tbuckley/cabot-search huggingface dataset:
Analysis of Transcription Factors Key for Mouse Pancreatic Development Establishes NKX2-2 and MNX1 Mutations as Causes of Neonatal Diabetes in Man
Authors: Sarah E. Flanagan, Elisa De Franco, Hana Lango Allen, Michele Zerah, Majedah M. Abdul-Rasoul, Julie A. Edge, Helen Stewart, Elham Alamiri, Khalid Hussain, Sam Wallis, Liat de Vries, Oscar Rubio-Cabezas, Jayne A.L. Houghton, Emma L. Edghill, Ann-Marie Patch, Sian Ellard, Andrew T. Hattersley
Journal: Cell Metabolism (2014)

Understanding transcriptional regulation of pancreatic development is required to advance current efforts in developing beta cell replacement therapies for patients with diabetes. Current knowledge of key transcriptional regulators has predominantly come from mouse studies, with rare, naturally occurring mutations establishing their relevance in man. This study used a combination of homozygosity analysis and Sanger sequencing in 37 consanguineous patients with permanent neonatal diabetes to search for homozygous mutations in 29 transcription factor genes important for murine pancreatic development. We identified homozygous mutations in 7 different genes in 11 unrelated patients and show that NKX2-2 and MNX1 are etiological genes for neonatal diabetes, thus confirming their key role in development of the human pancreas. The similar phenotype of the patients with recessive mutations and mice with inactivation of a transcription factor gene support there being common steps critical for pancreatic development and validate the use of rodent models for beta cell development.
Plasma lipids and lipoproteins in liver disease.
Authors: N McIntyre
Journal: Gut (1978)

There are many changes in the plasma, lipids, and lipoproteins in patients with liver disease. They have proved difficult to study but our understanding of these changes has increased greatly during recent years. In obstructive jaundice hyperlipidaemia is a fairly constant finding and this appears to be due to the regurgitation of phospholipid from the obstructed biliary tree. The plasma lipids tend to fall with parenchymal liver disease. The composition of the lipoproteins depends on the activity of the plasma enzyme lecithin: cholesterol acyl transferase. When LCAT activity is high the individual lipoprotein fractions are normal. When it is reduced all of the lipoprotein fractions are affected but the pattern found with obstruction is quite different from that found with parenchymal disease. The changes in plasma lipoproteins appear to be associated with change in the lipid composition of cellular membranes and this may have important functional implications.
Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG)
Authors: A. Conconi, G. Martinelli, A. Lopez-Guillermo, P.L. Zinzani, A.J.M. Ferreri, L. Rigacci, L. Devizzi, U. Vitolo, S. Luminari, F. Cavalli, E. Zucca
Journal: Annals of Oncology (2010)
The Three Es of Cancer Immunoediting
Authors: Gavin P. Dunn, Lloyd J. Old, Robert D. Schreiber
Journal: Annual Review of Immunology (2004)

After a century of controversy, the notion that the immune system regulates cancer development is experiencing a new resurgence. An overwhelming amount of data from animal models--together with compelling data from human patients--indicate that a functional cancer immunosurveillance process indeed exists that acts as an extrinsic tumor suppressor. However, it has also become clear that the immune system can facilitate tumor progression, at least in part, by sculpting the immunogenic phenotype of tumors as they develop. The recognition that immunity plays a dual role in the complex interactions between tumors and the host prompted a refinement of the cancer immunosurveillance hypothesis into one termed "cancer immunoediting." In this review, we summarize the history of the cancer immunosurveillance controversy and discuss its resolution and evolution into the three Es of cancer immunoediting--elimination, equilibrium, and escape.
EBUS TBNA with Fast Trak. A cost effective and efficient alternative to ROSE – Is there really a need for ROSE?
Authors: Amir M. Khan, Filiz Oezkan, Dirk Theegarten, Lutz Freitag, Kaid Darwiche
Journal: European Respiratory Journal (2014)

Intro:  Rapid on site cytology- ROSE with EBUS TBNA is thought to increase diagnostic yield eliminate the need for additional bronchoscopic procedures in initial diagnosis of lung cancer. Recently the importance of ROSE & its associated increase costs has been questioned. Currently there are limited reported alternatives to ROSE.   Aims/Objective: The aim of our study is to assess our FAST TRAK times, & to see if it is a suitable alternative to ROSE.   Methods & Material:  A retrospective review of 105 consecutive cases of CP-EBUS TBNA with recorded FAST TRAK times. All patients underwent rigid intubation, jet ventilation & IV GA with muscle relaxants.Samples were taken to the cytologist to have an initial verbal report, followed by a written report. Age & gender, FAST TRAK times, Avg total no. of lymph nodes biopsied, & final diagnosis & complications were recorded for all patients.   Results:  Of the total 105 cases of EBUS TBNA, 92 patients were identified with FAST TRAK times. 12 patients had missing data. Of the 80 patients identified there were 54 men & 26 women with an Avg age of 68.6 years. The avg. total FAST TRAK time was 24mts:37 secs. Avg total no. of lymph node biopsied were 3.3. The overall disease prevalence was 56.2% (45 positive cases, 31 NSCLC, 11 SCLC, 1 case each of lymphoma, sarcoma, & sarcoidosis). The overall FAST TRAK reported specificity was 97.1%, sensitivity was 93.3%, PPV 97.6% & NPV 91.8%. No complications were recorded.   Conclusion:  We conclude that reliable & fast results can be obtained with FAST TRAK with EBUS TBNA. FAST TRAK maybe a cost effective & efficient alternative to ROSE & may play an important role in diagnosis & treatment of lung cancer.
Aortic valve morphology influences regurgitant volume in aortic regurgitation: in vivo evaluation
Authors: P. A Grayburn, E. J Eichhorn, R. C Eberhart, J. B Bedotto, M E. Brickner, A. L Taylor
Journal: Cardiovascular Research (1991)

Journal Article Aortic valve morphology influences regurgitant volume in aortic regurgitation: in vivo evaluation Get access Paul A Grayburn, Paul A Grayburn Search for other works by this author on: Oxford Academic PubMed Google Scholar Eric J Eichhorn, Eric J Eichhorn Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert C Eberhart, Robert C Eberhart Search for other works by this author on: Oxford Academic PubMed Google Scholar John B Bedotto, John B Bedotto Search for other works by this author on: Oxford Academic PubMed Google Scholar M Elizabeth Brickner, M Elizabeth Brickner Search for other works by this author on: Oxford Academic PubMed Google Scholar Anne L Taylor Anne L Taylor Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 1, January 1991, Pages 73–79, https://doi.org/10.1093/cvr/25.1.73 Published: 01 January 1991 Article history Received: 06 June 1990 Accepted: 19 July 1990 Published: 01 January 1991
Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD
Authors: D Singh, J Brooks, G Hagan, A Cahn, B J O'Connor
Journal: Thorax (2008)

The combination of salmeterol and fluticasone propionate (SFC) and tiotropium bromide (TIO) are commonly used treatments in chronic obstructive pulmonary disease (COPD) but there are few data on their effectiveness when used together. We compared the effects of SFC 50/500 microg twice daily in addition to TIO 18 microg once daily with the individual treatments alone.41 patients with COPD participated in a randomised, double blind, double dummy, three way crossover study with 2 week washout periods between treatments. Lung function assessment included plethysmography and spirometry. The primary end point was post-dose specific airways conductance (sGaw) area under the curve (AUC(0-4 h)) on day 14.AUC(0-4 h) sGaw was significantly higher on day 14 after SFC+TIO compared with TIO (22%) or SFC alone (27%) (both p<0.001). SFC+TIO significantly improved trough forced expiratory volume in 1 s compared with TIO alone (212 ml, p<0.001) and SFC alone (110 ml, p = 0.017) on day 14. Inspiratory capacity measurements also showed significant benefits for triple therapy over individual components on day 14. Subjects receiving SFC+TIO had clinically relevant improvements in Transition Dyspnoea Index (TDI) total score of 2.2 compared with TIO alone (p<0.001) (but not SFC alone, 0.7; NS) and used significantly less rescue medication (1.0 occasion less daily than TIO (p<0.001) and 0.6 less than SFC (p = 0.01)).SFC+TIO triple therapy led to greater improvements in bronchodilation compared with TIO and SFC alone. The advantages of triple therapy are observed across a range of physiologically important parameters, including airway conductance and lung volumes. Triple therapy also led to patient related benefits by improving TDI and use of rescue medication.
Chronic obstructive pulmonary disease (COPD) patient experiences of pulmonary rehabilitation (PR): A longitudinal qualitative UK study
Authors: Adam Lewis, Anne Bruton, Maggie Donovan-Hall
Journal: European Respiratory Journal (2012)

Introduction and Background  Attendance at PR in the UK is sub-optimal. Reasons for this have been explored. However, patient experiences have rarely been explored longitudinally through a PR programme regardless of patient participation. Furthermore, limited research has been performed in patient experiences of PR in primary care.  Aims and Objectives  This research aimed to explore COPD patient experiences before and after PR, whether they completed, did not attend, or dropped out of PR.  Method  Fifteen participants were interviewed before and after PR regardless of patient completion. COPD patients were recruited from 2 Primary Care Trusts in the UK. Data were collected during semi-structured interviews using phenomenological research methodology.  Results  Of the 15 participants, 8 completed and 7 did not complete PR. Participants experienced uncertainty with regard to COPD, the care they received, PR, and their comparison with others. Prior to PR, uncertainty manifested itself in participants9 experience of panic and vulnerability. The experience of uncertainty reduced following PR programme completion. Non-completers seemed angry with their care, less able to cope with comorbidities or wished to remain naive regarding COPD.  Conclusion  Patient experiences of PR in primary care have been explored. Uncertainty was experienced by participants prior to PR which reduced following PR completion. Completers appeared better able to cope with comorbidities than non-completers. The importance of social comparison in PR requires further research.
Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study
Authors: Ian Hickie, Tracey Davenport, Denis Wakefield, Ute Vollmer-Conna, Barbara Cameron, Suzanne D Vernon, William C Reeves, Andrew Lloyd
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To delineate the risk factors, symptom patterns, and longitudinal course of prolonged illnesses after a variety of acute infections. <b>Design</b> Prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), <i>Coxiella burnetii</i> (Q fever), or Ross River virus (epidemic polyarthritis). <b>Setting</b> The region surrounding the township of Dubbo in rural Australia, encompassing a 200 km geographical radius and 104 400 residents. <b>Participants</b> 253 patients enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment. <b>Outcome measures</b> Detailed medical, psychiatric, and laboratory evaluations at six months to apply diagnostic criteria for chronic fatigue syndrome. Premorbid and intercurrent illness characteristics recorded to define risk factors for chronic fatigue syndrome. Self reported illness phenotypes compared between infective groups. <b>Results</b> Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness rather than by demographic, psychological, or microbiological factors. <b>Conclusions</b> A relatively uniform post-infective fatigue syndrome persists in a significant minority of patients for six months or more after clinical infection with several different viral and non-viral micro-organisms. Post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to chronic fatigue syndrome.
A New Intellectual Framework for Psychiatry
Authors: Eric R. Kandel
Journal: American Journal of Psychiatry (1998)

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.
E2F1-Regulated MicroRNAs Impair TGFβ-Dependent Cell-Cycle Arrest and Apoptosis in Gastric Cancer
Authors: Fabio Petrocca, Rosa Visone, Mariadele Rapazzotti Onelli, Manisha H. Shah, Milena S. Nicoloso, Ivana de Martino, Dimitrios Iliopoulos, Emanuela Pilozzi, Chang-Gong Liu, Massimo Negrini, Luigi Cavazzini, Stefano Volinia, Hansjuerg Alder, Luigi P. Ruco, Gustavo Baldassarre, Carlo M. Croce, Andrea Vecchione
Journal: Cancer Cell (2008)
Relationships between LDH-A, Lactate, and Metastases in 4T1 Breast Tumors
Authors: Asif Rizwan, Inna Serganova, Raya Khanin, Hazem Karabeber, Xiaohui Ni, Sunitha Thakur, Kristen L. Zakian, Ronald Blasberg, Jason A. Koutcher
Journal: Clinical Cancer Research (2013)

Abstract Purpose: To investigate the relationship between lactate dehydrogenase A (LDH-A) expression, lactate concentration, cell metabolism, and metastases in murine 4T1 breast tumors. Experimental Design: Inhibition of LDH-A expression and protein levels were achieved in a metastatic breast cancer cell line (4T1) using short hairpin RNA (shRNA) technology. The relationship between tumor LDH-A protein levels and lactate concentration (measured by magnetic resonance spectroscopic imaging, MRSI) and metastases was assessed. Results: LDH-A knockdown cells (KD9) showed a significant reduction in LDH-A protein and LDH activity, less acid production, decreased transwell migration and invasion, lower proliferation, reduced glucose consumption and glycolysis, and increase in oxygen consumption, reactive oxygen species (ROS), and cellular ATP levels, compared with control (NC) cells cultured in 25 mmol/L glucose. In vivo studies showed lower lactate levels in KD9, KD5, and KD317 tumors than in NC or 4T1 wild-type tumors (P &amp;lt; 0.01), and a linear relationship between tumor LDH-A protein expression and lactate concentration. Metastases were delayed and primary tumor growth rate decreased. Conclusions: We show for the first time that LDH-A knockdown inhibited the formation of metastases, and was accompanied by in vivo changes in tumor cell metabolism. Lactate MRSI can be used as a surrogate to monitor targeted inhibition of LDH-A in a preclinical setting and provides a noninvasive imaging strategy to monitor LDH-A–targeted therapy. This imaging strategy can be translated to the clinic to identify and monitor patients who are at high risk of developing metastatic disease. Clin Cancer Res; 19(18); 5158–69. ©2013 AACR.
A HER 1-2 Punch: Dual EGFR Targeting Deals Resistance a Deadly Blow
Authors: Don L. Gibbons, Lauren Averett Byers
Journal: Cancer Discovery (2014)

Abstract Summary: Ten years after the approval of erlotinib, EGFR inhibitor resistance remains a major clinical challenge. The translation of afatinib plus cetuximab into the clinic provides a promising new option for the treatment of patients with EGFR-mutated lung cancer. Cancer Discov; 4(9); 991–4. ©2014 AACR. See related article by Janjigian et al., p. 1036
Nuclear and Cytoplasmic Survivin: Molecular Mechanism, Prognostic, and Therapeutic Potential
Authors: Roland H. Stauber, Wolf Mann, Shirley K. Knauer
Journal: Cancer Research (2007)

Abstract Survivin's proposed dual role as an apoptosis inhibitor and a mitotic effector positioned it in the front line of cancer research. Notably, survivin is detected as a cytoplasmic and nuclear protein in cancer patients, which stimulated numerous studies to investigate and to speculate on the functional and prognostic significance of its dynamic localization. Recent evidence shows that the direct interaction of survivin with the nuclear export receptor Crm1 is critically involved in its intracellular localization and cancer-relevant functions. Here, we review our current understanding of the Crm1/survivin interface and discuss its potential prognostic and therapeutic relevance. [Cancer Res 2007;67(13):5999–6002]
Gut goes from strength to strength
Authors: Emad M El-Omar
Journal: Gut (2011)

2011 was an excellent year for the Gut family. Our team of dedicated associate editors, editorial staff, publishers and reviewers ensured that the journal continues to deliver the highest quality clinical science from all corners of the globe. Our impact factor climbed from 9.3 to 10.6, which is a major achievement for our journal. In 2011, we have received a record number of manuscripts allowing us the luxury of selecting the very best for publication. We instituted a maximal drive towards efficiency and boast arguably the most favourable editorial handling times for any major journal. The most crucial marker is the average time to reach decision for reviewed manuscripts, which now stands at 19 days. This means that the overwhelming number of reviewed manuscripts receive a decision in less than 3 weeks. I am very proud of my team for achieving …
TIMs: central regulators of immune responses
Authors: David A. Hafler, Vijay Kuchroo
Journal: The Journal of Experimental Medicine (2008)

Exhaustion of T cell responses during chronic viral infections has been observed in both mouse and man and has been attributed to up-regulation of PD-1 on the surface of exhausted T cells. In patients with chronic human HIV infection, T cell exhaustion leads to opportunistic infections associated with AIDS. However, not all the exhausted T cells express PD-1, suggesting that other molecules may be involved in the phenotype. A new study now demonstrates a central role for T cell immunoglobulin and mucin domain–containing protein-3 (TIM-3) in T cell exhaustion during chronic HIV infection and suggests that TIM-3 may be a novel therapeutic target in chronic viral diseases.
Interleukin-4 in the treatment of AIDS-related Kaposi’s sarcoma
Authors: A. Tulpule, B. Joshi, N. DeGuzman, B.M. Espina, R. Mocharnuk, O. Prakash, D. Templeton, A.M. Levine, P.S. Gill
Journal: Annals of Oncology (1997)
Recommendations for Preparticipation Screening and the Assessment of Cardiovascular Disease in Masters Athletes
Authors: Barry J. Maron, Claudio Gil S. Araújo, Paul D. Thompson, Gerald F. Fletcher, Antonio Bayés de Luna, Jerome L. Fleg, Antonio Pelliccia, Gary J. Balady, Francesco Furlanello, Steven P. Van Camp, Roberto Elosua, Bernard R. Chaitman, Terry L. Bazzarre
Journal: Circulation (2001)
Slcyt, a Newly Identified Sex-Linked Gene, Has Recently Moved onto the X Chromosome in Silene latifolia (Caryophyllaceae)
Authors: V. B. Kaiser, R. Bergero, D. Charlesworth
Journal: Molecular Biology and Evolution (2009)

The sex chromosomes of the plant species Silene latifolia (white campion) are very young (only 5-10 My old), and all 11 X-linked genes so far described have Y-linked homologues. Theory predicts that X chromosomes should accumulate a nonrandom set of genes. However, little is known about the importance of gene movements between the X and the autosomes in plants, or in any very young sex chromosome system. Here, we isolate from cDNA a new gene, Slcyt, on the S. latifolia X, which encodes a cytochrome B protein. We genetically mapped SlCyt and found that it is located approximately 1 cM from the pseudoautosomal region. Genes in this region of the X chromosome have low divergence values from their homologous Y-linked genes, indicating that the X only recently stopped recombining with the Y. Genetic mapping in Silene vulgaris suggests that Slcyt originally belonged to a different linkage group from that of the other S. latifolia X-linked genes. Silene latifolia has no Y-linked homologue of Slcyt, and also no autosomal paralogues seem to exist. Slcyt moved from an autosome to the X very recently, as the Cyt gene is also X linked in Silene dioica, the sister species to S. latifolia, but is probably autosomal in Silene diclinis, implying that a translocation to the X probably occurred after the split between S. diclinis and S. latifolia/S. dioica. Diversity at Slcyt is extremely low (pi(syn) = 0.16%), and we find an excess of high frequency-derived variants and a negative Tajima's D, suggesting that the translocation was driven by selection.
Pulmonary vascular input impedance in the newborn and infant pig
Authors: G. SE, J. RJ, S. G HAWORTH
Journal: Cardiovascular Research (1985)

The input impedance of the main pulmonary artery in 26 pigs aged from 1 h to 2 weeks has been calculated from measurements of pressure and flow. From these data we have derived estimates of the hydraulic power output of the right heart. The impedance spectra were similar in form to those in many other studies and were consistent with the presence of a single reflection site within the lung. The frequency of the (single) minimum decreased steadily with increasing age as did the corresponding zero crossing point on the phase curve. From estimates of propagation velocity the position of this “reflection site” was found to coincide with the position of the lung periphery in each age group. An overall fall in characteristic impedance with increasing age was found to be due to the increasing diameter of the pulmonary artery rather than to changes in its elasticity. The total power output/body weight of the right heart fell from 10.4 to 4.8 mW·kg−1 from birth to 4 weeks of age. During this period the ratio of pulsatile to steady power fell from 0.5 to 0.31. We conclude that this fall is related to a reduction in the effective reflection of pressure and flow waves within the lung due to increasing attenuation and possibly to a reduction in the magnitude of the lumped reflection coefficient itself.