tbuckley/cabot-search huggingface dataset:
THU0230 Anti-tnfa therapy with infliximab in the treatment of hla b27 associated acute anterior uveitis
Authors: Y El-Shabrawi, J Hermann
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Application of topical corticosteroids is the first-line treatment of anterior uveitis. Its most common form is HLA B27 associated. Of these patients approximately 55% suffer from additional systemic diseases, such as ankylosing spondylitis or chronic inflammatory bowel disease. In a recent report Brandt, <i>et al</i>.<sup>1</sup> reported a dramatic response to Infliximab in patients with ankylosing spondylitis. In about 50% of uveitis patients additional periocular or oral corticosteroids or both are needed because no adequate response to intensive (hourly) topical corticosteroid therapy can be achieved. This together with the fact that recurrent treatment of these young patients with corticosteroids dramatically increases the risk of steroid-induced side effects such as glaucoma, cataract or, in the case of oral or intravenous application, hypertension, diabetes mellitus or osteoporosis new approaches to the therapy of acute uveitis are highly needed. <h3>Objectives</h3> To evaluate the potentials of Infliximab, a neutralising Anti-TNFa antibody in the therapy of patients with an acute HLA B27 associated anterior uveitis. <h3>Methods</h3> Seven consecutive patients with an acute onset of an HLA B 27 associated anterior uveitis, with at least 3+ anterior chamber cells were included in this prospective non-comparative case series. Infliximab (Centocor, Malvern, Pa.) at a dose of 10 mg/kg body weight given intravenously was used as the sole anti-inflammatory drug. Anterior chamber cells and flare were evaluated prior to Infliximab treatment and at defined time points after treatment. CRP levels were assessed in all patients prior to intravenous delivery of Infliximab and re-evaluated after one week. <h3>Results</h3> Patients were followed for a mean period of 194 ± 32 days. No patient treated showed clinical signs of a spondylarthropathy. Seven patients received a single Infiximab infusion of 10 mg/kg body weight. A second infusion was administered in one patient 21 days after first dosage due to a reactivation of the uveitis. The median duration (± SD) of uveitis of 8 ± 12 days. All patients responded to Infliximab with an rapid improvement of clinical symptoms a decrease of anterior chamber cells. Only in one patient a total resolution of the uveitis was not achieved using Infliximab. <h3>Conclusion</h3> In our study Infliximab proofed to be a powerful therapeutic agent in acute HLA B27 associated uveitis. It therefore seems to be an excellent alternative or an additive to steroid treatment. Only in patients with a systemic sign of an inflammatory disease additional local, systemic low dose corticosteroids or immunosuppressive agents might be needed. <h3>Reference</h3> Brandt J, Haibel H, Cornely D, Golder W, Gonzalez J, Reddig J, Thriene W, Sieper J, Braun J. Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab. Arthritis Rheum. 2000;43(6):1346–52
Abstract IA18: Clinically relevant mutational signatures in childhood cancer
Authors: Adam Shlien
Journal: Cancer Research (2020)

Abstract Mutagenic processes leave imprints on the genome in the form of mutations in a specific nucleotide context, forming a unique signature. The driving forces of rarer signatures, especially those seen in relapsed childhood cancers, are mostly unknown. In this talk, I will present data showing the contribution of intrinsic and extrinsic mutators to childhood cancer, and analyses using mutation signatures to accurately predict past mutagen exposure and inform therapeutic choice for ongoing patients. Citation Format: Adam Shlien. Clinically relevant mutational signatures in childhood cancer [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA18.
Abstract IA07: Making it easier to participate in research: A patient’s perspective
Authors: Liz Salmi
Journal: Clinical Cancer Research (2020)

Abstract Today’s patients exist in a new culture of “peer health advice” where people with similar lived experiences are crowdsourcing health questions and relying on the advice of others. Additionally, Google reports there are 70,000 health-related searches happening every 60 seconds. People are naturally turning to social media and the Internet for health information, and yet it is quite difficult for most people to gain access to the detailed information in their own health records. Medical record requests—whether for transitions in care, for greater understanding, or as a requirement to participate in research—take time and effort, and costs are often involved. This creates a massive barrier and delay to accessing potentially life-saving information. In this presentation Liz Salmi will share her own patient experience and the barriers she faced in participating in research. Based on her personal experience, and now her work with the OpenNotes research team, she will outline simple steps health systems and researchers can put into place to make it easier for patients to engage more meaningfully in the health information that is their own. Citation Format: Liz Salmi. Making it easier to participate in research: A patient’s perspective [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr IA07.
Conservation epidemiology of predators and scavengers to reduce zoonotic risk
Authors: Christopher J O'Bryan, Alexander R Braczkowski, Ricardo J Soares Magalhães, Eve McDonald-Madden
Journal: The Lancet Planetary Health (2020)

Conservation epidemiology of predators and scavengers to reduce zoonotic riskThe increasing instances of epidemics and pandemics of zoonotic origin-diseases maintained in animal populations but transmitted to humans-show that humanity is fundamentally off track with predator and scavenger conservation.We are off track because most diseases of pandemic potential are zoonotic, with natural reservoirs in predators and scavengers. 1,2redators and scavengers, species that consume other animals either live or dead, also play a role in maintaining ecosystem structure and reducing zoonotic risk. 3,4Leopards, polar bears, insectivorous bats, and carrion-eating vultures are just a few examples of these species that are crucially positioned in food webs, controlling densities of disease hosts and vectors through feeding 5 or competitive exclusion. 6However, most of these species are at increased risk of extinction globally. 3,4Their decline, coupled with expanding environmental destruction, is known to be a strong driver of zoonotic spillover.Mammalian predator and scavenger reservoir hosts are found globally, with species richness hotspots in North America, Africa, southeast Asia (eg, order Carnivora; appendix p 1), and central and South America (eg, bats, possums, armadillos, shrews, and anteaters; appendix p 1).Although zoonotic risk is homogeneous among mammalian and avian taxonomic orders, 7 predator and scavenger species have been linked to some of the most serious epidemics in recent history, serving as reservoir hosts for cross-species transmission. 1Masked palm civets, raccoon dogs, and horseshoe bats are just three of the species that have been linked to severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2. Across the world, these and other predator and scavenger species are regularly sold in live animal markets.Indeed, capturing, handling, storing, and processing predators and scavengers for consumption from reservoir hotspots inherently increases zoonotic risk.Predator and scavenger populations are declining and it is predicted that their numbers will continue to drop in the next 20 years due to overharvesting, habitat loss, and conflict with humans. 3,4The reduction in the number of predators can increase the risk of zoonotic We declare no competing interests.
Causal learning in CTC: Adaptive and collaborative
Authors: Netanel Weinstein, Dare Baldwin
Journal: Behavioral and Brain Sciences (2020)

Abstract Osiurak and Reynaud highlight the critical role of technical-reasoning skills in the emergence of human cumulative technological culture (CTC), in contrast to previous accounts foregrounding social-reasoning skills as key to CTC. We question their analysis of the available evidence, yet for other reasons applaud the emphasis on causal understanding as central to the adaptive and collaborative dynamics of CTC.
Assessment of Lupus Anticoagulant Positivity in Patients With Coronavirus Disease 2019 (COVID-19)
Authors: Morayma Reyes Gil, Mohammad Barouqa, James Szymanski, Jesus D. Gonzalez-Lugo, Shafia Rahman, Henny H. Billett
Journal: JAMA Network Open (2020)

This cohort study assesses the prevalence of lupus anticoagulant (LA) positivity in patients with coronavirus disease 2019 (COVID-19) and examines the association of LA positivity with patient outcomes.
RUNX1 mutations in blast-phase chronic myeloid leukemia associate with distinct phenotypes, transcriptional profiles, and drug responses
Authors: Shady Adnan Awad, Olli Dufva, Aleksandr Ianevski, Bishwa Ghimire, Jan Koski, Pilvi Maliniemi, Daniel Thomson, Andreas Schreiber, Caroline A. Heckman, Perttu Koskenvesa, Matti Korhonen, Kimmo Porkka, Susan Branford, Tero Aittokallio, Matti Kankainen, Satu Mustjoki
Journal: Leukemia (2020)

Abstract Blast-phase chronic myeloid leukemia (BP-CML) is associated with additional chromosomal aberrations, RUNX1 mutations being one of the most common. Tyrosine kinase inhibitor therapy has only limited efficacy in BP-CML, and characterization of more defined molecular subtypes is warranted in order to design better treatment modalities for this poor prognosis patient group. Using whole-exome and RNA sequencing we demonstrate that PHF6 and BCORL1 mutations, IKZF1 deletions, and AID/RAG-mediated rearrangements are enriched in RUNX1 mut BP-CML leading to typical mutational signature. On transcriptional level interferon and TNF signaling were deregulated in primary RUNX1 mut CML cells and stem cell and B-lymphoid factors upregulated giving a rise to distinct phenotype. This was accompanied with the sensitivity of RUNX1 mut blasts to CD19-CAR T cells in ex vivo assays. High-throughput drug sensitivity and resistance testing revealed leukemia cells from RUNX1 mut patients to be highly responsive for mTOR-, BCL2-, and VEGFR inhibitors and glucocorticoids. These findings were further investigated and confirmed in CRISPR/Cas9-edited homozygous RUNX1 −/− and heterozygous RUNX1 −/mut BCR-ABL positive cell lines. Overall, our study provides insights into the pathogenic role of RUNX1 mutations and highlights personalized targeted therapy and CAR T-cell immunotherapy as potentially promising strategies for treating RUNX1 mut BP-CML patients.
Prediction, Not Association, Paves the Road to Precision Medicine
Authors: Danilo Bzdok, Gael Varoquaux, Ewout W. Steyerberg
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
Associations Between Reproductive and Hormone-Related Factors and Risk of Nonalcoholic Fatty Liver Disease in a Multiethnic Population
Authors: Jun Wang, Anna H. Wu, Frank Z. Stanczyk, Jacqueline Porcel, Mazen Noureddin, Norah A. Terrault, Lynne R. Wilkens, Veronica Wendy Setiawan
Journal: Clinical Gastroenterology and Hepatology (2020)
Oral Microbiome Geography: Micron-Scale Habitat and Niche
Authors: Jessica L. Mark Welch, S. Tabita Ramírez-Puebla, Gary G. Borisy
Journal: Cell Host & Microbe (2020)

The mouth presents a multiplicity of local environments in communication with one another via saliva. The spatial organization of microbes within the mouth is shaped by opposing forces in dynamic equilibrium—salivary flow and adhesion, shedding and colonization—and by interactions among and between microbes and the host. Here we review recent evidence confirming that oral microbes are specialized for individual habitats within the mouth and that microbial habitats and niches are defined by micron-scale gradients in combination with short- and long-range interactions. Micron-scale structure illuminates the roles of individual taxa and provides insight into their community ecology and potential pathogenicity.
Trends in Daily Use of Biotin Supplements Among US Adults, 1999-2016
Authors: Danni Li, Mary R. Rooney, Lynn A. Burmeister, Nicole E. Basta, Pamela L. Lutsey
Journal: JAMA (2020)

This pharmacoepidemiology study uses NHANES data to characterize the prevalence and trends in use of high-dosage biotin supplementation among US adults between 1999 and 2016.
Addressing Disparities in Graduate Medical Education—A Call to Action
Authors: Jennifer LaFemina, Ulises Torres, Jennifer S. Davids
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
Abstract #2786: Apoptosis induced by JAK2 inhibition requires Bim and is enhanced by a BH3 mimetic ABT-737 in JAK2 mutant human erythroid cells
Authors: Tanya Siddiqi, Britta Will, Daniel Costa, Ulrich Steidl, Daniel Tenen, Susumu Kobayashi
Journal: Cancer Research (2009)

The activating mutation JAK2V617F has been shown to play a central role in the pathogenesis of polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis. Inhibition of mutant JAK2 activity leads to growth inhibition and apoptosis in cells with mutated JAK2. However, the pro-apoptotic proteins involved in JAK2 inhibition-induced apoptosis remain unclear. Recently, it has been shown that the BH3-only protein Bim is one of the main effectors of tyrosine kinase inhibitor-mediated apoptosis in BCR-ABL positive chronic myelogenous leukemia cells, EGFR mutant lung cancer cells, and B-RAF mutant tumor cells. They show striking initial response to small molecule tyrosine kinase inhibitors and may use Bim as a common mediator during apoptosis. Therefore, we hypothesized that up-regulation of active Bim may be necessary for apoptosis induced by JAK2 inhibition in cells carrying constitutively activated JAK2 mutations. In this study, we examined two JAK2 mutant cell lines, HEL and CHRF-288-11 cells and observed that JAK2 inhibition-induced apoptosis led to inactivation of STAT5 and ERK1/2, up-regulation of de-phosphorylated Bim, as well as down-regulation of the anti-apoptotic protein Bcl-xL, suggesting that balance of Bim/BCL-xL may be critical for JAK2 inhibition-induced apoptosis. The BH3 mimetic agent ABT-737 induced apoptosis in a dose-dependent fashion in HEL cells. Knockdown of Bim in stably transfected HEL cells using a small hairpin RNA construct completely inhibited apoptosis induced by JAK2 inhibition. Knockdown of Bim led to lack of Bax activation and failure of inner mitochondrial membrane potential breakdown with JAK2 inhibition. Addition of ABT-737 fully restored induction of apoptosis with JAK2 inhibition in the Bim knockdown HEL cells. Thus, these data confirmed that the intrinsic apoptosis pathway was inactive in the absence of Bim. In addition, ABT-737 enhanced the apoptosis induced by JAK2 inhibition in wild type HEL cells. Moreover, the combination of JAK Inhibitor I and ABT-737 reduced the number of erythroid colonies derived from primary CD34 positive cells from PV patients more efficiently than either drug alone. Progenitor cells committed to the granulocytic or monocytic lineages were not significantly impaired by this combination of agents. Taken together, our data indicate that Bim is a key effector molecule in JAK2 inhibition-induced apoptosis and that manipulation of the apoptotic pathway could provide a novel therapeutic strategy for patients with myeloproliferative disorders carrying activating mutations of the tyrosine kinase JAK2.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2786.
Fibrinogen-like protein 2 aggravates nonalcoholic steatohepatitis via interaction with TLR4, eliciting inflammation in macrophages and inducing hepatic lipid metabolism disorder
Authors: Junjian Hu, Hongwu Wang, Xitang Li, Yonggang Liu, Yuqiang Mi, Hongyan Kong, Dong Xi, Weiming Yan, Xiaoping Luo, Qin Ning, Xiaojing Wang
Journal: Theranostics (2020)

The functions of fibrinogen-like protein 2 (fgl2) have been studied in many inflammatory and neoplastic diseases, but the role of fgl2 in nonalcoholic fatty liver disease has not yet been elucidated. In this study, we sought to investigate the role of fgl2 in the pathogenesis of nonalcoholic steatohepatitis (NASH).
Health Impact and Cost-Effectiveness of Volume, Tiered, and Absolute Sugar Content Sugar-Sweetened Beverage Tax Policies in the United States
Authors: Yujin Lee, Dariush Mozaffarian, Stephen Sy, Junxiu Liu, Parke E. Wilde, Matti Marklund, Shafika Abrahams-Gessel, Thomas A. Gaziano, Renata Micha
Journal: Circulation (2020)

Background: Sugar-sweetened beverage taxes are a rapidly growing policy tool and can be based on absolute volume, sugar content tiers, or absolute sugar content. Yet, their comparative health and economic impacts have not been quantified, in particular, tiered or sugar content taxes that provide industry incentives for sugar reduction. Methods: We estimated incremental changes in diabetes mellitus and cardiovascular disease, quality-adjusted life-years, costs, and cost-effectiveness of 3 sugar-sweetened beverage tax designs in the United States, on the basis of (1) volume ($0.01/oz), (2) tiers (&lt;5 g of added sugar/8 oz: no tax; 5–20 g/8 oz: $0.01/oz; and &gt;20 g/8 oz: $0.02/oz), and (3) absolute sugar content ($0.01 per teaspoon added sugar), each compared with a base case of modest ongoing voluntary industry reformulation. A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey, policy effects and sugar-sweetened beverage-related diseases from meta-analyses, and industry reformulation and health-related costs from established sources. Results: Over a lifetime, the volume, tiered, and absolute sugar content taxes would generate $80.4 billion, $142 billion, and $41.7 billion in tax revenue, respectively. From a healthcare perspective, the volume tax would prevent 850 000 cardiovascular disease (95% CI, 836 000–864 000) and 269 000 diabetes mellitus (265 000–274 000) cases, gain 2.44 million quality-adjusted life-years (2.40–2.48), and save $53.2 billion net costs (52.3–54.1). Health gains and savings were approximately doubled for the tiered and absolute sugar content taxes. Results were robust for societal and government perspectives, at 10 years follow-up, and with lower (50%) tax pass-through. Health gains were largest in young adults, blacks and Hispanics, and lower-income Americans. Conclusions: All sugar-sweetened beverage tax designs would generate substantial health gains and savings. Tiered and absolute sugar content taxes should be considered and evaluated for maximal potential gains.
Abstract 03: Model regularization and considerations: Tuning dynamic borrowing in a hybrid clinical trial under Bayesian and frequentist framework
Authors: Ruilin Li, Jiawen Zhu, Jane Fridlyand
Journal: Clinical Cancer Research (2020)

Abstract There has been growing interest in leveraging existing external control data to facilitate clinical trial inferences and decision making. In recent years, the quality of real-world data (RWD) improved significantly, allowing it to be considered for being used as an external control. Borrowing by directly pooling from such external controls to underpowered randomized study has a potential to lead to biased estimates, and a dynamic borrowing framework is recommended to better control false positive outcomes (Lewis et al., 2019). However, the parameter tuning of Bayesian methods of dynamic borrowing remains challenging in order to optimize trial operating characteristics. To provide a general guidance on prior selection and parameter tuning, we implemented and evaluated multiple popular Bayesian prior settings through computational simulations and provided a described relationship to the corresponding frequentist model with regularization. Recommended prior distribution characteristics and practical considerations are proposed. Note: This abstract was not presented at the conference. Citation Format: Ruilin Li, Jiawen Zhu, Jane Fridlyand. Model regularization and considerations: Tuning dynamic borrowing in a hybrid clinical trial under Bayesian and frequentist framework [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 03.
Putting social cognitive mechanisms back into cumulative technological culture: Social interactions serve as a mechanism for children's early knowledge acquisition
Authors: Amanda S. Haber, Kathleen H. Corriveau
Journal: Behavioral and Brain Sciences (2020)

Abstract Osiurak and Reynaud offer a unified cognitive approach to cumulative technological culture, arguing that it begins with non-social cognitive skills that allow humans to learn and develop new technical information. Drawing on research focusing on how children acquire knowledge through interactions others, we argue that social learning is essential for humans to acquire technical information.