tbuckley/cabot-search huggingface dataset:
Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma
Authors: Jonathan A. Trujillo, Jason J. Luke, Yuanyuan Zha, Jeremy P. Segal, Lauren L. Ritterhouse, Stefani Spranger, Karen Matijevich, Thomas F. Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> While cancer immunotherapies including checkpoint blockade antibodies, adoptive T cell therapy, and even some vaccines have given rise to major clinical responses with durability in many cases, a subset of patients who initially respond subsequently develop secondary resistance to therapy. Tumor-intrinsic mechanisms of acquired immunotherapy resistance are incompletely understood. <h3>Methods</h3> Baseline and treatment-resistant tumors underwent molecular analysis via transcriptional profiling or genomic sequencing for oncogenic alterations and histologic analysis for T cell infiltration to investigate mechanisms contributing to T cell exclusion and acquired resistance to immunotherapy<b>.</b> <h3>Results</h3> We describe two patients with metastatic melanoma who initially showed a durable partial response to either a melanoma-peptide/interleukin-12 vaccine or combined anti-CTLA-4 + anti-PD-1 therapy, but subsequently developed new treatment-resistant metastases. In the first case, the recurrent tumor showed new robust tumor expression of β-catenin, whereas in the second case genomic sequencing revealed acquired PTEN loss. Both cases were associated with loss of T cell infiltration, and both pathways have been mechanistically linked to immune resistance preclinically. <h3>Conclusion</h3> Our results suggest that secondary resistance to immunotherapies can arise upon selection for new oncogenic variants that mediate T cell exclusion. To identify the spectrum of underlying mechanisms of therapeutic resistance, similar evaluation for the emergence of tumor-intrinsic alterations in resistant lesions should be done prospectively at the time of relapse in a range of additional patients developing secondary resistance.
Inotuzumab Ozogamicin Post-Transplant for Acute Lymphocytic Leukemia
Authors: Leland Metheny, Ronald Sobecks, Benjamin K. Tomlinson, Folashade Otegbeye, Brenda Cooper, Navneet S. Majhail, Paolo Caimi, Kirsten M Boughan, Molly M Gallogly, Ehsan Malek, Erin Galloway, Betty K. Hamilton, Matt Kalaycio, Aaron T. Gerds, Marcos de Lima
Journal: Blood (2019)
AG-636 for the Treatment of Adults with Advanced Lymphoma: Initiation of a Phase 1 Clinical Study
Authors: Scott F. Huntington, Avyakta Kallam, Frank G. Basile, Danielle Ulanet, Huansheng Xu, Feng Yin, Michelle Mobilia, Michael Cooper, Bijal Shah, John P. Leonard, Gottfried R. von Keudell, Ajay K. Gopal
Journal: Blood (2019)
The "Costoclavicular Syndrome"
Authors: M. A. Falconer
Journal: BMJ (1947)

MEDBIIJURNAL69it was shown that treatment of certain proteins, such as casein, with iodine under mildly alkaline conditions produced iodo- proteins which exhibited thyroid activity by the oral route and from which thyroxine could be isolated after hydrolysis.Since iodocasein could be made quite readily from available materials it was evident that here was a cheap and plentiful supply of artificial thyroid hormone lending itself to easy administration to cows under practical conditions.Large-scale experiments.
Synergistic Targeting of BTK and E-Selectin/CXCR4 in the Microenvironment of Mantle Cell Lymphomas
Authors: Mahesh Basyal, Weiguo Zhang, Nalini B Patel, Sujan Piya, Hongying Zhang, William E. Fogler, William G Rice, John L. Magnani, Gautam M. Borthakur, Michael Andreeff
Journal: Blood (2019)
Comprehensive genomic and transcriptomic profiling in advanced-stage cancers and rare malignancies: Clinical results from the MASTER trial of the German Cancer Consortium
Authors: P. Horak, S. Kreutzfeldt, A. Mock, C. Heining, C.E. Heilig, L. Möhrmann, S. Uhrig, D. Hübschmann, K. Beck, D. Richter, R.F. Schlenk, B. Klink, B. Hutter, W. Weichert, A. Stenzinger, E. Schröck, B. Brors, H. Glimm, S. Fröhling
Journal: Annals of Oncology (2019)
Adoptive Cell Therapy and Immune Check Points Inhibitors As a Salvage Treatment for Patient Affected By Relapsed/Refractory Hodgkin's Lymphoma
Authors: Fabio Guolo, Paola Minetto, Filippo Ballerini, Elisabetta Tedone, Paola Contini, Rosa Mangerini, Alessandra Bo, Maria Carla De Luigi, Paolo Carlier, Alberto Serio, Paolo Strada, Silvia Luchetti, Marco Gobbi, Emanuela Marcenaro, Roberto Massimo Lemoli
Journal: Blood (2019)
A Microbial Siderophore-Inspired Self-Gelling Hydrogel for Noninvasive Anticancer Phototherapy
Authors: Seungbeom Ko, Joo Yeon Park, Yu-Kyoung Oh
Journal: Cancer Research (2019)

Abstract Microbial carboxyl and catechol siderophores have been shown to have natural iron-chelating abilities, suggesting that hyaluronic acid (HA) and the catechol compound, gallic acid (GA), may have iron-coordinating activities. Here, a photoresponsive self-gelling hydrogel that was both injectable and could be applied to the skin was developed on the basis of the abilities of HA and GA to form coordination bonds with ferric ions (Fe3+). The conjugate of HA and GA (HA–GA) instantly formed hydrogels in the presence of ferric ions and showed near-infrared (NIR)-responsive photothermal properties. Following their subcutaneous injection into mice, HA–GA and ferric ion formed a hydrogel, which remained at the injection site for at least 8 days. Intratumoral injection of HA-GA/Fe hydrogel into mice allowed repeated exposure of the tumor to NIR irradiation. This repeated NIR irradiation resulted in complete tumor ablation in KB carcinoma cell–xenografted mice and suppressed lung metastasis of 4T1-Luc orthotopic breast tumors. Application of HA-GA/Fe hydrogel to the skin of A375 melanoma-xenografted tumor sites, followed by NIR irradiation, also resulted in complete tumor ablation. These findings demonstrate that single applications of HA–GA/Fe hydrogel have photothermal anticancer effects against both solid tumors and skin cancers. Significance: These findings provide new insights into noninvasive anticancer phototherapy using self-gelling hydrogels. Application of these hydrogels in preclinical models reduces the sizes of solid tumors and skin cancers without surgery, radiation, or chemotherapy.
Mitochondrial Metagenomics Reveals the Ancient Origin and Phylodiversity of Soil Mites and Provides a Phylogeny of the Acari
Authors: Paula Arribas, Carmelo Andújar, María Lourdes Moraza, Benjamin Linard, Brent C Emerson, Alfried P Vogler
Journal: Molecular Biology and Evolution (2019)

High-throughput DNA methods hold great promise for phylogenetic analysis of lineages that are difficult to study with conventional molecular and morphological approaches. The mites (Acari), and in particular the highly diverse soil-dwelling lineages, are among the least known branches of the metazoan Tree-of-Life. We extracted numerous minute mites from soils in an area of mixed forest and grassland in southern Iberia. Selected specimens representing the full morphological diversity were shotgun sequenced in bulk, followed by genome assembly of short reads from the mixture, which produced >100 mitochondrial genomes representing diverse acarine lineages. Phylogenetic analyses in combination with taxonomically limited mitogenomes available publicly resulted in plausible trees defining basal relationships of the Acari. Several critical nodes were supported by ancestral-state reconstructions of mitochondrial gene rearrangements. Molecular calibration placed the minimum age for the common ancestor of the superorder Acariformes, which includes most soil-dwelling mites, to the Cambrian-Ordovician (likely within 455-552 Ma), whereas the origin of the superorder Parasitiformes was placed later in the Carboniferous-Permian. Most family-level taxa within the Acariformes were dated to the Jurassic and Triassic. The ancient origin of Acariformes and the early diversification of major extant lineages linked to the soil are consistent with a pioneering role for mites in building the earliest terrestrial ecosystems.
QOLP-33. ACCEPTABILITY RANDOMIZED CONTROLLED TRIAL A COUPLES-BASED MIND-BODY INTERVENTION FOR PATIENTS WITH HIGH GRADE GLIOMA AND THEIR PARTNERS
Authors: Kathrin Milbury, Shiao- Pei Weathers, Sania Durrani, Yisheng Li, Cindy Carmack, Eduardo Bruera
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Given the incurable nature, short survival and high symptom burden of high grade glioma (HGG), patients and their partners are at risk of experiencing psychological and existential/spiritual distress. To address these concerns, we developed a dyadic intervention integrating meditation training with emotional disclosure exercises. The primary aim was to examine feasibility and acceptability of the intervention study procedures. METHODS Dyads completed baseline self-report measures and were randomized to a couple-based mind-body (CBMB) or a waitlist control (WLC) group. Couples in the CBMB groups attended 4 weekly (60 min each) therapist-led sessions that were delivered via FaceTime. The CBMB program focused on cultivating mindfulness, compassion, gratitude and purpose. All groups were reassessed, 1 month and 3 months after baseline. RESULTS We approached 60 eligible patient-partner dyads of which 37 (62%) consented and 18 were randomized to the CBMB and 16 to the WLC group. Of those randomized, 23 dyads (67%) completed all assessments (n= 12 in CBMB; n=11 in WLC). Attrition was due to patients’ death (n=3), symptom burden (n=5) or passive withdrawal (n=3). Patients (57% male; mean age=57 years) and partners’ (59% female; mean age=54 years) attended a mean of 3.17 sessions (SD=1.2) with 83% attending at least 2 sessions. All dyads in the CBMB group reported the intervention as beneficial and useful and would recommend this program to other couples. Of note, 60% of couples would have preferred in-person delivery and 95% of patients but only 33% of partners stated that a dyadic intervention is their preference. CONCLUSION It seems to be feasible, acceptable and possibly efficacious to deliver a dyadic intervention via FaceTime to couples coping with HGG. Although both members of the dyad reported to have benefited, dyadic delivery appears to be less desirable for partners.
Abstract 241: Legal Risk of Bystander Cardiopulmonary Resuscitation
Authors: Travis Murphy, Sonora Windermere, Tareyn Morris, John Slish, Liam Holtzman, Torben Becker
Journal: Circulation (2019)

Background: Research has shown disparities between provision of bystander CPR among different race, gender and age groups. Reasons for this disparity have included concern of legal liability by responders. We propose that bystanders are more likely to face litigation for lack of intervention as opposed to providing bystander CPR. This review of the legal literature seeks to quantify the number of cases brought against responders in the USA over the past 30 years. Methods: The Westlaw legal research database was searched for jury verdicts, settlements, and appellate opinions from all 50 states from 1989 to 2019, in which the use or non-use of CPR gave rise to a personal injury or wrongful death lawsuit. A total of 274 cases were initially identified and manually reviewed. Outcomes recorded included case jurisdiction, location, date, plaintiff and defendant demographics, bystander training, motivation for the lawsuit, including claims of battery for performing CPR or negligence related to injuries or death following CPR or AED use. Results: Preliminary data shows that 41.1% (114 of 274) of all cases screened were directly due to the provision of bystander CPR or lack thereof. Among the relevant cases, 64% (73 of 114) were due to inadequate or untimely bystander CPR. Battery cases due to providing CPR amounted to 32% (32 of 114), but of these, 59.4% (19 of 32) were ruled in favor of the defendant. Conclusions: This represents the largest study of legal cases involving bystander CPR in the medical literature, limitations include a lack of a national repository of trial data thus underestimating the total number of cases involving bystander CPR. The likelihood of facing litigation is significantly higher in cases where bystander CPR was delayed or not provided. The authors propose the inclusion of this data and reiteration of protective statutes in all 50 states during CPR training to reassure and encourage trainees.
In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non-overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment
Authors: Christina Adamichou, Dionysis Nikolopoulos, Irini Genitsaridi, Alessandra Bortoluzzi, Antonis Fanouriakis, Emmanouil Papastefanakis, Eleni Kalogiannaki, Irini Gergianaki, Prodromos Sidiropoulos, Dimitrios T Boumpas, George K Bertsias
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Classification criteria are biased towards classifying long-standing disease. We compared the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)-2019, Systemic Lupus International Collaborating Clinics (SLICC)-2012 and ACR-1997 criteria in an early (median 48 months) systemic lupus erythematosus (SLE) cohort. Methods Patients diagnosed with SLE (n=690) or control diseases (n=401). Sensitivity, specificity of the criteria and time-to-classification were calculated. Modified classification algorithms were derived from a random 80% and validated in the remaining 20% of the dataset running multiple iterations. Results At last assessment, sensitivities of ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria were 85.7%, 91.3% and 88.6%, with specificities 93.0%, 93.8% and 97.3%, respectively. Both SLICC and EULAR/ACR enabled earlier classification. Only 76.7% of patients with SLE met all three criteria suggesting non-overlapping groups. Notably, unclassified patients had high prevalence of British Isles Lupus Assessment Group moderate/severe manifestations (43.3%–60%) and SLICC/ACR organ damage (30%–50%). At diagnosis, criteria missed 25.6%–30.5% of patients. Modification of EULAR/ACR and SLICC algorithms to include hypocomplementaemia and/or positive anti-phospholipid antibodies as alternative entry criterion, and/or allow classification with fewer clinical criteria from multiple organs, increased their sensitivity at diagnosis (median 82.0% and 86.2%) and overall (93.7% and 97.1%) with modest decreases in specificity. Importantly, patients who were still missed by the modified criteria had lower incidence of major organ involvement, use of immunosuppressive/biological therapies and organ damage. Conclusions The SLICC and EULAR/ACR are more sensitive than the ACR and the EULAR/ACR criteria have superior specificity in early SLE, although patients with significant disease can be missed. Combination and/or modification of the classification algorithms may enhance their sensitivity, allowing earlier classification and treatment of more patients with high disease burden.
Vitamin D as a Public Health Problem
Authors: G. C. Arneil
Journal: BMJ (1964)

27 June, p. 1653).I feel that this editorial, perhaps unintentionally, was exceedingly patronizing to both the World Health Organization and to Scotland.Further, it only advanced the arguments supporting the present somewhat negative "party line" and made no effort to review or consider many obvious points that can be made for such a Centre with all ,the three suggested functions-namely, epi- .demiology,communications, and biomedical research.Judging by recent reported state- ments by the Minister of Science and the 'Secretary of State for Scotland, there is now wide acceptance of the first two functions, and, if the W.H.O.proposed such a Centre, then it appears likely that the United King- dom will support an invitation to site the Centre in Scotland.However, your editorial, and since then the Parliamentary Secretary, Ministry of Health, appear strongly opposed to an
Long-Term Cardiovascular Risk in Women With Hypertension During Pregnancy
Authors: Michael C. Honigberg, Seyedeh Maryam Zekavat, Krishna Aragam, Derek Klarin, Deepak L. Bhatt, Nandita S. Scott, Gina M. Peloso, Pradeep Natarajan
Journal: Journal of the American College of Cardiology (2019)
PDTM-12. ADGRB3 IS EPIGENETICALLY SILENCED IN WNT-MEDULLOBLASTOMA AND ITS REACTIVATION HAS THERAPEUTIC BENEFITS
Authors: Debanjan Bhattacharya, Dan Zhu, Satoru Osuka, Stefan Kaluz, Narra Devi, Erwin Van Meir
Journal: Neuro-Oncology (2019)

Abstract Medulloblastoma (MB) are the most aggressive primary malignant brain tumors in children and are classified into four major molecular subgroups. WNT-MB is characterized by an activated WNT signature and has relatively better prognosis with treatment. However, young WNT-MB patients who survive after conventional treatment suffer from long-term irreversible neurocognitive and endocrine side effects leading to poor quality of life. ADGRB3 is a member of the ADGRB1-3 subfamily of adhesion GPCR transmembrane proteins, which are highly expressed in the cerebellum and hippocampal neurons. Our recent analysis of RNA-seq data from a published panel of MB tumor samples and RT-PCR experiments with tumor samples showed that ADGRB3 mRNA expression is selectively repressed in WNT-MB tumors compared to the other molecular subgroups and normal human cerebellum. We detected hypermethylation of the ADGRB3 promoter exclusively in WNT-MB samples. ChIP assays revealed enrichment of repressive methyl CpG binding MBD2 protein and trimethylated histone H3K9me3 in the ADGRB3 promoter region. We found that ATP dependent chromatin remodeler protein BRG-1 regulates ADGRB3 expression through epigenetic reprogramming at the gene promoter. Lentiviral reconstitution of ADGRB3 inhibited growth and WNT signaling in UW288-1, and PFSK-1 cells in culture. ADGRB3 reconstitution in UW288-1 MB cells causes a significant reduction in tumor growth and WNT target gene activation in orthotopic xenografts in nude mice. Furthermore, we found that ADGRB3 reactivation could be achieved using a blood brain barrier permeable MBD2 antagonist and an EZH2 inhibitor and this can significantly reduce cell growth and inhibit WNT signaling targets. Altogether, our findings define an epigenetic mechanism for ADGRB3 silencing in WNT-MB and demonstrated that reactivation of ADGRB3 can prevent WNT-MB tumor growth by suppressing WNT signaling. Our study supports translating epigenetic reactivation of ADGRB3 as a novel therapeutic intervention for children affected with WNT-MB.
Personal Use of Drug Samples by Physicians and Office Staff
Authors: Susan Reynolds
Journal: JAMA (1997)

To the Editor.  —I was surprised by a statement in the article-by Dr Westfall and colleagues 1 that the average wholesale price of samples taken for personal or family use was greater than $7000, with a retail cost of nearly $10 000. I realize that medical costs are high, but this is astounding. Do the authors mean the average incident of sample usage cost $7000, that the average person surveyed took a total of $7000 in medication, that the residency program used $7000 in samples per month for its staff, or that the residency used $7000 in samples every year?
Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation: Comparing Post-Transplant Cyclophosphamide Versus Anti-T-Lymphocyte Globulin As Graft-Versus-Host Disease Prophylaxis in a Retrospective Cohort Study
Authors: Rashit Bogdanov, Saskia Leserer, Evren Bayraktar, Nikolaos Tsachakis-Mück, Lara Kasperidus, Markus Ditschkowski, Dietrich W. Beelen, Amin T. Turki
Journal: Blood (2019)
Sterilization of Syringes
Authors: C. Riesenfeld, J. C. H. Hanson
Journal: BMJ (1948)

rectum about 3 in.(7.6 cm.) from the anal orifice.This was producing almost complete obstruction.Operation was firmly refused and she died on March 17, 1946.It is tempting to relate the final condition to the ring episode.Unfortunately no post-mortem examination was.allowed, so no pathological evidence exists.Certainly I had at the time no doubt that clinically the growth was a carcinoma.-Iam, etc., Bridlington, Yorks.
Pediatric Preclinical Testing Consortium Evaluation of the Novel Anti-Microtubule Drug E7130 in Xenograft Models of Early T-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Richard B. Lock, Kathryn Evans, Connor D Jones, Narimanne El-Zein, Katerina Bendak, Cara E Toscan, Chelsea Mayoh, Stephen W Erickson, Beverly A Teicher, Malcolm A Smith
Journal: Blood (2019)
Imatinib in Children with Chronic Myeloid Leukemia in Chronic Phase: Long-Term Results of the French National Phase IV Trial
Authors: Hélène Deutsch, Andre Baruchel, Joelle Guilhot, Arnaud Petit, Thierry Leblanc, Yves Bertrand, Brigitte Nelken, Catherine Paillard, Cécile Verite, Yves Réguerre, Francoise Mechinaud, Francois Guilhot, Frederic Millot
Journal: Blood (2019)
Detection of Subclonal SETBP1 and JAK3 Mutations in Patients with Juvenile Myelomonocytic Leukemia Using Droplet Digital PCR
Authors: Manabu Wakamatsu, Hideki Muramatsu, Norihiro Murakami, Yusuke Okuno, Hironobu Kitazawa, Seiji Kojima, Yoshiyuki Takahashi
Journal: Blood (2019)
Clinical Utility of Chromosomal Microarray in Establishing Clonality and High Risk Features in Patients with Richter Transformation
Authors: James Kalmuk, Daynna Wolff, Cynthia Schandl, Sandra Mazzoni, Iya Znoyko, Zane Chiad, Lindsey Hendrickson, Irl Brian Greenwell, Brian T. Hess
Journal: Blood (2019)
Longitudinal Serum Ferritin Cut-Off Level for Cardiac Iron Overload Prediction in Transfusion-Dependent Thalassemia in a Resource Limited Country
Authors: Supachai Ekwattanakit, Pairash Saiviroonporn, Kleebsabai Sanpakit, Noppadol Siritanaratkul, Jassada Buaboonnam, Archrob Khuhapinant, Boonying Rerkudom, Stephan Erberich, John C Wood, Rungroj Krittayaphong, Vip Viprakasit
Journal: Blood (2016)
The Inspire Study in Higher-Risk Myelodysplastic Syndrome (HR-MDS): A Novel Phase 3 Study Adaptive Design for Hematological Malignancies in Adults
Authors: Anna Jonasova, Selina M. Luger, Aref Al-Kali, David Valcarcel, Richard C. Woodman, Afoluso Ronnee Adesanya, Nozar Azarnia, Matthew Parris, Erica D. Warlick, Wieslaw W. Jedrzejczak, María Díez-Campelo, Guillermo Garcia-Manero
Journal: Blood (2019)