tbuckley/cabot-search huggingface dataset:
Self-harm, Traumatic Brain Injury, and Suicide
Authors: Simon Fleminger, Jessica Fleminger
Journal: JAMA (2018)

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Abstract 20166: Development of a Risk Prediction Model for 1-Year Mortality After Surgical vs. Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis
Authors: Suzanne J Baron, David J Cohen, Sunil Suchindran, Michael Pencina, Dadi Dai, Roland Matsouaka, J M Brennan
Journal: Circulation (2016)

Introduction: Treatment options for patients (pts) with severe aortic stenosis (AS) include surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). Although rand...
Multicenter, Open-Label, 3-Arm Study of Gilteritinib, Gilteritinib Plus Azacitidine, or Azacitidine Alone in Newly Diagnosed FLT3 Mutated (FLT3mut+) Acute Myeloid Leukemia (AML) Patients Ineligible for Intensive Induction Chemotherapy: Findings from the Safety Cohort
Authors: Jordi Esteve, Rik Schots, Teresa Bernal Del Castillo, Je-Hwan Lee, Eunice S. Wang, Shira Dinner, Mark D. Minden, Olga Salamero, Jorge Sierra, Goichi Yoshimoto, Kamel Laribi, Janusz Halka, Pau Montesinos, Shufang Liu, Elizabeth Shima Rich, Erkut Bahceci
Journal: Blood (2018)
mRNA-Based Genetic Reprogramming
Authors: Luigi Warren, Cory Lin
Journal: Molecular Therapy (2018)

The discovery that ordinary skin cells can be turned into pluripotent stem cells by the forced expression of defined factors has raised hopes that personalized regenerative treatments based on immunologically compatible material derived from a patient's own cells might be realized in the not-too-distant future. A major barrier to the clinical use of induced pluripotent stem cells (iPSCs) was initially presented by the need to employ integrating viral vectors to express the factors that induce an embryonic gene expression profile, which entails potentially oncogenic alteration of the normal genome. Several "non-integrating" reprogramming systems have been developed over the last decade to address this problem. Among these techniques, mRNA reprogramming is the most unambiguously "footprint-free," most productive, and perhaps the best suited to clinical production of stem cells. Herein, we discuss the origins of the mRNA-based reprogramming system, its benefits and drawbacks, recent technical improvements that simplify its application, and the status of current efforts to industrialize this approach to mass-produce human stem cells for the clinic.
HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice
Authors: Huacheng Luo, Ganqian Zhu, Jianfeng Xu, Qian Lai, Bowen Yan, Ying Guo, Tsz Kan Fung, Bernd B. Zeisig, Ya Cui, Jie Zha, Christopher Cogle, Fei Wang, Bing Xu, Feng-Chun Yang, Wei Li, Chi Wai Eric So, Yi Qiu, Mingjiang Xu, Suming Huang
Journal: Cancer Cell (2019)
A phase I clinical trial on intratumoral administration of autologous CD1c (BDCA-1)+ myeloid dendritic cells (myDC) in combination with ipilimumab (IPI) and avelumab (AVE) plus intravenous low-dose nivolumab (NIVO) in patients with advanced solid tumors
Authors: J.K. Schwarze, G. Awada, I. Van Riet, B. Neyns
Journal: Annals of Oncology (2018)

Background: Intratumoral (IT) myDC play a pivotal role in initiating anti-tumor immune responses and in "re-licensing" of anti-tumor cytotoxic T-lymphocytes within the tumor microenvironment. IT injection of anti-PD-L1 IgG1 mAb AVE and anti-CTLA-4 IgG1 mAb IPI may reduce the number of regulatory T cells and lyse PD-L1+ tumor cells increasing the release of tumor antigens that can be captured and processed by IT co-administered CD1c (BDCA-1)+ myDC, reinvigorating the cancer immunity cycle. Methods: Patients (pts) with advanced solid tumors who failed standard-of-care treatment were eligible for this phase I trial with IT injections of ≥ 1 non-visceral metastasis with IPI (max total dose of 10 mg) and AVE (max total dose of 40 mg) plus IV NIVO (10 mg) on day 1 followed by IT injection of autologous, non-manipulated CD1c (BDCA-1)+ myDC on day 2. Administration of AVE, IPI, and NIVO was repeated every 14 days thereafter. Primary endpoints were safety and feasibility. Clinical responses were defined according to iRECIST criteria. Results: In this ongoing trial, 4 pts (3 primary melanoma, 1 epithelial ovarian carcinoma) were treated with IT injection of a median of 30.5x106 (range 10-43x106) CD1c (BDCA-1)+ myDC. A median of 5.5 (range 4-7) study drug administrations were performed. One confirmed partial response was documented in a melanoma patient who previously progressed on immune checkpoint inhibitors. In 2 additional melanoma pts regression of the injected subcutaneous metastases coincided with progression of non-injected metastases. Overall, study treatment was well tolerated and adverse events consisted of transient grade 2 local pain at the injection site in 2 pts, grade 1 pruritus in 2 pts, grade 2 pneumonitis in 1 patient, and pruritus and redness of the skin overlaying the injected lesion in 1 patient. Conclusions: IT injection of autologous, non-manipulated CD1c (BDCA-1)+ myDC with IT co-injection of AVE and IPI plus IV low-dose NIVO is feasible and tolerable and resulted in encouraging early signs of anti-tumor activity in injected as well as non-injected lesions. Clinical trial identification: EudraCT: 2017-003280-35. Legal entity responsible for the study: Universitair Ziekenhuis Brussel. Funding: Kom op Tegen Kanker. Disclosure: All authors have declared no conflicts of interest.
Current Status and Future Opportunities in Lung Precision Medicine Research with a Focus on Biomarkers. An American Thoracic Society/National Heart, Lung, and Blood Institute Research Statement
Authors: Ann Chen Wu, James P. Kiley, Patricia J. Noel, Shashi Amur, Esteban G. Burchard, John P. Clancy, Joshua Galanter, Maki Inada, Tiffanie K. Jones, Jonathan A. Kropski, James E. Loyd, Lawrence M. Nogee, Benjamin A. Raby, Angela J. Rogers, David A. Schwartz, Don D. Sin, Avrum Spira, Scott T. Weiss, Lisa R. Young, Blanca E. Himes
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Thousands of biomarker tests are either available or under development for lung diseases. In many cases, adoption of these tests into clinical practice is outpacing the generation and evaluation of sufficient data to determine clinical utility and ability to improve health outcomes. There is a need for a systematically organized report that provides guidance on how to understand and evaluate use of biomarker tests for lung diseases.We assembled a diverse group of clinicians and researchers from the American Thoracic Society and leaders from the National Heart, Lung, and Blood Institute with expertise in various aspects of precision medicine to review the current status of biomarker tests in lung diseases. Experts summarized existing biomarker tests that are available for lung cancer, pulmonary arterial hypertension, idiopathic pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, sepsis, acute respiratory distress syndrome, cystic fibrosis, and other rare lung diseases. The group identified knowledge gaps that future research studies can address to efficiently translate biomarker tests into clinical practice, assess their cost-effectiveness, and ensure they apply to diverse, real-life populations.We found that the status of biomarker tests in lung diseases is highly variable depending on the disease. Nevertheless, biomarker tests in lung diseases show great promise in improving clinical care. To efficiently translate biomarkers into tests used widely in clinical practice, researchers need to address specific clinical unmet needs, secure support for biomarker discovery efforts, conduct analytical and clinical validation studies, ensure tests have clinical utility, and facilitate appropriate adoption into routine clinical practice.Although progress has been made toward implementation of precision medicine for lung diseases in clinical practice in certain settings, additional studies focused on addressing specific unmet clinical needs are required to evaluate the clinical utility of biomarkers; ensure their generalizability to diverse, real-life populations; and determine their cost-effectiveness.
Abstract 20074: Intracardiac Devices Like Permanent Pacemakers or Cardioverter-Defibrillators Do Not Increase Stroke Risk in Patients With Patent Foramen Ovale
Authors: Manijeh Assar, Michael Sultan, Martha Gulati, Salem Al Rabadi, Sumit Agarwal, Erica Flores, Adnan Habib, Supriya Bhardwaj, Srilekha Sridhara, Orazio Amabile, Mark Tasset, George Gellert, Vidette Villareal-Argente, Claire Kelley, Zuhdi Jasser, Sharon Kusne, Michael Morris, Timothy Byrne, Wilbur Su, Kenith Fang, Ashish Pershad, Divya Ratan Verma
Journal: Circulation (2017)

Hypothesis: To evaluate the risk of stroke in patients with known patent foramen ovale (PFO) undergoing implantation of intracardiac devices Background: The risk of stroke in patients with known PF...
Association of Educational Attainment and Cardiovascular Risk in Hispanic Individuals
Authors: Fatima Rodriguez, David Leonard, Laura DeFina, Carolyn E. Barlow, Benjamin L. Willis, William L. Haskell, David J. Maron
Journal: JAMA Cardiology (2018)

Hispanic individuals are the fastest growing ethnic group in the United States and face lower socioeconomic status compared with non-Hispanic white (NHW) individuals. However, Hispanic individuals tend to experience better health outcomes than expected, a phenomenon known as the Hispanic paradox. Little is known about how higher socioeconomic status is associated with Hispanic cardiovascular risk factor burden and outcomes.
Neuroendocrine features of attachment in infants and nonhuman primates
Authors: Leslie J. Seltzer, Seth D. Pollak
Journal: Behavioral and Brain Sciences (2009)

Comparing adults and infants of our own species must be considered as carefully as comparisons between humans and other primates. While many of the same neuroendocrine systems are present in each, there are also important behavioral and adaptive distinctions which, if not precisely defined, may lead to erroneous conclusions about evolutionary history.
Immune synapses between mast cells and γδ T cells limit viral infection
Authors: Chinmay Kumar Mantri, Ashley L. St. John
Journal: Journal of Clinical Investigation (2018)

Mast cells (MCs) are immune sentinels, but whether they also function as antigen-presenting cells (APCs) remains elusive. Using mouse models of MC deficiency, we report on MC-dependent recruitment and activation of multiple T cell subsets to the skin and draining lymph nodes (DLNs) during dengue virus (DENV) infection. Newly recruited and locally proliferating γδ T cells were the first T cell subset to respond to MC-driven inflammation, and their production of IFN-γ was MC dependent. MC–γδ T cell conjugates were observed consistently in infected peripheral tissues, suggesting a new role for MCs as nonconventional APCs for γδ T cells. MC-dependent γδ T cell activation and proliferation during DENV infection required T cell receptor (TCR) signaling and the nonconventional antigen presentation molecule endothelial cell protein C receptor (EPCR) on MCs. γδ T cells, not previously implicated in DENV host defense, killed infected targeted DCs and contributed to the clearance of DENV in vivo. We believe immune synapse formation between MCs and γδ T cells is a novel mechanism to induce specific and protective immunity at sites of viral infection.
Neonatal Septal Deviations
Authors: S E Kent, A P Reid, E R Nairn, D J Brain
Journal: Journal of the Royal Society of Medicine (1988)

In a review of 1000 consecutive neonates of all races, nasal septal deformity was identified in 29, an incident of 2.9%; significantly fewer cases were found in negroid babies (0.1 greater than P greater than 0.05). Ten cases (35%) underwent manipulation of the deviated septum. Six-monthly review revealed that symptoms associated with the septal deformity are rare. In 7 (44%) of the 16 cases not manipulated, the septum straightened spontaneously during the first few months of life. The appearance of the deviation is not of a dislocation of the caudal edge of the cartilage but a smooth concavity. In vitro compression of the neonatal nasal cavity reproduced this C-shaped deformity, but only temporarily. Histological serial sections of 6 postmortem nasal cavities showed that the high laminae of the vomer prevent any caudal dislocation of the septal cartilage.
Durable Responses with Ipilimumab Plus Lenalidomide after Allogeneic and Autologous Stem Cell Transplantation for Patients with Lymphoid Malignancies
Authors: Issa F. Khouri, Jorge A Borin Scutti, Denái R. Milton, Courtney Nicholas, Mariana Pineda, Elias J. Jabbour, Roland L. Bassett, Shalini S Yadav, Luis M Vence, James P Allison, Alison Gulbis, Padmanee Sharma
Journal: Blood (2018)
Robin Peter Bonner-Morgan
Authors: B Bonner-Morgan
Journal: BMJ (2018)

Robin Peter Bonner-Morgan (“Rob”) was one of the last of the generalists—consultant ophthalmologists who covered all the surgical and medical needs of any eye patient. He always tried to simulate the meticulous eye surgery of H B Stallard, whom he greatly admired, from St Bartholomew’s Hospital in London, where Rob and his wife, Barbara, both trained (as did his father before him). He later took a post under Stallard, in the eye department at Barts.

In 1966 an ophthalmologist from Australia saw Rob complete the consultant’s operating list, while he was approaching the end of his training at Bristol Eye Hospital. The Australian—who was visiting the UK and US with the intention of appointing someone—was very impressed by the skill of this young doctor and offered him a post in his extensive private eye practice in Victoria, Australia. Rob and Barbara (also an ophthalmologist) departed with their three young daughters for seven exciting years in private practice.

After working in the NHS they were both embarrassed by the idea of their secretary sending accounts for work they’d have preferred to do without charge. Fees would sometimes need to be waived because there was no health service in Australia at that time. The practice was thriving, and Barbara always assisted in the practice and the surgery. Melbourne was a hundred miles away, and Rob conducted a weekly clinic at Prince Henry’s, a teaching hospital that no longer exists. Two lovely new well equipped hospitals had been constructed …
Responses in multiple myeloma should be assigned according to serum, not urine, free light chain measurements
Authors: Thomas Dejoie, Jill Corre, Helene Caillon, Philippe Moreau, Michel Attal, Hervé Avet Loiseau
Journal: Leukemia (2018)

The most recent update to the International Myeloma Working Group consensus criteria places a strong emphasis on the need for more sensitive haematological markers of response driven by the success of novel therapies. One such marker is serum free light chain (sFLC) analysis, which was first incorporated into the definition of stringent complete response in 2006. However, over the past decade there has been some reluctance to extend the role of the sFLC assays to replace 24 h urine electrophoresis for monitoring multiple myeloma (MM). In this review, we lay out the evidence in favour of serum over urine for monoclonal FLC measurements and propose modified criteria for response assignment in myeloma.
Health Care Reimbursement and Service Utilization Among Medicare Beneficiaries with Multiple Myeloma Receiving Autologous Hematopoietic Cell Transplantation in Inpatient and Outpatient Settings
Authors: Neil Dunavin, Lih-Wen Mau, Christa Lea Meyer, Clint Divine, Al-Ola Abdallah, Susan Leppke, Anita D'Souza, Ellen Denzen, Wael Saber, Linda J. Burns, Siddhartha Ganguly
Journal: Blood (2018)
Inhibiting antibiotic-resistant Enterobacteriaceae by microbiota-mediated intracellular acidification
Authors: Matthew T. Sorbara, Krista Dubin, Eric R. Littmann, Thomas U. Moody, Emily Fontana, Ruth Seok, Ingrid M. Leiner, Ying Taur, Jonathan U. Peled, Marcel R.M. van den Brink, Yael Litvak, Andreas J. Bäumler, Jean-Luc Chaubard, Amanda J. Pickard, Justin R. Cross, Eric G. Pamer
Journal: The Journal of Experimental Medicine (2018)

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Foxp3+ T lymphocytes: immune regulators within the lung allograft
Authors: Elizabeth A. Lendermon, John F. McDyer
Journal: Journal of Clinical Investigation (2018)

Antibody-mediated rejection (AMR) has emerged as an important cause of lung graft failure. In the current issue of the JCI, a study by Li et al. identifies a critical role of Foxp3+ T cells residing within lung allografts in the regulation of AMR. This study not only provides new insights into the nature of lung allografts as a primary site where T and B cell priming and immune regulation can occur, but also introduces the mouse orthotopic lung transplant as a model for studying the immunobiology of AMR. Because AMR can be so difficult to effectively treat in lung transplant recipients, the development of an animal model is a major advance in understanding the immunopathogenesis of AMR.
P080 Efficacy and Safety of Docetaxel Plus Ramucirumab: A Consecutive Analysis of 68 Patients with Advanced NSCLC
Authors: S. Yokota, H. Horinouchi, S. Kanda, Y. Fujiwara, S. Murakami, Y. Goto, Y. Matsumoto, R. Morita, Y. Ohe
Journal: Journal of Thoracic Oncology (2018)
Magnetic Regulation of Thermo‐Chemotherapy from a Cucurbit[7]uril‐Crosslinked Hybrid Hydrogel
Authors: Haishi Qiao, Jing Jia, Wei Chen, Bin Di, Oren A. Scherman, Chi Hu
Journal: Advanced Healthcare Materials (2018)

Abstract The fabrication, characterization, and therapy efficiency of a noncovalent‐bonded hydrogel network, which is assembled by utilizing cucurbit[7]uril as a supramolecular linker to “stick” superparamagnetic γ‐Fe 2 O 3 nanoparticles onto the polymer backbone of catechol‐functionalized chitosan are described. The unique barrel‐shaped structure of cucurbit[7]uril not only facilitates host–guest recognition with the catechol derivatives, but also forms robust electrostatic interactions between its carbonyl portals and the γ‐Fe 2 O 3 nanoparticles in a supramolecular manner, which leaves the physical and chemical properties of the nanoparticles intact. The γ‐Fe 2 O 3 nanoparticles display vibrational movement and heat generation under an alternating magnetic field, endowing the formed hybrid supramolecular hydrogel with both thermo‐ and chemotherapy modalities, which are demonstrated both in vitro and in vivo. Here, a facile strategy is introduced to construct noncovalent interactions between a polymer matrix and the incorporated nanoparticles, which is amendable to a wide range of biomedical and industrial applications.
Anti-tumor effects of a small molecule C-C chemokine receptor 4 inhibitor in mouse tumor models
Authors: C. Li, J.J. Campbell, L.S. Ertl, Z. Miao, V. Chhina, A. Kumamoto, S. Yau, T. Dang, P. Zhang, T.J. Schall, R. Singh
Journal: Annals of Oncology (2018)

Background: Chemokines and their receptors influence many hallmark processes in cancer. C-C Chemokine receptor 4 (CCR4) and its ligands are highly expressed in many types of human tumors, and are often associated with poor prognosis. CCR4 antagonism has been demonstrated to reduce tumor growth in various mouse tumor models. Here we have assessed a small molecule inhibitior of CCR4 as a therapeutic agent to potentiate the effects of anti-CTLA-4 in the CT26 and KCM tumor models. Methods: The subcutaneous CT26 colon cancer model and the orthotopic KCM pancreatic cancer model were used to assess the effects of CCX6239, a CCR4 inhibitor, in combination with anti-CTLA-4 antibody. Mice implanted with CT26 cells were randomized into study groups on day 7 based on the pre-treatment tumor sizes. KCM cells were implanted directly into the pancreas. Dosing of CCX6239 and anti-CTLA-4 began on day 7. CCX6239 was dosed orally twice daily at 30mg/kg, and anti-CTLA-4 was dosed intraperitoneally on days 7, 11, and 15 at 100μg/mouse. Results: Combined treatment with anti-CTLA-4 and CCR4 inhibitor significantly decreased tumor size and increased the proportion of long-term survivors in the CT26 model. Mice with tumor regression exhibited a high proportion of CD8 T cells that recognized a CT26-specific neoantigen, and these mice were resistant to re-inoculation with CT26 cells (without further dosing of either drug), while another type of tumor grew well in the same mice. In the KCM model, anti-CTLA-4 alone provided substantial tumor growth inhibition, which was further enhanced by CCX6239. Interestingly, CCX6239 alone also significantly reduced tumor burden in this model. Conclusions: A specific CCR4 inhibitor reduces tumor growth either alone or in combiniation with anti-CTLA-4 in two preclinical models, suggesting CCR4 is a potential new target for cancer treatment. Legal entity responsible for the study: ChemoCentryx Inc. Funding: ChemoCentryx Inc. Disclosure: C. Li, J.J. Campbell, L.S. Ertl, Z. Miao, V. Chhina, A. Kumamoto, S. Yau, T. Dang, P. Zhang, T.J. Schall, R. Singh: Full time employee and stock holder of ChemoCentryx Inc.
An Original Case of an Association of Eosinophilic Fasciitis with Cholangitis Induced by Nivolumab
Authors: Erwan Le Tallec, Charles Ricordel, Louise Triquet, Arnaud Deniel, Pascale Marcorelles, Hervé Lena, Patrick Jego, Nicolas Belhomme
Journal: Journal of Thoracic Oncology (2018)