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Background To explore the clinicopathological significance of tumor budding (TB) on oral squamous cell carcinoma (OSCC) prognosis. Methods Data of 200 patients with OSCC were retrieved from the cancer registration database in Taipei Veterans General Hospital. Clinicopathological characteristics and survival relevant to TB were analyzed. Results The data showed that TB was predominant in the tongue and floor of the mouth in younger patients with OSCC and correlated with several pathological factors, such as perineural invasion and lymphovascular invasion. Patients with TB have significantly lower recurrence‐free survival (P ≤ .0001). TB was significantly associated with lymph node metastasis in patients with early cancer stage (P = .042). Multivariate analysis demonstrated extranodal extension and TB as independent predictors of lymph node recurrence (adjusted hazard ratio = 9.90 and 3.89, respectively). Conclusion TB is a significant predictor of tumor aggression with locoregional failure even in the revised 8th American Joint Committee on Cancer staging system.

Pituitary growth hormone (GH)1 plays a key role in the regulation of postnatal growth and metabolism of fat, protein, and carbohydrate in animals (for a review, see Ref. 1). At the tissue level, these pleiotropic actions of GH result from the interaction of GH with a specific cell surface receptor, the GH receptor. The promoter-regulatory regions of the murine (2-4), ovine (5, 6), and human (7) GH receptor have been partially characterized. Heterogeneity in the 5Ј-untranslated regions of the GH receptor transcripts emerges as a feature common to the GH receptor gene from these different species. The two transcripts characterized in the mouse, termed L1 and L2, arise from alternate splicing (2, 8). The L2 sequence is G ϩ C-rich with an overall G/C content of 71%; in contrast the L1 transcript has a G/C content of 41% (8). Expression of the L1 and L2 transcripts is regulated in a tissue-and developmentspecific manner. Late pregnant mouse liver and placenta both express GH receptor mRNAs containing L1 and L2 sequences (8). The L1 GH receptor transcript is expressed in the liver only during pregnancy (8). In the placenta, GH receptor transcripts containing L2 untranslated regions are more abundant than transcripts containing L1 untranslated regions.In the mouse, an enhancer element located Ϫ3 kb from the major start site of the L1 transcript interacts with the transcription factor CTF/NF-1 in COS-7 cells (3). The most distal cis-element identified to date, termed FP42, is located Ϫ3.5 kb from the major transcription start site. Previous reports from this laboratory have described studies that suggest that both double-and single-stranded DNA-binding proteins conjointly regulate the expression of the L1 transcript of the murine GH receptor gene by interacting with the FP42 site (2, 4).In the present report, we establish the identity of both the double-and single-stranded DNA-binding proteins. Based on the characteristics of the DNA-protein contact points, we deduced that the double-stranded DNA binding activity represented protein(s) belonging to the family of CCAAT box-binding proteins. These studies resulted in the identification of the double-stranded DNA-binding protein (DSBP) as NF-Y. In the case of the single-stranded DNA-binding protein (SSBP), we screened a phage cDNA expression library to identify a cDNA encoding a protein that interacts with the upper (coding) strand of the FP42 regulatory element. Further studies established the identity of this protein to be MSY-1, a member of the Y-box family of proteins. Our studies indicate that MSY-1 functions as a repressor of GH receptor gene expression and may play a role in the pregnancy-specific expression of the GH receptor gene. EXPERIMENTAL PROCEDURESOligonucleotides-The following synthetic oligonucleotides were used in these experiments (residues altered in the mutant oligonucleotide are indicated in lowercase type): FP42-US, CTGGTTAGTTCATAT-TGTTGTTCCACCAATAGGGTTGCAGAC; FP42(⌬C.Box)-US, CTGGTTAGTTCATATTGTTGTTCCACacATAGGGTTGCAGAC; E ␣ (NF-Y)-US, ATTTTTCTGATTGGT...

Our results suggest that nurses should assess older adults living in rural areas for nutritional health and nutrition knowledge. Based on this assessment, nurses should develop easy, practical and accessible nutritional programmes for this population.

The aim of this work is to optimize a peptide targeted macrocyclic MRI contrast agent for detection and risk-stratification of aggressive prostate cancer. The optimized agent was prepared using click chemistry in the presence of CuSO and ascorbate at room temperature. The T and T relaxivities of ZD2-N3-Gd(HP-DO3A) are 5.44 and 7.10 mM s at 1.4 T, and 5.53 and 7.81 mM s at 7 T, respectively, higher than the previously reported ZD2-Gd(HP-DO3A). The specific tumor enhancement of the agent was investigated in male nude mice bearing aggressive PC3 human prostate cancer xenografts and slow-growing LNCaP tumor xenografts. Contrast enhanced MR images were acquired using a 2D spin-echo sequence and a 3D FLASH sequence with a 7 T small animal scanner. ZD2-N3-Gd(HP-DO3A) produced robust contrast enhancement in aggressive PC3 tumors and little enhancement in slow-growing LNCaP tumors. It produced 400% and 100% CNR increases in the T-weighted 2D spin-echo MR images and 3D FLASH images of PC3 tumors, respectively, for at least 30 min at a dose of 0.1 mmol/kg. In contrast, less than 20% CNR increase was observed in the LNCaP tumors with both sequences. The optimized targeted contrast agent has higher relaxivities and are effective to detect aggressive PC3 tumors and differentiate the aggressive cancer from the slow-growing LNCaP prostate cancer in contrast enhanced MRI. ZD2-N3-Gd(HP-DO3A) has the promise for accurate detection and risk-stratification of aggressive prostate cancer.

The aim of this study was to analyze the impact of clinical factors on the outcomes of otosclerosis surgery and support patients' access to evidence-based information in pre-operative counseling to optimize their choices. A total of 109 ears in 93 patients undergoing stapes surgery in a tertiary referral center were included. Variables with a potential impact on hearing outcomes were recorded, with an emphasis on factors that were readily available pre-operatively. Hearing success was defined as a post-operative air-bone gap ≤10 dB. Logistic regression analysis was used to determine the factors independently contributing to the prediction of hearing success. The mean follow-up period was 18.0 months. Univariate and multivariate analyses indicated that none of the pre-operative factors (piston type, age, sex, affected side, tinnitus, vertigo, and pre-operative hearing thresholds) affected hearing success significantly (all p > 0.05). In conclusion, self-crimping Nitinol piston provides comparable hearing outcomes with conventional manual-crimping prostheses. However, Nitinol piston offers a technical simplification of a surgical procedure and an easier surgical choice for patients. In addition, age is not a detriment to hearing gain and instead might result in better use of hearing aids in older adults, thus facilitating social hearing recovery. Finally, hearing success does not depend on the extent of pre-operative hearing loss. Hence, patients with poor cochlear function should not be considered poor candidates for surgery. The predictive model has established recommendations for otologists for better case selection, and factors that are readily available pre-operatively may inform patients more explicitly about expected post-operative audiometric results.

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