bluuebunny/crossref_metadata_2025_split huggingface dataset:
A rehabilitation programme for people with multimorbidity versus usual care
Authors: Barker Kathryn , Holland Anne E , Lee Annemarie L , Ritchie Kathryn , Boote Claire , Lowe Stephanie , Pazsa Fiona , Thomas Lee , Turczyniak Monica , Skinner Elizabeth H 
Published: July 2018

Background: Multimorbidity, the coexistence of two or more chronic conditions, is common in clinical practice. Rehabilitation for people with multimorbidity may provide access to a rehabilitation programme that can address common symptoms and risk factors for multiple chronic diseases. Objective: The aims of this study were to (1) evaluate the feasibility of a rehabilitation programme compared to usual medical care (UMC) in people with multimorbidity and (2) gather preliminary data regarding clinical effects and impact on functional exercise capacity, activities of daily living, health-related quality of life and resource utilization. Design: A pilot feasibility parallel randomized controlled trial was undertaken. Adults with multimorbidity were randomized to the rehabilitation programme (intervention) or UMC (control). The duration of the rehabilitation programme was 8 weeks and comprised exercise (1 h, twice weekly) and education (1 h, once weekly). The UMC group did not participate in a structured exercise programme. Results: One hundred people were screened to recruit 16 participants, with a 71% completion rate for the intervention group. The rehabilitation group achieved a mean (standard deviation) improvement in 6-minute walk distance of 44 (41) m and the UMC group of 23 (29) m. Conclusions: This study suggests that it would be feasible to conduct a larger randomized control trial investigating a rehabilitation programme for people with multimorbidity. Low uptake of the study suggests that refinement of the inclusion criteria, recruitment sources and programme model will be needed to achieve the number of participants required.
A Biomechanical and Structural Comparison of Articular Cartilage and Subchondral Bone of the Glenoid and Humeral Head
Authors: Loy Bo Nasmyth , Zimel Melissa , Gowda Ashok Laxman , Tooley Trevor Richard , Maerz Tristan , Bicos James , Guettler Joseph 
Published: July 2018

Background: The underlying cause of glenohumeral arthritis is poorly understood. Glenohumeral arthrosis patterns have been classified and described, and differential contact stresses within the joint have been implicated as a cause of joint degeneration, but the intrinsic cause of degeneration patterns in the glenohumeral joint (GHJ) remains largely unknown. Purpose/Hypothesis: The purpose of this study was to assess morphological and mechanical differences in articular cartilage (AC) and subchondral bone (SCB) of the glenoid and humeral head in matched cadaveric specimens. We hypothesized that there would be significant zone-dependent differences between the intrinsic characteristics (AC thickness, SCB thickness, compressive forces) of the glenoid and humeral head. Study Design: Descriptive laboratory study. Methods: Ten human cadaveric GHJs (mean age, 60.2 years) were dissected to expose articular surfaces to facilitate biomechanical testing. A 2-mm and 6-mm osteochondral plug was harvested at 5 zones (central, anterior, posterior, inferior, superior) on the glenoid and humeral head (N = 200 plugs). Each 2-mm core was histologically sectioned and stained with hematoxylin and eosin. AC thickness measurements were taken using light microscopy. The 6-mm plugs were imaged using micro–computed tomography to measure SCB thickness. After imaging, AC specimens were removed from the SCB and tested in confined compression. The compressive aggregate modulus (HA0), compressive stiffening coefficient (β), and compressive modulus at 16% strain (HA0.16) and at 50% strain (HA0.50) were calculated. Results: The overall AC thickness was significantly greater on the glenoid. The glenoid also had significantly thicker AC at the inferior, posterior, and superior zones as well as significantly higher SCB thickness overall and significantly greater SCB thickness at the anterior and central zones. The glenoid had significantly greater overall HA0.50 and HA0.50 values at the superior zone and had a significantly greater overall compressive stiffening coefficient (β). Conclusion: The glenoid had thicker AC, thicker SCB, and greater compressive stiffness at high strain. Clinical Relevance: These intrinsic differences may help better elucidate the cause of differential degeneration patterns between the glenoid and humeral head.
Access to and delivery of acute ischaemic stroke treatments: A survey of national scientific societies and stroke experts in 44 European countries
Authors: Aguiar de Sousa Diana , von Martial Rascha , Abilleira Sònia , Gattringer Thomas , Kobayashi Adam , Gallofré Miquel , Fazekas Franz , Szikora Istvan , Feigin Valery , Caso Valeria , Fischer Urs 
Published: July 2018

Introduction Acute stroke unit care, intravenous thrombolysis and endovascular treatment significantly improve the outcome for patients with ischaemic stroke, but data on access and delivery throughout Europe are lacking. We assessed best available data on access and delivery of acute stroke unit care, intravenous thrombolysis and endovascular treatment throughout Europe. Methods A survey, drafted by stroke professionals (ESO, ESMINT, EAN) and a patient organisation (SAFE), was sent to national stroke societies and experts in 51 European countries (World Health Organization definition) requesting experts to provide national data on stroke unit, intravenous thrombolysis and endovascular treatment rates. We compared both pooled and individual national data per one million inhabitants and per 1000 annual incident ischaemic strokes with highest country rates. Population estimates were based on United Nations data, stroke incidences on the Global Burden of Disease Report. Results We obtained data from 44 European countries. The estimated mean number of stroke units was 2.9 per million inhabitants (95% CI 2.3–3.6) and 1.5 per 1000 annual incident strokes (95% CI 1.1–1.9), highest country rates were 9.2 and 5.8. Intravenous thrombolysis was provided in 42/44 countries. The estimated mean annual number of intravenous thrombolysis was 142.0 per million inhabitants (95% CI 107.4–176.7) and 72.7 per 1000 annual incident strokes (95% CI 54.2–91.2), highest country rates were 412.2 and 205.5. Endovascular treatment was provided in 40/44 countries. The estimated mean annual number of endovascular treatments was 37.1 per million inhabitants (95% CI 26.7–47.5) and 19.3 per 1000 annual incident strokes (95% CI 13.5–25.1), highest country rates were 111.5 and 55.9. Overall, 7.3% of incident ischaemic stroke patients received intravenous thrombolysis (95% CI 5.4–9.1) and 1.9% received endovascular treatment (95% CI 1.3–2.5), highest country rates were 20.6% and 5.6%. Conclusion We observed major inequalities in acute stroke treatment between and within 44 European countries. Our data will assist decision makers implementing tailored stroke care programmes for reducing stroke-related morbidity and mortality in Europe.
Sex Differences in Patients With Chronic Heart Failure With Reference to Left Ventricular Ejection Fraction
Authors: Sakata Yasuhiko , Miyata Satoshi , Nochioka Kotaro , Miura Masanobu , Shiroto Takashi , Shimokawa Hiroaki 
Published: July 2018

Background: Data on sex differences in heart failure (HF) with reference to left ventricular ejection fraction (LVEF) are limited. Methods and Materials: We examined 4683 consecutive patients (mean 69 years) with HF in the CHART-2 study. Results: Compared to men (N = 3188), women with HF (N = 1495) were older and had a lower prevalence of ischemic heart disease and cancer, received less implementation of evidence-based treatment, and were characterized by more severe HF in terms of higher New York Heart Association (NYHA) functional class and increased brain natriuretic peptide (BNP) levels, despite greater preservation of LVEF. During the median 6.3-year follow-up, all-cause mortality was comparable between women and men (32.8% vs 33.2%, P = .816), while women had higher cardiovascular mortality, particularly among those with LVEF ≥50%. Although no sex differences existed in cause of death among patients with LVEF ≤ 40% and 41% to 49%, women had a higher proportion of cardiovascular death and lower proportion of noncardiovascular death than men among those with LVEF ≥ 50%. Multivariable Cox regression models showed that women with HF had reduced risk of both cardiovascular and noncardiovascular death, regardless of LVEF category. Beta-blockers were associated with improved mortality in women but not men with LVEF ≤ 40%, while renin–angiotensin system inhibitors were not associated with improved mortality in women with LVEF ≥ 50% but were in men. Conclusion: In addition to sex-specific differences in the age of onset, etiology and response to treatment, women with heart failure and preserved left ventricular ejection fraction (LVEF ≥ 50%) have higher cardiovascular mortality than men. Sex-related management of congestive heart failure should include a consideration of LVEF.
A novel predictive approach for GVHD after allogeneic SCT based on clinical variables and cytokine gene polymorphisms
Authors: Martínez-Laperche Carolina , Buces Elena , Aguilera-Morillo M. Carmen , Picornell Antoni , González-Rivera Milagros , Lillo Rosa , Santos Nazly , Martín-Antonio Beatriz , Guillem Vicent , Nieto José B. , González Marcos , de la Cámara Rafael , Brunet Salut , Jiménez-Velasco Antonio , Espigado Ildefonso , Vallejo Carlos , Sampol Antonia , Bellón José María , Serrano David , Kwon Mi , Gayoso Jorge , Balsalobre Pascual , Urbano-Izpizua Álvaro , Solano Carlos , Gallardo David , Díez-Martín José Luis , Romo Juan , Buño Ismael 
Published: July 2018

Key PointsA risk model using donor and recipient cytokine gene polymorphisms and clinical variables significantly improves GVHD risk stratification. The model is useful in identifying patients with low-risk of developing severe GVHD, but results must be confirmed in prospective studies.
Platelet transfusions improve hemostasis and survival in a substudy of the prospective, randomized PROPPR trial
Authors: Cardenas Jessica C. , Zhang Xu , Fox Erin E. , Cotton Bryan A. , Hess John R. , Schreiber Martin A. , Wade Charles E. , Holcomb John B. 
Published: July 2018

Key PointsEarly platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding trauma patients.
Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment
Authors: Attard Gerhardt , Borre Michael , Gurney Howard , Loriot Yohann , Andresen-Daniil Corina , Kalleda Ranjith , Pham Trinh , Taplin Mary-Ellen ,   on behalf of the PLATO collaborators
Published: July 2018

Purpose Enzalutamide resistance could result from raised androgens and be overcome by combination with abiraterone acetate. PLATO ( ClinicalTrials.gov identifier: NCT01995513) interrogated this hypothesis using a randomized, double-blind, placebo-controlled design. Patients and Methods In period one, men with chemotherapy-naïve metastatic castration-resistant prostate cancer received open-label enzalutamide 160 mg daily. Men with no prostate-specific antigen (PSA) increase at weeks 13 and 21 were treated until PSA progression (≥ 25% increase and ≥ 2 ng/mL above nadir), then randomly assigned at a one-to-one ratio in period two to abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily with either enzalutamide or placebo (combination or control group, respectively) until disease progression as defined by the primary end point: progression-free survival (radiographic or unequivocal clinical progression or death during study). Secondary end points included time to PSA progression and PSA response in period two. Results Of 509 patients enrolled in period one, 251 were randomly assigned in period two. Median progression-free survival was 5.7 months in the combination group and 5.6 months in the control group (hazard ratio, 0.83; 95% CI, 0.61 to 1.12; P = .22). There was no difference in the secondary end points. Grade 3 hypertension (10% v 2%) and increased ALT (6% v 2%) or AST (2% v 0%) were more frequent in the combination than the control group. Conclusion Combining enzalutamide with abiraterone acetate and prednisone is not indicated after PSA progression during treatment with enzalutamide alone; hypertension and elevated liver enzymes are more frequent with combination therapy.
Feminizing Adrenocortical Carcinoma: The Source of Estrogen Production and the Role of Adrenal-Gonadal Dedifferentiation
Authors: Wu Luming , Xie Jing , Jiang Lei , Su TingWei , Ye Lei , Zhou Weiwei , Jiang Yiran , Zhang Cui , Ning Guang , Wang Weiqing 
Published: July 2018

Abstract

Background
Feminizing adrenocortical carcinoma (ACC) is rare. The source of estrogen production and the underlying mechanism remain unclear.

Objective
In the current study, we investigated the source and the molecular mechanism of estrogen production in feminizing ACC.

Methods
A total of 46 consecutive patients with a diagnosis of ACC were recruited in our center. We described the clinical characteristics and steroid hormone profile of the peripheral and adrenal vein. In both feminizing ACC tissues and cell lines, we investigated the expression of steroidogenic biomarkers and β-catenin pathways by quantitative PCR and immunohistochemical staining. The effects of Wnt inhibitors on steroidogenesis were also analyzed in NCI-H295R cells.

Results
A total of 46 consecutive patients with ACC were analyzed, and 25 had functional ACC. Four patients received a diagnosis of feminizing ACC based on feminizing manifestations, high levels of estradiol that were normalized after surgery, and histological Weiss score. Gonadal steroidogenic biomarkers including CYP19A1, HSD17B3, and LHCGR were markedly elevated in the feminizing ACC tissues. Adrenal vein sampling and liquid chromatography–tandem mass spectrometry suggested high CYP19A1 activity in the adrenal mass. β-catenin expression was also elevated. When treated with niclosamide and PNU-74654, the H295R cell line showed a decrease in β-catenin expression, cell proliferation, and steroid secretion. All steroid hormone enzymes were inhibited, whereas CYP19A1, HSD17B3, and LHCGR mRNA increased.

Conclusions
Feminizing ACC can express high levels of CYP19A1, thus ectopically producing estrogens. Wnt pathway activation and dedifferentiation toward common adrenal-gonadal precursor cells may be the underlying mechanisms.
The Stress Hormone Cortisol Enhances Interferon-ϒ–Mediated Proinflammatory Responses of Human Immune Cells
Authors: Yeager Mark P. , Guyre Cheryl A. , Sites Brian D. , Collins Jane E. , Pioli Patricia A. , Guyre Paul M. 
Published: July 2018

BACKGROUND:
Cortisol is a prototypical human stress hormone essential for life, yet the precise role of cortisol in the human stress response to injury or infection is still uncertain. Glucocorticoids (GCs) such as cortisol are widely understood to suppress inflammation and immunity. However, recent research shows that GCs also induce delayed immune effects manifesting as immune stimulation. In this study, we show that cortisol enhances the immune-stimulating effects of a prototypical proinflammatory cytokine, interferon-ϒ (IFN-ϒ). We tested the hypothesis that cortisol enhances IFN-ϒ–mediated proinflammatory responses of human mononuclear phagocytes (monocyte/macrophages [MOs]) stimulated by bacterial endotoxin (lipopolysaccharide [LPS]).

METHODS:
Human MOs were cultured for 18 hours with or without IFN-ϒ and/or cortisol before LPS stimulation. MO differentiation factors granulocyte-macrophage colony stimulating factor (GM-CSF) or M-CSF were added to separate cultures. We also compared the inflammatory response with an acute, 4-hour MO incubation with IFN-ϒ plus cortisol and LPS to a delayed 18-hour incubation with cortisol before LPS exposure. MO activation was assessed by interleukin-6 (IL-6) release and by multiplex analysis of pro- and anti-inflammatory soluble mediators.

RESULTS:
After the 18-hour incubation, we observed that cortisol significantly increased LPS-stimulated IL-6 release from IFN-ϒ–treated undifferentiated MOs. In GM-CSF–pretreated MOs, cortisol increased IFN-ϒ–mediated IL-6 release by >4-fold and release of the immune stimulant IFN-α2 (IFN-α2) by >3-fold, while suppressing release of the anti-inflammatory mediator, IL-1 receptor antagonist to 15% of control. These results were reversed by either the GC receptor antagonist RU486 or by an IFN-ϒ receptor type 1 antibody antagonist. Cortisol alone increased expression of the IFN-ϒ receptor type 1 on undifferentiated and GM-CSF–treated MOs. In contrast, an acute 4-hour incubation of MOs with IFN-ϒ and cortisol showed classic suppression of the IL-6 response to LPS.

CONCLUSIONS:
These results reveal a surprisingly robust proinflammatory interaction between the human stress response hormone cortisol and the immune activating cytokine IFN-ϒ. The results support an emerging physiological model with an adaptive role for cortisol, wherein acute release of cortisol suppresses early proinflammatory responses but also primes immune cells for an augmented response to a subsequent immune challenge. These findings have broad clinical implications and provide an experimental framework to examine individual differences, mechanisms, and translational implications of cortisol-enhanced immune responses in humans.
Vascular endothelial growth factor signaling in development and disease
Authors: Karaman Sinem , Leppänen Veli-Matti , Alitalo Kari 
Published: July 2018

ABSTRACT
Vascular endothelial growth factors (VEGFs) are best known for their involvement in orchestrating the development and maintenance of the blood and lymphatic vascular systems. VEGFs are secreted by a variety of cells and they bind to their cognate tyrosine kinase VEGF receptors (VEGFRs) in endothelial cells to elicit various downstream effects. In recent years, there has been tremendous progress in elucidating different VEGF/VEGFR signaling functions in both the blood and lymphatic vascular systems. Here, and in the accompanying poster, we present key elements of the VEGF/VEGFR pathway and highlight the classical and newly discovered functions of VEGF signaling in blood and lymphatic vessel development and pathology.
Probiotics against airway allergy: host factors to consider
Authors: Spacova Irina , Ceuppens Jan L. , Seys Sven F. , Petrova Mariya I. , Lebeer Sarah 
Published: July 2018

ABSTRACT
The worldwide prevalence of allergic diseases has drastically increased in the past decades. Recent studies underline the importance of microbial exposure for the development of a balanced immune system. Consequently, probiotic bacteria are emerging as a safe and natural strategy for allergy prevention and treatment. However, clinical probiotic intervention studies have so far yielded conflicting results. There is increasing awareness about the importance of host-associated factors that determine whether an individual will respond to a specific probiotic treatment, and it is therefore crucial to promote a knowledge-based instead of an empirical selection of promising probiotic strains and their administration regimen.
In this Review, we summarize the insights from animal model studies of allergic disease, which reveal how host-related factors – such as genetic makeup, sex, age and microbiological status – can impact the outcomes of preventive or curative probiotic treatment. We explore why and how these factors can influence the results of probiotic studies and negatively impact the reproducibility in animal experiments. These same factors might profoundly influence the outcomes of human clinical trials, and can potentially explain the conflicting results from probiotic intervention studies. Therefore, we also link these host-related factors to human probiotic study outcomes in the context of airway allergies.
The CCM1–CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity
Authors: Lisowska Justyna , Rödel Claudia Jasmin , Manet Sandra , Miroshnikova Yekaterina A. , Boyault Cyril , Planus Emmanuelle , De Mets Richard , Lee Hsiao-Hui , Destaing Olivier , Mertani Hichem , Boulday Gwénola , Tournier-Lasserve Elisabeth , Balland Martial , Abdelilah-Seyfried Salim , Albiges-Rizo Corinne , Faurobert Eva 
Published: July 2018

ABSTRACT
Endothelial integrity relies on a mechanical crosstalk between intercellular and cell–matrix interactions. This crosstalk is compromised in hemorrhagic vascular lesions of patients carrying loss-of-function mutations in cerebral cavernous malformation (CCM) genes. RhoA/ROCK-dependent cytoskeletal remodeling is central to the disease, as it causes unbalanced cell adhesion towards increased cell–extracellular matrix adhesions and destabilized cell–cell junctions. This study reveals that CCM proteins directly orchestrate ROCK1 and ROCK2 complementary roles on the mechanics of the endothelium. CCM proteins act as a scaffold, promoting ROCK2 interactions with VE-cadherin and limiting ROCK1 kinase activity. Loss of CCM1 (also known as KRIT1) produces excessive ROCK1-dependent actin stress fibers and destabilizes intercellular junctions. Silencing of ROCK1 but not ROCK2 restores the adhesive and mechanical homeostasis of CCM1 and CCM2-depleted endothelial monolayers, and rescues the cardiovascular defects of ccm1 mutant zebrafish embryos. Conversely, knocking down Rock2 but not Rock1 in wild-type zebrafish embryos generates defects reminiscent of the ccm1 mutant phenotypes. Our study uncovers the role of the CCM1–CCM2 complex in controlling ROCK1 and ROCK2 to preserve endothelial integrity and drive heart morphogenesis. Moreover, it solely identifies the ROCK1 isoform as a potential therapeutic target for the CCM disease.
Σωματικές εμπειρίες, εικόνα σώματος και κοινωνική ταυτότητα ατόμων με τυφλότητα: ποιοτική μελέτη στην Ελλάδα
Authors: Κούτρα Λίνα , Τόγκας Κωνσταντίνος , Αλεξιάς Γεώργιος , Σαββάκης Μάνος , Στρατοπούλου Ιφιγένεια 
Published: July 2018

Μολονότι η τύφλωση αποτελεί συχνή μορφή αναπηρίας, οι σωματικές εμπειρίες, η εικόνα σώματος και η κοινωνική ταυτότητα των τυφλών δεν έχουν ερευνηθεί εκτεταμένα. Πραγματοποιήθηκε ποιοτική έρευνα με συνεντεύξεις σε επτά τυφλούς και τα αποτελέσματα έδειξαν ότι η αίσθηση ταυτότητάς τους είναι ισχυρά δομημένη, χωρίς στιγματισμό και χωρίς προβλήματα στην κοινωνικοποίησή τους. Οι τυφλοί αρνούνται τη διαφορετική αντιμετώπιση και βασίζονται στις αισθήσεις τους μόνο για την καθημερινή επιβίωση. Οι σωματικές εμπειρίες είναι βασικές για την αναγνώριση του περιβάλλοντός τους και η εξωτερική εμφάνιση αποτελεί συστατικό στοιχείο της εικόνας εαυτού. Τα άτομα με προβλήματα όρασης δεν εμφανίζουν αβεβαιότητα και δυσαρέσκεια για το σώμα τους και δεν έχουν προβλήματα με την ανάπτυξη και διατήρηση της θετικής εικόνας του σώματος. Τα αποτελέσματα μπορούν να χρησιμοποιηθούν για την πληρέστερη ψυχοκοινωνική φροντίδα τους.
Ergonomia aplicada na qualificação da ambiência do espaço de nascer.
Authors: Silva Cristiane Neves da 
Published: July 2018

Este estudo tem como objetivo rever as evidências disponíveis sobre o projeto de ambientes destinados ao nascimento, mais especificamente os quartos PPP (pré- parto, parto e puerpério), a fim de identificar características relativas aos aspectos ergonomicos dos ambientes e equipamentos utilizados que possam auxiliar na diminuição do estresse materno e facilitar a fisiologia do parto. Entendendo-se a ergonomia como uma disciplina dedicada a relacionar o entendimento das interações entre os seres humanos e outros elementos ou sistemas dos ambientes e relacionando-a com as proposições relativas aos estudos de ambiência, que atentam para os aspectos subjetivos que influenciam na percepção do ambiente, busca-se identificar elementos projetuais e ergonômicos que contribuam para experiências de nascimento seguras e satisfatórias para todas as mulheres.