bluuebunny/crossref_metadata_2025 huggingface dataset:
NSF BIGDATA PI Meeting - Domain-Specific Research Directions and Data Sets
Authors: Singh Lisa , Deshpande Amol , Zhou Wenchao , Banerjee Arindam , Bowers Alex , Friedler Sorelle , Jagadish H.V. , Karypis George , Obradovic Zoran , Vullikanti Anil , Zuo Wangda
Published: February 2019

In March 2017, PIs and co-PIs funded through the NSF BIGDATA program were brought together along with selected industry and government invitees to discuss current research, identify current challenges, discuss promising future directions, foster new collaborations, and share accomplishments, at BDPI-2017. Given that two recent NITRD [2] and NSF [1] meeting reports contained a set of recommendations, grand challenges, and high impact priorities for Big Data, the organizers of this meeting shifted the focus of the breakout sessions to discuss problems and available data sets that exist in five application domains - policy, health, education, economy & finance, and environment & energy. These domains were selected based on a survey of the PIs/co-PIs and should not be interpreted as being more important than others. Slides that were presented by the different breakout group leaders are available at https://www.bi.vt.edu/ nsf-big-data/. We hope this report will serve as a blueprint for promising big data research in five application domains.
Dagstuhl Seminar on Big Stream Processing
Authors: Sakr Sherif , Rabl Tilmann , Hirzel Martin , Carbone Paris , Strohbach Martin
Published: February 2019

Stream processing can generate insights from big data in real time as it is being produced. This paper reports findings from a 2017 seminar on big stream processing, focusing on applications, systems, and languages.
Intestinal iNKT cells migrate to liver and contribute to hepatocyte apoptosis during alcoholic liver disease
Authors: Lee Kuei-Chuan , Chen Peng , Maricic Igor , Inamine Tatsuo , Hu Jingjuan , Gong Shenhai , Sun Julia C. , Dasgupta Suryasarathi , Lin Han-Chieh , Lin Yi-Tsung , Loomba Rohit , Stärkel Peter , Kumar Vipin , Schnabl Bernd
Published: February 2019

We investigated the migration of intestinal immune cells to the liver and their contribution to alcoholic liver disease. In mice fed ethanol, we found that an increased number of invariant natural killer T (iNKT) cells, which respond to the antigen presented by CD1d, migrated from mesenteric lymph nodes to the liver. iNKT cells react to lipid antigens, so we studied their activities in mice with intestinal epithelial cell-specific deletion of Pparg ( PpargΔIEC) as a model for altering intestinal lipidomic profiles. Levels of CD1d increased in intestines of ethanol-fed PpargΔIEC mice, and in cell-tracking experiments, more iNKT cells migrated to the liver, compared with mice without disruption of Pparg. Livers of PpargΔIEC mice had increased markers of apoptosis and liver injury after ethanol feeding. iNKT cells isolated from livers of ethanol-fed PpargΔIEC mice induced apoptosis of cultured hepatocytes. An inhibitor of iNKT cells reduced ethanol-induced liver injury in PpargΔIEC mice. Duodenal tissues from patients with alcohol-use disorder have been found to have increased levels of CD1d compared with tissues from patients without alcohol overuse. Ethanol use, therefore, activates iNKT cells in the intestine to migrate to liver, where they—along with the resident hepatic iNKT cells—contribute to hepatocyte death and injury.

NEW & NOTEWORTHY In this article, we studied migration of intestinal immune cells into the liver in response to ethanol-induced liver disease. We found that chronic ethanol feeding induces expression of CD1d by enterocytes, which activate invariant natural killer T (iNKT) cells in mesenteric lymph nodes; activation is further increased with loss of peroxisome proliferator-activated receptor gamma gene and altered lipid profiles. The activated iNKT cells migrate into the liver, where they promote hepatocyte apoptosis. Patients with alcohol use disorder have increased expression of CD1d in the small intestine. Strategies to block these processes might be developed to treat alcoholic liver disease.
Effect of Trendelenburg position and lower-body positive pressure on neck fluid distribution
Authors: Yadollahi Azadeh , Singh Bhajan , Millar Philip J. , Vena Daniel , Floras John S. , Bradley T. Douglas
Published: February 2019

Fluid that shifts out of the legs and into the neck when supine can contribute to upper-airway narrowing. The present study investigates the relative contributions of vascular and extravascular fluid to the total accumulation of neck fluid volume (NFV). In 22 healthy awake participants (8 women), aged 42 ± 9 yr, we measured NFV with bioelectrical impedance, internal jugular vein volume (IJVV) with ultrasound, and extravascular NFV (NFVEV) as the difference between NFV and IJVV. Participants were randomly allocated to control and intervention, both of which were conducted on the same day. Measurements were made at baseline and every 5 min thereafter during control and intervention. During intervention, participants received 40 mmHg lower-body positive pressure (LBPP) when supine, followed by LBPP plus 10° Trendelenburg position, then LBPP when supine again, followed by recovery. During control, participants lay supine for equal time. LBPP and LBPP plus Trendelenburg position both increased NFV from baseline compared with control ( P < 0.001), with significant contributions from IJVV ( P < 0.001). Returning to supine with LBPP, IJVV returned to baseline, but NFV remained elevated because of accumulation of NFVEV. These findings suggest that contributions of IJVV to NFV are immediate but transient, whereas sustained elevation in NFV when supine is likely a result of NFVEV. These findings add new insights into the mechanism by which fluid accumulates in the neck by rostral fluid shift.

NEW & NOTEWORTHY This study demonstrates that lying supine for 30 min as well as increased fluid shift out of the legs to simulate nocturnal rostral fluid shift causes fluid to accumulate mainly in the extravascular space of the neck rather than in the internal jugular veins. Therefore, in subjects without fluid-retaining states, extravascular neck fluid accumulation overnight might play a more significant role in the pathophysiology of upper-airway narrowing than intravascular fluid accumulation.
How Adhesion Molecule Patterns Change While Neutrophils Traffic through the Lung during Inflammation
Authors: Konrad Franziska M. , Wohlert Julia , Gamper-Tsigaras Jutta , Ngamsri Kristian-Christos , Reutershan Jörg
Published: February 2019

In acute pulmonary inflammation, polymorphonuclear cells (PMNs) pass a transendothelial barrier from the circulation into the lung interstitium followed by a transepithelial migration into the alveolar space. These migration steps are regulated differentially by a concept of adhesion molecules and remain—despite decades of research—incompletely understood. Current knowledge of changes in the expression pattern of adhesion molecules mainly derives from in vitro studies or from studies in extrapulmonary organ systems, where regulation of adhesion molecules differs significantly. In a murine model of lung inflammation, we determined the expression pattern of nine relevant neutrophilic adhesion molecules on their way through the different compartments of the lung. We used a flow cytometry-based technique that allowed describing spatial distribution of the adhesion molecules expressed on PMNs during their migration through the lung in detail. For example, the highest expression of CD29 was found in the intravascular compartment, highlighting its impact on the initial adhesion to the endothelium. CD47 showed its peak of expression on the later phase of transendothelial migration, whereas CD11b and CD54 expression peaked interstitial. A pivotal role for transepithelial migration was found for the adhesion molecule CD172a. Thereby, expression may correlate with functional impact for specific migration steps. In vitro studies further confirmed our in vivo findings. In conclusion, we are the first to determine the changes in expression patterns of relevant adhesion molecules on their migration through the different compartments of the lung. These findings may help to further understand the regulation of neutrophil trafficking in the lung.
High-Fat Diet Alters Immunogenic Properties of Circulating and Adipose Tissue-Associated Myeloid-Derived CD45+DDR2+ Cells
Authors: Sidles Sara J. , Xiong Ying , Young M. Rita I. , LaRue Amanda C.
Published: February 2019

Chronic inflammation is evident in the adipose tissue and periphery of patients with obesity, as well as mouse models of obesity. T cell subsets in obese adipose tissue are skewed towards Th1- and Th17-associated phenotypes and their secreted cytokines contribute to obesity-associated inflammation. Our lab recently identified a novel, myeloid-derived CD45+DDR2+ cell subset that modulates T cell activity. The current study sought to determine how these myeloid-derived CD45+DDR2+ cells are altered in the adipose tissue and peripheral blood of preobese mice and how this population modulates T cell activity. C57BL/6 mice were fed with a diet high in milkfat (60%·kcal, HFD) ad libitum until a 20% increase in total body weight was reached, and myeloid-derived CD45+DDR2+ cells and CD4+ T cells in visceral adipose tissue (VAT), mammary gland-associated adipose tissue (MGAT), and peripheral blood (PB) were phenotypically analyzed. Also analyzed was whether mediators from MGAT-primed myeloid-derived CD45+DDR2+ cells stimulate normal CD4+ T cell cytokine production. A higher percentage of myeloid-derived CD45+DDR2+ cells expressed the activation markers MHC II and CD80 in both VAT and MGAT of preobese mice. CD4+ T cells were preferentially skewed towards Th1- and Th17-associated phenotypes in the adipose tissue and periphery of preobese mice. In vitro, MGAT from HFD-fed mice triggered myeloid-derived CD45+DDR2+ cells to induce CD4+ T cell IFN-γ and TNF-α production. Taken together, this study shows that myeloid-derived CD45+DDR2+ cells express markers of immune activation and suggests that they play an immune modulatory role in the adipose tissue of preobese mice.
Role of Combined Lipoic Acid and Vitamin D3 on Astrocytes as a Way to Prevent Brain Ageing by Induced Oxidative Stress and Iron Accumulation
Authors: Molinari Claudio , Morsanuto Vera , Ghirlanda Sabrina , Ruga Sara , Notte Felice , Gaetano Laura , Uberti Francesca
Published: February 2019

Brain ageing is a complex multifactorial process characterized by gradual and continuous loss of neuronal functions. It is hypothesized that at the basis of brain ageing as well as age-related diseases, there is an impairment of the antioxidant defense system leading to an increase of oxidative stress. In this study, two different biological aspects involved in brain ageing and neurodegeneration have been investigated: oxidative stress and iron accumulation damage. In primary mouse astrocytes, the stimulation with 50 μM lipoic acid (LA) and 100 nM vitamin D (vitD) was first investigated in a time-course study to determine the dosages to be used in combination and then in a permeability test using an in vitro blood-brain barrier. In a second set of experiments, the role of oxidative stress was investigated pretreating astrocytes with 200 μM H2O2 for 30 min. The ability of vitD and LA alone and combined together to prevent or repair the damage caused by oxidative stress was investigated after 24 h of stimulation by the MTT test, mitochondrial membrane potential measurement, and Western blot analysis. To induce neurodegeneration, cells were pretreated with 300 μM catalytic iron for 6 days and then treated with vitD and LA alone and combined for additional 6 days to investigate the protection exerted by combination, analyzing viability, ROS production, iron concentration, and activation of intracellular pathways. In our study, the combination of LA and vitD showed beneficial effects on viability of astrocytes, since the substances are able to cross the brain barrier. In addition, combined LA and vitD attenuated the H2O2-induced apoptosis through the mitochondrial-mediated pathway. The combination was also able to counteract the adverse conditions caused by iron, preventing its accumulation. All these data support the hypothesis of the synergistic and cooperative activity exerted by LA and vitD in astrocytes indicating a possible new strategy to slow down ageing.
Current Challenges in Cancer Immunotherapy: Multimodal Approaches to Improve Efficacy and Patient Response Rates
Authors: Sambi Manpreet , Bagheri Leila , Szewczuk Myron R.
Published: February 2019

Cancer immunotherapy is a promising innovative treatment for many forms of cancer, particularly melanoma. Although immunotherapy has been shown to be efficacious, patient response rates vary and, more often than not, only a small subset of the patients within a large cohort respond favourably to the treatment. This issue is particularly concerning and becomes a challenge of immunotherapy to improve the effectiveness and patient response rates. Here, we review the specific types of available immunotherapy options, their proposed mechanism(s) of action, and the reasons why the patient response to this treatment is variable. The potential favourable options to improve response rates to immunotherapy will be discussed with an emphasis on adopting a multimodal approach on the novel role that the gut microbiota may play in modulating the efficacy of cancer immunotherapy.
The Numerical and Experimental Investigation of the Change of the Thermal Conductivity of Expanded Polystyrene at Different Temperatures and Densities
Authors: Doğan Battal , Tan Hüsamettin
Published: February 2019

The determination of the thermal conductivity of insulation materials depending on which parameters in the application as well as the production is very important. In this direction, the parameters affecting thermal conductivity should be determined to improve the efficiency of the insulation materials. It is also a fact that expanded polystyrene blocks have different thermal conductivities at the same density value depending on the production process. In this study, it was determined, experimentally and numerically, that the thermal conductivity of expanded polystyrene material at different densities is dependent on which parameters and changes in temperature. Expanded polystyrene materials consist of blocks of 30×30 cm with density of 16, 21, and 25 kg/m3 and a thickness of 20 mm. Thermal conductivity measurements were performed in FOX 314 (Laser Comp., USA) operating in accordance with ISO 8301 and EN 12667 standards. The measurements were made for expanded polystyrene blocks at the average temperatures of 10°C, 20°C, 30°C, and 40°C. The numerical study has three stages as the acquisition of electron microscope images (SEM) of expanded polystyrene blocks, modeling of internal structure geometry with CAD program, and realization of solutions with a finite element-based ANSYS program. Findings from experimental and numerical studies and the parameters affecting thermal conductivity were determined. Finally, it is thought that numerical methods can be used to obtain a preliminary idea for EPS material in determining thermal conductivity by comparing the findings of experimental and numerical studies.
Melatonin Enhances Cisplatin and Radiation Cytotoxicity in Head and Neck Squamous Cell Carcinoma by Stimulating Mitochondrial ROS Generation, Apoptosis, and Autophagy
Authors: Fernandez-Gil Beatriz I. , Guerra-Librero Ana , Shen Ying-Qiang , Florido Javier , Martínez-Ruiz Laura , García-López Sergio , Adan Christian , Rodríguez-Santana César , Acuña-Castroviejo Darío , Quiñones-Hinojosa Alfredo , Fernández-Martínez José , Abdel Moneim Ahmed E. , López Luis C. , Rodríguez Ferrer José M. , Escames Germaine
Published: February 2019

Head and neck cancer is the sixth leading cancer by incidence worldwide. Unfortunately, drug resistance and relapse are the principal limitations of clinical oncology for many patients, and the failure of conventional treatments is an extremely demoralizing experience. It is therefore crucial to find new therapeutic targets and drugs to enhance the cytotoxic effects of conventional treatments without potentiating or offsetting the adverse effects. Melatonin has oncostatic effects, although the mechanisms involved and doses required remain unclear. The purpose of this study is to determine the precise underlying mitochondrial mechanisms of melatonin, which increase the cytotoxicity of oncological treatments, and also to propose new melatonin treatments in order to alleviate and reverse radio- and chemoresistant processes. We analyzed the effects of melatonin on head and neck squamous cell carcinoma (HNSCC) cell lines (Cal-27 and SCC-9), which were treated with 0.1, 0.5, 1, and 1.5 mM melatonin combined with 8 Gy irradiation or 10 μM cisplatin. Clonogenic and MTT assays, as well as autophagy and apoptosis, involving flow cytometry and western blot, were performed in order to determine the cytotoxic effects of the treatments. Mitochondrial function was evaluated by measuring mitochondrial respiration, mtDNA content (RT-PCR), and mitochondrial mass (NAO). ROS production, antioxidant enzyme activity, and GSH/GSSG levels were analyzed using a fluorometric method. We show that high concentrations of melatonin potentiate the cytotoxic effects of radiotherapy and CDDP in HNSCC, which are associated with increased mitochondrial function in these cells. In HNSCC, melatonin induces intracellular ROS, whose accumulation plays an upstream role in mitochondria-mediated apoptosis and autophagy. Our findings indicate that melatonin, at high concentrations, combined with cisplatin and radiotherapy to improve its effectiveness, is a potential adjuvant agent.
Oxidized Low-Density Lipoprotein (Ox-LDL) and Triggering Receptor-Expressed Myeloid Cell (TREM-1) Levels Are Associated with Cardiometabolic Risk in Nonobese, Clinically Healthy, and Young Adults
Authors: Vázquez Cecilia Maria Passos , Costa Jamille Oliveira , Bomfim Lays Gisele Santos , Pires Liliane Viana , da Silva Danielle Góes , Fukutani Kiyoshi Ferreira , de Jesus Amélia Ribeiro , de Jesus Silva Natanael , de Jesus Santana Gleiciane , de Moura Tatiana Rodrigues , Barbosa Kiriaque
Published: February 2019

Oxidative and inflammatory substances play an important role in the genesis of processes related to cardiometabolic risk. High levels of oxidized low-density lipoprotein (Ox-LDL) and of triggering receptor-expressed myeloid cells (TREM-1) are associated with cardiovascular and inflammatory diseases. In this study, we evaluate the association of the plasma concentrations of Ox-LDL and serum levels of circulating TREM-1 (sTREM-1) with the components of cardiometabolic risk (CMR) and other associated risk parameters. Although the individuals in this study were young, nonobese, and did not have signs, symptoms, and diagnosis of diseases, they already presented components of CMR. Ox-LDL lipid fraction correlated positively with CMR-related markers: body mass index (BMI), waist circumference (WC), body fat percentage, total cholesterol, LDL-c, VLDL-c, triglycerides, atherogenic cholesterol, and atherogenic index. Among these parameters, atherogenic cholesterol had a greater predictive effect for Ox-LDL alterations. Individuals with higher serum concentrations of sTREM-1 presented higher values for BMI, WC, triglycerides, VLDL-c, and atherogenic cholesterol. WC showed an effect on the association between the sTREM-1’s inflammatory response and the components of CMR. The association of oxidative and inflammatory markers with anthropometric parameters and atherogenic cholesterol in nonobese, clinically healthy, and young individuals suggests the importance of early evaluation of these markers in order to prevent future cardiac events.
Gender- and Age-Specific Differences in the Association of Hyperuricemia and Hypertension: A Cross-Sectional Study
Authors: Lin Xiaoyun , Wang Xiqian , Li Xin , Song Lili , Meng Zhaowei , Yang Qing , Zhang Wenjuan , Gao Yuxia , Yang Zhenwen , Cai Heng , Bian Bo , Li Yongle , Yu Xuefang , Du Xin , Xu Shaopeng , Nie Jing , Liu Ming , Sun Jinhong , Zhang Qing , Gao Ying , Song Kun , Wang Xing , Zhao Li , Fan Yaguang
Published: February 2019

Objective. Both hyperuricemia and hypertension have important clinical implications, but their relationship in terms of gender and age is still a matter of debate. In this study, we aimed to explore gender- and age-specific differences in this association between hyperuricemia and hypertension in a Chinese population. Methods. A total of 78596 ostensibly healthy subjects (47781 men and 30815 women) were recruited. The association between hyperuricemia and hypertension was analyzed by multivariate logistic regression, and the analyses were stratified by gender and age. Results. Overall prevalence of hypertension and hyperuricemia was significantly higher in males than in females. Increasing trends of hypertension prevalence in both genders as well as hyperuricemia prevalence in females were found along with aging. However, males showed a reduced trend in hyperuricemia prevalence with aging. Higher hypertension and hyperuricemia prevalence was found in young and middle-aged men than in women, but not in elderly people older than 70 years. Significantly increased risk of hypertension from hyperuricemia was found only in men with an adjusted odds ratio of 1.131 (P<0.01), especially in the middle-aged male participants. However, such significant results were not found in women. Similarly, hyperuricemia was also an independent risk factor of increased systolic blood pressure and diastolic blood pressure in males, but not in females. Conclusion. We observed significantly higher overall prevalence of hyperuricemia and hypertension in men than in women. Men with hyperuricemia (particularly in middle age) had a significantly increased susceptibility of hypertension, while this significant association was not observed in women.
Indoor Air Quality in Inpatient Environments: A Systematic Review on Factors that Influence Chemical Pollution in Inpatient Wards
Authors: Gola Marco , Settimo Gaetano , Capolongo Stefano
Published: February 2019

Introduction. Indoor air quality is one the main issues in which governments are focusing. In healing spaces, several research studies are reporting a growing number of data analysis and research works in order to guarantee and prevent health of users and workers. Currently the main investigations are about biological and physical risks; otherwise chemical ones are less investigated. Several countries are carrying out indoor air quality monitoring in those professional workplaces in which chemicals are used but also in some typically indoor (generic) spaces for the building hygiene assessment. The indoor air is affected by several factors that currently are analyzed punctually, without a whole scenario of all the variable performances. The authors have done a systematic review on the current state of the art and knowledge related to chemical pollution in healing spaces and the emerging strategies, supported by scientific literature, for healthy inpatient rooms and their indoor air.Methodology. The systematic review has been done through the analysis of papers from SCOPUS, DOAJ, and PubMed databases. The survey sample considered 483 scientific articles, between 1989 and 2017, and starting the systematic reading and analysis of the abstracts, only 187 scientific papers were selected, and only 96 were accessible.Discussion. Since scientific literature reports very different outputs and results, the resulting work from the survey is divided into specific fields of interest related to construction and finishing materials, installations, components, ventilation systems, processes, etc. Starting from the systematic reading, the paper classifies the factors of indoor air in four macroareas: outdoor air and microclimatic factors (temperature, relative humidity, air velocity, air change, etc.); management activities (management and maintenance activities, ventilation systems, HVAC, cleaning and disinfectant activities, etc.); design factors (room dimensions, furniture, finishing materials, etc.); and human presence and medical activities (users’ presence, their health status, and medical activities carried out in inpatient rooms).Conclusion. The systematic review gives rise to a broad scenario on the existing knowledge regarding the indoor air pollution, design, and management strategies for healthy spaces and several emerging topics. Although the aim of the investigation is strictly related to chemical pollution, several considerations from the biological point of view have been listed. The systematic review, supported by the existing scientific literature, becomes a starting point for considering the importance of the topic and to stimulate the knowledge around this field of interest for improving studies, analysis, and simulations.
Vagus Nerve Stimulation Attenuates Acute Skeletal Muscle Injury Induced by Ischemia-Reperfusion in Rats
Authors: Zhang Yifeng , Li Hewei , Wang Menglong , Meng Guannan , Wang Zhenya , Deng Jielin , Wang Meng , Zhang Qianqian , Yang Shengli , Jiang Hong
Published: February 2019

Vagus nerve stimulation (VNS) has been shown to attenuate ischemia-reperfusion (I/R) injury in multiple organs. The present study aimed at investigating whether VNS could exert protective effects against I/R injury in the skeletal muscle. Male Sprague-Dawley rats were randomly divided into 3 groups: the control, I/R, and I/R+VNS groups. The skeletal muscle I/R (SMI/R) model was induced by occlusion of the left femoral artery for 2.5 hours followed by reperfusion for 2 hours. The vagal nerve trunk was separated, and VNS was performed during the whole I/R process. The intensity of VNS was optimized in each rat to obtain a 10% reduction in the heart rate relative to the value before stimulation. After the experiment, the blood sample and left gastrocnemius muscle tissues were collected for histological examination, biochemical analysis, and molecular biological detection. During the I/R process, VNS significantly reduced cellular apoptosis, necrosis, and inflammatory cell infiltration compared to sham VNS. The VNS treatment also decreased the inflammatory response, alleviated oxidative stress, and improved vascular endothelial function (p<0.05 for each). In contrast, the I/R group showed an opposite effect compared to the control group. The present study indicated that VNS could protect against SMI/R injury by suppressing excessive inflammation, alleviating oxidative stress, and preserving vascular endothelial function.
The Precuneus – A Witness for Excessive Aβ Gathering in Alzheimer’s Disease Pathology
Authors: Aghakhanyan Gayane , Vergallo Andrea , Gennaro Marta , Mazzarri Sara , Guidoccio Federica , Radicchi Claudia , Ceravolo Roberto , Tognoni Gloria , Bonuccelli Ubaldo , Volterrani Duccio
Published: February 2019

Evidence of cortical beta-amyloid (Aβ) load, assessed by Aβ positron emission tomography (Aβ-PET), is an established in vivo biomarker of Alzheimer’s disease (AD)-related pathophysiology. Qualitative assessment of Aβ-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aβ burden along the continuum of AD. Methods: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aβ-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αβ distribution pattern considering age as a nuisance covariate. Results: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-flor­betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. Conclusions: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aβ depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aβ. We found a positive association between the overall Aβ-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aβ deposition continuously takes place as the disease progresses.
Hematopoietic Chimera in a Male Blood Donor and His Dizygotic Twin Sister
Authors: Miola Marcos P. , Lopes Alessandro G. , Silva Alessandra P. , Gomes Edney G.C. , Machado Leticia A.F. , Veloso Wanessa A. , Costa Carlos A. , Fachini Roberta M. , Ricci Junior Octávio , Brandão de Mattos Cinara C. , de Mattos Luiz Carlos
Published: February 2019

Twin hematopoietic chimera in humans is a phenomenon that was discovered accidentally and the prevalence of which remains unclear. The resolution of chimera cases requires studying family medical records, data analysis, and investigations of hematopoietic cells and cells from other tissues. The interactions among ABO, Lewis, and secretor histo-blood group systems are explored to resolve cases of hematopoietic chimera. Here we report a rare case of hematopoietic chimera where twins present a mixed field reaction in the ABO, Rh, and Kidd red blood cell phenotyping. Using red blood cells separated from the mixed field as well as molecular approaches and investigations of family members, we identify inconsistent genotypes with the Mendelian inheritance pattern when comparing the peripheral blood with the buccal epithelium of the male twin and his twin sister. Analysis of the ABO, Lewis, and secretor phenotypes, and genomic DNA from buccal epithelium showed the genotypes ABO*A1.01/ABO*B.01 and FUT2*01N.02/ FUT2*01N.02 in the male twin and the genotypes ABO*O.01.01/ABO*O.01.02 and FUT2*01/FUT2*01 in the female twin. The results of the HLA-DRB1 genotyping showed inconsistency between the male and his twin sister. We conclude that the serological analyses combined with molecular approaches used in this study are good tools to resolve cases of hematopoietic chimera.
Efficacy of Internal Limiting Membrane Flap Techniques with Vitrectomy for Macular Detachment Associated with an Optic Disc Pit
Authors: Pastor-Idoate Salvador , Gómez-Resa María , Karam Sarah , Copete Sergio , Kyriakou Danai , García-Arumí Fusté Claudia , Pastora Natalia , Nadal Jeroni , García-Arumí José
Published: February 2019

Purpose: To compare the anatomical and functional outcome of adjuvant pars plana vitrectomy (PPV) procedures using the techniques of translocation of an internal limiting membrane (ILM) flap and transplantation of an inverted ILM flap for the treatment of chronic and/or refractory optic disc pit (ODP) maculopathy. Methods: In this prospective interventional case series study, 9 patients (9 eyes) with chronic and/or refractory ODP maculopathy underwent PPV with either translocation of an ILM flap or transplantation of an inverted ILM flap as adjuvant techniques along with gas tamponade. The anatomical success, rates of macular reattachment, and visual improvement were assessed. Results: The mean preoperative central retinal thickness (CRT) was 723.4 µm (range: 366–1,151). The mean postoperative CRT was 398.1 ± 212.2 µm (range: 210–758). An increased preoperative CRT was associated with a lower chance of postoperative reattachment of the macula (p = 0.047). The overall reattachment rate at the end of the follow-up period was 56% (n = 5). The mean preoperative visual acuity (logMAR unit [Snellen acuity]) was 0.48 (20/60) (range: 1.30 [20/400] to 0.10 [20/25]). The mean change in best corrected visual acuity (BCVA) was 0.48 ± 0.233 logMAR units (approx. 3 lines of visual improvement). Conclusions: ILM flap techniques are logical and straightforward approaches as adjuvants to PPV treatment of ODP maculopathy. They could be viable adjuvant treatments for improvement in BCVA and CRT in patients with ODP maculopathy.
The Prevalence of Metabolically Healthy and Unhealthy Obesity according to Different Criteria
Authors: Liu Chunxiao , Wang Chunxiu , Guan Shaochen , Liu Hongjun , Wu Xiaoguang , Zhang Zhongying , Gu Xiang , Zhang Yanlei , Zhao Yan , Tse Lap Ah , Fang Xianghua
Published: February 2019

Objective: Obesity-related disease risks may vary depending on whether the subject has metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO). At least 5 definitions/criteria of obesity and metabolic disorders have been documented in the literature, yielding uncertainties in a reliable international comparison of obesity phenotype prevalence. This report aims to compare differences in MHO and MUO prevalence according to the 5 most frequently used definitions. Methods: A random sample of 4,757 adults aged 35 years and older (male 51.1%) was enrolled. Obesity was defined either according to body mass index or waist circumference, and the definitions of metabolic abnormalities were derived from 5 different criteria. Results: In MHO, the highest prevalence was obtained when using the homeostasis model assessment (HOMA) criteria (13.6%), followed by the Chinese Diabetes Society (11.4%), Adult Treatment Panel III (10.3%), Wildman (5.2%), and Karelis (4.2%) criteria; however, the MUO prevalence had an opposite trend to MHO prevalence. The magnitude of differences in the age-specific prevalence of MHO and MUO varied greatly and ranked in different orders. The proportion of insulin resistance for MHO and MUO individuals differed significantly regardless of which metabolic criterion was used. Conclusion: The prevalence of MHO and MUO in the Chinese population varies according to different definitions of obesity and metabolic disorders.
The Living Hand of the Past: The Role of Technology in Development
Authors: Pea Roy , Cole Michael
Published: February 2019

“Technology” is lately equated with hardware and software, but for the Ancient Greeks, a technology combined two linked features: the doing of an art/craft (techne) and theorizing about the doing (technologia). We thus consider a “technology” as a “sociotechnical system” – an entanglement of humans with one another, the tools, arts, crafts, practices and institutionalized forms of life of their time. Writing systems and new media are each relevant to understanding the roles of technologies in development, considered at an ontogenetic or historical level. We consider two ostensibly conflicting claims by Piaget that lead to the question of how the postnatal environment fundamentally differs from the intrauterine environment and how this difference changes the process of development. Vygotsky’s focus on the cultural/historical mediation of social relations helps us understand the dynamic interplay of technology and development as part of a single process of human development – and to resolve Piaget’s multifaceted views. To illustrate the insights offered by our cultural-historical approach, we compare the ancient period coupled with the development of literacy/numeracy and current historical circumstances in which new digital technologies are the focus. These two cases illuminate ways current changes are replaying in new circumstances a developmental process as old as Homo sapiens.
Assessment of the Silver Penetration and Distribution in Carious Lesions of Deciduous Teeth Treated with Silver Diamine Fluoride
Authors: Li Yihong , Liu Yingyi , Psoter Walter J. , Nguyen Olivia M. , Bromage Timothy G. , Walters Marc A. , Hu Bin , Rabieh Sasan , Kumararaja Fancy C.
Published: February 2019

The aim of this study was to determine the effects of 38% silver diamine fluoride (SDF) on carious lesions of human deciduous teeth. Ten extracted deciduous incisors with caries were collected and treated with SDF. After the treatment, the teeth were sectioned through the center of the carious lesion. The extent of sliver precipitation was examined using quantitative backscattered electron scanning electron microscopy (qBSE-SEM), energy-dispersive X-ray spectroscopy (EDX), and micro-computed tomography (micro-CT). The qBSE-SEM images revealed that the silver particles could penetrate through the pellicle complex, along with the rod sheaths into the demineralized enamel rods and the dentinal tubules, and form silver-enriched barriers surrounding the carious lesions at depths up to 2,490.2 μm (mean 744.7 ± 448.7 μm) within the dentinal tubules of the carious lesions, but less likely in the sound enamel. The EDX spectrum analysis revealed that carbon, oxygen, phosphorus, chlorine, silver, and calcium were the main elements detected in the lesions treated with SDF. Additionally, sodium, magnesium, aluminum, silicon, zinc, sulfur, and fluorine were detected as the minor elements within the SDF precipitation “zone.” The micro-CT analysis further showed that in the deep cavitated lesions, the silver precipitation could be observed in the pulp chamber. These findings provide new evidence defining the SDF mode of action for arresting caries and suggest that the application of a highly concentrated SDF solution on deciduous teeth should be used with caution for various carious lesions.
Genetic Knowledge within a National Australian Sample: Comparisons with Other Diverse Populations
Authors: Dar-Nimrod Ilan , MacNevin Georgia , Godwin Alexandra , Lynch Kate , Magory Cohen Tali , Ganesan Asha , Morandini James
Published: February 2019

Background: Genetic knowledge, which plays important functions in our understanding of science, health, social groupings, and even behaviour, has been evaluated in past studies with various populations. This wide reach of genetics means that different types of items are used to assess genetic knowledge, which restricts meaningful comparisons across time- and locale-based studies. Aim: The present study addresses this limitation by recruiting an Australia-wide sample and evaluating their genetic knowledge using items sourced from four diverse samples. Method: Seven hundred and eighty Australians completed a variety of items assessing their genetic knowledge as well as several demographic indicators. Results: The results show superior overall genetic knowledge in the current sample compared with previous samples. Additionally, the study finds that genetic knowledge about health and illness seems to be the most accurate, whereas such knowledge about social categorisations and behaviours seems to be the most error-prone. In the current sample, being a female and having interest in genetics were positive predictors of genetic knowledge; surprisingly educational attainment was not a significant predictor. Conclusion: Compared with previous surveys, the current sample showed significantly better genetic knowledge. However, certain areas that relate to public understating still indicate rampant misperceptions.
Reduced Opioid-Demand and Fewer Pulmonary Complications after Laparoscopic Liver Resection in the Posterior Segments
Authors: Del Pino Sabrina , Fischer Lutz , Nashan Björn , Li Jun
Published: February 2019

This single-centre study aims to evaluate the advantages and limitations of laparoscopic liver resection (LLR) of lesions in the posterior segments (segments 6 and 7) in comparison to the open procedure. Institutional database between June 2014 and October 2017 was retrieved. The perioperative data and the surgical outcomes were analysed retrospectively. Out of 366 consecutive liver resections, 35 patients who met the inclusion criteria were identified. Twenty patients underwent open liver resection, while 15 patients underwent pure LLR. The technical challenge of laparoscopic access for lesions in the posterior segments could be avoided by positioning the patient in a left lateral decubitus position. The median operative time was 316 vs. 242 min (p < 0.05) in the laparoscopic and the open group respectively. Despite a comparable rate of postoperative complications, according to the Dindo-Clavien classification, less pulmonary complications and a lower opioid-demand were found in the LLR group (p < 0.05). No 90-day mortality was observed in both groups. The LLR of posterior lesions is found to be a safe and feasible approach in selected cases with significantly less postoperative pulmonary complications and lower opioid-demand, even during the learning phase.
Transthoracic Pulmonary Artery Denervation for Pulmonary Arterial Hypertension
Authors: Huang Yuan , Liu Yi-Wei , Pan Hai-Zhou , Zhang Xiao-Ling , Li Jun , Xiang Li , Meng Jian , Wang Pei-He , Yang Jun , Jing Zhi-Cheng , Zhang Hao
Published: February 2019

Objective—

Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and persistently elevated mean pulmonary artery pressures and pulmonary vascular resistance. We aimed to investigate whether transthoracic pulmonary artery denervation (TPADN) attenuated pulmonary artery (PA) remodeling, improved right ventricular (RV) function, and affected underlying mechanisms. We also explored the distributions of sympathetic nerves (SNs) around human PAs for clinical translation.

Approach and Results—

We identified numerous SNs in adipose and connective tissues around the main PA trunks and bifurcations in male Sprague Dawley rats, which were verified in samples from human heart transplant patients. Pulmonary arterial hypertensive rats were randomized into TPADN and sham groups. In the TPADN group, SNs around the PA trunk and bifurcation were completely and accurately removed under direct visualization. The sham group underwent thoracotomy. Hemodynamics, RV function, and pathological changes in PA and RV tissues were measured via right heart catheterization, cardiac magnetic resonance imaging, and pathological staining, respectively. Compared with the sham group, the TPADN group had lower mean pulmonary arterial pressures, less PA and RV remodeling, and improved RV function. Furthermore, TPADN inhibited neurohormonal overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system and regulated abnormal expressions and signaling of neurohormone receptors in local tissues.

Conclusions—

There are numerous SNs around the rat and human main PA trunks and bifurcations. TPADN completely and accurately removed the main SNs around PAs and attenuated pulmonary arterial hypertensive progression by inhibiting excessive activation of the sympathetic nervous system and renin-angiotensin-aldosterone system neurohormone-receptor axes.
Tuning the Thromboinflammatory Response to Venous Flow Interruption by the Ectonucleotidase CD39
Authors: Anyanwu Anuli C. , Kanthi Yogendra , Fukase Keigo , Liao Hui , Mimura Tekashi , Desch Karl C. , Gruca Martin , Kaskar Saabir , Sheikh-Aden Hussein , Chi Liguo , Zhao Raymond , Yadav Vinita , Wakefield Thomas W. , Hyman Matthew C. , Pinsky David J.
Published: February 2019

Objective—

Leukocyte flux contributes to thrombus formation in deep veins under pathological conditions, but mechanisms that inhibit venous thrombosis are incompletely understood. Ectonucleotide di(tri)phosphohydrolase 1 (
ENTPD1
or
Cd39
), an ectoenzyme that catabolizes extracellular adenine nucleotides, is embedded on the surface of endothelial cells and leukocytes. We hypothesized that under venous stasis conditions, CD39 regulates inflammation at the vein:blood interface in a murine model of deep vein thrombosis.

Approach and Results—

CD39-null mice developed significantly larger venous thrombi under venous stasis, with more leukocyte recruitment compared with wild-type mice. Gene expression profiling of wild-type and
Cd39
-null mice revealed 76 differentially expressed inflammatory genes that were significantly upregulated in
Cd39
-deleted mice after venous thrombosis, and validation experiments confirmed high expression of several key inflammatory mediators. P-selectin, known to have proximal involvement in venous inflammatory and thrombotic events, was upregulated in
Cd39
-null mice. Inferior vena caval ligation resulted in thrombosis and a corresponding increase in both P-selectin and VWF (von Willebrand Factor) levels which were strikingly higher in mice lacking the
Cd39
gene. These mice also manifest an increase in circulating platelet-leukocyte heteroaggregates suggesting heterotypic crosstalk between coagulation and inflammatory systems, which is amplified in the absence of CD39.

Conclusions—

These data suggest that CD39 mitigates the venous thromboinflammatory response to flow interruption.
Sedentary Behavior, Exercise, and Cardiovascular Health
Authors: Lavie Carl J. , Ozemek Cemal , Carbone Salvatore , Katzmarzyk Peter T. , Blair Steven N.
Published: February 2019

Sedentary behavior and physical inactivity are among the leading modifiable risk factors worldwide for cardiovascular disease and all-cause mortality. The promotion of physical activity and exercise training (ET) leading to improved levels of cardiorespiratory fitness is needed in all age groups, race, and ethnicities and both sexes to prevent many chronic diseases, especially cardiovascular disease. In this state-of-the-art review, we discuss the negative impact of sedentary behavior and physical inactivity, as well as the beneficial effects of physical activity /ET and cardiorespiratory fitness for the prevention of chronic noncommunicable diseases, including cardiovascular disease. We review the prognostic utility of cardiorespiratory fitness compared with obesity and the metabolic syndrome, as well as the increase of physical activity /ET for patients with heart failure as a therapeutic strategy, and ET dosing. Greater efforts at preventing sedentary behavior and physical inactivity while promoting physical activity, ET, and cardiorespiratory fitness are needed throughout the healthcare system worldwide and particularly in the United States in which the burden of cardiometabolic diseases remains extremely high.