bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the road to elimination: a 5-year evaluation of implementation strategies associated with hepatitis C treatment in the veterans health administration
Authors: Yakovchenko Vera , Morgan Timothy R. , Chinman Matthew J. , Powell Byron J. , Gonzalez Rachel , Park Angela , Malone Patrick S. , Chartier Maggie , Ross David , Rogal Shari S. 
Published: December 2021

Abstract
Background
While few countries and healthcare systems are on track to meet the World Health Organization’s hepatitis C virus (HCV) elimination goals, the US Veterans Health Administration (VHA) has been a leader in these efforts. We aimed to determine which implementation strategies were associated with successful national viral elimination implementation within the VHA.

Methods
We conducted a five-year, longitudinal cohort study of the VHA Hepatic Innovation Team (HIT) Collaborative between October 2015 and September 2019. Participants from 130 VHA medical centers treating HCV were sent annual electronic surveys about their use of 73 implementation strategies, organized into nine clusters as described by the Expert Recommendations for Implementing Change taxonomy. Descriptive and nonparametric analyses assessed strategy use over time, strategy attribution to the HIT, and strategy associations with site HCV treatment volume and rate of adoption, following the Theory of Diffusion of Innovations.

Results
Between 58 and 109 medical centers provided responses in each year, including 127 (98%) responding at least once, and 54 (42%) responding in all four implementation years. A median of 13–27 strategies were endorsed per year, and 8–36 individual strategies were significantly associated with treatment volume per year. Data warehousing, tailoring, and patient-facing strategies were most commonly endorsed. One strategy—“identify early adopters to learn from their experiences”—was significantly associated with HCV treatment volume in each year. Peak implementation year was associated with revising professional roles, providing local technical assistance, using data warehousing (i.e., dashboard population management), and identifying and preparing champions. Many of the strategies were driven by a national learning collaborative, which was instrumental in successful HCV elimination.

Conclusions
VHA’s tremendous success in rapidly treating nearly all Veterans with HCV can provide a roadmap for other HCV elimination initiatives.
The implementation potential of a method to monitor empirically-supported children’s mental health treatment through claims data
Authors: Walker Sarah Cusworth , Gubner Noah , Iztguttinov Aniyar , Rodriguez Felix , Davis Paul , Lyon Aaron , Kerns Suzanne , Bruns Eric , Qian Jiage , Sedlar Georganna 
Published: December 2021

Abstract
Background
The delivery of evidence-supported treatments (EST) in children’s mental health could be a valuable measure for monitoring mental healthcare quality; however, efforts to monitor the use of EST in real world systems are hindered by the lack of pragmatic methods. This mixed methods study examined the implementation and agency response rate of a pragmatic, claims-based measure of EST designed to be applied as a universal quality measure for child psychotherapy encounters in a state Medicaid system.

Methods
Implementation potential of the EST measure was assessed with healthcare leader rankings of the reporting method’s acceptability, appropriateness and feasibility (n = 53), and post-implementation ratings of EST rate accuracy. Ability of the healthcare system to monitor EST through claims was measured by examining the agency responsivity in using the claims-based measure across 98 Medicaid-contracted community mental health (CMH) agencies in Washington State.

Results
The analysis found the reporting method had high implementation potential. The method was able to measure the use of an EST for 83% of children covered by Medicaid with 58% CMH agencies reporting > 0 ESTs in one quarter. Qualitative analyses revealed that the most significant barrier to reporting ESTs was the operability of electronic health record systems and agencies’ mixed views regarding the accuracy and benefits of reporting.

Conclusions
Measurement of child mental health ESTs through Medicaid claims reporting has acceptable implementation potential and promising real world responsiveness from CMH agencies in one state. Variation in reporting by agency site and low to moderate perceived value by agency leaders suggests the need for additional implementation supports for wider uptake.
Defining a patient-centered approach to cancer survivorship care: development of the patient centered survivorship care index (PC-SCI)
Authors: Mead K. Holly , Wang Yan , Cleary Sean , Arem Hannah , Pratt-Chapman Mandi L. 
Published: December 2021

AbstractPurposeThis study presents the validation of an index that defines and measures a patient-centered approach to quality survivorship care.MethodsWe conducted a national survey of 1,278 survivors of breast, prostate, and colorectal cancers to identify their priorities for cancer survivorship care. We identified 42 items that were “very important or absolutely essential” to study participants. We then conducted exploratory and confirmatory factor analyses (EFA/CFA) to develop and validate the Patient-Centered Survivorship Care Index (PC-SCI).ResultsA seven-factor structure was identified based on EFA on a randomly split half sample and then validated by CFA based on the other half sample. The seven factors include: (1) information and support in survivorship (7 items), (2) having a medical home (10 items) (3) patient engagement in care (3 items), (4) care coordination (5 items), (5) insurance navigation (3 items), (6) care transitions from oncologist to primary care (3 items), and (7) prevention and wellness services (5 items). All factors have excellent composite reliabilities (Cronbach’s alpha 0.84-0.94, Coefficient of Omega: 0.81-0.94).ConclusionsProviding quality post-treatment care is critical for the long-term health and well-being of survivors. The PC-SCI defines a patient-centered approach to survivorship care to complement clinical practice guidelines. The PC-SCI has acceptable composite reliability, providing the field with a valid instrument of patient-centered survivorship care. The PC-SCI provides cancer centers with a means to guide, measure and monitor the development of their survivorship care to align with patient priorities of care.Trial registrationClinicalTrials.gov ID:NCT02362750, 13 February 2015
Direct phone communication to primary care physician to plan discharge from hospital: feasibility and benefits
Authors: Enzinger Lukas , Dumanoir Perrine , Boussat Bastien , Couturier Pascal , Francois Patrice 
Published: December 2021

Abstract
Background
The discharge summary is the main vector of communication at the time of hospital discharge, but it is known to be insufficient. Direct phone contact between hospitalist and primary care physician (PCP) at discharge could ensure rapid transmission of information, improve patient safety and promote interprofessional collaboration. The objective of this study was to evaluate the feasibility and benefit of a phone call from hospitalist to PCP to plan discharge.

Methods
This study was a prospective, single-center, cross-sectional observational study. It took place in an acute medicine unit of a French university hospital. The hospitalist had to contact the PCP by telephone within 72 h prior discharge, making a maximum of 3 call attempts. The primary endpoint was the proportion of patients whose primary care physician could be reached by telephone at the time of discharge. The other criteria were the physicians’ opinions on the benefits of this contact and its effect on readmission rates.

Results
275 patients were eligible. 8 hospitalists and 130 PCPs gave their opinion. Calls attempts were made for 71% of eligible patients. Call attempts resulted in successful contact with the PCP 157 times, representing 80% of call attempts and 57% of eligible patients. The average call completion rate was 47%. The telephone contact was perceived by hospitalist as useful and providing security. The PCPs were satisfied and wanted this intervention to become systematic. Telephone contact did not reduce the readmission rate.

Conclusions
Despite the implementation of a standardized process, the feasibility of the intervention was modest. The main obstacle was hospitalists lacking time and facing difficulties in reaching the PCPs. However, physicians showed desire to communicate directly by telephone at the time of discharge.

Trial registration
French C.N.I.L. registration number 2108852. Registration date October 12, 2017.
Integrative utility of long read sequencing-based whole genome analysis and phenotypic assay on differentiating isoniazid-resistant signature of Mycobacterium tuberculosis
Authors: Yu Ming-Chih , Hung Ching-Sheng , Huang Chun-Kai , Wang Cheng-Hui , Liang Yu-Chih , Lin Jung-Chun 
Published: December 2021

Abstract
Background
With the advancement of next generation sequencing technologies (NGS), whole-genome sequencing (WGS) has been deployed to a wide range of clinical scenarios. Rapid and accurate classification of drug-resistant Mycobacterium tuberculosis (MTB) would be advantageous in reducing the amplification of additional drug resistance and disease transmission.

Methods
In this study, a long-read sequencing approach was subjected to the whole-genome sequencing of clinical MTB clones with susceptibility test profiles, including isoniazid (INH) susceptible clones (n = 10) and INH resistant clones (n = 42) isolated from clinical specimens. Non-synonymous variants within the katG or inhA gene associated with INH resistance was identified using Nanopore sequencing coupled with a corresponding analytical workflow.

Results
In total, 54 nucleotide variants within the katG gene and 39 variants within the inhA gene associated with INH resistance were identified. Consistency among the results of genotypic profiles, susceptibility test, and minimal inhibitory concentration, the high-INH resistance signature was estimated using the area under the receiver operating characteristic curve with the existence of Ser315Thr (AUC = 0.822) or Thr579Asn (AUC = 0.875).

Conclusions
Taken together, we curated lists of coding variants associated with differential INH resistance using Nanopore sequencing, which may constitute an emerging platform for rapid and accurate identification of drug-resistant MTB clones.
Prognostic value and immune infiltration of novel signatures in colon cancer microenvironment
Authors: Lin Yilin , Pan Xiaoxian , Chen Zhihua , Lin Suyong , Shen Zhanlong , Chen Shaoqin 
Published: December 2021

Abstract
Background
Growing evidence has shown that the prognosis for colon cancer depends on changes in microenvironment. The purpose of this study was to elucidate the prognostic value of long noncoding RNAs (lncRNAs) related to immune microenvironment (IM) in colon cancer.

Methods
Single sample gene set enrichment analysis (ssGSEA) was used to identify the subtypes of colon cancer based on the immune genomes of 29 immune signatures. Cox regression analysis identified a lncRNA signatures associated with immune infiltration. The Tumor Immune Estimation Resource database was used to analyze immune cell content.

Results
Colon cancer samples were divided into three subtypes by unsupervised cluster analysis. Cox regression analysis identified an immune infiltration-related 5-lncRNA signature. This signature combined with clinical factors can effectively improve the predictive ability for the overall survival (OS) of colon cancer. At the same time, we found that the expression of H19 affects the content of B cells and macrophages in the microenvironment of colon cancer and affects the prognosis of colon cancer. Finally, we constructed the H19 regulatory network and further analyzed the possible mechanisms. We found that knocking down the expression of H19 can significantly inhibit the expression of CCND1 and VEGFA. At the same time, the immunohistochemical assay found that the expression of CCND1 and VEGFA protein was significantly positively correlated with the infiltration of M2 type macrophages.

Conclusion
The findings may help to formulate clinical strategies and understand the underlying mechanisms of H19 regulation. H19 may be a biomarker for targeted treatment of colon cancer.
Global, regional, and national quality of care of gallbladder and biliary tract cancer: a systematic analysis for the global burden of disease study 1990–2017
Authors: Khanali Javad , Malekpour Mohammad-Reza , Azangou-Khyavy Mohammadreza , Saeedi Moghaddam Sahar , Rezaei Negar , Kolahi Ali-Asghar , Abbasi-Kangevari Mohsen , Mohammadi Esmaeil , Rezaei Nazila , Yoosefi Moein , Keykhaei Mohammad , Farzi Yosef , Gorgani Fateme , Larijani Bagher , Farzadfar Farshad 
Published: December 2021

Abstract
Background
To improve health outcomes to their maximum level, defining indices to measure healthcare quality and accessibility is crucial. In this study, we implemented the novel Quality of Care Index (QCI) to estimate the quality and accessibility of care for patients with gallbladder and biliary tract cancer (GBBTC) in 195 countries, 21 Global Burden of Disease (GBD) regions, Socio-demographic Index (SDI) quintiles, and sex groups.

Method
This cross-sectional study extracted estimates on GBBTC burden from the GBD 2017, which presents population-based estimates on GBBTC burden for higher than 15-year-old patients from 1990 to 2017. Four secondary indices indicating quality of care were chosen, comprising Mortality to incidence, Disability-Adjusted Life Year (DALY) to prevalence, prevalence to incidence, and years of life lost (YLL) to years lived with disability (YLD) ratios. Then, the whole dataset was analyzed using Principal Component Analysis to combine the four indices and create a single all-inclusive measure named QCI. The QCI was scaled to the 0–100 range, with 100 indicating the best quality of care among countries. Gender Disparity Ratio (GDR) was defined as the female to male QCI ratio to show gender inequity throughout the regions and countries.

Results
Global QCI score for GBBTC was 33.5 in 2017, which has increased by 29% since 1990. There was a considerable gender disparity in favor of men (GDR = 0.74) in 2017, showing QCI has moved toward gender inequity since 1990 (GDR = 0.85). Quality of care followed a heterogeneous pattern among regions and countries and was positively correlated with the countries’ developmental status reflected in SDI (r = 0.7; CI 95%: 0.61–0.76; P value< 0.001). Accordingly, High-income North America (QCI = 72.4) had the highest QCI; whereas, Eastern Sub-Saharan Africa (QCI = 3) had the lowest QCI among regions. Patients aged 45 to 80 had lower QCI scores than younger and older adults. The highest QCI score was for the older than 95 age group (QCI = 54), and the lowest was for the 50–54 age group (QCI = 26.0).

Conclusions
QCI improved considerably from 1990 to 2017; however, it showed heterogeneous distribution and inequity between sex and age groups. In each regional context, plans from countries with the highest QCI and best gender equity should be disseminated and implemented in order to decrease the overall burden of GBBTC.
Effect of comorbidities and risk conditions on death from COVID-19 in migrants in Mexico
Authors: Martínez-Martínez Oscar A. , Valenzuela-Moreno Karla A. , Coutiño Brenda 
Published: December 2021

Abstract
Background
Comorbidities increase the risk of death for patients with COVID-19, however, little is known about how it affects the prognosis of migrants who contract the virus. Therefore, this article aims to determine which comorbidities and risk conditions are associated with the probability of death among migrants infected with COVID-19 in Mexico.

Methods
We use a sample of migrants with a positive diagnosis for COVID-19 (N = 2126) registered in the public database published in the National Epidemiological Surveillance System of the Mexican Ministry of Health; the technique used was a Probit regression.

Results
The findings show that most of the comorbidities commonly associated with death from COVID-19 in the native-born population were actually not significant when present in migrants infected with COVID-19. Additionally, migrants have lower comorbidities than locals. The results further indicate that the factors related to the death of migrants infected with COVID-19 are: age, intubation, nationality group, pneumonia and the Health Care Management of Patients.

Conclusions
In contrast to preceding studies with native-born populations with COVID-19, where pre-existing diseases aggravated the diagnosis of COVID-19 and sometimes led to death, in the case of migrants, only pneumonia was the significant comorbidity associated with mortality among migrants diagnosed with COVID-19.
circCHST15 is a novel prognostic biomarker that promotes clear cell renal cell carcinoma cell proliferation and metastasis through the miR-125a-5p/EIF4EBP1 axis
Authors: Gui Cheng-Peng , Liao Bing , Luo Cheng-Gong , Chen Yu-Hang , Tan Lei , Tang Yi-Ming , Li Jia-Ying , Hou Yi , Song Hong-De , Lin Hai-Shan , Xu Quan-Hui , Yao Gao-Sheng , Yao Hao-Hua , Xi-Liu  , Luo Jun-Hang , Cao Jia-Zheng , Wei Jin-Huan 
Published: December 2021

Abstract
Background
Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC.

Methods
circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization.

Results
The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression.

Conclusions
We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.
Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing
Authors: He Juan , Zeng Zhen , Wang Yuelong , Deng Jiaojiao , Tang Xin , Liu Fujun , Huang Jianhan , Chen Hongxu , Liang Ruichao , Zan Xin , Liu Zhiyong , Tong Aiping , Guo Gang , Xu Jianguo , Zhu Xiaofeng , Zhou Liangxue , Peng Yong 
Published: December 2021

Abstract
Background
Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown.

Methods
In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays.

Results
We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer β-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation.

Conclusions
Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of β-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.
CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer
Authors: Jiang Tao , Wang Hongyu , Liu Lianyu , Song Hu , Zhang Yi , Wang Jiaqi , Liu Lei , Xu Teng , Fan Ruizhi , Xu Yixin , Wang Shuai , Shi Linsen , Zheng Li , Wang Renhao , Song Jun 
Published: December 2021

Abstract
Background
Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored.

Methods
CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT–PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R.

Results
CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression.

Conclusions
Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.