tbuckley/cabot-search huggingface dataset:
Vascular Endothelial Growth Factor Receptor-1 Is Synthetic Lethal to Aberrant β-Catenin Activation in Colon Cancer
Authors: Snehal Naik, Robin S. Dothager, Jayne Marasa, Cory L. Lewis, David Piwnica-Worms
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The Wnt/β-catenin (β-cat) signaling cascade is a key regulator of development, and dysregulation of Wnt/β-cat contributes to selected cancers, such as colorectal, breast, and hepatocellular carcinoma, through abnormal activation of Wnt target genes. To identify novel modulators of the Wnt/β-cat pathway that may emerge as therapeutic targets, we did an unbiased high-throughput RNA interference screen. Experimental Design: A synthetic oligonucleotide small interfering RNA library targeting 691 known and predicted human kinases was screened in Wnt3a-stimulated human cells in a live cell luciferase assay for modulation of Wnt/β-cat–dependent transcription. Follow-up studies of a selected high-confidence “hit” were conducted. Results: A robust quartile-based statistical analysis and secondary screen yielded several kinases worthy of further investigation, including Cdc2L1, Lmtk3, Pank2, ErbB3, and, of note, vascular endothelial growth factor receptor (VEGFR)1/Flt1, a receptor tyrosine kinase (TK) with putative weak kinase activity conventionally believed to be a negative regulator of angiogenesis. A series of loss-of-function, genetic null, and VEGFR TK inhibitor assays further revealed that VEGFR1 is a positive regulator of Wnt signaling that functions in a glycogen synthase kinase-3β (GSK3β)–independent manner as a potential synthetic lethal target in Wnt/β-cat–addicted colon carcinoma cells. Conclusions: This unanticipated non-endothelial link between VEGFR1 TK activity and Wnt/β-cat signaling may refine our understanding of aberrant Wnt signaling in colon carcinoma and points to new combinatorial therapeutics targeted to the tumor cell compartment, rather than angiogenesis, in the context of colon cancer. (Clin Cancer Res 2009;15(24):7529–37)
Water Intake and Cancer Prevention
Authors: Yair Bar David, Benjamin Gesundheit, Jacob Urkin, Joseph Kapelushnik
Journal: Journal of Clinical Oncology (2004)

and Hortobagyi for carefully reading our article and for providing the opportunity to further discuss our results.Their comments reflect concerns regarding: (1) the accuracy of our Surveillance, Epidemiology, and End-Results (SEER)defined inflammatory breast carcinoma (IBC) patients, and (2) the heterogeneity among our patients with noninflammatory locally advanced breast carcinoma (LABC).First, IBC patients (n ϭ 2,237) were defined with SEER extent of disease (EOD) code 70, corresponding to AJCC T4 d and consistent with Haagensen's classic diagnostic criteria [1][2][3].Sixty-six percent (n ϭ 1,488 of 2,237 [66.5%]) of patients with SEER-defined IBCs (EOD 70, T4 d) had matching International Classification of Diseases for Oncology (ICDO)-2 pathologic code 8530 because of documented dermal lymphatic invasion [4].The remaining 33% (n ϭ 749 of 2,237) had ICDO-2 pathologic codes other than 8530, including designations for ductal, tubular, lobular, medullary, and other morphologic subtypes.Undoubtedly, some of the remaining 33% had dermal lymphatic infiltration but for uncertain reasons did not receive ICDO-2 code 8530 from their local pathologists.Cristofanilli et al suggested that there was no information for the remaining 33% to support the distinction from LABC.However, Figure 4 in our article demonstrated identical agespecific incidence rate patterns for the 66.5% and 33% of our SEER-defined IBC cases (EOD 70, T4 d), irrespective of ICDO-2 code 8530 [5].A major thesis of our article was that similar age-specific rate curves suggested similar biology [5,6].However, differing rate patterns between IBC and LABC implied that all SEER-defined IBC cases (EOD 70, T4 d) were distinct from LABC.Second, Cristofanilli et al correctly noted that our LABC patients (n ϭ 7,985) included those with operable (stage IIIA) as well as inoperable (stage IIIB) disease.In fact, 61% of the LABC cases were operable stage IIIA (4,845 of 7,985 cases), compared with 39% with inoperable stage IIIB (n ϭ 3,140 of 7,985).SEER EOD codes 40 to 60 defined inoperable LABC (stage IIIB), corresponding to AJCC T4a-c [1,2].Cristofanilli et al suspected that operable stage IIIA biased our results.However, conclusions were not affected by removing operable stage IIIA from our analysis, as
The Technology of Medicine
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1971)

TECHNOLOGY assessment has become a routine exercise for the scientific enterprises on which the country is obliged to spend vast sums for its needs. Brainy committees are continually evaluating the effectiveness and cost of doing various things in space, defense, energy, transportation and the like, to give advice about prudent investments for the future.Somehow medicine, for all the 60-odd billion dollars that it is said to cost the nation, has not yet come in for much of this analytical treatment. It seems taken for granted that the technology of medicine simply exists, take it or leave it, and the . . .
Intrapersonal Conflict in Goals and Values of Patients with Unipolar Depression
Authors: Ulrich Stangier, Uwe Ukrow, Karin Schermelleh-Engel, Martin Grabe, Wolf Lauterbach
Journal: Psychotherapy and Psychosomatics (2007)

&lt;i&gt;Background:&lt;/i&gt; Although increased conflicts between attitudes and beliefs about certain goals or values are often discussed as important factors in depression, there are only few empirical studies investigating these relations among patients with depressive disorders. &lt;i&gt;Methods:&lt;/i&gt; In the present study, we used the Intrapersonal Conflict Test to assess cognitive inconsistencies in goals or values. A total of 53 inpatients with unipolar depression and 24 nondepressed controls (inpatients of an internal and a surgery ward) participated in the study. In addition to the Intrapersonal Conflict Test, patients completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Inventory of Interpersonal Problems as well as the Problem Solving Inventory. &lt;i&gt;Results:&lt;/i&gt; Compared with controls, patients with depressive disorders showed significantly higher scores for global inconsistencies, inconsistencies within different goals/values, as well as between goals/values and their perceived realization. Significant correlations were found between conflict measures and the Inventory of Interpersonal Problems, as well as the Problem Solving Inventory. Path analyses show that group differences in intrapersonal conflicts were partially mediated by interpersonal problems but not by depressive symptoms or cognitive vulnerability factors. &lt;i&gt;Conclusions:&lt;/i&gt; Given the cross-sectional design of the study, the findings of this exploratory study do not allow for conclusions regarding the role of intrapersonal conflicts in the development and course of depression. Nevertheless, the high levels of intrapersonal conflicts observed in the study suggest that inconsistencies in goals or values should be considered in the psychological treatment of depression.
Rheumatoid arthritis and metabolic syndrome
Authors: György Kerekes, Michael T. Nurmohamed, Miguel A. González-Gay, Ildikó Seres, György Paragh, Zsófia Kardos, Zsuzsa Baráth, László Tamási, Pál Soltész, Zoltán Szekanecz
Journal: Nature Reviews Rheumatology (2014)
Reverberation reconsidered: On the path to cognitive theory
Authors: Eric Chown
Journal: Behavioral and Brain Sciences (1995)

Abstract Amit's work addresses a critical issue in cognitive science: the structure of neural representations. The use of Hebbian cell assemblies is a positive step, and we now need to consider its role in a larger cognitive theory. When considering the dynamics of a system built out of attractors, a more limited version of reverberation becomes necessary.
Simple test for insulin antibodies in sera, using 131-I-insulin and ethanol precipitation.
Authors: T. A. Welborn, R. Richards, T. R. Fraser
Journal: BMJ (1967)

It is now common knowledge that all diabetics on insulin treatment develop some insulin antibodies, though only very rarely to an extent which interferes with their treatment.Evidence for circulating antibodies to insulin was obtained in vitro by Arquilla and Stavitsky (1956), using a haemagglutination technique; and in vivo by Berson et al.
Ptk2 And Eif3s3 Genes May Be Amplification Targets At 8Q23–Q24 and Are Associated With Large Hepatocellular Carcinomas
Authors: Hiroyuki Okamoto, Kohichiroh Yasui, Chen Zhao, Shigeki Arii, Johji Inazawa
Journal: Hepatology (2003)

We investigated 39 primary hepatocellular carcinomas (HCCs) for aberrations in DNA copy number, using comparative genomic hybridization (CGH). Gain of DNA at 8q was common in these tumors; high-level gains, indicative of gene amplification, occurred most frequently at 8q23-q24. Gains of 8q correlated with large (>5 cm) tumor size. To identify targets of the amplification events involving 8q, we determined expression levels of 14 candidate genes within that region in a total of 41 HCCs by means of real-time quantitative reverse-transcription polymerase chain reactions (RT-PCR). Significant correlation was found between elevated levels of expression and increases in copy number for PTK2 (located at 8q24.3) and EIF3S3 (at 8q23.3), but for none of the other candidates, which included MYC (8q24.1). Southern blot analyses confirmed that PTK2 and EIF3S3 were amplified, respectively, in 5 (19%) and 7 (26%) of the 27 tumors examined in accordance with expression patterns, an indication that expression of PTK2 and EIF3S3 was probably up-regulated by the amplification mechanism. When we analyzed potential relationships between elevated expression of PTK2 and EIF3S3 and clinicopathologic parameters, high expression of the 2 transcripts was significantly associated with large (>5 cm) tumor size and with hepatitis B virus (HBV) infection. In conclusion, PTK2 and EIF3S3, which, respectively, encode focal adhesion kinase and the p40 subunit of the eukaryotic initiation factor 3, were probable targets within the amplification at 8q23-q24 and may be involved in progression of HCC.
Satratoxin G from the Black Mold <i>Stachybotrys chartarum</i> Evokes Olfactory Sensory Neuron Loss and Inflammation in the Murine Noseand Brain
Authors: Zahidul Islam, Jack R. Harkema, James J. Pestka
Journal: Environmental Health Perspectives (2006)

Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin produced by Stachybotrys chartarum, the "black mold" suggested to contribute etiologically to illnesses associated with water-damaged buildings. Using an intranasal instillation model in mice, we found that acute SG exposure specifically induced apoptosis of olfactory sensory neurons (OSNs) in the olfactory epithelium. Dose-response analysis revealed that the no-effect and lowest-effect levels at 24 hr postinstillation (PI) were 5 and 25 microg/kg body weight (bw) SG, respectively, with severity increasing with dose. Apoptosis of OSNs was identified using immunohistochemistry for caspase-3 expression, electron microscopy for ultrastructural cellular morphology, and real-time polymerase chain reaction for elevated expression of the proapoptotic genes Fas, FasL, p75NGFR, p53, Bax, caspase-3, and CAD. Time-course studies with a single instillation of SG (500 microg/kg bw) indicated that maximum atrophy of the olfactory epithelium occurred at 3 days PI. Exposure to lower doses (100 microg/kg bw) for 5 consecutive days resulted in similar atrophy and apoptosis, suggesting that in the short term, these effects are cumulative. SG also induced an acute, neutrophilic rhinitis as early as 24 hr PI. Elevated mRNA expression for the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-6 (IL-6) , and IL-1 and the chemokine macrophage-inflammatory protein-2 (MIP-2) were detected at 24 hr PI in both the ethmoid turbinates of the nasal airways and the adjacent olfactory bulb of the brain. Marked atrophy of the olfactory nerve and glomerular layers of the olfactory bulb was also detectable by 7 days PI along with mild neutrophilic encephalitis. These findings suggest that neurotoxicity and inflammation within the nose and brain are potential adverse health effects of exposure to satratoxins and Stachybotrys in the indoor air of water-damaged buildings.
OXIDATIVE STRESS AND INFLAMMATORY BIOMARKERS IN PRE-HYPERTENSIVE AND NORMOTENSIVE AFRICAN AMERICANS
Authors: Keith M. Diaz, Deborah L. Feairheller, Kathleen M. Sturgeon, Sheara Williamson, Praveen Veerabhadrappa, Deborah Crabbe, Michael D. Brown
Journal: Journal of the American College of Cardiology (2010)
Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat
Authors: Christophe Boixel, Vincent Fontaine, Catherine Rücker-Martin, Paul Milliez, Liliane Louedec, Jean-Baptiste Michel, Marie-Paule Jacob, Stéphane N Hatem
Journal: Journal of the American College of Cardiology (2003)
Deaths from lung cancer in non-smokers are higher in men than in women
Authors: J. Wise
Journal: BMJ (2008)

The death rate from lung cancer among lifelong non-smokers is higher in men than in women, a large data review has found. The research contradicts assertions that the risk of lung cancer in people who have never smoked is growing and that the incidence of the cancer is higher among non-smoking women than non-smoking men.

The study pooled information from 13 large cohort studies that included more than 630 000 people for incidence analyses and 1.8 million people for mortality analyses ( PLoS Med 2008;5(9):e185, doi:10.1371/journal.pmed.0050185).

The studies spanned 1960 to 2004 and were based in North America, Europe, and Asia. They were supplemented with data from 22 cancer registries from 10 countries reported to have a low prevalence of smoking among women. The …
Impairment of Red Cell Transit through the Canine Lungs following Injections of Hypertonic Fluids
Authors: Richard M. Effros
Journal: Circulation Research (1972)

Rapid injections of hypertonic sucrose, sodium chloride, and urea solutions were given in the jugular veins of anesthetized dogs, and samples of blood were collected from the aorta. Following each of these injections, hemoglobin and plasma protein concentrations in the collected blood declined because fluid was extracted from the lungs. Injections of sucrose and sodium chloride, but not of urea, caused the hemoglobin concentration to fall more than the plasma protein concentration and slowed the movement of labeled red cells relative to that of labeled albumin when these two substances were injected at the same time and site as were the hypertonic solutions. The net flux of plasma through the lungs exceeded that of red cells for several seconds, indicating that plasma might pass around the more slowly moving red cells and through the smaller vessels of the lung. Impairment of red cell movement through the lungs is attributed primarily to red cell dehydration and loss of deformability. Unlike sucrose and sodium chloride, urea rapidly equilibrates between red cells and plasma and can only transiently dehydrate red cells. No impairment of red cell movement was seen after injections of hypertonic solutions of urea.
OBSERVATIONS ON THE IMPLANTATION OF TESTOSTERONE PELLETS
Authors: JOSEPH EIDELSBERG
Journal: JAMA (1941)

Within the past few years the literature on testosterone has become voluminous. In large part it deals with laboratory experiments, animal studies and the like. Carefully controlled clinical observations over long periods of time have been comparatively few. Still, the ultimate goal is the actual clinical application, for without such its importance is reduced and its value largely academic. In our clinic we have treated a large number of patients suffering with a wide diversity of conditions, including the postcastration status, eunuchoidism, hypogonadism of other types such as Lorain-Levi infantilism and hypopituitarism, impotence and others. For clarity and brevity only selected cases will be reported at this time, others being left for later communications. This report deals with observations on patients chosen from the "hypogenital groups," numbering in all 60, of whom 30 have been given further treatment by implantation, 30 having been treated by injections only. The 30 patients
Role of 5-hydroxytryptamine in the progression of monocrotaline induced pulmonary hypertension in rats
Authors: Y. Kanai, S. Hori, T. Tanaka, M. Yasuoka, K. Watanabe, N. Aikawa, Y. Hosoda
Journal: Cardiovascular Research (1993)

The aim was to clarify the role of serotonin (5-hydroxytryptamine, 5-HT) in monocrotaline induced pulmonary hypertension.Plasma 5-HT levels, pulmonary capillary platelet count, and vascular responsiveness to 5-HT were evaluated in the model. The effects of the selective 5-HT2 receptor antagonist, DV-7028, on the development of pulmonary hypertension were also investigated.Plasma 5-HT was raised 12 h to 3 d after monocrotaline administration (60 mg.kg-1), coinciding with accumulation of platelets in the pulmonary circulation. Isolated pulmonary arteries showed hyperreactivity to 5-HT at 14 and 21 d after monocrotaline. Administration of DV-7028 (20 mg.kg-1 x d-1) attenuated the increase in pulmonary arterial pressure, right ventricular hypertrophy, and medial thickening of the pulmonary arteries.The present study suggests that 5-HT released from platelets contributes to the initiation and progression of monocrotaline induced pulmonary hypertension.
England and Wales "achieve more with less" on cancer outcomes than other countries
Authors: M. Limb
Journal: BMJ (2011)

Researchers say a new study challenges government assertions that the NHS has a poor record internationally in treating cancer.

The study found the NHS was “comparatively effective and efficient” achieving sustained improvement in cancer outcomes over a 27 year period that rivalled other major developed countries.

The research was published in the British Journal of Cancer (doi:10.1038/bjc.2011.393). It compared cancer mortality with the amount spent on health as a proportion of gross domestic product (GDP) in England and Wales with nine other developed countries from 1979 to 2006.

The authors conclude the NHS “achieved more with proportionately less than other major developed countries.”

Ministers have criticised the UK’s record on cancer, citing poorer survival and death rates compared with Europe among their reasons …
Optimal Left Ventricular Endocardial Pacing Sites for Cardiac Resynchronization Therapy in Patients With Ischemic Cardiomyopathy
Authors: David D. Spragg, Jun Dong, Barry J. Fetics, Robert Helm, Joseph E. Marine, Alan Cheng, Charles A. Henrikson, David A. Kass, Ronald D. Berger
Journal: Journal of the American College of Cardiology (2010)
How Much Atrial Fibrillation Is Too Much Atrial Fibrillation?
Authors: Gervasio Lamas
Journal: New England Journal of Medicine (2012)

Modern cardiac pacemakers and defibrillators function as permanently implanted cardiac monitors, detecting atrial and ventricular arrhythmias. Although the principal purpose of collecting this information is to manage the patient's cardiac rhythm, these data can also be used to detect and study clinically inapparent arrhythmias and their consequences. In this issue of the Journal, Healey and coworkers1 report the results of a prospective study involving patients in whom a pacemaker or defibrillator had recently been implanted (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial [ASSERT]1,2; ClinicalTrials.gov number, NCT00256152). This study . . .
Simple Procedure for Red Blood Cell Labeling with Tc-99m HMPAO
Authors: MARTTI VORNE, RISTO LATINEN
Journal: Clinical Nuclear Medicine (1992)

Clinical applications for Tc-99m HMPAO labeled red blood cells have not been previously reported. The authors describe a simple, aseptic, closed, one-step centrifugal procedure for red blood cell labeling with Tc-99m HMPAO and isolation from whole blood, and they report the preliminary results of using these labeled red blood cells to detect acute gastrointestinal bleeding in 11 patients. Whole blood was radiolabeled with Tc-99m HMPAO preparation and blood cells were separated by centrifugation (30 min, 200 g, 20°C) using Polyprep density gradient medium. Red blood cells contained about 50% of the radioactivity. Four out of the 11 patients imaged with a gamma camera after reinjection of labeled autologous red blood cells showed abnormal accumulation, suggesting gastrointestinal bleeding that was verified at surgery and was at the site of abnormal activity in all cases. Image quality with Tc-99m HMPAO was comparable to that of Tc-99m pertechnetate labeled pretinned red blood cells. Tc-99m HMPAO can be used as a red blood cell labeler; however, its elution rate from red blood cells limits its applicability in some investigations.
Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England
Authors: T. Lee, R. Blanks, C. Rees, K. Wright, C. Nickerson, S. Moss, A. Chilton, A. Goddard, J. Patnick, R. McNally, M. Rutter
Journal: Endoscopy (2012)

<b>Background and study aims: </b>Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. <b>Patients and methods: </b>The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 – 8.9, 9 – 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. <b>Results: </b>In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (<i>P</i> < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (<i>P</i> < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. <b>Conclusions: </b>This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy.
Stop protecting the NHS budget
Authors: Des Spence
Journal: BMJ (2013)

I met a friend in Lidl. We shook our heads. I said in a hushed voice, “They constantly complain, bringing their own bags to conceal the fact they’re shopping at Lidl, and they don’t the follow the queuing etiquette. Bloody Marks and Spencer types!” The middle class are moving to Lidl, taking our trolleys and buying up all the risotto rice and vanilla pods. Next, middle class children will be getting a Megabus pass rather than a car on their 18th birthday, and spend their gap year working in Primark in Chelmsford. This is the economic reality, and it is delivering a social …