tbuckley/cabot-search huggingface dataset:
Bone health management in early breast cancer patients: An Italian osteoncology center experience.
Authors: Federica Recine, Alberto Bongiovanni, Valentina Fausti, Laura Mercatali, Nada Riva, Sebastiano Calpona, Marina Faedi, Alessandro De Vita, Chiara Liverani, Chiara Spadazzi, Giacomo Miserocchi, Flavia Foca, Roberto Vespignani, Andrea Rocca, Dino Amadori, Toni Ibrahim
Journal: Journal of Clinical Oncology (2017)

e12055 Background: Bone health evaluation is important for the optimal management of early stage breast cancer (BC) both in post and pre-menopausal setting. Adjuvant endocrine therapy (ET), including luteinizing hormone-releasing hormone (LHRH) analogues with tamoxifen (TAM) and aromatase inhibitors (AI), may affect bone health resulting in a reduction of the bone mineral density (BMD), leading to an increased risk of bone fractures. The objective of this observational study performed at an Italian Osteoncology Center was to evaluate the prevalence of vertebral fractures in pre and post women with BC treated with adjuvant ET. Methods: Data on patients (pts) with early BC were collected from 2011 to 2016 in a single Institution. We investigated the prevalence of vertebral fractures in pre and post pts treated with ET and other potential independent risk factors associated to bone fractures. To evaluate association with bone fractures and clinical factors, univariate logistic models were carried out. P-value of less than 0.05 was considered significant. Results: A total of 1,165 women with early pre and post-menopausal BC were evaluated; for 702 (60.2%) pts treated with ET was available a X-Ray of the spine and they were included in the analysis. The median age was 61 year-old (31-86 y). A total of 124 were pre-menopausal and 578 were post-menopausal pts. Frequency of bone fractures was 17.6% in post-menopausal and, among them, the major risk of bone fractures was associated with AI treatment (OR:4.37, p:0.005); in pre-menopausal pts bone fractures incidence was 6.4% and the major risk was associated to LHRH+AI treatment (OR:2.18, p:0.307). Higher risk of bone fractures was associated with presence of back-pain (OR:1.81, p:0.006), a lower BMD (OR:2.91, p: &lt; 0.001 for pts with BMD≤2.5) and lower level of Vitamin D (OR:2.06, p:0.030 for pts with ≤10) in univariate analysis. Further analysis are ongoing. Conclusions: This Italian experience confirms the importance of bone health evaluation in order to prevent bone fractures in the management of pre and post-menopausal early BC treated with ET.
Occurrence of metachronous basal cell carcinomas: a prognostic model
Authors: H. Smedinga, J.A.C. Verkouteren, E.W. Steyerberg, A. Hofman, T. Nijsten, Y. Vergouwe
Journal: British Journal of Dermatology (2017)

A third of patients with a first basal cell carcinoma (BCC) will develop subsequent (metachronous) BCCs. To study the prognostic effect of the number of previous BCC diagnosis dates a patient has experienced to derive a prediction model to assess the risk of metachronous BCCs that may inform individualized decision making on surveillance. We considered participants of north‐western European ancestry from a prospective population‐based cohort study (Rotterdam Study). After linkage with the Dutch Pathology Registry, 1077 patients with a first BCC were included. Candidate predictors for metachronous BCCs included patient, lifestyle and tumour characteristics. The prognostic model was developed with Fine and Gray regression analysis to account for competing risk of death. We used bootstrapping to correct for within‐patient correlation and statistical optimism in predictive performance. Second to fifth BCCs occurred in 293, 122, 58 and 36 patients, with median follow‐up times of 3·0, 2·1, 1·7 and 1·8 years after the previous BCC, respectively. The risk of a new BCC was higher for patients with more metachronous BCCs. Having more than one BCC at diagnosis was another strong predictor of metachronous BCCs. Discriminative ability of the model was reasonable with an optimism‐corrected c‐index of 0·70 at 3 years. The number of previous BCC diagnosis dates was a strong prognostic factor and should be considered when predicting the risk of metachronous BCCs. When the number of previous BCC diagnosis dates is combined with other readily available characteristics into a prognostic model, patients at high risk of a new BCC can be identified.
Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma
Authors: Apinya Jusakul, Ioana Cutcutache, Chern Han Yong, Jing Quan Lim, Mi Ni Huang, Nisha Padmanabhan, Vishwa Nellore, Sarinya Kongpetch, Alvin Wei Tian Ng, Ley Moy Ng, Su Pin Choo, Swe Swe Myint, Raynoo Thanan, Sanjanaa Nagarajan, Weng Khong Lim, Cedric Chuan Young Ng, Arnoud Boot, Mo Liu, Choon Kiat Ong, Vikneswari Rajasegaran, Stefanus Lie, Alvin Soon Tiong Lim, Tse Hui Lim, Jing Tan, Jia Liang Loh, John R. McPherson, Narong Khuntikeo, Vajaraphongsa Bhudhisawasdi, Puangrat Yongvanit, Sopit Wongkham, Yasushi Totoki, Hiromi Nakamura, Yasuhito Arai, Satoshi Yamasaki, Pierce Kah-Hoe Chow, Alexander Yaw Fui Chung, London Lucien Peng Jin Ooi, Kiat Hon Lim, Simona Dima, Dan G. Duda, Irinel Popescu, Philippe Broet, Sen-Yung Hsieh, Ming-Chin Yu, Aldo Scarpa, Jiaming Lai, Di-Xian Luo, André Lopes Carvalho, André Luiz Vettore, Hyungjin Rhee, Young Nyun Park, Ludmil B. Alexandrov, Raluca Gordân, Steven G. Rozen, Tatsuhiro Shibata, Chawalit Pairojkul, Bin Tean Teh, Patrick Tan
Journal: Cancer Discovery (2017)

Abstract Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters—fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3′ untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein–DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores—mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer. Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes. Cancer Discov; 7(10); 1116–35. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 1047
The Identification of Cells From Induced and Spontaneous Leukoses of Dilute Brown Mice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Lewis, Margaret Reed, Mider, G. Burroughs
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article The Identification of Cells From Induced and Spontaneous Leukoses of Dilute Brown Mice Get access Margaret Reed Lewis, Margaret Reed Lewis research associate Department of Embryology, Carnegie Institution of Washington Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Burroughs Mider G. Burroughs Mider research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 2, October 1941, Pages 115–122, https://doi.org/10.1093/jnci/2.2.115 Published: 01 October 1941
Trends in rates of modified radical mastectomies and bilateral mastectomies in unilateral breast cancer.
Authors: Ajaz Bulbul, Tareq Braik, Sadaf Rashad, Emilio Araujo Mino, Adrianna Bautista, Masoud Khorsand-Sahbaie, Debu Tripathy
Journal: Journal of Clinical Oncology (2017)

569 Background: Women with unilateral breast cancer (BC) without genetic predisposition have a low risk for local and contralateral recurrence with breast conservation surgery (BCS) and adjuvant treatment. We aimed to study the pattern of surgical care across centers in rural New Mexico and its correlation to clinical outcomes. Methods: We retrospectively evaluated 533 patients with Stage 1-3 BC diagnosed between January 1989 to October 2015. Clinical Outcomes with BCS, sentinel lymph node dissection (SLND), simple mastectomy (SM), modified radical mastectomy (MRM) and Bilateral Mastectomy (BM) were studied. Descriptive statistics were performed to describe the proportion of surgery types. Predictors of clinical outcomes were evaluated by multivariate logistic regression. Results: Out of 533 patients, 510 (82%) had early stage (0-3) resectable BC. Among these, 48% (246/510) had either MRM (209/510) or BM (37/510). MRM was performed in 3% of stage 0 (6/209), 23% (49/209) stage I, 46%(97/209) of stage II and 27% (57/209) of Stage III patients. Overall, the rate of SLND was 42% among Early stage Breast cancer. Of 41 patients treated with bilateral mastectomy, 10 were positive for BRCA mutation, 6 for family history and 3 for contralateral disease. Median age of BM was 53 +12 y. The local recurrence rate was 8.8% (45/510), and metastatic recurrence rate was 15.5% (79/510). Lymphedema rate was 9.2% (47/510). Using MRM as reference, the Odds Ratio (OR) for lymphedema after BM and BCT were 2.15 (95% CI, 0.84-5.50) and 0.58 (0.28-1.22), respectively. With 9.6 years of median follow up, the predictive probabilities of lymphedema after BCT, SM, MRM and BM were 1%, 4%, 9% and 18%. The OR for local recurrence in women with BCT were 1.46 (95 th C/I: 0.72-2.95), SM 0.27 (0.03-2.13), BM 2.06 (95 th C/I:0.70-6.06). Conclusions: Less BCT and more aggressive procedures are being performed, and the latter is associated with more lymphedema. No significant differences were noted in local recurrences. Presence of a genetic mutation was not the sole indicator of BM’s in our patient population. There is a need for evidence-based shared decision-making and surgical management of breast cancer, especially in a rural community setting.
Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer.
Authors: Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, Luca Boni
Journal: Journal of Clinical Oncology (2016)

3521 Background: STAR-01 is a randomized phase III trial investigating the effect of adding oxaliplatin (OXA) to preoperative (preop) 5-fluorouracil (FU)-based pelvic chemoradiation (CRT) in patients (pts) with resectable locally advanced rectal cancer (LARC). No benefit from adding OXA could be demonstrated on primary tumor response to preoperative chemoradiation (Aschele, J Clin Oncol, 2011). Methods: Eligibility required a resectable, biopsy-proven rectal adenocarcinoma within 12 cm from the anal verge with radiological evidence of perirectal fat or nodal involvement. Randomization was between infused FU (225 mg/msq/day) concomitant to external-beam pelvic radiation (50.4 Gy in 28 daily fractions) (arm A) or the same regimen + weekly OXA (60 mg/msq x 6) (Arm B). Overall survival (OS) was the primary endpoint (252 deaths required to have a log-rank test with 80% power to detect a 30% reduction in mortality rates at the 5% two-sided significance level). Results: From November 2003 through August 2008, 739 eligible patients were enrolled at 41 Italian institutions. With a median follow up of 8.8 years (IQR 8.1-9.9), 132 and 109 deaths were recorded in Arm A and B, respectively (HR 0.82, CI 0.64-1.06, p=0.126). The corresponding 5 and 10 years OS rates were 77.6 vs 80.4 % and 62.3 vs 67.4 % (Arm A vs B). Preoperative/intraoperative progressions were thrice higher in Arm A (28, vs 10 in Arm B) while recurrences and deaths without recurrence were evenly distributed between the 2 arms (83/81 and 14/19 in Arm A/B, respectively). The corresponding event-free survival rates were 70.6 vs 74.2 % and 66.3 vs 69.2 % in Arm A vs B, at 3 and 5 years, respectively (HR 0.89, CI 0.69-1.15, p=0.374). Conclusions: This study did not meet its primary endpoint of a 30% reduction in mortality rates. The observed differences are consistent with a more limited impact on OS and warrants further investigation with pooled analyses of similar studies investigating OXA added to FP-based preop CRT. The large reduction in the number of early progressions is coherent with an effect of OXA on micrometastatic disease but was not paralleled by an improvement in recurrences after surgery.
Cryptic t(3;8)(q27;q24) and/or MYC-BCL6 linkage associated with MYC expression by immunohistochemistry is frequent in multiple-hit B-cell lymphomas
Authors: H Ohno, M Nakagawa, C Kishimori, K Fukutsuka, G Honjo
Journal: Blood Cancer Journal (2017)

Cryptic  t (3;8)(q27;q24) and/or MYC-BCL6 linkage associated with MYC expression by immunohistochemistry is frequent in multiple-hit B-cell lymphomas
Influence of Genetic Modifiers on Levels of Invariant Natural Killer T-Cells in Patients with Sickle Cell Anemia
Authors: Ahmed Al-Yarabi, Tahar Al-Shabibi, Nasser Ambu-Ali, Shoaib Al-Zadjali, Abeer Al-Zubaidi, Murtadha K. Al-Khabori, Mohammed Al-Huneini, Salam Al-Kindi, Yasser Wali, Mohamed-Rachid Boulassel
Journal: Blood (2016)
Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen inKRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study
Authors: B. Schultheis, D. Reuter, M.P. Ebert, J. Siveke, A. Kerkhoff, W.E. Berdel, R. Hofheinz, D.M. Behringer, W.E. Schmidt, E. Goker, S. De Dosso, M. Kneba, S. Yalcin, F. Overkamp, F. Schlegel, M. Dommach, R. Rohrberg, T. Steinmetz, M. Bulitta, D. Strumberg
Journal: Annals of Oncology (2017)
Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis
Authors: Jan Gaertner, Waldemar Siemens, Joerg J Meerpohl, Gerd Antes, Cornelia Meffert, Carola Xander, Stephanie Stock, Dirk Mueller, Guido Schwarzer, Gerhild Becker
Journal: BMJ (2017)

<b>Objective</b>&nbsp;To assess the effect of specialist palliative care on quality of life and additional outcomes relevant to patients in those with advanced illness. <b>Design</b>&nbsp;Systematic review with meta-analysis. <b>Data sources</b>&nbsp;Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and trial registers searched up to July 2016. <b>Eligibility criteria for selecting studies</b>&nbsp;Randomised controlled trials with adult inpatients or outpatients treated in hospital, hospice, or community settings with any advanced illness. Minimum requirements for specialist palliative care included the multiprofessional team approach. Two reviewers independently screened and extracted data, assessed the risk of bias (Cochrane risk of bias tool), and evaluated the quality of evidence (GRADE tool). <b>Data synthesis</b>&nbsp;Primary outcome was quality of life with Hedges’ g as standardised mean difference (SMD) and random effects model in meta-analysis. In addition, the pooled SMDs of the analyses of quality of life were re-expressed on the global health/QoL scale (item 29 and 30, respectively) of the European Organization for Research and Treatment of Cancer QLQ-C30 (0-100, high values=good quality of life, minimal clinically important difference 8.1). <b>Results</b>&nbsp;Of 3967 publications, 12 were included (10 randomised controlled trials with 2454 patients randomised, of whom 72% (n=1766) had cancer). In no trial was integration of specialist palliative care triggered according to patients’ needs as identified by screening. Overall, there was a small effect in favour of specialist palliative care (SMD 0.16, 95% confidence interval 0.01 to 0.31; QLQ-C30 global health/QoL 4.1, 0.3 to 8.2; n=1218, six trials). Sensitivity analysis showed an SMD of 0.57 (−0.02 to 1.15; global health/QoL 14.6, −0.5 to 29.4; n=1385, seven trials). The effect was marginally larger for patients with cancer (0.20, 0.01 to 0.38; global health/QoL 5.1, 0.3 to 9.7; n=828, five trials) and especially for those who received specialist palliative care early (0.33, 0.05 to 0.61, global health/QoL 8.5, 1.3 to 15.6; n=388, two trials). The results for pain and other secondary outcomes were inconclusive. Some methodological problems (such as lack of blinding) reduced the strength of the evidence. <b>Conclusions</b>&nbsp;Specialist palliative care was associated with a small effect on QoL and might have most pronounced effects for patients with cancer who received such care early. It could be most effective if it is provided early and if it identifies though screening those patients with unmet needs. <b>Systematic review registration</b>&nbsp;PROSPERO CRD42015020674.
Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study
Authors: Morten Gersel Stokholm, Alex Iranzo, Karen Østergaard, Mónica Serradell, Marit Otto, Kristina Bacher Svendsen, Alicia Garrido, Dolores Vilas, Per Borghammer, Joan Santamaria, Arne Møller, Carles Gaig, David J Brooks, Eduardo Tolosa, Nicola Pavese
Journal: The Lancet Neurology (2017)
Serum Albumin Levels As a Predictor of Post-Operative Complications in Patients Undergoing Upper Gastrointestinal Surgery
Authors: RS Prichard, BJ Manning, A Ryan, S Rowley, N Ravi, J Reynolds
Journal: Endoscopy (2006)

Introduction: In surgical patients, hypoalbuminaemia has been demonstrated to be associated with poor outcome and an increase in both morbidity and mortality. This study determined whether albumin levels on the first post-operative day were a reliable indicator of patient morbidity and mortality.
Abstract 357: Branched-Chain Amino Acid Metabolic Reprogramming in Heart Failure
Authors: Haipeng Sun, Kristine Olson, Meiyi Zhou, Domenick Prosdocimo, Chen Gao, Zhihua Wang, Darwin Jeyaraj, Ji-Youn Youn, Shuxun Ren, Ching-Pin Chang, Hua Cai, Peipei Ping, Christian Schulze, Christopher Lynch, Mukesh Jain, Yibin Wang
Journal: Circulation Research (2013)

Metabolic remodeling is an integral part of heart failure. Current studies are largely focusing on glucose and fatty acid metabolism, while little is known about the changes in amino acid homeostasis during heart failing process. Branched chain amino acids (BCAAs), including leucine, isoleucine, and valine, serve as not only essential building blocks for protein synthesis, but also important energy source and signaling molecules that have significant effects on cell growth and function. In this study, we demonstrated that the BCAA catabolic intermediate branched-chain keto acid (BCKA) accumulated in both mouse and human failing heart. BCAA catabolic genes were selectively and significantly down-regulated at both mRNA and protein levels in failing heart in mice, mimicking a similar expression pattern observed in neonatal heart. Using both in vitro and in vivo models, we established that BCAA catabolic genes were regulated by Krüppel-like factor 15 (KLF15), a key transcriptional regulator for glucose, fat, and amino acid nutrient homeostasis, suggesting that the KLF15-mediated BCAA catabolic regulation is part of the metabolic remodeling during heart failure. Genetic ablation of PP2Cm, a key regulator of BCAA catabolism, led to a significant impairment of BCAA catabolic activities and accumulation of BCKA in cardiac tissue. Importantly, PP2Cm deficiency accelerated heart failure under pressure overload. PP2Cm deficiency or elevated BCKA induced oxidative stress in cardiomyocytes and impairment of oxygen consumption and ATP production of mitochondria. Antioxidant treatment ameliorated the heart failure progression in PP2Cm deficient animals. Taken together, our data established for the first time that BCAA catabolic reprogramming is an integral component of metabolic remodeling during heart failure, and this remodeling can significantly contribute to heart failure progression.
Genomics of Adaptation Depends on the Rate of Environmental Change in Experimental Yeast Populations
Authors: Florien A. Gorter, Martijn F.L. Derks, Joost van den Heuvel, Mark G.M. Aarts, Bas J. Zwaan, Dick de Ridder, J. Arjan G.M. de Visser
Journal: Molecular Biology and Evolution (2017)

The rate of directional environmental change may have profound consequences for evolutionary dynamics and outcomes. Yet, most evolution experiments impose a sudden large change in the environment, after which the environment is kept constant. We previously cultured replicate Saccharomyces cerevisiae populations for 500 generations in the presence of either gradually increasing or constant high concentrations of the heavy metals cadmium, nickel, and zinc. Here, we investigate how each of these treatments affected genomic evolution. Whole-genome sequencing of evolved clones revealed that adaptation occurred via a combination of SNPs, small indels, and whole-genome duplications and other large-scale structural changes. In contrast to some theoretical predictions, gradual and abrupt environmental change caused similar numbers of genomic changes. For cadmium, which is toxic already at comparatively low concentrations, mutations in the same genes were used for adaptation to both gradual and abrupt increase in concentration. Conversely, for nickel and zinc, which are toxic at high concentrations only, mutations in different genes were used for adaptation depending on the rate of change. Moreover, evolution was more repeatable following a sudden change in the environment, particularly for nickel and zinc. Our results show that the rate of environmental change and the nature of the selection pressure are important drivers of evolutionary dynamics and outcomes, which has implications for a better understanding of societal problems such as climate change and pollution.
Preterm and low weight births rise again in the US
Authors: Janice Hopkins Tanne
Journal: BMJ (2017)

The number of preterm births, the leading cause of death for newborn babies in the US, has risen for the second year after declines over the past seven years. The low birth weight rate also increased for the second year, according to the annual report from the National Center for Health Statistics.1

US preterm birth rates rose from 9.63% in 2015 to 9.84% in 2016. The low birth weight rate increased from 8.07% in 2015 to 8.16% in 2016. Both rates had declined between 2007 and 2014.

Proposed cuts to Medicaid, which pays for about half of all US births,2 would mean that 6.5 million women of childbearing age would lose health insurance …