tbuckley/cabot-search huggingface dataset:
SSBP1 Suppresses TGFβ-Driven Epithelial-to-Mesenchymal Transition and Metastasis in Triple-Negative Breast Cancer by Regulating Mitochondrial Retrograde Signaling
Authors: Hong-Lin Jiang, He-Fen Sun, Shui-Ping Gao, Liang-Dong Li, Sheng Huang, Xin Hu, Sheng Liu, Jiong Wu, Zhi-Ming Shao, Wei Jin
Journal: Cancer Research (2015)

Triple-negative breast cancer (TNBC) is a highly aggressive tumor subtype lacking effective prognostic indicators or therapeutic targets. Mitochondrial function is dysregulated frequently in cancer cells to allow for adaptation to a harsh tumor microenvironment. Targeting mitochondrial biogenesis and bioenergetics is, therefore, an attractive therapeutic strategy. In this study, we performed quantitative proteomic analyses in human parental and metastatic breast cancer cell lines to identify mitochondrial proteins involved in TNBC metastasis. We found that single-strand DNA-binding protein 1 (SSBP1) was downregulated in highly metastatic breast cancer cells. Moreover, SSBP1 downregulation promoted TNBC cell metastasis in vitro and in vivo. Mechanistically, SSBP1 loss decreased mitochondrial DNA copy number, thereby potentiating calcineurin-mediated mitochondrial retrograde signaling that induced c-Rel/p50 nuclear localization, activated TGFβ promoter activity, and TGFβ-driven epithelial-to-mesenchymal transition. Low SSBP1 expression correlated with tumor progression and poor prognosis in patients. Collectively, our findings identified SSBP1 as a novel metastasis suppressor and elucidated the mechanisms by which dysregulated mitochondrial signaling contributes to metastatic potential, providing potential new prognostic indicators for patients with TNBC.
Health and Economic Impact of Switching from a 4-Valent to a 9-Valent HPV Vaccination Program in the United States
Authors: Marc Brisson, Jean-François Laprise, Harrell W. Chesson, Mélanie Drolet, Talía Malagón, Marie-Claude Boily, Lauri E. Markowitz
Journal: JNCI Journal of the National Cancer Institute (2015)

Randomized clinical trials have shown the 9-valent human papillomavirus (HPV) vaccine to be highly effective against types 31/33/45/52/58 compared with the 4-valent. Evidence on the added health and economic benefit of the 9-valent is required for policy decisions. We compare population-level effectiveness and cost-effectiveness of 9- and 4-valent HPV vaccination in the United States. We used a multitype individual-based transmission-dynamic model of HPV infection and disease (anogenital warts and cervical, anogenital, and oropharyngeal cancers), 3% discount rate, and societal perspective. The model was calibrated to sexual behavior and epidemiologic data from the United States. In our base-case, we assumed 95% vaccine-type efficacy, lifelong protection, and a cost/dose of $145 and $158 for the 4- and 9-valent vaccine, respectively. Predictions are presented using the mean (80% uncertainty interval [UI] = 10th−90th percentiles) of simulations. Under base-case assumptions, the 4-valent gender-neutral vaccination program is estimated to cost $5500 (80% UI = 2400–9400) and $7300 (80% UI = 4300−11 000)/quality-adjusted life-year (QALY) gained with and without cross-protection, respectively. Switching to a 9-valent gender-neutral program is estimated to be cost-saving irrespective of cross-protection assumptions. Finally, the incremental cost/QALY gained of switching to a 9-valent gender-neutral program (vs 9-valent girls/4-valent boys) is estimated to be $140 200 (80% UI = 4200−>1 million) and $31 100 (80% UI = 2100−>1 million) with and without cross-protection, respectively. Results are robust to assumptions about HPV natural history, screening methods, duration of protection, and healthcare costs. Switching to a 9-valent gender-neutral HPV vaccination program is likely to be cost-saving if the additional cost/dose of the 9-valent is less than $13. Giving females the 9-valent vaccine provides the majority of benefits of a gender-neutral strategy.
Wellcome Trust increases investment in fossil fuels despite calls to divest
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

The UK medical research charity the Wellcome Trust has ignored calls to stop investing in fossil fuels and has instead increased its portfolio of shares in coal, oil, and gas during 2015, an analysis has found.

Campaigners have called the trust’s action “ridiculous” and “on the wrong side of history.”

In June this year health professionals were invited to sign an online letter calling for the trust, which has an investment portfolio of £18bn (€25bn; $28bn), to end its investment in fossil fuel companies because of the serious effect that their businesses had on “human and planetary health.”1 2

More than 1000 doctors and other health professionals have now signed the letter, which was coordinated by the health campaigning organisations MedAct and the Climate and Health …
Payments for Debts Associated With Exercise Can Become Higher as We Age and Limit Exercise Capacity⁎⁎Editorials published in the Journal of American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Edward G. Lakatta, Paul D. Chantler
Journal: Journal of the American College of Cardiology (2006)
The microRNA, let-7, significantly impacts the radiation response in Radelegans and mammalian cells
Authors: Imran Babar, Frank Slack, Joanne Weidhaas
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3103 

Purpose/Objectives:

MicroRNAs (miRNAs) are novel global regulatory RNAs originally discovered in C. elegans and found to play a significant role as human cancer loci. MiRNAs are aberrantly expressed in tumors compared to normal tissues and regulate proteins known to be critical for pro-survival pathways. These findings indicate that miRNA misregulation likely plays a role in tumor cell transformation. We hypothesized that miRNAs might play a role in a cancer cell's response to cytotoxic therapy and therefore might be a potential target to impact the radiation response.

Materials/Methods:

We have developed a tissue-model of radiation-induced reproductive cell death in the nematode C. elegans, called Radelegans. Reproductive cell death is the primary mode of death in tissue clonogens, the targets of cytotoxic therapy, responsible for solid tumor eradication. We began by evaluating the impact of the miRNA let-7 on the radiosensitivity phenotype in this system. To validate the significance of let-7 on the radiation response we performed miRNA microarrays post-irradiation as well as evaluated the effect of altering expression levels of let-7 in a well-established cell culture system.

Results:

We have found that the miRNA, let-7, significantly impacts the radiation response in Radelegans, with its loss leading to radioresistance and its overexpression leading to radiosensitivity. This is likely due to its regulation of the RAS oncogene as well as numerous additional downstream targets. We further have found that in mammalian cells all but one of the let-7 homologues is immediately downregulated in response to radiation, implicating this family of miRNAs in the cell's response to radiation. In addition, using a tissue-culture system we have found that altering the levels of let-7 in mammalian cells is a means to alter the radiation response. These findings will be further validated in mouse models.
Abstract 230: Factors Associated with Postarrest Withdrawal of Life-Sustaining Therapy
Authors: Anne V Grossestreuer, David F Gaieski, Benjamin S Abella, Douglas J Wiebe, Jason S Haukoos, Sarah M Perman
Journal: Circulation (2014)

Background: Most successfully resuscitated cardiac arrest patients do not survive to hospital discharge. Many of those have withdrawal of life sustaining therapy (WLST) as a result of a poor neurologic prognosis. Objectives: Determine characteristics of patients who have WLST post-arrest and the differences in their post-arrest care. Methods: We identified comatose post-arrest adult patients from 27 hospitals between 2000-2014. We stratified patients by whether they had WLST and analyzed demographic, arrest, and post-arrest variables. Results: Of 1439 patients analyzed, 558 (39%) patients had WLST. These patients differed in demographic, arrest, and post-arrest characteristics and treatments (Table 1). In multivariate regression analysis, patients who had WLST were more likely to have post-arrest neurology consults (OR 3.5; 95% CI: 2.3-5.3), less likely to go to the cardiac catheterization (OR 0.3; 95% CI: 0.2-0.5) or electrophysiology labs (OR 0.3; 95% CI: 0.1-0.8), and had shorter hospital stays (OR 0.9; 95% CI: 0.8-0.9). When multivariate regression was limited to patient demographics and arrest characteristics, patients with WLST were older (OR 1.01; 95% CI: 1.00-1.02), had longer downtime (OR 1.01, 95% CI: 1.01-1.02), were more likely to be female (OR: 1.5; 95% CI: 1.2-2.0), were less likely to have an initial rhythm of VF/VT (OR 0.5; 95% CI: 0.4-0.7), and were less likely to have a witnessed arrest (OR 0.7; 95% CI: 0.5-0.9). Patients were less likely to have WLST at an academic medical center (OR 0.6, 95% CI: 0.4-1.0, p=0.04). Conclusions: Comatose post-arrest patients who had WLST in the hospital were older, were more likely to have a longer arrest downtime, be female, have an initial non-shockable rhythm, have an unwitnessed arrest, and less likely to be at an academic medical center. They are more likely to have post-arrest neurology consults, less likely to go to the cardiac catheterization or electrophysiology labs, and have a shorter hospital stay.
Suicide Attempts in the US Army—Reply
Authors: Robert J. Ursano, Ronald C. Kessler, Murray B. Stein
Journal: JAMA Psychiatry (2015)

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
Next-generation sequencing analysis of high-quality and high-quantity cell-free circulating DNA prepared from droplet volumes of patient plasma.
Authors: Chen-Hsiung Yeh, Jonathan Spurgin, Andrew Ford, John Athanasuleas, Jennifer McLarty, Michael Mullen
Journal: Journal of Clinical Oncology (2015)

e22008 Background: It is in agreement and the growing belief that “liquid biopsy” can provide a global longitudinal picture of cancer progression beyond the heterogeneity presented in the primary tumor. Cell-free DNA (cfDNA) circulating in the bloodstream could become the unprecedented non-invasive, standard-of-care molecular marker for the treatment and management of cancer. However, cfDNA is highly fragmented and presented at very low concentrations; therefore, its isolation is challenging because of the requirement of large volume input, costs, and labor-intensity. A proprietary cfDNA enrichment process with novel characteristic of ultra-low input (as low as 20 uL of plasma) and high output ( > 300 ng/mL of cfDNA) has been developed and compared to the industry standard. Methods: The performance of our method was evaluated side-by-side with two leading extraction methods based on throughput, sample volume, yield, and cfDNA amplifiablity. The enriched products were further subjected to NGS on the Ion Torrent PGM to detect mutations. Results: Compared to the leading cfDNA extraction methods using different chemistries and workflows, our enrichment approach allows high-yield isolation of cfDNA directly from a small volume of unprocessed plasma, leading to a significant increase in isolation efficiency and > 20-fold recovery. The cfDNA prepared by our proprietary method displayed a high-degree genomic representation as demonstrated by SNP Cytochip array. Further NGS studies on cfDNA from 10 colorectal cancer plasma and 2 spiked samples demonstrated the superiority of our protocol in generating more usable, on-target, high-quality ≥ Q20 sequencing reads, and detecting more mutations over Qiagen kit. Conclusions: A seamless sample-preparation process is critical when analyzing low-quantity cfDNA in high-noise background. Our cfDNA enrichment process is the first non-invasive method that allows accurate NGS genomic analyses directly from droplet volumes of plasma. This protocol can be applied to a broad range of clinical genetic tests with the advantages of minimal sample volume, maximal yield, streamlined workflow with reduced costs and turnaround time.
Geriatric Assessment in Older Patients with Breast Cancer
Authors: Heidi Klepin, Supriya Mohile, Arti Hurria
Journal: Journal of the National Comprehensive Cancer Network (2009)

Most cases of breast cancer are diagnosed in older adults. Older women have an increased risk for breast cancer–specific mortality and are at higher risk for treatment-associated morbidity than younger women. However, they are also less likely to be offered preventive care or adjuvant therapy for this disease. Major gaps in evidence exist regarding the optimal evaluation and treatment of older women with breast cancer because of significant underrepresentation in clinical trials. Chronologic age alone is an inadequate predictor of treatment tolerance and benefit in this heterogeneous population. Multiple issues uniquely associated with aging impact cancer care, including functional impairment, comorbidity, social support, cognitive function, psychological state, and financial stress. Applying geriatric principles and assessment to this older adult population would inform decision making by providing estimates of life expectancy and identifying individuals most vulnerable to morbidity. Ongoing research is seeking to identify which assessment tools can best predict outcomes in this population, and thus guide experts in tailoring treatments to maximize benefits in older adults with breast cancer.
Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology
Authors: Tim Y. Hou, Laurie A. Davidson, Eunjoo Kim, Yang-Yi Fan, Natividad R. Fuentes, Karen Triff, Robert S. Chapkin
Journal: Annual Review of Nutrition (2016)

The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as “carcinogenic to humans” on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer.
Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial<i>(STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study)</i>
Authors: Bruno Fautrel, Thao Pham, Toni Alfaiate, Frédérique Gandjbakhch, Violaine Foltz, Jacques Morel, Emmanuelle Dernis, Philippe Gaudin, Olivier Brocq, Elisabeth Solau-Gervais, Jean-Marie Berthelot, Jean-Charles Balblanc, Xavier Mariette, Florence Tubach
Journal: Annals of the Rheumatic Diseases (2015)

Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission.The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission.The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%).64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression.Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings.ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.
Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes
Authors: Zobair M. Younossi, Aaron B. Koenig, Dinan Abdelatif, Yousef Fazel, Linda Henry, Mark Wymer
Journal: Hepatology (2015)

Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56).As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous. (Hepatology 2016;64:73-84).
Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation
Authors: Nobuhiro Tsukada, Hisaya Akiba, Tetsuji Kobata, Yoshifusa Aizawa, Hideo Yagita, Ko Okumura
Journal: Blood (2000)
Circulating protein synthesis rates reveal skeletal muscle proteome dynamics
Authors: Mahalakshmi Shankaran, Chelsea L. King, Thomas E. Angel, William E. Holmes, Kelvin W. Li, Marc Colangelo, John C. Price, Scott M. Turner, Christopher Bell, Karyn L. Hamilton, Benjamin F. Miller, Marc K. Hellerstein
Journal: Journal of Clinical Investigation (2015)

Here, we have described and validated a strategy for monitoring skeletal muscle protein synthesis rates in rodents and humans over days or weeks from blood samples. We based this approach on label incorporation into proteins that are synthesized specifically in skeletal muscle and escape into the circulation. Heavy water labeling combined with sensitive tandem mass spectrometric analysis allowed integrated synthesis rates of proteins in muscle tissue across the proteome to be measured over several weeks. Fractional synthesis rate (FSR) of plasma creatine kinase M-type (CK-M) and carbonic anhydrase 3 (CA-3) in the blood, more than 90% of which is derived from skeletal muscle, correlated closely with FSR of CK-M, CA-3, and other proteins of various ontologies in skeletal muscle tissue in both rodents and humans. Protein synthesis rates across the muscle proteome generally changed in a coordinate manner in response to a sprint interval exercise training regimen in humans and to denervation or clenbuterol treatment in rodents. FSR of plasma CK-M and CA-3 revealed changes and interindividual differences in muscle tissue proteome dynamics. In human subjects, sprint interval training primarily stimulated synthesis of structural and glycolytic proteins. Together, our results indicate that this approach provides a virtual biopsy, sensitively revealing individualized changes in proteome-wide synthesis rates in skeletal muscle without a muscle biopsy. Accordingly, this approach has potential applications for the diagnosis, management, and treatment of muscle disorders.