tbuckley/cabot-search huggingface dataset:
BSG/BBSRC
Authors: H Andreyev, D Cunningham, A Norman, H Schneider, S Sampson3, P Clarke, Ascites Parsons, S Watson, S Amar, R Steele
Journal: Gut (1996)

Metastatic cancers share several common properties with lymphocytes, in particular their ability to colonise lymph nodes and permeate tissues.CD44 is a cell surface protein expressed on lvmphocytes which facilitates both these functions.The discovern that variant forms of CD44 are expressed on certain tumour cells may lead to further understanding of carcinogenesis.This study was perfonned to examine the relationship between the expression of v6 variant (CD44v6) and clinical outcome in early colorectal cancer. METHODS:The records at 2 district general hospitals were reviewed to identify patients who had undergone potentially curative bowel resection for early colorectal cancer between 1987 and 1994.The pathology was reviewed.Expression of the CD44v6 variant protein w;as determined immunohistochemically using tissue blocks from the original tumour.Staining was assessed by an independent observer.Details of clinical outcome were obtained from hospital records and by contacting the patients' General Practitioners.Outoome measures used were evidence of disease relapse and death from recurrence.RESULTS: 97 patients were identified who had early primary colorectal cancers (85 Dukes A, 12 Duk-es B) treated by surgical resection between 1987-94. 45were men and 52 women.Median age was 70 years (range 33-90).Median follow up was 37 months (range 0.5-8 vears). 14patients had disease relapse. 11died and 3 patients underwent further surgery for local recurrence.36 tumours were positive for CD44v6.Staining was heterogeneous and generally of low intensity when compared with a positive control of normal keratinocvtes. 3of 11 cancer deaths and 1 of 3 local recurrences were CD44 6 positive.Of the 14 patents with disease relapse, 9 (60%) did not express CD44v6. CONCLUSION:CD44v6 expression did not correlate with recurrence, sunrival or any histological mark-er examined.
Kidney biopsy.
Authors: M S Knapp, R P Burden, D H Rose, P Davies
Journal: BMJ (1980)

right thigh with discoloration and bruising.The superficial epithelium had sloughed off.Her lungs, spleen, and liver were congested.Str pyogenes was isolated from her skin and subcutaneous tissue, but not from her heart blood or spleen.Her right hip showed no underlying abnormality.This is another example of a patient with Str pyogenes infection who did not have a classical presentation.This case also emphasises the fulminating nature of the infection, as she died despite having been on appropriate high doses of benzylpenicillin for 20 hours.
BOOK REVIEW
Authors: E. L. WYNDER
Journal: JNCI Journal of the National Cancer Institute (1995)

BOOK REVIEW Get access Cancer Prevention and Control Peter Greenwald , Barnett S. Kramer , Douglas L. Weed , eds. New York : Marcel Dekker, Inc. , 1995 , 824 pp. illus. $195. ISBN-0-8247-9258-0 ERNST L. WYNDER, M.D. ERNST L. WYNDER, M.D. American Health Foundation320 E. 43rd St. New York, NY 10017 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 11, 7 June 1995, Page 844, https://doi.org/10.1093/jnci/87.11.844 Published: 07 June 1995
Effectiveness of first-line therapy in patients with advanced non-clear renal cell carcinoma (nccRCC).
Authors: Sophie Laramee, Sunita Ghosh, Christian K. Kollmannsberger, Aaron Richard Hansen, Lori Wood, Denis Soulieres, Christina M. Canil, Ramy Saleh, Vincent Castonguay, Georg A. Bjarnason, Naveen S. Basappa, Rodney H. Breau, Daniel Yick Chin Heng, Frederic Pouliot, Anil Kapoor, Aly-Khan A. Lalani
Journal: Journal of Clinical Oncology (2022)

304 Background: Current treatment principles for advanced nccRCC have been largely extrapolated from guidelines for clear cell RCC. Given the emerging randomized data for select nccRCC subtypes, real-world outcomes for these patients are informative particularly in the contemporary checkpoint inhibitor era. Methods: We performed an analysis using the Canadian Kidney Cancer information system (CKCis), a prospective database involving 14 academic centers, on nccRCC patients undergoing first-line systemic therapy between January 2011 – December 2019. Treatment groups were defined as receipt of: vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-TKI), mammalian target of rapamycin inhibitors (mTORi), and PD-1/PD-L1 immune checkpoint inhibitors (ICI, mono- or combination therapy). Primary outcome was 1-yr overall survival (OS) rate. Secondary outcomes were median time to treatment failure ((TTF, months), defined as treatment discontinuation, change or death) and objective response rate (ORR, %). Results: We identified 265 nccRCC patients: 204 (77.0%) received VEGF-TKI, 19 (7.2%) received mTORi and 42 (15.8%) received ICI-based first-line therapy (Table). Overall, median age was 64 years, 75% were male, 84% were classified as IMDC intermediate/poor risk, and 16% underwent prior nephrectomy. Twenty-three percent of patients were enrolled in clinical trials. Patients received primarily sunitinib (81%) or pazopanib (15%) in the VEGF-TKI group (other: 4%), while mTORi-treated patients received temsirolimus (74%) or everolimus (26%). For the ICI-based treatment group, most patients received combination therapy as ipilimumab-nivolumab (71%) or pembrolizumab-axitinib (26%), with 3% receiving ICI monotherapy. 1-yr OS was 65.2% for VEGF-TKI, 57.9% for mTORi and 69.0% for ICI-treated patients. Median TTF was 3.3 for VEGF-TKI, 3.5 for mTORi and 7.1 mos for ICI-treated patients. ORR was 17%, 5%, and 37% respectively for the VEGF-TKI, mTORi and ICI-treated groups. Conclusions: We describe the effectiveness of first-line therapy for patients with nccRCC from a national database. This real-world data suggests an association between first-line ICI-based therapies and improved outcomes, albeit with cabozantinib not available for the indication during this time. Our data supports consensus recommendations for preferred use of ICI-based or VEGF-TKI over mTORi as first-line therapy in nccRCC.[Table: see text]
Abstract 137: The Impact of Psychological Distress on Six-Month Recovery Perceptions in Survivors of Cardiac Arrest
Authors: Alex Presciutti, Evie Sobczak, David J Roh, Soojin Park, Jan Claassen, Ian Kronish, Jennifer Sumner, Sachin Agarwal
Journal: Circulation (2018)

Introduction: To determine the association of depressive and posttraumatic stress disorder symptoms with cardiac arrest (CA) survivors’ long-term recovery perceptions, after accounting for cognitive status, functional independence, and medical comorbidities. Hypothesis: We recently demonstrated that posttraumatic stress and depressive symptoms, not cognitive or functional impairment, were associated with cardiac arrest survivors’ negative recovery perceptions at hospital discharge. Current study aims to extend this work by examining the correlates of perceived recovery in these CA survivors at 6 months after their hospital discharge. Methods: Perceived recovery of 78 prospectively enrolled CA survivors at 6-months post-discharge was assessed through the question, “Do you feel that you have made a complete recovery from your arrest?” Psychological symptoms were measured using the Center for Epidemiological Studies-Depression scale (CES-D) and the PTSD Checklist-Specific (PCL-S). Logistic regression was utilized to assess the association between depression and PTSD symptoms with positive and negative recovery perceptions, adjusting for demographics, cognitive impairment (Repeatable Battery for Assessment of Neuropsychological Status or Telephone Interview for Cognitive Status), functional dependence (Modified Lawton Instrumental Activities of Daily Living), and medical comorbidities (Charlson Comorbidity Index). Results: At 6 months, 53% of patients (n=41) had a negative recovery perception. 32.1% (n = 25) of patients screened for depression and 28.2% (n = 22) for PTSD. Patients with higher CES-D scores were significantly more likely to have a negative recovery perception in both unadjusted (Odds Ratio (OR): 1.10, 95% Confidence Interval (CI) [1.4, 1.16], p&lt;0.001) and adjusted analyses (OR: 1.10, 95% CI [1.03, 1.16], p&lt;0.01). PCL-S scores were significantly associated with negative recovery perception in an unadjusted model (OR: 1.05, 95% CI [1.01, 1.10], p &lt; 0.01), but not after adjustment of covariates. Conclusions: In contrast with cognitive and functional measures, psychological symptoms were strongly associated with cardiac arrest survivors’ negative recovery perceptions at 6-months post-discharge.
Psychosurgery.
Authors: P K Bridges, J R Bartlett
Journal: BMJ (1973)

this effect is unknown and findings are the opposite to those on serum corticosteroids in immobilized patients, which are significantly raised.2There may be either reduced testicular response to gonadotrophins or decreased hypothalamus-pituitary gland activity.It would seem that both extremes of physical activity have significant effects on serum androgens in men.-We are, etc.,
Medical News
Journal: JAMA (1970)

<h3>Chinese tree yields drug effective against cancer</h3> Ten of 17 patients with advanced cancer had favorable short-term responses to camptothecin sodium in a preliminary, dose-establishment study at NCI Encouraging preliminary clinical results with a chemotherapeutic agent derived from a Chinese tree have been reported by investigators at the National Cancer Institute. Favorable short-term responses were seen in 10 of 16 patients with advanced metastatic solid tumors and in one patient with acute myelogenous leukemia treated with camptothecin sodium. The responses were only brief—the median was just under two months. But coming at the end of long courses of disease, these responses may have some clinical significance, Jeffrey A. Gottlieb, MD, told the American Association for Cancer Research in Philadelphia. Camptothecin is a novel alkaloid, unrelated to any other chemotherapeutic agent. It is derived from the heartwood of<i>Camptotheca acuminata</i>, a tree native to the mainland of China. As a
Food Poisoning
Authors: C. Lundie
Journal: BMJ (1947)

stimulating effect.Barcroft's work suggests that it may well be of the greatest value where the normal mechapism is failing and the organism possibly having to rely on a, more primitive one.If this is so, it is but one more example of the clinical acumen of our forefathers which has been discredited not because it was wrong but because its mode of action was misunderstood, or because the conditions of the physiological experiment were such as to prevent its giving a correct answer."The proper study of mankind is man," and though cats and dogs are useful, they can never replace the acid test of human experiment.I suggest that those with the requisite opportunities might try the application of Barcroft's work in the way I have indicated.-I am, etc., Winsford, Cheshire W. N. LEAK.Artificial Insemination SIR,-Dr.Eustace Chessers letter (May 24, p. 738) is a valuable contribution towards a correct assessment of the problem of heterogeneous insemination.He admits having dealt with cases of homologous and heterogeneous insemination and now condemns the latter.Recently in Newcastle we were addressed on the legal prob- lems of this matter, which was dealt with from every aspect.We were informed that the donor should be a married man with one or two children and of proved health.I made, inter alia, the following remarks: "Artificial insemination of cattle is justifiable, as it involves no ethical problem.The majority of the males are castrated and it is only reasonable for commercial purposes that the remainder may distribute their favours, as after all we eat the progeny.I have never done homologous insemination, but I would consider it ethically correct to aid fertilization if, for example, coitus was impossible owing to vaginismus or some other abnormality.Heterogeneous insemi- nation brings in a special factor which revolts one.What type of individual can the donor be who hawks his seminal fluid round the countryside at so much per c.c.?"Judging by the way a large mixed audience received my remarks, from personal talks, letters, and phone messages, I am sure that the bulk of them felt-as I did.Dr. Chesser'
Trends of kidney cancer burden from 1990 to 2019 in European Union 15+ countries.
Authors: Nour Abdallah, Chinmay Jani, Christian Mouchati, Ruchi Tusharkumar Jani, Padmanabh Bhatt, Justin Salciccioli, Prateek Khanna, Harpreet Singh, Joseph Shalhoub, Rana R. McKay, Dominic C Marshall
Journal: Journal of Clinical Oncology (2022)

393 Background: Kidney cancer is among the most common cancers worldwide and is increasing in incidence. During 2020, around 400,000 new cases of kidney cancer were reported, with 180,000 estimated deaths. In recent decades, significant variability in the incidence and mortality of kidney cancer has been universally reported. This study aimed to compare geographical trends in incidence, mortality, and disability-adjusted life years from kidney cancer between European Union (EU) 15+ countries from 1990 to 2019. Methods: The mortality data of kidney cancer were extracted from the Global Burden of Disease Study database. Versions 10 and 9 of the International Classification of Diseases were adopted. Age-standardized incidence rates (ASIR), age-standardized death rates (ASDR), and disability-adjusted life years (DALYs) were collected, per year and per country of the EU15+ group. Mortality-to-incidence ratios (MIR) were calculated. Data was then dichotomized into males and females. Joinpoint regression was done for analysis of trends. Results: From 1990 to 2019, ASIRs increased in most of the countries except for Luxembourg for males, the United States of America (USA) for females, and Austria and Sweden for both sexes. The largest rises of ASIRs were in Denmark for males and females (+89.3% and +82.8%, respectively). ASDRs increased in 10/19 countries for males and 9/19 in females, with the highest rise in Denmark for males and females (+41.7% and +37.7% respectively), and the largest drop in Austria for males and females (-33.8% and -35.8% respectively). MIRs decreased in all countries, for both sexes, with the widest declines in Portugal for males (-29.0%) and in Ireland for females (-26.6%). Trends in DALYs were variable, with the highest rise in Denmark for males and females (+38.6% and +30.2% respectively) and the largest drop in Austria for males and females (-39.5% and -41.2%, respectively). In 2019, the highest ASIR was observed in the USA for males (16.7/100,000) and in Finland for females (8.3/100,000), the highest ASDR in the Netherlands for males (6.1/100,000) and Finland for females (3.0/100,000), highest MIR in Sweden for both genders (0.6/100,000 each), and highest DALYs in the Netherlands for males (132.3/100,000) and in Finland for females (62.6/100,000). Conclusions: The incidence and mortality from kidney cancer rose in most EU15+ countries from 1990 to 2019. Interestingly, an improvement in the outcomes is predicted by the drop in MIR in all countries.[Table: see text]
HIF-pathway genes prognostic for progression-free and overall survival in metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Patrick Tamukong, Paige Kuhlmann, Sungyong You, Shengchen Su, Yanping Wang, Eric Jay Small, Brian I. Rini, Susan Halabi, Jessica Janes, Stephen J. Freedland, Hyung Lae Kim
Journal: Journal of Clinical Oncology (2022)

370 Background: Clear cell renal cell carcinoma (ccRCC) is characterized by defects in the Von Hippel-Lindau/hypoxia-inducible factor (VHL/HIF) pathway. Several FDA-approved RCC therapies target the products of HIF-response genes. HIF2A is a promising new target and drugs targeting HIF2A are undergoing clinical testing. A better understanding of HIF-related genes may reveal useful biomarkers and drug targets. Methods: Gene expression was determined from 324 archival pretreatment nephrectomy specimens available from the Cancer and Leukemia Group B (CALGB) 90206, a phase III trial of patients treated with INF-α vs. INF-α plus bevacizumab. TaqMan RT-qPCR was performed on the OpenArray platform using RNA extracted from tumor tissue macrodissected based on review of H&amp;E staining by a genitourinary pathologist. HIF pathway genes were assessed across both treatment arms, utilizing the proportional hazards model as predictors of OS and PFS, with time from randomization to death or disease progression as endpoints. Results: A total of 28 HIF-related genes (involved either in canonical or non-canonical HIF regulation) were assessed in univariate PH. Nine of these genes were associated with OS (i.e., HIF2A , VEGFC, VEGFD, TGFA, VHL, CCND1, EGFR, EGLN3 and HSP90AA1); and 6 of them were also associated with PFS (i.e., HIF2A , TGFA, VHL, CCND1 and EGLN3, and HSP90AA1). The HIF isotypes HIF1A and HIF3A were not prognostic, likewise VEGFA and VEGFB. Prolyl hydroxylase domain (PHD) proteins efficiently hydroxylate HIFα in normoxic conditions. PHD isotypes EGLN (1-3) were evaluated and only EGLN3 was associated with OS and PFS. HIF is also regulated by non-canonical pathways that function independent of oxygen concentration. HSP90AA1 was the only non-canonical pathway gene that was prognostic, and it predicted both OS and PFS. When the 9 genes that were prognostic in univariate analysis were used in a backward stepwise multivariate cox regression, VEGFD, TGFA and EGLN3 predicted OS while HIF2A, VHL and TGFA predicted PFS. Conclusions: VHL, HIF2A (but not HIF1A and HIF3A), EGLN3 (but not EGLN1 and EGLN2) and some of the HIF-response genes were prognostic of both OS and PFS. HSP90AA1 was prognostic for OS and PFS, suggesting that the non-canonical HIF pathway also plays a role in disease progression. Future studies should consider these HIF pathway genes as potential drug targets, and as predictors of response to treatments targeting the hypoxia pathway and angiogenesis.[Table: see text]
Cervical cytology.
Authors: R E Sloan
Journal: BMJ (1979)

and on both occasions a blizzard prevailed.The Mercury, a Hobart newspaper, reported on 21 September 1903, "They had to face a snowstorm, with a strong south-westerly wind.Many of them were dressed only in singlets and light knickers, ... and the top sides of the mountain were covered with some feet of snow...." One of the participants noted some years later, "They were lying over logs, on the ground, and under trees, too exhausted to continue."Thus the deaths were a result-of hypothermia, the end result of exhaustion and inadequate or wet clothing in a cold, windy environment.It is clear that lightly clad runners are vulnerable to environmental conditions, both hot and cold, and the organisers of any community jogging events should realise that weather conditions can create a medical nightmare out of a "fun run."
DENDRITIC COMPUTATION
Authors: Michael London, Michael Häusser
Journal: Annual Review of Neuroscience (2005)

One of the central questions in neuroscience is how particular tasks, or computations, are implemented by neural networks to generate behavior. The prevailing view has been that information processing in neural networks results primarily from the properties of synapses and the connectivity of neurons within the network, with the intrinsic excitability of single neurons playing a lesser role. As a consequence, the contribution of single neurons to computation in the brain has long been underestimated. Here we review recent work showing that neuronal dendrites exhibit a range of linear and nonlinear mechanisms that allow them to implement elementary computations. We discuss why these dendritic properties may be essential for the computations performed by the neuron and the network and provide theoretical and experimental examples to support this view.
A VA Federal Supply Schedule (VAFSS)–based cost-effectiveness analysis of immunotherapy-tyrosine kinase inhibitor (IO-TKI) regimens and sunitinib in the treatment of metastatic renal cell carcinoma (mRCC).
Authors: Manish Kohli, Zachary Cutshall, Maura Dougherty, Richard Nelson, Minkyoung Yoo
Journal: Journal of Clinical Oncology (2022)

312 Background: Recent FDA approvals for mRCC treatment have resulted in increased effectiveness, drug choices, and costs. We performed a cost effectiveness analysis (CEA) of six recently approved IO-TKI drug combinations and sunitinib. Methods: We used a Markov simulation model from the healthcare sector perspective with a lifetime time horizon. The 7 treatment drug strategies considered in this model included: (1) atezolizumab + bevacizumab (AB), (2) avelumab + axitinib (AA), (3) pembrolizumab + axitinib (PA), (4) nibolumab + ipilimumab(NI), (5) nibolumab + cabozantinib (NC), (6) lenvatinib + pembrolizumab (LP), and (7) sunitinib (S). Input parameters of drug effectiveness and toxicities to construct the model were based on published randomized studies that led to drug approvals. Direct costs for treatment were derived using the VA Federal Supply Schedule (VAFSS). Markov model simulates patient transition between 3 health states at monthly intervals: progression free, progressive disease, and death. The cost-effectiveness outcome in our model were and life-years (LYs), progression-free life-years (PFLYs) gained, and quality-adjusted life-years (QALYs) with utility values based on published literature. Results: The table highlights results of the CEA. The least expensive drug combination was NI ($442,218) while the most expensive was LP ($963,610). AA yielded the most LYs (5.51) and QALYs (5.62) and LP yielded the most PFLYs (1.64) while NL yielded the least LYs (4.35) and PFLYs (1.47) and LP yielded the least QALYs (4.19). AB and S were absolutely dominated strategies yielding less effectiveness and cost more in terms of effectiveness measures. Depending on acceptable willingness-to-pay (WTP) and effectiveness measures, PA or AA were the most cost-effective strategies. Conclusions: Our analyses suggest that based on direct cost acquisition using VA FSS, PA or AA were cost-effective strategies for mRCC with WTP of $20,000 to $200,000 per QALY.[Table: see text]
Blood substitutes: two ways to get there
Authors: V. S. Cowart
Journal: JAMA (1983)

When T T hen a US meeting devoted specifically to blood substitutes was held in 1974 under the sponsorship of the National Institutes of Health, the program committee had trouble finding enough speakers to fill out the program. These days at such meetings,<i>limiting</i>the number of speakers is the problem. And so it was at the recent International Symposium on Blood Substitutes, which reflected burgeoning interest in the subject over the past eight years. The symposium was held at Letterman Army Institute of Research (LAIR) at the Presidio of San Francisco; it was sponsored by the US Army Medical Research and Development Command, Fort Detrick, Md, and the National Heart, Lung, and Blood Institute, Bethesda, Md. "I hope people don't think this was a shoot-out," said symposium co-chair Robert P. Geyer, MD, in his summation remarks at the end of the three-day program. He was referring to the profound