tbuckley/cabot-search huggingface dataset:
Prospective Multicenter Study Evaluating the Survival of Patients With Locally Advanced Cervical Cancer Undergoing Laparoscopic Para-Aortic Lymphadenectomy Before Chemoradiotherapy in the Era of Positron Emission Tomography Imaging
Authors: Sebastien Gouy, Philippe Morice, Fabrice Narducci, Catherine Uzan, Alejandra Martinez, Annie Rey, Enrica Bentivegna, Patricia Pautier, Desiree Deandreis, Denis Querleu, Christine Haie-Meder, Eric Leblanc
Journal: Journal of Clinical Oncology (2013)

The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy.We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded.Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed tomography [CT] results)-16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001).To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.
Clinical and molecular genetics of the human GnRH receptor
Authors: B. Karges, W. Karges, N. de Roux
Journal: Human Reproduction Update (2003)

A functional GnRH receptor (GnRH‐R) in the anterior pituitary is critical for normal LH/FSH secretion, pubertal development and reproduction. Inactivating mutations of the GnRH‐R have been identified in patients with idiopathic hypogonadotrophic hypogonadism. In this article we summarize phenotypic characteristics of these patients and focus on specific functional alterations of the human GnRH‐R. In‐vitro studies using recombinant receptor constructs demonstrate that GnRH‐R missense mutations result in impaired ligand binding and reduced signal transduction, causing gonadotrophin deficiency. A detailed molecular understanding of receptor inactivation may help to design new GnRH agonists to therapeutically modulate GnRH‐R function.
Expert group advises separating risk and benefit information from cancer screening invitations
Authors: S. Mayor
Journal: BMJ (2012)

The public in England should be given more balanced information explaining the risks as well as the benefits of cancer screening, and this information should be separate from an invitation to be screened, an expert group has recommended in a consultation report.1

“Until now, the approach to information about the NHS cancer screening programmes has been, broadly, to encourage screening—while providing information on benefits and harms. But there is a growing imperative to provide comprehensive and balanced information on the benefits and harms of cancer screening, in order to facilitate an informed choice,” said Amanda Ramirez, national clinical lead for information for patients with cancer. 

In 2011 the national cancer director, Mike Richards, announced that there would …
Definition of target antigens for naturally occurring CD4+ CD25+ regulatory T cells
Authors: Hiroyoshi Nishikawa, Takuma Kato, Isao Tawara, Kanako Saito, Hiroaki Ikeda, Kagemasa Kuribayashi, Paul M. Allen, Robert D. Schreiber, Shimon Sakaguchi, Lloyd J. Old, Hiroshi Shiku
Journal: The Journal of Experimental Medicine (2005)

The antigenic targets recognized by naturally occurring CD4+ CD25+ regulatory T cells (T reg cells) have been elusive. We have serologically defined a series of broadly expressed self-antigens derived from chemically induced mouse sarcomas by serological identification of antigens by recombinant expression cloning (SEREX). CD4+ CD25+ T cells from mice immunized with SEREX-defined self-antigens had strong suppressive activity on peptide-specific proliferation of CD4+ CD25− T cells and CD8+ T cells. The suppressive effect was observed without in vitro T cell stimulation. Foxp3 expression in these CD4+ CD25+ T cells from immunized mice was 5–10 times greater than CD4+ CD25+ T cells derived from naive mice. The suppressive effect required cellular contact and was blocked by anti-glucocorticoid–induced tumor necrosis factor receptor family–related gene antibody. In vitro suppressive activity essentially disappeared 8 wk after the last immunization. However, it was regained by in vitro restimulation with cognate self-antigen protein but not with control protein. We propose that SEREX-defined self-antigens such as those used in this study represent self-antigens that elicit naturally occurring CD4+ CD25+ T reg cells.
Collagenase Increases the Transcapillary Pressure Gradient and Improves the Uptake and Distribution of Monoclonal Antibodies in Human Osteosarcoma Xenografts
Authors: Live Eikenes, Øyvind S. Bruland, Christian Brekken, Catharina de Lange Davies
Journal: Cancer Research (2004)

Abstract Cancer therapy based on tumor-selective macromolecules may fail due to the elevated interstitial fluid pressure (IFP) that reduces the transvascular and interstitial convection in solid tumors. Modulation of the tumor extracellular matrix (ECM) may reduce IFP and enhance transvascular filtration and interstitial transport of macromolecules. We therefore measured the effect of the ECM-degrading enzyme collagenase on IFP and microvascular pressure (MVP) in human osteosarcoma xenografts using the wick-in-needle and micropipette methods, respectively. The tumor uptake and distribution of a systemically administered osteosarcoma-associated monoclonal antibody (TP-3) after i.v. injection of collagenase were analyzed using confocal laser scanning microscopy. Collagenase (0.1%) reduced both IFP (45%) and MVP (60%), but the kinetics of the recoveries differed, because MVP had recovered by the time IFP reached its minimum level. Thus, collagenase increased the transcapillary pressure gradient, inducing a 2-fold increase in the tumor uptake and improving the distribution of the monoclonal antibody, which was localized further into the tumor. To study the mechanism of the reduction in MVP, mean arterial blood pressure was measured and found not to be affected by the collagenase treatment. The reduction in MVP was rather due to reduced vascular resistance because microvascular-associated collagen was totally or partially disintegrated. Although collagenase may favor metastasis and thus not be clinically relevant, this study shows proof of principle that degradation of the ECM leads to a favorable change in the transvascular pressure gradient, thereby increasing antibody penetration and binding to tumor cells.
Role of NMDA receptor–dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries
Authors: Changiz Taghibiglou, Henry G S Martin, Ted Weita Lai, Taesup Cho, Shiv Prasad, Luba Kojic, Jie Lu, Yitao Liu, Edmund Lo, Shu Zhang, Julia Z Z Wu, Yu Ping Li, Yan Hua Wen, Joon-Hyuk Imm, Max S Cynader, Yu Tian Wang
Journal: Nature Medicine (2009)
Large and prolonged food-borne multistate hepatitis A outbreak in Europe associated with consumption of frozen berries, 2013 to 2014
Authors: E Severi, L Verhoef, L Thornton, B R Guzman-Herrador, M Faber, L Sundqvist, R Rimhanen-Finne, A M Roque-Afonso, S L Ngui, F Allerberger, A Baumann-Popczyk, L Muller, K Parmakova, V Alfonsi, L Tavoschi, H Vennema, M Fitzgerald, M Myrmel, M Gertler, J Ederth, M Kontio, C Vanbockstael, S Mandal, M Sadkowska-Todys, M E Tosti, B Schimmer, J O’Gorman, Kathrine Stene-Johansen, J J Wenzel, G Jones, K Balogun, A R Ciccaglione, L O’Connor, L Vold, J Takkinen, C Rizzo
Journal: Eurosurveillance (2015)

In May 2013, Italy declared a national outbreak of hepatitis A, which also affected several foreign tourists who had recently visited the country. Molecular investigations identified some cases as infected with an identical strain of hepatitis A virus subgenotype IA. After additional European Union/European Economic Area (EU/EEA) countries reported locally acquired and travel-related cases associated with the same outbreak, an international outbreak investigation team was convened, a European outbreak case definition was issued and harmonisation of the national epidemiological and microbiological investigations was encouraged. From January 2013 to August 2014, 1,589 hepatitis A cases were reported associated with the multistate outbreak; 1,102 (70%) of the cases were hospitalised for a median time of six days; two related deaths were reported. Epidemiological and microbiological investigations implicated mixed frozen berries as the vehicle of infection of the outbreak. In order to control the spread of the outbreak, suspected or contaminated food batches were recalled, the public was recommended to heat-treat berries, and post-exposure prophylaxis of contacts was performed. The outbreak highlighted how large food-borne hepatitis A outbreaks may affect the increasingly susceptible EU/EEA general population and how, with the growing international food trade, frozen berries are a potential high-risk food.
A Clinical Perspective on the Relevance of Research Domain Criteria in Electronic Health Records
Authors: Thomas H. McCoy, Victor M. Castro, Hannah R. Rosenfield, Andrew Cagan, Isaac S. Kohane, Roy H. Perlis
Journal: American Journal of Psychiatry (2015)

Objective: The limitations of the DSM nosology for capturing dimensionality and overlap in psychiatric syndromes, and its poor correspondence to underlying neurobiology, have been well established. The Research Domain Criteria (RDoC), a proposed dimensional model of psychopathology, may offer new insights into psychiatric illness. For psychiatric clinicians, however, because tools for capturing these domains in clinical practice have not yet been established, the relevance and means of transition from the categorical system of DSM-5 to the dimensional models of RDoC remains unclear. The authors explored a method of extracting these dimensions from existing electronic health record (EHR) notes. Method: The authors used information retrieval and natural language processing methods to extract estimates of the RDoC dimensions in the EHRs of a large health system. They parsed and scored EHR documentation for 2,484 admissions covering 2,010 patients admitted to a psychiatric inpatient unit between 2011 and 2013. These domain scores were compared with DSM-IV-based ICD-9 codes to assess face validity. As a measure of predictive validity, these scores were examined for association with two outcomes: length of hospital stay and time to all-cause hospital readmission. Together, these analyses were intended to address the extent to which RDoC symptom domains might capture clinical features already available in narrative notes but not reflected in DSM diagnoses. Results: In mixed-effects models, loadings for the RDoC cognitive and arousal domains were associated with length of hospital stay, while the negative valence and social domains were associated with hazard of all-cause hospital readmission. Conclusions: These findings show that a computationally derived tool based on RDoC workgroup reports identifies symptom distributions in clinician notes beyond those captured by ICD-9 codes, and these domains have significant predictive validity. More generally, they point to the possibility that clinicians already document RDoC-relevant symptoms, albeit not in a quantified form.
Removal of the Great Toe and Part of the Metatarsal Bone, under the Influence of Aether
Authors: T. H. Barker
Journal: BMJ (1847)

INHALATION OF JATHER..133X raised, eyelids closed, and all the usual signs of insen- siVility to pain.The circular incision was now made through the skin, and he cried out most lustily, and continued doing so through the whole stage of the ope- ration.After it was all over he stated he felt the first cut, and also the bone sawed, but he was in a dream, and smoking a pipe, wbich some one tried to take from law.I can only view this case as a failure, and I think it right alike to report all, whether failures or not.The other cases were decidedly successful.I may state in the above operation tho moutb-piece did not nicely fit the mouth, and he appeared to have inhaled fresh air by its side.Albion House, Cheltenham,
Glycopeptide Antibiotic Resistance
Authors: Jeff Pootoolal, John Neu, Gerard D. Wright
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Glycopeptide antibiotics are integral components of the current antibiotic arsenal that is under strong pressures as a result of the emergence of a variety of resistance mechanisms over the past 15 years. Resistance has manifested itself largely through the expression of genes that encode proteins that reprogram cell wall biosynthesis and thus evade the action of the antibiotic in the enterococci, though recently new mechanisms have appeared that afford resistance and tolerance in the more virulent staphylococci and streptococci. Overcoming glycopeptide resistance will require innovative approaches to generate new antibiotics or otherwise to inhibit the action of resistance elements in various bacteria. The chemical complexity of the glycopeptides, the challenges of discovering and successfully exploiting new targets, and the growing number of distinct resistance types all increase the difficulty of the current problem we face as a result of the emergence of glycopeptide resistance.
Different Protein Tyrosine Phosphatase Superfamilies Resulting from Different Gene Reading Frames
Authors: J.-F. Huang
Journal: Molecular Biology and Evolution (2003)

Protein tyrosine phosphatases (PTPs) are comprised of two superfamilies, the phosphatase I superfamily containing a single low-molecular-weight PTP (lmwPTP) family and the phosphatase II superfamily including both the higher-molecular-weight PTP (hmwPTP) and the dual-specificity phosphatase (DSP) families. The phosphatase I and II superfamilies are often considered to be the result of convergent evolution. The PTP sequence and structure analyses indicate that lmwPTPs, hmwPTPs, and DSPs share similar structures, functions, and a common signature motif, although they have low sequence identities and a different order of active sites in sequence or a circular permutation. The results of this work suggest that lmwPTPs and hmwPTPs/DSPs are remotely related in evolution. The earliest ancestral gene of PTPs could be from a short fragment containing about 90∼120 nucleotides or 30∼40 residues; however, a probable full PTP ancestral gene contained one transcript unit with two lmwPTP genes. All three PTP families may have resulted from a common ancestral gene by a series of duplications, fusions, and circular permutations. The circular permutation in PTPs is caused by a reading frame difference, which is similar to that in DNA methyltransferases. Nevertheless, the evolutionary mechanism of circular permutation in PTP genes seems to be more complicated than that in DNA methyltransferase genes. Both mechanisms in PTPs and DNA methyltransferases can be used to explain how some protein families and superfamilies came to be formed by circular permutations during molecular evolution.
Prevention of Colon Cancer by Low Doses of Celecoxib, a Cyclooxygenase Inhibitor, Administered in Diet Rich in ω-3 Polyunsaturated Fatty Acids
Authors: Bandaru S. Reddy, Jagan M. Patlolla, Barbara Simi, S.H. Wang, Chinthalapally V. Rao
Journal: Cancer Research (2005)

Epidemiologic and animal studies suggest that a high-fat diet containing mixed lipids promotes colorectal cancer, whereas fish oil lacks promoting effect. Although cyclooxygenase-2 (COX-2) inhibitors are effective chemopreventive agents against colon carcinogenesis, administration of high doses of these agents over time may induce side effects. Here, we compared the efficacy of moderately high and low doses of celecoxib administered in diets high in mixed lipids (HFML) or fish oil (HFFO) against azoxymethane-induced colon carcinogenesis in male F344 rats. One day after the last azoxymethane treatment (15 mg/kg body weight once weekly for 2 weeks), groups of rats were fed the HFML and HFFO diets containing 0, 250, 500, and 1,000 ppm celecoxib. Rats were killed 26 weeks later and colon tumors were subjected to histopathologic examination and analyzed for total COX and COX-2 synthetic activities and COX-2 expression. Rats fed the HFFO diet showed significantly lower colon tumor incidence and multiplicity compared with rats fed the HFML diet. Celecoxib at 250, 500, and 1,000 ppm in either diet significantly suppressed colon carcinogenesis. Inhibition of colon adenocarcinomas were more pronounced in animals given 250 ppm celecoxib in HFFO diet compared with 250 ppm celecoxib given in HFML diet, suggesting some synergism between omega-3 polyunsaturated fatty acids (PUFA) and celecoxib. Inhibition of colon tumors by celecoxib was associated with lower levels of COX-2 activity and expression in colon tumors. These studies support the use of low doses of celecoxib in omega-3 PUFA-rich diet as a promising approach for clinical trials.
β1 Receptors Protect the Renal Afferent Arteriole of Angiotensin-Infused Rabbits from Norepinephrine-Induced Oxidative Stress
Authors: Dan Wang, Pedro Jose, Christopher S. Wilcox
Journal: Journal of the American Society of Nephrology (2006)

Renal afferent arterioles (Aff) from angiotensin II (AngII)-infused rabbits have enhanced contractions to AngII that are normalized by tempol (superoxide dismutase mimetic), whereas contractions to norepinephrine (NE) are normal and unaffected by tempol. Tested was the hypothesis that beta-receptor stimulation with NE prevents enhanced reactivity and superoxide generation. Preconstricted Aff from AngII- or vehicle-infused rabbits were perfused at physiologic pressure. Aff from vehicle-infused rabbits had strong, endothelium-independent relaxations to dobutamine (beta(1)-receptor agonist; 78 +/- 6%; P < 0.0001; mean +/- SD) but only weak relaxations to salbutamol (beta(2)-receptor agonist; 13 +/- 3%; P < 0.05) or BRL-37,344 (beta(3)-receptor agonist; 14 +/- 3%; P < 0.05). Contractions to NE were similar in Aff from vehicle- and AngII-infused rabbits (-36 +/- 5 versus -34 +/- 3%; NS) and were unaffected by tempol (-32 +/- 4%; NS). In contrast, phenylephrine contractions (alpha(1) agonist) were enhanced in Aff from AngII-infused rabbits (-59 +/- 6 versus -46 +/- 4%; P < 0.05) and normalized by tempol. NE contractions in Aff from AngII-infused rabbits (-34 +/- 4%) were enhanced (P < 0.01) by propranolol (nonselective beta antagonist; -53 +/- 6%), CGP-20,712A (selective beta(1)-receptor antagonist; -61 +/- 9%), or Rp-cAMP (competitive inhibitor of cAMP; -56 +/- 4%); were normalized by tempol; but were unaffected by ICI-118,551 (selective beta(2)-receptor antagonist) or SR-59,230A (selective beta(3)-receptor antagonist). Superoxide generation in Aff from AngII-infused rabbits that were assessed from ethidium:dihydroethidium was enhanced by addition of CGP-20,712A to NE but was normalized by tempol. Aff have robust alpha(1)-receptor contraction and beta(1)-receptor dilation. NE elicits beta(1) signaling via cAMP that moderates oxidative stress and contractions in Aff from AngII-infused rabbits.
Occupation-Related Differences in the Prevalence of Metabolic Syndrome
Authors: Miguel-Angel Sánchez-Chaparro, Eva Calvo-Bonacho, Arturo González-Quintela, Carlos Fernández-Labandera, Martha Cabrera, Juan-Carlos Sáinz, Ana Fernández-Meseguer, José R. Banegas, Luis-Miguel Ruilope, Pedro Valdivielso, Javier Román-García
Journal: Diabetes Care (2008)

To investigate the prevalence of metabolic syndrome in the Spanish working population and determine how the prevalence varies according to occupation and sex.This was a cross-sectional study of 259,014 workers (mean age 36.4 years, range [16-74]; 72.9% male) who underwent a routine medical checkup. The Adult Treatment Panel III (2001) definition for metabolic syndrome was used.The prevalence of metabolic syndrome was 11.6% (95% CI 11.5-11.7) in male subjects and 4.1% (4.0-4.2) in female subjects and increased with age. The prevalence of metabolic syndrome varied in the different categories of occupational activity depending on the sex considered. Among female subjects, the age-adjusted prevalence of metabolic syndrome was higher in blue-collar than in white-collar workers, but this difference was not evident among male workers.The prevalence of metabolic syndrome varies in the different categories of occupational activity in the Spanish working population. This variation also depends on sex.
Disabling dyspnoea in patients with advanced disease: lack of effect of nebulized morphine
Authors: A Noseda, JP Carpiaux, C Markstein, A Meyvaert, V de Maertelaer
Journal: European Respiratory Journal (1997)

The purpose of this placebo-controlled, double-blind, randomized study was to assess the effect of nebulized morphine on dyspnoea perceived at rest by patients with advanced disease. Seventeen hospital in-patients with disabling dyspnoea received isotonic saline or morphine via nebulization for 10 min through a mouthpiece, combined with oxygen via nasal prongs. On four consecutive days, they were given one of the four following treatments in random order: saline with 2 L x min(-1) oxygen; 10 mg morphine with 2 L x min(-1) oxygen; 20 mg morphine with 2 L x min(-1) oxygen; and 10 mg morphine without oxygen (prongs fixed, no flow). Dyspnoea was assessed on a bipolar visual analogue scale (VAS) (-100% much more short of breath, +100% much less short of breath), and arterial oxygen saturation (Sa,O2) and respiratory frequency (fR) were recorded at the end of nebulization and 10 min later. In 14 subjects who completed the study, mean VAS ratings 10 min after the end of nebulization ranged +30 to +43%, with no significant difference between the four study days (VAS 20 mg morphine minus VAS saline, 95% confidence interval (95% CI) -6 to +8%). Sa,O2 significantly increased on the 3 days with supplemental oxygen, and remained stable on the zero flow day. Respiratory frequency significantly decreased on the 4 days, with a trend to correlation between VAS rating and parallel change in respiratory frequency (Spearman's rank correlation coefficient (r(s))=0.46; p=0.09). We conclude that the subjects benefited from saline or morphine via a placebo effect and/or a nonspecific effect, and that nebulized morphine had no specific effect on dyspnoea.