Crowdsourcing to Improve HIV and Sexual Health Outcomes: a Scoping Review.

PURPOSE OF REVIEW: This review synthesizes evidence on the use of crowdsourcing to improve HIV/sexual health outcomes. RECENT FINDINGS: We identified 15 studies, including four completed randomized controlled trials (RCTs), one planned RCT, nine completed observational studies, and one planned observational study. Three of the four RCTs suggested that crowdsourcing is an effective, low-cost approach for improving HIV testing and condom use among key populations. Results from the observational studies revealed diverse applications of crowdsourcing to inform policy, research, and intervention development related to HIV/sexual health services. Crowdsourcing can be an effective tool for informing the design and implementation of HIV/sexual health interventions, spurring innovation in sexual health research, and increasing community engagement in sexual health campaigns. More research is needed to examine the feasibility, acceptability, and effectiveness of crowdsourcing interventions, particularly in low- and middle-income countries

Crystal Structure of Human AKT1 with an Allosteric Inhibitor Reveals a New Mode of Kinase Inhibition

AKT1 (NP_005154.2) is a member of the serine/threonine AGC protein kinase family involved in cellular metabolism, growth, proliferation and survival. The three human AKT isozymes are highly homologous multi-domain proteins with both overlapping and distinct cellular functions. Dysregulation of the AKT pathway has been identified in multiple human cancers. Several clinical trials are in progress to test the efficacy of AKT pathway inhibitors in treating cancer. Recently, a series of AKT isozyme-selective allosteric inhibitors have been reported. They require the presence of both the pleckstrin-homology (PH) and kinase domains of AKT, but their binding mode has not yet been elucidated. We present here a 2.7 Å resolution co-crystal structure of human AKT1 containing both the PH and kinase domains with a selective allosteric inhibitor bound in the interface. The structure reveals the interactions between the PH and kinase domains, as well as the critical amino residues that mediate binding of the inhibitor to AKT1. Our work also reveals an intricate balance in the enzymatic regulation of AKT, where the PH domain appears to lock the kinase in an inactive conformation and the kinase domain disrupts the phospholipid binding site of the PH domain. This information advances our knowledge in AKT1 structure and regulation, thereby providing a structural foundation for interpreting the effects of different classes of AKT inhibitors and designing selective ones

Assessing Patients\u27 Perceptions of Clinician Communication: Acceptability of Brief Point-of-Care Surveys in Primary Care

BACKGROUND: Improving patient-centered (PC) communication is a priority in many healthcare organizations. Most PC communication metrics are distal to the care encounter and lack clear attribution, thereby reducing relevance for leaders and clinicians. OBJECTIVE: We assessed the acceptability of measuring PC communication at the point-of-care. DESIGN: A brief patient survey was conducted immediately post-primary care appointments at one Veterans Affairs Medical Center. Audit-feedback reports were created for clinicians and discussed in qualitative interviews. PARTICIPANTS: A total of 485 patients completed the survey. Thirteen interviews were conducted with clinicians and hospital leaders. MAIN MEASURE(S): Measures included collaboRATE (a 3-item tool measuring PC communication), a question about how well needs were met, and overall visit satisfaction. Data were analyzed using descriptive statistics to characterize the mean and distribution of collaboRATE scores and determine the proportion of patients giving clinicians a top score on each item. Associations among responses were examined. Interviews focused on the value of measuring PC communication and were analyzed using a framework approach. KEY RESULTS: The proportion of patients giving PC communication top scores ranged from 41 to 92% for 16 clinicians who had \u3e /= 25 completed surveys. Among patients who gave top scores for PC communication, the odds of reporting that needs were completely met were 10.8 times higher (p \u3c .001) and the odds of reporting being very satisfied with their care were 13.3 times higher (p \u3c .001) compared with patients who did not give top scores. Interviewees found clinician-specific feedback useful; concerns included prioritizing this data when other measures are used to evaluate clinicians\u27 performance. Difficulties improving PC communication given organizational structures were noted. Recommendations for interventions included peer-to-peer education and mentoring by top-scoring clinicians. CONCLUSIONS: Assessing provider communication at the point-of-care is acceptable and useful to clinicians. Challenges remain to properly incentivize and support the use of this data for improving PC communication

Prevalence and associated factors of Internet gaming disorder among community dwelling adults in Macao, China

Background and aims: Internet gaming disorder (IGD) has been mainly studied among adolescents, and no research to date has examined its prevalence in general Chinese adult populations. This study estimated the prevalence of probable IGD in community-dwelling adults in Macao, China. Associations between IGD and psychological distress (i.e., depression and anxiety) as well as IGD and character strength (i.e., psychological resilience and purpose in life) were also tested. Methods: A random, representative sample of 1,000 Chinese residents (44% males; mean age = 40.0) was surveyed using a telephone poll design from October to November 2016. Results: The estimated prevalence of probable IGD was 2.0% of the overall sample and 4.3% among the recent gamers (n = 473), with no statistically significant sex and age effects observed (p > .05). The two most prevalent IGD symptoms were mood modification and continued engagement, despite negative consequences. Probable IGD respondents were more vulnerable to psychological distress (25.0% and 45.0% for moderate or above levels of depression and anxiety, respectively) than their non-IGD counterparts. They also reported a lower level of psychological resilience than non-IGD respondents. No significant buffering effect of the two character strength variables on the distress–IGD relationship was found. Discussion and conclusions: These results provide empirical evidence that IGD is a mental health threat not only to adolescents but also to adults. IGD was significantly associated with psychological distress, which should be addressed in conjunction with IGD symptoms in interventions. Inclusion of gamers of both sexes and different age groups in future prevention programs is also recommended

Crowdsourcing Methods to Enhance HIV and Sexual Health Services: A Scoping Review and Qualitative Synthesis.

BACKGROUND:Crowdsourcing is increasingly used to improve community engagement in HIV and sexual health research. In this scoping review, we reviewed studies using crowdsourcing approaches in HIV and sexual health research to identify strengths, opportunities for expansion, and limitations of such approaches. METHODS:We searched CINAHL, Web of Science, Embase, and PubMed. Studies were included if they involved crowdsourcing activities, were in the field of HIV or sexual health, and described the methodology in sufficient detail. We conducted a qualitative synthesis of eligible articles. RESULTS:Our search strategy yielded 431 nonduplicate articles. After screening, 16 articles met the inclusion criteria, including 4 publications that described research from high-income countries, 7 from middle-income countries, 1 from a low-income country, and 4 that had a global focus. There were 4 categories of crowdsourcing: open contests, hackathons, open forums, and incident reporting systems. We identified common phases for data acquisition and dissemination: (1) preparation; (2) problem framing and crowd solicitation; (3) judging submissions; and (4) sharing selected submissions. Strengths of using crowdsourcing approaches include greater innovation due to crowd heterogeneity, encouragement of multisectoral collaboration, empowerment of vulnerable populations, cost-effectiveness, and relevance to local cultures and styles. Weaknesses among some methods include reliance on the internet, temporal transience, and difficulty in sustaining long-term community engagement. CONCLUSIONS:Crowdsourcing may be useful for HIV implementation research. Further research on crowdsourcing related to HIV and sexual health is needed

The major barriers to evidence-informed conservation policy and possible solutions.

Conservation policy decisions can suffer from a lack of evidence, hindering effective decision-making. In nature conservation, studies investigating why policy is often not evidence-informed have tended to focus on Western democracies, with relatively small samples. To understand global variation and challenges better, we established a global survey aimed at identifying top barriers and solutions to the use of conservation science in policy. This obtained the views of 758 people in policy, practice, and research positions from 68 countries across six languages. Here we show that, contrary to popular belief, there is agreement between groups about how to incorporate conservation science into policy, and there is thus room for optimism. Barriers related to the low priority of conservation were considered to be important, while mainstreaming conservation was proposed as a key solution. Therefore, priorities should focus on convincing the public of the importance of conservation as an issue, which will then influence policy-makers to adopt pro-environmental long-term policies

Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease

r84, a Novel Therapeutic Antibody against Mouse and Human VEGF with Potent Anti-Tumor Activity and Limited Toxicity Induction

Vascular endothelial growth factor (VEGF) is critical for physiological and pathological angiogenesis. Within the tumor microenvironment, VEGF functions as an endothelial cell survival factor, permeability factor, mitogen, and chemotactic agent. The majority of these functions are mediated by VEGF-induced activation of VEGF receptor 2 (VEGFR2), a high affinity receptor tyrosine kinase expressed by endothelial cells and other cell types in the tumor microenvironment. VEGF can also ligate other cell surface receptors including VEGFR1 and neuropilin-1 and -2. However, the importance of VEGF-induced activation of these receptors in tumorigenesis is still unclear. We report the development and characterization of r84, a fully human monoclonal antibody that binds human and mouse VEGF and selectively blocks VEGF from interacting with VEGFR2 but does not interfere with VEGF∶VEGFR1 interaction. Selective blockade of VEGF binding to VEGFR2 by r84 is shown through ELISA, receptor binding assays, receptor activation assays, and cell-based functional assays. Furthermore, we show that r84 has potent anti-tumor activity and does not alter tissue histology or blood and urine chemistry after chronic high dose therapy in mice. In addition, chronic r84 therapy does not induce elevated blood pressure levels in some models. The ability of r84 to specifically block VEGF∶VEGFR2 binding provides a valuable tool for the characterization of VEGF receptor pathway activation during tumor progression and highlights the utility and safety of selective blockade of VEGF-induced VEGFR2 signaling in tumors

Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. As novel and improved immunotherapies may fill this need, we dissected the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 25 tumors (10 pre- and 15 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas were infiltrated by NK, T and B cells, and immunosuppressive myeloid populations. NK cells showed reduced cytotoxicity and T cells had a dysfunctional profile. Interaction analysis revealed a vast immunoregulatory network and identified NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduced neuroblastoma growth, with complete responses in vivo. Moreover, addition of TIGIT blockade to standard relapse treatment in a chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model significantly improved survival. Concluding, our integrative analysis of neuroblastoma’s vast immunoregulatory network provides novel targets and a rationale for immunotherapeutic combination strategies

Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes

Background The diagnosis of acute appendicitis can be surprisingly difficult without computed tomography, which carries significant radiation exposure. Circulating blood cells may carry informative changes in their RNA expression profile that would signal internal infection or inflammation of the appendix. Methods Genome-wide expression profiling was applied to whole blood RNA of acute appendicitis patients versus patients with other abdominal disorders, in order to identify biomarkers of appendicitis. From a large cohort of emergency patients, a discovery set of patients with surgically confirmed appendicitis, or abdominal pain from other causes, was identified. RNA from whole blood was profiled by microarrays, and RNA levels were filtered by a combined fold-change (\u3e2) and p value (\u3c0.05). A separate set of patients, including patients with respiratory infections, was used to validate a partial least squares discriminant (PLSD) prediction model. Results Transcript profiling identified 37 differentially expressed genes (DEG) in appendicitis versus abdominal pain patients. The DEG list contained 3 major ontologies: infection-related, inflammation-related, and ribosomal processing. Appendicitis patients had lower level of neutrophil defensin mRNA (DEFA1,3), but higher levels of alkaline phosphatase (ALPL) and interleukin-8 receptor-ß (CXCR2/IL8RB), which was confirmed in a larger cohort of 60 patients using droplet digital PCR (ddPCR). Conclusions Patients with acute appendicitis have detectable changes in the mRNA expression levels of factors related to neutrophil innate defense systems. The low defensin mRNA levels suggest that appendicitis patient’s immune cells are not directly activated by pathogens, but are primed by diffusible factors in the microenvironment of the infection. The detected biomarkers are consistent with prior evidence that biofilm-forming bacteria in the appendix may be an important factor in appendicitis