bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Embolism: novel corona virus versus tuberculosis
Authors: Dhamecha Nidhi , Nagadiya Qury , Gupta Anurag , Patel Nehal , Thanvi Rashmi , Pandav Ghosha 
Published: October 2020

Abstract
This series describes six paediatric cases who presented as severe acute respiratory illness during the pandemic of covid-19 with high D-dimer levels. All six patients tested negative for novel corona virus. They were diagnosed as having tuberculosis on detailed investigations; High D-dimer levels are one of the most important indicators of the pulmonary embolism. Pulmonary embolism is a rare presentation of tuberculosis and this study emphasizes the need of keeping tuberculosis as an important differential diagnosis of those who present as acute respiratory distress syndrome.
Discovery of LAMP-2A as Potential Biomarkers for Glioblastoma Development by Modulating Apoptosis through N-CoR Degradation
Authors: Wang Yongjie , Zhang Buyi , Wang Jianli , Wu Haijian , Xu Shenbin , Zhang Jianmin , Wang Lin 
Published: October 2020

Abstract
Background: Lysosome-associated membrane protein type 2A (LAMP-2A) is the key component of chaperone-mediated autophagy (CMA), a cargo-selective lysosomal degradation pathway. Aberrant LAMP-2A expression and CMA activation have been demonstrated in various human malignancies. The study focusing on the intrinsic role of LAMP-2A and CMA in glioblastoma (GBM), and downstream mechanism could provide valuable insight into the pathogenesis and novel therapeutic modality of GBM. Methods: The levels of LAMP-2A, nuclear receptor co-repressor (N-CoR), unfolded protein reaction (UPR) and apoptosis were examined in clinical samples. LAMP-2A siRNA and shRNA were constructed to manipulate CMA activation. The role of CMA and downstream mechanism through degradation of N-CoR and arresting UPR mediated apoptosis were explored in GBM cells and nude mouse xenograft model. Results: Elevated LAMP-2A and associated decreased N-CoR expression were observed in GBM as compared with peritumoral region and low-grade glioma. Inhibited UPR and apoptosis were observed in GBM with high LAMP-2A expression. In vitro study demonstrated co-localization and interaction between LAMP-2A and N-CoR. LAMP-2A silencing up-regulated N-CoR and aroused UPR pathway, leading to apoptosis, while N-CoR silencing led to an opposite result. In vivo study further confirmed that LAMP-2A inhibition arrested tumor growth by promoting apoptosis.Conclusions: Our results demonstrated the central role of CMA in mediating N-CoR degradation and protecting GBM cells against UPR and apoptosis, and provided evidence of LAMP-2A as potential biomarker. Further research focusing on CMA with other tumorigenic process is needed and selective modulators of LAMP-2A remain to be investigated to provide a novel therapeutic strategy for GBM.
Applying Implementation and Team Science Principles to Facilitate Cancer Program Implementation in Remote, Under-resourced Areas
Authors: Crabtree-Ide Christina , Sevdalis Nick , Bellohusen Patricia , Constine Louis S. , Fleming Fergal , Holub David , Rizvi Irfan , Rodriguez Jennifer , Sharda Pradeep , Sharda Varsha , Shayne Michelle , Termer Nancy , Tomaszewski Ken , Noyes Katia 
Published: October 2020

Abstract
Background: Failed implementation of health programs is common and may contribute to health disparities in resource-poor communities. We aimed to (1) evaluate barriers and facilitators for implementation of cancer survivorship services in rural communities and to (2) identify optimal strategies for successful implementation of survivorship care programs in these settings. Methods: The study design was guided by the Consolidated Framework for Implementation Research (CFIR) and based on the core principles of effective teamwork. We collected qualitative and quantitative data to assess barriers and facilitators to implementation of rural cancer survivorship care (3 focus groups, size 8, 31, and 77). Data were collected using both in-person and web-based approaches (semi-structured interviews, stakeholder surveys, ThinkTank, project online portal, Google Analytics). Stakeholders included cancer survivors, their families and caregivers, local public services administrators, health providers, and allied health-care professionals from rural and remote communities in Upstate New York. Results: Patients reported preferences for cross-region team-based survivorship care and emphasized the importance of including local providers on regional care teams and networks. Synthesis of results was guided by teamwork principles. Most rural patient stakeholders trusted recommendations received from their local providers (n=6, 86%) and preferred receiving care locally (n=6, 86%). Involvement of rural patient navigators (average rank 1.5 out of 5) and county care managers (1.9) was ranked more favorably than reliance on telemedicine alone (3.3) or visiting practice facilitators (3.3). Rural counties that have existing formal and informal networks involved in cancer care scored higher on the metrics of teamwork and demonstrated more advanced readiness to change in regards to survivorship program implementation. Conclusions: Our analysis identified a unique combination of community socio-economic factors, geographic isolation, and limited provider supply common in rural care settings as barriers to optimal delivery of cancer survivorship care in rural settings. We propose teamwork training and facilitation as an innovative implementation strategy to overcome these barriers and minimize their effect on patient access to care. Merging implementation science and team science frameworks could further assist with program adaptation to minimize implementation failure and improve continuity of care for complex cancer pathway management.
Barriers and facilitators to implementing a mobile intervention with task shifting in the treatment of depressive symptoms in people with diabetes and / or hypertension in Brazil: A study protocol using the CFIR.
Authors: Castro Hellen Carolina Martins , Couto Marcia Thereza , Daley Kate , Rocha Thais Izabel Ugeda , Aschar Suzana Crismanis de Almeida Lopes , Santos Daniela Vera Cruz dos , Claro Heloisa Garcia , Araya Ricardo , Menezes Paulo Rossi 
Published: October 2020

Abstract
Background: Task-shifting and eHealth have been proposed as ways of approaching the mental health treatment gap in low and middle-income countries (LMIC). The Latin America Treatment & Innovation Network in Mental Health (LATIN-MH) developed CONEMO (Emotional Control), a behavioral intervention used to treat depressive symptoms in a sample of patients with diabetes and hypertension in Sao Paulo, Brazil. The intervention uses task shifting and is delivered via a smartphone app. The effectiveness of this intervention was tested in two randomized trials in these countries. Aim: This paper aims to present the protocol for a study that will explore perceived barriers and facilitators to implementing this intervention to help future scale-up. Methods: We will conduct qualitative research with users of the CONEMO intervention and health professionals who participated directly and indirectly in the trial in Brazil. We will use semi-structured interviews, and we will adopt the Consolidated Framework for Implementation Research (CFIR) for data analysis. Discussion: Task-shifting and eHealth are potentially important tools to help decrease the mental health treatment gap in Latin America. This study will increase our understanding of the factors which may facilitate or hinder the implementation of mobile behavioral mental health interventions, using task-shifting, within LMICs. Findings could be used in future design and planning to facilitate successful implementation and treatment. Registration in Clinical Trials (www.clinical.trials.gov) NCT028406662
Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.
Authors: Aomar-MIllán Ismael Francisco , Salvatierra Juan , Torres-Parejo Ursula , Faro-Miguez Naya , Callejas-Rubio José Luis , Ceballos-Torres Angel , Cruces-Moreno María Teresa , Gómez-Jimenez Francisco Javier , Vinuesa-García David , Quero José Hernández , Anguita-Santos Francisco 
Published: October 2020

Abstract
Introduction: Little evidence appears to exists for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state. Patients and Methods: A retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed.Results: 74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265-0.910; p=0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications.Conclusions: In patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients, and may improve their prognosis.
A questionnaire-based study to comprehensively assess the status quo of rare disease patients in China
Authors: Li Xuefeng , Liu Meiling , Li Bingzhe , Zhang Xiangyu , Zhang Shu , Lu Zijuan , Zhang Jianyong , Zhou Jincheng , Ou Li 
Published: October 2020

Abstract
Background: There are over 16.8 million rare disease patients in China, representing a large community that should not be neglected. To provide a basis for policy-makers, a comprehensive analysis of the status quo, unmet needs, difficulty caused by the rare disease is essential.Methods: Therefore, a questionnaire-based study of patients and care-givers was performed.Findings: A total of 1,959 patients and care-givers participated, representing 104 rare diseases, such as lysosomal diseases, hemophilia, and muscular dystrophy. The diagnosis was delayed for 1.4 ± 3.0 years, and patients experienced 1.6 ± 3.8 misdiagnoses between 3.2 ± 2.4 hospitals. The hospitals where diagnoses made were highly concentrated in 10 large hospitals (43.8%) and 5 big cities (42.1%), indicating a significant inequality of medical resources. The disease often led to difficulty in social life, education, and employment, as well as financial burden that was seldom covered by medical insurance. A battery of standardized tests, including SF-36, PHQ-9, PHQ-15, GAD-7, and PSQI, demonstrated poor health status, depression, somatization, anxiety, and sleeping issues among both patients and care-givers (p<0.05).To examine the influence of age, disease type, and relationship to patients on the scores in these tests, statistical analysis with a general linear model was conducted. It was also shown that poor health, anxiety, depression, somatization, and sleeping problems were more prevalent in patients than in care-givers, and more prevalent in more severe diseases (e.g., hemophilia, Dravet) or undiagnosed than in other diseases.Interpretations: This study identified the lack of rare disease awareness and legislative support as the major challenge to rare diseases in China, and makes key recommendations for policy-makers, including legislating orphan drug act, raising rare disease awareness, and protecting rights in education and employment.
Atg7 Mediates Metformin Protected Abdominal Aortic Aneurysm by Inducing Autophagy
Authors: Guo Jingjing , Wang Zhu , Xue Ming , Mi Lei , Zhao Mengpeng , Ma Chao , Wu Jian , Han Xinqiang 
Published: October 2020

Abstract
BackgroundAbdominal aortic aneurysm (AAA) is pathologic dilation of the abdominal aorta and is often asymptomatic but has high susceptibility to rupture. Our previous study showed that metformin protected the pathophysiology of AAA by reducing the activation of PI3K/AKT/mTOR pathway. MethodsAngiotensin II (Ang-II) was used to construct the AAA model in vascular smooth muscle cells (VSMCs). The expression of Atg7 and Atg4 was determined by qRT-PCR and Western blot. Atg7 expression was regulated by overexpressed plasmid or siRNA to examine the cell proliferation, cell migration, cell apoptosis and autophagy caused by Ang-II. ResultsAng-II induced the expression of Atg7 and metformin reversed this effect. Suppression of Atg7 inhibited cell proliferation and cell migration, reduced cell apoptosis and autophagy, while overexpression of Atg7 enhanced cell proliferation and cell migration, induced cell apoptosis and autophagy. Moreover, the expression of autophagy related protein was regulated by Atg7 in Ang-II treated VSMCs. We further showed that the Atg7 mediated-autophagy was attenuated by metformin. ConclusionMetformin-reduced autophagy in AAA was mediated by Atg7, suggesting that Atg7 was a potential downstream effector of metformin in protecting the pathophysiology of AAA.
Predictive Social Norms of Physicians’ Intention to Use Liver Cancer Screening: Based on an Extended Theory of Planned Behavior
Authors: Deng Qingwen , Liu Wenbin 
Published: October 2020

Abstract
Background: Globally, liver cancer is one of the most malignant tumors and has become a great concern to public health. The serious context of liver cancer prevention and control urges researchers to find more evidence about liver cancer screening and to expand its use. The purpose of this study was to determine the predictors associated with physicians’ intention to use liver cancer screening. Methods: We took contrast-enhanced ultrasound (CEUS) as an example, and developed the research framework by adding socials norms to the Theory of Planned Behavior (TPB). Data was collected via a cross-sectional questionnaire survey on a sample of 292 physicians randomly selected from Fujian and Jiangxi provinces in China with a high and low incidence of liver cancer, respectively. Due to the multicollinearity problem of the data, ridge regression was applied to determine the influencing factors of physicians’ intention to use CEUS. Results: Most of the participants (87.30%) reported that they were willing to use liver cancer screening in their clinical practice. The scores of TPB variables were generally higher than those of social norms variables. Regression results indicated that the proposed model was explanatory, which has accounted for 72.6% of the total variance in physicians’ intention. Analyses also illustrated the significant role of TPB variables (attitude and perceived behavioral control) and social norms variables (personal norms, organizational norms, and industrial norms) on the physicians’ intention to use CEUS. Conclusions: The study extended the Theory of Planned Behavior (TPB) by including the concepts of social norms, which is not only conducive to expanding the knowledge of factors associated with physicians’ intention to use liver cancer screening, but also provide implications for developing strategies to promote the use of certain health services or products, such as playing the roles of core members, holding the panel meeting, and establishing an information push system.
Lower Starting Dose of Afatinib for the Treatment of Metastatic Lung Adenocarcinoma Harboring Exon 21 and Exon 19 Mutations
Authors: Chen Yi-Chieh , Tsai Ming-Ju , Lee Mei-Hsuan , Kuo Chia-Yu , Shen Mei-Chiou , Tsai Ying-Ming , Chen Huang-Chi , Hung Jen-Yu , Huang Ming-Shyan , Chong Inn-Wen , Yang Chih-Jen 
Published: October 2020

Abstract
BackgroundAfatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. MethodsWe designed a retrospective study, enrolled all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg afatinib as their starting dose in three Kaohsiung Medical University-affiliated hospitals in TaiwanResultsA total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (74% vs. 82%, p = 0.1661), median PFS (14.5 months vs. 14.80 months, log-rank p = 0.465) and median OS (34 months vs 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients with the lower starting dose had fewer ADRs compared with patients receiving 40 mg as their starting dose. The overall incidence of moderate (49% vs 77%, p=0.002) or severe (7% vs 24%, p<0.0001) ADRs was significantly lower in patients receiving 30 mg afatinib compared with those receiving 40 mg. ConclusionPatients receiving 30 mg afatinib as their starting dose had non-inferior RRs, PFS, OS and significantly fewer serious ADRs compared with those patients who received standard 40 mg afatinib as their starting dose.
Combining Tissue and Circulating Tumor DNA Increases the Detection Rate of CTNNB1 Mutation in Hepatocellular Carcinoma
Authors: Oversoe Stine Karlsen , Clement Michelle Simone , Weber Britta , Grønbæk Henning , Hamilton-Dutoit Stephen Jacques , Sorensen Boe Sandahl , Kelsen Jens 
Published: October 2020

Abstract
Background and aims: Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations.This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC.Methods: We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during three years of follow up. Results: In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, we found a CTNNB1 mutation rate of 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA indicated a clonal evolution of HCC or arising of multicentric tumors with separate genetic profiles.Conclusion: Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.
Dichloroacetate and PX-478 Exhibit Strong Synergistic Effects in a Various Number of Cancer Cell Lines.
Authors: Parczyk Jonas , Ruhnau Jérôme , Pelz Carsten , Schilling Max , Wu Hao , Piaskowski Nicole Nadine , Eickholt Britta , Kühn Hartmut , Danker Kerstin , Klein Andreas 
Published: October 2020

Abstract
Background: One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Further, the likelihood of drug resistance is reduced. Distinct alterations in tumour metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy. Recently, we found evidence for a synergism between dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor and HIF1-α inhibitor PX-478. In this study, we aimed to analyse this synergism in cell lines of different cancer types and to identify the underlying biochemical mechanisms.Methods: The dose-dependent antiproliferative effects of the single drugs and their combination were assessed using MTT or SRB assays. FACS, Western blot and HPLC analyses were performed to investigate changes in reactive oxygen species levels, apoptosis and the cell cycle. Additionally, real-time metabolic analyses (Seahorse) were performed with DCA-treated MCF-7 cells.Results: The combination of DCA and PX-478 produced synergistic effects in all eight cancer cell lines tested, including colorectal, lung, breast, cervical, liver and brain cancer. Reactive oxygen species generation and apoptosis played important roles in this synergism. Furthermore, cell proliferation was inhibited by the combination treatment.Conclusions: Here, we found that these cancer metabolism-targeting compounds exhibited potent synergism across all tested cancer cell lines. Thus, we highly recommend the combination of these two compounds for progression to in vivo translational and clinical trials.