Miracle-dz/UniFAR-FTUs huggingface dataset:
Broad Neutralization of Human Immunodeficiency Virus Type 1 (HIV-1) Elicited from Human Rhinoviruses That Display the HIV-1 gp41 ELDKWA Epitope

ABSTRACT In efforts to develop AIDS vaccine components, we generated combinatorial libraries of recombinant human rhinoviruses that display the well-conserved ELDKWA epitope of the membrane-proximal external region of human immunodeficiency virus type 1 (HIV-1) gp41. The broadly neutralizing human monoclonal antibody 2F5 was used to select for viruses whose ELDKWA conformations resemble those of HIV. Immunization of guinea pigs with different chimeras, some boosted with ELDKWA-based peptides, elicited antibodies capable of neutralizing HIV-1 pseudoviruses of diverse subtypes and coreceptor usages. These recombinant immunogens are the first reported that elicit broad, albeit modest, neutralization of HIV-1 using an ELDKWA-based epitope and are among the few reported that elicit broad neutralization directed against any recombinant HIV epitope, providing a critical advance in developing effective AIDS vaccine components.
Efficacy and safety of telaprevir in patients with genotype 1 hepatitis C infection

Chronic hepatitis C infection represents a significant and growing health problem worldwide. Patients with genotype 1 hepatitis C respond poorly to the current standard of care, pegylated interferon and ribavirin, which is frequently associated with unpleasant side effects. Consequently new agents with improved efficacy and tolerability are needed. The efficacy and safety of the direct-acting antiviral agent telaprevir in the treatment of genotype 1 hepatitis C infection have been demonstrated in a number of clinical trials. The addition of telaprevir to standard therapy considerably improves response rates and allows response-guided shortening of treatment duration in a substantial number of treatment-naïve patients. Side effects associated with telaprevir therapy include rash, anaemia, gastrointestinal disturbance and anorectal discomfort. Telaprevir-resistant variants have been identified in patients who have failed telaprevir-containing therapy, and whether selection of these variants will compromise future therapeutic options is currently unknown. The efficacy and safety of telaprevir in the treatment of the most challenging patients, including those with recurrent hepatitis C following liver transplantation and those co-infected with HIV, remains to be established.
Age, systolic blood pressure, hemoglobin level, the combination of BMI and percent body fat measured by bioelectrical impedance method, and under-nutrition influence the brain natriuretic peptide level

Background The objective of this study was to identify factors influencing brain natriuretic peptide (BNP). Methods and Results The subjects were 2,670 examinees undergoing a health checkup. Multiple regression analysis concerning log-transformed BNP was performed, and the following findings were clarified: (1) age, systolic blood pressure, and the hemoglobin level were important explanatory factors, (2) there was marked variation in the standard regression coefficient (β) of the percent body fat and body mass index (BMI), (3) there was a high frequency of an opposite sign of β for the BMI and percent body fat, and (4) there were larger absolute values of β for cholinesterase and albumin. Findings (2) and (3) indicate that the combination of the BMI and percent body fat measured by bioelectrical impedance analysis is an important explanatory factors and we proposed that the difference between the BMI and percent body fat serves as a factor representing the body fluid volume or dehydration. Finding (4) suggest that undernutrition elevates the BNP level. Conclusion Age, systolic blood pressure, and the hemoglobin level are important factors influencing BNP. The BMI alone is not a so important predictor, but the combination of the BMI and percent body fat measured by bioelectrical impedance analysis is an important predictor. In addition, under-nutrition elevates the BNP level.
ANEURYSM OF THE HEART

Although aneurysm of the heart has been recognized for almost two centuries, it is only recently that the antemortem diagnosis has been made with any assurance. The advent of more thorough study of patients with heart disease by roentgenologic methods has considerably increased the frequency with which the correct diagnosis is made. The first account of aneurysm of the ventricle was by Galeati 1 in 1757, but the first detailed description of the condition was given by Matthew Baillie 2 in 1793. Since then, from time to time, other papers have appeared dealing with the subject. These have been fully reviewed by Hall, 3 Sternberg 4 and Parkinson, Bedford and Thomson, 5 who added cases of their own. The first case in which the condition was diagnosed by means of roentgen rays was reported by Sezary and Alibert 6 in 1922. Since then, in many of the cases reported it has been recognized
Stool DNA testing for cancer surveillance in inflammatory bowel disease: an early view

Patients with inflammatory bowel disease (IBD) are at increased risk for colorectal cancer (CRC). Despite weak supporting evidence, important logistic barriers and high cost, colonoscopy is currently the only recommended approach to CRC surveillance in patients with IBD. As such, there is imperative to explore alternative or complementary strategies with potential to improve the efficiency and effectiveness of surveillance in IBD. Given our increasing understanding of tumorigenesis in IBD and the accompanying cascade of molecular alterations, there is a strong rationale to pursue biomarker assays for this application. Stool-based DNA testing with advanced technology has been shown to be highly discriminatory for detection of sporadic colorectal cancer and advanced precancers. In early observations, stool DNA testing also shows promise for the accurate detection of IBD-associated colorectal neoplasms. These findings raise important clinical and translational questions about how to best evaluate and develop this technology, and devise clinical algorithms that will complement colonoscopy to improve patient outcomes.
Suppression of a Morphogenic Mutant in Rous Sarcoma Virus Capsid Protein by a Second-Site Mutation: a Cryoelectron Tomography Study

ABSTRACT Retrovirus assembly is driven by polymerization of the Gag polyprotein as nascent virions bud from host cells. Gag is then processed proteolytically, releasing the capsid protein (CA) to assemble de novo inside maturing virions. CA has N-terminal and C-terminal domains (NTDs and CTDs, respectively) whose folds are conserved, although their sequences are divergent except in the 20-residue major homology region (MHR) in the CTD. The MHR is thought to play an important role in assembly, and some mutations affecting it, including the F167Y substitution, are lethal. A temperature-sensitive second-site suppressor mutation in the NTD, A38V, restores infectivity. We have used cryoelectron tomography to investigate the morphotypes of this double mutant. Virions produced at the nonpermissive temperature do not assemble capsids, although Gag is processed normally; moreover, they are more variable in size than the wild type and have fewer glycoprotein spikes. At the permissive temperature, virions are similar in size and spike content as in the wild type and capsid assembly is restored, albeit with altered polymorphisms. The mutation F167Y-A38V (referred to as FY/AV in this paper) produces fewer tubular capsids than wild type and more irregular polyhedra, which tend to be larger than in the wild type, containing ∼30% more CA subunits. It follows that FY/AV CA assembles more efficiently in situ than in the wild type and has a lower critical concentration, reflecting altered nucleation properties. However, its infectivity is lower than that of the wild type, due to a 4-fold-lower budding efficiency. We conclude that the wild-type CA protein sequence represents an evolutionary compromise between competing requirements for optimization of Gag assembly (of the immature virion) and CA assembly (in the maturing virion).
Antibody Preparations from Human Transchromosomic Cows Exhibit Prophylactic and Therapeutic Efficacy against Venezuelan Equine Encephalitis Virus

ABSTRACT Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne RNA virus that causes low mortality but high morbidity rates in humans. In addition to natural outbreaks, there is the potential for exposure to VEEV via aerosolized virus particles. There are currently no FDA-licensed vaccines or antiviral therapies for VEEV. Passive immunotherapy is an approved method used to protect individuals against several pathogens and toxins. Human polyclonal antibodies (PAbs) are ideal, but this is dependent upon serum from convalescent human donors, which is in limited supply. Non-human-derived PAbs can have serious immunoreactivity complications, and when “humanized,” these antibodies may exhibit reduced neutralization efficiency. To address these issues, transchromosomic (Tc) bovines have been created, which can produce potent neutralizing human antibodies in response to hyperimmunization. In these studies, we have immunized these bovines with different VEEV immunogens and evaluated the protective efficacy of purified preparations of the resultant human polyclonal antisera against low- and high-dose VEEV challenges. These studies demonstrate that prophylactic or therapeutic administration of the polyclonal antibody preparations (TcPAbs) can protect mice against lethal subcutaneous or aerosol challenge with VEEV. Furthermore, significant protection against unrelated coinfecting viral pathogens can be conferred by combining individual virus-specific TcPAb preparations. IMPORTANCE With the globalization and spread or potential aerosol release of emerging infectious diseases, it will be critical to develop platforms that are able to produce therapeutics in a short time frame. By using a transchromosomic (Tc) bovine platform, it is theoretically possible to produce antigen-specific highly neutralizing therapeutic polyclonal human antibody (TcPAb) preparations in 6 months or less. In this study, we demonstrate that Tc bovine-derived Venezuelan equine encephalitis virus (VEEV)-specific TcPAbs are highly effective against VEEV infection that mimics not only the natural route of infection but also infection via aerosol exposure. Additionally, we show that combinatorial TcPAb preparations can be used to treat coinfections with divergent pathogens, demonstrating that the Tc bovine platform could be beneficial in areas where multiple infectious diseases occur contemporaneously or in the case of multipathogen release.
Quality of life of older people in residential care home: a literature review

Aim. To integrate the research evidence on quality of life of older people living in a residential care home setting. Background. Residential care is provided for older people who are unable to live in their own home due to various health and social reasons. A number of studies have been published that have focused on diverse quality of life issues of residential care home elders. Consolidating the evidence from these studies may provide insights into enhancing quality of life of this particular group of older people. Design. A literature review of research evidence on quality of life issues among residential care home elders. Method. A systematic search of the literature published between 1994–January 2008 was undertaken to identify research evidence on quality of life of older people living in residential care home. Information about the study design, research objectives, study setting, sample characteristics, and key findings were extracted for comparison and integration. Three aspects about quality of life of the residential care home elders were identified: views of residential care home elders on quality of life, factors affecting quality of life of residential care home elders and methods to improve quality of life in residential care home elders. Results. Eighteen publications were identified. Older people perceived their ability to maintain independence, autonomy and individuality as the most important criteria for determining quality of life. Interventions designed to improve quality of life of older people living in residential facilities corresponded to these criteria. A range of interventions including a walking program, mental stimulation and environmental modification were proposed and evaluated to improve quality of life of residential care home elders. Among these interventions, environmental modification that targeted at improving the residential care homes and quality of services appears to be promising. Conclusion. Quality of life in residential care home elders is a complex issue that may be determined by the elders’ independence, individuality and autonomy, and influenced by quality of residential care and facilities. Environmental modification appears to be a way to improve the quality of life of residential care home elders. Relevance to clinical practice. The knowledge of understanding quality of life of residential care home elders provides insights into the implementation of appropriate residential care services. Programs that aim to de-institutionalise the residential care home settings are important to the enhancement of residential care services.
The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions

We discuss the tripartite pathophysiological circuit of inflammatory bowel disease (IBD), involving the intestinal microbiota, barrier function, and immune system. Dysfunction in each of these physiological components (dysbiosis, leaky gut, and inflammation) contributes in a mutually interdependent manner to IBD onset and exacerbation. Genetic and environmental risk factors lead to disruption of gut homeostasis: genetic risks predominantly affect the immune system, environmental risks predominantly affect the microbiota, and both affect barrier function. Multiple genetic and environmental ‘hits’ are likely necessary to establish and exacerbate disease. Most conventional IBD therapies currently target only one component of the pathophysiological circuit, inflammation; however, many patients with IBD do not respond to immune-modulating therapies. Hope lies in new classes of therapies that target the microbiota and barrier function.
Systematic review and meta-analysis: the effects of fermented milk with Bifidobacterium lactis CNCM I-2494 and lactic acid bacteria on gastrointestinal discomfort in the general adult population

Background: It has been suggested that probiotics may improve gastrointestinal discomfort. Not all probiotics exhibit the same effects and consequently meta-analyses on probiotics should be confined to well-defined strains or strain combinations. The aim of this study was to evaluate the effectiveness of a probiotic fermented milk (PFM) that includes Bifidobacterium lactis (B. lactis) CNCM I-2494 and lactic acid bacteria on gastrointestinal discomfort in the general adult population. Methods: Double-blind randomized controlled trials in the general adult population comparing PFM with a control dairy product for at least 4 weeks were searched from multiple literature databases (up to February 2015). Meta-analyses using random-effects models, with individual participant data were undertaken to calculate an odds ratio (OR) or standard mean difference (SMD), with a 95% confidence interval (CI). Results: The search strategy identified 12,439 documents. Overall, three trials with a total of 598 adults (female = 96.5%) met the inclusion criteria. Consumption of the PFM product was associated with a significant improvement in overall gastrointestinal discomfort compared with the control product (OR = 1.48; 95% CI 1.07–2.05), with a number needed to treat (NNT) of 10.24 (95% CI 5.64–55.93). PFM was also superior to the control in reducing digestive symptoms, as measured using a composite score (SMD = −0.21; 95% CI −0.37 to −0.05). Sensitivity analyses produced similar results, and the heterogeneity between studies was minimal. Conclusions: This meta-analysis shows that the consumption of PFM with B. lactis CNCM I-2494 and lactic acid bacteria is associated with a modest but consistent and significant improvement of outcomes related to gastrointestinal discomfort in healthy adults.
Longer V1V2 Region with Increased Number of Potential N-Linked Glycosylation Sites in the HIV-1 Envelope Glycoprotein Protects against HIV-Specific Neutralizing Antibodies

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) has the ability to adapt to the host environment by escaping from host immune responses. We previously observed that escape from humoral immunity, both at the individual and at a population level, coincided with longer variable loops and an increased number of potential N-linked glycosylation sites (PNGS) in the viral envelope glycoprotein (Env) and, in particular, in variable regions 1 and 2 (V1V2). Here, we provide several lines of evidence for the role of V1V2 in the resistance of HIV-1 to neutralizing antibodies. First, we determined that the increasing neutralization resistance of a reference panel of tier-categorized neutralization-sensitive and -resistant HIV-1 variants coincided with a longer V1V2 loop containing more PNGS. Second, an exchange of the different variable regions of Env from a neutralization-sensitive HIV-1 variant into a neutralization-resistant escape variant from the same individual revealed that the V1V2 loop is a strong determinant for sensitivity to autologous-serum neutralization. Third, exchange of the V1V2 loop of neutralization-sensitive HIV-1 variants from historical seroconverters with the V1V2 loop of neutralization-resistant HIV-1 variants from contemporary seroconverters decreased the neutralization sensitivity to CD4-binding site-directed antibodies. Overall, we demonstrate that an increase in the length of the V1V2 loop and/or the number of PNGS in that same region of the HIV-1 envelope glycoprotein is directly involved in the protection of HIV-1 against HIV-specific neutralizing antibodies, possibly by shielding underlying epitopes in the envelope glycoprotein from antibody recognition.
Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

ABSTRACT The newly identified retrovirus—the xenotropic murine leukemia virus-related virus (XMRV)—has recently been shown to be strongly associated with familial prostate cancer in humans (A. Urisman et al., PLoS Pathog. 2:e25, 2006). While that study showed evidence of XMRV infection exclusively in the prostatic stromal fibroblasts, a recent study found XMRV protein antigens mainly in malignant prostate epithelial cells (R. Schlaberg et al., Proc. Natl. Acad. Sci. U. S. A. 106:16351-16356, 2009). To help elucidate the mechanisms behind XMRV infection, we show that prostatic fibroblast cells express Xpr1, a known receptor of XMRV, but its expression is absent in other cell lines of the prostate (i.e., epithelial and stromal smooth muscle cells). We also show that certain amino acid residues located within the predicted extracellular loop (ECL3 and ECL4) sequences of Xpr1 are required for efficient XMRV entry. Although we found strong evidence to support XMRV infection of prostatic fibroblast cell lines via Xpr1, we learned that XMRV was indeed capable of infecting cells that did not necessarily express Xpr1, such as those of the prostatic epithelial and smooth muscle origins. Further studies suggest that the expression of Xpr1 and certain genotypes of the RNASEL gene, which could restrict XMRV infection, may play important roles in defining XMRV tropisms in certain cell types. Collectively, our data reveal important cellular determinants required for XMRV entry into different human prostate cells in vitro, which may provide important insights into the possible role of XMRV as an etiologic agent in human prostate cancer.
Transsituational Individual-Specific Biopsychological Classification of Emotions

The goal of automatic biopsychological emotion recognition of companion technologies is to ensure reliable and valid classification rates. In this paper, emotional states were induced via a Wizard-of-Oz mental trainer scenario, which is based on the valence-arousal-dominance model. In most experiments, classification algorithms are tested via leave-out cross-validation of one situation. These studies often show very high classification rates, which are comparable with those in our experiment (92.6%). However, in order to guarantee robust emotion recognition based on biopsychological data, measurements have to be taken across several situations with the goal of selecting stable features for individual emotional states. For this purpose, our mental trainer experiment was conducted twice for each subject with a 10-min break between the two rounds. It is shown that there are robust psychobiological features that can be used for classification (70.1%) in both rounds. However, these are not the same as those that were found via feature selection performed only on the first round (classification: 53.0%).
THE CAUSE OF DIFFUSE PERITONITIS COMPLICATING APPENDICITIS AND ITS PREVENTION.: CHAIRMAN'S ADDRESS, DELIVERED BEFORE THE SECTION ON SURGERY AND ANATOMY, AT THE FIFTY-SECOND ANNUAL MEETING OF THE A. M. A., AT ST. PAUL, MINN., JUNE 4-7, 1901.

Every surgeon who treats patients suffering from acute appendicitis must be impressed with the fact that an unfavorable outcome in any given case means that the infection which was originally confined to the small space occupied by the vermiform appendix itself has first invaded the tissues immediately surrounding this organ and has then been distributed over the entire peritoneal cavity. In other words, in fatal cases the patient practically always dies as the result of a diffuse peritonitis. Other conditions may arise which may result in a fatal issue. There may be a septic thrombosis of the vessels in the vicinity of the appendix or an empyema, or even pyemia, but by far the greatest number of deaths occurs from diffuse peritonitis, and if it is possible to prevent this, the mortality from appendicitis must at once fall enormously. In order to plan a means for the prevention of this
A system aproach for reducing power consumption of multimedia devices with a low QoE impact

Power consumption is a major issue for handheld devices like mobile phones that decode and display multimedia streams through networks. Their power consumption during video playback directly depends on (1) network communications required to access video streams (2) video decoding process which complexity increases according to video characteristics (codec and video dimension). This paper describes a novel system approach to reduce power consumption through video resizing. This transformation implemented on an external device (i.e. a home gateway that transport video streams from the Internet to the embedded devices) reduces the computation complexity on the handled device up to 70% and reduce its amount of network communications up to 50%.