tbuckley/cabot-search huggingface dataset:
All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on 462 293 adults in Taiwan
Authors: Chi Pang Wen, Ting Yuan David Cheng, Min Kuang Tsai, Yen Chen Chang, Hui Ting Chan, Shan Pou Tsai, Po Huang Chiang, Chih Cheng Hsu, Pei Kun Sung, Yi Hua Hsu, Sung Feng Wen
Journal: The Lancet (2008)
Social Ties and Susceptibility to the Common Cold
Authors: S Cohen, W J Doyle, D P Skoner, B S Rabin, J M Gwaltney
Journal: JAMA (1997)

To examine the hypothesis that diverse ties to friends, family, work, and community are associated with increased host resistance to infection.After reporting the extent of participation in 12 types of social ties (eg, spouse, parent, friend, workmate, member of social group), subjects were given nasal drops containing 1 of 2 rhinoviruses and monitored for the development of a common cold.Quarantine.A total of 276 healthy volunteers, aged 18 to 55 years, neither seropositive for human immunodeficiency virus nor pregnant.Colds (illness in the presence of a verified infection), mucus production, mucociliary clearance function, and amount of viral replication.In response to both viruses, those with more types of social ties were less susceptible to common colds, produced less mucus, were more effective in ciliary clearance of their nasal passages, and shed less virus. These relationships were unaltered by statistical controls for prechallenge virus-specific antibody, virus type, age, sex, season, body mass index, education, and race. Susceptibility to colds decreased in a dose-response manner with increased diversity of the social network. There was an adjusted relative risk of 4.2 comparing persons with fewest (1 to 3) to those with most (6 or more) types of social ties. Although smoking, poor sleep quality, alcohol abstinence, low dietary intake of vitamin C, elevated catecholamine levels, and being introverted were all associated with greater susceptibility to colds, they could only partially account for the relation between social network diversity and incidence of colds.More diverse social networks were associated with greater resistance to upper respiratory illness.
The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis
Authors: C. Eng
Journal: JAMA (1996)

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making.Correlative survey study of 477 MEN 2 families.Eighteen tertiary referral centers worldwide.A total of 477 independent MEN 2 families.Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family.There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B--specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors.This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.
THE ANTI-PLATELET EFFECT OF PRE-TREATMENT WITH CLOPIDOGREL IN PATIENTS UNDERGOING PRIMARY PERCUTANEOUS ANGIOPLASTY FOR ST SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Roy Beigel, Paul Fefer, Boris Shenkman, Noam Fink, Elad Asher, Hanoch Hod, Shlomi Matetzky
Journal: Journal of the American College of Cardiology (2011)
Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage
Authors: D A J Connolly, M P McHugh, O I Padilla-Zakour
Journal: British Journal of Sports Medicine (2006)

Numerous antioxidant and anti-inflammatory agents have been identified in tart cherries.To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage.This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 x 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect.Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p = 0.017). Relaxed elbow angle (time by treatment p = 0.85) and muscle tenderness (time by treatment p = 0.81) were not different between trials.These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.
Short Telomeres Result in Organismal Hypersensitivity to Ionizing Radiation in Mammals
Authors: Fermín A. Goytisolo, Enrique Samper, Juan Martín-Caballero, Paul Finnon, Eloísa Herrera, Juana M. Flores, Simon D. Bouffler, María A. Blasco
Journal: The Journal of Experimental Medicine (2000)

Here we show a correlation between telomere length and organismal sensitivity to ionizing radiation (IR) in mammals. In particular, fifth generation (G5) mouse telomerase RNA (mTR)−/− mice, with telomeres 40% shorter than in wild-type mice, are hypersensitive to cumulative doses of gamma rays. 60% of the irradiated G5 mTR−/− mice die of acute radiation toxicity in the gastrointestinal tract, lymphoid organs, and kidney. The affected G5 mTR−/− mice show higher chromosomal damage and greater apoptosis than similarly irradiated wild-type controls. Furthermore, we show that G5 mTR−/− mice show normal frequencies of sister chromatid exchange and normal V(D)J recombination, suggesting that short telomeres do not significantly affect the efficiency of DNA double strand break repair in mammals. The IR-sensitive phenotype of G5 mTR−/− mice suggests that telomere function is one of the determinants of radiation sensitivity of whole animals.
CHRONIC LEAD NEPHROPATHY
Authors: P W Craswell
Journal: Annual Review of Medicine (1987)

Chronic lead nephropathy remains a cause of morbidity and mortality in Queensland, Australia, and in other parts of the industrial world. It is underdiagnosed because it is not considered in the differential diagnosis of chronic renal disease and because the established methods for estimating the body burden of lead are cumbersome, time consuming, and sometimes inaccurate.
A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool
Authors: Lorea Manterola, Elizabeth Guruceaga, Jaime Gállego Pérez-Larraya, Marisol González-Huarriz, Patricia Jauregui, Sonia Tejada, Ricardo Diez-Valle, Victor Segura, Nicolás Samprón, Cristina Barrena, Irune Ruiz, Amaia Agirre, Ángel Ayuso, Javier Rodríguez, Álvaro González, Enric Xipell, Ander Matheu, Adolfo López de Munain, Teresa Tuñón, Idoya Zazpe, Jesús García-Foncillas, Sophie Paris, Jean Yves Delattre, Marta M. Alonso
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients. To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients. We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis. Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.
Duplication is more common among laterally transferred genes than among indigenous genes
Authors: Sean D Hooper, Otto G Berg
Journal: Genome biology (2003)

Recent developments in the understanding of paralogous evolution have prompted a focus not only on obviously advantageous genes, but also on genes that can be considered to have a weak or sporadic impact on the survival of the organism. Here we examine the duplicative behavior of a category of genes that can be considered to be mostly transient in the genome, namely laterally transferred genes. Using both a compositional method and a gene-tree approach, we identify a number of proposed laterally transferred genes and study their nucleotide composition and frequency of duplication. It is found that duplications are significantly overrepresented among potential laterally transferred genes compared to the indigenous ones. Furthermore, the GC3 distribution of potential laterally transferred genes was found to be largely uniform in some genomes, suggesting an import from a broad range of donors. The results are discussed not in a context of strongly optimized established genes, but rather of genes with weak or ancillary functions. The importance of duplication may therefore depend on the variability and availability of weak genes for which novel functions may be discovered. Therefore, lateral transfer may accelerate the evolutionary process of duplication by bringing foreign genes that have mainly weak or no function into the genome.
Reduction in Preretinal Neovascularization by Ribozymes That Cleave the A <sub>2B</sub> Adenosine Receptor mRNA
Authors: A. Afzal, L.C. Shaw, S. Caballero, P.E. Spoerri, A.S. Lewin, D. Zeng, L. Belardinelli, M.B. Grant
Journal: Circulation Research (2003)

Adenosine modulates a variety of cellular functions by interacting with specific cell surface G protein–coupled receptors (A 1 , A 2A , A 2B , and A 3 ) and is a potential mediator of angiogenesis through the A 2B receptor. The lack of a potent, selective A 2B receptor inhibitor has hampered its characterization. Our goal was to design a hammerhead ribozyme that would specifically cleave the A 2B receptor mRNA and examine its effect on retinal angiogenesis. Ribozymes specific for the mouse and human A 2B receptor mRNAs were designed and cloned in expression plasmids. Human embryonic kidney (HEK) 293 cells were transfected with these plasmids and A 2B receptor mRNA levels were determined by quantitative real-time RT-PCR. Human retinal endothelial cells (HRECs) were also transfected and cell migration was examined. The effects of these ribozymes on the levels of preretinal neovascularization were determined using a neonatal mouse model of oxygen-induced retinopathy (OIR). We produced a ribozyme with a V max of 515±125 pmol/min and a K cat of 36.1±8.3 min −1 ( P ≤1×10 −5 ). Transfection of HEK293 cells with the plasmid expressing the ribozyme reduced A 2B receptor mRNA levels by 45±4.8% ( P =5.1×10 −5 ). Transfection of HRECs reduced NECA-stimulated migration of cells by 47.3±1.2% ( P =7×10 −4 ). Intraocular injection of the constructs into the mouse model reduced preretinal neovascularization by 53.5±8.2% ( P =4.5×10 −5 ). Our results suggest that the A 2B receptor ribozyme will provide a tool for the selective inhibition of this receptor and provide further support for the role of A 2B receptor in retinal angiogenesis.
Estimating the Value of Intravenous Calcium and Magnesium in Ameliorating Oxaliplatin-Induced Neuropathy
Authors: Carl D. Atkins
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: The purpose of the N08CB trial (Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving OxaliplatinBased Combination Chemotherapy) was to confirm the clinically significant effect of calcium and magnesium supplementation in ameliorating oxaliplatin-induced neurotoxicity that was reported in the only other fully published, randomized, placebo-controlled trial of this approach, namely N04C7 (Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity Caused By Oxaliplatin in Patients Receiving Combination Chemotherapy for Stage II, Stage III, or Stage IV Colorectal Cancer That Has Been Completely Removed By Surgery). How are we to reconcile the seemingly contradictory results of these two trials? The primary end point of N04C7 was the incidence of grades 2 to 3 neuropathy according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Given that this end point was also measured in N08CB, it is helpful to compare the 95% CIs for the difference in this measure between the treatment and placebo groups in both trials (ignoring the group in N08CB that received no supplements after oxaliplatin, because this represents a different treatment). Although this statistic was not provided in either report, it is easily calculated from the data provided. In N04C7, the primary end point was recorded in 22% of patients receiving active treatment and 41% receiving placebo for an absolute difference of 19% (95% CI, 1% to 37%). In N08CB, this end point was recorded in 43% of patients receiving active treatment and 46% receiving placebo for an absolute difference of 3% (95% CI, 10 to 16%). Note that these data are compatible with each other, that is, both trials are consistent with an absolute reduction of neurotoxicity that is between 1% and 16%. The authors’ suggestion that the benefit seen in N04C7 was an artifact that resulted from early stopping is not cogent. Results may be exaggerated when trials are stopped early because of a finding of treatment effect, but this bias would not be introduced when a trial is stopped because of concern about off-target effects, as was the case with N04C7. The data from N08CB improve our estimate of the magnitude of benefit to expect from the use of calcium and magnesium supplementation in ameliorating oxaliplatin-induced neurotoxicity. A much larger trial would be required to exclude type II error and decisively show a lack of benefit. Oncologists and patients will need to decide whether the clinical benefit that is suggested by the combined data of N08CB and N04C7 is sufficient to warrant the time and expense of the additional treatment with calcium and magnesium.
Infantile myofibromatosis. Report of two cases in one family
Authors: P.Y. VENENCIE, P. BIGEL, C. DESGRUELLES, S. LORTAT-JACOB, J.L. DUFIER, J.H. SAURAT
Journal: British Journal of Dermatology (1987)

Two brothers with infantile myofibromatosis are reported. Both had cutaneous and skeletal myofibromas with spontaneous and complete healing of their cutaneous lesions. These cases suggest autosomal recessive inheritance of this rare disorder.
Novel strategies for liver therapy using stem cells
Authors: Tamir Rashid, Takanori Takebe, Hiromitsu Nakauchi
Journal: Gut (2014)

Liver disease is an increasing clinical burden, causing over 10 000 deaths last year in the UK alone (http://www.britishlivertrust.org.uk). Liver insufficiency describes the clinical situation in which cumulative (chronic) or one-off massive (acute) insults exceed the liver's normal physiological capacity to functionally regenerate. Untreated, liver insufficiency invariably leads to death. The current gold standard of care in this setting is whole organ transplantation. Due to the increasing burden of disease within the population, however, the number of patients requiring transplantation far exceeds the number of available donor organs. As a result, many patients with liver insufficiency die prematurely.1

The liver is composed of several cell types (endothelial cells, stellate cells, biliary ductal cells, Kupffer cells and natural killer cells) which together provide a supportive niche for the principle cell type—the hepatocyte.2 Treatment of liver disease by hepatocyte replacement therefore appears a logical alternative to whole organ transplant (figure 1i). Along these lines, intrahepatic hepatocyte transplantation (I-HTx) has repeatedly proven efficacious in small animal models of numerous liver diseases. Results from human applications have unfortunately proven less convincing however with the best, possibly only, positive results observed in paediatric patients suffering from hepatocyte driven inherited metabolic disorders.3 This suggests targeting the surrounding niche may be as important as replacing diseased hepatocytes themselves if one is to treat the majority of liver diseases.4 Such efforts to manipulate the complex nature of the surrounding niche will no doubt be far from trivial. So an alternative, more tangible approach that targets more specific clinical problem could be to use hepatocytes in extra-hepatic anatomical sites to ‘bridge’ patients with liver insufficiency to transplant or self repair (E-HTx).5 Some preliminary clinical experiences suggest a therapeutic effect for alginate-bead encapsulated hepatocytes delivered into the peritoneum of paediatric patients with acute liver failure …
Comparison of composite measures of disease activity in an early seropositive rheumatoid arthritis cohort
Authors: V. K Ranganath, J. Yoon, D. Khanna, G. S Park, D. E Furst, D. A Elashoff, D. Jawaheer, J. T Sharp, R. H Gold, E. C Keystone, H. E Paulus
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To evaluate concordance and agreement of the original DAS44/ESR-4 item composite disease activity status measure with nine simpler derivatives when classifying patient responses by European League of Associations for Rheumatology (EULAR) criteria, using an early rheumatoid factor positive (RF+) rheumatoid arthritis (RA) patient cohort. <h3>Methods:</h3> Disease-modifying anti-rheumatic drug-naïve RF+ patients (n = 223; mean duration of symptoms, 6 months) were categorised as ACR none/20/50/70 responders. One-way analysis of variance and two-sample t tests were used to investigate the relationship between the ACR response groups and each composite measure. EULAR reached/change cut-point scores were calculated for each composite measure. EULAR (good/moderate/none) responses for each composite measure and the degree of agreement with the DAS44/ESR-4 item were calculated for 203 patients. <h3>Results:</h3> Patients were mostly female (78%) with moderate to high disease activity. A centile-based nomogram compared equivalent composite measure scores. Changes from baseline in the composite measures in patients with ACRnone were significantly less than those of ACR20/50/70 responders, and those for ACR50 were significantly different from those for ACR70. EULAR reached/change cut-point scores for our cohort were similar to published cut-points. When compared with the DAS44/ESR-4 item, EULAR (good/moderate/none) percentage agreements were 92 with the DAS44/ESR-3 item, 74 with the Clinical Disease Activity Index, and 80 with the DAS28/ESR-4 item, the DAS28/CRP-4 item and the Simplified Disease Activity Index. <h3>Conclusion:</h3> The relationships of nine different RA composite measures against the DAS44/ESR-4 item when applied to a cohort of seropositive patients with early RA are described. Each of these simplified status and response measures could be useful in assessing patients with RA, but the specific measure selected should be pre-specified and described for each study.
Is There Evidence to Support Use of Premixed or Prandial Insulin Regimens in Insulin-Naive or Previously Insulin-Treated Type 2 Diabetic Patients?
Authors: Hannele Yki-Järvinen, Anna Kotronen
Journal: Diabetes Care (2013)

Regarding the question of how to use insulin in type 2 diabetes, a systematic review conforming to methods of the Cochrane collaboration was published in 2006 (1). This review included studies published in Medline until May 2004. The analysis compared insulin monotherapy with combination therapy with insulin and oral hypoglycemic agent (OHA) in previously insulin-naive patients. With use of the methods detailed in the review (1), 13 randomized controlled trials (RCTs) could be identified and included 1,811 participants with a mean age of 60 years and duration of diabetes of 10 years. The authors concluded that bedtime NPH insulin combined with oral antihyperglycemic agents provides glycemic control comparable with that provided by insulin monotherapy with twice daily insulin or basal/bolus insulin regimens but is associated with less weight gain if metformin is used. However, since May 2004 there has been an exponential increase in the number of patients participating in RCTs comparing basal insulin plus OHA with other insulin regiments with similar OHA (vide infra). Such studies have become possible thanks to the development of rapid- and long-acting insulin analogs and commercial support for studies addressing insulin therapy.

This review focuses on comparison of different insulin treatment regimens in both insulin-naive (first objective) and previously insulin-treated (second objective) patients with type 2 diabetes. We wished to examine whether there is an advantage (glycemic control, weight gain, or hypoglycemia) of using premixed and basal-bolus regimens with or without OHA compared with basal insulin and OHA. For the first objective, we used the principles outlined in the previous Cochrane review (1) to compare glycemic control between basal insulin/OHA and other regimens. The latter included regimens with premixed insulin twice daily with or without OHA or regimens using prandial insulin three times daily or multiple insulin injection therapy (basal and prandial three times …
Potential serum biomarkers of treatment response to ustekinumab in patients with psoriasis: a pilot study
Authors: A.J. Onderdijk, A.S. Ijpma, S.P. Menting, E.M. Baerveldt, E.P. Prens
Journal: British Journal of Dermatology (2015)

Currently available biologics for psoriasis target the function of TNF-α, IL-17A or IL-12/23 and include etanercept (anti-TNF receptor fusion protein), adalimumab and infliximab (anti-TNFα antibodies), anti-IL-17(receptor) molecules and ustekinumab. Ustekinumab is a fully human immunoglobulin monoclonal antibody targeting the p40 subunit shared by IL-12 and IL-23. This prevents binding to the IL-12Rβ1 receptor unit on immune cells and subsequent signaling. The Psoriasis Area and Severity Index (PASI) is used for evaluation of the efficacy of therapies in psoriasis. This article is protected by copyright. All rights reserved