bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in fetal hemoglobin parameters and predicted hemoglobin S polymerization in sickle cell children in the first two years of life: Parisian Prospective Study on Sickle Cell Disease
Authors: Maier-Redelsperger M , Noguchi CT , de Montalembert M , Rodgers GP , Schechter AN , Gourbil A , Blanchard D , Jais JP , Ducrocq R , Peltier JY 
Published: November 2019

Abstract
Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical manifestations of this hemoglobinopathy. We have measured the sequential changes in HbF, F reticulocytes, and F cells in the first 2 years of life in 25 children with SCD and compared the results with those obtained in 30 normal children (AA). We have also calculated HbF per F cell (F/F cell), the preferential survival of F cells versus non-F cells, as measured by the ratio F cells versus F reticulocytes (FC/FR) and polymer tendency at 40% and 70% oxygen saturation. HbF levels decreased from about 80.4% +/- 4.0% at birth to 9.2% +/- 2.9% at 24 months. During this time, we observed a regular decrease of the F reticulocytes and the F cells. The kinetics of the decline of F/F cell was comparable with the decline of HbF, rapid from birth (mean, 27.0 +/- 3.6 pg) to 12 months of age (mean, 8.5 +/- 1.5 pg) and then slower from 12 to 24 months of age (mean, 6.2 +/- 1.0 pg) in the SCD children. In the AA children, the decrease in HbF, due to changes in both numbers of F cells and F/F cell, was more precipitous, reaching steady-state levels by 10 months of age. Calculated values for mean polymer tendency in the F-cell population showed that polymerization should begin to occur at 40% oxygen saturation at about 3 months and increase progressively with age, whereas polymerization at 70% oxygen saturation would not occur until about 24 months. These values correspond to HbF levels of 50.8% +/- 10.8% and 9.2% +/- 2.9%, respectively, and F/F cell levels of 15.6 +/- 4.5 pg and 6.2 +/- 1.0 pg, respectively. In the non--F-cell population, polymerization was expected at birth at both oxygen saturation values. Three individuals had significantly greater predicted polymerization tendency than the remainder of the group because of early decreases in HbF. These individuals in particular, the remainder of the cohort, as well as other recruited newborns, will be studied prospectively to ascertain the relationship among hematologic parameters, which determine polymerization tendency and the various clinical manifestations of SCD.
Effectiveness of interventions to alleviate emergency department crowding by older adults: a systematic review
Authors: Hesselink Gijs , Sir Özcan , Schoon Yvonne 
Published: November 2019

AbstractBackgroundThe growing demand for elderly care often exceeds the ability of emergency department (ED) services to provide quality of care within reasonable time. The purpose of this systematic review is to assess the effectiveness of interventions on reducing ED crowding by older patients, and to identify core characteristics shared by successful interventions.MethodsSix major biomedical databases were searched for (quasi)experimental studies published between January 1990 and March 2017 and assessing the effect of interventions for older patients on ED crowding related outcomes. Two independent reviewers screened and selected studies, assessed risk of bias and extracted data into a standardized form. Data were synthesized around the study setting, design, quality, intervention content, type of outcome and observed effects.ResultsOf the 16 included studies, eight (50%) were randomized controlled trials (RCTs), two (13%) were non-RCTs and six (34%) were controlled before-after (CBA) studies. Thirteen studies (81%) evaluated effects on ED revisits and four studies (25%) evaluated effects on ED throughput time. Thirteen studies (81%) described multicomponent interventions. The rapid assessment and streaming of care for older adults based on time-efficiency goals by dedicated staff in a specific ED unit lead to a statistically significant decrease of ED length of stay (LOS). An ED-based consultant geriatrician showed significant time reduction between patient admission and geriatric review compared to an in-reaching geriatrician.ConclusionInter-study heterogeneity and poor methodological quality hinder drawing firm conclusions on the intervention’s effectiveness in reducing ED crowding by older adults. More evidence-based research is needed using uniform and valid effect measures.Trial registrationThe protocol is registered with the PROSPERO International register of systematic reviews: ID = CRD42017075575).
Comparison of model-building strategies for excess hazard regression models in the context of cancer epidemiology
Authors: Maringe Camille , Belot Aurélien , Rubio Francisco Javier , Rachet Bernard 
Published: November 2019

Abstract
Background
Large and complex population-based cancer data are becoming broadly available, thanks to purposeful linkage between cancer registry data and health electronic records. Aiming at understanding the explanatory power of factors on cancer survival, the modelling and selection of variables need to be understood and exploited properly for improving model-based estimates of cancer survival.

Method
We assess the performances of well-known model selection strategies developed by Royston and Sauerbrei and Wynant and Abrahamowicz that we adapt to the relative survival data setting and to test for interaction terms.

Results
We apply these to all male patients diagnosed with lung cancer in England in 2012 (N = 15,688), and followed-up until 31/12/2015. We model the effects of age at diagnosis, tumour stage, deprivation, comorbidity and emergency presentation, as well as interactions between age and all of the above. Given the size of the dataset, all model selection strategies favoured virtually the same model, except for a non-linear effect of age at diagnosis selected by the backward-based selection strategies (versus a linear effect selected otherwise).

Conclusion
The results from extensive simulations evaluating varying model complexity and sample sizes provide guidelines on a model selection strategy in the context of excess hazard modelling.
Sarcopenia prevalence and associations with mortality and hospitalisation by various sarcopenia definitions in 85–89 year old community-dwelling men: a report from the ULSAM study
Authors: Sobestiansky Sigvard , Michaelsson Karl , Cederholm Tommy 
Published: November 2019

Abstract
Background
Operational definitions of sarcopenia, i.e. loss of muscle function and mass, have been proposed by the European Working Group on Sarcopenia in Older People (EWGSOP) and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). The aim of this study was to analyse the prevalence and outcome, i.e. all-cause mortality and hospitalisation, of sarcopenia and its diagnostic components in octogenarian community-dwelling men.

Methods
In total 287 men, aged 85–89 y, participating in the Uppsala Longitudinal Study of Adult Men (ULSAM) underwent Dual X-ray Absorptiometry (DXA), measurement of hand grip strength (HGS), gait speed (GS), and a five-times chair stand test (CS). Sarcopenia and probable sarcopenia were defined according to EWGSOP (2010), EWGSOP2 (2018), and FNIH (2014). All-cause mortality and hospitalisations over 3 years were registered.

Results
Sarcopenia according to EWGSOP, EWGSOP2 and FNIH was observed in 21%, 20%, and 8% of the men, respectively, while probable sarcopenia (EWGSOP2; eq. reduced muscle strength only) was seen in 73%. “Sarcopenia (EWGSOP)” and “probable sarcopenia (EWGSOP2)” were associated with increased mortality (HR 1.95, 95% CI 1.12–3.40 and HR 3.26, 95% CI 1.38–7.70, respectively). “Probable sarcopenia (EWGSOP2)” was associated with days of hospitalisation (RR 2.12, 95% CI 1.36–3.30), whereas sarcopenia according to FNIH showed an association with the number of hospitalisations (RR 1.75, 95% CI 1.10–2.81).

Conclusions
In very old men, reduced muscle strength, i.e. probable sarcopenia, was common and associated with mortality and length of stay during hospitalisation. When combined with low muscle mass (according to DXA), i.e. sarcopenia, the various definitions were associated more weakly with the adverse outcomes. The findings support the emphasis on reduced muscle strength as the major determinant of sarcopenia.
Healthcare professionals’ experiences of providing individualized nutritional care for Older People in hospital and home care: a qualitative study
Authors: Hestevik Christine Hillestad , Molin Marianne , Debesay Jonas , Bergland Astrid , Bye Asta 
Published: November 2019

Abstract
Background
Recent studies indicate inadequate nutritional care practices in healthcare institutions and identify several barriers to perform individualized nutritional care to older persons. Organisation of care can become rigid and standardised, thus failing to be respectful of and responsive to each person’s needs and preferences. There is limited research exploring health professionals’ views on how structure of care allows them to individualize nutritional care to older persons. In this study we aim to explore how healthcare professionals’ experience providing individualised nutritional care within the organisational frames of acute geriatric hospital care and home care.

Methods
Semi-structured interviews with 23 healthcare professionals from hospital acute geriatric care and home care. Interviews were analyzed using thematic analysis.

Results
Two main themes and six sub-themes emerged from the material. Theme 1: ‘Meeting patients with complex nutritional problems’ with the sub-themes: ‘It is much more complex than just not eating’ and ‘seeing nutrition as a part of the whole’. Theme 2: ‘The structure of the nutritional care’, with the sub-themes: ‘Nutritional routines: Much ado, but for what?’, ‘lack of time to individualize nutritional care’, ‘lack of interdisciplinary collaboration in nutritional care’ and ‘meeting challenging situations with limited resources in home care’.

Conclusions
The healthcare professionals described having a high focus on and priority of nutritional care when caring for older persons. They did however find it challenging to practice individualized nutritional care due to the complexity of the patients’ nutritional problems and constraints in the way nutritional care was organised. By describing the challenges the healthcare professionals face when trying to individualize the nutritional care, this study may provide important knowledge to health professionals and policy makers on how to decrease the gap between older patients’ preferences for care and nutritional care practice.
Prediction model for pneumonia in primary care patients with an acute respiratory tract infection: role of symptoms, signs, and biomarkers
Authors: Groeneveld G. H. , van ’t Wout J. W. , Aarts N. J. , van Rooden C. J. , Verheij T. J. M. , Cobbaert C. M. , Kuijper E. J. , de Vries J. J. C. , van Dissel J. T. 
Published: November 2019

Abstract
Background
Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care.

Methods
From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model.

Results
Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (− 4%); however, CRP helped guidance of the decision which patients should be given antibiotics.

Conclusions
Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners.
Rationale and design of a multicenter Chronic Kidney Disease (CKD) and at-risk for CKD electronic health records-based registry: CURE-CKD
Authors:   on behalf of the CURE-CKD investigators, Norris Keith C. , Duru O. Kenrik , Alicic Radica Z. , Daratha Kenn B. , Nicholas Susanne B. , McPherson Sterling M. , Bell Douglas S. , Shen Jenny I. , Jones Cami R. , Moin Tannaz , Waterman Amy D. , Neumiller Joshua J. , Vargas Roberto B. , Bui Alex A. T. , Mangione Carol M. , Tuttle Katherine R. 
Published: November 2019

Abstract
Background
Chronic kidney disease (CKD) is a global public health problem, exhibiting sharp increases in incidence, prevalence, and attributable morbidity and mortality. There is a critical need to better understand the demographics, clinical characteristics, and key risk factors for CKD; and to develop platforms for testing novel interventions to improve modifiable risk factors, particularly for the CKD patients with a rapid decline in kidney function.

Methods
We describe a novel collaboration between two large healthcare systems (Providence St. Joseph Health and University of California, Los Angeles Health) supported by leadership from both institutions, which was created to develop harmonized cohorts of patients with CKD or those at increased risk for CKD (hypertension/HTN, diabetes/DM, pre-diabetes) from electronic health record data.

Results
The combined repository of candidate records included more than 3.3 million patients with at least a single qualifying measure for CKD and/or at-risk for CKD. The CURE-CKD registry includes over 2.6 million patients with and/or at-risk for CKD identified by stricter guide-line based criteria using a combination of administrative encounter codes, physical examinations, laboratory values and medication use. Notably, data based on race/ethnicity and geography in part, will enable robust analyses to study traditionally disadvantaged or marginalized patients not typically included in clinical trials.

Discussion
CURE-CKD project is a unique multidisciplinary collaboration between nephrologists, endocrinologists, primary care physicians with health services research skills, health economists, and those with expertise in statistics, bio-informatics and machine learning. The CURE-CKD registry uses curated observations from real-world settings across two large healthcare systems and has great potential to provide important contributions for healthcare and for improving clinical outcomes in patients with and at-risk for CKD.
Bone mesenchymal stem cell therapy for ovariectomized osteoporotic rats: a systematic review and meta-analysis
Authors: Jin Zhenxiong , Chen Jinman , Shu Bing , Xiao Yanhua , Tang Dezhi 
Published: November 2019

AbstractBackgroundPrevious studies have found that bone mesenchymal stem cells (BMSCs) were capable of self-replication, multi-differentiation, and regeneration. The aim of this study was to carry out a systematic review and meta-analysis of the efficacy of BMSC therapy for ovariectomized rats.MethodsThe PubMed, Embase, Web of Science, China National Knowledge Infrastructure, VIP, and Chinese Sinomed databases were searched systematically from their initiation date to October 5, 2018. Two researchers independently screened the literatures, which used the bone mineral density (BMD), total bone volume by total tissue volume (BV/TV) (%), and trabecular thickness/spacing (Tb/Sp) as the outcome measures.ResultsFive eligible studies were selected. In the BMSC treatment groups, the BMD values and normalized BV/TV values remarkably increased. In addition, in the BMSCs plus other treatment groups, the BMD and Tb/Sp values significantly increased.ConclusionThis study showed that BMSCs could accelerate callus maturity, ossification and restore mechanical properties of bones in osteoporotic fractures.
Mediating effects of depression on anxiety and leisure constraints in patients with breast cancer
Authors: Huang Hsiu-Mei , Lai Jun-Hung , Huang Tsai-Wei 
Published: November 2019

Abstract
Background
Patients with breast cancer often exhibit high levels of anxiety and depression and a considerable decrease in their ability to participate in leisure activities, which result in the long-term disruption of their daily lives. This study intended to explore the relationships among anxiety, leisure constraints, and depression and evaluate whether depression mediates the effects of anxiety on leisure constraints in patients with breast cancer.

Method
This prospective study included 106 patients with breast cancer. All the patients completed the Taiwanese version of the Hospital Anxiety and Depression Scale and Leisure constraints questionnaire. Path analysis was used to test the mediating role of depression.

Results
Leisure constraints, anxiety, and depression were positively interrelated and co-occurred in the patients. The accelerated bootstrapping confidence intervals of the indirect effect did not include zero (0.276–1.663). Moreover, depression completely mediated the effects of anxiety on leisure constraints in patients with earlier cancer stages but not in patients with advanced cancer stages.

Conclusions
Depression is a crucial mechanism underlying the relationship between anxiety and leisure constraints in patients with breast cancer. Although many patients experience minimal disruption of activities and roles during survivorship, they are unable to perform functional activities and satisfactorily play their roles. This is the first study to explore leisure constraints in patients with breast cancer and investigate the mediating role of depression that underlies the relationship between anxiety and leisure constraints. The current findings are clinically crucial because they suggest the need to consider the simultaneous management of anxiety and depression for alleviating leisure constraints.
The impact of gender and academic achievement on the violation of academic integrity for medical faculty students, a descriptive cross-sectional survey study
Authors: Özcan Müesser , Yeniçeri Neşe , Çekiç Edip Güvenç 
Published: November 2019

Abstract
Purpose
The aim of this study is to determine the characteristics of medical faculty students about violations of academic integrity.

Method
From the whole population of the 572 students of the Muğla Sıtkı Koçman University Faculty of Medicine, 271 students participated voluntarily in a descriptive cross-sectional survey. Descriptive data were recorded in the survey and a five-point Likert-type instrument, namely the Tendency towards Academic Dishonesty Scale, was used as the data collection tool in the study. The scale included 22 items’ means that are considered to evaluate “Tendency towards academic dishonesty” (TTAD) score. In addition, four subscales, namely “Tendency towards cheating”, “Dishonesty in works such as assignments and projects”, “Tendency towards dishonesty in research and reporting processes” and “Tendency towards citation dishonesty” scores were evaluated separately.

Results
Of the participants, 138 (53.3%) were male. TTAD scores were 2.15 ± 0.61, showing a slight tendency towards academic dishonesty, according to the scale. TTAD scores and standard deviations (SD) were 2.26 ± 0.65 and 2.04 ± 0.55 for men and women, respectively (P = 0.005). There was no difference in the TTAD scores for students whether they had read the ethics code. Significant differences were observed in the TTAD scores for students with gender, different academic achievements and in different academic years. However, when multivariate analysis was performed, the significance shown in the results disappeared.

Conclusion
In our study, a slight tendency to academic dishonesty was found for medical faculty students and there were no differences between all of the recorded individual factors of students.
EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression
Authors: Peng Shunli , Wang Rong , Zhang Xiaojuan , Ma Yueyun , Zhong Longhui , Li Ke , Nishiyama Akihiro , Arai Sachiko , Yano Seiji , Wang Wei 
Published: November 2019

Abstract
Background
The ATLANTIC trial reported that higher PD-L1 expression in tumors was involved in a higher objective response in patients with EGFR+/ALK+ non-small cell lung cancer (NSCLC), indicating the possibility of anti-PD-1/PD-L1 therapy as a third-line (or later) treatment for advanced NSCLC. Therefore, the determination of status and regulatory mechanisms of PD-L1 in EGFR mutant NSCLC before and after acquired EGFR-TKIs resistance are meaningful.

Methods
The correlation among PD-L1, c-MET, and HGF was analyzed based on TCGA datasheets and paired NSCLC specimens before and after acquired EGFR-TKI resistance. EGFR-TKI resistant NSCLC cells with three well-known mechanisms, c-MET amplification, hepatocyte growth factor (HGF), and EGFR-T790M, were investigated to determinate PD-L1 expression status and immune escape ability. PD-L1-deleted EGFR-TKIs sensitive and resistant cells were used to evaluate the immune escape ability of tumors in mice xenograft models.

Results
Positive correlations were found among PD-L1, c-MET, and HGF, based on TCGA datasheets and paired NSCLC specimens. Moreover, the above three resistant mechanisms increased PD-L1 expression and attenuated activation and cytotoxicity of lymphocytes in vitro and in vivo, and downregulation of PD-L1 partially restored the cytotoxicity of lymphocytes. Both MAPK and PI3K pathways were involved in the three types of resistance mechanism-induced PD-L1 overexpression, whereas the NF-kappa B pathway was only involved in T790M-induced PD-L1 expression.

Conclusions
HGF, MET-amplification, and EGFR-T790M upregulate PD-L1 expression in NSCLC and promote the immune escape of tumor cells through different mechanisms.