tbuckley/cabot-search huggingface dataset:
Abstract IA08: Organoid modeling of tumor and tissue microenvironments
Authors: Calvin J. Kuo
Journal: Cancer Research (2020)

Abstract Within the tumor microenvironment are diverse populations including fibroblasts, vasculature, and immune cells, all of which critically regulate cancer progression. A major historical impediment to basic and translational cancer studies has been the lack of in vitro methods that allow tumor epithelium to be robustly cultured together with stromal components. This talk will describe advances in 3D tumor organoid culture that allow tumor cells to be grown in a manner that preserves their native interaction with diverse tumor-infiltrating immune cells and allows analysis of immune checkpoint inhibition. Such organoid modeling of the tumor immune microenvironment within human clinical cancer biopsies will facilitate basic and translational immune-oncology studies. Additional applications to nonmalignant diseases will also be discussed. Citation Format: Calvin J. Kuo. Organoid modeling of tumor and tissue microenvironments [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA08.
Abstract 17850: Changes in Myocardial Fibrosis After Aortic Valve Replacement in Patients With Severe Aortic Stenosis: Cardiac Magnetic Resonance Study
Authors: In-Chang Hwang, Hyung-Kwan Kim, Jun-Bean Park, Eun-Ah Park, Whal Lee, Seung-Pyo Lee, Kyung-Hwan Kim, Yong-Jin Kim, Hyuk Ahn, Dae-Won Sohn
Journal: Circulation (2017)

Background: Cardiac magnetic resonance (CMR) enables the detection of diffuse myocardial fibrosis by T1 mapping, and replacement fibrosis by late gadolinium enhancement (LGE). We assessed the chang...
Atezolizumab with or without bevacizumab in unresectable hepatocellular carcinoma (GO30140): an open-label, multicentre, phase 1b study
Authors: Michael S Lee, Baek-Yeol Ryoo, Chih-Hung Hsu, Kazushi Numata, Stacey Stein, Wendy Verret, Stephen P Hack, Jessica Spahn, Bo Liu, Heba Abdullah, Yulei Wang, Aiwu Ruth He, Kyung-Hun Lee, Y-J Bang, J Bendell, Y Chao, J-S Chen, H C Chung, S L Davis, A Dev, E Gane, B George, A R He, H Hochster, C-H Hsu, M Ikeda, J Lee, M Lee, A Mahipal, G Manji, M Morimoto, K Numata, M Pishvaian, S Qin, D Ryan, B-Y Ryoo, N Sasahira, S Stein, J Strickler, N Tebbutt
Journal: The Lancet Oncology (2020)
Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China
Authors: Xin Xu, Jian Sun, Sheng Nie, Huiyuan Li, Yaozhong Kong, Min Liang, Jinlin Hou, Xianzhong Huang, Dongfeng Li, Tean Ma, Jiaqing Peng, Shikui Gao, Yong Shao, Hong Zhu, Johnson Yiu-Nam Lau, Guangyu Wang, Chunbao Xie, Li Jiang, Ailong Huang, Zhenglin Yang, Kang Zhang, Fan Fan Hou
Journal: Nature Medicine (2020)
BMA urges plan to tackle backlog of patients awaiting non-covid treatment
Authors: Elisabeth Mahase
Journal: BMJ (2020)

The government urgently needs to set out a plan to reduce the huge backlog of patients waiting for NHS treatments unrelated to covid-19 in the wake of the pandemic, the BMA has said.

The call came as the BMA released the results of its latest survey of over 8000 doctors. It found that more than half (3754 of 7238) were either not very confident or not confident at all that their department would be able to manage patient demand as NHS services resumed.1

“The government must be honest with the public about the surge to come and start meaningful conversations with frontline clinicians …
Ventilator Sharing during an Acute Shortage Caused by the COVID-19 Pandemic
Authors: Jeremy R. Beitler, Aaron M. Mittel, Richard Kallet, Robert Kacmarek, Dean Hess, Richard Branson, Murray Olson, Ivan Garcia, Barbara Powell, David S. Wang, Jonathan Hastie, Oliver Panzer, Daniel Brodie, Laureen L. Hill, B. Taylor Thompson
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force
Authors: Amy L. McGuire, Mark P. Aulisio, F. Daniel Davis, Cheryl Erwin, Thomas D. Harter, Reshma Jagsi, Robert Klitzman, Robert Macauley, Eric Racine, Susan M. Wolf, Matthew Wynia, Paul Root Wolpe
Journal: The American Journal of Bioethics (2020)

The COVID-19 pandemic has raised a host of ethical challenges, but key among these has been the possibility that health care systems might need to ration scarce critical care resources. Rationing policies for pandemics differ by institution, health system, and applicable law. Most seem to agree that a patient's ability to benefit from treatment and to survive are first-order considerations. However, there is debate about what clinical measures should be used to make that determination and about other factors that might be ethically appropriate to consider. In this paper, we discuss resource allocation and several related ethical challenges to the healthcare system and society, including how to define benefit, how to handle informed consent, the special needs of pediatric patients, how to engage communities in these difficult decisions, and how to mitigate concerns of discrimination and the effects of structural inequities.
Better reporting standards are needed to enhance the quality of hop testing in the setting of ACL return to sport decisions: a narrative review
Authors: Paul Read, Sean Mc Auliffe, Mathew G Wilson, Gregory D Myer
Journal: British Journal of Sports Medicine (2020)

Background/aim There is a lack of consistency in return to sport (RTS) assessments, in particular hop tests to predict who will sustain a reinjury following anterior cruciate ligament (ACL) reconstruction. Inconsistent test battery content and methodological heterogeneity might contribute to variable associations between hop test performance and subsequent injury. Our aim was to investigate whether commonly used hop tests are administered in a consistent manner and in accordance with reported guidelines. Methods We conducted a narrative review of studies that examined whether hop testing could differentiate RTS pass rates, reinjury and rerupture in athletes after ACL reconstruction. Our specific focus was on the methodological procedures of hop testing as this component is widely used to evaluate patients’ function and readiness to RTS. Main findings Substantial variation exists in RTS hop test administration, scoring and interpretation. Authors often failed to report important details of methods such as warm up activities, randomisation, number of trials, rest periods and landing requirements. Conclusion We recommend researchers provide clearer descriptions of how hop tests are performed to increase standardisation and promote accurate data collection. Absence of reporting to describe test methods and using different test procedures makes it difficult to compare study findings.
Abstract A36: Organoid models for deciphering roles of the evolving landscape of epigenetic heterogeneity during aging in cancer development
Authors: Yong Tao, Byunghak Kang, Daniel Petkovich, Steve Baylin, Hariharan Easwaran
Journal: Cancer Research (2020)

Abstract Background: Tumor initiation and development occur not necessarily by genetic changes alone, but in the context of the epigenome and cell microenvironment. Growing evidence indicate that cancer risk factors, such as aging and inflammation, may primarily modulate the epigenome, causing predisposition to cancer development by driver mutations. Thus, there is a need to study and model epigenetic changes preceding and associating with cancer development. We have developed ex vivo models for investigating the evolution and roles of DNA methylation changes during normal cell divisions and how these epigenetic changes play critical roles in early stages of tumor development. Results: We showed that spontaneous epigenetic changes, specifically promoter-DNA hypermethylation, have a very important role in tumor initiation by oncogenic driver mutations. We addressed the precursor role of aging-like spontaneous promoter-DNA hypermethylation in initiating tumorigenesis. Using mouse colon-derived organoids, we show promoter hypermethylation spontaneously arises in cells mimicking the human “aging-like” phenotype. The silenced genes activate the Wnt pathway, causing a stemlike state and differentiation defects. These changes render aged organoids profoundly more sensitive than young ones to transformation by BrafV600E producing the typical human proximal BRAFV600E-driven colon adenocarcinomas characterized by extensive, abnormal gene promoter CGI methylation or the methylator phenotype (CIMP). Conversely, CRISPR-mediated simultaneous inactivation of a panel of the silenced genes markedly sensitized to BrafV600E-induced transformation. We showed that “spontaneous” promoter hypermethylation, arising in an “aging-like” scenario, sufficiently affects genes with roles in negative regulation of Wnt pathway. Inactivation of these genes leads to increased stem cell state and defects in differentiation. Conclusion: Our studies tightly link aging-like epigenetic abnormalities to intestinal cell fate changes and predisposition to oncogene-driven colon tumorigenesis. The organoid-based model opens up an opportunity to study mechanisms underlying epigenetic heterogeneity arising during normal cellular processes and their role in cancer predisposition. Citation Format: Yong Tao, Byunghak Kang, Daniel Petkovich, Steve Baylin, Hariharan Easwaran. Organoid models for deciphering roles of the evolving landscape of epigenetic heterogeneity during aging in cancer development [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A36.
Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis
Authors: Amy S. Paller, Linda Stein Gold, Jennifer Soung, Anna M. Tallman, David S. Rubenstein, Melinda Gooderham
Journal: Journal of the American Academy of Dermatology (2020)

Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for atopic dermatitis (AD) and psoriasis treatment.A phase 2b, double-blind, vehicle-controlled study randomly assigned adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, once or twice daily, for 12 weeks with a 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body surface area affected, pruritus numeric rating scale scores, patients' impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores.Overall, 191 of 247 randomized patients completed the study. Week 12 IGA responses were higher in the tapinarof groups versus the vehicle group, reaching statistical significance with tapinarof 1% twice daily, ≥75%/90% improvement in EASI from baseline were significantly higher in the tapinarof groups (except 0.5% once daily and 0.5% twice daily), EASI scores were significantly improved in all tapinarof groups, and body surface area affected was significantly reduced in the tapinarof groups (except 0.5% twice daily). More patients reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups, and POEM improvements were observed in all groups. Most adverse events were mild or moderate.Larger prospective studies are required to confirm the reported analyses.Tapinarof is a potential important advance in topical medicine development for AD.
Risk associations for intestinal parasites in symptomatic and asymptomatic schoolchildren in central Mozambique
Authors: A.S. Muadica, S. Balasegaram, K. Beebeejaun, P.C. Köster, B. Bailo, M. Hernández-de-Mingo, A. Dashti, E. Dacal, J.M. Saugar, I. Fuentes, D. Carmena
Journal: Clinical Microbiology and Infection (2020)
THU0385 SAFETY OF TOFACITINIB THERAPY IN HBSAG CARRIERS WITH ANKYLOSING SPONDYLITIS: A PROSPECTIVE STUDY
Authors: L. Fang, Z. Lin, Z. Liao, O. Jin, J. Gu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Targeted synthetic DMARDs (ts-DMARDs) are becoming more available and affordable in developing countries, where the prevalence of hepatitis B virus (HBV) infection is still an important public health issue. The safety of ts-DMARDs therapy in terms of the reactivation of hepatitis B virus (HBV) infection need more concern. Rare data from a prospective study focus on the use of ts-DMARDs in patients with concurrent ankylosing spondylitis (AS) and HBV infection were available by now. Objectives: To evaluate the influence of tofacitinib on reactivation of HBV infection in HBsAg carriers with AS. Methods: In this 52 weeks observation, HBsAg carriers with active AS (BASDAI ≥ 4) despite failed treatment with at least two NSAIDs and sulfasalazine (for patients with persistent peripheral arthritis) were studied. Patients must be positive for HBsAg and have a normal liver function prior to study. All patients received therapy with tofacitinib (5mg twice daily). Entecavir were prescribed preventively regardless of individual viral load. Pre-existing NSAIDs and sulfasalazine were allowed. Liver enzymes (AST/ALT) and HBV viral load were monitored every 4 weeks. Increased viral load and abnormal liver function were managed according to expert opinion. Results: Eleven patients (9 male) were recruited. Eight patients had a baseline viral load &gt;2000 copy/ml (group 1), and the other 3 patients had a viral load ≤ 2000 copy/ml (group 2). Two patients from group 1 discontinued tofacitinib at week 12 due to ineffectiveness, and both continued taking Entecavir for another 3 months after the discontinuation of tofacitinib. One patients (male, 26 years old) from group 1 underwent a mild increase of both ALT and AST (67 and 56 IU/L, respectively) at week 16, but no elevated viral load (2.1e3 copies/ml, baseline 2.8e3) or a HBV YMDD mutant was found. The tofacitinib treatment continued. After prescription of polyene phosphatidyl choline, the liver enzyme of this patient decreased to normal range in 4 weeks and remained normal throughout the study. No reactivation of hepatitis B was observed in patients from group 2. Conclusion: Tofacitinib treatment may be a safe and effective option for HBsAg carriers with AS refractory to traditional treatment. Prophylaxis strategy with effective anti-viral drugs is recommended. References: [1]Chen YM, Huang WN, Wu YD, et al. Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib: a real-world study. Ann Rheum Dis 2018; 77:780-2. Disclosure of Interests: None declared
AB1031 DYSKERATOTIC CELLS IN PERSISTENT PRURITIC SKIN LESIONS AS A PROGNOSTIC FACTOR IN ADULT-ONSET STILL’S DISEASE.
Authors: S. Inotani, Y. Taniguchi, H. Nishikawa, N. Maeda-Aoyama, K. Nakajima, K. Arii, Y. Terada
Journal: Annals of the Rheumatic Diseases (2020)

Background: Adult-onset Still’s disease (AOSD), a systemic inflammatory disorder, is characterized by high fever, evanescent rash, arthritis, and hyperferritinaemia. AOSD is also reported to be associated with other skin lesions, including persistent pruritic papules and plaques. Objectives: This study aimed to assess the significance of dyskeratotic skin lesions in Japanese AOSD patients. Methods: We retrospectively assessed the histology of persistent pruritic skin lesions and evanescent rashes and the relationship between dyskeratotic cells, serum markers, and outcomes in 20 Japanese AOSD patients, comparing AOSD histology with that of dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD). Results: Persistent pruritic lesions were characterized by scattered single keratinocytes with an apoptotic appearance confined to the upper layer of the epidermis and horny layer without inflammatory infiltrate. In contrast to AOSD, the histology of DM, drug eruption, and GVHD demonstrated dyskeratotic cells in all layers of the epidermis with inflammatory infiltrate. AOSD with evanescent rash showed no dyskeratotic cells. The dyskeratotic cells in pruritic AOSD lesions stained positive for ssDNA and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, indicating apoptosis. Serum IL-18 was significantly higher in AOSD patients with dyskeratotic cells than those without, and generally required higher doses of glucocorticoids, immunosuppressants, and biologic agents. Two of ten AOSD patients with dyskeratotic cells died from haemophagocytic lymphohistiocytosis. Conclusion: Persistent pruritic AOSD skin lesions are characterized by dyskeratotic cells with apoptotic features, involving the upper layers of the epidermis. There may be a link to elevated IL-18. This dyskeratosis may be a negative prognostic indicator. Disclosure of Interests: None declared
Abstract A11: Urine sample-derived cerebral organoids suitable for modeling brain development and pathogenesis
Authors: Jiangnan Hu, Victor Lin, Mark Goldberg, Yu-chieh Wang
Journal: Cancer Research (2020)

Abstract Human cerebral organoids (COs) have been leveraged in many recent studies that led to significant discoveries regarding developmental biology, disease mechanisms, and pharmacologic responses in the central nervous system. Here, we intend to establish cerebral organoids suitable for modeling brain development and pathogenesis based on somatic cells that are isolated noninvasively. The development of such organoids began with the collection of urinary epithelial cells (UECs) from human urine samples. We have obtained multiple lines of human UEC-derived induced pluripotent stem cells (hUEC-iPSCs) by cell reprogramming. COs were generated from hUEC-iPSCs using a protocol optimized by our group. To comprehensively characterize the cellular and molecular features of our COs, we examined samples at different developmental time points. The hUEC-iPSC-developed COs exhibit normal development with neurogenesis and maturation of neuronal cells forming brain layers. These COs produce neurotropic and anti-inflammatory factors that are presumably critical for neurogenesis and neural repair. Several metalloproteases that may facilitate cell migration and microenvironment rearrangement are also present. After transplantation into the mouse cerebrum, vascularization quickly develops in the implanted COs, suggesting their viability and ability to interact with the environment. To gauge cellular plasticity of hUEC-iPSC-developed COs along their development, we exposed the COs that were developed using three different protocols and initially committed to telencephalic development to culture media containing FGF2 and FGF19. Multiple markers of the developing hindbrain were highly upregulated in the COs, indicating that their cellular plasticity and potential to be reprogrammed into noncerebral neural tissue in response to optimized stimuli. Overall, our work begins to reveal the promise of generating personalized COs from cells that are isolated from urine samples. These COs present with cellular plasticity that permits a possibility of generating neural tissue of various brain regions by converting prosencephalic organoids into a mesencephalic or rhombencephalic fate. With further adaptation, this human CO platform could form a unique and personalized model for the investigation of neural development influenced by oncogenic signaling and facilitate the development of novel therapies for treating neurologic malignancy. Citation Format: Jiangnan Hu, Victor Lin, Mark Goldberg, Yu-chieh Wang. Urine sample-derived cerebral organoids suitable for modeling brain development and pathogenesis [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A11.
Incidence of COVID‐19 in Patients With Rheumatic Diseases Treated With Targeted Immunosuppressive Drugs: What Can We Learn From Observational Data?
Authors: Ennio Giulio Favalli, Sara Monti, Francesca Ingegnoli, Silvia Balduzzi, Roberto Caporali, Carlomaurizio Montecucco
Journal: Arthritis & Rheumatology (2020)

To describe the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases treated with targeted synthetic or biologic disease-modifying antirheumatic drugs (DMARDs) compared with that in the general population living in the same Italian region.Patients followed up at 2 rheumatology referral centers in Lombardy from February 25, 2020 to April 10, 2020 were invited to participate in a survey designed to identify patients who had confirmed COVID-19, close contact with others with confirmed COVID-19, or symptoms of the infection, and to detect changes in work, behavior, and disease management made in an attempt to prevent infection. The incidence of COVID-19 in the Lombardy population was obtained from the National Institute of Statistics. COVID-19 cases were confirmed by nasopharyngeal swab.The survey was given to 955 patients (531 patients with rheumatoid arthritis, 203 patients with psoriatic arthritis, 181 patients with spondyloarthritis, and 40 patients with connective tissue diseases, vasculitides, or autoinflammatory diseases). These patients had a mean age of 53.7 years, and 67.4% were women. The rate of response to the survey was 98.05%, and the incidence of confirmed COVID-19 cases was consistent with that in the general population (0.62% versus 0.66%; P = 0.92). None of the patients had severe complications or required intensive care treatment, and all of the patients who tested positive for COVID-19 temporarily discontinued ongoing targeted synthetic drug or biologic DMARD therapy. Almost all patients took precautions to prevent the COVID-19 infection (90.6%), and almost all continued treatment with targeted synthetic drugs or biologic DMARDs (93.2%). Disease activity remained stable in 89.5% of patients.Our results reflected the attitude of patients with rheumatic diseases regarding the prevention of the infection while maintaining their long-term treatment regimens. The incidence and severity of COVID-19 in patients treated with targeted synthetic drugs or biologic DMARDs was not significantly different from that in the general population in the same region.