tbuckley/cabot-search huggingface dataset:
Abstract P5-20-04: Eribulin mesylate + trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer: results from a phase 2, multicenter, single-arm study
Authors: L Vahdat, L Schwartzberg, S Wilks, J Rege, J Liao, D Cox, J O'Shaughnessy
Journal: Cancer Research (2012)

Abstract Background: Eribulin mesylate, a novel non-taxane microtubule dynamics inhibitor, has been approved for patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for MBC. This study evaluates efficacy and safety of eribulin + trastuzumab (TRAZ) as first-line therapy for human epidermal growth factor receptor 2 positive (HER2+) locally recurrent or MBC. Methods: Patients received eribulin mesylate at 1.4 mg/m2 IV on days 1, 8 and TRAZ initial dose of 8 mg/kg IV on day 1 every 21 days, followed by 6 mg/kg on day 1 of each subsequent cycle. For study inclusion, patients could have been previously treated with TRAZ, but at least 12 months should have passed since any prior neoadjuvant or adjuvant chemotherapy was used. Endpoints include objective response rate (ORR) (primary), safety, progression free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments are evaluated every 6 weeks for the first 6 cycles and every 6–12 weeks thereafter per RECIST 1.1. Results: Updated results presented here as of June 1, 2012; 37 of 52 planned patients have been treated. Patient characteristics are as follows: median age: 58 years (range, 31–81), 70% have luminal subtype, 95% are stage IV disease, and 73% have visceral disease, 46% had prior neo/adjuvant, 22% had prior anthracycline and 32% had prior taxane, 35% had original diagnosis of MBC. Patients received median of 7 (1,20) cycles for eribulin and 9 (1,23) cycles for TRAZ. The most common treatment related AEs are reported in Table 1. Treatment-related serious AEs were reported for 4 (11%) patients; neutropenia 3 (8%) and febrile neutropenia 2 (6%) patients each. Eight patients have discontinued treatment due to disease progression (PD). Best patient responses are found in Table 2. Conclusions: Based on the updated preliminary results of this Phase II study, the combination of eribulin + trastuzumab as first-line therapy for HER2+ locally recurrent or MBC appears to demonstrate an acceptable safety profile with considerable tumor responses, including in patients with ER/PR+ disease. Accrual is ongoing and study completion is anticipated prior to SABCS 2012. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-04.
Activation of Mitochondrial Biogenesis by Heme Oxygenase-1–mediated NF-E2–related Factor-2 Induction Rescues Mice from Lethal <i>Staphylococcus</i> <i>aureus</i> Sepsis
Authors: Nancy Chou MacGarvey, Hagir B. Suliman, Raquel R. Bartz, Ping Fu, Crystal M. Withers, Karen E. Welty-Wolf, Claude A. Piantadosi
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Mitochondrial damage is an important component of multiple organ failure syndrome, a highly lethal complication of severe sepsis that lacks specific therapy. Mitochondrial quality control is regulated in part by the heme oxygenase-1 (HO-1; Hmox1) system through the redox-regulated NF-E2-related factor-2 (Nrf2) transcription factor, but its role in mitochondrial biogenesis in Staphylococcus aureus sepsis is unknown.To test the hypothesis that Nrf2-dependent up-regulation of the HO-1/carbon monoxide (CO) system would preserve mitochondrial biogenesis and rescue mice from lethal S. aureus sepsis.A controlled murine S. aureus peritonitis model with and without inhaled CO was examined for HO-1 and Nrf2 regulation of mitochondrial biogenesis and the resolution of hepatic mitochondrial damage.Sepsis survival was significantly enhanced using inhaled CO (250 ppm once-daily for 1 h), and linked mechanistically to Hmox1 induction and mitochondrial HO activity through Nrf2 transcriptional and Akt kinase activity. HO-1/CO stimulated Nrf2-dependent gene expression and nuclear accumulation of nuclear respiratory factor-1, -2α (Gabpa), and peroxisome proliferator-activated receptor gamma coactivator-1α; increased mitochondrial transcription factor-A and citrate synthase protein levels; and augmented mtDNA copy number. CO enhanced antiinflammatory IL-10 and reduced proinflammatory tumor necrosis factor-α production. By contrast, Nrf2(-/-) and Akt1(-/-) mice lacked CO induction of Hmox1 and mitochondrial biogenesis, and CO rescued neither strain from S. aureus sepsis.We identify an inducible Nrf2/HO-1 regulatory cycle for mitochondrial biogenesis that is prosurvival and counter-inflammatory in sepsis, and describe targeted induction of mitochondrial biogenesis as a potential multiple organ failure therapy.
Stress, Tobacco, and Coronary Disease in North American Professional Groups
Authors: Henry I. Russek
Journal: JAMA (1965)

A survey of 12,000 professional men in 14 occupational categories was conducted to determine the interrelationship among smoking habits, occupation-related emotional stress, and coronary heart disease prevalence. The distribution of the disease among professional groups in the United States showed a marked gradient which was unassociated with heredity or diet but strikingly related to the relative stressfulness of occupational activity. This increase in prevalence rate with advance in stress was shown to be remarkably consistent by age. Smoking was not only found to be stress-related but also statistically correlated with the reported frequency of ischemic heart disease in these professional groups. An entirely unexpected finding was the higher prevalence of coronary heart disease among nonsmokers (6.54%) than among exsmokers (2.34%). This paradox casts doubt upon the alleged role of smoking in the genesis of coronary heart disease and adds further emphasis to the probable influence of emotional factors in its causation.
Nf-κb and AP-1 activation is associated with late lumen loss after porcine coronary angioplasty and antiproliferative beta-irradiation
Authors: C DEINER, E SHAGDARSUREN, P SCHWIMMBECK, P ROSENTHAL, C LODDENKEMPER, U RAUCH, M PAUSCHINGER, R DIETZ, H SCHULTHEISS, R DECHEND
Journal: Cardiovascular Research (2007)

Despite the success of antiproliferative therapies, restenosis remains a common problem after percutaneous transluminal coronary angioplasty (PTCA). Longer-term clinical results of brachytherapy (intracoronary radiation), the lack of long-term clinical results after implantation of drug eluting stents, and the occurrence of late thrombosis after both procedures leave room for skepticism. Neointimal proliferation is not substantially inhibited at late time points after brachytherapy, and late lumen loss with a "catch-up" proliferation can occur. We hypothesized that the transcription factors nuclear factor-{kappa}B (NF-kappaB) and activator protein-1 (AP-1) are involved in these processes. We addressed the role of these mediators in a porcine model of coronary restenosis.Thirty-nine pigs underwent PTCA in two major coronary arteries. One of the two balloon-injured arteries was randomly assigned to receive immediate 20 Gy beta-irradiation (Brachy group) using a noncentered source train ((90)Sr/Y Beta-Cath, Novoste). Animals were sacrificed after 1 day, 14 days, or 28 days. Proliferating cells were labeled prior to euthanasia.At late time points, lumen area was significantly smaller and the inflammatory response was more pronounced in the Brachy group than in the PTCA group. These findings coincided with sustained activation of MMP-9 and transcription factors like NF-kappaB and AP-1. Initially, cell proliferation was reduced in the Brachy group; however, at late time points, differences between the two treatment groups were no longer significant.Brachytherapy initially inhibits cell proliferation; however, cellular and molecular inflammatory processes (e.g. activation of NF-kappaB) are enhanced within the arterial wall. This proinflammatory side effect may be responsible for the observed delayed proliferation and the resulting lumen loss.
The power of stories over statistics
Authors: T. B Newman
Journal: BMJ (2003)

Neonatal jaundice and infant safety on aeroplanes provide two lessons on the power of narrative, rather than statistical evidence, in determining practice 

I've always been more comfortable with numbers than with narrative, demanding data rather than accepting anecdotes. Recently, however, as a result of research in two unrelated areas—neonatal jaundice and infant safety on aeroplanes—I've been increasingly impressed with the power of stories over statistics. So I've decided to branch out from my usual publication format and tell a few stories of my own.

The jaundice story is one of me trying to treat jaundice in newborns according to the best evidence. Ironically, the more of an expert on the evidence I have become, the more difficulty I have practising according to that evidence. This is because becoming a “jaundice expert” means becoming familiar with rare but tragic stories of children with kernicterus. These stories are so powerful that it is hard to keep them from trumping other evidence in determining practice.

My neonatal jaundice story starts in the early 1980s, when I was a resident in paediatrics at the University of California, San Francisco. At that time, we treated babies with phototherapy when they had bilirubin concentrations above 14 mg/dl (239 μmol/l), and did exchange transfusions for concentrations above 20 mg/dl (342 μmol/l). Unfortunately, the early 1980s was not a good time to be transfusing blood in San Francisco. Although we did not know it then, the blood supply was contaminated with HIV. We also did not know that most of these exchange transfusions were unnecessary.

   ![][1] 

There's a story behind the “kinder, gentler” treatment thresholds for jaundice in newborns

Credit: JAMES STEVENSON/SPL

In 1983, in an article entitled “Bilirubin 20mg/dL = vigintiphobia,” Watchko and Oski questioned the “fear of twenty” that led to exchange transfusions for jaundice in healthy …

 [1]: /embed/graphic-1.gif
A Multivariate Analysis of Anatomic Success of Recurrent Retinal Detachment Treated with Pneumatic Retinopexy
Authors: Tarun Sharma, Sengamedu Srinivasa Badrinath, Bickol N. Mukesh, Lingam Gopal, Mahesh P. Shanmugam, Pramod Bhende, Muna Bhende, Nitin S. Shetty, Rajat Agrawal
Journal: Ophthalmology (1997)
Value of Routine Abdominal Nuclide Angiography as Part of Liver Scan
Authors: RENE A. ECHEVARRIA, CAROL BONANNO
Journal: Clinical Nuclear Medicine (1979)

Routine performance of a dynamic study as part of the liver scan results in a significant rate of discovery (19%) of intraabdominal abnormalities such as aortic aneurysms, cystic masses, ischemic intestinal diseases and collateral circulation. The procedure aids in the demonstration of space-occupying hepatic lesions and is often decisive in the diagnosis of chronic liver disease. Alterations in the perfusion of the liver as reflected in the dynamic scan may have a predictive value in the course of alcoholic hepatic disease as to the ultimate development of cirrhosis. Therefore, the dynamic study assumes an important role in the management of the alcoholic patient.
Reactivation of Chronic Hepatitis B Virus Infection by Cancer Chemotherapy
Authors: J. H. Hoofnagle, G. M. Dusheiko, D. F. Schafer, E. A. Jones, K. C. Micetich, R. C. Young, J. Costa
Journal: Annals of Internal Medicine (1982)

Two patients referred for cancer chemotherapy were found to be chronic, asymptomatic hepatitis B surface antigen (HBsAg) carriers. They had normal serum aminotransferase levels, but their sera were positive for HBsAg and antibody to hepatitis B e antigen. Both patients developed acute, icteric hepatitis within 3 months of starting cycled chemotherapy. In both cases, the disease seemed to be caused by a recurrence of type B hepatitis; it was accompanied by a marked increase in HBsAg titer and the appearance of hepatitis B virus DNA and DNA polymerase in the serum. One patient had a second episode of acute hepatitis after a second course of chemotherapy, but both patients ultimately recovered and became seronegative for HBsAg. Thus, it seems that cancer chemotherapeutic agents can reactivate type B hepatitis in asymptomatic HBsAg carriers. This reactivation is most likely due to an increase in hepatitis B virus synthesis followed by a rebound in host immune responses to hepatitis B virus infection when therapy is stopped. Such a phenomenon could have important implications for the therapy of chronic hepatitis B virus infection.
New York City's Health Care Crisis: AIDS, the Poor, and Limited Resources
Authors: Bohdan A. Oryshkevich
Journal: JAMA (1989)

To the Editor.—  The commentary by Drs Ron and Roger 1 on the impact of the human immunodeficiency virus (HIV)-1 epidemic on New York City was both timely and correct in pointing to the critical and destabilizing effect of that virus on New York City.  Their proposals were limited largely to increased federal funds for New York City for an expansion of acute care beds. Such a proposal is not likely to meet with enthusiasm in Washington, nor is it likely to solve New York's critical health care problems.  What is urgently needed is broad reassessment and reform of New York's care institutions and services in light of the HIV health epidemic. Such reform must begin with a solid understanding of why and how New York City, with its tremendous wealth and medical resources, became the incubator of, the disseminator of, and an endemic area for HIV. This reassessment must
Acute pancreatitis complicating Crohn's disease: mere coincidence or causality?
Authors: A Tromm, D Huppe, G H Micklefield, U Schwegler, B May
Journal: Gut (1992)

An example of acute pancreatitis developing five weeks after initial treatment with 5-aminosalicylic acid (5-ASA) and methylprednisolone for severe Crohn9s disease is reported in a 37 year old female patient. She had undergone cholecystectomy for gall stones some years earlier. There was no evidence of acute or chronic pancreatitis. No morphological changes of the upper gastrointestinal tract were found except for some irregularity of the main pancreatic duct and the secondary ducts on endoscopic retrograde pancreatography. Rechallenge with 5-ASA did not induce recurrent pancreatitis or changes in pancreatic enzymes. This case report supports the concept of an association between acute pancreatitis and Crohn9s disease.
The loneliness of the left handed surgeon
Authors: Roger Dobson
Journal: BMJ (2004)

<h3>ABSTRACT</h3> CRISPR/Cas approaches have largely replaced conventional gene targeting strategies. However, homology-directed repair (HDR) in the mouse genome is not very efficient, and precisely inserting longer sequences using HDR remains challenging, given that donor constructs preferentially integrate as concatemers. Here, we show that injecting 5’biotinylated donor DNA in mouse embryos at the two-cell stage leads to efficient single-copy HDR (scHDR) alleles. Our dedicated genotyping strategy showed that these alleles occurred with a frequency of 19%, 20%, and 26%, respectively, in three independent gene loci, indicating that scHDR is dramatically boosted by 5’biotinylation. Thus, we suggest that a combination of a 5’biotinylated donor and diligent analysis of concatemer integration are prerequisites for efficiently and reliably generating conditional alleles or other large fragment knock-ins into the mouse genome.
Eating disorders in insulin dependent diabetes mellitus: Authors' reply
Authors: C. Fairburn, B. Davies, R. Peveler, J I Mann, R. Mayou
Journal: BMJ (1991)

with the eating attitude test.This is clearly incorrect.Furthermore, their criticism ofour use of the paired t test in our analysis is without founda- tion.The skewness of the distributions for the scores, which concerned them, is irrelevent because what matters is the distribution of the differences between diabetic patients and controls, which was symmetric.They themselves acknowledge that their study may well exhibit a type 2 statistical error, whereas this is much less likely for our considerably larger study.Finally, the statement that "insulin misuse in young women is not thought to be common" is surprising.This type of behaviour is extremely common in young women, even in the absence ofan eating disorder.4Whether or not eating disorders fulfilling the criteria in the Diagnostic and Statistical Manual of Mental Disorders Third Edition are shown to be commoner in diabetic women, the Oxford group agrees that abnormal attitudes to food and body image are commoner in that group.In our opinion this is of great clinical importance.These problems cause much distress and poor control, contributing to the development of serious diabetic complica- tions.
Indoor Cycling for the Cardiac Patient
Authors: Nathaniel Shafer
Journal: JAMA (1971)

<h3>To the Editor.—</h3> When the patient with coronary disease is "back on his feet" and regular daily exercise is considered essential to keeping him there, I prescribe indoor cycling, and the prescription is as specific as any written for his medication. There are many reasons for preferring indoor cycling to walking, swimming, jogging, and golf. It is less likely to result in accidents; it does not depend on the weather. A patient housebound by wintry blasts or spring rains can exercise regularly, unhampered by outdoor clothing. If tired, he need not look for a park bench or step to rest on. The exercise can be done at regular intervals throughout the day as prescribed. If the patient is a busy executive, he can install a cycle in his office as well as at home and take his exercise while on the job. Patients with back conditions may find some forms
Tuberculosis in Dialyzed Patients
Authors: Roger S. Mitchell
Journal: JAMA (1974)

<h3>To the Editor.—</h3> I was most interested to read the article and learn of the greatly increased risk of active tuberculosis among patients with renal failure on maintenance dialysis. I do not believe that the authors have evidence that "patients on maintenance dialysis have a greater chance of contracting tuberculous infection." Rather, they have presented evidence that their patients had developed manifest clinical tuberculosis while undergoing dialysis. To my mind, it is far more likely that they were already infected and that the immunosuppressive effect of hemodialysis permitted a flare-up of endogenous tuberculous infection.
A7.6 Comparative Transcriptome Analysis of Human and Mouse Synovial Fibroblast Responses to TNF
Authors: Thomas Häupl, Till Sörensen, Bijana Smiljanovic, Marc Bonin, Andreas Grützkau, Christoforos Nikolaou, Ioannis Pandis, George Kollias, Anthony Rowe
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Animal models are essential for development of new therapeutics to test their effectiveness and to control for side effects. Targeted therapies with biologics reveal differences in responsiveness and suggest substantial differences in the molecular pathomechanisms of human as well as murine arthritis. In order to characterise such differences, we started a pilot investigation based on published transcriptomes to develop bioinformatic strategies of interspecies gene expression comparison. <h3>Materials and Methods</h3> A GEO repository search for compatible data sets on arthritis in human and mouse revealed the Affymetrix based transcriptomes of synovial fibroblasts from rheumatoid arthritis (RA) and osteoarthritis (OA) patients (GEO-accession: GSE13837) and mouse BALBc wt (GSE17160) with similar stimulation (TNF-alpha) and time point after stimulation (12 hours). MAS5 algorithms of signal extraction and pairwise comparison were performed. The BioRetis database was used for group comparisons, candidate gene selection and data sharing. Differentially expressed genes were exported for interspecies comparison in a filemaker database. Affymetrix annotation files were used for mapping of orthologous genes. <h3>Results</h3> The number of differentially expressed genes induced by TNF in synovial fibroblast from RA, OA and BALBc were 1584, 1476 and 503 respectively. Comparison of genes overexpressed in RA and OA revealed up to 70% (1034 genes) overlap. Murine and human response was similar for 197 genes in all three groups, 45 only between BALBc and RA and 24 only between BALBc and OA. Ranking the genes by dominance in change call and/or fold change, 7 genes were overlapping between the top 10 of both human cells, OA and RA, and 13 out of the top 20. All overlapping genes in human revealed a high correlation (R = 0.795). In contrast, overlap between RA and BALBc SFbl responses revealed only 4 genes out of the top 10 and 5 out of the top 20 in each and a weaker correlation (0.392). Pathway tools including IPA may identify TNF as one potential upstream regulator. However, the reference list of expected gene candidates for scoring in IPA seemed to be about 2.5 fold longer in human and to include less than 60% of the murine reference candidates. <h3>Conclusions</h3> Interspecies comparison in this defined experiment revealed first insight in common responses but also demonstrates that differences can be observed even in most dominant candidate genes. Therefore, systematic investigations are needed to provide a reliable basis for comparative mapping of the molecular pathomechanisms in mouse models and human disease. <h3>Acknowledgement</h3> BTCure IMI grant agreement no. 115142
Carcinogenicity of oil shale tars, some of their components, and commercial products.
Authors: P A Bogovski, F Vinkmann
Journal: Environmental Health Perspectives (1979)

Bioassays for carcinogenicity of various primary processing products (crude oils or tars) and commercial products obtained from Estorian oil shale have been carried out since 1951. The products (undiluted or diluted) were painted twice weekly 50 times on the interscapular area of the skin of random-bred or CC57Br mice. The products processed at high temperatures have a higher carcinogenic activity. Blends of products containing over 10% of high temperature crude oil (chamber furnace oil) have about the same carcinogenic activity as the latter. There is no strict correlation between the concentration of benzo(a)pyrene (BP) in oil shale products and their carcinogenic activity. Determination of BP in such products can serve as an approximate estimate of carcinogenic properties. The results of animal experiments with chromatographic fractions of the high temperature shale oil demonstrated the presence of compounds which lengthen the latency period of the carcinogenic effect of BP in the aromatic fraction of this oil as well as other carcinogens and compounds enhancing the activity of carcinogenic compounds. Under industrial conditions, contact of workers with carcinogenic shale oils can be reduced by means of coking the carcinogenic oils, which results in production of solid coke and of distillate which is recycled. Medical vaseline potentiates the carcinogenic action of BP and similar compounds. Dilution of shale oils with oils containing aliphatic hydrocarbons cannot be considered as diminution of the carcinogenic potency of these products.
THE BLOOD GLUTATHIONE (GSH) LEVEL IN MENTAL DISEASES
Authors: Arthur T. Brice
Journal: American Journal of Psychiatry (1935)

1. There appears to be a statistically highly significant difference in the blood glutathione (GSH) level between groups of mental patients and adequate individuals. 2. This difference is greatest in catatonic dementia præcox. It is also marked in hebephrenic and paranoid præcox, and in general paresis. It is less marked but still statistically significant in manic-depressive psychosis. In the small number of cases of epilepsy examined it was not statistically significant. 3. Diurnal variation and exercise have been ruled out as influences affecting the validity of conclusions based on the data accumulated in this study.