bluuebunny/crossref_metadata_2025_split huggingface dataset:
Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes
Authors: Iram Tal , Ramirez-Ortiz Zaida , Byrne Michael H. , Coleman Uwanda A. , Kingery Nathan D. , Means Terry K. , Frenkel Dan , El Khoury Joseph 
Published: May 2016

Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) expressed on astrocytes and myosatellite cells, and recessive mutations in humans result in early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD). Here we report that Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytesex vivo. We also report that cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons and that Megf10 binds with high affinity to C1q, an eat-me signal for apoptotic cells. In contrast, cells expressing Megf10 with EMARDD mutations have impaired apoptotic cell clearance and impaired binding to C1q. Our studies reveal that Megf10 is a receptor for C1q and identify a novel role for Megf10 in clearance of apoptotic cells in the mammalian developing brain with potential relevance to EMARDD patients and other CNS disorders.SIGNIFICANCE STATEMENTApoptosis is a universal homeostatic process and occurs in many disease conditions. Multiple EGF-like domains 10 (Megf10) is emerging as an essential receptor for synaptic pruning, clearance of neuronal debris, and for muscle differentiation. Here we define a novel Megf10-dependent pathway for apoptotic cell clearance and show that Megf10 is a receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the surface of apoptotic cells. Understanding the pathways by which apoptotic cells are cleared in the CNS is relevant to many physiological and pathological conditions of the CNS.
Selectivity of Neuromodulatory Projections from the Basal Forebrain and Locus Ceruleus to Primary Sensory Cortices
Authors: Kim Jae-Hyun , Jung A-Hyun , Jeong Daun , Choi Ilsong , Kim Kwansoo , Shin Soowon , Kim Sung June , Lee Seung-Hee 
Published: May 2016

Acetylcholine and noradrenaline are major neuromodulators that affect sensory processing in the cortex. Modality-specific sensory information is processed in defined areas of the cortex, but it is unclear whether cholinergic neurons in the basal forebrain (BF) and noradrenergic neurons in the locus ceruleus (LC) project to and modulate these areas in a sensory modality-selective manner. Here, we mapped BF and LC projections to different sensory cortices of the mouse using dual retrograde tracing. We found that while the innervation of cholinergic neurons into sensory cortices is predominantly modality specific, the projections of noradrenergic neurons diverge onto multiple sensory cortices. Consistent with this anatomy, optogenetic activation of cholinergic neurons in BF subnuclei induces modality-selective desynchronization in specific sensory cortices, whereas activation of noradrenergic LC neurons induces broad desynchronization throughout multiple sensory cortices. Thus, we demonstrate a clear distinction in the organization and function of cholinergic BF and noradrenergic LC projections into primary sensory cortices: cholinergic BF neurons are highly selective in their projections and modulation of specific sensory cortices, whereas noradrenergic LC neurons broadly innervate and modulate multiple sensory cortices.SIGNIFICANCE STATEMENTNeuromodulatory inputs from the basal forebrain (BF) and locus ceruleus (LC) are widespread in the mammalian cerebral cortex and are known to play important roles in attention and arousal, but little is known about the selectivity of their cortical projections. Using a dual retrobead tracing technique along with optogenetic stimulation, we have identified anatomic and functional differences in the way cholinergic BF neurons and noradrenergic LC neurons project into primary sensory cortices. While BF projections are highly selective to individual sensory cortices, LC projections diverge into multiple sensory cortices. To our knowledge, this is the first definitive proof that BF and LC projections to primary sensory cortices show both anatomic and functional differences in selectivity for modulating cortical activity.
Transcranial Random Noise Stimulation of Visual Cortex: Stochastic Resonance Enhances Central Mechanisms of Perception
Authors: van der Groen Onno , Wenderoth Nicole 
Published: May 2016

Random noise enhances the detectability of weak signals in nonlinear systems, a phenomenon known as stochastic resonance (SR). Though counterintuitive at first, SR has been demonstrated in a variety of naturally occurring processes, including human perception, where it has been shown that adding noise directly to weak visual, tactile, or auditory stimuli enhances detection performance. These results indicate that random noise can push subthreshold receptor potentials across the transfer threshold, causing action potentials in an otherwise silent afference. Despite the wealth of evidence demonstrating SR for noise added to a stimulus, relatively few studies have explored whether or not noise added directly to cortical networks enhances sensory detection. Here we administered transcranial random noise stimulation (tRNS; 100–640 Hz zero-mean Gaussian white noise) to the occipital region of human participants. For increasing tRNS intensities (ranging from 0 to 1.5 mA), the detection accuracy of a visual stimuli changed according to an inverted-U-shaped function, typical of the SR phenomenon. When the optimal level of noise was added to visual cortex, detection performance improved significantly relative to a zero noise condition (9.7 ± 4.6%) and to a similar extent as optimal noise added to the visual stimuli (11.2 ± 4.7%). Our results demonstrate that adding noise to cortical networks can improve human behavior and that tRNS is an appropriate tool to exploit this mechanism.SIGNIFICANCE STATEMENTOur findings suggest that neural processing at the network level exhibits nonlinear system properties that are sensitive to the stochastic resonance phenomenon and highlight the usefulness of tRNS as a tool to modulate human behavior. Since tRNS can be applied to all cortical areas, exploiting the SR phenomenon is not restricted to the perceptual domain, but can be used for other functions that depend on nonlinear neural dynamics (e.g., decision making, task switching, response inhibition, and many other processes). This will open new avenues for using tRNS to investigate brain function and enhance the behavior of healthy individuals or patients.
High prevalence of abdominal aortic calcification in patients with primary hyperparathyroidism as evaluated by Kauppila score
Authors: Pepe Jessica , Diacinti Daniele , Fratini Emanuela , Nofroni Italo , D’Angelo Antonella , Pilotto Roberta , Savoriti Claudio , Colangelo Luciano , Raimo Orlando , Cilli Mirella , Cipriani Cristiana , Minisola Salvatore 
Published: May 2016

ObjectiveThe prevalence of abdominal aortic calcification (AAC) in primary hyperparathyroidism (PHPT) is unknown. We assessed both prevalence and severity of AAC in PHPT postmenopausal women.MethodsIn this study 70 PHPT postmenopausal women and 70 age- and sex-matched controls were enrolled. Each participant underwent biochemical evaluation, lateral spine radiograph, bone mineral density (BMD) measurement (lumbar, femoral, radial sites), and kidney ultrasound. Lateral lumbar films were analyzed in the region of L1–L4 vertebrae and the Kauppila score (a semi-quantitative grading system) was used to assess the severity of AAC.ResultsThere were no differences regarding demographic and cardiovascular risk factors in the two groups. PHPT patients had higher prevalence of kidney stones (30% vs 7%,P=0.0008) and lower radial BMD values (0.558±0.071 vs 0.588±0.082 g/cm2,P<0.05) compared with controls. PHPT patients showed higher prevalence of AAC (31 vs 18,P=0.03), with more severe calcifications (Kauppila score 7.35±6.1 vs 5.05±3.5,P=0.007). PHPT patients with AAC were older and had been suffering from the disease for a longer period compared with those without ACC. Moreover, PHPT patients with severe AAC had mean higher serum parathyroid hormone levels compared with patients with moderate or mild calcifications. In PHPT patients with AAC, multiple regression analysis, adjusted for age and years since diagnosis, showed that only parathyroid hormone significantly correlated with Kauppila score.ConclusionWe found a higher prevalence and severity of AAC in PHPT related to parathyroid hormone effect.
Double adrenocortical adenomas harboring independent KCNJ5 and PRKACA somatic mutations
Authors: Nanba Kazutaka , Omata Kei , Tomlins Scott A , Giordano Thomas J , Hammer Gary D , Rainey William E , Else Tobias 
Published: May 2016

Objective
Co-secretion of cortisol and aldosterone can be observed in adrenal adenomas. The aim of this study was to investigate the molecular characteristics of a co-existing aldosterone- and a cortisol-producing adenoma (CPA) in the same patient.

Design and methods
Two different adenomas within the same adrenal gland from a 49-year-old female patient with primary aldosteronism (PA) and Cushing's syndrome (CS) were studied. Multiple formalin-fixed paraffin-embedded tumor blocks were used for the analysis. Immunohistochemistry (IHC) was performed using a specific antibody against aldosterone synthase (CYP11B2). DNA and RNA were isolated separately from CYP11B2-positive and -negative tumor regions based on CYP11B2 IHC results.

Results
CYP11B2 IHC clearly demonstrated that three pieces from one adenoma were positive for CYP11B2 and the remaining three from the other adenoma were negative for CYP11B2. In quantitative real-time RT-PCR, CYP11B2 mRNA was upregulated in CYP11B2-positive tumor specimens (219-fold vs CYP11B2-negative tumor specimens). Targeted next-generation sequencing (NGS) detected novel KCNJ5 gene mutations (p.T148I/T149S, present in the same reads) and a PRKACA gene hotspot mutation (p.L206R) in the CYP11B2-positive and -negative tumors, respectively. Sanger sequencing of DNA from each tumor specimen (CYP11B2-positive tumor, n=3; CYP11B2-negative tumor, n=3) showed concordant results with targeted NGS.

Conclusion
Our findings illustrate the co-existence of two different adrenocortical adenomas causing the concurrent diagnosis of PA and CS in the same patient. Molecular analysis was able to demonstrate that the two diseases resulted from independent somatic mutations seen in double adrenocortical adenomas.
Breastfeeding and Risk of Kawasaki Disease: A Nationwide Longitudinal Survey in Japan
Authors: Yorifuji Takashi , Tsukahara Hirokazu , Doi Hiroyuki 
Published: May 2016

BACKGROUND AND OBJECTIVES:Kawasaki disease (KD) is the most common cause of childhood-acquired heart disease in developed countries. However, the etiology of KD is not known. Aberrant immune responses are considered to play key roles in disease initiation and breastfeeding can mature immune system in infants. We thus examined the association between breastfeeding and the development of KD.METHODS:We used a nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 37 630 children who had data on their feeding during infancy. Infant feeding practice was queried at 6 to 7 months of age, and responses to questions about hospital admission for KD during the period from 6 to 30 months of age were used as outcome. We conducted logistic regression analyses controlling for child and maternal factors with formula feeding without colostrum as our reference group.RESULTS:A total of 232 hospital admissions were observed. Children who were breastfed exclusively or partially were less likely to be hospitalized for KD compared with those who were formula fed without colostrum; odds ratios for hospitalization were 0.26 (95% confidence interval: 0.12–0.55) for exclusive breastfeeding and 0.27 (95% confidence interval: 0.13–0.55) for partial breastfeeding. Although the risk reduction was not statistically significant, feeding colostrum only also provided a protective effect.CONCLUSIONS:We observed protective effects of breastfeeding on the development of KD during the period from 6 to 30 months of age in a nationwide, population-based, longitudinal survey in Japan, the country in which KD is most common.
Material Deprivation in Poland and Slovakia – a Comparative Analysis
Authors: Šoltés Erik , Ulman Paweł 
Published: May 2016

One of the key targets of the EU’s 2020 Strategy is to substantially reduce the number of people at risk of poverty or social exclusion. The EU seeks to reduce poverty by lifting at least 20 million people out of the risk of poverty or social exclusion by 2020. The monitoring of progress towards this target is based on the headline indicator AROPE – people at risk of poverty or social exclusion. The indicator applies to people either at risk of poverty or severely materially deprived or living in a household with a very low work intensity. This article focuses on material deprivation, one of the three components monitored to evaluate the social situation in the EU. The article deals with material deprivation and severe material deprivation in Slovak and Polish households. The two main goals of this article are to examine which factors have a significant effect on material deprivation and to determine the influence of those relevant factors on material deprivation of Slovak and Polish households. The article provides a comparative analysis of the material deprivation of Slovak and Polish households.We used microdata from EU SILC 2012 from Poland and Slovakia and association analysis including logistic regression. These statistical methods were applied using SAS Enterprise Guide.
Are More Choices Better? An Experimental Investigation of the Effects of Multiple Tax Incentives
Authors: Bobek Donna D. , Chen Jason C. , Hageman Amy M. , Tian Yu 
Published: May 2016

ABSTRACT
The U.S. federal income tax system includes numerous incentives intended to encourage many behaviors. However, these incentives add complexity. This study investigates how one source of complexity, the number of different incentives, affects individuals' use of tax incentives. The results from two experiments detect no evidence that having more (versus fewer) incentive choices (i.e., high choice complexity) affects individuals' decisions to engage in the targeted behavior or select an incentive. However, the results do show that individuals faced with high choice complexity are more likely to make errors and less likely to choose the optimal incentive. Further, high choice complexity leads to greater perceived complexity and difficulty, which, in turn, is related to less positive emotions and more anxiety. Thus, high choice complexity has negative consequences on individuals. This study also contributes to the choice complexity literature by examining its effect on making an optimal choice.
Readaptation from Simulated Microgravity as a Stimulus for Improved Orthostatic Tolerance: Role of the Renal, Cardioendocrine, and Cardiovascular Systems
Authors: Grenon Marlene S. , Hurwitz Shelley , Xiao Xinshu , Sheynberg Natalie , Ramsdell Craig D. , Kim Christine , Cohen Richard J. , Williams Gordon H. 
Published: May 2016

Background Microgravity and simulated microgravity (SM) lead to important changes in orthostatic tolerance (OT), the autonomic nervous system (ANS), and the volume-regulating systems. After one is exposed to microgravity or SM, a period of readaptation to gravity is known to take place, but it is not certain if orthostatic function returns to baseline within the initial recovery and what mechanisms are involved. We hypothesized that after a period of recovery, OT, ANS, and volume-regulating systems would return to pre-SM levels. Methods To test this hypothesis, 24 healthy men were placed on a constant diet for 3 to 5 days, after which a tilt-stand test (pre-TST) was performed. The TST was repeated after 14 to 16 days of head-down tilt bed rest (HDTB) (post-TST) and a 3-day period of recovery (rec-TST), at which times measurements of renal, cardioendocrine, and cardiovascular systems were conducted. Results Presyncope occurred in 46% of subjects pre-TST, in 72% post-TST, and in 23% during rec-TST. OT was significantly better during the recovery period than at baseline ( p = .03). There was a significant decrease in urinary sodium and potassium excretion, along with a decrease in plasma renin activity and serum and urine aldosterone compared with baseline. Serum norepinephrine and sympathetic responsiveness remained below baseline values. Conclusion In summary, OT improved compared with baseline after a period of readaptation. Retention of electrolytes (sodium, potassium) could be involved. These findings indicate that recovery after SM is not simply a gradual return to baseline values but is instead a dynamic process reflecting interaction of multiple regulatory systems.
Association of Body Weight with the Risk for Malignancies in Hospitalized Patients with or without Diabetes Mellitus in Taiwan
Authors: Hsieh Sheng-Hwu , Chiou Wen-Ko , Wang Ming-Hsu , Lin Jen-Der 
Published: May 2016

Background The purpose of this study was to determine the risk for cancers in patients with and without type 2 diabetes mellitus (DM) stratified by body mass index (BMI). Methods Patients hospitalized from January 2000 to December 2010 with a diagnosis of malignant neoplasm ( International Classification of Diseases, Ninth Revision, codes 140-208.91) were included. Diabetes mellitus was defined as a fasting blood glucose of 126 mg/dL or greater or a postprandial blood glucose of 200 mg/dL or greater. The patients were categorized according to BMI criteria for Asians: normal weight, BMI of less than 24 kg/m2; overweight, BMI of greater than 24 kg/m2; and obese, BMI of greater than 27 kg/m2. Results A total of 42,229 patients were included, of which 24,884 (59%) were normal weight, 10,096 (24%) were overweight, and 7,249 (17%) were obese. There were 4,195 (16.9%), 2,056 (20.4%), and 1,625 (22.4%) patients with DM in the normal weight, overweight, and obese groups, respectively. Regardless of weight, the diabetic patients were more likely to have pancreas, liver, urinary tract, prostate, skin, hematological, lung, secondary, and gastric malignancies but were less likely to have cervical, oropharyngeal, nasopharyngeal, breast, or thyroid cancer. Regardless of sex or the presence or the absence of DM, the patients with more than 1 malignancy were more likely to die than were those with only 1 malignancy. Furthermore, the obese diabetic patients had higher mortality than did the obese nondiabetic patients with the same number of cancers. Conclusions Regardless of weight category (normal, overweight, or obese), diabetic patients are more likely to have pancreas, liver, urinary tract, prostate, skin, hematological, lung, secondary, and gastric malignancies. Diabetic patients may benefit from increased surveillance for these cancers.
Serum Vitamin D and C-Reactive Protein Levels are Independently Associated with Diastolic Dysfunction
Authors: Akin Fatih , Ayça Burak , Köse Nuri , Celik Omer , Yilmaz Yücel , Akin Melike Nur , Arinc Hüseyin , Ozkok Abdullah , Covic Adrian , Kanbay Mehmet 
Published: May 2016

Background and Aim Vitamin D deficiency is common and may contribute to cardiovascular diseases. We hypothesized that serum 25-hydroxyvitamin D [25(OH)D] levels would be inversely associated with inflammation and with diastolic dysfunction. We therefore investigated the link between serum vitamin D levels (i) echocardiographic measures and (ii) inflammatory parameters. Methods The cross-sectional study included 281 patients who were referred to coronary angiography for stable angina pectoris. Patients were recruited between December 2010 and November 2011. Patients with established congestive heart failure, gout, chronic kidney disease (estimated glomeruler filtration rate <60 mL/min per 1.73 m2), and acute infection were not included. We measured serum 25(OH)D levels, C-reactive protein and fibrinogen levels. A radioimmunoassay procedure was used to measure 25(OH)D (DiaSorin, Stillwater, MN). We also performed standardized left ventricular (LV) echocardiograms, and echocardiographic data were used for classification of systolic and diastolic dysfunction. We analyzed the relation between serum levels of 25(OH)D and inflammatory markers and echocardiographic measures of LV mass and diastolic dysfunction. Results At baseline, subjects had a mean age of 59.5 ± 10 years, and 43.4% were women. Left ventricular mass index, left atrial diameter, isovolumic relaxation time, and E/E′ ratio were significantly higher in patients with lower 25(OH)D levels. In ordinal logistic regression analysis, higher 25(OH)D was negatively associated only with LV mass index (odds ratio [OR], 0.965; 95% confidence interval [95% CI], 0.939–0.992; P = 0.015), isovolumic relaxation time (OR, 0.962; 95% CI, 0.939–0.985; P = 0.001), E/E′ ratio (OR, 0.874; 95% CI, 0.811–0.942; P = 0.008), and C-reactive protein (OR, 0.802; 95% CI, 0.668–0.962; P = 0.021). Conclusions Serum levels of 25(OH)D are significantly associated with LV diastolic dysfunction and LV mass index, although the effect size is rather small. Longitudinal studies in larger populations are needed to establish firmly or refute a causal relationship between vitamin D levels and diastolic dysfunction and LV mass index.
The Effects of Suplatast Tosilate Treatment and Prophylaxis on Lung Histopathology in a Mouse Model of Chronic Asthma
Authors: Tuncel Tuba , Karaman Meral , Ayyildiz Zeynep Arıkan , Uysal Pinar , Kiray Muge , Bagriyanik Alper H. , Yilmaz Osman , Karaman Ozkan , Uzuner Nevin 
Published: May 2016

Introduction Suplatast tosilate is a medication that inhibits TH2-type cytokines. We aimed to investigate the effects of suplatast tosilate treatment and prophylaxis on lung histopathology and cytokine levels in a mouse model of chronic asthma. Materials and Methods Forty-two BALB/c mice were divided into 6 groups: group I (control), group II (vehicle control), group III (dexamethasone), group IV (prophylaxis with suplatast tosilate), group V (treatment with suplatast tosilate), and group VI (prophylaxis and treatment with suplatast tosilate). All of the groups, except for the control and vehicle control groups, were sensitized and challenged with ovalbumin. The mice in the study groups, except those in the group receiving suplatast tosilate for prophylaxis only, were treated with study drugs. After the mice were killed, IL-4, IL-5, and interferon- γ levels were quantified in the lung tissue, which were examined histologically by light and electron microscopy. Results There were significant improvements in all histopathological parameters in the group treated with suplatast tosilate compared with the vehicle control group. Similar improvements were observed when the group receiving prophylaxis and treatment with suplatast tosilate was compared with the vehicle control as well. There were no significant differences between the group receiving only prophylaxis with suplatast tosilate and the vehicle control group. Cytokine levels were significantly higher in the vehicle control group when compared with the control group. Although all of the groups had lower cytokine levels than those of the vehicle control group, the differences were not statistically significant. Conclusions Treatment with suplatast tosilate was effective in improving all histopathological parameters in a mouse model of chronic asthma. It was observed that the use of prophylactic suplatast tosilate was ineffective and had no additional effects when administered together with treatment.