bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelled Economic Analysis for Dacomitinib–A Cost Effectiveness Analysis in Treating Patients With EGFR-Mutation-Positive Non-Small Cell Lung Cancer in China
Authors: Yu Yong-feng , Luan Luan , Zhu Fan-fan , Dong Peng , Ma Li-Heng , Li Lan-ting , Gao Lan , Lu Shun 
Published: December 2021

ObjectivesTo establish the cost-effectiveness of dacomitinib compared to gefitinib from the Chinese healthcare system perspective.PatientsAdvanced non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations.MethodsPartitioned survival analysis was undertaken to examine the cost-effectiveness of dacomitinib utilising individual patient data (IPD) from the pivotal randomised controlled trial (RCT) (ARCHER 1050). The three health states modelled were progression-free, post-progression, and death. Parametric survival distributions were fitted to IPD against the Kaplan-Meier survival curves corresponding to progression-free survival (PFS) and overall survival (OS) outcomes by randomised groups. Costs included drug acquisition and administration, outpatient management (outpatient consultation and examinations), and best supportive care costs. Utility weights were sourced from the pivotal trial and other published literature. The incremental cost-effectiveness ratio (ICER) was calculated with costs and quality-adjusted life years (QALYs) discounted at an annual rate of 5%. Both deterministic and probabilistic sensitivity analyses were undertaken.ResultsIn the base case, dacomitinib (CNY 265,512 and 1.95 QALY) was associated with higher costs and QALY gains compared to gefitinib (CNY 247,048 and 1.61 QALYs), resulting in an ICER of CNY 58,947/QALY. Using the empirical WTP/QALY threshold, dacomitinib is a cost-effective treatment strategy for patients with EGFR-mutation-positive advanced NSCLC. The probabilistic sensitivity analysis suggested that dacomitinib had a 97% probability of being cost-effective.ConclusionsDacomitinib is a cost-effective treatment strategy in treating patients with EGFR-mutation-positive NSCLC from the Chinese healthcare system perspective. The uncertainty around the cost-effectiveness of dacomitinib could be reduced if long-term survival data become available. Clinical Trial RegistrationNCT01024413
Clinical Values and Markers of Radiation-Induced Liver Disease for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Treated With Stereotactic Body Radiotherapy
Authors: Jia Jun , Sun Jing , Duan Xuezhang , Li Wengang 
Published: December 2021

BackgroundInformation about radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC) patients preexisting hepatitis B cirrhosis with portal vein tumor thrombus (PVTT) extended to the main portal vein treated with stereotactic body radiotherapy (SBRT) is still inadequate and the predictive markers for RILD have not been cleared in these patients. The aim of the study is to identify factors that can be used to predict RILD and to evaluate the influence of RILD in these patients.MethodsIn our study, 59 patients were analyzed and evaluated from December 2015 to June 2019, according to the entry criteria. After treatment, 59 patients were followed up within the first month and then every 3 months. Hematology test, tumor markers, three-phasic CT scan of the lungs, and CT or MRI scan of the liver were performed at each follow up.ResultsMedian overall survival time was 10.7 months (range, 5.8 to 14.9). RILD appeared in 17 of the 59 patients (28.8%) at the 3rd month after SBRT. In the univariate analysis, not only the CP score class (A or B) but also each different pretreatment CP score (p &lt; 0.05) was a significant predictive factor of RILD. More RILD cases were detected with the increase of CP score. The recovery rate decreased as the baseline CP score increased (p &lt; 0.05). It was found that the overall survival time was affected by only baseline CP score and RILD (p &lt; 0.05).ConclusionsThe development of RILD has a dependency on the CP score in these patients. CP scores before treatment and RILD are significantly associated with overall survival. SBRT is an effective and safe method for patients with CP ≤ B7. For patients with CP-B8, liver function should be monitored more frequently. It is not safe enough for the SBRT treatment in CP-B9 patients.
CD248+ Cancer-Associated Fibroblasts: A Novel Prognostic and Therapeutic Target for Renal Cell Carcinoma
Authors: Xu Chao , Zhang Keying , Yang Fa , Zhou Xiang , Liu Shaojie , Li Yu , Ma Shanjin , Zhao Xiaolong , Lu Tong , Lu Shiqi , Zhang JiaYu , Li Hongji , Han Donghui , Wen Weihong , Qin Weijun 
Published: December 2021

BackgroundThe tumor microenvironment (TME) plays an important role in the progression of renal cell carcinoma (RCC). Cancer-associated fibroblasts (CAFs) are considered to constitute a major component of the TME and participate in various tumor-promoting molecular events. We have previously confirmed that CD248 represents a promising biomarker of CAFs, which may provide insight into CAF-based tumor-promoting effects. However, CAF-mediated tumor progression and the potential mechanism of CD248 remain largely unknown in RCC patients.MethodsExpression profiling and clinical data of RCC patients were obtained from The Cancer Genome Atlas (TCGA) database. An MCP-counter algorithm and Kaplan–Meier survival analysis were performed to explore the prognostic value of CAFs and CD248, respectively. A Pearson correlation coefficient test and Student’s t-test were employed to evaluate the relationship between immunosuppressive TME and CD248 or CAFs. Immunohistochemistry and immunofluorescence staining were performed to confirm CD248 expression within CAFs. CD248-specific siRNA was used to investigate the potential function of CD248 in CAF tumor promotion. Differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and enrichment analysis were conducted to clarify the function of CD248+ CAFs in RCC progression and the associated regulatory mechanism.ResultsCD248 overexpression and CAF infiltration could predict poor RCC prognosis, which may involve the immunosuppressive TME. CD248 may serve as a promising CAFs biomarker and be involved with the tumor-promoting effect of CAFs. Moreover, CD248+ CAF infiltration may contribute to RCC progression and an immunosuppressive TME through cell-extracellular matrix (ECM) interactions and metabolism regulation.ConclusionCD248+ CAFs participate in the regulation of RCC progression and immunosuppressive TME, which may represent a novel prognostic and therapeutic target for RCC.
Antibacterial Activity and Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae
Authors: Yu Wei , Chen Yunbo , Shen Ping , Ji Jinru , Ying Chaoqun , Liu Zhiying , Xiong Luying , Qiu Yunqing , Xiao Yonghong 
Published: December 2021

Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP).Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations.Results: The MIC90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried blaKPC-2 and blaNDM-1. A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%.Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.
Machine Learning Prediction of Cardiac Resynchronisation Therapy Response From Combination of Clinical and Model-Driven Data
Authors: Khamzin Svyatoslav , Dokuchaev Arsenii , Bazhutina Anastasia , Chumarnaya Tatiana , Zubarev Stepan , Lyubimtseva Tamara , Lebedeva Viktoria , Lebedev Dmitry , Gurev Viatcheslav , Solovyova Olga 
Published: December 2021

Background: Up to 30–50% of chronic heart failure patients who underwent cardiac resynchronization therapy (CRT) do not respond to the treatment. Therefore, patient stratification for CRT and optimization of CRT device settings remain a challenge.Objective: The main goal of our study is to develop a predictive model of CRT outcome using a combination of clinical data recorded in patients before CRT and simulations of the response to biventricular (BiV) pacing in personalized computational models of the cardiac electrophysiology.Materials and Methods: Retrospective data from 57 patients who underwent CRT device implantation was utilized. Positive response to CRT was defined by a 10% increase in the left ventricular ejection fraction in a year after implantation. For each patient, an anatomical model of the heart and torso was reconstructed from MRI and CT images and tailored to ECG recorded in the participant. The models were used to compute ventricular activation time, ECG duration and electrical dyssynchrony indices during intrinsic rhythm and BiV pacing from the sites of implanted leads. For building a predictive model of CRT response, we used clinical data recorded before CRT device implantation together with model-derived biomarkers of ventricular excitation in the left bundle branch block mode of activation and under BiV stimulation. Several Machine Learning (ML) classifiers and feature selection algorithms were tested on the hybrid dataset, and the quality of predictors was assessed using the area under receiver operating curve (ROC AUC). The classifiers on the hybrid data were compared with ML models built on clinical data only.Results: The best ML classifier utilizing a hybrid set of clinical and model-driven data demonstrated ROC AUC of 0.82, an accuracy of 0.82, sensitivity of 0.85, and specificity of 0.78, improving quality over that of ML predictors built on clinical data from much larger datasets by more than 0.1. Distance from the LV pacing site to the post-infarction zone and ventricular activation characteristics under BiV pacing were shown as the most relevant model-driven features for CRT response classification.Conclusion: Our results suggest that combination of clinical and model-driven data increases the accuracy of classification models for CRT outcomes.
Look at the Audience? A Randomized Controlled Study of Shifting Attention From Self-Focus to Nonsocial vs. Social External Stimuli During Virtual Reality Exposure to Public Speaking in Social Anxiety
Authors: Wechsler Theresa F. , Pfaller Michael , Eickels Rahel E. van , Schulz Luise H. , Mühlberger Andreas 
Published: December 2021

Background: Enhanced self-focused attention plays a central role in the maintenance and treatment of Social Anxiety and is targeted in contemporary cognitive behavioral therapy. Actual developments use Virtual Reality (VR) for behavioral training. However, no VR attention training combining exposure to public speaking with shifting attention from self-focus to external focus has been investigated, and no experimental evidence exists on different kinds of external cues as targets of attention. Therefore, we investigated the effects of an attention training during public speaking in VR and examined differential effects of an external focus on nonsocial vs. social stimuli.Methods: In this randomized controlled study, highly socially anxious participants were instructed to focus on either objects or the audience within a virtual speech task. We assessed the pre-post effects on affective reactions, self-perception, and attentional processes during public speaking as well as general Social Anxiety using subjective, physiological, and eye-tracking measures. Repeated-measures analyses of variance (ANOVAs) were calculated to detect changes from pretest to posttest over both groups, and time × group interaction effects.Results: Within the analysis sample (n = 41), anxiety during public speaking and fear of negative evaluation significantly decreased, with no significant differences between groups. No significant time effect, but a significant time × group effect, was found for the looking time proportion on the audience members' heads. Follow-up tests confirmed a significant increase in the social-focus group and a significant decrease in the nonsocial-focus group. For all other variables, except external focus and fear of public speaking, significant improvements were found over both groups. Further significant time x group effects were found for positive affect during public speaking, with a significant increase in the social focus, and no significant change in the nonsocial-focus group.Conclusion: Our findings suggest that attention training to reduce self-focus can be successfully conducted in VR. Both training versions showed positive short-term effects in the highly socially anxious, with particular advantages of an external social focus concerning eye contact to the audience and positive affect. Further research should investigate whether social focus is even more advantageous long term and if reinterpretations of dysfunctional beliefs could be achieved by not avoiding social cues.
Epidemiological Characteristics and Transmissibility of Human Immunodeficiency Virus in Nanning City, China, 2001–2020
Authors: Lin Qian , Deng Bin , Rui Jia , Guo Song-Bai , Hu Qingqing , Chen Qiuping , Tang Chi , Zhou Lina , Zhao Zeyu , Lin Shengnan , Zhu Yuanzhao , Yang Meng , Wang Yao , Xu Jingwen , Liu Xingchun , Yang Tianlong , Li Peihua , Li Zhuoyang , Luo Li , Liu Weikang , Liu Chan , Huang Jiefeng , Yao Min , Nong Mengni , Nong Liping , Wu Jinglan , Luo Na , Chen Shihai , Frutos Roger , Yang Shixiong , Li Qun , Cui Jing-An , Chen Tianmu 
Published: December 2021

Background: Human immunodeficiency virus (HIV) is a single-stranded RNA virus that can weaken the body's cellular and humoral immunity and is a serious disease without specific drug management and vaccine. This study aimed to evaluate the epidemiologic characteristics and transmissibility of HIV.Methods: Data on HIV follow-up were collected in Nanning City, Guangxi Zhuang Autonomous, China. An HIV transmission dynamics model was built to simulate the transmission of HIV and estimate its transmissibility by comparing the effective reproduction number (Reff) at different stages: the rapid growth period from January 2001 to March 2005, slow growth period from April 2005 to April 2011, and the plateau from May 2011 to December 2019 of HIV in Nanning City.Results: High-risk areas of HIV prevalence in Nanning City were mainly concentrated in suburbs. Furthermore, high-risk groups were those of older age, with lower income, and lower education levels. The Reff in each stage (rapid growth, slow growth, and plateau) were 2.74, 1.62, and 1.15, respectively, which suggests the transmissibility of HIV in Nanning City has declined and prevention and control measures have achieved significant results.Conclusion: Over the past 20 years, the HIV incidence in Nanning has remained at a relatively high level, but its development trend has been curbed. Transmissibility was reduced from 2.74 to 1.15. Therefore, the prevention and treatment measures in Nanning City have achieved significant improvement.
FUENTES BIBLIOGRÁFICAS GENERALES PARA EL ESTUDIO DE LA FRASEOLOGÍA ESPAÑOLA DESDE LA PERSPECTIVA DIDÁCTICA Y DE LA ENSEÑANZA DEL ESPAÑOL COMO LENGUA EXTRANJERA
Authors: Salem Tarek Shaban Mohammad 
Published: December 2021

El campo de la fraseología ha suscitado el interés en los investigadores a lo largo de muchos años. Esto fue motivo de la aparición de decenas de trabajos relacionados con diferentes perspectivas de dicha disciplina. Este artículo viene como una continuación de algunos trabajos de investigación que hemos realizado a lo largo de los últimos cinco años. En este trabajo incluimos los trabajos que tratan la fraseología desde la perspectiva didáctica de la lengua además de aquellos relacionados con la enseñanza del español como lengua extranjera. Esta relación bibliográfica recoge principalmente los trabajos publicados hasta 2018, es decir que está actualizada. Por ende, los investigadores de esta rama lingüística podrán tener una idea clara y global sobre los temas planteados al respecto. En este repertorio bibliográfico tratamos la fraseología desde su concepción amplia, es decir, que abarca las colocaciones, las locuciones, los enunciados fraseológicos e incluso las paremias. Para una fácil consulta, hemos dividido las fuentes en este repertorio en varias secciones: artículos publicados en revistas y en congresos, capítulos de libros y libros completos que tratan el tema; y memorias de máster y tesis doctorales. Estamos seguros de que estas fuentes representan una guía imprescindible para el estudio de este campo lingüístico.
PALABRAS CLAVE: Fuentes bibliográficas; Fraseología; Didáctica; Español como lengua extranjera.
GENERAL BIBLIOGRAPHICAL SOURCES FOR THE STUDY OF SPANISH PHRASEOLOGY FROM THE DIDACTIC PERSPECTIVE AND THE TEACHING OF SPANISH AS A FOREIGN LANGUAGE
ABSTRACT
Phraseology has received great interest by researchers over time. This is why we found dozens of works related to different perspectives of this discipline. It should be noted that this article comes as a continuation of some research works we have done over the past five years. The present paper includes the works that deal with phraseology from the didactic perspective and teaching Spanish as a foreign language. This bibliographical list mainly includes works published until 2018, that is, it has been updated for contemporary scholars in this branch of linguistics to provide them with a clear and global idea of the topics discussed in this regard. In this bibliographical repertoire, we deal with phraseology in its broad sense, that is, it encompasses collocations, idioms, phraseological statements and even proverbs. For easy consultation of this repertoire, we have divided the sources into several sections: articles published in journals and conferences; books or chapters of books dealing with the subject; and master's and doctoral dissertations. We are sure that these sources present a helpful guide for the study of this linguistic field.
KEYWORDS: Bibliographic Sources; Phraseology; Didactics; Spanish as a Foreign Language.
UN ACERCAMIENTO A LAS INTERRELACIONES DIDÁCTICAS ENTRE LA ANTROPOLOGÍA Y LA DIDÁCTICA DE LA HISTORIA
Authors: Fernández Naranjo Roberto 
Published: December 2021

El poder reflexionar sobre la didáctica de la Historia desde una visión más general y culturológica como nos ofrece la antropología sociocultural, ha devenido en tarea priorizada para poder encontrar los fundamentos teóricos que sustentan los estudios que sobre didáctica de la Historia y las ciencias sociales, realizamos los docentes investigadores que nos ocupamos de esta área del saber, poder reflexionar sobre la categoría Hecho histórico cultural deviene en plataforma teórica para el análisis de la cuestión racial, la marginalidad, tomado como centro la cultura como epicentro fundamental para poder realizar estos análisis.
PALABRAS CLAVE: Antropología; Hecho histórico cultural; Didáctica de la Historia.
AN APPROACH TO DIDACTIC INTERRELATIONS BETWEEN ANTHROPOLOGY AND DIDACTICS OF HISTORY
ABSTRACT
Being able to reflect on the didactics of history from a more general and cultural perspective as sociocultural anthropology offers us, has become a priority task to be able to find the theoretical foundations that support the studies that on didactics of history and social sciences, we carry out The research professors that deal with this area of knowledge, to be able to reflect on the category Cultural historical fact becomes a theoretical platform for the analysis of the racial issue, marginality, taking culture as a fundamental epicenter to perform these analyzes.
KEYWORDS: Anthropology; Cultural Historical Fact; Didactics of History.
ROL DE LA FAMILIA EN EL PROCESO DE RECUPERACIÓN DE LAS PERSONAS DROGODEPENDIENTES
Authors: Velázquez Cedeño John F. , Cevallos Arteaga Cristhian A. 
Published: December 2021

La familia ejerce roles complejos en la recuperación del adicto, en donde los valores, sentimientos, emociones, son parte de un sistema en continua evolución y cambio, adaptándose, transformándose en relación con las presiones del medio en que se desenvuelven, siendo la relación familiar de gran importancia. Se considera a la familia como una herramienta de intervención valiosa para romper la negación de la persona adicta y así iniciar el proceso recuperación, pero en ocasiones suele ser la principal causa de que el paciente abandone el tratamiento e incluso provocar desliz y/o recaídas. Un elemento clave en la recuperación de las adicciones son sus familiares, tanto en su detección, aceptación, orientación, canalización, tratamiento y mantenimiento de la abstinencia provocada por la dependencia del consumo de una sustancia. Lo principal es que los familiares se integren en el proceso de recuperación de las personas drogodependientes, buscando estrategias preventivas para evitar el abandono del tratamiento basado en el manejo y entendimiento de la problemática de las drogas, así como también se busca que la familia sea parte activa promoviendo una recuperación de calidad que contribuya a fortalecer la personalidad de cada uno de los internos tanto en la familia como en la sociedad en general.
PALABRAS CLAVE: Rol de la familia; proceso de recuperación; drogodependencia.
ROLE OF THE FAMILY IN THE PROCESS OF RECOVERY OF DROGODEPENDENT PERSONS
ABSTRACT
The family exercises complex roles in the recovery of the addict, where the values, feelings, emotions, are part of a system in continuous evolution and change, adapting, transforming in relation to the pressures of the environment in which they operate, being the family relationship of great importance. The family is considered as a valuable intervention tool to break the denial of the addicted person and thus initiate the recovery process, but sometimes it is usually the main cause of the patient leaving the treatment and even causing slip and / or relapses. A key element in the recovery of addictions are their relatives, both in their detection, acceptance, orientation, channeling, treatment and maintenance of abstinence caused by the dependence of the consumption of a substance. The main thing is that the families are integrated into the recovery process of drug addicts, looking for preventive strategies to avoid the abandonment of the treatment based on the management and understanding of the problem of drugs, as well as seeking to make the family part of the family active promoting a recovery of quality that contributes to strengthen the personality of each of the inmates both in the family and in society in general.
KEYWORDS: Role of the family; recovery process; drug addiction.