Miracle-dz/UniFAR-FTUs huggingface dataset:
Inequality and ethics in paediatric HIV remission research: From Mississippi to South Africa and back

ABSTRACT In 2013, physician-researchers announced that a baby in Mississippi had been ‘functionally cured’ of HIV [Persaud, D. , Gay, H. , Ziemniak, C. F. , Chen, Y. H. , Piatak, M. , Chun, T. -W. , … Luzuriaga, K. (2013b, March). Functional HIV cure after very early ART of an infected infant. Paper presented at the 20th conference on retroviruses and opportunistic infections, Atlanta, GA]. Though the child later developed a detectable viral load, the case remains unprecedented, and trials to build on the findings are planned [National Institute of Allergy and Infectious Diseases. (2014). ‘Mississippi baby’ now has detectable HIV, researchers find. Retrieved from http://www.niaid. nih.gov/news/newsreleases/2014/pages/mississippibabyhiv.aspx]. Whether addressing HIV ‘cure’ or ‘remission’, scrutiny of this case has focused largely on scientific questions, with only introductory attention to ethics. The social inequalities and gaps in care that made the discovery possible – and their ethical implications for paediatric HIV remission – have gone largely unexamined. This paper describes structural inequalities surrounding the ‘Mississippi baby’ case and a parallel case in South Africa, where proof-of-concept studies are in the early stages. We argue that an ethical programme of research into infant HIV remission ought to be ‘structurally competent’, and recommend that paediatric remission studies consider including a research component focused on social protection and barriers to care.
A vitamin-B2-sensing mechanism that regulates gut protease activity to impact animal’s food behavior and growth

To survive challenging environments, animals acquired the ability to evaluate food quality in the intestine and respond to nutrient deficiencies with changes in food-response behavior, metabolism and development. However, the regulatory mechanisms underlying intestinal sensing of specific nutrients, especially micronutrients such as vitamins, and the connections to downstream physiological responses in animals remain underexplored. We have established a system to analyze the intestinal response to vitamin B2 (VB2) deficiency in Caenorhabditis elegans, and demonstrated that VB2 level critically impacts food uptake and foraging behavior by regulating specific protease gene expression and intestinal protease activity. We show that this impact is mediated by TORC1 signaling through reading the FAD-dependent ATP level. Thus, our study in live animals uncovers a VB2-sensing/response pathway that regulates food-uptake, a mechanism by which a common signaling pathway translates a specific nutrient signal into physiological activities, and the importance of gut microbiota in supplying micronutrients to animals. DOI: http://dx.doi. org/10.7554/eLife.26243. 001
A Novel Hybrid Plasmid Carrying Multiple Antimicrobial Resistance and Virulence Genes in Salmonella enterica Serovar Dublin

ABSTRACT Virulence plasmids and antibiotic resistance plasmids are usually maintained separately in Salmonella spp. ; however, we report an instance of a hybrid plasmid (pN13-01125) in Salmonella enterica serovar Dublin. Review of the complete sequence of the 172,265-bp plasmid suggests that pN13-01125 is comprised of the previously described pSDVr and pSH696_135 plasmids and that the mechanism of hybridization likely involves IS6 (IS26) insertion sequence elements. The plasmid has a low conjugation frequency, confers resistance to six classes of antimicrobials, and contains a complete spv virulence operon.
PlMAPK10, a Mitogen-Activated Protein Kinase (MAPK) in Peronophythora litchii, Is Required for Mycelial Growth, Sporulation, Laccase Activity, and Plant Infection

Mitogen-activated protein kinase (MAPK) pathways are ubiquitous and evolutionarily conserved signal transduction modules directing cellular respond to a diverse array of stimuli, in the eukaryotic organisms. In this study, PlMAPK10 was identified to encode a MAPK in Peronophythora litchii, the oomycete pathogen causing litchi downy blight disease. PlMAPK10, containing a specific and highly conserved dual phosphorylation lip sequence SEY (Serine-Glutamic-Tyrosine), represents a novel group of MAPKs as previously reported. Transcriptional profiling showed that PlMAPK10 expression was up-regulated in zoospore and cyst stages. To elucidate its function, the PlMAPK10 gene was silenced by stable transformation. PlMAPK10 silence did not impair oospore production, sporangium germination, zoospore encyst, or cyst germination but hindered hyphal growth, sporulation, pathogenicity, likely due to altering laccase activity. Over all, our results indicated that a MAPK encoded by PlMAPK10 gene in P. litchii is important for pathogenic development.
Approximation Multivariate Distribution with Pair Copula Using the Orthonormal Polynomial and Legendre Multiwavelets Basis Functions

We concentrate on constructing higher dimensional distributions using a fast growing graphical model called Vine/ pair-copula model which has been introduced and developed by Joe, Cooke, Bedford, Kurowica, Daneshkhah, and others. They first construct a n-dimensional copula density by stacking together n(n − 1)/2 bivariate copula density, and they then approximate arbitrarily well these bivariate copulas and the corresponding multivariate distribution using a semi-parametric method. One constructive approach involves the use of minimum information copulas that can be specified to any required degree of precision based on the available data (or possibly based on the experts’ judgments). By using this method, one is able to use a fixed finite dimensional family of copulas to be employed in terms of a vine construction, with the promise of a uniform level of approximation. The basic idea behind this method is to use a two-dimensional ordinary polynomial series to approximate any log-density of a bivariate copula function by truncating the series at an appropriate point. We make this approximation method more accurate and computationally faster by using the orthonormal polynomial and Legendre multiwavelets (LMW) series as the basis functions. We show the derived approximations are more precise and computationally faster with better properties than the one proposed previous method in the literature. We then apply our method to modeling a dataset of Norwegian financial data that was previously analyzed in the series of articles, and finally compare our results by them. At the end, we present a method to simulate from the approximated models, and validate our approximation using the simulation results to recover the same dependency structure of the original data.
Consistency of Self-Reported Neurocognitive Symptoms, Post-Traumatic Stress Disorder Symptoms, and Concussive Events From End of First Deployment to Veteran Health Administration Comprehensive Traumatic Brain Injury Evaluation by Operations Enduring Freedom/Iraqi Freedom/New Dawn Veterans

Objective This study examined the consistency of self-reported symptoms and concussive events in combat veterans who reported experiencing concussive events. Method One hundred and forty, single deployed, Operation Enduring Freedom, Operation Iraqi Freedom and Operation New Dawn combat veterans with Veteran Health Administration (VHA) Comprehensive Traumatic Brain Injury Evaluations (CTBIE) and no post-deployment head injury were examined to assess consistency of self-reported (a) traumatic brain injury (TBI)-related symptoms, (b) post-traumatic stress disorder (PTSD)-related symptoms, and (c) TBI-related concussive events from soon after deployment to time of VHA CTBIE. Results Compared to their self-report of symptoms and traumatic events at the time of their Post-Deployment Health Assessment, at the time of their comprehensive VHA evaluation, subjects reported significantly greater impairment in concentration, decision making, memory, headache, and sleep. In addition, although half the subjects denied any PTSD symptoms post-deployment, approximately three quarters reported experiencing all four PTSD screening symptoms near the time of the VHA CTBIEs. At the latter time, subjects also reported significantly more TBI-related concussive events, as well as more post-concussive sequelae such as loss of consciousness immediately following these concussive events. Finally, although 84% reported a level of impairment so severe as to render all but the simplest activity doable, the vast majority simultaneously reported working and/or attending college. Conclusions These findings raise questions regarding the accuracy of veteran self-report of both near and distant traumatic events, and argue for the inclusion of contemporaneous Department of Defense (DOD) records in veteran assessment and treatment planning.
Yoga for the management of pain and sleep in rheumatoid arthritis: a pilot randomized controlled trial

OBJECTIVE The aim of the present study was to determine the feasibility of a relaxation-based yoga intervention for rheumatoid arthritis, designed and reported in accordance with Delphi recommendations for yoga interventions for musculoskeletal conditions. METHODS Participants were recruited from a hospital database, and randomized to either eight weekly 75-min yoga classes or a usual care control. Feasibility was determined by recruitment rates, retention, protocol adherence, participant satisfaction and adverse events. Secondary physical and psychosocial outcomes were assessed using self-reported questionnaires at baseline (week 0), week 9 (primary time point) and week 12 (follow-up). RESULTS Over a 3-month period, 26 participants with mild pain, mild to moderate functional disability and moderate disease activity were recruited into the study (25% recruitment rate). Retention rates were 100% for yoga participants and 92% for usual care participants at both weeks 9 and 12. Protocol adherence and participant satisfaction were high. Yoga participants attended a median of seven classes; additionally, seven of the yoga participants (54%) reported continuing yoga at home during the follow-up period. No serious adverse events were related to the study. Secondary outcomes showed no group effects of yoga compared with usual care. CONCLUSIONS A relaxation-based yoga programme was found to be feasible and safe for participants with rheumatoid arthritis-related pain and functional disability. Adverse events were minor, and not unexpected from an intervention including physical components. This pilot provides a framework for larger intervention studies, and supports further exploration of yoga as a complex intervention to assist with the management of rheumatoid arthritis.
Use of Information and Communication Technologies Among Older People With and Without Frailty: A Population-Based Survey

Background Use of information and communication technologies (ICT) among seniors is increasing; however, studies on the use of ICT by seniors at the highest risk of health impairment are lacking. Frail and prefrail seniors are a group that would likely benefit from preventive nutrition and exercise interventions, both of which can take advantage of ICT. Objective The objective of the study was to quantify the differences in ICT use, attitudes, and reasons for nonuse among physically frail, prefrail, and nonfrail home-dwelling seniors. Methods This was a population-based questionnaire study on people aged 65-98 years living in Northern Finland. A total of 794 eligible individuals responded out of a contacted random sample of 1500. Results In this study, 29.8% (237/794) of the respondents were classified as frail or prefrail. The ICT use of frail persons was lower than that of the nonfrail ones. In multivariable logistic regression analysis, age and education level were associated with both the use of Internet and advanced mobile ICT such as smartphones or tablets. Controlling for age and education, frailty or prefrailty was independently related to the nonuse of advanced mobile ICT (odds ratio, OR=0.61, P=.01), and frailty with use of the Internet (OR=0.45, P=.03). The frail or prefrail ICT nonusers also held the most negative opinions on the usefulness or usability of mobile ICT. When opinion variables were included in the model, frailty status remained a significant predictor of ICT use. Conclusions Physical frailty status is associated with older peoples’ ICT use independent of age, education, and opinions on ICT use. This should be taken into consideration when designing preventive and assistive technologies and interventions for older people at risk of health impairment.
Huge recurrent gastric neuroendocrine tumor: a second-line chemotherapeutic dilemma

Chemotherapy is considered “state of the art” for the treatment of poorly differentiated neuroendocrine neoplasms. Unfortunately, there is no standard effective post-first-line treatment for relapsing high-grade gastroenteropancreatic neuroendocrine neoplasms. We report the case of a patient with a gastric neuroendocrine carcinoma stage IV, with massive gastrointestinal bleeding at diagnosis. After the first line of platin-based chemotherapy a major tumoral response was documented, but the patient relapsed after 4 months. A second line of chemotherapy treatment was given, with the FOLFOX regimen, and the patient has been free of progression for almost 2 years. There is no second-line standard treatment accepted for this type of carcinoma, but 5-fluorouracil combined with oxaliplatin showed interesting antitumor activity.
High-Throughput Genomics and Clinical Outcome in Hard-to-Treat Advanced Cancers: Results of the MOSCATO 01 Trial.

High-throughput genomic analyses may improve outcomes in patients with advanced cancers. MOSCATO 01 is a prospective clinical trial evaluating the clinical benefit of this approach. Nucleic acids were extracted from fresh-frozen tumor biopsies and analyzed by array comparative genomic hybridization, next-generation sequencing, and RNA sequencing. The primary objective was to evaluate clinical benefit as measured by the percentage of patients presenting progression-free survival (PFS) on matched therapy (PFS2) 1.3-fold longer than the PFS on prior therapy (PFS1). A total of 1,035 adult patients were included, and a biopsy was performed in 948. An actionable molecular alteration was identified in 411 of 843 patients with a molecular portrait. A total of 199 patients were treated with a targeted therapy matched to a genomic alteration. The PFS2/PFS1 ratio was >1.3 in 33% of the patients (63/193). Objective responses were observed in 22 of 194 patients (11%; 95% CI, 7%-17%), and median overall survival was 11.9 months (95% CI, 9.5-14.3 months). Significance: This study suggests that high-throughput genomics could improve outcomes in a subset of patients with hard-to-treat cancers. Although these results are encouraging, only 7% of the successfully screened patients benefited from this approach. Randomized trials are needed to validate this hypothesis and to quantify the magnitude of benefit. Expanding drug access could increase the percentage of patients who benefit. Cancer Discov; 7(6); 586-95. ©2017 AACR.See related commentary by Schram and Hyman, p. 552This article is highlighted in the In This Issue feature, p. 539.
Resurgence of Malaria Following Discontinuation of Indoor Residual Spraying of Insecticide in an Area of Uganda With Previously High-Transmission Intensity

Background Indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) are the primary tools for malaria prevention in Africa. It is not known whether reductions in malaria can be sustained after IRS is discontinued. Our aim in this study was to assess changes in malaria morbidity in an area of Uganda with historically high transmission where IRS was discontinued after a 4-year period followed by universal LLIN distribution. Methods Individual-level malaria surveillance data were collected from 1 outpatient department and 1 inpatient setting in Apac District, Uganda, from July 2009 through November 2015. Rounds of IRS were delivered approximately every 6 months from February 2010 through May 2014 followed by universal LLIN distribution in June 2014. Temporal changes in the malaria test positivity rate (TPR) were estimated during and after IRS using interrupted time series analyses, controlling for age, rainfall, and autocorrelation. Results Data include 65 421 outpatient visits and 13 955 pediatric inpatient admissions for which a diagnostic test for malaria was performed. In outpatients aged <5 years, baseline TPR was 60%-80% followed by a rapid and then sustained decrease to 15%-30%. During the 4-18 months following discontinuation of IRS, absolute TPR values increased by an average of 3.29% per month (95% confidence interval, 2.01%-4.57%), returning to baseline levels. Similar trends were seen in outpatients aged ≥5 years and pediatric admissions. Conclusions Discontinuation of IRS in an area with historically high transmission intensity was associated with a rapid increase in malaria morbidity to pre-IRS levels.
Neural Networks for Beat Perception in Musical Rhythm

Entrainment of cortical rhythms to acoustic rhythms has been hypothesized to be the neural correlate of pulse and meter perception in music. Dynamic attending theory first proposed synchronization of endogenous perceptual rhythms nearly 40 years ago, but only recently has the pivotal role of neural synchrony been demonstrated. Significant progress has since been made in understanding the role of neural oscillations and the neural structures that support synchronized responses to musical rhythm. Synchronized neural activity has been observed in auditory and motor networks, and has been linked with attentional allocation and movement coordination. Here we describe a neurodynamic model that shows how self-organization of oscillations in interacting sensory and motor networks could be responsible for the formation of the pulse percept in complex rhythms. In a pulse synchronization study, we test the model's key prediction that pulse can be perceived at a frequency for which no spectral energy is present in the amplitude envelope of the acoustic rhythm. The result shows that participants perceive the pulse at the theoretically predicted frequency. This model is one of the few consistent with neurophysiological evidence on the role of neural oscillation, and it explains a phenomenon that other computational models fail to explain. Because it is based on a canonical model, the predictions hold for an entire family of dynamical systems, not only a specific one. Thus, this model provides a theoretical link between oscillatory neurodynamics and the induction of pulse and meter in musical rhythm.
Packetostatics: deployment of massively dense sensor networks as an electrostatics problem

We investigate the spatial distribution of wireless nodes that can transport a given volume of traffic in a sensor network, while requiring the minimum number of wireless nodes. The traffic is created at a spatially distributed set of sources, and must arrive at a spatially distributed set of sinks. Under a general assumption on the physical and medium access control (MAC) layers, the optimal distribution of nodes induces a traffic flow identical to the electrostatic field that would exist if the sources and sinks of traffic were substituted with an appropriate distribution of electric charge. This analogy between electrostatics and wireless sensor networks can be extended in a number of different ways. For example, Thomson's theorem on the distribution of electric charge on conductors gives the optimal distribution of traffic sources and sinks (that minimizes the number of nodes needed) when we have a limited degree of freedom on their initial placement. Electrostatics problems with Neumann boundary conditions and topologies with different types of dielectric materials can also be interpreted in the context of wireless sensor networks. The analogy also has important limitations. For example, if we move to a three dimensional topology, adapting our general assumption on the physical and MAC layers accordingly, or we stay in the two dimensional plane but use an alternative assumption, that is more suited to ultra wide band communication, the optimal traffic distribution is not in general irrotational, and so can not be interpreted as an electrostatic field. Finally, the analogy cannot be extended to include networks that support more than one type of traffic.
Role of the intercalated disc in cardiac propagation and arrhythmogenesis

This review article discusses mechanisms underlying impulse propagation in cardiac muscle with specific emphasis on the role of the cardiac cell-to-cell junction, called the “intercalated disc. ”The first part of this review deals with the role of gap junction channels, formed by connexin proteins, as a determinant of impulse propagation. It is shown that, depending on the underlying structure of the cellular network, decreasing the conductance of gap junction channels (so-called “electrical uncoupling”) may either only slow, or additionally stabilize propagation and reverse unidirectional propagation block to bidirectional propagation. This is because the safety factor for propagation increases with decreasing intercellular electrical conductance. The role of heterogeneous connexin expression, which may be present in disease states, is also discussed. The hypothesis that so-called ephaptic impulse transmission plays a role in heart and can substitute for electrical coupling has been revived recently. Whereas ephaptic transmission can be demonstrated in theoretical simulations, direct experimental evidence has not yet been presented. The second part of this review deals with the interaction of three protein complexes at the intercalated disc: (1) desmosomal and adherens junction proteins, (2) ion channel proteins, and (3) gap junction channels consisting of connexins. Recent work has revealed multiple interactions between these three protein complexes which occur, at least in part, at the level of protein trafficking. Such interactions are likely to play an important role in the pathogenesis of arrhythmogenic cardiomyopathy, and may reveal new therapeutic concepts and targets.
A Fluorescent Biofunctional DNA Hydrogel Prepared by Enzymatic Polymerization

DNA has arisen as a promising building material for the construction of hydrogels owing to its unique properties such as designability and biocompatibility. All‐DNA hydrogels with only DNA molecules may have limited applications; hence a composite DNA hydrogel with multifunctional moieties is highly desired to cater for specific applications. Herein, a multifunctional DNA hydrogel is created by incorporating DNA with silver nanoclusters (AgNCs), in which AgNCs render the hydrogel simultaneously with fluorescent and antibacterial functions. A circular DNA is rationally designed, which allows for the elongation of DNA chain via an enzymatic polymerization as well as the formation of AgNCs onto DNA scaffolds. The resultant hybrid DNA hydrogel not only shows distinctive morphology and mechanical properties, but also exhibits fluorescent and antibacterial functions. These characteristics, along with its biocompatibility, will allow the hydrogel to be suitable for a variety of potential biomedical applications such as tissue engineering, wound dressing, biosensing, and bioimaging.