tbuckley/cabot-search huggingface dataset:
Access to medicines in Latin America and the Caribbean (LAC): a scoping study
Authors: Isabel Cristina Martins Emmerick, Maria Auxiliadora Oliveira, Vera Lucia Luiza, Thiago Botelho Azeredo, Maryam Bigdeli
Journal: BMJ (2013)

Objective: To assess scientific publication and map research gaps on access to medicines (ATM) in Latin American and the Caribbean low-income and middleincome countries (LMIC). Design: Scoping review. Two independent reviewers assessed studies for inclusion and extracted data from each study. Information sources: Search strategies were developed and the following databases were searched: MEDLINE, ISI, SCOPUS and Lilacs, from 2000 to 2010. Eligibility criteria: Research articles and reviews published in English, Spanish and Portuguese were included. Studies including only high-income countries were excluded, as well as those carried out in very limited settings and discussion papers. Results: The 77 articles retained were categorised through consensus among the research team according to the level of the health system addressed, ATM domain and research issues covered. Publications on ATM have increased over time during the study period (r 0.93, p=0.00; R 2 0.85). The top five countries covered were Brazil (68.8%), Mexico (15.6%), Colombia (11.7%), Argentina (10.4%) and Peru (10.4%). ‘Health services delivery’ and ‘patients, household and communities’ were the health system levels most frequently covered. The ATM domains ‘leadership and governance’, ‘sustainable financing, affordability and price of medicines’, ‘medicines selection and use’ and ‘availability of medicines’ were the top four explored. There are research gaps in important areas such as ‘human resources for health’, ‘global policies and human rights’, ‘production of medicines’ and ‘traditional medicine’. Conclusions: The upward trend on scientific publication reflects a growing research capacity in the region, which is concentrated on research teams in selected countries. The gaps on research capacity could be overcome through research collaboration among countries. It is important to strengthen these collaborations, assuring that interests and needs from the LMIC are addressed and local capacity building is promoted.
Abstract PO-21: Investigating the role of exosomes derived from chemotherapy-resistant leukemia cells as mediators of cellular plasticity
Authors: Taismara Garnica, Jéssika Lesbon, Arina Rochetti, Chantell Payton, Rhona Muirhead, Lisa Pang, David Argyle, Juliano da Silveira, Heidge Fukumasu
Journal: Blood Cancer Discovery (2020)

Abstract Adult T-cell leukemia/lymphoma (ATLL) is a type of cancer with aggressive and rapid progression and has been linked to infection with the human T-cell lymphotropic virus type 1 (HTLV-1). Standard treatment consists of chemotherapy, radiation therapy, and stem-cell transplant, but the development of chemoresistance is common. Despite major advances in understanding the pathogenesis of the disease, patients who do not respond or achieve only transient responses remain a challenge for clinicians. Exosomes are small extracellular vesicles (30-150 nm in diameter) involved in intercellular communication and biologic material transference (including mRNA, miRNA, lipids, and metabolites) between the cells. Exosomes are an emerging key to understanding cancer cell communication and signaling pathway activation during the chemoresistance process. Our hypothesis is that exosomes secreted by chemoresistant (CR) ATLL cells can drive phenotypic changes in nonresistant ATLL cells. For this purpose, we induced chemoresistance using the CHOP protocol (dexamethasone, doxorubicin, and vincristine cocktail) in Jurkat cells (human acute T-cell leukemia/lymphoma). We determined IC50 values as 1 nM of dexamethasone, 0.05 μM of doxorubicin, and 1 nM of vincristine. Acquisition of chemoresistance was demonstrated by increased cell viability after treatment using IC50 of drugs cocktail. We found that Jurkat-CR have slower doubling time compared to respective naïve cells, 26 hours and 21 hours to CR-Jurkat and naïve, respectively. Exosomes derived from the putative chemoresistant were isolated and used to treat their respective naïve cells. There was an increase in cell proliferation after the exosome's treatment comparing to control for Jurkat (P&amp;lt;0.0035). However, there was no difference in proliferation comparing the treatment using exosomes derived from naïve cells and those derived from CR cells (P=0.91). The cell proliferation was higher after 78 hours of exosomes' treatment (P&amp;lt;0.001). Those results are preliminary data. Despite the differences in proliferation related to exosomes treatment, further experiments are required to prove our initial hypothesis. Citation Format: Taismara Garnica, Jéssika Lesbon, Arina Rochetti, Chantell Payton, Rhona Muirhead, Lisa Pang, David Argyle, Juliano da Silveira, Heidge Fukumasu. Investigating the role of exosomes derived from chemotherapy-resistant leukemia cells as mediators of cellular plasticity [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-21.
Viral Dynamics of SARS-CoV-2 in Critically Ill Allogeneic Hematopoietic Stem Cell Transplant Recipients and Immunocompetent Patients with COVID-19
Authors: Kevin Roedl, Silke Heidenreich, Susanne Pfefferle, Dominik Jarczak, Tatiana Theresa Urbanowicz, Dominik Nörz, Martin Aepfelbacher, Nicolaus Kröger, Stefan Kluge, Marc Lütgehetmann, Maximilian Christopeit, Dominic Wichmann
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Aortic Arch Obstruction After the Norwood Procedure for Hypoplastic Left-Heart Syndrome: Is it Inevitable? Is it Preventable?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: John J. Lamberti
Journal: Journal of the American College of Cardiology (2011)
Genomics and Epigenomics in Parathyroid Neoplasia: from Bench to Surgical Pathology Practice
Authors: C. Christofer Juhlin, Lori A. Erickson
Journal: Endocrine Pathology (2020)

Abstract The majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually a straightforward diagnosis in endocrine pathology when in the appropriate clinical setting, although subsets of cases will exhibit atypical histological features that may warrant additional immunohistochemical and genetic analyses to estimate the malignant potential. Parathyroid carcinomas on the other hand, are bona fide malignant tumors characterized by their unequivocal invasion demonstrated through routine histology or metastasis. The ultimate endpoint for any molecular marker discovered through laboratory investigations is to be introduced in clinical routine practice and guide the surgical pathologist in terms of diagnostics and prognostication. For parathyroid tumors, the two main diagnostic challenges include the distinction between parathyroid adenoma and parathyroid carcinoma, as well as the pinpointing of hereditable disease for familial screening purposes. While numerous markers on genetic, epigenetic, and protein levels have been proposed as discriminative in these aspects, this review aims to condense the scientific coverage of these enigmatic topics and to propose a focused surgical pathology approach to the subject.
Endothelial eNAMPT amplifies pre-clinical acute lung injury: efficacy of an eNAMPT-neutralising monoclonal antibody
Authors: Hector Quijada, Tadeo Bermudez, Carrie L. Kempf, Daniel G. Valera, Alexander N. Garcia, Sara M. Camp, Jin H. Song, Evelyn Franco, Jessica K. Burt, Belinda Sun, Joseph B. Mascarenhas, Kimberlie Burns, Amir Gaber, Radu C. Oita, Vivian Reyes Hernon, Christy Barber, Liliana Moreno-Vinasco, Xiaoguang Sun, Anne E. Cress, Diego Martin, Zhonglin Liu, Ankit A. Desai, Viswanathan Natarajan, Jeffrey R. Jacobson, Steven M. Dudek, Christian Bime, Saad Sammani, Joe G.N. Garcia
Journal: European Respiratory Journal (2020)

Rationale The severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 pandemic has highlighted the serious unmet need for effective therapies that reduce acute respiratory distress syndrome (ARDS) mortality. We explored whether extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a ligand for Toll-like receptor (TLR)4 and a master regulator of innate immunity and inflammation, is a potential ARDS therapeutic target. Methods Wild-type C57BL/6J or endothelial cell (EC)-c NAMPT −/− knockout mice (targeted EC NAMPT deletion) were exposed to either a lipopolysaccharide (LPS)-induced (“one-hit”) or a combined LPS/ventilator (“two-hit”)-induced acute inflammatory lung injury model. A NAMPT-specific monoclonal antibody (mAb) imaging probe ( 99m Tc-ProNamptor) was used to detect NAMPT expression in lung tissues. Either an eNAMPT-neutralising goat polyclonal antibody (pAb) or a humanised monoclonal antibody (ALT-100 mAb) were used in vitro and in vivo . Results Immunohistochemical, biochemical and imaging studies validated time-dependent increases in NAMPT lung tissue expression in both pre-clinical ARDS models. Intravenous delivery of either eNAMPT-neutralising pAb or mAb significantly attenuated inflammatory lung injury (haematoxylin and eosin staining, bronchoalveolar lavage (BAL) protein, BAL polymorphonuclear cells, plasma interleukin-6) in both pre-clinical models. In vitro human lung EC studies demonstrated eNAMPT-neutralising antibodies (pAb, mAb) to strongly abrogate eNAMPT-induced TLR4 pathway activation and EC barrier disruption. In vivo studies in wild-type and EC-c NAMPT −/− mice confirmed a highly significant contribution of EC-derived NAMPT to the severity of inflammatory lung injury in both pre-clinical ARDS models. Conclusions These findings highlight both the role of EC-derived eNAMPT and the potential for biologic targeting of the eNAMPT/TLR4 inflammatory pathway. In combination with predictive eNAMPT biomarker and NAMPT genotyping assays, this offers the opportunity to identify high-risk ARDS subjects for delivery of personalised medicine.
A Novel Function of Sphingolipid Signaling via S1PR3 in Hematopoietic and Leukemic Stem Cells
Authors: Chong Yang, Masayuki Yamashita, Toshio Suda
Journal: Blood Cancer Discovery (2020)

In this issue of Blood Cancer Discovery, Xie and colleagues describe a novel function of sphingosine-1-phosphate receptor 3 (S1PR3) to regulate myeloid differentiation and activate inflammatory programs in both human hematopoietic stem cells and leukemic stem cells. They propose S1PR3 as a major downstream signaling pathway of a TNFα-NF-κB axis in this study and unlock potential therapeutic opportunities to improve outcomes of patients with acute myeloid leukemia by modulating sphingolipid signaling via S1PR3.See related article by Xie et al., p. 32.
Therapeutic Potential of NTRK3 Inhibition in Desmoplastic Small Round Cell Tumor
Authors: Koichi Ogura, Romel Somwar, Julija Hmeljak, Heather Magnan, Ryma Benayed, Amir Momeni Boroujeni, Anita S. Bowman, Marissa S. Mattar, Inna Khodos, Elisa de Stanchina, Achim Jungbluth, Marina Asher, Igor Odintsov, Alifiani B. Hartono, Michael P. LaQuaglia, Emily Slotkin, Christine A. Pratilas, Sean Bong Lee, Lee Spraggon, Marc Ladanyi
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Desmoplastic small round cell tumor (DSRCT) is a highly lethal intra-abdominal sarcoma of adolescents and young adults. DSRCT harbors a t(11;22)(p13:q12) that generates the EWSR1-WT1 chimeric transcription factor, the key oncogenic driver of DSRCT. EWSR1-WT1 rewires global gene expression networks and activates aberrant expression of targets that together mediate oncogenesis. EWSR1-WT1 also activates a neural gene expression program. Experimental Design: Among these neural markers, we found prominent expression of neurotrophic tyrosine kinase receptor 3 (NTRK3), a druggable receptor tyrosine kinase. We investigated the regulation of NTRK3 by EWSR1-WT1 and its potential as a therapeutic target in vitro and in vivo, the latter using novel patient-derived models of DSRCT. Results: We found that EWSR1-WT1 binds upstream of NTRK3 and activates its transcription. NTRK3 mRNA is highly expressed in DSRCT compared with other major chimeric transcription factor–driven sarcomas and most DSRCTs are strongly immunoreactive for NTRK3 protein. Remarkably, expression of NTRK3 kinase domain mRNA in DSRCT is also higher than in cancers with NTRK3 fusions. Abrogation of NTRK3 expression by RNAi silencing reduces growth of DSRCT cells and pharmacologic targeting of NTRK3 with entrectinib is effective in both in vitro and in vivo models of DSRCT. Conclusions: Our results indicate that EWSR1-WT1 directly activates NTRK3 expression in DSRCT cells, which are dependent on its expression and activity for growth. Pharmacologic inhibition of NTRK3 by entrectinib significantly reduces growth of DSRCT cells both in vitro and in vivo, providing a rationale for clinical evaluation of NTRK3 as a therapeutic target in DSRCT.
Lotus seedpod-inspired internal vascularized 3D printed scaffold for bone tissue repair
Authors: Xiaoyu Han, Mingjie Sun, Bo Chen, Qimanguli Saiding, Junyue Zhang, Hongliang Song, Lianfu Deng, Peng Wang, Weiming Gong, Wenguo Cui
Journal: Bioactive Materials (2020)

In the field of bone defect repair, 3D printed scaffolds have the characteristics of personalized customization and accurate internal structure. However, how to construct a well-structured vascular network quickly and effectively inside the scaffold is essential for bone repair after transplantation. Herein, inspired by the unique biological structure of "lotus seedpod", hydrogel microspheres encapsulating deferoxamine (DFO) liposomes were prepared through microfluidic technology as "lotus seeds", and skillfully combined with a three-dimensional (3D) printed bioceramic scaffold with biomimetic "lotus" biological structure which can internally grow blood vessels. In this composite scaffold system, DFO was effectively released by 36% in the first 6 h, which was conducive to promote the growth of blood vessels inside the scaffold quickly. In the following 7 days, the release rate of DFO reached 69%, which was fundamental in the formation of blood vessels inside the scaffold as well as osteogenic differentiation of bone mesenchymal stem cells (BMSCs). It was confirmed that the composite scaffold could significantly promote the human umbilical vein endothelial cells (HUVECs) to form the vascular morphology within 6 h in vitro. In vivo, the composite scaffold increased the expression of vascularization and osteogenic related proteins Hif1-α, CD31, OPN, and OCN in the rat femoral defect model, significantly cutting down the time of bone repair. To sum up, this "lotus seedpod" inspired porous bioceramic 3D printed scaffold with internal vascularization functionality has broad application prospects in the future.
241MO Survival impact of pretreatment absolute lymphocyte count in cervical cancer patients receiving definitive chemoradiation
Authors: Y.H.E. Chuk, S.W.S. Tse, C.Y.R. Ho, H.Y. Wong, N.Y. Yeung, K.M. Cheung, J.C.H. Chow, K.H. Wong
Journal: Annals of Oncology (2020)
Hormone replacement therapy and asthma onset in menopausal women: National cohort study
Authors: Syed A. Shah, Holly Tibble, Rebecca Pillinger, Susannah McLean, Dermot Ryan, Hilary Critchley, David Price, Catherine M. Hawrylowicz, Colin R. Simpson, Ireneous N. Soyiri, Francis Appiagyei, Aziz Sheikh, Bright I. Nwaru
Journal: Journal of Allergy and Clinical Immunology (2020)

There is uncertainty about the role of hormonal replacement therapy (HRT) in the development of asthma.We investigated whether use of HRT and duration of use was associated with risk of development of asthma in perimenopausal and postmenopausal women.We constructed a 17-year (from January 1, 2000, to December 31, 2016) open cohort of 353,173 women (aged 46-70 years) from the Optimum Patient Care Database, a longitudinal primary care database from across the United Kingdom. HRT use, subtypes, and duration of use; confounding variables; and asthma onset were defined by using the Read Clinical Classification System. We fitted multilevel Cox regression models to estimate hazard ratios (HRs) with 95% CIs.During the 17-year follow-up (1,340,423 person years), 7,614 new asthma cases occurred, giving an incidence rate of 5.7 (95% CI = 5.5-5.8) per 1,000 person years. Compared with nonuse of HRT, previous use of any (HR = 0.83; 95% CI = 0.76-0.88), estrogen-only (HR = 0.89; 95% CI = 0.84-0.95), or combined estrogen and progestogen (HR = 0.82; 95% CI = 0.76-0.88) HRT was associated with a reduced risk of asthma onset. This was also the case with current use of any (HR = 0.79; 95% CI = 0.74-0.85), estrogen-only (HR = 0.80; 95% CI = 0.73-0.87), and combined estrogen and progestogen (HR = 0.78; 95% CI = 0.70-0.87) HRT. Longer duration of HRT use (1-2 years [HR = 0.93; 95% CI = 0.87-0.99]; 3-4 years [HR = 0.77; 95% CI = 0.70-0.84]; and ≥5 years [HR = 0.71; 95% CI = 0.64-0.78]) was associated with a dose-response reduced risk of asthma onset.We found that HRT was associated with a reduced risk of development of late onset asthma in menopausal women. Further cohort studies are needed to confirm these findings.
15904 Efficacy and safety of long-term tildrakizumab for plaque psoriasis: 4-year results from reSURFACE 1
Authors: Jeffrey Crowley, Neil J. Korman, Lynda Spelman, Atsuyuki Igarashi, Aditya K. Gupta, Alan M. Mendelsohn, Stephen J. Rozzo, Kimberly M. Eads, Scott T. Guenthner
Journal: Journal of the American Academy of Dermatology (2020)
261P Clinical outcomes of early-progressed follicular lymphoma in Korea: A multicenter, retrospective analysis
Authors: J.H. Yi, W.S. Kim, S.J. Kim, D.H. Yoon, C. Suh, W-S. Lee, D.H. Yang, J-C. Jo, Y. Koh, J-O. Lee, B.S. Kim, S.N. Lim, M.H. Heo, B.S. Sohn, Y.S. Choi, J. Park, H.J. Kim, S.I.L. Lee, S.Y. Oh
Journal: Annals of Oncology (2020)
WORLD CANCER RESEARCH DAY: A Call to Action for a Coordinated International Research Effort to Prevent, Diagnose, and Treat Cancer
Authors: Marta Puyol, Joan Seoane, Esther Aguilar, Lisa B. Vozza, Isabel Orbe, Katherine H. Crawford, Ana Fernández, Freddie Bray, Sonali E. Johnson, Satish Gopal
Journal: Clinical Cancer Research (2020)

Cancer is a major public health problem and the second leading cause of death worldwide. The burden of cancer continues to grow and is projected to double by 2040. This situation calls for coordinated action and emphasizes the need to join efforts on worldwide initiatives, including World Cancer Research Day (WCRD), which aims to create and consolidate a yearly momentum to raise awareness and commitment for research on cancer. Cancer research is a key driver of advances in prevention and therapeutic strategies that will benefit tomorrow's cancer patients. In 2016, 10 international organizations partnered to launch the WCRD initiative. Five years later, a total of 89 organizations and more than half a million people have joined this global movement that helps raise awareness of the importance of cancer research, demonstrating that a collaborative research culture is essential to address current challenges and create opportunities to accelerate impactful cancer research for a better future.
Time to Address the Cardiac Metabolic “Triple Whammy”: Ischemic Heart Failure in Diabetic Patients⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: John D. Horowitz, Jennifer A. Kennedy
Journal: Journal of the American College of Cardiology (2006)
Usual and Rare Abdominal Location of Giant Cell Arteritis Diagnosed and Follow-up With 18F-FDG PET/CT
Authors: Pierre-Benoît Bonnefoy, Julie Goutte, Nicolas Jacquet-Francillon, Vincent Habouzit, Nathalie Prevot
Journal: Clinical Nuclear Medicine (2020)

Giant cell arteritis is not an uncommon disease, and its extension is furthermore finely assessed with new-generation PET/CT system. 18F-FDG PET/CT is increasingly used in case of large-vessel vasculitis for optimal diagnosis, activity monitoring (even when treated with interleukin 6 receptor inhibitor), and evaluation damage progression. We reported the case of a 61-year-old woman with common giant cell arteritis pattern on 18F-FDG PET/CT (aorta and large arteries) and uptakes in all aorta branches, mainly impressive and uncommon in the abdomen. After 2 years of therapeutic optimization including IV tocilizumab and monitoring with 18F-FDG PET/CT, a complete metabolical response was assessed.
Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU
Authors: Arnaud Fekkar, Alexandre Lampros, Julien Mayaux, Corentin Poignon, Sophie Demeret, Jean-Michel Constantin, Anne-Geneviève Marcelin, Antoine Monsel, Charles-Edouard Luyt, Marion Blaize
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question.