bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is the atopic march related to confounding by genetics and early‐life environment? A systematic review of sibship and twin data
Authors: Khan S. J. , Dharmage S. C. , Matheson M. C. , Gurrin L. C. 
Published: June 2017

AbstractA popular hypothesis known as the atopic march proposes a set of sequential allergy and respiratory disorders in early childhood contributes enormously to the burden of disease in developed countries. Although the concept of the atopic march has been refined and strengthened by many cross‐sectional and longitudinal studies linking eczema as the initial manifestation with progression to hay fever and then asthma, there is yet no definitive proof that the atopic march is the primary causal factor in childhood allergic disease. This debate is mainly related to the controversy around potential confounding of these associations by genetic and environmental factors. Family studies are ideally suited to unravelling the role of these factors. While multiple reviews have synthesized evidence from studies investigating this question, no review to date has explored specific evidence generated by twin and sibling studies to understand the aetiology of atopic march diseases. Our aim was to conduct a systematic review of twin and sibling studies that examine the allergic phenotypes that form the atopic march, to determine whether such analyses of data from these studies attempt to control for the effect confounding by shared factors, and to report estimates of the magnitude of associations between multiple phenotypes. Our review suggests that (1) genetics play a bigger role predisposing eczema to hay fever and eczema to asthma than environmental factors, and (2) the link between eczema and asthma and hay fever is independent of shared early‐life environmental factors.
Spaces of connectivity: The formation of medical travel destinations in Delhi National Capital Region (India)
Authors: Kaspar Heidi , Reddy Sunita 
Published: June 2017

AbstractExisting research on the formation of Asian medical travel destinations has highlighted a variety of activities that attract and accommodate patients from abroad. This paper contributes to the literature by drawing insights from an Indian case study, a major transnational health‐care hub in Asia that has gained little scholarly attention thus far. Using connectivity as an analytical lens, we understand medical travel destinations as a contingent product of relating, connecting and assembling. We study how connectivity is embodied and how it unfolds in care encounters at corporate hospitals in the capital of New Delhi and surrounding urban areas. The following entities are the most effectual in the networks that constitute medical travel destinations in the National Capital Region: (i) circulating narrations of personal experiences; (ii) language interpreters; and (iii) commission fees. We further elaborate on how these connectors work to link foreign patients with Indian hospitals and how they affect itineraries as well as patients and other involved actors. Finally, we suggest that the approach deployed provides a suitable framework for future research aimed at gaining a better understanding of the wider impacts of medical travel by following these connections and examining their workings at places both close and distant.
Romiplostim monotherapy in thrombocytopenic patients with myelodysplastic syndromes: long‐term safety and efficacy
Authors: Fenaux Pierre , Muus Petra , Kantarjian Hagop , Lyons Roger M. , Larson Richard A. , Sekeres Mikkael A. , Becker Pamela S. , Orejudos Amelia , Franklin Janet 
Published: June 2017

SummaryRomiplostim can improve platelet counts in about 50% of patients with low‐ or intermediate 1‐risk (lower risk) myelodysplastic syndromes (MDS) and thrombocytopenia, but its long‐term toxicity and efficacy are not known. This open‐label extension study evaluated the long‐term safety and efficacy of romiplostim in 60 patients with lower risk MDS and platelet counts ≤50 × 109/l. The primary endpoint was adverse event (AE) incidence. Secondary endpoints were efficacy parameters, including bleeding events and platelet response. Median (range) treatment time in the extension study and the median observation times thereafter were 25 (2–181) and 57 (11–209) weeks, respectively. Treatment‐related AEs and serious AEs were reported in 14/60 (23%) and 4/60 (7%) patients, respectively. Progression to acute myeloid leukaemia (AML) occurred in two patients after 44 and 46 weeks. Patients (n = 34, 57%) with a platelet response were further evaluated for length of response. Median (range) response duration was 33 (7–174) weeks; 28/34 (82%) patients had a continuous response. Five of 34 patients (15%) had grade ≥3 bleeding events; three when the platelet count was >50 × 109/l. There were no new safety concerns and the rate of progression to AML was low; response to romiplostim was maintained for most patients.
Changes in the inflow of saline water into the Bornholm Basin (SW Baltic Sea) during the past 7100 years – evidence from benthic foraminifera record
Authors: Binczewska Anna , Moros Matthias , Polovodova Asteman Irina , Sławińska Joanna , Bąk Małgorzata 
Published: June 2017

The Baltic Sea (~393 000 km2) is the largest brackish sea in the world and its hydrographic and environmental conditions are strongly dependent on the frequency of saline water inflows from the North Sea. To improve our understanding of the natural variability of the Baltic Sea ecosystem detailed reconstructions of past saline water inflow changes based on palaeoecological archives are needed. Here we present a high‐resolution study of benthic foraminiferal assemblages accompanied by sediment geochemistry (loss on ignition, total organic carbon) and other microfossil data (ostracods and cladocerans) from a well‐dated 8‐m‐long gravity core taken in the Bornholm Basin. The foraminiferal diversity in the core is low and dominated by species of Elphidium. The benthic foraminiferal faunas in the central Baltic require oxic bottom water conditions and salinities >11–12 PSU. Consequently, shell abundance peaks in the record reflect frequent saline water inflow phases. The first appearance of foraminiferal tests and ostracods in the investigated sediment core is dated to c. 6.9 cal. ka BP and attributed to the first inflows of saline and oxygenated bottom waters into the Bornholm Basin during the Littorina Sea transgression. The transgression terminated the Ancylus Lake phase, reflected in the studied record by abundant cladocerans. High absolute foraminiferal abundances are found within two time intervals: (i) c. 5.5–4.0 cal. ka BP (Holocene Thermal Maximum) and (ii) c. 1.3–0.75 cal. ka BP (Medieval Climate Anomaly). Our data also show three intervals of absent or low saline water inflows: (i) c. 6.5–6.0 cal. ka BP, (ii) c. 3.0–2.3 cal. ka BP and (iii) c. 0.5–0.1 cal. ka BP (Little Ice Age). Our study demonstrates a strong effect of saline and well‐oxygenated water inflows from the Atlantic Ocean on the Baltic Sea ecosystem over millennial time scales, which is linked to the major climate transitions over the last 7 ka.
Pythons, parasites, and pests: anthropogenic impacts on Sarcocystis (Sarcocystidae) transmission in a multi‐host system
Authors: Devan‐Song Anne , Luz Sonja , Mathew Abraham , Low Mary‐Ruth , Bickford David P. 
Published: June 2017

AbstractParasites are essential components of ecosystems and can be instrumental in maintaining host diversity and populations; however, their role in trophic interactions has often been overlooked. Three apicomplexan parasite species of Sarcocystis (S. singaporensis, S. zamani, and S. villivillosi) use the reticulated python as their definitive hosts and several species within the Rattus genus as intermediate hosts, and they form a system useful for studying interactions between host–parasite and predator–prey relationships, as well as anthropogenic impacts on parasite transmission. Based on predictions from a 1998 survey, which detected an inverse relationship between urban development and Sarcocystis infection in Rattus, we tested the hypothesis that Sarcocystis transmission in Singapore will decrease over time due to anthropogenic activities. Despite a large proportion of the reticulated python diet consisting of Rattus species at all sizes of pythons, Sarcocystis infection rates decreased from 1998 to 2010. Pythons found in industrial areas had lower Sarcocystis infection rates, particularly in the western industrial area of Singapore Island. Average python size also decreased, with implications that we predict may disrupt host–parasite relationships. Anthropogenic activities such as habitat modification, fragmentation, and systematic removal and translocation of pythons have negative impacts on Sarcocystis transmission in Singapore, which in turn may augment pest rat populations. Trends observed may ultimately have negative impacts on human health and biodiversity in the region.
Withasteroid B from D. metel L. regulates immune responses by modulating the JAK/STAT pathway and the IL-17+RORγt+/IL-10+FoxP3+ ratio
Authors: Su Y , Wang Q , Yang B , Wu L , Cheng G , Kuang H 
Published: June 2017

Summary
Datura metel L. is a medicinal herb that contains withasteroids and has a wide range of biological activities. We isolated seven withasteroids from the flowers of D. metel L and examined their ability to inhibit immune responses in vitro and in vivo. Among the withasteroids, withasteroid B2 exhibited the strongest inhibitory effect on immune responses comparing B2 with other isolated compounds from D. metel L., including suppressing the differentiation of CD4+ T cells by inhibiting the expression and production of T cell lineage-specific master regulators and cytokines and directly suppressing the cytokine-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathways. In the interleukin (IL)-23-induced mouse ear model of skin disease, B2 repressed disease development by inhibiting the expression of proinflammatory mediators in murine ear skin. Moreover, B2 affected the maturation of dendritic cells (DCs) in vitro which, in turn, induced T cell differentiation with an increased regulatory T cell (Treg) phenotype and decreased T helper type 17 (Th17) phenotype. This study provides new evidence that B2 might ameliorate chronic inflammatory skin diseases by suppressing pathogenic CD4+ T cell differentiation and the IL-17+retinoic-acid-receptor-related orphan receptor gamma t (RORγt)+/IL-10+forkhead box protein 3 (FoxP3)+ ratio. These findings suggest that B2 might mediate the therapeutic effects observed in psoriasis patients following treatment with D. metel L.
The Turner syndrome life course project: Karyotype‐phenotype analyses across the lifespan
Authors: Cameron‐ Pimblett Antoinette , La Rosa Clementina , King Thomas F. J. , Davies Melanie C. , Conway Gerard S. 
Published: June 2017

SummaryIntroductionTurner syndrome (TS) is associated with a variety of morbidities affecting nearly every body system, some of which increase in prevalence in adult life. The severity of clinical features in TS is roughly in parallel with the magnitude of the deficit of X‐chromosome material. The aim of this study was to extend the established karyotype‐phenotype relationships using data from a large adult cohort.Materials and MethodsKaryotypes were available in 656 women with TS. 611 of whom could be classified into five major groups within the cohort: 45,X; 45,X mosaicism (45,X/46,XX); isochromosome X (isochromosome Xq); mosaicism 45,X/46,XY and ring X.Continuous variables such as blood pressure and biochemical markers from clinic data were binarised allocating those in the upper quartile to represent at‐risk individuals. With the exception of bone mineral density T‐score for which the lower quartile was allocated as at risk. For comorbidities, initiation of formal treatment was recorded.Results45,X/46,XX had considerably lower frequency of comorbidities compared to 45,X. The isochromosome group experienced similar outcomes to 45,X. Novel associations were found between the XY mosaic karyotype group and a decreased prevalence of thyroid disease and severe hearing loss. A previously unreported increased incidence of metabolic syndrome was noted within the ring chromosome subgroup.ConclusionsKaryotype may play an important factor against stratifying risk of comorbidity in TS and should be taken into consideration when managing adults with TS. Further investigations of the isochromosome (Xq) and ring groups are necessary to further clarify their associations with comorbidities.
Incidence of parathyroid disorders in Indian adult male population: A 25‐year follow‐up study
Authors: Hari Kumar K.V.S. , Patnaik S.K. 
Published: June 2017

SummaryContext and objectiveDetailed information on the epidemiology of parathyroid disorders in India is lacking. Most of the available data pertain to primary hyperparathyroidism (PHPT) rather than the overall burden of parathyroid disorders. We studied the incidence of parathyroid disorders in a cohort of service personnel followed for a long duration.Design, setting and patients:The data for this retrospective, descriptive epidemiological study were derived from the electronic medical records (EMR) of health care personnel enrolled between 1990 and 2015. Subjects were recruited between the ages of 17 and 20 years in good health, and the data pertaining to parathyroid disorders were derived from the EMR.Main outcomes measuresWe calculated the incidence rates per person‐years of parathyroid disorders using appropriate statistical methods.ResultsOur analysis includes 51 217 participants (median age 33, range 17‐54 years) with a mean follow‐up of 12.5 years. Yearly evaluation of the data gave cumulative follow‐up duration of 613 925 person‐years. PHPT was diagnosed in 37 patients and hypoparathyroidism in 16 patients, giving incidence rates of 6 and 2.6 per 100 000 person‐years, respectively. Only one patient was diagnosed with pseudohypoparathyroidism (0.16 per 100 000 person‐years). Of the 37 patients with PHPT, 16 (43%) developed postsurgical hypoparathyroidism.ConclusionsOur cohort had a low incidence of PHPT when compared to Western populations. Long‐term epidemiological studies are essential to identify the demographic trends of metabolic bone disorders in India.
SAV1 represses the development of human colorectal cancer by regulating the Akt‐mTOR pathway in a YAP‐dependent manner
Authors: Jiang Jianwu , Chang Wei , Fu Yang , Gao Yongshun , Zhao Chunlin , Zhang Xiefu , Zhang Shuijun 
Published: June 2017

AbstractObjectivesSAV1 is a human homologue of Salvador that contains two protein‐protein interaction modules known as WW domains and acts as a scaffolding protein. SAV1 participates in the development of diverse types of cancer. We aimed to investigate the role of SAV1 in human colorectal cancer.Materials and methodsHuman colorectal cancer samples were used to study the expression of SAV1 and YAP. Loss‐of‐function and gain‐of‐function strategies were used to study the effects of SAV1 on colorectal cancer cell growth. Rapamycin was used to treat cells and mice to investigate the effect of mTOR signalling.ResultsSAV1 represses the development of colorectal cancer by inhibiting the Akt‐mTOR signalling in a YAP‐dependent manner. The mRNA and protein levels of SAV1 are down‐regulated in human colorectal cancer tissues compared with adjacent non‐cancer tissues. SAV1 knockdown promotes the growth of colorectal cancer cells in vitro and in vivo, whereas SAV1 overexpression leads to opposing results. SAV1 represses the activation of the Akt‐mTOR signalling, and rapamycin treatment blunts the effects of SAV1 on in vitro and in vivo growth of colorectal cancer cells. Finally, we show that SAV1 promotes the phosphorylation and inactivation of YAP, which contributes to the effect of SAV1 on Akt‐mTOR signalling pathway.ConclusionsSAV1 is a repressor during the development of human colorectal cancer by inhibiting the YAP‐Akt‐mTOR signalling pathway.
Tiger abundance and gene flow in Central India are driven by disparate combinations of topography and land cover
Authors: Reddy P. Anuradha , Cushman Samuel A. , Srivastava Ankita , Sarkar Mriganka Shekhar , Shivaji Sisinthy 
Published: June 2017

AbstractAimEffective conservation of the endangered tiger depends upon reliable knowledge of factors driving genetic differentiation and population connectivity. Connectivity models frequently use resistance surfaces not optimized with actual movement or genetic data which limits reliability. Our aim is to use empirical data on genetic diversity of tiger populations to optimize landscape resistance to gene flow and identify factors that predict local population abundance across Central India.LocationThe study area covers 697,000 km2 across Madhya Pradesh and parts of Rajasthan, Jharkhand and Maharashtra.MethodsWe used genetic data of 309 tigers and restricted multivariate optimization of correlation between landscape variables and genetic distance in a reciprocal causal modelling framework to parameterize a resistance surface for gene flow. We further evaluated the association between effective population size and landscape connectivity using all‐subsets logistic regression with model averaging based on AICc.ResultsGene flow is primarily related to topographic roughness and slope position and secondarily to human footprint and land cover. It is much higher in areas of rough topography and ridge tops and is facilitated by forest cover in areas with low human footprint. In contrast, effective population size in protected areas is primarily driven by extent of protected areas and surrounding forest cover, and is not significantly related to resistant kernel connectivity value.Main ConclusionsThis is the first study to use a rigorous multivariate optimization approach to identify factors which limit gene flow of tigers. Tiger movement is highly affected by landscape features, and dispersing tigers move through rough terrain along forested ridges, avoiding non‐forest areas with high human footprint, while local tiger population density is driven primarily by the extent of protected forested habitat. These results have important implications for tiger conservation and can be used to develop empirically supported prioritization of core areas and corridors.
Losing concentration? Lessons from a Swedish aid policy reform
Authors: Hagen Rune Jansen 
Published: June 2017

AbstractSweden is one of the donor countries that signed up for the Paris Agenda, which among other things advocated reducing aid dispersion. It also adopted its own geographical concentration policy in 2007. My empirical analysis shows that Sweden managed to achieve this goal only for two years following the reform and that this was followed by backsliding. Moreover, its current aid policy framework barely mentions the topic. I argue that a major reason was the failure to institutionalize the policy. This left it vulnerable to the regular politics of aid, which tend to generate both geographic and thematic spread. Reduced peer pressure, as the international community has moved away from the Paris Agenda, might also have contributed.
BCRP mRNA and FLT3‐ITD are independent poor risk factors in adult patients with acute myeloid leukemia and intermediate or normal karyotype
Authors: Nasiłowska‐Adamska Barbara , Warzocha Krzysztof , Solarska Iwona , Borg Katarzyna , Pieńkowska‐Grela Barbara , Czyż Anna 
Published: June 2017

AbstractPurposeFMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) is aberration associated with poor prognosis in AML. We have analyzed the expression of MDR‐1, MRP‐1, and BCRP mRNA in relation to FLT3‐ITD in 100 AML adult patients with normal and intermediate karyotype.MethodsThe RQ‐PCR method was performed to assess the expression of MDR‐1, MRP‐1, and BCRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule.ResultsAccording to univariate analysis, the following pretreatment variables negatively influenced disease‐free survival (DFS): WBC count ≥25×109/L (P=.037), MRP‐1 mRNA ≥1.6818 (P=.028), BCRP mRNA ≥1.1892 (P=.004), FLT3‐ITD (P=.005) and overall survival (OS): WBC count ≥25×109/L (P=.031), MRP‐1 mRNA ≥1.6818 (P=.01), BCRP mRNA ≥1.1892 (P=.01), FLT3‐ITD (P=.001). When all prognostic variables were pooled into a multivariate model, we found that WBC count ≥25×109/L (P=.026) and BCRP mRNA ≥1.1892 (P=.011). We observed trend in negative influence of FLT3‐ITD on DFS (P=.057). BCRP mRNA ≥1.1892 (P=.035) and FLT3‐ITD (P=.006) negatively, independently influenced the OS.ConclusionsThe high expressions of BCRP mRNA calculated with Pfaffl's rule and FLT3‐ITD are independent poor risk factors in adult patients with AML and intermediate or normal karyotype.
ABCG2 and CD200 define patients at high risk of relapse in ELN favorable subgroup of AML
Authors: Tiribelli Mario , Geromin Antonella , Cavallin Margherita , Di Giusto Sara , Simeone Erica , Fanin Renato , Damiani Daniela 
Published: June 2017

AbstractObjectiveOverexpression of ABCG2 and CD200 has been independently associated with poor outcome in acute myeloid leukemia (AML). However, no data are available on the role of these two factors in patients with core‐binding factor (CBF)‐positive or FLT3‐negative/NPM1‐mutated cytogenetically normal (CN) AML.MethodsWe analyzed 65 adult AML patients with CBF+ (n=16) or FLT3−/NPM1+ CN (n=49), evaluating clinical and biological factors associated with complete remission attainment, leukemia‐free survival (LFS) and overall survival (OS).ResultsABCG2 was expressed in 36 (55%) cases, and CD200 was positive in 33 (51%) cases, six at high levels. Both ABCG2 and CD200 positivity have a negative impact on relapse risk: 3‐year LFS was 51% vs 82% in ABCG2+ cases (RR 3.3), 49% vs 82% in CD200+ patients (RR=4.4), and 25% in CD200− high cases (RR=17.1). ABCG2 and CD200 affected also OS with 3‐year OS of 39% in ABCG2+ (compared to 71% in ABCG2−; RR=2.6) and CD200+ (compared to 68% in CD200−; RR=2.5) patients.ConclusionsOur data confirm a negative impact of ABCG2 and CD200 overexpression also in AML patients considered at favorable risk according to ELN cytogenetic/molecular classification.
Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open‐label clinical study with cannabidiol
Authors: Rosenberg Evan C. , Louik Jay , Conway Erin , Devinsky Orrin , Friedman Daniel 
Published: June 2017

SummaryRecent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment‐resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver‐reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open‐label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9‐point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure‐reducing effects; however, further studies in placebo‐controlled, double‐blind trials are necessary to confirm this finding.