bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton pump inhibitor and histamine‐2 receptor antagonist use and risk of liver cancer in two population‐based studies
Authors: Tran K. T. , McMenamin Ú. C. , Hicks B. , Murchie P. , Thrift A. P. , Coleman H. G. , Iversen L. , Johnston B. T. , Lee A. J. , Cardwell C. R. 
Published: May 2018

SummaryBackgroundProton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs) are commonly used.PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans.AimsTo investigatePPIs and H2RAs and risk of primary liver cancer in two large independent study populations.MethodsWe conducted a nested case‐control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95%CIs) for associations with prescribedPPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within theUKBiobank using self‐reported medication use and cancer‐registry recorded primary liver cancer. Hazard ratios (HRs) and 95%CIs were calculated using Cox regression.ResultsIn thePCCIUcase‐control analysis, 434 liver cancer cases were matched to 2103 controls. In theUKBiobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use ofPPIs was associated with increased liver cancer risk (adjustedOR1.80, 95%CI1.34, 2.41 and adjustedHR1.99, 95%CI1.34, 2.94 respectively). There was little evidence of association with H2RAuse (adjustedOR1.21, 95%CI0.84, 1.76 and adjustedHR1.70, 95%CI0.82, 3.53 respectively).ConclusionsWe found some evidence thatPPIuse was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.
Language barriers and epistemic injustice in healthcare settings
Authors: Peled Yael 
Published: May 2018

AbstractContemporary realities of global population movement increasingly bring to the fore the challenge of quality and equitable health provision across language barriers. While this linguistic challenge is not unique to immigration contexts and is likewise shared by health systems responding to the needs of aboriginal peoples and other historical linguistic minorities, the expanding multilingual landscape of receiving societies renders this challenge even more critical, owing to limited or even non‐existing familiarity of modern and often monolingual health systems with the particular needs of new linguistic minorities. The centrality of language to health beliefs, attitudes, practices, cultural scripts, and conceptual frameworks emphasizes its pivotal role in the healthcare process, and consequently in the adverse effects of treatment that is language‐insensitive and unaware. Such an attitude on the part of medical authorities risks considerable epistemic injustice in the form of a (mis)judgement of patients’ intelligence, credibility, and rationality based on the language that they speak and the manner in which they speak it, consequently impacting the quality and equity of care provided. This danger, I argue, may be effectively countered by fostering among the participants in the healthcare process a sense of epistemic humility through greater metalinguistic awareness. Outlining a range of operative steps that can be used to facilitate this. I argue that the reality of language barriers in the healthcare process, while not entirely eliminable, may nevertheless be successfully addressed, in order to mitigate the challenge of quality and equitable healthcare provision in multilingual societies.
Astrocytes, an active player in Aicardi–Goutières syndrome
Authors: Sase Sunetra , Takanohashi Asako , Vanderver Adeline , Almad Akshata 
Published: May 2018

AbstractAicardi–Goutières syndrome (AGS) is an early‐onset, autoimmune and genetically heterogeneous disorder with severe neurologic injury. Molecular studies have established that autosomal recessive mutations in one of the following genes are causative: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 and IFIH1/MDA5. The phenotypic presentation and pathophysiology of AGS is associated with over‐production of the cytokine Interferon–alpha (IFN‐α) and its downstream signaling, characterized as type I interferonopathy. Astrocytes are one of the major source of IFN in the central nervous system (CNS) and it is proposed that they could be key players in AGS pathology. Astrocytes are the most ubiquitous glial cell in the CNS and perform a number of crucial and complex functions ranging from formation of blood‐brain barrier, maintaining ionic homeostasis, metabolic support to synapse formation and elimination in healthy CNS. Involvement of astrocytic dysfunction in neurological diseases—Alexander's disease, Epilepsy, Alzheimer's and amyotrophic lateral sclerosis (ALS)—has been well‐established. It is now known that compromised astrocytic function can contribute to CNS abnormalities and severe neurodegeneration, nevertheless, its contribution in AGS is unclear. The current review discusses known molecular and cellular pathways for AGS mutations and how it stimulates IFN‐α signaling. We shed light on how astrocytes might be key players in the phenotypic presentations of AGS and emphasize the cell‐autonomous and non‐cell‐autonomous role of astrocytes. Understanding the contribution of astrocytes will help reveal mechanisms underlying interferonopathy and develop targeted astrocyte specific therapeutic treatments in AGS.
Alexander disease: an astrocytopathy that produces a leukodystrophy
Authors: Sosunov Alexander , Olabarria Markel , Goldman James E. 
Published: May 2018

AbstractAlexander Disease (AxD) is a degenerative disorder caused by mutations in the GFAP gene, which encodes the major intermediate filament of astrocytes. As other cells in the CNS do not express GFAP, AxD is a primary astrocyte disease. Astrocytes acquire a large number of pathological features, including changes in morphology, the loss or diminution of a number of critical astrocyte functions and the activation of cell stress and inflammatory pathways. AxD is also characterized by white matter degeneration, a pathology that has led it to be included in the “leukodystrophies.” Furthermore, variable degrees of neuronal loss take place. Thus, the astrocyte pathology triggers alterations in other cell types. Here, we will review the neuropathology of AxD and discuss how a disease of astrocytes can lead to severe pathologies in non‐astrocytic cells. Our knowledge of the pathophysiology of AxD will also lead to a better understanding of how astrocytes interact with other CNS cells and how astrocytes in the gliosis that accompanies many neurological disorders can damage the function and survival of other cells.
Genetic defects disrupting glial ion and water homeostasis in the brain
Authors: Min Rogier , van der Knaap Marjo S. 
Published: May 2018

AbstractElectrical activity of neurons in the brain, caused by the movement of ions between intracellular and extracellular compartments, is the basis of all our thoughts and actions. Maintaining the correct ionic concentration gradients is therefore crucial for brain functioning. Ion fluxes are accompanied by the displacement of osmotically obliged water. Since even minor brain swelling leads to severe brain damage and even death, brain ion and water movement has to be tightly regulated. Glial cells, in particular astrocytes, play a key role in ion and water homeostasis. They are endowed with specific channels, pumps and carriers to regulate ion and water flow. Glial cells form a large panglial syncytium to aid the uptake and dispersal of ions and water, and make extensive contacts with brain fluid barriers for disposal of excess ions and water. Genetic defects in glial proteins involved in ion and water homeostasis disrupt brain functioning, thereby leading to neurological diseases. Since white matter edema is often a hallmark disease feature, many of these diseases are characterized as leukodystrophies. In this review we summarize our current understanding of inherited glial diseases characterized by disturbed brain ion and water homeostasis by integrating findings from MRI, genetics, neuropathology and animal models for disease. We discuss how mutations in different glial proteins lead to disease, and highlight the similarities and differences between these diseases. To come to effective therapies for this group of diseases, a better mechanistic understanding of how glial cells shape ion and water movement in the brain is crucial.
Vanishing white matter: a leukodystrophy due to astrocytic dysfunction
Authors: Bugiani Marianna , Vuong Caroline , Breur Marjolein , van der Knaap Marjo S. 
Published: May 2018

AbstractVWM is one of the most prevalent leukodystrophies with unique clinical, pathological and molecular features. It mostly affects children, but may develop at all ages, from birth to senescence. It is dominated by cerebellar ataxia and susceptible to stresses that act as factors provoking disease onset or episodes of rapid neurological deterioration possibly leading to death. VWM is caused by mutations in any of the genes encoding the five subunits of the eukaryotic translation initiation factor 2B (eIF2B). Although eIF2B is ubiquitously expressed, VWM primarily manifests as a leukodystrophy with increasing white matter rarefaction and cystic degeneration, meager astrogliosis with no glial scarring and dysmorphic immature astrocytes and increased numbers of oligodendrocyte progenitor cells that are restrained from maturing into myelin‐forming cells. Recent findings point to a central role for astrocytes in driving the brain pathology, with secondary effects on both oligodendroglia and axons. In this, VWM belongs to the growing group of astrocytopathies, in which loss of essential astrocytic functions and gain of detrimental functions drive degeneration of the white matter. Additional disease mechanisms include activation of the unfolded protein response with constitutive predisposition to cellular stress, failure of astrocyte‐microglia crosstalk and possibly secondary effects on the oxidative phosphorylation. VWM involves a translation initiation factor. The group of leukodystrophies due to defects in mRNA translation is also growing, suggesting that this may be a common disease mechanism. The combination of all these features makes VWM an intriguing natural model to understand the biology and pathology of the white matter.
N‐back Working Memory Task: Meta‐analysis of Normative fMRI Studies With Children
Authors: Yaple Zachary , Arsalidou Marie 
Published: May 2018

The n‐back task is likely the most popular measure of working memory for functional magnetic resonance imaging (fMRI) studies. Despite accumulating neuroimaging studies with the n‐back task and children, its neural representation is still unclear. fMRI studies that used the n‐back were compiled, and data from children up to 15 years (n = 260) were analyzed using activation likelihood estimation. Results show concordance in frontoparietal regions recognized for their role in working memory as well as regions not typically highlighted as part of the working memory network, such as the insula. Findings are discussed in terms of developmental methodology and potential contribution to developmental theories of cognition.
Examining Ecological Constraints on the Intergenerational Transmission of Attachment Via Individual Participant Data Meta‐analysis
Authors: Verhage Marije L. , Fearon R.M. Pasco , Schuengel Carlo , van IJzendoorn Marinus H. , Bakermans‐Kranenburg Marian J. , Madigan Sheri , Roisman Glenn I. , Oosterman Mirjam , Behrens Kazuko Y. , Wong Maria S. , Mangelsdorf Sarah , Priddis Lynn E. , Brisch Karl‐Heinz ,   The Collaboration on Attachment Transmission Synthesis
Published: May 2018

Parents’ attachment representations and child–parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta‐analysis. Analyses on 4,396 parent–child dyads (58 studies, child age 11–96 months) revealed a combined effect size of r = .29. IPD meta‐analyses revealed that effect sizes for the transmission of autonomous‐secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent–child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta‐analysis are discussed.
Assessment and management of bone health in women with oestrogen receptor‐positive breast cancer receiving endocrine therapy: Position statement of the Endocrine Society of Australia, the Australian and New Zealand Bone & Mineral Society, the Australasian Menopause Society and the Clinical Oncology Society of Australia
Authors: Grossmann Mathis , Ramchand Sabashini K. , Milat Frances , Vincent Amanda , Lim Elgene , Kotowicz Mark A. , Hicks Jill , Teede Helena 
Published: May 2018

SummaryTo formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor‐positive early breast cancer receiving endocrine therapy, representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence‐informed position statement addressing 5 key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman treated with tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss; additionally, denosumab has proven antifracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight‐bearing exercise, vitamin D and calcium sufficiency are recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T‐score (or Z‐scores in women <50 years) of <−2.0 at any site, or if annual bone loss is ≥5%, considering baseline BMD and other fracture risk factors. Duration of antiresorptive treatment can be individualized based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with antiresorptive treatments are low. Skeletal health should be considered in the decision‐making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimized by nonpharmacological intervention and where indicated antiresorptive treatment, in an individualized, multidisciplinary approach. Clinical trials are needed to better delineate long‐term fracture risks of adjuvant endocrine therapy and to determine the efficacy of interventions designed to minimize these risks.
Why did the industrial diet triumph? The massification of dairy consumption in Spain, 1965–90
Authors: Collantes Fernando 
Published: May 2018

AbstractThe rise of a mass, agri‐industrial diet after the Second World War was crucial for the culmination of the nutritional transition that western countries had been involved in since the second half of the nineteenth century—but why did the industrial diet triumph? This article takes the massification of dairy consumption in Spain 1965–90 as a study case. Using a newly constructed database and qualitative material within an evolutionary socio‐economic framework, the article reaches two conclusions. First, the massification of dairy consumption was linked to most households’ transition to a softer budget constraint, which was driven mainly by increasing household incomes (and only secondarily by consumer price reductions caused by food industrialization). Second, the reason why the softening of the budget constraint played such a major role was that it was joined by a substantial increase in consumer trust in dairy products, which in turn resulted from industrial standardization. The article is in line with recent work that underlines the dietary change brought about by food industrialization, but questions whether the latter's major contribution was of a quantitative, price‐related nature and suggests that more attention should be paid to the qualitative, preferences‐related dimension.
Help‐seeking beliefs for mental disorders among medical and nursing students
Authors: Picco Louisa , Seow Esmond , Chua Boon Yiang , Mahendran Rathi , Verma Swapna , Xie Huiting , Wang Jia , Chong Siow Ann , Subramaniam Mythily 
Published: May 2018

AimThe current study aimed to investigate beliefs about help‐seeking, treatment options and expected outcomes for people with alcohol abuse, dementia, depression, obsessive‐compulsive disorder and schizophrenia, using a vignette‐based approach, among a sample of nursing and medical students.MethodsThis was a cross‐sectional online study among medical and nursing students (n = 1002) who were randomly assigned 1 of 5 vignettes. Questions were asked about whom could best help the person in the vignette, the likely helpfulness of a broad range of interventions, and the likely outcome for the person in the vignette with and without appropriate help.ResultsA total of 45.1% of students recommended seeing a psychiatrist, which was the most common source of help reported for all 5 vignettes. Help‐seeking preferences were significantly associated with age, academic year and vignette type. Respondents rated seeing a psychiatrist as the most helpful intervention (92.4%) and dealing with the problem on their own as the most harmful (68.1%). Then, 81.5% of students indicated that the condition of the person in the vignette would worsen if appropriate help was not sought.ConclusionMedical and nursing students most commonly recommended seeking help from a psychiatrist for mental health‐related problems, where help‐seeking preferences were associated with various age, academic year and vignette type. As these students will be the future medical and nursing workforce, they need to be equipped with the skills and ability to recognize signs and symptoms of mental illness, to aid timely and appropriate treatment for people with mental illness.
Structural causality in Spinoza's Ethics
Authors: Hulatt Owen 
Published: May 2018

AbstractIn this paper, I argue that Spinoza's claim at E1P15 that “Whatever is, is in God, and nothing can be or be conceived without God” remains exegetically troubling. Briefly noting some unresolved difficulties with the two dominant interpretations of Spinoza's account of the relationship between finite modes and God (these being the inherence and causal dependence readings), I move to claim that there is a third, neglected reading available which deserves consideration. I argue that, perhaps surprisingly, Althusser's notion of “structural causality,” putatively derived from Spinoza himself, can be used to construct this reading. Althusser's original notion of “structural causality” is explained and clarified further, its advantages outlined over competing readings of Spinoza, and exegetical evidence for its applicability to Spinoza is then produced.
Direct oral anticoagulants: When to consider laboratory testing?
Authors: ten Cate H. , Olie R. H. , ten Cate‐Hoek A. J. , Henskens Y. M. C. 
Published: May 2018

AbstractIntroductionDirect oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic stroke, as well as for prevention and treatment of venous thromboembolism. Dose adjustment based on laboratory testing is not required; however, there are several potential situations that deserve insight into a DOAC plasma activity level.MethodsBased on a series of real‐life case descriptions, we discuss indications for dedicated DOAC testing, as well as the interpretation and consequences.ResultsTesting of DOACs in selected patients may help to better interpret acute situations such as bleeding or thrombosis while on anticoagulation, but also suspected drug failure, drug accumulation, or lack of adherence.ConclusionThe 24/7 availability of target‐specific tests with adequate calibration is recommended to support the clinician in the interpretation and where needed adjustment of the management of patients on DOACs. The relevance of laboratory‐guided DOAC management, particularly in the elderly, merits further study.
Primary red cell hydration disorders: Pathogenesis and diagnosis
Authors: Caulier A. , Rapetti‐Mauss R. , Guizouarn H. , Picard V. , Garçon L. , Badens C. 
Published: May 2018

AbstractHydration status is critical for erythrocyte survival and is mainly determined by intracellular cation content. Active pumps, passive transporters, and ion channels are the key components of volume homeostasis, whereas water passively fits ionic movements. Whenever cation content increases, erythrocyte swells, whereas it shrinks when cation content decreases. Thus, inappropriate cation leak causes erythrocyte hydration disorders, hemolytic anemia, and characteristic red cell shape abnormalities named stomatocytosis. All types of stomatocytosis either overhydrated or dehydrated are linked to inherited or de novo mutations in genes encoding ion transporters or channels. Although intracellular ion content can be assessed by experimental methods, laboratory diagnosis is guided by a combination of red blood cell parameters and deformability measurement when possible, and confirmed by sequencing of the putative genes. A better knowledge of the mechanisms underlying erythrocyte hydration imbalance will further lead to therapeutic improvements.
Prenatal and preimplantation diagnosis of hemoglobinopathies
Authors: Vrettou C. , Kakourou G. , Mamas T. , Traeger‐Synodinos J. 
Published: May 2018

AbstractThe hemoglobinopathies, as a group, are one of the most common serious monogenic diseases in the world. An accepted and widely adopted approach to reduce the number of new cases involves carrier‐screening programs, with the option of prenatal diagnosis (PND) or preimplantation diagnosis (preimplantation genetic testing for monogenic disease, PGT‐M) for carrier couples. The aim of PND is to provide an accurate result as early in pregnancy as possible, which necessitates prior identification of the parental disease‐causing mutations, as well as safe and timely biopsy of fetal material. PGT‐M aims to characterize the genetic status of in vitro fertilized embryos during assisted reproductive technology (ART), in a few cells biopsied from oocytes/zygotes or embryos, in order to initiate an unaffected pregnancy. Another application of PGT‐M is preimplantation genetic diagnosis for human leukocyte antigen (PGD‐HLA), which, in addition to identifying unaffected embryos, also characterizes the embryos that are HLA compatible with an existing affected child requiring a hemopoietic stem cell transplantation (HSCT). This review outlines the current practices related to these procedures, with emphasis on the aspects related to laboratory techniques. Finally, future prospects related to developments in noninvasive prenatal diagnosis are discussed.