bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic mucocutaneous candidiasis: characterization of a family with STAT-1 gain-of-function and development of an ex-vivo assay for Th17 deficiency of diagnostic utility
Authors: Dhalla F , Fox H , Davenport E E , Sadler R , Anzilotti C , van Schouwenburg P A , Ferry B , Chapel H , Knight J C , Patel S Y 
Published: December 2015

Summary
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent and persistent superficial infections, with Candida albicans affecting the mucous membranes, skin and nails. It can be acquired or caused by primary immune deficiencies, particularly those that impair interleukin (IL)−17 and IL-22 immunity. We describe a single kindred with CMC and the identification of a STAT1 GOF mutation by whole exome sequencing (WES). We show how detailed clinical and immunological phenotyping of this family in the context of WES has enabled revision of disease status and clinical management. Together with analysis of other CMC cases within our cohort of patients, we used knowledge arising from the characterization of this family to develop a rapid ex-vivo screening assay for the detection of T helper type 17 (Th17) deficiency better suited to the routine diagnostic setting than established in-vitro techniques, such as intracellular cytokine staining and enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants. We demonstrate that cell surface staining of unstimulated whole blood for CCR6+CXCR3–CCR4+CD161+ T helper cells generates results that correlate with intracellular cytokine staining for IL-17A, and is able to discriminate between patients with molecularly defined CMC and healthy controls with 100% sensitivity and specificity within the cohort tested. Furthermore, removal of CCR4 and CD161 from the antibody staining panel did not affect assay performance, suggesting that the enumeration of CCR6+CXCR3–CD4+ T cells is sufficient for screening for Th17 deficiency in patients with CMC and could be used to guide further investigation aimed at identifying the underlying molecular cause.
Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes
Authors: Adikari T N , Gomes L , Wickramasinghe N , Salimi M , Wijesiriwardana N , Kamaladasa A , Shyamali N L A , Ogg G S , Malavige G N 
Published: December 2015

Summary
Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P &lt; 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.
The pathogenesis of multiple sclerosis
Authors: Goodin Douglas S. 
Published: December 2015

AbstractThe pathogenesis of multiple sclerosis (MS) involves both genetic‐susceptibility and, at least, three sequential environmental‐events. The first environmental‐event is a maternal‐factor, which acts near birth. The second acts subsequently but prior to approximately age 15 years and the third acts long after these first two events have already taken place. Two environmental‐events strongly implicated in MS‐pathogenesis are vitamin D deficiency and Epstein‐Barr viral (EBV) infection. These factors seem well‐suited to the first two environmental‐events in this causal chain. If this notion is correct, it is likely that interrupting either of these factors (e.g. the timely supplementation of Vitamin D or the development of an EBV vaccine might be simple and effective methods for achieving primary disease prevention. In addition to these environmental‐events, genetic factors are both crucial and complex. More than 110 genomic‐regions have now been associated with MS‐susceptibility and only a very small fraction of the population is genetically‐susceptible. However, the actual genes involved are much more poorly defined than is often thought. For example, it turns out that the well‐established association with the DRB1*1501 allele on chromosome 6, is, likely, not due to this allele itself but, rather, to something else that resides on the SNP‐haplotype, which usually harbors this allele. Also, despite women being the large majority of MS patients, men are more likely to be genetically‐susceptible. Nevertheless, women are more responsive to the changing environmental‐exposures, which have occurred recently; thereby accounting for the changes in sex‐ratio and MS‐prevalence in women, which have been found in many regions.
Anti‐myelin oligodendrocyte glycoprotein antibody in demyelinating diseases
Authors: Nakashima Ichiro 
Published: December 2015

AbstractAnti‐myelin oligodendrocyte glycoprotein (MOG) antibody, which is specifically detected using a cell‐based assay (CBA), has been identified in various demyelinating diseases, including neuromyelitis optica spectrum disorders (NMOSD), acute idiopathic optic neuritis (ON), and pediatric multiphasic disseminated encephalomyelitis. Although its pathogenic role has not been established, antibody seropositive cases appear to share several characteristic features, such as a preferable response to steroid therapy and a good prognosis. Antibody detection at the onset of a demyelinating disease is important to predict the prognosis. Further analysis of the clinical features and investigation of the pathogenic roles of the antibody are required to establish the disease spectrum associated with the antibody. Although the associated diseases appear to have a relatively good prognosis, treatment recommendations are offered for patients with severe symptoms or frequent relapses.
Association of multiple sclerosis with lateral olfactory tract usher substance (LOTUS), a possible endogenous inhibitor of axonal degeneration
Authors: Takahashi Keita , Takei Kohtaro , Tanaka Fumiaki 
Published: December 2015

AbstractNeuronal regeneration in the adult mammalian central nervous system (CNS) is restricted after brain injury, and some of myelin components and their common receptor, Nogo receptor‐1 (NgR1), have been identified as the key molecules for limiting axonal regeneration in the CNS. They have been widely studied as therapeutic targets to overcome the limitation of neuronal regeneration, and strategies using antagonism to NgR1 are expected for the development of the most promising therapies. Recently signaling through NgR1 was shown to be an underlying mechanism of axonal degeneration in multiple sclerosis (MS). Although MS is generally considered an autoimmune demyelinating disorder, axonal degeneration has recently attracted attention as an important pathological feature and one of the mechanisms leading to progressive neurological disability. These pathological and clinical features of MS suggest that molecules involved in limitation of axonal growth can be potential candidates for MS biomarker and therapeutic target, and recent studies have supported these hypotheses. We have previously identified a novel endogenous NgR1 antagonist and named it lateral olfactory tract usher substance (LOTUS). Our data showed that LOTUS promotes axonal growth through blocking of NgR1 signaling, suggesting that LOTUS could be an endogenous inhibitor of axonal degeneration. Furthermore, our recent study demonstrated an interesting variation of LOTUS level in the cerebrospinal fluid of MS patients that was well correlated with disease activity. Here, we review the association of MS with the molecules related to axonal growth including LOTUS, and discuss the clinical application of LOTUS as a promising biomarker and therapeutic target.
Advance of genetics in multiple sclerosis
Authors: Matsushita Takuya 
Published: December 2015

AbstractMultiple sclerosis (MS) is characterized by temporal and spatial dissemination of demyelination in the central nervous system and the pathogenesis results from both genetic and environmental factors. Elaborate surveys have revealed familial accumulation of MS and provide unequivocal evidence that genetic factors contribute to the susceptibility. Family studies strongly suggest a polygenic model of inheritance explained by relatively common allelic variants. The major histocompatibility complex (MHC) in chromosome 6p21.3 has been identified as a genetic risk locus for MS from 1970s, but it was not until genome wide association studies (GWAS) were conducted in MS that genetic risks outside of MHC were identified. International collaboration and the development of new laboratory and analytical methods enabled detection of risk loci with comparably low effect size. Currently, more than 100 risk loci outside of MHC were identified. However, the heritability is not fully explained by the genetic risks that have been identified by GWAS. The knowledge of genetic effects on clinical phenotype is also incomplete.
Recombinant human bone morphogenetic protein 2 outcomes for maxillary sinus floor augmentation: a systematic review and meta‐analysis
Authors: Lin Guo‐Hao , Lim Glendale , Chan Hsun‐Liang , Giannobile William V. , Wang Hom‐Lay 
Published: December 2015

AbstractAimsTo study the effect of the recombinant human bone morphogenetic protein 2 (rhBMP‐2) on sinus volumetric and histometric changes after sinus floor augmentation compared to a conventional approach of non‐biologic bone grafting materials.Materials and methodsAn electronic search of 4 databases (January 1990–February 2015), including PubMed/MEDLINE, EMBASE, Web of Science and Cochrane Central, and a hand search of peer‐reviewed journals for relevant articles were performed. Human clinical trials with data on comparison of sinus volumetric and/or histometric outcomes with and without the use of rhBMP‐2 in sinus grafting procedures, with ≥10 augmentation sites in each study group, and with a follow‐up period of at least 6 months, were included. Random‐effects meta‐analyses were performed to analyze weighted mean difference (WMD) and confidence interval (CI) for the recorded variables according to PRISMA guidelines.ResultsSix randomized controlled trials (RCTs) were included. The results of the meta‐analyses showed that the WMD of vertical bone height gain was −0.14 mm (95% CI = −1.91 to 1.62 mm, P = 0.87), the WMD of bone density was −142.42 mg/cm3 (95% CI = −310.62–25.78 mg/cm3, P = 0.10), the WMD of the percentage of vital bone was −4.59% (95% CI = −11.73–2.56%, P = 0.21), and the WMD of the percentage of residual bone grafting materials was −9.90% (95% CI = −26.38–6.58%, P = 0.21). The comparison of implant survival rate presented an overall risk ratio of 1.00 (95% CI = 0.94–1.07). The two approaches (conventional bone grafting compared to BMPs) demonstrated comparable effectiveness for both clinical and histomorphometric measures.ConclusionsThis systematic review revealed that the use of rhBMP‐2 in maxillary sinus floor augmentation achieved similar clinical and histometric outcomes when compared to conventional sinus grafting procedures after a healing period of 6–9 months. However, previous studies showed the morbidity and other patient‐reported outcomes were improved in rhBMP‐2 approaches as compared to bone autograft procedures (both intraoral and extraoral bone harvesting because no donor site is required). Long‐term studies are required to determine the cost‐benefit of sinus floor augmentation procedures for patients requiring implant reconstruction.
Growing Healthy Families: Household Production, Food Security, and Well‐Being in South Wollo, Ethiopia
Authors: Cafer Anne M. , Willis Mary S. , Beyene Shimelis , Mamo Martha 
Published: December 2015

AbstractAlthough many studies have focused on the socio‐economic and nutritional status of Ethiopians, few have incorporated anthropometric measurements and structured questionnaires to explore the links between agriculture, development, and nutrition. Additionally, the research design included interviews with development agents, university faculty and staff, and community leaders from the Ethiopian highlands. A survey of 120 households in three districts of Ethiopia's famine belt revealed that a majority of households suffer from severe malnutrition. Anthropometric measures demonstrated that wasting and stunting rates are high. Furthermore, water usage, particularly irrigation and access to farmland, plays a significant role in crop diversity, food security, and household nutritional status. Interviews with farmers suggest there is a critical need for agricultural extension, with an emphasis on addressing gender‐related issues, and research as it relates to crop and water management.
Neoliberal Environmentality among Elites: Becoming “Responsible Producers” in Santarém, Brazil
Authors: Adams Ryan Thomas 
Published: December 2015

AbstractSoybean agriculture is expanding into the Brazilian Amazon, with certification programs in place to limit the environmental impact. Based on an ethnographic study with soybean farmers in Santarém, Pará State, Brazil, I claim that, through their enrollment in this conservation program, soybean farmers have come to see themselves as “responsible producers.” Despite their self‐identification as responsible producers, they treat environmental restrictions as a necessary cost imposed by civil society as they strive to transform the region into a commercial agriculture center, in contrast to alternative socio‐ecological production practices, thus exemplifying neoliberal environmentality. Through studying up with landed elites, this work demonstrates a distinct form of neoliberal environmentality.
External Intervention, Local Environment, and Knowledge Erosion: A Forest‐Based Community of South India
Authors: Kodirekkala Koteswara Rao 
Published: December 2015

AbstractIn the context of ongoing discussions of the erosion of indigenous knowledge, this report provides an analysis of how the factors “external” to a particular society may interact with “internal” (localized) factors to affect such knowledge, with a case study of the Konda Reddi of Andhra Pradesh, India. The external factor of market‐oriented developmental intervention in the form of the Girijan Cooperative Corporation (GCC) is affecting the local forest resources and the knowledge related to them. The GCC interplay with the local environment has affected the minor forest resources, subsequently eroding and changing that knowledge. [traditional ecological knowledge, indigenous knowledge, minor forest produce, knowledge loss, Konda Reddis]
Aggression‐related alcohol expectancies and barroom aggression among construction tradespeople
Authors: Zinkiewicz Lucy , Smith Georgia , Burn Michele , Litherland Steven , Wells Samantha , Graham Kathryn , Miller Peter 
Published: December 2015

AbstractIntroduction and AimsFew studies have investigated the relationship of barroom aggression with both general and barroom‐specific alcohol expectancies. The present study investigated these associations in a rarely studied and high‐risk population: construction tradespeople.Design and MethodsMale construction tradespeople (n = 211) aged 18–35 years (M = 21.91, SD = 4.08 years) participated in a face‐to‐face questionnaire assessing general and barroom‐specific alcohol expectancies and perpetration of physical and verbal barroom aggression as well as control variables, age, alcohol consumption and trait aggression.ResultsSequential logistic regression analyses revealed that general alcohol‐aggression expectancies of courage or dominance were not predictive of either verbal or physical barroom aggression after controlling for age, alcohol consumption and trait aggression. However, barroom‐specific alcohol expectancies were associated with both verbal and physical barroom aggression, with positive associations found for expected hyper‐emotionality and protective effects for expected cognitive impairment.Discussion and ConclusionsIn a population where rates of risky drinking and barroom aggression are high, specific expectations about the effects of drinking in bars may influence subsequent aggressive behaviour in bars. [Zinkiewicz L, Smith G, Burn M, Litherland S, Wells S, Graham K, Miller P. Aggression‐related alcohol expectancies and barroom aggression among construction tradespeople. Drug Alcohol Rev 2016;35:549–556]
Perinatal asphyxia syndrome
Authors: Gold J. R. 
Published: December 2015

SummaryHypoxic ischaemic encephalopathy (HIE) has been described in foals for over 80 years. This condition has a diversity of names including ‘dummy foals', ‘wanderers', ‘barkers', neonatal encephalopathy, neonatal maladjustment syndrome (NMS) and perinatal asphyxia syndrome (PAS). The latter descriptive terms are all encompassing for a syndrome that has varying degrees of multi‐systemic effects rather than just neurological disease. While foals with PAS are commonly reported in the literature, the aetiology and underlying pathophysiology are still very poorly understood, with a majority of the information extrapolated from human and animal models. Currently, no antemortem test exists and diagnosis is made based on the history of the mare and foal as well as reliance on clinical signs. Recent studies have shown that neuroactive pregnanes may play a key role in the syndrome; however, further research is needed to clarify these findings. Another investigation compared neurobiomarkers for brain injury in both sick and normal neonatal foals. The mainstay of therapy for PAS is supportive treatment. Specific therapies such as antioxidants and neuroprotectants are used by some clinicians but little scientific evidence exists that proves the therapeutic protocols implemented improve overall outcome. Prevention of PAS in foals revolves around the health of the mare including, but not limited to, the prevention of placentitis or other illnesses and observation and/or intervention during parturition when necessary. More research is necessary to fully comprehend this syndrome, its diagnosis and treatment options.
Active surveillance for prostate cancer
Authors: Romero‐Otero Javier , García‐Gómez Borja , Duarte‐Ojeda José M , Rodríguez‐Antolín Alfredo , Vilaseca Antoni , Carlsson Sigrid V , Touijer Karim A 
Published: December 2015

AbstractIt is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non‐curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low‐risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low‐risk prostate cancer without compromising cancer‐specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side‐effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.
The Effectiveness of Norway's Readmission Agreements with Iraq and Ethiopia
Authors: Janmyr Maja 
Published: December 2015

AbstractThis article offers an analysis of the effectiveness of Norway's readmission agreements with Iraq and Ethiopia. Through the use of readmission agreements, Norway aims to reduce irregular presence by increasing the number of both voluntary and forced returns, as well as discourage future irregular migration by sending a “clear signal” to individuals without protection needs that they will be returned when their asylum applications are rejected. The effectiveness of these agreements thus lies in the extent to which they fulfill these objectives. While Norway's agreements with Iraq and Ethiopia have been explicitly highlighted as effective by Norwegian authorities, this article argues that readmission agreements may be expected to limit, but not to eliminate, return problems. Readmission agreements, however streamlined, will have different effects on different groups. It finds that Norway's readmission agreements have been only partially successful with Iraq, and wholly unsuccessful with Ethiopia.
Is the Same‐sex Marriage Debate Really Just about Marriage?
Authors: Arroyo Christopher 
Published: December 2015

AbstractIn What is Marriage? One Man and One Woman: A Defense, Sherif Girgis, Ryan Anderson and Robert George defend the ‘conjugal marriage’ while claiming to make no moral judgments about homosexuality. My contention in this article is that the argument of What is Marriage is not sufficiently different from the arguments of classical new natural law theorists (NNLT), and, therefore, What is Marriage does not remain neutral on the question of whether homosexuality is moral. First, I give an overview of some classical NNLT arguments on the nature of marriage and their sexual ethic. Next, I present What is Marriage's account of conjugal marriage as a comprehensive union of two people, focusing on what makes a genuinely bodily union. I then move to the central contention of this article. By drawing on its understanding of genuinely bodily union and its account of the harm of same‐sex marriage, I argue that What is Marriage is committed to the view that same‐sex sexual unions cannot be good, since on its account of things there can be no shared sexual goods in a same‐sex sexual ‘union’.