tbuckley/cabot-search huggingface dataset:
Reconsidering the management of patients with cancer with viral hepatitis in the era of immunotherapy
Authors: Dimitrios C Ziogas, Frosso Kostantinou, Evangelos Cholongitas, Amalia Anastasopoulou, Panagiotis Diamantopoulos, John Haanen, Helen Gogas
Journal: Journal for ImmunoTherapy of Cancer (2020)

In the evolving immune-oncology landscape, numerous patients with cancer are constantly treated with immune checkpoint inhibitors (ICPIs) but among them, only sporadic cases with pre-existing hepatitis B virus (HBV) and hepatitis C virus (HCV) are recorded. Despite the global dissemination of HBV and HCV infections, viral hepatitis-infected patients with cancer were traditionally excluded from ICPIs containing trials and current evidence is particularly limited in case reports, retrospective cohort studies and in few clinical trials on advanced hepatocellular carcinoma. Thus, many concerns still remain about the overall oncological management of this special subpopulation, including questions about the efficacy, toxicity and reactivation risks induced by ICPIs. Here, we examine the natural course of both HBV and HCV in cancer environment, review the latest antiviral guidelines for patients undergoing systematic cancer therapies, estimating treatment-related immunosuppression and relocate immunotherapy in this therapeutic panel. Among the ICPIs-treated cases with prior viral hepatitis, we focus further on those experienced HBV or HCV reactivation and discuss their host, tumor and serological risk factors, their antiviral and immunological management as well as their hepatitis and tumor outcome. Based on a low level of evidence, immunotherapy in these specific cancer cases seems to be associated with no inferior efficacy and with a relevantly low reactivation rate. However, hepatitis reactivation and subsequent irreversible complications appeared to have poor response to deferred antiviral treatment. While, the prophylactic use of modern antiviral drugs could eliminate or diminish up front the viral load in most cases, leading to cure or long-term hepatitis control. Taking together the clinical significance of preventive therapy, the low but existing reactivation risk and the potential immune-related hepatotoxicity, a comprehensive baseline assessment of liver status, including viral hepatitis screening, before the onset of immunotherapy should be suggested as a reasonable and maybe cost-effective strategy but the decision to administer ICPIs and the necessity of prophylaxis should always be weighed at a multidisciplinary level and be individualized in each case, up to be established by future clinical trials.
Effectiveness of Deep Sedation for Patients With Intractable Electrical Storm Refractory to Antiarrhythmic Drugs
Authors: Raphaël P. Martins, Jean-Marie Urien, Nicolas Barbarot, Guillaume Rieul, Jean-Marc Sellal, Lionel Borella, Nicolas Clementy, Arnaud Bisson, Charles Guenancia, Audrey Sagnard, Stéphane Schumacher, Estelle Gandjbakhch, Josselin Duchateau, Romain Tixier, Angélique Goepp, David Hamon, Nicolas Lellouche, Laure Champ-Rigot, Paul Milliez, Eloi Marijon, Emilie Varlet, Rodrigue Garcia, Bruno Degand, Pierre Bouju, Philippe Mabo, Christophe Leclercq, Nathalie Behar, Dominique Pavin, Christian de Chillou, Frédéric Sacher, Vincent Galand
Journal: Circulation (2020)
Gene Editing of TRAC Locus Utilizing Megatal Nucleases Increases Expression of Transgenic TCRs Delivered Via Lentiviral Vector-Mediated Gene Transfer
Authors: Michael S Magee, Iulia Diaconu, Mark Pogson, Ankit Gupta, Amy Jensen-Smith, Brian Collette, Andrew Chavkin, Eli Pasackow, Aaron Edwards, Kevin M. Friedman, Alexander Astrakhan, Michael T Certo, Jordan Jarjour, Richard A. Morgan
Journal: Blood (2017)
Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study
Authors: Lena M.S. Carlsson, Kajsa Sjöholm, Peter Jacobson, Johanna C. Andersson-Assarsson, Per-Arne Svensson, Magdalena Taube, Björn Carlsson, Markku Peltonen
Journal: New England Journal of Medicine (2020)

Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. (Funded by the Swedish Research Council and others; SOS ClinicalTrials.gov number, NCT01479452.).
Prognostic Utility of Right Ventricular Remodeling Over Conventional Risk Stratification in Patients With COVID-19
Authors: Jiwon Kim, Alexander Volodarskiy, Razia Sultana, Meridith P. Pollie, Brian Yum, Lakshmi Nambiar, Romina Tafreshi, Hannah W. Mitlak, Arindam RoyChoudhury, Evelyn M. Horn, Ingrid Hriljac, Nupoor Narula, Sijun Kim, Lishomwa Ndhlovu, Parag Goyal, Monika M. Safford, Leslee Shaw, Richard B. Devereux, Jonathan W. Weinsaft
Journal: Journal of the American College of Cardiology (2020)
Abstract 13146: Natural Compounds for the Prevention and Treatment of Cardiac Fibrosis and Diastolic Dysfunction
Authors: Katharina Schimmel, Gorka San Jose, Javier Beaumont, Ke Xiao, Christian Baer, Quoc-Tuan Do, Robert Geffers, Jan Hinrich Bräsen, Nicola Wilck, Volkhard Kaever, Sandor Batkai, Jan Fiedler, Ronglih Liao, Javier Diez, Arantxa González, Thomas Thum
Journal: Circulation (2018)

Introduction: Adverse extracellular matrix remodeling following hypertension is mainly attributed to activation of cardiac fibroblasts, leading to myocardial stiffening with concomitant decline of ...
Editor's Note: Overexpression of Aurora-A Contributes to Malignant Development of Human Esophageal Squamous Cell Carcinoma
Authors: Tong Tong, Yali Zhong, Jianping Kong, Lijia Dong, Yongmei Song, Ming Fu, Zhihua Liu, Mingrong Wang, Liping Guo, Shixin Lu, Ming Wu, Qimin Zhan
Journal: Clinical Cancer Research (2020)

The editors are publishing this note to alert readers to an error in [this article][1] ([1][2]): the article text and Table 1 state that there were 64 clinical tumor specimens. The correct number of specimens is 65.

1.  1.[↵][3]1.  Tong T,     2.  Zhong Y,     3.  Kong J,     4.  Dong L,
Linked Color Imaging Focused on Neoplasm Detection in the Upper Gastrointestinal Tract
Authors: Shoko Ono, Kenro Kawada, Osamu Dohi, Shinji Kitamura, Tomoyuki Koike, Shinichiro Hori, Hiromitsu Kanzaki, Takahisa Murao, Nobuaki Yagi, Fumisato Sasaki, Keiichi Hashiguchi, Shiro Oka, Kazuhiro Katada, Ryo Shimoda, Kazuhiro Mizukami, Mitsuhiko Suehiro, Toshihisa Takeuchi, Shinichi Katsuki, Momoko Tsuda, Yuji Naito, Tatsuyuki Kawano, Ken Haruma, Hideki Ishikawa, Keita Mori, Mototsugu Kato
Journal: Annals of Internal Medicine (2020)

Background: Linked color imaging (LCI) is a new image-enhanced endoscopy technique that allows users to recognize slight differences in mucosal color. Objective: To compare the performance of LCI with white light imaging (WLI) in detecting neoplastic lesions in the upper gastrointestinal tract. Design: A controlled, multicenter trial with randomization using minimization. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000023863) Setting: 16 university hospitals and 3 tertiary care hospitals in Japan. Patients: 1502 patients with known previous or current cancer of the gastrointestinal tract and undergoing surveillance for gastrointestinal cancer. Intervention: WLI followed by LCI examination (WLI group) or LCI followed by WLI examination (LCI group). Measurements: Diagnosis of 1 or more neoplastic lesions in the pharynx, esophagus, or stomach in the first examination (primary outcome) and 1 or more neoplastic lesions overlooked in the first examination (secondary outcome). Results: 752 patients were assigned to the WLI group and 750 to the LCI group. The percentage of patients with 1 or more neoplastic lesions diagnosed in the first examination was higher with LCI than with WLI (60 of 750 patients or 8.0% [95% CI, 6.2% to 10.2%] vs. 36 of 752 patients or 4.8% [CI, 3.4% to 6.6%]; risk ratio, 1.67 [CI, 1.12 to 2.50; P = 0.011]). The proportion with overlooked neoplasms was lower in the LCI group than in the WLI group (5 of 750 patients or 0.67% [CI, 0.2% to 1.6%] vs. 26 of 752 patients or 3.5% [CI, 2.3% to 5.0%]; risk ratio, 0.19 [CI, 0.07 to 0.50]). Limitation: Endoscopists were not blinded. Conclusion: LCI is more effective than WLI for detecting neoplastic lesions in the pharynx, esophagus, and stomach. Primary Funding Source: Fujifilm Corporation.
Performance of prediction models for COVID-19: the Caudine Forks of the external validation
Authors: Glen P. Martin, Matthew Sperrin, Giovanni Sotgiu
Journal: European Respiratory Journal (2020)

Healthcare systems worldwide have observed significant changes to meet demands due to the coronavirus disease 2019 (COVID-19) pandemic. The uncertainty surrounding optimal treatment, the rapid public health urgency and clinical emergencies have caused a chaotic disruption of the cases and their related contacts at inpatient and outpatient settings. Developing more tailored healthcare plans based on the currently available scientific evidence, could help improve clinical efficacy, treatment outcomes, prognosis, and health efficiency. Existing evidence suggests that none of the COVID -19 prediction models can be supported for clinical use. Here we discuss "what next" in COVID-19 prediction. <https://bit.ly/2SMtoLV>
Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers
Authors: Elisabetta Zucchi, Valentina Bonetto, Gianni Sorarù, Ilaria Martinelli, Piero Parchi, Rocco Liguori, Jessica Mandrioli
Journal: Molecular Neurodegeneration (2020)

Abstract Motor neuron diseases (MNDs) are etiologically and biologically heterogeneous diseases. The pathobiology of motor neuron degeneration is still largely unknown, and no effective therapy is available. Heterogeneity and lack of specific disease biomarkers have been appointed as leading reasons for past clinical trial failure, and biomarker discovery is pivotal in today’s MND research agenda. In the last decade, neurofilaments (NFs) have emerged as promising biomarkers for the clinical assessment of neurodegeneration. NFs are scaffolding proteins with predominant structural functions contributing to the axonal cytoskeleton of myelinated axons. NFs are released in CSF and peripheral blood as a consequence of axonal degeneration, irrespective of the primary causal event. Due to the current availability of highly-sensitive automated technologies capable of precisely quantify proteins in biofluids in the femtomolar range, it is now possible to reliably measure NFs not only in CSF but also in blood. In this review, we will discuss how NFs are impacting research and clinical management in ALS and other MNDs. Besides contributing to the diagnosis at early stages by differentiating between MNDs with different clinical evolution and severity, NFs may provide a useful tool for the early enrolment of patients in clinical trials. Due to their stability across the disease, NFs convey prognostic information and, on a larger scale, help to stratify patients in homogenous groups. Shortcomings of NFs assessment in biofluids will also be discussed according to the available literature in the attempt to predict the most appropriate use of the biomarker in the MND clinic.
Development of CAR T Cells Expressing a Suicide Gene Plus a Chimeric Antigen Receptor Targeting Signaling Lymphocytic-Activation Molecule F7
Authors: Christina Amatya, Melissa A. Pegues, Norris Lam, Danielle Vanasse, Claudia Geldres, Stephanie Choi, Stephen M. Hewitt, Steven A. Feldman, James N. Kochenderfer
Journal: Molecular Therapy (2020)

Chimeric antigen receptors (CARs) are fusion proteins that contain antigen-recognition domains and T cell signaling domains. Signaling lymphocytic-activation molecule F7 (SLAMF7) is a promising target for CAR T cell therapies of the plasma cell malignancy multiple myeloma (MM) because SLAMF7 is expressed by MM but not normal nonhematopoietic cells. We designed CARs targeting SLAMF7. We transduced human T cells with anti-SLAMF7 CARs containing either CD28 or 4-1BB costimulatory domains. T cells expressing CD28-containing CARs or 4-1BB-containing CARs recognized SLAMF7 in vitro. SLAMF7-specific cytokine release was higher for T cells expressing CARs with CD28 versus 4-1BB domains. In murine solid tumor and disseminated tumor models, anti-tumor activity of T cells was superior with CD28-containing CARs versus 4-1BB-containing CARs. Because of SLAMF7 expression on some normal leukocytes, especially natural killer cells that control certain viral infections, the inclusion of a suicide gene with an anti-SLAMF7 CAR is prudent. We designed a construct with a CD28-containing anti-SLAMF7 CAR and a suicide gene. The suicide gene encoded a dimerization domain fused to a caspase-9 domain. T cells expressing the anti-SLAMF7 CAR plus suicide-gene construct specifically recognized SLAMF7 in vitro and eliminated tumors from mice. T cells expressing this construct were eliminated on demand by administering the dimerizing agent AP1903 (rimiducid).
Sensible Medicine—Balancing Intervention and Inaction During the COVID-19 Pandemic
Authors: Christopher W. Seymour, Erin K. McCreary, Jacob Stegenga
Journal: JAMA (2020)

Sensible Medicine-Balancing Intervention and Inaction During the COVID-19 PandemicMore than 38 million people worldwide have been infected with the severe acute respiratory syndrome (SARS) coronavirus 2, creating intense pressure on clinicians to offer state-of-the-art, life-saving treatment to patients. 1 The conundrum is that few effective treatments are available, and among those treatments tested in clinical trials, even fewer have demonstrated benefit compared with no treatment.Treating patients with coronavirus disease 2019 (COVID-19) is challenging, and clinicians encounter harrowing emergencies in the intensive care unit where, early during the pandemic, 1 in 4 critically ill patients with severe COVID-19 died. 2 The natural response at the bedside of a patient with COVID-19 is to act and to act decisively. 3Imbued with determination, clinicians seek to make a difference for patients who are seriously ill.In 2012, Taleb 4 described an "illusion of control that leads to a default to action rather than inaction."For many medical emergencies, such as cardiac arrest, pulmonary embolism, or tension pneumothorax, this illusion is a reality for clinicians because immediate intervention can prevent avoidable death.But what if it is unclear what to do?What if no medication or device will lead to a cure?Should clinicians do VIEWPOINT
MYC Translocations Identified By Sequencing Panel in Smoldering Multiple Myeloma Strongly Predict for Rapid Progression to Multiple Myeloma
Authors: Niamh Keane, Caleb K Stein, Daniel Angelov, Shulan Tian, David Viswanatha, Shaji K Kumar, Angela Dispenzieri, Veronica Gonzalez De La Calle, Kristine Misund, Robert A Kyle, Michael E O'Dwyer, Rafael Fonseca, A. Keith Stewart, Esteban Braggio, Yan Asmann, S. Vincent Rajkumar, P. Leif Bergsagel
Journal: Blood (2017)
Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial
Authors: Shengli Xia, Yuntao Zhang, Yanxia Wang, Hui Wang, Yunkai Yang, George Fu Gao, Wenjie Tan, Guizhen Wu, Miao Xu, Zhiyong Lou, Weijin Huang, Wenbo Xu, Baoying Huang, Huijuan Wang, Wei Wang, Wei Zhang, Na Li, Zhiqiang Xie, Ling Ding, Wangyang You, Yuxiu Zhao, Xuqin Yang, Yang Liu, Qian Wang, Lili Huang, Yongli Yang, Guangxue Xu, Bojian Luo, Wenling Wang, Peipei Liu, Wanshen Guo, Xiaoming Yang
Journal: The Lancet Infectious Diseases (2020)
AODTU-010 Ileal inflammation at the resection margin is associated with an increased risk of recurrence of post-operative ileal crohn’s disease over a 10-year follow up
Authors: I Hay, L Lynch, E Saffouri, D Watts
Journal: Gut (2017)

Introduction  Crohn’s disease recurrence following ileocolonic resection is a well-recognised clinical complication of surgical management. Studies report conflicting data regarding the preventive efficacy of immunomodulatory therapy, and there is no accepted standard of postoperative treatment. Identifying risk factors for postoperative disease recurrence may allow an opportunity to treat high-risk patients effectively. Ileal inflammation at the surgical resection margin may be such a risk factor for disease recurrence but there is little published data to support this.  Method  We undertook a retrospective review of ileal marginal histology for all ileocolonic resections for Crohns disease in Forth Valley from 2005 – 2012. The data was correlated to radiological and endoscopic outcomes. Chi-squared statistical analysis was undertaken across the groups with no marginal disease against those with evidence of ileal marginal disease activity.  Results  69 patients were seen to have no evidence of ileal marginal disease at resection. Of these, 23 developed recurrent ileal disease over 10 year follow up. This contrasts with a significantly higher rate of relapse in those with ileal inflammtory disease at the resection margin, in whom 18/27 patients developed post-operative disease recurrence (p=0.003).  Conclusion  This study confirms that the rate of postoperative disease recurrence is higher in those patients with inflammatory disease activity at the ileal resection margin at index surgery (follow up 3–10 years). There is a significant difference in relapse rates between the two groups, where disease recurrence is defined by evidence of inflammation at either postoperative MRE or colonoscopy, or both. Validation by larger studies is required but may allow the identification of a new cohort of Crohn’s patients with a higher risk of post-operative disease relapse in whom targeted immunomodulatory therapy might be justified.  Disclosure of Interest  None Declared
Pervasive intra-tumour heterogeneity and subclonal selection across cancer types
Authors: Stefan Dentro, Ignaty Leshchiner, Kerstin Haase, Jeff Wintersinger, Amit Deshwar, Maxime Tarabichi, Yulia Rubanova, Kaixian Yu, Ignacio Vazquez Garcia, Geoff Macintyre, Kortine Kleinheinz, Dimitri Livitz, Salem Malikic, Nilgun Donmez, Subhajit Sengupta, Yuan Ji, Jonas Demeulemeester, Pavana Anur, Clemency Jolly, Marek Cmero, Daniel Rosebrock, Steve Schumacher, Yu Fan, Matthew Fittall, Xiaotong Yao, Juhee Lee, Matthias Schlesner, Hongtu Zhu, David Adams, Gad Getz, Paul Boutros, Marcin Imielinski, Rameen Beroukhim, Cenk Sahinalp, Martin Peifer, Inigo Martincorena, Florian Markowetz, Ville Mustonen, Ke Yuan, Moritz Gerstung, Wenyi Wang, Paul Spellman, Quaid Morris, David Wedge, Peter Van Loo
Journal: Cancer Research (2018)
Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma
Authors: Anusha Kalbasi, Mito Tariveranmoshabad, Kevin Hakimi, Sarah Kremer, Katie M. Campbell, Juan M. Funes, Agustin Vega-Crespo, Giulia Parisi, Ameya Champekar, Christine Nguyen, Davis Torrejon, Daniel Shin, Jesse M. Zaretsky, Robert D. Damoiseaux, Daniel E. Speiser, Pedro P. Lopez-Casas, Marisol Quintero, Antoni Ribas
Journal: Science Translational Medicine (2020)

Interferon-independent MHC class I induction restores T cell immunity.
Covid-19’s known unknowns
Authors: George Davey Smith, Michael Blastland, Marcus Munafò
Journal: BMJ (2020)

<h3>Background</h3> A fall-height threshold is important when evaluating the likelihood of structural head injury or abusive head trauma. This study investigates witnessed falls to correlate the fall characteristics with the extent of injury. <h3>Method</h3> Case–control study of children aged ≤48 months who attended one hospital following a fall from &lt;3 m (10 ft), comparing cases who sustained a skull fracture or intracranial injury (ICI) with controls, who had minor head injuries. Characteristics included: the mechanism of injury, surface of impact, site of impact to the head and fall height. <h3>Results</h3> Forty-seven children had a skull fracture or ICI, while 416 children had minor head injuries. The mean fall height for minor head injuries was significantly lower than that causing skull fracture/ICI (p&lt;0.001). No skull fracture/ICI was recorded in children who fell &lt;0.6 m (2 ft), based on the height of the head centre of gravity. Skull fractures/ICI were more likely in children aged ≤12 months (p&lt;0.001) from impacts to the temporal/parietal or occipital region (p&lt;0.001), impacts onto wood (p=0.004) and falls from a carer9s arms, particularly when on stairs (p&lt;0.001). No significant difference was reported between the mean fall heights of children who had a simple skull fracture (n=17) versus those who had a complex fracture or ICI (n=30). <h3>Conclusions</h3> An infant is more likely to sustain a skull fracture/ICI from a fall above a 0.6 m (2 ft) threshold, based on the height of the head centre of gravity, or with a parietal/temporal or occipital impact. These variables should be recorded when evaluating the likelihood of skull fracture/ICI.
Current Advances on 3D‐Bioprinted Liver Tissue Models
Authors: Liang Ma, Yutong Wu, Yuting Li, Abdellah Aazmi, Hongzhao Zhou, Bin Zhang, Huayong Yang
Journal: Advanced Healthcare Materials (2020)

Abstract The liver, the largest gland in the human body, plays a key role in metabolism, bile production, detoxification, and water and electrolyte regulation. The toxins or drugs that the gastrointestinal system absorbs reach the liver first before entering the bloodstream. Liver disease is one of the leading causes of death worldwide. Therefore, an in vitro liver tissue model that reproduces the main functions of the liver can be a reliable platform for investigating liver diseases and developing new drugs. In addition, the limitations in traditional, planar monolayer cell cultures and animal tests for evaluating the toxicity and efficacy of drug candidates can be overcome. Currently, the newly emerging 3D bioprinting technologies have the ability to construct in vitro liver tissue models both in static scaffolds and dynamic liver‐on‐chip manners. This review mainly focuses on the construction and applications of liver tissue models based on 3D bioprinting. Special attention is given to 3D bioprinting strategies and bioinks for constructing liver tissue models including the cell sources and hydrogel selection. In addition, the main advantages and limitations and the major challenges and future perspectives are discussed, paving the way for the next generation of in vitro liver tissue models.