tbuckley/cabot-search huggingface dataset:
Non-colonic features of irritable bowel syndrome.
Authors: P J Whorwell, M McCallum, F H Creed, C T Roberts
Journal: Gut (1986)

In 100 patients with irritable bowel syndrome a wide variety of non-gastrointestinal symptoms were significantly more common than in a group of 100 age, sex, and social class matched controls. Nocturia, frequency and urgency of micturition, incomplete bladder emptying, back pain, an unpleasant taste in the mouth, a constant feeling of tiredness and in women dyspareunia were particularly prominent (p less than 0.001). With reference to non-colonic gastrointestinal symptoms nausea, vomiting, dysphagia and early satiety were very common (p less than 0.0001). This symptom diversity was observed irrespective of whether the patient had a psychiatric disorder or not. Patients smoked more than controls (p = 0.02) drank more caffeine containing drinks (p = 0.03) and 26% had taken at least one week off work in the previous 12 months. Thirty three per cent of patients had a family history of irritable bowel syndrome. Cognisance of these diverse symptoms may prevent referral to the wrong medical specialty and inappropriate investigation. They may also be indicative of a much more diffuse disorder of smooth muscle than has previously been appreciated.
The Potential of Circulating Tumor Cells as a Liquid Biopsy to Guide Therapy in Prostate Cancer
Authors: Klaus Pantel, Catherine Alix-Panabières
Journal: Cancer Discovery (2012)

Miyamoto and colleagues present data that prostate-specific antigen/prostate-specific membrane antigen (PSA/PSMA)-based measurements of androgen receptor (AR) signaling in circulating tumor cells (CTC) enable real-time quantitative monitoring of intratumoral AR signaling. This finding indicates that measuring AR signaling within CTCs may help to guide therapy in metastatic prostate cancer and highlights the use of CTCs as liquid biopsy.
Elemental carbon exposure and lung function in schoolchildren from Mexico City
Authors: A. Barraza-Villarreal, M.C. Escamilla-Nuñez, L. Hernández-Cadena, J.L. Texcalac-Sangrador, J.J. Sienra-Monge, B.E. del Río-Navarro, M. Cortez-Lugo, P.D. Sly, I. Romieu
Journal: European Respiratory Journal (2011)

Though exposure to air pollution has a detrimental effect on respiratory health, few studies have examined the association between elemental carbon exposure and lung function among schoolchildren. The aim of the present study was to present the association between short-term elemental carbon exposure and lung function in schoolchildren from Mexico City. 55 asthmatic and 40 non-asthmatic children were followed for an average of 22 weeks. A spirometry test was performed every 15 days during follow-up. Portable air samplers collected particulate matter onto Teflon filters. Gravimetric analysis was conducted and elemental carbon was quantified using transmission densitometry. The association between the main variables was analysed using linear mixed effects models. The mean± sd of elemental carbon light absorption was 92.7±54.7 Mm −1 . An increase of one interquartile range in the 24-h average of elemental carbon (100.93 Mm −1 ) was associated with a significant negative impact on forced expiratory volume in 1 s (FEV 1 ) (-62.0 (95% CI -123.3– -1.2) mL) and forced expiratory flow at 25–75% of forced vital capacity (FVC) (FEF 25–75% ) (-111 (95% CI -228.3– -4.1) mL) among asthmatic children, equal to 3.3% and 5.5%, respectively; and on FEV 1 (-95.0 (95% CI -182.3– -8.5) mL) and FVC (-105.0 (95% CI -197.0– -13.7) mL) among non-asthmatic children. Exposure to elemental carbon resulted in an important negative effect on lung function in atopic schoolchildren, regardless of asthma status.
Fly Motion Vision
Authors: Alexander Borst, Juergen Haag, Dierk F. Reiff
Journal: Annual Review of Neuroscience (2010)

Fly motion vision and resultant compensatory optomotor responses are a classic example for neural computation. Here we review our current understanding of processing of optic flow as generated by an animal's self-motion. Optic flow processing is accomplished in a series of steps: First, the time-varying photoreceptor signals are fed into a two-dimensional array of Reichardt-type elementary motion detectors (EMDs). EMDs compute, in parallel, local motion vectors at each sampling point in space. Second, the output signals of many EMDs are spatially integrated on the dendrites of large-field tangential cells in the lobula plate. In the third step, tangential cells form extensive interactions with each other, giving rise to their large and complex receptive fields. Thus, tangential cells can act as matched filters tuned to optic flow during particular flight maneuvers. They finally distribute their information onto postsynaptic descending neurons, which either instruct the motor centers of the thoracic ganglion for flight and locomotion control or act themselves as motor neurons that control neck muscles for head movements.
Intention to Lose Weight, Weight Changes, and 18-y Mortality in Overweight Individuals without Co-Morbidities
Authors: Thorkild I.A Sørensen, Aila Rissanen, Maarit Korkeila, Jaakko Kaprio
Journal: PLoS Medicine (2005)

Weight loss in the obese improves risk factors for cardiovascular diseases and diabetes. However, several studies have shown inconsistent long-term effects of weight loss on mortality. We investigated the influence on mortality of intention to lose weight and subsequent weight changes among overweight individuals without known co-morbidities.In 1975, a cohort of individuals reported height, weight, and current attempts (defined as "intention") to lose weight, and in 1981, they reported current weight. Mortality of the 2,957 participants with body mass index > or = 25 kg/m2 in 1975 and without pre-existing or current diseases was followed from 1982 through 1999, and 268 participants died. The association of intention to lose weight in 1975 and actual weight change until 1981 with mortality was analysed while controlling for behavioural and psychosocial risk factors and hypertension as possible confounders. Compared with the group not intending to lose and able to maintain stable weight, the hazard ratios (with 95% confidence intervals) in the group intending to lose weight were 0.84 (0.49-1.48) for those with stable weight, 1.86 (1.22-2.87) for those losing weight, and 0.93 (0.55-1.56) for those gaining weight. In the group not intending to lose weight, hazard ratios were 1.17 (0.82-1.66) for those who did lose weight, and 1.57 (1.08-2.30) for those gaining weight.Deliberate weight loss in overweight individuals without known co-morbidities may be hazardous in the long term. The health effects of weight loss are complex, possibly composed of oppositely acting processes, and need more research.
Cellular transport of l-histidine in Hartnup disease
Authors: Sverre Halvorsen, Olof Hygstedt, Rudolf Jagenburg, Ottar Sjaastad
Journal: Journal of Clinical Investigation (1969)

The urinary excretion, the intestinal absorption, and the elimination of histidine from blood were studied in two patients with Hartnup disease. On standard diet the patients lost a great proportion of the dietary histidine in the urine, whereas the fecal loss was negligible. A high oral dose of L-histidine gave only a slight increase in plasma histidine and no increase in fecal histidine, but a considerable increase in the urinary histidine output. Intravenously administered L-histidine was eliminated more rapidly than in controls. The lack of increase in plasma histidine after the oral loading may be explained by the rapid elimination from the blood. This was mainly due to a rapid cellular uptake of histidine which is supposed to be a normal reaction of histidine-deprived cells. Thus the only obvious defect in the histidine transport in Hartnup disease is the reabsorption defect in the renal tubules. A generally impaired cellular transport of L-histidine is improbable.
Disruption of a <i>Sirt1</i>-Dependent Autophagy Checkpoint in the Prostate Results in Prostatic Intraepithelial Neoplasia Lesion Formation
Authors: Michael J. Powell, Mathew C. Casimiro, Carlos Cordon-Cardo, Xiaohong He, Wen-Shuz Yeow, Chenguang Wang, Peter A. McCue, Michael W. McBurney, Richard G. Pestell
Journal: Cancer Research (2010)

Abstract The Sirtuin family of proteins (SIRT) encode a group of evolutionarily conserved, NAD-dependent histone deacetylases, involved in many biological pathways. SIRT1, the human homologue of the yeast Silent Information Regulator 2 (Sir2) gene, deacetylates histones, p300, p53, and the androgen receptor. Autophagy is required for the degradation of damaged organelles and long-lived proteins, as well as for the development of glands such as the breast and prostate. Herein, homozygous deletion of the Sirt1 gene in mice resulted in prostatic intraepithelial neoplasia (PIN) associated with reduced autophagy. Genome-wide gene expression analysis of Sirt1−/− prostates demonstrated that endogenous Sirt1 repressed androgen responsive gene expression and induced autophagy in the prostate. Sirt1 induction of autophagy occurred at the level of autophagosome maturation and completion in cultured prostate cancer cells. These studies provide novel evidence for a checkpoint function of Sirt1 in the development of PIN and further highlight a role for SIRT1 as a tumor suppressor in the prostate. Cancer Res; 71(3); 964–75. ©2010 AACR.
The Harlequin sign
Authors: Duneesha De Fonseka, Adriana Lama-Lopez, Tim Batchelor, Anthony Edey, Nicholas A Maskell
Journal: Thorax (2015)

A 28-year-old woman was incidentally found to have a large right apical mass (figure 1) on a chest radiograph. She denied having any respiratory symptoms but had noted asymmetric flushing of her face following strenuous exercise (figure 2). On closer questioning she also described hypohydrosis affecting the right side of her face.



Figure 1 
Chest radiograph showing a large right apical opacity and evidence of thinning of the right …
The Effect of Simvastatin on mRNA Expression of Transforming Growth Factor‐β1, Bone Morphogenetic Protein‐2 and Vascular Endothelial Growth Factor in Tooth Extraction Socket
Authors: Chang Liu, Zhe Wu, Hong‐chen Sun
Journal: International Journal of Oral Science (2009)

To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor‐β1 (TGF‐β1), bone morphogenetic protein‐2 (BMP‐2) and vascular endothelial growth factor (VEGF) in the tooth sockets of rat. Forty‐eight male Wistar rats were randomly divided into experimental and control groups (n=24). Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF‐β1, BMP‐2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. The fusiform stroma cells in the tooth extraction socket began to express TGF‐β1, BMP‐2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF‐β1 and BMP‐2 mRNA in the experimental group was significantly up‐regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.
Fhit Modulates the DNA Damage Checkpoint Response
Authors: Hideshi Ishii, Koshi Mimori, Hiroshi Inoue, Taeko Inageta, Kazuhiro Ishikawa, Shuho Semba, Teresa Druck, Francesco Trapasso, Kenzaburo Tani, Andrea Vecchione, Carlo M. Croce, Masaki Mori, Kay Huebner
Journal: Cancer Research (2006)

Abstract In preneoplastic lesions, the DNA damage checkpoint is induced and loss of heterozygosity at the FRA3B/FHIT common chromosome fragile region precedes or is coincident with activation of the checkpoint response in these early stages. Introduction of exogenous Fhit into cells in vitro led to modulation of expression of checkpoint proteins Hus1 and Chk1 at mid-S checkpoint, a modulation that led to induction of apoptosis in esophageal cancer cells but not in noncancerous primary cultures. Mutation of the conserved Fhit tyrosine 114 resulted in failure of this function, confirming the importance of this residue. The results suggest that the DNA damage–susceptible FRA3B/FHIT chromosome fragile region, paradoxically, encodes a protein that is necessary for protecting cells from accumulation of DNA damage through its role in modulation of checkpoint proteins, and inactivation of Fhit contributes to accumulation of abnormal checkpoint phenotypes in cancer development. (Cancer Res 2006; 66(23): 11287-92)
Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons
Authors: Jian-Sheng Gong, Shin-ya Morita, Mariko Kobayashi, Tetsurou Handa, Shinobu C Fujita, Katsuhiko Yanagisawa, Makoto Michikawa
Journal: Molecular Neurodegeneration (2007)

Since the majority of apolipoprotein E (apoE) existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should focus on the role of the apoE-HDL complex rather than on that of free apoE in cholesterol metabolism in the central nervous system. However, the apoE-isoform-specific effect of apoE-HDL on cholesterol transport remains unclarified.Here we show that apoE3-HDL induced a marked cholesterol release from neurons, while apoE4-HDL induced little. To elucidate the mechanism underlying this phenomenon, we used a complex of lipid emulsion (EM) with recombinant apoE3 or apoE4 (apoE-EM) at various apoE concentrations. When a small number of apoE molecules were associated with EM, apoE3- and apoE4-EM, induced a marked cholesterol release to a level similar to that induced by EM alone. However, when apoE at given concentrations was incubated with EM, apoE3-EM induced a marked cholesterol release, while apoE4-EM induced little. Under these conditions, a greater number of apoE4 molecules were associated with EM than apoE3 molecules. When an increasing number of apoE molecules were associated with EM, both apoE3-EM and apoE4-EM induced little cholesterol release. Preincubation with beta-mercaptoethanol increased the number of apoE3 molecules associated with EM similar to that of apoE4 molecules, indicating that the presence (apoE3) or absence (apoE4) of intermolecular disulfide bond formation is responsible for the association of a greater number of apoE4 molecules to EM than apoE3 molecules.These results suggest that although apoE and a lipid particle are lipid acceptors, when apoE and a lipid particle form a complex, apoE on the particle surface inhibits the lipid particle-mediated cholesterol release from cells in an apoE-concentration-dependent manner.
Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications
Authors: Elisa Fabbrini, Shelby Sullivan, Samuel Klein
Journal: Hepatology (2009)

Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and export (as triglyceride within very low-density lipoprotein). Therefore, an excessive amount of intrahepatic triglyceride (IHTG) represents an imbalance between complex interactions of metabolic events. The presence of steatosis is associated with a constellation of adverse alterations in glucose, fatty acid, and lipoprotein metabolism. It is likely that abnormalities in fatty acid metabolism, in conjunction with adipose tissue, hepatic, and systemic inflammation, are key factors involved in the development of insulin resistance, dyslipidemia, and other cardiometabolic risk factors associated with NAFLD. However, it is not clear whether NAFLD causes metabolic dysfunction or whether metabolic dysfunction is responsible for IHTG accumulation, or possibly both. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD will provide important insights into the mechanisms responsible for the cardiometabolic complications of obesity. (Hepatology 2009.)
Practical Problems With Clinical Guidelines for Breast Cancer Prevention Based on Remaining Lifetime Risk
Authors: A. S. Quante, A. S. Whittemore, T. Shriver, J. L. Hopper, K. Strauch, M. B. Terry
Journal: JNCI Journal of the National Cancer Institute (2015)

Clinical guidelines for breast cancer chemoprevention and MRI screening involve estimates of remaining lifetime risk (RLR); in the United States, women with an RLR of 20% or higher meet "high-risk" criteria for MRI screening. We prospectively followed 1764 women without breast cancer to compare the RLRs and 10-year risks assigned by the risk models International Breast Cancer Intervention Study (IBIS) and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and to compare both sets of model-assigned 10-year risks to subsequent incidence of breast cancer in the cohort. We used chi-square statistics to assess calibration and the area under the receiver operating characteristic curve (AUC) to assess discrimination. All statistical tests are two-sided. The models classified different proportions of women as high-risk (IBIS = 59.3% vs BOADICEA = 20.1%) using the RLR threshold of 20%. The difference was smaller (IBIS = 52.9% vs BOADICEA = 43.2%) using a 10-year risk threshold of 3.34%. IBIS risks (mean = 4.9%) were better calibrated to observed breast cancer incidence (5.2%, 95% confidence interval (CI) = 4.2% to 6.4%) than were those of BOADICEA (mean = 3.7%) overall and within quartiles of model risk ( P = .20 by IBIS and P = .07 by BOADICEA). Both models gave similar discrimination, with AUCs of 0.67 (95% CI = 0.61 to 0.73) using IBIS and 0.68 (95% CI = 0.62 to 0.74) using BOADICEA. Model sensitivities at thresholds for a 20% false-positive rate were also similar, with 41.8% using IBIS and 38.0% using BOADICEA. RLR-based guidelines for high-risk women are limited by discordance between commonly used risk models. Guidelines based on short-term risks would be more useful, as models are generally developed and validated under a short fixed time horizon (≤10 years).
Improvement and Emergence of Insulin Restriction in Women With Type 1 Diabetes
Authors: Ann E. Goebel-Fabbri, Barbara J. Anderson, Janna Fikkan, Debra L. Franko, Kimberly Pearson, Katie Weinger
Journal: Diabetes Care (2011)

To determine the distinguishing characteristics of women who report stopping insulin restriction at 11 years of follow-up from those continuing to endorse insulin restriction as well as those characteristics differing in patients who continue to use insulin appropriately from new insulin restrictors.This is an 11-year follow-up study of 207 women with type 1 diabetes. Insulin restriction, diabetes self-care behaviors, diabetes-specific distress, and psychiatric and eating disorder symptoms were assessed using self-report surveys.Of the original sample, 57% participated in the follow-up study. Mean age was 44 ± 12 years, diabetes duration was 28 ± 11 years, and A1C was 7.9 ± 1.3%. At follow-up, 20 of 60 baseline insulin restrictors had stopped restriction. Women who stopped reported improved diabetes self-care and distress, fewer problems with diabetes self-management, and lower levels of psychologic distress and eating disorder symptoms. Logistic regression indicated that lower levels of fear of weight gain with improved blood glucose and fewer problems with diabetes self-management predicted stopping restriction. At follow-up, 34 women (23%) reported new restriction, and a larger proportion of new insulin restrictors, relative to nonrestrictors, endorsed fear of weight gain with improved blood glucose.Findings indicate that fear of weight gain associated with improved blood glucose and problems with diabetes self-care are core issues related to both the emergence and resolution of insulin restriction. Greater attention to these concerns may help treatment teams to better meet the unique treatment needs of women struggling with insulin restriction.
Abstract MP05: Leisure-Time Running and Incident Type 2 Diabetes
Authors: Duck-chul Lee, Carl J. Lavie, Timothy S. Church, Xuemei Sui, Steven N. Blair
Journal: Circulation (2015)

Introduction: There is still little evidence on the dose-response relation between leisure-time running and incident type 2 diabetes (T2D). Hypothesis: We examined the hypothesis that running reduces the risk of developing T2D. Methods: Participants were 19,347 adults aged 18 to 100 years (mean age, 44) who received an extensive preventive medical examination during 1974-2006 in the Aerobics Center Longitudinal Study. Participants were free of cardiovascular disease, cancer, and T2D at baseline. Running and other physical activities were assessed on the medical history questionnaire by self-reported leisure-time activities during the past 3 months. We defined T2D as fasting glucose ≥126 mg/dl, insulin use, or physician-diagnosis during follow-up medical examinations. Cox regression was used to quantify the association between running and T2D after adjusting for baseline age, sex, examination year, body mass index, smoking status, heavy alcohol drinking, abnormal electrocardiogram, hypertension, hypercholesterolemia, and levels of other physical activities. Results: During an average follow-up of 6.5 years, 1,015 adults developed T2D. Approximately 30% of adults participated in leisure-time running. Runners had a 29% lower risk of developing T2D compared with non-runners. The hazard ratios (95% confidence intervals) of T2D were 0.97 (0.74-1.27), 0.66 (0.49-0.89), 0.62 (0.45-0.85), 0.78 (0.58-1.03), and 0.57 (0.42-0.79) across quintiles (Q) of running time (minutes/week); 0.99 (0.76-1.30), 0.60 (0.44-0.82), 0.72 (0.55-0.94), 0.65 (0.47-0.90), and 0.63 (0.47-0.86) across Q of running distance (miles/week); 1.08 (0.83-1.40), 0.67 (0.50-0.90), 0.70 (0.53-0.93), 0.61 (0.45-0.83), and 0.53 (0.36-0.76) across Q of running frequency (times/week); 0.95 (0.73-1.24), 0.70 (0.52-0.94), 0.62 (0.45-0.84), 0.73 (0.55-0.97), and 0.58 (0.42-0.80) across Q of total amount of running (MET-minutes/week); and 0.95 (0.71-1.28), 0.76 (0.59-0.99), 0.59 (0.42-0.83), 0.66 (0.51-0.85), and 0.62 (0.43-0.90) across Q of running speed (mph), respectively, compared with no running after adjusting for confounders including levels of other physical activities. Conclusions: Participating in leisure-time running is associated with markedly lower risk of developing T2D in adults. Except for those in the very lowest Q for running doses, even relatively low running doses (starting with Q 2) were associated with marked reductions in T2D risk over time, supporting the prescription of running to reduce T2D.
Towards a Unified Model of RAF Inhibitor Resistance
Authors: David B. Solit, Neal Rosen
Journal: Cancer Discovery (2014)

ATP-competitive RAF inhibitors elicit profound but often temporary antitumor responses in patients with BRAF-mutant melanoma. Analysis of tumor samples collected at the time of disease progression indicates that alterations within the extracellular signal-regulated kinase (ERK) pathway that result in reactivation of ERK signaling are present in most patients. Mutations in the phosphoinositide 3-kinase/AKT pathway that enhance the adaptive response to RAF inhibitors also contribute to RAF inhibitor resistance in a subset of patients.