tbuckley/cabot-search huggingface dataset:
Cytosine Usage Modulates the Correlation between CDS Length and CG Content in Prokaryotic Genomes
Authors: X. Xia
Journal: Molecular Biology and Evolution (2006)

Previous studies have argued that, given the AT-rich nature of stop codons, the length and CG% of coding sequences (CDSs) should be positively correlated. This prediction is generally supported empirically by prokaryotic genomes. However, the correlation is weak for a number of species, with 4 species showing a negative correlation. Here we formulate a more general hypothesis incorporating selection against cytosine (C) usage to explain the lack of strong positive correlation between the length and GC% of CDSs. Two factors contribute to the selection against C usage in long CDSs. First, C is the least abundant nucleotide in the cell, and a long CDS should have fewer Cs to increase transcription efficiency. Second, C is prone to mutation to U/T and selection for increased reliability should reduce C usage in long CDSs. Empirical data from prokaryotic genomes lend strong support for this new hypothesis.
Mechanics and crossbridge kinetics of tracheal smooth muscle in two inbred rat strains
Authors: F-X. Blanc, C. Coirault, S. Salmeron, D. Chemla, Y. Lecarpentier
Journal: European Respiratory Journal (2003)

The aim of the study was to determine whether the nonspecific in vivo airway hyperresponsiveness of the inbred Fisher F‐344 rat strain was associated with differences in the intrinsic contractile properties of tracheal smooth muscle (TSM) when compared with Lewis rats. Isotonic and isometric contractile properties of isolated TSM from Fisher and Lewis rats (each n=10) were investigated, and myosin crossbridge (CB) number, force and kinetics in both strains were calculated using Huxley's equations adapted to nonsarcomeric muscles. Maximum unloaded shortening velocity and maximum extent of muscle shortening were higher in Fisher than in Lewis rats (∼46% and ∼42%, respectively), whereas peak isometric tension was similar. The curvature of the hyperbolic force/velocity relationship did not differ between strains. Myosin CB number and unitary force were similar in both strains. The duration of CB detachment and attachment was shorter in Fisher than in Lewis rats (∼−46% and −34%, respectively). In Fisher rats, these results show that inherited, genetically determined factors of airway hyperresponsiveness are associated with changes in crossbridge kinetics, contributing to an increased tracheal smooth muscle shortening capacity and velocity.
Association of polymorphism in the transforming growth factor 1 gene with disease outcome and mortality in rheumatoid arthritis
Authors: D L Mattey
Journal: Annals of the Rheumatic Diseases (2005)

To investigate whether polymorphism in the transforming growth factor beta1 (TGFbeta1) gene is associated with disease outcome in rheumatoid arthritis.208 patients with established rheumatoid arthritis were genotyped for the TGFbeta1 T869C polymorphism using an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Disease severity was assessed by measuring radiographic damage by Larsen score and functional outcome by the health assessment questionnaire (HAQ). Patients were tracked on the NHS central register for notification of death, and the relation between TGFbeta1 polymorphism and mortality was analysed using Cox proportional hazards regression.Patients carrying a TGFbeta1 T allele had a higher mean HAQ score than those without this allele (1.60 v 1.22, p = 0.04). The T allele was also associated with higher five year mean area under the curve (MAUC) erythrocyte sedimentation rate (ESR), and nodular disease. Larsen score was higher in patients with the TT genotype compared with CC + CT genotypes, although this was not significant after correction for disease duration. There was a trend of increasing mortality risk with T allele dose after adjustment for age, sex, and disease duration (hazard ratio = 1.6 (95% confidence interval, 1.1 to 2.4), p = 0.01).TGFbeta1 T869C gene polymorphism is associated with disease outcome in rheumatoid arthritis. Carriage of the T allele (putatively associated with decreased TGFbeta1 production) was associated with increased inflammatory activity and poor functional outcome, while increasing T allele dose was associated with worse survival.
Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a &lt;EMPH TYPE="ITAL"&gt;BRCA1&lt;/EMPH&gt; or &lt;EMPH TYPE="ITAL"&gt;BRCA2&lt;/EMPH&gt; Mutation
Authors: Amy Finch
Journal: JAMA (2006)

Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort.To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy.Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up.Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not.The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates.After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100,000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100,000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003).Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.
Multicenter Study of a Frozen Glove to Prevent Docetaxel-Induced Onycholysis and Cutaneous Toxicity of the Hand
Authors: Florian Scotté, Jean-Marc Tourani, Eugeniu Banu, Michel Peyromaure, Eric Levy, Sandrine Marsan, Emmanuelle Magherini, Elisabeth Fabre-Guillevin, Jean-Marie Andrieu, Stéphane Oudard
Journal: Journal of Clinical Oncology (2005)

Purpose Onycholysis and skin toxicity occur in approximately 30% of patients treated with docetaxel. We investigated the efficacy and safety of an Elasto-Gel (84400 APT Cedex, Akromed, France) frozen glove (FG) for the prevention of docetaxel-induced onycholysis and skin toxicity. Patients and Methods Patients receiving docetaxel 75 mg/m 2 alone or in combination chemotherapy were eligible for this case-control study. Each patient wore an FG for a total of 90 minutes on the right hand. The left hand was not protected and acted as the control. Onycholysis and skin toxicity were assessed at each cycle by National Cancer Institute Common Toxicity Criteria and documented by photography. Wilcoxon matched-pairs rank test was used. Results Between August 2002 and September 2003, 45 patients were evaluated. Onycholysis and skin toxicity were significantly lower in the FG-protected hand compared with the control hand (P = .0001). Onycholysis was grade (G) 0 in 89% v 49% and G1 to 2 in 11% v 51% for the FG-protected hand and the control hand, respectively. Skin toxicity was G0 in 73% v 41% and G1 to 2 in 27% v 59% for the FG-protected and the control hand, respectively. Median time to nail and skin toxicity occurrence was not significantly different between the FG-protected and the control hand, respectively (106 v 58 days for nail toxicity; 57 v 58 days for skin toxicity). Five patients (11%) experienced discomfort due to cold intolerance. Conclusion FG significantly reduces the nail and skin toxicity associated with docetaxel and provides a new tool in supportive care management to improve a patient's quality of life.
Small Fiber Neuropathy in Patients With Latent Autoimmune Diabetes in Adults: Table 1
Authors: Uazman Alam, Omar Asghar, Ioannis N. Petropoulos, Maria Jeziorska, Hassan Fadavi, Georgios Ponirakis, Andrew Marshall, Mitra Tavakoli, Andrew J.M. Boulton, Nathan Efron, Rayaz A. Malik
Journal: Diabetes Care (2015)

The prevalence of latent autoimmune diabetes in adults (LADA) in patients diagnosed with type 2 diabetes mellitus (T2DM) ranges from 7 to 10% (1). They present at a younger age and have a lower BMI but poorer glycemic control, which may increase the risk of complications (2). However, a recent analysis of the Collaborative Atorvastatin Diabetes Study (CARDS) has demonstrated no difference in macrovascular or microvascular events between patients with LADA and T2DM, but neuropathy was not assessed (3). Previous studies quantifying neuropathy in patients with LADA are limited. In this study, we aimed to accurately quantify neuropathy in subjects with LADA compared with matched patients with T2DM.
Hepatocyte Growth Factor Gene Therapy and Angiotensin II Blockade Synergistically Attenuate Renal Interstitial Fibrosis in Mice
Authors: Junwei Yang, Chunsun Dai, Youhua Liu
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Tubulointerstitial fibrosis is considered to be common endpoint result of many forms of chronic renal diseases. Except for renal replacement, chronic renal fibrosis is presently incurable. This study demonstrates that the combination of hepatocyte growth factor (HGF) gene therapy with inhibition of the renin-angiotensin system produced synergistic beneficial effects leading to dramatic attenuation of renal tubulointerstitial fibrosis in obstructive nephropathy in mice. The combined treatment with human HGF gene and losartan, an angiotensin II (AngII) type I receptor blocker, preserved renal mass and gross morphology of the obstructed kidneys. Although HGF gene therapy alone inhibited the expression of α-smooth muscle actin (αSMA) by approximately 54% and 60% at day 7 and day 14 after surgery, respectively, its combination with losartan almost completely abolished αSMA induction in the obstructed kidneys. The combined therapy also synergistically inhibited the accumulation of interstitial matrix components, such as fibronectin and collagen I, and suppressed renal expression of transforming growth factor-β1 (TGF-β1) and its type I receptor. <i>In vitro</i> studies revealed that AngII by itself did not induce αSMA, but it drastically potentiated TGF-β1-initiated αSMA expression in tubular epithelial cells. Furthermore, HGF abrogated <i>de novo</i> αSMA expression induced by TGF-β1 plus AngII. These results suggest that many factors are implicated in the pathogenesis of renal interstitial fibrosis; therefore, a combined therapy aimed at simultaneously targeting multiple pathologic pathways may be necessary for halting the progression of chronic renal diseases. These findings may provide the basis for designing future therapeutic regimens for blocking progressive renal fibrosis in patients. E-mail: liuy@msx.upmc.edu
Motorcycle racing injuries on track and road circuits in Ireland.
Authors: C H Horner, A A O'Brien
Journal: British Journal of Sports Medicine (1986)

A retrospective study was carried out on all motorcycle injuries occurring at Mondelo Park racetrack for the 1983 and 1984 seasons. In this sport there were a total of 57 injuries for the two year period, 27 occurring in 1983 and 30 in 1984. Soft tissue injuries accounted for 66.7%, fractures 22.8% and head injuries 10.5% of the total. In the fracture group, 2 patients suffered spinal fractures which is noteworthy in that neither were wearing back protectors which as yet are not compulsory safety equipment in Eire. These figures were compared with data from the same two year period on the Ulster road circuit. The incidence of each type of injury was similar and equally low in both groups. Motorcycle racing injuries compared favourably with motor car racing injuries and had a lower incidence of serious head injury. In comparison with road traffic accidents involving motorcyclists the overall number of injuries, the number of serious head, abdominal and chest injuries and the overall fatality rate, are much lower. The two most relevant factors in our lower injury incidence were lack of alcohol and the absence of collision with cars. Experience, medical attention and speed had no direct influence on our injury incidence.
Small Sized EGFR1 and HER2 Specific Bifunctional Antibody for Targeted Cancer Therapy
Authors: Li Ding, Caiping Tian, Song Feng, Guissi Fida, Congying Zhang, Yuxiang Ma, Guanhua Ai, Samuel Achilefu, Yueqing Gu
Journal: Theranostics (2015)

Targeting tumors using miniature antibodies is a novel and attractive therapeutic approach, as these biomolecules exhibit low immunogenicity, rapid clearance, and high targeting specificity.However, most of the small-sized antibodies in existence do not exhibit marked anti-tumor effects, which limit their use in targeted cancer immunotherapy.To overcome this difficulty in targeting multiple biomarkers by combination therapies, we designed a new bifunctional antibody, named MaAbNA (multivalent antibody comprised of nanobody and affibody moieties), capable of targeting EGFR1 and HER2, which are widely overexpressed in a variety of tumor types.The small-sized (29 kDa) MaAbNA, which was expressed in E.coli, consists of one anti-EGFR1 nanobody and two anti-HER2 affibodies, and possesses high affinity (K D ) for EGFR1 (~4.1 nM) and HER2 (~4.7 nM).In order to enhance its anti-tumor activity, MaAbNA was conjugated with adriamycin (ADM) using a PEG2000 linker, forming a new complex anticancer drug, MaAbNA-PEG2000-ADM.MaAbNA exhibited high inhibitory effects on tumor cells over-expressing both EGFR1 and HER2, but displayed minimal cytotoxicity in cells expressing low levels of EGFR1 and HER2.Moreover, MaAbNA-PEG2000-ADM displayed increased tumoricidal effects than ADM or MaAbNA alone, as well exhibited greater antitumor efficacy than EGFR1 (Cetuximab) and HER2 (Herceptin) antibody drugs.The ability of MaAbNA to regulate expression of downstream oncogenes c-jun, c-fos, c-myc, as well as AEG-1 for therapeutic potential was evaluated by qPCR and western-blot analyses.The antitumor efficacy of MaAbNA and its derivative MaAbNA-PEG2000-ADM were validated in vivo, highlighting the potential for use of MaAbNA as a highly tumor-specific dual molecular imaging probe and targeted cancer therapeutic.
Towards a descriptivist psychology of reasoning and decision making
Authors: Jonathan St. B. T. Evans, Shira Elqayam
Journal: Behavioral and Brain Sciences (2011)

Abstract Our target article identified normativism as the view that rationality should be evaluated against unconditional normative standards. We believe this to be entrenched in the psychological study of reasoning and decision making and argued that it is damaging to this empirical area of study, calling instead for a descriptivist psychology of reasoning and decision making. The views of 29 commentators (from philosophy and cognitive science as well as psychology) were mixed, including some staunch defences of normativism, but also a number that were broadly supportive of our position, although critical of various details. In particular, many defended a position that we call “soft normativism,” which sees a role for normative evaluation within boundaries alongside more descriptive research goals. In this response, we clarify our use of the term “instrumental rationality” and add discussion of “epistemic rationality,” defining both as descriptive and non-normative concepts. We consider the debate with reference to dual-process theory, the “new paradigm” psychology of reasoning, and empirical research strategy in these fields. We also discuss cognitive variation by age, intelligence, and culture, and the issue of relative versus absolute definitions of norms. In conclusion, we hope at least to have raised consciousness about the important boundaries between norm and description in the psychology of thinking.
GPs in Glasgow are in favour of primary care emergency centres
Authors: J. O'Neil
Journal: BMJ (1996)

erence ranges.We therefore suggest that the problems of standardising the reporting of results for anticoagulation clinics would be reduced by use of the proportion of patients achieving therapeutic international normalised ratios, the percentage of time for which the ratios are within the therapeutic reference range, and the mean (±1 SD) ratio.The model of care reported by Macgregor and colleagues may have a place in anticoagulant treat- ment, but their small observational study cannot draw the broad conclusion that ifwe "are willing to devolve management to pharmacists then good therapeutic control is achievable in the surgery."
Aneurysm of the Internal Pudendal Artery
Authors: E. Harris Pierce
Journal: JAMA (1968)

No previously reported aneurysm of the internal pudendal artery was found on review of the literature. A high index of suspicion is necessary for any diagnosis. "Egg shell" crepitation is one physical sign of an aneurysm. The use of a pediatric stethoscope in an unusual place confirmed the bruit and diagnosis of aneurysm.
Androgenicity of Progestins in Hormonal Contraceptives and the Risk of Gestational Diabetes Mellitus
Authors: Monique M. Hedderson, Assiamira Ferrara, Michelle A. Williams, Victoria L. Holt, Noel S. Weiss
Journal: Diabetes Care (2007)

OBJECTIVE—There is some evidence that use of hormonal contraceptives, particularly the more androgenic formulations, can alter a woman's glucose tolerance. We examined the association between hormonal contraceptive use, categorized by the androgenicity of the progestin component, and risk of gestational diabetes mellitus (GDM) in a nested case-control study. RESEARCH DESIGN AND METHODS—Case (n = 356) and control (n = 368) subjects were selected from a multiethnic cohort of 14,235 women who delivered a singleton live birth between 1 January 1996 and 30 June 1998, who were screened for GDM at 24–28 gestational weeks, and who were members of Kaiser Permanente for at least 5 years before pregnancy. GDM was defined using the National Diabetes Data Group plasma glucose cutoffs. Information concerning hormonal contraceptive use during the 5 years before pregnancy was obtained from medical charts and some pharmacy data. RESULTS—There was a suggestion that compared with no hormonal contraceptive use, use of a low-androgen hormonal contraceptive before pregnancy was associated with a slight reduction in risk of GDM (odds ratio 0.84 [95% CI 0.58–1.22]), whereas use of a high-androgen hormonal contraceptive was associated with a modest increase in GDM risk (1.43 [0.92–2.22]). CONCLUSIONS—The effects of hormonal contraceptive use on GDM risk may vary by the androgenicity of the progestin component.
Downregulation of miR-138 Sustains NF-κB Activation and Promotes Lipid Raft Formation in Esophageal Squamous Cell Carcinoma
Authors: Hui Gong, Libing Song, Chuyong Lin, Aibin Liu, Xi Lin, Jueheng Wu, Mengfeng Li, Jun Li
Journal: Clinical Cancer Research (2013)

Constitutive activation of NF-κB signaling plays vital roles in esophageal squamous cell carcinoma (ESCC) progression. The aim of this study was to evaluate the effect of miR-138 on NF-κB activation and ESCC progression.Expression of miR-138 in ESCC cell lines, ESCC tissues, and 205 archived ESSC specimens was determined using real-time PCR analysis. Anchorage-independent growth, chicken chorioallantoic membrane, Transwell matrix invasion and Annexin V-binding assays, and a xenograft tumor model were used to determine the role of miR-138 in ESCC progression. The effect of miR-138 on NF-κB activation was investigated using IKK in vitro kinase, electrophoretic mobility shift, lipid raft isolation, and luciferase reporter assays.miR-138 was downregulated and inversely correlated with tumor progression and patient survival in ESCCs. Downregulation of miR-138 enhanced, whereas upregulation of miR-138 reduced, the aggressive phenotype of ESCC cells both in vitro and in vivo. Silencing miR-138 promoted K63-linked polyubiquitination of the NF-κB signaling intermediaries TRAF2 and RIP1 and sustained NF-κB activation. Furthermore, downregulation of miR-138 induced lipid raft formation via upregulating multiple components of lipid rafts, including FLOT1, FLOT2, and caveolin-1. Importantly, the in vitro analysis was consistent with a significant inverse correlation between miR-138 expression and NF-κB hyperactivation in a cohort of human ESCC specimens.Our results show that miR-138 functions as a tumor-suppressive miRNA and that downregulation of miR-138 contributes to constitutive NF-κB activation and ESCC progression.
Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia
Authors: Rogier M. Determann, Julian L. Millo, Sébastien Gibot, Johanna C. Korevaar, Margreeth B. Vroom, Tom van der Poll, Christopher S. Garrard, Marcus J. Schultz
Journal: Intensive Care Medicine (2005)
An EGFR Targeted PET Imaging Probe for the Detection of Colonic Adenocarcinomas in the Setting of Colitis
Authors: N. Selcan Turker, Pedram Heidari, Raju Kucherlapati, Melanie Kucherlapati, Umar Mahmood
Journal: Theranostics (2014)

Colorectal cancer is a serious complication associated with inflammatory bowel disease, often indistinguishable by screening with conventional FDG PET probes.We have developed an alternative EGFR-targeted PET imaging probe that may be used to overcome this difficulty, and successfully assessed its utility for neoplastic lesion detection in preclinical models.Cetuximab F(ab′)2 fragments were enzymatically generated, purified, and DOTA-conjugated.Radiolabeling was performed with 67 Ga for cell based studies and 64 Cu for in vivo imaging.Competitive binding studies were performed on CT26 cells to assess affinity (K D ) and receptors per cell (B max ).In vivo imaging using the EGFR targeted PET probe and 18 F FDG was performed on CT26 tumor bearing mice in both control and dextran sodium sulfate (DSS) induced colitis settings.Spontaneous adenomas in genetically engineered mouse (GEM) models of colon cancer were additionally imaged.The EGFR imaging agent was generated with high purity (> 98%), with a labeling efficiency of 60 ± 5% and ≥99% radiochemical purity.The K D was 6.6 ± 0.7 nM and the B max for CT26 cells was 3.3 ± 0.1 × 10 6 receptors/cell.Target to background ratios (TBR) for CT26 tumors compared to colonic uptake demonstrated high values for both 18 F-FDG (3.95 ± 0.13) and the developed 64 Cu-DOTA-cetuximab-F(ab′)2 probe (4.42 ± 0.11) in control mice.The TBR for the EGFR targeted probe remained high (3.78 ± 0.06) in the setting of colitis, while for 18 F FDG, this was markedly reduced (1.54 ± 0.08).Assessment of the EGFR targeted probe in the GEM models demonstrated a correlation between radiotracer uptake in spontaneous colonic lesions and the EGFR staining level ex vivo.A clinically translatable PET imaging probe was successfully developed to assess EGFR.The imaging agent can detect colonic tumors with a high TBR for detection of in situ lesions in the setting of colitis, and opens the possibility for a new approach for screening high-risk patients.