ALBERT

Description: Aim Combined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines. Purpose Characterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey. Methods A cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment. Results 176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment in 2019. 2DR that included INSTI and PI were more commonly used in cases of drug resistance, while a combination of INSTI and NNRTI was used in all other 2DR indications. A switch to 2DR induced a mean CD4 T cell increase from 599 cells/μl at treatment initiation to 680 cells/μl at 96 weeks of treatment p

Description: Historically, the database search algorithms have been the de facto standard for inferring peptides from mass spectrometry (MS) data. Database search algorithms deduce peptides by transforming theoretical peptides into theoretical spectra and matching them to the experimental spectra. Heuristic similarity-scoring functions are used to match an experimental spectrum to a theoretical spectrum. However, the heuristic nature of the scoring functions and the simple transformation of the peptides into theoretical spectra, along with noisy mass spectra for the less abundant peptides, can introduce a cascade of inaccuracies. In this paper, we design and implement a Deep Cross-Modal Similarity Network called SpeCollate, which overcomes these inaccuracies by learning the similarity function between experimental spectra and peptides directly from the labeled MS data. SpeCollate transforms spectra and peptides into a shared Euclidean subspace by learning fixed size embeddings for both. Our proposed deep-learning network trains on sextuplets of positive and negative examples coupled with our custom-designed SNAP-loss function. Online hardest negative mining is used to select the appropriate negative examples for optimal training performance. We use 4.8 million sextuplets obtained from the NIST and MassIVE peptide libraries to train the network and demonstrate that for closed search, SpeCollate is able to perform better than Crux and MSFragger in terms of the number of peptide-spectrum matches (PSMs) and unique peptides identified under 1% FDR for real-world data. SpeCollate also identifies a large number of peptides not reported by either Crux or MSFragger. To the best of our knowledge, our proposed SpeCollate is the first deep-learning network that can determine the cross-modal similarity between peptides and mass-spectra for MS-based proteomics. We believe SpeCollate is significant progress towards developing machine-learning solutions for MS-based omics data analysis. SpeCollate is available at https://deepspecs.github.io/.

Description: When pharmaceutical interventions are unavailable to deal with an epidemic outbreak, adequate management of communication strategies can be key to reduce the contagion risks. On the one hand, accessibility to trustworthy and timely information, whilst on the other, the adoption of preventive behaviors may be both crucial. However, despite the abundance of communication strategies, their effectiveness has been scarcely evaluated or merely circumscribed to the scrutiny of public affairs. To study the influence of communication strategies on the spreading dynamics of an infectious disease, we implemented a susceptible-exposed-infected-removed-dead (SEIRD) epidemiological model, using an agent-based approach. Agents in our systems can obtain information modulating their behavior from two sources: (i) through the local interaction with other neighboring agents and, (ii) from a central entity delivering information with a certain periodicity. In doing so, we highlight how global information delivered from a central entity can reduce the impact of an infectious disease and how informing even a small fraction of the population has a remarkable impact, when compared to not informing the population at all. Moreover, having a scheme of delivering daily messages makes a stark difference on the reduction of cases, compared to the other evaluated strategies, denoting that daily delivery of information produces the largest decrease in the number of cases. Furthermore, when the information spreading relies only on local interactions between agents, and no central entity takes actions along the dynamics, then the epidemic spreading is virtually independent of the initial amount of informed agents. On top of that, we found that local communication plays an important role in an intermediate regime where information coming from a central entity is scarce. As a whole, our results highlight the importance of proper communication strategies, both accurate and daily, to tackle epidemic outbreaks.

Description: Background Migrants are not routinely screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in the Netherlands. We estimated the prevalence and determined factors associated with HBV, HCV and/or HIV infections among undocumented migrants and uninsured legal residents. Methods In this cross-sectional study, undocumented migrants and uninsured legal residents were recruited at a non governmental organization (NGO), healthcare facility in the Netherlands and were invited to be tested for hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibodies (anti-HBcAb), HCV-RNA, and anti-HIV antibodies or HIV antigen at a local laboratory. Results Of the 1376 patients invited, 784 (57%) participated. Participants originated from Africa (35%), Asia (30%) and North/South America (30%). 451/784 (58%) participants went to the laboratory for testing. Of participants 30% were HBV exposed (anti-HBcAb-positive), with 27% (n = 119/438, 95% CI 23.1% to 31.6%) having resolved HBV infection (HBsAg-negative) and 2.5% (n = 11/438, 95%CI 1.3% to 4.5%, 64% new infection) having chronic HBV infection (HBsAg-positive). Compared to HBV non-exposed, HBV exposed individuals were older (p = 0.034) and more often originated from Africa (p

Description: Introduction Sex-based clinical outcome differences in sickle cell disease (SCD) remain largely unknown despite evidence that female sex is associated with an increased lifespan. To better characterize sex-based differences in SCD, we assessed pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. Methods The SCDIC consists of eight comprehensive SCD centers and one data coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Eligibility criteria included: 15 to 45 years of age and a confirmed diagnosis of SCD. Self-report surveys were completed and data were also abstracted from the participants’ medical records. Results A total of 2,124 participants were included (mean age: 27.8 years; 56% female). The majority had hemoglobin SS SCD genotype. Females had worse reports of pain severity (mean (SD) T-score 51.6 (9.6) vs 49.3 (10), p

Description: Despite the often emphasized importance of water awareness, and notwithstanding the fact that calls for increasing public awareness are becoming commonplace, most studies do not define the concept, let alone operationalise it into measurable units. This is, however, essential to measure and evaluate efforts related to water awareness such as public campaigns, customer communication and behavioural interventions. To address this gap, we conceptualise, operationalise and assess tap water awareness, hereby differentiating between cognitive awareness (head), affectional awareness (heart), and behavioural awareness (hands). In parallel, we also differentiate between tap water quality, quantity and system. By building on a variety of contemporary conceptual insights in literature and a series of expert interviews, an assessment framework is developed. A cohesive set of nine awareness components are identified and operationalised into a set of tangible questions which are put to the test in a large-scale online survey (n = 1003) in the Netherlands, applying both a traditional and modern segmentation approach based on four types of perspectives (‘quality & health concerned’, ‘aware & committed’, ‘egalitarian & solidary’, and ‘down to earth & confident’). Based on the analysis of the results of the first empirical application of our tap water awareness assessment framework, we conclude that—with a score 53.5 points out of 100—tap water awareness in the Netherlands shows ample room for improvement. Interestingly, most significant variations in awareness are generally not related to sociodemographic factors but rather apply to the four customer perspectives on drinking water that are based on people’s subjective views and preferences.

Description: Background High prevalence of tobacco smoking among young students remains a serious health concern given the positive association between smoking and NCDs. More recently, some studies also noted young smokers were more likely to get infected with COVID-19 compared to non-smokers. This study aims to assess the factors that influence smoking uptake among young students in Samoa. Findings from this study will provide valuable insight to policymakers and health authorities on policies and strategies to combat smoking among youth in Samoa and the Pacific Island Countries (PICs). Methods The 2017 Global Youth Tobacco Survey data of Samoa, available from the World Health Organization is used in the analysis. We use the multinominal logistic model to investigate the effects of socio-economic and demographics factors on young students’ uptake of smoking in Samoa. Result The main findings of this study indicate that sex, age, friendship, parental smoking, family discussion, outside influence, pocket money, and mother’s education are important determinants of tobacco smoking initiation among youths in Samoa. Conclusion Our findings contribute towards the evidence of the imperative health impact of friends, parents, and public smoking on students in Samoa. This warrants strategies that are effective in discouraging parents from smoking and implement measures that prevent smoking in public places. Moreover, educational efforts, particularly those that encourage more discussion at home settings on the harmful effects of smoking are strongly recommended. Parents are strongly encouraged to regularly monitor children’s spending behaviour.

Description: Reverse translation of polypeptide sequences to expressible mRNA constructs is a NP-hard combinatorial optimization problem. Each amino acid in the protein sequence can be represented by as many as six codons, and the process of selecting the combination that maximizes probability of expression is termed codon optimization. This work investigates the potential impact of leveraging quantum computing technology for codon optimization. A Quantum Annealer (QA) is compared to a standard genetic algorithm (GA) programmed with the same objective function. The QA is found to be competitive in identifying optimal solutions. The utility of gate-based systems is also evaluated using a simulator resulting in the finding that while current generations of devices lack the hardware requirements, in terms of both qubit count and connectivity, to solve realistic problems, future generation devices may be highly efficient.

Description: Surveillance of the SARS-CoV-2 variants including the quickly spreading mutants by rapid and near real-time sequencing of the viral genome provides an important tool for effective health policy decision making in the ongoing COVID-19 pandemic. Here we evaluated PCR-tiling of short (~400-bp) and long (~2 and ~2.5-kb) amplicons combined with nanopore sequencing on a MinION device for analysis of the SARS-CoV-2 genome sequences. Analysis of several sequencing runs demonstrated that using the long amplicon schemes outperforms the original protocol based on the 400-bp amplicons. It also illustrated common artefacts and problems associated with PCR-tiling approach, such as uneven genome coverage, variable fraction of discarded sequencing reads, including human and bacterial contamination, as well as the presence of reads derived from the viral sub-genomic RNAs.

Description: Background Measurement of health-related quality of life (HRQOL) of people with chronic illnesses has become extremely important as the mortality rates associated with such illnesses have decreased and survival rates have increased. Thereby, such measurements not only provide insights into physical, mental and social dimensions of patient’s health, but also allow monitoring of the results of interventions, complementing the traditional methods based on morbidity and mortality. Objective The present study was conducted to describe the HRQOL of patients suffering from Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD), and to identify socio-demographic and clinical factors as predictors of HRQOL. Methodology A cross-sectional study was conducted to assess the HRQOL among 702 RF and RHD patients using EuroQol 5-dimensions 5-levels instrument (EQ-5D-5L), EuroQol Visual Analogue Scale and Time Trade off method. Mean EQ-5D-5L quality of life scores were calculated using EQ5D index value calculator across different stages of RF and RHD. Proportions of patients reporting problems in different attributes of EQ-5D-5L were calculated. The impact of socio-economic determinants on HRQOL was assessed. Results The mean EQ-5D-5L utility scores among RF, RHD and RHD with Congestive heart failure patients (CHF) were estimated as 0.952 [95% Confidence Interval (CI): 0.929–0.975], 0.820 [95% CI: 0.799–0.842] and 0.800 [95% CI: 0.772–0.829] respectively. The most frequently reported problem among RF/RHD patients was pain/discomfort (33.8%) followed by difficulty in performing usual activities (23.9%) patients, mobility (22.7%) and anxiety/depression (22%). Patients with an annual income of less than 50,000 Indian National Rupees (INR) reported the highest EQ-5D-5L score of 0.872, followed by those in the income group of more than INR 200,000 (0.835), INR 50,000–100,000 (0.832) and INR 100,000–200,000 (0.828). Better HRQOL was reported by RHD patients (including RHD with CHF) who underwent balloon valvotomy (0.806) as compared to valve replacement surgery (0.645). Conclusion RF and RHD significantly impact the HRQOL of patients. Interventions aiming to improve HRQOL of RF/RHD patients should focus upon ameliorating pain and implementation of secondary prevention strategies for reducing the progression from ARF to RHD and prevention of RHD-related complications.