tbuckley/cabot-search huggingface dataset:
Clinical outcomes following DAA therapy in patients with HCV-related cirrhosis depend on disease severity
Authors: Lisette A.P. Krassenburg, Raoel Maan, Alnoor Ramji, Michael P. Manns, Markus Cornberg, Heiner Wedemeyer, Robert J. de Knegt, Bettina E. Hansen, Harry L.A. Janssen, Robert A. de Man, Jordan J. Feld, Adriaan J. van der Meer
Journal: Journal of Hepatology (2020)

HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score.Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death.In total, 868 patients were included with a median age of 59 (IQR 54-65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20-36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27-0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67-2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7-67.1 vs. 48.9%; 95% CI 38.1-59.7, respectively, p = 0.99).Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome.Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.
Integrated molecular drivers coordinate biological and clinical states in melanoma
Authors: Jake R. Conway, Felix Dietlein, Amaro Taylor-Weiner, Saud AlDubayan, Natalie Vokes, Tanya Keenan, Brendan Reardon, Meng Xiao He, Claire A. Margolis, Jason L. Weirather, Rizwan Haq, Bastian Schilling, F. Stephen Hodi, Dirk Schadendorf, David Liu, Eliezer M. Van Allen
Journal: Nature Genetics (2020)
16481 Sunscreens (SPF15) provide sun protection (UVA+UVB) as well as prevent formation of free radicals and skin darkening better than vitamin C
Authors: None Mruthunjaya, S. Pavithra, Satish Kumar, Ashish Vaidya, Praful Lahorkar, Rajkumar Perumal, Manoj Misra, Savitha Rajkumar, Arindam Roy, Sudipta Ghoshdastidar, Surendra Nagalakshmi
Journal: Journal of the American Academy of Dermatology (2020)
16346 Peak Pruritus Numeric Rating Scale response with abrocitinib in patients with moderate to severe atopic dermatitis: Results from a randomized phase 3 clinical trial
Authors: Eric L. Simpson, Sonja Ständer, Gil Yosipovitch, Michael C. Cameron, Marco DiBonaventura, David Williams, Svitlana Tatulych, Chudy Nduaka, Hernan Valdez
Journal: Journal of the American Academy of Dermatology (2020)
Head and neck squamous cell carcinoma
Authors: Daniel E. Johnson, Barbara Burtness, C. René Leemans, Vivian Wai Yan Lui, Julie E. Bauman, Jennifer R. Grandis
Journal: Nature Reviews Disease Primers (2020)

Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative and HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent pre-malignant lesion. Traditional staging of HNSCC using the tumour–node–metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment is generally multimodal, consisting of surgery followed by chemoradiotherapy (CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where comorbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least-toxic therapies. Head and neck squamous cell carcinomas (HNSCCs) originate from the mucosal epithelium in the oral cavity, pharynx and larynx and are commonly associated with viral infection and tobacco use. This Primer provides an overview of the epidemiology, pathogenesis and treatment of HNSCCs of different aetiologies and the effects of the cancer and its treatment on patient quality of life.
Abstract 13437: Thromboembolic and Bleeding Risks in Acute Myocardial Infarction Patients With Cancer Who Received Drug-Eluting Stent Implantation and Dual-Antiplatelet Therapy
Authors: Hiroya Hayashi, Yu Kataoka, Hayato Hosoda, Takahiro Nakashima, Satoshi Honda, Masashi Fujino, Kazuhiro Nakao, Shuichi Yoneda, Fumiyuki Otsuka, Yasuhide Asaumi, Teruo Noguchi, Minoru Yoshiyama, Satoshi Yasuda
Journal: Circulation (2019)

Introduction: The number of patients with cancer who present for cardiovascular disease has been increasing due to their improved survival rate. Since cancer induces hypercoagurable state and eleva...
IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors
Authors: Alessandra Nerviani, Marie-Astrid Boutet, Wang Sin Gina Tan, Katriona Goldmann, Nirupam Purkayastha, Tamas Ajtos Lajtos, Rebecca Hands, Myles Lewis, Stephen Kelly, Costantino Pitzalis
Journal: Annals of the Rheumatic Diseases (2020)

To determine the relationship between synovial versus skin transcriptional/histological profiles in patients with active psoriatic arthritis (PsA) and explore mechanistic links between diseased tissue pathology and clinical outcomes.Twenty-seven active PsA patients were enrolled in an observational/open-label study and underwent biopsies of synovium and paired lesional/non-lesional skin before starting anti-tumour necrosis factor (TNF) (if biologic-naïve) or ustekinumab (if anti-TNF inadequate responders). Molecular analysis of 80-inflammation-related genes and protein levels for interleukin (IL)-23p40/IL-23p19/IL-23R were assessed by real-time-PCR and immunohistochemistry, respectively.At baseline, all patients had persistent active disease as per inclusion criteria. At primary end-point (16-weeks post-treatment), skin responses favoured ustekinumab, while joint responses favoured anti-TNF therapies. Principal component analysis revealed distinct clustering of synovial tissue gene expression away from the matched skin. While IL12B, IL23A and IL23R were homogeneously expressed in lesional skin, their expression was extremely heterogeneous in paired synovial tissues. Here, IL-23 transcriptomic/protein expression was strongly linked to patients with high-grade synovitis who, however, were not distinguishable by conventional clinimetric measures.PsA synovial tissue shows a heterogeneous IL-23 axis profile when compared with matched skin. Synovial molecular pathology may help to identify among clinically indistinguishable patients those with a greater probability of responding to IL-23 inhibitors.
38P Evaluation of the prognostic value of innate immunity-related biomarkers in early breast cancer (BC)
Authors: V. Martini, F. D'Avanzo, F. Platini, M. Allesina, F. Favero, D. Corà, A. Rua, C. Saggia, V. Rossi, F.M. Varughese, P.M. Maggiora, D. Ferrante, R. Boldorini, A. Gennari
Journal: Annals of Oncology (2020)
Correspondence on: ‘EULAR definition of difficult-to-treat rheumatoid arthritis’
Authors: Marta Novella-Navarro, Chamaida Plasencia-Rodríguez, Carolina Tornero, Victoria Navarro-Compán, José Luis Cabrera-Alarcón, Diana Peiteado, Laura Nuño, Irene Monjo, Karen Franco-Gómez, Alejandro Villalba, Alejandro Balsa
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the publication entitled ‘EULAR definition of difficult-to-treat rheumatoid arthritis’, which sought not only to provide a uniform terminology, but also to formulate an adequate definition to classify those patients with difficult-to-treat rheumatoid arthritis (RA).1 Resolution of this issue promises to be very useful in clinical practice and in the design of studies for future research.

Our group has recently published a study based on the clinical factors that could serve as possible predictors for identifying those patients with RA who are more susceptible to multiple failures to biological therapy.2 This study was designed and conducted prior to the publication of this paper establishing the definition of difficult-to-treat RA. Based on previous works published on this concept,3–8 we defined ‘multi-refractory’ patients as those who have received ≥2 biologic disease-modifying antirheumatic drugs (bDMARDs) with different mechanism of action or ≥3 bDMARDs with the same target. This definition seemed to us the most appropriate option for the classification of difficult-to-treat patients in terms of drug use.

As the European League Against Rheumatism (EULAR) group of experts did, we did not include in our definition of multirefractory …
Target delivery of drug carriers in mice kidney glomeruli via renal artery. Balance between efficiency and safety
Authors: Ekaterina S. Prikhozhdenko, Olga I. Gusliakova, Oleg A. Kulikov, Oksana A. Mayorova, Natalia A. Shushunova, Arkady S. Abdurashitov, Daniil N. Bratashov, Nikolay A. Pyataev, Valery V. Tuchin, Dmitry A. Gorin, Gleb B. Sukhorukov, Olga A. Sindeeva
Journal: Journal of Controlled Release (2020)
Comprehensive analysis of cutaneous and uveal melanoma liver metastases
Authors: Esmee P Hoefsmit, Elisa A Rozeman, Trieu My Van, Petros Dimitriadis, Oscar Krijgsman, Jordan W Conway, Ines Pires da Silva, Jacqueline E van der Wal, Steven L C Ketelaars, Kaspar Bresser, Annegien Broeks, Ron M Kerkhoven, Jason W Reeves, Sarah Warren, Pia Kvistborg, Richard A Scolyer, Ellen W Kapiteijn, Daniel S Peeper, Georgina V Long, Ton N M Schumacher, Christian U Blank
Journal: Journal for ImmunoTherapy of Cancer (2020)

The profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB.Tumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level.Comparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases.While TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered.
Prefrontal Cortex Development in Health and Disease: Lessons from Rodents and Humans
Authors: Mattia Chini, Ileana L. Hanganu-Opatz
Journal: Trends in Neurosciences (2020)

The role of the prefrontal cortex (PFC) takes center stage among unanswered questions in modern neuroscience. The PFC has a Janus-faced nature: it enables sophisticated cognitive and social abilities that reach their maximum expression in humans, yet it underlies some of the devastating symptoms of psychiatric disorders. Accordingly, appropriate prefrontal development is crucial for many high-order cognitive abilities and dysregulation of this process has been linked to various neuropsychiatric diseases. Reviewing recent advances in the field, with a primary focus on rodents and humans, we highlight why, despite differences across species, a cross-species approach is a fruitful strategy for understanding prefrontal development. We briefly review the developmental contribution of molecules and extensively discuss how electrical activity controls the early maturation and wiring of prefrontal areas, as well as the emergence and refinement of input-output circuitry involved in cognitive processing. Finally, we highlight the mechanisms of developmental dysfunction and their relevance for psychiatric disorders.
Abstract PO-045: Multiplex analysis of coronavirus and influenza antibodies using the ZIVA multiplex platform
Authors: Jon Schmuke, Ben Miller, Linda Meeh, Byran Witherbee
Journal: Clinical Cancer Research (2020)

Abstract Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. We have used Arrayed Imaging Reflectometry (AIR™), a label-free protein microarray technology that relies on the target binding-induced perturbation of an antireflective coating on the surface of a silicon chip, to create a multiplex antibody detection array. ZIVA is a new multiplex protein detection platform that leverages AIR™ technology. We have used ZIVA technology to develop an acute respiratory virus panel capable of detecting the presence of antibodies specific for coronavirus and influenza including, but not limited to, detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43), and multiple strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects and provides quantitative information about total IgG, as well as IgG- and IgM-specific responses. Samples may also be evaluated with ZIVA cytokine assays to monitor the cytokine storm in conjunction with viral antibody response. Citation Format: Jon Schmuke, Ben Miller, Linda Meeh, Byran Witherbee. Multiplex analysis of coronavirus and influenza antibodies using the ZIVA multiplex platform [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-045.
Looking Into the Left Atrial Crystal Ball: A Ray of Hope for Patients With Organic Mitral Regurgitation**Editorials published in Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Robert A. Levine, Stanley Nattel
Journal: Journal of the American College of Cardiology (2010)
A Critical Review of the Social and Behavioral Contributions to the Overdose Epidemic
Authors: Magdalena Cerdá, Noa Krawczyk, Leah Hamilton, Kara E. Rudolph, Samuel R. Friedman, Katherine M. Keyes
Journal: Annual Review of Public Health (2020)

More than 750,000 people in the United States died from an overdose between 1999 and 2018; two-thirds of those deaths involved an opioid. In this review, we present trends in opioid overdose rates during this period and discuss how the proliferation of opioid prescribing to treat chronic pain, changes in the heroin and illegally manufactured opioid synthetics markets, and social factors, including deindustrialization and concentrated poverty, contributed to the rise of the overdose epidemic. We also examine how current policies implemented to address the overdose epidemic may have contributed to reducing prescription opioid overdoses but increased overdoses involving illegal opioids. Finally, we identify new directions for research to understand the causes and solutions to this critical public health problem, including research on heterogeneous policy effects across social groups, effective approaches to reduce overdoses of illegal opioids, and the role of social contexts in shaping policy implementation and impact.
Abstract 21074: Long-Term Clinical and Angiographical Outcomes in 25 Patients With Buerger’s Disease Treated With Endovascular Therapy
Authors: Yoonjee Park, Seung-Woon Rha, Ae-Young Her, Yong Hoon Kim, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Ahmed Mashaly, Won Young Jang, WooHyeun Kim, Jah Yeon Choi, Eun Jin Park, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Circulation (2017)

Background: Thromboangiitis Obliterans (TAO), commonly Buerger’s disease, is associated with high risk of adverse outcomes, particularly higher amputation rate despite all the effort. The role of endovascular therapy (EVT) in TAO has been questioned owing to the technically challenging distal distribution of lesions and high rate of restenosis. Methods: Among 765 consecutive patients (pts) with significant peripheral artery disease (PAD) who underwent endovascular therapy (EVT) from Jan 2004 to June 2016, we identified 25 patients diagnosed as TAO with critical limb ischemia (CLI) who underwent EVT . Various clinical, coronary and peripheral angiographic characteristics and 5-year clinical outcomes were examined. Results: The prevalence of TAO among PAD pts undergoing EVT was 3.27% (23 males; 3.86% and 1.18% among total male and female, respectively). The mean age was 48.6 ± 16.8 (SD) and 23 (92%) had a history of smoking. Pts commonly presented with lower limb wounds, gangrene, claudication, diabetic foot and resting pain in deceasing order [N(%): 15(60), 11(44), 9(36), 5(20) and 1(4)], with 77.4% of limbs higher than Rutherford grade 2. A total 25 pts, 31 limbs and 81 lesions were treated with stent or balloon angioplasty [24 (29.6%) and 53 (65.4%) lesions, respectively], achieving clinical success in 73 (90.1%) lesions. Over half lesions were chronic total occlusions (56, 69.1%) and distributed peripherally (Table). Although nearly half patients underwent repeated procedures, limb salvage was achieved in most patients after 5 years. Conclusion: TAO is known for its poor prognosis in terms of limb salvage and peripherally located lower extremity lesions which are technically difficult to approach. Our experience with 25 patients with 81 lesions show promising long-term limb salvage outcomes following repetitive EVT with optimal medical therapy.
Tau and other proteins found in Alzheimer’s disease spinal fluid are linked to retromer-mediated endosomal traffic in mice and humans
Authors: Sabrina Simoes, Jessica L. Neufeld, Gallen Triana-Baltzer, Setareh Moughadam, Emily I. Chen, Milankumar Kothiya, Yasir H. Qureshi, Vivek Patel, Lawrence S. Honig, Hartmuth Kolb, Scott A. Small
Journal: Science Translational Medicine (2020)

Endosomal secreted proteins can be detected in the CSF and inform on how Alzheimer’s defective trafficking pathway can contribute to disease spread.
Abstract 11666: Elevated Levels of Vap-1 in Carcinoid Heart Disease - A New Therapeutic Target?
Authors: Vandana M Sagar, Papakyriacou Pantelitsa, Tahir Shah, Desley Neil, Gideon Hirschfield, Shishir Shetty, Chris Weston, Richard P Steeds
Journal: Circulation (2018)

Introduction: Carcinoid heart disease (CHD) affects 20% of patients with carcinoid syndrome due to neuroendocrine tumours (NET). The characteristic finding of fibrotic plaques on valve leaflets, ch...
Rock 'n Roll Ventricle of the Dyssynchronous Heart: Clinical Significance of Rocking Motion in Selection of Patient for Cardiac Resynchronization Therapy⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Jae K. Oh, Chinami Miyazaki
Journal: JACC. Cardiovascular imaging (2009)