bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the care providers version of the Rainbow Model of Integrated Care-measurement tool in Chinese primary care systems
Authors: Huang Yixiang , Zhu Paiyi , Chen Lijin , Wang Xin , Valentijn Pim 
Published: August 2020

Abstract
Background
The original Rainbow Model of Integrated Care Measurement Tool (RMIC-MT) is based on the Rainbow Model of Integrated Care (RMIC), which provides a comprehensive theoretical framework for integrated care. To translate and adapt the original care provider version of the RMIC-MT and evaluate its psychometric properties by a pilot study in Chinese primary care systems.

Methods
The translation and adaptation process were performed in four steps, forward and back-translation, experts review and pre-testing. We conducted a cross-sectional study with 1610 community care professionals in all 79 community health stations in the Nanshan district. We analyzed the distribution of responses to each item to study the psychometric sensitivity. Exploratory factor analysis with principal axis extraction method and promax rotation was used to assess the construct validity. Cronbach’s alpha was utilized to ascertain the internal consistency reliability. Lastly, confirmation factor analysis was used to evaluate the exploratory factor analysis model fit.

Results
During the translation and adaptation process, all 48 items were retained with some detailed modifications. No item was found to have psychometric sensitivity problems. Six factors (person- & community-centeredness, care integration, professional integration, organizational integration, cultural competence and technical competence) with 45 items were determined by exploratory factor analysis, accounting for 61.46% of the total variance. A standard Cronbach’s alpha of 0.940 and significant correlation among all items in the scale (> 0.4) showed good internal consistency reliability of the tool. And, the model passed the majority of goodness-to-fit test by confirmation factor analysis.

Conclusions
The results showed initial satisfactory psychometric properties for the validation of the Chinese RMIC-MT provider version. Its application in China will promote the development of people-centered integrated primary care. However, further psychometric testing is needed in multiple primary care settings with both public and private community institutes.
Experiences from implementation of internet-delivered cognitive behaviour therapy for insomnia in psychiatric health care: a qualitative study applying the NASSS framework
Authors: Kadesjö Banck Josefin , Bernhardsson Susanne 
Published: August 2020

Abstract
Background
Insomnia is a common diagnosis among patients in psychiatric health care and effective treatments are highly demanded. Previous research suggests that internet-delivered cognitive behavioural therapy for insomnia (ICBT-i) is helpful for a variety of patients and may be effective for psychiatric health care patients. Little is known about implementation of ICBT-i in psychiatric health care. The aim of this study was to explore experiences among therapists and managers who participated in a pilot implementation of ICBT-i in outpatient psychiatric health care, and to identify determinants for the implementation.

Methods
Semi-structured interviews were conducted with 7 therapists and 5 managers working in outpatient psychiatric health care and directly involved with the pilot implementation. Data were analysed using qualitative content analysis guided by the NASSS framework, combining inductive and deductive approaches.

Results
The analysis revealed 32 facilitators, 21 barriers, and 2 determinants that were both a barrier and a facilitator, organised in 1–5 themes under each of the 7 NASSS domains. Key facilitators included: meeting a demand for treatment options with the ICBT-i programme, the experienced benefits of ICBT-i as a treatment option for insomnia, training and support, engagement and support from managers and the wider system, and a long-term organisation for maintenance of the technology. Key barriers included: low interest in ICBT-i among therapists, difficulty in recruiting patients, perceived low ability in therapists to deliver treatment online, technical problems, and therapists’ competing demands leading to low priority of ICBT-i. Complexity analysis assessed two NASSS domains as simple, four as complicated, and one as complex.

Conclusions
The study contributes new knowledge and insights into the implementation process of ICBT-i in psychiatric health care. Our findings highlight the importance of providing training, support, and guidance in online treatment for therapists when implementing a technological innovation. Technical problems should be minimised and the maintenance and demand-side value for the technology must be clear. Support from managers at all levels is crucial, particularly support to therapists in everyday prioritisation among competing demands. Besides taking the identified determinants into account, managing complexity is important for successful scale-up implementation.
Timely estimation of National Admission, readmission, and observation-stay rates in medicare patients with acute myocardial infarction, heart failure, or pneumonia using near real-time claims data
Authors: Li Shu-Xia , Wang Yongfei , Lama Sonam D. , Schwartz Jennifer , Herrin Jeph , Mei Hao , Lin Zhenqiu , Bernheim Susannah M. , Spivack Steven , Krumholz Harlan M. , Suter Lisa G. 
Published: August 2020

Abstract
Background
To estimate, prior to finalization of claims, the national monthly numbers of admissions and rates of 30-day readmissions and post-discharge observation-stays for Medicare fee-for-service beneficiaries hospitalized with acute myocardial infarction (AMI), heart failure (HF), or pneumonia.

Methods
The centers for Medicare & Medicaid Services (CMS) Integrated Data Repository, including the Medicare beneficiary enrollment database, was accessed in June 2015, February 2017, and February 2018. We evaluated patterns of delay in Medicare claims accrual, and used incomplete, non-final claims data to develop and validate models for real-time estimation of admissions, readmissions, and observation stays.

Results
These real-time reporting models accurately estimate, within 2 months from admission, the monthly numbers of admissions, 30-day readmission and observation-stay rates for patients with AMI, HF, or pneumonia.

Conclusions
This work will allow CMS to track the impact of policy decisions in real time and enable hospitals to better monitor their performance nationally.
Circ_0007841 promotes the progression of multiple myeloma through targeting miR-338-3p/BRD4 signaling cascade
Authors: Wang Yan , Lin Quande , Song Chunge , Ma Ruojin , Li Xiaojie 
Published: August 2020

Abstract
Background
The pathogenesis of multiple myeloma (MM) is not completely known. Uncovering the potential mechanism of MM initiation and progression is essential for identifying novel diagnostic and therapeutic targets. Herein, we explored the function and the working mechanism of circular RNA circ_0007841 in MM progression.

Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of circ_0007841, microRNA-338-3p (miR-338-3p) and bromodomain containing 4 (BRD4). Cell proliferation ability was analyzed through cell counting kit-8 (CCK8) assay, colony formation assay and flow cytometry. Transwell assays were conducted to measure the migration and invasion abilities of MM cells. Cell apoptosis was also assessed by flow cytometry. The interaction between miR-338-3p and circ_0007841 or BRD4 was confirmed by dual-luciferase reporter assay and RNA-pull down assay.

Results
Circ_0007841 was highly expressed in bone marrow (BM)-derived plasma cells of MM patients and MM cell lines than that in healthy volunteers and normal plasma cell line nPCs. Circ_0007841 promoted the proliferation, cell cycle and metastasis and impeded the apoptosis of MM cells. miR-338-3p was a direct target of circ_0007841 in MM cells and circ_0007841 accelerated the progression of MM through targeting miR-338-3p. BRD4 could directly bind to miR-338-3p in MM cells and miR-338-3p exerted an anti-tumor role through targeting BRD4. Circ_0007841 promoted the activation of PI3K/AKT signaling via miR-338-3p/BRD4 axis. Exosomes generated from mesenchymal stromal cells (MSCs) elevated the malignant behaviors of MM cells via circ_0007841.

Conclusion
Circ_0007841 acted as an oncogene to promote the proliferation, cell cycle and motility and restrain the apoptosis of MM cells through sequestering miR-338-3p to up-regulate the expression of BRD4.
Prognostic value of a five-lncRNA signature in esophageal squamous cell carcinoma
Authors: zhang Lan , Li Pan , Liu Enjie , Xing Chenju , Zhu Di , Zhang Jianying , Wang Weiwei , Jiang Guozhong 
Published: August 2020

Abstract
Background
The aim of this study was to identify prognostic long non-coding RNAs (lncRNAs) and develop a multi-lncRNA signature for suvival prediction in esophageal squamous cell carcinoma (ESCC).

Methods
The clinical and gene expression data from Gene Expression Omnibus database (GSE53624, n = 119) were obtianed as training set. A total of 98 paired ESCC tumor and normal tissues were detected by RNA sequencing and used as test set. Another 84 ESCC tissues were used for real-time quantitative PCR(qRT-PCR) and as an independent validation cohort. Survival analysis, Cox regression and Kaplan–Meier analysis were performed.

Results
We screened a prognostic marker of ESCC from the GSE53624 dataset and named it as the five-lncRNA signature including AC007179.1, MORF4L2-AS1, RP11-488I20.9, RP13-30A9.2, RP4-735C1.6, which could classify patients into high- and low-risk groups with significantly different survival(median survival: 1.75 years vs. 4.01 years, log rank P < 0.05). Then test dataset and validation dataset confirmed that the five-lncRNA signature can determine the prognosis of ESCC patients. Predictive independence of the prognostic marker was proved by multivariable Cox regression analyses in the three datasets (P < 0.05). In addition, the signature was found to be better than TNM stage in terms of prognosis.

Conclusion
The five-lncRNA signature could be a good prognostic biomarker for ESCC patients and has important clinical value.
Self-powered portable melt electrospinning for in situ wound dressing
Authors: Zhao Ying-Tao , Zhang Jun , Gao Yuan , Liu Xiao-Fei , Liu Jiang-Jun , Wang Xiao-Xiong , Xiang Hong-Fei , Long Yun-Ze 
Published: August 2020

AbstractBackgroundElectrospun (e-spun) nanofibers for wound dressing have attracted wide attention due to its large specific surface area, large porosity and breathability. Compared with solution electrospinning (e-spinning), melt e-spinning is more bio-friendly without toxic solvent participation, which provides the possibility of in situ e-spinning on wounds directly. However, previously reported melt e-spinning devices were usually bulky and cumbersome due to their necessary heating unit, and different components were separated to avoid electrostatic interference.ResultsIn this article, we report on a self-powered hand-held melt e-spinning gun which can work without any external power supply (outdoors). The problem of electrostatic interference for this integrated device was solved by using a special high heat transfer insulation unit. The apparatus is easy and safe to operate by a single hand due to its small volume (24 × 6 × 13 cm3) and light weight (about 450 g). Some biodegradable polymers, for example, polycaprolactone (PCL) fibers were successful e-spun onto wounds directly by using this dressing gun.ConclusionsPCL fibrous membrane has good biocompatibility and can be in situ electrospun to wound surface as a wound dressing by the portable melt e-spinning gun. Besides wound dressing, this hand-held melt e-spinning gun may be used in 3D printing and experimental teaching demonstration aids.
Microglial burden, activation and dystrophy patterns in frontotemporal lobar degeneration
Authors: Woollacott Ione O. C. , Toomey Christina E. , Strand Catherine , Courtney Robert , Benson Bridget C. , Rohrer Jonathan D. , Lashley Tammaryn 
Published: August 2020

Abstract
Background
Microglial dysfunction is implicated in frontotemporal lobar degeneration (FTLD). Although studies have reported excessive microglial activation or senescence (dystrophy) in Alzheimer’s disease (AD), few have explored this in FTLD. We examined regional patterns of microglial burden, activation and dystrophy in sporadic and genetic FTLD, sporadic AD and controls.

Methods
Immunohistochemistry was performed in frontal and temporal grey and white matter from 50 pathologically confirmed FTLD cases (31 sporadic, 19 genetic: 20 FTLD-tau, 26 FTLD-TDP, four FTLD-FUS), five AD cases and five controls, using markers to detect phagocytic (CD68-positive) and antigen-presenting (CR3/43-positive) microglia, and microglia in general (Iba1-positive). Microglial burden and activation (morphology) were assessed quantitatively for each microglial phenotype. Iba1-positive microglia were assessed semi-quantitatively for dystrophy severity and qualitatively for rod-shaped and hypertrophic morphology. Microglia were compared in each region between FTLD, AD and controls, and between different pathological subtypes of FTLD, including its main subtypes (FTLD-tau, FTLD-TDP, FTLD-FUS), and subtypes of FTLD-tau, FTLD-TDP and genetic FTLD. Microglia were also compared between grey and white matter within each lobe for each group.

Results
There was a higher burden of phagocytic and antigen-presenting microglia in FTLD and AD cases than controls, but activation was often not increased. Burden was generally higher in white matter than grey matter, but activation was greater in grey matter. However, microglia varied regionally according to FTLD subtype and disease mechanism. Dystrophy was more severe in FTLD and AD than controls, and more severe in white than grey matter, but this also varied regionally and was particularly extensive in FTLD due to progranulin (GRN) mutations. Presence of rod-shaped and hypertrophic microglia also varied by FTLD subtype.

Conclusions
This study demonstrates regionally variable microglial involvement in FTLD and links this to underlying disease mechanisms. This supports investigation of microglial dysfunction in disease models and consideration of anti-senescence therapies in clinical trials.
Comparison between repeat anterior and posterior decompression and fusion in the treatment of two-level symptomatic adjacent segment disease after anterior cervical arthrodesis
Authors: Cao Junming , Qi Can , Yang Yipeng , Lei Tao , Wang Linfeng , Shen Yong 
Published: August 2020

Abstract
Background
Two-level symptomatic adjacent segment disease (ASD) is rarely reported, but remains a challenge after anterior cervical arthrodesis. The purpose of this study was to compare the clinical and radiological outcomes of repeat anterior and posterior decompression and fusion procedures for two-level symptomatic ASD.

Methods
Thirty-two patients with two-level symptomatic ASD were retrospectively reviewed and underwent repeat anterior cervical discectomy and fusion (ACDF) or posterior decompression and fusion (PDF). Clinical outcomes (JOA, NDI, and VAS scores), perioperative parameters (blood loss, operation time, and length of hospital stay), radiological parameters (cervical lordosis and ROM), and complications were compared.

Results
Eighteen patients underwent ACDF, and 14 patients underwent PDF. Patients who underwent PDF were older, more frequently presented with myelopathic deficits, and were fused at more levels. Patients who underwent ACDF experienced significantly shorter surgery time (p < 0.001), lower blood loss (p < 0.001), and reduced hospital stay (p = 0.002). Both groups exhibited significant increases in JOA scores and decreases in NDI and both neck pain and arm pain VAS scores (p < 0.05), but patients who underwent PDF had significantly higher NDI scores (p = 0.012), neck pain VAS scores (p = 0.019), loss of cervical lordosis (p < 0.001), and loss of ROM (p = 0.001). Three patients developed dysphagia in the ACDF group, and two patients had C5 root palsy and one had hematoma in the PDF group. Recurrent ASD after the second operation occurred in two patients in the ACDF group but no patients in the PDF group.

Conclusions
For patients with two-level symptomatic ASD, both anterior and posterior decompression and fusion were effective for improving the neurological function. For patients with radicular symptoms, ACDF had less surgical trauma, better restoration of lordosis, and less postoperative neck pain, but higher chance of recurrent ASD. PDF was an effective surgical option for older patients with myelopathy developing in adjacent segments.
Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application
Authors: Sun Yu-Meng , Chen Yue-Qin 
Published: August 2020

AbstractNoncoding RNAs (ncRNAs) are a large segment of the transcriptome that do not have apparent protein-coding roles, but they have been verified to play important roles in diverse biological processes, including disease pathogenesis. With the development of innovative technologies, an increasing number of novel ncRNAs have been uncovered; information about their prominent tissue-specific expression patterns, various interaction networks, and subcellular locations will undoubtedly enhance our understanding of their potential functions. Here, we summarized the principles and innovative methods for identifications of novel ncRNAs that have potential functional roles in cancer biology. Moreover, this review also provides alternative ncRNA databases based on high-throughput sequencing or experimental validation, and it briefly describes the current strategy for the clinical translation of cancer-associated ncRNAs to be used in diagnosis.
Therapeutic role of recurrent ESR1-CCDC170 gene fusions in breast cancer endocrine resistance
Authors: Li Li , Lin Ling , Veeraraghavan Jamunarani , Hu Yiheng , Wang Xian , Lee Sanghoon , Tan Ying , Schiff Rachel , Wang Xiao-Song 
Published: August 2020

Abstract
Background
Endocrine therapy is the most common treatment for estrogen receptor (ER)-positive breast cancer, but its effectiveness is limited by high rates of primary and acquired resistance. There are likely many genetic causes, and recent studies suggest the important role of ESR1 mutations and fusions in endocrine resistance. Previously, we reported a recurrent ESR1 fusion called ESR1-CCDC170 in 6–8% of the luminal B breast cancers that has a worse clinical outcome after endocrine therapy. Despite being the most frequent ESR1 fusion, its functional role in endocrine resistance has not been studied in vivo, and the engaged mechanism and therapeutic relevance remain uncharacterized.

Methods
The endocrine sensitivities of HCC1428 or T47D breast cancer cells following genetic perturbations of ESR1-CCDC170 were assessed using clonogenic assays and/or xenograft mouse models. The underlying mechanisms were investigated by reverse phase protein array, western blotting, immunoprecipitation, and bimolecular fluorescence complementation assays. The sensitivity of ESR1-CCDC170 expressing breast cancer cells to concomitant treatments of tamoxifen and HER/SRC inhibitors was assessed by clonogenic assays.

Results
Our results suggested that different ESR1-CCDC170 fusions endow different levels of reduced endocrine sensitivity in vivo, resulting in significant survival disadvantages. Further investigation revealed a novel mechanism that ESR1-CCDC170 binds to HER2/HER3/SRC and activates SRC/PI3K/AKT signaling. Silencing of ESR1-CCDC170 in the fusion-positive cell line, HCC1428, downregulates HER2/HER3, represses pSRC/pAKT, and improves endocrine sensitivity. More important, breast cancer cells expressing ectopic or endogenous ESR1-CCDC170 are highly sensitive to treatment regimens combining endocrine agents with the HER2 inhibitor lapatinib and/or the SRC inhibitor dasatinib.

Conclusion
ESR1-CCDC170 may endow breast cancer cell survival under endocrine therapy via maintaining/activating HER2/HER3/SRC/AKT signaling which implies a potential therapeutic strategy for managing these fusion positive tumors.
An evolutionary driver of interspersed segmental duplications in primates
Authors: Cantsilieris Stuart , Sunkin Susan M. , Johnson Matthew E. , Anaclerio Fabio , Huddleston John , Baker Carl , Dougherty Max L. , Underwood Jason G. , Sulovari Arvis , Hsieh PingHsun , Mao Yafei , Catacchio Claudia Rita , Malig Maika , Welch AnneMarie E. , Sorensen Melanie , Munson Katherine M. , Jiang Weihong , Girirajan Santhosh , Ventura Mario , Lamb Bruce T. , Conlon Ronald A. , Eichler Evan E. 
Published: August 2020

Abstract
Background
The complex interspersed pattern of segmental duplications in humans is responsible for rearrangements associated with neurodevelopmental disease, including the emergence of novel genes important in human brain evolution. We investigate the evolution of LCR16a, a putative driver of this phenomenon that encodes one of the most rapidly evolving human–ape gene families, nuclear pore interacting protein (NPIP).

Results
Comparative analysis shows that LCR16a has independently expanded in five primate lineages over the last 35 million years of primate evolution. The expansions are associated with independent lineage-specific segmental duplications flanking LCR16a leading to the emergence of large interspersed duplication blocks at non-orthologous chromosomal locations in each primate lineage. The intron-exon structure of the NPIP gene family has changed dramatically throughout primate evolution with different branches showing characteristic gene models yet maintaining an open reading frame. In the African ape lineage, we detect signatures of positive selection that occurred after a transition to more ubiquitous expression among great ape tissues when compared to Old World and New World monkeys. Mouse transgenic experiments from baboon and human genomic loci confirm these expression differences and suggest that the broader ape expression pattern arose due to mutational changes that emerged in cis.

Conclusions
LCR16a promotes serial interspersed duplications and creates hotspots of genomic instability that appear to be an ancient property of primate genomes. Dramatic changes to NPIP gene structure and altered tissue expression preceded major bouts of positive selection in the African ape lineage, suggestive of a gene undergoing strong adaptive evolution.