Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards

Objective:We investigated the dynamics of HIV RNA and HIV DNA levels after the commencement of raltegravir-based antiretroviral therapy (ART) in primary (PHI) and chronically HIV-infected (CHI) individuals (the PINT study). Design:We recruited 8 PHI and 8 CHI ART-naive individuals who commenced a 1-year combination regimen of Truvada and the integrase inhibitor raltegravir. Methods:Nonlinear mixed effects modelling was used to determine multiphasic decay of plasma HIV RNA levels (pVL), as well as dynamics of total, episomal [2-long terminal repeats (LTR)] and integrated HIV DNA in CD4+ T cells from peripheral blood. Results:Although pVL decreased faster through first and second phase for PHI individuals there was no difference in the final level reaching a mean of 9 copies/ml by week 16 that was maintained thereafter. Total HIV DNA and integrated HIV DNA levels from CHI patients were significantly higher than from PHI patients. However, at no time did 2-LTR levels differ between groups. Of note, 2-LTR circles exhibited an initial increase peaking at week 3 followed by biphasic decay with a half-life of 29 days. Second phase integrated HIV DNA levels were significantly correlated with duration of infection and consistent with this form of infection occurring at approximately 100 000 integration events per day in the absence of ART, achieving its 50% level 2 years after infection. Conclusions:Integrated HIV DNA levels accumulate with duration of untreated HIV infection. The relatively short half-life and high levels of 2-LTR circles after 1 year support continued HIV transmission during ART.
The role of individual-based models in understanding the potential impact of antiretroviral therapy for prevention.

The increasing evidence of the sustained success of antiretroviral therapy (ART) in suppressing viral replication in adherent individuals [1,2] and the fact that such suppression substantially reduces infectivity [3], together with the pressing public health need to find new effective ways to prevent transmission of HIV, has led to much discussion over the potential role of extended treatment with ART. There is scope for extending ART in two main ways. The first is to provide ART to people in need of ART for their own health, but who are not aware of their HIV status because they have not been tested for HIV, by increasing the coverage and frequency of HIV testing. The second is to provide ART to all people diagnosed with HIV regardless of CD4 cell count. In the extreme, policies of ‘test and treat’ in which entire populations are tested frequently and those found to be HIV-positive put on ART, regardless of CD4 cell count, have been proposed [4]. There are several considerations that arise when considering such a strategy. In this issue of AIDS, Estill et al. [5] perform a modelling study to estimate the impact of two strategies to monitor people on ARTon thenumberof new HIV infections by measuring viral load or CD4 cell count, particularly in the context of a strategy in which ART is provided for all people diagnosed.
Burden of influenza-like illness and effectiveness of influenza vaccination among working adults aged 50-64 years.

BACKGROUND Uncertainties regarding influenza disease impact and benefits of vaccination may contribute to low vaccination rates among adults aged 50-64 years. METHODS This prospective cohort study assessed the burden of influenza-like illness (ILI) among working adults aged 50-64 years and the effectiveness of influenza vaccination in reducing the rate of ILI and productivity losses. Employees of the University of Minnesota (Minneapolis) were invited via e-mail to participate in the study during October 2006. The study data were collected using internet-based surveys at baseline (October 2006) and during the follow-up period (from November 2006 through April 2007). Months included in the 2006-2007 influenza season were identified retrospectively from Minnesota Department of Health surveillance data. Vaccine effectiveness for reducing the rate of ILI, ILI-associated health care use, the number of days of illness, work loss, and reduced on-the-job productivity during the influenza season were assessed using multivariable regression models after controlling for important confounders. RESULTS Four hundred ninety-seven persons were included in the study, 85 (17.1%) of whom experienced an ILI. Among unvaccinated participants, ILI was responsible for 45% of all days of illness during the influenza season, 39% of all illness-related work days lost, and 49% of all days with illness-related reduced on-the-job productivity. In the multivariable regression analyses, vaccination was associated with a significant reduction in the rate of ILI (adjusted odds ratio, 0.48; 95% confidence interval, 0.27-0.86) and fewer days of illness, absenteeism, and impaired on-the-job performance. CONCLUSION ILIs were common among our study participants, accounting for a large portion of illness, work loss, and impaired work performance during the influenza season. Vaccination was associated with substantial health and productivity benefits. Vaccine delivery should be improved for this high-priority group.
Multiwalled CNT-pHEMA composite conduit for peripheral nerve repair.

A nerve conduit is designed to improve peripheral nerve regeneration by providing guidance to the nerve cells. Conductivity of such guides is reported to enhance this process. In the current study, a nerve guide was constructed from poly(2-hydroxyethyl methacrylate) (pHEMA), which was loaded with multiwalled carbon nanotubes (mwCNT) to introduce conductivity. PHEMA hydrogels were designed to have a porous structure to facilitate the transportation of the compounds needed for cell nutrition and growth and also for waste removal. We showed that when loaded with relatively high concentrations of mwCNTs (6%, w/w in hydrogels), the pHEMA guide was more conductive and more hydrophobic than pristine pHEMA hydrogel. The mechanical properties of the composites were better when they carried mwCNT. Elastic modulus of 6% mwCNT loaded pHEMA was twofold higher (0.32 ± 0.06 MPa) and similar to that of the soft tissues. Electrical conductivity was significantly improved (11.4-fold) from 7 × 10(-3) Ω(-1). cm(-1) (pHEMA) to 8.0 × 10(-2) Ω(-1). cm(-1) (6% mwCNT loaded pHEMA). On application of electrical potential, the SHSY5Y neuroblastoma cells seeded on mwCNTs carrying pHEMA maintained their viability, whereas those on pure pHEMA could not, indicating that mwCNT helped conduct electricity and make them more suitable as nerve conduits.
Incident tuberculosis and risk factors among HIV-infected children in Tanzania

Objective— To describe the burden of pediatric tuberculosis (TB) in a human immunodeficiency virus (HIV)-infected population and explore the demographic and clinical factors associated with the occurrence of pediatric TB. Design— Longitudinal analysis of a cohort of HIV-infected children. Methods— The endpoint of the study was clinically diagnosed TB. Cox proportional hazard regression was used to explore the predictors of incident TB among HIV-infected children under age 15 years after enrollment into the HIV program. Results— The cohort comprised of 5040 children [median age: 5 years, interquartile range (IQR): 1–9 years]. During a median follow-up of 0.8 (IQR: 0.1–2.5) years, 376 out of 5040 children met the case definition for TB. The overall incidence of TB was 5.2/100 person-years. In multivariate analyses, older age at enrollment [relative risk (RR): 1.7, 95%, confidence interval (CI): 1.5–1.8], severe wasting (RR: 1.8, 95% CI: 1.3 –2.5), severe immune-suppression (RR: 2.6, 95% CI: 1.8– 3.8), anemia (RR: 1.4, 95% CI: 1.0–1.9) and World Health Organization (WHO) stage IV (RR: 4.5, 95% CI: 2.4–8.5) were all independently associated with a higher risk of TB. In addition, the use of antiretroviral drugs for more than 180 days reduced the risk of TB by 70% (RR: 0.3, 95% CI: 0.2–0.4). Conclusions— ART use is strongly associated with a reduced risk of tuberculosis among HIV-infected children, and should therefore be included in HIV care and treatment programs. Trials of interventions designed to improve the nutritional and hematologic status of these children should also be performed.
Vitamin D deficiency is related to worse emotional state

AbstractThe aim was to evaluate vitamin D levels in young healthy Lithuanian males in winter and to find possible associations of vitamin D concentration to body composition, cognitive functioning, emotional state. Subjects and Methods A total of 130 healthy males (age range, 18–26 years) were divided into the subgroups according to vitamin D concentration. The Profile of Mood States (POMS) questionnaire and Hospital Anxiety and Depression Scale were employed in the assessment of emotional state. Cognitive functioning was assessed by the Trail Making Test and the Digit Symbol Test of the Wechsler Adult Intelligence Scale. Results The mean concentration of vitamin D for the entire sample was 13.0±5.3 ng/ml. Only 2 persons (1.6%) had the recommended vitamin D level. Nearly half (45.4%) of study participants had vitamin D deficiency. Lower concentrations were associated with a significantly higher score on the POMS confusion-bewilderment scale. A tendency toward a lower mean depression-dejection score in the participants with a sufficient vitamin D level was observed. Vitamin D concentration correlated positively with body mass index (BMI) and inversely with the confusion-bewilderment score. In conclusion almost half of the young healthy males participating in the study were detected to have vitamin D deficiency in winter. Low vitamin D concentrations are associated with a worse emotional state.
The impact of quadrivalent human papillomavirus (HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years.

BACKGROUND Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. METHODS We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotyping was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. RESULTS Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. CONCLUSIONS HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for approximately 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type. TRIAL REGISTRATION ClinicalTrials.gov identifiers: NCT00092521 , NCT00092534 , and NCT00092482.
Laboratory Challenges Conducting International Clinical Research in Resource-Limited Settings

Abstract:There are many challenges to performing clinical research in resource-limited settings. Here, we discuss several of the most common laboratory issues that must be addressed. These include issues relating to organization and personnel, laboratory facilities and equipment, standard operating procedures, external quality assurance, shipping, laboratory capacity, and data management. Although much progress has been made, innovative ways of addressing some of these issues are still very much needed.
Benefits of Dispersed Central‐Place Foraging: An Individual‐Based Model of a Polydomous Ant Colony

Colonies of many ant species are not confined to a single nest but inhabit several dispersed nests, a colony organization referred to as polydomy. The benefits of polydomy are not well understood. It has been proposed that increased foraging efficiency promotes polydomy. In a spatially explicit individual‐based model, I compare the foraging success of monodomous and polydomous colonies in environments with varying food distributions. Multiple nests increased the colony’s foraging success if food sources were randomly scattered in the environment. Monodomous and polydomous colonies did not differ in foraging success if food sources were clustered in one or three locations. These results support the hypothesis that foraging success serves as a driver for polydomous colony organization. Because transport may occur between the dispersed nests of a polydomous colony, I tested the efficiency of a simple mechanism of food exchange between nests. This mechanism, as introduced previously in the literature, proves insufficient to equalize the level of food between nests. While the importance of transport between nests remains unclear, the model results indicate that polydomy may increase the foraging success of ant colonies and that this effect may be robust across a range of food distributions.
Bacteriolytic Activity in the Ejaculate of an Insect

The rapid evolution of ejaculate components is considered to be largely driven by sexual selection. Less attention has been paid to the fact that sperm and microorganisms frequently meet; we consequently predict selection for substances that protect a male’s ejaculate. We report, for the first time, bacteriolytic activity (lysozyme‐like immune activity [LLA]) in the ejaculate of an animal, the common bedbug Cimex lectularius. We also show that in almost half the males LLA in the seminal fluid exceeded LLA in the hemolymph. We detected no antimicrobial peptide activity in seminal fluid. Because lysozymes degrade only bacteria, our results suggest that sperm‐microbe interactions are probably important in the evolution of ejaculate components and thereby provide a route for natural selection to account for some of the diversity of seminal components.
Characteristics of O157 versus non-O157 Shiga toxin-producing Escherichia coli infections in Minnesota, 2000-2006.

BACKGROUND Escherichia coli O157:H7 (O157) is the Shiga toxin-producing E. coli (STEC) serotype most frequently isolated and most often associated with hemolytic uremic syndrome (HUS) in the United States. Non-O157 STEC serotypes can also cause serious illness, but their impact as pathogens remains undefined. We compared characteristics of non-O157 and O157 STEC infections identified through sentinel surveillance. METHODS Sentinel sites included a metropolitan health maintenance organization laboratory and a hospital laboratory serving a small city and rural area. We received sorbitol-MacConkey agar plates from every stool culture performed at both sites during 2000-2006. Colony sweeps were screened for stx1 and stx2 by polymerase chain reaction. E. coli identity, serotype, and presence of stx1 and/or stx2 were confirmed on individual isolates. RESULTS Two hundred six STEC isolates were identified: 108 (52%) were non-O157 serotypes, and 98 (48%) were O157. Of non-O157 cases, 54% involved bloody diarrhea, and 8% involved hospitalization. Non-O157 isolates with at least stx2 were not more likely to cause severe illness (bloody diarrhea, hospitalization, or HUS) than were non-O157 isolates with only stx1. O157 cases were more likely than non-O157 cases to involve bloody diarrhea (78% vs 54%; P < .001), hospitalization (34% vs 8%; P < .001 and HUS (7% vs 0%; P = .005). When including only isolates with at least stx2, O157 cases were still more likely to involve bloody diarrhea (78% vs 56%; P = .02) and hospitalization (33% vs 12%; P = .01) than non-O157 cases. CONCLUSIONS Differences in severity among STEC infections could not be explained by stx2, suggesting that additional factors are important in STEC virulence.
Impact of Age on Retention in Care and Viral Suppression

Background:Retention in care is important for all HIV-infected persons and is strongly associated with initiation of antiretroviral therapy and viral suppression. However, it is unclear how retention in care and age interact to affect viral suppression. We evaluated whether the association between retention and viral suppression differed by age at entry into care. Methods:Cross-sectional analysis (2006–2010) involving 17,044 HIV-infected adults in 14 clinical cohorts across the United States and Canada. Patients contributed 1 year of data during their first full-calendar year of clinical observation. Poisson regression examined associations between retention measures [US National HIV/AIDS Strategy (NHAS), US Department of Health and Human Services (DHHS), 6-month gap, and 3-month visit constancy] and viral suppression (HIV RNA ⩽200 copies/mL) by age group: 18–29 years, 30–39 years, 40–49 years, 50–59 years, and 60 years or older. Results:Overall, 89% of patients were retained in care using the NHAS measure, 74% with the DHHS indicator, 85% did not have a 6-month gap, and 62% had visits in 3–4 quarters of the year; 54% achieved viral suppression. For each retention measure, the association with viral suppression was significant for only the younger age groups (18–29 and 30–39 years): 18–29 years [adjusted prevalence ratio (APR) = 1.33, 95% confidence interval (CI): 1.03 to 1.70]; 30–39 years (APR = 1.23, 95% CI: 1.01 to 1.49); 40–49 years (APR = 1.06, 95% CI: 0.90 to 1.22); 50–59 (APR = 0.92, 95% CI: 0.75 to 1.13); ≥60 years (APR = 0.99, 95% CI: 0.63 to 1.56) using the NHAS measure as a representative example. Conclusions:These results have important implications for improving viral control among younger adults, emphasizing the crucial role retention in care plays in supporting viral suppression in this population.
Meta‐Analysis and the Comparative Phylogenetic Method

Meta‐analysis has contributed substantially to shifting paradigms in ecology and has become the primary method for quantitatively synthesizing published research. However, an emerging challenge is the lack of a statistical protocol to synthesize studies and evaluate sources of bias while simultaneously accounting for phylogenetic nonindependence of taxa. Phylogenetic nonindependence arises from homology, the similarity of taxa due to shared ancestry, and treating related taxa as independent data violates assumptions of statistics. Given that an explicit goal of meta‐analysis is to generalize research across a broad range of taxa, then phylogenetic nonindependence may threaten conclusions drawn from such reviews. Here I outline a statistical framework that integrates phylogenetic information into conventional meta‐analysis when (a) taking a weighted average of effect sizes using fixed‐ and random‐effects models and (b) testing for homogeneity of variances. I also outline how to test evolutionary hypotheses with meta‐analysis by describing a method that evaluates phylogenetic conservatism and a model‐selection framework that competes neutral and adaptive hypotheses to explain variation in meta‐analytical data. Finally, I address several theoretical and practical issues relating to the application and availability of phylogenetic information for meta‐analysis.
Matrix metalloproteinase-based photodynamic molecular beacons for targeted destruction of bone metastases in vivo

The metastatic spread of cancer from the primary site or organ is one of its most devastating aspects, being responsible for up to 90% of cancer-associated mortality. Bone is one of the common sites of metastatic spread, including the vertebrae. Regardless of the treatment strategy, the clinical goals for patients with vertebral metastases are to improve the quality of life by preventing neurologic decline, to achieve durable pain relief and enhance local tumor control. However, in part due to the close proximity of the spinal cord, current treatment options are limited. We propose a novel therapeutic strategy with the use of photodynamic molecular beacons (PMBs) for targeted destruction of spinal metastases, particularly to de-bulk lesions as an adjuvant to vertebroplasty or kyphoplasty in order to mechanically stabilize weak or fractured vertebrae. The PDT efficacy of a matrix metalloproteinase-specific PMB is reported in a metstatic model that recapitulates the clinical features of tumor growth within the bone. We demonstrate that not only does tumor cell destruction occur but also the killing of bone stromal cells. The potential of PMB-PDT to destroy metastatic tumors, disrupt the osteolytic cycle and better preserve critical organs with an increased therapeutic window compared with conventional photosensitizers is demonstrated.
Individual and Community Factors Associated With Geographic Clusters of Poor HIV Care Retention and Poor Viral Suppression

Background:Previous analyses identified specific geographic areas in Philadelphia (hotspots) associated with negative outcomes along the HIV care continuum. We examined individual and community factors associated with residing in these hotspots. Methods:Retrospective cohort of 1404 persons newly diagnosed with HIV in 2008–2009 followed for 24 months after linkage to care. Multivariable regression examined associations between individual (age, sex, race/ethnicity, HIV transmission risk, and insurance status) and community (economic deprivation, distance to care, access to public transit, and access to pharmacy services) factors and the outcomes: residence in a hotspot associated with poor retention-in-care and residence in a hotspot associated with poor viral suppression. Results:In total, 24.4% and 13.7% of persons resided in hotspots associated with poor retention and poor viral suppression, respectively. For persons residing in poor retention hotspots, 28.3% were retained in care compared with 40.4% of those residing outside hotspots (P < 0.05). Similarly, for persons residing in poor viral suppression hotspots, 51.4% achieved viral suppression compared with 75.3% of those outside hotspots (P < 0.0.05). Factors significantly associated with residence in poor retention hotspots included female sex, lower economic deprivation, greater access to public transit, shorter distance to medical care, and longer distance to pharmacies. Factors significantly associated with residence in poor viral suppression hotspots included female sex, higher economic deprivation, and shorter distance to pharmacies. Conclusions:Individual and community-level associations with geographic hotspots may inform both content and delivery strategies for interventions designed to improve retention-in-care and viral suppression.