bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Prophylactic Traditional Chinese Medicine on Skin Toxicity of Afatinib in EGFR Mutation-Positive Advanced Lung Adenocarcinoma: A Single-Center, Prospective, Double-Blinded, Randomized-Controlled Pilot Trial
Authors: Li Chia-Ling , Hsia Te-Chun , Yang Su-Tso , Chao Kun-San Clifford , Tu Chih-Yen , Chen Hung-Jen , Li Chia-Hsiang 
Published: March 2022

Objectives: To evaluate the efficacy of prophylactic traditional Chinese medicine (TCM) on skin toxicities in patients with advanced lung adenocarcinoma treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a randomized-controlled trial (RCT). Materials and methods: This pilot study was a prospective, single-center, double-blinded RCT. The study enrolled patients with a new diagnosis of locally advanced and metastatic lung adenocarcinoma harboring EGFR mutations who were treated with first-line afatinib from July 1, 2016 to December 31, 2017. Thirty patients who met the inclusion and exclusion criteria were assigned to the TCM and placebo groups with simple randomization. TCM and placebo were initiated at the same time as afatinib and were administered for 3 months. The survival of each subject was followed until 3 years. Results: There were 36 patients with newly diagnosed lung adenocarcinoma during the study period. After the exclusion of 6 patients, the remaining 30 patients were assigned to the TCM (n = 14) and placebo (n = 16) groups comprising the intention-to-treat population. The time to first skin toxicity was 22.3 days in the TCM group and 17.6 days in the placebo group (P = .510) in the per-protocol population. The analysis of the present pilot study results determined that the difference in time to first skin toxicity between the 2 groups would reach statistical significance with a sample size of 237 based on a power of 0.8. There were significant differences in certain subscales of quality of life between the TCM and placebo groups; however, there was no significant difference in progression-free survival or overall survival between the 2 groups. Conclusions: Integrative TCM may prolong the time to first skin toxicity in patients with advanced lung adenocarcinoma treated with first-line afatinib. Prophylactic TCM could delay skin toxicity of any grade and reduce the incidence of grade 3 skin toxicity. Future large-scale RCTs are warranted to validate these findings. Trial Registration: ClinicalTrials.gov, NCT05204758. Registered on 24 Jan 2022.
A Comparison of Hospital Area Measurement in Germany, Canada, Australia, and the United States: Part 1
Authors: Viergutz Hannah-Kathrin Silja , Apple Michael 
Published: March 2022

Objectives: This article compares national standards for area measurements of healthcare facilities in four countries and examines the risks and differences that can arise when comparing building areas of healthcare facilities internationally. Background: In the planning and management of healthcare facilities, the utilization and comparison of building floor areas plays a major role. Differences in terminology, classification, and methodology help to reduce planning and cost risks when applied on a local and national level. The proper allocation of building floor space is vital in the design of room programs, determination of floor space, construction costs, and operating costs. Methods: Each of the four hospital area measurement standards is compared to discern similarities and differences. Results: Most countries use a three-tier system of hospital area measurement: building gross area, department gross area, and department net area. Few differences were found between country standards for department area, though the German standards do not fully address this tier. Variation is found in whether a country includes certain functions in the hospital area—such as research space, shell space, or central energy plants—which can have a significant impact on the overall hospital area. Conclusions: This article informs further development of individual country standards and highlights principles to consider for international hospital area comparison.
Dental Service and Resource Needs during COVID-19 among Underserved Populations
Authors: Johnson V. , Brondani M. , von Bergmann H. , Grossman S. , Donnelly L. 
Published: March 2022

Introduction: In response to the coronavirus disease 2019 (COVID-19) outbreak, dental services in British Columbia, Canada, were restricted to urgent and emergency cases between March 16 and May 18, 2020. It is unclear how the curtailment of oral health services has affected underserved populations who already often have limited access to dental care due to cost, fear, stigma, and discrimination. Objectives: To explore the experiences of underserved populations and their community organizations when accessing oral health services and information in British Columbia and identify their coping mechanisms employed during the curtailment of oral health care services. Methods: Semistructured, remote interviews were conducted with 13 staff and 18 members from 6 community-based organizations. These organizations serve men and women with a history of incarceration and/or experiencing poverty and homelessness, persons living with human immunodeficiency virus/AIDS, adults living with mental illness, and older adults in long-term care facilities. The interviews were audio-recorded, transcribed verbatim, and coded for emerging themes using NVivo 12 software. Thematic analysis was performed. Results: The pandemic raised concerns and hesitancy among underserved populations and further reduced access to care. In turn, those with unmet dental needs resorted to coping mechanisms, including turning to community support or medical services, self-management of dental issues, and not dealing with dental issues altogether. Community organizers and members outlined needed resources such as assistance navigating the dental care system, having a contact for dental-related questions, and member preparation for dental service changes, while emphasizing the importance of positive relationships with dental providers. Conclusion: Underserved populations who already face barriers to oral health care services experienced increased difficulty in addressing their oral health needs and concerns during the beginning of the COVID-19 pandemic. Strategies aimed at reaching out to this population and those who support them are needed to help mitigate negative coping strategies and increased oral health disparities. Knowledge Transfer Statement: This study depicts ways of addressing unmet oral health–related issues during the COVID-19 pandemic for underserved populations and their community organizations with policy implications as well as practical strategies.
Hemogen/BRG1 cooperativity modulates promoter and enhancer activation during erythropoiesis
Authors: Guo Xiang , Zhao Yangu , Kim Juhyun , Dean Ann 
Published: March 2022

Abstract
Hemogen is a hematopoietic tissue–specific gene that regulates the proliferation and differentiation of hematopoietic cells; however, the mechanism underlying its function in erythropoiesis is unknown. We found that depletion of hemogen in human CD34+ erythroid progenitor cells and HUDEP2 cells significantly reduced the expression of genes associated with heme and hemoglobin synthesis, supporting a positive role for hemogen in erythroid maturation. In human K562 cells, hemogen antagonized the occupancy of corepressors nucleosome remodeling and histone deacetylase (NuRD) complex and facilitated LDB1 complex–mediated chromatin looping. Hemogen recruited SWI/SNF complex ATPase BRG1 as a coactivator to regulate nucleosome accessibility and H3K27ac enrichment for promoter and enhancer activity. To determine whether hemogen/BRG1 cooperativity is conserved in mammalian systems, we generated hemogen-knockout/knockin mice and investigated hemogen/BRG1 function in murine erythropoiesis. Loss of hemogen in embryonic days 12.5 to 16.5 fetal liver cells impeded erythroid differentiation through reducing the production of mature erythroblasts. Chromatin immunoprecipitation sequencing in wild-type and hemogen-knockout animals revealed that BRG1 is largely dependent on hemogen to regulate chromatin accessibility at erythroid gene promoters and enhancers. In summary, the hemogen/BRG1 interaction in mammals is essential for fetal erythroid maturation and hemoglobin production through its active role in promoter and enhancer activity and chromatin organization.
Clinical characterization of familial hypercholesterolemia due to an amish founder mutation in Apolipoprotein B
Authors: Williams Katie B. , Horst Michael , Young Millie , Pascua Christine , Puffenberger Erik G. , Brigatti Karlla W. , Gonzaga-Jauregui Claudia , Shuldiner Alan R. , Gidding Samuel , Strauss Kevin A. , Chowdhury Devyani 
Published: March 2022

Abstract
Background
Familial hypercholesterolemia (FH) due to a founder variant in Apolipoprotein B (ApoBR3500Q) is reported in 12% of the Pennsylvania Amish community. By studying a cohort of ApoBR3500Q heterozygotes and homozygotes, we aimed to characterize the biochemical and cardiac imaging features in children and young adults with a common genetic background and similar lifestyle.

Methods
We employed advanced lipid profile testing, carotid intima media thickness (CIMT), pulse wave velocity (PWV), and peripheral artery tonometry (PAT) to assess atherosclerosis in a cohort of Amish ApoBR3500Q heterozygotes (n = 13), homozygotes (n = 3), and their unaffected, age-matched siblings (n = 9). ApoBR3500Q homozygotes were not included in statistical comparisons.

Results
LDL cholesterol (LDL-C) was significantly elevated among ApoBR3500Q heterozygotes compared to sibling controls, though several ApoBR3500Q heterozygotes had LDL-C levels in the normal range. LDL particles (LDL-P), small, dense LDL particles, and ApoB were also significantly elevated among subjects with ApoBR3500Q. Despite these differences in serum lipids and particles, CIMT and PWV were not significantly different between ApoBR3500Q heterozygotes and controls in age-adjusted analysis.

Conclusions
We provide a detailed description of the serum lipids, atherosclerotic plaque burden, vascular stiffness, and endothelial function among children and young adults with FH due to heterozygous ApoBR3500Q. Fasting LDL-C was lower than what is seen with other forms of FH, and even normal in several ApoBR3500Q heterozygotes, emphasizing the importance of cascade genetic testing among related individuals for diagnosis. We found increased number of LDL particles among ApoBR3500Q heterozygotes but an absence of detectable atherosclerosis.
Construction of immune-related lncRNA signature to predict aggressiveness, immune landscape, and drug resistance of colon cancer
Authors: Xue Yonggan , Ning Bobin , Liu Hongyi , Jia Baoqing 
Published: March 2022

Abstract
Background
Colon cancer remains one of the most common malignancies across the world. Thus far, a biomarker, which can comprehensively predict the survival outcomes, clinical characteristics, and therapeutic sensitivity, is still lacking.

Methods
We leveraged transcriptomic data of colon cancer from the existing datasets and constructed immune-related lncRNA (irlncRNA) pairs. After integrating with clinical survival data, we performed differential analysis and identified 11 irlncRNAs signature using Lasso regression analysis. We next plotted the 1-, 5-, and 10-year curve lines of receiver operating characteristics, calculated the areas under the curve, and recognized the optimal cutoff point. Then, we validated the pair-risk model in terms of the survival outcomes of the patients involved. Moreover, we tested the reliability of the model for predicting tumor aggressiveness and therapeutic susceptibility of colon cancer. Additionally, we reemployed the 11 of irlncRNAs involved in the pair-risk model to construct an expression-risk model to predict the prognostic outcomes of the patients involved.

Results
We recognized a total of 377 differentially expressed irlncRNAs (DEirlcRNAs), including 28 low-expressed and 349 high-expressed irlncRNAs in colon cancer patients. After performing a univariant Cox analysis, we identified 115 risk irlncRNAs that were significantly correlated with survival outcomes of patients involved. By taking the overlap of the DEirlcRNAs and the risk irlncRNAs, we ultimately recognized 55 irlncRNAs as core irlncRNAs. Then, we established a Cox HR model (pair-risk model) as well as an expression HR model (exp-risk model) based on 11 of the 55 core irlncRNAs. We found that both of the two models significantly outperformed the commonly used clinical characteristics, including age, T, N, and M stages when predicting survival outcomes. Moreover, we validated the pair-risk model as a potential tool for studying the tumor microenvironment of colon cancer and drug susceptibility. Additionally, we noticed that combinational use of the pair-risk model and the exp-risk model yielded a more robust approach for predicting the survival outcomes of patients with colon cancer.

Conclusions
We recognized 11 irlncRNAs and created a pair-risk model and an exp-risk model, which have the potential to predict clinical characteristics of colon cancer, either solely or conjointly.
The cognitive profile of Friedreich ataxia: a systematic review and meta-analysis
Authors: Naeije Gilles , Schulz Jörg B , Corben Louise A 
Published: March 2022

Abstract
Background
Study the cognitive profile of individuals with Friedreich ataxia (FRDA) and seek evidence for correlations between clinical, genetic and imaging characteristics and neuropsychological impairments.

Methods
Based on PRISMA guidelines, a meta-analysis was realized using the Pubmed and Scopus databases to identify studies (1950–2021) reporting neuropsychological test results in genetically confirmed FRDA and control participants in at least one of the following cognitive domains: attention/executive, language, memory and visuo-spatial functions as well as emotion. Studies using identical outcomes in a minimum of two studies were pooled. Pooled effect sizes were calculated with Cohen’s d.

Results
Eighteen studies were included. Individuals with FRDA displayed significantly lower performance than individuals without FRDA in most language, attention, executive function, memory visuospatial function, emotion regulation and social cognitive tasks. Among the included studies, thirteen studies examined the relationship between neuropsychological test results and clinical parameters and reported significant association with disease severity and six studies reviewed the relationship between neuroimaging measures and cognitive performance and mainly reported links between reduced cognitive performance and changes in cerebellar structure.

Conclusions
Individuals with FRDA display significantly lower performances in many cognitive domains compared to control participants. The spectrum of the cognitive profile alterations in FRDA and its correlation with disease severity and cerebellar structural parameters suggest a cerebellar role in the pathophysiology of FRDA cognitive impairments.
Clinical significance of Osaka prognostic score based on nutritional and inflammatory status in patients with esophageal squamous cell carcinoma
Authors: Feng Jifeng , Wang Lifen , Wang Liang , Yang Xun , Lou Guangyuan 
Published: March 2022

Abstract
Background
It has been reported that Osaka prognostic score (OPS), based on C-reactive protein (CRP), total lymphocyte counts (TLC) and albumin (ALB), was relevant to prognosis in colorectal cancer. However, the role of OPS regarding prognosis in patients with esophageal squamous cell carcinoma (ESCC) has not been reported. The current study aimed to explore the clinical outcome of OPS and establish and validate a nomogram for survival prediction in ESCC after radical resection.

Methods
This retrospective study included 395 consecutive ESCC patients with radical resection. Then patients were randomly divided into two cohorts: training cohort (276) and validation cohort (119). The OPS, based on TLC, CRP and ALB, was constructed to verify the prognostic value by Kaplan-Meier curves and Cox analyses. A nomogram model for prognosis prediction of cancer-specific survival (CSS) was developed and validated in two cohorts.

Results
Kaplan-Meier curves regarding the 5-year CSS for the groups of OPS 0, 1, 2 and 3 were 55.3, 30.6, 17.3 and 6.7% (P < 0.001) in the training cohort and 52.6, 33.3, 15.8 and 9.1% (P < 0.001) in the validation cohort, respectively. Then the OPS score in multivariate Cox analysis was confirmed to be a useful independent score. Finally, a predictive OPS-based nomogram was developed and validated with a C-index of 0.68 in the training cohort and 0.67 in the validation cohort, respectively. All above results indicated that the OPS-based nomogram can accurately and effectively predict survival in ESCC after radical resection.

Conclusion
The OPS serves as a novel, convenient and effective predictor in ESCC after radical resection. The OPS-based nomogram has potential independent prognostic value, which can accurately and effectively predict individual CSS in ESCC after radical resection.
Oncologist responses to advanced cancer patients’ lived illness experiences and effects: an applied conversation analysis study
Authors: van Meurs Jacqueline , Stommel Wyke , Leget Carlo , van de Geer Joep , Kuip Evelien , Vissers Kris , Engels Yvonne , Wichmann Anne 
Published: March 2022

AbstractBackgroundAn advanced cancer patient’s life is often disturbed by fear of cancer recurrence, cancer progress, approaching suffering, and fear of dying. Consequently, the role of the medical oncologist is not only to provide best quality anti-cancer treatment, but also to address the impact of disease and treatment on a patient’s life, the lived illness experience. We aimed to gain insights into whether and how medical oncologists working at an outpatient clinic identify and explore lived illness experiences raised by patients with advanced cancer, and how this influences patients’ responses.MethodsConversation Analysis was applied to analyse 16 verbatim transcribed audio-recorded consultations.ResultsWe identified 37 fragments in which patients expressed a lived experience from 11 of the 16 consultations. We found differing responses from different oncologists. Patients continued talking about their lived experiences if the listener produced a continuer such as humming or tried to capture the experience in their own words. In contrast, a response with optimistic talking or the presentation of medical evidence prevented patients from further unfolding the experience. In consultations in which the lived illness experience was most extensively unfolded, medical oncologists and patients could constantly see each other’s facial expressions.ConclusionsWhen a patient with advanced cancer spontaneously introduces a lived illness experience, it helps to identify and explore it when the medical oncologist produces a continuer or tries to capture this experience in their own words.Our findings can be implemented in training sessions, followed by frequent reinforcement in daily care.
Supply-demand matching of medical services at a city level under the background of hierarchical diagnosis and treatment - based on Didi Chuxing Data in Haikou, China
Authors: Shao Haiyan , Jin Cheng , Xu Jing , Zhong Yexi , Xu Bing 
Published: March 2022

Abstract
Background
Implementation of the Healthy China Strategy and the hierarchical diagnosis and treatment system has injected new vitality into medical services. Given the insufficient supply of medical services and increasing demand for medical treatment, exploring the supply-demand pattern of medical services has become an urgent theoretical and practical problem to be solved. The equity of healthcare facilities has received widespread attention, but due to limited data, there is little research on the supply-demand pattern of medical services. This study focuses on evaluating the supply-demand matching pattern of medical services at different levels in Haikou City with big geographic data and promoting the realization of a balance between medical supply and demand.

Methods
This study utilizes spatial data of medical institutions, Didi Chuxing Data, and population density data. Firstly, use the two-step floating catchment area method and GIS spatial analysis to explore characteristics of the supply-demand patterns of medical services at different levels in Haikou. Secondly, we mine residents’ demand for medical treatment based on Didi Chuxing Data. Then combined with population density data, divide supply-demand matching of medical institutions into four types. Finally, propose optimization strategies for the problems.

Results
The accessibility pattern of high-level medical institutions in Haikou presents high in the north and low in the south. The accessibility pattern of low-level medical institutions is the opposite. High-level medical institutions have a strong demand for medical treatment, which is less hampered by distance. The healthcare demand of low-level medical institutions is small, and they mainly are medium- and short-distance medical travel. The types of medical services at different levels are mainly “low supply - low demand” and “high supply - low demand” types.

Conclusions
Medical services at different levels in Haikou are mainly in supply-demand imbalance. Therefore, we put forward optimization strategies to promote the equity of primary medical services, such as propelling the establishment and improvement of the hierarchical diagnosis and treatment system, building a new model of medical and health service supply, and strengthening balanced coverage of primary medical institutions. The mining of big geographic data is beneficial to alleviate the mismatch between medical supply and demand, although the data and methods need to be improved.