Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms Involved in Stimulation of Human Immunodeficiency Virus Type 1 Replication by Aminooxypentane RANTES

ABSTRACT Aminooxypentane (AOP)-RANTES is a potent inhibitor of nonsyncytium-inducing (NSI), CCR5-tropic (R5) human immunodeficiency virus type 1 (HIV-1) isolates. Although classical chemotactic responses are not induced in primary leukocytes by AOP-RANTES, recent studies suggest that a remnant of cell signaling occurs upon binding of receptor to this compound. We have detected a breakthrough of NSI/R5 replication from the inhibitory effects of high AOP-RANTES concentrations (<100 nM). A stimulation of different primary syncytium-inducing (SI), CXCR4-tropic (X4) HIV-1 isolates was also observed in the presence of AOP-RANTES. This stimulation was also observed after 110 h in PCR and RT-PCR for minus-strand strong-stop DNA and unspliced and multiply spliced RNA, respectively. However, there was significant variability between different SI/X4 or NSI/R5 HIV-1 isolates with regard to this AOP-RANTES-mediated stimulation or breakthrough, respectively. To further define the mechanism(s) responsible for this AOP-RANTES effect, we performed detailed retroviral replication studies with an NSI/R5 (B-92BR021) and SI/X4 (D-92UG021) HIV-1 isolate in the presence of the drug. Treatment of peripheral blood mononuclear cells with 125 nM AOP-RANTES and virus did not alter coreceptor expression, HIV-1 entry, reverse transcription, or mRNA transcription from the long terminal repeat, but it did result in increased HIV-1 integration. This AOP-RANTES-mediated increase in HIV-1 integration was diminished by treatment with pertussis toxin. Phosphorylation of the mitogen-activated protein kinase (MAPK) isoforms, extracellular signal-regulated kinase 1 (ERK1) and ERK2, was increased in a CD4+ CCR5+ U87 cell line treated with AOP-RANTES or with an NSI/R5 HIV-1 isolate. These findings suggest that AOP-RANTES may induce a MAPK/ERK signal transduction pathway upon binding to a G-protein-coupled receptor. MAPK/ERK1 and -2 appear to phosphorylate the HIV-1 preintegration complex, a step necessary for nuclear translocation and successful integration.
Understanding Recession and Self-Rated Health with the Partial Proportional Odds Model: An Analysis of 26 Countries

Introduction Self-rated health is demonstrated to vary substantially by both personal socio-economic status and national economic conditions. However, studies investigating the combined influence of individual and country level economic indicators across several countries in the context of recent global recession are limited. This paper furthers our knowledge of the effect of recession on health at both the individual and national level. Methods Using the Life in Transition II study, which provides data from 19,759 individuals across 26 European nations, we examine the relationship between self-rated health, personal economic experiences, and macro-economic change. Data analyses include, but are not limited to, the partial proportional odds model which permits the effect of predictors to vary across different levels of our dependent variable. Results Household experiences with recession, especially a loss of staple good consumption, are associated with lower self-rated health. Most individual-level experiences with recession, such as a job loss, have relatively small negative effects on perceived health; the effect of individual or household economic hardship is strongest in high income nations. Our findings also suggest that macroeconomic growth improves self-rated health in low-income nations but has no effect in high-income nations. Individuals with the greatest probability of “good” self-rated health reside in wealthy countries ($23,910 to $50, 870 GNI per capita). Conclusion Both individual and national economic variables are predictive of self-rated health. Personal and household experiences are most consequential for self-rated health in high income nations, while macroeconomic growth is most consequential in low-income nations.
Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors

Inhibitor of DNA binding (Id) proteins, including Id1–4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent studies have identified that Id3 plays a tumor-suppressor role in the development of Burkitt’s lymphoma in humans and hepatosplenic T cell lymphomas in mice. In this article, we report rapid lymphoma development in Id2/Id3 double-knockout mice that is caused by unchecked expansion of invariant NKT (iNKT) cells or a unique subset of innate-like CD1d-independent T cells. These populations began to expand in neonatal mice and, upon malignant transformation, resulted in mortality between 3 and 11 mo of age. The malignant cells also gave rise to lymphomas upon transfer to Rag-deficient and wild-type hosts, reaffirming their inherent tumorigenic potential. Microarray analysis revealed a significantly modified program in these neonatal iNKT cells that ultimately led to their malignant transformation. The lymphoma cells demonstrated chromosome instability along with upregulation of several signaling pathways, including the cytokine–cytokine receptor interaction pathway, which can promote their expansion and migration. Dysregulation of genes with reported driver mutations and the NF-κB pathway were found to be shared between Id2/Id3 double-knockout lymphomas and human NKT tumors. Our work identifies a distinct premalignant state and multiple tumorigenic pathways caused by loss of function of Id2 and Id3. Thus, conditional deletion of Id2 and Id3 in developing T cells establishes a unique animal model for iNKT and relevant innate-like lymphomas.
Knowledge and perceptions on antibiotic use and resistance among high school students and teachers in New Delhi, India: A qualitative study

Objective: To explore the perceptions and knowledge of school teachers and students about antibiotic use, resistance, and suggestions for practical interventions for the rational use of antibiotics. Methodology: Five focus group discussions (FGDs) with high school students (Class: 9–11) and five with teachers were conducted in two private and three public schools (one teacher and one student FGD per school) in five municipal wards of Delhi. Qualitative data on antibiotic knowledge, resistance, and behaviors with respect to antibiotics use were collected. There were 4–8 persons per teacher FGD and 15–20 persons per student FGD. FGDs were analyzed using “thematic analyses. ” Results: Students had poor knowledge regarding antibiotics and antibiotic resistance, while only some teachers had a basic understanding. Four broad themes needing attention emerged: definition of antibiotic and antibiotic resistance, antibiotic use behavior, doctor–patient relationship, and interventional strategies suggested to curtail the misuse of antibiotics and to spread awareness. In order to tackle these problems, both groups suggested a multipronged approach including robust public awareness campaigns also involving schools, better doctor–patient relationships, and stronger regulations. Conclusions: Although students and teachers exhibited poor knowledge about antibiotic use and resistance, they were keen to learn about these issues. School education programs and public education could be used to shape correct perceptions about antibiotic use among all stakeholders including children. This may help in the containment of antibiotic resistance and thus preservation of antibiotics for future generations.
Stable patients and patients with advanced disease: consensus definitions to support sustained scale up of antiretroviral therapy

As guidelines are evolving towards recommending starting antiretroviral therapy (ART) in all HIV‐positive individuals irrespective of clinical and immunological status, HIV programmes will be challenged to manage an increasingly diverse set of patient needs. To support global guideline recommendations for differentiated service delivery, WHO developed consensus definitions for two distinct patient populations: patients presenting with advanced disease and patients who are stable on ART.
Comparison of baseline and post-concussion ImPACT test scores in young athletes with stimulant-treated and untreated ADHD

ABSTRACT Objectives: Baseline and post-concussion neurocognitive testing is useful in managing concussed athletes. Attention deficit hyperactivity disorder (ADHD) and stimulant medications are recognized as potential modifiers of performance on neurocognitive testing by the Concussion in Sport Group. Our goal was to assess whether individuals with ADHD perform differently on post-concussion testing and if this difference is related to the use of stimulants. Methods: Retrospective case-control study in which 4373 athletes underwent baseline and post-concussion testing using the ImPACT battery. 277 athletes self-reported a history of ADHD, of which, 206 reported no stimulant treatment and 69 reported stimulant treatment. Each group was matched with participants reporting no history of ADHD or stimulant use on several biopsychosocial characteristics. Non-parametric tests were used to assess ImPACT composite score differences between groups. Results: Participants with ADHD had worse verbal memory, visual memory, visual motor speed, and reaction time scores than matched controls at baseline and post-concussion, all with p ≤ . 001 and |r|≥ 0.100. Athletes without stimulant treatment had lower verbal memory, visual memory, visual motor speed, and reaction time scores than controls at baseline (p ≤ 0.01, |r|≥ 0.100 [except verbal memory, r = −0.088]) and post-concussion (p = 0.000, |r|> 0.100). Athletes with stimulant treatment had lower verbal memory (Baseline: p = 0.047, r = −0.108; Post-concussion: p = 0.023, r = −0.124) and visual memory scores (Baseline: p = 0.013, r = −0.134; Post-concussion: p = 0.003, r = −0.162) but equivalent visual motor speed and reaction time scores versus controls at baseline and post-concussion. Conclusions: ADHD-specific baseline and post-concussion neuropsychological profiles, as well as stimulant medication status, may need to be considered when interpreting ImPACT test results. Further investigation into the effects of ADHD and stimulant use on recovery from sport-related concussion (SRC) is warranted.
First Steps into the Wild – Exploration Behavior of European Bison after the First Reintroduction in Western Europe

Biodiversity is rapidly declining globally. One strategy to help to conserve species is to breed species in captivity and release them into suitable habitats. The way that reintroduced animals explore new habitats and/or disperse from the release site is rarely studied in detail and represents key information for the success of reintroduction projects. The European bison (Bison bonasus L. 1758) was the largest surviving herbivore of the post-glacial megafauna in Europe before it became extinct in the wild, surviving only in captivity since 1919. We investigated the exploration behavior of a herd of European bison reintroduced into the Rothaargebirge, a commercial forest in low range mountain intensively used and densely populated by humans, in the first six months after release. We focused on three questions: (1) how did the European bison move and utilize the habitat on a daily basis, (2) how did the animals explore the new environment, and (3) did their habitat preferences change over time. The European bison dispersed away from their previous enclosure at an average rate of 539 m/month, with their areas of daily use ranging from 70 to 173 ha, their movement ranging from 3.6 km to 5.2 km per day, and their day-to-day use of areas ranged between 389 and 900 m. We could identify three major exploration bouts, when the animals entered and explored areas previously unknown to them. During the birthing phase, the European bison reduced daily walking distances, and the adult bull segregated from the herd for 58 days. Around rut, roaming behavior of the herd increased slightly. The animals preferred spruce forest, wind thrown areas and grassland, all of which are food abundant habitat types, and they avoided beech forest. Habitat preference differed slightly between phases of the study period, probably due to phenological cycles. After six months, the complete summer home range was 42.5 km2. Our study shows that a small free-ranging herd of European bison can live in an area intensively used by humans and describes in detail the initial roaming behavior and habitat utilization of the animals.
Optimization of the EC26-2A4 Epitope in the gp41 Membrane Proximal External Region Targeted by Neutralizing Antibodies from an Elite Controller

Abstract The analysis of patient derived HIV neutralizing antibodies (nAbs) and their target epitopes in the viral envelope (Env) protein provides important basic information for vaccine design. In this study we optimized an epitope, EC26-2A4, that is targeted by neutralizing antibodies from an elite controller (EC26) and localizes in the membrane-proximal external region from the gp41 transmembrane protein. Due to its overlap with the epitope of the first generation broadly neutralizing monoclonal Ab (mAb) 2F5 associated with autoreactivity, we first defined the minimal core epitope reacting with antibodies from EC26 plasma, but not with mAb 2F5. The optimized minimal epitope, EC26-2A4ΔM, was able to induce neutralizing antibodies in vaccinated mice. We further analyzed the frequency of antibodies against the EC26-2A4ΔM peptide in HIV-positive patient sera from a treated cohort and an untreated long-term nonprogressor (LTNP) cohort. Interestingly, 27% of the LTNP sera reacted with the peptide, whereas only 9% showed reactivity in the treated cohort. Although there was no association between the presence of antibodies against the EC26-2A4ΔM epitope and viral load or CD4 count in these patients, the CD4 nadir in the treated cohort was higher in patients positive for EC26-2A4ΔM antibodies, in particular in patients having such antibodies at an early and a late timepoint after infection.
Ordering Information in Working Memory and Modulation of Gamma by Theta Oscillations in Humans

Abstract Ordering information is a critical process underlying several cognitive functions, especially working memory. Theta phase‐gamma amplitude coupling is regarded as a neurophysiological representation of ordering information during working memory performance. However, direct evidence has been lacking in humans. Seventy healthy subjects performed the N‐back task, a working memory task that tests ordering information at 3 different levels of difficulties and with 3 different types of trials. Using electroencephalography (EEG) during N‐back performance, theta‐gamma coupling was assessed during response trials. Multivariate general linear model (GLM) and discriminant analysis were used to assess coupling and theta and gamma power across the N‐back conditions and the trial types. During the N‐back trials that required ordering of information, N‐back condition had independent effects on coupling and on theta and gamma power, with equal contributions among these 3 variables. Theta‐gamma coupling contribution declined significantly on the trials that did not require ordering and was intermediate on trials that favored but not necessarily required ordering. Our findings demonstrate for the first time the role of theta‐gamma coupling as a mechanism that supports ordering information. They also highlight the potential of using theta‐gamma coupling as a neurophysiological marker of brain function in health or disease states.
Assessing the influence of knowledge translation platforms on health system policy processes to achieve the health millennium development goals in Cameroon and Uganda: a comparative case study

Abstract There is a scarcity of empirical data on the influence of initiatives supporting evidence-informed health system policy-making (EIHSP), such as the knowledge translation platforms (KTPs) operating in Africa. To assess whether and how two KTPs housed in government-affiliated institutions in Cameroon and Uganda have influenced: (1) health system policy-making processes and decisions aiming at supporting achievement of the health millennium development goals (MDGs); and (2) the general climate for EIHSP. We conducted an embedded comparative case study of four policy processes in which Evidence Informed Policy Network (EVIPNet) Cameroon and Regional East African Community Health Policy Initiative (REACH-PI) Uganda were involved between 2009 and 2011. We combined a documentary review and semi structured interviews of 54 stakeholders. A framework-guided thematic analysis, inspired by scholarship in health policy analysis and knowledge utilization was used. EVIPNet Cameroon and REACH-PI Uganda have had direct influence on health system policy decisions. The coproduction of evidence briefs combined with tacit knowledge gathered during inclusive evidence-informed stakeholder dialogues helped to reframe health system problems, unveil sources of conflicts, open grounds for consensus and align viable and affordable options for achieving the health MDGs thus leading to decisions. New policy issue networks have emerged. The KTPs indirectly influenced health policy processes by changing how interests interact with one another and by introducing safe-harbour deliberations and intersected with contextual ideational factors by improving access to policy-relevant evidence. KTPs were perceived as change agents with positive impact on the understanding, acceptance and adoption of EIHSP because of their complementary work in relation to capacity building, rapid evidence syntheses and clearinghouse of policy-relevant evidence. This embedded case study illustrates how two KTPs influenced policy decisions through pathways involving policy issue networks, interest groups interaction and evidence-supported ideas and how they influenced the general climate for EIHSP.
Predicting the absorption rate of chemicals through mammalian skin using machine learning algorithms

Machine learning (ML) methods have been applied to the analysis of a range of biological systems. This thesis evaluates the application of these methods to the problem domain of skin permeability. ML methods offer great potential in both predictive ability and their ability to provide mechanistic insight to, in this case, the phenomena of skin permeation. Historically, refining mathematical models used to predict percutaneous drug absorption has been thought of as a key factor in this field. Quantitative Structure-Activity Relationships (QSARs) models are used extensively for this purpose. However, advanced ML methods successfully outperform the traditional linear QSAR models. In this thesis, the application of ML methods to percutaneous absorption are investigated and evaluated. The major approach used in this thesis is Gaussian process (GP) regression method. This research seeks to enhance the prediction performance by using local non-linear models obtained from applying clustering algorithms. In addition, to increase the model’s quality, a kernel is generated based on both numerical chemical variables and categorical experimental descriptors. Monte Carlo algorithm is also employed to generate reliable models from variable data which is inevitable in biological experiments. The datasets used for this study are small and it may raise the over-fitting/under-fitting problem. In this research I attempt to find optimal values of skin permeability using GP optimisation algorithms within small datasets. Although these methods are applied here to the field of percutaneous absorption, it may be applied more broadly to any biological system.
Weather and Prey Predict Mammals’ Visitation to Water

Throughout many arid lands of Africa, Australia and the United States, wildlife agencies provide water year-round for increasing game populations and enhancing biodiversity, despite concerns that water provisioning may favor species more dependent on water, increase predation, and reduce biodiversity. In part, understanding the effects of water provisioning requires identifying why and when animals visit water. Employing this information, by matching water provisioning with use by target species, could assist wildlife management objectives while mitigating unintended consequences of year-round watering regimes. Therefore, we examined if weather variables (maximum temperature, relative humidity [RH], vapor pressure deficit [VPD], long and short-term precipitation) and predator-prey relationships (i.e., prey presence) predicted water visitation by 9 mammals. We modeled visitation as recorded by trail cameras at Sevilleta National Wildlife Refuge, New Mexico, USA (June 2009 to September 2014) using generalized linear modeling. For 3 native ungulates, elk (Cervus Canadensis), mule deer (Odocoileus hemionus), and pronghorn (Antilocapra americana), less long-term precipitation and higher maximum temperatures increased visitation, including RH for mule deer. Less long-term precipitation and higher VPD increased oryx (Oryx gazella) and desert cottontail rabbits (Sylvilagus audubonii) visitation. Long-term precipitation, with RH or VPD, predicted visitation for black-tailed jackrabbits (Lepus californicus). Standardized model coefficients demonstrated that the amount of long-term precipitation influenced herbivore visitation most. Weather (especially maximum temperature) and prey (cottontails and jackrabbits) predicted bobcat (Lynx rufus) visitation. Mule deer visitation had the largest influence on coyote (Canis latrans) visitation. Puma (Puma concolor) visitation was solely predicted by prey visitation (elk, mule deer, oryx). Most ungulate visitation peaked during May and June. Coyote, elk and puma visitation was relatively consistent throughout the year. Within the diel-period, activity patterns for predators corresponded with prey. Year-round water management may favor species with consistent use throughout the year, and facilitate predation. Providing water only during periods of high use by target species may moderate unwanted biological costs.