instruction:
Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
question:
In the most recent version of the UICC TNM classification system for thyroid carcinoma, tumors with minimal extrathyroid extension were classified as T3. In this study, we investigated whether this upgrading is appropriate for papillary thyroid carcinoma.', 'We investigated the difference in the relapse-free survival (RFS) rate between patients with tumors having no, minimal, and massive extrathyroid extension in a series of 502 patients over the age of 45 years.', 'Patients with tumors showing massive extension showed a worse RFS rate except for those with tumors measuring 1 cm or less. However, there was no significant difference in RFS between tumors measuring 4 cm or less showing no or minimal extension. In an investigation of 409 patients without any clinically apparent node metastasis, the RFS of patients with tumors larger than 4 cm with massive extension was significantly worse than those with tumors measuring 4 cm or less, while the RFS of patients with tumors with either no or minimal extension did not depend on the tumor size.
answer:
Does minimal extrathyroid extension affect the relapse-free survival of patients with papillary thyroid carcinoma measuring 4 cm or less over the age of 45 years?


question:
Anxiety and depression frequently co-occur in the elderly and in patients with dementia. Prior research has shown that depression is related to the risk of dementia, but the effect of anxiety on dementia remains unclear. We studied whether anxiety symptoms and anxiety disorders are associated with the risk of dementia and cognition.', 'We studied 2,708 nondemented participants from the prospective, population-based Rotterdam Study who underwent the Hospital Anxiety and Depression Scale (HADS) (sample I, baseline 1993-1995) and 3,069 nondemented participants who underwent screening for anxiety disorders (sample II, baseline 2002-2004). In 1993-1995, anxiety symptoms were assessed using the HADS. In 2002-2004, anxiety disorders were assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. In both study samples, participants were continuously monitored for dementia until January 1, 2011. Cognition was tested in 2002-2004 and at a follow-up visit in 2009-2011 in sample II only.', 'In sample I, 358 persons developed dementia, and in sample II, 248 persons developed dementia. We did not find an association with the risk of dementia for anxiety symptoms (hazard ratio 1.05, 95% confidence interval: 0.77-1.43, Wald statistic 0.08, p\xa0= 0.77, df\xa0= 1) or for anxiety disorders (hazard ratio 0.92, 95% confidence interval: 0.58-1.45, Wald statistic 0.14, p\xa0= 0.71, df\xa0= 1). We could demonstrate an association of anxiety disorders with poor cognition cross-sectionally, but this attenuated after additional adjustments.
answer:
Is anxiety associated with the risk of dementia or cognitive decline : the Rotterdam Study?


question:
It is well established that environmental toxins, such as exposure to arsenic, are risk factors in the development of urinary bladder cancer, yet recent genome-wide association studies (GWAS) provide compelling evidence that there is a strong genetic component associated with disease predisposition. A single-nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12, residing 6 kb upstream of the important cell-cycle regulator and proto-oncogene, Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer predisposition has been unclear because it lies within a non-coding region of the genome. Here, it is demonstrated that bladder cancer cells heterozygous for this SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription occurring from the risk allele. Furthermore, using chromatin immunoprecipitation assays, a novel enhancer element was identified within the first intron of CCNE1 that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP in high-linkage disequilibrium with rs8102137 residing in the center of a KLF5 motif, alters KLF5 binding to this genomic region. Through luciferase assays and CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element controlling CCNE1 transcription is characterized. These studies uncover how a cancer-associated polymorphism mechanistically contributes to an increased predisposition for bladder cancer development.
answer:

Does transcription Factor KLF5 bound a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk?