tbuckley/cabot-search huggingface dataset:
Mutual interaction between YAP and CREB promotes tumorigenesis in liver cancer
Authors: Jiayi Wang, Lifang Ma, Wenhao Weng, Yongxia Qiao, Yue Zhang, Jiangtu He, Hongmei Wang, Weifan Xiao, Lanlan Li, Qinghua Chu, Qiuhui Pan, Yongchun Yu, Fenyong Sun
Journal: Hepatology (2013)

Yes-associated protein (YAP), the downstream effecter of the Hippo-signaling pathway as well as cyclic adenosine monophosphate response element-binding protein (CREB), has been linked to hepatocarcinogenesis. However, little is known about whether and how YAP and CREB interact with each other. In this study, we found that YAP-CREB interaction is critical for liver cancer cell survival and maintenance of transformative phenotypes, both in vitro and in vivo . Moreover, both CREB and YAP proteins are highly expressed in a subset of human liver cancer samples and are closely correlated. Mechanistically, CREB promotes YAP transcriptional output through binding to −608/−439, a novel region from the YAP promoter. By contrast, YAP promotes protein stabilization of CREB through interaction with mitogen-activated protein kinase 14 (MAPK14/p38) and beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC). Gain-of-function and loss-of-function studies demonstrated that phosphorylation of CREB by MAPK14/p38 at ser133 ultimately leads to its degradation. Such effects can be enhanced by BTRC through phosphorylation of MAPK14/p38 at Thr180/Tyr182. However, YAP negatively controls phosphorylation of MAPK14/p38 through inhibition of BTRC expression. Conclusion : There is a novel positive autoregulatory feedback loop underlying the interaction between YAP and CREB in liver cancer, suggesting that YAP and CREB form a nexus to integrate the protein kinase A, Hippo/YAP, and MAPK14/p38 pathways in cancer cells and thus may be helpful in the development of effective diagnosis and treatment strategies against liver cancer. (Hepatology 2013;53:1011–1020)
Current knowledge of the aetiology of human tubal ectopic pregnancy
Authors: J. L. V. Shaw, S. K. Dey, H. O. D. Critchley, A. W. Horne
Journal: Human Reproduction Update (2010)

An ectopic pregnancy is a pregnancy which occurs outside of the uterine cavity, and over 98% implant in the Fallopian tube. Tubal ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy. The epidemiological risk factors for tubal ectopic pregnancy are well established and include: tubal damage as a result of surgery or infection (particularly Chlamydia trachomatis), smoking and in vitro fertilization. This review appraises the data to date researching the aetiology of tubal ectopic pregnancy. Scientific literature was searched for studies investigating the underlying aetiology of tubal ectopic pregnancy. Existing data addressing the underlying cause of tubal ectopic pregnancy are mostly descriptive. There are currently few good animal models of tubal ectopic pregnancy. There are limited data explaining the link between risk factors and tubal implantation. Current evidence supports the hypothesis that tubal ectopic pregnancy is caused by a combination of retention of the embryo within the Fallopian tube due to impaired embryo-tubal transport and alterations in the tubal environment allowing early implantation to occur. Future studies are needed that address the functional consequences of infection and smoking on Fallopian tube physiology. A greater understanding of the aetiology of tubal ectopic pregnancy is critical for the development of improved preventative measures, the advancement of diagnostic screening methods and the development of novel treatments.
Monozygotic twinning, cerebral palsy and congenital anomalies
Authors: P.O.D. Pharoah, Y. Dundar
Journal: Human Reproduction Update (2009)

BACKGROUNDThe majority of cases of cerebral palsy (CP) have their pathogenesis during fetal development and are a form of congenital anomaly, the aetiology of which is uncertain. Anomalous development of other organs evident at birth is also a congenital anomaly. A small proportion of these are known to be caused by chromosomal or gene abnormalities, environmental tetratogens and dietary deficiencies. The majority are of unknown aetiology.
Praise for a critical perspective
Authors: David C. Airey, Richard C. Shelton
Journal: Behavioral and Brain Sciences (2006)

The target article skillfully evaluates data on mental disorders in relation to predictions from evolutionary genetic theories of neutral evolution, balancing selection, and polygenic mutation-selection balance, resulting in a negative outlook for the likelihood of success finding genes for mental disorders. Nevertheless, new conceptualizations, methods, and continued interactions across disciplines provide hope.
EAACI/GA<sup>2</sup>LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria
Authors: T. Zuberbier, R. Asero, C. Bindslev‐Jensen, G. Walter Canonica, M. K. Church, A. Giménez‐Arnau, C. E. H. Grattan, A. Kapp, H. F. Merk, B. Rogala, S. Saini, M. Sánchez‐Borges, P. Schmid‐Grendelmeier, H. Schünemann, P. Staubach, G. A. Vena, B. Wedi, M. Maurer
Journal: Allergy (2009)

This guideline, together with its sister guideline on the management of urticaria [Zuberbier T, Asero R, Bindslev‐Jensen C, Canonica GW, Church MK, Giménez‐Arnau AM et al. EAACI/GA²LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 2009; 64 :1427–1443] is the result of a consensus reached during a panel discussion at the 3rd International Consensus Meeting on Urticaria, Urticaria 2008 , a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU‐funded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO). Urticaria is a frequent disease. The life‐time prevalence for any subtype of urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors, and pathomechanisms. In addition, it outlines evidence‐based diagnostic approaches for different subtypes of urticaria. The correct management of urticaria, which is of paramount importance for patients, is very complex and is consequently covered in a separate guideline developed during the same consensus meeting. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).
Illuminating the Base of the Annelid Tree Using Transcriptomics
Authors: Anne Weigert, Conrad Helm, Matthias Meyer, Birgit Nickel, Detlev Arendt, Bernhard Hausdorf, Scott R. Santos, Kenneth M. Halanych, Günter Purschke, Christoph Bleidorn, Torsten H. Struck
Journal: Molecular Biology and Evolution (2014)

Annelida is one of three animal groups possessing segmentation and is central in considerations about the evolution of different character traits. It has even been proposed that the bilaterian ancestor resembled an annelid. However, a robust phylogeny of Annelida, especially with respect to the basal relationships, has been lacking. Our study based on transcriptomic data comprising 68,750–170,497 amino acid sites from 305 to 622 proteins resolves annelid relationships, including Chaetopteridae, Amphinomidae, Sipuncula, Oweniidae, and Magelonidae in the basal part of the tree. Myzostomida, which have been indicated to belong to the basal radiation as well, are now found deeply nested within Annelida as sister group to Errantia in most analyses. On the basis of our reconstruction of a robust annelid phylogeny, we show that the basal branching taxa include a huge variety of life styles such as tube dwelling and deposit feeding, endobenthic and burrowing, tubicolous and filter feeding, and errant and carnivorous forms. Ancestral character state reconstruction suggests that the ancestral annelid possessed a pair of either sensory or grooved palps, bicellular eyes, biramous parapodia bearing simple chaeta, and lacked nuchal organs. Because the oldest fossil of Annelida is reported for Sipuncula (520 Ma), we infer that the early diversification of annelids took place at least in the Lower Cambrian.
ErbB family receptor inhibitors as therapeutic agents in breast cancer: Current status and future clinical perspective
Authors: Ruchi Saxena, Anila Dwivedi
Journal: Medicinal Research Reviews (2010)

Abstract Breast cancer is the most common cancer diagnosed in women and the second most common cause of female cancer‐related deaths, with more than one million new cases diagnosed per year throughout the world. With the recent advances in the knowledge of cellular processes and signaling pathways involved in the pathogenesis of breast cancer, the current focus of researchers and clinicians is to develop novel treatment strategies that can be included in the armamentarium against breast cancer. With the failure of endocrine‐targeted therapy and the development of resistance to existing chemotherapy, the most explored pathway as next generation target for breast cancer therapy has been the epidermal growth factor receptor (EGFR) (ErbB‐1)/herceptin‐2 (HER‐2) (ErbB‐2) pathway. This review focuses on the rationale for targeting members of ErbB receptor family and numerous agents that are in use for inhibiting the pathway. The mechanism of action, preclinical and clinical trial data of the agents that are in use for targeting the EGFR/HER‐2 pathway and the current status, thereof, have been discussed in detail. In addition, the future clinical trial promises these agents hold either as monotherapy or as combination therapy with conventional agents or with other antisignaling agents have been pondered, so as to provide better and more efficacious treatment strategies for breast cancer patients. © 2010 Wiley Periodicals, Inc. Med Res Rev 32:166‐215, 2012
Emergency care for complainants of sexual assault
Authors: A. Williams
Journal: Journal of the Royal Society of Medicine (2005)

Erdheim-Chester diseaseDr Lee and his colleagues (April 2005 JRSM 1 ) describe a case of renal failure in which the radiographic appearance of bone pointed to Erdheim-Chester disease, a histiocytosis.Among the organs affected in this condition they mention pericardium.We think it important to emphasize the frequency with which heart, pericardium and great vessels are affected.Recording 6 new patients with cardiovascular involvement, Haroche et al. 2 have reviewed all 178 reported cases of Erdheim-Chester disease.56% had periaortic fibrosis, 44% pericardial infiltration and/or effusions and 31% myocardial infiltration.Interestingly, 6 patients had a right atrial myxoma.Of the 58 patients with follow-up data, 31% died from cardiovascular complications.
Effect of TGF-beta 1 and TNF-alpha on the plasminogen system of rat proximal tubular epithelial cells.
Authors: J J Kanalas, U Hopfer
Journal: Journal of the American Society of Nephrology (1997)

Rat proximal tubular epithelial cells derived from Wistar-Kyoto and spontaneously hypertensive rats were grown to confluency on semipermeable tissue culture inserts, and the plasminogen system of these cells was analyzed using enzyme assays, Western analysis, zymography, and reverse transcriptase-polymerase chain reaction. The tubular epithelial cells are capable of activating exogenous plasminogen to plasmin by endogenous plasminogen activators. The cells produce tissue-plasminogen activator, urokinase-plasminogen activator, plasminogen activator inhibitor-1, and urokinase-plasminogen activator receptor. These cells also produce the Heymann nephritis autoantigen, gp330 (megalin), and an associated protein of 45 kd (RAP). Incubation with transforming growth factor-beta 1 resulted in a decrease in plasminogen activation, primarily because of an increase in plasminogen activator inhibitor-1 RNA and protein and a decrease in u-PA RNA as noted by quantitative reverse transcriptase-polymerase chain reaction, Western analysis, and zymography. Incubation of these cells with tumor necrosis factor-alpha resulted in an increase in plasminogen activating ability, presumably through an increase in urokinase. Gp330 and the associated 45-kd protein (RAP) RNA were decreased in cells treated with tumor necrosis factor-alpha. The data presented indicates that these transformed proximal tubular epithelial cells may be used to study changes that may occur during Heymann nephritis with respect to the plasminogen system and the autoantigen gp330.
Visual hallucinations in children receiving decongestants.
Authors: R J Sankey, A J Nunn, J A Sills
Journal: BMJ (1984)

Actifed (triprolidine and pseudoephedrine; Wellcome) and Actifed compound linctus (with codeine) are commonly pre- scribed decongestants in hospital and community practice.They are also often bought from pharmacies without prescrip- tion.They are used for their efficacy and because they are believed to be innocuous at the recommended dosage.Side effects are seldom reported and usually occur when inappropriate doses have been taken.We report on three children aged 2'-31 who suffered severe
Pancreatic Cancer Cell Radiation Survival and Prenyltransferase Inhibition: The Role of K-Ras
Authors: Thomas B. Brunner, Keith A. Cengel, Stephen M. Hahn, Junmin Wu, Douglas L. Fraker, W. Gillies McKenna, Eric J. Bernhard
Journal: Cancer Research (2005)

Abstract Activating K-ras mutations are found in ∼90% of pancreatic carcinomas and may contribute to the poor prognosis of these tumors. Because radiotherapy is frequently used in pancreatic cancer treatment, we assessed the contribution of oncogenic K-ras signaling to pancreatic cancer radiosensitivity. Seven human pancreatic carcinoma lines with activated K-ras and two cell lines with wild-type ras were used to examine clonogenic cell survival after Ras inhibition. Ras inhibition was accomplished by small interfering RNA (siRNA) knockdown of K-ras expression and by blocking Ras processing using a panel of prenyltransferase inhibitors of differing specificity for the two prenyltransferases that modify K-Ras. K-ras knockdown by siRNA or inhibition of prenyltransferase activity resulted in radiation sensitization in vitro and in vivo in tumors with oncogenic K-ras mutations. Inhibition of farnesyltransferase alone was sufficient to radiosensitize most K-ras mutant tumors, although K-Ras prenylation was not blocked. These results show that inhibition of activated K-Ras can promote radiation killing of pancreatic carcinoma in a superadditive manner. The finding that farnesyltransferase inhibition alone radiosensitizes tumors with K-ras mutations implies that a farnesyltransferase inhibitor–sensitive protein other than K-Ras may contribute to survival in the context of mutant K-ras. Farnesyltransferase inhibitors could therefore be of use as sensitizers for pancreatic carcinoma radiotherapy.
Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit.
Authors: J J Badimon, L Badimon, V Fuster
Journal: Journal of Clinical Investigation (1990)

The effects of homologous plasma HDL and VHDL fractions on established atherosclerotic lesions were studied in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a 0.5% cholesterol-rich diet for 60 d (group 1). Another group of animals were maintained on the same diet for 90 d (group 2). A third group was also fed the same diet for 90 d but received 50 mg HDL-VHDL protein per wk (isolated from normolipemic rabbit plasma) during the last 30 d (group 3). Aortic atherosclerotic involvement at the completion of the study was 34 +/- 4% in group 1, 38.8 +/- 5% in group 2, and 17.8 +/- 4% in group 3 (P less than 0.005). Aortic lipid deposition was also significantly reduced in group 3 compared with group 1 (studied at only 60 d) and group 2. This is the first in vivo, prospective evidence of the antiatherogenic effect of HDL-VHDL against preexisting atherosclerosis. Our results showed that HDL plasma fractions were able to induce regression of established aortic fatty streaks and lipid deposits. Our results suggest that it may be possible not only to inhibit progression but even to reduce established atherosclerotic lesions by HDL administration.
Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab Combination Therapy in Patients With Richter's Syndrome or Fludarabine-Refractory Chronic Lymphocytic Leukemia
Authors: Apostolia M. Tsimberidou, William G. Wierda, William Plunkett, Razelle Kurzrock, Susan O'Brien, Sijin Wen, Alessandra Ferrajoli, Farhad Ravandi-Kashani, Guillermo Garcia-Manero, Zeev Estrov, Thomas J. Kipps, Jennifer R. Brown, Albert Fiorentino, Susan Lerner, Hagop M. Kantarjian, Michael J. Keating
Journal: Journal of Clinical Oncology (2008)

Richter's syndrome (RS) and fludarabine-refractory chronic lymphocytic leukemia (CLL) are associated with poor clinical outcomes. We conducted a phase I-II trial of oxaliplatin, fludarabine, cytarabine, and rituximab (OFAR) in these diseases.The OFAR regimen consisted of increasing doses of oxaliplatin (17.5, 20, or 25 mg/m(2)/d) on days 1 to 4 (phase I), fludarabine 30 mg/m(2) on days 2 to 3, cytarabine 1 g/m(2) on days 2 to 3, rituximab 375 mg/m(2) on day 3 of cycle 1 and day 1 of subsequent cycles, and pegfilgrastim 6 mg on day 6, every 4 weeks for a maximum of six courses. Dose-limiting toxicity (DLT) was defined as any nonhematologic, treatment-related toxicity >/= grade 3.Fifty patients were treated (20 patients had RS, and 30 had CLL). The highest tolerated oxaliplatin dose was 25 mg/m(2), which was the highest dose tested. DLT was not observed. Pharmacodynamic analyses demonstrated enhanced leukemia cell killing by oxaliplatin in the presence of fludarabine and cytarabine. The overall response rates were 50% in RS and 33% in fludarabine-refractory CLL. The overall response rate in 14 patients with age >/= 70 years was 50%. Responses were achieved in seven (35%) of 20 patients with 17p deletion, two (29%) of seven patients with 11q deletion, all four patients with trisomy 12, and two (40%) of five patients with 13q deletion. The median response duration was 10 months. Toxicities were mainly hematologic; prolonged myelosuppression was not observed.The OFAR regimen is highly active in RS and has activity in fludarabine-refractory patients with CLL. This regimen warrants further investigation in the treatment of these disorders.
A1C for Screening and Diagnosis of Type 2 Diabetes in Routine Clinical Practice
Authors: Zhong X. Lu, Karen Z. Walker, Kerin O'Dea, Ken A. Sikaris, Jonathan E. Shaw
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate A1C for screening and diagnosis of undiagnosed type 2 diabetes defined by oral glucose tolerance testing in clinical and general populations. RESEARCH DESIGN AND METHODS A1C cut offs (≤5.5% to rule out diabetes; ≥7.0% to rule in diabetes) were derived from a clinical group (Melbourne Pathology [MP] group: n = 2,494; undiagnosed diabetes 34.6%) and then evaluated in a population-based sample (AusDiab group: n = 6,015; undiagnosed diabetes 4.6%). RESULTS For diabetes in the MP and AusDiab groups, A1C at 5.5% gave sensitivities of 98.7 and 83.5%, while A1C at 7.0% gave specificities of 98.2 and 100%, respectively. Many (61.9–69.3%) with impaired A1C (5.6–6.9%) in both populations had abnormal glucose status. CONCLUSIONS A1C ≤5.5% and ≥7.0% predicts absence or presence of type 2 diabetes, respectively, while at A1C 6.5–6.9% diabetes is highly probable in clinical and population settings. A high proportion of people with impaired A1C have abnormal glucose status requiring follow-up.
The minimally important difference in the Rhinoconjunctivitis Total Symptom Score in grass-pollen-induced allergic rhinoconjunctivitis
Authors: P. Devillier, O. Chassany, E. Vicaut, O. de Beaumont, B. Robin, J. F. Dreyfus, P. J. Bousquet
Journal: Allergy (2014)

Background The minimally important difference (MID) has been defined as the smallest improvement considered worthwhile by a patient. The MID has not been estimated for the Rhinoconjunctivitis Total Symptom Score (RTSS). Methods In a prospective multicentre study, patients consulting for grass-pollen-induced allergic rhinitis (AR) recorded a 15-point global rating of change scale (GRCS) score and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score on a weekly basis and the individual symptom scores comprising the RTSS on a daily basis over two consecutive weeks. The MID in the RTSS was determined with anchor-based methods (using the GRCS and the RQLQ) and a distribution-based method [based on the RTSS' standard deviation (SD)]. Results The study population comprised 806 patients (253 children, 250 adolescents and 303 adults). During the first week of the study, the mean ± SD RTSSs for these age groups were 6.5 ± 3.3, 6.8 ± 3.4 and 7.0 ± 3.4, respectively. For an improvement of 2 points in the GRCS or 0.5 points in the RQLQ score, the regression analysis yielded MIDs in the RTSS of 1.24 ± 0.17 and 1.12 ± 0.14 in children, 1.33 ± 0.14 and 1.20 ± 0.13 in adolescents and 1.13 ± 0.14 and 0.89 ± 0.12 in adults, respectively. When applying distribution-based methods, the MID ranged from 1.09 to 1.13 (based on 0.33 SDs of the first-week RTSS) and from 1.22 to 1.40 (based on 0.5 SDs of the difference in RTSSs between the first and second weeks). Conclusion The MID in the RTSS was consistently estimated as 1.1–1.3 (and could conceivably be rounded to 1) in patients with grass-pollen-induced AR.
Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells
Authors: Zhihui Zhong, Hristelina Ilieva, Lee Hallagan, Robert Bell, Itender Singh, Nicole Paquette, Meenakshisundaram Thiyagarajan, Rashid Deane, Jose A. Fernandez, Steven Lane, Anna B. Zlokovic, Todd Liu, John H. Griffin, Nienwen Chow, Francis J. Castellino, Konstantin Stojanovic, Don W. Cleveland, Berislav V. Zlokovic
Journal: Journal of Clinical Investigation (2009)

Activated protein C (APC) is a signaling protease with anticoagulant activity. Here, we have used mice expressing a mutation in superoxide dismutase-1 (SOD1) that is linked to amyotrophic lateral sclerosis (ALS) to show that administration of APC or APC analogs with reduced anticoagulant activity after disease onset slows disease progression and extends survival. A proteolytically inactive form of APC with reduced anticoagulant activity provided no benefit. APC crossed the blood–spinal cord barrier in mice via endothelial protein C receptor. When administered after disease onset, APC eliminated leakage of hemoglobin-derived products across the blood–spinal cord barrier and delayed microglial activation. In microvessels, motor neurons, and microglial cells from SOD1-mutant mice and in cultured neuronal cells, APC transcriptionally downregulated SOD1. Inhibition of SOD1 synthesis in neuronal cells by APC required protease-activated receptor–1 (PAR1) and PAR3, which inhibited nuclear transport of the Sp1 transcription factor. Diminished mutant SOD1 synthesis by selective gene excision within endothelial cells did not alter disease progression, which suggests that diminished mutant SOD1 synthesis in other cells, including motor neurons and microglia, caused the APC-mediated slowing of disease. The delayed disease progression in mice after APC administration suggests that this approach may be of benefit to patients with familial, and possibly sporadic, ALS.