TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets.', 'Direct interactions of uPAR with interactors were demonstrated by immunoprecipitations and proximity ligation assays. For stable knockdowns of target proteins, lentiviral vectors were used and the effects were analysed by immunoblottings and using in vitro cell viability, migration and invasion assays. Immunohistochemical and statistical analyses of biomarkers and clinical parameters were conducted in a TNBC cohort (n\u2009=\u2009174).', 'Direct tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor receptor 1 (IGF1R) were shown in TNBC cells and these interactions were significantly reduced (p\u2009=\u20090.001) when uPAR was downregulated. The combined knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell viability, migration and invasion of the model cell lines. In TNBC tissue, the complexes formed by uPAR with uPA or with IGF1R significantly correlated with the histological grade (p\u2009=\u20090.0019) as well as with cathepsin B and D (p\u2009≤\u20090.0001) that are implicated in cell invasion and metastasis.\Question: Does uPAR enhance malignant potential of triple-negative breast cancer by directly interacting with uPA and IGF1R?

SOLUTION: Our outcomes show that not only overexpressed biomarkers promote tumourigenesis, but rather their interactions further potentiate tumour progression. This study emphasises the potential of combined approaches targeting uPAR and its interactors with regard to an improved therapy of TNBC.

PROBLEM: Context: Remote renal ischemia-reperfusion injury (IRI) following infra-renal aortic occlusion leads to acute kidney injury and systemic inflammation. Hydrogen sulfide is a mediator of IRI and can ameliorate tissue injury in many organ systems. Its role in vascular surgery has yet to be established. We assessed the role of hydrogen sulfide in a rodent model of aortic occlusion.', 'Wistar rats were divided into sham, control, and treatment groups (n = 6). Inflammation was assessed using a nonrecovery protocol. The infra-renal aorta was cross-clamped for 60 min and animals were reperfused for 120 min. Ten minutes before clamp release, treatment animals received hydrogen sulfide (10, 30, or 50 μg/kg) and control animals received 0.9% saline injected into the retroperitoneum. Renal injury and histology were assessed by a recovery protocol. The procedure was identical to the nonrecovery arm but with a single dose of hydrogen sulfide (30 μg/kg) and animals were recovered for 7 days.', 'There was no difference in animal weight between the groups (P = 0.337). In the nonrecovery arm, there was a reduction in serum levels of tumor necrosis factor alpha in sulfide-treated animals compared with controls (909 ± 98 vs. 607 ± 159 pg/mL; P = 0.0038). There was also a reduction in myeloperoxidase-positive cells in renal tissue in the sulfide-treated animals compared with controls (8 ± 4 vs. 17 ± 9; P = 0.03). There was no difference in histological injury score or endothelin-1 levels. In the recovery arm, there was no difference in renal function, Kidney Injury Molecule-1 levels, or histological injury scores.\Question: Does hydrogen sulfide reduce inflammation following abdominal aortic occlusion in rats?

SOLUTION: Hydrogen sulfide has systemic and renal anti-inflammatory effects in remote IRI following aortic occlusion in rats.

PROBLEM: Context: To describe the prevalence and correlates of hazardous drinking among female sex workers (FSWs) at 13 sites throughout Mexico.', 'FSWs (N = 1089) who were enrolled in a brief sexual risk reduction intervention (Mujer Segura) were queried about their sexual risk and substance use practices and their work contexts. Participants were classified as hazardous or non-hazardous drinkers based on the Alcohol Use Disorders test (AUDIT-C). Logistic regression models were used to examine individual, contextual, and community-level factors as correlates of hazardous drinking.', 'Ninety-two percent of participants reported alcohol consumption in the past month. Among drinkers (N = 1001), 83% met AUDIT-C criteria for hazardous drinking. Factors that were independently associated with hazardous drinking included: drug use in the past month (adjusted odds ratio (AOR) = 3.31; 95% CI 1.29-8.45), being a cigarette smoker (AOR = 1.71; 95% CI 1.13-2.58), being a barmaid or dance hostess (AOR = 3.40; 95% CI 1.95-5.91), alcohol use before or during sex with clients (AOR = 7.78; 95% CI 4.84-12.52), and working in a city with a higher marginalization index (AOR = 1.07; 95% CI 1.04-1.11).\Question: Does prevalence and correlate of Hazardous Drinking among Female Sex Workers in 13 Mexican Cities?

SOLUTION:
Findings support the high prioritization by public health authorities of alcohol prevention and treatment programs for FSWs.