer patients, SGLT2 was increased in thyroid cancer and positively related to cyclin D3.ConclusionsSGLT2 inhibition may limit glucose uptake resulting in energetic crisis, following oxidative stress mediated DNA damage and cell cycle arrest, which resulted to the increased cell apoptosis and decreased proliferation of thyroid cancer cells, suggesting a potential use for SGLT2 inhibitors as thyroid cancer therapeutics.
A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study
Authors: Miyoshi Jinsei , Zhu Zhongxu , Luo Aiping , Toden Shusuke , Zhou Xuantong , Izumi Daisuke , Kanda Mitsuro , Takayama Tetsuji , Parker Iqbal M. , Wang Minjie , Gao Feng , Zaidi Ali H. , Baba Hideo , Kodera Yasuhiro , Cui Yongping , Wang Xin , Liu Zhihua , Goel Ajay 
Published: February 2022

Abstract
Background
Currently, there is no clinically relevant non-invasive biomarker for early detection of esophageal squamous cell carcinoma (ESCC). Herein, we established and evaluated a circulating microRNA (miRNA)-based signature for the early detection of ESCC using a systematic genome-wide miRNA expression profiling analysis.

Methods
We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n = 108, 238, and 216) and the candidate miRNAs were confirmed in tissue specimens (n = 64) by qRT-PCR. Using a serum training cohort (n = 408), we conducted multivariate logistic regression analysis to develop an ESCC circulating miRNA signature and the signature was subsequently validated in two independent retrospective and two prospective cohorts.

Results
We identified eighteen initial miRNA candidates from three miRNA expression datasets (n = 108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confirmed the overexpression of 8 miRNAs (miR-103, miR-106b, miR-151, miR-17, miR-181a, miR-21, miR-25, and miR-93) in serum specimens. Using a serum training cohort, we developed a circulating miRNA signature (AUC:0.83 [95%CI:0.79–0.87]) and the diagnostic performance of the miRNA signature was confirmed in two independent validation cohorts (n = 126, AUC:0.80 [95%CI:0.69–0.91]; and n = 165, AUC:0.89 [95%CI:0.83–0.94]). Finally, we demonstrated the diagnostic performance of the 8-miRNA signature in two prospective cohorts (n = 185, AUC:0.92, [95%CI:0.87–0.96]); and (n = 188, AUC:0.93, [95%CI:0.88–0.97]). Importantly, the 8-miRNA signature was superior to current clinical serological markers in discriminating early stage ESCC patients from healthy controls (p < 0.001).

Conclusions
We have developed a novel and robust circulating miRNA-based signature for early detection of ESCC, which was successfully validated in multiple retrospective and prospective multinational, multicenter cohorts.
The impact of peer support on testing, linkage to and engagement in HIV care for people who inject drugs in Indonesia: qualitative perspectives from a community-led study
Authors: Iryawan Arif Rachman , Stoicescu Claudia , Sjahrial Faisyal , Nio Kuntanto , Dominich Alexa 
Published: February 2022

AbstractIntroductionPeople who use, including those who inject, drugs in Indonesia are disproportionately affected by HIV, but tend to be diagnosed at a late stage of infection, delay initiation to and have poor rates of retention in antiretroviral treatment, resulting in high rates of morbidity and mortality. In addition to legal, policy and health system barriers, PWID may be hesitant to engage in HIV, treatment and care due to lack of knowledge, distrust of the health care system, and stigma related to their dual drug use and HIV status. Implementation of formal peer support initiatives may reduce provider- and individual-level barriers and increase testing, linkage to, and engagement in HIV care among people who use drugs.MethodsWe conducted a community-led qualitative study to explore the impacts of peer support for people who inject drugs on HIV care access and engagement in Indonesia. Semi-structured, in-depth interviews were conducted with 20 participants in Jakarta and Bandung. Thematic analysis was used to explore how people who inject drugs living with HIV (PWID LHIV) (n = 8), peer support workers (n = 6), and service providers (n = 6) perceived peer support provision by non-governmental organisations.ResultsParticipants unanimously described peer support as beneficial. Peer support workers were widely credited with facilitating access to HIV testing, referral to care, uptake of and adherence to antiretroviral treatment, as well as sustaining engagement in care for PWID. Support mechanisms that facilitated positive peer experiences included provision of HIV knowledge and awareness, emotional support, help with navigating complex bureaucracy, developing trust in health care services, enhancing confidence and motivation, and supporting peers to navigate a wide range of health and social welfare services beyond HIV-related care.ConclusionsFindings indicate that peer support can enhance access to testing, linkage to, and engagement in HIV care for people who use drugs living with HIV in Indonesia. In a context of an ongoing HIV epidemic among people who use drugs, reduced funding and policy attention to HIV and harm reduction, there is an urgent need to prioritize peer support interventions to identify people who use drugs facing health risks and link them to appropriate services.
Prison inmates with court-ordered treatments: are they really different?
Authors: D’Orta Isabella , Herrmann François R. , Giannakopoulos Panteleimon 
Published: February 2022

Abstract
Background
Both the frequency of court-ordered treatments (COT) for offenders and prevalence of mental disorders among regular prison inmates steadily increased in most western countries. Whether there are major sociodemographic and clinical differences between these two populations is still matter of debate.

Methods
We compared the sociodemographic and clinical characteristics in a representative sample of 139 regular prison inmates versus 61 offenders with COT admitted during a 5-year period in an acute psychiatric care unit located in the central prison of the Geneva county. Fisher exact, unpaired Student’s t and Mann–Whitney U tests were used to compare demographic and clinical variables between COT patients and regular inmates. In addition, univariate and multivariable ordered logistic regression models were built to identify the sociodemographic and clinical determinants of COT.

Results
COT patients were significantly older, less frequently married, with better education attainment, predominantly French-speaking, of the Christian religious group and with regular religious practice. History of psychiatric outpatient care was significantly more frequent in this group. Unlike the significantly higher occurrence of adjustment disorders in regular prisoners, psychosis was the main diagnosis in COT patients. When all diagnostic categories were taken into account in multivariable models, the presence of personality and psychotic disorders were the stronger predictors of COT status.

Conclusions
Our data reveal that offenders with COT represent a clinically distinct group with an overrepresentation of personality and psychotic disorders. Moreover, they show that, at least in the Swiss penitentiary system, COT patients are less exposed to acculturation issues compared to regular inmates.
The use of cell salvage during second-stage reimplantation for the treatment of chronic hip periprosthetic joint infection: a retrospective cohort study
Authors: Liu Zunhan , Yang Xuetao , Zhao En-Ze , Wan Xufeng , Cao Guorui , Zhou Zongke 
Published: February 2022

Abstract
Introduction
Given the possibility of inadvertent bacterial contamination of salvaged blood, the use of cell salvage is relatively contraindicated in cases of reimplantation for chronic hip periprosthetic joint infection (PJI). However, there are no published data supporting this assertion. The purpose of the current study was to compare the reinfection rate and rate of postoperative allogeneic blood transfusion (ABT) in second-stage reimplantation for PJI with or without intraoperative cell salvage reinfusion.

Materials and methods
We identified 125 patients who underwent two-stage exchange for chronic hip PJI between November 2012 and April 2019. The groups of patients who had (n = 61) and had not (n = 64) received intraoperative cell salvage reinfusion were compared with respect to the curative infection-free rate. Moreover, we compared the need for postoperative ABT and identified independent factors associated with ABT using multiple regression analysis.

Results
The log-rank survival curve with an endpoint of infection eradication failure was not significantly different between the cell salvage group (98.4%, 95% CI 95.3–99.9%) and the control group (95.3%, 95% CI 90.2–99.9%) at one year (log rank, P = .330). The rates of postoperative ABT in the cell salvage group were significantly lower than those in the control group (11.5% vs 26.6%, P = .041). In multivariable models, patient age, body mass index, preoperative hemoglobin level, and intraoperative cell salvage were independent predictors of ABT exposure (P < .05).

Conclusions
The use of cell salvage during reimplantation in two-stage exchange for chronic hip PJI did not appear to increase the reinfection rate, while it significantly reduced the rate of postoperative allogeneic red blood transfusion. Greater age, lower BMI, lower preoperative hemoglobin, and non-intraoperative cell salvage reinfusion were associated with higher rate of allogeneic red blood transfusion.
Sublobar resection versus ablation for stage I non-small-cell lung cancer: a meta-analysis
Authors: Li Yong , Yang Fang , Huang Ya-Yong , Wang Tao 
Published: February 2022

Abstract
Background
Stage I non-small-cell lung cancer (NSCLC) can be treated by both ablation and sublobar resection (SR). This meta-analysis was therefore designed to better compare the relative safety and efficacy of these two approaches to treating stage I NSCLC.

Materials and methods
Relevant studies published through November 2020 in the Cochrane Library, Embase, and PubMed databases were identified for analyses which were conducted with RevMan v5.3.

Results
In total, 816 potentially relevant articles were identified, of which 8 were ultimately included in the final meta-analysis. Patients in the SR group exhibited a signficantly lower pooled local recurrence (LR) rate (5.0% vs. 25.4%, P < 0.0001), although pooled distant recurrence (DR) rates were similar in both groups (25.7% vs. 23.1%, P = 0.75). The pooled hazard ratio (HR) for overall survival (OS) (HR: 1.23; 95% CI: 1.13–1.33, P < 0.00001), progression-free survival (PFS) (HR: 1.34; 95% CI: 1.15–1.55, P = 0.0002), and cancer-specific survival (HR: 1.39; 95% CI: 1.15–1.70, P = 0.0009) all indicated better survival outcomes among patients that underwent HR treatment, while pooled complication rates were similar in both groups (27.7% vs. 43.8%, P = 0.27). Patients that underwent ablation exhibited significantly shorter pooled post-operative hospitalization relative to those in the SR group (MD: 5.93; 95% CI: 0.78–11.07, P = 0.02). No evidence of publication bias was detected through funnel plot analyses.

Conclusions
SR treatment of stage I NSCLC patients was associated with a lower LR rate and longer survival as compared to ablation.
A validation study of potential prognostic DNA methylation biomarkers in patients with acute myeloid leukemia using a custom DNA methylation sequencing panel
Authors: Šestáková Šárka , Cerovská Ela , Šálek Cyril , Kundrát Dávid , Ježíšková Ivana , Folta Adam , Mayer Jiří , Ráčil Zdeněk , Cetkovský Petr , Remešová Hana 
Published: February 2022

Abstract
Background
Multiple studies have reported the prognostic impact of DNA methylation changes in acute myeloid leukemia (AML). However, these epigenetic markers have not been thoroughly validated and therefore are still not considered in clinical practice. Hence, we aimed to independently verify results of selected studies describing the relationship between DNA methylation of specific genes and their prognostic potential in predicting overall survival (OS) and event-free survival (EFS).

Results
Fourteen studies (published 2011–2019) comprising of 27 genes were subjected to validation by a custom NGS-based sequencing panel in 178 newly diagnosed non-M3 AML patients treated by 3 + 7 induction regimen. The results were considered as successfully validated, if both the log-rank test and multivariate Cox regression analysis had a p-value ≤ 0.05. The predictive role of DNA methylation was confirmed for three studies comprising of four genes: CEBPA (OS: p = 0.02; EFS: p = 0.03), PBX3 (EFS: p = 0.01), LZTS2 (OS: p = 0.05; EFS: p = 0.0003), and NR6A1 (OS: p = 0.004; EFS: p = 0.0003). For all of these genes, higher methylation was an indicator of longer survival. Concurrent higher methylation of both LZTS2 and NR6A1 was highly significant for survival in cytogenetically normal (CN) AML group (OS: p < 0.0001; EFS: p < 0.0001) as well as for the whole AML cohort (OS: p = 0.01; EFS < 0.0001). In contrast, for two studies reporting the poor prognostic effect of higher GPX3 and DLX4 methylation, we found the exact opposite, again linking higher GPX3 (OS: p = 0.006; EFS: p < 0.0001) and DLX4 (OS: p = 0.03; EFS = 0.03) methylation to a favorable treatment outcome. Individual gene significance levels refer to the outcomes of multivariate Cox regression analysis.

Conclusions
Out of twenty-seven genes subjected to DNA methylation validation, a prognostic role was observed for six genes. Therefore, independent validation studies are necessary to reveal truly prognostic DNA methylation changes and to enable the introduction of these promising epigenetic markers into clinical practice.
Allergic rhinitis, allergic contact dermatitis and disease comorbidity belong to separate entities with distinct composition of T-cell subsets, cytokines, immunoglobulins and autoantibodies
Authors: Chai Wenjia , Zhang Xuyi , Lin Meixiong , Chen Zhuo , Wang Xiaolin , Wang Changqing , Chen Aoyan , Wang Caisheng , Wang Hongwu , Yue Honghong , Gui Jingang 
Published: February 2022

AbstractBackgroundAllergic rhinitis (AR) and allergic contact dermatitis (ACD) are prevalent allergic diseases and have significant impacts on patients’ daily life. Despite many studies on AR or ACD have been conducted separately, little is known about the immune responses in patients of AR combined with ACD and the interplay between AR and ACD. Our study compared various aspects of immune elements in patients with AR or/and ACD, aiming to characterize the immune responses in AR, ACD, and AR combined with ACD.MethodsA total of 57 patients diagnosed with AR or/and ACD and 28 healthy volunteers were included. AR patients were further divided into seasonal AR (SAR) and perennial AR (PAR). All subjects’ blood samples were taken to assess the concentration of immunoglobulins, complement C3, C4, autoantibodies and cytokines in serum by immunoturbidimetry, ELISA or Luminex200 platform. Peripheral blood mononuclear cells (PBMCs) were subjected to the analysis of lymphocyte subpopulations by flow cytometry.ResultsIt indicated that AR disease caused elevated levels of IgE, IgA, IgG, IgG4, as well as IL-4, IL-15, IL-8 and IL-6 in serum. AR patients possessed a decreased CD4/CD8 ratio and an increased proportion of memory CD4 + T-cell subset, with a skewed Th2 response and an enhanced CD8 + T-cell activation. Compared with patients with sole AR or ACD condition, AR + ACD patients presented with a significantly increased proportion of memory CD8 + T-cell subset and were prone to autoimmune disorders as indicated by the increased autoantibodies. The immune elements in patients with ACD only were least affected compared with those in other conditions. Additionally, seasonal or perennial AR patients exhibited different cytokine profiles and proportions of memory T-cell subsets.ConclusionsIn this study, we illuminated the respective characteristics of immune responses in AR, ACD, and AR combined with ACD. Meanwhile, we discovered that the PAR and SAR patients possessed different cytokine profiles and T-cell compartments. It suggested that these allergic conditions belong to different disease entities. Characterizing the detailed immune changes in these allergic diseases would help to develop proper treatments targeting particular immune elements in different allergic diseases.
Ryanodine receptor RyR1-mediated elevation of Ca2+ concentration is required for the late stage of myogenic differentiation and fusion
Authors: Qiu Kai , Wang Yubo , Xu Doudou , He Linjuan , Zhang Xin , Yan Enfa , Wang Lu , Yin Jingdong 
Published: February 2022

Abstract
Background
Cytosolic Ca2+ plays vital roles in myogenesis and muscle development. As a major Ca2+ release channel of endoplasmic reticulum (ER), ryanodine receptor 1 (RyR1) key mutations are main causes of severe congenital myopathies. The role of RyR1 in myogenic differentiation has attracted intense research interest but remains unclear.

Results
In the present study, both RyR1-knockdown myoblasts and CRISPR/Cas9-based RyR1-knockout myoblasts were employed to explore the role of RyR1 in myogenic differentiation, myotube formation as well as the potential mechanism of RyR1-related myopathies. We observed that RyR1 expression was dramatically increased during the late stage of myogenic differentiation, accompanied by significantly elevated cytoplasmic Ca2+ concentration. Inhibition of RyR1 by siRNA-mediated knockdown or chemical inhibitor, dantrolene, significantly reduced cytosolic Ca2+ and blocked multinucleated myotube formation. The elevation of cytoplasmic Ca2+ concentration can effectively relieve myogenic differentiation stagnation by RyR1 inhibition, demonstrating that RyR1 modulates myogenic differentiation via regulation of Ca2+ release channel. However, RyR1-knockout-induced Ca2+ leakage led to the severe ER stress and excessive unfolded protein response, and drove myoblasts into apoptosis.

Conclusions
Therefore, we concluded that Ca2+ release mediated by dramatic increase in RyR1 expression is required for the late stage of myogenic differentiation and fusion. This study contributes to a novel understanding of the role of RyR1 in myogenic differentiation and related congenital myopathies, and provides a potential target for regulation of muscle characteristics and meat quality.