tbuckley/cabot-search huggingface dataset:
Abstract OT1-01-05: AIPAC (Active Immunotherapy PAClitaxel): A randomized, double blind, placebo controlled, multinational phase IIb trial evaluating the efficacy of eftilagimod alpha (a soluble LAG-3 fusion protein) in combination with paclitaxel in hormone receptor positive metastatic breast cancer
Authors: Luc Dirix, Hans Wildiers, Manon T Huizing, Eveline De Cuypere, Carolina P Schröder, Anne C Armstrong, Jans Huober, Frederik Marmé, Andreas Schneeweiss, Sarah Khan, Fréderic Triebel
Journal: Cancer Research (2020)

Abstract Background: Eftilagimod alpha (efti, previously IMP321) is a recombinant LAG-3Ig fusion protein that binds to MHC class II and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. Efti may lead to the activation of the dendritic cell network and to a strong anti-tumor CD8 T cell response when injected s.c. after chemotherapy at a time when these APC are loaded with tumor antigens. AIPAC (Active Immunotherapy PAClitaxel; NCT02614833) is a Phase IIb trial in hormone receptor (HR)-positive metastatic breast carcinoma patients receiving efti or placebo as adjunctive to weekly paclitaxel as a first-line chemotherapy. The randomized double blinded part (stage 2) has finished recruitment in June 2019. Primary analysis is expected Q1 2020. Methods: This clinical trial is a placebo-controlled, double-blind, 1:1 randomized Phase IIb study aimed to enrol 226 patients at multiple centres across 7 different European countries. Patients with metastatic, HR-positive breast adenocarcinoma receiving first line chemotherapy with weekly paclitaxel and with measurable disease according to RECIST 1.1 are eligible. Patients suitable for Her2/neu targeted therapy are excluded from the trial. In the first treatment phase, paclitaxel (80 mg/m² IV at D1, D8, D15 plus efti (30 mg s.c.) or placebo at D2, D16 will be administered for 6 cycles (1 cycle = 4 weeks). This is followed by a maintenance phase in which stable or responding patients will receive efti or placebo for up to additional 52 weeks (12 injections). The primary endpoint is progression-free survival (PFS) by blinded independent central imaging review. Secondary endpoints include PFS by local assessment, overall survival, tumor response according to RECIST 1.1., time to and duration of response, duration of stable disease and quality of life. Citation Format: Luc Dirix, Hans Wildiers, Manon T Huizing, Eveline De Cuypere, Carolina P Schröder, Anne C Armstrong, Jans Huober, Frederik Marmé, Andreas Schneeweiss, Sarah Khan, Fréderic Triebel. AIPAC (Active Immunotherapy PAClitaxel): A randomized, double blind, placebo controlled, multinational phase IIb trial evaluating the efficacy of eftilagimod alpha (a soluble LAG-3 fusion protein) in combination with paclitaxel in hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-05.
B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches
Authors: Nina Shah, Ajai Chari, Emma Scott, Khalid Mezzi, Saad Z. Usmani
Journal: Leukemia (2020)

Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response. Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients. As there is no cure for MM, patients eventually become resistant to therapies, leading to development of relapsed/refractory MM. Therefore, an unmet need exists for MM treatments with novel mechanisms of action that can provide durable responses, evade resistance to prior therapies, and/or are better tolerated. B-cell maturation antigen (BCMA) is preferentially expressed by mature B lymphocytes, and its overexpression and activation are associated with MM in preclinical models and humans, supporting its potential utility as a therapeutic target for MM. Moreover, the use of BCMA as a biomarker for MM is supported by its prognostic value, correlation with clinical status, and its ability to be used in traditionally difficult-to-monitor patient populations. Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy. We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE® (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody-drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M. Notable antimyeloma activity and high minimal residual disease negativity rates have been observed with several of these treatments. These clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM. Importantly, clinical results to date suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM.
Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust
Authors: Carmen Reid
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build TrustFREECarmen ReidCarmen ReidEmory University, Atlanta, Georgia (C.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0014 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Voices of Medical Students and Residents: What Can Be Done to Build Trust "Voices of Medical Students and Residents: What Can Be Done to Build Trust," by Carmen Reid (Duration 4:09)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Emory University, Atlanta, Georgia (C.R.)Current Author Address: Carmen Reid; e-mail, carmen.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
A Commentary on the Latin American Paradox
Authors: Ana F. Abraído-Lanza, Sonia Mendoza-Grey, Karen R. Flórez
Journal: JAMA Network Open (2020)

Yingxi Chen, MD, PhD; Neal D. Freedman, PhD; Erik J. Rodriquez, PhD; Meredith S. Shiels, PhD; Anna M. Napoles, PhD; Diana R. Withrow, PhD; Susan Spillane, PhD; Byron Sigel, MS; Eliseo J. Perez-Stable, MD; Amy Berrington de González, DPhil
The psychological impact of quarantine and how to reduce it: rapid review of the evidence
Authors: Samantha K Brooks, Rebecca K Webster, Louise E Smith, Lisa Woodland, Simon Wessely, Neil Greenberg, Gideon James Rubin
Journal: The Lancet (2020)

The December, 2019 coronavirus disease outbreak has seen many countries ask people who have potentially come into contact with the infection to isolate themselves at home or in a dedicated quarantine facility. Decisions on how to apply quarantine should be based on the best available evidence. We did a Review of the psychological impact of quarantine using three electronic databases. Of 3166 papers found, 24 are included in this Review. Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable.
Treatment of Childhood-Onset Lupus Erythematosus Panniculitis With Rituximab
Authors: Colleen K. Correll, Daniel D. Miller, Sheilagh M. Maguiness
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> Childhood-onset lupus erythematosus panniculitis (LEP) is a rare and chronic disfiguring disease. A paucity of literature exists on the clinical manifestations of this disease and how best to treat it. <h3>Objectives</h3> To describe the clinical features of childhood-onset LEP and report on the use of rituximab in treatment-refractory childhood-onset LEP. <h3>Design, Setting, and Participants</h3> A retrospective, observational case series study was conducted of 4 patients with childhood-onset LEP who presented to a single-center, tertiary care clinic with pediatric dermatology and pediatric rheumatology clinics between July 1, 2014, and July 1, 2018, and were treated with rituximab. A literature review was conducted of the clinical features and treatment of childhood-onset LEP. <h3>Exposure</h3> Rituximab therapy for childhood-onset LEP. <h3>Main Outcomes and Measures</h3> Reduction in the number and size of erythematous and tender subcutaneous nodules (both visually and by palpation), reduction of facial atrophy (documented with serial photography), and tolerability of rituximab at 2 to 22 months after initiation of therapy. <h3>Results</h3> Four patients (3 male; mean [SD] age at treatment, 15 [5.9] years) with refractory childhood-onset LEP were successfully treated with rituximab. All patients had a rapid and sustained response to therapy with rituximab. One patient (25%) had minor infusion reactions; otherwise, treatment was well tolerated. <h3>Conclusions and Relevance</h3> This case series suggests that rituximab may hold promise as a treatment for refractory, childhood-onset LEP. Larger, prospective studies are needed to validate these findings; however, given the rarity of disease, large studies may be difficult to conduct.
Plant lectins and their usage in preparing targeted nanovaccines for cancer immunotherapy
Authors: Bhavika Gupta, Daizy Sadaria, Vaishnavi U. Warrier, Anuradha Kirtonia, Ravi Kant, Amit Awasthi, Prakash Baligar, Jayanta K. Pal, Eiji Yuba, Gautam Sethi, Manoj Garg, Rajesh Kumar Gupta
Journal: Seminars in Cancer Biology (2020)
Correction: HDAC3 Deficiency Promotes Liver Cancer through a Defect in H3K9ac/H3K9me3 Transition
Authors: Hongjie Ji, Yongjie Zhou, Xiang Zhuang, Yongjie Zhu, Zhenru Wu, Yannrong Lu, Shengfu Li, Yong Zeng, Qing R Lu, Yanying Huo, Yujun Shi, Hong Bu
Journal: Cancer Research (2020)

In the original version of [this article][1] ([1][2]), the image used in Fig. 2C to represent immunostaining of rH2A.X in HDAC2-knockout liver was inadvertently taken from the wild-type liver. This image has been replaced with the intended image for HDAC2-knockout liver and the figure has been
Care Redesign for Emergency General Surgery in Older Adults
Authors: Shelley R. McDonald, Mitchell T. Heflin, Sandhya A. Lagoo-Deenadayalan
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Abstract P6-03-04: Microenvironment-induced epigenetic reprogramming imposes drug-tolerant states in breast cancer cells
Authors: Tiina A Jokela, Dustin Schones, Mark A LaBarge
Journal: Cancer Research (2020)

Abstract Development of resistance to breast cancer (BC) therapy is frustratingly common. Multiple mechanisms of resistance have been identified including selection of genetic resistance, redundant signaling, and others. More recently, rare cancer cells were shown to be sporadically reprogrammed by the presence of anti-cancer drugs into transiently resistant states, then to expand later after cessation of therapy. We have demonstrated that the physical character and composition of tumor microenvironment (ME) components are determinants of BC cell drug resistance, however, the mechanism by which this phenomenon occurs is unclear. We hypothesize that epigenetic reprogramming is not rare or sporadic, indeed, that specific tumor ME components impose epigenetic states that beget the expression of gene clusters that put cancer cells into drug-tolerant states. Our current pharmacopeia targets cancer cells, not their ME. Some tumor ME components, e.g. extracellular matrices (ECM), have half-lives that span years, and growth factors with typically short half-lives can be stabilized by direct association with ECM. Thus, a ME-imposed drug tolerance mechanism would explain how resistance can arise rapidly, in multiple locations, without the need for genetic selection. Because ME-cell interactions lead to activation of specific pathways, based on canonical receptor-ligand models, we should be able to circumvent ME-imposed drug tolerance by addition of molecules that alter ME-induced signaling. Clusters of genes that are activated in multidrug resistant breast cancer cells identified potential markers of drug tolerance. ME-drivers of the drug tolerance markers were identified in high-throughput cell-based screens with the MicroEnvironment MicroArray (MEMA) platform. BC cells were exposed in parallel to over 1000 unique combinatorial MEs, which were chosen to mimic normal mammary gland, and luminal or basal BC tumor MEs. Single-cell resolution analysis revealed MEs that induce and maintain drug-tolerance markers. Longer-term functional experiments validated that the identified MEs also increased BC cells drug tolerance. Chromatin accessibility profiling with ATAC-sequencing demonstrated that BC cells cultured in those drug-tolerance inducing MEs exhibit chromatin opening in promoter regions of genes linked to epithelial plasticity (e.g. Axl, SNAI2, Vimentin, TWIST1) within 24h of exposure. These results support the concept that specific MEs drive drug-tolerant cellular phenotypes and suggest a novel interventional avenue for preventing acquired therapy resistance. Citation Format: Tiina A Jokela, Dustin Schones, Mark A LaBarge. Microenvironment-induced epigenetic reprogramming imposes drug-tolerant states in breast cancer cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-04.
Kidney to bone via bedside to bench…and back?
Authors: Alexander Grabner, Myles Wolf
Journal: Journal of Clinical Investigation (2020)

The rapid rise in circulating fibroblast growth factor 23 (FGF23) associated with kidney injury results in calcitriol deficiency, altered calcium homeostasis, and secondary hyperparathyroidism, and may contribute to cardiovascular complications and death. However, the mechanisms of increased FGF23 in states of kidney injury remain unclear. In this issue of the JCI, Simic et al. screened plasma taken from the renal vein of patients undergoing cardiac catheterization and identified glycerol-3-phosphate (G-3-P) as the most significant correlate of simultaneous arterial FGF23 levels. When G-3-P was administered to mice, FGF23 production increased in bone. In a series of elegant mouse studies, the authors discovered a pathway linking increased G-3-P to increased FGF23 via increases in lysophosphatidic acid (LPA), which activates the LPA receptor 1 in FGF23-secreting cells in the bone and bone marrow. Although the authors present human data that broadly support the results from the mouse models, further research is needed to determine whether targeting the G-3-P/FGF23 pathway has the potential to modify FGF23-related complications in the clinic.
Oral antibiotic use and chronic disease: long-term health impact beyond antimicrobial resistance and <i>Clostridioides difficile</i>
Authors: Jessica Queen, Jiajia Zhang, Cynthia L Sears
Journal: Gut Microbes (2020)

We recently reported an increased colon cancer risk associated with oral antibiotic use in a large United Kingdom population. This association between antibiotic exposure and cancer risk adds to a growing body of evidence that antibiotic use has unintended off-target long-term health consequences. This addendum highlights major studies linking antibiotic use and chronic disease in pediatric and adult populations. Microbiota dysbiosis is the key proposed mechanism underlying antibiotic:disease associations, resulting in alterations in gene expression, epigenetic modification, colonization by pathogenic bacteria, instigation of biofilms, and immune regulation and inflammation. These adverse outcomes of antibiotic exposure underscore the need for diagnostic and antibiotic stewardship, as well as the urgency for further development of non-antibiotic therapies for bacterial infections.
Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7
Authors: Elena Crisà, Austin G. Kulasekararaj, Vera Adema, Esperanza Such, Julie Schanz, Detlef Haase, Katayoon Shirneshan, Steven Best, Syed A Mian, Aytug Kizilors, José Cervera, Nicholas Lea, Dario Ferrero, Ulrich Germing, Barbara Hildebrandt, Ana Belén Valencia Martínez, Valeria Santini, Guillermo F. Sanz, Francesc Solé, Ghulam J. Mufti
Journal: Leukemia (2020)
Abstract P3-08-71: Medication use to reduce mammographic breast density in premenopausal women: A systematic review
Authors: Ana S. Salazar, Malika Rakhmankulova, Laura E. Simmon, Adetunji Toriola
Journal: Cancer Research (2020)

Abstract Background: Mammographic breast density (MBD) is a strong modifiable risk factor for breast cancer, especially in premenopausal women. It is estimated that up to 39% of breast cancer cases in premenopausal women could potentially be prevented by reducing dense breasts to non-dense breasts. Therefore, reducing breast density through targeted interventions is an excellent opportunity to substantially reduce breast cancer incidence in premenopausal women. We performed a critical evaluation of the literature to determine the associations of chemoprevention agents use with MBD. This will guide the management of premenopausal women at risk for breast cancer. Methods: Eleven databases were searched on July 2019. We included interventional, cross-sectional, longitudinal or observational studies in Englishreporting the associations of medication with mammographic breast density in premenopausal womenwith no history of breast cancer. Two researchers extracted the data and assessed the quality of the studies. Supplements not otherwise specified were excluded. Results: After de-duplication process, 1,464 citations were screened for eligibility. Seven studies met our inclusion criteria: two observational, four randomized controlled, and one non-randomized controlled trials (RCT). There were two categories of medications: dietary supplements (i.e. vitamin D, calcium, isoflavone) and drugs (non-steroidal anti-inflammatory drugs [NSAIDs], selective estrogen receptor modulators (SERMs) goserelin, and GnRHA deslorelin acetate). In observational studies, calcium use was associated with a significant reduction in MBD, while vitamin D and NSAIDs showed no reduction6. Likewise, Isoflavone and vitamin D in doses of 1000, 2000 or 3,000IU/day were not associated with a reduction in MBD in two different RCT. Groselin, GnRHA, deslorein acetate, statins were not associated with MBD reduction in an RCT’s. SERMs (tamoxifene and raloxifene) were the only drugs associated with reductions in MBD in RCTs. Conclusions: Only a very limited number of medications (SERMs) are associated with reductions in MBD. In view of their low uptake and adherence, identifying other medications that can reduce MBD is crucial, as these could have utility in breast cancer prevention. Citation Format: Ana S. Salazar, Malika Rakhmankulova, Laura E. Simmon, Adetunji Toriola. Medication use to reduce mammographic breast density in premenopausal women: A systematic review [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-71.
Co-delivery of Cu(I) chelator and chemotherapeutics as a new strategy for tumor theranostic
Authors: Tao Sun, Guangping Zhang, Zhongyuan Guo, Qinjun Chen, Yujie Zhang, Yongchao Chu, Qin Guo, Chao Li, Wenxi Zhou, Yiwen Zhang, Peixin Liu, Hongyi Chen, Haijun Yu, Liping Jiang, Chen Jiang
Journal: Journal of Controlled Release (2020)
Real-time colorectal cancer diagnosis using PR-OCT with deep learning
Authors: Yifeng Zeng, Shiqi Xu, William C. Chapman, Shuying Li, Zahra Alipour, Heba Abdelal, Deyali Chatterjee, Matthew Mutch, Quing Zhu
Journal: Theranostics (2020)

Prior reports have shown optical coherence tomography (OCT) can differentiate normal colonic mucosa from neoplasia, potentially offering an alternative technique to endoscopic biopsy -the current gold-standard colorectal cancer screening and surveillance modality.To help clinical translation limited by processing the large volume of generated data, we designed a deep learning-based pattern recognition (PR) OCT system that automates image processing and provides accurate diagnosis potentially in real-time.Method: OCT is an emerging imaging technique to obtain 3-dimensional (3D) "optical biopsies" of biological samples with high resolution.We designed a convolutional neural network to capture the structure patterns in human colon OCT images.The network is trained and tested using around 26,000 OCT images acquired from 20 tumor areas, 16 benign areas, and 6 other abnormal areas. Results:The trained network successfully detected patterns that identify normal and neoplastic colorectal tissue.Experimental diagnoses predicted by the PR-OCT system were compared to the known histologic findings and quantitatively evaluated.A sensitivity of 100% and specificity of 99.7% can be reached.Further, the area under the receiver operating characteristic (ROC) curves (AUC) of 0.998 is achieved.Conclusions: Our results demonstrate that PR-OCT can be used to give an accurate real-time computer-aided diagnosis of colonic neoplastic mucosa.Future development of this system as an "optical biopsy" tool to assist doctors in real-time for early mucosal neoplasms screening and treatment evaluation following initial oncologic therapy is planned.