bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Patient Navigator: Can a systematically developed online health information tool improve patient participation and outcomes related to the consultation in older patients newly diagnosed with colorectal cancer?
Authors: de Looper Melanie , Smets Ellen M. A. , Schouten Barbara C. , Bolle Sifra , Belgers Eric H. J. , Eddes Eric H. , Leijtens Jeroen W. A. , van Weert Julia C. M. 
Published: January 2022

Abstract
Background
Older cancer patients may search for health information online to prepare for their consultations. However, seeking information online can have negative effects, for instance increased anxiety due to finding incorrect or unclear information. In addition, existing online cancer information is not necessarily adapted to the needs of older patients, even though cancer is a disease often found in older individuals.

Objective
The aim of this study was to systematically develop, implement and evaluate an online health information tool for older cancer patients, the Patient Navigator, providing information that complements the consultation with healthcare providers.

Method
For the development and evaluation of the Patient Navigator, the four phases of the MRC framework were used. In the first and second phase the Patient Navigator was developed and pilot tested based on previous research and sub-studies. During the third phase the Patient Navigator was implemented in four Dutch hospitals. In the last phase, a pilot RCT was conducted to evaluate the Patient Navigator in terms of usage (observational tracking data), user experience (self-reported satisfaction, involvement, cognitive load, active control, perceived relevance of the tool), patient participation (observational data during consultation), and patient outcomes related to the consultation (questionnaire data regarding anxiety, satisfaction, and information recall). Recently diagnosed colorectal cancer patients (N = 45) were randomly assigned to the control condition (usual care) or the experimental condition (usual care + Patient Navigator).

Results
The Patient Navigator was well used and evaluated positively. Patients who received the Patient Navigator contributed less during the consultation by using less words than patients in the control condition and experienced less anxiety two days after the consultation than patients in the control condition.

Conclusion
Since the Patient Navigator was evaluated positively and decreased anxiety after the consultation, this tool is potentially a valuable addition to the consultation for patients. Usage of the Patient Navigator resulted in patients using less words during consultations, without impairing patients’ satisfaction, possibly because information needs might be fulfilled by usage of the Patient Navigator. This could create the possibility to personalize communication during consultations and respond to other patient needs.
An observational study of workflows to support fecal testing for colorectal cancer screening in primary care practices serving Medicaid enrollees
Authors: Mojica Cynthia M. , Gunn Rose , Pham Robyn , Miech Edward J. , Romer Ann , Renfro Stephanie , Clark Khaya D. , Davis Melinda M. 
Published: January 2022

Abstract

Background
Screening supports early detection and treatment of colorectal cancer (CRC). Provision of fecal immunochemical tests/fecal occult blood tests (FIT/FOBT) in primary care can increase CRC screening, particularly in populations experiencing health disparities. This study was conducted to describe clinical workflows for FIT/FOBT in Oregon primary care practices and to identify specific workflow processes that might be associated (alone or in combination) with higher (versus lower) CRC screening rates.

Methods
Primary care practices were rank ordered by CRC screening rates in Oregon Medicaid enrollees who turned age 50 years from January 2013 to June 2014 (i.e., newly age-eligible). Practices were recruited via purposive sampling based on organizational characteristics and CRC screening rates. Data collected were from surveys, observation visits, and informal interviews, and used to create practice-level CRC screening workflow reports. Data were analyzed using descriptive statistics, qualitative data analysis using an immersion-crystallization process, and a matrix analysis approach.

Results
All participating primary care practices (N=9) used visit-based workflows, and four higher performing and two lower performing used population outreach workflows to deliver FIT/FOBTs. However, higher performing practices (n=5) had more established workflows and staff to support activities. Visit-based strategies in higher performing practices included having dedicated staff identify patients due for CRC screening and training medical assistants to review FIT/FOBT instructions with patients. Population outreach strategies included having clinic staff generate lists and check them for accuracy prior to direct mailing of kits to patients. For both workflow types, higher performing clinics routinely utilized systems for patient reminders and follow-up after FIT/FOBT distribution.

Conclusions
Primary care practices with higher CRC screening rates among newly age-eligible Medicaid enrollees had more established visit-based and population outreach workflows to support identifying patients due for screening, FIT/FOBT distribution, reminders, and follow up. Key to practices with higher CRC screening was having medical assistants discuss and review FIT/FOBT screening and instructions with patients. Findings present important workflow processes for primary care practices and may facilitate the implementation of evidence-based interventions into real-world, clinical settings.
Effect of tumour size ratio on liver recurrence-free survival of patients undergoing hepatic resection for colorectal liver metastases
Authors: Zhai Yana , Bai Weijun , Zhou Jin , Dong Qian , Zhang Jingdong 
Published: January 2022

Abstract
Background
The study aimed to assess the impact of size differences of multiple liver metastases on liver recurrence-free survival (RFS) in patients undergoing hepatic resection for colorectal liver metastases (CRLMs).

Methods
Overall, 147 patients with CRLMs who underwent hepatic resection between January 2010 and December 2016 were retrospectively analysed. Tumour size ratio (TSR) was defined as the maximum diameter of the largest liver lesion over the maximum diameter of the smallest liver lesion. The univariate and multivariate analyses were performed to determine independent prognostic risk factors. The prognostic value of the TSR was further explored in each Tumour Burden Score (TBS) zone. Log-rank survival analyses were used to compare liver RFS in the new clinical score and the Fong clinical score.

Results
Based on the TSR, patients were classified into three groups: TSR < 2, 2 ≤ TSR < 4, and TSR ≥ 4. According to the multivariate analysis, TSR of 2–4 (hazard ratio [HR], 2.580; 95% confidence interval [CI] 1.543–4.312; P < 0.001) and TSR < 2 (HR, 4.435; 95% CI 2.499–7.872; P < 0.001) were associated with worse liver RFS. As TSR decreased, liver RFS worsened. TSR could further stratify patients in zones 1 and 2 into different risk groups according to the TBS criteria (zone 1: median liver RFS, 3.2 and 8.9 months for groups 1 and 2, respectively, P = 0.003; zone 2: median liver RFS, 3.5, 5.0, and 10.9 months for groups 1, 2, and 3, respectively, P < 0.05). The predictive ability of the new clinical score, which includes TSR, was superior to that of the Fong clinical score.

Conclusions
TSR, as a prognostic tool, could accurately assess the effect of size differences across multiple liver metastases on liver RFS in patients undergoing hepatectomy for CRLMs.

Trial registration
Retrospectively registered
Identification of TIMELESS and RORA as key clock molecules of non-small cell lung cancer and the comprehensive analysis
Authors: Xian Haocheng , Li Yuan , Zou Boliang , Chen Yajuan , Yin Houqing , Li Xuejun , Pan Yan 
Published: January 2022

Abstract
Background
The incidence rate of non-small cell lung cancer (NSCLC) has been increasing worldwide, and the correlation of circadian rhythm disruption with a raised risk of cancer and worse prognosis has been shown by accumulating evidences recently. On the other hand, drug resistance and the impact of tumor heterogeneity have been inevitable in NSCLC therapy. These both lead to an urgent need to identify more useful prognostic and predictive markers for NSCLC diagnosis and treatment, especially on the aspect of circadian clock genes.

Methods
The expression of the main clock genes in cancer was probed with TIMER and Oncomine databases. The prognostic value of key clock genes was probed systematically with the Kaplan–Meier estimate and Cox regression on samples from TCGA database. RT-qPCR was performed on patient tissue samples to further validate the results from databases. The functional enrichment analysis was performed using the “ClusterProfiler” R package, and the correlation of key clock genes with tumor mutation burden, immune checkpoint, and immune infiltration levels were also assessed using multiple algorithms including TIDE, TIMER2.0, and XCELL.

Results
TIMELESS was significantly upregulated in lung tissue of clinical lung cancer patients as well as TCGA and Oncomine databases, while RORA was downregulated. Multivariate Cox regression analysis indicated that TIMELESS (P = 0.004, HR = 1.21 [1.06, 1.38]) and RORA (P = 0.047, HR = 0.868 [0.755, 0.998]) has a significant correlation with overall survival in NSCLC. Genes related to TIMELESS were enriched in the cell cycle and immune system, and the function of RORA was mainly focused on oncogenic signaling pathways or glycosylation and protein activation. Also, TIMELESS was positively correlated with tumor mutation burden while RORA was negatively correlated with it. TIMELESS and RORA were also significantly correlated with immune checkpoint and immune infiltration levels in NSCLC. Additionally, TIMELESS showed a significant positive relationship with lipid metabolism.

Conclusions
TIMELESS and RORA were identified as key clock genes in NSCLC, and were independent prognostic factors for overall survival in NSCLC. The function of them were assessed in many aspects, indicating the strong potential of the two genes to serve as biomarkers for NSCLC progression and prognosis.
The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration
Authors: Li Jiahua , Shi Hui , Yuan Zhanyuan , Wu Zhiheng , Li Haohao , Liu Yuelong , Lu Ming , Lu Ming 
Published: January 2022

AbstractOsteosarcoma is an aggressive malignant bone sarcoma worldwide. A causal gene network with specific functions underlying both the development and progression of OS was still unclear. Here we firstly identified the differentially expressed genes (DEGs) between control and OS samples, and then defined the hub genes and top clusters in the protein–protein interaction (PPI) network of these DEGs. By focusing on the hub geneTYROBPin the top 1 cluster, a conservedTYROBPco-expression network was identified. Then the effect of the network on OS overall survival was analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Set Enrichment Analysis (GSEA) were used to explore the functions of the network. XCell platform and ssGSEA algorithm were conducted to estimate the status of immune infiltration. ChEA3 platform, GSEA enrichment analysis, and Drug Pair Seeker (DPS) were used to predict the key transcription factor and its upstream signal. We identified the downregulated SPI1-TYROBP-FCER1G network in OS, which were significantly enriched in immune-related functions. We also defined a two-gene signature (SPI1/FCER1G) that can predict poorer OS overall survival and the attenuated immune infiltration when downregulated. The SPI1-TYROBP-FCER1G network were potentially initiated by transcription factor SPI1 and would lead to the upregulated CD86, MHC-II, CCL4/CXCL10/CX3CL1 and hence increased immune infiltrations. With this study, we could better explore the mechanism of OS oncogenesis and metastasis for developing new therapies.
Evaluating factors that influenced the successful implementation of an evidence-based neonatal care intervention in Chinese hospitals using the PARIHS framework
Authors: Yue Jieya , Liu Jun , Zhao Yingxi , Williams Sarah , Zhang Bo , Zhang Lin , Zhang Qiannan , Liu Xin , Wall Stephen , Zhao Gengli 
Published: January 2022

Abstract
Background
Evidence based interventions (EBIs) can improve patient care and outcomes. Understanding the process for successfully introducing and implementing EBIs can inform effective roll-out and scale up. The Promoting Action on Research Implementation in Health Services (PARIHS) framework can be used to evaluate and guide the introduction and implementation of EBIs. In this study, we used kangaroo mother care (KMC) as an example of an evidence-based neonatal intervention recently introduced in selected Chinese hospitals, to identify the factors that influenced its successful implementation. We also explored the utility of the PARIHS framework in China and investigated how important each of its constructs (evidence, context and facilitation) and sub-elements were perceived to be to successful implementation of EBIs in a Chinese setting.

Method
We conducted clinical observations and semi-structured interviews with 10 physicians and 18 nurses in five tertiary hospitals implementing KMC. Interview questions were organized around issues including knowledge and beliefs, resources, culture, implementation readiness and climate. We used directed content analysis to analyze the interview transcript, amending the PARIHS framework to incorporate emerging sub-themes. We also rated the constructs and sub-elements on a continuum from “low (weak)”, “moderate” or “high (strong)” highlighting the ones considered most influential for hospital level implementation by study participants.

Results
Using KMC as an example, our finding suggest that clinical experience, culture, leadership, evaluation, and facilitation are highly influential elements for EBI implementation in China. External evidence had a moderate impact, especially in the initial awareness raising stages of implementation and resources were also considered to be of moderate importance, although this may change as implementation progresses. Patient experience was not seen as a driver for implementation at hospital level.

Conclusion
Based on our findings examining KMC implementation as a case example, the PARIHS framework can be a useful tool for planning and evaluating EBI implementation in China. However, it’s sub-elements should be assessed and adapted to the implementation setting.
Adapting an evidence-based contraceptive behavioural intervention delivered by mobile phone for young people in Zimbabwe
Authors: McCarthy Ona L , Mavodza Constancia , Chikwari Chido Dziva , Dauya Ethel , Tembo Mandikudza , Hlabangana Portia , Dembetembe Regedzai , Mpakami Nyasha , Bandason Tsitsi , Free Caroline , Smith Chris , Ferrand Rashida A 
Published: January 2022

Abstract
Background
Despite the availability of a range of contraceptive methods, young people around the world still face barriers in accessing and using them. The use of digital technology for the delivery of health interventions has expanded rapidly. Intervention delivery by mobile phone can be a useful way to address young people’s needs with regard to sexual and reproductive health, because the information can be digested at a time of the recipients’ choosing. This study reports the adaptation of an evidence-based contraceptive behavioural intervention for young people in Zimbabwe.

Methods
Focus group discussions and in depth interviews were used to evaluate the ‘fit’ of the existing intervention among young people in Harare, Zimbabwe. This involved determining how aligned the content of the existing intervention was to the knowledge and beliefs of young Zimbabweans plus identifying the most appropriate intervention deliver mode. The verbatim transcripts were analysed using a thematic analysis. The existing intervention was then adapted, tested and refined in subsequent focus group discussions and interviews with young people in Harare and Bulawayo.

Results
Eleven key themes resulted from the discussions evaluating the fit of the intervention. While there were many similarities to the original study population, key differences were that young people in Zimbabwe had lower levels of personal and smart mobile phone ownership and lower literacy levels. Young people were enthusiastic about receiving information about side effects/side benefits of the methods. The iterative testing and refinement resulted in adapted intervention consisting of 97 messages for female recipients (94 for male), delivered over three months and offered in English, Shona and Ndebele.

Conclusions
Young people in Zimbabwe provided essential information for adapting the existing intervention. There was great support for the adapted intervention among the young people who took part in this study. The adapted intervention is now being implemented within an integrated community-based sexual and reproductive health service in Zimbabwe.
A novel prognostic model based on single-cell RNA sequencing data for hepatocellular carcinoma
Authors: Lu Juan , Chen Yanfei , Zhang Xiaoqian , Guo Jing , Xu Kaijin , Li Lanjuan 
Published: January 2022

Abstract
Background
The tumour heterogeneous make-up of immune cell infiltrates is a key factor for the therapy response and prognosis of hepatocellular carcinoma (HCC). However, it is still a major challenge to comprehensively understand the tumour immune microenvironment (TIME) at the genetic and cellular levels.

Methods
HCC single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database, and gene expression data were retrieved from The Cancer Genome Atlas (TCGA) database and International Cancer Genome Consortium (ICGC) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was performed to evaluate the abundance of immune infiltrating cells. We employed weighted gene coexpression network analysis (WGCNA) to construct a gene coexpression network. Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were further used to construct a risk model. Moreover, the expression levels of model genes were assessed by qPCR.

Results
We defined 25 cell clusters based on the scRNA-seq dataset (GSE149614), and the clusters were labelled as various cell types by marker genes. Then, we constructed a weighted coexpression network and identified a total of 6 modules, among which the brown module was most highly correlated with tumours. Moreover, we found that the brown module was most closely related to monocytes (cluster 21). Through univariate Cox and LASSO analyses, we constructed a 3-gene risk model (RiskScore = 0.257*Expression CSTB + 0.263* Expression TALDO1 + 0.313* Expression CLTA). This risk model showed excellent predictive efficacy for prognosis in the TCGA-LIHC and ICGC cohorts. Additionally, patients with high risk scores were found to be less likely to benefit from immunotherapy.

Conclusions
We developed a 3-gene signature (including CLTA, TALDO1 and CSTB) based on the heterogeneity of the TIME to predict the survival outcome and immunotherapy response.
Good performance of the criteria of American College of Medical Genetics and Genomics/Association for Molecular Pathology in prediction of pathogenicity of genetic variants causing thoracic aortic aneurysms and dissections
Authors: Ponińska Joanna Kinga , Bilińska Zofia Teresa , Truszkowska Grażyna , Michalak Ewa , Podgórska Anna , Stępień-Wojno Małgorzata , Chmielewski Przemysław , Lutyńska Anna , Płoski Rafał 
Published: January 2022

Abstract
Background
The identification of pathogenic variant in patients with thoracic aortic aneurysms and dissections (TAAD) was previously found to be a significant indicator pointing to earlier need for surgical intervention. In order to evaluate available methods for classifying identified genetic variants we have compared the event-free survival in a cohort of TAAD patients classified as genotype-positive versus genotype-negative by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) criteria or by ClinVar database.

Methods
We analyzed previously unreported cohort of 132 patients tested in the routine clinical setting for genetic variants in a custom panel of 30 genes associated with TAAD or the TruSight Cardio commercial panel of 174 genes associated with cardiac disease. The identified variants were classified using VarSome platform. Kaplan–Meier survival curves were constructed to compare the event-free survival between probands defined as ‘genotype-positive’ and ‘genotype-negative’ using different classifications in order to compare their performance.

Results
Out of 107 rare variants found, 12 were classified as pathogenic/likely pathogenic by ClinVar, 38 were predicted to be pathogenic/likely pathogenic by ACMG. Variant pathogenicity as assessed by ACMG criteria was a strong predictor of event free survival (event free survival at 50 years 83% vs. 50%, for genotype positive patients vs. reference, respectively, p  = 0.00096). The performance of ACMG criteria was similar to that of ClinVar (event free survival at 50 years 87% vs. 50%, for genotype positive patients vs. reference, respectively p  = 0.023) but independent from it as shown by analysing variants with no ClinVar record (event free survival at 50 years 80% vs. 50%, p  = 0.0039). Variants classified as VUS by ACMG criteria or ClinVar did not affect event-free survival. TAAD specific custom gene panel performed similar to the larger universal cardiac panel.

Conclusions
In our cohort of unrelated TAAD patients ACMG classification tool available at VarSome was useful in assessing pathogenicity of novel genetic variants. Gene panel containing the established genes associated with the highest risk of hereditary TAAD (ACTA1, COL3A1, FBN1, MYH11, SMAD3, TGFB2, TGFBR1, TGFBR2, MYLK) was sufficient to identify prevailing majority of variants most likely to be causative of the disease.