tbuckley/cabot-search huggingface dataset:
Pancreatic cancer <i>SLUG</i>ged
Authors: Rachel H. Josselsohn, David A. Tuveson
Journal: The Journal of Experimental Medicine (2020)

In this issue of JEM, Recouvreux et al. (https://doi.org/10.1084/jem.20200388) describe the role of nutrient sensing in the induction of epithelial–mesenchymal transition. Glutamine-deficient pancreatic cancer cells up-regulate classic EMT regulator Slug, providing a link between nutrient stress and metastasis.
Author Correction: Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate
Authors: Brett S. Carver, Jennifer Tran, Anuradha Gopalan, Zhenbang Chen, Safa Shaikh, Arkaitz Carracedo, Andrea Alimonti, Caterina Nardella, Shohreh Varmeh, Peter T. Scardino, Carlos Cordon-Cardo, William Gerald, Pier Paolo Pandolfi
Journal: Nature Genetics (2020)
Does Degarelix Hold Potential for the Treatment of Pedophilic Disorder?—Reply
Authors: Christoffer Rahm, Valdemar Landgren, Stefan Arver
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Nonpharmacologic and Pharmacologic Management of Acute Pain From Non–Low Back, Musculoskeletal Injuries in Adults: A Clinical Guideline From the American College of Physicians and American Academy of Family Physicians
Authors: Amir Qaseem, Robert M. McLean, David O'Gurek, Pelin Batur, Kenneth Lin, Devan L. Kansagara
Journal: Annals of Internal Medicine (2020)

Description: The American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) developed this guideline to provide clinical recommendations on nonpharmacologic and pharmacologic management of acute pain from non–low back, musculoskeletal injuries in adults in the outpatient setting. The guidance is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. This guideline does not address noninvasive treatment of low back pain, which is covered by a separate ACP guideline that has also been endorsed by AAFP. Methods: This guideline is based on a systematic evidence review on the comparative efficacy and safety of nonpharmacologic and pharmacologic management of acute pain from non–low back, musculoskeletal injuries in adults in the outpatient setting and a systematic review on the predictors of prolonged opioid use. We evaluated the following clinical outcomes using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system: pain (at ≤2 hours and at 1 to 7 days), physical function, symptom relief, treatment satisfaction, and adverse events. Target Audience and Patient Population: The target audience is all clinicians, and the target patient population is adults with acute pain from non–low back, musculoskeletal injuries. Recommendation 1: ACP and AAFP recommend that clinicians treat patients with acute pain from non–low back, musculoskeletal injuries with topical nonsteroidal anti-inflammatory drugs (NSAIDs) with or without menthol gel as first-line therapy to reduce or relieve symptoms, including pain; improve physical function; and improve the patient's treatment satisfaction (Grade: strong recommendation; moderate-certainty evidence). Recommendation 2a: ACP and AAFP suggest that clinicians treat patients with acute pain from non–low back, musculoskeletal injuries with oral NSAIDs to reduce or relieve symptoms, including pain, and to improve physical function, or with oral acetaminophen to reduce pain (Grade: conditional recommendation; moderate-certainty evidence). Recommendation 2b: ACP and AAFP suggest that clinicians treat patients with acute pain from non–low back, musculoskeletal injuries with specific acupressure to reduce pain and improve physical function, or with transcutaneous electrical nerve stimulation to reduce pain (Grade: conditional recommendation; low-certainty evidence). Recommendation 3: ACP and AAFP suggest against clinicians treating patients with acute pain from non–low back, musculoskeletal injuries with opioids, including tramadol (Grade: conditional recommendation; low-certainty evidence).
Covid-19: Health worker strikes, limited testing, and clinic closures hamper Zimbabwe’s response
Authors: Ryan Truscott
Journal: BMJ (2020)

Official figures on the impact of covid-19 in Zimbabwe belie a country grappling with health worker strikes, limited testing, and a closure of health facilities.The country had had 141 deaths from covid-19 and 5378 recorded cases as of 20 August, nearly five months after the first fatality on 23 March.The people infected include 480 health workers, said the Ministry of Health.
Survey showed most anaesthetists have no experience of shifts
Authors: T. Pickersgill
Journal: BMJ (1995)

EDITOR,--Peter Mackenzie reports a survey of anaesthetists in training that asked about the new deal.1 This survey does no more than show junior doctors' apathy and misconceptions about the new deal in general and shift systems in particular. Less than a tenth of the respondents were working partial shifts, full shifts, or hybrid rotas, and only a quarter had had experience of them. This calls into question the validity of the opinions that are cited in the …
A randomized phase III trial to determine the efficacy of postoperative antimicrobial prophylaxis in gastric cancer surgery (OGSG0501)
Authors: K. Inoue, H. Imamura, Y. Kimura, K. Fujitani, Y. Miyake, J. Matuyama, M. Tatsumi, T. Shimokawa, Y. Kurokawa, H. Furukawa
Journal: Journal of Clinical Oncology (2009)

e15576 Background: In Japan, antimicrobial prophylaxis (AMP) is typically administered for 3 to 4 days postoperatively in gastric cancer surgery. This far exceeds the recommended 24h or less laid out by the Centers for Disease Control (CDC) guidelines for the prevention of surgical-site infections, after a clean-contaminated operation. Methods: A multicenter randomized phase III trial was designed to evaluate the effect of postoperative AMP in gastric cancer surgery. Patients (pts) were required to have histologically proven gastric cancer which was curable by distal gastrectomy, be classifiable as ASA 1 or 2, and have adequate organ function. Pts were randomized to: (A) perioperative AMP (cefazolin 1g, at &lt;30min before incision, every 3h intraoperative supplements) plus postoperative AMP (cefazolin 1g, twice daily for 2 postoperative days) or (B) perioperative AMP alone. Pts were stratified by institution and ASA. The primary endpoint was the incidence of surgical site infection (SSI). With 171 pts per arm, this study had 80% power to demonstrate non-inferiority with 5% margin of peri-AMP alone and 0.05 1-sided alpha. Results: 355 patients were recruited (A: 179, B: 176) in 7 centers between June 2005 and December 2007. The surgical-site infection rate was 9.0 percent (16 of 178) for peri-/post AMP and 4.5 percent (8 of 176) for peri-AMP alone, with no significant differences (Fisher's exact test: P=0.14, RR=1.98 [95%CI, 0.89–4.44]), but showing a significant non-inferiority (P&lt;0.001). The remote site infection rate was 3.4 percent (6 of 178) for peri-/post AMP and 5.1 percent (9 of 175) for peri-AMP alone, with no significant differences (P=0.44, RR=0.66 [95%CI, 0.25- 1.70]). Conclusions: This multicenter randomized phase III trial confirms that postoperative AMP is unnecessary in patients undergoing distal gastrectomy for gastric cancer. No significant financial relationships to disclose.
Abstract 1457: Cbl, E3 Ubiquitin Ligase, is a Regulator of Focal Adhesion Protein Proteasomal Degradation during Cardiomyocyte Anoikis
Authors: Khadija Rafiq, Rachid Seqqat, Marie Hanscom, Steven R Houser, Abdelkarim Sabri
Journal: Circulation (2007)

Proteasome degradation of ubiquitin-targeted proteins is an important mechanism that negatively controls activated signaling pathways. The proto-oncogene Casitas b-lineage lymphoma (Cbl) is an adaptor protein with an intrinsic E3 ubiquitin ligase activity that targets receptor tyrosine kinase signaling, resulting in their ubiquitination and down-regulation. We have shown previously that neutrophil derived protease cathepsin G (Cat.G) induced focal adhesion (FA) protein degradation and myocyte apoptosis by anoikis. We hypothesized that Cbl is involved in myocyte apoptosis in response to Cat.G through ubiquitination and downregulation of FA proteins. Results : Immunoprecitpitation and western blot studies showed increased Cbl tyrosine phosphorylation in response to Cat.G that was associated with its interaction with FA proteins, FAK and paxillin. This led to an increase in FAK and Paxillin ubiquitination and degradation at 2 hrs after Cat.G addition. Inhibition of the ubiquitin proteasome system, with MG132 or lactacystin, or adenoviral expression of dominant negative mutant Cbl significantly reduced FAK and paxillin degradation. In contrast, adenoviral expression of wild type Cbl enhanced FAK and paxillin ubiquitination and degradation in response to Cat.G. Interestingly, Cbl activation was involved in Cat.G-induced myocyte apoptosis as overexpression of dominant negative Cbl significantly reduced caspase-3 activation and DNA fragmentation induced by Cat.G. Concomitant with these changes in vitro, heart tissue samples from patients with ischemic or dilated cardiomyopathy showed a marked increase in Cbl accumulation and FAK and paxillin degradation compared to heart controls. Conclusion : These studies show that Cbl abundance is increased in human ischemic and dilated cardiomyopathy and that activation of Cbl increases FA protein degradation and myocyte apoptosis. These results indicate that Cbl is a positive regulator of FA protein degradation and myocyte apoptosis and may play an important role in mediating the effect of neutrophil derived proteases during the progression of congestive heart failure.
Dominant atopy risk mutations identified by mouse forward genetic analysis
Authors: Jeffrey A. SoRelle, Zhe Chen, Jianhui Wang, Tao Yue, Jin Huk Choi, Kuan‐wen Wang, Xue Zhong, Sara Hildebrand, Jamie Russell, Lindsay Scott, Darui Xu, Xiaowei Zhan, Chun Hui Bu, Tao Wang, Mihwa Choi, Miao Tang, Sara Ludwig, Xiaoming Zhan, Xiaohong Li, Eva Marie Y. Moresco, Bruce Beutler
Journal: Allergy (2020)

Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice.We screened mice carrying homozygous and heterozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation.Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations.Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.
Abstract 17544: Utilization of Intensive Lipid-Lowering Therapy After an Acute Coronary Syndrome: Insights From the Triton-TIMI 38 Trial
Authors: Dylan L Steen, Amarachi A Umez-Eronini, Elaine B Hoffman, Elliott M Antman, Stephen D Wiviott
Journal: Circulation (2013)

BACKGROUND: Reduction of LDL cholesterol with intensive lipid-lowering therapy (I-LLT) reduces CV ischemic events after an acute coronary syndrome (ACS). Data suggest that despite benefits, I-LLT i...
Discrimination in US Surgical Training Programs—Reply
Authors: Tarik K. Yuce, Karl Y. Bilimoria, Yue-Yung Hu
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Complement C3 and allergic asthma: a cohort study of the general population
Authors: Signe Vedel-Krogh, Katrine L. Rasmussen, Børge G. Nordestgaard, Sune F. Nielsen
Journal: European Respiratory Journal (2020)

Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration is associated with high risks of asthma hospitalisation and exacerbation. We prospectively assessed the risk of asthma hospitalisation in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608 and rs448260 determining levels of complement C3. Risk of asthma exacerbation was further assessed in 2248 individuals with allergic asthma. The multivariable adjusted hazard ratio of asthma hospitalisation was 1.23 (95% CI 1.04–1.45) for individuals in the highest tertile (&gt;1.19 g·L −1 ) of plasma complement C3 compared with those in the lowest tertile (&lt;1.03 g·L −1 ). The C3 rs448260 genotype was associated with risk of asthma hospitalisation with an observed hazard ratio of 1.17 (95% CI 1.06–1.28) for the CC genotype compared with the AA genotype. High plasma complement C3 was associated with high levels of blood eosinophils and IgE (p for trends ≤6×10 −9 ), but only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count (p=3×10 −4 ) and IgE level (p=3×10 −4 ). In allergic asthma, the multivariable adjusted incidence rate ratio for risk of exacerbation was 1.69 (95% CI 1.06–2.72) for individuals in the highest plasma complement C3 tertile (&gt;1.24 g·L −1 ) versus the lowest (&lt;1.06 g·L −1 ). In conclusion, a high concentration of plasma complement C3 was associated with a high risk of asthma hospitalisation in the general population and with a high risk of asthma exacerbation in individuals with allergic asthma. Our findings support a causal role of the complement system in asthma severity.
Measuring outcomes other than safety is feasible
Authors: T Dowswell, J. Thornton, J Hewison, R. Lilford
Journal: BMJ (1996)

Should there be a trial ofhome versus hospital delivery in the United Kingdom?We received a letterfrom Dowswell and colleagues on thefeasibility ofconducting a trial to compare the effects of birth at home and in hospital.We asked a midwife, an epidemiologist, a generalpractitioner, the director ofthe National Childbirth Trust, and an obstetrician for their comments.Measuring outcomes other than safety is feasible
The association of dietary patterns with cognition through the lens of neuroimaging—a Systematic review
Authors: Belina Rodrigues, Evans A. Asamane, Ricardo Magalhães, Nuno Sousa, Janice L. Thompson, Nadine Correia Santos
Journal: Ageing Research Reviews (2020)

Despite the reported benefits of diet on cognition in older adults, randomized controlled trials (RCT) testing the impact of dietary interventions on cognitive scores have yielded less promising results when cognition was assessed via neuropsychological tests. More recently, neuroimaging has been used to identify more subtle brain-related changes associated to cognition. Hence, employing a combination of neuroimaging techniques with neuropsychological tests could clarify this controversy. To determine the effect of diet on cognitive performance, we conducted a systematic review of PubMed and Scopus databases for all studies, on middle-aged and older adults, combining neuroimaging, neuropsychological tests, and data on dietary patterns. The inclusion criteria were met by 14 observational studies and no RCTs. The range of brain measures assessed varied from volumes to white matter integrity, functional connectivity, brain glucose metabolism and beta-amyloid deposition. Given the variability of methods used in assessing cognitive performance, diet and brain correlates, conducting a meta-analysis was not possible. Here the evidence suggests that, in observational studies, dietary patterns may be associated with brain correlates that have been shown to precede cognitive decline. As such, neuroimaging should be included in future RCTs to identify any benefits of diet on brain measures linked with cognitive health.
An inconvenient truth
Authors: J A Hickling
Journal: BMJ (2008)

tackling alcohol misuse Needs in adolescentsParker et al's review of alcohol misuse did not deal with the problems and needs of adolescent drinkers, who often present to emergency departments when drunk. 1 Alcohol misuse is common in this age group and its incidence is rising, at great cost to individuals, families, and wider society.It is significantly associated with risk of suicide, violence, and accidents-the most common causes of death for young people. 2 It is also an important marker of serious social problems, which should be explored with all those who present to health services. 3 Despite this, emergency department doctors often don't screen for alcohol misuse in young people and are poor at recognising it without formalised screening tools.AUDIT and its derivatives can be used in adolescents, although lower cut-off scores than for adults are probably wise.Just asking, "How often do you get drunk?"identifies young people at risk of traumatic injury through drinking, 4 and the Paddington alcohol test identifies "binge" drinkers. 5 Testing blood alcohol levels at presentation is no substitute for formally investigating drinking habits and risk behaviour because young people are drunk at lower blood alcohol concentrations than adults and binge drinking is intermittent.Although it has been reported that young people are more prone than adults to hypoglycaemia when drunk, this is rare.Other pathologies must be considered in intoxicated adolescents with hypoglycaemia, including infection or additional toxic and metabolic insults.
Prognostic Significance of Cardiac Amyloidosis in Patients With Aortic Stenosis
Authors: Fabrizio Ricci, Laura Ceriello, Mohammed Y. Khanji, George Dangas, Chiara Bucciarelli-Ducci, Michele Di Mauro, Artur Fedorowski, Marco Zimarino, Sabina Gallina
Journal: JACC. Cardiovascular imaging (2020)
KRAS Controls Pancreatic Cancer Cell Lipid Metabolism and Invasive Potential through the Lipase HSL
Authors: Cody N. Rozeveld, Katherine M. Johnson, Lizhi Zhang, Gina L. Razidlo
Journal: Cancer Research (2020)

Abstract Oncogene-induced metabolic reprogramming is a hallmark of pancreatic cancer (PDAC), yet the metabolic drivers of metastasis are unclear. In PDAC, obesity and excess fatty acids accelerate tumor growth and increase metastasis. Here, we report that excess lipids, stored in organelles called lipid droplets (LD), are a key resource to fuel the energy-intensive process of metastasis. The oncogene KRAS controlled the storage and utilization of LD through regulation of hormone-sensitive lipase (HSL), which was downregulated in human PDAC. Disruption of the KRAS–HSL axis reduced lipid storage, reprogrammed tumor cell metabolism, and inhibited invasive migration in vitro and metastasis in vivo. Finally, microscopy-based metabolic analysis revealed that migratory cells selectively utilize oxidative metabolism during the process of migration to metabolize stored lipids and fuel invasive migration. Taken together, these results reveal a mechanism that can be targeted to attenuate PDAC metastasis. Significance: KRAS-dependent regulation of HSL biases cells towards lipid storage for subsequent utilization during invasion of pancreatic cancer cells, representing a potential target for therapeutic intervention. See related commentary by Man et al., p. 4886
The Prothrombin 20210 A Allele Is Frequently Coinherited in Young Carriers of the Factor V Arg 506 to Gln Mutation With Venous Thrombophilia
Authors: S. Ehrenforth, G. Ludwig, S. Klinke, M. Krause, I. Scharrer, U. Nowak-Göttl
Journal: Blood (1998)
Paneth Cell-Derived Lysozyme Defines the Composition of Mucolytic Microbiota and the Inflammatory Tone of the Intestine
Authors: Shiyan Yu, Iyshwarya Balasubramanian, Daniel Laubitz, Kevin Tong, Sheila Bandyopadhyay, Xiang Lin, Juan Flores, Rajbir Singh, Yue Liu, Carlos Macazana, Yanlin Zhao, Fabienne Béguet-Crespel, Karuna Patil, Monica T. Midura-Kiela, Daniel Wang, George S. Yap, Ronaldo P. Ferraris, Zhi Wei, Edward M. Bonder, Max M. Häggblom, Lanjing Zhang, Veronique Douard, Michael P. Verzi, Ken Cadwell, Pawel R. Kiela, Nan Gao
Journal: Immunity (2020)