tbuckley/cabot-search huggingface dataset:
Effect of the use of low and high potency statins and sepsis outcomes
Authors: Shu-Yu Ou, Hsi Chu, Pei-Wen Chao, Shuo-Ming Ou, Yi-Jung Lee, Shu-Chen Kuo, Szu-Yuan Li, Chia-Jen Shih, Yung-Tai Chen
Journal: Intensive Care Medicine (2014)
Cullin 1 Functions as a Centrosomal Suppressor of Centriole Multiplication by Regulating Polo-like Kinase 4 Protein Levels
Authors: Nina Korzeniewski, Leon Zheng, Rolando Cuevas, Joshua Parry, Payel Chatterjee, Brittany Anderton, Anette Duensing, Karl Münger, Stefan Duensing
Journal: Cancer Research (2009)

Abnormal centrosome and centriole numbers are frequently detected in tumor cells where they can contribute to mitotic aberrations that cause chromosome missegregation and aneuploidy. The molecular mechanisms of centriole overduplication in malignant cells, however, are poorly characterized. Here, we show that the core SKP1-cullin-F-box component cullin 1 (CUL1) localizes to maternal centrioles and that CUL1 is critical for suppressing centriole overduplication through multiplication, a recently discovered mechanism whereby multiple daughter centrioles form concurrently at single maternal centrioles. We found that this activity of CUL1 involves the degradation of Polo-like kinase 4 (PLK4) at maternal centrioles. PLK4 is required for centriole duplication and strongly stimulates centriole multiplication when aberrantly expressed. We found that CUL1 is critical for the degradation of active PLK4 following deregulation of cyclin E/cyclin-dependent kinase 2 activity, as is frequently observed in human cancer cells, as well as for baseline PLK4 protein stability. Collectively, our results suggest that CUL1 may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles.
Obese Premenopausal African-American Women With Normal and Impaired Glucose Tolerance Have a Similar Degree of Insulin Resistance but Differ in β-Cell Function
Authors: Anne E. Sumner, Nicole M. Farmer, Craig S. Cochran, Nancy G. Sebring, Konstantina Vanevski, James C. Reynolds, Ahalya Premkumar, Raymond C. Boston
Journal: Diabetes Care (2001)

OBJECTIVE—To determine whether insulin resistance and secretion differ in obese premenopausal African-American women with and without glucose intolerance. RESEARCH DESIGN AND METHODS—A total of 63 women underwent oral glucose tolerance tests (OGTTs). A total of 48 women underwent frequently sampled intravenous glucose tolerance tests (FSIGTs). Insulin resistance was determined from the insulin sensitivity index (SI) from the FSIGT. Insulin secretion during the OGTT was determined by (I30 min − I0 min)/(G30 min − G0 min) and during the FSIGT by the acute insulin response to glucose (AIRg). The disposition index, the product of AIRg and SI, was used to determine whether AIRg was adequate to compensate for insulin resistance. Statistical analyses included one-way analysis of variance with Bonferroni corrections for multiple comparisons and regression analyses. RESULTS—The women were divided into three groups: nonobese glucose tolerant (n = 32), obese glucose tolerant (n = 17), and obese glucose intolerant (n = 14). The BMI of the three groups were 24.8 ± 2.3, 37.8 ± 5.5, and 42.0 ± 7.6 kg/m2 (mean ± SD), respectively (P &amp;lt; 0.0001). The ages of the three groups were 34.9 ± 8.4, 32.1 ± 5.0, and 41.1 ± 6.3 years (P = 0.011). SI was higher in the nonobese women than in the obese glucose-tolerant women (3.99 ± 1.44 vs. 2.66 ± 2.14 l · mU−1 · min−1, P = 0.03). SI was similar in the obese glucose-intolerant and obese glucose-tolerant women (2.12 ± 1.27 vs. 2.66 ± 2.14 l · mU−1 · min−1, P = 0.9). OGTT showed that insulin secretion was lower in the glucose-intolerant than the obese glucose-tolerant women (1.73 ± 1.38 vs. 3.62 ± 2.11, P = 0.005). FSIGT showed that AIRg was not significantly lower in glucose-intolerant than in obese glucose-tolerant women (807 ± 665 vs. 1,253 ± 655 mU · l−1 · min, P = 0.078). The disposition index was lower in glucose-intolerant than in obese glucose-tolerant women (1,324 ± 1,061 vs. 2,656 ± 1,415, P = 0.014). CONCLUSIONS—Obese premenopausal African-American women with and without glucose intolerance have a similar degree of insulin resistance but differ in insulin secretion.
p53 Mutation as a Genetic Trait of Typical Medullary Breast Carcinoma
Authors: P de Cremoux, A V Salomon, S Liva, R Dendale, B Bouchind'homme, E Martin, X Sastre-Garau, H Magdelenat, A Fourquet, T Soussi
Journal: JNCI Journal of the National Cancer Institute (1999)
ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients.
Authors: Suzanne V Frankfort, Valerie D Doodeman, Remco Bakker, Linda R Tulner, Jos PCM van Campen, Paul HM Smits, Jos H Beijnen
Journal: Molecular Neurodegeneration (2006)

Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.
Insulin Resistance Is Associated With Decreased Quadriceps Muscle Strength in Nondiabetic Adults Aged ≥70 Years
Authors: Joshua I. Barzilay, George A. Cotsonis, Jeremy Walston, Ann V. Schwartz, Suzanne Satterfield, Iva Miljkovic, Tamara B. Harris
Journal: Diabetes Care (2009)

OBJECTIVE Lower-limb muscle strength is reduced in many people with diabetes. In this study, we examined whether quadriceps muscle strength is reduced in relation to insulin resistance in well-functioning ambulatory nondiabetic individuals. RESEARCH DESIGN AND METHODS Participants (age ≥70 years) underwent dual-energy X-ray absorptiometry (DEXA) scanning to ascertain muscle and fat mass, tests of quadriceps strength, computed tomography scanning of the quadriceps to gauge muscle lipid content, and fasting insulin and glucose level measurements from which homeostasis model assessment of insulin resistance (HOMA-IR) was derived. RESULTS In regression analysis, quadriceps strength per kilogram of muscle mass was negatively associated (P &amp;lt; 0.0001) with HOMA-IR independent of other factors negatively associated with strength such as increased age, female sex, low-physical activity, impaired fasting glucose, and increased total body fat. Muscle lipid content was not associated with strength. CONCLUSIONS A small decrease in quadriceps muscle force is associated with increased HOMA-IR in well-functioning nondiabetic adults, suggesting that diminished quadriceps muscle strength begins before diabetes.
Hospital admissions for self harm after discharge from psychiatric inpatient care: cohort study
Authors: D. Gunnell, K. Hawton, D. Ho, J. Evans, S. O'Connor, J. Potokar, J. Donovan, N. Kapur
Journal: BMJ (2008)

<b>Objective</b> To determine the risk of non-fatal self harm in the 12 months after discharge from psychiatric inpatient care. <b>Design</b> Cohort study based on national hospital episode statistics. <b>Setting</b> England. <b>Population</b> Patients aged 16-64 years discharged from psychiatric inpatient care between 1 April 2004 and 31 March 2005 and followed up for one year. <b>Results</b> 75 401 people were discharged from psychiatric inpatient care over the study period, 4935 (6.5%) of whom were admitted at least once for self harm in the following 12 months. Risk of self harm was greatest in the four weeks after discharge; one third (32%, n=1578) of admissions for self harm occurred in this period. The strongest risk factor for self harm after discharge was admission for self harm in the previous 12 months (hazard ratio 4.9, 95% confidence interval 4.6 to 5.2). The risk of self harm was also higher in females, younger people, those with diagnoses of depression, personality disorders, and substance misuse, and those with short lengths of stay. <b>Conclusion</b> More than 6% of patients discharged from psychiatric inpatient care are readmitted for an episode of self harm within 12 months, with one third of these episodes occurring in the month after discharge. Self harm after discharge from hospital shares many of the features of suicide after discharge. Interventions should be developed to reduce risk in this period.
Ketokonazol treatment prevents the progress of “allergic march” in children with atopic dermatitis—Prospective studies
Authors: A.M. Hofman, T. Hofman
Journal: Journal of Allergy and Clinical Immunology (2005)

RATIONALE: The aim of this study was to estimate the influence of ketokonazol treatment on evolution of "atopic march" in children with atopic dermatitis (AD). METHODS: 97 children aged up to 24 months of life with AD were examined. They were on constant observation up to 12 year of life. In 4th year of life patients were devided into 2 groups: one-53 children had additional treatment by ketokonazol (taken periodically) and diet without sugar (K+ group), and second- 36 children without this treatment (K- group). RESULTS: In 1st year of life 9,3 % of children suffered also from bronchial asthma (BA), and 4,1 % had inhalant allergy. In 4th year of life BA occurred in 16,8% children from K+ group, and 13,8 % from K- group. And inhalant allergy was observed in 7,5% K+ and 8,4% K-. In children aged 8 in K+ group BA occurred in 26,4%, however in K- in 33,3%. And inhalant allergy similar in 26,4% K+ and 33,3% K-. In 12 year of life BA decreased to 11,3% in K+ group, but increased to 41,6% in K- group. The same percent was noted due to inhalant allergy- 11,3% in K+ and 44,4% in K- group. Moreover, in K- group also venom allergy occurred, which was not met in K+ group. CONCLUSIONS: Ketokonazol treatment in children with AD prevents development of " allergic march", BA and inhalant allergy.
Acute HIV-1 Infection
Authors: Myron S. Cohen, George M. Shaw, Andrew J. McMichael, Barton F. Haynes
Journal: New England Journal of Medicine (2011)

More than 33 million people are living with HIV-1, and more than 2.5 million additional cases are detected each year. This review addresses recent advances in our understanding of the transmission of HIV-1 and of acute HIV-1 infection.
Fasciitis first before tendinopathy: does the anatomy hold the key?
Authors: Andrew Franklyn-Miller, Eanna Falvey, Paul McCrory
Journal: British Journal of Sports Medicine (2009)

There has been recent discussion in the journal regarding the pathophysiological mechanisms of the development of tendinopathy.1 2 To date there has been no discussion on the role of the enveloping fascia in this condition. In other related musculotendinous conditions, there is evidence that inflammation of the fascia occurs, for example, in plantar fasciitis.3 Histological examination of this condition demonstrates a reactive-type inflammatory infiltrate with accompanying proteoglycan production and oedema seen with collagen thickening. The process is well demonstrated more diffusely in eosinophillic fasciitis, a rare scleroderma-type condition first described in 1974 by Shulman,4 which has a wide and varied clinical presentation.

Cook and Purdam1 propose a model of tendinopathy beginning with reactive change, although with no inflammatory component, which in turn leads on to tendon disrepair and ultimately tendon degeneration. What may well be missing is the “progenitor” stage, and by ignoring the potential role of the fascia and the fascia–tendon interface, we are potentially missing a critical aspect of this condition.

The gross fascial anatomy of the lower limb is poorly documented, …
Registries and Randomized Trials in Assessing the Effects of Bevacizumab in Colorectal Cancer: Is There a Common Theme?
Authors: Herbert I. Hurwitz, Gary H. Lyman
Journal: Journal of Clinical Oncology (2012)

Results (SEER) – based analysis of bevacizumab in the treatment of metastatic colorectal cancer. Given the large number of patients with metastatic colorectal cancer who have been treated with bevacizumab— on and off clinical trials—there is now the potential to compare outcomes among multiple data sets. To the authors’ credit, SEER data sets can now be added to that list. These findings are particularly important if they truly reflect patients who are treated in everyday practice. The authors evaluated a large SEER-Medicare database that links patient diagnostic codes with billing records and clinical information, including survival. The key finding of this study was that, in the overall population, there was a statistically significant benefit from the addition of bevacizumab to fluorouracil-based chemotherapy. However, this benefit was felt to be “modest” and “no more than marginally effective.” Moreover, subset analyses found little to no benefit in patients treated with oxaliplatin. These findings, or at least the conclusions, seem to depart from the majority of previously published data from randomized controlled clinical trials (RCTs), registries, and meta-analyses, including those that have focused on elderly patients. 2-13 How can this discordance be reconciled? First, the primary end point of the current SEER-Medicare anal
Tomosyn: a Syntaxin-1–Binding Protein that Forms a Novel Complex in the Neurotransmitter Release Process
Authors: Yasuyuki Fujita, Hiromichi Shirataki, Toshiaki Sakisaka, Takeshi Asakura, Takeshi Ohya, Hirokazu Kotani, Shigekazu Yokoyama, Hideo Nishioka, Yoshiharu Matsuura, Akira Mizoguchi, Richard H Scheller, Yoshimi Takai
Journal: Neuron (1998)
Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery
Authors: J. Wilson, I. Woods, J. Fawcett, R. Whall, W. Dibb, C. Morris, E. McManus
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome. <b>Design:</b> Randomised controlled trial with double blinding between inotrope groups. <b>Setting:</b>York District Hospital, England. <b>Subjects:</b>138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. <b>Interventions:</b> Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluidand either adrenaline or dopexamine to increase oxygen delivery.Inotropic support was continued during surgery and for at least12&nbsp;hours afterwards. The third group (control) received routine perioperative care. <b>Main outcome measures:</b> Hospital mortality and morbidity. <b>Results:</b> Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%)patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95%confidence interval 2% to 41%) and 28&nbsp;patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital. <b>Conclusion:</b> Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.
Deletion of the p16 and p15 Genes in Human Bladder Tumors
Authors: I. Orlow, L. Lacombe, G. J. Hannon, M. Serrano, I. Pellicer, G. Dalbagni, V. E. Reuter, Z.-F. Zhang, D. Beach, C. Cordon-Cardo
Journal: JNCI Journal of the National Cancer Institute (1995)

Two genes, p16 (also known as CDKN2, INK4A, or MTS1) and p15 (also described as INK4B or MTS2), are found in tandem at chromosome 9p21. These genes are designated as candidate tumor suppressor genes because they encode proteins that function as negative cell cycle regulators. (The encoded polypeptides inactivate specific cyclin-protein kinase complexes that are required for progression through the cell cycle.) Molecular genetic studies have revealed that deletion of the p16 and p15 genes occurs frequently in cancer cell lines and in certain malignant neoplasms.We evaluated the frequency of p16 and p15 gene alterations in a well-characterized cohort of human transitional cell bladder cancers, and we explored potential associations between alterations in these genes and tumor stage and/or grade.Tumor tissue and normal tissue from 110 patients with transitional cell carcinoma of the urinary bladder were examined. The status of the p16 and p15 genes in these tissues was determined by Southern blotting and hybridization with gene-specific probes, by coupled polymerase chain reaction and single-strand conformation polymorphism analysis (PCR-SSCP), and by sequencing DNA fragments produced during PCR. Associations between alterations in the genes and tumor stage and/or grade were evaluated using the two-tailed Fisher's exact test.Homozygous deletion (both alleles lost) of the p16 and the p15 genes was observed in 11 and nine bladder tumors, respectively. Eight of the 11 tumors exhibiting complete loss of the p16 gene also displayed homozygous deletion of the p15 gene. Exclusive loss of either gene was detected in only three tumors. Hemizygous deletion (one allele lost, also referred to as loss of heterozygosity [LOH] of the p16 and/or p15 genes was observed in eight tumors. Rearrangement of the two genes was indicated in three additional tumors. No point mutations were identified in either gene. The overall frequency of alteration in this cohort of bladder tumors was approximately 18% for each gene (in 20 [18.3%, 95% confidence interval (CI) = 11.1%-25.6%] of 109 informative tumors for the p16 gene and in 18 [18%, 95% CI = 10.5%-25.5%] of 100 informative tumors for the p15 gene). A statistically significant association between p16 gene alteration and bladder tumors of low stage (P < .01) and grade (P < .01) was observed; a significant association between p15 gene alteration and tumors of low stage (P < .01) was also detected.Alteration of the p16 and p15 genes, especially coincident homozygous deletion, appears to be a common event in bladder cancer.
The elusive coypu: the importance of collateral flow and the search for an alternative to the dog
Authors: D Hearse
Journal: Cardiovascular Research (2000)

There are several ‘villains’ in this story: (i) researchers who convinced themselves that myocytes could stay alive without blood; (ii) authors who discarded (or journal editors who refused to publish) negative studies; (iii) dogs that had too much and too variable a collateral flow; (iv) legislation and animal suppliers that made the use of canine preparations (and an intriguing alternative, see Fig. 1) impossible or prohibitively expensive; and (v) a UK government plot to exterminate the coypu (nutria).



Fig. 1 
Myocastor coypus molina (known as the coypu or nutria). A giant rat-like beast about 60 cm long and weighting up to 9 kg. Photo: courtesy of Michael Haramis of the Maryland Department of Natural Resources.



For anyone interested in myocardial injury and protection, the 1970s and 1980s were both confusing and exciting. Almost every copy of every journal contained a new paper in which yet another drug reduced infarct size in a canine model of coronary artery occlusion and myocardial infarction. The interventions ranged from the well known (beta blockers, calcium antagonists, vasodilators and glucose) through the surprising and sometimes disasterous (steroids) to the bizarre (rutosides, cobra venom and hyaluronidase). Opinion leaders in the field vigorously promoted the concept that just because myocardial tissue lay within the distribution of a recently occluded coronary artery did not mean that it was necessarily condemned to death — despite the absence of reperfusion. For those of us who believed that early reperfusion was an absolute prerequisite for the salvage of severely ischemic tissue this seemed like heresy!

Astounding claims resounded from the dog labs but, despite this, clinical trials were consistently disappointing and no single intervention was ever adopted for widespread clinical use as an anti-infarct agent in patients with myocardial infarction. Clearly, something was wrong — possibly the design of the trials, the choice …
Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-l-aspartyl chlorin e6)
Authors: Keisuke Mori, Shin Yoneya, Masataka Ohta, Akemi Sano, Kaname Anzai, Gholam A Peyman, Darius M Moshfeghi
Journal: Ophthalmology (1999)
ACE Gene Polymorphism: Ischemic Heart Disease and Longevity in 10 150 Individuals
Authors: Birgit Agerholm-Larsen, Børge G. Nordestgaard, Rolf Steffensen, Thorkild I.A. Sørensen, Gorm Jensen, Anne Tybjærg-Hansen
Journal: Circulation (1997)

Homozygosity for the deletion allele (D) of the angiotensin-converting enzyme (ACE) gene insertion-deletion polymorphism has been suggested to be a potent risk factor for myocardial infarction. With one exception, the samples studied so far have been small and/or ethnically heterogeneous, and most investigators have studied men only.We investigated the association between ACE genotype and myocardial infarction as well as other manifestations of ischemic heart disease for both women and men in a case-referent study (n = 10,150) as well as in a retrospective cohort study (n = 7263). The cohort was from the ethnically homogeneous Danish population. Case subjects were from the same geographic area and had ischemic heart disease. Irrespective of the assumed degree of relative penetrance of the D allele, the odds ratios were not significantly different from 1.0 (P > .05) for ischemic heart disease, severe stenosis on coronary angiography, or myocardial infarction. There was also no association between ACE genotype and phenotypic variation in recognized risk factors for ischemic heart disease. Finally, the relative frequency of the D allele did not change as a function of age in subjects aged from 20 to > or = 80 years.In two large studies, a case-referent study and a retrospective cohort study in an ethnically homogeneous white population, there was no evidence for a statistically significant difference in the development of myocardial infarction or any other manifestations of ischemic heart disease between genotype classes of the ACE gene polymorphism in either women or men.
Social Interactomes for Enabling Research Communities
Authors: Justin Guinney, Rodrigo Dienstmann, Charles Ferté, Stephen Friend, Frank McCormick
Journal: Cancer Discovery (2014)

Data-driven analyses of scientific abstracts with web apps such as "abstract interactomes" provide a new visualization tool for the biomedical research community to interactively navigate a rich assembly of investigators and identify common research topics. Alternative conference formats such as "social interactomes," with structured, albeit informal, discussions among attendees, are able to engage fellows and top investigators, facilitate the exchange of ideas, and encourage data sharing and future collaborations.