tbuckley/cabot-search huggingface dataset:
Prevalence of interlobar collateral ventilation in COPD patients
Authors: Dominik Herzog, Stefan Hippenstiel, Dirk Schürmann, Felix Döllinger, Alexander Pöllinger, Bettina Temmesfeld-Wollbrück, Norbert Suttorp, Ralf-Harto Hübner
Journal: European Respiratory Journal (2014)

The prevalence and distribution of collateral ventilation (CV) in emphysematous lungs are not well-described endobronchially under physiological conditions. Recently, an endobronchial catheter (Chartis, Pulmonx) has become routine in the clinical evaluation of CV status, which is important for clinical success in endoscopic lung volume reduction (ELVR) with endobronchial valves (EBV).  The distribution of 325 Chartis assessments of 125 COPD patients with severe emphysema was analyzed and classified according to 4 phenotypes: CV positive (CV+), CV negative (CV-), Low Flow (LF) and Low Plateau (LP), using measurements of increases in resistance index, changes in total exhaled volumeand decline in expiratory flow. Analysis focused on patients having completed measurements in both left and right lung to assess suitability for EBV treatment. Respective lungs were considered CV- if at least one lobe had no collateral ventilation detected. The Chi-squared test was used for statistical analysis.  80 patients had at least one measurement in each lung. CV status results are summarized in the table.  Left lungs were more frequently observed to be CV- than right lungs (68.75% vs. 32.5% p=0.03). Only 27.5% of the patients had both CV+ left and right lungs.  In this study, bilateral Chartis lung measurements showed that 72.5% of the patients with severe emphysema COPD had at least one lobe that was absent of collateral ventilation. Left lung demonstrated less frequent collateral ventilation than right lung and may be a better target for valve therapy.
Transcranial magnetic stimulation to understand pathophysiology and as potential treatment for neurodegenerative diseases
Authors: Zhen Ni, Robert Chen
Journal: Translational Neurodegeneration (2015)

Common neurodegenerative diseases include Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Transcranial magnetic stimulation (TMS) is a noninvasive and painless method to stimulate the human brain. Single- and paired-pulse TMS paradigms are powerful ways to study the pathophysiological mechanisms of neurodegenerative diseases. Motor evoked potential studied with single-pulse TMS is increased in PD, AD and ALS, but is decreased in HD. Changes in motor cortical excitability in neurodegenerative diseases may be related to functional deficits in cortical circuits or to compensatory mechanisms. Reduction or even absence of short interval intracortical inhibition induced by paired-pulse TMS is common in neurodegenerative diseases, suggesting that there are functional impairments of inhibitory cortical circuits. Decreased short latency afferent inhibition in AD, PD and HD may be related to the cortical cholinergic deficits in these conditions. Cortical plasticity tested by paired associative stimulation or theta burst stimulation is impaired in PD, AD and HD. Repetitive TMS (rTMS) refers to the application of trains of regularly repeating TMS pulses. High-frequency facilitatory rTMS may improve motor symptoms in PD patients whereas low-frequency inhibitory stimulation is a potential treatment for levodopa induced dyskinesia. rTMS delivered both to the left and right dorsolateral prefrontal cortex improves memory in AD patients. Supplementary motor cortical stimulation in low frequency may be useful for HD patients. However, the effects of treatment with multiple sessions of rTMS for neurodegenerative diseases need to be tested in large, sham-controlled studies in the future before they can be adopted for routine clinical practice.
Population whole-genome bisulfite sequencing across two tissues highlights the environment as the principal source of human methylome variation
Authors: Stephan Busche, Xiaojian Shao, Maxime Caron, Tony Kwan, Fiona Allum, Warren A. Cheung, Bing Ge, Susan Westfall, Marie-Michelle Simon, Amy Barrett, Jordana T. Bell, Mark I. McCarthy, Panos Deloukas, Mathieu Blanchette, Guillaume Bourque, Timothy D. Spector, Mark Lathrop, Tomi Pastinen, Elin Grundberg
Journal: Genome biology (2015)

CpG methylation variation is involved in human trait formation and disease susceptibility. Analyses within populations have been biased towards CpG-dense regions through the application of targeted arrays. We generate whole-genome bisulfite sequencing data for approximately 30 adipose and blood samples from monozygotic and dizygotic twins for the characterization of non-genetic and genetic effects at single-site resolution. Purely invariable CpGs display a bimodal distribution with enrichment of unmethylated CpGs and depletion of fully methylated CpGs in promoter and enhancer regions. Population-variable CpGs account for approximately 15–20 % of total CpGs per tissue, are enriched in enhancer-associated regions and depleted in promoters, and single nucleotide polymorphisms at CpGs are a frequent confounder of extreme methylation variation. Differential methylation is primarily non-genetic in origin, with non-shared environment accounting for most of the variance. These non-genetic effects are mainly tissue-specific. Tobacco smoking is associated with differential methylation in blood with no evidence of this exposure impacting cell counts. Opposite to non-genetic effects, genetic effects of CpG methylation are shared across tissues and thus limit inter-tissue epigenetic drift. CpH methylation is rare, and shows similar characteristics of variation patterns as CpGs. Our study highlights the utility of low pass whole-genome bisulfite sequencing in identifying methylome variation beyond promoter regions, and suggests that targeting the population dynamic methylome of tissues requires assessment of understudied intergenic CpGs distal to gene promoters to reveal the full extent of inter-individual variation.
Reproductive Factors and Risk of Intermediate- or High-Grade B-Cell Non-Hodgkin’s Lymphoma in Women
Authors: Rebecca A. Nelson, Alexandra M. Levine, Leslie Bernstein
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The incidence rates of non-Hodgkin’s lymphoma (NHL) unrelated to human immunodeficiency virus infection are lower for women than for men; yet, few factors have been identified that may account for this difference in risk. NHL is difficult to study epidemiologically because this disorder represents a group of malignancies that differ in terms of morphologic presentation, immunologic features, genetic characteristics, prognosis, and etiology. PATIENTS AND METHODS: We conducted a population-based case-control study in women to determine whether reproductive factors or hormonal exposures might be related to the risk of high- or intermediate-grade B-cell NHL. We interviewed 177 female residents of Los Angeles County who were diagnosed with high- or intermediate-grade B-cell NHL between 1989 and 1992; each case patient was individually matched on age and race to a control subject who lived in her neighborhood. RESULTS: Women who had used oral contraceptives had significantly lower risk of intermediate- or high-grade NHL (multivariate odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.26 to 0.86) than women who had never used these compounds. Among parous women, those who had used lactation suppressants (which contain high levels of estrogen) had significantly lower risk of NHL (multivariate OR = 0.50; 95% CI, 0.29 to 0.85) than unexposed women. Postmenopausal women had a somewhat greater risk of NHL than premenopausal women, whereas those postmenopausal women who had used hormone replacement therapy (HRT) (primarily estrogen) had somewhat lower risk than those who had not used HRT. CONCLUSION: Exogenous estrogens seem to have a protective effect on the risk of high- and intermediate-grade B-cell NHL. Although the mechanisms for such protection are not known, alterations in immune reactivity, cytokine expression, or B-cell modulation may play a role.
G06 : A randomized, double-blind, placebo-controlled phase III trial of TSU-68 (orantinib) combined with transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma
Authors: J.-W. Park, A.-L. Cheng, M. Kudo, J.H. Park, P.-C. Liang, H. Hidaka, N. Izumi, J. Heo, Y.J. Lee, I-S. Sheen, C.-F. Chiu, H. Arioka, S. Morita, Y. Arai
Journal: Journal of Hepatology (2015)
Response to Letter-to-Editor by M. Tenhunen and S. Himanen: “Assessment of respiratory effort during sleep: Esophageal pressure versus noninvasive monitoring techniques”
Authors: Nele L. Vandenbussche, Sebastiaan Overeem, Johannes P. van Dijk, Pieter Jan Simons, Dirk A. Pevernagie
Journal: Sleep Medicine Reviews (2015)
Abstract 13370: Long-term Outcomes of Patients with Pseudoaneurysms and a History of Prior Cardiovascular Surgery
Authors: Michael Chenier, Krishna Patel, Gosta Pettersson, Bruce Lytle, Jose Navia, Joseph Sabik, Leonardo Rodriguez, Richard Grimm, Brian Griffin, Milind Desai
Journal: Circulation (2014)

Background: Data regarding long-term outcomes in patients with cardiovascular (CV) pseudoaneurysms (PSA) is sparse. In patients with prior CV surgery, we sought to assess outcomes in patients with PSAs (defined as paravalvular, aortic root, or ascending aorta PSAs) &amp; compare them with matched controls. Methods: As part of a cohort study (total n=342), we included 114 patients with prior CV surgery who presented with paravalvular (n=71, 59 at the aortic valve &amp; 12 at the mitral valve) &amp; ascending aortic (n=43) PSAs. A control group of patients (n=228) with prior CV surgery, matched in a 2:1 fashion based on age, gender, type &amp; time of CV surgery, were also included. Standard clinical, echocardiographic &amp; surgical data was collected &amp; Euroscore was calculated. A composite endpoint of death &amp; stroke during follow-up were recorded. Results: Baseline data are shown in Figure A. 80% of patients in each group underwent redo CV surgery during follow-up. Over a follow-up of 6.7±4 years, there were 78 (23%) events (32 or 28% in PSA group &amp; 46 or 20% in control group). 30-day events occurred in 7% of the PSA group &amp; 1% of controls. Kaplan-Meier survival curves for the 2 groups are shown in Figure B. In the multivariate Cox Survival Analysis, Euroscore (HR 1.18 [1.10-1.27]) &amp; the presence of PSA (HR 2.83 [1.66-4.85]) predicted a higher rate of events, while subsequent CV surgery (as a time-dependent covariate HR 0.38 [0.22-0.67])) &amp; antibiotic use (HR 0.29 [0.27-0.31]) predicted improved freedom from events (all p&lt;0.01). Conclusion: In patients with prior CV surgery, the presence of a cardiac PSA was associated with increased long-term adverse events, while redo CV surgery and antibiotic use improved outcomes.
The transfer of genetically engineered lymphocytes in melanoma patients: a Phase I dose escalation study
Authors: Courtney Regan, Michael Nishimura, I Caroline Le Poole, Constantine Godellas, Patrick Stiff, Elizabeth Garrett-Mayer, Mingli Li, Keisuke Shirai, Jonathan Eby, Heather Embree, Boro Dropulic, Ann Lau Clark, Kelli Hutchens, Joseph I Clark
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Genetically engineered T cells have broadened the opportunity for use of T cell immunotherapy in cancer patients. The possibility of improving T cell efficacy via introduction of additional genes potentially gives them an advantage over TIL. Studies in adoptive T cell transfer
Survival impact of neoadjuvant treatment in cervical cancer stage IIB
Authors: H. F. Oliveira, F. M. Peria, J. M. Andrade, H. R. Marana, A. C. Santos, L. M. Mendonça, J. Elias
Journal: Journal of Clinical Oncology (2009)

e16559 Background: A few previous studies demonstrated that neoadjuvant chemotherapy, followed by preoperative radiotherapy in diagnosed IIB cervical cancer patients, had similar therapeutic results as the standard protocol with concurrent chemoradiotherapy, considering complete response; overall survival; disease free survival and toxicity; requiring its evaluation as an alternative approach. Methods: One hundred sixteen women with IIB stage cervical cancer stages were submitted to a platinum combined based neoadjuvant chemotherapy followed by chemoradiotherapy with cisplatin. Those who had a good response, allowing a surgical approach, underwent the Wertheim-Meigs procedure. Those that could not be submitted to surgery remained in clinical follow-up. Results: The age of the patients were 22 to 75 years old (48.7±11.4 years). The average follow-up was about 48 months (1–120). The good response to the neoadjuvant treatment was found in 76 patients (65.5%), and surgery was possible in 86 (74%). The pathological complete response was found in 39 (33%), and the partial response in 40%. The global recurrence was diagnosed in 37 (32%) patients. In the operated group (n = 86), the overall-five years survival was 76%, and in the non-operated group (n = 30) was 17,5%. The five years-global survival was 79,2% in “good response” (GR) patients, and 27.4% in that with “no-good response” (NGR) to combined neoadjuvant treatment ( p &lt; 0.01). The free-relapse survival was 79.4% in GR, and 32.5% in NGR group (p &lt; 0.01). Conclusions: Amongst the studied prognostic factors, the most important one for interval of relapse and survival (global and free-relapse) was a good response to the neoadjuvant treatment, and that this treatment had an acceptable toxicity and could be considered in other trials as an option to standard treatment. No significant financial relationships to disclose.
Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trial.
Authors: Mary L. Disis, Manish R. Patel, Shubham Pant, Jeffrey R. Infante, A. Craig Lockhart, Karen Kelly, Joseph Thaddeus Beck, Michael S. Gordon, Glen J. Weiss, Samuel Ejadi, Matthew Hiram Taylor, Anja von Heydebreck, Kevin M. Chin, Jean-Marie Cuillerot, James L. Gulley
Journal: Journal of Clinical Oncology (2015)

5509 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers. Avelumab (proposed INN) (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody currently being investigated in clinical trials. Here we present results from a cohort of patients (pts) with recurrent or refractory ovarian cancer in an ongoing phase Ib study (NCT01772004). Methods: Pts with ECOG PS 0-1 received avelumab at 10 mg/kg Q2W. Best overall response (BOR) and progression-free survival (PFS) were assessed according to RECIST 1.1. Adverse events (AEs) were evaluated by CTCAE v4.0. A prespecified analysis of 23 pts with follow-up of ≥ 2 months showed confirmed and unconfirmed partial responses (PRs), leading to cohort expansion to 75 pts. Results: Seventy-five pts were enrolled from November 2013 to November 2014 (median age 62 [range 38-84]; ECOG PS 0 [41%] or 1 [59%]; median of four prior lines of therapy). As of January 2015, median duration of treatment with avelumab was 10 weeks (range 2-54 weeks), and 27 pts remained on treatment. Efficacy data from the 23 pts followed-up for ≥ 2 months (range 2–8 months) demonstrated 4 pts (17.4%, [95% CI, 5.0%, 38.8%]) achieved an unconfirmed BOR of PR,11 (47.8%) had stable disease, and 2 pts had >30% tumor shrinkage after progression was reported. Median PFS was 11.9 weeks (95% CI, 5.9, not reached), and the PFS rate at 24 weeks was 33.3% (95% CI, 11.5, 57.2). Drug-related treatment-emergent AEs (TEAEs; all grades) were reported in 18 pts (78.3%), and 2 pts (8.7%) experienced grade ≥ 3 drug-related TEAEs (increased lipase [1] and elevated creatine kinase and autoimmune myositis that led to discontinuation [1]). No drug-related serious TEAEs occurred. The most commonly reported drug-related TEAEs (> 10%) were fatigue, nausea, and diarrhea. Conclusions: These data represent the largest reported dataset of pts with recurrent ovarian cancer treated with anti-PD-L1 therapy. Avelumab demonstrated an acceptable safety profile and is clinically active in this heavily pretreated ovarian cancer pt population. Clinical trial information: NCT01772004.
Updated Results from a Large, Ongoing, Treatment IND Study Using Defibrotide for Patients with Hepatic Veno-Occlusive Disease
Authors: Paul G. Richardson, Angela R. Smith, Brandon M. Triplett, Nancy A. Kernan, Stephan A. Grupp, Sally Arai, Joseph H. Antin, Leslie E. Lehmann, Valeria Bandiera, Robin L. Hume, Alison L. Hannah, Bijan Nejadnik, Robert J. Soiffer, Defibrotide Study Group
Journal: Blood (2014)
Hepatic expression of UGT enzymes and implications in pharmacokinetic variations in Asians during chemotherapy
Authors: B. Chowbay, S. Lal, X. Shu, S. Jada, L. Ooi, Y. Liu, Y. Ong
Journal: Journal of Clinical Oncology (2007)

14089 Background: The objective of this study was to screen the promoter and relevant coding regions in the UGT1A1 and UGT1A9 genes and genotypically quantitate expression of these genes in hepatic tissues obtained from Asian cancer patients undergoing hepatectomy. Methods: Non-cancerous Asian hepatic tissues (Chinese: N=36; Malay: N=1; Indian: N=3) were obtained from the institution’s central tissue repository bank. Messenger RNA was isolated from each tissue sample and reverse transcribed to cDNA followed by real time PCR experiments. Results from these gene expression experiments were normalized against GAPDH transcripts. DNA was also extracted from the hepatocytes, screened for variations in the promoter regions (UGT1A1*60, g.3140G&gt;A and UGT1A1*28) and exon 1 (UGT1A1*6) of the UGT1A1 and UGT1A9 (UGT1A9*22, I399C&gt;T) genes. Results: Large interindividual variations were observed in the hepatic expression pattern of UGT1A1 and UGT1A9 mRNA with respect to the different polymorphic variants. There was no significant association between hepatic expression of UGT1A1 mRNA and UGT1A1*60, g-3140G&gt;A and *6 genotypes (P&gt;0.05 in each case). The median expression level of UGT1A1 mRNA was approximately 2-fold higher in liver tissues harboring UGT1A1 6/6 (reference) genotype (N=27, median = 0.478; range: 0.065 to 3.125) compared to the heterozygous 6/7 genotype (N=9, median = 0.254; range: 0.042 to 1.894; P=0.77). The median expression levels of UGT1A9 mRNA were approximately 3-fold higher in liver tissues harboring I399CC genotype (N=3, median = 2.735; range: 0.702 to 3.375) when compared with the homozygous variant TT genotype (N=8, median = 0.973; range: 0.652 to 4.155; P=0.88). Conclusions: The results showed that polymorphisms in the UGT1A genes may influence the expression pattern of the respective proteins and could contribute to the high degree of interpatient variability in the glucuronidation dependent metabolism and elimination of chemotherapeutic agents in Asian cancer patients. No significant financial relationships to disclose.
Tubular Secretion in CKD
Authors: Astrid M. Suchy-Dicey, Thomas Laha, Andrew Hoofnagle, Rick Newitt, Tammy L. Sirich, Timothy W. Meyer, Ken E. Thummel, N. David Yanez, Jonathan Himmelfarb, Noel S. Weiss, Bryan R. Kestenbaum
Journal: Journal of the American Society of Nephrology (2015)

Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation.
Use of multiparametric MRI to alter management pathways: Treatment patterns of prostate cancer in the targeted biopsy era.
Authors: Raju Chelluri, Thomas P Frye, Arvin George, Michele Fascelli, Richard Ho, Steven Abboud, Annerleim Walton-Diaz, Sandeep Sankineni, Baris Turkbey, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2015)

56 Background: As the use of multiparametric MRI (mpMRI) to diagnose prostate cancer (PCa) becomes established, better knowledge of treatment patterns is needed to counsel patients. Prior studies have shown 40-55% undergo Radical Prostatectomy (RP), while only 6% prefer Active Surveillance (AS), and that stratification by risk does not greatly alter treatment pathways. We aim to delineate the distribution of PCa treatment modalities in the MRI/US fusion-guided prostate biopsy (FB) era. Methods: A retrospective review was performed of all patients who underwent FB at the NIH from 2010 to present. Demographics, Gleason scores, MRI Suspicion scores and treatment outcomes were recorded. Patients were stratified according to D’Amico Risk Criteria, and outcomes were coded into four categories: AS; RP; Radiation (XRT, Brachytherapy); and Other (Systemic or Focal therapy). Results: 839 men were reviewed. Mean age was 62.6 years old and mean PSA was 9.7 ng/mL. Total cancer detection rate was 70% (n = 589). Of FB positive men, 474 had treatment information available. Overall 225 (47.5%) entered AS, 158 (33.3%) underwent RP, 61 (12.9%) received XRT, and 30 (6.3%) received other intervention. Subgroup analysis by MRI suspicion score (Table) showed 47.4% frequency of RP in the high vs. 30.9% and 19.4% for moderate and low suspicion groups, respectively. Analysis by D’Amico Risk (Table) showed 86% of low risk men chose AS vs. 0% of high risk men. Conversely 9.7% of low, 44.5% of intermediate and 55.7% of high risk men underwent RP. Conclusions: FB was associated with a higher rate of AS choice as a treatment modality for low risk disease. However most patients with clinically significant PCa still chose RP as their treatment. FB is an additional tool that allows the urologist to better counsel patients and provides individualized treatment for PCa. [Table: see text]