tbuckley/cabot-search huggingface dataset:
Physical characterization of liposomal drug formulations using multi-detector asymmetrical-flow field flow fractionation
Authors: J. Parot, F. Caputo, D. Mehn, V.A. Hackley, L. Calzolai
Journal: Journal of Controlled Release (2020)

Liposomal formulations for the treatment of cancer and other diseases are the most common form of nanotechnology enabled pharmaceuticals (NEPs) submitted for market approval and in clinical application today. The accurate characterization of their physical-chemical properties is a key requirement; in particular, size, size distribution, shape, and physical-chemical stability are key among properties that regulators identify as critical quality attributes. Here we develop and validate an optimized method, based on multi-detector asymmetrical-flow field flow fractionation (MD-AF4) to accurately and reproducibly separate liposomal drug formulations into their component populations and to characterize their associated size and size distribution, whether monomodal or polymodal in nature. In addition, the results show that the method is suitable to measure liposomes in the presence of serum proteins and can yield information on the shape and physical stability of the structures. The optimized MD-AF4 based method has been validated across different instrument platforms, three laboratories, and multiple drug formulations following a comprehensive analysis of factors that influence the fractionation process and subsequent physical characterization. Interlaboratory reproducibility and intra-laboratory precision were evaluated, identifying sources of bias and establishing criteria for the acceptance of results. This method meets a documented high priority need in regulatory science as applied to NEPs such as Doxil and can be adapted to the measurement of other NEP forms (such as lipid nanoparticle therapeutics) with some modifications. Overall, this method will help speed up development of NEPS, and facilitate their regulatory review, ultimately leading to faster translation of innovative concepts from the bench to the clinic. Additionally, the approach used in this work (based on international collaboration between leading non-regulatory institutions) can be replicated to address other identified gaps in the analytical characterization of various classes of NEPs. Finally, a plan exists to pursue more extended interlaboratory validation studies to advance this method to a consensus international standard.
Sex specific effect of ATPase inhibitory factor 1 on body weight: studies in high fat diet induced obese mice and genetic association studies in humans
Authors: So-Young Kwak, InHyeok Chung, Joon Kang, Nikolaos Perakakis, Eun Hye Yoo, Juhee Lee, Hun Taek Jung, Bo-Ram Mun, Won-Seok Choi, Oh Yoen Kim, Seolsong Kim, Eun-Kyoung Kim, Hannah Oh, Christos S. Mantzoros, Ji Hyung Chung, Hyeon Soo Kim, Min-Jeong Shin
Journal: Metabolism (2020)
Allergen alters IL‐2/αIL‐2‐based Treg expansion but not tolerance induction in an allergen‐specific mouse model
Authors: Cordula Köhler, Ursula Smole, Bernhard Kratzer, Doris Trapin, Klaus G. Schmetterer, Winfried F. Pickl
Journal: Allergy (2020)

Regulatory T lymphocytes (Treg) play an important role in preventing allergic diseases. We characterized Treg expansion kinetics, marker profiles, and recirculation behavior in allergen-challenged mice, which had been pretreated with IL-2/αIL-2 complexes in the presence or absence of allergen. Moreover, the ability of induced Treg to control airway hyperreactivity and effector functions of lung T cells was determined.Humanized TCR/HLA-transgenic allergy mice were treated in vivo with recombinant IL-2 complexed to the anti-IL-2 mAb JES6-1 in the presence or absence of mugwort pollen extract (MPE) on days 0-2. Afterward, they were intranasally challenged with MPE (days 13-15) followed by determination of airway hyperreactivity and lung T cell effector functions. Multiparametric flow cytometry on peripheral blood T cells was performed on a daily basis.IL-2/αIL-2 complexes highly efficiently expanded peripheral Treg cells, while concomitant allergen exposure altered the phenotype of expanded Treg cells. Notably, application of allergen together with IL-2/αIL-2 complexes induced expression of Treg marker molecules CTLA4, NRP1, Helios, and GITR on conventional T cells. Apart from CD25, GARP was identified as the most reliable surface-expressed lineage discrimination marker of Treg expanded in the presence of IL-2/αIL-2 complexes and allergen. Finally, IL-2/αIL-2 complex-expanded Treg cells could be recalled upon allergen challenge, which was associated with suppression of lung-specific Th2 responses long after initial treatment.The characterization of reliable surface and transcription markers of IL-2/αIL-2 complex-expanded Treg along with their expansion kinetics and function will help to identify protocols for their long-term expansion in vivo.
A World of Collaboration in Sports Medicine: the 2020 American Medical Society for Sports Medicine issue
Authors: Stephen Paul, Alex Benjamin Diamond, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2020)

With this issue, we celebrate the important collaboration between the American Medical Society for Sports Medicine (AMSSM), BJSM and sports and exercise medicine colleagues around the world. We also are excited to promote and preview the upcoming AMSSM annual meeting in Atlanta on 24–29 April 2020, ‘A World of Collaboration in Sports Medicine’. As the rigor of peer review and demand for the highest quality research continues for eligible content in BJSM, we are thankful for the number of article submissions from AMSSM members. We encourage our members to continue to raise the level of their research to advance our discipline and match the high BJSM standard for future consideration.

This issue features two AMSSM position statements. The first, an update from the original paper from the 1990s, reviews bloodborne pathogens in the context of sport participation by Dr Chris McGrew and colleagues (See page 200) . This statement expands the list of bloodborne pathogens and more importantly updates information for the sport medicine practitioner and participant on transmission, effect on exercise and the current role of education to prevent transmission.

AMSSM past-presidents Dr Cindy Chang and Dr Margot Putukian also led an AMSSM position statement on Mental Health Issues and Psychological Factors in Athletes: Detection, Management, Effect on Performance and Prevention (See page 216) . This paper …
MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC
Authors: Chenggong Sun, Wenyu Cao, Chunping Qiu, Chengcheng Li, Samina Dongol, Zhiwei Zhang, Ruifen Dong, Kun Song, Xingsheng Yang, Qing Zhang, Beihua Kong
Journal: Journal of Hematology & Oncology (2020)

Abstract Background PARP inhibitors have been the most promising target drugs with widely proven benefits among ovarian cancer patients. Although platinum-response, HR-related genes, or HRD genomic scar detection are acceptably used in assessment of Olaparib response, there are still evident limitations in the present approaches. Therefore, we aim to investigate more accurate approaches to predict Olaparib sensitivity and effective synergistic treatment strategies. Methods We probed two databases (TCGA and Qilu Hospital) in order to quest novel miRNAs associated with platinum-sensitivity or HR-related genes. Cellular experiments in vitro or in vivo and PDX models were utilized to validate their role in tumor suppression and Olaparib sensitizing. Furthermore, HR gene mutation was analyzed through WES to explore the relation between HR gene mutation and Olaparib response. Results High miR-509-3 expression indicated better response to platinum and longer progression-free and overall survival in two independent ovarian cancer patient cohorts (high vs. low miR-509-3 expression; PFS: TCGA P &lt; 0.05, Qilu P &lt; 0.05; OS: TCGA P &lt; 0.05, Qilu P &lt; 0.01). MiR-509-3 could impair the proliferation, migration, and invasion ability but enhance the sensitivity to Olaparib of ovarian cancer cell in vitro and in vivo by directly targeting HMGA2 and RAD51. In two PDX cases (PDX1 and PDX9), miR-509-3 could significantly increase the sensitivity to Olaparib along with the decrease of RAD51 positive rate (mean tumor weight NC + Olaparib vs. miR-509 + Olaparib; PDX1 P &lt; 0.05, PDX9 P &lt; 0.05). Additionally, in PDX8, miR-509-3 treatment dramatically reversed the Olaparib insensitivity ( P &lt; 0.05) by downregulating RAD51 expression. RAD51 functional detection revealed that all Olaparib sensitive cases exhibited low RAD51 positive rate (lesser than 50%) in treated groups. Furthermore, among the four HR gene mutation patients, three harbored HR core gene mutation and were sensitive to Olaparib while the remaining one with non-HR core gene mutation did not respond well to Olaparib. Conclusions MiR-509-3 can sensitize ovarian cancer cells to Olaparib by impeding HR, which makes it a potential target in PARPi synergistic treatment. HR core gene analysis and RAD51 functional detection are prospectively feasible in prediction of PARPi response.
Removal of a proximally migrated 5-Fr pancreatic stent with a 5–4–3-Fr catheter using a wedge technique
Authors: Theodore W. James, Todd H. Baron
Journal: Endoscopy (2020)

A 44-year-old woman underwent pancreatic sphincterotomy with placement of a 5-Fr, 3-cm pancreatic duct stent (Geenen Sof-Flex; Cook Endoscopy, Winston-Salem, NC, USA). The stent did not pass spontaneously and migrated upstream ([Fig. 1]). Attempts to grasp the stent with a pediatric biopsy forceps failed ([Fig. 2]), but inadvertently advanced the stent toward the pancreatic tail. A 0.018-inch wire was advanced through the stent lumen. A 5-Fr stent retriever was not available. Attempts to retrieve the stent with over-the-wire snare and basket failed ([Fig. 3]). Finally, a 5–4–3-Fr biliary catheter (Contour; Boston Scientific, Marlborough, MA, USA) was forcefully wedged into the stent lumen ([Fig. 4]). The stent was withdrawn ([Video 1]).
Biochemical mechanisms of aggregation in TGFBI-linked corneal dystrophies
Authors: Nadia Sukusu Nielsen, Ebbe Toftgaard Poulsen, Marie V. Lukassen, Connie Chao Shern, Emilie Hage Mogensen, Christian E. Weberskov, Larry DeDionisio, Leif Schauser, Tara C.B. Moore, Daniel E. Otzen, Jesper Hjortdal, Jan J. Enghild
Journal: Progress in Retinal and Eye Research (2020)
First Case of 2019 Novel Coronavirus in the United States
Authors: Michelle L Holshue, Chas DeBolt, Scott Lindquist, Kathy H Lofy, John Wiesman, Hollianne Bruce, Christopher Spitters, Keith Ericson, Sara Wilkerson, Ahmet Tural, George Diaz, Amanda Cohn, LeAnne Fox, Anita Patel, Susan I Gerber, Lindsay Kim, Suxiang Tong, Xiaoyan Lu, Steve Lindstrom, Mark A Pallansch, William C Weldon, Holly M Biggs, Timothy M Uyeki, Satish K Pillai
Journal: New England Journal of Medicine (2020)

An outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient's initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.
Risk Factors for First and Subsequent CVD Events in Type 1 Diabetes: The DCCT/EDIC Study
Authors: Ionut Bebu, David Schade, Barbara Braffett, Mikhail Kosiborod, Maria Lopes-Virella, Elsayed Z. Soliman, William H. Herman, David A. Bluemke, Amisha Wallia, Trevor Orchard, John M. Lachin
Journal: Diabetes Care (2020)

The Diabetes Control and Complications Trial (DCCT) and its observational follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) demonstrated the dominant role of glycemia, second only to age, as a risk factor for a first cardiovascular event in type 1 diabetes (T1D). We now investigate the association between established risk factors and the total cardiovascular disease (CVD) burden, including subsequent (i.e., recurrent) events.CVD events in the 1,441 DCCT/EDIC participants were analyzed separately by type (CVD death, acute myocardial infarction [MI], stroke, silent MI, angina, percutaneous transluminal coronary angioplasty/coronary artery bypass graft [PTCA/CABG], and congestive heart failure [CHF]) or as composite outcomes (CVD or major adverse cardiovascular events [MACE]). Proportional rate models and conditional models assessed associations between risk factors and CVD outcomes.Over a median follow-up of 29 years, 239 participants had 421 CVD events, and 120 individuals had 149 MACE. Age was the strongest risk factor for acute MI, silent MI, stroke, and PTCA/CABG, while glycemia was the strongest risk factor for CVD death, CHF, and angina, second strongest for acute MI and PTCA/CABG, third strongest for stroke, and not associated with silent MI. HbA1c was the strongest modifiable risk factor for a first CVD event (CVD: HR 1.38 [95% CI 1.21, 1.56] per 1% higher HbA1c; MACE: HR 1.54 [1.30, 1.82]) and also for subsequent CVD events (CVD: incidence ratio [IR] 1.28 [95% CI 1.09, 1.51]; MACE: IR 1.89 [1.36, 2.61]).Intensive glycemic management is recommended to lower the risk of initial CVD events in T1D. After a first event, optimal glycemic control may reduce the risk of recurrent CVD events and should be maintained.
Novel tobacco products including electronic cigarette and heated tobacco products increase risk of allergic rhinitis and asthma in adolescents: Analysis of Korean youth survey
Authors: Soo Jie Chung, Byung‐Keun Kim, Ji Hyun Oh, Ji‐Su Shim, Yoon‐Seok Chang, Sang‐Heon Cho, Min‐Suk Yang
Journal: Allergy (2020)

Abstract Background The effect of novel tobacco products, such as electronic cigarettes (EC) and heated tobacco products (HTP), on allergic rhinitis (AR) and asthma is not well known. Objective To evaluate the health effect of novel tobacco products on asthma and AR. Methods This study was conducted using large survey data on Korean middle and high school students. The relationship between current asthma/AR and novel tobacco products user status was evaluated. In order to compare the combined effects of conventional cigarette (CC), EC, and HTP use on current allergic diseases, the participants were classified into 18 groups based on CC (current, former, and never), EC (current, former, and never), and HTP (ever and never) status. Results A total of 60,040 participants representing 2,850,118 Korean adolescents were analyzed. Of all participants, 6.7%, 2.7%, and 2.9% were current CC, current EC, and ever HTP users, respectively. Current CC and ever HTP use was significantly associated with current asthma and AR in adjusted models. Current EC showed association with current AR but the association with asthma disappeared in the adjusted model. Among 18 groups, the groups including current CC use showed higher risk of current AR and asthma than never HTP‐never EC‐never CC group. The odds ratio of current asthma especially increased more in those who used EC and/or HTP with CC concurrently than those in the never HTP‐never EC‐current CC user group. Conclusion Using EC and/or HTP in adolescents might enhance the adverse effect of CC on AR and asthma.
Long Term Follow‐up Data and Health‐Related Quality of Life in Frontline Therapy of Fit Patients Treated With FCR Versus BR (CLL10 Trial of the GCLLSG)
Authors: Nadine Kutsch, Jasmin Bahlo, Sandra Robrecht, Jeremy Franklin, Can Zhang, Christian Maurer, Nisha De Silva, Elisabeth Lange, Rudolf Weide, Michael G. Kiehl, Martin Sökler, Rudolf Schlag, Ursula Vehling‐Kaiser, Georg Köchling, Christoph Plöger, Michael Gregor, Torben Plesner, Marco Herling, Kirsten Fischer, Hartmut Döhner, Michael Kneba, Clemens‐Martin Wendtner, Wolfram Klapper, Karl‐Anton Kreuzer, Sebastian Böttcher, Stephan Stilgenbauer, Anna Maria Fink, Michael Hallek, Barbara Eichhorst
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
Improving the diagnostic yield for filaggrin: Concealed mutations in the Dutch population
Authors: Frank S. van Leersum, Ivo F. Nagtzaam, Carolien N. van Oosterhoud, Stijn A.I. Ghesquiere, Roel R.H.F.J. Brandts, Antoni Gostyński, Peter M. Steijlen, Michel van Geel
Journal: Journal of Allergy and Clinical Immunology (2020)
Autonomous Vehicles and Public Health
Authors: David Rojas-Rueda, Mark J. Nieuwenhuijsen, Haneen Khreis, Howard Frumkin
Journal: Annual Review of Public Health (2020)

Autonomous vehicles (AVs) have the potential to shape urban life and significantly modify travel behaviors. "Autonomous technology" means technology that can drive a vehicle without active physical control or monitoring by a human operator. The first AV fleets are already in service in US cities. AVs offer a variety of automation, vehicle ownership, and vehicle use options. AVs could increase some health risks (such as air pollution, noise, and sedentarism); however, if proper regulated, AVs will likely reduce morbidity and mortality from motor vehicle crashes and may help reshape cities to promote healthy urban environments. Healthy models of AV use include fully electric vehicles in a system of ridesharing and ridesplitting. Public health will benefit if proper policies and regulatory frameworks are implemented before the complete introduction of AVs into the market.
Genetic lineage tracing reveals poor angiogenic potential of cardiac endothelial cells
Authors: Tea Kocijan, Michael Rehman, Andrea Colliva, Elena Groppa, Matteo Leban, Simone Vodret, Nina Volf, Gabriele Zucca, Ambra Cappelletto, Giulia Maria Piperno, Lorena Zentilin, Mauro Giacca, Federica Benvenuti, Bin Zhou, Ralf H Adams, Serena Zacchigna
Journal: Cardiovascular Research (2020)

Abstract Aims Cardiac ischaemia does not elicit an efficient angiogenic response. Indeed, lack of surgical revascularization upon myocardial infarction results in cardiomyocyte death, scarring, and loss of contractile function. Clinical trials aimed at inducing therapeutic revascularization through the delivery of pro-angiogenic molecules after cardiac ischaemia have invariably failed, suggesting that endothelial cells in the heart cannot mount an efficient angiogenic response. To understand why the heart is a poorly angiogenic environment, here we compare the angiogenic response of the cardiac and skeletal muscle using a lineage tracing approach to genetically label sprouting endothelial cells. Methods and results We observed that overexpression of the vascular endothelial growth factor in the skeletal muscle potently stimulated angiogenesis, resulting in the formation of a massive number of new capillaries and arterioles. In contrast, response to the same dose of the same factor in the heart was blunted and consisted in a modest increase in the number of new arterioles. By using Apelin-CreER mice to genetically label sprouting endothelial cells we observed that different pro-angiogenic stimuli activated Apelin expression in both muscle types to a similar extent, however, only in the skeletal muscle, these cells were able to sprout, form elongated vascular tubes activating Notch signalling, and became incorporated into arteries. In the heart, Apelin-positive cells transiently persisted and failed to give rise to new vessels. When we implanted cancer cells in different organs, the abortive angiogenic response in the heart resulted in a reduced expansion of the tumour mass. Conclusion Our genetic lineage tracing indicates that cardiac endothelial cells activate Apelin expression in response to pro-angiogenic stimuli but, different from those of the skeletal muscle, fail to proliferate and form mature and structured vessels. The poor angiogenic potential of the heart is associated with reduced tumour angiogenesis and growth of cancer cells.
Facets of shame are differently expressed in dermatological disease: a prospective observational study
Authors: E. Aberer, M. Hiebler‐Ragger, M. Zenker, W. Weger, A. Hofer, H.F. Unterrainer
Journal: British Journal of Dermatology (2020)

in assessing NB-UVB-induced response in vitiligo, and may also be used as a marker in monitoring disease progression.
Association of MRI-derived radiomic biomarker with disease-free survival in patients with early-stage cervical cancer
Authors: Jin Fang, Bin Zhang, Shuo Wang, Yan Jin, Fei Wang, Yingying Ding, Qiuying Chen, Liting Chen, Yueyue Li, Minmin Li, Zhuozhi Chen, Lizhi Liu, Zhenyu Liu, Jie Tian, Shuixing Zhang
Journal: Theranostics (2020)

Pre-treatment survival prediction plays a key role in many diseases. We aimed to determine the prognostic value of pre-treatment Magnetic Resonance Imaging (MRI) based radiomic score for disease-free survival (DFS) in patients with early-stage (IB-IIA) cervical cancer. Methods: A total of 248 patients with early-stage cervical cancer underwent radical hysterectomy were included from two institutions between January 1, 2011 and December 31, 2017, whose MR imaging data, clinicopathological data and DFS data were collected. Patients data were randomly divided into the training cohort (n = 166) and the validation cohort (n=82). Radiomic features were extracted from the pre-treatment T2-weighted (T2w) and contrast-enhanced T1-weighted (CET1w) MR imagings for each patient. Least absolute shrinkage and selection operator (LASSO) regression and Cox proportional hazard model were applied to construct radiomic score (Rad-score). According to the cutoff of Rad-score, patients were divided into low- and high- risk groups. Pearson's correlation and Kaplan-Meier analysis were used to evaluate the association of Rad-score with DFS. A combined model incorporating Rad-score, lymph node metastasis (LNM) and lymphovascular space invasion (LVI) by multivariate Cox proportional hazard model was constructed to estimate DFS individually. Results: Higher Rad-scores were significantly associated with worse DFS in the training and validation cohorts (P<0.001 and P=0.011, respectively). The Rad-score demonstrated better prognostic performance in estimating DFS (C-index, 0.753; 95% CI: 0.696-0.805) than the clinicopathological features (C-index, 0.632; 95% CI: 0.567-0.700). However, the combined model showed no significant improvement (C-index, 0.714; 95%CI: 0.642-0.784). Conclusion: The results demonstrated that MRI-derived Rad-score can be used as a prognostic biomarker for patients with early-stage (IB-IIA) cervical cancer, which can facilitate clinical decision-making.
Abstract 16004: Subclinical Cardiotoxicity Post Anthracycline in an African Population
Authors: Joseph O Abuodha, Asim J Shaikh, Jasmit Shah, Jeilan Mohamed, Anders Barasa
Journal: Circulation (2019)

Introduction: Anthracyclines, though known to improve survival in some malignancies, is known to be associated with cardiotoxicity. Early detection of cardiotoxicity provides an opportunity for tre...
Transcatheter Mitral Valve Replacement: Rationale and Current Status
Authors: Paul N. Fiorilli, Howard C. Herrmann
Journal: Annual Review of Medicine (2020)

Mitral regurgitation (MR) is the most prevalent form of moderate or severe valve disease in the developed world. MR can result from impairment of any part of the mitral valve apparatus and is classified as primary (disease of the leaflets) or secondary (functional). The presence of at least moderate MR is associated with increased morbidity and mortality. With the goal of avoiding the risks of traditional surgery, transcatheter mitral valve therapies have been developed. The current transcatheter repair techniques are limited by therapeutic target and incomplete MR reduction, and thus transcatheter mitral valve replacement (TMVR) has been pursued. Several devices (both transapical and transseptal) are under development, with both early feasibility and pivotal trials under way. As this field develops, the decision to treat with TMVR will require a heart team approach that takes patient-, disease-, and device-specific factors into account.