Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutralizing Polyclonal IgG Present during Acute Infection Prevents Rapid Disease Onset in Simian-Human Immunodeficiency Virus SHIVSF162P3-Infected Infant Rhesus Macaques

ABSTRACT Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIV-infected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIVSF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression.
Efficacy of amlodipine and olmesartan medoxomil in patients with hypertension: the AZOR Trial Evaluating Blood Pressure Reductions and Control (AZTEC) study

The aim of the present study was to use ambulatory blood pressure (BP) monitoring (ABPM) to determine the efficacy of a fixed-dose combination of amlodipine (AML) and olmesartan medoxomil (OM) over the 24-hour dosing interval. This 12-week, titrate-to-goal study was conducted in 185 patients with hypertension. Patients were initially treated with AML 5 mg/ day and uptitrated to AML/OM 5/20, 5/40, and 10/40 mg/day every 3 weeks if mean seated BP (SeBP) was ≥120/80 mmHg. The primary efficacy endpoint was the change from baseline in mean 24-hour systolic BP at week 12 as assessed by ABPM. At baseline, the mean 24-hour ambulatory BP (±standard deviation [SD]) was 144.8±11.1/85.7±7.9 mmHg. At week 12, the change from baseline in mean 24-hour ambulatory BP (±standard error of the mean [SEM]) was -21.4±0.8/-12.7±0.5 mmHg (p < 0.0001 versus baseline). At baseline, the mean SeBP (±SD) was 158.2±12.6/92.8±8.6 mmHg and at week 12, the mean SeBP change (±SEM) from baseline (last observation carried forward) was -24.1±1.1/-12.1±0.7 mmHg (p < 0.0001 versus baseline). Proportions of patients achieving mean 24-hour ambulatory BP prespecified study targets were 70.9% (<130/80 mmHg), 48.3% (<125/75 mmHg), and 40.7% (<120/80 mmHg). Cumulatively, 76.8% of patients uptitrated to AML/OM 10/40 mg/day attained an SeBP goal of <140/90 mmHg. The study drug was well tolerated with few adverse events (peripheral edema, 2.2%; dizziness, 1.1%). An AML/OM-based titration regimen effectively reduces BP in patients with hypertension.
An Exploratory Trial of Cyclooxygenase Type 2 Inhibitor in HIV-1 Infection: Downregulated Immune Activation and Improved T Cell-Dependent Vaccine Responses

ABSTRACT Chronic HIV infection is characterized by chronic immune activation and dysfunctional T cells with elevated intracellular cyclic AMP (cAMP), which inhibits the T cell activation capability. cAMP may be induced by prostaglandin E2 following lipopolysaccharide (LPS)-induced upregulation of cyclooxygenase type 2 (COX-2) in monocytes due to the elevated LPS levels in patients with chronic HIV infection. This hypothesis was tested using celecoxib, a COX-2 inhibitor, for 12 weeks in HIV-infected patients without antiretroviral treatment in a prospective, open, randomized exploratory trial. Thirty-one patients were randomized in the trial; 27 completed the study, including 13 patients on celecoxib. Celecoxib reduced chronic immune activation in terms of CD38 density on CD8+ T cells (−24%; P = 0.04), IgA levels (P = 0.04), and a combined score for inflammatory markers (P < 0.05). Celecoxib further reduced the inhibitory surface receptor programmed death 1 (PD-1) on CD8+ T cells (P = 0.01), including PD-1 on the HIV Gag-specific subset (P = 0.02), enhanced the number of CD3+ CD4+ CD25+ CD127lo/− Treg or activated cells (P = 0.02), and improved humoral memory recall responses to a T cell-dependent vaccine (P = 0.04). HIV RNA (P = 0.06) and D dimers (P = 0.07) tended to increase in the controls, whereas interleukin-6 (IL-6) possibly decreased in the treatment arm (P = 0.10). In conclusion, celecoxib downmodulated the immune activation related to clinical progression of chronic HIV infection and improved T cell-dependent functions in vivo.
Human Papillomaviruses Modulate Expression of MicroRNA 203 upon Epithelial Differentiation to Control Levels of p63 Proteins

ABSTRACT Human papillomaviruses (HPV) link their life cycles to epithelial differentiation and induce productive replication of viral DNA in suprabasal cells. Viral-DNA amplification requires cells to remain active in the cell cycle upon differentiation. This is in contrast to normal cells, which lose proliferative capability upon differentiation. One factor that negatively regulates proliferative capability upon differentiation is microRNA 203 (miR-203), which is expressed primarily in suprabasal epithelial cells. Although HPVs do not encode their own microRNAs (miRNAs), they modulate expression of cellular miRNAs to regulate the activities of cellular proteins. We show that the HPV E7 protein downregulates miR-203 expression upon differentiation, which may occur through the mitogen-activated protein (MAP) kinase/protein kinase C (PKC) pathway. One target of miR-203 is the p63 family of transcription factors, and we demonstrate that HPV-positive cells maintain significantly higher levels of these factors upon differentiation than do normal keratinocytes. Several downstream targets of p63, CARM-1, p21, and Bax, were also increased in E7-expressing cells, and their levels were inversely correlated with amounts of miR-203. Introduction of expression vectors for miR-203 into keratinocytes that stably maintain HPV episomes resulted in short-term elevation of HPV genome copy numbers, but these were rapidly lost upon subsequent passage. When HPV-positive cells expressing high levels of miR-203 were induced to differentiate in methylcellulose, impaired genome amplification was observed. We conclude that high levels of miR-203 are inhibitory to HPV amplification and that HPV proteins act to suppress expression of this microRNA to allow productive replication in differentiating cells.
Swine Influenza Virus PA and Neuraminidase Gene Reassortment into Human H1N1 Influenza Virus Is Associated with an Altered Pathogenic Phenotype Linked to Increased MIP-2 Expression

ABSTRACT Swine are susceptible to infection by both avian and human influenza viruses, and this feature is thought to contribute to novel reassortant influenza viruses. In this study, the influenza virus reassortment rate in swine and human cells was determined. Coinfection of swine cells with 2009 pandemic H1N1 virus (huH1N1) and an endemic swine H1N2 (A/swine/Illinois/02860/09) virus (swH1N2) resulted in a 23% reassortment rate that was independent of α2,3- or α2,6-sialic acid distribution on the cells. The reassortants had altered pathogenic phenotypes linked to introduction of the swine virus PA and neuraminidase (NA) into huH1N1. In mice, the huH1N1 PA and NA mediated increased MIP-2 expression early postinfection, resulting in substantial pulmonary neutrophilia with enhanced lung pathology and disease. The findings support the notion that swine are a mixing vessel for influenza virus reassortants independent of sialic acid distribution. These results show the potential for continued reassortment of the 2009 pandemic H1N1 virus with endemic swine viruses and for reassortants to have increased pathogenicity linked to the swine virus NA and PA genes which are associated with increased pulmonary neutrophil trafficking that is related to MIP-2 expression. IMPORTANCE Influenza A viruses can change rapidly via reassortment to create a novel virus, and reassortment can result in possible pandemics. Reassortments among subtypes from avian and human viruses led to the 1957 (H2N2 subtype) and 1968 (H3N2 subtype) human influenza pandemics. Recent analyses of circulating isolates have shown that multiple genes can be recombined from human, avian, and swine influenza viruses, leading to triple reassortants. Understanding the factors that can affect influenza A virus reassortment is needed for the establishment of disease intervention strategies that may reduce or preclude pandemics. The findings from this study show that swine cells provide a mixing vessel for influenza virus reassortment independent of differential sialic acid distribution. The findings also establish that circulating neuraminidase (NA) and PA genes could alter the pathogenic phenotype of the pandemic H1N1 virus, resulting in enhanced disease. The identification of such factors provides a framework for pandemic modeling and surveillance.
Modeling and Identification of Nonlinear Systems: A Review of the Multimodel Approach—Part 1

The efficacy of the multimodel framework (MMF) in modeling and identification of complex, nonlinear, and uncertain systems has been widely recognized in the literature owing to its simplicity, transparency, and mathematical tractability, allowing the use of well-known modeling analysis and control design techniques. The approach proved to be effective in addressing some of the shortcomings of other modeling techniques such as those based on a single nonlinear autoregressive network with exogenous inputs model or neural networks. A great number of researchers have contributed to this active field. Due to the significant amount of contributions and the lack of a recent survey, the review of recent developments in this field is vital. In this two-part paper, we attempt to provide a comprehensive coverage of the multimodel approach for modeling and identification of complex systems. The study contains a classification of different methods, the challenges encountered, as well as recent applications of MMF in various fields. Part 1 of this paper presents an overview of MMF for modeling and identification of nonlinear systems as well as the review of recent developments in the partitioning strategies employed.
Effects of Manipulating Apoptosis on Sindbis Virus Infection of Aedes aegypti Mosquitoes

ABSTRACT Improved control of vector-borne diseases requires an understanding of the molecular factors that determine vector competence. Apoptosis has been shown to play a role in defense against viruses in insects and mammals. Although some observations suggest a correlation between apoptosis and resistance to arboviruses in mosquitoes, there is no direct evidence tying apoptosis to arbovirus vector competence. To determine whether apoptosis can influence arbovirus replication in mosquitoes, we manipulated apoptosis in Aedes aegypti mosquitoes by silencing the expression of genes that either positively or negatively regulate apoptosis. Silencing of the A. aegypti anti-apoptotic gene iap1 (Aeiap1) caused apoptosis in midgut epithelium, alterations in midgut morphology, and 60 to 70% mosquito mortality. Mortality induced by Aeiap1 silencing was rescued by cosilencing the initiator caspase gene Aedronc, indicating that the mortality was due to apoptosis. When mosquitoes which had been injected with Aeiap1 double-stranded RNA (dsRNA) were orally infected with Sindbis virus (SINV), increased midgut infection and virus dissemination to other organs were observed. This increase in virus infection may have been due to the effects of widespread apoptosis on infection barriers or innate immunity. In contrast, silencing the expression of Aedronc, which would be expected to inhibit apoptosis, reduced SINV midgut infection and virus dissemination. Thus, our data suggest that some level of caspase activity and/or apoptosis may be necessary for efficient virus replication and dissemination in mosquitoes. This is the first study to directly test the roles of apoptosis and caspases in determining mosquito vector competence for arboviruses.
Echocardiographic assessment of aortic valve annular and left ventricular outflow tract diameter in conscious and anesthetized adult sheep prior to prosthetic aortic valve implantation

Objective: Prosthetic heart valve implantation is commonly performed in patients that have valvular heart disease. Prior to clinical evaluation of newly developed prostheses, preclinical animal studies are performed for the assessment of both acute and chronic valvular function. Commonly, one size of valve is used in these preclinical studies, which can present difficulties with the implantation procedure and assessing valve function. Due to these potential problems, we developed a preoperative screening assessment in potential ovine candidates for prosthetic aortic valve implantation. By determining if there is a correlation between conscious and anesthetized echocardiographic examinations, an improvement in surgical confidence can predict that the animal is deemed a suitable candidate for a particular size of prosthetic valve for implantation prior to subjecting the animal to anesthesia and surgery. Methods: A total of 53 crossbred sheep (Ovis aries), male and female, 10–37 months of age, weighing between 41 and 77 kg, underwent conscious echocardiography and a subset of 29 of these animals underwent echocardiographic assessment under anesthesia for a preoperative valve size comparison in these animals prior to surgical prosthetic aortic valve implantation. Using 2D echocardiographic assessment, left ventricular outflow tract (LVOT) dimensions were assessed. Results: The mean paired difference between anesthetized and conscious LVOT diameter measurement was −0.87 mm (p = 0.0066, standard deviation 1.598, 95% confidence interval, −0.4796, −0.26378, n = 29). Conclusion: This pilot study evaluation revealed that conscious echocardiographic assessment can play a role preoperatively in selecting potential candidates for surgical prosthetic aortic valve implantation, thereby minimizing the potential in prosthetic-native annular mismatching, which can contribute to altered LVOT function.
Structure of Simian Immunodeficiency Virus Envelope Spikes Bound with CD4 and Monoclonal Antibody 36D5

ABSTRACT The human immunodeficiency virus type 1 (HIV-1)/simian immunodeficiency virus (SIV) envelope spike (Env) mediates viral entry into host cells. The V3 loop of the gp120 component of the Env trimer contributes to the coreceptor binding site and is a target for neutralizing antibodies. We used cryo-electron tomography to visualize the binding of CD4 and the V3 loop monoclonal antibody (MAb) 36D5 to gp120 of the SIV Env trimer. Our results show that 36D5 binds gp120 at the base of the V3 loop and suggest that the antibody exerts its neutralization effect by blocking the coreceptor binding site. The antibody does this without altering the dynamics of the spike motion between closed and open states when CD4 is bound. The interaction between 36D5 and SIV gp120 is similar to the interaction between some broadly neutralizing anti-V3 loop antibodies and HIV-1 gp120. Two conformations of gp120 bound with CD4 are revealed, suggesting an intrinsic dynamic nature of the liganded Env trimer. CD4 binding substantially increases the binding of 36D5 to gp120 in the intact Env trimer, consistent with CD4-induced changes in the conformation of gp120 and the antibody binding site. Binding by MAb 36D5 does not substantially alter the proportions of the two CD4-bound conformations. The position of MAb 36D5 at the V3 base changes little between conformations, indicating that the V3 base serves as a pivot point during the transition between these two states. IMPORTANCE Glycoprotein spikes on the surfaces of SIV and HIV are the sole targets available to the immune system for antibody neutralization. Spikes evade the immune system by a combination of a thick layer of polysaccharide on the surface (the glycan shield) and movement between spike domains that masks the epitope conformation. Using SIV virions whose spikes were “decorated” with the primary cellular receptor (CD4) and an antibody (36D5) at part of the coreceptor binding site, we visualized multiple conformations trapped by the rapid freezing step, which were separated using statistical analysis. Our results show that the CD4-induced conformational dynamics of the spike enhances binding of the antibody.
CONGENITAL CATARACTS IN SISTERS WITH CONGENITAL ECTODERMAL DYSPLASIA

To the Editor:— I have read with great interest the suggestion of Dr. S. J. Thannhauser (Differential Diagnosis of Ectodermal Dysplasia and of Rothmund's syndrome,The Journal, January 26, p. 238) that the patients described are examples of Rothmund's syndrome. I am inclined to agree with his suggestion after looking up the pertinent literature on the subject (including Rothmund, A.: Ueber Katarakt in Verbindung mit einer eigenthumlichen Hautdegeneration, Arch. f. Ophth. 14 : 159, 1868. Seefelder, R.: Ueber familiares Auftreten von Katarakt und Poikilodermie, Ztschr. f. Augenh. 86 :81 [May] 1935. Schnyder, H. F.: Ueber Katarakt bei poikilodermieartiger Hauterkrankung, Klin. Monatsbl. f. Augenh. 92 :408, 1934. Thannhauser, S. J.: Wermer's Syndrome [Progeria of the Adult] and Rothmund's Syndrome: Two Types of Closely Related Heredofamilial Atrophic Dermatoses with Juvenile Cataracts and Endocrine Features: A Critical Study with Five New Cases, Ann. Int. Med. 23 :559 [Oct.] 1945). I apologize that this syndrome
A Comparison of the Dietary Intake of Institutionlized Elderly Fed in Two Different Settings

The effect of dining location on dietary intake was evaluated for the institutionalized elderly. Eating with a group provided a significantly greater percentage of the Recommended Dietary Allowance for vitamin E while dining in rooms provided diets which were significantly more nutrient dense for vitamin D, riboflavin, calcium, and phosphorus. Regardless of where residents ate, at least nine of the 16 nutrients studied were present in amounts less than predicted. From a dietary standpoint, perhaps greater attention to what nursing home residents eat is more important than where food is eaten.
Brazilian Begomovirus Populations Are Highly Recombinant, Rapidly Evolving, and Segregated Based on Geographical Location

ABSTRACT The incidence of begomovirus infections in crop plants sharply increased in Brazil during the 1990s following the introduction of the invasive B biotype of the whitefly vector, Bemisia tabaci. It is believed that this biotype transmitted begomoviruses from noncultivated plants to crop species with greater efficiency than indigenous B. tabaci biotypes. Either through rapid host adaptation or selection pressure in genetically diverse populations of noncultivated hosts, over the past 20 years various previously unknown begomovirus species have became progressively more prevalent in cultivated species such as tomato. Here we assess the genetic structure of begomovirus populations infecting tomatoes and noncultivated hosts in southeastern Brazil. Between 2005 and 2010, we sampled and sequenced 126 DNA-A and 58 DNA-B full-length begomovirus components. We detected nine begomovirus species in tomatoes and eight in the noncultivated host samples, with four species common to both tomatoes and noncultivated hosts. Like many begomoviruses, most species are obvious interspecies recombinants. Furthermore, species identified in tomato have probable parental viruses from noncultivated hosts. While the population structures of five well-sampled viral species all displayed geographical subdivision, a noncultivated host-infecting virus was more genetically variable than the four predominantly tomato-infecting viruses.
Low-noise ASIC and New Layout of Multipolar Electrode for both High ENG Selectivity and Parasitic Signal Rejection

In order to extract and separate Action Potential (AP) signals according to their nerve fascicule origins, we propose a new architecture of a multipolar cuff electrode and an optimized integrated acquisition circuit. The proposed electrode has a specific layout of a large number of poles in order to both reject parasitic signals, such as electromyogram and provide a maximum of spatial selectivity for ENG signals. For one channel to be recorded, we need to consider seven recording sites. A low-noise integrated circuit (ASIC) has been designed in order to perform this first step of analog processing on each set of seven considered poles.
Comparação entre citrato trissódico e heparina como solução para selo de cateter em pacientes em hemodiálise

INTRODUCAO: A elevada incidencia de pacientes iniciando ou sendo mantidos em tratamento dialitico atraves de cateteres venosos tem aumentado o numero de infeccoes da corrente sanguinea relacionadas aos cateteres e suas consequencias, obrigando a busca de substâncias que tenham propriedades anticoagulantes e que tambem impecam a contaminacao dos mesmos. OBJETIVOS: Comparar a utilizacao de heparina e citrato trissodico como selo de cateteres de longa permanencia quanto a ocorrencia de pirogenia, bacteremia, internacoes hospitalares relacionadas a infeccao, trombose e obito. METODOS: [. ]
Reliability Evaluation for an Information Network With Node Failure Under Cost Constraint

The quality of service is an important index to measure the performance of an information system. This paper constructs a stochastic-flow network to model the information system. In this network, each node and arc having a designated capacity will have different lower levels due to various partial and complete failures. The studied problem is to evaluate the possibility that a given amount of multicommodity can be sent through an information network under the cost constraint. Such a possibility, which is named the mission reliability, is an appropriate performance index to measure the quality level. The terminology "flow" represents the quantity of data transmitted via such a network, and "demand" represents the required data from clients. Based on the properties of minimal paths, a simple algorithm is first proposed to generate all lower boundary points for the demand; then, the mission reliability can be calculated in terms of such points. The lower boundary point for the demand is a minimal vector, which represents the capacity of each component (arc or node), such that the demand can be fulfilled. Extending the stochastic-flow network to the node failure case, another algorithm is proposed to calculate the mission reliability