Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of Proinflammatory Factors in Renal Cortex Induced by Methylmalonic Acid

Background: Methylmalonic aciduria is an inborn error of metabolism that causes renal failure and tubulointerstitial (TI) nephritis as complications. This study aimed to examine the levels of expression of several genes related to inflammation, oxidative stress, and mitochondrial function in the renal cortex of rats receiving methylmalonic acid (MMA). Methods: Rats received MMA subcutaneously for a month. Tumor necrosis factor alpha (TNFα), nuclear factor-kappa B, interleukin 1 beta (IL-1β), and cyclooxygenase 2 (COX-2) genes were examined by real-time polymerase chain reaction. We also examined transforming growth factor beta (TGF-β) related to TI fibrosis, c-FOS, belonging to the immediate early gene family of transcription factors, and expression of SIRT1, related to energy production. Results: There was significantly higher expression of TNFα and a trend toward a higher level of TGF-β transcripts in the methylmalonic model group compared with the controls. However, SIRT1 expression was not different among the groups. Urinary MMA excretion correlated positively with mRNA level of TGF-β. The expression of COX-2 was positively associated with the expression of c-FOS and inversely related to the expression of IL-1β. Conclusions: The higher levels of TNFα and TGF-β transcripts suggest inflammation and differentiation processes in the renal cortex in rats because of MMA. After 1 month of MMA injections, expression levels of SIRT1 were not affected, suggesting mitochondrial preservation in early stages of the disease.
High-level expression of adeno-associated virus (AAV) Rep78 or Rep68 protein is sufficient for infectious-particle formation by a rep-negative AAV mutant

Adeno-associated virus (AAV) codes for four closely related nonstructural proteins (Rep) required for AAV DNA replication and gene regulation. In vitro studies have revealed that either Rep78 or Rep68 alone is sufficient for AAV DNA replication. Rep52 and Rep40 are not required for DNA replication but have been reported to enhance the efficiency of accumulation of single-stranded progeny DNA. Previous studies on rep-expressing cell lines had indicated that only a subset of the four Rep proteins are required for the production of infectious AAV. We therefore set out to determine the minimal set of Rep proteins sufficient for the generation of infectious AAV. Transient cotransfections in HeLa cells of constructs for high-level expression of individual Rep proteins with a rep-negative AAV genome revealed that either Rep78 or Rep68 alone could complement for a full replication cycle yielding infectious virus. This result was confirmed by transfection studies in the cell line HeM2, which selectively expresses Rep78 at rather low levels under the control of the glucocorticoid-responsive mouse mammary tumor virus long terminal repeat (C. Hölscher, M. Hörer, J. A. Kleinschmidt, H. Zentgraf, A. Bürkle, and R. Heilbronn, J. Virol. 68:7169-7177, 1994). Increasing the level of Rep78 expression by transfection of a glucocorticoid receptor expression construct resulted in a higher level of DNA replication of a cotransfected rep-negative AAV genome and in the production of infectious rep-negative AAV particles. We further report on the generation of a new rep-expressing cell line, HeCM1, which was obtained by stable supertransfection of a construct for constitutive Rep40 expression into HeM1 cells (Hölscher et al., J. Virol. 68:7169-7177). Transfection of rather large amounts of rep-negative AAV DNA led to detectable virus production in HeCM1 cells even in the absence of the cotransfected glucocorticoid receptor expression construct, but higher yields were obtained after increasing the Rep78 level by coexpression of the glucocorticoid receptor. These data demonstrate that all Rep functions required for the productive replication of AAV in HeLa cells are contained within both Rep78 and Rep68.
Formation of the Ventricles

The formation of the ventricles of the heart involves numerous carefully regulated temporal events, including the initial specification and deployment of ventricular progenitors, subsequent growth and maturation of the ventricles through “ballooning” of chamber myocardium, the emergence of trabeculations, the generation of the compact myocardium, and the formation of the interventricular septum. Several genes have been identified through studies on mouse knockout and transgenic models, which have contributed to our understanding of the molecular events governing these developmental processes. Interpretation of these studies highlights the fact that even the smallest perturbation at any stage of ventricular development may lead to cardiac malformations that result in either early embryonic mortality or a manifestation of congenital heart disease.
Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer

Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12–3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99–3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio (Ptrend = 0.55 and Ptrend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519–24. ©2017 AACR.
Low Bone Mineral Density and Risk of Incident Fracture in HIV-Infected Adults

Background Prevalence rates of low bone mineral density (BMD) and bone fractures are higher among HIV-infected adults compared with the general United States (US) population, but the relationship between BMD and incident fractures in HIV-infected persons has not been well described. Methods Dual energy X-ray absorptiometry (DXA) results of the femoral neck of the hip and clinical data were obtained prospectively during 2004-2012 from participants in two HIV cohort studies. Low BMD was defined by a T-score in the interval >-2.5 to <-1.0 (osteopenia) or ≤-2.5 (osteoporosis). We analysed the association of low BMD with risk of subsequent incident fractures, adjusted for sociodemographics, other risk factors and covariables, using multivariable proportional hazards regression. Results Among 1,006 participants analysed (median age 43 years [IQR 36–49], 83% male, 67% non-Hispanic white, median CD4+ T-cell count 461 cells/mm3 [IQR 311–658]), 36% (n=358) had osteopenia and 4% (n=37) osteoporosis; 67 had a prior fracture documented. During 4,068 person-years of observation after DXA scanning, 85 incident fractures occurred, predominantly rib/sternum (n=18), hand (n=14), foot (n=13) and wrist (n=11). In multivariable analyses, osteoporosis (adjusted hazard ratio [aHR] 4.02, 95% CI 2.02, 8.01) and current/prior tobacco use (aHR 1.59, 95% CI 1.02, 2.50) were associated with incident fracture. Conclusions In this large sample of HIV-infected adults in the US, low baseline BMD was significantly associated with elevated risk of incident fracture. There is potential value of DXA screening in this population.
Validity of an upper-body-mounted accelerometer to measure peak vertical and resultant force during running and change-of-direction tasks

This study assessed the validity of a tri-axial accelerometer worn on the upper body to estimate peak forces during running and change-of-direction tasks. Seventeen participants completed four different running and change-of-direction tasks (0°, 45°, 90°, and 180°; five trials per condition). Peak crania-caudal and resultant acceleration was converted to force and compared against peak force plate ground reaction force (GRF) in two formats (raw and smoothed). The resultant smoothed (10 Hz) and crania-caudal raw (except 180°) accelerometer values were not significantly different to resultant and vertical GRF for all running and change-of-direction tasks, respectively. Resultant accelerometer measures showed no to strong significant correlations (r = 0.00–0.76) and moderate to large measurement errors (coefficient of variation [CV] = 11.7–23.9%). Crania-caudal accelerometer measures showed small to moderate correlations (r = − 0.26 to 0.39) and moderate to large measurement errors (CV = 15.0–20.6%). Accelerometers, within integrated micro-technology tracking devices and worn on the upper body, can provide a relative measure of peak impact force experienced during running and two change-of-direction tasks (45° and 90°) provided that resultant smoothed values are used.
Efficacy and safety of evolocumab in reducing lipids and cardiovascular events.

BACKGROUND Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. We conducted two extension studies to obtain longer-term data. METHODS In two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2:1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined. RESULTS As compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P<0.001). Most adverse events occurred with similar frequency in the two groups, although neurocognitive events were reported more frequently in the evolocumab group. The risk of adverse events, including neurocognitive events, did not vary significantly according to the achieved level of LDL cholesterol. The rate of cardiovascular events at 1 year was reduced from 2.18% in the standard-therapy group to 0.95% in the evolocumab group (hazard ratio in the evolocumab group, 0.47; 95% confidence interval, 0.28 to 0.78; P=0.003). CONCLUSIONS During approximately 1 year of therapy, the use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis. (Funded by Amgen; OSLER-1 and OSLER-2 ClinicalTrials.gov numbers, NCT01439880 and NCT01854918.).
Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic‐ischemic brain injury

Complement is an essential component of inflammation that plays a role in ischemic brain injury. Recent reports demonstrate novel functions of complement in normal and diseased CNS, such as regulation of neurogenesis and synapse elimination. Here, we examined the role of complement‐derived peptide C3a in unilateral hypoxia‐ischemia (HI), a model of neonatal HI encephalopathy. HI injury was induced at postnatal day 9 (P9), and loss of hippocampal tissue was determined on P31. We compared WT mice with transgenic mice expressing C3a under the control of glial fibrillary acidic protein promoter, which express biologically active C3a only in CNS and without the requirement of a priori complement activation. Further, we injected C3a peptide into the lateral cerebral ventricle of mice lacking the C3a receptor (C3aR) and WT mice and assessed HI‐induced memory impairment 41 d later. We found that HI‐induced tissue loss in C3a overexpressing mice was reduced by 50% compared with WT mice. C3a peptide injected 1 h after HI protected WT but not C3aR‐deficient mice against HI‐induced memory impairment. Thus, C3a acting through its canonical receptor ameliorates behavioral deficits after HI injury, and C3aR is a novel therapeutic target for the treatment of neonatal HI encephalopathy. —Järlestedt, K. , Rousset, C. I. , Ståhlberg, A. , Sourkova, H. , Atkins, A. L. , Thornton, C. , Barnum, S. R. , Wetsel, R. A. , Dragunow, M. , Pekny, M. , Mallard, C. , Hagberg, H. , Pekna, M. , Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic‐ischemic brain injury. FASEB J. 27, 3797–3804 (2013). www.fasebj. org
Interventions minimizing fatigue in children/adolescents with cancer: An integrative review

Fatigue is among the most common, debilitating, and distressing symptoms associated with chronic condition in pediatric population. The purpose of this study was to identify non-pharmacological fatigue interventions in children and adolescents with cancer. For this, we carried out an integrative review of the literature from January 2000 to December 2016. A comprehensive search of four databases was conducted: Cumulative Index to Nursing and Allied Health Literature, Psychology Information, Medline via PubMed, and Web of Science. Randomized controlled trial, quasi-experimental, case-control and cohort studies were included in this review. Thirteen relevant studies were included for analysis. Seven papers reported positive outcomes for exercise, exercise plus leisure activities, healing touch and acupressure. In another six papers using exercise, exercise plus psychological intervention and massage, no effectiveness was found. Effective management of fatigue in children and adolescents is important but research in this area is limited, so the results of this review should be interpreted cautiously. Future researchers are encouraged to test the effective interventions in homogenous cancer populations and in other groups where fatigue is a common concern.
Limits to Sulfur Accumulation in Transgenic Lupin Seeds Expressing a Foreign Sulfur-Rich Protein

The low sulfur amino acid content of legume seeds restricts their nutritive value for animals. We have investigated the limitations to the accumulation of sulfur amino acids in the storage proteins of narrow leaf lupin (Lupinus angustifolius) seeds. Variation in sulfur supply to lupin plants affected the sulfur amino acid accumulation in the mature seed. However, when sulfur was in abundant supply, it accumulated to a large extent in oxidized form, rather than reduced form, in the seeds. At all but severely limiting sulfur supply, addition of a transgenic (Tg) sink for organic sulfur resulted in an increase in seed sulfur amino acid content. We hypothesize that demand, or sink strength for organic sulfur, which is itself responsive to environmental sulfur supply, was the first limit to the methionine (Met) and cysteine (Cys) content of wild-type lupin seed protein under most growing conditions. In Tg, soil-grown seeds expressing a foreign Met- and Cys-rich protein, decreased pools of free Met, free Cys, and glutathione indicated that the rate of synthesis of sulfur amino acids in the cotyledon had become limiting. Homeostatic mechanisms similar to those mediating the responses of plants to environmental sulfur stress resulted in an adjustment of endogenous protein composition in Tg seeds, even when grown at adequate sulfur supply. Uptake of sulfur by lupin cotyledons, as indicated by total seed sulfur at maturity, responded positively to increased sulfur supply, but not to increased demand in the Tg seeds.
Ad Hoc Networking Solutions

The decentralization of wireless networks to reduce the dependence on fixed infrastructures such as base stations has become the subject of vast interest in the past few years. In the future, this might form the backbone of general commercial mobile networks too. Such a system would be quite attractive for network operators and users alike, as it is inherently better suited to respond robustly to any unforeseen situation. At the same time, it does not require a fixed infrastructure that reduces both the setup and maintenance costs of a network. However, decentralization gives rise to various network setup and management issues on different open systems interconnection (OSI) layers. In this article, we present a few solutions, on different OSI layers, that provide a good end-to-end performance of such a scheme while ensuring that the network is decentralized and operates in a self-organized manner.
PI3-Kinase Upregulation and Involvement in Spontaneous Tone in Arteries From DOCA-Salt Rats: Is p110&dgr; the Culprit?

Abstract—Increased expression of phosphoinositide 3-kinase (PI3-kinase) mediates elevated tone in the aorta from hypertensive deoxycorticosterone acetate (DOCA)-salt rats. In this article, we hypothesized that (1) alterations observed with respect to PI3-kinase observed in the aorta would also occur in mesenteric resistance arteries responsible for determining total peripheral resistance (TPR) and (2) p110&dgr; activity was increased and localized to vascular smooth muscle cells (VSMCs), and was responsible for the increase in spontaneous tone in aortae from DOCA-salt rats. Mesenteric resistance arteries and aorta were isolated from DOCA-salt (190±3 mm Hg) and sham (121±2 mm Hg) rats. Myograph experiments revealed LY294002 (20 &mgr;mol/L), a PI3-kinase inhibitor, significantly decreased tone in mesenteric resistance arteries from DOCA-salt rats as compared with sham (−49±12 mg versus −10±7 mg). Western analyses of resistance artery protein homogenate revealed p85&agr; and p110&dgr; subunit protein, with significantly elevated levels of p110&dgr; protein in the DOCA-salt compared with sham rats (0.30±0.07 versus 0.16±0.04% smooth muscle alpha-actin arbitrary units). Immunohistochemistry revealed p110&dgr;-specific staining in VSMCs, with more intense staining in aortae from DOCA-salt rats. Compared with aortae from sham, p110&dgr;-associated PI3-kinase activity was increased in DOCA-salt (158% of sham) and likely responsible for spontaneous tone because the p110&dgr; specific inhibitor IC87114 decreased spontaneous tone in a concentration-dependent manner. Collectively, these data further implicate the p110&dgr; isoform of PI3-kinase in arterial hyperresponsiveness in hypertension at the level of both large and small arteries.
The clinical spectrum of Castleman's disease

Castleman's disease (CD) is a rare, poorly understood lymphoproliferative disease. The spectrum of symptoms and course of disease are broad, but there is no large study describing the natural history of this disease. Basic clinic and laboratory data from the records of 113 patients with CD evaluated at the Mayo Clinic and University of Nebraska were abstracted. The impact of these variables on overall survival (OS) from time of diagnosis was evaluated. Sixty patients had multicentric disease. Of the patients with multicentric CD, 32% had criteria sufficient for a diagnosis of POEMS syndrome. For all patients, 2, 5, and 10‐year OS was 92%, 76%, 59%, respectively. Most of the factors identified as risk factors for death on univariate analysis cosegregated with diagnostic criteria for POEMS syndrome, which supported the concept of four categories of CD, which are (along with their 5‐year OS): (1) unicentric CD (91%); (2) multicentric CD associated with the osteosclerotic variant of POEMS syndrome (90%); (3); multicentric CD without POEMS syndrome (65%); and (4) multicentric CD with POEMS syndrome without osteosclerotic lesions (27%). We have demonstrated that CD represents a spectrum of disease that can be differentiated by simple prognostic factors that provide a framework for further study. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Book Review: Beyond Racial Gridlock: Embracing Mutual Responsibility

Sea la Luz: The Making of Mexican Protestantism in the American Southwest, 1829-1900 By Juan Francisco Martinez Denton, EX: University of North Texas Press 2006, xii, I96pp. , cloth. $24.95 Reviewed by Samuel Escobar This is a well-documented study of the missionary efforts of Protestant denominations among the 100.000 Spanish-speaking Mexicans who became part of the U.S.A. population after the conquest that took from Mexico that vast portion of territory known today as the southwestern United States. It only covers developments during the nineteenth century up to 1900, but it deals with burning missiological questions that are still alive today, not only in that region, such as “the relationship between the nationalist agenda of a powerful nation and the missional goals of a church that reaps the benefits of being a part of that nation” (2). The author is Assistant Dean for the Hispanic Church Studies Department and Associate Professor of Hispanic Studies and Pastoral Leadership at Fuller Theological Seminary in Pasadena, California. His book is missiology at its best because the author’s commitment to Christian mission and his familiarity with the Hispanic churches is evident, but at the same time he has made good use of critical historical and sociological approaches to throw light on his complex subject. In the first three chapters, Martinez guides the reader through a wide variety of sources of missionary literature of that period and draws up a sober critical picture of the mixed and confused motivations of mission practitioners and promoters. He deals especially with Presbyterians, Methodists, and Baptists, and an outstanding common note is the intense anti-Catholic bias, which reflects the mood of U.S.A. Protestantism at the time in which a flood of Catholic immigrants from Europe was changing the religious map of the developing nation. For Martinez, “Americanization stood out as the overarching motive among Protestant missionaries for working with Mexican Americans in the Southwest during the nineteenth century” (49). Chapter four deals with mission efforts prior to the Civil War, and the post-war period is covered in a chapter about Texas, one about New Mexico and one about Colorado, Arizona, and California. The final chapter offers a picture of the Mexican American Protestant community as a whole. Like mission history in general, Martinez has found very few written sources that represent the perspective of the receivers of missionary action. However, through his book, it is possible to grasp something of the drama, the tensions, and the dilemmas of those that embraced the gospel in these borderlands. Mexican American Protestantism became a part of the Borderlands religious identity: “A shared experience of radical conversion, religious persecution and social isolation gave these people a common identity” (145). They were hopeful people, and their motto was “Sea la luz” (Let there be light) because they expected that the light of their testimony would spread through their land. Martinez has offered us a critical missiological study but a hopeful one.