tbuckley/cabot-search huggingface dataset:
Abstract 863: Transfer learning for gene expression prediction with deep neural networks
Authors: Emre Arslan, Kunal Rai
Journal: Cancer Research (2020)

Abstract Conventional machine learning approaches try to solve problems in an isolated manner whereas humans utilize previous experiences between similar tasks. Transfer learning (TL) imitates this efficient approach and transfer knowledge that was learned in a source/domain task and employ that knowledge to improve learning in a related target task. We propose a deep convolutional neural networks (CNNs) structure to predict gene expression via epigenomic signals around the TSS. This structure allows to transfer knowledge that we learn in a cancer type to another one. We use H3K4me1, H3K4me3, H3K27Ac, H3K4me3, H3K27me3 histone modification marks for breast, lung, colon, glioma, ovarian, melanoma, and pancreas cancers as input and predict gene expression for each sample. Our model with transfer learning has improved prediction rates for various cancer types compared to the other established methods like Support Vector Machine (SVM), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost). We also compared performances for different percentages of data with previously proposed DeepChrome algorithm. We checked normal datasets contribution for cancer samples as well. For this purpose, we train our model with normal samples from Roadmap Epigenome Project (REMC) repository first and passed the learned parameters to cancer datasets. It seems normal samples do not have common epigenomic patterns with cancer ones as we do not see any prediction of gene expression improvement. To our knowledge, there is no proposed transfer learning method in epigenetic data analysis. The proposed transfer learning mechanism will lead to avoid generating a significant amount of epigenomic data for different cancer types and will accelerate epigenomic studies in different cancer types. Citation Format: Emre Arslan, Kunal Rai. Transfer learning for gene expression prediction with deep neural networks [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 863.
Factors Associated With Risk of Recurrent Transient Global Amnesia
Authors: Ken A. Morris, Alejandro A. Rabinstein, Nathan P. Young
Journal: JAMA Neurology (2020)

<h3>Importance</h3> Transient global amnesia (TGA) is usually considered a benign event with a low recurrence rate. However, recurrence rates vary considerably among studies and there are no known risk factors for TGA. <h3>Objective</h3> To examine risk factors for the recurrence of TGA. <h3>Design, Setting, and Participants</h3> This retrospective cohort study involved medical record review of patients with isolated or recurrent TGA presenting to the Mayo Clinic in Rochester, Minnesota, between August 1, 1992, and February 28, 2018. A total of 1491 cases were reviewed and 1044 met diagnostic inclusion criteria for TGA, with the remainder excluded owing to indeterminate or alternate diagnoses or limited information available in the medical record. <h3>Exposures</h3> Single vs recurrent episodes of TGA. <h3>Main Outcomes and Measures</h3> Demographics, precipitating factors, migraine history, imaging and electrodiagnostic findings, and family history of TGA were collected. The main outcome measure was TGA recurrence. <h3>Results</h3> Of 1044 included patients, 575 (55.1%) were male, and the mean (SD) age at inclusion was 75.0 (11.5) years. A total of 901 patients (86.3%) had a single episode of TGA and 143 (13.7%) had recurrent episodes of TGA. The 2 groups were similar in age at inclusion, sex, identifiable triggers, and duration of anterograde amnesia. The number of recurrences ranged from 1 to 9, with 137 individuals (95.8%) having 3 or fewer recurrences. The mean (SD) age at first episode of TGA was 65.2 (10.0) years for individuals with a single episode vs 58.8 (10.3) years for those with recurrent episodes (<i>P</i> &lt; .001). There was a personal history of migraine in 180 individuals (20.0%) with a single episode of TGA and 52 individuals (36.4%) with recurrent episodes of TGA (<i>P</i> &lt; .001), and a family history of migraine in 167 individuals (18.5%) with a single episode of TGA and 44 individuals (30.8%) with recurrent episodes of TGA (<i>P</i> = .001). There were no electroencephalographic findings associated with increased risk of TGA recurrence. Acute and subacute temporal lobe abnormalities on results of magnetic resonance imaging were seen rarely and did not require intervention. A family history of TGA was identified in 12 individuals (1.3%) with a single episode of TGA and 4 individuals (2.8%) with recurrent episodes of TGA. <h3>Conclusions and Relevance</h3> This study suggests that, in this large cohort of patients with TGA, recurrent TGA was associated with earlier age at the time of first TGA episode and higher prevalence of both personal and family history of migraine compared with isolated cases. These results can be used to counsel patients about risks of recurrence and may have implications for the understanding of TGA pathophysiology.
Balancing the Public Health Costs of Psychosis vs Mass Incarceration With the Legalization of Cannabis
Authors: Jordan E. DeVylder, Vijay A. Mittal, Jason Schiffman
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
Predictors of Death Within Six Months of Cardiac Resynchronisation Therapy
Authors: D.P. Leong, U. Hoke, J.J. Bax, V. Delgado, D. Auger, K.H. Yiu, E. Abate, J. Thijssen, M.J. Schalij, N.A. Marsan
Journal: Circulation (2011)
PML-RARα interaction with TRIB3 impedes PPARγ/RXR function and triggers dyslipidemia in acute promyelocytic leukemia
Authors: Ke Li, Feng Wang, Zhao-Na Yang, Bing Cui, Ping-Ping Li, Zhen-Yu Li, Zhuo-Wei Hu, Hong-Hu Zhu
Journal: Theranostics (2020)

Although dyslipidemia commonly occurs in patients with acute promyelocytic leukemia (APL) in response to anti-APL therapy, the underlying mechanism and the lipid statuses of patients with newly diagnosed APL remain to be addressed. Methods: We conducted a retrospective study to investigate the lipid profiles of APL patients. PML-RARα transgenic mice and APL cells-transplanted mice were used to assess the effects of APL cells on the blood/liver lipid levels. Subsequently, gene set enrichment analysis, western blot and dual luciferase reporter assay were performed to examine the role and mechanism of PML-RARα and TRIB3 in lipid metabolism regulation in APL patients at pretreatment and after induction therapy. Results: APL patients exhibited a higher prevalence of dyslipidemia before anti-APL therapy based on a retrospective study. Furthermore, APL cells caused secretion of triglycerides, cholesterol, and PCSK9 from hepatocytes and degradation of low-density lipoprotein receptors in hepatocytes, which elevated the lipid levels in APL cell-transplanted mice and Pml-Rarα transgenic mice. Mechanistically, pseudokinase TRIB3 interacted with PML-RARα to inhibit PPARγ activity by interfering with the interaction of PPARγ and RXR and promoting PPARγ degradation. Thus, reduced PPARγ activity in APL cells decreased leptin but increased resistin expression, causing lipid metabolism disorder in hepatocytes and subsequent dyslipidemia in mice. Although arsenic/ATRA therapy degraded PML-RARα and restored PPARγ expression, it exacerbated dyslipidemia in APL patients. The elevated TRIB3 expression in response to arsenic/ATRA therapy suppressed PPARγ activity by disrupting the PPARγ/RXR dimer, which resulted in dyslipidemia in APL patients undergoing therapy. Indeed, the PPAR activator not only enhanced the anti-APL effects of arsenic/ATRA by suppressing TRIB3 expression but also reduced therapy-induced dyslipidemia in APL patients. Conclusion: Our work reveals the critical role of the PML-RARα/PPARγ/TRIB3 axis in the development of dyslipidemia in APL patients, potentially conferring a rationale for combining ATRA/arsenic with the PPAR activator for APL treatment.
THU0025 Serum levels of stromelysin-1 (mmp-3), gelatinase b (mmp-9), timp-1 and timp-2 in histological variants of rheumatoid synovitis
Authors: PA Klimiuk, S Sierakowski, R Latosiewicz, B Cylwik, J Skowronski, J Chwiecko
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid synovitis is a chronic progressive disease with an invasive and tissue destructive infiltrate of lymphocytes, macrophages and synoviocytes. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) produced by these cells play an important role in the remodelling of the articular tissue in rheumatoid arthritis (RA). <h3>Objectives</h3> In the study we investigated whether the histological appearance of the disease could be predicted from the serum concentration of MMPs and their inhibitors. <h3>Methods</h3> The study included tissue and serum samples taken from 37 patients with clinically active RA and 30 with osteoarthritis (OA). Two types of RA were distinguished after morphological analysis of synovial specimens. Twenty two samples presented only diffuse infiltrates of mononuclear cells without any further microanatomical organisation, whereas lymphocytic conglomerates with germinal centre-like structures were found in 15 specimens. Serum concentrations of stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were assessed by means of ELISA method. <h3>Results</h3> The unique serum profiles of MMPs and TIMPs were determined in both histological types of RA synovitis. In comparison with OA patients constituting a control group, there were detected higher serum concentrations of MMP-3 and MMP-9 in RA patients (in both cases p &lt; 0.001). Elevated concentrations of MMPs were found in the serum of RA patients with follicular synovitis than in those with diffuse (p &lt; 0.01 and p &lt; 0.001 respectively). Serum of RA patients presented also elevated levels of TIMP-1 and TIMP-2 in comparison with OA patients (p &lt; 0.001 and p &lt; 0.01 respectively). TIMP-1 dominated in the serum of RA patients with follicular synovitis comparing with those with diffuse (p &lt; 0.05). The serum concentrations of MMPs and TIMP-1 could clearly identify patients with two different histological types of rheumatoid synovitis and with OA. The clinical data analysed in our study implicated that rheumatoid disease in patients with follicular synovitis was more severe than in those with diffuse infiltrates. <h3>Conclusion</h3> The distinct histological appearance of rheumatoid synovitis correlated with serum profile of MMPs or TIMP-1 reflects varied clinical activity of the disease and confirms its heterogeneity. These associations also suggest that patients with different morphological forms of RA might require different treatment regimens.
Abstract A37: PAX8 drives ovarian cancer angiogenesis through interaction with SOX17
Authors: Daniele Chaves-Moreira, Marilyn A. Mitchell, Jessica Rendi, Robbin Nameki, Donita C. Brady, Simone Sidoli, Benjamin Garcia, Patrice J. Morin, Kate Lawrenson, Ronny Drapkin
Journal: Clinical Cancer Research (2020)

Abstract A major problem in the treatment of ovarian cancer is the heterogeneity among ovarian tumors. DNA and RNA sequencing studies have demonstrated both intertumoral and intratumoral genetic variation. Despite efforts to elucidate common signaling pathways among various ovarian cancer subtypes, few have led to meaningful patient stratification or individualized targeted molecular therapies. A theoretical new approach to the treatment of ovarian cancer would be to target the signaling pathways that are essential to the development of the HGSOC progenitor cells, the secretory epithelium of the fallopian tube (FT). PAX8, a transcription factor that identifies and sustains high-grade serous ovarian carcinomas (HGSOC), is also the main regulator of FT development. We investigated whether blocking the ability of PAX8 to influence its gene targets, either by interrupting PAX8 protein-protein interactions or by inhibiting the products of PAX8-driven signaling, has the potential to eliminate the primary growth stimulus for high-grade serous tumors. Herein, we have identified SOX17 as a bona fide PAX8-interacting partner and elucidated their collaborative impact on HGSOC. We observed that PAX8 and SOX17 are master regulators of HGSOC identity, as both were found binding in super-enhancer regions regulating most of the same set of genes. Ontology analysis after PAX8 or SOX17 loss showed alteration in three main pathways: cell cycle, apoptosis, and angiogenesis. Most remarkably, we discovered that PAX8 and SOX17 regulate angiogenesis in vitro and in vivo by suppressing SERPINE1, which enables VEGFR2 signaling pathway. These results broaden our understanding of the roles of PAX8 and SOX17 in the regulation of angiogenesis and suggest novel therapeutic strategies that could overcome ovarian cancer heterogeneity and resistance. Citation Format: Daniele Chaves-Moreira, Marilyn A. Mitchell, Jessica Rendi, Robbin Nameki, Donita C. Brady, Simone Sidoli, Benjamin Garcia, Patrice J. Morin, Kate Lawrenson, Ronny Drapkin. PAX8 drives ovarian cancer angiogenesis through interaction with SOX17 [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A37.
Plantar heel pain: should you consult a general practitioner or a podiatrist?
Authors: Hylton B Menz, Matthew P Cotchett, Glen A Whittaker, Shannon E Munteanu, Karl B Landorf
Journal: British Journal of Sports Medicine (2020)

In British Journal of Sports Medicine , Rasenberg and colleagues1 report the findings of the Soles as Treatment Against Pain in feet (STAP) randomised trial comparing the effectiveness of usual general practitioner (GP) care to referral to a podiatrist for custom insoles or sham insoles in 185 people with plantar heel pain.1 After 12 weeks, the usual GP care group reported less pain during activity compared with the custom insole group (assessed using an 11-point Numerical Rating Scale), although this difference was small (less than one point) and did not meet the minimal clinically important difference for this outcome measure. Secondary outcomes favoured the GP group but were mostly small in magnitude. The authors concluded that referral to a podiatrist for custom insoles does not lead to better outcomes compared with usual GP care, and as such, healthcare providers should be ‘reserved’ in prescribing custom insoles for the treatment of plantar heel pain.

This is a generally well-designed pragmatic trial and the first to be undertaken in a primary care …
Abstract B79: Effect of HIPEC on immune microenvironment in epithelial ovary cancer
Authors: Arshi Rizwan, Mukurdipi Ray
Journal: Clinical Cancer Research (2020)

Abstract Introduction: Women with epithelial ovary cancer with impaired immunity develop life-threatening clinical disease, implying that these patients have some form of altered immune response against disease prognosis. Frequent findings of tumor-associated lymphocytes as well as differential immunologic markers from tumor specimen after surgery for EOC are explicit evidence of immunologic sensitivity to this. Despite several treatment modalities, the majority of these patients will eventually relapse. However, several i.p. therapies have been advocated to command the disease progress. In this context, hyperthermia is one of the effective i.p. therapies to boost the therapeutic efficacy, showing its impact by killing tumor cells as well as inducing an efficient anticancer immune response, therefore providing insight into hyperthermic intraperitoneal chemotherapy (HIPEC)-associated immunotherapy, a new therapeutic treatment for cancer. Rationale: In a vast majority of the cases the disease is confined to the peritoneal cavity for a long time. Even in recurrent cases, disease remains confined to peritoneal cavity only. Intraperitoneal administration of chemotherapy results in high peritoneal to plasma ratios for pick concentration of chemotherapeutic drugs. Mechanisms of immune activation: Surface molecular expression—Heated tumor cells increase the surface expression of MHC class I, making the tumor cells more sensitive to lysis by CD8+T (T cytotoxic) cells. Expression of HSPs—Heated tumor cells release heat shock protein (HSPs), which activate natural killer (NK) cells and antigen-presenting cells (APCs), cross present the antigen to CD8+T cells. Exosome production—Heated tumor cells release exosomes, containing potential antigens, and antigen-presenting cells, cross present the antigen to CD8+ T cells. Direct effect on immune cells, NK cells, CD8+ T cells and dendritic cells (DC), tumor vasculature—Increases the permeability of tumor vasculature. Changed vasculature within the tumor may help immune cell mobilization. Conclusion: HIPEC elicits antitumor immune responses by enabling tumor cells to stimulate the immune system through increased surface expression of MHC class I, release of HSPs, exosomes, directly activating intratumoral immune cells and improving immune-cell trafficking. Note: This abstract was not presented at the conference. Citation Format: Arshi Rizwan, Mukurdipi Ray. Effect of HIPEC on immune microenvironment in epithelial ovary cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B79.
Hepatic Decompensation in Cirrhotic Patients Receiving Antiviral Therapy for Chronic Hepatitis B
Authors: Hye Won Lee, Terry Cheuk-Fung Yip, Yee-Kit Tse, Grace Lai-Hung Wong, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Do Young Kim, Henry Lik-Yuen Chan, Sang Hoon Ahn, Vincent Wai-Sun Wong
Journal: Clinical Gastroenterology and Hepatology (2020)
Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet
Authors: Fernanda Cristofori, Mariaelena Tripaldi, Giusi Lorusso, Flavia Indrio, Vincenzo Rutigliano, Domenico Piscitelli, Stefania Castellaneta, Vincenzo Bentivoglio, Ruggiero Francavilla
Journal: Clinical Gastroenterology and Hepatology (2020)
Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo
Authors: Colby R. Maldini, Daniel T. Claiborne, Ken Okawa, Tao Chen, Derrick L. Dopkin, Xiaochuan Shan, Karen A. Power, Radiana T. Trifonova, Katharine Krupp, Meredith Phelps, Vladimir D. Vrbanac, Serah Tanno, Timothy Bateson, George J. Leslie, James A. Hoxie, Christian L. Boutwell, James L. Riley, Todd M. Allen
Journal: Nature Medicine (2020)
1200 high-quality metagenome-assembled genomes from the rumen of African cattle and their relevance in the context of sub-optimal feeding
Authors: Toby Wilkinson, Daniel Korir, Moses Ogugo, Robert D. Stewart, Mick Watson, Edith Paxton, John Goopy, Christelle Robert
Journal: Genome biology (2020)

The Boran (Bos indicus), indigenous Zebu cattle breed from sub-Saharan Africa, is remarkably well adapted to harsh tropical environments. Due to financial constraints and low-quality forage, African livestock are rarely fed at 100% maintenance energy requirements (MER) and the effect of sub-optimal restricted feeding on the rumen microbiome of African Zebu cattle remains largely unexplored. We collected 24 rumen fluid samples from six Boran cattle fed at sub-optimal and optimal MER levels and characterised their rumen microbial composition by performing shotgun metagenomics and de novo assembly of metagenome-assembled genomes (MAGs). These MAGs were used as reference database to investigate the effect of diet restriction on the composition and functional potential of the rumen microbiome of African cattle.
SEP-1 Septic Shock Bundle Guidelines Not Applicable to Inpatients—Reply
Authors: Jonathan D. Baghdadi, Daniel Z. Uslan, Mitchell D. Wong
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