bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation analysis of 419 family and prenatal diagnosis of 339 cases of spinal muscular atrophy in China
Authors: Sun Yingjie , Kong Xiangdong , Zhao Zhenhua , Zhao Xuechao 
Published: June 2020

Abstract
Background
Spinal muscular atrophy (SMA) is a common and lethal autosomal recessive neurodegenerative disease caused by mutations in the survival motor neuron 1 (SMN1) gene. At present, gene therapy medicine for SMA, i.e., Spinraza (Nusinersen), has been approved by the FDA, bringing hope to SMA patients and families. Accurate diagnosis is essential for treatment. Our goal was to detect genetic mutations in SMA patients in China and to show the results of the prenatal diagnosis of SMA.

Methods
In this study, we examined 419 patients in our hospital from January 2010 to September 2019. Multiplex ligation-dependent probe amplification analysis was used to determine the copy numbers of SMN1 and SMN2. Long-range PCR combined with nested PCR was used to detect point mutations in SMN1. In addition to the above detection methods, we also used QF-PCR in prenatal diagnosis to reduce the impact of maternal contamination. We conducted a total of 339 prenatal diagnoses from January 2010 to September 2019.

Results
Homozygous deletion of SMN1 exon 7 was detected in 96.40% (404/419) of patients. Homozygous deletion of SMN1 exon 7 alone was detected in 15 patients (3.60%). In total, 10 point mutations were detected in the 15 pedigrees. Most patients with SMA Type I have 1 ~ 2 copies of the SMN2 gene. Patients with SMA Type II have 2 or 3 copies of the SMN2 gene. The results of prenatal diagnoses showed that 118 fetuses were normal, 149 fetuses were carriers of heterozygous variants, and the remaining 72 fetuses harbored compound heterozygous variants or homozygous variants.

Conclusions
Our study found that the most common mutation in SMA was homozygous deletion of SMN1 exon 7 in our study. We suggest that detecting only the deletion of exon 7 of SMN1 can meet most of the screening needs. We also believe that SMN2 copy numbers can help infer the disease classification and provide some reference for future treatment options.
Suppression of Mig-6 overcomes the acquired EGFR-TKI resistance of lung adenocarcinoma
Authors: Kang Da Hyun , Jung Sung Soo , Yeo Min-Kyung , Lee Da Hye , Yoo Geon , Cho Sang Yeon , Oh In-Jae , Kim Ju-Ock , Park Hee Sun , Chung Chaeuk , Lee Jeong Eun 
Published: June 2020

Abstract
Background
The resistance of lung cancer to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the unconquered frontiers in chemotherapy. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR). Similarly, numerous studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical investigations revealed that lung cancer patients with elevated expression of Mig-6 are associated with a poor prognosis. More recent work showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function as a protagonist or an antagonist of EGFR-TKI resistant lung cancer.

Methods
We compared the expression and phosphorylation status of Mig-6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We investigated the function of Mig-6 by either depletion or overexpression of Mig-6 in those cells and evaluated the efficacy of combining of Mig-6 knock-down and EGFR-TKI treatment in PC9/GR. The correlation between Mig-6 expressions and the prognoses of lung adenocarcinoma was examined by The Cancer Genome Atlas (TCGA) data and clinical samples.

Results
Our results indicated that the expression of Mig-6 was significantly increased in PC9/GR cells compared to that of PC9 cells. The significant portion of Mig-6 existed as a phosphorylated form in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance of PC9/GR cells. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions positively correlate with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma.

Conclusion
Our findings reinforce scientific notion of Mig-6 as an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.
Immune landscape of human prostate cancer: immune evasion mechanisms and biomarkers for personalized immunotherapy
Authors: Bou-Dargham Mayassa J. , Sha Linlin , Sang Qing-Xiang Amy , Zhang Jinfeng 
Published: June 2020

AbstractBackgroundDespite recent advances in cancer immunotherapy, the efficacy of these therapies for the treatment of human prostate cancer patients is low due to the complex immune evasion mechanisms (IEMs) of prostate cancer and the lack of predictive biomarkers for patient responses.MethodsTo understand the IEMs in prostate cancer and apply such understanding to the design of personalized immunotherapies, we analyzed the RNA-seq data for prostate adenocarcinoma from The Cancer Genome Atlas (TCGA) using a combination of biclustering, differential expression analysis, immune cell typing, and machine learning methods.ResultsThe integrative analysis identified eight clusters with different IEM combinations and predictive biomarkers for each immune evasion cluster. Prostate tumors employ different combinations of IEMs. The majority of prostate cancer patients were identified with immunological ignorance (89.8%), upregulated cytotoxic T lymphocyte-associated protein 4 (CTLA4) (58.8%), and upregulated decoy receptor 3 (DcR3) (51.6%). Among patients with immunologic ignorance, 41.4% displayed upregulated DcR3 expression, 43.26% had upregulated CTLA4, and 11.4% had a combination of all three mechanisms. Since upregulated programmed cell death 1 (PD-1) and/or CTLA4 often co-occur with other IEMs, these results provide a plausible explanation for the failure of immune checkpoint inhibitor monotherapy for prostate cancer.ConclusionThese findings indicate that human prostate cancer specimens are mostly immunologically cold tumors that do not respond well to mono-immunotherapy. With such identified biomarkers, more precise treatment strategies can be developed to improve therapeutic efficacy through a greater understanding of a patient’s immune evasion mechanisms.
Correlation of binocular refractive error and calculation of intraocular Lens power for the second eye
Authors: Zhang Pengcheng , Yang Yuhuan , Yan Hong , Zhang Jie , Yan Weijia 
Published: June 2020

Abstract
Background
Reducing refractive error has always been a tricky problem. The aim of this study was to verify the correlation between binocular refractive error (RE) after sequential cataract surgery and explore an individualized calculation method of intraocular lens (IOL) for the second eye.

Methods
This was a prospective study. One hundred eighty-eight affected eyes in 94 age-related cataract patients who underwent sequential cataract surgery in the Department of Ophthalmology, Tangdu Hospital, China, were recruited. Complete case data were included for a correlation analysis of binocular RE. Data obtained in patients with RE values greater than 0.50 diopters (D) in the first eye were extracted and the patients divided randomly into two groups: Group A and B. In the adjustment group, group A, we modified the IOL power for the second eyes as 50% of the RE of the first eye. In group B, the control group, there was no modification. The mean absolute refractive error (MARE) values of the second eyes were evaluated one month after surgery.

Results
The correlation coefficient of the binocular RE after sequential cataract surgery was 0.760 (P < 0.001). After the IOL power of the second eyes was adjusted, the MARE of the second eyes was 0.57 ± 0.41 D, while the MARE of the first eyes was 1.18 ± 0.85 D, and the difference was statistically significant (P < 0.001).

Conclusions
Binocular REs were positively correlated after sequential cataract surgery. The RE of the second eye can be reduced by adjusting the IOL power based on 50% of the postoperative RE of the first eye.
General practice patients starting treatment for substance use problems: observations from two data sources across levels of care
Authors: Boffin Nicole , Antoine Jerome , Van Baelen Luk , Moreels Sarah , Doggen Kris 
Published: June 2020

Abstract
Background
In Belgium, the incidence of treatment episodes for substance use problems is monitored by the Network of Sentinel General Practices (SGP), and at higher, specialist care levels by the Treatment Demand Indicator (TDI) surveillance. Using both data sources, we examine 1) how patients starting specialist treatment for substance use problems on referral by their GP compare to those that were referred by non-GP caregivers; 2) how patients starting GP treatment for substance use problems without receiving concurrent specialist treatment compare to those who did.

Methods
Both surveillances are based on the TDI protocol for reporting data to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) on individuals starting treatment as a result of their substance use. Data from 2016 and 2017 were examined using 95% confidence intervals and multivariate logistic regression.

Results
According to TDI-data (n = 16,543), determinants of being referred by a GP (versus by a non-GP caregiver) for specialist treatment were age ≥ median (OR 1.25; 95% CI 1.13–1.38), education ≥ secondary level (OR 1.27; 95% CI 1.15–1.41), recent employment (OR 1.71; 1.56–1.88), recent stable accommodation (3.62; 95% CI 3.08–4.26), first treatment episode (OR 1.72; 95% CI 1.57–1.87), recent daily primary substance use (OR 1.46; 95% CI 1.33–1.59) and mono substance use (OR 1.23; 95% CI 1.04–1.48). Type of substance use was a significant determinant with higher odds of using pharmaceuticals (and alcohol) (OR 1.24; 95% CI 1.04–1.48), and lower odds of using cannabis only/primarily (OR 0.73; 95% CI 0.62–0.86), with reference to street drugs minus cannabis only/primarily. According to SGP data (n = 314), determinants of starting GP treatment without concurrent specialist treatment were recent employment (OR 2.58; 95% CI 1.36–4.91), first treatment episode (OR 2.78; 95% CI 1.39–5.55) and living in the Brussels or Walloon region (OR 1.97; 95% CI 1.06–3.66).

Conclusions
This study provides a useful insight into the general practice population treated for substance use problems. It shows that both surveillances consistently found a relatively favourable profile of general practice patients with substance use problems.
Data driven decision making to characterize clinical personas of parents of children with cystic fibrosis: a mixed methods study
Authors: Szczesniak Rhonda D. , Pestian Teresa , Duan Leo L. , Li Dan , Stamper Sophia , Ferrara Brycen , Kramer Elizabeth , Clancy John P. , Grossoehme Daniel 
Published: June 2020

AbstractBackgroundBeginning at a young age, children with cystic fibrosis (CF) embark on demanding care regimens that pose challenges to parents. We examined the extent to which clinical, demographic and psychosocial features inform patterns of adherence to pulmonary therapies and how these patterns can be used to develop clinical personas, defined as aspects of adherence barriers that are presented by parents and/or perceived by clinicians, in order to enhance personalized CF care delivery.MethodsWe undertook an explanatory sequential mixed-methods study consisting of i) multivariate clustering to create clusters corresponding to parental adherence patterns (quantitative phase); ii) parental participant interviews to create clinical personas interpreted from clustering (qualitative phase). Clinical, demographic and psychosocial features were used in supervised clustering against clinical endpoints, which included adherence to airway clearance and aerosolized medications and self-efficacy score, which was used as a feature for modeling adherence. Clinical implications were developed for each persona by combing quantitative and qualitative data (integration phase).ResultsThe quantitative phase showed that the 87 parent participants were segmented into three distinct patterns of adherence based on use of aerosolized medication and practice of airway clearance. Patterns were primarily influenced by self-efficacy, distance to CF care center and child BMI percentile. The two key patterns that emerged for the self-efficacy model were most heavily influenced by distance to CF care center and child BMI percentile. Eight clinical personas were developed in the qualitative phase from parent and clinician participant feedback of latent components from these models. Findings from the integration phase include recommendations to overcome specific challenges with maintaining treatment regimens and increasing support from social networks.ConclusionsAdherence patterns from multivariate models and resulting parent personas with their corresponding clinical implications have utility as clinical decision support tools and capabilities for tailoring intervention study designs that promote adherence.
Characteristics and health related quality of life in a population with advanced chronic obstructive pulmonary disease, a cross-sectional study
Authors: Bove D. G. , Lavesen M. , Lindegaard B. 
Published: June 2020

AbstractBackgroundIt is important to understand the total burden of COPD and thereby be able to identify patients who need more intensive palliative care to avoid deteriorated quality of life. The aim of this study was to describe the psychosocial and demographic characteristics of a population with advanced COPD in a stable phase of the disease.MethodsThis study was cross-sectional based on a prospective observational cohort. The following questionnaires were administered: Chronic Respiratory Disease Questionnaire (CRQ), The COPD Assessment Test (CAT), The Hospital and Anxiety and Depression Scale (HADS), The Medical Research Council dyspnoea scale (MRC), and self-rate general health.ResultsWe included 242 patients with advanced COPD from a Danish pulmonary outpatient clinic. Their mean FEV1was 38% (±12.7) and 19% were treated with long term oxygen. The mean CRQ domain score was CRQ-dyspnea 4.21 (±1.4), CRQ-Mastery 4.88 (±1.3), CRQ-Emotional 4.81 (±1.2), CRQ-Fatigue 3.93 (±1.3). The mean CAT-score was 18.4 (± 6.7), and 44% had a CAT score > 20. The mean score on the subscale for anxiety (HADS-A) and depression (HADS-D) was 5.07 (±3.9) and 5.77 (±3.9), respectively. Thirty percent self-rated their health as bad or very bad and 19.8% were current smokers.ConclusionsThis study describes the characteristics of a population with advanced COPD in a stable phase of their disease. Our results illustrate how the population although treated in an outpatient structure already focusing on palliative needs, still live with unmet palliative needs and impaired quality of life.
Could the connectedness of primary health care workers involved in social networks affect their job burnout? A cross-sectional study in six counties, Central China
Authors: Mao Yiqing , Fu Hang , Feng Zhanchun , Feng Da , Chen Xiaoyu , Yang Jian , Li Yuanqing 
Published: June 2020

Abstract
Background
This study aimed to reveal the effects of the connectedness of primary health care (PHC) workers in social networks on their job burnout.

Methods
Cross-sectional survey data of rural PHC workers in China were analyzed. A total of 663 respondents were enrolled. Chi-square and cumulative logistic regression were used to determine the effects of the connectedness of PHC workers in social networks on their job burnout.

Results
PHC workers in rural China had high levels of emotional exhaustion (24.1%), depersonalization (15.7%), and lack of personal accomplishment (34.7%). More than half of the participants were in the middle connectedness level in terms of their advisory (70.4%) and friendship (70.3%) networks. The degree of emotional exhaustion seemed to increase when participants had a low connectedness in their friendship networks (β = 0.769, 95% CI = 0.080–1.458, P = 0.029). Respondents with the middle level of connectedness in advisory networks had higher levels of depersonalization (β = 0.739, 95% CI = 0.130–1.348, P = 0.017) and lack of personal accomplishment (β = 0.583, 95% CI = 0.111–1.055, P = 0.015) than those with the high degree of connectedness in advisory networks.

Conclusions
The connectedness of PHC workers in social networks influenced their job burnout. Thus, organizations should establish an informal communication platform and information feedback mechanism, promote and manage friendship networks, and help PHC workers overcome emotional exhaustion. Managers should also encourage individuals with a high level of connectedness in advisory networks play the role of “opinion leader” so that they can help others mitigate burnout.
The cirrhosis care Alberta (CCAB) protocol: implementing an evidence-based best practice order set for the management of liver cirrhosis - a hybrid type I effectiveness-implementation trial
Authors: Carbonneau Michelle , Eboreime Ejemai Amaize , Hyde Ashley , Campbell-Scherer Denise , Faris Peter , Gramlich Leah , Tsuyuki Ross T. , Congly Stephen E. , Shaheen Abdel Aziz , Sadler Matthew , Zeman Marilyn , Spiers Jude , Abraldes Juan G. , Sugars Benjamin , Sia Winnie , Green Lee , Abdellatif Dalia , Schaefer Jeffrey P. , Selvarajah Vijeyakumar , Marr Kaleb , Ryan David , Westra Yolande , Bakshi Neeja , Varghese Jayant C. , Tandon Puneeta 
Published: June 2020

Abstract
Background
Liver cirrhosis is a leading cause of morbidity, premature mortality and acute care utilization in patients with digestive disease. In the province of Alberta, hospital readmission rates for patients with cirrhosis are estimated at 44% at 90 days. For hospitalized patients, multiple care gaps exist, the most notable stemming from i) the lack of a structured approach to best practice care for cirrhosis complications, ii) the lack of a structured approach to broader health needs and iii) suboptimal preparation for transition of care into the community. Cirrhosis Care Alberta (CCAB) is a 4-year multi-component pragmatic trial which aims to address these gaps. The proposed intervention is initiated at the time of hospitalization through implementation of a clinical information system embedded electronic order set for delivering evidence-based best practices under real-world conditions. The overarching objective of the CCAB trial is to demonstrate effectiveness and implementation feasibility for use of the order set in routine patient care within eight hospital sites in Alberta.

Methods
A mixed methods hybrid type I effectiveness-implementation design will be used to evaluate the effectiveness of the order set intervention. The primary outcome is a reduction in 90-day cumulative length of stay. Implementation outcomes such as reach, adoption, fidelity and maintenance will also be evaluated alongside other patient and service outcomes such as readmission rates, quality of care and cost-effectiveness. This theory-based trial will be guided by Normalization Process Theory, Consolidated Framework on Implementation Research (CFIR) and the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) Framework.

Discussion
The CCAB project is unique in its breadth, both in the comprehensiveness of the multi-component order set and also for the breadth of its roll-out. Lessons learned will ultimately inform the feasibility and effectiveness of this approach in “real-world” conditions as well as adoption and adaptation of these best practices within the rest of Alberta, other provinces in Canada, and beyond.

Trial registration
ClinicalTrials.gov: NCT04149223, November 4, 2019.
Occurrence, risk factors and genotypes of Enterocytozoon bieneusi in dogs and cats in Guangzhou, southern China: high genotype diversity and zoonotic concern
Authors: Wang Haiyan , Lin Xuhui , Sun Yongxiang , Qi Nanshan , Lv Minna , Xiao Wenwan , Chen Yuancai , Xiang Ruiping , Sun Mingfei , Zhang Longxian 
Published: June 2020

Abstract
Background
Enterocytozoon bieneusi, a common opportunistic fungal pathogen, has a wide range of hosts. Limited epidemiological data on E. bieneusi intestinal infections in companion animals (dogs and cats) in China exists. In this study, fecal samples (651 from dogs and 389 from cats) in Guangzhou city, Guangdong Province, China, were collected, and the ribosomal internal transcribed (ITS) spacer region from the DNA extracted from them was Polymerase Chain Reaction (PCR)-amplified and sequenced.

Results
Based on the sequencing data, E. bieneusi was identified in the fecal samples collected from 149 (22.9%) and 79 (20.3%) dogs and cats. Of the factors investigated, poor living conditions appeared to be the major risk factor for contracting the pathogen. Eleven E. bieneusi genotypes, six known (PtEb IX, GD1, D, CD9, EbpC, I) and five novel (designated here as GD2– GD6), were found in dogs. Eight genotypes, six known (PtEb IX, GD1, D, CD9, EbpC, Type IV) and two novel (GD2 and GC1), were identified in cats. Genotype PtEb IX was most common in both dogs and cats, followed by genotype GD1.

Conclusions
Although PtEb IX was the most common E. bieneusi genotype in dogs, this is the first report of this genotype dominating in cats. The same genotype distribution of the pathogen between the two different companion animals species in the same geographic area indicates that inter-species transmission is probable. The widespread existence of zoonotic E. bieneusi genotypes (D, EbpC, Type IV) in companion animals indicates that they are potential sources of environmental contamination and infections in humans.