tbuckley/cabot-search huggingface dataset:
Dealing with patients with HIV infection
Authors: H. Curtis, P. P Walker, E. F Fox, N. A Smith, C. S Bradbeer, P. Daggett
Journal: BMJ (1997)

Data are not now collected by ethnic group in South AfricaEditor-Claire Hilton notes that since April 1995 British hospitals have had to collect data on each patient's ethnic group. 1 In the United States this is standard practice.In the Morbidity and Mortality Weekly Report data on numerous variables relating to the health and ill health of black and white people are regularly given 2 -as also, on occasion, are data on Hispanics, American Indians, Inuits, and Pacific Islanders.In South Africa precisely the converse has occurred.Ethnic subdivisions have stopped appearing in reports from the Central Statistics Services, and thus mortalities are no longer given for the constituent populations (black, Asian, coloured (Eur-African-Malay), and white), only for the combined population.Additionally, in our big cities annual reports from public health departments provide only combined data on morbidity and mortality.Disadvantages are many.Recently, colleagues and I reviewed changes in the total death rate and the death rate from coronary heart disease in South African populations. 3 We found that, from 1978 to 1989, mortality from coronary heart disease fell by 56% in the white population and by 36% in each of the Indian and coloured populations.Because changes in mortality from this foremost "killer" are continuing we intended to update our information.But this is now precluded.Currently, desegregation does not apply to our national cancer registry.But if it did how, for example, could benefits from Papanicolaou smear tests be assessed?The incidences of cervical cancer in the black and coloured populations are among the highest in the world.The constituent populations of South Africa have a wider divergence in the occurrence of a variety of diseases than occurs in any other country: coronary heart disease, appendicitis, colon cancer, and hip fractures.Interethnic differences in the occurrence of disease, reactivity, and metabolism are well known elsewhere. 4 In South Africa the change to using combined data will make it harder to identify and quantify the target populations who are in most need of help, as well as severely stultifying research on the occurrence of disease and on combating it.Hilton is right, of course, that the level of treatment is affected by ethnic group.Recently, in the United States the effect of race and income on mortality and the use of services among beneficiaries of Medicare was investigated; both race and income were shown as having substantial prejudicial effects, that of race being much more pronounced than that of income. 5This is a matter of universal shame.
A framework to assess the cost effectiveness of predictive biomarkers in oncology: Test Incremental Cost Effectiveness Ratio (TICER).
Authors: Anton Safonov, Weiwei Shi, James Platt, Bilge Aktas, Tomoko Kurita, Lajos Pusztai, Christos Hatzis
Journal: Journal of Clinical Oncology (2015)

6621 Background: Cost effectiveness of predictive biomarkers is currently assessed by Markov Chain (MC) simulations, requiring resources and expertise. Our goal was to develop a practical index to aid clinicians in biomarker cost utility estimation at an early stage of development. Methods: We used decision trees to derive a test incremental cost-effectiveness ratio (TICER) index that combines six parameters including biomarker prevalence, progression free survival (PFS), health-related quality of life (HRQoL), cost of testing, cost of treatment, and cost of progression. We assessed the model on existing (HER2, ALK, OncotypeDx) and emerging (PDL1 expression) predictive biomarkers. We conducted one-way and multivariate probabilistic sensitivity analyses (PSA) and generated cost-effectiveness acceptability curves (CEAC). Benefit was expressed as quality-adjusted progression-free years (QAPFY). Results: We used literature reported values for base case and varied the parameters over a broad range to estimate the contribution of each variable to TICER. TICER was calculated by one-way PSA for each variable as the median CEAC (cost at 50% probability of acceptance), while sampling the remaining variables from their respective distributions. The table shows the base case and range of TICER compared to literature values and the acceptance probability considering a cutoff of $200K/QAPFY, providing a relative ranking in terms of cost effectiveness. The TICER model is driven primarily by PFS and HRQoL while biomarker prevalence and test costs have a lesser effect. Conclusions: TICER is flexible to a variety of clinical scenarios and does not require assumptions about health states up to death like MC-based methods do. The cost effectiveness of a predictive test is driven by the efficacy and QOL associated with biomarker-directed therapy rather than marker prevalence or assay cost. Biomarker Base Case TICER ($K/QAPFY) Range of TICER by PSA ($K/QAPFY) Acceptance Probability of $200K/QAPFY Literature Value ($K/QALY) HER2 155.2 113 to 235 74.9% 145 ALK 258.3 206 to 433.2 18.4% 256 PD-L1 280.7 227 to 482 12.8% N/A OncotypeDx -5.1 (negative indicate cost saving) -13.2 to – 2.8 99.5% -6.7
TCTAP C-056 Implantation of Bioresorbable Vascular Scaffold After Rotational Atherectomy in Patient with Heavy Calcified Coronary Stenosis
Authors: Seung Hwa Lee, Joo-Yong Hahn, Jeong Hoon Yang, Young Bin Song, Jin-Ho Choi, Seung Hyuk Choi, Hyeon-Cheol Gwon, Sang Hoon Lee
Journal: Journal of the American College of Cardiology (2016)
Virus Particles in Primordial Germ Cells of Fetal Guinea Pigs2
Authors: Virginia H. Black
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Virus Particles in Primordial Germ Cells of Fetal Guinea Pigs Get access Virginia H. Black Virginia H. Black Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 545–551, https://doi.org/10.1093/jnci/52.2.545 Published: 01 February 1974 Article history Received: 27 August 1973 Accepted: 26 September 1973 Published: 01 February 1974
Lack of the expression of EBNA-2 and LMP-1 in T-cell neoplasms possessing Epstein-Barr virus
Authors: H Suzushima, N Asou, T Fujimoto, S Nishimura, T Okubo, H Yamasaki, M Osato, M Matsuoka, A Tsukamoto, K Takai
Journal: Blood (1995)
Abstract 16013: The Dominant Role of the Systolic over the Diastolic Component of Blood Pressure Non-dipping as a Determinant of Target Organ Damage in Never Treated Hypertension. Implications in Dipping Definition
Authors: D. Syrseloudis, C. Tsioufis, L. Lioni, E. Andrikou, M. Giakoumis, A. Kordalis, M. Poulakis, D. Flessas, C. Stefanadis
Journal: Circulation (2010)

Introduction:  Blood pressure (BP) non- dipping has been associated with target organ damage (TOD) and adverse outcomes in hypertension. Diverse definitions of non- dipping appear in the literature regarding the BP components taken into account.   Hypothesis:  Isolated systolic compared to diastolic and to combined systolic and diastolic non- dipping is accompanied by increased markers of TOD and represents a more powerful predictor of TOD in never treated hypertensives.   Methods:  475 subjects with never treated essential hypertension stage I, II were divided according to a nocturnal BP reduction of    Results:  SND as compared to DND and SDND were of similar age, body mass index, waist circumference and metabolic profile (p=NS for all cases). In comparison with DND they had higher 24h systolic and pulse pressure (136±12 vs 128±11 and 52±6 vs 46±7 mmHg, p 2.7 , p 10 (c-f PWV) (0.94±0.07 vs 0.86±0.05 vs 0.91±0.07 m/s, p 10 (ACR) (1.2±0.5 vs 0.9±0.3 vs1.1±0.4 mg/g, p   Conclusions:  Isolated systolic BP non- dippers exhibit higher LVMI, c-f PWV and ACR in comparison with isolated diastolic and combined systolic- diastolic BP non- dippers. Moreover systolic non- dipping was related as an independent prognosticator with the above indices of TOD while diastolic non- dipping was not. In conclusion isolated systolic BP non- dipping may provide sufficient prognostic data, as regards the above surrogates of cardiovascular risk.
New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain
Authors: Julio D. Perez, Nimrod D. Rubinstein, Catherine Dulac
Journal: Annual Review of Neuroscience (2016)

Mammalian evolution entailed multiple innovations in gene regulation, including the emergence of genomic imprinting, an epigenetic regulation leading to the preferential expression of a gene from its maternal or paternal allele. Genomic imprinting is highly prevalent in the brain, yet, until recently, its central roles in neural processes have not been fully appreciated. Here, we provide a comprehensive survey of adult and developmental brain functions influenced by imprinted genes, from neural development and wiring to synaptic function and plasticity, energy balance, social behaviors, emotions, and cognition. We further review the widespread identification of parental biases alongside monoallelic expression in brain tissues, discuss their potential roles in dosage regulation of key neural pathways, and suggest possible mechanisms underlying the dynamic regulation of imprinting in the brain. This review should help provide a better understanding of the significance of genomic imprinting in the normal and pathological brain of mammals including humans.
Absorption of I125-labeled homologous albumin by rat kidney proximal tubule cells. A study of microperfused single proximal tubules by electron microscopic autoradiography and histochemistry. 1966.
Authors: A B Maunsbach
Journal: Journal of the American Society of Nephrology (1997)

Journal of the American Society of Nephrology : JASN 8(2):p 323-351, February 1997. | DOI: 10.1681/ASN.V82323
Case 8-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Alfred Kranes, Robert E. Scully
Journal: New England Journal of Medicine (1971)

Presentation of Case First admission. A 70-year-old woman entered the hospital because of chills and fever.She had been in good health until six years previously, when leukoplakia of the tongue was found. Three years later a lingual biopsy revealed squamous-cell carcinoma, which was treated by local resection and later by left hemiglossectomy. She was well thereafter until seven months before admission, when a mass was found in the left side of the neck; a radical neck dissection disclosed squamous-cell carcinoma in two of five lymph nodes removed. Diabetes mellitus was found and was managed by diet alone. Three . . .
Immune-mediated brain tumor regression requires HMGB1 release and subsequent TLR2 activation on tumor infiltrating dendritic cells
Authors: James Curtin, Matthew Edwards, Kathrin Michelsen, Kurt Kroeger, Marianela Candolfi, Chunyan Liu, Mary Clark, Moshe Arditi, Begonya Comin-Andiux, Antoni Ribas, Pedro Lowenstein, Maria Castro
Journal: Cancer Research (2008)
TCTAP A-073 Procedural, Early and Long-Term Outcomes After Transcatheter Closure of Atrial Septal Defects: Comparison Between Adult Patients with Large and Very Large Defect Groups
Authors: Se Yong Jung, Jeong Yoon Kim, Nam Kyun Kim, Jo Won Jung, Lucy Youngmin Eun, Jae Young Choi
Journal: Journal of the American College of Cardiology (2016)
Five Years Ago You'd Be Dead
Authors: Jack Coulehan
Journal: Annals of Internal Medicine (2016)

Ad Libitum3 May 2016Five Years Ago You'd Be DeadJack Coulehan, MD, MPHJack Coulehan, MD, MPHFrom Coram, New York.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-0330 Audio Reading - “Five Years Ago You'd Be Dead” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Five Years Ago You'd Be Dead," by J. Coulehan. 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 My doctor rides on the shouldersof magnets and molecules, perchedlike a Hindu prince on an elephant,secure in believing my maliciousinvader, fatal then, will now succumbto reason. His confidence predictingthe past unnerves me. Should I beoverjoyed to learn how accidentalmy fragile thread's endurance is?These days, he tells me, the tumoris hardly worse than a winter cold,a week of summer insomnia,or a busted sparkplug. I'd like to slipthe illusion into my breast pocketand keep it close for ten years. Author, Article, and Disclosure InformationAffiliations: From Coram, New York.Current Author Address: Jack Coulehan, MD, MPH; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Five Years Ago You'd Be Dead” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Five Years Ago You'd Be Dead," by J. Coulehan. 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 May 2016Volume 164, Issue 9Page: 632KeywordsInsomniaShoulders ePublished: 3 May 2016 Issue Published: 3 May 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Author response to letter: colonic stenting in patients on P2Y12 receptor antagonists and direct oral anticoagulants—are current BSG/ESGE guidelines practical?
Authors: Andrew Veitch, Jean-Marc Dumonceau
Journal: Gut (2016)

We thank the authors for their interest in the recently published British Society of Gastroenterology and European Society of Gastrointestinal Endoscopy (ESGE) guidelines on endoscopy in patients on antiplatelet or anticoagulant therapy.1 As stated in the summary of recommendations, these guidelines refer to the management of elective endoscopic procedures. …
Abstract 1694: Preclinical evaluation of a novel bispecific targeted toxin for the treatment of sarcomas
Authors: Antonella Borgatti, Amber Winter, Kathleen Stuebner, Joseph Koopmeiners, Jaime F. Modiano, Daniel Vallera
Journal: Cancer Research (2015)

Abstract Introduction: EGFuPA is a bispecific ligand-targeted toxin consisting of epidermal growth factor (EGF) and urokinase (uPA) on the same molecule with truncated Pseudomonas exotoxin. The toxin was mutated to remove amino acids recognized by B-cells. EGFuPA is uniquely designed to simultaneously target EGF receptors (EGFR) and/or urokinase receptors (uPAR) on tumor cells and uPAR in the microenvironment. EGFuPA is safe and effective in laboratory animals and has excellent in vitro activity against sarcomas. Because EGFuPA crosses species platforms, an adaptive phase 1/2 study was undertaken using canine hemangiosarcoma (HSA) as a model of a highly aggressive, metastatic vascular sarcoma. We hypothesized that six-month survival would exceed 50% for dogs enrolled. Canine HSA is a tumor derived from blood vessel forming cells, which can overexpress both uPAR and EGFR rendering it an excellent target for the drug. It bears similarity to human angiosarcoma. Methods: Enrollment began in November 2012. Dogs with histologically confirmed, non-metastatic stage-I or II splenic HSA were eligible after splenectomy. EGFuPA was administered intravenously for one cycle on Days 1, 3, and 5. Adjuvant doxorubicin was given according to standard of care (SOC) protocols starting seven days after the last dose of EGFuPA. Results: EGFuPA was detectable in the systemic circulation 5 minutes post-infusion with clearance by 15 minutes. The drug was well tolerated with self-limiting, reversible hypovolemia at the highest dose. Thus far, 50 μg/kg appears to be the optimal dose. When compared to a historical control group of 19 dogs treated with SOC between 2008 and 2011, median survival is significantly longer for all 16 dogs treated with EGFuPA (SRCBST group, 240 vs. 129 days, p = 0.03) and for the 10 dogs in the Optimal Dose group (MS not reached, p = 0.01). Six-month survival for the Optimal Dose group was 65%. Overall survival at 400 days was 7% for the SOC group, 32.7% for the SRCBST group, and 56% for the Optimal Dose group. Outcomes were not affected by the presence of neutralizing antibodies. Conclusions: A biologically active dose of EGFuPA was established and found to be safe in companion dogs with HSA in the minimal residual disease setting. The unique nature of its bispecific targeting and the observed significant, biologic activity warrants consideration of EGFuPA for a phase 1 study for drug-refractory sarcomas in human patients. Citation Format: Antonella Borgatti, Amber Winter, Kathleen Stuebner, Joseph Koopmeiners, Jaime F. Modiano, Daniel Vallera. Preclinical evaluation of a novel bispecific targeted toxin for the treatment of sarcomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1694. doi:10.1158/1538-7445.AM2015-1694
Hypoxia upregulates neutrophil degranulation and potential for tissue injury
Authors: Kim Hoenderdos, Katharine M Lodge, Robert A Hirst, Cheng Chen, Stefano G C Palazzo, Annette Emerenciana, Charlotte Summers, Adri Angyal, Linsey Porter, Jatinder K Juss, Christopher O'Callaghan, Edwin R Chilvers, Alison M Condliffe
Journal: Thorax (2016)

The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown.Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release.Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion.
The utility of serum CA9 in prognostication in prostate cancer.
Authors: Alan D. Smith, Mathew Truong, Rob Bristow, Bradley Wouters, Michael F. Milosevic, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2016)

309 Background: Solid tumours are invariably less well-oxygenated than their normal tissue counterparts. Tumour hypoxia is important because it leads to resistance to radiotherapy and anticancer chemotherapy, and has been associated with prognosis in localized prostate cancer. Carbonic anhydrase IX (CA9), a member of a family of metalloenzymes that catalyze the reversible hydration of carbon dioxide, is considered to be one of the best biomarkers of cellular hypoxia. Although CA9 has been negatively correlated with survival in various cancers, no published data has demonstrated prognostic significance in prostate cancer. Methods: We retrospectively assessed CA9 in samples from 68 men with localized high-risk prostate cancer (LD) treated with radical prostatectomy (RP) or radiotherapy (RT), and twenty men with CRPC treated with docetaxel chemotherapy (DC). Samples were taken before treatment with RP and RT (in LD) or DC (in CRPC) from 2010 to 2012 at the Princess Margaret Cancer Center. Results: Of the 68 patients with LD, 57 patients underwent RP and 11 patients underwent RT. The proportion of patients with recurrence was 74% for RP and 55% for RT. Median CA9 for patients with LD and recurrence was 147 (range 60-1061) and 114 (range 48-1293) for those with no recurrence. Baseline CA9 was not associated with recurrence or PSA in these patients (p 0.79 and 0.09 respectively). Median follow-up for patients with CRPC was 14.1 months and 17 of 20 patients had confirmed death at the end of follow-up. The median CA9 level before DC was 155 pg/mL (range 38-1086). CA9 level before chemotherapy correlated with overall survival -0.41, however this did not reach statistical significance (p 0.10). There was no association between CA9 and PSA in CRPC (p 0.51). Conclusions: Absolute CA9 level negatively correlated with survival in men with CRPC, with a level that approached statistical significance in this small cohort. CA9 was not associated with recurrence of disease in men with LD, treated with either RP or RT. More data evaluating the relationship between hypoxia, CA9 and outcome in prostate cancer is needed before recommending its use as a biomarker in CRPC.
CBIO-08IGFBP2 IS A NOVEL MOLECULAR DETERMINANT IN TRAIL-RESISTANT SUBPOPULATIONS OF GBM CELL LINES
Authors: Ahmet Cingoz, Zeynep H. Gümüş, Tugba Bagci-Onder
Journal: Neuro-Oncology (2015)

Glioblastoma Multiforme (GBM) is the most common and aggressive brain tumor, as survival rate is less than 12 months after diagnosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells; therefore, it has appeared as a strong candidate for cancer treatment. Studies have shown that many cancer cell lines are resistant to TRAIL, however the mechanisms regulating this resistance are not well understood. Moreover, a number of cancer cells exhibit partial sensitivity to TRAIL. In this study, we describe TRAIL-resistant cell line models. Firstly, we selected TRAIL-resistant subpopulations of a GBM cell line, which displays partial TRAIL sensitivity. U87MG, mid-TRAIL sensitive cell line, was treated with different, but fixed concentrations of TRAIL for several weeks, after which the surviving cell fractions were expanded in TRAIL-free conditions. Cell viability and caspase assays revealed that these cells exhibited sustained TRAIL-resistance. To examine the molecular differences in subpopulations, we examined the expression of apoptosis-related genes with qPCR and observed that Bcl-xL was significantly upregulated in TRAIL-resistant populations. We used genome wide RNA sequencing for understanding the gene expression changes and observed upregulation of IGFBP2 gene in resistant subpopulations compared with control cells. Our future efforts are directed at understanding the role of IGFBP2 gene for resistance mechanisms Our results will provide further understanding of molecular mechanisms of tumor heterogeneity in GBM cells, and help with the novel treatment strategies.
Design, execution, and preliminary biomarker results from paired tumor biopsy cohorts of the AZD9291 AURA trial
Authors: Kenneth Thress, James Leeson, Joseph Geradts, Martin Schuler, Myung-Ju Ahn, Juergen Wolf, Kathryn A. Gold, James Chih-Hsin Yang, Fiona Blackhall, Wu-Chou Su, Vivien Jacobs, Neil R. Smith, Helen Angell, Kathryn Brown, Karthick Vishwanathan, J. Carl Barrett, Mireille Cantarini, Pasi A. Jaenne
Journal: Journal of Thoracic Oncology (2015)