tbuckley/cabot-search huggingface dataset:
Critical Considerations on the Clinical Translation of Upconversion Nanoparticles (UCNPs): Recommendations from the European Upconversion Network (COST Action CM1403)
Authors: Helena Oliveira, Artur Bednarkiewicz, Andreas Falk, Eleonore Fröhlich, Darja Lisjak, Adriele Prina‐Mello, Susanne Resch, Christa Schimpel, Ivana Vinković Vrček, Edyta Wysokińska, Hans H. Gorris
Journal: Advanced Healthcare Materials (2018)

Abstract The unique photoluminescent properties of upconversion nanoparticles (UCNPs) have attracted worldwide research interest and inspired many bioanalytical applications. The anti‐Stokes emission with long luminescence lifetimes, narrow and multiple absorption and emission bands, and excellent photostability enable background‐free and multiplexed detection in deep tissues. So far, however, in vitro and in vivo applications of UCNPs are restricted to the laboratory use due to safety concerns. Possible harmful effects may originate from the chemical composition but also from the small size of UCNPs. Potential end users must rely on well‐founded safety data. Thus, a risk to benefit assessment of the envisioned combined therapeutic and diagnostic (“theranostic”) applications is fundamentally important to bridge the translational gap between laboratory and clinics. The COST Action CM1403 “The European Upconversion Network—From the Design of Photon‐Upconverting Nanomaterials to Biomedical Applications” integrates research on UCNPs ranging from fundamental materials synthesis and research, detection instrumentation, biofunctionalization, and bioassay development to toxicity testing. Such an interdisciplinary approach is necessary for a better and safer theranostic use of UCNPs. Here, the status of nanotoxicity research on UCNPs is compared to other nanomaterials, and routes for the translation of UCNPs into clinical applications are delineated.
Death and readmissions after hospital discharge during the December holiday period: cohort study
Authors: Lauren Lapointe-Shaw, Peter C Austin, Noah M Ivers, Jin Luo, Donald A Redelmeier, Chaim M Bell
Journal: BMJ (2018)

Abstract Objective To determine whether patients discharged from hospital during the December holiday period have fewer outpatient follow-ups and higher rates of death or readmission than patients discharged at other times. Design Population based retrospective cohort study. Setting Acute care hospitals in Ontario, Canada, 1 April 2002 to 31 January 2016. Participants 217 305 children and adults discharged home after an urgent admission, during the two week December holiday period, compared with 453 641 children and adults discharged during two control periods in late November and January. Main outcome measures The primary outcome was death or readmission, defined as a visit to an emergency department or urgent rehospitalisation, within 30 days. Secondary outcomes were death or readmission and outpatient follow-up with a physician within seven and 14 days after discharge. Multivariable logistic regression with generalised estimating equations was used to adjust for characteristics of patients, admissions, and hospital. Results 217 305 (32.4%) patients discharged during the holiday period and 453 641 (67.6%) discharged during control periods had similar baseline characteristics and previous healthcare utilisation. Patients who were discharged during the holiday period were less likely to have follow-up with a physician within seven days (36.3% v 47.8%, adjusted odds ratio 0.61, 95% confidence interval 0.60 to 0.62) and 14 days (59.5% v 68.7%, 0.65, 0.64 to 0.66) after discharge. Patients discharged during the holiday period were also at higher risk of 30 day death or readmission (25.9% v 24.7%, 1.09, 1.07 to 1.10). This relative increase was also seen at seven days (13.2% v 11.7%, 1.16, 1.14 to 1.18) and 14 days (18.6% v 17.0%, 1.14, 1.12 to 1.15). Per 100 000 patients, there were 2999 fewer follow-up appointments within 14 days, 26 excess deaths, 188 excess hospital admissions, and 483 excess emergency department visits attributable to hospital discharge during the holiday period. Conclusions Patients discharged from hospital during the December holiday period are less likely to have prompt outpatient follow-up and are at higher risk of death or readmission within 30 days.
Characterization of 18-Fluorodeoxyglucose Uptake Pattern in Infective Endocarditis After Transcatheter Aortic Valve Implantation
Authors: Sovannarith San, Mukedaisi Abulizi, Amina Moussafeur, Leopold Oliver, Raphael Lepeule, Louis Nahory, Laureline Faivre, Raphaëlle Huguet, Annabelle Nguyen, Sebastien Gallien, David Hamon, Nicolas Lellouche, Antonio Fiore, Romain Gallet, Emmanuel Teiger, Jean-Luc Dubois-Randé, Berivan Emsen, Emmanuel Itti, Julien Ternacle, Pascal Lim
Journal: JACC. Cardiovascular imaging (2018)
HMGCLL1 is a predictive biomarker for deep molecular response to imatinib therapy in chronic myeloid leukemia
Authors: Jong-Ho Park, Young Min Woo, Emilia Moonkyung Youm, Nada Hamad, Hong-Hee Won, Kazuhito Naka, Eun-Ju Park, June-Hee Park, Hee-Jin Kim, Sun-Hee Kim, Hyeoung-Joon Kim, Jae Sook Ahn, Sang Kyun Sohn, Joon Ho Moon, Chul Won Jung, Silvia Park, Jeffrey H. Lipton, Shinya Kimura, Jong-Won Kim, Dennis (Dong Hwan) Kim
Journal: Leukemia (2018)

Achieving a deep molecular response (DMR) to tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) remains challenging and at present, there is no biomarker to predict DMR in this setting. Herein, we report that an HMGCLL1 genetic variant located in 6p12.1 can be used as a predictive genetic biomarker for intrinsic sensitivity to imatinib (IM) therapy. We measured DMR rate according to HMGCLL1 variant in a discovery set of CML patients (n = 201) and successfully replicated it in a validation set (n = 270). We also investigated the functional relevance of HMGCLL1 blockade with respect to response to TKI therapy and showed that small interfering RNA mediated blockade of HMGCLL1 isoform 3 results in significant decrease in viability of BCR-ABL1-positive cells including K562, CML-T1 or BaF3 cell lines with or without ABL1 kinase domain mutations such as T315I mutation. Decreased cell viability was also demonstrated in murine CML stem cells and human hematopoietic progenitor cells. RNA sequencing showed that blockade of HMGCLL1 was associated with G0/G1 arrest and the cell cycle. In summary, the HMGCLL1 gene polymorphism is a novel genetic biomarker for intrinsic sensitivity to IM therapy in CML patients that predicts DMR in this setting.
T-Cell–Inflamed Gene-Expression Profile, Programmed Death Ligand 1 Expression, and Tumor Mutational Burden Predict Efficacy in Patients Treated With Pembrolizumab Across 20 Cancers: KEYNOTE-028
Authors: Patrick A. Ott, Yung-Jue Bang, Sarina A. Piha-Paul, Albiruni R. Abdul Razak, Jaafar Bennouna, Jean-Charles Soria, Hope S. Rugo, Roger B. Cohen, Bert H. O’Neil, Janice M. Mehnert, Juanita Lopez, Toshihiko Doi, Emilie M.J. van Brummelen, Razvan Cristescu, Ping Yang, Kenneth Emancipator, Karen Stein, Mark Ayers, Andrew K. Joe, Jared K. Lunceford
Journal: Journal of Clinical Oncology (2018)

Biomarkers that can predict response to anti-programmed cell death 1 (PD-1) therapy across multiple tumor types include a T-cell-inflamed gene-expression profile (GEP), programmed death ligand 1 (PD-L1) expression, and tumor mutational burden (TMB). Associations between these biomarkers and the clinical efficacy of pembrolizumab were evaluated in a clinical trial that encompassed 20 cohorts of patients with advanced solid tumors.KEYNOTE-028 ( ClinicalTrials.gov identifier: NCT02054806) is a nonrandomized, phase Ib trial that enrolled 475 patients with PD-L1-positive advanced solid tumors who were treated with pembrolizumab 10 mg/kg every 2 weeks for 2 years or until confirmed disease progression or unacceptable toxicity occurred. The primary end point was objective response rate (ORR; by RECIST v1.1, investigator review). Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). Relationships between T-cell-inflamed GEP, PD-L1 expression, and TMB and antitumor activity were exploratory end points.ORRs (with 95% CIs) ranged from 0% (0.0% to 14.2%) in pancreatic cancer to 33% (15.6% to 55.3%) in small-cell lung cancer. Across cohorts, median (95% CI) PFS ranged from 1.7 months (1.5 to 2.9 months) to 6.8 months (1.9 to 14.1 months) in pancreatic and thyroid cancers, respectively, and median OS from 3.9 months (2.8 to 5.5 months) to 21.1 months (9.1 to 22.4 months) in vulvar and carcinoid tumors, respectively. Higher response rates and longer PFS were demonstrated in tumors with higher T-cell-inflamed GEP, PD-L1 expression, and/or TMB. Correlations of TMB with GEP and PD-L1 were low. Response patterns indicate that patients with tumors that had high levels of both TMB and inflammatory markers (GEP or PD-L1) represent a population with the highest likelihood of response. Safety was similar and consistent with prior pembrolizumab reports.A T-cell--inflamed GEP, PD-L1 expression, and TMB predicted response to pembrolizumab in multiple tumor types. These biomarkers (alone/in combination) may help identify patients who have a higher likelihood of response to anti-PD-1 therapies across a broad spectrum of cancers.
Telephone Call After Pediatric Discharge
Authors: Lisa Hoyland, Jeffrey Forrest, Ralph Nanan
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
The Problem for Children in America
Authors: Edward W. Campion
Journal: New England Journal of Medicine (2018)

Children in America are dying or being killed at rates that are shameful. The sad fact is that a child or adolescent in the United States is 57% more likely to die by the age of 19 years than those in other wealthy nations.1 In 2016, there were more than 20,000 deaths of Americans 1 to 19 years of age. Physical injury accounted for 61% of this tragic total. As the Special Report by Cunningham et al.2 in this issue of the Journal documents, America’s children and adolescents are at far higher risk for death than are youth in other . . .
Incidence and Type of Opportunistic Infections during Ibrutinib Treatment at a Single Academic Center
Authors: Kerry A. Rogers, Mousa Luay, Qiuhong Zhao, Tracy Wiczer, Lauren Levine, El Boghdadly Zeinab, James S. Blachly, John C. Byrd, Tomas Guerrero, Jeffrey A. Jones, Shindiapina Polina, Audrey Sigmund, Matthew Sullivan, Farrukh T. Awan, Jennifer A. Woyach
Journal: Blood (2017)
A Neutralizing Monoclonal Antibody (PF-06741086) Against Tissue Factor Pathway Inhibitor in Combination with Activated Prothrombin Complex Concentrate Increases Hemostasis in Inhibitor Hemophilia Plasmas without Excessive Thrombin Generation
Authors: Swapnil Rakhe, Sheryl Bowley, John E. Murphy, Debra D Pittman
Journal: Blood (2018)
Simulation in surgical training: Prospective cohort study of access, attitudes and experiences of surgical trainees in the UK and Ireland
Authors: R. Nicholas, G. Humm, K.E. MacLeod, S. Bathla, A. Horgan, D.M. Nally, J. Glasbey, J.M. Clements, C. Fleming, H.M. Mohan
Journal: International Journal of Surgery (2019)
Concordance Between Intracervical and Fundal Injections for Sentinel Node Mapping in Patients With Endometrial Cancer?
Authors: Marjaneh Farazestanian, Zohreh Yousefi, Leili Zarifmahmoudi, Malihe Hasanzadeh Mofrad, Sima Kadkhodayan, Ramin Sadeghi
Journal: Clinical Nuclear Medicine (2018)

A major controversy in sentinel node (SN) biopsy of endometrial cancer is the injection site of mapping material. We compared lymphatic drainage pathways of the uterine cervix and uterine body in the same patients by head-to-head comparison of intracervical radiotracer and fundal blue dye injections.All patients with pathologically proven endometrial cancer were included. Each patient received 2 intracervical injections of Tc-phytate. At the time of laparotomy, the uterus was exposed, and each patient was injected with 2 aliquots of patent blue V (2 mL each) in the subserosal fundal midline locations. The anatomical locations of all hot, blue, or hot/blue SNs were recorded.Overall, 45 patients entered the study. At least 1 SN could be identified in 75 of 90 hemipelves (83.3% overall detection rate, 82.2% for radiotracer [intracervical] alone, and 81.1% for blue dye [fundal] alone). In 71 hemipelves, SNs were identified with both blue dye (fundal) and radiotracer (intracervical) injections. In 69 of these 71 hemipelves, at least 1 blue/hot SN could be identified (97.18% concordance rate). In 10 patients, para-aortic SNs were identified. All of these nodes were identified by fundal blue dye injection, and only 2 were hot.Our study shows that lymphatic drainage to the pelvic area from the uterine corpus matches the lymphatic pathways from the cervix, and both intracervical and fundal injections of SN mapping materials go to the same pelvic SNs.
Abstract 18786: Use of Argon as a Short-Term Post-Conditioning Stimulus Does Not Protect Coronary Artery Endothelial Cells From Hypoxia/Reoxygenation Injury
Authors: Michele M Salzman, Tim R Matsuura, Demetris Yannopoulos, Jason A Bartos, Tom P Aufderheide, Matthias L Riess
Journal: Circulation (2016)

Introduction: Cardiac arrest (CA) is a leading cause of death. Even with the best CPR, many patients still die or suffer severe cardio-cerebral damage. Reintroduction of blood flow at the start of ...
A Pilot Study of Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy with Ex Vivo Generated Polyomavirus-Specific T-Cells
Authors: Irene Cortese, Austin John Barrett, David F. Stroncek, Steven Highfill, Erin Beck, Frances Andrada, Joan Ohayon, Jennifer Dwyer, Matthew Schindler, Georg Aue, Daniel Reich, Avindra Nath, Pawel Muranski
Journal: Blood (2018)
Hydrogen cross-feeders of the human gastrointestinal tract
Authors: Nick W. Smith, Paul R. Shorten, Eric H. Altermann, Nicole C. Roy, Warren C. McNabb
Journal: Gut Microbes (2018)

Hydrogen plays a key role in many microbial metabolic pathways in the human gastrointestinal tract (GIT) that have an impact on human nutrition, health and wellbeing. Hydrogen is produced by many members of the GIT microbiota, and may be subsequently utilized by cross-feeding microbes for growth and in the production of larger molecules. Hydrogenotrophic microbes fall into three functional groups: sulfate-reducing bacteria, methanogenic archaea and acetogenic bacteria, which can convert hydrogen into hydrogen sulfide, methane and acetate, respectively. Despite different energy yields per molecule of hydrogen used between the functional groups, all three can coexist in the human GIT. The factors affecting the numerical balance of hydrogenotrophs in the GIT remain unconfirmed. There is increasing evidence linking both hydrogen sulfide and methane to GIT diseases such as irritable bowel syndrome, and strategies for the mitigation of such health problems through targeting of hydrogenotrophs constitute an important field for further investigation.
Response by Zhao et al to Letter Regarding Article, “Lack of Cardiac Improvement After Cardiosphere-Derived Cell Transplantation in Aging Mouse Hearts”
Authors: Zhen-Ao Zhao, Wei Lei, Shumei Miao, Jie Wu, Zhuangzhuang Yang, Xinglong Han, Jingjing Li, Mengchao Yao, Xing-Ai Lu, Lingjuan He, Yihuan Chen, Bin Zhou, Shijun Hu
Journal: Circulation Research (2018)
Inhibition of Notch Signaling Enhances Chemosensitivity in B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Paul Takam Kamga, Giada Dal Collo, Martina Midolo, Annalisa Adamo, Pietro Delfino, Angela Mercuri, Simone Cesaro, Elda Mimiola, Massimiliano Bonifacio, Angelo Andreini, Marco Chilosi, Mauro Krampera
Journal: Cancer Research (2018)

Abstract Notch3 and Notch4 support survival of primary B-cell acute lymphoblastic leukemia (B-ALL) cells, suggesting a role for Notch signaling in drug response. Here we used in vitro, in silico, and in vivo mouse xenograft model-based approaches to define the role of the Notch pathway in B-ALL chemosensitivity. We observed significant Notch receptor and ligand expression in B-ALL primary cells and cell lines. Primary leukemia cells from high-risk patients overexpressed Notch3, Notch4, and Jagged2 while displaying a reduction in expression levels of Notch1-4 following chemotherapy. We then analyzed in vitro cell survival of B-ALL cells treated with conventional chemotherapeutic agents alone or in combination with Notch signaling inhibitors. Gamma-secretase inhibitors (GSI) and anti-Notch4 were all capable of potentiating drug-induced cell death in B-ALL cells by upregulating intracellular levels of reactive oxygen species, which in turn modulated mTOR, NF-κB, and ERK expression. In NOG-mouse-based xenograft models of B-ALL, co-administration of the Notch inhibitor GSI-XII with the chemotherapeutic agent Ara-C lowered bone marrow leukemic burden compared with DMSO or Ara-C alone, thus prolonging mouse survival. Overall, our results support the potential effectiveness of Notch inhibitors in patients with B-ALL. Significance: Inhibition of Notch signaling enhances the chemosensitivity of B-ALL cells, suggesting Notch inhibition as a potential therapeutic strategy to improve the outcome of patients with B-ALL.
Human PD-1/OX40 double knock-in mouse, a novel model for evaluating in vivo efficacy of the combination therapy of immune-oncology drugs
Authors: T. Gan, Y. Li, Y. Shen, Y. Guo
Journal: Annals of Oncology (2018)

Background: Over the past years, monoclonal antibodies have been successfully utilized in clinical trials to block or activate key mediators of immune checkpoint pathways, including CTLA-4, PD-1, PD-L1 and OX40 et.al. Although significant benefits including complete regression and long-term survival were reported among the majority of participants, not all patients respond. In order to optimize the efficacy and minimize toxicities of anticancer immunotherapies, immune checkpoint antibodies are being tested in combination with other conventional therapeutics and newer immunotherapies. However, along the IO drug development process, in vivo efficacy models have always been a rate-limiting step, especially for the combination therapy of two IO antibodies. Methods: Here, we generated human PD-1 knock-in (B-hPD-1) mice with a chimeric PD-1 receptor, which is recognizable by human PD-1 antibodies, and can be used to test human PD-1 antibody. Mouse colon cancer MC38 were genetically modified with over-expression of hPD-L1 and knock-out of mPD-L1 (MC38-hPD-L1) and used to evaluate the in vivo efficacy of human PD-L1 antibodies. RNA and protein expression of human PD-1 were evaluated by RT-PCR and flow cytometry. We utilized this humanized PD-1 mice and implanted MC38-hPD-L1 subcutaneously, followed by treating mice with Keytruda/Tecentriq and/or Cisplatin. In this way, we also generated double humanized PD-1/OX40 mouse (B-hPD-1/hOX40) to evaluate the in vivo efficacy of combination therapy. The synergistic effect of Keytruda and human OX40 Ab were evaluated by using humanized double Knock-in B-hPD-1/hOX40 mice pairing with three syngeneic tumor models respectively. Results: Both the FDA approved human PD-1 antibody Keytruda and human PD-L1 antibody Tecentriq showed a synergistic effect with chemotherapy Cisplatine in B-hPD-1 mice inoculated with MC38-hPD-L1 cells. Keytruda and anti-human OX40 mAb shown clear combination effect in B-hPD-1/OX40 mouse with not only hot tumor MC38, but also moderate tumor EL4 and cold tumor B16F10. Conclusions: B-hPD-1 mouse and B-hPD-1/hOX40 mouse, represent useful in vivo efficacy models for evaluation of the combination effects of IO/Chemotherapy drugs and IO/IO. Legal entity responsible for the study: Beijing Biocytogen Co., Ltd. Funding: Beijing Biocytogen Co., Ltd. Disclosure: All authors have declared no conflicts of interest.
Arterial Occlusive Events in Chronic Myeloid Leukemia Patients Treated with Ponatinib in the Real-Life Practice: Prophylaxis and Identification of Risk Factors
Authors: Giovanni Caocci, Olga Mulas, Elisabetta Abruzzese, Alessandra Iurlo, Imma Attolico, Sara Galimberti, Luigia Luciano, Nicola Sgherza, Massimiliano Bonifacio, Mario Annunziata, Antonella Gozzini, Ester Maria Orlandi, Fabio Stagno, Gianni Binotto, Claudio Fozza, Malgorzata Monika Trawinska, Daniele Cattaneo, Francesco Albano, Claudia Baratè, Fiorenza De Gregorio, Luigi Scaffidi, Chiara Elena, Matteo Molica, Giorgio La Nasa, Robin Foà, Massimo Breccia
Journal: Blood (2018)
Growth in head and neck cancer clinical research in the NCRN and NCRI: Expanding opportunities for patients across the United Kingdom.
Authors: Matthew T. Seymour, Rachel Moser, Matthew Cooper, Sheila Fisher, Karen Poole, Christopher Nutting
Journal: Journal of Clinical Oncology (2012)

e16007 Background: The National Institute for Health Research Cancer Research Network (NCRN) was established in 2001 to benefit patients by improving the coordination, integration and speed of cancer research. Networks were established in England (NCRN), Scotland, Wales and Northern Ireland, supporting recruitment to a national portfolio across the NHS. In a decade recruitment to cancer studies has increased five fold in England to 20% of new incident cases. Head and Neck cancers affect basic functions including breathing and eating; particularly devastating for patients. The NCRI Head and Neck Cancer Clinical Studies Group is one of 23 Groups funded by NCRI members with a UK wide remit to develop a national portfolio of clinical studies. All CSGs include patients and carers as members resulting in active patient involvement in trial design, patient information and strategic direction of the portfolio. Methods: The last decade has seen unprecedented growth in the Head and Neck portfolio, which now includes 43 studies from only three studies in 2003/4. By 2010/11, 95% of UK Cancer Local Research Networks (37 networks) were recruiting to Head and Neck studies from only 2 networks in 2001/2, expanding trial access for patients and developing Head and Neck research expertise in new sites and with new investigators. Results: Numbers of patients participating in Head and Neck studies has grown exponentially. Since 2006/7 UK patient recruitment has risen 15-fold from 126 to 1890, representing almost 25% new incident cases of Head and Neck cancer. Conclusions: Rapid portfolio growth and associated network activity has expanded opportunities for patients with Head and Neck cancer; providing access to new therapeutic agents and treatment modalities, including NIHR CRN-adopted commercial trials and studies in a surgical setting. Participation in studies demonstrating the effectiveness of Intensity Modulated Radiotherapy in reducing xerostomia (including PARSPORT), has supported integration of this technique into cancer service.