TASK DEFINITION: In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.
PROBLEM: Productive infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile, reverse transcripts. We have previously identified G1b as the cell cycle stage required for the optimal completion of the reverse transcription process in T lymphocytes. However, the mechanism(s) involved in the blockage of reverse transcription remains undefined. In this study we investigated whether nucleotide levels influence viral reverse transcription in G0 cells. For this purpose the role of the enzyme ribonucleotide reductase was bypassed, by adding exogenous deoxyribonucleosides to highly purified T cells in the G0 or the G1a phase of the cell cycle. Our data showed a significant increase in the efficiency of the reverse transcription process following the addition of the deoxyribonucleosides. To define the stability and functionality of these full reverse transcripts, we used an HIV-1 reporter virus that expresses the murine heat-stable antigen on the surfaces of infected cells. Following activation of infected quiescent cells treated with exogenous nucleosides, no increased rescue of productive infection was seen. Thus, in addition to failure to complete reverse transcription, there was an additional nonreversible blockage of productive infection in quiescent T cells. These experiments have important relevance in the gene therapy arena, in terms of improving the ability of lentivirus vectors to enter metabolically inactive cells, such as hematopoietic stem cells.

SOLUTION: Nonproductive human immunodeficiency virus type 1 infection in nucleoside-treated G0 lymphocytes.

PROBLEM: The hygiene hypothesis is thought to be a significant contributor to the growing incidence of inflammatory bowel disease (IBD) around the world, although the evidence for specific factors that underlie the hygiene hypothesis in IBD is unclear. We aimed to systematically review the literature to determine which hygiene-related factors are associated with the development of IBD. Publications identified from a broad based MEDLINE and Current Contents search between 1966 and 2007 on key terms relevant to the 'hygiene hypothesis' and IBD including H pylori exposure, helminths, cold chain hypothesis, measles infection and vaccination, antibiotic use, breastfeeding, family size, sibship, urban upbringing, day care attendance and domestic hygiene were reviewed. The literature suggests that the hygiene hypothesis and its association with decreased microbial exposure in childhood probably plays an important role in the development of IBD, although the strength of the supporting data for each of the factors varies considerably. The most promising factors that may potentially be associated with development of IBD include H pylori exposure, helminths, breastfeeding and sibship. However, the vast majority of studies in this area are plagued by serious methodological shortcomings, particularly the reliance on retrospective recall of information making it difficult to truly ascertain the importance of a 'hygiene hypothesis' in IBD. The 'hygiene hypothesis' in IBD is an important area of research that may give clues to the aetiology of this disease. Directions for future research are recommended.

SOLUTION: Hygiene hypothesis in inflammatory bowel disease: a critical review of the literature.

PROBLEM: IMPORTANCE The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab.
OBJECTIVE To characterize the association of pembrolizumab with tumor response and overall survival among patients with advanced melanoma.
DESIGN, SETTINGS, AND PARTICIPANTS Open-label, multicohort, phase 1b clinical trials (enrollment, December 2011-September 2013). Median duration of follow-up was 21 months. The study was performed in academic medical centers in Australia, Canada, France, and the United States. Eligible patients were aged 18 years and older and had advanced or metastatic melanoma. Data were pooled from 655 enrolled patients (135 from a nonrandomized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 from randomized cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]). Cutoff dates were April 18, 2014, for safety analyses and October 18, 2014, for efficacy analyses. EXPOSURES Pembrolizumab 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks continued until disease progression, intolerable toxicity, or investigator decision.
MAIN OUTCOMES AND MEASURES The primary end point was confirmed objective response rate (best overall response of complete response or partial response) in patients with measurable disease at baseline per independent central review. Secondary end points included toxicity, duration of response, progression-free survival, and overall survival.
RESULTS Among the 655 patients (median [range] age, 61 [18-94] years; 405 [62%] men), 581 had measurable disease at baseline. An objective response was reported in 194 of 581 patients (33% [95% CI, 30%-37%]) and in 60 of 133 treatment-naive patients (45% [95% CI, 36% to 54%]). Overall, 74% (152/205) of responses were ongoing at the time of data cutoff; 44% (90/205) of patients had response duration for at least 1 year and 79% (162/205) had response duration for at least 6 months. Twelve-month progression-free survival rates were 35% (95% CI, 31%-39%) in the total population and 52% (95% CI, 43%-60%) among treatment-naive patients. Median overall survival in the total population was 23 months (95% CI, 20-29) with a 12-month survival rate of 66% (95% CI, 62%-69%) and a 24-month survival rate of 49% (95% CI, 44%-53%). In treatment-naive patients, median overall survival was 31 months (95% CI, 24 to not reached) with a 12-month survival rate of 73% (95% CI, 65%-79%) and a 24-month survival rate of 60% (95% CI, 51%-68%). Ninety-two of 655 patients (14%) experienced at least 1 treatment-related grade 3 or 4 adverse event (AE) and 27 of 655 (4%) patients discontinued treatment because of a treatment-related AE. Treatment-related serious AEs were reported in 59 patients (9%). There were no drug-related deaths.
CONCLUSIONS AND RELEVANCE Among patients with advanced melanoma, pembrolizumab administration was associated with an overall objective response rate of 33%, 12-month progression-free survival rate of 35%, and median overall survival of 23 months; grade 3 or 4 treatment-related AEs occurred in 14%.
TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01295827.

SOLUTION:
Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma.