tbuckley/cabot-search huggingface dataset:
Strain-level dissection of the contribution of the gut microbiome to human metabolic disease
Authors: Chenhong Zhang, Liping Zhao
Journal: Genome Medicine (2016)

The gut microbiota has been linked with metabolic diseases in humans, but demonstration of causality remains a challenge. The gut microbiota, as a complex microbial ecosystem, consists of hundreds of individual bacterial species, each of which contains many strains with high genetic diversity. Recent advances in genomic and metabolomic technologies are facilitating strain-level dissection of the contribution of the gut microbiome to metabolic diseases. Interventional studies and correlation analysis between variations in the microbiome and metabolome, captured by longitudinal sampling, can lead to the identification of specific bacterial strains that may contribute to human metabolic diseases via the production of bioactive metabolites. For example, high-quality draft genomes of prevalent gut bacterial strains can be assembled directly from metagenomic datasets using a canopy-based algorithm. Specific metabolites associated with a disease phenotype can be identified by nuclear magnetic resonance-based metabolomics of urine and other samples. Such multi-omics approaches can be employed to identify specific gut bacterial genomes that are not only correlated with detected metabolites but also encode the genes required for producing the precursors of those metabolites in the gut. Here, we argue that if a causative role can be demonstrated in follow-up mechanistic studies--for example, using gnotobiotic models--such functional strains have the potential to become biomarkers for diagnostics and targets for therapeutics.
The Diagnosis and Management of Arteritis
Authors: N D Karanjia, S J Cawthorn, A E B Giddings
Journal: Journal of the Royal Society of Medicine (1993)

Inflammatory arterial disease is often insidious and associated with a substantial morbidity and mortality. Early recognition is vital. Patients with arteritis ( n=106) were studied and divided into five groups. Two of these were subgroups of giant cell arteritis classified by site into either cranial —arteritis (66), or upper limb arteritis (7). Three other groups were identified; chronic periaortitis (with or without inflammatory aortic aneurysm) (7), polyarteritis nodosa (14), and small vessel arteritis (12). Clinicians are not sufficiently aware of arteritis and its many atypical presentations. Delay in management is associated with a significant morbidity and mortality. In this district serving 200 000 people at least one patient per month is seriously at risk from the disease. Improved outlook depends on early recognition of the clinical syndromes and rapid appropriate treatment.
Psoriasis is associated with increased risk of abdominal aortic aneurysm, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

People with psoriasis may have an increased risk of developing abdominal aortic aneurysm, a Danish study has found, and the risk seems to increase with the severity of psoriasis.1

Abdominal aortic aneurysm becomes more common with age, and emerging evidence has shown that it has a distinct inflammatory component rather than occurring simply as a result of atherosclerosis.

Striking similarities had already been found between the inflammatory pathways causing the …
The Mechanism of the Production of Duroziez's Murmur
Authors: George G. Rowe, Skoda Afonso, Cesar A. Castillo, David H. McKenna
Journal: New England Journal of Medicine (1965)

ACCORDING to the description of Duroziez, as presented by Major1 and by Willius and Keys,2 the intermittent to-and-fro crural murmur associated with aortic insufficiency is produced by blood flow into the lower extremity during systole and back from the extremity toward the aorta during diastole. Although this may seem elementary there has been a considerable amount of investigation attempting to prove or disprove this hypothesis, and varying explanations have been suggested. Thus, Blumgart and Ernstene3 concluded, in 1933, that the diastolic portion of Duroziez's murmur arose either from backflow in the femoral artery during diastole, as seen in severe aortic . . .
Patterns of Palliative Care Consultation Among Elderly Patients With Cancer
Authors: Eric J. Roeland, Daniel P. Triplett, Rayna K. Matsuno, Isabel J. Boero, Lindsay Hwang, Heidi N. Yeung, Loren Mell, James D. Murphy
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: The role of palliative care has expanded over the past several decades, although the oncology-specific regional evolution of this specialty has not been characterized at the population-based level. Methods: This study defined the patterns of palliative care delivery using a retrospective cohort of patients with advanced cancer within the SEER-Medicare linked database. We identified 83,022 patients with metastatic breast, prostate, lung, and colorectal cancers. We studied trends between 2000 through 2009, and determined patient-level and regional-level predictors of palliative care delivery. Results: Palliative care consultation rates increased from 3.0% in 2000 to 12.9% in 2009, with most consultations occurring in the last 4 weeks of life (77%) in the inpatient hospital setting. The rates of palliative care delivery were highest in the West (7.6%) and lowest in the South (3.2%). The likelihood of palliative care consultation increased with decreasing numbers of regional acute care hospital beds per capita. The use of palliative care consultation increased with increasing numbers of regional physicians. The use of palliative care decreased with increasing regional Medicare expenditure with a $1,387 difference per beneficiary between the first and fourth quartiles of palliative care use. Conclusions: Geographic location influences a patient's options for palliative care in the United States. Although the overall rates of palliative care are increasing, future effort should focus on improving palliative care services in regions with the least access.
Monthly Triamcinolone Acetonide for Severe, Refractory, Life-Threatening Asthma in Children
Authors: Nadia L. Krupp, Andrea Weist, Cindy Fiscus
Journal: Journal of Allergy and Clinical Immunology (2016)

Treatment modalities for severe, therapy-resistant asthma in children are not well studied. Triamcinolone acetonide has been described in adults, but pediatric data on its use is limited. At our institution, triamcinolone acetonide has been used recently for children who have demonstrated severe, life-threatening asthma refractory to NHLBI Guidelines step 6 therapy. Retrospective chart review for children treated with intramuscular triamcinolone acetonide (TA) was performed. The following data were extracted: medication history, hospitalizations per year before and during TA therapy, life threatening events (cardiac arrest, intubation, CPR, ECMO). Five children have been treated with intramuscular TA at our hospital beginning in March 2014. Age at time of initiation of TA therapy ranged from 7.8 to 14.8 years. Patient histories were notable for the following asthma-related events: Patient 1 – three cardiac arrests; Patient 2 - ECMO and multiple intubations; Patient 3 – multiple intubations; Patient 4 – ICU admissions monthly; Patient 5 – cardiorespiratory failure twice requiring CPR and emergent intubation. All had failed treatment with daily oral corticosteroids, and had either failed or were not candidates for omalizumab and/or theophylline. Starting TA dose ranged from 60 to 120mg, was dosed monthly, and weaning was begun after 2-3 months of stability. In the year prior to intiation of TA therapy, the five patients combined for 28 hospital admissions. To date, after initiation of TA therapy none of the patients have been hospitalized. Monthly injection of triamcinolone acetonide is a viable therapeutic modality for children with life-threatening severe refractory asthma.
Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients
Authors: P. Griseri, O. Garrone, A. Lo Sardo, M. Monteverder, M. Rusmini, F. Tonissi, M. Merlano, P. Bruzzi, I. Ceccherini
Journal: Annals of Oncology (2015)
Carcinoembryonic Antigen in Extracts of Pulmonary Cancers
Authors: P. Sizaret, F. Martin
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Carcinoembryonic Antigen in Extracts of Pulmonary Cancers Get access P. Sizaret, P. Sizaret International Agency for Research on Cancer, 150 Cours Albert- Thomas 69008, Lyon, France; and Laboratoire de Médecine Expérimentale, Faculte de Médecine, 7 Bd. Jeanne d'Arc 21033, Dijon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Martin F. Martin International Agency for Research on Cancer, 150 Cours Albert- Thomas 69008, Lyon, France; and Laboratoire de Médecine Expérimentale, Faculte de Médecine, 7 Bd. Jeanne d'Arc 21033, Dijon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 3, March 1973, Pages 807–810, https://doi.org/10.1093/jnci/50.3.807 Published: 01 March 1973 Article history Received: 07 December 1972 Accepted: 15 December 1972 Published: 01 March 1973
Clinical benefit of erlotinib in male smokers with squamous-cell NSCLC
Authors: G. M. Clark, T. Cameron, A. Das Gupta
Journal: Journal of Clinical Oncology (2006)

7166 Background: Previous NSCLC trials have suggested female non-smokers with adenocarcinoma are most likely to benefit from treatment with EGFR inhibitors such as erlotinib. Thus, male smokers with squamous-cell carcinoma might be expected to fail treatment with erlotinib monotherapy. Methods: In a double-blind, placebo-controlled study of 731 patients with incurable stage IIIB/IV NSCLC who had failed 1 or 2 prior chemotherapy regimens, patients were randomized in a 2:1 ratio to receive either erlotinib 150 mg or placebo (Shepherd et al NEJM 2005; 353(2):123–132). For a subset of male patients with squamous-cell carcinoma and a history of smoking, median survival was estimated from Kaplan-Meier survival curves. The hazard ratio (HR) for death and corresponding 95% confidence interval (CI) were calculated from a univariate Cox model and statistical significance was described by a log-rank statistic. Results: In the ITT population the adjusted HR for death between the erlotinib and placebo arms was 0.73 (P &lt; 0.001). Among male smokers with squamous-cell carcinoma, overall survival was significantly improved among patients receiving erlotinib (N = 100) compared with patients with similar attributes in the placebo arm (N = 57): HR = 0.66, 95% CI 0.47 to 0.92, P = 0.016. This difference resulted in median survival time of 5.5 months in the erlotinib arm compared with 3.4 months in the placebo arm. Conclusions: Although male smokers with squamous-cell carcinoma have not been considered ideal candidates for treatment with erlotinib, survival benefits were observed in this subset of patients. [Table: see text]
Single-cell sequencing in stem cell biology
Authors: Lu Wen, Fuchou Tang
Journal: Genome biology (2016)

Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.
MYC Is a Crucial Mediator of TGFβ-Induced Invasion in Basal Breast Cancer
Authors: Magdalena A. Cichon, Megan E. Moruzzi, Tiziana A. Shqau, Erin Miller, Christine Mehner, Stephen P. Ethier, John A. Copland, Evette S. Radisky, Derek C. Radisky
Journal: Cancer Research (2016)

Basal subtype breast cancers have a particularly poor prognosis, with high invasiveness and resistance to most targeted therapies. TGFβ and MYC drive central features of basal breast cancer: TGFβ is an autocrine and paracrine signaling factor that drives cell invasion and metastasis, and MYC is a central regulator of cellular proliferation that is upregulated in many cancer types. We show here that genetic or pharmacologic inhibition of MYC in MCF10A basal breast cells results in increased sensitivity to TGFβ-stimulated invasion and metastasis and also show that this signaling loop is dependent on activation of SRC. Analysis of human breast cancer datasets and additional experiments with breast cancer cell lines further suggest the relevance of this signaling loop in basal, but not luminal, breast cancers. Our results imply precaution should be taken when utilizing therapeutic inhibitors of MYC with basal breast cancer patients as this could lead to increased metastasis; however, simultaneous pharmacologic inhibition of SRC and MYC for these patients could facilitate the antiproliferative effects of MYC inhibition while blocking the consequent promotion of metastasis. Cancer Res; 76(12); 3520-30. ©2016 AACR.
Changes in the Delivery of Care under Comprehensive Health Care Reform
Authors: A M Epstein
Journal: New England Journal of Medicine (1993)

Physicians occupy a pivotal position in the health care system. Economist Victor Fuchs has called them the captain of the ship, responsible for the large majority of decisions that direct the treatment of patients and determine what happens to them1. Physicians also understand the health care system as no one else can. They know when the system works and when it fails. The critical test of the Health Security Act will lie in the day-to-day practice of medicine. How will it work for patients? How will it work for doctors? Will reform through the Health Security Act foster better . . .
Cushing's Syndrome Caused by Corticotropin Secretion by Pulmonary Tumorlets
Authors: Elif Arioglu, John Doppman, Mario Gomes, David Kleiner, David Mauro, Carolee Barlow, Dimitris A. Papanicolaou
Journal: New England Journal of Medicine (1998)

The term “pulmonary tumorlets” describes multiple microscopic nests of neuroendocrine cells in the lungs.1 Like bronchial carcinoid tumors and small-cell carcinomas, pulmonary tumorlets arise from Kulchitsky's cells. In the lung the abnormalities in these cells range from hyperplasia to malignant transformation, since control over cellular growth is lost.2 Both bronchial carcinoid tumors and small-cell lung carcinomas may secrete corticotropin in sufficient quantities to cause Cushing's syndrome. We describe a patient with Cushing's syndrome due to ectopic secretion of corticotropin in whom the source of the excess corticotropin was ultimately found to be hundreds of tumorlets in one lobe of the . . .
The Volume of Primary Angioplasty Procedures and Survival after Acute Myocardial Infarction
Authors: John G. Canto, Nathan R. Every, David J. Magid, William J. Rogers, Judith A. Malmgren, Paul D. Frederick, William J. French, Alan J. Tiefenbrunn, Vijay K. Misra, Catarina I. Kiefe, Hal V. Barron
Journal: New England Journal of Medicine (2000)

There is an inverse relation between mortality from cardiovascular causes and the number of elective cardiac procedures (coronary angioplasty, stenting, or coronary bypass surgery) performed by individual practitioners or hospitals. However, it is not known whether patients with acute myocardial infarction fare better at centers where more patients undergo primary angioplasty or thrombolytic therapy than at centers with lower volumes.
Extraction of a Murine Tumor-Specific Transplantation Antigen With 1-Butanol. I. Partial Purification by Isoelectric Focusing&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S J LeGrue, B D Kahan, N R Pellis
Journal: JNCI Journal of the National Cancer Institute (1980)

Treatment of whole viable MCA-F murine sarcoma cells from syngeneic female C3H/HeJ mice with a single-phase solution of 2.5% (vol/vol) 1-butanol yielded a crude membrane protein extract without loss of cell viability. 1-Butanol-extracted cells were capable of in vitro proliferation. Variations in extraction conditions significantly influenced not only protein yield but also viability. The crude butanol extract (CBE) contained a tumor-specific transplantation antigen (TSTA) more potent than that obtained by 3-M KCl extraction of MCA-F cells: a specific activity of 40 TSTA U/mg protein in the former and 2 U/mg in the latter. The antigen was specific and protected host against challenge with MCA-F cells but not the antigenically different MCA-D cells. The growth of MCA-F cells was not reduced by pretreatment with equivalent doses of CBE obtained from MCA-D cells. Partial purification of the antigenic activity by preparative isoelectric focusing revealed that most activity focused in the pH 6.4 fraction, which increased the specific activity to 1,000 TSTA U/mg protein. Thus 1-butanol was an effective agent for the extraction of certain membrane polypeptides, including an immunogenic TSTA, from whole cells.
DISEASE CONTROL RATE AT 8 WEEKS PREDICTS SUBSEQUENT SURVIVAL IN PLATINUM-TREATED EXTENSIVE STAGE SMALL CELL LUNG CANCER (ES-SCLC): A PATIENT LEVEL ANALYSIS OF SWOG TRIALS
Authors: Primo Lara, James Moon, Mary Redman, Karen Kelly, Jeffrey Allen, Barbara Gitlitz, Philip Mack, David Gandara
Journal: Journal of Thoracic Oncology (2013)
Actionable targets in pancreatic cancer detected by immunohistochemistry (IHC), microarray (MA) fluorescent in situ hybridization (FISH), and mutational analysis.
Authors: Daniel D. Von Hoff, Ramesh K. Ramanathan, Douglas B. Evans, Michael J. Demeure, Todd Maney, Brian Wright, Zoran Gatalica, Matthew Jerome McGinniss
Journal: Journal of Clinical Oncology (2012)

4013 Background: A great need exists for new therapeutic approaches for patients with pancreatic cancer. Methods: The study cohort included 1029 patients analyzedfor a.) up to 29 different immunohistochemical biomarkers – (e.g., COX-2, MGMT, PGP, RRM1, TOPOI, TOPOII, SPARC etc.)b.); in up to 450 patients’ specimens a whole genome expression analysis was performed using HumanHT-12 v4 beadChips ( Illumina Inc.,San Diego, CA) c.) in up to 695 patients FISH for c-Myc, EGFR, HER2 and TOPO2A gene copy amplifications; and d.) in up to 783 patients sequencing for KRAS, EGFR, PI3CA and BRAF, was performed. Results: IHC identified actionable targets included; 74% high COX-2; 57% negative ERCC1; 8% negative MGMT; 22% negative MRP1; 47% negative PGP; 77% low RRM1, 44% high SPARC; 30% high TOPO2A; 61% high TOPOI and 73% negative TS. Other biologically important findings by IHC for possible new therapeutics included 27% negative PTEN; and 20% high PDGFR. Microarray results presented multiple overexpressed targets for consideration including 36% of specimens with overexpressed adenosine deaminase; 28% asparagine synthase; 17% BCL2; 20% survivin; 23% carboxylesterase; 67% DNMT1; 40% thymidine phosphatase; 49% EPHA2 (and others in the src family of kinases); 57% FOLR2; 41% HDAC1; 62% HiF1α; 23% IL2RA (CD25); 46% NFkB1; 48% OGFR; 32% RARA; 26% VEGFR; and 43% vitamin D receptor. FISH yielded 2% amplified EGFR and 10% amplified Her2neu. Sequencing noted 73% mutated KRAS and 3% mutated PIK3CA. Conclusions: Examining actionable targets in patients’ pancreatic cancers (a)reiterates the commonality and importance of KRAS mutations in this disease (needs renewed targeting effort) (b)suggests that TOPO2 inhibitors (particularly if transport into tumor can be improved) should be examined in this disease (c)suggests other pathways to target including DNA repair, epigenetic, Src and inflammation (d) suggests protein turnover, amino acid targets and folate receptor2 as fresh areas to explore against the disease. Supported in part by a Stand Up To Cancer Dream Team Award.
PTU-051 Diagnostic yield of oesophago-gastro-duodenoscopy as the initial investigation for patients presenting with haematochezia
Authors: H Boyd-Carson, S Ishaq, BR Disney
Journal: Gut (2015)

<h3>Introduction</h3> It is suggested that 15% of patients presenting with haematochezia will have an upper gastrointestinal (UGI) source of bleeding.<sup>1</sup>Current surgical school of thought recommends oesophago-gastro-duodenoscopy (OGD) as first-line investigation for patients with haematochezia.<sup>2</sup>More recent thinking suggests that a nasogastric lavage should be undertaken in this patient group to identify an UGI source of bleed.<sup>2</sup>We aimed to investigate whether the reported figure was an accurate representation and whether OGD should be undertaken primarily. <h3>Method</h3> Patients who presented with haematochezia were identified between January 2010 and June 2014, using clinical coding. Data collected included demographics, presentation, initial haemoglobin and urea serum levels, OGD findings and results from further endoscopic investigation. <h3>Results</h3> A total of 231 patients were identified (mean age 68 years, 55% male). Of these, 42 underwent OGD as first-line investigation. The majority of these (73%) had a normal endoscopy. The following pathologies where identified in the remaining endoscopies; duodenitis (7%), gastric ulcer (4%), gastritis (2.3%), oesophagitis (2.3%), oesophageal telangiectasia (2.3%), gastric erosions (2.3%), oesophageal ulcer (2.3%) and oesophageal varices (2.3%) Of those with a normal OGD, 80% had a further lower GI endoscopy. 60% of these patients had a clear LGI pathology accounting for their presentation. These findings demonstrate that of the patients who underwent OGD first line, only 7% had significant UGI pathology at OGD (peptic ulcer, oesophageal varices) with 2% actively bleeding (oesophageal varices). The mean haemaglobin for this population was 98 g/L (range 32–142 g/L). The median serum urea level was 9.2 mmol/L (range 1–13.2 mmol/L). In those with a normal OGD, 35% had a raised serum urea (mean 8.3 mmol/L, range 1.0–46.2 mmol/L). Whilst in those with an identified attributable UGI pathology, serum urea was raised in 100% of the cases (mean 8.8 mg/dl, range 7.9–9.9 mg/dl.) <h3>Conclusion</h3> We suggest an incidence of UGI pathology leading to haematochezia of 7%, which is far lower that the quoted figure of 15%. We therefore challenge surgical recommendation that OGD should be the first line investigation in this patient group unless haemodynamic instability or clinical suspicion is suggestive. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Jensen DM, Machicado GA. Diagnosis and treatment of severe hematochezia. The role of urgent colonoscopy after purge. Gastroenterology 1988;95(6):1569–74 Jensen DM, Ghassemi KA. Lower GI Bleeding: epidemiology and management. Curr Gastroenterol Rep. 2013;15(7):333