Miracle-dz/UniFAR-FTUs huggingface dataset:
Virion incorporation of integrin α4β7 facilitates HIV-1 infection and intestinal homing

Anti–integrin α4β7 therapy might directly interfere with the ability of HIV to home to intestinal reserviors. Taking HIV to the gut Antiretroviral therapy (ART) effectively limits HIV replication, but HIV+ individuals are medicated for life because ART withdrawal results in rebound of persistent virus. Developing therapies that keep viral loads low in the long term and prevent reinfection remains an important goal—one emerging approach is an antibody against integrin α4β7. Integrin α4β7 is a receptor that facilitates homing of CD4+ T cells to the gut, a key site for HIV persistence. ART-suppressed macaques that received antibodies against integrin α4β7 controlled the virus even after ART withdrawal. Here, Guzzo et al. demonstrate that integrin α4β7 is incorporated into the HIV envelope, suggesting that antibody treatment may directly interfere with the ability of HIV to target intestinal tissues. Their results change our perception of the role of integrin α4β7, a promising therapeutic target in HIV pathogenesis. The intestinal mucosa is a key anatomical site for HIV-1 replication and CD4+ T cell depletion. Accordingly, in vivo treatment with an antibody to the gut-homing integrin α4β7 was shown to reduce viral transmission, delay disease progression, and induce persistent virus control in macaques challenged with simian immunodeficiency virus (SIV). We show that integrin α4β7 is efficiently incorporated into the envelope of HIV-1 virions. Incorporated α4β7 is functionally active as it binds mucosal addressin cell adhesion molecule–1 (MAdCAM-1), promoting HIV-1 capture by and infection of MAdCAM-expressing cells, which in turn mediate trans-infection of bystander cells. Functional α4β7 is present in circulating virions from HIV-infected patients and SIV-infected macaques, with peak levels during the early stages of infection. In vivo homing experiments documented selective and specific uptake of α4β7+ HIV-1 virions by high endothelial venules in the intestinal mucosa. These results extend the paradigm of tissue homing to a retrovirus and are relevant for the pathogenesis, treatment, and prevention of HIV-1 infection.
Long-Term Survival in Adults 65 Years and Older With White Matter Hyperintensity: Association With Performance on the Digit Symbol Substitution Test

Objective White matter hyperintensity (WMH) confers increased mortality risk in patients with cardiovascular diseases. However, little is known about differences in survival times among adults 65 years and older who have WMH and live in the community. To characterize the factors that may reduce mortality risk in the presence of WMH, measures of race, sex, apolipoprotein E4, neuroimaging, and cardiometabolic, physiological, and psychosocial characteristics were examined, with a particular focus on information processing as measured by the Digit Symbol Substitution Test (DSST). Methods Cox proportional models were used to estimate mortality risks in a cohort of 3513 adults (74.8 years, 58% women, 84% white) with WMH (0–9 points), DSST (0–90 points), risk factor assessment in 1992 to 1994, and data on mortality and incident stroke in 2009 (median follow-up [range] = 14.2 [0.5–18.1] years). Results WMH predicted a 48% greater mortality risk (age-adjusted hazard ratio [HR; 95% confidence interval {CI}] for WMH >3 points = 1.48 [1.35–1.62]). This association was attenuated after adjustment for DSST (HR [CI] = 1.38 [1.27–1.51]) or lacunar infarcts (HR [CI] = 1.37 [1.25,1.50]) but not after adjustment for other factors. The interaction between DSST and WMH was significant (p = .011). In fully adjusted models stratified by WMH of 3 or higher, participants with DSST greater than or equal to median had a 34% lower mortality risk among those with WMH of 3 or higher (n = 532/1217) and a 28% lower mortality risk among those with WMH lower than 3 (n = 1364/2296), compared with participants with DSST less than median (HR [95% CI] = 0.66 [0.55–0.81] and 0.72 [0.62–0.83], respectively). Conclusions WMH is associated with increased long-term mortality risk in community-dwelling adults 65 years and older. The increased risk is attenuated for those with higher DSST. Assessment of cognitive function with DSST may improve risk stratification of individuals with WMH.
Countercurrent Chromatographic Separation of Proteins Using an Eccentric Coiled Column with Synchronous and Nonsynchronous Type-J Planetary Motions

Protein separation was performed using the high-speed countercurrent chromatograph (HSCCC) at both synchronous and nonsynchronous type-J planetary motions. The partition efficiency was evaluated with two different column configurations, eccentric coil and toroidal coil, on the separation of a set of stable protein samples including cytochrome C, myoglobin and lysozyme with a polymer phase system composed of 12.5% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate. Better peak resolution was obtained by the eccentric coil than by the toroidal coil using either lower or upper phase as the mobile phase. The peak resolution was further improved using the eccentric coil by the nonsynchronous type-J planetary motion with the combination of 1066 rpm of column rotation and 1000 rpm of revolution.
Analysis of Biological Signals Using Wavelet Coefficients for Finding the Cardiac Diseases and Their Severity

This study deals with feature extraction of Bio Medical signals using the continuous wavelet transform CWT and corresponding coefficients. The signal features are analyzed, in various points of time and at different localization levels with multiple scales of the cwt. The digital data were collected using the electrocardiogram for finding the heart disease considering data sets of twenty different disease cases using mat lab. The ECG data was filtered for hum noise and muscle noise, using a series of filters and applied the zero cross algorithm for finding the no of zero crossings and the heart rate of each disease case.
Extracellular matrix and traumatic brain injury

The brain extracellular matrix (ECM) plays a crucial role in both the developing and adult brain by providing structural support and mediating cell‐cell interactions. In this review, we focus on the major constituents of the ECM and how they function in both normal and injured brain, and summarize the changes in the composition of the ECM as well as how these changes either promote or inhibit recovery of function following traumatic brain injury (TBI). Modulation of ECM composition to facilitates neuronal survival, regeneration and axonal outgrowth is a potential therapeutic target for TBI treatment.
Implementing liquid biopsies into clinical decision making for cancer immunotherapy

During the last decade, novel immunotherapeutic strategies, in particular antibodies directed against immune checkpoint inhibitors, have revolutionized the treatment of different malignancies leading to an improved survival of patients. Identification of immune-related biomarkers for diagnosis, prognosis, monitoring of immune responses and selection of patients for specific cancer immunotherapies is urgently required and therefore areas of intensive research. Easily accessible samples in particular liquid biopsies (body fluids), such as blood, saliva or urine, are preferred for serial tumor biopsies. Although monitoring of immune and tumor responses prior, during and post immunotherapy has led to significant advances of patients’ outcome, valid and stable prognostic biomarkers are still missing. This might be due to the limited capacity of the technologies employed, reproducibility of results as well as assay stability and validation of results. Therefore solid approaches to assess immune regulation and modulation as well as to follow up the nature of the tumor in liquid biopsies are urgently required to discover valuable and relevant biomarkers including sample preparation, timing of the collection and the type of liquid samples. This article summarizes our knowledge of the well-known liquid material in a new context as liquid biopsy and focuses on collection and assay requirements for the analysis and the technical developments that allow the implementation of different high-throughput assays to detect alterations at the genetic and immunologic level, which could be used for monitoring treatment efficiency, acquired therapy resistance mechanisms and the prognostic value of the liquid biopsies.
Engineering soya bean seeds as a scalable platform to produce cyanovirin‐N, a non‐ARV microbicide against HIV

Summary There is an urgent need to provide effective anti‐HIV microbicides to resource‐poor areas worldwide. Some of the most promising microbicide candidates are biotherapeutics targeting viral entry. To provide biotherapeutics to poorer areas, it is vital to reduce the cost. Here, we report the production of biologically active recombinant cyanovirin‐N (rCV‐N), an antiviral protein, in genetically engineered soya bean seeds. Pure, biologically active rCV‐N was isolated with a yield of 350 μg/g of dry seed weight. The observed amino acid sequence of rCV‐N matched the expected sequence of native CV‐N, as did the mass of rCV‐N (11 009 Da). Purified rCV‐N from soya is active in anti‐HIV assays with an EC50 of 0.82–2.7 nM (compared to 0.45–1.8 nM for E. coli‐produced CV‐N). Standard industrial processing of soya bean seeds to harvest soya bean oil does not diminish the antiviral activity of recovered rCV‐N, allowing the use of industrial soya bean processing to generate both soya bean oil and a recombinant protein for anti‐HIV microbicide development.
Deliverable 2 . 5 . 1 Domain Knowledge and Multimodal Grounding

This document addresses Knowledge Representation issues for the development of COMPANIONS, which are seen as Embodied Conversational Agents possessing cog-nitive abilities that make them believable, as well as user-friendly, in their role of assistants to daily activities. We first review the knowledge models implemented in as-sistive cognitive systems and draw conclusions on the possibility to unify the representation of user activities and domain knowledge used Planning technologies. We then introduce our choice of Planning formalism and how it could support multiple modes of interventions for a COMPANION. Representing user tasks and activities may not suffice to capture the complexity of certain domains, which require additional modelling in the traditional knowledge acquisition sense, so as to support domain inference in those areas where COMPANIONS are meant to assist (such as elementary " Medical " knowledge in the area of Healthy lifestyles). Finally, because COMPANIONS are meant to be embodied and situated in the user's environment, it is necessary to discuss how their knowledge representations can be anchored into the real world they advise about, which we will address under the concept of grounding. Throughout the document we shall make reference to the application domains of the two major project prototypes: the Health and Fitness Companion (HFC) and the Senior Companion (SC).
Neurocognitive function in paediatric obsessive-compulsive disorder

Abstract Objectives: The small body of neuropsychological research in paediatric obsessive-compulsive disorder (OCD) yields inconsistent results. A recent meta-analysis found small effect sizes, concluding that paediatric OCD may not be associated with cognitive impairments, stressing the need for more research. We investigated neuropsychological performance in a large sample of youths with OCD, while assessing potential moderators. Methods: Participants with OCD (n = 102) and matched controls (n = 161) were thoroughly screened and blindly evaluated for comorbidities, and completed a neuropsychological battery assessing processing speed, visuospatial abilities (VSA), working memory (WM), non-verbal memory (NVM), and executive functions (EF). Results: Compared to controls, youths with OCD exhibited underperformance on tasks assessing processing speed. On tests of VSA and WM, underperformance was found only on timed tasks. There were no differences on NVM and EF tasks. Notably, the OCD group’s standardised scores were in the normative range. Test performance was not associated with demographic or clinical variables. Conclusions: Youths with OCD exhibited intact performance on memory and EF tests, but slower processing speed, and underperformance only on timed VSA and WM tasks. While the OCD group performed in the normative range, these findings reveal relative weaknesses that may be overlooked. Such an oversight may be of particular importance in clinical and school settings.
Prevalence of estimated GFR reporting among US clinical laboratories.

BACKGROUND Routine laboratory reporting of estimated glomerular filtration rate (eGFR) may help clinicians detect kidney disease. The current national prevalence of eGFR reporting in clinical laboratories is unknown; thus, the extent of the situation of laboratories not routinely reporting eGFR with serum creatinine results is not quantified. DESIGN Observational analysis. SETTING National Kidney Disease Education Program survey of clinical laboratories conducted in 2006 to 2007 by mail, web, and telephone follow-up. PARTICIPANTS A national random sample, 6,350 clinical laboratories, drawn from the Federal Clinical Laboratory Improvement Amendments database and stratified by 6 major laboratory types/groupings. PREDICTORS Laboratory reports serum creatinine results. OUTCOMES Reporting eGFR values with serum creatinine results. MEASUREMENTS Percentage of laboratories reporting eGFR along with reporting serum creatinine values, reporting protocol, eGFR formula used, and style of reporting cutoff values. RESULTS Of laboratories reporting serum creatinine values, 38.4% report eGFR (physician offices, 25.8%; hospitals, 43.6%; independents, 38.9%; community clinics, 47.2%; health fair/insurance/public health, 45.5%; and others, 43.2%). Physician office laboratories have a reporting prevalence lower than other laboratory types (P < 0.001). Of laboratories reporting eGFR, 66.7% do so routinely with all adult serum creatinine determinations; 71.6% use the 4-variable Modification of Diet in Renal Disease Study equation; and 45.3% use the ">60 mL/min/1.73 m(2)" reporting convention. Independent laboratories are least likely to routinely report eGFR (50.6%; P < 0.05) and most likely to report only when specifically requested (45.4%; P < 0.05). High-volume laboratories across all strata are more likely to report eGFR (P < 0.001). LIMITATIONS Self-reporting by laboratories, federal database did not have names of laboratory directors/managers (intended respondents), assumed accuracy of federal database for sample purposes. CONCLUSIONS Routine eGFR reporting with serum creatinine values is not yet universal, and laboratories vary in their reporting practices.
A Multi-objective GRASP Algorithm for Joint Optimization of Energy Consumption and Schedule Length of Precedence-Constrained Applications

We address the problem of scheduling precedence-constrained scientific applications on a heterogeneous distributed processor system with the twin objectives of minimizing simultaneously energy consumption and schedule length. Previous research efforts on scheduling have focused on the minimization of a quality of service metric based on the completion time of applications (e.g., the schedule length). Recently, many researchers are working on the design of new scheduling algorithms that consider the minimization of energy consumption. We report a new scheduling algorithm accounting for both objectives. The new scheduling algorithm is based on a multi-start randomized adaptive search technique (GRASP framework) that adopts Dynamic Voltage Scaling technique to minimize energy consumption. This technique enables processors to operate in different voltage supply levels at the cost of sacrificing clock frequencies. This multiple voltage implies a trade-off between the quality of the schedules and energy consumption. Therefore, the new proposed approach is designed as a multi-objective algorithm that simultaneously optimize both objectives. Simulation results on a set of real-world applications emphasize the robust performance of the proposed approach.
Written on the Writer’s Face: Facial Width-to-Height Ratio among Nominees and Laureates of the Nobel Prize in Literature

This study examined the relationship between facial width-to-height ratio (fWHR), an established marker of testosterone level and dominance, and eminent writers’ achievement. The fWHR of laureates (N = 39) and nominees (N = 247) of the Nobel Prize in Literature 1901–1950 was measured together with historiometric data. It was demonstrated that although high-fWHR writers were nominated at a younger age, they waited longer for the prize than their low-fWHR counterparts. The probability of being awarded was predicted by the number of nominations, but fWHR moderated this association—the relationship between the number of nominations and the award probability was stronger among high-fWHR writers. Theoretical explanations of these findings are presented.
Decoding the network of Trypanosoma brucei proteins that determines sensitivity to apolipoprotein-L1

In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein-L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non-infectious to humans. While the mechanisms of TLF1 uptake, apoL1 membrane integration, and T. b. gambiense and T. b. rhodesiense apoL1-resistance have been extensively characterised, our understanding of the range of factors that drive apoL1 action in T. b. brucei is limited. Selecting our bloodstream-form T. b. brucei RNAi library with recombinant apoL1 identified an array of factors that supports the trypanocidal action of apoL1, including six putative ubiquitin modifiers and several proteins putatively involved in membrane trafficking; we also identified the known apoL1 sensitivity determinants, TbKIFC1 and the V-ATPase. Most prominent amongst the novel apoL1 sensitivity determinants was a putative ubiquitin ligase. Intriguingly, while loss of this ubiquitin ligase reduces parasite sensitivity to apoL1, its loss enhances parasite sensitivity to TLF1-dominated normal human serum, indicating that free and TLF1-bound apoL1 have contrasting modes-of-action. Indeed, loss of the known human serum sensitivity determinants, p67 (lysosomal associated membrane protein) and the cathepsin-L regulator, ‘inhibitor of cysteine peptidase’, had no effect on sensitivity to free apoL1. Our findings highlight a complex network of proteins that influences apoL1 action, with implications for our understanding of the anti-trypanosomal action of human serum.
Time since first sexual intercourse and the risk of cervical cancer

Young age at first sexual intercourse (AFI) is an important risk factor for cervical cancer, but no simple statistical model of its influence has been established. We investigated the relationship between risk of cervical carcinoma and time since first intercourse using data on monogamous women (5,074 cases and 16,137 controls) from the International Collaboration of Epidemiological Studies of Cervical Cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from pooled data on 20 studies using conditional logistic regression. The OR for invasive cervical carcinoma is approximately proportional to the square of time since first intercourse (exponent 1.95, 95% CI: 1.76–2.15) up to age 45. First cervical infection with human papillomavirus (HPV) often occurs soon after first sexual intercourse, so early AFI is a reasonable proxy for early age at first exposure to HPV. In addition, age‐specific incidence rates of cervical cancer in unscreened populations remain fairly constant above age 45. Cervical cancer thus resembles other cancers caused by strong early‐stage carcinogens, with incidence rates proportional to a power of time since first exposure and also resembles cancers of the breast and other hormone‐dependent epithelia, where a similar flattening of age‐specific incidence rates is seen at the time menopausal changes start. Taken together, these observations suggest that HPV vaccination may prevent the majority of cervical cancers by delaying HPV infection without necessarily providing lifetime protection against HPV.
Analytical and biological variation of biomarkers of oxidative stress during the menstrual cycle

Abstract Little information is available on the intra-individual variability of oxidative stress biomarkers in healthy individuals and even less in the context of the menstrual cycle. The objective of this study was to characterize the analytical and biological variability of a panel of 21 markers of oxidative damage, antioxidant defence and micronutrients in nine healthy, regularly menstruating women aged 18–44 years. Analyses included measurement of lipid peroxidation, antioxidant enzymes and antioxidant vitamins. Blood specimens were collected, processed and stored using standardized procedures on days 2, 7, 12, 13, 14, 18, 22 and 28 in one cycle for each subject. Replicate analyses of markers were performed and two-way nested random effects ANOVA was used to describe analytical, intra-individual and inter-individual variability. No statistically significant differences at α=0.05, or temporal effects across the menstrual cycle were observed. Analytical variability was the smallest component of variance for all variables. The ICC among replicates ranged from 0.80 to 0.98. Imprecision based on quality control materials ranged from 1 to 11%. The critical differences between serial results varied greatly between assays ranging from 6 to 216% of the mean level. These results provide important initial information on the variability of biomarkers of oxidative stress, antioxidant defence and micronutrients across the menstrual cycle.
Using Meda-data to Search for Clinical Records: RMIT at TREC 2012 Medical Track

Abstract : Clinical records contain International Classification of Diseases (ICD) codes summarizing the primary and/or secondary diseases of patients; these codes can be used as evidence to find relevant documents. In this paper we propose a novel approach to locally build a knowledge source from the existing data set to be used for query expansion, exploiting the ICD codes. While this approach does not rely on any external knowledge sources, it proves to be significantly superior to our global expansion and baseline systems.
Uncoupling T‐cell expansion from effector differentiation in cell‐based immunotherapy

Adoptive cellular immunotherapy (ACT) is a potentially curative therapy for patients with advanced cancer. Eradication of tumor in mouse models and humans correlates with both a high dose of adoptively transferred cells and cells with a minimally differentiated phenotype that maintain replicative capacity and multipotency. We speculate that response to ACT not only requires transfer of cells with immediate cytolytic effector function to kill the bulk of fast‐growing tumor but also transfer of tumor‐specific cells that maintain an ability for self‐renewal and the capacity to produce a continual supply of cytolytic effector progeny until all malignant cells are eliminated. Current in vitro methods to expand cells to sufficient numbers and still maintain a minimally differentiated phenotype are hindered by the biological coupling of clonal expansion and effector differentiation. Therefore, a better understanding of the physiologic mechanism that couples cell expansion and differentiation in CD8+ T cells may improve the efficacy of ACT.