Miracle-dz/UniFAR-FTUs huggingface dataset:
The Significance of Ventricular Volume in the Evaluation of Secondary Cardiomyopathy at Autopsy

Background: The weight, shape and consistency of the heart, and the thickness of the ventricular wall are used as parameters for evaluating postmortem heart and diagnosing cardiomyopathy at autopsy. Methods: The weight and volume of the ventricles and the thickness of the left ventricular wall of 58 hearts were measured and analyzed. Results: In the group of dilated hearts, the ventricular weight, ventricular volume, ventricular volume/ventricular weight, and left ventricular volume/right ventricular volume increased, whereas ventricular wall thickness decreased. In the group of hypertrophied hearts, the ventricular weight, ventricular volume, and thickness of the ventricular wall increased but ventricular volume/ventricular weight and left ventricular volume/ right ventricular volume did not change significantly. In the group of undetermined hearts, it was later found that four of the cases should have been included in the dilated heart group and another two cases in the hypertrophied heart group. Conclusions: In addition to conventional methods, the measuring ventricular volume is useful for evaluating a postmortem heart and may suggest postmortem differential diagnoses of dilated or hypertrophied forms of secondary cardiomyopathies.
How to design a dose-finding study on combined agents: Choice of design and development of R functions

Background In oncology, the aim of dose-finding phase I studies is to find the maximum tolerated dose for further studies. The use of combinations of two or more agents is increasing. Several dose-finding designs have been proposed for this situation. Numerous publications have however pointed out the complexity of evaluating therapies in combination due to difficulties in choosing between different designs for an actual trial, as well as complications related to their implementation and application in practice. Methods In this work, we propose R functions for Wang and Ivanova’s approach. These functions compute the dose for the next patients enrolled and provide a simulation study in order to calibrate the design before it is applied and to assess the performance of the design in different scenarios of dose-toxicity relationships. This choice of the method was supported by a simulation study which the aim was to compare two designs in the context of an actual phase I trial: i) in 2005, Wang and Ivanova developed an empirical three-parameter model-based method in Bayesian inference, ii) in 2008, Yuan and Yin proposed a simple, adaptive two-dimensional dose-finding design. In particular, they converted the two-dimensional dose-finding trial to a series of one-dimensional dose-finding sub-trials by setting the dose of one drug at a fixed level. The performance assessment of Wang’s design was then compared with those of designs presented in the paper by Hirakawa et al. (2015) in their simulation context. Results and conclusion It is recommended to assess the performances of the designs in the context of the clinical trial before beginning the trial. The two-dimensional dose-finding design proposed by Wang and Ivanova is a comprehensive approach that yields good performances. The two R functions that we propose can facilitate the use of this design in practice.
Exploring structural dynamics of a membrane protein by combining bioorthogonal chemistry and cysteine mutagenesis

The functional mechanisms of membrane proteins are extensively investigated with cysteine mutagenesis. To complement cysteine-based approaches, we engineered a membrane protein with thiol-independent crosslinkable groups using azidohomoalanine (AHA), a non-canonical methionine analogue containing an azide group that can selectively react with cycloalkynes through a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. We demonstrate that AHA can be readily incorporated into the Shaker Kv channel in place of methionine residues and modified with azide-reactive alkyne probes in Xenopus oocytes. Using voltage-clamp fluorometry, we show that AHA incorporation permits site-specific fluorescent labeling to track voltage-dependent conformational changes similar to cysteine-based methods. By combining AHA incorporation and cysteine mutagenesis in an orthogonal manner, we were able to site-specifically label the Shaker Kv channel with two different fluorophores simultaneously. Our results identify a facile and straightforward approach for chemical modification of membrane proteins with bioorthogonal chemistry to explore their structure-function relationships in live cells.
Parkinson’s Disease and Symptomatic Osteoarthritis Are Independent Risk Factors of Falls in the Elderly

Objectives: Deteriorating functionality and loss of mobility, resulting from Parkinson’s disease, may be worsened by osteoarthritis, which is the most common form of joint disease causing pain and functional impairment. We assessed the association between symptomatic hip or knee osteoarthritis, falls, and the ability to walk among patients with Parkinson’s disease compared to a control group. Methods: A total of 136 patients with Parkinson’s disease in Southern Estonia and 142 controls with an average age of 76.8 and 76.3 years, respectively, were enrolled in a retrospective case-control study. Information on falls and related fractures during the previous year was collected from the patients with Parkinson’s disease and controls. Covariates included gender, age, mobility, duration of Parkinson’s disease, and fractures. Results: Patients with Parkinson’s disease were at an increased risk of falls compared to the control group, and for the higher risk of fractures. Symptomatic knee or hip osteoarthritis was a significant independent predictor of falls in both patients with Parkinson’s disease and controls. The higher risk for fractures during the previous year was demonstrated in symptomatic osteoarthritis. Risk factors for falls included also female gender, use of sleep pills, and the inability to walk 500 m. Conclusions: Symptomatic hip and knee osteoarthritis are risk factors for falls and related fractures among the elderly population with and without Parkinson’s disease. The inability to walk 500 m could be used as a simple predictive factor for the increased risk of falls among elderly populations.
Determinant Factors of Public Acceptance of Stress Management Apps: Survey Study

Background Chronic stress is a major public health concern. Mobile health (mHealth) apps can help promote coping skills in daily life and prevent stress-related issues. However, little is known about the determinant factors of public acceptance of stress management in relation to preferences for psychological services. Objective The aim of this survey study was to (1) assess determinant factors of public acceptance (behavioral use intention) of stress management apps based on an adapted and extended version of the Unified Theory of Acceptance and Use of Technology (UTAUT) model and (2) explore preferences for mHealth apps compared with other mental health services. Methods Using convenience sampling, participants completed a multiscale 54-item Web-based survey. Based on significant correlations with acceptance, hierarchical stepwise regression analysis was performed within three blocks: (1) background and stress-related control variables, (2) beliefs and attitudes toward using mHealth, and (3) the core UTAUT determinants. The preference for mHealth apps in comparison with nine other mental health services (operationalized as readiness to use) was analyzed using paired t tests. Results Of 141 participants, nearly half (69/141, 48.9%) indicated prior mHealth use. Acceptance of stress coping apps was moderate (mean 3.10, SD 1.03, range 1-5). Hierarchical stepwise regression including four of 11 variables (R2=.62; P=.01, f2=1.63) identified positive attitudes toward using mHealth for stress coping (beta=0.69, P<.001, 46% R2 increase above block 1, f2=0.85), skepticism/perceived risks (beta=−0.14, P=.01, f2=0.16), and stress symptoms (beta=0.12, P=.03, f2=0.14) as significant predictors of acceptance. UTAUT determinants added no predictive contribution beyond attitudes (all P>.05, R2 increase of 1%), whereas post hoc analysis showed significant R2 increases of attitudes and skepticism/perceived risks beyond UTAUT determinants (all P<.001, R2 increase of 13%). The readiness to use apps was equivalent to or significantly higher than most service types, but lower than information websites. Conclusions Attitudes may be at least as predictive for the acceptance of stress management apps as for more elaborated outcome beliefs. Efforts aimed at improving the public adoption of mHealth could put more emphasis on the pleasant aspects of app use, address misconceptions, offer stress screening tools on health websites, and increase options to try high-quality apps.
Incidence, comorbidities, and treatment patterns of nontuberculous mycobacterial infection in South Korea

Abstract Nontuberculous mycobacteria (NTM) are important pathogens in humans, and hospital-based studies have shown an increased incidence of NTM infection. However, little is known about the treatment pattern of NTM infection with respect to the number of cases per population in South Korea. This study evaluated the trends in the incidence of NTM infection, respiratory comorbidities, and treatment patterns in South Korea. National claims data from the Health Insurance Review and Assessment service database for the years 2009 to 2015 were reviewed, and codes related to NTM infection, respiratory comorbidities occurring from one year before NTM infection and associated treatments were identified. In total, 52,551 patients were included in the study and the average annual incidence per 100,000 person-years was 12.8. The annual incidence was found to have increased from 6.6 to 26.6 per 100,000 persons. Accompanied comorbidities were tuberculosis (33.7%), followed by bronchial asthma (33.2%), chronic obstructive pulmonary disease (25.6%), and lung cancer (5.8%). A total of 76.6% of patients did not receive any combination treatment within one year after the diagnosis of NTM infection. Macrolide-based treatment was administered to 18.8% of patients. A dramatic increase in the incidence of NTM infection was noted in the population of South Korea. Approximately three-fourth of the patients with NTM infection were clinically observed without treatment for at least 1 year after the identification of NTM infection and most patients who treated NTM infection received macrolide-based combination therapy.
Stigma and Discrimination Among Children Living with Hiv (clhiv) in South India

This study was a descriptive correlational survey performed to find the stigma and discrimination experienced children living with HIV (CLHIV). The subjects were 50 CLHIV selected using purposive sampling, living in one of the districts of South India attending ART plus centre of Distrcit hospital. Among 50 CLHIV, 23(46.1%) of the belonged to the age group of 16-18 years and 28 (56%) subjects were males. Level of stigma and discrimination was low in majority of the CLHIV(90%). Majority43(86%) of the subjects were found to have low social support.45(90%) samples’ are adherence to ART.
Microbial functional diversity: From concepts to applications

Abstract Functional diversity is increasingly recognized by microbial ecologists as the essential link between biodiversity patterns and ecosystem functioning, determining the trophic relationships and interactions between microorganisms, their participation in biogeochemical cycles, and their responses to environmental changes. Consequently, its definition and quantification have practical and theoretical implications. In this opinion paper, we present a synthesis on the concept of microbial functional diversity from its definition to its application. Initially, we revisit to the original definition of functional diversity, highlighting two fundamental aspects, the ecological unit under study and the functional traits used to characterize it. Then, we discuss how the particularities of the microbial world disallow the direct application of the concepts and tools developed for macroorganisms. Next, we provide a synthesis of the literature on the types of ecological units and functional traits available in microbial functional ecology. We also provide a list of more than 400 traits covering a wide array of environmentally relevant functions. Lastly, we provide examples of the use of functional diversity in microbial systems based on the different units and traits discussed herein. It is our hope that this paper will stimulate discussions and help the growing field of microbial functional ecology to realize a potential that thus far has only been attained in macrobial ecology.
Emergence of new variants of antibiotic resistance genomic islands among multidrug-resistant Salmonella enterica in poultry.

Non-typhoidal Salmonella enterica (NTS) are diverse and important bacterial pathogens consisting of more than 2600 different serovars, with varying host-specificity. Here, we characterized the poultry-associated serovars in Israel, analyzed their resistome and illuminated the molecular mechanisms underlying common multidrug resistance (MDR) patterns. We show that at least four serovars including Infantis, Muenchen, Newport and Virchow present a strong epidemiological association between their temporal trends in poultry and humans. Worrisomely, 60% from all of the poultry isolates tested (n=188) were multidrug resistant, mediated by chromosomal SNPs and different mobile genetics elements. A novel streptomycin-azithromycin resistance island and previously uncharacterized versions of the mobilized Salmonella genomic island 1 (SGI1) were identified and characterized in S. Blockley and S. Kentucky isolates, respectively. Moreover, we demonstrate that the acquisition of SGI1 does not impose fitness cost during growth under nutrient-limited conditions or in the context of Salmonella infection in the mouse model. Overall, our data emphasize the role of the poultry production as a pool of specific epidemic MDR strains and autonomous genetic elements, which confer resistance to heavy metals and medically relevant antibiotics. These are likely to disseminate to humans via the food chain and fuel the increasing global antibiotic resistance crisis. This article is protected by copyright. All rights reserved.
Comparative Proteomics Analysis of Human Liver Microsomes and S9 Fractions

Human liver microsomes (HLM) and human liver S9 fractions (HLS9) are commonly used to study drug metabolism in vitro. However, a quantitative comparison of HLM and HLS9 proteomes is lacking, resulting in the arbitrary selection of one hepatic preparation over another and in difficulties with data interpretation. In this study, we applied a label-free global absolute quantitative proteomics method to the analysis of HLS9 and the corresponding HLM prepared from 102 individual human livers. A total of 3137 proteins were absolutely quantified, and 3087 of those were determined in both HLM and HLS9. Protein concentrations were highly correlated between the two hepatic preparations (R = 0.87, P < 0.0001). We reported the concentrations of 98 drug-metabolizing enzymes (DMEs) and 51 transporters, and demonstrated significant differences between their abundances in HLM and HLS9. We also revealed the protein-protein correlations among these DMEs and transporters and the sex effect on the HLM and HLS9 proteomes. Additionally, HLM and HLS9 displayed distinct expression patterns for protein markers of cytosol and various cellular organelles. Moreover, we evaluated the interindividual variability of three housekeeping proteins, and identified five proteins with low variation across individuals that have the potential to serve as new internal controls for western blot experiments. In summary, these results will lead to better understanding of data obtained from HLM and HLS9 and assist in in vitro-in vivo extrapolations. Knowing the differences between HLM and HLS9 also allows us to make better-informed decisions when choosing between these two hepatic preparations for in vitro drug metabolism studies. SIGNIFICANCE STATEMENT This investigation revealed significant differences in protein concentrations of drug-metabolizing enzymes and transporters between human liver microsomes and S9 fractions. We also determined the protein-protein correlations among the drug-metabolizing enzymes and transporters and the sex effect on the proteomes of these two hepatic preparations. The results will help interpret data obtained from these two preparations and allow us to make more informed decisions when choosing between human liver microsomes and S9 fractions for in vitro drug metabolism studies.
Real-world evidence of the effectiveness of ombitasvir-paritaprevir/r ± dasabuvir ± ribavirin in patients monoinfected with chronic hepatitis C or coinfected with human immunodeficiency virus-1 in Spain

Aim We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain. Material and methods Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven “National HCV plan. ” Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded. Results Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8–97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of −2.2% (90% CI, −4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin. Conclusions Our results confirm that OBV/PTV/r ± DSV ± RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV.
The Prevalence and Predictors of Significant Coronary Artery Disease by Preoperative Coronary Angiography Prior to Aortic Syndrome Surgery

Coronary artery disease (CAD) is commonly associated with aortic aneurysm in patients. A routine coronary angiogram (CAG) was performed to evaluate coronary artery anatomy in patients prior to the repair of aortic syndrome in King Chulalongkorn Memorial Hospital. This prevalence of significant coronary artery disease has never been reported in Thailand before. We also correlated the risk factors for CAD in these patients. Methods: Two hundred and eighty-nine patients that underwent aortic syndrome surgery were studied from January 2002 - 2007 in a retro- prospective study. Only 126 of these 289 patients that had CAG performed were reviewed for this study. Eighty-three were retrospectively studied while 43 were prospectively studied. All their data were collected from hospital data and telephone call interviews. Clinical atherosclerotic risk factors and types of aortic surgery were subjected to univariate and multivariate analysis in order to determine predictors for significant CAD. Results: Forty-seven of 126 (36%) patients had significant stenosis of at least one major coronary artery, 18 patients (38%) received medication, 5 patients (11%) received percutaneous transluminal coronary angioplasty (PTCA)(3 patients in POBA, 2 patients in PTCA with stent) and 24 patients (51%) underwent coronary artery bypass grafts (CABG). The overall mortality of the126 patients undergoing aortic syndrome surgery was 15 (12%). Of these deaths 11 patients (9%) were considered to be in the non-significant CAD group while 4 patients (3%) were in the significant CAD group. No perioperative myocardial infarction (MI) was noted after aortic syndrome surgery. Univariate and multivariate analysis indicated only an infrarenal type of abdominal aortic aneurysm (AAA)(odds ratio = 4.14, 95% confidence interval = 1.89- 9.08) and a New York Heart Association (NYHA) functional class ≥ 2 (odds ratio = 2.67, 95% confidence interval = 1.2- 5.9) significant for significant CAD in patients undergoing aortic syndrome surgery. Conclusions: The prevalence of significant CAD in patients who underwent CAG for aortic syndrome surgery in King Chulalongkorn Memorial Hospital was 36%. Infrarenal AAA and a NYHA functional Class ≥ 2 were correlated with significant CAD. In patients who did not have infrarenal AAA and NYHA functional class 2 or more may not necessitate a CAG before surgical repair. But more large studies are required to assess the risk in these patients so as to facilitate the development of guidelines in Thailand.
Trypanosoma brucei infection protects mice against malaria

Sleeping sickness and malaria are parasitic diseases with overlapping geographical distributions in sub-Saharan Africa. We hypothesized that the immune response elicited by an infection with Trypanosoma brucei, the etiological agent of sleeping sickness, would inhibit a subsequent infection by Plasmodium, the malaria parasite, decreasing the severity of its associated pathology. To investigate this, we established a new co-infection model in which mice were initially infected with T. brucei, followed by administration of P. berghei sporozoites. We observed that a primary infection by T. brucei significantly attenuates a subsequent infection by the malaria parasite, protecting mice from experimental cerebral malaria and prolonging host survival. We further observed that an ongoing T. brucei infection leads to an accumulation of lymphocyte-derived IFN-γ in the liver, limiting the establishment of a subsequent hepatic infection by P. berghei sporozoites. Thus, we identified a novel host-mediated interaction between two parasitic infections, which may be epidemiologically relevant in regions of Trypanosoma/Plasmodium co-endemicity.