Miracle-dz/UniFAR-FTUs huggingface dataset:
Maraviroc and reverse transcriptase inhibitors combinations as potential preexposure prophylaxis candidates

Objective:Receptive anal intercourse in both men and women is associated with the highest probability for sexual acquisition of HIV infection. As part of a program to develop an effective prevention strategy, we performed an ex-vivo preclinical evaluation to determine the efficacy of multiple double combinations of maraviroc (MVC) and reverse transcriptase inhibitors (RTIs). Design:The entry inhibitor, MVC, a nucleotide RTI, tenofovir and two non-nucleoside RTIs, UC781 and TMC120 (dapivirine, DPV), were used in double, combinations against a panel of CCR5-using clade B and clade C HIV-1 isolates and against MVC-escape variants. A gel-formulated version of MVC-DPV combination was also tested. Methods:Indicator cells, cocultures of immature dendritic cells with CD4+T cells, and colorectal tissue explants were used to assess antiviral activity of drug combinations. Results:All dual MVC-RTI combinations tested inhibited MVC-sensitive and resistant isolates in cellular and colorectal explants models. All the combinations were positive with no reduction in the activity of MVC. In tissue explants, the combinations against all viral isolates tested produced an increase in the activity of MVC. An initial gel-formulation of MVC-DPV combination showed greater and prolonged antiviral activity of MVC in mucosal tissue explants. Conclusion:This study demonstrates that combinations based on antiretroviral drugs inhibiting HIV transmission at viral entry and reverse transcription have potential as prevention strategies against colorectal transmission of HIV-1 including MVC-resistant isolates. Preclinical evaluation with colorectal tissue explants indicates that a gel-formulation of MVC-DPV is an effective candidate colorectal microbicide.
Methanogenesis in subglacial sediments.

Methanogenic archaea have a unique role in Earth's global carbon cycle as producers of the greenhouse gas methane (CH4 ). However, despite the fact that ice covers 11% of Earth's continental landmass, evidence for methanogenic activity in subglacial environments has yet to be clearly demonstrated. Here we present genetic, biochemical and geochemical evidence indicative of an active population of methanogens associated with subglacial sediments from Robertson Glacier (RG), Canadian Rockies. Porewater CH4 was quantified in two subglacial sediment cores at concentrations of 16 and 29 ppmv. Coenzyme M (CoM), a metabolic biomarker for methanogens, was detected at a concentration of 1.3 nmol g sediment(-1) corresponding to ∼3 × 10(3) active cells g sediment(-1) . Genetic characterization of communities associated with subglacial sediments indicated the presence of several archaeal 16S rRNA and methyl CoM reductase subunit A (mcrA) gene phylotypes, all of which were affiliated with the euryarchaeal order Methanosarcinales. Further, CH4 was produced at 9-51 fmol g dry weight sediment(-1) h(-1) in enrichment cultures of RG sediments incubated at 4°C. Collectively, these findings have important implications for the global carbon cycle in light of recent estimates indicating that the Earth's subglacial biome ranges from 10(4) to 10(6) km(3) sediment.
A multi-proxy study of anaerobic ammonium oxidation in marine sediments of the Gullmar Fjord, Sweden.

Anaerobic ammonium oxidation (anammox) is an important process for nitrogen removal in marine pelagic and benthic environments and represents a major sink in the global nitrogen cycle. We applied a suite of complementary methods for the detection and enumeration of anammox activity and anammox bacteria in marine sediments of the Gullmar Fjord, and compared the results obtained with each technique. (15) N labelling experiments showed that nitrogen removal through N2 production was essentially limited to the upper 2 cm of the sediment, where anammox contributed 23-47% of the total production. The presence of marine anammox bacteria belonging to the genus 'Candidatus Scalindua' was shown by 16S rRNA gene sequence comparison. FISH counts of anammox bacteria correlated well with anammox activity, while quantitative PCR may have underestimated the number of anammox bacterial 16S rRNA gene copies at this site. Potential nitrogen conversion by anammox ranged from 0.6 to 4.8 fmol N cell(-1) day(-1) , in agreement with previous measurements in the marine environment and in bioreactors. Finally, intact ladderane glycerophospholipid concentrations better reflected anammox activity and abundance than ladderane core lipid concentrations, most likely because the core lipid fraction contained a substantial fossil component, especially deeper in the sediment.
Heart disease and mid-age women: focusing on gender and age

Abstract This paper explores the experiences of Australian mid-age women with reported heart disease with specific reference to gender and age. This is a collaborative study with the Australian Longitudinal Study on Women’s Health. The heart disease study focused on the mid-age cohort of 14,011 women, of whom 2.3% (319) reported having been told by a doctor that they had heart disease. The methods comprised 1) a national questionnaire survey about women’s experiences of heart disease; and 2) in-depth interviews with women with reported heart disease. The paper focuses on the reported problems of delayed diagnosis of the women with heart disease, in particular those women presenting with heart attacks. Most women in this age group considered heart disease to be a gendered disease, primarily a disease of men. This research points to the importance of exploring understandings of illness and its impact on health care practice.
Allometric Slopes and Independent Contrasts: A Comparative Test of Kleiber’s Law in Primate Ranging Patterns

At the most fundamental level, the size of an animal’s home range is determined by its energy needs. In the absence of confounding variables, home range size should therefore scale with body mass according to Kleiber's exponent for metabolic rate of 0.75. Comparative studies in a wide range of taxa have failed to confirm this prediction: home range size has commonly been found to scale with an exponent significantly >0.75. We develop a comparative measure of metabolic needs that incorporates both mass‐specific metabolic rate and social‐group size. We test the prediction that home range size in primates scales isometrically with this measure when an appropriate linear model is applied to data corrected for phylogenetic bias. Analyses using species values as data points indicate an exponent consistent with Kleiber’s law. This result is misleading, however, because ecological factors confound the analysis, and the slopes within some ecologically homogeneous taxa are steeper. Accordingly, in analyses based on independent contrasts with reduced major axis, slopes are significantly greater than predicted by Kleiber's law. We examine the effects of other variables, and we find that systematic variation in substrate use, home range overlap, and diet account for the steeper than expected relationship between home range size and metabolic needs based on Kleiber’s law. We therefore conclude that the scaling of home range size is subject to Kleiber's law but in combination with other factors. These results emphasize that the study of allometry requires detailed attention to statistical models and control of confounding variables.
Why Do Large Mothers Produce Large Offspring? Theory and a Test

To explain the general tendency of large mothers to produce large offspring, we developed two models in which either the rate at which each single offspring extracts resources from the mother or the rate at which the mother supplies resources to all the offspring is limited (terminal‐ or upper‐stream‐limitation on resource transport, respectively). We also reanalyzed the data of Erythronium japonicum to test the models. The terminal‐stream‐limitation model predicted that the optimal offspring size that maximizes the fitness of the mother increases with an increase in the maximum rate of resource extraction by each single offspring. Thus, large mothers produce large offspring if the maximum resource extraction rate is high in those mothers. The upper‐stream‐limitation model predicted that the optimal offspring size decreases with an increase in the maximum rate of resource supply by the mother to all the offspring. In E. japonicum, the maximum growth rate of a seed was independent of the number of seeds of a plant, suggesting that the resource extraction rate is limited at the individual seed level. The maximum growth rate was high in large plants and had a strong positive effect on final seed mass. Thus, the results were consistent with the terminal‐stream‐limitation model.
Impact of aging on neurocognitive performance in previously antiretroviral-naive HIV-infected individuals on their first suppressive regimen

Background: Despite treatment with virologically suppressive antiretroviral therapy (ART), neurocognitive impairment may persist or develop de novo in aging HIV-infected individuals. We evaluated advancing age as a predictor of neurocognitive impairment in a large cohort of previously ART-naive individuals on long-term ART. Design: The AIDS Clinical Trials Group Longitudinal Linked Randomized Trials was a prospective cohort study of HIV-infected individuals originally enrolled in randomized ART trials. This analysis examined neurocognitive outcomes at least 2 years after ART initiation. Methods: All participants underwent annual neurocognitive testing consisting of Trail making A and B, the wechsler adult intelligence scale-revised Digit Symbol and Hopkins Verbal Learning Tests. Uni and multivariable repeated measures regression models evaluated factors associated with neurocognitive performance. Predictors at parent study entry (ART naive) included entry demographics, smoking, injection drug use, hepatitis B surface antigen, hepatitis C virus serostatus, history of stroke, ART regimen type, pre-ART nadir CD4+ cell count, and plasma viral load and as well as time-updated plasma viral load and CD4+ cell count. Results: The cohort comprised 3313 individuals with median pre-ART age of 38 years, 20% women; 36% Black, non-Hispanic; 22% Hispanic. Virologic suppression was maintained at 91% of follow-up visits. Neurocognitive performance improved with years of ART. After adjusting for the expected effects of age using norms from HIV-negative individuals, the odds of neurocognitive impairment at follow-up visits among the HIV infected increased by nearly 20% for each decade of advancing age. Conclusion: Despite continued virologic suppression and neurocognitive improvement in the cohort as a whole, older individuals were more likely to have neurocognitive impairment than younger individuals.
On the Use of the Time Axis for Ecological Separation: Diel Rhythms as an Evolutionary Constraint

Temporal partitioning as a mechanism of coexistence among competitors has seldom been explored and is considered uncommon (Schoener 1986). Understanding ecological and evolutionary plasticity in use of the temporal niche axis is significant for assessing the potential for temporal partitioning and may be key to understanding the relative rarity of this phenomenon. Daily rhythms in mammalian physiology, hormone concentrations, biochemistry, and behavior are driven by an internal circadian clock that is entrained to the predictable 24-h change in light intensity (Heldmaier et al. 1989; Refinetti et al. 1992; Smith et al. 1998). Entrainment to this overriding cue (“zeitgeber”) allows mammals to choose the right time for a given response or activity without being easily misled by minor environmental disturbances (Aronson et al. 1993). Thus, a degree of rigidity to environmental nonphotic stimuli is built into the circadian system. However, under laboratory conditions, small mammals can be forced to shift their locomotor activity patterns by nonphotic stimuli (Mistlberger 1991; Cambras et al. 1993; Challet et al. 1997; Brinkhof et al. 1998), indicating that activity is not tightly controlled by the circadian clock
The location of the carboxy-terminal region of chains in fibrinogen and fibrin D domains

Elongated fibrinogen molecules are comprised of two outer “D” domains, each connected through a “coiled-coil” region to the central “E” domain. Fibrin forms following thrombin cleavage in the E domain and then undergoes intermolecular end-to-middle D:E domain associations that result in double-stranded fibrils. Factor XIIIa mediates crosslinking of the C-terminal regions of γ chains in each D domain (the γXL site) by incorporating intermolecular ɛ-(γ-glutamyl)lysine bonds between amine donor γ406 lysine of one γ chain and a glutamine acceptor at γ398 or γ399 of another. Several lines of evidence show that crosslinked γ chains extend “transversely” between the strands of each fibril, but other data suggest instead that crosslinked γ chains can only traverse end-to-end-aligned D domains within each strand. To examine this issue and determine the location of the γXL site in fibrinogen and assembled fibrin fibrils, we incorporated an amine donor, thioacetyl cadaverine, into glutamine acceptor sites in fibrinogen in the presence of XIIIa, and then labeled the thiol with a relatively small (0.8 nm diameter) electron dense gold cluster compound, undecagold monoaminopropyl maleimide (Au11). Fibrinogen was examined by scanning transmission electron microscopy to locate Au11-cadaverine-labeled γ398/399 D domain sites. Seventy-nine percent of D domain Au11 clusters were situated in middle to proximal positions relative to the end of the molecule, with the remaining Au11 clusters in a distal position. In fibrin fibrils, D domain Au11 clusters were located in middle to proximal positions. These findings show that most C-terminal γ chains in fibrinogen or fibrin are oriented toward the central domain and indicate that γXL sites in fibrils are situated predominantly between strands, suitably aligned for transverse crosslinking.
Assisted partner notification services are cost-effective for decreasing HIV burden in western Kenya

Background: Assisted partner services (aPS) or provider notification for sexual partners of persons diagnosed HIV positive can increase HIV testing and linkage in Sub-Saharan Africa and is a high yield strategy to identify HIV-positive persons. However, its cost-effectiveness is not well evaluated. Methods: Using effectiveness and cost data from an aPS trial in Kenya, we parameterized an individual-based, dynamic HIV transmission model. We estimated costs for both a program scenario and a task-shifting scenario using community health workers to conduct the intervention. We simulated 200 cohorts of 500 000 individuals and projected the health and economic effects of scaling up aPS in a region of western Kenya (formerly Nyanza Province). Findings: Over a 10-year time horizon with universal antiretroviral therapy (ART) initiation, implementing aPS in western Kenya was projected to reach 12.5% of the population and reduce incident HIV infections by 3.7%. In sexual partners receiving aPS, HIV-related deaths were reduced by 13.7%. The incremental cost-effectiveness ratio of aPS was $1094 (US dollars) (90% model variability $823–1619) and $833 (90% model variability $628–1224) per disability-adjusted life year averted under the program and task-shifting scenario, respectively. The incremental cost-effectiveness ratios for both scenarios fall below Kenya's gross domestic product per capita ($1358) and are therefore considered very cost-effective. Results were robust to varying healthcare costs, linkage to care rates, partner concurrency rates, and ART eligibility thresholds (⩽350 cells/&mgr;l, ⩽500 cells/&mgr;l, and universal ART). Interpretation: APS is cost-effective for reducing HIV-related morbidity and mortality in western Kenya and similar settings. Task shifting can increase program affordability.
Trends in antiretroviral therapy prescription, durability and modification: new drugs, more changes, but less failure

Objective: To evaluate the real world durability of contemporary ART for treatment-naïve people living with HIV (PLWH). Design: A retrospective follow-up study in a multisite cohort. Methods: This study of the CNICS (CFAR Network of Integrated Clinical Systems) cohort integrates data from eight Center for AIDS Research (CFARs). PLWH initiating ART between 2007 and 2014 were included. Durability was defined as time from the initiation until discontinuation/modification using Kaplan–Meier survival curves. Cox Proportional Hazards measured associations with various sociodemographic and clinical characteristics. Results: Among 5373 PLWH, the initial regimen was modified in 2285 (43%) patients. Efavirenz/emtricitabine/tenofovir (n = 2173, 40%) was the most commonly prescribed initial ART regimen; elvitegravir/cobicistat/emtricitabine/tenofovir became more common after 2012. Median durability for all regimens was 48.6 months. There were statistically significant differences in median durability for NNRTI, InSTI, and protease inhibitor-based regimens, which lasted 61, 44, and 32 months, respectively. Female sex (aHR = 1.4; 95% CI 1.2–1.6), intravenous drug use (aHR = 1.6; 95% CI 1.3–1.9), and CD4+ cell count less than 200 cells/&mgr;l (aHR = 1.2; 95% CI 1.1–1.3) were significantly associated with regimen modification. Compared with InSTI, those receiving an InSTI/protease inhibitor (aHR = 2.7; 95% CI 2.0–3.7) or protease inhibitor-based ART (aHR = 1.9; 95% CI 1.6–2.2) were significantly more likely to be modified; but those receiving NNRTI (aHR = 1.1; 95% CI 0.9–1.3) were not. Conclusion: In treatment-naive PLWH, NNRTI and InSTI-based ART were most durable, relative to protease inhibitor and InSTI/protease inhibitor-based ART, and were least likely to be modified/discontinued. A greater understanding of reasons for regimen modification/discontinuation is needed to analyze contemporary regimen durability.
Effects of Productivity and Disturbance on Species Richness: A Neutral Model

Productivity and disturbance are major determinants of species diversity, and results from theoretical models predict that species richness should peak at intermediate levels of both factors. Such “unimodal” responses have been documented in many field and laboratory studies and have usually been attributed to differences among species in competitive ability and/or trade‐offs between competitive ability and tolerance to disturbance. Here we show that most documented patterns of disturbance‐richness and productivity‐richness relationships, as well as the observed interactions between the two factors, can be explained by a simple neutral model where all species are ecologically identical and lack trade‐offs in species characteristics. This finding suggests that current neutral theories can be extended to explain patterns of species responses to productivity and disturbance.
Adaptive Introgression of Herbivore Resistance Traits in the Weedy Sunflower Helianthus annuus

The role of hybridization in adaptive evolution is contentious. While many cases of adaptive trait introgression have been proposed, the relevant traits have rarely been identified, resulting in a lack of clear examples of this process. Here, we examine a purported case of adaptive introgression in which the annual sunflower Helianthus annuus annuus has captured alleles from a congener (Helianthus debilis) to form a stabilized hybrid, Helianthus annuus texanus. We tested the hypotheses that herbivore resistance traits have introgressed from H. debilis to H. annuus and have increased adaptation in the latter. In two common gardens, fitness (estimated by seed production) was on average 55% higher in H. a. texanus than in H. a. annuus. For H. a. texanus, three damage traits (of seven tested) differed significantly from the H. a. annuus parent in one or both sites and were shifted in the direction of the more resistant H. debilis. Natural selection favored H. a. \documentclass{aastex} \usepackage{amsbsy} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{bm} \usepackage{mathrsfs} \usepackage{pifont} \usepackage{stmaryrd} \usepackage{textcomp} \usepackage{portland,xspace} \usepackage{amsmath,amsxtra} \usepackage[OT2,OT1]{fontenc} \newcommand\cyr{ \renewcommand\rmdefault{wncyr} \renewcommand\sfdefault{wncyss} \renewcommand\encodingdefault{OT2} \normalfont \selectfont} \DeclareTextFontCommand{\textcyr}{\cyr} \pagestyle{empty} \DeclareMathSizes{10}{9}{7}{6} \begin{document} \landscape $$annuus\times H. $$ \end{document} debilis BC1 hybrids (synthesized to mimic the ancestors of H. a. texanus) with H. debilis–like resistance to seed midges Neolasioptera helianthis and to receptacle/seed feeding Lepidoptera at one or both sites. Assuming similar herbivore pressures in the past, these results suggest that introgression of biotic resistance traits was important in the adaptation of H. annuus to central and southern Texas.
Social Indicators Affecting Post-Tsunami Trauma of Survivors

The study examines whether widow/widower status, educational level and family income influence post-tsunami trauma of survivors. The data were collected 14 months after the tsunami from 416 adult survivors in nine semi-urban habitations of Nagapattinam district in the state of Tamilnadu (India). Post-tsunami trauma was assessed using inventories of post-traumatic stress, depression, negative and positive affectivity, physical health symptoms and anxiety. Post-tsunami trauma of survivors has increased with increasing age, female gender and more exposure. Controlling the confounding effects of age, gender, and exposure; widow/widower status, illiteracy and lower family income are found to intensify trauma and are the risk factors for post-tsunami morbidity. Only illiterates do not report more physical health symptoms than literates, and lower family income neither heightens depression and negative affectivity nor lessens positive affectivity.
Impact of a diagnosis of psychosis: user-led qualitative study

AIMS AND METHOD To explore the impact of diagnosis on people who experience psychosis. Eight participants were interviewed about the impact that diagnosis had on them. RESULTS The research found that the impact of diagnosis can involve both positive and negative elements. It can be a ‘means of access’ as well as a ‘ cause of disempowerment’. It can help by ‘naming the problem’ and hinder by ‘labelling the person’. It is a ‘ cause of social exclusion’ for all, but despite this service users can be successful in ‘achieving social inclusion’. CLINICAL IMPLICATIONS The findings have implications for how diagnosis is imparted by psychiatrists if they are to help to facilitate recovery and social inclusion.