tbuckley/cabot-search huggingface dataset:
In Vivo Measurement of Mitral Leaflet Surface Area and Subvalvular Geometry in Patients With Asymmetrical Septal Hypertrophy
Authors: Dae-Hee Kim, Mark D. Handschumacher, Robert A. Levine, Yun-Sil Choi, Yun Jeong Kim, Sung-Cheol Yun, Jong-Min Song, Duk-Hyun Kang, Jae-Kwan Song
Journal: Circulation (2010)

Background— Analyzing the determinants of systolic anterior motion of the mitral valve and consequent left ventricular outflow tract (LVOT) obstruction in patients with asymmetrical septal hypertrophy requires a comprehensive 3-dimensional analysis of mitral leaflet (ML) area, papillary muscle (PM) geometry, and the distribution of left ventricular hypertrophy. Methods and Results— Real-time 3-dimensional echocardiography was performed in 47 patients with asymmetrical septal hypertrophy and 32 normal controls. Patients included 20 with resting LVOT obstruction (group I) and 27 without (group II). Customized software (Omni 4D) provided a validated measure of ML surface area, LVOT area, mitral annular area and nonplanarity, LVOT hypertrophy index by topography (percent area with wall thickness &gt;16 mm), and 3-dimensional PM positions relative to annulus. ML area was more than twice as large in group I than normal and 1.4 times normal in group II ( P &lt;0.001). Group I patients were also characterized by higher LVOT hypertrophy index and medial and anterior displacements of both PMs, resulting in a shorter inter-PM distance. Independent determinants of LVOT obstruction were indexed total ML area (adjusted odds ratio, 5.651; 95% confidence interval, 1.573 to 20.304; P =0.008) and inter-PM distance (adjusted odds ratio, 0.416; 95% confidence interval, 0.203 to 0.854; P =0.0169). Minimal LVOT area during systole correlated well with peak LVOT pressure gradient ( R 2 =0.83, P &lt;0.001); its independent determinants were left ventricular end-systolic volume ( P =0.0183), indexed total ML area ( P =0.0108), inter-PM distance ( P =0.0378), annular height ( P =0.0047), and LVOT hypertrophy index ( P =0.0098). Conclusions— Myocardium is not the only tissue affected in patients with asymmetrical septal hypertrophy, and primary changes of the mitral apparatus, including ML area increase and PM displacement, are independent determinants of LVOT obstruction and provide a comprehensive mechanism that determines leaflet slack and anteriorly directed motion. Abnormal PM–mitral valve geometry assessed by real-time 3-dimensional echocardiography can provide reasonable new targets for individualized intervention.
Anemia predicts mortality after COPD exacerbation
Authors: Aida Munoz Ferrer, Carlos Martínez, Karina Portillo, Pere Serra, María Luisa Martínez, Ignasi Garcia Olivé, Marisol Prats, Joan Ruiz Manzano, Josep Morera
Journal: European Respiratory Journal (2011)

Anemia is a recognised pronostic factor in many chronic illnesses,but there is limited information about its impact on outcomes in patients hospitalized due to an acute COPD exacerbation (AECOPD).

Aim: To investigate whether anemia exert an effect on mortality after 1 year of follow-up.

Methods: From November 2007 to November 2009 we recruited 117 patients who required hospitalisation due to an AECOPD.We collected demogrhaphic data, nutritional status, hemoglobin (Hb), hematocrite (Ht) and lung function. Patients were followed up during 1 year. Mortality and days-to-death were collected.

Results: Mean age 72 (SD±9); FEV1 38 (SD±12); mortality after 1 year was 21,4%. Comparing those who died to those who survived we found significant differences (p 1 exacerbation in the previous year was 6 (CI: 1,3-127,1).

![Figure][1] 



Conclusion: Anemia and previous exacerbations were independent predictors of mortality after 1 year in patients hospitalized due to ACOPD.

 [1]: pending:yes
Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies
Authors: Joanne Kurtzberg, Vinod K. Prasad, Shelly L. Carter, John E. Wagner, Lee Ann Baxter-Lowe, Donna Wall, Neena Kapoor, Eva C. Guinan, Stephen A. Feig, Elizabeth L. Wagner, Nancy A. Kernan
Journal: Blood (2008)
Prognostic Acceptance and the Well-Being of Patients Receiving Palliative Care for Cancer
Authors: Genevieve N. Thompson, Harvey M. Chochinov, Keith G. Wilson, Christine J. McPherson, Srini Chary, Fiona M. O'Shea, David R. Kuhl, Robin L. Fainsinger, Pierre R. Gagnon, Karen A. Macmillan
Journal: Journal of Clinical Oncology (2009)

To identify the impact of prognostic acceptance/nonacceptance on the physical, psychological, and existential well-being of patients with advanced cancer.A Canadian multicenter prospective national survey was conducted of patients diagnosed with advanced cancer with an estimated survival duration of 6 months or less (n = 381) receiving palliative care services.Of the total number of participants, 74% reported accepting their situation and 8.6% reported accepting with "moderate" to "extreme" difficulty. More participants with acceptance difficulties than without acceptance difficulties met diagnostic criteria for a depressive or anxiety disorder (chi(2) = 8.67; P < .01). Nonacceptors were younger (t = 4.13; P < .000), had more than high school education (chi(2) = 4.69; P < .05), and had smaller social networks (t = 2.53; P < .05) than Acceptors. Of the Nonacceptors, 42% described their experience as one of "moderate" to "extreme" suffering compared with 24.1% of Acceptors (chi(2) = 5.28; P < .05). More than one third (37.5%) of Nonacceptors reported feeling hopeless compared with 8.6% who had no difficulty accepting (chi(2) = 24.76; P < .000). Qualitatively, participants described active and passive coping strategies that helped them accept what was happening to them, as well as barriers that made it difficult to come to terms with their current situation.The challenge of coming to terms with a terminal prognosis is a complex interplay between one's basic personality, the availability of social support, and one's spiritual and existential views on life. Nonacceptance appears to be highly associated with feelings of hopelessness, a sense of suffering, depression, and anxiety, along with difficulties in terms of social-relational concerns.
Hepatic glucose sensing is required to preserve β cell glucose competence
Authors: Pascal Seyer, David Vallois, Carole Poitry-Yamate, Frédéric Schütz, Salima Metref, David Tarussio, Pierre Maechler, Bart Staels, Bernard Lanz, Rolf Grueter, Julie Decaris, Scott Turner, Anabela da Costa, Frédéric Preitner, Kaori Minehira, Marc Foretz, Bernard Thorens
Journal: Journal of Clinical Investigation (2013)

Liver glucose metabolism plays a central role in glucose homeostasis and may also regulate feeding and energy expenditure. Here we assessed the impact of glucose transporter 2 (Glut2) gene inactivation in adult mouse liver (LG2KO mice). Loss of Glut2 suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate-responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was initially normal after Glut2 inactivation, but LG2KO mice exhibited progressive impairment of glucose-stimulated insulin secretion even though β cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinated downregulation of cholesterol biosynthesis genes in LG2KO mice that was associated with reduced hepatic cholesterol in fasted mice and reduced bile acids (BAs) in feces, with a similar trend in plasma. We showed that chronic BAs or farnesoid X receptor (FXR) agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from Fxr–/– mice. Collectively, our data show that glucose sensing by the liver controls β cell glucose competence and suggest BAs as a potential mechanistic link.
Hereditary proctalgia fugax and constipation: report of a second family.
Authors: A F Celik, P Katsinelos, N W Read, M I Khan, T C Donnelly
Journal: Gut (1995)

A second family with hereditary proctalgia fugax and internal anal sphincter hypertrophy associated with constipation is described. Anorectal ultrasonography, manometry, and sensory tests were conducted in two symptomatic and one asymptomatic subjects within the same family and further clinical information was obtained from other family members. The inheritance would correspond to an autosomal dominant condition with incomplete penetration, presenting after the second decade of life. Physiological studies showed deep, ultraslow waves and an absence of internal anal sphincter relaxation on rectal distension in the two most severely affected family members, suggesting the possibility of a neuropathic origin. Both of these patients had an abnormally high blood pressure. After treatment with a sustained release formulation of the calcium antagonist, nifedipine, their blood pressure returned to normal, anal tone was reduced, and the frequency and intensity of anal pain was suppressed. These together improved the quality of the patients9 sleep, which had previously been very troubled because of night time attacks of anal pain.
Interindividual Variability of Response to Rituximab: From Biological Origins to Individualized Therapies
Authors: Guillaume Cartron, Ralf Ulrich Trappe, Philippe Solal-Céligny, Michael Hallek
Journal: Clinical Cancer Research (2011)

Rituximab has markedly changed the treatment of B-cell malignancies. Despite its widespread use, however, its precise mode of action and the impact of host- and tumor-related factors on rituximab-activated biological pathways were only recently clarified. Biological mechanisms resulting in complete resistance to rituximab may exist at both the cellular and subcellular level; however, their frequency and their impact on clinical response are unclear. The identification of Fcγ receptor polymorphisms that can influence anti-CD20 antibody activity has resulted in the development of third-generation anti-CD20 antibodies. However, it is also now appreciated that pharmacokinetic variability is a major factor affecting clinical response to anti-CD20 antibodies. The concept of antigenic mass, which takes into account the total tumor load and the expression levels of the target antigen CD20, is able to explain the correlation between rituximab plasma concentrations and treatment responses. Thus, it can be hypothesized that dosing regimens that take this information into account will help to improve response rates.
16-kDa Prolactin Down-Regulates Inducible Nitric Oxide Synthase Expression through Inhibition of the Signal Transducer and Activator of Transcription 1/IFN Regulatory Factor-1 Pathway
Authors: Sok-hyong Lee, Michiya Nishino, Tuhina Mazumdar, Gabriela E. Garcia, Matthew Galfione, Florence L. Lee, Cynthia L. Lee, Albert Liang, Jeri Kim, Lili Feng, N. Tony Eissa, Sue-Hwa Lin, Li-yuan Yu-Lee
Journal: Cancer Research (2005)

Abstract Angiogenesis plays a key role in promoting tumorigenesis and metastasis. Several antiangiogenic factors have been shown to inhibit tumor growth in animal models. Understanding their mechanism of action would allow for better therapeutic application. 16-kDa prolactin (PRL), a NH2-terminal natural breakdown fragment of the intact 23-kDa PRL, exerts potent antiangiogenic and antitumor activities. The signaling mechanism involved in 16-kDa PRL action in endothelial cells remains unclear. One of the actions of 16-kDa PRL is to attenuate the production of nitric oxide (NO) through the inhibition of inducible NO synthase (iNOS) expression in endothelial cells. To delineate the signaling mechanism from 16-kDa PRL, we examined the effect of 16-kDa PRL on interleukin IL-1β–inducible iNOS expression, which is regulated by two parallel pathways, one involving IFN regulatory factor 1 (IRF-1) and the other nuclear factor-κB (NF-κB). Our studies showed that 16-kDa PRL specifically blocked IRF-1 but not NF-κB signaling to the iNOS promoter. We found that IL-1β regulated IRF-1 gene expression through stimulation of p38 mitogen-activated protein kinase (MAPK), which mediated signal transducer and activator of transcription 1 (Stat1) serine phosphorylation and Stat1 nuclear translocation to activate the IRF-1 promoter. 16-kDa PRL effectively inhibited IL-1β–inducible p38 MAPK phosphorylation, resulting in blocking Stat1 serine phosphorylation, its subsequent nuclear translocation and activation of the Stat1 target gene IRF-1. Thus, 16-kDa PRL inhibits the p38 MAPK/Stat1/IRF-1 pathway to attenuate iNOS/NO production in endothelial cells.
B cells, IgE and mechanisms of type I hypersensitivity in eosinophilic oesophagitis
Authors: D. J Mulder, C. J Justinich
Journal: Gut (2009)

The pathogenesis of eosinophilic oesophagitis (EO) is unknown. EO has recently been defined as significantly elevated intraepithelial eosinophils (⩾15 per high-power field) throughout the oesophageal mucosa, coupled with clinical and endoscopic signs of oesophagitis that cannot be attributed to gastro-oesophageal reflux disease (GORD) or other causes.1 2 This inflammatory condition is more likely to occur in atopic individuals and is limited to the oesophagus where Th2 cytokines and mast cells are also abnormally elevated.1 Removal of specific protein or all proteins from the diet may resolve the inflammatory response in some patients.3 Animal models point to antigen exposure in lung or nasal mucosa leading to local inflammation and oesophagitis.4 EO may indeed be the manifestation of an oesophageal hypersensitivity response to food or environmental antigens, but since a systemic response is not present, local mucosal immune events may be important in this disease.

Patients with EO have increased numbers of cells required for local immunoglobulin E (IgE) antibody production. Lucendo et al used sensitive immunohistochemical evaluation to quantify B cells (CD20+);5 however, very few intraepithelial B cells were detected in oesophagitis (EO and GORD), and the numbers did not reach statistical significance.

Mucosal mast cells are also increased in the oesophagus in EO, and these cells stain positively for IgE.5 6 7 …
Characterization of the Recurrent 8p11-12 Amplicon Identifies PPAPDC1B, a Phosphatase Protein, as a New Therapeutic Target in Breast Cancer
Authors: Isabelle Bernard-Pierrot, Nadège Gruel, Nicolas Stransky, Anne Vincent-Salomon, Fabien Reyal, Virginie Raynal, Céline Vallot, Gaëlle Pierron, François Radvanyi, Olivier Delattre
Journal: Cancer Research (2008)

Abstract The 8p11-12 chromosome region is one of the regions most frequently amplified in breast carcinoma (10–15% of cases). Several genes within this region have been identified as candidate oncogenes, as they are both amplified and overexpressed. However, very few studies have explored the role of these genes in cell transformation, with the aim of identifying valuable therapeutic targets. An analysis of comparative genomic hybridization array and expression profiling data for a series of 152 ductal breast carcinomas and 21 cell lines identified five genes (LSM1, BAG4, DDHD2, PPAPDC1B, and WHSC1L1) within the amplified region as consistently overexpressed due to an increased gene copy number. The use of small interfering RNA to knock down the expression of each of these genes showed the major role played by two genes, PPAPDC1B and WHSC1L1, in regulating the survival and transformation of two different cell lines harboring the 8p amplicon. The role of these two genes in cell survival and cell transformation was also confirmed by long-term knockdown expression studies using short hairpin RNAs. The potential of PPAPDC1B, which encodes a transmembrane phosphatase, as a therapeutic target was further shown by the strong inhibition of growth of breast tumor xenografts displaying 8p11-12 amplification induced by the silencing of PPAPDC1B. The oncogenic properties of PPAPDC1B were further shown by its ability to transform NIH-3T3 fibroblasts, inducing their anchorage-independent growth. Finally, microarray experiments on PPAPDC1B knockdown indicated that this gene interfered with multiple cell signaling pathways, including the Janus-activated kinase-signal transducer and activator of transcription, mitogen-activated protein kinase, and protein kinase C pathways. PPAPDC1B may also potentiate the estrogen receptor pathway by down-regulating DUSP22. [Cancer Res 2008;68(17):7165–75]
Asthma self-management skills and the use of asthma education during pregnancy
Authors: V. E. Murphy, P. G. Gibson, P. I. Talbot, C. G. Kessell, V. L. Clifton
Journal: European Respiratory Journal (2005)

During pregnancy, patients with asthma are at risk of poor outcomes, particularly when asthma is poorly controlled. The aim of this study was to determine the level of asthma self-management skills and knowledge among pregnant subjects and describe the implementation of an asthma education programme delivered in an antenatal clinic setting. Pregnant subjects with asthma were assessed by an asthma educator at 20 (n = 211) and 33 weeks gestation (n = 149). Lung function, symptoms, medication use, adherence, knowledge and inhaler technique were assessed. They were asked whether they had a written asthma action plan, or performed peak flow monitoring. Asthma was classified as mild, moderate or severe. At the first visit with the asthma educator, 40% of females reported nonadherence to inhaled corticosteroids, inhaler technique was assessed as inadequate in 16% and 42% had inadequate medication knowledge. Peak flow monitoring was performed by 3% and 15% had a written action plan. There were significant improvements in all aspects of asthma self-management following education. In females with severe asthma, night symptoms and reliever medication use significantly decreased after education. In conclusion, during pregnancy, patients with asthma have poor asthma knowledge and skills, and may benefit from self-management education as part of their obstetric care.
Plantar Tissue Thickness Is Related to Peak Plantar Pressure in the High-Risk Diabetic Foot
Authors: Frag Abouaesha, Carine H.M. van Schie, Gareth D. Griffths, Robert J. Young, Andrew J.M. Boulton
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate the relationship among plantar foot pressure, plantar subcutaneous tissue thickness, severity of neuropathy (vibration perception threshold [VPT]), callus, and BMI in a large group of neuropathic diabetic patients at risk of foot ulceration. RESEARCH DESIGN AND METHODS—A total of 157 diabetic neuropathic patients (VPT &amp;gt;25 V) without either peripheral vascular or ulcer history were studied. Plantar foot pressure and plantar tissue thickness were measured at each metatarsal head (MTH) using an optical pedobarograph and an ultrasound scanning platform, respectively. RESULTS—A significant association was observed between peak plantar pressure and plantar tissue thickness at all MTHs (−0.26 &amp;lt; r &amp;lt; −0.61, P &amp;lt; 0.0001), with the least pronounced association at the first MTH. In addition, the pressure time integral was significantly associated with plantar tissue thickness (−0.24 &amp;lt; r &amp;lt; −0.57, P &amp;lt; 0.0001). BMI was significantly related to plantar tissue thickness (0.18 &amp;lt; r &amp;lt; 0.45, P &amp;lt; 0.05), but not to peak forefoot pressures. Subjects with callus had significantly reduced plantar tissue thickness at all MTHs except the first MTH and increased peak pressures at all MTHs (P &amp;lt; 0.001). CONCLUSIONS—This study confirms a strong inverse relationship between plantar tissue thickness and dynamic foot pressure measurements. Long-term follow-up of this patient population will confirm whether reduced plantar tissue thickness predicts the development of diabetic foot ulcers.
Quantitative genomics of starvation stress resistance in Drosophila.
Authors: Susan T Harbison, Sherman Chang, Kim P Kamdar, Trudy FC Mackay
Journal: Genome biology (2005)

Abstract Background A major challenge of modern biology is to understand the networks of interacting genes regulating complex traits, and the subset of these genes that affect naturally occurring quantitative genetic variation. Previously, we used P -element mutagenesis and quantitative trait locus (QTL) mapping in Drosophila to identify candidate genes affecting resistance to starvation stress, and variation in resistance to starvation stress between the Oregon-R (Ore) and 2b strains. Here, we tested the efficacy of whole-genome transcriptional profiling for identifying genes affecting starvation stress resistance. Results We evaluated whole-genome transcript abundance for males and females of Ore, 2b, and four recombinant inbred lines derived from them, under control and starved conditions. There were significant differences in transcript abundance between the sexes for nearly 50% of the genome, while the transcriptional response to starvation stress involved approximately 25% of the genome. Nearly 50% of P -element insertions in 160 genes with altered transcript abundance during starvation stress had mutational effects on starvation tolerance. Approximately 5% of the genome exhibited genetic variation in transcript abundance, which was largely attributable to regulation by unlinked genes. Genes exhibiting variation in transcript abundance among lines did not cluster within starvation resistance QTLs, and none of the candidate genes affecting variation in starvation resistance between Ore and 2b exhibited significant differences in transcript abundance between lines. Conclusions Expression profiling is a powerful method for identifying networks of pleiotropic genes regulating complex traits, but the relationship between variation in transcript abundance among lines used to map QTLs and genes affecting variation in quantitative traits is complicated.