tbuckley/cabot-search huggingface dataset:
RNA-seq in grain unveils fate of neo- and paleopolyploidization events in bread wheat (Triticum aestivum L.)
Authors: Caroline Pont, Florent Murat, Carole Confolent, Sandrine Balzergue, Jérôme Salse
Journal: Genome biology (2011)

Whole genome duplication is a common evolutionary event in plants. Bread wheat (Triticum aestivum L.) is a good model to investigate the impact of paleo- and neoduplications on the organization and function of modern plant genomes. We performed an RNA sequencing-based inference of the grain filling gene network in bread wheat and identified a set of 37,695 non-redundant sequence clusters, which is an unprecedented resolution corresponding to an estimated half of the wheat genome unigene repertoire. Using the Brachypodium distachyon genome as a reference for the Triticeae, we classified gene clusters into orthologous, paralogous, and homoeologous relationships. Based on this wheat gene evolutionary classification, older duplicated copies (dating back 50 to 70 million years) exhibit more than 80% gene loss and expression divergence while recent duplicates (dating back 1.5 to 3 million years) show only 54% gene loss and 36 to 49% expression divergence. We suggest that structural shuffling due to duplicated gene loss is a rapid process, whereas functional shuffling due to neo- and/or subfunctionalization of duplicates is a longer process, and that both shuffling mechanisms drive functional redundancy erosion. We conclude that, as a result of these mechanisms, half the gene duplicates in plants are structurally and functionally altered within 10 million years of evolution, and the diploidization process is completed after 45 to 50 million years following polyploidization.
Endoscopic cyanoacrylate injection versus -blocker for secondary prophylaxis of gastric variceal bleed: a randomised controlled trial
Authors: S. R. Mishra, B. Chander Sharma, A. Kumar, S. K. Sarin
Journal: Gut (2010)

<h3>Background and aims</h3> Bleeding from gastric varices is often severe and difficult to manage. Endoscopic injection of gastric varices with cyanoacrylate is effective in prevention of rebleeding. The efficacy of β-blockers in secondary prophylaxis of gastric variceal bleed has not been well studied. A comparison of the efficacy of β-blocker treatment and cyanoacrylate injection for the prevention of gastric variceal rebleeding was carried out. <h3>Methods</h3> Patients with gastro-oesophageal varices type 2 (GOV2) with eradicated oesophageal varices or isolated gastric varices type 1 (IGV1) who had bled from gastric varices were randomised to cyanoacrylate injection (n=33) or β-blocker treatment (n=34). Baseline and follow-up upper gastrointestinal endoscopy and hepatic venous pressure gradient (HVPG) measurements were performed. Primary end points were gastric variceal rebleeding or death. <h3>Results</h3> The probability of gastric variceal rebleeding rate in the cyanoacrylate group was significantly lower than in the β-blocker group (15% vs 55%, p=0.004) and the mortality rate was lower (3% vs 25%, p=0.026) during a median follow-up of 26 months. The median baseline and follow-up HVPG in the cyanoacrylate group were 15 (10–23) and 17 (11–24) mm Hg (p=0.001) and for the β-blocker group 14 (11–24) and 13 (8–25) mm Hg (p=0.003). While no patient showed reduction of HVPG in the cyanoacrylate group, in the β-blocker group 12 of 28 (42%) patients were responders, of which 5 (41% of responders) bled. On multivariate analysis, treatment method, portal hypertensive gastropathy and size of the gastric varix &gt;20 mm independently correlated with gastric variceal rebleeding. Gastric variceal rebleeding independently correlated with mortality. <h3>Conclusions</h3> Cyanoacrylate injection is more effective than β-blocker treatment for the prevention of gastric variceal rebleeding and improving survival. <h3>Clinical trial number</h3> NCT00888784.
Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer
Authors: Xiaoxin S Xu, Le Wang, Judith Abrams, Gan Wang
Journal: Journal of Hematology & Oncology (2011)

Abstract Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence ( p &lt; 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer ( p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors.
Conspicuous synovial lymphatic capillaries in juvenile idiopathic arthritis synovitis with rice bodies
Authors: E Rovenska
Journal: Annals of the Rheumatic Diseases (2005)

<h3>Abstract</h3> <h3>Objective</h3> Modeling of the ophthalmologist’s decision-making process for activity detection in neovascular age-related macular degeneration with a multi-task convolutional deep neuronal network which takes intra- and subretinal fluid into account. <h3>Design</h3> A cohort study to evaluate the multi-task deep learning model for activity detection. <h3>Participants</h3> <i>n</i> = 70 patients (46 female, 24 male) attended the University Eye Hospital Tübingen between 21.2.2018 and 27.6.2018. 3762 optical coherence tomography B-scans (right eye: 2011, left eye: 1751) were acquired from them with Heidelberg Spectralis, Heidelberg, Germany. <h3>Methods</h3> B-scans were graded by a retina specialist and an ophthalmology resident, and then used to develop a multi-task deep learning model to concurrently predict disease activity in neovascular age-related macular degeneration along with the presence of sub- and intraretinal fluid. <h3>Main outcome measures</h3> Performance metrics compared to single-task networks, visualization of the representation driving the DNN-based decisions using t-distributed stochastic neighbor embedding and analysis of the model’s decisions via clinically validated saliency mapping techniques. <h3>Results</h3> The multi-task model surpassed single-task networks in accuracy for activity detection. Visualizations via t-distributed stochastic neighbor embedding and saliency maps highlighted that the network’s decisions for activity of neovascular age-related macular degeneration were based on the presence of sub- and intraretinal fluids, the optical coherence tomography characteristics used for treatment decision in clinical routine. <h3>Conclusion</h3> Multi-task learning increases the performance of neuronal networks for predicting disease activity, while providing clinicians with an easily accessible decision control, which resembles human reasoning.
Designing Dose-Escalation Trials With Late-Onset Toxicities Using the Time-to-Event Continual Reassessment Method
Authors: Daniel Normolle, Theodore Lawrence
Journal: Journal of Clinical Oncology (2006)

The standard design for phase I trials of combined chemotherapy and radiation, which enters either three or six patients per dose level, has little statistical basis and is subject to opening and closing because of delayed toxicities that disrupt patient accrual. We compared the operating characteristics of this standard design and the time-to-event continual reassessment method (TITE-CRM) for dose-escalation trials of combination chemotherapy and radiation.The operating characteristics were determined by Monte Carlo simulation of 60,000 phase I trials.Compared with the standard trial design, in studies with delayed toxicity (ie, where four or more patients are expected to enter onto the study during a single previously enrolled patient's observation for toxicity), TITE-CRM trials are significantly shorter when toxicity observation times are long, treat more patients at or above the maximum-tolerated dose, identify the maximum-tolerated dose (MTD) more accurately, and provide phase II information, but do not expose patients to significant additional risk. Estimation precision and overdose control of TITE-CRM increase as the design assumptions more closely resemble the true state of nature, but are reduced if, for instance, the toxicity of treatment has been grossly underestimated.Compared with the standard design, if there is any prior knowledge concerning the toxicity profile of a treatment, TITE-CRM can leverage it to produce more accurate estimates of the MTD and does not expose patients to significant excess risk, but requires timely communication between clinical investigators, data managers, and study statisticians.
OUR OBSTETRIC AND GYNECOLOGIC RESPONSIBILITIES
Authors: GEORGE GRAY WARD
Journal: JAMA (1926)

The specialty of obstetrics and gynecology—it will be noted that I speak of "the specialty," not the "specialties"—is composed of two parts, which are so related and interwoven that they cannot be divorced without disadvantage to both. This specialty comprises the study of the physiology and pathology of the reproductive system of woman, and as such should be considered in toto. As one of the most important sections of this great association representing one of the fundamental departments of medicine, we must appreciate the responsibilities which rest on us when we realize that obstetrics is the general practitioner's specialty, and that with the possible exception of pediatrics, there is no one of the special departments of our profession which concerns him so greatly and which touches so vitally the welfare of the community. What may be said here is broadcast to the general medical public and is rightfully regarded as
Biatrial Activation in Isthmus-Dependent Atrial Flutter
Authors: Luz-Maria Rodriguez, Carl Timmermans, Ashish Nabar, Leonard Hofstra, Hein J.J. Wellens
Journal: Circulation (2001)

The aim of this study was to determine the biatrial activation pattern in isthmus-dependent atrial flutter (AFL) to understand the functional interatrial connections and the activation pattern of the left atrium (LA).Biatrial activation was performed, using an electroanatomic mapping system, in 10 patients undergoing right atrial isthmus ablation for counterclockwise (n=7) or clockwise (n=3) AFL. The AFL circuit was peritricuspid and propagated slowly (0.5+/-0.2 m/s) through the isthmus. LA was activated by two wave fronts, with discrete breakthroughs in the superior, mid, or inferior atrial septum. The activation of LA overlapped 50+/-16% of the AFL cycle length. In counterclockwise AFL, at least one breakthrough was located in the inferior atrial septum. LA activation began immediately after the exit of the flutter wave from the isthmus and was directed inferosuperiorly in all patients, being synchronous with the atrial septal activation. The septal breakthroughs in patients with clockwise AFL were variably located. The direction of LA activation was superoinferior in 2 and inferosuperior in 1 patient.The circuit of isthmus-dependent AFL was entirely in the right atrium. LA activation was a bystander and followed trans-septal conduction across the inferior coronary sinus-LA connection, Bachmann's bundle, and/or fossa ovalis.
Influence of a preventive training program on the lower limbs kinematics and vertical jump height of male volleyball athletes
Authors: G Leporace, L Metsavaht, J Praxedes, G Pereira, S Pinto, D Chagas, F Chame, L A Batista
Journal: British Journal of Sports Medicine (2011)

Background The effectiveness of preventive training programs (PTP) aiming at changing the biomechanical behaviour related to anterior cruciate ligament injuries is subject to pre-existing risk. However, these assumptions are based on studies in females. Moreover, it is unclear what influence this training has on performance of young male athletes. Objective To examine the influence of a PTP on changes in kinematics during landings and in maximum vertical jump height (VJH) in males. Design 6 weeks prospective exercise intervention. Setting Young male volleyball athletes. Participants 15 male volleyball athletes (13±0.7 years, 1.70±0.12 m, 60±12 kg). Interventions PTP consisting of plyometric, balance and core stability exercises three times per week for 6 weeks. Bilateral vertical jumps with double leg (DL) and single leg (SL) landings were performed to measure the effects of training. Main outcome measurements Kinematics of knee and hip before and after training and VJH attained during both tasks after training. The hypothesis was that the PTP would produce improvements in VJH, but would not generate great changes in biomechanical behaviour. Results The only change revealed for the SL was the longest duration of landing (p=0.0273), while in the DL was the largest angular displacement of the knee (p=0.0371). The training did not significantly alter the VJH in the SL (diff: 2.7 cm, p=0.3054) or DL condition (diff: 3.5 cm, p=0.3635). Conclusion Despite the alterations in the kinematics behaviour, the changes observed are specific for each landing task, which highlights the importance of the principle of specificity. Despite the absence of significant increases in the VJH after training, the absolute differences pre to post training showed an increase consistent with other studies that compared the results with control groups. The present study showed that short time PTP in low-risk populations, although generating little influence on the kinematics, are capable of enhancing performance.
Mood-Congruent Bias in Affective Go/No-Go Performance of Unmedicated Patients With Major Depressive Disorder
Authors: Kristine Erickson, Wayne C Drevets, Luke Clark, Dara M Cannon, Earle E Bain, Carlos A Zarate, Dennis S Charney, Barbara J Sahakian
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Neuropsychological studies of major depressive disorder have described attentional biases for affectively laden stimuli, but these reports were based on measures obtained from medicated subjects. This study investigated performance of unmedicated depressed patients on the Affective Go/No-Go Task. METHOD: Twenty depressed patients and 20 healthy comparison subjects, matched for age, gender, and IQ, performed the Affective Go/No-Go Task as well as tests of attention and memory for nonaffective stimuli. RESULTS: Depressed patients did not differ from healthy subjects on memory task performance, but they made more omission errors on the attention task. On the Affective Go/No-Go Task, depressed patients made more omission errors during happy than sad word blocks and required more time to respond to happy than to sad words. In contrast, healthy subjects required more time to respond to sad than to happy words. CONCLUSIONS: Unmedicated depressed patients do not show a pattern of generalized cognitive impairment but, rather, specifically display an attentional deficit and a mood-congruent bias toward salient stimuli.
CaMKII Negatively Regulates Calcineurin–NFAT Signaling in Cardiac Myocytes
Authors: Scott M. MacDonnell, Jutta Weisser-Thomas, Hajime Kubo, Marie Hanscome, Qinghang Liu, Naser Jaleel, Remus Berretta, Xiongwen Chen, Joan H. Brown, Abdel-Karim Sabri, Jeffery D. Molkentin, Steven R. Houser
Journal: Circulation Research (2009)

Pathological cardiac myocyte hypertrophy is thought to be induced by the persistent increases in intracellular Ca(2+) needed to maintain cardiac function when systolic wall stress is increased. Hypertrophic Ca(2+) binds to calmodulin (CaM) and activates the phosphatase calcineurin (Cn) and CaM kinase (CaMK)II. Cn dephosphorylates cytoplasmic NFAT (nuclear factor of activated T cells), inducing its translocation to the nucleus where it activates antiapoptotic and hypertrophic target genes. Cytoplasmic CaMKII regulates Ca(2+) handling proteins but whether or not it is directly involved in hypertrophic and survival signaling is not known.This study explored the hypothesis that cytoplasmic CaMKII reduces NFAT nuclear translocation by inhibiting the phosphatase activity of Cn.Green fluorescent protein-tagged NFATc3 was used to determine the cellular location of NFAT in cultured neonatal rat ventricular myocytes (NRVMs) and adult feline ventricular myocytes. Constitutively active (CaMKII-CA) or dominant negative (CaMKII-DN) mutants of cytoplasmic targeted CaMKII(deltac) were used to activate and inhibit cytoplasmic CaMKII activity. In NRVM CaMKII-DN (48.5+/-3%, P<0.01 versus control) increased, whereas CaMKII-CA decreased (5.9+/-1%, P<0.01 versus control) NFAT nuclear translocation (Control: 12.3+/-1%). Cn inhibitors were used to show that these effects were caused by modulation of Cn activity. Increasing Ca(2+) increased Cn-dependent NFAT translocation (to 71.7+/-7%, P<0.01) and CaMKII-CA reduced this effect (to 17.6+/-4%). CaMKII-CA increased TUNEL and caspase-3 activity (P<0.05). CaMKII directly phosphorylated Cn at Ser197 in CaMKII-CA infected NRVMs and in hypertrophied feline hearts.These data show that activation of cytoplasmic CaMKII inhibits NFAT nuclear translocation by phosphorylation and subsequent inhibition of Cn.
Function of cAMP response element modulator in a murine asthma model
Authors: Eva Verjans, Kathleen Reiss, Norbert Wagner, Stefan Uhlig, Klaus Tenbrock, Christian Martin
Journal: European Respiratory Journal (2011)

Introduction:  Several isoforms of the cAMP response element modulator (CREM) act as transcriptional repressors or activators binding to the cAMP response element of different promoters. In contact dermatitis we previously demonstrated the importance of CREM for antigen presenting cell-dependent and independent T cell function and termination of T cellular immune response. In this study we investigated the role of CREM in murine ovalbumin (OVA)-induced airway inflammation.   Method:  Male wild type (WT) and CREM-knockout animals (CREM-KO) were sensitized i.p. with 10μg OVA in aluminum hydroxide solution (day 0, 14 and 21) and with aerosol (1% OVA on day 28 and 29). On day 35 bronchial responses to nebulized acetylcholine (0.001-1mg) were examined using the flexiVent system (SCIREQ, Montreal, Canada). Inflammatory responses were evaluated by cell counts, cytokine- and IgE measurements in bronchoalveloar lavage (BAL) and serum. Changes in lung tissue were investigated by histology and calculation of the wet/dry-ratio.   Results:  CREM-KO mice showed an increase in airway responsiveness by elevation in central airway (177%) and tissue resistance (214%) compared to WT (100%). In addition, higher numbers of eosinophils and lymphocytes as well as upregulated Th2 cytokines were found in the BAL of CREM-KO mice. Lung histology indicated increased pulmonary cell infiltration, stronger mucus production and goblet cell hyperplasia.   Conclusion:  CREM deficiency drives Th2 immune response and influences airway tone as well as mucus production. Our findings suggest that the presence of CREM at least partially protects from the development of asthmatic disease by immunological and non-immunological mechanisms.
Systemic and Pulmonary Vascular Dysfunction in Children Conceived by Assisted Reproductive Technologies
Authors: Urs Scherrer, Stefano F. Rimoldi, Emrush Rexhaj, Thomas Stuber, Hervé Duplain, Sophie Garcin, Stefano F. de Marchi, Pascal Nicod, Marc Germond, Yves Allemann, Claudio Sartori
Journal: Circulation (2012)

Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring.We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7 ± 1.6% versus 8.6 ± 1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally.Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself.URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.
Anxiety caused by a short-life hypnotic.
Authors: K Morgan, I Oswald
Journal: BMJ (1982)

A comprehensive understanding of the changes in gene expression in cell types involved in idiopathic pulmonary fibrosis (IPF) will shed light on the mechanisms underlying the loss of alveolar epithelial cells, and development of honeycomb cysts and fibroblastic foci. We sought to understand changes in IPF lung cell transcriptomes and gain insight into innate immune aspects of pathogenesis. We investigated IPF pathogenesis using single cell RNA-sequencing of fresh lung explants, comparing human IPF fibrotic lower lobes reflecting late disease, upper lobes reflecting early disease and normal lungs. IPF lower lobes showed increased fibroblasts, and basal, ciliated, goblet and club cells, but decreased alveolar epithelial cells, and marked alterations in inflammatory cells. We found three discrete macrophage subpopulations in normal and fibrotic lungs, one expressing monocyte markers, one highly expressing <i>FABP4</i> and <i>INHBA</i> (FABP4<sup>hi</sup>), and one highly expressing <i>SPP1</i> and <i>MERTK</i> (SPP1<sup>hi</sup>). SPP1<sup>hi</sup> macrophages in fibrotic lower lobes showed highly upregulated <i>SPP1</i> and <i>MERTK</i> expression. Low-level local proliferation of SPP1<sup>hi</sup> macrophages in normal lungs was strikingly increased in IPF lungs. Co-localisation and causal modelling supported the role for these highly proliferative SPP1<sup>hi</sup> macrophages in activation of IPF myofibroblasts in lung fibrosis. These data suggest SPP1<sup>hi</sup> macrophages contribute importantly to lung fibrosis in IPF, and that therapeutic strategies targeting MERTK and macrophage proliferation may show promise for treatment of this disease.