tbuckley/cabot-search huggingface dataset:
Health Care System and Socioeconomic Factors Associated With Variance in Use of Sentinel Lymph Node Biopsy for Melanoma in the United States
Authors: Karl Y. Bilimoria, Charles M. Balch, Jeffrey D. Wayne, David C. Chang, Bryan E. Palis, Sydney M. Dy, Julie R. Lange
Journal: Journal of Clinical Oncology (2009)

Guidelines recommend sentinel lymph node biopsy (SLNB) for patients with clinical stage IB/II melanomas, but not clinical stage IA melanoma. This study examines factors associated with SLNB use for clinically node-negative melanoma.Patients diagnosed with clinically node-negative invasive melanoma in 2004 and 2005 were identified from the National Cancer Data Base. Regression models were developed to assess the association of clinicopathologic (sex, age, race/ethnicity, comorbidities, T stage), socioeconomic (insurance status, educational level, income), and hospital (hospital type, geographic area) factors with SLNB use.A total of 16,598 patients were identified: 8,073 patients with clinical stage IA and 8,525 patients with clinical stage IB/II melanoma. For clinical stage IB/II melanoma, SLNB use was reported in 48.7% of patients. Patients with clinical stage IB/II melanoma were less likely to undergo SLNB if they were older than 75 years; had T1b tumors, no tumor ulceration, or head/neck or truncal lesions; were covered by Medicaid or Medicare; or lived in the Northeast, South, or West census regions. SLNB use was reported in 13.3% of patients with clinical stage IA melanoma and was more likely in patients who were younger than 56 years or lived in the Mountain or Pacific census regions. Patients treated at National Comprehensive Cancer Network-or National Cancer Institute-designated hospitals were most likely to undergo SLNB in adherence with national consensus guidelines.SLNB use was associated with clinicopathologic factors but also with health system factors, including type of insurance, geographic area, and hospital type. These findings have implications for provider education and health policy.
Construct Validity of a Tool for Assessing Competency in Polypectomy
Authors: S. Gupta, R. Man, N. Suzuki, M. E. Vance, S. Thomas-Gibson
Journal: Gut (2011)

<h3>Introduction</h3> There is a void in the formal assessment of technical skills in polypectomy which is now considered an integral part of colonoscopy. It has been shown to reduce the incidence of colorectal cancer but does have associated complications. Polypectomy competency assessment should arguably be a part of the certification process for all endoscopists. A polypectomy competency assessment tool (Direct Observation of Polypectomy Skills-DOPyS) has been developed and its construct validity, examined. <h3>Methods</h3> To determine construct validity of the DOPyS. Thirty-two polypectomy videos (incorporating the endoscopic view only) were collected from real patient procedures performed by two experienced (&gt;1000 colonoscopies) endoscopists (17 videos) and six intermediate level (100–500 colonoscopies) endoscopists (15 videos). The videos were edited to include only the entire polypectomy procedure, arranged in random order, and assessed blindly by two experienced endoscopy assessors. Both assessors underwent a polypectomy assessment training session using the DOPyS prior to scoring. The DOPyS incorporates a 33-point procedure-specific checklist and an overall competency score. The differences in overall competency scores (range 1–4; scores ≥3=competency) for the expert and intermediate groups were compared, and considered significant (p value&lt;0.05) using Fisher9s exact test. <h3>Results</h3> <h3>Conclusion</h3> The results of the analysis suggested that both blinded assessors were able to reliably differentiate between endoscopists of varying experience using the DOPyS (the expert group had higher scores than the intermediate group). Large-scale validation studies are required to further strengthen evidence for the use of this tool for routine polypectomy competency assessment. <h3>Competing interests</h3> None.
Effect of increasing Helicobacter pylori ammonia production by urea infusion on plasma gastrin concentrations.
Authors: R S Chittajallu, W D Neithercut, A M Macdonald, K E McColl
Journal: Gut (1991)

It has been proposed that the hypergastrinaemia in subjects with Helicobacter pylori infection is caused by the action of the ammonia produced by the organism9s urease activity on the antral G cells. To investigate this hypothesis we examined the effect on plasma gastrin of increasing the bacterium9s ammonia production by infusing urea intragastrically to eight H pylori positive duodenal ulcer patients. After a 60 minute control intragastric infusion of dextrose solution at 2 ml/minute, a similar infusion containing urea (50 mmol/l) was continued for four hours. During the urea infusion, the median gastric juice urea concentration rose from 1.1 mmol/l (range 0.3-1.6) to 15.5 mmol/l (range 7.9-21.3) and this resulted in an increase in the ammonium concentration from 2.3 mmol/l (range 1.3-5.9) to 6.1 mmol/l (range 4.2-11.9) (p less than 0.01). This appreciable rise in ammonia production did not result in any change in the plasma gastrin concentration. The experiment was repeated one month after eradication of H pylori, at which time the median basal gastrin was 20 ng/l (range 15-25), significantly less than the value before eradication (30 ng/l range 15-60) (p less than 0.05). On this occasion, the gastric juice ammonium concentration was considerably reduced at 0.4 mmol/l (range 0.1-0.9) and the urea infusion did not raise the ammonium concentration or change the plasma gastrin concentration. In conclusion, augmenting H pylori ammonia production does not cause any early change in plasma gastrin.
Leptin modulates autophagy in human CD4+CD25− conventional T cells
Authors: Silvana Cassano, Valentina Pucino, Claudia La Rocca, Claudio Procaccini, Veronica De Rosa, Gianni Marone, Giuseppe Matarese
Journal: Metabolism (2014)

ObjectiveIn this report we show that the adipocytokine leptin directly modulates autophagy in human CD4+CD25− conventional (Tconv) T cells.ResultsIn vitro treatment with recombinant human leptin determined an inhibition of autophagy during T cell receptor (TCR) stimulation, and this phenomenon was dose- and time-dependent. The events were secondary to the activation of the mammalian-target of rapamycin (mTOR)-pathway induced by leptin, as testified by its reversion induced by mTOR inhibition with rapamycin. At molecular level these phenomena associated with Bcl-2 up-regulation and its interaction with Beclin-1, whose complex exerts a negative effect on autophagy.Materials/methodsThe impact of leptin on autophagy of Tconv cells was determined at biochemical level by western blotting and by flow cytometry; the interaction between BCL-2 and Beclin-1 by co-immunoprecipitation assays.ConclusionsOur results, suggest that in unconditioned, freshly-isolated human Tconv cells, autophagy and proliferation are controlled by leptin during TCR-engagement, and that both phenomena occur alternatively indicating a balance between these processes during immune activation.
Genetic and Pharmacologic Inhibition of mTORC1 Promotes EMT by a TGF-β–Independent Mechanism
Authors: Ivan Mikaelian, Mouhannad Malek, Rudy Gadet, Jean Viallet, Amandine Garcia, Anaïs Girard-Gagnepain, Cédric Hesling, Germain Gillet, Philippe Gonzalo, Ruth Rimokh, Marc Billaud
Journal: Cancer Research (2013)

Epithelial-to-mesenchymal transition (EMT) is a transdifferentiation process that converts epithelial cells into highly motile mesenchymal cells. This physiologic process occurs largely during embryonic development but is aberrantly reactivated in different pathologic situations, including fibrosis and cancer. We conducted a siRNA screening targeted to the human kinome with the aim of discovering new EMT effectors. With this approach, we have identified mTOR complex 1 (mTORC1), a nutrient sensor that controls protein and lipid synthesis, as a key regulator of epithelial integrity. Using a combination of RNAi and pharmacologic approaches, we report here that inhibition of either mTOR or RPTOR triggers EMT in mammary epithelial cells. This EMT was characterized by the induction of the mesenchymal markers such as fibronectin, vimentin, and PAI-1, together with the repression of epithelial markers such as E-cadherin and ZO-3. In addition, mTORC1 blockade enhanced in vivo migratory properties of mammary cells and induced EMT independent of the TGF-β pathway. Finally, among the transcription factors known to activate EMT, both ZEB1 and ZEB2 were upregulated following mTOR repression. Their increased expression correlated with a marked reduction in miR-200b and miR-200c mRNA levels, two microRNAs known to downregulate ZEB1 and ZEB2 expression. Taken together, our findings unravel a novel function for mTORC1 in maintaining the epithelial phenotype and further indicate that this effect is mediated through the opposite regulation of ZEB1/ZEB2 and miR-200b and miR-200c. Furthermore, these results suggest a plausible etiologic explanation for the progressive pulmonary fibrosis, a frequent adverse condition associated with the therapeutic use of mTOR inhibitors.
I. RENAL FUNCTION INFLUENCED BY INTESTINAL OBSTRUCTION
Authors: Irvine McQuarrie, G. H. Whipple
Journal: The Journal of Experimental Medicine (1919)

Associated with the intoxication of intestinal obstruction there exists a definite impairment of the excretory function of the kidneys. The degree of functional depression corresponds roughly with the intensity of the clinical intoxication. The decrease in the urea ratio and in the capacity of the kidneys to excrete sodium chloride is more marked than is the percentage decrease of phenolsulfonephthalein elimination. The great increase in the non-protein nitrogen of the blood usually observed in acute intestinal obstruction, which has hitherto been explained as being due entirely to an increased rate of protein catabolism, is due in part to retention of the products released from the injured cell protein. It is probable that the impaired renal function is due to direct action of the toxic substances upon the renal epithelium. The actual demonstration of this renal injury is perhaps the strongest evidence so far obtained to prove the presence of an actual toxic substance in the blood during intestinal obstruction. This obscure disability of the kidneys during the height of the intoxication of acute ileus should always be considered in the clinical management of this condition. It may also serve as a guide to indicate the degree of intoxication.
The stimulation of cardiac prostaglandin production by blood plasma and its relationship to the regulation of coronary flow in isolated isovolumic rabbit hearts.
Authors: R L Moretti, S Abraham, R R Ecker
Journal: Circulation Research (1976)

Infusion of small amounts of blood plasma into isolated, isovolumic rabbit hearts perfused with Tyrode's solution resulted in coronary vasoconstriction followed by a decrease in left ventricular developed pressure and dP/dt. Maximal effects were obtained with a perfusate plasma concentration of 1%. Increasing the plasma concentration beyond 1% did not appreciably increase the coronary vasoconstriction. During perfusion with 2% plasma, the coronary flow-oxygen uptake ratio was unchanged over a range of perfusion pressures (40-100 mm Hg) and vascular resistance increased with pressure. In the absence of plasma, the coronary flow-oxygen uptake ratio increased with pressure and vascular resistance decreased. Thus, cardiac regulation of coronary flow in response to changes in perfusion pressure occurred in the presence of plasma but not in its absence. The effects of plasma were reduced with two different inhibitors of prostaglandin synthesis (5,9,11,14-eicosatetraynoic acid and indomethacin). At a perfusate concentration of 50 mug/ml, indomethacin abolished the effects of 2% plasma. Rat stomach strip bioassay for prostaglandin activity indicated that the vasoconstrictor effect of plasma was accompanied by a 4-fold increase in the release of prostaglandin activity by the isolated hearts. The vasoconstrictor effect of plasma also was accompanied by an increase in the conversion of 3H-arachidonate to radiolabeled prostaglandins E2 and F2alpha. These results indicate that a relationship exists between a coronary vasoconstrictor in plasma, cardiac prostaglandin synthesis, and the regulation of coronary flow in response to changes in perfusion pressure in isolated rabbit hearts.
Influence of Allogeneic Effect on 7,12-Dimethylbenz[a] anthracene Carcinogenesis in Mice2
Authors: Carlo D. Baroni, Stefania Uccini, Luigi Ruco, Giovanna Soravito
Journal: JNCI Journal of the National Cancer Institute (1975)

Charles River mice either untreated or treated at birth with 7,12-dimethylbenz]alpha[anthracene (DMBA) were given allogeneic spleen cells from adult C57BL/Cas donors. These spleen cells were given as a single injection to mice at birth or at 7 or 14 days of age. Allogeneic treatment of mice at birth significantly increased the incidence of DMBA-induced lymphomas and shortened the latency period of the tumors. The incidence of subcutaneous tumors was moderately increased in DMBA-treated mice given grafts of allogeneic cells at 7 days of age. Lung tumors appeared to be decreased in the group given DMBA at birth and allogeneic cells 14 days later. Treatment with only allogeneic cells gave results essentially similar to those observed in untreated controls.
Majority-Rule Consensus of Phylogenetic Trees Obtained by Maximum-Likelihood Analysis
Authors: L. S. Jermiin, G. J. Olsen, K. L. Mengerson, S. Easteal
Journal: Molecular Biology and Evolution (1997)

The maximum-likelihood (ML) approach is a powerful tool for reconstructing molecular phylogenies.In conjunction with the Kishino-Hasegawa test, it allows direct comparison of alternative evolutionary hypotheses.A commonly occurring outcome is that several trees are not significantly different from the ML tree, and thus there is residual uncertainty about the correct tree topology.We present a new method for producing a majority-rule consensus tree that is based on those trees that are not significantly less likely than the ML tree.Five types of consensus trees are considered.These differ in the weighting schemes that are employed.Apart from incorporating the topologies of alternative trees, some of the weighting schemes also make use of the differences between the log likelihood estimate of the ML tree and those of the other trees and the standard errors of those differences.The new approach is used to analyze the phylogenetic relationship of psbA proteins from four free-living photosynthetic prokaryotes and a chloroplast from green plants.We conclude that the most promising weighting scheme involves exponential weighting of differences between the log likelihood estimate of the ML tree and those of the other trees standardized by the standard errors of the differences.A consensus tree that is based on this weighting scheme is referred to as a standardized, exponentially weighted consensus tree.The new approach is a valuable alternative to existing treeevaluating methods, because it integrates phylogenetic information from the ML tree with that of trees that do not differ significantly from the ML tree.
Pinopodes: a questionable role in endometrial receptivity
Authors: C.E. Quinn, R.F. Casper
Journal: Human Reproduction Update (2008)

A better understanding of endometrial receptivity is crucial to the creation and optimization of tests to assess the window of implantation in a clinical setting. Testing endometrial receptivity via scanning electron microscopy of endometrial samples reveals that pinopodes are a very good marker of endometrial receptivity in the rat. There is still disagreement in the literature as to their usefulness as a receptivity marker in both mice and humans. Publications related to the discovery, study and usefulness of pinopodes as a marker of endometrial preparation for implantation in both rodents and humans were identified through MEDLINE and other bibliographic databases. There is substantial evidence that pinopodes are good markers of endometrial receptivity in the rat. Pinopodes are not useful in the mouse or human as consistent markers of endometrial receptivity for implantation. In the human, pinopodes have a prolonged (>5 days) presence in the luteal phase and fail to delineate the brief (24–48 h) window of receptivity. While there are many publications arising from one group supporting the use of pinopodes as a reliable marker of human endometrial receptivity, few independent groups have been able to confirm these results. The clinical usefulness of pinopodes to delineate a period of endometrial receptivity seems unlikely following recent findings that pinopodes are present throughout the luteal phase of the menstrual cycle.
Anaphylaxis and Related Allergic Emergencies Including Reactions due to Insect Stings
Authors: Roy Patterson
Journal: JAMA (1982)

ALLERGIC emergencies refer to acute reactions mediated by immunologic mechanisms of such severity as to require immediate treatment. These immunologic reactions involve antigen-antibody interactions that result in the release of chemical mediators, and resultant signs and symptoms. The main thrust of this section will deal with systemic anaphylaxis and acute laryngeal edema. A discussion of status asthmaticus is handled separately in this volume (see chapter 1). Likewise, anaphylactoid reactions or pseudoallergies, such as reactions to radiographic contrast media or aspirin and nonsteroidal anti-inflammatory agents will not be covered here, since an immunologic basis has not been demonstrated; nevertheless, the same general principles of treatment apply, since an airway must always be maintained and hypotension and shock must be treated in a similar manner as the treatment of an anaphylactic reaction. Although it was once thought that allergic persons might be more susceptible to such reactions, strong evidence for such a
Activity of Ancient RTE Retroposons during the Evolution of Cows, Spiral-Horned Antelopes, and Nilgais (Bovinae)
Authors: M.A. Nilsson, D. Klassert, M.F. Bertelsen, B.M. Hallström, A. Janke
Journal: Molecular Biology and Evolution (2012)

In the genome of Artiodactyla (cow, sheep, pigs, camels, and whales), a major retroposon group originated from a presumable horizontal transfer of BovB, a retrotransposon-like element retroposon, between 52 and 70 million years ago. Since then, BovB retroposons have proliferated and today occupy a quarter of the cow's genome sequence. The BovB-related short interspersed elements (SINEs) were used for resolving the phylogeny of Bovinae (cows, spiral-horned antelopes, and nilgais) and their relatives. In silico screening of 55,000 intronic retroposon insertions in the cow genome and experimental validation of 126 introns resulted in 29 informative retroposon markers for resolving bovine evolutionary relationships. A transposition-in-transposition analysis identifies three different phases of SINE activity and show how BovB elements have expanded in the cattle genome.
Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis.
Authors: A B Hawthorne, C O Record, C D Holdsworth, M H Giaffer, D A Burke, M L Keech, C J Hawkey
Journal: Gut (1993)

Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator9s overall assessment of response. Patient9s assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed.
Non-inferiority trials
Authors: P. Sedgwick
Journal: BMJ (2011)

<h3>Significance Statement</h3> Patients on hemodialysis (HD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mount poor neutralizing antibody responses after two-dose vaccination. Although serological responses have been associated with reduced rates of reinfection, the relationship between cellular immunogenicity and protection has not been established. We report, for the first time, high incidence of reinfection in patients on HD who are vaccine naive (25%), which identifies that T cell responses do not predict protection against reinfection. Instead, patients on HD who went on to become reinfected had mounted highly variable and sometimes robust proliferative T cell responses to a broad array of SARS-CoV-2 peptide pools during the primary infection. The understanding that SARS-CoV-2–specific T cell responses are not predictive of protection against future infection will be a critical issue when measuring clinical efficacy of vaccination in these vulnerable cohorts, particularly when facing rapidly emerging variants of concern.