bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational Analysis of the BRAF Gene in Transitional Cell Carcinoma of the Bladder
Authors: Boulalas Ioannis , Zaravinos Apostolos , Delakas Demetrios , Spandidos Demetrios A. 
Published: January 2018

Purpose Mutational activation of the MAP kinase pathway is frequently found in many types of cancer. Recently, activating mutations in the BRAF gene, an important activator of this pathway, have been described in several tumor types including melanoma, colorectal and papillary thyroid cancer. The most frequent mutation in exon 15 (V600E) as well as several other mutations within exons 11 and 15 result in constitutive activation of the oncoprotein. Materials and methods Our study aimed to investigate BRAF mutations in 30 human bladder tumors and their adjacent normal tissues. The V600E mutation was screened by PCR/RFLP and exons 11, 14 and 15 of BRAF including intron-exon boundaries were sequenced. Results We detected two tumor specimens bearing two different mutations, both of which were found in exon 15. One sample showed the T1799A (V600E) and the other the G1798T (V600L) mutation. The first specimen was stage pT1a and grade II, whereas the second was stage pT2b and grade III. No mutations within the coding region of exons 11, 14, 15 and the intron-exon junctions for the remaining samples were found. Conclusions Our results suggest that involvement of BRAF mutations in the development of transitional cell carcinoma of the bladder is infrequent.
Cytokeratin and Vimentin Expression in Breast Cancer
Authors: Vora Hemangini H. , Patel Nupur A. , Rajvik Kruti N. , Mehta Shalvi V. , Brahmbhatt Birwa V. , Shah Manoj J. , Shukla Shilin N. , Shah Pankaj M. 
Published: January 2018

Background The transition from epithelial keratin to mesenchymal vimentin expression marks an important step in the malignant progression of breast cancer. This study analyzed the clinical significance of cytokeratin and vimentin in patients with breast cancer. Materials and methods Expression of cytokeratin and vimentin was evaluated by immunohistochemistry on paraffin-embedded tissue sections of patients with breast cancer. Results Loss of cytokeratin was seen in 11% of the patients. A clearer trend towards loss of cytokeratin was observed in patients with stage IV disease and PR negativity. Weak cytokeratin expression was present in patients who developed recurrence or metastatic disease. Loss of cytokeratin was associated with reduced overall survival in univariate and multi-variate analysis, gain of vimentin expression was seen in 57% of breast carcinoma patients. It was higher in patients with lymph node positivity, advanced stage, HER2 positivity, and disease recurrence or metastasis. Multivariate survival analysis indicated that gain of vimentin expression was associated with reduced relapse-free survival. Conclusion Loss of cytokeratin and gain of vimentin expression are indicators of biologically aggressive breast carcinoma.
Gene-Specific Methylation: Potential Markers for Colorectal Cancer
Authors: Prabhu Jyothi S. , Korlimarla Aruna , Banerjee Arindam , Wani Shivangi , Payal K , Sahoo Rashmita 
Published: January 2018

Purpose Aberrant methylation of the promoter region is associated with silencing of many genes in neoplasia. CpG island methylation is an epigenetic mechanism for transcriptional silencing that occurs at various stages of colon tumorigenesis. In this study, we tested the promoter methylation and expression of seven genes from various pathways of DNA repair, apoptosis and inflammation, i.e., sFRP1, MLH1, RASSF1A, CDA, v-fgr, LYN-B, and TNFR10d. Method The genes were analyzed by quantitative polymerase chain reaction for the level of gene expression. The promoter methylation status of the genes was studied by methylation-specific polymerase chain reaction. Result The correlation of promoter methylation status with suppressed gene expression patterns suggested a potential role for the silencing these genes in colon cancer progression. Conclusion Promoter methylations of the studied genes could be explored as promising biomarkers for new diagnostic, prognostic and therapeutic targets of colorectal cancer.
E-Cadherin and Metalloproteinase-1 and -7 Polymorphisms in Colorectal Cancer
Authors: de Lima Jacqueline Miranda , de Souza Lessileia Gomes , da Silva Ismael Dale Cotrim Guerreiro , Forones Nora Manoukian 
Published: January 2018

Purpose E-cadherin (CDH1) and metalloproteinase (MMP) polymorphisms could play a crucial role in cancer invasion. Our aim was to investigate the influence of the -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 polymorphisms on the frequency and progression of colorectal cancer (CRC). Experimental design A total of 130 patients with CRC and 130 noncancer controls were studied. The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Results Patients with the 1G allele and a family history of CRC showed a six times higher risk of developing CRC (OR: 6.45, 95%CI: 2.02–20.6, p=0.001). The A/A CDH1 genotype was associated with a higher risk of metastatic disease (OR: 3.43, 95%CI: 1.27–9.27, p=0.023). A higher marginal risk of metastatic disease was observed for MMP-1 genotypes 1G/1G and 1G/2G (OR: 2.97, 95%CI: 0.93–9.47, p=0.098). Conclusions The -160C/A CDH1, -1607ins/delG MMP-1 and -181A/G MMP-7 single nucleotide polymorphisms did not modify the risk of CRC development. Patients with the 1G/1G or 1G/2G genotype and a family history of CRC presented a higher risk of CRC. The AA CDH1 and 1G/1G and 1G/2G MMP-1 genotypes might be associated with advanced metastatic disease, but are not markers of lymphatic metastasis.
Association of the AA genotype of the BCL2 (–938C>A) promoter polymorphism with better survival in ovarian cancer
Authors: Heubner Martin , Wimberger Pauline , Otterbach Friedrich , Kasimir-Bauer Sabine , Siffert Winfried , Kimmig Rainer , Nückel Holger 
Published: January 2018

Background Bcl-2 plays a key role in the regulation of apoptosis. Recently, a novel regulatory single nucleotide polymorphism (–938C>A) in the inhibitory P2 BCL2 promoter was described. In this study we investigated its potential association with survival in epithelial ovarian cancer. Experimental design Patients (n=110) with primary epithelial ovarian cancer were retrospectively genotyped by pyrosequencing. Results Genotype distribution was not significantly different between 110 ovarian cancer patients and 120 healthy controls, suggesting that genotypes of this polymorphism do not increase the susceptibility to ovarian cancer. Kaplan-Meier curves showed a significant association of the AA genotype with increased survival (p=0.002). Multivariate analysis revealed that the BCL2–938AC/CC genotype (hazard ratio 4.5; p=0.003) was an independent prognostic factor compared to other prognostic factors such as age, histological grade or tumor stage. Conclusion The results suggest a role for the BCL2-938C>A polymorphism as a marker for survival in patients with epithelial ovarian cancer.
Comparative evaluation of the erbB2 and hormone receptor status of neighboring invasive and in situ components of ductal carcinomas of the breast
Authors: Peres Raquel Mary Rodrigues , Serra Kátia Piton , Derchain Sophie F.M. , Yoon Jung Hyun , Pinto Glauce Aparecida , Alvarenga Marcelo , Soares Fernando Augusto , Heinrich Juliana K. , Da Cunha Isabela Werneck , Vassallo Jose , Sarian Luís Otávio 
Published: January 2018

Background It remains unknown whether erbB2 expression and hormone receptor status predict the invasive potential of ductal carcinoma in situ (DCIS) of the breast. Objectives To examine erbB2 and estrogen/progesterone receptor (ER/PR) status in the precise areas where DCIS turns into invasive ductal carcinoma (IDC). Subjects and methods Eighty-seven cases of breast malignancies harboring contiguous regions of DCIS and IDC were selected. Separate histological samples from the DCIS and the neighboring IDC were obtained using tissue microarrays. The erbB2 and ER/PR statuses were assessed using immunohistochemistry (erbB2 and ER/PR) and fluorescence in situ hybridization (FISH – only erbB2). Results The expression of erbB2 did not differ in the DCIS and IDC components of the breast tumors (p=0.35). There was good agreement in sample-by-sample comparisons of erbB2 (intraclass correlation coefficient [ICC]=0.78), PR (ICC=0.61) and ER (ICC=0.70) expression in the DCIS and IDC components. Conclusion Our findings suggest that the expressions of erbB2 and ER/PR do not differ in the contiguous regions from DCIS to IDC.
Cutoff value of carcinoembryonic antigen and carbohydrate antigen 19-9 elevation levels for monitoring recurrence in patients with resectable gastric adenocarcinoma
Authors: Qiu Miao-Zhen , Lin Jun-Zhong , Wang Zhi-Qiang , Wang Feng-Hua , Pan Zhi-Zhong , Luo Hui-Yan , Li Yu-Hong , Zhou Zhi-Wei , He You-Jian , Xu Rui-Hua 
Published: January 2018

Background The aim of this longitudinal study was to try and improve the specificity of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in monitoring tumor recurrence in patients with resectable gastric adenocarcinoma by setting suitable elevation levels. Methods One hundred eighty-one patients with resectable gastric adenocarcinoma were considered. Serum samples were obtained preoperatively and every 3 months postoperatively. Results Preoperative CEA and CA19-9 positivity rates were 19.9% and 18.2%. The specificity and sensitivity of CEA elevation to monitor recurrence were 92.9% and 23.4% versus 76.5% and 78.9% in CEA-negative versus CEA-positive patients, respectively. For CA19-9 the specificity and sensitivity were 95.0% and 18.8% versus 60.0% and 83.3% in CA19-9-negative versus CA19-9-positive patients, respectively. When we set the elevation level of CEA at 5 ng/mL, the specificity of CEA elevation to monitor recurrence increased to 94.1% for CEA-positive patients. The specificity increased to 93.3% for CA19-9-positive patients when the CA19-9 elevation level was set at 100 U/mL. Conclusions For CEA- or CA19-9-positive patients with resectable gastric adenocarcinoma we can increase the specificity of CEA and CA19-9 by setting the elevation level of CEA at 5 ng/mL and CA19-9 at 100 U/mL.
Malignancy and Meckel's diverticulum: A systematic literature review and 14‐year experience at a tertiary referral center
Authors: van Malderen Kathleen , Vijayvargiya Priya , Camilleri Michael , Larson David W , Cima Robert 
Published: January 2018

BackgroundMeckel's diverticulum is present in about 2% of the population. The literature reports 3.2% incidence of tumors within Meckel's diverticulum; the tumors are predominantly benign.Objective and methodsThe purpose of this study was to evaluate malignant tumors in Meckel's diverticulum through systematic review of the literature and review of electronic medical records including pathology reports over 14 years at the Mayo Clinic, Rochester, USA.ResultsA literature review over the last 10 years identified 37 citations with 402 patients (median age: 58 years; 68.9% males). The predominant malignancy reported was neuroendocrine tumor 84.6%, followed by gastrointestinal stromal tumor 8.2%, and adenocarcinoma 6%. At the time of diagnosis, 29.5% of patients had metastases. In the Mayo Clinic electronic medical records review, there were 19 patients (5.1% of them surgically removed Meckel's diverticulum) who had a malignancy associated with Meckel's diverticulum: 63.2% neuroendocrine tumor, 10.5% gastrointestinal stromal tumor, 5.3% adenocarcinoma, 5.3% pancreatic epithelial neoplasia, and 15.8% metastases from secondary location. Median size of the malignancy was 7 mm, and 17/19 malignancies were coincidental findings. Most neuroendocrine tumors infiltrated the submucosa, while gastrointestinal stromal tumor and adenocarcinoma invaded the serosa. At the time of diagnosis, 33.3% of patients had metastases.ConclusionAbout 5% of Meckel's diverticulums resected were associated with malignant tumors, most commonly neuroendocrine tumor, and a significant portion of Meckel's diverticulum malignancy was metastatic at the time of discovery.
A Comprehensive Evaluation of Factors Affecting Healing, Range of Motion, Strength, and Patient-Reported Outcomes After Arthroscopic Rotator Cuff Repair
Authors: Wylie James D. , Baran Sean , Granger Erin K. , Tashjian Robert Z. 
Published: January 2018

Background: Rotator cuff repair (RCR) leads to improved patient outcomes, which may or may not coincide with biological healing of the tendon. Many patient factors may play a role in subjective and objective patient outcomes of surgery. Purpose: To evaluate the effect of various patient factors and tendon healing on range of motion, strength, and functional outcomes after arthroscopic RCR. Study Design: Case-control study; Level of evidence, 3. Methods: We reviewed patients who underwent arthroscopic RCR. Postoperative endpoints included physical examination, repeat magnetic resonance imaging (MRI), and patient-reported outcome measures. The Short Form–36 (SF-36) was also completed at enrollment. Physical examination included range of motion and strength testing. Preoperative tear characteristics and postoperative healing on MRI were recorded. Associations between these characteristics and rotator cuff healing were determined. Multivariate models investigated factors affecting healing and final outcomes. Results: A total of 81 patients had MRI before and a minimum of 1 year after RCR. Patient-reported outcomes were available for all patients at mean 2.7 years (range, 1-7.7 years) after RCR. Seventy-five patients had physical examination data. Patients were less likely to heal if they had tears involving multiple tendons ( P = .037), tears >2.2 cm ( P = .037), tears retracted >2.0 cm ( P = .006), and tears with cumulative Goutallier grade ≥3 ( P = .003). Patients who healed were stronger on manual muscle testing in forward elevation ( P < .001) and external rotation ( P = .005) and on forward elevation isometric testing ( P = .033), and they reported better patient-reported outcomes ( P ≤ .01) at final follow-up. In multivariate models, tendon healing was associated with less pain ( P = .019) and better patient-reported outcomes (all P ≤ .006). Lower SF-36 mental component summary (MCS) score was associated with increased pain ( P = .025) and lower final American Shoulder and Elbow Surgeons score ( P = .035), independent of healing status. Conclusion: Larger, more retracted tears with greater fatty infiltration are less likely to heal per MRI. Patients who do not heal are weaker and have worse patient-reported outcome measures. Lower SF-36 MCS score was associated with poorer patient-reported outcomes independent of tendon healing.
Hif-1α and Hif-2α regulate hemogenic endothelium and hematopoietic stem cell formation in zebrafish
Authors: Gerri Claudia , Marass Michele , Rossi Andrea , Stainier Didier Y. R. 
Published: January 2018

Key PointsHypoxia regulates EHT through Hif-1α and Hif-2α. The Hif pathway functions upstream of Notch signaling in HSC formation.
Onset of action for loratadine tablets for the symptomatic control of seasonal allergic rhinitis in adults challenged with ragweed pollen in the Environmental Exposure Unit: a post hoc analysis of total symptom score
Authors: Tenn Mark W. , Steacy Lisa M. , Ng Charlene C. , Ellis Anne K. 
Published: January 2018

Abstract
Background
Loratadine is a second-generation, non-sedating antihistamine used for the relief of allergic rhinitis symptoms. Previous studies reported that when loratadine was encapsulated, the onset of action for symptom relief was 180 min. However, unmodified loratadine tablets were not evaluated at that time. Using data from a previously published Environmental Exposure Unit (EEU) study comparing azelastine nasal spray with loratadine tablets, cetirizine tablets, and placebo, this post hoc analysis determines the onset of action of loratadine tablets (i.e. unmodified) by analyzing the total symptom score for the relief of nasal and ocular seasonal allergic rhinitis (SAR) symptoms.

Methods
A Phase IV, randomized, single-center, double-blind, placebo-controlled, double-dummy, four-way crossover study was conducted in the EEU. Seventy participants were randomized sequentially into one of the four treatments during ragweed pollen exposure. Nasal and ocular symptom scores were self-reported by the participants and recorded. The original study analysis was carried out by evaluating the nasal symptom scores only. For this post hoc analysis, both nasal and ocular data from the loratadine and placebo treatment arms were analyzed. The primary endpoint for this analysis was the onset of action of loratadine as measured by the change in total symptom score (TSS) from baseline in comparison to placebo. The onset of ocular symptom relief using the total ocular symptom score (TOSS) was also reported.

Results
Loratadine tablets demonstrated a significant and durable improvement in both TSS (P = .005) and TOSS (P = .013) at 75 min post-treatment administration compared to placebo. The mean proportion of participants reporting none or mild for all component symptoms of TSS and TOSS at 75 min and thereafter was significantly higher in the loratadine (TSS, P = .0005; TOSS, P ≤ .0001) vs. placebo treatment arm.

Conclusions
The onset of action of loratadine tablets was 75 min for the relief of nasal and ocular symptoms in adults with SAR. These results suggest a faster onset of action for loratadine tablets (75 min) compared to previously reported studies which were conducted with modified (i.e. gelatin-encapsulated) loratadine tablets (180 min).
Trial registration Clinicaltrials.gov identifier NCT00561717
Free-style puzzle flap as a cross-leg pedicled flap: the concept of re-using a flap in acute burns, a case report
Authors: Serror Kevin , Chaouat Marc , Romano Golda , Schmidt Magali , Blet Alice , Mimoun Maurice , Boccara David 
Published: January 2018

Abstract

Background
In well-selected cases, flaps can play a pivotal role in optimizing outcomes in the acute phase of burns. A previous redundant flap could be reused or recycled as a donor site from which a new flap could be raised.

Case presentation
We report the case of a patient with full thickness burns on both legs, leading to the exposure of joints of the right ankle and the right foot and left patellar tendon. The right lower extremity was covered with a free musculo-cutaneous latissimus dorsi flap. Then, a musculo-cutaneous cross-leg flap pedicled on the anterior branch and centered on a perforator was harvested from the previous redundant flap to cover the controlateral knee.

Conclusion
Sequential flap coverage can be considered in cases of extensive soft tissue defects and particularly in burns. This case illustrates that re-using a redundant part of a previous flap to cover another defect is a safe and interesting alternative in the event of a lack of donor sites or to save donor sites for later reconstruction of contracted burn scars.
Qualitative Analysis of Palliative Care for Pediatric Patients With Cancer at Bugando Medical Center: An Evaluation of Barriers to Providing End-of-Life Care in a Resource-Limited Setting
Authors: Esmaili B. Emily , Stewart Kearsley A. , Masalu Nestory A. , Schroeder Kristin M. 
Published: January 2018

Purpose Palliative care remains an urgent, neglected need in the developing world. Global disparities in end-of-life care for children, such as those with advanced cancers, result from barriers that are complex and largely unstudied. This study describes these barriers at Bugando Medical Center, one of three consultant hospitals in Tanzania, to identify areas for palliative care development suitable to this context. Methods In-depth interviews were conducted with 20 caregivers of pediatric patients with cancer and 14 hospital staff involved in pediatric end-of-life care. This was combined with 1 month of participant observation through direct clinical care of terminally ill pediatric patients. Results Data from interviews as well as participant observation revealed several barriers to palliative care: financial, infrastructure, knowledge and cultural (including perceptions of pediatric pain), and communication challenges. Although this study focused on barriers, what also emerged were the unique advantages of end-of-life care in this setting, including community cohesiveness and strong faith background. Conclusion This study provides a unique but focused description of barriers to palliative care common in a low-resource setting, extending beyond resource needs. This multidisciplinary qualitative approach combined interviews with participant observation, providing a deeper understanding of the logistical and cultural challenges in this setting. This new understanding will inform the design of more effective—and more appropriate—palliative care policies for young patients with cancer in the developing world.
Rapid Decoloration of Photochromic 3H-Naphthopyran Attached to Three-Dimensional Poly(dimethylsiloxane) Network
Authors: Ubukata Takashi , Ozawa Yasushi , Saito Masako , Hiwatari Ken-ichiro , Yokoyama Yasushi 
Published: January 2018

Abstract
The attachment of 3H-naphthopyran to a three-dimensional network of polysiloxane elastomer was carried out by hydrosilylation reactions using 3H-9-(5-hexenyloxy)naphthopyran. The photochemical coloration and subsequent thermal decoloration behaviors of polysiloxane-bound 3H-naphthopyran molecules were examined by comparing their properties with those of a model 9-hexyloxy-3H-naphthopyran compound doped in a polysiloxane film, a PMMA film, and in solutions. The decoloration reaction rate of polysiloxane-bound naphthopyran was basically the same as that in the polysiloxane-doped system and in solutions. However, the polysiloxane-bound system is superior to the doped system due to: (1) more concentrated incorporation of naphthopyran molecules in the polysiloxane film; (2) less degradation of naphthopyran molecules during film preparation; and (3) less temperature dependence in the thermal decoloration rate.
Good and Bad Variance Premia and Expected Returns
Authors: Kilic Mete , Shaliastovich Ivan 
Published: January 2018

We measure “good” and “bad” variance premia that capture risk compensations for the realized variation in positive and negative market returns, respectively. The two variance premium components jointly predict excess returns over the next one and two years with statistically significant positive (negative) coefficients on the good (bad) component. The R2s reach about 10% for aggregate equity and portfolio returns and 20% for corporate bond returns. To explain the new empirical evidence, we develop a model that highlights the differential impact of upside and downside risk on equity and variance risk premia. The online appendix is available at https://doi.org/10.1287/mnsc.2017.2890 . This paper was accepted by Neng Wang, finance.