tbuckley/cabot-search huggingface dataset:
3D Mathematical modeling of glioblastoma suggests that transdifferentiated vascular endothelial cells promote resistance to current standard-of-care therapy.
Authors: Daniela Annenelie Bota, Huaming Yan, Monica Romero-López, Lesli Benitez, Kaijun Di, Hermann Frieboes, Christopher C.W. Hughes, John S Lowengrub
Journal: Journal of Clinical Oncology (2017)

e13535 Background: Glioblastoma (GBM), the most aggressive brain tumor in human patients, is highly heterogeneous and intensively vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and by promoting resistance to therapy. Recently, crosstalk between GSCs and vascular endothelial cells that line capillaries has been shown to considerably promote GSC self-renewal and tumor progression. GSCs have been shown to also transdifferentiate into bona-fide vascular endothelial cells (GEC). GECs inherit mutations present in GSCs and are resistant to traditional anti-angiogenic therapies. Methods: We develop a multispecies mathematical model to investigate the 3D spatiotemporal dynamics of vascularized GBM progression and response to cancer therapies. Results: The model predicts GSCs drive invasive fingering and that GECs spontaneously form a network within the hypoxic core, consistent with published experimental findings. We demonstrate that standard-of-care treatments using DNA-targeted therapy (radiation/chemo) together with anti-angiogenic therapies reduce GBM tumor sizes but increase invasiveness. Anti-GEC treatments block the GEC support of GSCs and reduce tumor sizes but can lead to increased invasiveness. Anti-GSC therapies that promote differentiation or disturb the stem cell niche effectively reduce tumor invasiveness and sizes, but are ultimately limited in reducing tumor sizes because GECs can maintain GSCs. Anti-GEC therapies are required to remove the tumor completely. Conclusions: Our results suggest that a combinatorial regimen targeting the vasculature, GSCs and GECs, using drugs already approved by the FDA, can reduce both tumor sizes and invasiveness and could lead to tumor eradication without recurrence when the treatment is stopped.
Dame Fortune Smiled. The Doctor's Story.
Journal: JAMA (1896)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Chicago
Journal: JAMA (1964)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 3958: Multi-Reg: An integrative parallel approach to uncover drivers of cancer
Authors: Uri David Akavia, Carla Danussi, Felix Sanchez-Garcia, Antonio Iavarone, Dana Pe'er
Journal: Cancer Research (2012)

Abstract Tumor samples harbor a vast number of genomic alterations of various kinds, and it is difficult to distinguish driver alterations that contribute to oncogenesis from passenger alterations. Most computational methods identify driver genes by focusing on the most frequent copy number alterations. Previous work in our lab has led to the development of CONEXIC, a Bayesian algorithm that identifies candidate driver genes in cancer and links them to gene expression signatures they govern by integrating copy number and gene expression (Akavia et al, Cell, 2010). This algorithm was applied to data from melanoma cell lines, where it correctly identified known drivers, such as MITF and KLF6, and connected them to their known targets. In addition, it predicted novel tumor dependencies not previously implicated in melanoma, which were validated experimentally. Drivers may act concurrently, where not only the strongest one is important. For example, either PTEN deletion or AKT activation can lead to a similar expression signature and phenotype. Therefore, we developed a new algorithm, based on the same principles as CONEXIC, with multiple improvements. The new algorithm - Multi-Reg - is capable of detecting multiple candidate regulators that can all act in parallel to regulate an expression signature, and is also capable of integrating mutations in addition to copy number and gene expression data. We applied Multi-Reg to glioblastoma data from The Cancer Genome Atlas (TCGA). This data includes copy number, gene expression and mutations for hundreds of primary tumor samples. Multi-Reg has identified putative drivers that were missed by CONEXIC, such as the known genes PDGFRA and NF1, in addition to EGFR &amp; ERB2 (identified by CONEXIC). Additionally, since Multi-Reg candidate drivers act in parallel, we can group them by shared targets. For example, EGFR &amp; ERRB2 induce the same genes, which represent the Mesenchymal subtype of glibolastoma. These same genes are repressed by PDGFRA &amp; NF1. This matches the known behavior of glioblastoma subtypes, where EGFR &amp; PDGFRA characterize the Mesenchymal and Proneural subtypes, respectively. Thus, our results correctly identify known drivers of glioblastoma. Additionally, Multi-Reg results identified RHPN2 as a novel oncogenic factor controlling a gene expression signature related to adhesion. Validation has shown that while RHPN2 has no effect on cell proliferation it induces invasiveness in glioblastoma cell lines. This shows that Multi-Reg cannot only discover drivers, but can link them to the oncogenic phenomena they controls, and suggest the appropriate biological validation for it. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3958. doi:1538-7445.AM2012-3958
SportsMedUpdate
Authors: Martin P Schwellnus
Journal: British Journal of Sports Medicine (2010)

In an animal model of an anterior cruciate ligament (ACL) injury, the application of a collagen-platelet composite (CPC) at the time of ACL reconstruction improved structural properties of the graft and reduced early antero-posterior knee laxity at 15 weeks after surgery. 1. Fleming BC, 2. Spindler KP, 3. Palmer MP, 4. et al . Am J Sports Med 2009;37:1554–63. [OpenUrl][1][Abstract/FREE Full Text][2] ### Background The outcome of ACL reconstruction is variable, and many patients have increased joint laxity postoperatively. ### Research question/s Does the placement of a CPC around the graft at the time of ACL reconstruction decrease postoperative knee laxity and improve the structural properties of the graft? ### Methodology Animal material: Thirteen immature pigs that underwent unilateral ACL reconstruction with a bone–patellar tendon–bone allograft following ACL resection. Experimental procedure: The animals were randomly assigned to a standard allograft (CON=6) or an allograft where a CPC was placed around the allograft (CPC=7). Animals were killed after 15 weeks and assessed clinically: AP laxity, structural properties (yield load, maximum load to failure, stiffness) and qualitative histology. Measures of outcome: Yield load, maximum load, stiffness (all as a percentage of reconstructed to intact side), histology. ### Main finding/s ### Conclusion/s In an animal model of an ACL injury, the application of a CPC at the time of … [1]: {openurl}?query=rft.jtitle%253DAm%2BJ%2BSports%2BMed%26rft_id%253Dinfo%253Adoi%252F10.1177%252F0363546509332257%26rft_id%253Dinfo%253Apmid%252F19336614%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=amjsports&resid=37/8/1554&atom=%2Fbjsports%2F44%2F13%2F987.atom
Septic thrombophlebitis. A surgical disorder
Authors: A. M. Munster
Journal: JAMA (1974)

The presence of signs of systemic sepsis, positive blood cultures, and signs of local inflammation over a cannulated vein that fail to respond rapidly to removal of the cannula and appropriate antibiotic therapy should lead to a suspected diagnosis of septic thrombophlebitis. Surgical exploration and, if the diagnosis is proven, interruption or resection of such a vein should be undertaken to avoid potentially life-threatening complications. (<i>JAMA</i>230:1010-1011, 1974)
United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results
Journal: BMJ (1988)

From 1979 to 1985, 2435 patients thought to have had a transient ischaemic attack or minor ischaemic stroke were allocated at random to receive long term blind treatment with either aspirin 600 mg twice daily (n=815), aspirin 300 mg once daily (806), or placebo (814). Treatment continued with about 85% compliance until September 1986 (mean four years). The odds of suffering one or more of four categories of event—namely, non-fatal myocardial infarction, non-fatal major stroke, vascular death, or non-vascular death—were 18% less in the two groups allocated to receive aspirin than in the group allocated to receive placebo (2p=0·01). The more relevant but less frequent composite event of disabling stroke or vascular death was reduced by only 7%; this reduction was not significantly different from zero, but nor was it significantly different from a 25% reduction. There was no definite difference between responses to the 300 mg and 1200 mg daily doses, except that the lower dose was significantly less gastrotoxic.
Treatment of Candida sepsis and Cryptococcus meningitis with 5-fluorocytosine. A new antifungal agent
Authors: D. Tassel
Journal: JAMA (1968)

The two patients whom we treated for systemic fungus infections with 5-fluorocytosine, an antifungal agent effective in experimental animal infection with Candida and cryptococci, had a satisfactory clinical response in association with therapy. One patient with Candida sepsis received 5-fluorocytosine for 21 days in a dose ranging from 2 to 4 gm daily. The other patient, with cryptococcal meningitis recurring after amphotericin B treatment, received 5-fluorocytosine in a dose of 2.25 to 9 gm daily for 50 days. There was little evidence of drug toxicity. The new agent deserves controlled clinical evaluation in systemic fungus infections.
HCV genotype in interferon non-responders treated for over one year . Central Blood Bank and West Penn Hospital, Pittsburgh, PA
Journal: Hepatology (1995)

Waddlia chondrophila is a strict intracellular microorganism belonging to the order Chlamydiales that has been isolated twice from aborted bovine fetuses, once in USA and once in Germany. This bacterium is now considered as an abortigenic agent in cattle. However, no information is available regarding the presence of this bacterium in Africa. Given the low sensitivity of cell culture to recover such an obligate intracellular bacterium, molecular-based diagnostic approaches are warranted. This report describes the development of a quantitative SYBR Green real-time PCR assay targeting the recA gene of W. chondrophila. Analytical sensitivity was 10 copies of control plasmid DNA per reaction. No cross-amplification was observed when testing pathogens that can cause abortion in cattle. The PCR exhibited a good intra-run and inter-run reproducibility. This real-time PCR was then applied to 150 vaginal swabs taken from Tunisian cows that have aborted. Twelve samples revealed to be Waddlia positive, suggesting a possible role of this bacterium in this setting. This new real-time PCR assay represents a diagnostic tool that may be used to further study the prevalence of Waddlia infection.
Managing mild hypertension.
Journal: BMJ (1976)

Managing mild hypertensionHypertension is a condition in which real therapeutic advances have been made in the past 30 years.Both the ravages of malignant hypertension and the attendant risks of high blood pressure not yet in the accelerated phase have been alleviated by drug treatment.Even though the drugs in use today have drawbacks, treatment is still compatible with a full and long life.But when it comes to mild hypertension many British doctors are still doubtful about the choices open to them, and in this respect British and American views differ.The two Veterans Administration Co-operative Studies on Antihypertensive Agents1 2 in the United States were arguably among the best-conducted trials of treatment in hypertension.
A New Antibacterial Agent for Infections of the Genitourinary Tract
Journal: JAMA (1965)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 4549: Macrophage-epithelial metabolic crosstalk impairs chemotherapy in pancreatic cancer
Authors: Christopher J. Halbrook, Corbin Pontious, Ilya Kovalenko, Laura Lapienyte, Stephan Dreyer, Yaqing Zhang, Barbara Nelson, Hanna Hong, Daivid Chang, Jennifer P. Morton, Marina Pasca di Magliano, Costas A. Lyssiotis
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDA) remains a leading cause of cancer related death, contrasting a relatively low incidence rate. A principle barrier in PDA treatment is the physiology of the tumors, characterized by a densely fibrotic stroma, rich with immune cell infiltration including macrophages. Macrophages are polarized by environmental cues which dictate their function. In PDA, macrophages within the tumor (tumor associated macrophages, or TAMs) are strongly immunosuppressive, inhibiting both infiltration and activation of cytotoxic T-cells. Additionally, TAMs have been shown to drive resistance to chemotherapy, though the mechanism for which remains unclear. Several pathways have been described by which PDA cells recruit and polarize macrophages into TAMs, and the effects that TAMs have on the tumor microenvironment. These pathways have largely focused on signaling proteins, however, metabolic byproducts also influence the behavior of immune cells within the tumor microenvironment. To explore potential metabolic crosstalk, we have profiled the metabolic factors exchanged between PDA cells and TAMs. Among these, we have found that TAMs release metabolites which can regulate the response of PDA cells to chemotherapy. Importantly, this response is consistent across several murine and patient-derived pancreatic cancer cell lines, and this metabolite release appears to be a general property of anti-inflammatory macrophage metabolism. We further validated these findings in vivo, using a combination of pharmacological and genetic models to modulate myeloid cells within the tumor microenvironment. Taken together, these data suggest that further development of interventions which target either PDA-mediated polarization of TAMs or TAM-mediated inhibition of chemotherapy represent opportunities to improve the efficacy of currently available treatment options. Citation Format: Christopher J. Halbrook, Corbin Pontious, Ilya Kovalenko, Laura Lapienyte, Stephan Dreyer, Yaqing Zhang, Barbara Nelson, Hanna Hong, Daivid Chang, Jennifer P. Morton, Marina Pasca di Magliano, Costas A. Lyssiotis. Macrophage-epithelial metabolic crosstalk impairs chemotherapy in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4549.
Screening With Prostate-Specific Antigen: Should We or Shouldn't We?-Reply
Authors: Paul H. Lange
Journal: JAMA (1993)

<h3>In Reply.</h3> —In my Editorial, I stated that if the tradition of a periodic prostate examination is to be continued, it now must include a serum prostate-specific antigen concentration and a digital rectal examination, and that the survival benefit of this examination is not yet proven but should be tested in randomized trials which are about to begin but will take more than 10 years to complete. Nonetheless, I recommended continued advocacy of the periodic prostate examination for now, although not necessarily its logical extension, screening. Dr Herbers chooses to differ; he aligns himself with the school of thought that believes that preventive examinations should include only what is definitely proven beneficial. This strategy is logical and preferable to many thoughtful physicians, especially those who are preoccupied with major preoccupation is cost-benefit ratios. I discussed reasons why a position in favor of the periodic prostatic examination is also logical. Briefly,
THE OMENTUM.
Journal: JAMA (1893)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
AMA Protests Final Rule on Loan Deferment
Journal: JAMA (1994)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Journal of the National Medical Association, New York
Journal: JAMA (1970)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal