bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment for Individuals With Severe Mental Illness Who Use Illicit Drugs While Maintained on Methadone
Authors: Wupperman Peggilee , Burns Nancy , Pugach Cameron P. , Edwards Emily 
Published: October 2019

Abstract
Substantial research has noted the serious consequences of 1) co-occurring severe mental illness (SMI) and substance use disorders, and 2) use of illicit drugs while maintained on methadone for opioid dependence. However, treatment needs of individuals who meet both of the above criteria remain largely unmet. This pilot study investigated the feasibility and acceptability of a 12-week, transdiagnostic group therapy (mindfulness and modification therapy [MMT]) tailored for opioid-dependent individuals (N = 6) with SMI and illicit drug use. Retention was 83%. At posttreatment and 2-month follow-up, participants rated the treatment as highly helpful (9 of 10; 8.67 of 10, respectively), reported routinely practicing the guided-mindfulness exercises, and reported high confidence that they would continue to practice. Assessments revealed clinically meaningful decreases in reported days of illicit drug use at posttreatment and follow-up, with large effect sizes. Preliminary evidence suggests that MMT may be a feasible and acceptable therapy that may improve treatment engagement in this underserved population.
Sexually Transmitted Infections in Pregnancy and Reproductive Health: Proceedings of the STAR Sexually Transmitted Infection Clinical Trial Group Programmatic Meeting
Authors: Wynn Adriane , Bristow Claire C. , Cristillo Anthony D. , Murphy Sara McCurdy , van den Broek Nynke , Muzny Christina , Kallapur Suhas , Cohen Craig , Ingalls Robin R. , Wiesenfeld Harold , Litch James A. , Morris Sheldon R. , Klausner Jeffrey D. 
Published: October 2019

Abstract
The goal of the STAR Sexually Transmitted Infection Clinical Trial Group (STI CTG) Programmatic meeting on Sexually Transmitted Infections (STIs) in Pregnancy and Reproductive Health in April 2018 was to review the latest research and develop recommendations to improve prevention and management of STIs during pregnancy. Experts from academia, government, nonprofit, and industry discussed the burden of STIs during pregnancy; the impact of STIs on adverse pregnancy and birth outcomes; interventions that work to reduce STIs in pregnancy, and the evidence, policy, and technology needed to improve STI care during pregnancy. Key points of the meeting are as follows: (i) alternative treatments and therapies for use during pregnancy are needed; (ii) further research into the relationship between the vaginal microbiome and STIs during pregnancy should be supported; (iii) more research to determine whether STI tests function equally well in pregnant as nonpregnant women is needed; (iv) development of new lower cost, rapid point-of-care testing assays could allow for expanded STI screening globally; (v) policies should be implemented that create standard screening and treatment practices globally; (vi) federal funding should be increased for STI testing and treatment initiatives supported by the Centers for Disease Control and Prevention (CDC), the Centers of Excellence in STI Treatment, public STD clinics, and the President's Emergency Plan for AIDS Relief (PEPFAR).
Corneal Endothelial Blebs Induced in Scleral Lens Wearers
Authors: Giasson Claude J. , Rancourt Josiane , Robillard Josiane , Melillo Marc , Michaud Langis 
Published: October 2019

SIGNIFICANCEIn the bleb phenomenon, some endothelial cells transiently lose their specular reflection. This has been reported during contact lens wear and goggle-induced hypoxia or hypercapnia.PURPOSEThe purposes of this study were to determine whether blebs appear after scleral lens wear and if their appearance is influenced by lens clearance and to compare bleb and cell sizes.METHODSTwenty-one subjects were fitted with two similar scleral lenses with different targeted clearances of 200 and 400 μm (the SL200 and SL400, respectively). Each lens was worn unilaterally for 25 minutes, whereas the other eye served as a control. Before and after lens wear, the endothelium was photographed using specular microscopy. The number of blebs and measurements of the areas of cells and blebs were analyzed. Pairedttests compared differences in the areas of cells and blebs. Differences in median bleb number were evaluated using the Wilcoxon test.RESULTSAfter wearing the SL200 and SL400 lenses, respectively, 9 and 14 subjects had at least one bleb. The median bleb number after wearing lenses was significantly different (SL200, 0.00; SL400, 1.00;P= .02). Bleb and cell areas were significantly different (blebs, 293 ± 28; cells, 370 ± 32 μm2;P< .0001).CONCLUSIONSAfter 25 minutes of wearing scleral lenses with each of the two targeted clearances, SL400 induced significantly more blebs than did SL200, suggesting evidence of reduced oxygen and/or increased carbon dioxide levels under scleral lenses fitted with excessive clearance. Blebs may occur more in smaller cells.
Brief Report: Association Between Low HIV-1 DNA and Western Blot Reactivity to HIV-1 Pol in Chronically Infected Individuals
Authors: Muccini Camilla , Galli Laura , Spagnuolo Vincenzo , Poli Andrea , Rolla Serena , Mastrangelo Andrea , Rinaldi Francesca , Castagna Antonella 
Published: October 2019

Background:
The aim of the study was to evaluate whether negative HIV-1 pol on Western blot (WB) was associated with low HIV-DNA in adults with chronic HIV-1 infection and suppressive antiretroviral therapy.

Methods:
Cross-sectional parent study of the APACHE trial, conducted in subjects with chronic infection, HIV-1 RNA <50 copies/mL for ≥10 years, no residual viremia for ≥5 years and CD4+ >500 cells/µL screened for HIV-1 DNA. HIV-1 DNA was quantified in peripheral blood mononuclear cells (PBMCs) by real-time polymerase chain reaction and HIV-1 serostatus was tested by HIV Blot 2.2 WB assay. Multivariate logistic regression was used to determine factors associated with low HIV-1 DNA.

Results:
We evaluated 96 patients: 78 (81%) and 18 (19%) subjects with HIV-1 DNA ≥100 copies/106 PBMCs and with HIV-1 DNA <100 copies/106 PBMCs, respectively. Median age was 32.5 (25.3–38.9), and 61 (64%) were men; moreover, we reported that nadir CD4+ was 253 (167–339) cells/µL and HIV-RNA <50 copies/mL for 11.7 (10.6–14.0) years. At multivariate analysis, higher nadir CD4+ [adjusted odds ratio (AOR) [95% confidence interval (CI) 1.35 (95% CI: 1.03 to 1.76), P = 0.029], longer years of HIV-1 RNA <50 copies/mL [AOR (95% CI) 2.98 (95% CI: 1.25 to 7.10), P = 0.014], a R5-tropic virus [AOR (R5 vs. non-R5) 0.20 (95% CI: 0.04 to 0.96), P = 0.044], and negative HIV-1 pol [AOR 6.59 (95% CI: 1.47 to 29.54), P = 0.014] were associated with low HIV-1 DNA.

Conclusions:
In patients with chronic HIV-1 infection and suppressive antiretroviral therapy, negative HIV-1 pol on WB was associated with low HIV-1 DNA as well as higher nadir CD4+, longer years of HIV-1 RNA <50 copies/mL, and a R5-tropic virus.
Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression
Authors: Musinguzi Nicholas , Castillo-Mancilla Jose , Morrow Mary , Byakwaga Helen , Mawhinney Samantha , Burdo Tricia H. , Boum Yap , Muzoora Conrad , Bwana Bosco M. , Siedner Mark J. , Martin Jeffrey N. , Hunt Peter W. , Bangsberg David R. , Haberer Jessica E. 
Published: October 2019

Background:
Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed.

Setting:
We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda.

Methods:
Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8+ T-cell activation (HLA-DR+/CD38+ coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers.

Results:
Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR+/CD8+ (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance.

Conclusions:
Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.
Ten Things We Need to Do to Achieve the Goals of the End the HIV Epidemic Plan for America
Authors: Kelly Jeffrey A. 
Published: October 2019

Problem:
DHHS announced a plan for Ending the HIV Epidemic (EtHE) by reducing new HIV infections in the United States by 75% within 5 years and 90% within 10 years through early diagnosis of all individuals with HIV, immediate treatment to achieve viral suppression, protection of high-risk but uninfected individuals including with pre-exposure prophylaxis (PrEP), and quickly responding to emerging HIV clusters.

Approach:
Ten steps are outlined that will help the field achieve EtHE Plan goals.

Findings:
Steps needed to reach EtHE goals are: (1) better reaching, understanding, and meeting the HIV prevention and care needs of Black men who have sex with men; (2) deployment of interventions that address social, cultural, behavioral, and structural determinants of HIV disparities; (3) improving uptake in biomedical HIV-prevention strategies in mid-sized cities across the country's center; (4) addressing with long-term commitment the urgent HIV-prevention needs in the US Southeast; (5) encouraging more frequent and regular HIV testing; (6) developing better strategies to not only encourage initiation but also the long-term and sustained use of PrEP by persons at high risk for contracting HIV infection; (7) improving the comfort and capacity of primary care providers to prescribe PrEP; (8) increasing HIV medical care retention and care re-engagement, especially among persons with competing life stressors; (9) developing sustainable implementation efforts; and (10) addressing policies that can facilitate or impede success in eliminating the HIV epidemic in the United States.

Conclusion:
EtHE goals are achievable but will require concerted, sustained effort.
Treatment as Prevention: Concepts and Challenges for Reducing HIV Incidence
Authors: Brault Marie A. , Spiegelman Donna , Hargreaves James , Nash Denis , Vermund Sten H. 
Published: October 2019

Background:
Four of the largest HIV prevention trials have been conducted in sub-Saharan Africa, enrolling hundreds of thousands of participants in catchment areas of millions of people. The trials have focused on community-level interventions to increase diagnosis and initiation of antiretroviral therapy (ART) to improve health and reduce HIV transmission. Universal test-and-treat strategies are deployed to achieve viral suppression thereby reducing risk to uninfected persons, known as treatment as prevention (TasP).

Purpose:
We review the work that found HIV plasma load to correlate with transmission risk, demonstrated that ART could reduce genital tract viral expression, and showed early treatment to be beneficial for persons living with HIV, and that HIV-uninfected sexual partners were protected from infection. We review the seemingly inconsistent findings of the major TasP trials: the TasP [National Agency for AIDS Research (ANRS) 12249] study in South Africa, the SEARCH trial in Kenya and Uganda, the Botswana Combination Prevention Project Ya Tsie study, and the HIV Prevention Trials Network 071 (PopART) trial in Zambia and South Africa.

Findings:
All the trials reinforce the critical need to identify approaches to optimize programs and incentivize uptake and engagement in HIV testing and ART-based care in ways that consistently reduce HIV transmission. That other chronic conditions can be screened for and treated in the same infrastructures suggests added value of HIV investments.

Conclusions:
Implementation challenges are a principal frontier in the global struggle to reduce HIV transmission and mortality using TasP, complementing efforts to find a cure for HIV and an effective, deployable vaccine.
Increasing Diversity and Capacity in HIV Behavioral and Social Science Research: Reflections and Recommendations From the Inaugural Cohort of the Mid-Atlantic CFAR Consortium (MACC) Scholars Program
Authors: Brown Lily A. , Dangerfield Derek T. , Meanley Steven , Hickson DeMarc 
Published: October 2019

Problem Statement:
There is a need to increase diversity among both researchers and participants in the area of HIV scholarship. The Mid-Atlantic Center for AIDS Research Consortium (MACC) Scholars Program was developed to promote diversity among HIV-related researchers and participants.

Approach:
Four Scholars were provided with mentorship from senior investigators at Johns Hopkins University, George Washington University, and the University of Pennsylvania. Each Scholar was awarded a grant to develop a pilot study on a topic related to HIV-prevention, treatment, or care. The paper will describe the benefits of the program, challenges that Scholars faced in their projects, and areas for growth of the program from the perspective of the Scholars.

Findings:
The Scholars unanimously agreed that the program was essential for gathering pilot data and for receiving practical training in grantsmanship and writing. For challenges, each Scholar encountered unanticipated delays in regulatory approval, resulting in a lag of project start-up. As an indication of the success of the program, Scholars reported on their productivity for grantsmanship, scientific publications, and grantsmanship over the first year of the program. Finally, the Scholars offered several suggestions for continuing to improve the MACC Program for future cohorts.

Conclusion:
The Scholars perceived the inaugural year of the MACC Scholars Program as extremely helpful and productive. Ongoing efforts should be made to continue to promote the development of diverse junior scientists in HIV research.
Prevalence and Correlates of Self-Rated Successful Aging Among Older Women Living With HIV
Authors: Rubtsova Anna A. , Wingood Gina M. , Ofotokun Ighovwerha , Gustafson Deborah , Vance David E. , Sharma Anjali , Adimora Adaora A. , Holstad Marcia 
Published: October 2019

Background:
Despite marked gains in longevity attributable to antiretroviral therapy (ART), older women living with HIV (OWLH) experience substantial health challenges, and few studies addressed whether they can achieve successful aging (SA). This is among the first studies examining prevalence and psychosocial correlates of self-rated SA (SRSA) among OWLH and women at risk of HIV.

Methods:
The sample included 386 OWLH and 137 HIV-seronegative women enrolled in the Women's Interagency HIV Study (WIHS) who were aged 50 years and older and participated in the “From Surviving to Thriving” (FROST) substudy. The FROST survey included measures of SRSA and positive psychosocial constructs.

Results:
Participants were on average 57 years (SD = 5.3), 74% African American and 30% unemployed. Among OWLH, 94% were on ART and 73% were virally suppressed. Compared with OWLH, a higher proportion of HIV-seronegative women had an annual income ≤ $6000, no health insurance, and reported lower optimism and health-related quality of life. We found no differences in SRSA prevalence by HIV status: 84% of OWLH and 83% of HIV-seronegative women reported SRSA ≥7 (range = 2–10, higher scores signify better SRSA). Having SRSA ≥7 was associated with higher levels of positive psychosocial characteristics (eg, resilience and optimism) among both OWLH and HIV-seronegative women.

Conclusions:
SRSA is achievable among older women with and at risk of HIV despite health complications. Among disadvantaged women, factors other than HIV may be primary drivers of SRSA. Future research is needed to examine determinants of SRSA and to design public health interventions enhancing SA within this population.
Changes in freshwater macroinvertebrate richness due to river impoundment in the United States
Authors: Trottier Gabrielle , Turgeon Katrine , Verones Francesca , Boisclair Daniel , Bulle Cécile , Margni Manuele 
Published: October 2019

ABSTRACTWhether it is for water supply, flood control or hydropower uses, the transformation of a river into a reservoir can impact freshwater ecosystems and their biodiversity. Using the National Lake Assessment (NLA; 148 reservoirs) and the National Rivers and Streams Assessment (NRSA; 2121 rivers and streams) of the United States Environmental Protection Agency (USEPA), we evaluated the impacts of river impoundment on macroinvertebrate biodiversity at three spatial scales (i.e., reservoir, ecoregion and country scale). We used a space-for-time substitution approach to model the impact of impoundment (i.e., we used rivers and streams as the before-impoundment conditions, and reservoirs as the after-impoundment conditions). We expressed the impact on biodiversity in terms of potentially disappeared fraction of species (PDF) to be used in the life cycle assessment (LCA) framework. To understand the role of regionalization, and some potentially influential variables, on changes in macroinvertebrate richness following impoundment in the United States, we used analyses of variance (ANOVAs) as well as variation partitioning, and developed empirical predictive models. Overall, 26% of macroinvertebrate taxa disappeared following impoundment in the United States, and PDFs followed a longitudinal gradient across ecoregions (i.e., higher PDFs in the western part of the country, lower PDFs in the eastern part). We also observed that large and oligotrophic reservoirs, located in high elevation had high PDFs. This study provides the first empirical PDF values for macroinvertebrates to be used as characterization factors (CFs) by LCA practitioners. We also provide strong support for regionalization and a simple predictive model to be used by LCA modellers.
Reorganization of the Primate Dorsal Horn in Response to a Deafferentation Lesion Affecting Hand Function
Authors: Fisher Karen M. , Garner Joseph , Darian-Smith Corinna 
Published: October 2019

AbstractThe loss of sensory input following a spinal deafferentation injury can be debilitating, and this is especially true in primates when the hand is involved. While significant recovery of function occurs, little is currently understood about the reorganization of the neuronal circuitry, particularly within the dorsal horn. This region receives primary afferent input from the periphery, and cortical input via the somatosensory subcomponent of the corticospinal tract (S1 CST), and is critically important in modulating sensory transmission, both in normal and lesioned states. To determine how dorsal horn circuitry alters to facilitate recovery post-injury, we used an established deafferentation lesion model (DRL/DCL – dorsal root/dorsal column) in male monkeys to remove sensory input from just the opposing digits (D1-D3) of one hand. This results in a deficit in fine dexterity that recovers over several months. Electrophysiological mapping, tract tracing, and immunolabeling techniques were combined to delineate specific changes to dorsal horn input circuitry. Our main findings show that (1) there is complementary sprouting of the primary afferent and S1 CST populations into an overlapping region of the reorganizing dorsal horn, (2) S1 CST and primary afferent inputs connect in different ways within this region to facilitate sensory integration (3) there is a loss of larger S1 CST terminal boutons in the affected dorsal horn, but no change in the size profile of the spared/sprouted primary afferent terminal boutons post-lesion. Understanding such changes helps to inform new and targeted therapies that best promote recovery.Significance statementSpinal injuries that remove sensation from the hand, can be debilitating, though functional recovery does occur. We examined changes to the neuronal circuitry of the dorsal horn in monkeys following a lesion that deafferented three digits of one hand. Little is understood about dorsal horn circuitry, despite the fact that this region loses most of its normal input after such an injury, and is clearly a major focus of reorganization. We found that both the spared primary afferents and somatosensory corticospinal efferents sprouted in an overlapping region of the dorsal horn after injury, and that larger (presumably faster) corticospinal terminals are lost, suggesting a significantly altered cortical modulation of primary afferents. Understanding this changing circuitry is important for designing targeted therapies.
Northstar enables automatic classification of known and novel cell types from tumor samples
Authors: Zanini Fabio , Berghuis Bojk A. , Jones Robert C. , Nicolis di Robilant Benedetta , Nong Rachel Yuan , Norton Jeffrey , Clarke Michael F. , Quake Stephen R. 
Published: October 2019

AbstractSingle cell transcriptomics is revolutionising our understanding of tissue and disease heterogeneity, yet cell type identificationl remains a partially manual task. Published algorithms for automatic cell annotation are limited to known cell types and fail to capture novel populations, especially cancer cells. We developed northstar, a computational approach to classify thousands of cells based on published data within seconds while simultaneously identifying and highlighting new cell states such as malignancies. We tested northstar on human glioblastoma and melanoma and obtained high accuracy and robustness. We collected eleven pancreatic tumors and identified three shared and five private neoplastic cell populations, offering insight into the origins of neuroendocrine and exocrine tumors. northstar is a useful tool to assign known and novel cell type and states in the age of cell atlases.
Interleukin-2 druggability is modulated by global conformational transitions controlled by a helical capping switch
Authors: De Paula Viviane S. , Jude Kevin M. , Nerli Santrupti , Glassman Caleb R. , Garcia K. Christopher , Sgourakis Nikolaos G. 
Published: October 2019

SUMMARYInterleukin-2 (IL-2) is a small α-helical cytokine that regulates immune cell homeostasis through its recruitment to a high-affinity heterotrimeric receptor complex (IL-2Rα/IL-2Rβ/γc). IL-2 has been shown to have therapeutic efficacy for immune diseases by preferentially expanding distinct T-cell compartments, and several Treg-biasing anti-IL-2 antibodies have been developed for combination therapies. The conformational plasticity of IL-2 plays an important role in its biological actions by modulating the strength of receptor and drug interactions. Through a NMR analysis of milliseconds-timescale dynamics of free mIL-2 we identify a global transition to an auto-inhibitory conformation controlled by an α-helical capping “switch”. Binding to either an anti-mouse IL-2 mAb or a small molecule inhibitor near the AB loop induces changes in dynamics at the core of the structure, and perturbations of the capping hydrogen-bond network abrogate Ab binding by destabilizing the auto-inhibitory conformation. Our results highlight a paradigm for designing precision therapeutics targeting a continuum of IL-2 conformational states.