tbuckley/cabot-search huggingface dataset:
Apigenin-mediated modulations of PI3K-Akt and MAPK signaling pathways causes growth Inhibition and cell cycle arrest in human prostate cancer cells
Authors: Sanjeev Shukla, Sanjay Gupta
Journal: Cancer Research (2007)

3350  Protein kinases play a critical role in signal transduction pathways regulating cellular proliferation, differentiation and apoptosis. Inhibition of these growth-related kinases might be significant in providing therapeutic modalities against cancer. Development of small molecules protein kinase inhibitors provide a new rational to combat cancer, however, highly selective or specific blocking of only one of the kinases has been associated with limited or sporadic responses during clinical trials. Therefore, agents which could regulate cellular growth by modulating kinases may be developed as effective anticancer agent. Apigenin, a dietary plant flavonoid has shown anti-proliferative and anticancer properties. Potential targets for apigenin include PI3K, Akt, MAPK, CDKs, and CK2. We therefore studied the molecular events of apigenin action in human prostate cancer cells. Treatment of asynchronized androgen-responsive LNCaP and androgen-refractory PC-3 cell lines with apigenin (1-40 μM) causes increase arrest of cells in G0-G1 phase of the cell cycle. Treatment of cells with apigenin decreased both retinoblastoma (Rb) protein phosphorylation at Ser780 and Ser807/811 and total Rb protein in dose- and time- dependent fashion. Apigenin treatment caused an increased phosphorylation of ERK1/2 and JNK1/2. This sustained activation of ERK1/2 and JNK1/2 resulted in decrease in ELK-1 phosphorylation and c-FOS expression thereby inhibiting cell survival. Use of cyclin-dependent kinase inhibitors and MEK1/2 inhibitor induced ERK1/2 phosphorylation albeit at different levels and did not contribute to cell cycle arrest in comparison to apigenin treatment. Despite activation of MAPK pathway, apigenin caused a significant decrease in cyclin D1 protein expression, an effect that occurred simultaneously with the loss of Rb phosphorylation and inhibition of cell cycle progression. The reduced expression of cyclin D1 protein correlated with decrease in protein expression and phosphorylation of p38 and PI3K-Akt, which are regulators of cyclin D1 protein. Interestingly, apigenin caused a marked reduction in cyclin D1, D2 and E and their regulatory partners CDK 2, 4 and 6 which are operative in G0-G1 phase of the cell cycle. This was accompanied by a loss of RNA polymerase II phosphorylation, suggesting the effectiveness of apigenin in inhibiting transcription of these proteins. This provides a possible mechanism by which apigenin can cause modulation in MAPK pathways and inhibition in Akt and Rb protein phosphorylation at multiple sites along with decrease in cyclin D1 causing arrest of cells in the G1→S phase transition. Taken together, this study provides an insight into the molecular mechanism of apigenin in modulating various tyrosine kinases and perturbs cell cycle progression, suggesting its future development and use as anticancer agent in humans.
Association Between Maternal Fluoride Exposure and Child IQ
Authors: Chen Xi Gong, Nicole Ellen James
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Disrupted ER membrane protein complex–mediated topogenesis drives congenital neural crest defects
Authors: Jonathan Marquez, June Criscione, Rebekah M. Charney, Maneeshi S. Prasad, Woong Y. Hwang, Emily K. Mis, Martín I. García-Castro, Mustafa K. Khokha
Journal: Journal of Clinical Investigation (2020)

Multipass membrane proteins have a myriad of functions, including transduction of cell-cell signals, ion transport, and photoreception. Insertion of these proteins into the membrane depends on the endoplasmic reticulum (ER) membrane protein complex (EMC). Recently, birth defects have been observed in patients with variants in the gene encoding a member of this complex, EMC1. Patient phenotypes include congenital heart disease, craniofacial malformations, and neurodevelopmental disease. However, a molecular connection between EMC1 and these birth defects is lacking. Using Xenopus, we identified defects in neural crest cells (NCCs) upon emc1 depletion. We then used unbiased proteomics and discovered a critical role for emc1 in WNT signaling. Consistent with this, readouts of WNT signaling and Frizzled (Fzd) levels were reduced in emc1-depleted embryos, while NCC defects could be rescued with β-catenin. Interestingly, other transmembrane proteins were mislocalized upon emc1 depletion, providing insight into additional patient phenotypes. To translate our findings back to humans, we found that EMC1 was necessary for human NCC development in vitro. Finally, we tested patient variants in our Xenopus model and found the majority to be loss-of-function alleles. Our findings define molecular mechanisms whereby EMC1 dysfunction causes disease phenotypes through dysfunctional multipass membrane protein topogenesis.
Recommendations for Providing Quality Sexually Transmitted Diseases Clinical Services, 2020
Authors: Roxanne Y. Barrow, Faruque Ahmed, Gail A. Bolan, Kimberly A. Workowski
Journal: MMWR Recommendations and Reports (2020)

This report (hereafter referred to as STD QCS) provides CDC recommendations to U.S. health care providers regarding quality clinical services for sexually transmitted diseases (STDs) for primary care and STD specialty care settings. These recommendations complement CDC's Sexually Transmitted Diseases Treatment Guidelines, 2015 (hereafter referred to as the STD Guidelines), a comprehensive, evidence-based reference for prevention, diagnosis, and treatment of STDs. STD QCS differs from the STD Guidelines by specifying operational determinants of quality services in different types of clinical settings, describing on-site treatment and partner services, and indicating when STD-related conditions should be managed through consultation with or referral to a specialist. These recommendations might also help in the development of clinic-level policies (e.g., standing orders, express visits, specimen panels, and reflex testing) that can facilitate implementation of the STD Guidelines. CDC organized the recommendations for STD QCS into eight sections: 1) sexual history and physical examination, 2) prevention, 3) screening, 4) partner services, 5) evaluation of STD-related conditions, 6) laboratory, 7) treatment, and 8) referral to a specialist for complex STD or STD-related conditions.CDC developed the recommendations by synthesizing relevant, evidence-based guidelines and recommendations issued by other experts; reviewing current practice in the United States; soliciting Delphi ratings by subject matter experts on STD care in primary care and STD specialty care settings; discussing the scientific evidence supporting the proposed recommendations at a consultation meeting of experts and institutional stakeholders held November 20, 2015, in Atlanta, Georgia; conducting peer reviews of draft recommendations and supporting evidence; and discussing draft recommendations and supporting evidence during meetings of the CDC/Health Resources and Services Administration Advisory Committee on HIV, Viral Hepatitis, and STD Prevention and Treatment STD Work Group. These recommendations are intended to help health care providers in primary care or STD specialty care settings offer STD services at their clinical settings and to help the persons seeking care live safer, healthier lives by preventing and treating STDs and related complications.
Can vitamin D levels affect your risk of melanoma?
Authors: U.E. Liyanage, M.H. Law, J.H. Barrett, M.M. Iles, S. MacGregor
Journal: British Journal of Dermatology (2020)

Melanoma, the most lethal form of skin cancer. According to Australian cancer database statistics, the incidence (meaning number of cases) of melanoma in 2018 was 14,778 and the number of deaths was 1,684. There is considerable debate in the medical literature (e.g. journals) on the role that vitamin D may play in melanoma risk. Some studies link vitamin D deficiency, meaning lower levels of vitamin D, with an increased risk of a range of different cancers. Studies into melanoma are fraught with difficulties because while higher ultraviolet radiation levels (UVR) from the sun increase the body's vitamin D levels, UVR exposure can also increase the risk of melanoma. In this project, the authors aimed to determine if vitamin D levels can affect melanoma risk. They performed Mendelian randomization (MR), a way of analysing different variants of genes that can be used to determine causality (cause and effect). The study used European ancestry genetic data, together with data linking genetic markers to vitamin D levels. The authors showed that even large predicted changes in vitamin D levels (a 20 nmol/L decrease), only negligibly affected melanoma risk. Whilst some studies have suggested that modifying vitamin D levels may reduce melanoma risk, this study provides no evidence that genetically determined vitamin D is causally associated (linked) with melanoma risk. This summary relates to the study: Is there a causal relationship between vitamin D and melanoma risk? A Mendelian randomization study
Improved Survival With Extracorporeal Cardiopulmonary Resuscitation Despite Progressive Metabolic Derangement Associated With Prolonged Resuscitation
Authors: Jason A. Bartos, Brian Grunau, Claire Carlson, Sue Duval, Adrian Ripeckyj, Rajat Kalra, Ganesh Raveendran, Ranjit John, Marc Conterato, Ralph J. Frascone, Alexander Trembley, Tom P. Aufderheide, Demetris Yannopoulos
Journal: Circulation (2020)

The likelihood of neurologically favorable survival declines with prolonged resuscitation. However, the ability of extracorporeal cardiopulmonary resuscitation (ECPR) to modulate this decline is unknown. Our aim was to examine the effects of resuscitation duration on survival and metabolic profile in patients who undergo ECPR for refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest.We retrospectively evaluated survival in 160 consecutive adults with refractory ventricular fibrillation/ventricular tachycardia out-of-hospital cardiac arrest treated with the University of Minnesota (UMN) ECPR protocol (transport with ongoing cardiopulmonary resuscitation [CPR] to the cardiac catheterization laboratory for ECPR) compared with 654 adults who had received standard CPR in the amiodarone arm of the ALPS trial (Amiodarone, Lidocaine, or Placebo Study). We evaluated the metabolic changes and rate of survival in relation to duration of CPR in UMN-ECPR patients.Neurologically favorable survival was significantly higher in UMN-ECPR patients versus ALPS patients (33% versus 23%; P=0.01) overall. The mean duration of CPR was also significantly longer for UMN-ECPR patients versus ALPS patients (60 minutes versus 35 minutes; P<0.001). Analysis of the effect of CPR duration on neurologically favorable survival demonstrated significantly higher neurologically favorable survival for UMN-ECPR patients compared with ALPS patients at each CPR duration interval <60 minutes; however, longer CPR duration was associated with a progressive decline in neurologically favorable survival in both groups. All UMN-ECPR patients with 20 to 29 minutes of CPR (8 of 8) survived with neurologically favorable status compared with 24% (24 of 102) of ALPS patients with the same duration of CPR. There were no neurologically favorable survivors in the ALPS cohort with CPR ≥40 minutes, whereas neurologically favorable survival was 25% (9 of 36) for UMN-ECPR patients with 50 to 59 minutes of CPR and 19% with ≥60 minutes of CPR. Relative risk of mortality or poor neurological function was significantly reduced in UMN-ECPR patients with CPR duration ≥60 minutes. Significant metabolic changes included decline in pH, increased lactic acid and arterial partial pressure of carbon dioxide, and thickened left ventricular wall with prolonged professional CPR.ECPR was associated with improved neurologically favorable survival at all CPR durations <60 minutes despite severe progressive metabolic derangement. However, CPR duration remains a critical determinate of survival.
Tumor characteristics and treatment (trt) patterns following disease recurrence in gastrointestinal stromal tumor (GIST) patients (pts) who received adjuvant imatinib (IM) as primary trt: A retrospective chart extract-based approach.
Authors: Geneviève Gauthier, Medha Sasane, Annie Guérin, Frances Annelies Schwiep, Christopher Hunt Keir, Matt Magestro, Eric Q. Wu, Anthony Paul Conley
Journal: Journal of Clinical Oncology (2013)

e21514 Background: Though adjuvant IM trt is associated with a reduced risk of GIST recurrence, little is known about tumor characteristics and trt patterns at the time of recurrence. The study describes tumor characteristics and trt patterns in pts with recurrent disease after completing treatment with adjuvant imatinib for resectable disease. Methods: An online tool was developed to collect clinical information for 410 pts treated with adjuvant IM for ≥6 months for primary resectable KIT+GIST, discontinued, had a recurrence following discontiuation, and then restarted IM or initiated sunitinib. Data were collected at two specific time points: primary diagnosis and disease recurrence. Results: Pts were, on average, 60.2 years of age, mostly male, and Caucasian. At primary diagnosis, most pts had intermediate/high risk profiles based on Fletcher score. Pts received adjuvant IM for a median of 360 days for primary GIST before discontinuing trt; the first recurrence occurred 281 days after IM discontinuation. At the time of recurrence, most patients had a multifocal (62%), unresectable (45%) or metastatic (40%) tumor and did not have a surgery (80%). Most patients had intermediate/high risk profiles at recurrence. 23% of pts had a recurrence outside the gastrointestinal (GI) system (39% of pts initiated on sunitinib; 19% of those who restarted IM, p=&lt;.001). 93% had recurrence inside the GI (85% of pts initiated on sunitinib; 95% of those who restarted IM; p=.002).The majoritiy of patients were restarted on IM (with surgery:74% without surgery:77%), with a 400mg dose (with surgery:79% without surgery: 63%). Conclusions: At the time of recurrence, most pts had high risk, unresectable/mestatstic multifocal tumor and re-started IM 400mg. [Table: see text]
Past medical history (PMH) in oncology: Which is the best source, the doctor or the patient? A prospective double blind study.
Authors: Monica Montiel, Carlos Fernando Garcia Gerardi, Ernesto Gil Deza, Eduardo L. Morgenfeld, Gaston Martin Reinas, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2013)

e17539 Background: The usual way in which Argentinean doctors (Dr) register a patient’s (Pt) PMH in the Clinical record (CR) is the anamnesis. It has proved to be quite heterogeneous. At the Instituto Oncológico Henry Moore (IOHM) a PMH form was designed to be filled out by the Pt before the interview. The objective of this paper is to compare and contrast the amount and quality of PMH information registered by Pt and Dr through a double blind study in order to assess the usefulness of the PMH form. Methods: Between Dec 13th and Dec 20th, 2012, data was collected from all new Pt assisted at the IOHM. In the case that the PMH registered a severe pre-existing condition that was not present in the CR, the physician in charge was made aware of this fact. By indication of the IRB, an interim analysis had to be carried out a week after the study had begun. If the quantity of information proved to be 25% greater or the quality proved to be 5% greater in favor of Pt, the study should be finished. Results: A total of 73 P were included in a prospective double blind study. Sex: 42 males/31 females; Mean age 58.7y (range 21-88); Tumor diagnosis: urological 24, gynecological 17, gastrointestinal 11, other 21. PMH forms filled out by Pt showed 878 pre-existing medical conditions: mean 12 (range 1-35); the CR filled out by Dr showed 453 pre-existing medical conditions: mean 6 (range 0-21). In 3 CR, Dr registered data that Pt had not. A total of 67 CR (92%) showed less data than the PMH, Mean 6 (range 1-21). Quality analysis demonstrated that 15% of the unregistered data could be relevant in medical decisions. Due to the overwhelming differences between registries, the study was finished and the Pt´s PMH form was included as part of the CR at the IOHM. Conclusions: 1) The quality and quantity of data acquired by using the PMH form far exceeds that of the data registered by doctors in CR. 2) In 15% of all the cases, this information could be relevant in medical decision making. 3) In only 3 cases, doctors registered more data than patients using the PMH form. 4) A form filled out by the patient and reviewed by the doctors could be a significant tool on preventing malpractice.
Transfusion strategies in non-bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine
Authors: Alexander P. Vlaar, Simon Oczkowski, Sanne de Bruin, Marije Wijnberge, Massimo Antonelli, Cecile Aubron, Philippe Aries, Jacques Duranteau, Nicole P. Juffermans, Jens Meier, Gavin J. Murphy, Riccardo Abbasciano, Marcella Muller, Akshay Shah, Anders Perner, Sofie Rygaard, Timothy S. Walsh, Gordon Guyatt, J. C. Dionne, Maurizio Cecconi
Journal: Intensive Care Medicine (2020)
Stress Testing and Risk Prediction in People With Known Symptomatic Multivessel Coronary Artery Disease
Authors: Sebhat Erqou, Cullen Soares, Wen-Chih Wu
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Pangenomic Classification of Pituitary Neuroendocrine Tumors
Authors: Mario Neou, Chiara Villa, Roberta Armignacco, Anne Jouinot, Marie-Laure Raffin-Sanson, Amandine Septier, Franck Letourneur, Ségolène Diry, Marc Diedisheim, Brigitte Izac, Cassandra Gaspar, Karine Perlemoine, Victoria Verjus, Michèle Bernier, Anne Boulin, Jean-François Emile, Xavier Bertagna, Florence Jaffrezic, Denis Laloe, Bertrand Baussart, Jérôme Bertherat, Stephan Gaillard, Guillaume Assié
Journal: Cancer Cell (2019)
Abstract 14858: CRD-733, a Novel Phosphodiesterase 9 Inhibitor, Reverses Pressure Overload-Induced Cardiac Hypertrophy in Mice
Authors: Daniel A Richards, Mark J Aronovitz, Richard H Karas, Daniel M Bloomfield, Michael E Mendelsohn, Robert M Blanton
Journal: Circulation (2018)

Introduction: Myocardial cyclic GMP (cGMP) elevation and activation of cGMP-dependent protein kinase (PKG) have been shown to attenuate pathological cardiac hypertrophy and remodeling. Expression o...
Comparing Percutaneous Coronary Intervention Access Sites for ST-Elevation Myocardial Infarction—Are Radial and Femoral Access Equally Safe?
Authors: Ranya N. Sweis
Journal: JAMA Cardiology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal