bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bayesian modeling of multiple structural connectivity networks during the progression of Alzheimer's disease
Authors: Peterson Christine B. , Osborne Nathan , Stingo Francesco C. , Bourgeat Pierrick , Doecke James D. , Vannucci Marina 
Published: February 2020

AbstractAlzheimer's disease is the most common neurodegenerative disease. The aim of this study is to infer structural changes in brain connectivity resulting from disease progression using cortical thickness measurements from a cohort of participants who were either healthy control, or with mild cognitive impairment, or Alzheimer's disease patients. For this purpose, we develop a novel approach for inference of multiple networks with related edge values across groups. Specifically, we infer a Gaussian graphical model for each group within a joint framework, where we rely on Bayesian hierarchical priors to link the precision matrix entries across groups. Our proposal differs from existing approaches in that it flexibly learns which groups have the most similar edge values, and accounts for the strength of connection (rather than only edge presence or absence) when sharing information across groups. Our results identify key alterations in structural connectivity that may reflect disruptions to the healthy brain, such as decreased connectivity within the occipital lobe with increasing disease severity. We also illustrate the proposed method through simulations, where we demonstrate its performance in structure learning and precision matrix estimation with respect to alternative approaches.
A comparative analysis of fibroblast growth factor receptor signalling during Xenopus development
Authors: Brunsdon Hannah , Isaacs Harry V. 
Published: February 2020

Background InformationThe fibroblast growth factor (FGF) signalling system of vertebrates is complex. In common with other vertebrates, secreted FGF ligands of the amphibian Xenopus signal through a family of four FGF receptor tyrosine kinases (fgfr1, 2, 3 and 4). A wealth of previous studies has demonstrated important roles for FGF signalling in regulating gene expression during cell lineage specification in amphibian development. In particular, FGFs have well‐established roles in regulating mesoderm formation, neural induction and patterning of the anteroposterior axis. However, relatively little is known regarding the role of individual FGFRs in regulating FGF‐dependent processes in amphibian development. In this study we make use of synthetic drug inducible versions of Xenopus Fgfr1, 2 and 4 (iFgfr1, 2 and 4) to undertake a comparative analysis of their activities in the tissues of the developing embryo.ResultsWe find that Xenopus Fgfr1 and 2 have very similar activities. Both Fgfr1 and Fgfr2 are potent activators of MAP kinase ERK signalling, and when activated in the embryo during gastrula stages regulate similar cohorts of transcriptional targets. In contrast, Fgfr4 signalling in naïve ectoderm and neuralised ectoderm activates ERK signalling only weakly compared to Fgfr1/2. Furthermore, our analyses indicate that in Xenopus neural tissue the Fgfr4 regulated transcriptome is very different from that of Fgfr1.Conclusion and significanceWe conclude that signalling downstream of Fgfr1 and 2 regulates similar processes in amphibian development. Interestingly, many of the previously identified canonical transcriptional targets of FGF regulation associated with germ layer specification and patterning are regulated by Fgfr1/Fgfr2 signalling. In contrast, the downstream consequences of Fgfr4 signalling are different, although roles for Fgfr4 signalling in lineage specification and anteroposterior patterning are also indicated.
The Role of Executive Functions in Socioeconomic Attainment Gaps: Results From a Randomized Controlled Trial
Authors: Blakey Emma , Matthews Danielle , Cragg Lucy , Buck Jessica , Cameron David , Higgins Ben , Pepper Lisa , Ridley Ellen , Sullivan Emma , Carroll Daniel J. 
Published: February 2020

AbstractThe socioeconomic attainment gap in mathematics starts early and increases over time. This study aimed to examine why this gap exists. Four‐year‐olds from diverse backgrounds were randomly allocated to a brief intervention designed to improve executive functions (N = 87) or to an active control group (N = 88). The study was preregistered and followed CONSORT guidelines. Executive functions and mathematical skills were measured at baseline, 1 week, 3 months, 6 months, and 1 year posttraining. Executive functions mediated the relation between socioeconomic status and mathematical skills. Children improved over training, but this did not transfer to untrained executive functions or mathematics. Executive functions may explain socioeconomic attainment gaps, but cognitive training directly targeting executive functions is not an effective way to narrow this gap.
Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes
Authors: Quandt Z , Young A , Anderson M 
Published: February 2020

Summary
Autoimmune diabetes mellitus is a rare but significant side effect of treatment with immune checkpoint inhibitors. Immune checkpoint inhibitor-induced diabetes mellitus (CPI-DM) is characterized by acute onset of dramatic hyperglycemia with severe insulin deficiency and occurrence following exposure to programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors rather than cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors. As a growing number of patients undergo immunotherapy, further understanding of the characteristics of CPI-DM patients is needed for improved prognostic and diagnostic application in order to reduce overall morbidity for this already at-risk population. Additionally, understanding of the features and mechanisms of CPI-DM may contribute to understanding mechanisms of spontaneous type I diabetes mellitus (T1DM). Here, we summarize the clinical features of CPI-DM and interrogate the genetic and cellular mechanisms that may contribute to the disease, as well as the clinical challenges for predicting and treating these patients as increasing cancer immunotherapies reach clinical utility.
Effect of high glucose levels and lipopolysaccharides‐induced inflammation on osteoblast mineralization over sandblasted/acid‐etched titanium surface
Authors: Ramenzoni Liza L. , Bösch Adrian , Proksch Susanne , Attin Thomas , Schmidlin Patrick R. 
Published: February 2020

AbstractBackground and PurposePoorly controlled diabetes mellitus has been related to higher risk of implant treatment complications due to increased susceptibility to infection and delayed wound healing. Lipopolysaccharides (LPS) stimulate cytokine production leading to chronic inflammation and immunological host response that accentuates the destruction of periodontal tissues. This study aimed to evaluate the effect of different glycemic conditions on secretion and mineralization of bone matrix under sterile inflammation induced by LPS on osteoblasts seeded over sandblasted/acid‐etched (SLA) titanium surface.Materials and MethodsOsteoblast cell viability was performed to determine the influence of different glucose concentrations (5.5, 8, 12, and 24 mM), which were chosen to reflect normal, postprandial, and high glucose values, similar to those typically seen in Diabetes mellitus under clinical conditions. Cells were seeded on titanium SLA discs (Straumann AG, Waldenburg, Switzerland) and exposed to glucose concentrations and LPS (1μg/mL) in order to test inflammatory response (qPCR) and mineralization (Alizarin Red staining).ResultsOsteoblast viability was severely decreased when exposed to higher glucose levels (≥12 mM) and LPS (P < .05) compared to control. When the osteoblasts were exposed to LPS and glucose at ≥8 mM, the gene transcripts of inflammatory cytokines were ≈2.5‐fold upregulated, while ≤8 mM glucose elicited no significant change compared to control without glucose treatment (P > .05). Osteoblasts exposed to LPS produced sparse extracellular matrix mineralization, especially combined with higher glucose values (≥12 mM), together with decreased calcium deposition compared to control (P < .05).ConclusionsHigh glucose levels combined with LPS inflammatory stimulation elicited an adverse effect on the volume and quality of mineralized hard tissue formation on SLA titanium surfaces in vitro. Hence, both normal glucose levels and infection control including low levels of circulating LPS during initial osseointegration period may be required to increase the success rate of dental implants.
Multiple chemical sensitivity (MCS) – a guide for dermatologists on how to manage affected individuals
Authors: Harter Katharina , Hammel Gertrud , Fleming Megan , Traidl‐Hoffmann Claudia 
Published: February 2020

SummaryMultiple chemical sensitivity (MCS) is a condition characterized by a subjectively perceived increase in sensitivity to environmental chemicals. Individuals affected report a wide variety of nonspecific complaints, and frequently attribute cutaneous and mucosal symptoms to chemical exposures. Dermatologists should therefore be familiar with this condition. MCS is a diagnosis of exclusion. Other causes for the patients’ symptoms should be ruled out by routine laboratory tests, allergy tests and, if indicated, monitoring for toxic (environmental) substances. The primary job of dermatologists is to rule out skin diseases or hypersensitivities as possible causes of the complaints. Interdisciplinary patient management is essential, especially in severe cases in which those affected have problems coping with everyday life. Relevant specialties in this context include environmental medicine, psychosomatic medicine as well as occupational and social medicine. Cutaneous symptoms are usually addressed with symptomatic treatment using basic skin care products. There are currently no evidence‐based treatment recommendations for MCS. It is crucial that MCS patients be protected from unnecessary treatments and thus from mental, social and financial strain. In addition to medical skills, managing MCS patients requires communicative and psychosocial competence in particular. Physicians involved in the treatment will benefit from training in psychotherapy. Irrespective of the mechanisms that lead to MCS, diagnosis and treatment of this condition require an actively supportive attitude towards these patients, a good doctor‐patient relationship and interdisciplinary cooperation.
The effect of dapagliflozin on apolipoprotein B and glucose fluxes in patients with type 2 diabetes and well‐controlled plasma LDL cholesterol
Authors: Bouter Kristien E. C. , van Bommel Erik J. M. , Jansen Hans , van Harskamp Dewi , Schierbeek Henk , Ackermans Mariëtte T. , Serlie Mireille J. , Schimmel Alinda W. M. , Nieuwdorp Max , Dallinga‐Thie Geesje M. , van Raalte Daniël H. 
Published: February 2020

AbstractAimTo dissect the effects of the sodium‐glucose linked transporter 2 inhibitor dapagliflozin on lipid metabolism and assess whether these effects could potentially offset cardiovascular benefit with this drug‐class.Materials and MethodsWe assessed the effect of dapagliflozin on lipid metabolism in 11 adults with uncomplicated type 2 diabetes. After 4 weeks of statin wash‐out and 4 weeks of rosuvastatin 10 mg treatment, participants were treated with dapagliflozin 10 mg once‐daily for 5 weeks. Before and after dapagliflozin, plasma lipids were measured and very low‐density lipoprotein (VLDL)‐1 and VLDL‐2 apolipoprotein (Apo)B fluxes were assessed using (5.5.5‐2H3)‐leucine tracer infusion. In addition, hepatic and peripheral insulin sensitivity as well as insulin‐mediated inhibition of peripheral lipolysis were measured during a two‐step hyperinsulinemic‐euglycaemic clamp using (6,6‐2H2)‐glucose and (1,1,2,3,3‐2H5)‐glycerol tracers.ResultsRosuvastatin decreased all plasma lipids significantly: total cholesterol from 4.5 (3.2–6.2) to 3.1 (2.5–3.8) mmol/L, LDL cholesterol from 2.6 (1.7–3.4) to 1.5 (1.1–2.2) mmol/L, HDL cholesterol from 1.34 (0.80–2.02) to 1.19 (0.74–1.89) mmol/L and triglycerides from 0.92 (0.31–3.91) to 0.79 (0.32–2.10) mmol/L. The addition of dapaglifozin to rosuvastatin did not raise either LDL cholesterol or total cholesterol, and only increased HDL cholesterol by 0.08 (−0.03–0.13) mmol/L (P = 0.03). In line with this, dapagliflozin did not affect VLDL‐1 or VLDL‐2 ApoB fluxes. Fasting endogenous glucose production tended to increase by 0.9 (−3.4–3.1) μmol kg−1 min−1 (P = 0.06), but no effect on hepatic and peripheral insulin sensitivity or on peripheral lipolysis was observed.ConclusionsDapagliflozin has no effect on plasma LDL‐cholesterol levels or VLDL‐apoB fluxes in the context of optimal lipid‐lowering treatment, which will thus not limit cardiovascular benefit when lipids are adequately controlled.
Development and topographic organization of subicular projections to lateral septum in the rat brain
Authors: Tsamis Konstantinos I. , Lagartos Donato Maria J. , Dahl Annelene G. , O'Reilly Kally C. , Witter Menno P. 
Published: February 2020

AbstractOne of the main subcortical targets of hippocampal formation efferents is the lateral septum. Previous studies on the subicular projections, as a main output structure of the hippocampus, have shown a clear topographic organization of septal innervation, related to the origin of the fibres along the dorsoventral axis of the subiculum in the adult brain. In contrast, studies on the developing brain depict an extensive rearrangement of subicular projections during the prenatal period, shifting from the medial septum to the lateral septum. Our study aimed to describe the postnatal development of subicular projections to the septum. We injected anterograde tracers into the subiculum of 57 pups of different postnatal ages. Injections covered the proximodistal and dorsoventral axis of the subiculum. The age of the pups at day of tracer injection ranged from the day of birth to postnatal day 30. Analyses revealed that from the first postnatal day projections from subiculum preferentially target the lateral septum. Sparse innervation in the lateral septum was already present in the first few postnatal days, and during the following 3 weeks, the axonal distribution gradually expanded. Subicular projections to the lateral septum are topographically organized depending on the origin along the dorsoventral axis of the subiculum, in line with the adult innervation pattern. Different origins along the proximodistal axis of the subiculum are reflected in changes in the strength of septal innervation. The findings demonstrate that in case of the development of subicular projections, axonal expansion is more prominent than axonal pruning.
Retinal ON and OFF pathways contribute to initial optokinetic responses with different temporal characteristics
Authors: Sugita Yuko , Miura Kenichiro , Furukawa Takahisa 
Published: February 2020

AbstractVisual information in the retina is processed via two pathways: ON and OFF pathways that originate from ON and OFF bipolar cells. The differences in the receptors that mediate signal transmission from photoreceptors imply that the response speed to light signals differs between ON and OFF pathways. We studied the initial optokinetic responses (OKRs) of mice using two‐frame motion stimuli presented with interstimulus intervals (ISIs) to understand functional difference of these pathways. When two successive image frames were presented with an ISI, observers often perceived motion in the opposite direction of the actual shift. This directional reversal results from the biphasic nature of the temporal filters in visual systems whose characteristics can be estimated from the dependence on ISIs. We examined the dependence on ISIs in the OKRs of TRPM1−/− mice, whose ON bipolar cells are dysfunctional, as well as in those of wild‐type control mice. Wild type and TRPM1−/− mice showed comparable OKRs in the veridical direction when no ISI was present. Both types of mice showed OKRs that decreased and eventually reversed as the ISI increased, but with a directional reversal at a shorter ISI in TRPM1−/− than wild‐type mice. In addition, the temporal filters of TRPM1−/− mice estimated from dependence on ISIs were tuned for higher frequencies, suggesting that compared with wild‐type mice, the visual system of TRPM1−/− mice responds to light signals with faster dynamics. We conclude that the ON and OFF pathways contribute to initial OKRs by providing visual signals processed with different temporal resolutions.
In transition: Avian biogeographic responses to a century of climate change across desert biomes
Authors: Iknayan Kelly J. , Beissinger Steven R. 
Published: February 2020

AbstractTransition zones between biomes, also known as ecotones, are areas of pronounced ecological change. They are primarily maintained by abiotic factors and disturbance regimes that could hinder or promote species range shifts in response to climate change. We evaluated how climate change has affected metacommunity dynamics in two adjacent biomes and across their ecotone by resurveying 106 sites that were originally surveyed for avian diversity in the early 20th century by Joseph Grinnell and colleagues. The Mojave, a warm desert, and the Great Basin, a cold desert, have distinct assemblages and meet along a contiguous, east–west boundary. Both deserts substantially warmed over the past century, but the Mojave dried while the Great Basin became wetter. We examined whether the distinctiveness and composition of desert avifaunas have changed, if species distributions shifted, and how the transition zone impacted turnover patterns. Avifauna change was characterized by (a) reduced occupancy, range contractions, and idiosyncratic species redistributions; (b) degradation of historic community structure, and increased taxonomic and climatic differentiation of the species inhabiting the two deserts; and (c) high levels of turnover at the transition zone but little range expansion of species from the warm, dry Mojave into the cooler, wetter Great Basin. Although both deserts now support more drier and warmer tolerant species, their bird communities still occupy distinct climatological space and differ significantly in climatic composition. Our results suggest a persistent transition zone between biomes contributes to limiting the redistribution of birds, and highlight the importance of understanding how transition zone dynamics impact responses to climate change.
The effect of vehicle on skin absorption of Mg2+ and Ca2+ from thermal spring water
Authors: Tarnowska M. , Briançon S. , Resende de Azevedo J. , Chevalier Y. , Arquier D. , Barratier C. , Bolzinger M.‐A. 
Published: February 2020

AbstractObjectiveThermal spring waters (TSW) are commonly used as active ingredients in cosmetics. Their biological activities directly depend on the ionic composition of the spring. However, in order to exhibit beneficial properties, the minerals need to reach viable skin layers. The present study addresses the incorporation of marketed TSW in model cosmetic formulations and the impact of the formulation on skin absorption of magnesium and calcium ions that are known to improve skin barrier function.MethodsMarketed TSW was introduced into five formulations. Liposomes were prepared using saturated or unsaturated phospholipids mixed with cholesterol by the thin layer evaporation technique. Emulsions water‐in‐oil (W/O), oil‐in‐water (O/W) or double: water‐in‐oil‐in‐water (W/O/W) were prepared by high‐shear mixing. Skin absorption of Mg2+ and Ca2+ from those formulations was studied in vitro using static Franz diffusion cells under infinite dose condition and under occlusion of the apparatus.ResultsMg2+ and Ca2+ penetrate skin samples from TSW. Encapsulating TSW into double emulsion (TSW/O/W) increased skin absorption of both cations of interest and kept the Ca2+/Mg2+ ratio equal to that of TSW in each skin layer. The dermal absorption of Mg2+ from the double emulsion departs from both single emulsions. Application of liposome suspension improved the skin absorption of Ca2+ while keeping constant that of Mg2+, leading to unbalanced Ca2+/Mg2+ ratio inside skin.ConclusionThe beneficial effects of TSW are not only due to their action on the skin surface. Their active components, especially Ca2+ and Mg2+ cations, reach viable skin layers in a formulation‐dependent manner. The distribution of ions inside skin depends on the type of formulation.
Effect of the sintering temperature on microstructure and properties of Al2O3–Cu–Ni hybrid composites obtained by PPS
Authors: Zygmuntowicz Justyna , Falkowski Paweł , Wachowski Marcin , Cymerman Konrad , Piotrkiewicz Paulina , Kaszuwara Waldemar 
Published: February 2020

AbstractIn the present research, the influence of sintering temperature on the microstructure and properties of Al2O3–Cu–Ni hybrid composites prepared by the Pulse Plasma Sintering (PPS) technique were described. In this research, three temperatures have been selected: 1250°C, 1300°C, and 1350°C. SEM observations were carried out to determine the distribution of the metallic phase in the composite depending on the sintering temperature. The conducted experiments and microscopic observations enabled a better understanding of the phenomena occurring between the ceramic matrix and metallic phase in the obtained materials. The mechanical properties like a hardness and fracture toughness were measured. The technology applied allowed us to obtain ceramic‐metal composites with a homogeneous microstructure. It was found that the sintering temperature influences the selected physical and mechanical properties of the composites produced. It was found that samples produced at 1300°C are characterized by the highest relative density and the mechanical properties.
DNA methylation‐mediated Siglec‐7 regulation in natural killer cells via two 5′ promoter CpG sites
Authors: Huang Hsin‐Ting , Su Shih‐Chi , Chiou Tzeon‐Jye , Lin Yen‐Hsi , Shih Yi‐Chen , Wu Yu‐Xuan , Fan Ting‐Hsi , Twu Yuh‐Ching 
Published: February 2020

SummaryFirst discovered on the natural killer (NK) cell, the cell surface inhibitory receptor sialic acid‐binding immunoglobulin‐like lectin‐7 (Siglec‐7) is known for regulating many important biological activities. However, the detail regulatory mechanism for Siglec‐7 expression in NK cells currently remains unclear. In this study, we aimed to investigate how cell surface Siglec‐7 expression is regulated and found that, in both NK cell lines and peripheral NK cells, transcription was the main regulatory step. Furthermore, when NK‐92MI and peripheral NK cells were treated with DNA methyltransferase (DNMT) inhibitor, the CpG island, with 9 CpG sites, in 5′ Siglec‐7 promoter became noticeably hypomethylated, and Siglec‐7 expression increased in both RNA transcript and surface protein. Within this CpG island, we identified both CpG 8 and CpG 9 as two key regulators responsible for Siglec‐7 expression. Additionally, by using histone deacetylases (HDAC) inhibitor, butyric acid, we showed that Siglec‐7 expression was also subjected to the histone modification. And a combined treatment with both 5‐azacytidine and butyric acid showed an additive effect on Siglec‐7 transcript expression in peripheral NK cells.