bluuebunny/crossref_metadata_2025_split huggingface dataset:
The management of benign non-infective pleural effusions
Authors: Bintcliffe Oliver J. , Lee Gary Y.C. , Rahman Najib M. , Maskell Nick A. 
Published: September 2016

The evidence base concerning the management of benign pleural effusions has lagged behind that of malignant pleural effusions in which recent randomised trials are now informing current clinical practice and international guidelines.The causes of benign pleural effusions are broad, heterogenous and patients may benefit from individualised management targeted at both treating the underlying disease process and direct management of the fluid. Pleural effusions are very common in a number of non-malignant pathologies, such as decompensated heart failure, and following coronary artery bypass grafting. Pleural fluid analysis forms an important basis of the diagnostic evaluation, and more specific assays and imaging modalities are helpful in specific subpopulations.Options for management beyond treatment of the underlying disorder, whenever possible, include therapeutically aspirating the fluid, talc pleurodesis and insertion of an indwelling pleural catheter. Randomised trials will inform clinicians in the future as to the risks and benefits of these options providing a guide as to how best to manage patient symptoms in this challenging clinical setting.
Dysfunctional breathing: a review of the literature and proposal for classification
Authors: Boulding Richard , Stacey Rebecca , Niven Rob , Fowler Stephen J. 
Published: September 2016

Dysfunctional breathing is a term describing breathing disorders where chronic changes in breathing pattern result in dyspnoea and other symptoms in the absence or in excess of the magnitude of physiological respiratory or cardiac disease. We reviewed the literature and propose a classification system for the common dysfunctional breathing patterns described. The literature was searched using the terms: dysfunctional breathing, hyperventilation, Nijmegen questionnaire and thoraco-abdominal asynchrony. We have summarised the presentation, assessment and treatment of dysfunctional breathing, and propose that the following system be used for classification. 1) Hyperventilation syndrome: associated with symptoms both related to respiratory alkalosis and independent of hypocapnia. 2) Periodic deep sighing: frequent sighing with an irregular breathing pattern. 3) Thoracic dominant breathing: can often manifest in somatic disease, if occurring without disease it may be considered dysfunctional and results in dyspnoea. 4) Forced abdominal expiration: these patients utilise inappropriate and excessive abdominal muscle contraction to aid expiration. 5) Thoraco-abdominal asynchrony: where there is delay between rib cage and abdominal contraction resulting in ineffective breathing mechanics.This review highlights the common abnormalities, current diagnostic methods and therapeutic implications in dysfunctional breathing. Future work should aim to further investigate the prevalence, clinical associations and treatment of these presentations.
Global impact of bronchiectasis and cystic fibrosis
Authors: Redondo Margarida , Keyt Holly , Dhar Raja , Chalmers James D. 
Published: September 2016

Educational aimsTo recognise the clinical and radiological presentation of the spectrum of diseases associated with bronchiectasis.To understand variation in the aetiology, microbiology and burden of bronchiectasis and cystic fibrosis across different global healthcare systems.Bronchiectasis is the term used to refer to dilatation of the bronchi that is usually permanent and is associated with a clinical syndrome of cough, sputum production and recurrent respiratory infections. It can be caused by a range of inherited and acquired disorders, or may be idiopathic in nature. The most well recognised inherited disorder in Western countries is cystic fibrosis (CF), an autosomal recessive condition that leads to progressive bronchiectasis, bacterial infection and premature mortality.Both bronchiectasis due to CF and bronchiectasis due to other conditions are placing an increasing burden on healthcare systems internationally. Treatments for CF are becoming more effective leading to more adult patients with complex healthcare needs. Bronchiectasis not due to CF is becoming increasingly recognised, particularly in the elderly population. Recognition is important and can lead to identification of the underlying cause, appropriate treatment and improved quality of life. The disease is highly diverse in its presentation, requiring all respiratory physicians to have knowledge of the different “bronchiectasis syndromes”. The most common aetiologies and presenting syndromes vary depending on geography, with nontuberculous mycobacterial disease predominating in some parts of North America, post-infectious and idiopathic disease predominating in Western Europe, and post-tuberculosis bronchiectasis dominating in South Asia and Eastern Europe.Ongoing global collaborative studies will greatly advance our understanding of the international impact of bronchiectasis and CF.
European Lung Foundation: from local to global
Authors: Powell Pippa , Williams Sîan , Smyth Dan 
Published: September 2016

Key pointsAlthough there are many patient organisations in Europe, this is not the case in all countries across the globe.Access to care is one of the main global issues highlighted by the European Lung Foundation International Patient Advisory Committee.The European Respiratory Society/European Lung Foundation Healthy Lungs for Life campaign can be used locally or globally to raise awareness of the risk factors for lung disease.Implementation science is a method that can be used to assess the feasibility of using research findings in routine healthcare in clinical settings in different parts of the world.Educational aimsTo show how patient- and public-focussed initiatives and activities can be adapted and modified to be effective in local, national and international settings, and to provide specific examples of these from the European Lung Foundation.
Hepatic stellate cells increase the immunosuppressive function of natural Foxp3+ regulatory T cells via IDO-induced AhR activation
Authors: Kumar Sudhir , Wang Jiang , Thomson Angus W , Gandhi Chandrashekhar R 
Published: September 2016

Abstract
Immunosuppressive, naturally occurring CD4+CD25+forkhead box p3+ (Foxp3+) regulatory T cells (nTregs) offer potential for the treatment of immune-mediated inflammatory disorders. However, potential instability of ex vivo-expanded nTregs following their adoptive transfer may be a significant limitation. LPS-stimulated hepatic stellate cells (HSCs) induce expansion and enhance the suppressive function and stability of allogeneic nTregs. We aimed to delineate mechanisms underlying HSC-induced expansion and increased potency of nTregs. HSCs and nTregs were isolated from mouse livers and spleens, respectively. Following coculture with LPS-pretreated allogeneic HSCs (LPS/HSCs), proliferation of nTregs was measured by CFSE dilution, and Foxp3 expression and acetylation were determined by immunoprecipitation (IP) and Western blotting analysis. Expression of various genes associated with immunologic tolerance was determined by quantitative RT-PCR (qRT-PCR). LPS stimulation increased the expression and activity of the immunoregulatory enzyme IDO1 in HSCs, and LPS/HSCs stimulated aryl hydrocarbon receptor (AhR) signaling in cocultured nTregs. Reciprocally, Tregs increased IDO1 expression in HSCs. IDO1−/− LPS/HSCs were inferior to WT LPS/HSCs in stimulating nTreg expansion. Pharmacologic inhibition of IDO1 in HSCs by 1-methyltryptophan (1MT) inhibited LPS/HSC-induced AhR signaling in nTregs, which was responsible for their expansion, Foxp3 expression, and stabilization of Foxp3 by increasing acetylation of lysine residues. Finally, HSCs cryopreserved, following 2–3 passages, were as potent as primary-cultured HSCs in expanding nTregs. In conclusion, LPS/HSCs expand allogeneic nTregs through an IDO-dependent, AhR-mediated mechanism and increase their stability through lysine-acetylation of Foxp3. nTregs expanded by cryopreserved HSCs may have potential for clinical use.
Dual inhibition of complement and Toll-like receptors as a novel approach to treat inflammatory diseases—C3 or C5 emerge together with CD14 as promising targets
Authors: Barratt-Due Andreas , Pischke Søren Erik , Nilsson Per H , Espevik Terje , Mollnes Tom Eirik 
Published: September 2016

Abstract
The host is protected by pattern recognition systems, including complement and TLRs, which are closely cross-talking. If improperly activated, these systems might induce tissue damage and disease. Inhibition of single downstream proinflammatory cytokines, such as TNF, IL-1β, and IL-6, have failed in clinical sepsis trials, which might not be unexpected, given the substantial amounts of mediators involved in the pathogenesis of this condition. Instead, we have put forward a hypothesis of inhibition at the recognition phase by “dual blockade” of bottleneck molecules of complement and TLRs. By acting upstream and broadly, the dual blockade could be beneficial in conditions with improper or uncontrolled innate immune activation threatening the host. Key bottleneck molecules in these systems that could be targets for inhibition are the central complement molecules C3 and C5 and the important CD14 molecule, which is a coreceptor for several TLRs, including TLR4 and TLR2. This review summarizes current knowledge of inhibition of complement and TLRs alone and in combination, in both sterile and nonsterile inflammatory processes, where activation of these systems is of crucial importance for tissue damage and disease. Thus, dual blockade might provide a general, broad-acting therapeutic regimen against a number of diseases where innate immunity is improperly activated.
Aziz: Bringing the SEG Wiki into the classroom
Authors: Farley Isaac 
Published: September 2016

This SEG Wiki interview, the fifth of the 2016 series, features Azie Sophia Aziz, Wiki Committee member and geophysicist at Lumina Technologies. Aziz joins Isaac Farley, SEG digital publications manager, to discuss how she would like to work to expand the reach of the SEG Wiki to universities and academics. [Figure: see text]
The Great Weaver from Kashmir by Halldór Laxness: sleepless nights in the Valley of Roses
Authors: Baldwin David S. 
Published: September 2016

SummaryThe novels of the Icelandic Nobel laureate Halldór Laxness depict individuals who are confronted by personal, familial and societal challenges in an isolated, sparsely populated and unpredictable but sublime and almost magical land. Novels which are currently available in English translation carefully illustrate the potentially damaging consequences of parentlessness, childhood abuse, physical illness, unexpected bereavement and marital desertion; the often corrosive effects of social and economic inequality; and the undermining of the lives and aspirations of women by patriarchal institutions. The Great Weaver from Kashmir is probably his least well-known novel but addresses many of these themes: most of its characters fall by the wayside and only a few thrive on adversity.
Tomorrow's world: current developments in the therapeutic use of technology for psychosis
Authors: O'Hanlon Puffn , Aref-Adib Golnar , Fonseca Andres , Lloyd-Evans Brynmor , Osborn David , Johnson Sonia 
Published: September 2016

SummaryThere is now an established evidence base for the use of information and communication technology (ICT) to support mental healthcare (‘e-mental health’) for common mental health problems. Recently, there have been significant developments in the therapeutic use of computers, mobile phones, gaming and virtual reality technologies for the assessment and treatment of psychosis. We provide an overview of the therapeutic use of ICT for psychosis, drawing on searches of the scientific literature and the internet and using interviews with experts in the field. We outline interventions that are already relevant to clinical practice, some that may become available in the foreseeable future and emerging challenges for their implementation.
An introduction to peer-supported open dialogue in mental healthcare
Authors: Razzaque Russell , Stockmann Tom 
Published: September 2016

SummaryPeer-supported open dialogue is a variant of the ‘open dialogue’ approach that is currently practised in Finland and is being trialled in several countries around the world. The core principle of the approach is the provision of care at the social network level, by staff who have been trained in family, systems and related approaches. These staff include peer workers, who will help to enhance the democratic nature of the meetings around which care is centred, as well as enabling such meetings to occur where networks are fragmented or lacking. Certain organisational and practice features and underlying themes are key to the approach. Crucially, open dialogue is also a system of service provision. Staff trained in peer-supported open dialogue from six National Health Service (NHS) trusts will launch pilot teams in 2016, as part of an intended national multicentre randomised controlled trial.
Language in psychiatry: a bedevilling dictionary
Authors: Pierre Joseph M. , Frances Allan 
Published: September 2016

SummaryThe language of psychiatry can be ambiguous and idiosyncratic, reflecting the elastic borders of mental illness and psychiatric disorder. This problem is not unique to psychiatry, but as the medical specialty moves closer towards a 'spectrum view’ of mental illness, psychiatric terminology increasingly risks misappropriation and conflation with lay concepts of normal suffering. Deciding what words mean and how psychiatric disorders are defined requires ongoing consideration of the pragmatic consequences, both intended and unintended. Refining the lexicon of psychiatry with an eye towards precision and the minimisation of stigma requires that terms be revised and updated from time to time, but often suitable word replacements remain elusive.
Psychopathy in childhood: Why should we care about grandiose–manipulative and daring–impulsive traits?
Authors: Salekin Randall T. 
Published: September 2016

SummaryCallous–unemotional traits have been incorporated into the DSM-5 and may be considered for the ICD-11. Despite the centrality of callous–unemotional traits, it is only one of three dimensions of child psychopathy. It is proposed that the grandiose–manipulative and daring–impulsive traits should be considered and potentially accepted as specifiers for conduct disorder in the DSM-5 and ICD-11.
Burkitt’s Lymphoma and B-Cell Lymphoma Unclassifiable With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt’s Lymphoma in Patients With HIV: Outcomes in a South African Public Hospital
Authors: Sissolak Gerhard , Seftel Matthew , Uldrick Thomas S. , Esterhuizen Tonya M. , Mohamed Nooroudien , Kotze Danie 
Published: September 2016

Purpose Burkitt’s lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. Methods We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa. Differences between BL and BL/DLBCL, survival outcomes, and factors associated with survival were analyzed. Results There were 35 patients with either HIV-associated BL (24) or BL/DLBCL (11) who met study criteria. Median CD4+ T-lymphocyte count at lymphoma diagnosis was 188 cells/μL (range, 10 to 535 cells/μL). Patients with BL/DLBCL were significantly older and had less bone marrow involvement and lower baseline serum lactase dehydrogenase than patients with BL. Eighty-nine percent of patients presented with advanced disease, and 25% had baseline CNS involvement. Chemotherapy regimens consisted of cytoreduction with low-dose cyclophosphamide, vincristine, and prednisone followed by induction with vincristine, methotrexate, cyclophosphamide, doxorubicin and prednisone (LMB 86; 57%); hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine (hyper-CVAD; 20%); cyclophosphamide, doxorubicin, vincristine, and prednisone and high-dose methotrexate with leucovorin rescue on day 10 with accompanying prophylactic IT chemotherapy (Stanford regimen; 14%); and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-like; 9%) regimens. Twenty-three patients received CNS treatment or prophylaxis, and 31 received concurrent combination antiretroviral therapy. Two-year overall survival was 38% (95% CI, 22% to 54%) and 2-year event-free survival was 23% (95% CI, 11% to 38%), with no difference between histologic subtypes. Common causes of death were infection (41%) and CNS disease progression or systemic relapse (41%). Conclusion Cure of HIV-associated BL and BL/DLBCL with intensive regimens is possible in resource-limited settings, but lower toxicity regimens, improved CNS prophylaxis, and increased resources for supportive care are required.
Cancer Care at Times of Crisis and War: The Syrian Example
Authors: Sahloul Eman , Salem Riad , Alrez Wessam , Alkarim Tayseer , Sukari Ammar , Maziak Wasim , Atassi M. Bassel 
Published: September 2016

Purpose As Syria enters its fifth year of conflict, the number of civilians killed and injured continues to rise sharply. Along with this conflict comes the rapid decline of medical care, specifically cancer care. To determine physician and equipment availability, cancer screening and management, and possible solutions relative to various major cities, a survey was distributed to physicians inside Syria through the help of the humanitarian organization Syrian American Medical Society. Methods Online surveys were distributed to both certified oncologists who work in cancer clinics and general physicians who work in rural and mobile clinics inside Syria. Variables assessed were physician specialty, location, population, cost, regional situation (besieged versus government controlled), and resource availability and access. Results were stratified by location and physician specialty. Results Survey results revealed a large shortage of specialized physicians and inhibited accessibility to screening and management options in besieged areas compared with government-controlled regions. Physicians within both government-controlled and besieged cities reported limited or no targeted agents, radiation therapy, clinical trials, bone marrow transplantation, positron emission tomography scans, magnetic resonance imaging, and genetic testing. Conclusion The Syrian civil war has resulted in suboptimal oncology care in the majority of the region. In consideration of specific deficiencies in cancer care, we recommend several solutions that may better the level of care in Syria: patient education on medical documentation and self-examination; online consultation; and cheap, effective screening methods. The implementation of these recommendations may change the course of cancer care in a country that has deteriorated into the worst humanitarian crisis of the century.
Adrenomedullin2 (ADM2)/Intermedin (IMD): A Potential Role in the Pathophysiology of Preeclampsia
Authors: Chauhan Madhu , Balakrishnan Meena , Vidaeff Alex , Yallampalli Uma , Lugo Fernando , Fox Karin , Belfort Michael , Yallampalli Chandra 
Published: September 2016

Context:
It is not known whether decreases in trophoblast invasion promoting the peptide, adrenomedullin2 (ADM2) system is associated with preeclampsia (PreE).

Objective:
The objective of the study was to assess the changes in ADM2 levels in plasma, placenta, and amniotic fluid (AF) and its receptor components in placenta from PreE pregnancy compared with the age-matched normal and study the effect of ADM2 on the synthesis of nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and matrix-metalloproteinase (MMP)-2 and MMP-9 in trophoblast cells.

Results:
PreE is associated with a decreased expression of ADM2 in plasma and placenta (P &lt; .05); ADM2 interacts with a seven-transmembrane G protein-coupled receptor, calcitonin receptor-like receptor (CRLR) in HTR-8/SVneo cells; placental expression of ADM2/CRLR complex is lower in PreE; mRNA for CRLR and receptor activity-modifying protein-3 are lower, whereas receptor activity-modifying protein-2 is higher in the PreE placenta (P &lt; .05); ADM2 levels in the second trimester are lower in the AF from pregnant women who develop PreE later in gestation (P &lt; .05); ADM2 is localized to the epithelium of the amnion and the ectoderm and mesoderm of the chorion in term fetal membranes; ADM2 increases NO production, eNOS, and MMP2/9-immunoreactivity, whereas ADM2 knockdown inhibits the expression of eNOS and MMP2/9 mRNA and S-nitrosylation in HTR-8/SVneo cells; and ADM2-induced increases in MMP2/9 activity is inhibited by L-nitro-arginine methyl ester in HTR-8SV/neo cells.

Conclusion:
Decreases in the ADM2 system in PreE at term, in AF from pregnant women during the second trimester who develop PreE later in gestation, and ADM2-induced increases in the NO and MMP-2/9 levels in trophoblast cells suggest a potential role for ADM2 via the NO-MMP system in the pathophysiology of PreE.
Effect of Linagliptin on Vascular Function: A Randomized, Placebo-controlled Study
Authors: Baltzis Dimitrios , Dushay Jody R. , Loader Jordan , Wu Jim , Greenman Robert L. , Roustit Matthieu , Veves Aristidis 
Published: September 2016

Context:The dipeptidyl peptidase-4 inhibitor, linagliptin, possesses pleiotropic vasodilatory, antioxidant, and anti-inflammatory properties in animals, independent of its glucose-lowering properties. Although large, randomized clinical trials are being conducted to better evaluate the efficacy and safety of linagliptin on cardiovascular outcomes, little is known about its effects on vascular function in humans.Objective:This study sought to evaluate the effect of linagliptin on surrogates of vascular and mitochondrial function.Design and Setting:This was a randomized, double-blind, placebo-controlled trial at a tertiary care center with a large type 2 diabetes referral base.Patients and Intervention:Forty participants with type 2 diabetes were included in a 12-wk treatment of either linagliptin 5mg/d or placebo.Main Outcome Measures:Micro- and macrovascular functions were assessed using laser Doppler coupled with iontophoresis and with brachial flow-mediated dilation, respectively. Mitochondrial function was assessed by phosphorus-31 metabolites changes in the calf muscle measured by magnetic resonance spectroscopy. Circulating endothelial progenitor cells, as well as inflammatory cytokines, growth factors, and biomarkers of endothelial function were also quantified.Results:Linagliptin was associated with an increase in axon reflex-dependent vasodilation, a marker of neurovascular function (P = .05). A trend indicating increased endothelium-dependent microvascular reactivity was observed (P = .07). These were associated with decreases in concentrations of IFNγ (P &lt; .05), IL-6 (P = .03), IL-12 (P &lt; .03), and MIP-1 (P &lt; .04) following linagliptin treatment when compared with placebo.Conclusions:This study demonstrates that linagliptin tends to improve endothelial and neurovascular microvascular function and is associated with decreased markers of inflammation in patients with type 2 diabetes. There was no significant effect of linagliptin on mitochondrial function, macrovascular function, or endothelial progenitor cells.