tbuckley/cabot-search huggingface dataset:
Abstract 045: Leisure Time Physical Activity is Associated With Higher Coronary Artery Calcium Density: The Multi-Ethnic Study of Atherosclerosis
Authors: Isac C Thomas, Matthew Allison, Nketi Forbang, Michelle Takemoto, Erin Michos, Robyn McClelland, Matthew Budoff, Michael Criqui
Journal: Circulation (2018)

Introduction: Leisure-time physical activity (LTPA) has favorable effects on many risk factors for cardiovascular disease (CVD). Paradoxically, LTPA has also been associated with higher amounts of coronary artery calcium (CAC) in athletes. Recently, a higher density of CAC was shown to significantly mitigate the risk of CVD associated with a given volume of CAC. The effects of LTPA and non-LTPA on the density and volume components of CAC among individuals with calcified coronary atherosclerosis are unknown. Methods: We evaluated 3,398 participants from the Multi-Ethnic Study of Atherosclerosis with prevalent CAC (50% of cohort). CAC was assessed via cardiac computed tomography, while physical activity was assessed via questionnaire and categorized by quintiles of moderate and vigorous LTPA (e.g. exercise) and non-LTPA (e.g. work). Multiple linear regression with mutual adjustment for LTPA, non-LTPA, demographics, and CVD risk factors was performed. Results: Mean age of the sample was 66 years, 58% were male, 44% were Caucasian, 24% were African-American, 20% were Hispanic, and 12% were Chinese-American. Compared to the lower four quintiles, LTPA above the threshold of 2567 MET-minutes/week (quintile 5) was associated with 0.057 (0.008, 0.105) higher CAC density-units after full adjustment. LTPA at any level was not associated with CAC volume. Conversely, non-LTPA was associated with both lower CAC density and higher CAC volume in a stepwise fashion, with the highest quintile meeting statistical significance for both (see Table). Conclusions: The highest quintile of LTPA was associated with higher CAC density but not higher CAC volume, suggesting a possible explanation for high CAC scores in athletes with favorable CVD risk factor profiles. Non-LTPA was associated with a less favorable CAC composition after adjustment for LTPA, an unexpected finding that merits further investigation.
Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/β-catenin signaling pathway
Authors: Gang Wang, Zi-jian Zhang, Wen-gang Jian, Pan-hong Liu, Wei Xue, Teng-da Wang, Yu-yang Meng, Chao Yuan, Hao-ming Li, Yi-peng Yu, Zhan-xin Liu, Qiong Wu, Da-ming Zhang, Cheng Zhang
Journal: Molecular Cancer (2019)

The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC).The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/β-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo.In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/β-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo.Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.
Long-Term Follow-up of the Randomized Controlled Study in Patients with Newly Diagnosed Severe Aplastic Anemia Treated with ATG, Cyclosporine, with or without G-CSF: On Behalf of the SAA Working Party of the EBMT
Authors: André Tichelli, Regis Peffault De Latour, Jakob R. Passweg, Cora Knol, Gérard Socié, Judith Marsh, Britta Hoechsmann, Hubert Schrezenmeier, Andrea Bacigalupo, Sujith Samarasinghe, Alicia Rovo, Austin G. Kulasekararaj, Dirk-Jan Eikema, Paul Bosman, Peter Bader, Antonio M. Risitano, Carlo Dufour
Journal: Blood (2018)
Regorafenib after failure of gemcitabine and platinum-based chemotherapy for locally advanced (nonresectable) and metastatic biliary tumors: A randomized double-blinded placebo-controlled phase II trial.
Authors: Anne Demols, Ivan Borbath, Marc Van Den Eynde, Ghislain Houbiers, Marc Peeters, Raphael Maréchal, Thierry Delaunoit, Jean Charles. Goeminne, Stéphanie Laurent, Stephane Holbrechts, Marianne Paesmans, Jean L. Van Laethem
Journal: Journal of Clinical Oncology (2019)

345 Background: A high clinical unmet need remains in treating advanced or metastatic biliary tract cancers (BTC) after failure of gemcitabine and platinum-based chemotherapy, with no standard of care. Regorafenib is potent oral multi-kinase inhibitor of kinases involved in tumor angiogenesis, oncogenesis and tumor microenvironment. It has demonstrated efficacy and acceptable safety in some GI tumors that have progressed on standard therapies. Methods: REACHIN (NCT02162914) is a multicenter double-blinded placebo-controlled randomized phase II study to evaluate the safety and efficacy of regorafenib (REG) in patients with locally advanced (non resectable) and metastatic histologically proven BTC, progressing after gemcitabine-platinum. 66 patients were randomized (1:1) to receive BSC plus REG160 mg od, 3 weeks on/ one week off (cycle = 4 weeks) or BSC + placebo (P) until progression or unacceptable toxicity. Sample size calculation was based on the logrank test, assuming a one-sided significance of 10%, 80% power, and an improvement in median PFS of 50% (6 to 12 weeks in the REG group). Primary endpoint is PFS. Secondary endpoints are response rate and OS. Results: Between May 2014 and February 2018, 68 (33 REG, 35 P) patients have been included (2 patients died before starting treatment and were replaced). Of 66 patients treated (26 F/ 40 M), tumors were intra-hepatic and hilar (n = 48), extra-hepatic (n = 10) and gallbladder (n = 8). One patient remains on REG treatment. Median PFS for REG is 3.0 months (95% CI: 2.3-4.9) and 1.5 months (95% CI : 1.2-2.0) for P with a HR of 0.48 (95% CI : 0.29-0.80), p = 0.004. Rates of PR+SD are 23/33 (70%) for REG and 11/33 (33%) for P (p = 0,002). Median treatment duration is 10,9 weeks for REG vs 6,3 weeks for P (p = 0,004). Dose reductions were applied in 14/33 patients in REG and in 5/33 patients in P. There is no unexpected/new safety signal. Median OS is 5.3 months for REG and 5.1 months for P (p = 0.21). Conclusions: Regorafenib significantly increases median PFS and tumor control in patients with previously treated metastatic/ unresectable biliary tract cancer. Clinical trial information: NCT02162914.
Risk Factors for Secondary Cancer in a Case-Control Study on 1,259 Patients with Myeloproliferative Neoplasms
Authors: Tiziano Barbui, Arianna Ghirardi, Arianna Masciulli, Alessandra Carobbio, Francesca Palandri, Nicola Vianelli, Valerio De Stefano, Silvia Betti, Ambra Di Veroli, Alessandra Iurlo, Daniele Cattaneo, Federica Delaini, Massimiliano Bonifacio, Luigi Scaffidi, Andrea Patriarca, Elisa Rumi, Clemency Stephenson, Paola Guglielmelli, Elena Maria Elli, Palova Miroslava, Laura Bertolotti, Daniel Erez, Montse Gomez, Kai Wille, Manuel Pérez-Encinas, Francesca Lunghi, Anna Angola Figueras, Maria Laura Fox, Eloise Beggiato, Giulia Benevolo, Giuseppe Carli, Rossella Rosari Cacciola, Mary Frances McMullin, Alessia Tieghi, Valle Recanses Flores, Monia Marchetti, Martin Griesshammer, Alberto Alvarez-Larran, Alessandro M. Vannucchi, Guido Finazzi
Journal: Blood (2018)
Patterns of adjuvant therapy use and survival outcomes in patients with rectal cancer not receiving neoadjuvant therapy in an Australian cohort.
Authors: Kate Jessica Wilkinson, Sharlyn Kang, Stephanie Hui-Su Lim, Cheok Soon Lee, Ray Asghari, Wei Chua, Weng Leong Ng, Hiren A. Mandaliya, Sarah Maloney, James Chen, Elias H. Nasser, Daniel Brungs
Journal: Journal of Clinical Oncology (2019)

675 Background: Consensus international guidelines recommend the use of neoadjuvant chemo-radiotherapy in patients with stage II-III rectal cancer. Despite this, due to factors including inaccurate/under-staging, patient co-morbidities and acute presentations, a proportion will undergo up-front surgical resection. The survival benefit of adjuvant therapy is unclear in this real world, non-trial population. Methods: A retrospective analysis of patients presenting with stage II-III rectal adenocarcinoma in South Western Sydney and Illawarra Shoalhaven Health Districts, Australia, between 2006 to 2015 was performed. Data was extracted from electronic health records, with institutional ethics approval. Treatment modalities, clinicopathological, recurrence and survival data were analyzed. The primary endpoint was overall survival (OS) by treatment modality. Results: 549 patients were identified, of which 295 (54%) underwent up-front surgical resection without neoadjuvant therapy. Of this cohort, 137 (46%) had no adjuvant therapy (Group A), 103 (35%) had adjuvant chemotherapy alone (Group B), and 55 (19%) had adjuvant radiotherapy +/- chemotherapy (Group C). Receipt of any adjuvant treatment was significantly associated with improved OS (5 year OS 56 vs. 79%, HR 0.44, 95% CI 0.3 – 0.6, p &lt; 0.0001) and recurrence free survival (5 yr RFS 25% vs. 47%, HR 0.66, 95% CI 0.5 – 0.9, p=0.01), but not cancer specific survival (5yr CSS 75 vs. 80%, HR 0.78, 95% CI 0.5 – 1.3, p = 0.30). Group B had improved OS compared to Group A (5 yr OS 56% vs. 80%, HR 0.35, 95% CI 0.22 – 0.55, p &lt; 0.0001). There was a trend to improved OS in Group C vs. Group A (5yr OS 56.0% vs. 69.2%, HR 0.79 95% CI 0.6 – 1.01, p = 0.052). The improved OS in Group B versus Group A remained significant in multivariate analysis (HR 0.41, 95% CI 0.22 – 0.77, p = 0.005). Conclusions: Adjuvant chemotherapy improved OS in this real world cohort, and there was a trend to a benefit with adjuvant chemo-radiotherapy. However, the lack of difference in cancer specific survival suggests that this benefit may be partly driven by patient selection bias. Further exploratory analyses to identify sub-groups deriving a cancer specific survival benefit are required.
Using novel real-time tracking to monitor postoperative recovery in a comprehensive cancer center.
Authors: Sharlene Dong, Rachel Barkley, Clancy Clark
Journal: Journal of Clinical Oncology (2019)

250 Background: Early mobilization is thought to be a key component of postoperative care following surgery. However, the benefit of early ambulation is not well studied. Normal and abnormal ambulatory patterns for postoperative cancer patients remains unknown. The aim of the current study is to characterize the postoperative movement patterns of the patients recovering from surgery at Comprehensive Cancer Center using an objective novel real-time location system (RTLS). Methods: In this retrospective cohort study, patient ambulatory movements were captured using RTLS. Clinical data was extracted from the medical record. A custom algorithm was created to measure postoperative ambulation and an ambulatory mobility event was defined as movement in and out of the patient’s room on the postoperative ward lasting from three to 60 minutes. Mobility data was analyzed to determine predictors of postoperative ambulation. Results: 358 postoperative patients (39.7% female, median age 62) were identified for inclusion in this study. 272 (76.0%) patients had a postoperative mobility event. Median number of walks 1.2 (IQR 0.7-2.2) per day was 6.7 (IQR) with median duration of 6.7 (IQR4.6-10.8) minutes. Time to first ambulatory event after surgery was 1.2 (IQR 0.9-2.0) days. Time to first ambulatory events varied by surgical service with Thoracic Surgery having the most patients ambulating on postoperative day zero (43.3%). In univariate analysis, young age, shorter operation length, and surgical service were predictors of early first ambulatory event (all p &lt; 0.05). In multiple variable analysis, young age and surgical service were predictors of early first ambulatory event (all p &lt; 0.05). Conclusions: The current study demonstrates the feasible application of RTLS to passively monitor the recovery of postoperative cancer patients In addition, this technology provides a novel opportunity to correlating patient movement with clinical outcomes, such as morbidity, mortality, and length of stay.
The difference of the gut microbiota of gastric cancer in relation to Helicobacter pylori negativity and positivity.
Authors: Mijin Seol, Yu Ra Lee, Kyung Mi Kim, Cheol Min Shin, Hyuk Yoon, Jae Ho Cho, Dong Jin Song, Nayoung Kim, Young Soo Park, Dong Ho Lee
Journal: Journal of Clinical Oncology (2019)

10 Background: Helicobacter pylori (HP) is a major risk factor for gastric cancer, however, only 1-2% of HP(+) people develop adenocarcinoma. In this study, we have compared the intestinal microbiota composition related to HP status among gastric cancer patient using 16SrRNA gene-based metagenomic sequencing analysis and culture-based method. Methods: Stool samples were collected from 18 gastric cancer patients. 16S rRNA genes were sequenced on the Illumina Miseq platform and further analyzed to evaluate the gut bacterial community. The bacteria strains of fecal sample were isolated in aerobic and anaerobic condition. Results: Metagenomics analysis of fecal sample showed four major phyla; Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria were dominant. Firmicutes were the most dominant phylum. Within this phylum, the relative abundance of Clostridiales including Ruminococcus was higher in the HP(-) group, whereas Lactobacillales including streptococcus was higher in HP(+) group. In addition the relative abundance of Bacteroidetes in HP(-) group and Actinobacteria (especially, genus Bifidobacterium) in HP(+) group was observed highly. In the bacterial culture-based approach, bacteria strains belonged to Clostridiales such as Clostridium perfringens, Ruminococcus feacis, Blautia sp., Coprococcus comes were isolated in HP(-) sample. In HP(+) sample, Klebsiella, Bacteroides, Bifidobacterium were isolated. Bacillus species, Escherichia/Shigella was enriched regardless of HP exist. Streptococcus was not cultivated in HP(+) group, but isolated in HP(-) group in contrast with metagenome data. Conclusions: We found the intestinal bacterial diversity in the HP(+) group was lower than those in the HP(-) and the microbial composition was different between HP(+) and HP(-). Metagenome analysis showed the order Clostridiales of the phylum Firmicutes were enriched in the HP(-) group while the order Lactobacillales (specially, Streptococcus) were enriched in the HP(+) group. Compared to isolates between two groups, bacteria species belonged to the order Clostridiales such as Clostridium, Ruminococcus , Blautia , Coprococcus were cultivated particularly in HP(-) sample.
A designer molecular chaperone against transmissible spongiform encephalopathy slows disease progression in mice and macaques
Authors: Keiichi Yamaguchi, Yuji O. Kamatari, Fumiko Ono, Hiroaki Shibata, Takayuki Fuse, Abdelazim Elsayed Elhelaly, Mayuko Fukuoka, Tsutomu Kimura, Junji Hosokawa-Muto, Takeshi Ishikawa, Minoru Tobiume, Yoshinori Takeuchi, Yutaka Matsuyama, Daisuke Ishibashi, Noriyuki Nishida, Kazuo Kuwata
Journal: Nature Biomedical Engineering (2019)
Abstract P359: Non-Alcoholic Fatty Liver Disease Severity is Associated With Aortic Stiffness Independently From Adiposity and Cardiovascular Risk Factors
Authors: Paulo Harada, Isabela M Bensenor, Alessandra C Goulart, Jose G Mill, Paulo A Lotufo
Journal: Circulation (2018)

Background: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions closely related to adiposity, hypertension, diabetes, and dyslipidemia. NAFLD has been consistently associated with adverse-health cardiovascular outcomes and subclinical atherosclerosis markers. However, there are contradictory findings (most of them with few participants) of the relationship between NAFLD and aortic stiffness: ones describing as an independent association, others as an association mediated by traditional cardiovascular risk factors. Hypothesis: NAFLD presence and severity is associated independently with aortic stiffness. Methods: We addressed this question among civil servants aged 35 to 74 years, 54% of them, women, and free of cardiovascular disease during the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The presence and severity of NAFLD were assessed by ultrasound hepatic attenuation validated with computerized tomography. Aortic stiffness was measured by the carotid-femoral pulse wave velocity (cf-PWV) by a non-invasive certified device (Complior SP). We applied ANOVA to compare the estimated cf-PWVs means and 95% Confidence according to NAFLD categories. These values were adjusted for age, sex, race, waist circumference, diabetes, dyslipidemia, high sensitivity C reactive protein, mean arterial pressure, and use of anti-hypertensive drugs. Results: Among 7,156 participants, 63.5% did not have NAFLD, 22.7% were classified as mild NAFLD, 11.7% as moderate, and 2.1% as severe. An overview of crude means from the absence of NAFLD to severe NAFLD there were slightly older individuals, a higher proportion of men, lower frequency of current smokers, and people with at least or hypertension or diabetes or dyslipidemia. In the fully adjusted analysis, the cf-PWV (m/s) values were similar among subjects with absence of NAFLD [9.27 (9.18 to 9.36)] compared with the presence of either grade of NAFLD [9.24 (9.15, 9.32)(p=0.285)]. However, there was a significant difference between cf-PWV for people without NAFLD [9.23 (9.15, 9.32)] compared with subjects with severe NAFLD [9.51 (9.31, 9.70). A significant high cf-PWV was significant thru NAFLD categories. (p-value for trend=0.045)]. There was no effect modification of this association across age strata, sex, race, waist circumference and body mass index strata, and presence of hypertension, diabetes, and dyslipidemia. Conclusion: In a population of individuals free of cardiovascular disease, NAFLD severity was associated with aortic stiffness regardless of adiposity and the traditional cardiometabolic risk factors.
Cross-cultural validation of a short-form of the Vitiligo Impact Patient scale (VIPs)
Authors: Khaled Ezzedine, Maggi Ahmed, Andrea Tovar-Garza, Carla Hajj, Maxine Whitton, Amit Pandya, Saad Altalhab, Julien Seneschal, John Harris, Charles Taieb
Journal: Journal of the American Academy of Dermatology (2019)
IgEhi Endophenotype in Those with Transient Desensitization after Peanut Oral Immunotherapy
Authors: Alexander R. Eaton, Agustin Calatroni, Huong G. Tang, Yamini V. Virkud, J. Christopher Love, Wayne G. Shreffler, Sarita U. Patil
Journal: Journal of Allergy and Clinical Immunology (2019)
US immigration authorities admit to force feeding detained hunger striking migrants
Authors: Owen Dyer
Journal: BMJ (2019)

US Customs and Immigration Enforcement (ICE) has acknowledged that it is force feeding 10 detainees who are on hunger strike at a facility in El Paso, Texas.

Nine of the detainees are from India, and one is from Nicaragua. One of the detainees, a 22 year old man from India, called the Associated Press (AP) to describe the process.

Three times a day he is removed from his cell and dragged to a bed, where he is strapped down. he …
Mesh study author failed to declare £100 000 from manufacturer
Authors: Gareth Iacobucci
Journal: BMJ (2019)

A senior medical consultant and researcher has acknowledged that he failed to declare £100 000 received from the manufacturer of a type of vaginal mesh implant that he assessed in a 2012 study.1

Mohamed Abdel-Fattah, a consultant urogynaecologist at Aberdeen Maternity Hospital, voluntarily published a correction to the paper on 18 January,2 more than six years after the paper was published. This came after a complaint was made to the General Medical Council about the failure to declare the £100 000 research grant from Coloplast.

The correction statement said, “A review of the funding in relation to this study revealed a further item that was inadvertently omitted from the original disclosure. This study was funded by the Henry Smith Charity. The University of Aberdeen also received a research grant from Coloplast. Coloplast had no input to any aspect of the study …
A retrospective study of a dexamethasone-sparing strategy of preventing acute and delayed emesis caused by CapeOx regimen with aprepitant for colorectal cancer.
Authors: Miho Nakatsuka, Daisuke Sakai, Yasushi Murachi, Naohiro Nishida, Toshihiro Kudo, Akie Kimura, Toru Otsuru, Hidekazu Takahashi, Norikatsu Miyoshi, Naotsugu Haraguchi, Chu Matsuda, Hiroko Kadowaki, Tomoya Yamamoto, Yoshitaka Kuritani, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Yoshihior Miwa, Taroh Satoh
Journal: Journal of Clinical Oncology (2019)

632 Background: CapeOx therapy which is combination with oxaliplatin (L-OHP) and capecitabine is one of the standard treatments for first line chemotherapy for unresectable colorectal cancer, or for postoperative adjuvant chemotherapy for stage III colon cancer. L-OHP-based regimen is classified as moderately emetogenic chemotherapy. In the SENRI trial which we previously conducted as phase III trial, aprepitant, an NK-1 antagonist, showed the efficacy for prevention of emesis against L-OHP. On the other hand, even when in highly emetogenic chemotherapy, it is reported that dexamethasone after day 2 could be spared. Methods: We retrospectively reviewed chemo-naive 94 patients with colorectal cancer who underwent CapeOx therapy at our institution from April 2012 to March 2017. We assessed the relationship between emesis during the first cycle of CapeOx (day1-5) and the use of dexamethasone on day 2-3. Results: 10 patients underwent CapeOx plus bevacizumab, and 84 underwent CapeOx. All patients received 5-HT3 receptor antagonist (palonosetron: 87, granisetron: 7). 50 patients received aprepitant on days 1-3 and dexamethasone on day 1 (APR+D1 group). 22 patients received aprepitant on days 1-3 and dexamethasone on days 1-3 (APR+D3 group). 15 were dexamethasone on days 1-3 without aprepitant (D3 group), and 7 were dexamethasone only on day 1 without aprepitant (D1 group). Acute complete response (CR; no vomiting and no rescue anti-emetics) rates were 100% in any groups. Delayed CR rate was 56% in APR+D1 group, 86% in APR+D3 group, 53% in D3 group, and 29% in D1 group, respectively. In multivariate linear regression with aprepitant, there was a significant difference in presence of dexamethasone (p = 0.028). Conclusions: Acute emesis could be prevented by even only 1-day administration of dexamethasone when combined with the triplet prophylactics. However, in order to sufficiently prevent delayed emesis induced by L-OHP, it was suggested that addition of DEX on days 2 and 3 might be better.