tbuckley/cabot-search huggingface dataset:
Leukocyte-derived biomimetic nanoparticulate drug delivery systems for cancer therapy
Authors: Yukun Huang, Xiaoling Gao, Jun Chen
Journal: Acta Pharmaceutica Sinica B (2018)

Precise drug delivery to tumors with low system toxicity is one of the most important and challenging tasks for pharmaceutical researchers. Despite progress in the field of nanotherapeutics, the use of artificially synthesized nanocarriers still faces several challenges, including rapid clearance from blood circulation and limited capability of overcoming multiple physiological barriers, which hamper the clinical application of nanoparticle-based therapies. Since leukocytes (including monocytes/macrophages, neutrophils, dendritic cells and lymphocytes) target tumors and can migrate across physiological barriers, leukocytes are increasing utilized as carriers to transfer nanoparticles to tumors. In this review we specifically focus on the molecular and cellular mechanisms of leukocytes that can be exploited as a vehicle to deliver nanoparticles to tumors and summarize the latest research on how leukocytes can be harnessed to improve therapeutic end-points. We also discuss the challenges and opportunities of this leukocyte-derived nanoparticle drug delivery system.
Case 1-2018: A 39-Year-Old Woman with Rapidly Progressive Respiratory Failure
Authors: Kathryn A. Hibbert, Jo-Anne O. Shepard, Rebekah J. Lane, Marwan M. Azar
Journal: New England Journal of Medicine (2018)

A 39-year-old woman who had a history of leukemia and double-unit cord-blood transplantation presented with fever, cough, dyspnea, and hypoxemia. Chest imaging showed ground-glass and peripheral nodular opacities in the upper lobe. Diagnostic test results were received.
ACL and meniscal injuries increase the risk of primary total knee replacement for osteoarthritis: a matched case–control study using the Clinical Practice Research Datalink (CPRD)
Authors: Tanvir Khan, Abtin Alvand, Daniel Prieto-Alhambra, David J Culliford, Andrew Judge, William F Jackson, Brigitte E Scammell, Nigel K Arden, Andrew James Price
Journal: British Journal of Sports Medicine (2018)

The aim of this study was to investigate whether ACL injury (ACLi) or meniscal injury increases the risk of end-stage osteoarthritis (OA) resulting in total knee replacement (TKR).A matched case-control study of all TKRs performed in the UK between January 1990 and July 2011 and recorded in the Clinical Practice Research Datalink (CPRD) was undertaken. The CPRD contains longitudinal data on approximately 3.6 million patients. Two controls were selected for each case of TKR, matched on age, sex and general practitioner location as a proxy for socioeconomic status. Individuals with inflammatory arthritis were excluded. The odds of having TKR for individuals with a CPRD-recorded ACLi were compared with those without ACLi using conditional logistic regression, after adjustment for body mass index, previous knee fracture and meniscal injury. The adjusted odds of TKR in individuals with a recorded meniscal injury compared with those without were calculated.After exclusion of individuals with inflammatory arthritis, there were 49 723 in the case group and 104 353 controls. 153 (0.31%) cases had a history of ACLi compared with 41 (0.04%) controls. The adjusted OR of TKR after ACLi was 6.96 (95% CI 4.73 to 10.31). 4217 (8.48%) individuals in the TKR group had a recorded meniscal injury compared with 669 (0.64%) controls. The adjusted OR of TKR after meniscal injury was 15.24 (95% CI 13.88 to 16.69).This study demonstrates that ACLi is associated with a sevenfold increased odds of TKR resulting from OA. Meniscal injury is associated with a 15-fold increase odds of TKR for OA.
Increasing trends of anaphylaxis-related events: An analysis of anaphylaxis nationwide data in Taiwan, 2001-2013
Authors: Tsung-Chieh Yao, Ya-Wen Huang, Hsiao-Ting Wu, Yu-Ting Tsai, Jiu-Yao Wang, Hui-Ju Tsai
Journal: Journal of Allergy and Clinical Immunology (2018)
Risk of Hypoglycemia Following Hospital Discharge in Patients With Diabetes and Acute Kidney Injury
Authors: Adriana M. Hung, Edward D. Siew, Otis D. Wilson, Amy M. Perkins, Robert A. Greevy, Jeffrey Horner, Khaled Abdel-Kader, Sharidan K. Parr, Christianne L. Roumie, Marie R. Griffin, T. Alp Ikizler, Theodore Speroff, Michael E. Matheny
Journal: Diabetes Care (2018)

OBJECTIVE Hypoglycemia is common in patients with diabetes. The risk of hypoglycemia after acute kidney injury (AKI) is not well defined. The purpose of this study was to compare the risk for postdischarge hypoglycemia among hospitalized patients with diabetes who do and do not experience AKI. RESEARCH DESIGN AND METHODS We performed a propensity-matched analysis of patients with diabetes, with and without AKI, using a retrospective national cohort of veterans hospitalized between 2004 and 2012. AKI was defined as a 0.3 mg/dL or 50% increase in serum creatinine from baseline to peak serum creatinine during hospitalization. Hypoglycemia was defined as hospital admission or an emergency department visit for hypoglycemia or as an outpatient blood glucose &amp;lt;60 mg/dL. Time to incident hypoglycemia within 90 days postdischarge was examined using Cox proportional hazards models. Prespecified subgroup analyses by renal recovery, baseline chronic kidney disease, preadmission drug regimen, and HbA1c were performed. RESULTS We identified 65,151 propensity score–matched pairs with and without AKI. The incidence of hypoglycemia was 29.6 (95% CI 28.9–30.4) and 23.5 (95% CI 22.9–24.2) per 100 person-years for patients with and without AKI, respectively. After adjustment, AKI was associated with a 27% increased risk of hypoglycemia (hazard ratio [HR] 1.27 [95% CI 1.22–1.33]). For patients with full recovery, the HR was 1.18 (95% CI 1.12–1.25); for partial recovery, the HR was 1.30 (95% CI 1.23–1.37); and for no recovery, the HR was 1.48 (95% CI 1.36–1.60) compared with patients without AKI. Across all antidiabetes drug regimens, patients with AKI experienced hypoglycemia more frequently than patients without AKI, though the incidence of hypoglycemia was highest among insulin users, followed by glyburide and glipizide users, respectively. CONCLUSIONS AKI is a risk factor for hypoglycemia in the postdischarge period. Studies to identify risk-reduction strategies in this population are warranted.
Production of Universal Anti-Bcma CAR-T Cells with Reduced Alloreactivity, but Potent Effector Function for the Treatment of Multiple Myeloma
Authors: Xinxin Wang, Burton Earle Barnett, Christopher Martin, David Hermanson, Xianghong Li, Jenessa Smith, Joann Wu, Stacey Cranert, Srinivas Rengarajan, Yening Tan, Min Tong, Rebecca Codde, Julian D Down, Eric M Ostertag, Devon J Shedlock
Journal: Blood (2017)
Markedly Decreasing Incidence of Blindness in People With and Without Diabetes in Southern Germany
Authors: Heiner Claessen, Tatjana Kvitkina, Maria Narres, Christoph Trautner, Iris Zöllner, Bernd Bertram, Andrea Icks
Journal: Diabetes Care (2018)

OBJECTIVE Studies comparing the incidence of blindness in persons with and without diabetes are scarce worldwide. In Germany, a decline in the incidence of blindness was found during the 1990s. The aim of this study was to analyze the recent time trend. RESEARCH DESIGN AND METHODS Data were based on administrative files in southern Germany to assess recipients of blindness allowance newly registered between 1 January 2008 and 31 December 2012. We estimated age- and sex-standardized incidence of blindness in people with and people without diabetes and the corresponding relative risk. Poisson regression was used to examine age- and sex-adjusted time trends. RESULTS We identified 1,897 new cases of blindness (23.7% of which were associated with diabetes). We observed a strong decrease in incidence in both the population with diabetes (2008, 17.3 per 100,000 person-years [95% CI 13.6–21.1], and 2012, 8.9 per 100,000 person-years [6.3–11.6]: 16% decrease [10–22] per year) and that without diabetes (2008, 9.3 per 100,000 person-years [8.3–10.3], and 2012, 6.6 [5.8–7.4]: 9% decrease [5–13] per year). The relative risk comparing those incidences was 1.70 (95% CI 1.32–2.16) and remained constant in the observation period. Regarding time trend, we found similar results for both sexes. CONCLUSIONS We found a significant reduction in incidence of blindness in the populations with and without diabetes, which was more prominent among individuals with diabetes compared with the 1990s. Our findings may be explained by effective secondary prevention therapies and improved ophthalmologic care beyond diabetic retinopathy, particularly regarding macular degeneration, which means earlier detection and earlier and better treatment.
Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8
Authors: Marie Dominique Ah Kioon, Claudio Tripodo, David Fernandez, Kyriakos A. Kirou, Robert F. Spiera, Mary K. Crow, Jessica K. Gordon, Franck J. Barrat
Journal: Science Translational Medicine (2018)

The production of CXCL4 and IFN-α by plasmacytoid DCs in response to TLR8 signaling contributes to skin fibrosis and systemic sclerosis.
Abstract 16146: Rivaroxaban Prevents the Development of Chronic Thromboembolic Pulmonary Hypertension in Mice - Novel Beneficial Effects of the FXa Inhibitor -
Authors: Md. Elias Al-Mamun, Kimio Satoh, Taijyu Satoh, Nobuhiro Yaoita, Mohammad Abdul Hai Siddique, Nobuhiro Kikuchi, Junichi Omura, Ryo Kurosawa, Shinichiro Sunamura, Masamichi Nogi, Tomohiro Ohtsuki, Hiroaki Shimokawa
Journal: Circulation (2017)

Background:  Chronic thromboembolic pulmonary hypertension (CTEPH) remains a fatal disorder. We have recently demonstrated that thrombin-activatable fibrinolysis inhibitor (TAFI) plays a crucial role in the development of CTEPH. However, the role of factor Xa (FXa) in the pathogenesis of CTEPH remains to be elucidated.   Methods and Results:  TAFI-overexpressing (TAFI-Tg) mice developed PH with phenotypes similar to CTEPH patients, including organized thrombus with multiple obstruction of pulmonary arteries and reduced survival under hypoxia. TAFI-Tg mice showed substantial pulmonary vascular remodeling, elevated right ventricular systolic pressure (RVSP), and RV hypertrophy (RVH) after 3 weeks of hypoxia. To evaluate the effect of FXa inhibition in CTEPH, we treated TAFI-Tg mice with rivaroxaban (1.2 g/kg PO) or vehicle during 3 weeks of hypoxia. After 3 weeks, 25% of the TAFI-Tg mice with vehicle died, whereas 13% of those treated with rivaroxaban did. Rivaroxaban significantly reduced RVSP and RVH in TAFI-Tg mice compared with vehicle ( n =12 each, both  P  n =5 each, all  P  + CD11b + Ly6G –  cells in the lungs were significantly increased in TAFI-Tg mice compared with controls, suggesting a crucial role of monocytes/macrophages in TAFI-mediated pulmonary artery inflammation. Importantly, rivaroxaban treatment significantly reduced the number of perivascular Mac3 +  cells compared with vehicle ( n =5 each,  P  n =6 each, all  P  n =4 each,  P    Conclusion:  These results indicate that rivaroxaban inhibits the development of mouse model of CTEPH through suppression of inflammation and cell proliferation.
Genes Predisposed to DNA Hypermethylation during Acquired Resistance to Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at Initial Diagnosis
Authors: Edward Curry, Constanze Zeller, Nahal Masrour, Darren K. Patten, John Gallon, Charlotte S. Wilhelm-Benartzi, Sadaf Ghaem-Maghami, David D. Bowtell, Robert Brown
Journal: Cancer Research (2018)

Abstract Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3 histone marks define gene sets poised for expression or silencing in differentiating embryonic stem (ES) cells. In cancer cells, aberrantly poised genes may facilitate changes in transcriptional states after exposure to anticancer drugs. In this study, we used ChIP-seq to characterize genome-wide positioning of H3K4me3- and H3K27me3-associated chromatin in primary high-grade serous ovarian carcinomas and in normal ovarian surface and fallopian tube tissue. Gene sets with proximal bivalent marks defined in this manner were evaluated subsequently as signatures of systematic change in DNA methylation and gene expression, comparing pairs of tissue samples taken from patients at primary presentation and relapse following chemotherapy. We found that gene sets harboring bivalent chromatin domains at their promoters in tumor tissue, but not normal epithelia, overlapped with Polycomb-repressive complex target genes as well as transcriptionally silenced genes in normal ovarian and tubal stem cells. The bivalently marked genes we identified in tumors before chemotherapy displayed increased promoter CpG methylation and reduced gene expression at relapse after chemotherapy of ovarian cancer. Overall, our results support the hypothesis that preexisting histone modifications at genes in a poised chromatin state may lead to epigenetic silencing during acquired drug resistance. Significance: These results suggest epigenetic targets for intervention to prevent the emergence of cancer drug resistance. Cancer Res; 78(6); 1383–91. ©2018 AACR.
Fractional Exhaled Nitric Oxide (FeNO) Measurements with the NIOX VERO ® in Children 4 to 6 Years Old using the 6 and 10 Second Exhalation Modes
Authors: Neal Jain, Richard L. Wasserman, Craig F. LaForce, Robert Anolik, Margot MacDonald-Berko, Kathleen A. Rickard
Journal: Journal of Allergy and Clinical Immunology (2018)
Activated and Expanded Natural Killer Cells Expressing an NKG2D-CAR Efficiently Target Multiple Myeloma Cells
Authors: Alejandra Leivas, Antonio Valeri, Paula Rio, Lucia Fernandez, Iñaki Pañero, Dean Anthony Lee, Daniel J. Powell, Juan Jose Lahuerta, Antonio Perez-Martinez, Joaquin Martinez-Lopez
Journal: Blood (2017)
Upsurge in attacks on hospitals in Syria condemned
Authors: Anne Gulland
Journal: BMJ (2018)

Medical charities have condemned a new wave of airstrikes against hospitals and health facilities in Syria in recent weeks.

The Union of Medical Care and Relief Organisations (UOSSM), an international umbrella organisation of charities providing medical aid to countries in crisis, said there had been 11 separate attacks on medical facilities in Idlib, Hama, and Eastern Ghouta since 26 December. It urged the United Nations to investigate and prosecute perpetrators for war crimes.

Ghanem Tayara, UOSSM international chairman and a GP in Bristol, said, “This fresh wave of attacks is sickening and unacceptable. These attacks force facilities to shut down, terrorise …
Abstract 20568: AMSA Combined With Prior Shock Outcome Predicts Defibrillation Success During CPR
Authors: Jason Coult, Heemun Kwok, Peter J Kudenchuk, Jennifer Blackwood, Lawrence D Sherman, Thomas D Rea
Journal: Circulation (2016)

Introduction: Amplitude spectrum area (AMSA) predicts defibrillation shock success. However, AMSA and other waveform measures require CPR interruption prior to shock, which can adversely influence ...
Bone Marrow Plasma Cell Infiltration in Light Chain Amyloidosis: Impact on Organ Involvement and Outcome
Authors: Carlos Fernandez de Larrea, Luis Gerardo Rodríguez-Lobato, Natalia Tovar, Laura Magnano, Ignacio Isola, Laura Rosinol, Joan Bladé, Mª Teresa Cibeira
Journal: Blood (2017)
Cost Effectiveness of Gene Expression Profile Testing in Community Practice
Authors: Young Chandler, Clyde B. Schechter, Jinani Jayasekera, Aimee Near, Suzanne C. O’Neill, Claudine Isaacs, Charles E. Phelps, G. Thomas Ray, Tracy A. Lieu, Scott Ramsey, Jeanne S. Mandelblatt
Journal: Journal of Clinical Oncology (2018)

Purpose Gene expression profile (GEP) testing can support chemotherapy decision making for patients with early-stage, estrogen receptor–positive, human epidermal growth factor 2–negative breast cancers. This study evaluated the cost effectiveness of one GEP test, Onco type DX (Genomic Health, Redwood City, CA), in community practice with test-eligible patients age 40 to 79 years. Methods A simulation model compared 25-year societal incremental costs and quality-adjusted life-years (QALYs) of community Onco type DX use from 2005 to 2012 versus usual care in the pretesting era (2000 to 2004). Inputs included Onco type DX and chemotherapy data from an integrated health care system and national and published data on Onco type DX accuracy, chemotherapy effectiveness, utilities, survival and recurrence, and Medicare and patient costs. Sensitivity analyses varied individual parameters; results were also estimated for ideal conditions (ie, 100% testing and adherence to test-suggested treatment, perfect test accuracy, considering test effects on reassurance or worry, and lowest costs). Results Twenty-four percent of test-eligible patients had Onco type DX testing. Testing was higher in younger patients and patients with stage I disease ( v stage IIA), and 75.3% and 10.2% of patients with high and low recurrence risk scores received chemotherapy, respectively. The cost-effectiveness ratio for testing ( v usual care) was $188,125 per QALY. Considering test effects on worry versus reassurance decreased the cost-effectiveness ratio to $58,431 per QALY. With perfect test accuracy, the cost-effectiveness ratio was $28,947 per QALY, and under ideal conditions, it was $39,496 per QALY. Conclusion GEP testing is likely to have a high cost-effectiveness ratio on the basis of community practice patterns. However, realistic variations in assumptions about key variables could result in GEP testing having cost-effectiveness ratios in the range of other accepted interventions. The differences in cost-effectiveness ratios on the basis of community versus ideal conditions underscore the importance of considering real-world implementation when assessing the new technology.
α-Synuclein accumulation and GBA deficiency due to L444P GBA mutation contributes to MPTP-induced parkinsonism
Authors: Seung Pil Yun, Donghoon Kim, Sangjune Kim, SangMin Kim, Senthilkumar S. Karuppagounder, Seung-Hwan Kwon, Saebom Lee, Tae-In Kam, Suhyun Lee, Sangwoo Ham, Jae Hong Park, Valina L. Dawson, Ted M. Dawson, Yunjong Lee, Han Seok Ko
Journal: Molecular Neurodegeneration (2018)

Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA +/L444P ) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin. We used GBA +/L444P mice, α-synuclein knockout (SNCA −/− ) mice at 8 months of age, and adeno-associated virus (AAV)-human GBA overexpression to investigate the rescue effect of DA neuronal loss and susceptibility by MPTP. Mitochondrial morphology and functional assay were used to identify mitochondrial defects in GBA +/L444P mice. Motor behavioral test, immunohistochemistry, and HPLC were performed to measure dopaminergic degeneration by MPTP and investigate the relationship between GBA mutation and α-synuclein. Mitochondrial immunostaining, qPCR, and Western blot were also used to study the effects of α-synuclein knockout or GBA overexpression on MPTP-induced mitochondrial defects and susceptibility. L444P GBA heterozygous mutation reduced GBA protein levels, enzymatic activity and a concomitant accumulation of α-synuclein in the midbrain of GBA +/L444P mice. Furthermore, the deficiency resulted in defects in mitochondria of cortical neurons cultured from GBA +/L444P mice. Notably, treatment with MPTP resulted in a significant loss of dopaminergic neurons and striatal dopaminergic fibers in GBA +/L444P mice compared to wild type (WT) mice. Levels of striatal DA and its metabolites were more depleted in the striatum of GBA +/L444P mice. Behavioral deficits, neuroinflammation, and mitochondrial defects were more exacerbated in GBA +/L444P mice after MPTP treatment. Importantly, MPTP induced PD-like symptoms were significantly improved by knockout of α-synuclein or augmentation of GBA via AAV5-hGBA injection in both WT and GBA +/L444P mice. Intriguingly, the degree of reduction in MPTP induced PD-like symptoms in GBA +/L444P α-synuclein (SNCA) −/− mice was nearly equal to that in SNCA −/− mice after MPTP treatment. Our results suggest that GBA deficiency due to L444P GBA heterozygous mutation and the accompanying accumulation of α-synuclein render DA neurons more susceptible to MPTP intoxication. Thus, GBA and α-synuclein play dual physiological roles in the survival of DA neurons in response to the mitochondrial dopaminergic neurotoxin, MPTP.
A novel gene is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood AML.
Authors: R J Jaju, C Fidler, O A Haas, A J Strickson, F Watkins, K Clark, P D Aplan, L Kearney, J Boultwood, J S Wainscoat
Journal: Blood (2000)
Early changes in the pharmacokinetic profile of vedolizumab-treated patients with IBD may predict response after dose optimisation
Authors: Célia Gouynou, Lieven Pouillon, Hélène Rousseau, Camille Zallot, Cédric Baumann, Laurent Peyrin-Biroulet
Journal: Gut (2018)

We read with interest the recent paper by Colombel et al 1 showing that vedolizumab is frequently used for patients with inflammatory bowel disease (IBD). There is evidence for an exposure–efficacy relationship for vedolizumab induction therapy.2 Increasing dosing frequency of vedolizumab to every 4 weeks leads to an improvement in clinical response in both ulcerative colitis (UC)3 and Crohn’s disease (CD).4 In contrast to anti-tumour necrosis factor (TNF) agents, the correlation between the response to dose optimisation and changes in the pharmacokinetic profile of vedolizumab-treated patients remains unknown. We performed a retrospective analysis of all vedolizumab-treated …
No Superiority of Autologous Stem Cell Transplantation over Chemotherapy Alone in Adult Ph-Negative ALL in First Complete Remission A Long Follow-Up Report Combining Results of LALA 85, 87 and 94 Trials
Authors: N. Dhedin, X. Thomas, F. Huguet, V. Lheritier, J. M. Boiron, J. M. Miclea, N. Vey, M. Kuentz, C. Charrin, C. Boucheix, J. Gabert, D. Fiere, J. P. Vernant
Journal: Blood (2002)
Immediate and Delayed Reactions to Cephalexin in Children with Confirmed Allergy to Amoxicillin
Authors: Ashley Tritt, Alexandra Langlois, Sofianne Gabrielli, Christine Lejtenyi, Thomas Eiwegger, Adelle Roberta Atkinson, Vy Hong-Diep Kim, Andrew O'Keefe, Yarden Yanishevsky, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2018)
Retraction Note: Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease
Authors: Xuebin Liu, Stewart Leung, Chunxia Wang, Zhu Tan, Ji Wang, Taylor B Guo, Lei Fang, Yonggang Zhao, Bing Wan, Xia Qin, Limin Lu, Runsheng Li, Heng Pan, Mingjuan Song, Ailian Liu, Jian Hong, Hongtao Lu, Jingwu Z Zhang
Journal: Nature Medicine (2013)
Abstract 15510: Canonical Wnt Signaling Reverses the ‘Aged/Senescent’ Phenotype of Human Endogenous Cardiac Stem Cells
Authors: Fiona C Lewis, Tze Shin Teoh, Eva Domenj -Vila, Thomas Theologou, Mark Field, Wael Awad, Georgina M Ellison-Hughes
Journal: Circulation (2016)

The adult human myocardium harbours endogenous, multi-potent cardiac stem cells (eCSCs), however aging/senescence of eCSCs determines their function and regenerative capacity. We assessed whether t...