tbuckley/cabot-search huggingface dataset:
Emerging immunotherapies in multiple myeloma
Authors: Urvi A Shah, Sham Mailankody
Journal: BMJ (2020)

ABSTRACT Despite considerable advances in treatment approaches in the past two decades, multiple myeloma remains an incurable disease. Treatments for myeloma continue to evolve with many emerging immunotherapies. The first immunotherapy used to treat hematologic cancers, including multiple myeloma, was an allogeneic stem cell transplant. In the mid-2000s, immunomodulatory drugs thalidomide, lenalidomide, and subsequently pomalidomide were proven to be effective in multiple myeloma and substantially improved survival. The next wave of immunotherapies for multiple myeloma included the monoclonal antibodies daratumumab and elotuzumab, which were approved by the Food and Drug Administration in 2015. Subsequently, a variety of immunotherapies have been developed for multiple myeloma, including chimeric antigen receptor T cells, bispecific antibodies, antibody drug conjugates, and checkpoint inhibitors. Many of these emerging treatments target the B cell maturation antigen, which is expressed on plasma cells, although several other novel receptors are also being studied. This review summarizes the evidence of these various immunotherapies, their mechanism of action, and data from clinical trials regarding the treatments’ safety and efficacy.
Nanocellulose Sponges: Sponges with Janus Character from Nanocellulose: Preparation and Applications in the Treatment of Hemorrhagic Wounds (Adv. Healthcare Mater. 17/2020)
Authors: Huan Cheng, Dongdong Xiao, Yujing Tang, Bijia Wang, Xueling Feng, Mujun Lu, G. Julius Vancso, Xiaofeng Sui
Journal: Advanced Healthcare Materials (2020)

In article number 1901796 by Huan Cheng, G. Julius Vancso, Xiaofeng Sui, and co-workers, develop afacile method to fabricate sponges with Janus character, based on cellulose nanofibers, by integrating heterogeneous mixing and freeze-drying. The constructs are hydrophobic on their outside and show hydrophilic hemostasis at their facet in contact with wounds. The sponges exhibit an outstanding blood clotting performance and can also prolong survival time in the carotid artery injury model.
Attachment of Ultralow Amount of Engineered Plant Viral Nanoparticles to Mesenchymal Stem Cells Enhances Osteogenesis and Mineralization
Authors: Ying‐Ying Lin, Juliane Schuphan, Christina Dickmeis, Eva Miriam Buhl, Ulrich Commandeur, Horst Fischer
Journal: Advanced Healthcare Materials (2020)

Abstract Hydrogel‐based materials are widely used to mimic the extracellular matrix in bone tissue engineering, although they often lack biofunctional cues. In the authors' previous work, Potato virus X (PVX), a flexible rod‐shaped biocompatible plant virus nanoparticle (VNP) with 1270 coat protein subunits, is genetically modified to present functional peptides for generating a bone substitute. Here, PVX is engineered to present mineralization‐ and osteogenesis‐associated peptides and laden in hydrogels at a concentration lower by two orders of magnitude. Its competence in mineralization is demonstrated both on 2D surfaces and in hydrogels and the superiority of enriched peptides on VNPs is verified and compared with free peptides and VNPs presenting fewer functional peptides. Alkaline phosphatase activity and Alizarin red staining of human mesenchymal stem cells increase 1.2–1.7 times when stimulate by VNPs. Engineered PVX adheres to cells, exhibiting a stimulation of biomimetic peptides in close proximity to the cells. The retention of VNPs in hydrogels is monitored and more than 80% of VNPs remain inside after several washing steps. The mechanical properties of VNP‐laden hydrogels are investigated, including viscosity, gelling temperature, and compressive tangent modulus. This study demonstrates that recombinant PVX nanoparticles are excellent candidates for hydrogel nanocomposites in bone tissue engineering.
Pleiotropic actions of factor Xa inhibition in cardiovascular prevention: mechanistic insights and implications for anti-thrombotic treatment
Authors: Hugo ten Cate, Tomasz J Guzik, John Eikelboom, Henri M H Spronk
Journal: Cardiovascular Research (2020)

Atherosclerosis is a chronic inflammatory disease in which atherothrombotic complications lead to cardiovascular morbidity and mortality. At advanced stages, myocardial infarction, ischaemic stroke, and peripheral artery disease, including major adverse limb events, are caused either by acute occlusive atherothrombosis or by thromboembolism. Endothelial dysfunction, vascular smooth muscle cell activation, and vascular inflammation are essential in the development of acute cardiovascular events. Effects of the coagulation system on vascular biology extend beyond thrombosis. Under physiological conditions, coagulation proteases in blood are pivotal in maintaining haemostasis and vascular integrity. Under pathological conditions, including atherosclerosis, the same coagulation proteases (including factor Xa, factor VIIa, and thrombin) become drivers of atherothrombosis, working in concert with platelets and vessel wall components. While initially atherothrombosis was attributed primarily to platelets, recent advances indicate the critical role of fibrin clot and plasma coagulation factors. Mechanisms of atherothrombosis and hypercoagulability vary depending on plaque erosion or plaque rupture. In addition to contributing to thrombus formation, factor Xa and thrombin can affect endothelial dysfunction, oxidative stress, vascular smooth muscle cell function as well as immune cell activation and vascular inflammation. By these mechanisms, they promote atherosclerosis and contribute to plaque instability. In this review, we first discuss the postulated vasoprotective mechanisms of protease-activated receptor signalling induced by coagulation enzymes under physiological conditions. Next, we discuss preclinical studies linking coagulation with endothelial cell dysfunction, thromboinflammation, and atherogenesis. Understanding these mechanisms is pivotal for the introduction of novel strategies in cardiovascular prevention and therapy. We therefore translate these findings to clinical studies of direct oral anticoagulant drugs and discuss the potential relevance of dual pathway inhibition for atherothrombosis prevention and vascular protection.
Duties When an Anonymous Student Health Survey Finds a Hot Spot of Suicidality
Authors: Arnold H. Levinson, M. Franci Crepeau-Hobson, Marilyn E. Coors, Jacqueline J. Glover, Daniel S. Goldberg, Matthew K. Wynia
Journal: The American Journal of Bioethics (2020)

Public health agencies regularly survey randomly selected anonymous students to track drug use, sexual activities, and other risk behaviors. Students are unidentifiable, but a recent project that included school-level analysis discovered a school with alarmingly prevalent student suicidality. Given confidentiality protocols typical of surveillance, the surveyors were uncertain whether and how to intervene. We searched literature for duties to warn at-risk groups discovered during public health surveillance, but we found no directly applicable guidance or cases. Reasoning by analogy, we conclude that surveyors should contact the school’s leaders to call attention to its outlier status, but public warning is unwarranted. However, such an ad hoc decision to issue a warning, even if only to school leaders, raises significant practical, legal and ethical issues. National public health and education associations should produce guidance that clarifies ethical and legal duties owed to schools and students involved in population health-risk surveillance.
Human SIRT1 Multispecificity Is Modulated by Active-Site Vicinity Substitutions during Natural Evolution
Authors: Adi Hendler, Eyal Akiva, Mahakaran Sandhu, Dana Goldberg, Eyal Arbely, Colin J Jackson, Amir Aharoni
Journal: Molecular Biology and Evolution (2020)

Many enzymes that catalyze protein post-translational modifications can specifically modify multiple target proteins. However, little is known regarding the molecular basis and evolution of multispecificity in these enzymes. Here, we used a combined bioinformatics and experimental approaches to investigate the evolution of multispecificity in the sirtuin-1 (SIRT1) deacetylase. Guided by bioinformatics analysis of SIRT1 orthologs and substrates, we identified and examined important amino acid substitutions that have occurred during the evolution of sirtuins in Metazoa and Fungi. We found that mutation of human SIRT1 at these positions, based on sirtuin orthologs from Fungi, could alter its substrate specificity. These substitutions lead to reduced activity toward K382 acetylated p53 protein, which is only present in Metazoa, without affecting the high activity toward the conserved histone substrates. Results from ancestral sequence reconstruction are consistent with a model in which ancestral sirtuin proteins exhibited multispecificity, suggesting that the multispecificity of some metazoan sirtuins, such as hSIRT1, could be a relatively ancient trait.
Hang in there! Climbing towards a new normal in sport and exercise medicine and sports physiotherapy
Authors: Arnlaug Wangensteen, Hilde Moseby Berge
Journal: British Journal of Sports Medicine (2020)

Flatanger in the middle of Norway is known for some of the hardest climbing routes in the world. The spectacular Hanshelleren cave (figure 1) is referred to as the ‘crown jewel’ in this area, attracting climbers from all over the world to test their physical and mental strength on high-quality rock. When you stand at the bottom, the massive overwhelming granite structure may appear frightening and entirely insurmountable. However, if you climb up and inside the cave, the perspective changes, revealing a stunning view of the fiords and the surroundings.



Figure 1 
From Flatanger cave (Norway), Lars Ole Gudvang climbs the route Nordic Flower (8c). Photographer: Henning Wang. Permission obtained.



The COVID-19 pandemic may have seemed as scary and frightening to us as standing at the bottom of the Hanshelleren cave. We have taken a significant fall:

Now, we are standing at the bottom of the cave facing a steep climb ahead. At the time of writing, the society in Norway is about to reopen. The athletic population is gradually returning to their sporting activities, in the setting of a new kind of normality.

In this issue, we therefore focus on returning to sport from a variety of perspectives. We place particular emphasis on the athlete’s heart, as the evidence regarding cardiorespiratory complications and/or consequences following COVID-19 is yet unclear.

Lockdown and quarantine life have had a negative impact on …
Enabling MedTech Translation in Academia: Redefining Value Proposition with Updated Regulations
Authors: Didier Letourneur, Kieran Joyce, Cédric Chauvierre, Yves Bayon, Abhay Pandit
Journal: Advanced Healthcare Materials (2020)

Abstract Academic institutions are becoming more focused on translating new technologies for clinical applications. A transition from “bench to bedside” is often described to take basic research concepts and methods to develop a therapeutic or diagnostic solution with proven evidence of efficacy at the clinical level while also fulfilling regulatory requirements. The regulatory environment is evolving in Europe with transition and grace periods for the full enforcement of the Medical Device Regulation 2017/745 (MDR), replacing the Medical Device Directive 93/42/EEC (MDD). These new guidelines increase demands for scientific, technical, and clinical data with reduced capacity in regulatory bodies creating uncertainty in future product certification. Academic translational activities will be uniquely affected by this new legislation. The barriers and threats to successful translation in academia can be overcome by strong clinical partnerships, close‐industrial collaborations, and entrepreneurial programs, enabling continued product development to overcome regulatory hurdles, reassuring their foothold of medical device development.
Patient Trajectories Among Persons Hospitalized for COVID-19
Authors: Brian T. Garibaldi, Jacob Fiksel, John Muschelli, Matthew L. Robinson, Masoud Rouhizadeh, Jamie Perin, Grant Schumock, Paul Nagy, Josh H. Gray, Harsha Malapati, Mariam Ghobadi-Krueger, Timothy M. Niessen, Bo Soo Kim, Peter M. Hill, M. Shafeeq Ahmed, Eric D. Dobkin, Renee Blanding, Jennifer Abele, Bonnie Woods, Kenneth Harkness, David R. Thiemann, Mary G. Bowring, Aalok B. Shah, Mei-Cheng Wang, Karen Bandeen-Roche, Antony Rosen, Scott L. Zeger, Amita Gupta
Journal: Annals of Internal Medicine (2020)

Risk factors for progression of coronavirus disease 2019 (COVID-19) to severe disease or death are underexplored in U.S. cohorts.
Fgr kinase is required for proinflammatory macrophage activation during diet-induced obesity
Authors: Rebeca Acín-Pérez, Salvador Iborra, Yolanda Martí-Mateos, Emma C. L. Cook, Ruth Conde-Garrosa, Anton Petcherski, Mª del Mar Muñoz, Raquel Martínez de Mena, Karthickeyan Chella Krishnan, Concepción Jiménez, Juan Pedro Bolaños, Markku Laakso, Aldon J. Lusis, Orian S. Shirihai, David Sancho, José Antonio Enríquez
Journal: Nature Metabolism (2020)
Speed Kills: Advancement in Th17 Cell Adoptive Cell Therapy for Solid Tumors
Authors: Steven N. Fiering, Gregory W. Ho
Journal: Cancer Research (2020)

IL6 is targeted as part of treatment in adoptive cell therapy (ACT) because of its protumor effects and its role in the cytokine release syndrome. However, another major role of IL6 is to polarize naïve CD4+ T cells from Tregs to Th17 cells. While Th17 T cells are associated with autoimmunity, they are present around many different solid tumor cancers and their role in tumor microenvironments is unclear. In this issue of Cancer Research, Knochelmann and colleagues show that Th17 cells with less in vitro expansion in IL6-driven Th17 ACT provide greater solid tumor control and robust immune memory, highlighting advancement in the field of ACT application to solid tumor immunotherapy.See related article by Knochelmann et al., p. 3920.
The Exact Shade of Code Grey—Sutter Psych Hospital
Authors: Sandra McPherson
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Re: Thulium Laser Transurethral Vaporesection of the Prostate Versus Transurethral Resection of the Prostate for Men with Lower Urinary Tract Symptoms or Urinary Retention (UNBLOCS): A Randomized Controlled Trial
Authors: Dmitry Enikeev, Mark Taratkin, Petr Glybochko
Journal: European Urology (2020)
BCMA-targeted immunotherapy for multiple myeloma
Authors: Bo Yu, Tianbo Jiang, Delong Liu
Journal: Journal of Hematology & Oncology (2020)

Abstract B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as well as BCMA-targeted immunotherapeutic agents in different stages of clinical development.
Efficacy and Safety of Continued Treatment With Mirikizumab in a Phase 2 Trial of Patients With Ulcerative Colitis
Authors: William J. Sandborn, Marc Ferrante, Bal R. Bhandari, Elina Berliba, Toshifumi Hibi, Geert R. D’Haens, Jay L. Tuttle, Kathryn Krueger, Stuart Friedrich, Michael Durante, Vipin Arora, April N. Naegeli, Jochen Schmitz, Brian G. Feagan
Journal: Clinical Gastroenterology and Hepatology (2020)

Mirikizumab is an antibody against the p19 subunit of interleukin 23 that has demonstrated clinical efficacy and was well tolerated following 12 weeks of induction treatment in a phase 2 trial of patients with moderate to severe ulcerative colitis. We present results of the open-label extended induction period in patients who did not initially respond to treatment with mirikizumab.This study was a continuation of I6T-MC-AMAC, a double-blind trial, performed at 75 sites in 14 countries, in which patients with moderate to severe ulcerative colitis were randomly assigned to 12 weeks induction therapy with 50 mg, 200 mg, or 600 mg mirikizumab or placebo. Patients without a clinical response (a 9-point decrease in Mayo subscore of ≥2 points and ≥35% from baseline and either a decrease of rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1) at week 12 were offered the opportunity to participate in an open-label, extended induction study for another 12 weeks, in which they received either 600 mg intravenous mirikizumab (n = 20) or, following a protocol amendment, 1000 mg intravenous mirikizumab (n = 64) every 4 weeks. At week 24, patients with a clinical response continued the extension maintenance period and received 200 mg subcutaneous mirikizumab. Endpoints included clinical remission (Mayo subscores of 0 for rectal bleeding, 0 or 1 with a 1-point decrease from baseline), clinical response, endoscopic remission (Mayo endoscopic subscore of 0), or endoscopic improvement (endoscopic subscore of 0 or 1), at study weeks 24 and 52. Data were analysed for patients who received mirikizumab or placebo during the induction phase of the study.Among participants who did not respond to induction mirikizumab, 50.0% of those who received the 12-week extension of 600 mg mirikizumab and 43.8% who received the extension of 1000 mg mirikizumab achieved a clinical response; 15.0% and 9.4% achieved clinical remission, respectively. Endoscopic improvement was achieved by 20.0% of subjects in the 600 mg mirikizumab group and 15.6% subjects in the 1000 mg mirikizumab group. Among initial nonresponders to mirikizumab who had clinical response at study week 24 and continued into maintenance therapy, 65.8% maintained the clinical response, 26.3% achieved clinical remission, and 34.2% had endoscopic improvement at week 52. No new safety concerns were identified.Extended doses of mirikizumab (600 mg and 1000 mg) for an additional 12 weeks produce a clinical response in up to 50% of patients who did not have a clinical response to 12 weeks of induction doses (50 mg, 200 mg, or 600 mg). Most of the responders to the extended doses maintained clinical response for up to 52 weeks. Clinicaltrials.gov no: NCT02589665.
Early Intervention with Lenalidomide in Patients with High-risk Chronic Lymphocytic Leukemia
Authors: Shanmugapriya Thangavadivel, Qiuhong Zhao, Narendranath Epperla, Lindsey Rike, Xiaokui Mo, Mohamed Badawi, Darlene M. Bystry, Mitch A. Phelps, Leslie A. Andritsos, Kerry A. Rogers, Jeffrey Jones, Jennifer A. Woyach, John C. Byrd, Farrukh T. Awan
Journal: Clinical Cancer Research (2020)

Infectious complications constitute a leading cause of morbidity and mortality in chronic lymphocytic leukemia (CLL). Patients respond poorly to vaccines, particularly pneumococcal polysaccharide and influenza vaccines. In addition, patients with genetically high-risk disease are at increased risk for early disease progression and death. Lenalidomide, an oral immunomodulatory agent with demonstrated clinical activity in CLL, can potentially restore immune system dysfunction associated with CLL while improving disease outcomes.Phase II study randomized 49 patients with genetically high-risk CLL or small lymphocytic lymphoma [SLL; defined as unmutated Ig heavy chain variable region, deletion(17p) or (11q), and/or complex abnormal karyotype], to receive lenalidomide either concurrent (arm A) or sequential to (arm B) two doses of 13-valent protein-conjugated pneumococcal vaccine (PCV13) administered 2 months apart, in patients not meeting International Workshop on Chronic Lymphocytic Leukemia treatment criteria.Four serotypes (3, 4, 5, 6B) achieved the additional seroprotection definition of a fourfold increase in arm A, and six serotypes (3, 4, 5, 6B, 19A, 19F) in arm B. All patients achieved the defined concentration of 0.35 μg/mL for at least one serotype tested. No significant difference was observed with the addition of lenalidomide. At median time on treatment of 3.6 years, median progression-free survival (PFS) was 5.8 years [95% confidence interval (CI), 3.1-not reached]. PFS at 1, 2, and 3 years was 85% (95% CI, 72-93), 79% (95% CI, 64-88), and 72% (95% CI, 57-83), respectively.Lenalidomide is efficacious with manageable toxicities as an early intervention strategy in patients with high-risk CLL, but did not enhance humoral response to PCV13 vaccine.
Clinical Laboratory Test Unit Homogeneity—an Urgent Need
Authors: Michele Mussap
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor–Related Cholangiohepatitis
Authors: Laura Moi, Hasna Bouchaab, Nuria Mederos, Tu Nguyen-Ngoc, Matthieu Perreau, Craig Fenwick, Julien Vaucher, Christine Sempoux, Solange Peters, Michel Obeid
Journal: Journal of Thoracic Oncology (2020)