instruction:
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.
question:
Context: To investigate patterns of detection and variables associated with early diagnosis of melanoma in a population at intermediate melanoma risk.', 'Survey.', 'Hospital and university centers belonging to the Italian Multidisciplinary Group on Melanoma.', 'Eight hundred sixteen patients who were consecutively diagnosed as having melanoma and treated at 11 participating centers.', "Relationship between patterns of detection and patient's and physician's delay with melanoma thickness, assessed by multivariate analysis.", "A statistically significant association with early diagnosis was found for female sex (odds ratio [OR] for a lesion >1 mm in thickness, 0.70; 95% confidence interval [CI], 0.50-0.97), higher educational level (OR, 0.44; 95% CI, 0.24-0.79), residence in northern and central Italy (compared with southern Italy) (OR, 0.44; 95% CI, 0.30-0.65 and OR, 0.24; 95% CI, 0.15-0.37, respectively), and the habit of performing a skin self-examination (OR, 0.65; 95% CI, 0.45-0.93). When adjusted for all the previously mentioned variables, only melanoma detection made by a dermatologist, maybe incidentally, was associated with a statistically significant additional effect on early diagnosis (OR, 0.45; 95% CI, 0.28-0.73). No significant effect of anatomical site (trunk compared with other sites: OR, 0.83; 95% CI, 0.59-1.17), presence of atypical nevi (OR, 0.78; 95% CI, 0.52-1.17), and patient's delay (>3 months compared with < or =3 months: OR, 1.12; 95% CI, 0.78-1.60) was found.\Question: Are dermatologist detection and skin self-examination associated with thinner melanomas : results from a survey of the Italian Multidisciplinary Group on Melanoma?
answer:
Future melanoma early diagnosis strategies should adequately stress the role of skin self-examination among the adult population, and should recommend that dermatologists perform a total skin examination to identify suspect lesions (such an examination should also be performed during consultations for other reasons).


question:
Context: The Guatemalan potato tuber moth, Tecia solanivora, has been the most important pest species in Hispanico-American potato fields since its first record on potatoes in 1956 in Guatemala. This insect pest has been spreading to other parts of the world, including the Canary Islands in Europe. Tuber moth control relies heavily on the use of insecticides, including pyrethroids. Here, we assessed the likelihood of control failures and performed concentration-response bioassays in five Colombian strains of T. solanivora to evaluate their susceptibilities to the pyrethroid permethrin.', 'Evidence of control failures was observed in four strains tested, which exhibited moderate resistance levels (i.e. ranging from 5.4- to 24.4-fold). However, no spatial dependence was observed between the permethrin LC\Question: Is pyrethroid resistance associated with a kdr-type mutation ( L1014F ) in the potato tuber moth Tecia solanivora?
answer:
This is the first identification of a target-site-alteration-based resistance in the Guatemalan potato tuber moth T. solanivora, which is widespread and exhibits high frequencies among geographically distant strains, indicating that pyrethroids are probably becoming ineffective for the control of this pest species. © 2016 Society of Chemical Industry.


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Context: Nitrogen-containing bisphosphonates (N-BPs) have been designed to inhibit osteoclast-mediated bone resorption. However, it is now accepted that part of their anti-tumor activities is related to interference with the mevalonate pathway.', 'We investigated the effects of zoledronic acid (ZOL), on cell proliferation and protein isoprenylation in two tumoral (LnCAP, PC-3,), and one normal established (PNT1-A) prostatic cell line. To assess if inhibition of geranyl-geranylation by ZOL impairs the biological activity of RhoA GTPase, we studied the LPA-induced formation of stress fibers. The inhibitory effect of ZOL on geranyl geranyl transferase I was checked biochemically. Activity of ZOL on cholesterol biosynthesis was determined by measuring the incorporation of 14C mevalonate in cholesterol.', 'ZOL induced dose-dependent inhibition of proliferation of all the three cell lines although it appeared more efficient on the untransformed PNT1A. Whatever the cell line, 20 microM ZOL-induced inhibition was reversed by geranyl-geraniol (GGOH) but neither by farnesol nor mevalonate. After 48 hours treatment of cells with 20 microM ZOL, geranyl-geranylation of Rap1A was abolished whereas farnesylation of HDJ-2 was unaffected. Inhibition of Rap1A geranyl-geranylation by ZOL was rescued by GGOH and not by FOH. Indeed, as observed with treatment by a geranyl-geranyl transferase inhibitor, treatment of PNT1-A cells with 20 microM ZOL prevented the LPA-induced formation of stress fibers. We checked that in vitro ZOL did not inhibit geranyl-geranyl-transferase I. ZOL strongly inhibited cholesterol biosynthesis up to 24 hours but at 48 hours 90% of this biosynthesis was rescued.\Question: Does zoledronic acid treatment impair protein geranyl-geranylation for biological effects in prostatic cells?
answer:

Although zoledronic acid is currently the most efficient bisphosphonate in metastatic prostate cancer management, its mechanism of action in prostatic cells remains unclear. We suggest in this work that although in first intention ZOL inhibits FPPsynthase its main biological actitivity is directed against protein Geranylgeranylation.