bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell sources for large‐scale manufacture of red blood cells
Authors: Kim S. , Baek E. J. 
Published: April 2018

Owing to the high demand for blood production to replace donated blood, there have been many developments in the production methods of red blood cells (RBCs) in the past decades. Although cord blood or adult haematopoietic stem cells were shown to mature into functional reticulocytes in vitro, their limited proliferative capacity led to the development of new strategies that use pluripotent stem cells or cell lines that have been immortalized using gene modification techniques. This research highlights embryonic stem cells, induced pluripotent stem cells and immortalized cell lines as possible sources of RBCs. Despite the low enucleation efficiency of erythroblasts derived from these pluripotent stem cells, recent studies have shown the possibility of an increased yield of final enucleated red cell products. In addition, primary erythroid early progenitor cells could be used as a cell source by culture conditioning or the exogenous overexpression of adequate genes for self‐renewal and proliferation. The strategy of directly establishing immortalized erythroid progenitor cell lines is suitable for the manufacture of RBCs, since these cell lines are easy to maintain and mature rapidly. In this review, different approaches for the manufacture of erythrocytes, using more expandable precursor sources, are discussed.
Tomás de Aquino y la relación entre filosofía y teología: una interpretación literal de la Suma de Teología I, Q. 1, Art. 1
Authors: Mendoza José María Felipe 
Published: April 2018

<p>El presente estudio indaga la posición de Tomás de Aquino sobre la relación entre filosofía y teología sagrada o sacra doctrina, tal como ha sido expuesta en la <em>Prima Pars</em>, q. 1, a. 1, de la <em>Suma de Teología</em>. Esta distinción busca fijar los límites entre ambas disciplinas a partir de su relación con la antropología, en la medida en que el Aquinate comprende la filosofía como esencialmente natural y racional, y la sacra doctrina como aquella ciencia cuyo fundamento es la gratuidad de la fe.</p><p> </p>
El placer humano y la percepción social de la justicia: apuntes para una teoría psicológica de las afecciones estructurales
Authors: Guerrero Ramos Miguel Ángel 
Published: April 2018

<p>El placer humano es considerado desde varios puntos de vista como un impulso vital interno sumamente importante; sin embargo, nuestra relación con el mismo es ambivalente, ya que es también un espacio de control institucional y de represión social en múltiples niveles. El placer tiene además un papel crucial en lo que atañe al modo como percibimos si vivimos en un mundo justo o no y, en la medida en que influye en dicha percepción, puede que el placer tenga asimismo un papel clave para determinar o por lo menos indagar en el psiquismo inconsciente de la sociedad. Se expone en este artículo, por tanto, la necesidad de lograr una teoría crítica que ligue los aspectos psíquicos, filosóficos y sociológicos del placer con las distintas formas de dominación en la moderna sociedad capitalista y de consumo.</p><p> </p>
La realidad según la física cuántica y la investigación-acción
Authors: Nani David Francisco 
Published: April 2018

<p>El presente artículo se enfoca en la investigación-acción y la física cuántica. Efectúa una comparación respecto a una idea central: el concepto de realidad. Explica la presencia de similitudes, por ejemplo, la realidad como representación y como entidad influenciada por el observador. Más aún, el investigador debe seleccionar entre diferentes marcos explicativos, pues lo real no puede ser abordado por medio de un único aparato teórico y metodológico. Aunque ambas visiones socavan la ciencia moderna, existen diferencias, en tanto que las particularidades de la investigación- acción son de un rango mayor y la realidad en esta es de índole social y debe ser mejorada.</p><p> </p>
MicroRNA-216a Inhibits NF-κB-Mediated Inflammatory Cytokine Production in Teleost Fish by Modulating p65
Authors: Xu Tianjun , Chu Qing , Cui Junxia , Huo Ruixuan 
Published: April 2018

ABSTRACT

Inflammation is the host self-protection mechanism to eliminate pathogen invasion. The excessive inflammatory response can result in uncontrolled inflammation, autoimmune diseases, or pathogen dissemination. Recent studies have widely shown that microRNAs (miRNAs) contribute to the regulation of inflammation in mammals by repressing gene expression at the posttranscriptional level. However, the miRNA-mediated mechanism in the inflammatory response in fish remains hazy. In the present study, the regulatory mechanism of the miR-216a-mediated inflammatory response in teleost fish was addressed. We found that the expression of miR-216a could be significantly upregulated in the miiuy croaker after challenge with
Vibrio anguillarum
and lipopolysaccharide. Bioinformatics predictions demonstrated a potential binding site of miR-216a in the 3′ untranslated region of the p65 gene, and the result was further confirmed by luciferase assay. Moreover, both the mRNA and protein levels of p65 in macrophages were downregulated by miR-216a. Deletion mutant analysis of the miR-216a promoter showed that the Ap1 and Sp1 transcription factor binding sites are indispensable for the transcription of miR-216a. Further study revealed that overexpression of miR-216a suppresses inflammatory cytokine expression and negatively regulates NF-κB signaling, which inhibit an excessive inflammatory response. The collective results indicate that miR-216a plays a role as a negative regulator involved in modulating the bacterium-induced inflammatory response.
The Functional Oligomeric State of Tegument Protein GP41 Is Essential for Baculovirus Budded Virion and Occlusion-Derived Virion Assembly
Authors: Li Yimeng , Shen Shu , Hu Liangbo , Deng Fei , Vlak Just M. , Hu Zhihong , Wang Hualin , Wang Manli 
Published: April 2018

ABSTRACT

gp41
, one of the baculovirus core genes, encodes the only recognized tegument (O-glycosylated) protein of the occlusion-derived virion (ODV) phenotype so far. A previous study using a temperature-sensitive Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) mutant showed that GP41 plays a crucial role in budded virion (BV) formation. However, the precise function of GP41 in the baculovirus replication cycle remains unclear. In this study, AcMNPV GP41 was found to accumulate around the ring zone (RZ) region within the infected nucleus and finally assembled into both BVs and ODVs. Deletion of
gp41
from the AcMNPV genome showed that BVs were no longer formed and ODVs were no longer assembled, suggesting the essential role of this gene in baculovirus virion morphogenesis. In infected cells, besides the 42-kDa monomers, dimers and trimers were detected under nonreducing conditions, whereas only trimeric GP41 forms were selectively incorporated into BVs or ODVs. Mutations of all five cysteines in GP41 individually had minor effects on GP41 oligomer formation, albeit certain mutations impaired infectious BV production, suggesting flexibility in the intermolecular disulfide bonding. Single mutations of key leucines within two predicted leucine zipper-like motifs did not interfere with GP41 oligomerization or BV and ODV formation, but double leucine mutations completely blocked oligomerization of GP41 and progeny BV production. In the latter case, the usual subcellular localization, especially RZ accumulation, of GP41 was abolished. The above findings clearly point out a close correlation between GP41 oligomerization and function and therefore highlight the oligomeric state as the functional form of GP41 in the baculovirus replication cycle.

IMPORTANCE
The tegument, which is sandwiched between the nucleocapsid and the virion envelope, is an important substructure of many enveloped viruses. It is composed of one or more proteins that have important functions during virus entry, replication, assembly, and egress. Unlike another large DNA virus (herpesvirus) that encodes an extensive set of tegument components, baculoviruses very likely exploit the major tegument protein, GP41, to execute functions in baculovirus virion morphogenesis and assembly. However, the function of this O-glycosylated baculovirus tegument protein remains largely unknown. In this study, we identified trimers as the functional structure of GP41 in baculovirus virion morphogenesis and showed that both disulfide bridging and protein-protein interactions via the two leucine zipper-like domains are involved in the formation of different oligomeric states. This study advances our understanding of the unique viral tegument protein GP41 participating in the life cycle of baculoviruses.
Risk factors and biomarkers of non-alcoholic fatty liver disease: an observational cross-sectional population survey
Authors: Hu Xiao-Yu , Li Yun , Li Long-Quan , Zheng Yuan , Lv Jia-Hong , Huang Shu-Chun , Zhang Weinong , Liu Liang , Zhao Ling , Liu Zhuiguo , Zhao Xiu-Ju 
Published: April 2018

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is a major public health burden in China, and its prevalence is increasing. This study aimed to determine the risk factors and biomarkers of NAFLD.DesignAn observational cross-sectional primary survey.SettingCentral China.ParticipantsThe study included 1479 participants aged over 18 and below 80 years, not currently being treated for cancer or infectious disease or no surgery in the previous year, and no history of cancer or an infectious disease. Participants underwent clinical examination, metabolomic assay and anthropometric assessment. Univariate and logistic regression analyses were used to evaluate associations between covariates and NAFLD.Main outcome measuresRisk factors and metabolic biomarkers including sex, body mass index, hypertension, body fat ratio, blood triglycerides, blood fasting glucose, liver enzyme elevation, uric acid and oleic acid-hydroxy oleic acid (OAHOA).ResultsData from the 447 participants (mean age 44.3±11.9 years) were analysed, and the prevalence of NAFLD was 24.7%. Male sex (OR 3.484, 95% CI 2.028 to 5.988), body mass index ≥24 kg/m2(OR 8.494, 95% CI 5.581 to 12.928), body fat ratio (≥25 for women, ≥20 for men) (OR 1.833, 95% CI 1.286 to 2.756), triglycerides ≥1.7 mmol/L (OR 1.340, 95% CI 1.006 to 1.785), fasting glucose ≥6.1 mmol/L (OR 3.324, 95% CI 1.888 to 5.850), blood pressure ≥140/90 mm Hg or antihypertensive drug treatment (OR 1.451, 95% CI 1.069 to 1.970), uric acid (≥357 μmol/L for women, ≥416 μmol/L for men) (OR 2.755, 95% CI 2.009 to 3.778) and OAHOA (<5 nmol/L) (OR 1.340, 95% CI 1.006 to 1.785) were independent predictors of NAFLD (all P<0.05). These results were verified by all 1479 participants.ConclusionsNAFLD was common among the study participants. In particular, NAFLD was correlated with uric acid. We identified OAHOA as a novel marker of NAFLD prevalence. It provides a reference on the prevention of NAFLD and related metabolic diseases with the rapid urbanisation, technological advancement and population ageing in China over the recent decades.
Association between serum lipids concentration and patients with age-related cataract in China: a cross-sectional, case–control study
Authors: Li Shengjie , Li Danhui , Zhang Yudong , Teng Jisen , Shao Mingxi , Cao Wenjun 
Published: April 2018

ObjectiveObesity and a high-fat diet have been found to be associated with an increased risk of age-related cataract (ARC). Thus, this study aimed to investigate whether serum lipid levels are associated with the incidence of ARC.DesignCross-sectional, case–control study.SettingEyeandENT Hospital of Fudan University, Shanghai, China.ParticipantsA total of 219 ARC (male=94, female=125) subjects and 218 (male=110, female=118) normal control subjects were recruited in this study.Outcome measuresA detailed eye and systematic examination was performed. Serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and cholesterol (CHO) levels were measured by enzymatic colorimetry, and serum apolipoprotein A (APOA) and apoB (APOB) levels were measured by immunoturbidimetry. The subgroups were classified according to gender and types of disease (cortical, nuclear and posterior subcapsular cataract). Logistic regression analyses were performed to identify the association between serum lipid levels and ARC.ResultsThe serum LDL-C, TG, CHO and APOA levels were significantly higher (p<0.05) in the ARC group than in the control group. A similar result was observed when the serum lipid concentrations were compared between the ARC and control groups both in male and female subgroups. A higher proportion of individuals in the ARC group had higher LDL-C, TG, CHO and APOA levels (fold=3.45, 17.37, 3.27 and11.91, respectively; p<0.0001 in all cases) than in the control group. Results of the logistic regression analyses revealed that high LDL-C (ORs=1.897, 95% CI 0.960 to 3.678) and TG (OR=1.854, 95% CI 1.232 to 2.791) were the independent risk factors for ARC.ConclusionThe serum LDL-C and TG levels were demonstrated to be independent risk factors for ARC.
New York City’s window guard policy: four decades of success
Authors: Toprani Amita , Robinson Martha , Middleton III James K , Hamade Ali , Merrill Thomas 
Published: April 2018

BackgroundPreventing child falls from windows is easily accomplished by installing inexpensive window-limiting devices but window falls remain a common cause of child injuries. This article describes the history and evolution of the New York City (NYC) window guard rule,which requires building owners to install window guards in apartments housing children aged ≤10 years. The NYC window guard rule was the first directive of its kind in the USA when it was adopted in 1976, and it has led to a dramatic and long-lasting reduction in child window fall-related injuries and deaths.MethodsData about the history of the window guard rule were obtained by reviewing programmatic records, correspondence, legal decisions and the published literature. In addition, key informant interviews were conducted with programme staff.Results and DiscussionThis article describes each stage of policy development, starting with epidemiological studies defining the scope of the problem in the 1960s and pilot-testing of the window guard intervention. We describe the adoption, implementation and enforcement of the rule. In addition, we show how the rule was modified over time and document the rule’s impact on window fall incidence in NYC. We describe litigation that challenged the rule’s constitutionality and discuss the legal arguments used by opponents of the rule. Finally, we discuss criminal and tort liability as drivers of compliance and summarise lessons learnt.
Epimorphin regulates the intestinal stem cell niche via effects on the stromal microenvironment
Authors: Vishy Courtney E. , Swietlicki Elzbieta A. , Gazit Vered , Amara Suneetha , Heslop Gabriela , Lu Jianyun , Levin Marc S. , Rubin Deborah C. 
Published: April 2018

Stem cell therapy is a potential therapeutic approach for disorders characterized by intestinal injury or loss of functional surface area. Stem cell function and proliferation are mediated by the stem cell niche. Stromal cells such as intestinal subepithelial myofibroblasts (ISEMFs) are important but poorly studied components of the stem cell niche. To examine the role of ISEMFs, we have previously generated mice with deletion of epimorphin ( Epim), an ISEMF protein and member of the syntaxin family of intracellular vesicle docking proteins that regulate cell secretion. Herein we explore the mechanisms for previous observations that Epim deletion increases gut crypt cell proliferation, crypt fission, and small bowel length in vivo. Stem cell-derived crypt culture techniques were used to explore the interaction between enteroids and myofibroblasts from Epim−/− and WT mice. Enteroids cocultured with ISEMFS had increased growth and crypt-like budding compared with enteroids cultured without stromal support. Epim deletion in ISEMFs resulted in increased enteroid budding and surface area compared with cocultures with wild-type (WT) ISEMFs. In primary crypt cultures, Epim−/− enteroids had significantly increased surface area and budding compared with WTs. However, stem cell assays comparing the number of Epim−/− vs. WT colony-forming units after first passage showed no differences in the absence of ISEMF support. Epim−/− vs. WT ISEMFs had increased Wnt4 expression, and addition of Wnt4 to WT cocultures enhanced budding. We conclude that ISEMFs play an important role in the stem cell niche. Epim regulates stem cell proliferation and differentiation via stromal contributions to the niche microenvironment. NEW & NOTEWORTHY The role of subepithelial intestinal myofibroblasts (ISEMFs) in the gut stem cell niche is controversial. We provide novel evidence supporting ISEMFs as important niche contributors. We show that the in vivo intestinal effects of deletion of myofibroblast Epim can be recapitulated in crypt stem cell cultures in vitro. ISEMFs support cocultured stem cell proliferation and enteroid growth, and these effects are augmented by deletion of Epim, a syntaxin that regulates myofibroblast cell secretion.
KLF2-mediated disruption of PPAR-γ signaling in lymphatic endothelial cells exposed to chronically increased pulmonary lymph flow
Authors: Morris Catherine J. , Kameny Rebecca J. , Boehme Jason , Gong Wenhui , He Youping , Zhu Terry , Maltepe Emin , Raff Gary W. , Fineman Jeffrey R. , Datar Sanjeev A. 
Published: April 2018

Lymphatic abnormalities associated with congenital heart disease are well described, yet the underlying mechanisms remain poorly understood. Using a clinically relevant ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated that lymphatic endothelial cells (LECs) exposed in vivo to chronically increased pulmonary lymph flow accumulate ROS and have decreased bioavailable nitric oxide (NO). Peroxisome proliferator-activated receptor-γ (PPAR-γ), which abrogates production of cellular ROS by NADPH oxidase, is inhibited by Krüppel-like factor 2 (KLF2), a flow-induced transcription factor. We hypothesized that chronically increased pulmonary lymph flow induces a KLF2-mediated decrease in PPAR-γ and an accumulation of cellular ROS, contributing to decreased bioavailable NO in LECs. To better understand the mechanisms that transduce the abnormal mechanical forces associated with chronically increased pulmonary lymph flow, LECs were isolated from the efferent vessel of the caudal mediastinal lymph node of control ( n = 5) and shunt ( n = 5) lambs. KLF2 mRNA and protein were significantly increased in shunt compared with control LECs, and PPAR-γ mRNA and protein were significantly decreased. In control LECs exposed to shear forces in vitro, we found similar alterations to KLF2 and PPAR-γ expression. In shunt LECs, NADPH oxidase subunit expression was increased, and bioavailable NO was significantly lower. Transfection of shunt LECs with KLF2 siRNA normalized PPAR-γ, ROS, and bioavailable NO. Conversely, pharmacological inhibition of PPAR-γ in control LECs increased ROS equivalent to levels in shunt LECs at baseline. Taken together, these data suggest that one mechanism by which NO-mediated lymphatic function is disrupted after chronic exposure to increased pulmonary lymph flow is through altered KLF2-dependent PPAR-γ signaling, resulting in increased NADPH oxidase activity, accumulation of ROS, and decreased bioavailable NO.NEW & NOTEWORTHY Lymphatic endothelial cells, when exposed in vivo to chronically elevated pulmonary lymph flow in a model of congenital heart disease with increased pulmonary blood flow, demonstrate Krüppel-like factor 2-dependent disrupted peroxisome proliferator-activated receptor-γ signaling that results in the accumulation of reactive oxygen species and decreased bioavailable nitric oxide.
Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators
Authors: Maron Barry J. , Casey Susan A. , Olivotto Iacopo , Sherrid Mark V. , Semsarian Christopher , Autore Camillo , Ahmed Aisha , Boriani Giuseppe , Francia Pietro , Winters Stephen L. , Giudici Michael , Koulova Anna , Garberich Ross , Rowin Ethan J. , Sears Samuel F. , Maron Martin S. , Spirito Paolo 
Published: April 2018

Background:
High-risk patients with hypertrophic cardiomyopathy (HCM) are identified by contemporary risk stratification and effectively treated with implantable cardioverter-defibrillators (ICDs). However, long-term HCM clinical course after ICD therapy for ventricular tachyarrhythmias is incompletely understood.

Methods and Results:
Cohort of 486 high-risk HCM patients with ICDs was assembled from 8 international centers. Clinical course and device interventions were addressed, and survey questionnaires assessed patient anxiety level and psychological well-being related to ICD therapy. Of 486 patients, 94 (19%) experienced appropriate ICD interventions terminating ventricular tachycardia/ventricular fibrillation, 3.7% per year for primary prevention, over 6.4±4.7 years. Of 94 patients, 87 were asymptomatic or only mildly symptomatic at the time of appropriate ICD interventions; 74 of these 87 (85%) remained in classes I/II without significant change in clinical status over the subsequent 5.9±4.9 years (up to 22). Among the 94 patients, there was one sudden death (caused by device failure; 1.1%); 3 patients died from other HCM-related processes unrelated to arrhythmic risk (eg, end-stage heart failure). Post-ICD intervention, freedom from HCM mortality was 100%, 97%, and 92% at 1, 5, and 10 years, distinctly lower than in ischemic or nonischemic cardiomyopathy ICD trials. HCM patients with ICD interventions reported heightened anxiety in expectation of future shocks, but with intact general psychological well-being and quality of life.

Conclusions:
In HCM, unlike ischemic heart disease, prevention of sudden death with ICD therapy is unassociated with significant increase in cardiovascular morbidity or mortality, or transformation to heart failure deterioration. ICD therapy does not substantially impair overall psychological and physical well-being.