tbuckley/cabot-search huggingface dataset:
The clinicopathological spectrum of HIV-associated lymphoma: Eleven-year-experience in a general hospital in Peru
Authors: L. Vera, R. Reategui, B. Beltran, D. Morales, A. Capellino, C. Desposorio, J. Castillo
Journal: Journal of Clinical Oncology (2009)

e19561 Background: The clinicopathological spectrum of HIV-associated lymphomas in developing countries has not been clearly defined. Thus, this study is aimed to describe these features in cases from a Peruvian population. Methods: This is a retrospective review of the clinical records of patients with diagnosis of HIV in our institution from March 1997 to March 2008. We reviewed 2502 clinical records. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Forty-eight patients with HIV-associated lymphoma were identified. Male:female ratio was 15:1. Median age was 42 years (range 27 to 70). 32 patients (67%) had clinical stage III-IV, B symptoms 35 (73%), the International Prognostic Index was low-risk 20 patients (42%), low-intermediate risk 15 patients (31%), high-intermediate risk 10 patients (21%) and high-risk 3 patients (6%). CD4 count lower than 100 cells/uL was 11 patients (23%). The CD4 count median was 184 cells/uL. The nodal localization in 27 patients (56%) was lightly higher. Forty-four cases (92%) were diagnosed with non-Hodgkin lymphoma (NHL) and 4 cases (8%) with Hodgkin lymphoma (HL). From the 44 NHL cases, 40 cases (91%) were of B-cell origin; 23 cases (57.5%) had diffuse large B-cell, 9 cases (22.5%) had Burkitt, 3 cases (7.5%) had plasmablastic, 2 cases (5%) had primary CNS, 2 cases (5%) had MALT and 1 case (2.5%) had primary effusion lymphoma. The remaining 4 cases (9%) were of T-cell origin; 3 cases (75%) had peripheral T-cell lymphoma NOS and 1 case (25%) was ALK-negative anaplastic large cell lymphoma. Only 16 patients (33%) were receiving HAART previously the diagnosis of NHL and 33 patients (68%) received any oncology treatment. Conclusions: This entity is aggressive and frequently has extranodal involvement. Also a high proportion of T-cells lymphomas are found. These findings are in concordance with one prior report of another general hospital from Peru. No significant financial relationships to disclose.
Epidemiology of Breast Cancer and Hair Dyes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E L Wynder, M Goodman
Journal: JNCI Journal of the National Cancer Institute (1983)

In a case-control study of 401 breast cancer cases and 625 age-matched controls, the possible etiologic role of hair dye usage was investigated. No association was found between hair dye use and breast cancer (odds ratio = 1.02; 95% confidence interval = 0.77-1.32) or any factors affecting dosage, frequency, duration, type, or color of hair dye. Important confounders of hair dye use included religion and smoking status. When stratified by 10-year age groups, there was no appreciable trend in risk status between case and referent populations. No dose-response relationship (frequency X duration X shade X type of dye used) was found, even after controlling for factors affecting hair dye use. A multiple logistic regression analysis supported the absence of this relationship.
ASSOCIATIONS OF LEG LENGTH INEQUALITY WITH PREVALENT, INCIDENT, AND PROGRESSIVE KNEE OSTEOARTHRITIS: A COHORT STUDY
Authors: WF Harvey, M Yang, Tdv Cooke, N Segal, N Lane, CE Lewis, DT Felson
Journal: Annals of Internal Medicine (2010)

Background
Leg length inequality is common in the general population and may accelerate development of knee osteoarthritis.
BEAM vs BuMelTT high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell infusion (HSCT) in the treatment of non-Hodgkin’s lymphoma
Authors: R. Zaucha, L. Holmberg, D. Maloney, O. Press, W. Bensinger
Journal: Journal of Clinical Oncology (2005)

6676 HDC with HSCT is widely used in the treatment of chemosensitive relapses of NHL. There are only limited data comparing toxicities and efficacy of particular HDC regimens used in NHL. We retrospectively compared two conditioning regimens: BEAM (carmustine, etoposide, cytosine-arabinoside, melphalan) and BuMelTT (busulphan, melphalan, thiotepa). Patients and Methods: Between January 1998 and May 2004 32 patients at a median age of 59 years (range 35–70 years) were treated with BEAM, and 54 patients (median age 51 years, range 35–65 years) with BuMelTT. Treatment groups were not significantly different with regard to histopathology and grade, sex, and former treatment, which consisted of 1 to 6 (median 3) chemotherapy regimens and a median of 9 cycles in both groups. There were significantly more patients with advanced disease (stage III and/or IV) in BEAM (81%) vs BuMelTT (58%). Radiotherapy had been given to 38% of BEAM vs 70% of BuMelTT patients. Age adjusted IPI 0–1 was diagnosed in 34% vs 47% patients, IPI 2 - 31% vs 19%, IPI 3 - 22% vs 15%, IPI 4 - 9% vs 6%, and unknown 3% vs 13% in BEAM vs BuMelT, respectively. Results: 16 of 53 (30%) patients treated with BuMelTT died, 4 due to treatment-related toxicity, one due to systemic aspergillosis, one due to stroke, and 10 (19%) of progressive disease. In contrast, 10 of 32 patients (31%) from the BEAM group died, one of treatment-related toxicity, and 9 (28%) of progressive disease. Median survival has not yet been reached, K-M estimates of 3-year OS for BEAM vs BuMelTT were 54% vs 63%, respectively. Conclusion: BEAM regimen appears less toxic than BuMelTT. It’s efficacy, however, may be inferior to BuMelTT. This observation needs to be confirmed in a randomized study. No significant financial relationships to disclose.
A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics
Authors: Regis A. James, Ian M. Campbell, Edward S. Chen, Philip M. Boone, Mitchell A. Rao, Matthew N. Bainbridge, James R. Lupski, Yaping Yang, Christine M. Eng, Jennifer E. Posey, Chad A. Shaw
Journal: Genome Medicine (2016)

Genome-wide data are increasingly important in the clinical evaluation of human disease. However, the large number of variants observed in individual patients challenges the efficiency and accuracy of diagnostic review. Recent work has shown that systematic integration of clinical phenotype data with genotype information can improve diagnostic workflows and prioritization of filtered rare variants. We have developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives. Our tool, "OMIM Explorer" ( http://www.omimexplorer.com ), extends the biomedical application of semantic similarity methods beyond those reported in previous studies. The tool also provides a simple interface for translating free-text clinical notes into HPO terms, enabling clinical providers and geneticists to contribute phenotypes to the diagnostic process. The visual approach uses semantic similarity with multidimensional scaling to collapse high-dimensional phenotype and genotype data from an individual into a graphical format that contextualizes the patient within a low-dimensional disease map. The map proposes a differential diagnosis and algorithmically suggests potential alternatives for phenotype queries—in essence, generating a computationally assisted differential diagnosis informed by the individual's personal genome. Visual interactivity allows the user to filter and update variant rankings by interacting with intermediate results. The tool also implements an adaptive approach for disease gene discovery based on patient phenotypes. We retrospectively analyzed pilot cohort data from the Baylor Miraca Genetics Laboratory, demonstrating performance of the tool and workflow in the re-analysis of clinical exomes. Our tool assigned to clinically reported variants a median rank of 2, placing causal variants in the top 1 % of filtered candidates across the 47 cohort cases with reported molecular diagnoses of exome variants in OMIM Morbidmap genes. Our tool outperformed Phen-Gen, eXtasy, PhenIX, PHIVE, and hiPHIVE in the prioritization of these clinically reported variants. Our integrative paradigm can improve efficiency and, potentially, the quality of genomic medicine by more effectively utilizing available phenotype information, catalog data, and genomic knowledge.
Abstract 19126: Novel Linkage Between Metabolic Sensor Mechanistic Target of Rapamycin (mTOR) and Canonical NF-kB Signaling Pathway Preserves Mitochondrial Integrity in Ventricular Myocytes During Hypoxia
Authors: Lorrie A. Kirshenbaum, Rimpy Dhingra, Hongying Gang, Yan Wang, Agnieszka Biala
Journal: Circulation (2013)

Background: TNFα and other pro-inflammatory cytokines activate the canonical NF-kB pathway through the IkBa kinase (IKK) signaling complex. IKKβ kinase is also critical for Akt-mediated NF-κB activation in ventricular myocytes. Akt activates the kinase (mechanistic target of rapamycin (mTOR), which mediates important processes such as metabolism protein synthesis and autophagy. However, mTOR’s role in regulating cardiac myocyte cell survival is unknown. Methods and Results: Herein, we demonstrate bi-directional regulation between NF-kB signaling and mTOR, the balance of which determines ventricular myoctye survival. Overexpression of IKKβ resulted in mTOR activation and conversely overexpression of mTOR lead to NF-κB activation. Loss of function approaches demonstrated that endogenous levels of IKKβ and mTOR also signal through this pathway. NF-kB activation by mTOR was medated by phosphorylation of the NF-kB p65 subunit at S276 increasing p65 nuclear translocation and activation of gene transcription. This circuit was also important for NF-κB activation by the canonical TNFα pathway. Inhibition of mTOR with rapamycin or during hypoxia decreased NF-kB activation resulting in increased mitochondrial PTP opening, maladaptive autophagy and necrotic cell death. Conversely, mTOR over-expression suppressed mitochondrial injury, autophagy and cell death of ventricular myocytes during hypoxia as well as nutrient deprivation. Conclusions: To our knowledge, these data provide the first evidence for a bi-directional link between NF-kB signaling and mTOR that is critical in the regulation of cardiac myocyte death. Hence, modulation of this axis may be cardioprotective in attenuating metabolic stress induced during hypoxia.
A Method To Measure Carcinoembryonic Antigen Neosynthesis by Cultured Colon Carcinoma Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: L Y Yang, B Drewinko
Journal: JNCI Journal of the National Cancer Institute (1980)

A double-antibody radioimmunoprecipitation assay was used to measure the rate of incorporation of radioactive precursors into carcinoembryonic antigen (CEA) newly synthesized by cultured human colon carcinoma (LoVo) cells. Mixtures of 125I-labeled CEA and standard CEA were used to construct titration curves as a function of concentration, time of incubation, and temperature for goat anti-CEA serum and rabbit antigoat serum. In contrast to the zirconyl phosphate gel method, the double-antibody technique did not precipitate compounds with low molecular weights. Similar slopes were observed when standard CEA was used to inhibit immunoprecipitation of 125I-labeled CEA by both the zirconyl phosphate gel and the double-antibody techniques. When CEA produced by the colon carcinoma cells (CEA-LoVo) was used to inhibit immunoprecipitation of radioactive 125 I-labeled CEA, the curve was superimposed upon that elicited for standard CEA. CEA-LoVo incorporated significant amounts of [N-acetyl-3H]glucosamine, and chromatography of the 3H-labeled CEA-LoVo eluted with a peak superimposed upon that of the First British Standard for CEA. This method was subsequently used to estimate changes in the rate of CEA neosynthesis by LoVo cells as a function of culture age. The rate of incorporation of [N-acetyl-3H]glucosamine into CEA of LoVo cells in stationary phase was about three times that measured for cells in exponential growth. The technique described in this report has the advantage that labeling of CEA results from actual metabolic cellular activity. Therefore, it provides a tracer method to study the localization and kinetics of CEA synthesis by cultured colon cells.
Therapeutic effectpredictors during sublingual immunotherapy for Japanese seasonal allergic rhinitis
Authors: Takechiyo Yamada, Masafumi Sakashita, Yoshimasa Imoto, Shigeharu Fujieda
Journal: European Respiratory Journal (2014)

Japanese seasonal allergic rhinitis (JSAR) differs markedly from other pollen allergies, and is characteristic to our country, what it recently called “national affliction” in Japan. Antigen-specific immunotherapy can change the natural course of AR and is recognized as a curative treatment against type I allergy without impaired performance. Recently, in Japan, sublingual immunotherapy (SLIT) has been developed and has become a safer and more beneficial immunotherapy for JSAR.  We have continued the SLIT for the patients of Japanese cedar pollinosis for several years, symptom medication scores were observed during the peak of high-pollen season. The levels of thirteen cytokines, chemokines, or integrin ligands including thymic stromal lymphopoietin (TSLP) in the serum were assessed using an ELISA kits or multiple assay kits.  The levels of TSLP and IL17A in the serum (year 4) significantly decreased during SLIT, and correlated with symptom scores during SLIT (year 4).The levels of TSLP in the serum correlate with symptom scores during SLIT (year 1).The TSLP-levels in the serum of year 1 correlate with the symptom scores of year 4 during SLIT.  The insights that have been provided over the last few years concerning the regulation of TSLP expression and production will have a marked impact on therapeutic interventions for inflammatory responses and allergic reactions.These suggest that SLIT modulates Th2 profile, and the level of serum TSLP could be one of the biomarkers or therapeutic effectpredictorsof the effectiveness of SLIT for JSAR.
Outcomes in HPV-associated oropharyngeal squamous cell carcinoma after postoperative or definitive nonsurgical therapy.
Authors: C. R. Spencer, H. Gay, B. H. Haughey, B. Nussenbaum, D. Adkins, D. I. Kuperman, I. El Naqa, J. S. Lewis, V. Auethavekiat, W. L. Thorstad
Journal: Journal of Clinical Oncology (2010)

5544 Background: Recent data has shown that for oropharyngeal squamous cell carcinoma (OPSCC), HPV association portends a good prognosis. HPV in situ hybridization (HPV ISH) and p16 immunohistochemistry have been used as biomarkers. Most studies show improved outcomes in this group after definitive chemoradiotherapy (CRT). At Washington University the favored approach for OPSCC is minimally invasive transoral laser microsurgery (TLM) with postoperative (PO) IMRT based radiation therapy (RT) or CRT. Patients who are not eligible or interested in surgery undergo definitive RT or CRT. Methods: 187 patients with OPSCC treated from 1997 to 2009 and tested for HPV and p16 were included in this study. 124 received PO therapy and 63 received definitive nonsurgical therapy. Locoregional control and survival outcomes were retrospectively analyzed. Results: The median follow-up was 47 months for living patients. 76% (142/187) of patients were p16+, 54% (98/183) were HPV+, 25% (46/183) were p16+/HPV-, and 24% (45/187) were p16-. The overall locoregional failure rate (LRF) was 7% (10/142) in p16+ patients and 31% (14/45) in p16- patients (p < 0.001). Interestingly 6 of 10 LRF in p16+ patients were HPV-. Disease-free survival at 2 and 5 years was 84% and 74% for p16+ patients and 47% and 25% for p16- patients, respectively (p < 0.001). Comparison between surgically and nonsurgically managed patients was not possible due to the inherent selection bias between groups. See Table for survival data (locoregional recurrence-free survival [RFS]; all 5-yr comparisons significant at p < 0.001 by log rank analysis). Conclusions: Our data support the recent literature showing the p16+ OPSCC has better survival and low locoregional failure rates following nonsurgical definitive IMRT based (C)RT and that p16 IHC identifies a larger improved prognostic group compared to HPV ISH. The analysis also provides new data showing excellent survival following TLM and PO (C)RT. Definitive % Post- Op % Stage I, II 3 5% 7 6% Stage III, IVA 42 72% 111 90% Stage IVB 13 22% 6 5% 2 yr 5 yr 2 yr 5 yr p16+ OS 74% 45% 88% 82% p16- OS 38% 21% 65% 32% p16+ RFS 83% 83% 96% 96% p16- RFS 50% 50% 94% 84% No significant financial relationships to disclose.
Survey on smoking cessation among patients in hospitals
Authors: Nikolay Antonov, Victoria Donitova, Galina Sakharova
Journal: European Respiratory Journal (2013)

Effectiveness of medical help in smoking cessation depends not only on the skills and knowledge of health workers, but also on the readiness and motivation of the patients. To assess the patients’ views 650 patients were surveyed in four medical institutions of Moscow. A self-completion questionnaire consisting of 30 questions was developed for that purpose.  Results. The prevalence of smoking: half of the respondents were active or former smoker and 60% of smokers have shown symptoms of a high nicotine dependence.  Secondhand smoking: 43% of respondents were exposed to secondhand smoking at home and 30% at work.  Influence of smoking on the development of the disease: two-thirds of respondents believed that passive smoking had an impact on the course of their disease, 39% of smokers (including former) felt that their smoking had an impact on the course of their disease.  Physician’s help: 71% of patients were asked by the doctor if they smoke. 46% of smokers received advice to quit smoking. Only 9% of smokers said they were not going to give up smoking, 65% wanted to quit smoking. 37% had tried to quit, and only 4% asked for medical assistance in smoking cessation.  Motivation to quit smoking: 45% of patients reported their desire to quit smoking has become stronger and 7% had quit smoking after hospitalization.  Conclusion: The majority of patients were aware of the hazards of smoking, and expressed a desire to quit, but no active actions were taken by patients as well as by physicians. In order to provide better help and involve more patients and physicians in smoking cessation doctor-patient communication should be improved and information should be distributed among patients as well as physicians.
Detection of clinically significant mutations in the epidermal growth factor receptor missed by direct sequencing using a highly sensitive DNA endonuclease
Authors: A. M. Borras, Y. Kuang, A. M. Rogers, A. J. Holmes, M. Gallegos Ruiz, V. A. Joshi, R. J. Distel, G. Giaccone, M. Taron, P. A. Janne
Journal: Journal of Clinical Oncology (2006)

10054 Background: Mutations in the epidermal growth factor receptor (EGFR) are associated with sensitivity and resistance to EGFR inhibitors gefitinib and erlotinib in patients with non-small cell lung carcinoma (NSCLC). Direct sequencing is currently used for mutation detection but sensitivity is limited and requires dissection to obtain a relatively pure population of tumor cells. We examined a DNA endonuclease, SURVEYOR, which cleaves mismatched heteroduplexed DNA, as a more sensitive method for EGFR mutation screening and compared it to direct sequencing. Methods: EGFR exons 18–21 from tumor DNA were amplified using PCR, digested with SURVEYOR, and the products analyzed by HPLC. Specimens that produced digestion products were re-analyzed by size separation or by denaturing HPLC followed by fractionation and sequencing. Tumor specimens from 191 NSCLC patients were analyzed: 61 frozen tumors specimens; 91 dissected formalin fixed paraffin embedded (FFPE) and 39 un-dissected FFPE tumor specimens from patients treated with gefitinib or erlotinib in whom clinical outcome was available. 173 specimens were independently analyzed by direct sequencing. Results: We detected 48 EGFR mutations by sequencing and 61 using SURVEYOR. All EGFR mutations identified by sequencing, including those using un-dissected tumor specimens, were detected by SURVEYOR and none were missed (sensitivity: 100%, negative predictive value: 100%). 13 mutations were detected by SURVEYOR not detected by sequencing. This included 5 mutations (4 exon 19 deletions; 1 L858R) in 7 (71%) patients who clinically had a PR to gefitinib or erlotinib but who were wild type by sequencing. In 4 patients, 2 with clinical acquired resistance to gefitinib, a T790M mutation was found which was undetected by sequencing. Conclusions: SURVEYOR analysis is a more sensitive method for EGFR mutation detection than direct sequencing. It can be used to detect EGFR mutations from un-dissected tumor specimens and can detect clinically significant activating or resistance associated EGFR mutations not detected by direct sequencing. [Table: see text]
Abstract 18541: Morning Surge of Ventricular Arrhythmias in a New Arrhythmogenic Canine Model of Heart Failure is Associated With Attenuation of Heart Rate and Autonomic Adaptation but Reduced Cardiac Chaos
Authors: Yujie Zhu, Mohamed A Hanafy, Cheryl R Killingsworth, Gregory P Walcott, Martin E Young, Steven M Pogwizd
Journal: Circulation (2013)

Introduction: Ventricular arrhythmias in heart failure (HF) can be modulated by autonomic stimulation that is reflected by heart rate variability (HRV). Noninvasive measures of nonlinear dynamics (NLD) assess cardiac chaos, decrease of which can be detrimental in patients with HF. Holter monitoring of HF patients (to assess HRV &amp; NLD) is limited by concurrent medication use. The aim of this study was to assess arrhythmia development, heart rate (HR) dynamics and nonlinear dynamics in a new arrhythmogenic canine model of HF. Methods: HF was induced in dogs (N=25) by aortic insufficiency &amp; aortic constriction and assessed by echocardiography. Holter monitoring was performed to study time-of-day variation in arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including Shannon entropy (SE), detrended fluctuations analysis α1 and α2 (DFAα1 &amp; DFAα2), and correlation dimension (CD)) at baseline, 240 days (240d) and 720 days (720d) after HF induction. Results: LV fractional shortening decreased from 43.4±0.7 vs 27.5±0.8 % (p&lt;0.01). Both PVCs and VT showed an early morning rise (2.1-fold &amp; 1.9-fold increase at 6AM-noon vs midnight-6AM). An early morning rise in HR at baseline (ΔHR=13.53±1.42 bpm) was attenuated with development of HF (ΔHR=7.06±0.26 and 6.69±2.44 bpm at 240d &amp; 720d; p&lt;0.01, p&lt;0.05), and was shifted to later in the day. Likewise early morning rise in the ratio of low frequency to high frequency (LF/HF, reflecting the ratio of sympathetic to parasympathetic inflow) at baseline was markedly attenuated with HF (p&lt;0.05 at 240d &amp; 720d), suggesting reduced early morning sympathetic adaptation. For nonlinear dynamics, SE, DFAα1, DFAα2, and CD all decreased with HF (3.04±0.02 vs 2.82±0.07, 0.67±0.03 to 0.46±0.03, 0.69±0.02 to 0.56±0.03, all p&lt;0.01; and 1.88±0.13 vs 1.12±0.25, p&lt;0.05 for baseline vs 720d), indicating decreased cardiac chaos in HF dogs. Conclusions: In this new arrhythmogenic canine model of HF, an early morning surge in ventricular arrhythmias was associated with attenuation of morning HR rise and blunting of autonomic oscillation. Measures of nonlinear dynamics reflected a consistent decrease in cardiac chaos and loss of complexity of heart rate that could be contributing to ventricular arrhythmias in this setting.