tbuckley/cabot-search huggingface dataset:
House Dust Endotoxin Association with Chronic Bronchitis and Emphysema
Authors: Angelico Mendy, Päivi M. Salo, Richard D. Cohn, Jesse Wilkerson, Darryl C. Zeldin, Peter S. Thorne
Journal: Environmental Health Perspectives (2018)

Endotoxin has been reported to be associated with chronic bronchitis or emphysema (CBE) at high occupational exposures. However, whether levels found in domestic environments have similar effects is unknown.We aimed to study the association between house dust endotoxin and CBE in a sample representative of the U.S. population.We analyzed data from 3,393 participants ≥20 y old from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. House dust from bedding and from bedroom floors was analyzed for endotoxin content. NHANES participants received questionnaires and underwent examination as well as extensive laboratory testing. Logistic regression was used to examine the association of endotoxin levels with CBE diagnosis and symptoms, adjusting for covariates. The survey design and weights were applied so that estimates were nationally representative and so that statistical inferences were made appropriately.The median endotoxin concentration in house dust was 14.61 EU/mg dust, and CBE was reported by 8.2% of participants. In the adjusted analysis, one unit (EU/mg) increase in log10-transformed endotoxin concentrations was associated with a 27% increase in the odds of CBE diagnosis [OR=1.27 (95% CI: 1.00, 1.61)] and a 78% increase in the odds of chronic bronchitis symptoms (defined as cough and phlegm for ≥3 mo in a year for ≥2 y) [OR=1.78 (95% CI: 1.01, 3.12)]. Sensitization to inhalant allergens (p=0.001) modified the relationship between endotoxin and CBE diagnosis, with stronger associations observed in sensitized participants [OR=2.46 (95% CI: 1.72, 3.50) for a unit increase in log10-endotoxin].In a population-based sample of U.S. adults, endotoxin levels in homes were associated with a self-reported history of CBE diagnosis and chronic bronchitis symptoms, with stronger associations among people sensitized to inhalant allergens. https://doi.org/10.1289/EHP2452.
Mechanisms of receptor tyrosine kinase activation in cancer
Authors: Zhenfang Du, Christine M. Lovly
Journal: Molecular Cancer (2018)

Receptor tyrosine kinases (RTKs) play an important role in a variety of cellular processes including growth, motility, differentiation, and metabolism. As such, dysregulation of RTK signaling leads to an assortment of human diseases, most notably, cancers. Recent large-scale genomic studies have revealed the presence of various alterations in the genes encoding RTKs such as EGFR, HER2/ErbB2, and MET, amongst many others. Abnormal RTK activation in human cancers is mediated by four principal mechanisms: gain-of-function mutations, genomic amplification, chromosomal rearrangements, and / or autocrine activation. In this manuscript, we review the processes whereby RTKs are activated under normal physiological conditions and discuss several mechanisms whereby RTKs can be aberrantly activated in human cancers. Understanding of these mechanisms has important implications for selection of anti-cancer therapies.
ACTR-56. A 2-PART SAFETY AND EXPLORATORY EFFICACY RANDOMISED DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF A 1:1 RATIO OF CANNABIDIOL AND DELTA-9-TETRAHYDROCANNABINOL (CBD:THC) PLUS DOSE-INTENSE TEMOZOLOMIDE IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME (GBM)
Authors: Susan C Short, Christian Little
Journal: Neuro-Oncology (2017)

Plant-derived cannabinoids have shown efficacy in GBM animal models when co-administered with TMZ. Activation of an endoplasmic reticulum stress-related signalling route promotes autophagy and the pro-apoptotic and anti-tumoural action of THC. CBD reduces the anxiogenic and psychoactive effects of THC. A 2-part study in first recurrent GBM patients following standard chemo-radiotherapy. Part 1: 6 patients received a maximum tolerated dose of CBD:THC oromucosal spray, adjunctive to dose-intense TMZ, to assess the safety of the combination. Part 2: patients receiving dose-intense TMZ were randomised to CBD:THC (12) or placebo (9). Part 1: no grade IV AE’s by CTC occurred, therefore Part 2 commenced. Part 2: in both treatment groups, mean age was 58 years and median baseline Karnofsky was 90. Median time from recurrent diagnosis to treatment initiation was 3.6 weeks in the CBD:THC group and 3.0 weeks in the placebo group. Median days dosed were 155 days [range: 50–356] for CBD:THC and 134 days [range: 13–359] for placebo. Multiple dosing with CBD:THC showed no drug-drug interaction (DDI) with TMZ. Geometric means for Cmax (CV%) were 4540 ng/mL (40%) and 4340 ng/mL (25%) for TMZ and TMZ plus CBD:THC, and for AUC0-6 were 13100 ng.h/mL (20%) and 12600 ng.h/mL (12%) for TMZ and TMZ plus CBD:THC. Similarly, there was no detectable effect on AIC, a downstream product of the primary active metabolite MTIC. Vomiting (12/18) and dizziness (11/18) were the most frequent treatment-emergent AE’s for CBD:THC patients. One year survival was 83% after CBD:THC exposure compared with 44% for placebo (p = 0.042); placebo data are consistent with the DIRECTOR Trial (Weller, 2015). Results of biomarker analyses are pending. The combination appeared safe and well tolerated with no evidence of a DDI with TMZ. CBD:THC offers some efficacy in recurrent GBM and warrants further study.
ENDOSCOPIC TREATMENT OF DELAYED FOREIGN BODY ESOPHAGEAL PERFORATION
Authors: OV Hernández Mondragón, D Espinosa Saavedra, JM Blancas Valencia, LA Lopez Valenzuela
Journal: Endoscopy (2018)

This is the case of a 61 years-old male whit a past medical history of type 2 diabetes, systemic arterial hypertension and ischemic hearth disease on medical treatment and well controlled.
Treatment patterns and clinical outcomes in high‐risk newly diagnosed multiple myeloma patients carrying the 17p deletion: An observational multi‐center retrospective study
Authors: Yael C. Cohen, Avi Saranga, Moshe E. Gatt, Noa Lavi, Chezi Ganzel, Hila Magen, Irit Avivi, Tamar Tadmor, Celia Suriu, Osnat Jarchowsky Dolberg, Amitai Papushado, Svetlana Trestman, Ron Ram
Journal: American Journal of Hematology (2018)

Abstract Del17p is a genomic imbalance occurring in ∼7%‐10% of myeloma at diagnosis newly diagnosed myeloma patients (NDMM) and comprises a poor prognostic factor. The goal of this study is to analyze real world data and outcomes among NDMM patients carrying 17p deletion. We report an observational, retrospective, multicenter study. Sixty consecutive patients diagnosed with multiple myeloma in the 8 participating centers diagnosed between 1/2008 and 1/2016 proven to carry 17p deletion by means of fluorescence in situ hybridization (FISH) were identified. Most received a bortezomib‐based induction, over half underwent autologous hematopoietic cell transplantation (HCT); 30% of the patients gained early access to new novel agents via clinical trials, access programs or private insurance. Overall response rate (ORR) after induction was 85%; 94% for transplant eligible (TE); and 75% for transplant ineligible (NTE), and declined in subsequent treatment lines, 64% achieved ≥ VGPR. Median overall survival (OS) was 43 months; median progression free survival (PFS) was 11 months, 19 months for TE and 7 for NTE. In multivariate analysis: higher M‐Spike, presence of extramedullary disease, and &gt;50% of cells baring del17p were associated with adverse PFS; Autologous HCT and higher hemoglobin were associated with longer PFS; OS was 59 months for patients with early access to newer agents. Older age and higher M‐Spike levels were associated with adverse OS, Autologous HCT was associated with favorable OS, 59.7 vs 28.7 months for NTE patients. Despite the improvement achieved with autologous HCT and new novel agents, the prognosis of patients with 17p deletion is still inferior, emphasizing the need for novel approaches.
Blockade of TNF receptor superfamily 1 (TNFR1)–dependent and TNFR1-independent cell death is crucial for normal epidermal differentiation
Authors: Xuehua Piao, Ryosuke Miura, Sanae Miyake, Sachiko Komazawa-Sakon, Masato Koike, Ryodai Shindo, Junji Takeda, Akito Hasegawa, Riichiro Abe, Chiharu Nishiyama, Tetsuo Mikami, Hideo Yagita, Yasuo Uchiyama, Hiroyasu Nakano
Journal: Journal of Allergy and Clinical Immunology (2018)
COMPARATIVE STUDY OF RADIATION PROCTITIS IN PROSTATE CANCER TREATED WITH CYBERKNIFE THERAPY AND CONVENTIONAL RADIOTHERAPY
Authors: EK Kang, HJ Kim, JW Choi, HC Jung, SB Ji, CM Lee, HC Jo, HJ Kim, TH Kim, WT Jung, OJ Lee, CY Ha
Journal: Endoscopy (2018)

Radiation proctitis (RP) is a common complication after pelvic radiation therapy (RT). RT could cause damage to the around tissue depending on the total dose of radiation or the therapeutic range of radiation. CyberKnife is known to have less effects on surrounding tissues and low complication rate compared with conventional RT. In this study, we evaluated the effects of CyberKnife and conventional RT in prostate cancer patients with RP.
Correlation of BMAL1 expression in colorectal cancer with resistance to anti-VEGFA therapy with bevacizumab.
Authors: Elke Burgermeister, Fagr Eladly, Wen Wu, Nadine Schulte, Johannes Betge, Nicolai Hartel, Timo Gaiser, Alexander Marx, Christel Weiss, Ralf Hofheinz, Ian S. Miller, Annette T. Byrne, Matthias Philip Ebert
Journal: Journal of Clinical Oncology (2018)

705 Background: Mechanisms underlying failure of colorectal cancer (CRC) patients to respond to anti-vascular endothelial growth factor A (VEGFA) therapy with bevacizumab in combination with chemotherapy are largely unknown, and novel predictive markers required. Methods: Tumours from patients/mice and CRC cell lines were analysed by IHC, PCR, EMSA, ChIP, ELISA and Western blot. Statistics of (pre)clinical data was calculated with SAS and Graphpad Prism. Response outcomes including progression-free survival (PFS) and restaging according to RECIST (PR/SD/PD) were analyzed. Results: Circadian rhythm transcription factor and heme receptor REVERBA and its target gene BMAL1 promoted binding to and activation of the -700kB RORE DNA-element in the VEGFA promoter resulting in increased VEGFA mRNA expression and VEGFA protein secretion from human CRC cell lines. Conversely, REVERBA siRNA and its antagonist (Fe3+) hemin inhibited VEGFA synthesis. In C57BL/6J Apcmin/+ mice treated with murinized VEGFA Ab (n=11 mu_chimeric_B20-4.1 vs. n=42 mock; 10 mg/kg*week; i.p.; 4 weeks), Vegfa mRNA was reduced, as was incidence (*p=0.0411 Fisher Exact Test) and multiplicity (*p=0.0157 Cochran Armitage Trend Test) of vascularized CRCs. However, Bmal1 mRNA was up-regulated, and high BMAL1 protein expression in tumor cells positively correlated with Ki67+ proliferation (n=3 B20 vs. n=3 mock; *p&lt;0.05 t-test) in treated Apcmin/+ CRCs. BMAL1 protein was also induced in xenografts from BALB/c nude mice s.c. implanted with the human CRC cell line HCT116 and treated with humanized VEGFA Ab (n=4 bevacizumab vs. n=4 vehicle; 10 mg/kg*week; i.p.; 3 weeks; *p&lt;0.05 t-test). In CRC patients, high BMAL1 protein expression in tumor cells was associated with clinical non-response to bevacizumab (n=15 SD vs. n=29 PD: BMAL1- vs. BMAL1+, *p=0.0061 Cochran Armitage Trend Test,*p=0.0130 Fisher Exact Test) and reduced PFS (BMAL1- [671 days] vs. BMAL1+ [368 days], *p=0.0030 log rank test, HR=0.4792 [95%CI 0.3103-0.7871], n=74). Conclusions: BMAL1 may represent a predictive marker for bevacizumab non-response. Due to its drugability, the REVERBA-BMAL1-VEGFA axis may be a potential target to prevent resistance to anti-angiogenic therapy in CRC.
Geriatric Nutritional Risk Index as a prognostic factor in patients with esophageal squamous cell carcinoma –retrospective cohort study
Authors: Ippei Yamana, Shinsuke Takeno, Hideki Shimaoka, Kanefumi Yamashita, Teppei Yamada, Hironari Shiwaku, Tatsuya Hashimoto, Yuichi Yamashita, Suguru Hasegawa
Journal: International Journal of Surgery (2018)
Vaccination Strategies During Shortages of Yellow Fever Vaccine—Reply
Authors: Lin H. Chen, Davidson H. Hamer
Journal: JAMA (2018)

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Near-Infrared Sentinel Lymph Node Identification in Non–Small Cell Lung Cancer
Authors: Christopher S. Digesu, Kathleen D. Weiss, Yolonda L. Colson
Journal: JAMA Surgery (2018)

This Surgical Innovation describes sentinal lymph node mapping with near-infrared imaging to target the first tumor-draining lymph node for sampling and for in-depth pathologic analysis in non–small cell lung cancer.
Lymphocyte changes and vaccination response in a child exposed to belimumab during pregnancy
Authors: Helle Bitter, Anne Noraas Bendvold, Monika Elisabeth Østensen
Journal: Annals of the Rheumatic Diseases (2018)

Apart from animal studies,1 no human studies exist to document the transfer of belimumab (BEL) to the fetus and immunological alterations caused in the neonate.2 We report the case of a mother treated with BEL for systemic lupus erythematosus (SLE) both before and during pregnancy and present the immunological changes observed in the child at birth and during 7 months of follow-up.

A 29-year-old woman with SLE from 2005 with arthritis and lupus skin disease. During her first pregnancy in 2005–2006, she had a severe flare of lupus with pericarditis and glomerulonephritis, hypertension and premature delivery at week 33. She recovered under therapy with prednisone, azathioprine (AZA; started after a normal thiopurine S-methyltransferase (TPMT) gen test) and hydroxychloroquine (HCQ), and experienced no relapse of lupus nephritis under continued triple therapy.

In 2013, she developed severe lupus skin disease …
Abstract 13000: Physical Activity is Associated With Reduced Left Ventricular Mass Index in Blacks: Insights From the Genetic Epidemiology Network of Arteriopathy (GENOA) Study
Authors: Daisuke Kamimura, Takeki Suzuki, Wanmei Wang, Thomas H Mosley, Kenneth R Butler, Michael E Hall
Journal: Circulation (2016)

Background: Physical activity (PA) has been associated with decreased left ventricular hypertrophy (LVH) in some clinical studies, however factors which influence this relationship have yet to be clarified. Blacks are disproportionately affected by cardiac diseases including LVH, partly due to higher rates of hypertension and obesity. Because other factors may also play a role, we investigated clinical factors that may affect the relationship between PA and LVH in blacks. Methods and Results: We evaluated 1314 black participants with preserved LV ejection fraction (EF&gt;50%) from the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.4 years, 73% women). LV mass index (LVMI) was calculated from echocardiography using the Devereux formula and indexed by height 2.7 . Total hours of PA per day (TPA hours) were assessed by self-report. The relationship between TPA hours and LVMI was evaluated by generalized estimating equation (GEE) with identity link, and adjusted for possible confounders. The effect of TPA hours on LVMI by age group, sex, body mass index (BMI), history of hypertension, diabetes or coronary heart disease, estimated glomerular filtration rate and current smoking status were plotted. After adjustment for these factors, longer TPA hours were independently associated with lower LVMI (p&lt;0.05). There were significant interactions between TPA hours and obesity (BMI≥30), and history of hypertension on LVMI (p for interaction &lt;0.05, for both, Figure). Longer TPA hours were associated with lower LVMI more in obese or hypertensive participants compared to non-obese or non-hypertensive participants. Conclusions: More PA was associated with lower LVMI in blacks. The protective effect of PA against LVH was present in obese and hypertensive black participants illustrating the importance of recommending increasing PA to prevent LVH and potentially reduce the risk of heart failure.
Expression levels of long non-coding RNAs are prognostic for AML outcome
Authors: Arvind Singh Mer, Johan Lindberg, Christer Nilsson, Daniel Klevebring, Mei Wang, Henrik Grönberg, Soren Lehmann, Mattias Rantalainen
Journal: Journal of Hematology & Oncology (2018)

Long non-coding RNA (lncRNA) expression has been implicated in a range of molecular mechanisms that are central in cancer. However, lncRNA expression has not yet been comprehensively characterized in acute myeloid leukemia (AML). Here, we assess to what extent lncRNA expression is prognostic of AML patient overall survival (OS) and determine if there are indications of lncRNA-based molecular subtypes of AML. We performed RNA sequencing of 274 intensively treated AML patients in a Swedish cohort and quantified lncRNA expression. Univariate and multivariate time-to-event analysis was applied to determine association between individual lncRNAs with OS. Unsupervised statistical learning was applied to ascertain if lncRNA-based molecular subtypes exist and are prognostic. Thirty-three individual lncRNAs were found to be associated with OS (adjusted p value < 0.05). We established four distinct molecular subtypes based on lncRNA expression using a consensus clustering approach. LncRNA-based subtypes were found to stratify patients into groups with prognostic information (p value < 0.05). Subsequently, lncRNA expression-based subtypes were validated in an independent patient cohort (TCGA-AML). LncRNA subtypes could not be directly explained by any of the recurrent cytogenetic or mutational aberrations, although associations with some of the established genetic and clinical factors were found, including mutations in NPM1, TP53, and FLT3. LncRNA expression-based four subtypes, discovered in this study, are reproducible and can effectively stratify AML patients. LncRNA expression profiling can provide valuable information for improved risk stratification of AML patients.
Abstract 12717: Changing Frequencies, Outcomes and Costs for Ischemic Strokes (ISs), Subarachnoid Hemorrhages (SAHs) and Other Hemorrhagic Strokes (OHSs), 2006-2013
Authors: Darryl T Gray, Anne M McLeod
Journal: Circulation (2016)

Background: While ISs, SAHs and OHSs differ in many key aspects, their results are combined in some reported statistics. Methods: For ICD-9-CM principal discharge (D/C) diagnosis codes of 430 (SAH), 431-432 (OHS) and 433-434 (IS), we estimated US nationwide adult stroke frequencies and outcomes using data from the Healthcare Cost and Utilization Project (HCUP). HCUP’s sampling frame captured ~90% of D/Cs from non-Federal acute care hospitals for 2006, and 95+% of such D/Cs by 2013. Data based on HCUP’s Nationwide/al Inpatient Sample (a stratified sample of 20% of HCUP hospital D/Cs) came from the HCUPnet on-line query system. Results: There were 653,429 adult stroke D/Cs (290.1/100,000) in 2006. Among ISs (82.0% of all cases), 4.4% died as inpatients, 49.3% were routine D/Cs and the rest (46.3%) went to other care settings. Mean length of stay (MLOS) was 4.8 days. Mean hospital costs (not charges) in 2015 US $ were $11,639/case. Among SAHs (4.1%), inpatient mortality was 23.1% and 35.2% were routine D/Cs. MLOS was 12.3 days. Mean costs were $48,533. Among OHSs (13.9%), 24.3% died as inpatients and 24.3% were routine D/Cs. MLOS was 7.8 days. Mean costs were $20,206. There were 684,620 adult cases (281.9/100,000) in 2013. Among ISs (82.3%), 3.7% died as inpatients; 44.9% were routine D/Cs. MLOS was 4.4 days. Mean costs were $12,101. Among SAHs (3.6 %), mortality was 19.6%; 38.0% were routine D/Cs. MLOS was 11.8 days. Mean costs were $53,202. Among OHSs (14.0%), mortality was 20.3%; 23.7% were routine D/Cs. MLOS was 7.1 days. Mean costs were $19,862. Each year in all stroke types, 85+ year olds had the highest incidence and mortality, especially compared to 18-44 YOs. Rankings by mean LOS and mean costs/case varied by age across stroke types. Discussion: Overall and age-specific incidence rates by stroke type changed slightly over time. Adult inpatient mortality and LOS fell for all types. Mean inflation-adjusted costs generally rose, implying increasing mean costs/day. Total aggregate costs (which do not include most rehabilitation costs) rose from $9.4 to 10.0 billion / year. ISs accounted for most cases. However, lower incidence rates, worse outcomes and higher resource use seen in OHSs and especially SAHs relative to ISs argue for separate tracking of stroke type results.
On Seeing Your Obituary in the Newspaper
Authors: Elizabeth Lahti
Journal: Annals of Internal Medicine (2018)

Ad Libitum3 April 2018On Seeing Your Obituary in the NewspaperElizabeth Lahti, MDElizabeth Lahti, MDOregon Health & Sciences University, Portland, Oregon (E.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-2708 Audio Reading - “On Seeing Your Obituary in the Newspaper” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "On Seeing Your Obituary in the Newspaper," by E. Lahti. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It's Sunday morning coffee and wafflesa newspaper folds open, I glanceand tie the small cleatsuddenly thrust upon my thighYou look up at me inblack and white, but I knowyour eyes are blueI never knew you with hairChipped dishes clatterin a syrup sticky sinkI tie the other cleatsend him to brush his teethWe would have been friends, you and Irolling our eyes over stacks of laundryhusbands who forget,bad calls on the sidelineI remember the way your scarf cradled your scalpthe way you tilted your head and asked how long?and sugar... Author, Article, and Disclosure InformationAffiliations: Oregon Health & Sciences University, Portland, Oregon (E.L.)Current Author Address: Elizabeth Lahti, MD; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “On Seeing Your Obituary in the Newspaper” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "On Seeing Your Obituary in the Newspaper," by E. Lahti. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 3 April 2018Volume 168, Issue 7Page: 524KeywordsCoffee ePublished: 3 April 2018 Issue Published: 3 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...