tbuckley/cabot-search huggingface dataset:
Abstract 14440: Growth Differentiation Factor-15 Predicts Mortality in Patients With Chronic Kidney Disease and Stable Coronary Heart Disease: A Subanalysis of the ANOX Study
Authors: Hiromichi Wada, Masahiro Suzuki, Morihiro Matsuda, Yoichi Ajiro, Tsuyoshi Shinozaki, Satoru Sakagami, Kazuya Yonezawa, Masatoshi Shimizu, Junichi Funada, Takashi Takenaka, Yukiko Morita, Toshihiro Nakamura, Kazuteru Fujimoto, Hiromi Matsubara, Toru Kato, Takashi Unoki, Daisuke Takagi, Shuichi Ura, Kyohma Wada, Moritake Iguchi, Nobutoyo Masunaga, Mitsuru Ishii, Hajime Yamakage, Akira Shimatsu, Kazuhiko Kotani, Noriko Satoh-Asahara, Mitsuru Abe, Masaharu Akao, Koji Hasegawa
Journal: Circulation (2018)

Background: Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine, which plays an important role in the regulation of the inflammatory response, growth and cell differentiation....
Prospective study into COVID-19-like symptoms in patients with and without immune-mediated inflammatory diseases or immunomodulating drugs
Authors: Lotte van Ouwerkerk, Andrea E van der Meulen-de Jong, Maarten K Ninaber, Y K Onno Teng, Tom WJ Huizinga, Cornelia F Allaart
Journal: Annals of the Rheumatic Diseases (2021)

With the arrival of SARS-CoV-2, it was asked whether our patients with immune-mediated inflammatory disorders, or who had an organ transplantation (IMDT patients) and/or use immunosuppressive medication (imed) are more susceptible to SARS-CoV-2 infection and/or a severe COVID-19 disease course. In the earliest reports on COVID-19, such patients were rarely described. Most reports were retrospectively collected, in various case series or cohorts without a control group.1–3 The Infection and Immunomodulation Inventory Initiative cohort study was started 10 March 2020 to prospectively register self-reported periods of illness with COVID-19-like symptoms (CLS) (see questionnaire in online supplemental table 1) and compare these between IMIDT patients with and without imed and controls as selected from the hospital database of the Leiden University Medical Center in March 2020. Patients were defined as being in outpatient care at the outpatient clinic for rheumatology, gastroenterology, pulmonology and/or nephrology and having an autoinflammatory or autoimmune disease or having had a solid organ transplantation with or without imed (verified from the medical records after participant’s informed consent). Controls were persons who had visited these outpatient clinics in the previous …
A deep learning-based smartphone platform for cutaneous lupus erythematosus classification assistance: Simplifying the diagnosis of complicated diseases
Authors: Haijing Wu, Heng Yin, Haipeng Chen, Moyuan Sun, Xiaoqing Liu, Yizhou Yu, Yang Tang, Hai Long, Bo Zhang, Jing Zhang, Ying Zhou, Yaping Li, Guiyuing Zhang, Peng Zhang, Yi Zhan, Jieyue Liao, Shuaihantian Luo, Rong Xiao, Yuwen Su, Juanjuan Zhao, Fei Wang, Jing Zhang, Wei Zhang, Jin Zhang, Kai Hu, Limei Yuan, Danqi Deng, Yunsheng Liang, Bin Yang, Qianjin Lu
Journal: Journal of the American Academy of Dermatology (2021)
Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens
Authors: Adam S Kibel, Brant A Inman, Russell K Pachynski, Tuyen Vu, Nadeem A Sheikh, Daniel P Petrylak
Journal: JNCI Journal of the National Cancer Institute (2021)

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video recorded during coculture. Here, we present video recordings and analyses of T cells from sipuleucel-T-treated subjects showing-for the first time-direct lysis of cells that express prostate cancer target antigens, prostate acid phosphatase, or prostate-specific antigen.
Abstract PS2-27: Benefits of a rapid diagnostic centre for breast cancer care during the COVID-19 pandemic
Authors: Gary Ko, Sharmy Sarvanantham, Sangita Sequeira, Vrutika Prajapati, David R. McCready, Vivianne Freitas, Tulin D. Cil
Journal: Cancer Research (2021)

Abstract BACKGROUND: Changes in access to breast imaging and suspension of mammographic screening during the COVID-19 pandemic had the potential to significantly delay breast cancer diagnostic pathways. The Gattuso Rapid Diagnostic Centre (GRDC) is an innovative clinic that provides a patient-centered approach for investigation of suspicious breast abnormalities and sees approximately 1200 patients per year. The aim of this study was to assess the impact of the pandemic on patient volumes and imaging at this high-volume breast rapid diagnostic centre. METHODS: A retrospective review of consecutive patients who presented to the GRDC from the start of the pandemic (March 12, 2020) until May 31, 2020 was performed. The number of patients, reason for referral, cancer detection rate (CDR), and waiting time from appointment to diagnosis were evaluated and compared to a corresponding time period in 2019. RESULTS: A total of 168 new patients presented to the GRDC during the study period, corresponding to a 32.3% decrease in the number of patients compared to 2019 (n=248). Seventy-eight patients (46.4%) were referred due to the presence of a clinical palpable abnormality, which represented an increase of 13.8% (n=81 [32.7%] in 2019; p=0.005). Out of 168 patients, 69 were diagnosed with a breast malignancy, yielding a CDR of 41.1% during the pandemic versus 111 patients in 2019 (CDR of 44.8%; p= 0.456). The average time from appointment at GRDC to diagnosis was lower at 0.76 days vs 1.21 days in 2019. The rate of same day diagnosis was significantly higher at 39.5% vs 27.0% in 2019 (p=0.008). Twenty-five patients (14.9%) received neoadjuvant systemic therapy compared to 16 patients (6.5%) in 2019 (p=0.005). CONCLUSION: There were fewer patients presenting for breast investigations during the pandemic period and a significant increase in the percentage of patients with palpable masses as the cause for referral with no appreciable change in the CDR. The presence of a rapid diagnostic breast center enabled patients with concerning breast symptoms to access and receive expedited assessment. This ensured patients did not undergo diagnostic delays despite the health care restrictions that emerged during the COVID-19 pandemic. Citation Format: Gary Ko, Sharmy Sarvanantham, Sangita Sequeira, Vrutika Prajapati, David R. McCready, Vivianne Freitas, Tulin D. Cil. Benefits of a rapid diagnostic centre for breast cancer care during the COVID-19 pandemic [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-27.
The impact of unrestricted access to direct-acting antiviral among incarcerated hepatitis C virus-infected patients
Authors: Yu Jun Wong, Prem Harichander Thurairajah, Rahul Kumar, Kwong Ming Fock, Ngai Moh Law, Sin-Yoong Chong, Fria Gloriba Manejero, Tiing-Leong Ang, Eng Kiong Teo, Jessica Tan
Journal: Clinical and Molecular Hepatology (2021)

Despite the disproportionally high prevalence rates of hepatitis C virus (HCV) amongst the incarcerated population, eradication remains challenging due to logistic and financial barriers. Although treatment prioritization based on disease severity is commonly practiced, the efficacy of such approach remained uncertain. We aimed to compare the impact of unrestricted access to direct-acting antiviral (DAA) among incarcerated HCV-infected patients in Singapore.
문맥압항진증 병태 생리의 최신 지견
Authors: 이준성
Journal: Clinical and Molecular Hepatology (2009)

Portal hypertension and its complications account for the majority of morbidity and mortality that occurs in patients with cirrhosis. Despite many major advances over the years, the pathogenesis of portal hypertension continues to be enigmatic. It is now well recognized that increased intrahepatic resistance is the primary initiator in the development of portal hypertension and that increased resistance occurs due to fibrosis and through dynamic changes in sinusoidal tone and structure. This article will highlight recent advances in our understanding of the vascular biology of cirrhosis and portal hypertension with an emphasis on how understanding mechanisms of these abnormalities may lead to future therapy.
Abstract PD13-05: Delivery and activity of SN-38 by sacituzumab govitecan in breast cancer brain metastases
Authors: Andrew J Brenner, Renu Pandey, Jennifer Chiou, John Floyd, Prathiba Surapreneni, Virginia Kaklamani, Kate Lathrop, Richard Crownover, Stefano Tiziani
Journal: Cancer Research (2021)

Abstract BACKGROUND: Sacituzumab Govitecan (SG, TRODELVY™) is an FDA approved antibody drug conjugate for treatment of metastatic triple negative breast cancer (TNBC). SG has payload and linker characteristics preferable for CNS delivery including a pH hydrolysable, a payload (SN-38) that is the active 1000-fold more potent than the parent compound CPT-11 and crosses the blood brain barrier. Our preliminary data showed SG activity in intracranial xenografts leading to our hypothesis that SG would achieve concentration of SN-38 within the breast cancer brain metastases (BCBM) that would be therapeutically relevant. METHODS: We undertook a single center, prospective, window of opportunity trial (NCT03995706) to examine the concentrations of SG, SN-38, and SN-38G in tumors patients undergoing craniotomy for BCBM (n=20) or recurrent glioblastoma (rGBM, n=10). A single dose of SG was administered at 10mg/kg IV the day prior to craniotomy. Tumor was collected and [SN-38] was analyzed via mass spectrometry (UHPLC-HRMS). following recovery patients resumed SG at 10mg/kg IV days 1 and 8 of 21 day cycle and were assessed for response or progression every third cycle by MRI. RESULTS: To date 21 patients have been treated, including 11 BCBM and 10 rGBM. UHPLC-HRMS analysis was performed in the first 10 tumors (n=4 and 6 respectively). For BCBM, total concentration of SN-38 varied from 173nM to 1160nM, with a mean concentration of 626nM. All GBM patients had residual measurable disease and 4 breast patients had measurable disease. With a median follow-up of 12 weeks from the first postoperative cycle in the first 14 patients, 2 partial responses from each group were observed (ORR of 28% and 50% at 12 weeks respectively). Updated results will be presented. CONCLUSIONS: SG achieves therapeutically relevant concentrations of SN-38 at 150-fold mean IC50s for BCBM. Early intracranial responses are encouraging and merit further evaluation. A multi-center trial of SG for HER2 negative BCBM (SWOG S2007) will be enrolling soon. Citation Format: Andrew J Brenner, Renu Pandey, Jennifer Chiou, John Floyd, Prathiba Surapreneni, Virginia Kaklamani, Kate Lathrop, Richard Crownover, Stefano Tiziani. Delivery and activity of SN-38 by sacituzumab govitecan in breast cancer brain metastases [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD13-05.
Abstract 15461: Outcomes of Cardiac Contractility Modulation: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Akshay Goel, Fuad Habash, Marwan Saad, Karam Ayoub, Srikanth Vallurupalli, Waddah Maskoun
Journal: Circulation (2018)

Background: Cardiac contractility modulation (CCM) is a promising device therapy for heart failure (HF) patients with reduced ejection fraction and narrow QRS. However, outcomes have varied among d...
Protective Role of Collectin 11 in a Mouse Model of Rheumatoid Arthritis
Authors: Na Wang, Weiju Wu, Cui Qiang, Ning Ma, Kunyi Wu, Dan Liu, Jia‐Xing Wang, Xiao Yang, Li Xue, Teng‐Yue Diao, Jia‐Yu Liu, Ang Li, Baojun Zhang, Zong‐Fang Li, Conrad A. Farrar, Nirmal K. Banda, Rafael Bayarri‐Olmos, Peter Garred, Wuding Zhou, Ke Li
Journal: Arthritis & Rheumatology (2021)

Collectin 11 (CL-11) is a soluble C-type lectin, a mediator of innate immunity. Its role in autoimmune disorders is unknown. We undertook this study to determine the role of CL-11 in a mouse model of rheumatoid arthritis (RA).A murine collagen-induced arthritis (CIA) model was used and combined two approaches, including gene deletion of Colec11 and treatment with recombinant CL-11 (rCL-11). Joint inflammation and tissue destruction, circulating levels of inflammatory cytokines, and adaptive immune responses were assessed in mice with CIA. Splenic CD11c+ cells were used to examine the influence of CL-11 on antigen-presenting cell (APC) function. Serum CL-11 levels in RA patients were also examined.Colec11-/- mice developed more severe arthritis than wild-type mice, as determined by disease incidence, clinical arthritis scores, and histopathology (P < 0.05). Disease severity was associated with significantly enhanced APC activation, Th1/Th17 responses, pathogenic IgG2a production and joint inflammation, as well as elevated circulating levels of inflammatory cytokines. In vitro analysis of CD11c+ cells revealed that CL-11 is critical for suppression of APC activation and function. Pharmacologic treatment of mice with rCL-11 reduced the severity of CIA in mice. Analysis of human blood samples revealed that serum CL-11 levels were lower in RA patients (n = 51) compared to healthy controls (n = 53). Reduction in serum CL-11 was inversely associated with the Disease Activity Score in 28 joints, erythrocyte sedimentation rate, and C-reactive protein level (P < 0.05).Our findings demonstrate a novel role of CL-11 in protection against RA, suggesting that the underlying mechanism involves suppression of APC activation and subsequent T cell responses.
Approval and Coverage of Cancer Drugs in England, Canada, and the US
Authors: Vinay Prasad, Myung S. Kim
Journal: JAMA Internal Medicine (2021)

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MERS-CoV and SARS-CoV-2 replication can be inhibited by targeting the interaction between the viral spike protein and the nucleocapsid protein
Authors: Byoung Kwon Park, Jinsoo Kim, Sangkyu Park, Dongbum Kim, Minyoung Kim, Kyeongbin Baek, Joon-Yong Bae, Man-Seong Park, Won-Keun Kim, Younghee Lee, Hyung-Joo Kwon
Journal: Theranostics (2021)

Background:The molecular interactions between viral proteins form the basis of virus production and can be used to develop strategies against virus infection.The interactions of the envelope proteins and the viral RNA-binding nucleocapsid (N) protein are essential for the assembly of coronaviruses including the Middle East respiratory syndrome coronavirus (MERS-CoV).Methods: Using co-immunoprecipitation, immunostaining, and proteomics analysis, we identified a protein interacting with the spike (S) protein in the cells infected with MERS-CoV or SARS-CoV-2.To confirm the interaction, synthetic peptides corresponding to the C-terminal domain of the S protein (Spike CD) were produced and their effect on the interaction was investigated in vitro.In vivo effect of the Spike CD peptides after cell penetration was further investigated using viral plaque formation assay.Phylogeographic analyses were conducted to deduce homology of Spike CDs and N proteins.Results: We identified a direct interaction between the S protein and the N protein of MERS-CoV that takes place during virus assembly in infected cells.Spike CD peptides of MERS-CoV inhibited the interaction between the S and N proteins in vitro.Furthermore, cell penetration by the synthetic Spike CD peptides inhibited viral plaque formation in MERS-CoV-infected cells.Phylogeographic analyses of Spike CDs and N proteins showed high homology among betacoronavirus lineage C strains.To determine if Spike CD peptides can inhibit the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we used the same strategy and found that the SARS-CoV-2 Spike CD peptide inhibited virus replication in SARS-CoV-2-infected cells.Conclusions: We suggest that the interaction between the S protein and the N protein can be targeted to design new therapeutics against emerging coronaviruses, including SARS-CoV-2.
Global Patterns of Recombination across Human Viruses
Authors: Juan Ángel Patiño-Galindo, Ioan Filip, Raul Rabadan
Journal: Molecular Biology and Evolution (2021)

Viral recombination is a major evolutionary mechanism driving adaptation processes, such as the ability of host-switching. Understanding global patterns of recombination could help to identify underlying mechanisms and to evaluate the potential risks of rapid adaptation. Conventional approaches (e.g., those based on linkage disequilibrium) are computationally demanding or even intractable when sequence alignments include hundreds of sequences, common in viral data sets. We present a comprehensive analysis of recombination across 30 genomic alignments from viruses infecting humans. In order to scale the analysis and avoid the computational limitations of conventional approaches, we apply newly developed topological data analysis methods able to infer recombination rates for large data sets. We show that viruses, such as ZEBOV and MARV, consistently displayed low levels of recombination, whereas high levels of recombination were observed in Sarbecoviruses, HBV, HEV, Rhinovirus A, and HIV. We observe that recombination is more common in positive single-stranded RNA viruses than in negatively single-stranded RNA ones. Interestingly, the comparison across multiple viruses suggests an inverse correlation between genome length and recombination rate. Positional analyses of recombination breakpoints along viral genomes, combined with our approach, detected at least 39 nonuniform patterns of recombination (i.e., cold or hotspots) in 18 viral groups. Among these, noteworthy hotspots are found in MERS-CoV and Sarbecoviruses (at spike, Nucleocapsid and ORF8). In summary, we have developed a fast pipeline to measure recombination that, combined with other approaches, has allowed us to find both common and lineage-specific patterns of recombination among viruses with potential relevance in viral adaptation.
ACE2 Elevation in Severe COVID-19
Authors: Roman Reindl-Schwaighofer, Sebastian Hödlmoser, Farsad Eskandary, Marko Poglitsch, Diana Bonderman, Robert Strassl, Judith H. Aberle, Rainer Oberbauer, Alexander Zoufaly, Manfred Hecking
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
Genetic susceptibility, elevated blood pressure, and risk of atrial fibrillation: a Mendelian randomization study
Authors: Milad Nazarzadeh, Ana-Catarina Pinho-Gomes, Zeinab Bidel, Dexter Canoy, Abbas Dehghan, Karl Smith Byrne, Derrick A. Bennett, George Davey Smith, Kazem Rahimi
Journal: Genome Medicine (2021)

Abstract Background Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual’s genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. Methods First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a population of one million Europeans in total. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. Results The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mmHg [OR] 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease. Conclusions The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF.
Acute myeloid leukemia: current progress and future directions
Authors: Hagop Kantarjian, Tapan Kadia, Courtney DiNardo, Naval Daver, Gautam Borthakur, Elias Jabbour, Guillermo Garcia-Manero, Marina Konopleva, Farhad Ravandi
Journal: Blood Cancer Journal (2021)

Abstract Progress in the understanding of the biology and therapy of acute myeloid leukemia (AML) is occurring rapidly. Since 2017, nine agents have been approved for various indications in AML. These included several targeted therapies like venetoclax, FLT3 inhibitors, IDH inhibitors, and others. The management of AML is complicated, highlighting the need for expertise in order to deliver optimal therapy and achieve optimal outcomes. The multiple subentities in AML require very different therapies. In this review, we summarize the important pathophysiologies driving AML, review current therapies in standard practice, and address present and future research directions.