tbuckley/cabot-search huggingface dataset:
Development of an interprofessional curriculum to improve team-based HIV care in sub-Saharan Africa: a training programme for undergraduate and early career health professionals
Authors: Elsie Kiguli-Malwadde, Jehan Budak, Evelyn Chilemba, Fred Semitala, Deborah von Zinkernagel, Mosepele Mosepele, Hoffie Conradie, Judy Khanyola, Clara Haruruvizhe, Michael J A Reid
Journal: The Lancet Global Health (2020)

BackgroundDespite evidence of the impact of interprofessional education (IPE) strategies to improve the efficiency and quality of training, few undergraduate health professions education programmes in sub-Saharan Africa have implemented such approaches. Furthermore, few pre-service health professions educational institutions have developed educational interventions that target trainees during the transition between pre-service training and professional practice. We developed HIV-specific, interprofessional, team-based resources to better support trainees during the transition period.MethodsBetween April 1 and July 31, 2019 ten faculty members representing nine medical and nursing schools in Uganda and South Africa developed a training package focused on core clinical, public health, IPE, and quality improvement (QI) domains related to HIV service delivery. Using small-group learning principles, they developed 17 case-based modules to address a diverse set of HIV-related topics, including, but not limited to, HIV prevention, diagnosis, linkage to care, treatment, and management of opportunistic infections. All modules were aimed at newly, or nearly, qualified health-care professionals, including nurses, doctors, pharmacists, and laboratory scientists and were intended to be taught in workshops that will complement existing institution-specific HIV curricula.FindingsTraining resources were launched in August, 2019; in the following 6 months, 66 nursing and medical schools and their affiliated training sites in 14 countries in sub-Saharan Africa used the training modules to support interprofessional training for health professionals in training. In the first 6 months of the project, 3500 learners participated in the training.InterpretationFurther evaluation of this project and its effects on pedagogical approaches, trainee competencies, as well as wider changes in the organisation and delivery of HIV care, are warranted. The collaborative, interinstitutional, interprofessional approach to curriculum development could provide a benchmark for how best-practice approaches to education can be rapidly disseminated and scaled up across training programmes in Africa.FundingHealth Resources and Services Administration, HRSA
Abstract B22: The human skin bacteria <i>Staphylococcus epidermidis</i> ameliorates UVB-induced free radicals through reduction of labile iron
Authors: Arun Balasubramaniam, Sunita Keshari, Prakaso Adi, Chun-Ming Huang
Journal: Cancer Research (2020)

Abstract UVB-induced skin damage results in various inflammatory disorders through the induced generation of reactive oxygen species (ROS) that quickly inundate tissue antioxidants and chronic disorders; in severe cases it can lead to skin cancer. We investigated efficacies of human skin commensal bacteria S. epidermidis (ATCC12228) with glycerol, which on fermentation produces electrons. In vivo affirmation on ICR mice has confirmed the antioxidative role of topically applied S. epidermidis with glycerol against UVB irradiation and maintained sufficient expression of 4-hydroxynonenal (4-HNE) and cyclobutane pyrimidine dimer (CPD), a major biomarker for lipid peroxidation and DNA damage. Upon UVB irradiation in keratinocyte cell lines treated with glycerol mediated S. epidermidis fermentation product show the reduced intracellular oxidative stress. S. epidermidis or glycerol alone in In vivo topical application in mice skin and in vitro fermentation product treatment in keratinocytes does not influence the level of oxidative stress. Further electrochemical behavior of glycerol mediated S. epidermidis fermented medium found to produce electron transfer; this result suggests the electrogenic and antioxidant property of S. epidermidis. The electrons produced by S. epidermidis fermentation product initiate reduction of free radicals by converting toxic Fe3+ (ferric ion) back to nontoxic Fe2+ (ferrous ion); thereby it terminates Fenton’s reaction and maintains iron hemostasis. The novel pathway linking electrons produced by probiotic skin bacteria and iron metabolism has been further analyzed. Note: This abstract was not presented at the conference. Citation Format: Arun Balasubramaniam, Sunita Keshari, Prakaso Adi, Chun-Ming Huang. The human skin bacteria Staphylococcus epidermidis ameliorates UVB-induced free radicals through reduction of labile iron [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B22.
Caring for patients with cancer in the COVID-19 era
Authors: Joris van de Haar, Louisa R. Hoes, Charlotte E. Coles, Kenneth Seamon, Stefan Fröhling, Dirk Jäger, Franco Valenza, Filippo de Braud, Luigi De Petris, Jonas Bergh, Ingemar Ernberg, Benjamin Besse, Fabrice Barlesi, Elena Garralda, Alejandro Piris-Giménez, Michael Baumann, Giovanni Apolone, Jean Charles Soria, Josep Tabernero, Carlos Caldas, Emile E. Voest
Journal: Nature Medicine (2020)
Abstract 253: The Efficacy of Left Ventricular versus Traditional Chest Compressions During Selective Aortic Arch Perfusion to Treat Traumatic Cardiopulmonary Arrest in a Swine Model
Authors: Benjamin Barringer, Maria Castaneda, Jason Rall, Kenton Anderson
Journal: Circulation (2019)

Introduction: Recent evidence has demonstrated that closed chest compressions (CC) directly over the left ventricle (LV) during traumatic cardiopulmonary arrest (TCPA) improve hemodynamics and return of spontaneous circulation (ROSC) when compared to traditional chest compressions. Selective Aortic Arch Perfusion (SAAP) is also able to improve hemodynamics as well as control hemorrhage during TCPA. Hypothesis: We hypothesized that LV compressions would increase ROSC when compared to traditional compressions in an animal model of TCPA where SAAP was being used. We also compared LV and Traditional compressions with SAAP to historical controls that received compressions without SAAP. Methods: Transthoracic echo was used to mark the location of the aortic root and the center of the left ventricle on animals (n=24, 12 in each arm) which were randomized to receive chest compressions in one of the two locations. One third of each animal’s blood volume was removed and ventricular fibrillation (VF) was induced to simulate traumatic cardiac arrest. After a period of ten minutes of VF, basic life support (BLS) with mechanical CPR was initiated and performed for ten minutes followed by advanced life support (ALS) and blood transfusion for an additional ten minutes. The SAAP balloon was inflated at minute 6 of BLS. Hemodynamic variables were averaged every two minutes. The same model was used for historical controls (n=26, 13 in each arm) without the use of SAAP, so comparisons were treated as a single study with a factorial design. Results: There were no differences in hemodynamic variables, ROSC (p=0.67) or survival (p=0.64) between SAAP groups. However, when the LV animals were compared to historic controls without SAAP, LV animals had higher ROSC (p=0.02) and survival rates (p=0.04) than Traditional animals. Conclusions: SAAP does not appear to show a synergistic effect with LV compressions, however, SAAP combined with LV compressions improves ROSC and survival when compared to Traditional compressions in our swine model of TCPA. More investigation into SAAP and compression position should be studied to improve treatment of TCPA.
Feasibility and Safety of Transnasal Transesophageal Echocardiography Guiding Left Atrial Appendage Closure Without General Anesthesia
Authors: Wei Sun, Bin Wang, Lin He, Meng Li, Shuyuan Wang, Yuji Xie, Yuman Li, Qing Lv, Li Zhang, Mingxing Xie
Journal: JACC. Cardiovascular imaging (2020)
Harnessing CAR T-cell Insights to Develop Treatments for Hyperinflammatory Responses in Patients with COVID-19
Authors: Sangya Agarwal, Carl H. June
Journal: Cancer Discovery (2020)

Abstract Summary: Cytokine release and macrophage activation contribute to immunopathology after SARS-CoV-2 infection. We discuss approaches to decrease the morbidity and mortality in patients with COVID-19 by repurposing existing drugs previously developed for cancer therapy.
Capivasertib, an AKT Kinase Inhibitor, as Monotherapy or in Combination with Fulvestrant in Patients with<i>AKT1</i>E17K-Mutant, ER-Positive Metastatic Breast Cancer
Authors: Lillian M. Smyth, Kenji Tamura, Mafalda Oliveira, Eva M. Ciruelos, Ingrid A. Mayer, Marie-Paule Sablin, Laura Biganzoli, Helen J. Ambrose, Jack Ashton, Alan Barnicle, Des D. Cashell, Claire Corcoran, Elza C. de Bruin, Andrew Foxley, Joana Hauser, Justin P.O. Lindemann, Rhiannon Maudsley, Robert McEwen, Michele Moschetta, Martin Pass, Vicky Rowlands, Gaia Schiavon, Udai Banerji, Maurizio Scaltriti, Barry S. Taylor, Sarat Chandarlapaty, José Baselga, David M. Hyman
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The activating mutation AKT1E17K occurs in approximately 7% of estrogen receptor–positive (ER+) metastatic breast cancer (MBC). We report, from a multipart, first-in-human, phase I study (NCT01226316), tolerability and activity of capivasertib, an oral AKT inhibitor, as monotherapy or combined with fulvestrant in expansion cohorts of patients with AKT1E17K-mutant ER+ MBC. Patients and Methods: Patients with an AKT1E17K mutation, detected by local (next-generation sequencing) or central (plasma-based BEAMing) testing, received capivasertib 480 mg twice daily, 4 days on, 3 days off, weekly or 400 mg twice daily combined with fulvestrant at the labeled dose. Study endpoints included safety, objective response rate (ORR; RECIST v1.1), progression-free survival (PFS), and clinical benefit rate at 24 weeks (CBR24). Biomarker analyses were conducted in the combination cohort. Results: From October 2013 to August 2018, 63 heavily pretreated patients received capivasertib (20 monotherapy, 43 combination). ORR was 20% with monotherapy, and within the combination cohort was 36% in fulvestrant-pretreated and 20% in fulvestrant-naïve patients, although the latter group may have had more aggressive disease at baseline. AKT1E17K mutations were detectable in plasma by BEAMing (95%, 41/43), droplet digital PCR (80%, 33/41), and next-generation sequencing (76%, 31/41). A ≥50% decrease in AKT1E17K at cycle 2 day 1 was associated with improved PFS. Combination therapy appeared more tolerable than monotherapy [most frequent grade ≥3 adverse events: rash (9% vs. 20%), hyperglycemia (5% vs. 30%), diarrhea (5% vs. 10%)]. Conclusions: Capivasertib demonstrated clinically meaningful activity in heavily pretreated patients with AKT1E17K-mutant ER+ MBC, including those with prior disease progression on fulvestrant. Tolerability and activity appeared improved by the combination.
PPE guidance for covid-19: be honest about resource shortages
Authors: Eoin D O’Sullivan
Journal: BMJ (2020)

Healthcare workers are acutely aware of the regional and international differences in personal protective equipment (PPE) guidance and practice, as discussed by Godlee. 1 The discordance between high level guidelines, such as those issued by larger organisations, and hospital level guidance is a major source of anxiety and might even foster mistrust of future guidance.
Clinical Characteristics of Covid-19 in New York City
Authors: Parag Goyal, Justin J Choi, Laura C Pinheiro, Edward J Schenck, Ruijun Chen, Assem Jabri, Michael J Satlin, Thomas R Campion, Musarrat Nahid, Joanna B Ringel, Katherine L Hoffman, Mark N Alshak, Han A Li, Graham T Wehmeyer, Mangala Rajan, Evgeniya Reshetnyak, Nathaniel Hupert, Evelyn M Horn, Fernando J Martinez, Roy M Gulick, Monika M Safford
Journal: New England Journal of Medicine (2020)

Covid-19 in New York City In this series of 393 consecutive patients admitted with Covid-19 to two New York City hospitals from March 3 to March 27, a third of patients received invasive mechanical...
The International Association for the Study of Lung Cancer Thymic Tumors Staging Project: The Impact of the Eighth Edition of the Union for International Cancer Control and American Joint Committee on Cancer TNM Stage Classification of Thymic Tumors
Authors: Enrico Ruffini, Wentao Fang, Francesco Guerrera, James Huang, Meinoshin Okumura, Dong Kwan Kim, Nicolas Girard, Andrea Billè, Souheil Boubia, Ayten Kayi Cangir, Frank Detterbeck, Conrad Falkson, Pier Luigi Filosso, Giuseppe Giaccone, Kazuya Kondo, Maurizio Infante, Marco Lucchi, Mirella Marino, Edith M. Marom, Andrew G. Nicholson, Andreas Rimner, Ramon Rami-Porta, Hisao Asamura
Journal: Journal of Thoracic Oncology (2019)
Enhancing the Functional Activity of the OCT-1 Influx Pump May Overcome the Negative Impact of Low OCT-1 Activity in Imatinib Treated CML Patients
Authors: Deborah White, Phuong Dang, Kelvin Groot Obbink, Amity Frede, Chung Kok, Timothy P Hughes, Richard D’Andrea
Journal: Blood (2008)
Photo-triggered self-destructive ROS-responsive nanoparticles of high paclitaxel/chlorin e6 co-loading capacity for synergetic chemo-photodynamic therapy
Authors: Xiaoye Yang, Xiaoqun Shi, Yanan Zhang, Jiangkang Xu, Jianbo Ji, Lei Ye, Fan Yi, Guangxi Zhai
Journal: Journal of Controlled Release (2020)
Targeting senescent cells to attenuate cardiovascular disease progression
Authors: Ping Song, Qiang Zhao, Ming-Hui Zou
Journal: Ageing Research Reviews (2020)

Cardiovascular disease (CVD) is the most common disease to increase as life expectancy increases. Most high-profile pharmacological treatments for age-related CVD have led to inefficacious results, implying that novel approaches to treating these pathologies are needed. Emerging data have demonstrated that senescent cardiovascular cells, which are characterized by irreversible cell cycle arrest and a distinct senescence-associated secretory phenotype, accumulate in aged or diseased cardiovascular systems, suggesting that they may impair cardiovascular function. This review discusses the evidence implicating senescent cells in cardiovascular ageing, the onset and progression of CVD, and the molecular mechanisms underlying cardiovascular cell senescence. We also review eradication of senescent cardiovascular cells by small-molecule-drug-mediated apoptosis and immune cell-mediated efferocytosis and toxicity as promising and precisely targeted therapeutics for CVD prevention and treatment.
Low-dose versus High-dose Carfilzomib with Dexamethasone (S1304) in Patients with Relapsed-Refractory Multiple Myeloma
Authors: Sikander Ailawadhi, Rachael Sexton, Suzanne Lentzsch, Muneer H. Abidi, Peter M. Voorhees, Adam D. Cohen, Eric M. Rohren, Stephen Heitner, Kevin Kelly, Niklas J. Mackler, David M. Baer, Antje Hoering, Brian Durie, Robert Z. Orlowski
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Treatment of multiple myeloma has evolved tremendously and optimal utilization of available therapies will ensure maximal patient benefits. Patients and Methods: We report the Southwest Oncology Group randomized phase II trial (S1304) comparing twice weekly low-dose (27 mg/m2; arm 1) to high-dose carfilzomib (56 mg/m2; arm 2), both with dexamethasone, administered for 12 cycles (11 months) for relapsed and/or refractory multiple myeloma with up to six prior lines of therapy (NCT01903811). The primary endpoint was progression-free survival (PFS), and patients on arm 1 could cross-over to arm 2 after progression on treatment. Results: Among 143 enrolled patients, of whom 121 were eligible and analyzable, the overall response rate was 42.8%, with no significant difference between the arms (P = 0.113). Also, neither the median PFS [5 months and 8 months, respectively; HR, 1.061; 80% Wald confidence interval (CI), 0.821–1.370; P = 0.384] nor the median overall survival were significantly different (26 and 22 months, respectively; HR, 1.149, 80% Wald CI, 0.841–.571; P = 0.284). Sixteen patients crossed over to arm 2 with a median PFS benefit of 3 months. Certain adverse events (AE) were more frequent in arm 2, including fatigue, thrombocytopenia, and peripheral neuropathy, but there was no significant difference in cardiopulmonary AEs. Conclusions: This randomized trial did not support a benefit of fixed duration, twice weekly 56 mg/m2 dosing of carfilzomib over the 27 mg/m2 dose for the treatment of relapsed and/or refractory multiple myeloma. However, treatment to progression in earlier patient populations with high-dose carfilzomib using different schedules should still be considered as part of the standard of care.
Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma
Authors: Lennart Raman, Malaïka Van der Linden, Kim Van der Eecken, Karim Vermaelen, Ingel Demedts, Veerle Surmont, Ulrike Himpe, Franceska Dedeurwaerdere, Liesbeth Ferdinande, Yolande Lievens, Kathleen Claes, Björn Menten, Jo Van Dorpe
Journal: Genome Medicine (2020)

Abstract Background Accurate lung cancer classification is crucial to guide therapeutic decisions. However, histological subtyping by pathologists requires tumor tissue—a necessity that is often intrinsically associated with procedural difficulties. The analysis of circulating tumor DNA present in minimal-invasive blood samples, referred to as liquid biopsies, could therefore emerge as an attractive alternative. Methods Concerning adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, our proof of concept study investigates the potential of liquid biopsy-derived copy number alterations, derived from single-end shallow whole-genome sequencing (coverage 0.1–0.5×), across 51 advanced stage lung cancer patients. Results Genomic abnormality testing reveals anomalies in 86.3% of the liquid biopsies (16/20 for adenocarcinoma, 13/16 for squamous cell, and 15/15 for small cell carcinoma). We demonstrate that copy number profiles from formalin-fixed paraffin-embedded tumor biopsies are well represented by their liquid equivalent. This is especially valid within the small cell carcinoma group, where paired profiles have an average Pearson correlation of 0.86 (95% CI 0.79–0.93). A predictive model trained with public data, derived from 843 tissue biopsies, shows that liquid biopsies exhibit multiple deviations that reflect histological classification. Most notably, distinguishing small from non-small cell lung cancer is characterized by an area under the curve of 0.98 during receiver operating characteristic analysis. Additionally, we investigated how deeper paired-end sequencing, which will eventually become feasible for routine diagnosis, empowers tumor read enrichment by insert size filtering: for all of the 29 resequenced liquid biopsies, the tumor fraction could be increased in silico, thereby “rescuing” three out of five cases with previously undetectable alterations. Conclusions Copy number profiling of cell-free DNA enables histological classification. Since shallow whole-genome sequencing is inexpensive and often fully operational at routine molecular laboratories, this finding has current diagnostic potential, especially for patients with lesions that are difficult to reach.
Antirheumatic agents in covid-19: is IL-6 the right target?
Authors: Pier Leopoldo Capecchi, Pietro Enea Lazzerini, Luca Volterrani, Maria Antonietta Mazzei, Barbara Rossetti, Giacomo Zanelli, David Bennett, Elena Bargagli, Federico Franchi, Matteo Cameli, Serafina Valente, Luca Cantarini, Bruno Frediani
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Abstract</h3> <h3>Objectives</h3> <i>Pseudomonas aeruginosa</i> is a key opportunistic pathogen causing a wide range of community- and hospital-acquired infections in immunocompromised or catheterized patients. Here, we report the complete genome sequence of a multidrug resistant (MDR) <i>P. aeruginosa</i> DMC30b in order to elucidate the genetic diversity, molecular epidemiology, and underlying mechanisms for antimicrobial resistance and virulence. <h3>Methods</h3> <i>P. aeruginosa</i> DMC30b was isolated from septic wound swab of a severe burn patient. Whole-genome sequencing (WGS) was performed under Ion Torrent platform. The genome was annotated using the SPAdes v. 3.12.01 in an integrated Genome Analysis Platform (IonGAP) for Ion Torrent sequence data. The genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). <i>In-silico</i> predictions of antimicrobial resistance genes (ARGs), virulence factor genes (VFGs) and metabolic functional potentials were performed using different curated bioinformatics tools. <h3>Results</h3> <i>P. aeruginosa</i> DMC30b was classified as MDR and belongs to sequence type 244 (ST244). The complete genome size is 6,994,756 bp with a coverage of 76.76x, G+C content of 65.7% and a BUSCO (Benchmarking Universal Single-Copy Orthologs) score of 100. The genome of <i>P. aeruginosa</i> DMC30b harboured two plasmids (e,g., IncP-6 plasmid p10265-KPC; 78,007 bp and ColRNAI_pkOIISD1; 9,359 bp), 35 resistomes (ARGs) conferring resistance to 18 different antibiotics (including four beta-lactam classes), and 214 VFGs. It was identified as the 167<sup>th</sup> ST244 strain among ∼ 5,800 whole-genome sequences of <i>P. aeruginosa</i> available in the NCBI database. <h3>Conclusion</h3> <i>P. aeruginosa</i> DMC30b belongs to ST244 and was identified as the 167<sup>th</sup> such isolate to be submitted to NCBI, and the first complete ST244 genome from Bangladesh. The complete genome data with high genetic diversity and underlying mechanisms for antimicrobial resistance and virulence of <i>P. aeruginosa</i> DMC30b (ST244) will aid in understanding the evolution and phylogeny of such high-risk clones and provide a solid basis for further research on MDR or extensively drug resistant strains.
Abstract 12805: High Brain Natriuretic Peptide Level is an Independent Predictor of Long-Term Mortality and Hospitalization Due to Heart Failure in Patients With Pacemaker Implantation
Authors: Yasuhiro Matsuda, Masaharu Masuda, Mitsutoshi Asai, Osamu Iida, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Takashi Kanda, Takuya Tsujimura, Shota Okuno, Hiroyuki Uematsu, Yuki Sato, Shodai Kawanami, Hiroki Sugae, Sho Nakao, Toshiaki Mano
Journal: Circulation (2019)

Introduction: Although heart failure is a major cause of mortality and hospitalization in patients with pacemaker implantation, its predictors have not been clarified. The purpose of this study was...
Abstract 14988: Measuring Strength and Physical Activity in Patients With Advanced Systolic Heart Failure With Left Ventricular Assist Devices
Authors: Alexandra Coston, Joronia Chery, Rachel Porth, Matthew Lawrence, Amanda R Vest
Journal: Circulation (2019)

Introduction: Patients with advanced systolic heart failure (HF) may receive a left ventricular assist device (LVAD) to improve functional capacity, quality of life (QoL), and survival. Multiple to...