tbuckley/cabot-search huggingface dataset:
NIMG-21. FROM BEYOND THE MARGIN: HIGH ANGULAR RESOLUTION Q-SPACE MRI MAY DETECT GLIOBLASTOMA TUMOR CELL INVASION INTO BRAIN PARENCHYMA
Authors: Owen Leary, Steven Toms, John Zepecki, Derek Merck, Nikos Tapinos, Richard Gilbert
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Invasion of glioblastoma tumor cells beyond the visible margins is hypothesized to mediate tumor spread and recurrence, and thereby affect poor survival. Radiomic biomarkers associated with the extent of tumor infiltration are virtually non-existent. METHODS Seven subjects diagnosed with glioblastoma underwent high resolution “Q-Space” diffusion-weighted MRI sequences (Siemens 3T scanner, 64 gradient directions, b-value=1000s/mm2) during pre-operative MRI workup. For each subject, the largest tumor was manually segmented, and patterns of probabilistic inter-voxel coherence intersecting each segmentation generated as tractograms using DSI Studio (length=0–200mm, AT=30º). Separately, immunodeficient (Nu/J) mice were injected sub-hippocampally with patient-derived glioma stem cells (GSCs) using stereotactic guidance. Two months after injection, mice were sacrificed, resected brains were scanned on a Bruker 7T MRI using cryoprobe with T2-weighted and diffusion-weighted sequences (512 directions), and tumor-intersecting tractography displayed. 3D whole-brain reconstruction of the same xenograft model, stained with anti-human mitochondrial antibody, was performed for comparison. In one patient undergoing resection of fronto-temporal glioblastoma, BrainLab intraoperative navigation was used for stereotactic biopsy of extra-tumor parenchymal samples localized according to proximity to tumor-intersecting tractography. RNA-seq was performed on all samples using Illumina HiSeq2500 by a blinded analyst. RESULTS All human tumors (n=7) displayed region-specific long projecting tracts extending into brain parenchyma (Mean=23.2mm, SD=3.1mm). Maximum tract length varied from 80–130mm (Mean=102mm, SD=20.4mm). Xenograft models displayed similar tumor-intersecting tractography (n=3), with 3D reconstruction of stained GSCs replicating that pattern. RNAseq data revealed significant overrepresentation (≥2-fold) of 528 transcripts in projecting tumor tract-associated samples compared to samples obtained from the tumor mass itself and brain parenchyma unassociated with projecting tumor tracts. Functional classification revealed that 62% of these transcripts regulate cell motility as part of inter-related networks. CONCLUSION These imaging data, backed by region-specific transcriptomic evidence, suggest that Q-Space MRI may discriminate localizable patterns of inter-voxel coherence representing tumor-associated infiltration pathways in glioblastoma.
Single-Nucleotide Polymorphism–Based Genetic Risk Score and Patient Age at Prostate Cancer Diagnosis
Authors: Rong Na, Craig Labbate, Hongjie Yu, Zhuqing Shi, Richard J. Fantus, Chi-Hsiung Wang, Gerald L. Andriole, William B. Isaacs, S. Lilly Zheng, Brian T. Helfand, Jianfeng Xu
Journal: JAMA Network Open (2019)

Few studies have evaluated the association between a single-nucleotide polymorphism-based genetic risk score (GRS) and patient age at prostate cancer (PCa) diagnosis.To test the association between a GRS and patient age at PCa diagnosis and to compare the performance of a GRS with that of family history (FH) in PCa risk stratification.A cohort study of 3225 white men was conducted as a secondary analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) chemoprevention trial, a 4-year, randomized, double-blind, placebo-controlled multicenter study conducted from March 2003 to April 2009 to evaluate the safety and efficacy of dutasteride in reducing PCa events. Participants were confirmed to be cancer free by prostate biopsy (6-12 cores) within 6 months prior to the study and underwent 10 core biopsies every 2 years per protocol. The dates for performing data analysis were from July 2016 to October 2019.A well-established, population-standardized GRS was calculated for each participant based on 110 known PCa risk-associated single-nucleotide polymorphisms, which is a relative risk compared with the general population. Men were classified into 3 GRS risk groups based on predetermined cutoff values: low (<0.50), average (0.50-1.49), and high (≥1.50).Prostate cancer diagnosis-free survival among men of different risk groups.Among 3225 men (median age, 63 years [interquartile range, 58-67 years]) in the study, 683 (21%) were classified as low risk, 1937 (60%) as average risk, and 605 (19%) as high risk based on GRS alone. In comparison, 2789 (86%) were classified as low or average risk and 436 (14%) as high risk based on FH alone. Men in higher GRS risk groups had a PCa diagnosis-free survival rate that was worse than that of those in the lower GRS risk group (χ2 = 53.3; P < .001 for trend) and in participants with a negative FH of PCa (χ2 = 45.5; P < .001 for trend). Combining GRS and FH further stratified overall genetic risk, indicating that 957 men (30%) were at high genetic risk (either high GRS or positive FH), 1667 men (52%) were at average genetic risk (average GRS and negative FH), and 601 men (19%) were at low genetic risk (low GRS and negative FH). The median PCa diagnosis-free survival was 74 years (95% CI, 73-75 years) for men at high genetic risk, 77 years (95% CI, 75 to >80 years) for men at average genetic risk, and more than 80 years (95% CI, >80 to >80 years) for men at low genetic risk. In contrast, the median PCa diagnosis-free survival was 73 years (95% CI, 71-76 years) for men with a positive FH and 77 years (95% CI, 76-79 years) for men with a negative FH.This study suggests that a GRS is significantly associated with patient age at PCa diagnosis. Combining FH and GRS may better stratify inherited risk than FH alone for developing personalized PCa screening strategies.
Correction: An Inhibitor of the Pleckstrin Homology Domain of CNK1 Selectively Blocks the Growth of Mutant KRAS Cells and Tumors
Authors: Martin Indarte, Roisin Puentes, Marco Maruggi, Nathan T. Ihle, Geoffrey Grandjean, Michael Scott, Zamal Ahmed, Emmanuelle J. Meuillet, Shuxing Zhang, Robert Lemos, Lei Du-Cuny, Fabiana I.A.L. Layng, Ricardo G. Correa, Laurie A. Bankston, Robert C. Liddington, Lynn Kirkpatrick, Garth Powis
Journal: Cancer Research (2019)

In the original version of this article (1), the name of the ninth author, Shuxing Zhang, is incorrect. The name has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Transcription Factor Induction of Ectopic Vascular Blood Stem Cell Niches In Vivo
Authors: Elliott J. Hagedorn, Julie R. Perlin, Rebecca J. Freeman, Clara Mao, Inés Fernández-Maestre, Madeleine L. Daily, Christopher R. D'Amato, Samuel J. Wattrus, Tianxiao Han, Michael J. Fairchild, Raquel Riquelme, Brian Li, Shelby E. Redfield, Samantha H. Collins, Asher Lichtig, Song Yang, Yi Zhou, Balvir Kunar, Jesus M Gomez-Salinero, Theresa T. Dinh, Junliang Pan, Karoline Holler, Eugene Butcher, Alexander Van Oudenaarden, Shahin Rafii, Jan Philipp Junker, Leonard I Zon
Journal: Blood (2019)
Abstract 16526: CTRP9-BCL2L13 Interaction Promotes Mitophagy, Protecting Against Myocardial Ischemia/Reperfusion Injury
Authors: Dajun Zhao, Lu Gan, Yue Chen, Dina Xie, Wenjun Yan, Rui guo, Wayne Bond Lau, Yajing Wang, Erhe Gao, Theodore Christopher, Bernard Lopez, Xin L Ma
Journal: Circulation (2017)

Background: Mitochondrial dysfunction and inappropriate mitophagy contribute to myocardial ischemia/reperfusion (MI/R) injury. The cardiokine CTRP9 exerts protective effect against myocardial ische...
<i>JAMA Network Open</i> Celebrates the 2020 New Year
Authors: Frederick P. Rivara, Stephan D. Fihn
Journal: JAMA Network Open (2020)

we will publish new research studies every workday, increasing from our now twice weekly schedule.JAMA Network Open covers over 40 specialties and topics in health, health care, and public health for readers around the world. 1 More than 40% of our submissions are from authors outside the United States, which allows us to meet our goal of publishing research that is relevant in a wide variety of settings.As an open access journal, our content is fully available to people anywhere in the world with an internet connection.We will continue to focus on special themes as well.This past year, we have issued calls for papers on palliative and end of life care, artificial intelligence and machine learning in health care, and the effects of climate change on health.We will issue other calls for specific topics in the coming months.All of these special themes are available to our readers as topic collections on the website.Work published in JAMA Network Open enjoys wide attention from the news media and social media.In 2019, JAMA Network Open had more than 30 000 media mentions, had 9 of the top 10 general medicine open access articles with Altmetric scores, and received more than 6.4 million views and downloads.Thank you for being part of our family of readers and users of the information published here.We look forward to continuing our mission of improving health and health care for people around the globe.We wish you all the best in 2020.
Эффективность рифаксимина в коррекции синдрома избыточного бактериального роста при хронических воспалительных и функциональных заболеваниях кишечника
Authors: Yu.M. Stepanov, N.S. Fedorova, E.V. Zyhalo
Journal: GASTROENTEROLOGY (2019)

Актуальность. Статья посвящена проблеме возникновения синдрома избыточного бактериального роста (СИБР) при хронических воспалительных заболеваниях кишечника (ХВЗК) и синдроме раздраженного кишечника (СРК) и путям его коррекции. Цель: определить частоту возникновения СИБР при болезни Крона (БК), неспецифическом язвенном колите (НЯК) и СРК с диареей и оценить эффективность рифаксимина в коррекции микрофлоры тонкой кишки у больных с данными нозологиями. Материалы и методы. Проведено обследование 62 больных ХВЗК и СРК (27 — с НЯК, 13 — с БК и 22 — с СРК) на наличие СИБР путем выполнения дыхательного водородного теста (ВДТ) с нагрузкой глюкозой. Все больные группы исследования с наличием СИБР в составе комплексной терапии принимали рифаксимин (Альфа Нормикс) в дозе 1200 мг в сутки в течение 10 дней. Эффективность терапии определялась по динамике показателей ВДТ на 10 и 30 день наблюдения. Результаты. СИБР отмечался у 39 пациентов общей группы, из них 24 (61,5 %) человека страдали ХВЗК, СРК с диареей — 15 человек (38,5 %). В группе больных ХВЗК с СИБР преобладали пациенты с НЯК (15 человек; 62,5 %) по сравнению с БК (9 человек; 37,5 %). ВДТ, проведенный через 10 дней от начала лечения рифаксимином у 24 больных ХВЗК и 15 больных СРК с наличием СИБР, был отрицательным у 28 человек (70,9 %), положительным — у 11 (29,1 %). Подобный результат отмечен через 30 дней. СИБР был устранен у 70,9 % больных на фоне приема рифаксимина. Выводы. У большинства пациентов группы исследования (у 60 % — с ХВЗК и 68,1% — с СРК с диареей) был СИБР. Кишечный антисептик рифаксимин продемонстрировал высокую эффективность в коррекции СИБР при НЯК, БК и СРК.
Study of BRAF mutations in melanoma and nevi from patients with germline mutation in the CDKN2A gene
Authors: C. Robert, J. Rouiller, C. Kannengiesser, A. Chompret, M. Avril, P. Dessen, S. Michiels, A. Sarasin, B. Bressac de Paillerets, A. Spatz
Journal: Journal of Clinical Oncology (2006)

10075 Background: Germline mutations in the CDKN2A tumor suppressor gene is a rare condition associated with a high risk of melanoma. Somatic activating mutations of the BRAF gene are frequently observed in cutaneous melanoma (40–60%) but their occurrence vary according to melanoma subtypes (cutaneous, vs mucosal or uveal) and are less frequent in melanoma located on chronically sun-exposed skin. It is thought that melanomas occurring in patients carrier of a CDKN2A germline mutation are associated a second inactivating genetic event in the tumor, facilitating cellular transformation by loss of function this crucial gatekeeper of the G1-S checkpoint. However, the potential role of the MAP-kinase pathway, and more precisely, the involvement of BRAF activation, in this particular population of patients, are still unknown. Thus, our objective was to evaluate the frequency of BRAF somatic mutations in melanoma and nevi developed by patients carrier of a CDKN2A germline mutation. Methods: DNA was extracted from paraffin-embedded tissues of 36 primary melanomas, 9 metastases and 20 nevi from 31 patients with CDKN2A germline mutation. Ten sporadic melanoma from patients harbouring no CDKN2A mutation were also studied as a control population. BRAF mutations were screened by direct sequencing of exon 11 and 15. Results: BRAF mutations (V599E) were found with a significantly lower frequency of 14% (5/36) in melanomas from patients with proven CDKN2A germline mutation, as compared to a frequency of 55% (5/9) in patients with no genetic predisposition (two-sided Fishers exact test, p=0.02). Frequencies of BRAF mutations in metastases and nevi from patients with CDKN2A germline mutation were 33%(3/9) and 10% (2/20) respectively. Conclusions: BRAF mutations seem to be less frequent in melanoma from patients with familial predisposition harbouring CDKN2A germ line mutation than in sporadic melanoma. These results suggest that CDKN2A loss of function gives rise to tumorigenic pathways where genetic events distinct from BRAF activating mutation can induce cell transformation. Additional biological studies are performed on this rare population of melanoma samples in order to better characterize the specificity of cellular transformation in the context of CDKN2A germ line mutation. No significant financial relationships to disclose.
Antibiotic use and colorectal cancer: a causal association?
Authors: Wenjie Ma, Andrew T Chan
Journal: Gut (2019)

Antibiotics have revolutionised our ability to fight infectious diseases that are major causes of morbidity and mortality. However, the widespread use of these powerful agents has led to unintended consequences that reflect their broad effects on microbial community structure. Even short-term antibiotic treatment causes shifts in gut microbiota including, but not limited to, alterations in the abundance of specific taxa and a decrease in overall diversity. Clostridium difficile colitis and vaginal candidiasis are established examples of conditions that originate from gut dysbiosis and opportunistic pathogen colonisation induced by short-term antibiotics. Emerging data also suggest that antibiotic-induced perturbations can persist for years after treatment and contribute to long-term dysregulation of host immune homeostasis.1 In turn, this can potentially increase susceptibility to chronic disorders with an immune basis, including asthma, inflammatory bowel disease and obesity.

Recent epidemiological studies have extended the association between antibiotic exposure and chronic disease to risk of colorectal adenoma and colorectal cancer (CRC).2 In parallel, increasing evidence has demonstrated a pivotal role for the interplay between the gut microbiome and lifestyle factors in initiating and promoting CRC.3 Several species of bacteria have been shown to be potential drivers of carcinogenesis through specific biological mechanisms. For example, Fusobacterium nucleatum expresses adhesins, including FadA and Fap2, which bind to tumour cells and directly promote carcinogenesis by activating oncogenic Wnt/β-catenin signalling and dysregulating immune cell infiltration and antitumour immunity. Enterotoxigenic Bacteroides fragilis forms biofilms in the colonic mucosal membrane, …
Clinical Validation of BASIC Classification for the Resect and Discard Strategy for Diminutive Colorectal Polyps
Authors: Emanuele Rondonotti, Cesare Hassan, Alida Andrealli, Silvia Paggi, Arnaldo Amato, Lucia Scaramella, Alessandro Repici, Franco Radaelli
Journal: Clinical Gastroenterology and Hepatology (2020)
Prospective Trial of Cetuximab Plus Irinotecan for Oxaliplatin and Irinotecan-Based Chemotherapy-Refractory Patients Advanced and/or Metastatic Colorectal Cancer, Evaluation of the Efficacy and Safety Based on Mutation Status of the EGFR Related Genes
Authors: H. Shimodaira, H. Soeda, M. Gamoh, H. Andoh, T. Yamaguchi, M. Watanabe, H. Ishobe, T. Sudo, S. Kato, C. Ishioka
Journal: Annals of Oncology (2012)
Impact of Reductions in Emissions from Major Source Sectors on Fine Particulate Matter–Related Cardiovascular Mortality
Authors: Geoffrey Colin L. Peterson, Christian Hogrefe, Anne E. Corrigan, Lucas M. Neas, Rohit Mathur, Ana G. Rappold
Journal: Environmental Health Perspectives (2020)

Reductions in ambient concentrations of fine particulate matter (PM2.5) have contributed to reductions in cardiovascular (CV) mortality.We examined changes in CV mortality attributed to reductions in emissions from mobile, point, areal, and nonroad sources through changes in concentrations of PM2.5 and its major components [nitrates, sulfates, elemental carbon (EC), and organic carbon (OC)] in 2,132 U.S. counties between 1990 and 2010.Using Community Multiscale Air Quality model estimated PM2.5 total and component concentrations, we calculated population-weighted annual averages for each county. We estimated PM2.5 total- and component-related CV mortality, adjusted for county-level population characteristics and baseline PM2.5 concentrations. Using the index of Emission Mitigation Efficiency for primary emission-to-particle pathways, we expressed changes in particle-related mortality in terms of precursor emissions by each sector.PM2.5 reductions represented 5.7% of the overall decline in CV mortality. Large point source emissions of sulfur dioxide accounted for 6.685 [95% confidence interval (CI): 5.703, 7.667] fewer sulfate-related CV deaths per 100,000 people. Mobile source emissions of primary EC and nitrous oxides accounted for 3.396 (95% CI: 2.772, 4.020) and 3.984 (95% CI: 2.472, 5.496) fewer CV deaths per 100,000 people respectively. Increased EC and OC emissions from areal sources increased carbon-related CV mortality by 0.788 (95% CI: -0.540, 2.116) and 0.245 (95% CI: -0.697, 1.187) CV deaths per 100,000 people.In a nationwide epidemiological study of emission sector contribution to PM2.5-related mortality, we found that reductions in sulfur-dioxide emissions from large point sources and nitrates and EC emissions from mobile sources contributed the largest reduction in particle-related mortality rates respectively. https://doi.org/10.1289/EHP5692.
Predominance of Central Memory T Cells with High T-Cell Receptor Repertoire Diversity is Associated with Response to PD-1/PD-L1 Inhibition in Merkel Cell Carcinoma
Authors: Ivelina Spassova, Selma Ugurel, Patrick Terheyden, Antje Sucker, Jessica C. Hassel, Cathrin Ritter, Linda Kubat, Daniel Habermann, Farnoush Farahpour, Mohammadkarim Saeedghalati, Lukas Peiffer, Rajiv Kumar, David Schrama, Daniel Hoffmann, Dirk Schadendorf, Jürgen C. Becker
Journal: Clinical Cancer Research (2020)

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer, which can be effectively controlled by immunotherapy with PD-1/PD-L1 checkpoint inhibitors. However, a significant proportion of patients are characterized by primary therapy resistance. Predictive biomarkers for response to immunotherapy are lacking.We applied Bayesian inference analyses on 41 patients with MCC testing various clinical and biomolecular characteristics to predict treatment response. Further, we performed a comprehensive analysis of tumor tissue-based immunologic parameters including multiplexed immunofluorescence for T-cell activation and differentiation markers, expression of immune-related genes and T-cell receptor (TCR) repertoire analyses in 18 patients, seven objective responders, and 11 nonresponders.Bayesian inference analyses demonstrated that among currently discussed biomarkers only unimpaired overall performance status and absence of immunosuppression were associated with response to therapy. However, in responders, a predominance of central memory T cells and expression of genes associated with lymphocyte attraction and activation was evident. In addition, TCR repertoire usage of tumor-infiltrating lymphocytes (TILs) demonstrated low T-cell clonality, but high TCR diversity in responding patients. In nonresponders, terminally differentiated effector T cells with a constrained TCR repertoire prevailed. Sequential analyses of tumor tissue obtained during immunotherapy revealed a more pronounced and diverse clonal expansion of TILs in responders indicating an impaired proliferative capacity among TILs of nonresponders upon checkpoint blockade.Our explorative study identified new tumor tissue-based molecular characteristics associated with response to anti-PD-1/PD-L1 therapy in MCC. These observations warrant further investigations in larger patient cohorts to confirm their potential value as predictive markers.
Immunotherapy of experimental melanoma with ICOS-Fc loaded in biocompatible and biodegradable nanoparticles
Authors: Nausicaa Clemente, Elena Boggio, Luca Casimiro Gigliotti, Davide Raineri, Benedetta Ferrara, Gianluca Miglio, Monica Argenziano, Annalisa Chiocchetti, Giuseppe Cappellano, Francesco Trotta, Fabrizio Caldera, Maria Teresa Capucchio, Junji Yagi, Maria Josè Rojo, Filippo Renò, Roberta Cavalli, Chiara Dianzani, Umberto Dianzani
Journal: Journal of Controlled Release (2020)
An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45
Authors: V. Bjelic-Radisic, F. Cardoso, D. Cameron, E. Brain, K. Kuljanic, R.A. da Costa, T. Conroy, E.C. Inwald, S. Serpentini, M. Pinto, J. Weis, O. Morag, G. Lindviksmoen Astrup, K.A. Tomaszweksi, K. Pogoda, P. Sinai, M. Sprangers, N. Aaronson, G. Velikova, E. Greimel, J. Arraras, A. Bottomley, Eveline Bleiker, Brigitte Bliem, Weichu Chie, Carien Creutzberg, Valerie Deville, Francois Duhoux, Kirsten Eilf, Sue Hartup, Michael Koller, Eva Nagele, Ourania Nicolatou-Galitis, Anne Oberguggenberger, Claudia Schmalz, Zoe Winters
Journal: Annals of Oncology (2020)
Corrections to “Waldenström’s macroglobulinaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up”
Authors: E. Kastritis, V. Leblond, M.A. Dimopoulos, E. Kimby, P. Staber, M.J. Kersten, A. Tedeschi, C. Buske
Journal: Annals of Oncology (2018)
Hrqol During Adjuvant Chemotherapy With Capecitabine in Patients After Surgery for Colon Cancer: Additional Study of JFMC37-0801
Authors: Y. Kinugasa, T. Shiroiwa, M. Nakamura, R. Nezu, S. Hazama, T. Fukuda, M. Ishiguro, J. Sakamoto, S. Saji, N. Tomita
Journal: Annals of Oncology (2012)