Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic assessment of ventilatory efficiency during recovery from peak exercise to enhance cardiopulmonary exercise testing

Background: While cardiopulmonary exercise testing (CPX) assessment is generally regarded as an optimal means to assess functional capacity in heart failure (HF) patients, strength parameters are omitted. CPX indices collected in recovery may provide additional insight regarding function, including strength. Design and methods: We performed a cross-sectional controlled study. Systolic HF patients (aged ≥50 years) and age-matched controls were assessed using CPX and strength evaluations. Standard CPX indices were assessed during exercise (peak oxygen consumption [VO2], first ventilatory threshold [1stVT], and ventilatory efficiency [VE/VCO2 slope]) as well as indices at 1-minute recovery (1 min VO2, 1 min VE/VCO2, and 1 min heart rate recovery [HRR]) and differences between peak and 1-minute recovery (ΔVO2 and ΔVE/VCO2). Lower extremity strength was evaluated using the 1-repetition maximum (1RM) and power. Results: Seventy adults (31 HF; 39 controls), mean age 66.2 ± 9.7 years were evaluated. Peak VO2 (15.4 ± 4.2 versus 23.4 ± 6.6 mlO2·kg−1·min−1, p < 0.0001) and 1stVT (10.9 ± 2.1 versus 14.4 ± 4.0mlO2·kg−1·min−1, p < 0.0001) were diminished in HF versus controls and VE/VCO2 slope was increased (42.3 ± 12.2 versus 35.4 ± 8.3, p < 0.01). HF patients had reduced 1minVO2 (13.1 ± 2.9 versus 16.3 ± 3.7 mlO2·kg−1·min−1, p < 0.0001), 1 min HRR (6.7 ± 11.4 versus 12.4 ± 7.6 beats, p < 0.02), and ΔVO2 (2.43 ± 2.3 versus 7.3 ± 5.0 mlO2·kg−1·min−1, p < 0.0001) as well as increased 1 min VE/VCO2 (37 ± 7.5 versus 31.5 ± 4.4, p < 0.001) and ΔVE/VCO2 (1.17 ± 3.0 versus −0.5 ± 1.3, p < 0.0001). Strength parameters were relatively lower in HF. While CPX exercise parameters correlated with strength, stronger correlations were observed between CPX recovery parameters and strength. Conclusions: CPX recovery indices corroborate disease-specific aerobic differences and distinguish differences in strength. Recovery ventilatory efficiency enhances CPX’s value as a comprehensive physical function tool.
Complete Genome Sequence of Bacillus cereus Bacteriophage BCP78

ABSTRACT Bacillus cereus is generally found in soil habitats, and it contaminates a wide variety of foods, causing food poisoning with symptoms such as vomiting and diarrhea. To develop a novel biocontrol agent to inhibit this pathogen, bacteriophage BCP78 belonging to the Siphoviridae family was isolated from a fermented food sample. Here we announce the complete genome sequence of BCP78, which may be useful for understanding its inhibition mechanism against B. cereus, and describe major findings from the genome annotation.
Human CD4+ T Cell Response to Human Herpesvirus 6

ABSTRACT Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell lines generated from healthy donors. CD4+ T cells responding to HHV-6 in peripheral blood were observed at frequencies below 0.1% of total T cells but could be expanded easily in vitro. Analysis of cytokines in supernatants of PBMC and T cell cultures challenged with HHV-6 preparations indicated that gamma interferon (IFN-γ) and interleukin-10 (IL-10) were appropriate markers of the HHV-6 cellular response. Eleven CD4+ T cell epitopes, all but one derived from abundant virion components, were identified. The response was highly cross-reactive between HHV-6A and HHV-6B variants. Seven of the CD4+ T cell epitopes do not share significant homologies with other known human pathogens, including the closely related human viruses human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers generated with these epitopes were able to detect HHV-6-specific T cell populations. These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses.
Characterization of the R263K Mutation in HIV-1 Integrase That Confers Low-Level Resistance to the Second-Generation Integrase Strand Transfer Inhibitor Dolutegravir

ABSTRACT Integrase (IN) strand transfer inhibitors (INSTIs) have been developed to inhibit the ability of HIV-1 integrase to irreversibly link the reverse-transcribed viral DNA to the host genome. INSTIs have proven their high efficiency in inhibiting viral replication in vitro and in patients. However, first-generation INSTIs have only a modest genetic barrier to resistance, allowing the virus to escape these powerful drugs through several resistance pathways. Second-generation INSTIs, such as dolutegravir (DTG, S/GSK1349572), have been reported to have a higher resistance barrier, and no novel drug resistance mutation has yet been described for this drug. Therefore, we performed in vitro selection experiments with DTG using viruses of subtypes B, C, and A/G and showed that the most common mutation to emerge was R263K. Further analysis by site-directed mutagenesis showed that R263K does confer low-level resistance to DTG and decreased integration in cell culture without altering reverse transcription. Biochemical cell-free assays performed with purified IN enzyme containing R263K confirmed the absence of major resistance against DTG and showed a slight decrease in 3′ processing and strand transfer activities compared to the wild type. Structural modeling suggested and in vitro IN-DNA binding assays show that the R263K mutation affects IN-DNA interactions.
Major depression and first-time hospitalization with ischemic heart disease, cardiac procedures and mortality in the general population: A retrospective Danish population-based cohort study

Objective We investigated the association between unipolar depression and incident hospital admissions due to ischemic heart disease, invasive cardiac procedures and mortality independent of other medical illnesses. Methods A population-based cohort of 4.6 million persons aged 15 years or older and born in Denmark was followed up from 1995–2009. Incidence rate ratio (IRR) and mortality rate ratio (MRR) were estimated by survival analysis, stratified by or adjusted for gender, age, severe chronic somatic comorbidity and calendar time. Results Adjusted risks of cardiac hospital admissions and death were significantly increased by up to 15% and 68%, respectively, in persons with hospital admissions due to depression, and were most increased in 15–59 year old women (IRR: 1.64; MRR: 2.57) and men with depression (IRR: 1.39; MRR: 2.21), and during the first 180 days after being diagnosed with depression (women: IRR: 1.38; MRR: 2.35; men: IRR: 1.42; MRR: 2.67). One-year mortality after new ischemic heart disease was elevated by 34% in women and men. By contrast, overall rates of invasive cardiac procedures following cardiac hospitalizations were significantly decreased by 34% in persons with depression but were twofold increased in men recently diagnosed with depression. Conclusion Clinical depression leading to hospitalization was a risk factor for new cardiac complications independent of somatic comorbidity in the magnitude of other cardiac risk factors, particularly in individuals between 15–59 years of age and during the first weeks following psychiatric admission. Our findings support recent cardiovascular disease prevention guidelines on assessing depression among other psychosocial factors in patients at increased cardiovascular disease (CVD) risk.
Outcome quality of in-patient cardiac rehabilitation in elderly patients – identification of relevant parameters

Background Outcome quality management requires the consecutive registration of defined variables. The aim was to identify relevant parameters in order to objectively assess the in-patient rehabilitation outcome. Methods From February 2009 to June 2010 1253 patients (70.9 ± 7.0 years, 78.1% men) at 12 rehabilitation clinics were enrolled. Items concerning sociodemographic data, the impairment group (surgery, conservative/interventional treatment), cardiovascular risk factors, structural and functional parameters and subjective health were tested in respect of their measurability, sensitivity to change and their propensity to be influenced by rehabilitation. Results The majority of patients (61.1%) were referred for rehabilitation after cardiac surgery, 38.9% after conservative or interventional treatment for an acute coronary syndrome. Functionally relevant comorbidities were seen in 49.2% (diabetes mellitus, stroke, peripheral artery disease, chronic obstructive lung disease). In three key areas 13 parameters were identified as being sensitive to change and subject to modification by rehabilitation: cardiovascular risk factors (blood pressure, low-density lipoprotein cholesterol, triglycerides), exercise capacity (resting heart rate, maximal exercise capacity, maximal walking distance, heart failure, angina pectoris) and subjective health (IRES-24 (indicators of rehabilitation status): pain, somatic health, psychological well-being and depression as well as anxiety on the Hospital Anxiety and Depression Scale). Conclusion The outcome of in-patient rehabilitation in elderly patients can be comprehensively assessed by the identification of appropriate key areas, that is, cardiovascular risk factors, exercise capacity and subjective health. This may well serve as a benchmark for internal and external quality management.
A prediction of the renal and cardiovascular efficacy of aliskiren in ALTITUDE using short-term changes in multiple risk markers

Introduction We recently developed and validated in existing trials a novel algorithm (PRE score) to predict long-term drug efficacy based on short-term (month-6) drug-induced changes in multiple risk markers. To show the value of the PRE score for ongoing and planned clinical trials, we here report the predicted long-term cardio-renal efficacy of aliskiren in type 2 diabetes, which was investigated in the ALTITUDE trial, but unknown at the time this study was conducted. Methods We established the relation between multiple risk markers and cardio-renal endpoints (as defined in ALTITUDE) using a background database from past clinical trials. The short-term effect of aliskiren on multiple risk markers was taken from the AVOID trial. A PRE score was developed by multivariate Cox analysis in the background population and was then applied to the baseline and month-6 measurements of the aliskiren treatment arm of the AVOID trial to predict cardio-renal risk. The net risk difference at these time-points, after correction for placebo effects, was taken to indicate the estimated long-term cardio-renal risk change. Results Based on the PRE score, we predicted that aliskiren treatment in ALTITUDE would confer a relative risk change of −7.9% (95% CI −2.5 to −13.4) for the cardio-renal endpoint, a risk change of −5.1% (−1.2 to −9.0) for the CV endpoint and a non-significant risk change of −19.9% (−42.1 to +2.1) for the renal endpoint. Conclusions PRE score estimations suggested that aliskiren has only a marginal additive protective effect on cardio-renal endpoints. These predictions were validated by the results of the ALTITUDE trial, confirming the potential of the PRE score to prospectively predict drug efficacy on cardio-renal outcomes.
Efficient Nef-Mediated Downmodulation of TCR-CD3 and CD28 Is Associated with High CD4+ T Cell Counts in Viremic HIV-2 Infection

ABSTRACT The role of the multifunctional accessory Nef protein in the immunopathogenesis of HIV-2 infection is currently poorly understood. Here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load, >500 copies/ml) and 16 nonviremic (<500) HIV-2-infected individuals. On average, nef alleles from both groups were equally active in modulating CD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity. Thus, many HIV-2-infected individuals efficiently control the virus in spite of efficient Nef function. However, the potency of nef alleles in downmodulating TCR-CD3 and CD28 to suppress the activation and apoptosis of T cells correlated with high numbers of CD4+ T cells in viremic patients. No such correlations were observed in HIV-2-infected individuals with undetectable viral load. Further functional analyses showed that the Nef-mediated downmodulation of TCR-CD3 suppressed the induction of Fas, Fas-L, PD-1, and CTLA-4 cell surface expression as well as the secretion of gamma interferon (IFN-γ) by primary CD4+ T cells. Moreover, we identified a single naturally occurring amino acid variation (I132T) in the core domain of HIV-2 Nef that selectively disrupts its ability to downmodulate TCR-CD3 and results in functional properties highly reminiscent of HIV-1 Nef proteins. Taken together, our data suggest that the efficient Nef-mediated downmodulation of TCR-CD3 and CD28 help viremic HIV-2-infected individuals to maintain normal CD4+ T cell homeostasis by preventing T cell activation and by suppressing the induction of death receptors that may affect the functionality and survival of both virally infected and uninfected bystander cells.
A real-time user Interest Meter and its applications in home video summarizing

In this paper, we propose the Interest Meter (IM), a system making computer conscious of user's reactions, to measure user's interest in real time. The Interest Meter takes account of users' spontaneous reactions when users interact with computers. In this work, we analyze variations of user's eye movement, blink, head motion, and facial expression. Furthermore, we propose an algorithm to combine those signals into interest score and determine important parts of video shots when people watch raw home videos. Experimental result shows that this new type of editing mechanism can effectively generate home video summaries.
Sex-specific predictors of the prehypertension-to-hypertension progression: community-based cohort of a West-Asian population

Background We aimed to predict prehypertension-to-hypertension progression rate among a West-Asian adult population. Methods We analyzed data on 3449 adults (mean age 41.0 years), prehypertensive at baseline, attending at least one follow-up visit, contributing 25,079 person-years follow-up. A proportional hazard regression analysis was implemented to model the interval-censored progression-free survival time data using readily-assessable, commonly-available information. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI) indices were calculated to examine whether simple clinical information could help improve prediction of prehypertension-to-hypertension progression rate based on the blood pressure measures. Results During a median seven-year follow-up 1412 prehypertensive patients progressed to hypertension with annual progression rate (95% confidence intervals (CIs)) being 56.9 (52.9–61.2) per 1000 women and 55.7 (51.7–60.0) per 1000 men (p = 0.007). High-density lipoprotein cholesterol levels were inversely associated with prehypertension-to-hypertension progression rate only among women (hazard ratio (1-SD): 0.93, 95% CIs: 0.86–0.100). Marital status retained its predictability among women even after multivariate adjustments. In both men and women, age, blood pressure measures, waist-to-height ratio, fasting plasma glucose and a history of cardiovascular disease independently predicted prehypertension-to-hypertension rate. The absolute (0.114, 95% CIs: 0.107–0.120) and relative (2.638, 95% CIs: 2.374–2.903) IDI and cutpoint-based (0.213, 95% CIs: 0.156–0.269) and cutpoint-free NRI (0.523, 95% CIs: 0.455–0.591) indicated that the prediction of the prehypertension-to-hypertension progression was improved by multivariable-models compared with blood pressure measures alone. Discussion Easily-assessable, commonly-available information helped improve predictability of blood pressure measures for prehypertension-to-hypertension progression. Women's psycho-social characteristics (marital status) should be considered in prevention of prehypertension-to-hypertension progression.
Coronary artery calcification outperforms thoracic aortic calcification for the prediction of myocardial infarction and all-cause mortality: The Heinz Nixdorf Recall Study

Background Thoracic aortic calcification (TAC) is associated with cardiovascular (CV) risk factors and prevalent coronary artery disease. We aimed to investigate whether TAC burden is associated with incident myocardial infarction (MI) and all-cause mortality in subjects without known coronary artery disease and to determine its predictive value for these endpoints. Methods We used longitudinal data from the population-based prospective Heinz Nixdorf Recall Study. TAC and coronary artery calcification (CAC) scores were quantified from non-contrast enhanced electron beam computed tomography. Cox regression analysis was used to determine the association of TAC with incident MI or all-cause mortality, adjusting for CV risk factors and additionally for CAC-score in a separate step. Predictive value of TAC was assessed using Harrell's C index. Results Overall, 4040 participants without known coronary artery disease (59.4 years, 47% male) were included in this analysis. During a mean follow-up of 8.0 ± 1.5 years, we observed 136 coronary events and 304 deaths. In subjects with TAC>0 vs TAC = 0, the incidence of nonfatal MI was 4.2% vs 2.0% (p < 0.001), and all-cause mortality was 8.9% vs 5.2% (p < 0.001). Risks for coronary events and for all-cause mortality increased significantly with increasing TAC-scores (p < 0.001). After adjustment for CV risk factors, body mass index (BMI) and CV medication, a unit increase of TAC on a logarithmic scale (log(TAC + 1)) remained independently associated with coronary events (hazard ratio (HR) (95% confidence interval (CI)): 1.06 (1.00–1.14), p = 0.03) and all-cause mortality (HR 1.06 (1.01–1.12), p < 0.01). After further adjustment for CAC-score (log(CAC + 1)), hazard ratios were attenuated for both endpoints (coronary events: 0.98 (0.91–1.05), p = 0.56, all-cause mortality: 1.03 (0.98–1.08), p = 0.33). When adding log(TAC + 1) to the model containing traditional risk factors and CAC, Harrell's C indices did not increase for coronary events (0.773–0.772, p = 0.66) or for all-cause mortality (0.741–0.743, p = 0.49). Conclusion TAC is associated with incident coronary events and all-cause mortality independent of traditional CV risk factors in the general population. TAC fails to improve event prediction over CAC in both coronary events and all-cause mortality.
Functionalization of inorganic nanoparticles for bioimaging applications.

Modern biomedical imaging technologies have led to significant advances in diagnosis and therapy. Because most disease processes occur at the molecular and cellular levels, researchers continue to face challenges in viewing and understanding these processes precisely and in real time. The ideal imaging resolution would be in nanometers, because most biological processes take place on this length scale. Therefore, the functionalization of nanoparticles (NPs) and their use in therapeutic and diagnostic applications are of great interest. Molecular and cellular imaging agents made from inorganic NPs have been developed to probe such biological events noninvasively. The conjugation of tiny NPs with specific biomolecules allows researchers to target the desired location, reduce overall toxicity, and boost the efficiency of the imaging probes. In this Account, we review recent research on the functionalization of NPs for bioimaging applications. Several types of NPs have been employed for bioimaging applications, including metal (Au, Ag), metal oxide (Fe(3)O(4)), and semiconductor nanocrystals (e.g. quantum dots (QDs) and magnetic quantum dots (MQDs)). The preparation of NPs for bioimaging applications can include a variety of steps: synthesis, coating, surface functionalization, and bioconjugation. The most common strategies of engineering NP surfaces involve physical adsorption or chemisorption of the desired ligands onto the surface. Chemisorption or covalent linkages are preferred, and the coated NPs should possess high colloidal stability, biocompatibility, water solubility, and functional groups for further bioconjugation. Many of the functionalization techniques that have been reported in the literature suffer from limitations such as complex synthesis steps, poor biocompatibility, low stability, and hydrophobic products. Coating strategies based on chemisorption and ligand exchange often provide a better way to tailor the surface properties of NPs. After conjugation with the appropriate targeting ligands, antibodies, or proteins, the NPs may exhibit highly selective binding, making them useful for fluorescence imaging, magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and multimodal imaging.
Modulation of the Myxoma Virus Plaque Phenotype by Vaccinia Virus Protein F11

ABSTRACT Vaccinia virus (VACV) produces large plaques consisting of a rapidly expanding ring of infected cells surrounding a lytic core, whereas myxoma virus (MYXV) produces small plaques that resemble a focus of transformed cells. This is odd, because bioinformatics suggests that MYXV carries homologs of nearly all of the genes regulating Orthopoxvirus attachment, entry, and exit. So why does MYXV produce foci? One notable difference is that MYXV-infected cells produce few of the actin microfilaments that promote VACV exit and spread. This suggested that although MYXV carries homologs of the required genes (A33R, A34R, A36R, and B5R), they are dysfunctional. To test this, we produced MYXV recombinants expressing these genes, but we could not enhance actin projectile formation even in cells expressing all four VACV proteins. Another notable difference between these viruses is that MYXV lacks a homolog of the F11L gene. F11 inhibits the RhoA-mDia signaling that maintains the integrity of the cortical actin layer. We constructed an MYXV strain encoding F11L and observed that, unlike wild-type MYXV, the recombinant virus disrupted actin stress fibers and produced plaques up to 4-fold larger than those of controls, and these plaques expanded ∼6-fold faster. These viruses also grew to higher titers in multistep growth conditions, produced higher levels of actin projectiles, and promoted infected cell movement, although neither process was to the extent of that observed in VACV-infected cells. Thus, one reason for why MYXV produces small plaques is that it cannot spread via actin filaments, although the reason for this deficiency remains obscure. A second reason is that leporipoxviruses lack vaccinia's capacity to disrupt cortical actin.