tbuckley/cabot-search huggingface dataset:
A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes
Authors: Yingtong Cui, Ying Huang, Xuejuan Zhang, Xiangyun Lu, Jun Xue, Guanlin Wang, Ping Hu, Xiao Yue, Ziyu Zhao, Xin Pan, Chuanbin Wu
Journal: Acta Pharmaceutica Sinica B (2021)

Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.
Pharmacological rescue of cognitive function in a mouse model of chemobrain
Authors: Lien D. Nguyen, Tom T. Fischer, Barbara E. Ehrlich
Journal: Molecular Neurodegeneration (2021)

Abstract Background After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of cognitive changes and the underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations as a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if a similar mechanism also underlay paclitaxel-induced chemobrain. Method Mice were injected with 4 doses of 20 mg/kg paclitaxel every other day to induced cognitive impairment. Memory acquisition was assessed with the displaced object recognition test. The morphology of neurons in the prefrontal cortex and the hippocampus was analyzed using Golgi-Cox staining, followed by Sholl analyses. Changes in protein expression were measured by Western blot. Results Mice receiving paclitaxel showed impaired short-term spatial memory acquisition both acutely 5 days post injection and chronically 23 days post injection. Dendritic length and complexity were reduced in the hippocampus and the prefrontal cortex after paclitaxel injection. Concurrently, the expression of protein kinase C α (PKCα), an effector in the InsP3R pathway, was increased. Treatment with lithium before or shortly after paclitaxel injection rescued the behavioral, cellular, and molecular deficits observed. Similarly, memory and morphological deficits could be rescued by pretreatment with chelerythrine, a PKC inhibitor. Conclusion We establish the InsP3R calcium pathway and impaired neuronal morphology as mechanisms for paclitaxel-induced cognitive impairment. Our findings suggest lithium and PKC inhibitors as candidate agents for preventing chemotherapy-induced cognitive impairment.
Long Term Prospective Predictors for Vascular Events and Cardiac Complications in Thalassemia Major Patients
Authors: Antonella Meloni, Pietro Giuliano, Laura Pistoia, Nicola Giunta, Rosamaria Rosso, Mario Rocca, Mauro Murgia, Antonella Quarta, Vincenzo Spadola, Francesca Miciotto, Aurelio Maggio, Stefania Renne, Vincenzo Positano, Alessia Pepe
Journal: Blood (2017)
Integrative Genomics Reveals Cancer Associated Mutations Are Common at Diagnosis of CML in Patients with Poor Response to TKI Therapy
Authors: Susan Branford, Paul Wang, David Yeung, Adrian Purins, Justine Ellen Marum, Nathalie Nataren, Hezrin Shahrin, Daniel Thomson, Carol Wadham, Christopher N Hahn, Anna L Brown, David M Ross, Agnes S.M. Yong, Naranie Shanmuganathan, Martin Müller, Christian Dietz, Dong-Wook Kim, Soo-Hyun Kim, Soo-Young Choi, Sa-Hee Park, Hamish S Scott, Andreas Schreiber, Timothy P. Hughes
Journal: Blood (2017)
AI-based monitoring of retinal fluid in disease activity and under therapy
Authors: Ursula Schmidt-Erfurth, Gregor S. Reiter, Sophie Riedl, Philipp Seeböck, Wolf-Dieter Vogl, Barbara A. Blodi, Amitha Domalpally, Amani Fawzi, Yali Jia, David Sarraf, Hrvoje Bogunović
Journal: Progress in Retinal and Eye Research (2021)

Retinal fluid as the major biomarker in exudative macular disease is accurately visualized by high-resolution three-dimensional optical coherence tomography (OCT), which is used world-wide as a diagnostic gold standard largely replacing clinical examination. Artificial intelligence (AI) with its capability to objectively identify, localize and quantify fluid introduces fully automated tools into OCT imaging for personalized disease management. Deep learning performance has already proven superior to human experts, including physicians and certified readers, in terms of accuracy and speed. Reproducible measurement of retinal fluid relies on precise AI-based segmentation methods that assign a label to each OCT voxel denoting its fluid type such as intraretinal fluid (IRF) and subretinal fluid (SRF) or pigment epithelial detachment (PED) and its location within the central 1-, 3- and 6-mm macular area. Such reliable analysis is most relevant to reflect differences in pathophysiological mechanisms and impacts on retinal function, and the dynamics of fluid resolution during therapy with different regimens and substances. Yet, an in-depth understanding of the mode of action of supervised and unsupervised learning, the functionality of a convolutional neural net (CNN) and various network architectures is needed. Greater insight regarding adequate methods for performance, validation assessment, and device- and scanning-pattern-dependent variations is necessary to empower ophthalmologists to become qualified AI users. Fluid/function correlation can lead to a better definition of valid fluid variables relevant for optimal outcomes on an individual and a population level. AI-based fluid analysis opens the way for precision medicine in real-world practice of the leading retinal diseases of modern times.
Vita Medica; Chapters of Medical Life and Work.
Journal: JAMA (1897)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Unique Gene Expressional Profile Associated with Lack of Quantifiable Terminal Erythroid Differentiation in Myelodysplastic Syndrome Patients
Authors: Abdullah Mahmood Ali, Yumin Huang, Diego Coutinho, Brian Chernak, Etienne De Clara, Daniela Hoehn, Joseph G. Jurcic, Mohandas Narla, Xiuli An, Azra Raza
Journal: Blood (2017)
Abstract 364: Cortical Bone Stem Cells Derived Exosomes as Potent Modulator of Cardiac Immune Response and Repair After Injury
Authors: Sadia Mohsin, Constantine D Troupes, Mohsin Khan, Yijun Yang, Jaslyn Johnson, Jennifer L Petovic, Timothy Starosta, Remus M Berretta, Hajime Kubo, Steven R Houser
Journal: Circulation Research (2016)

Rationale: Cortical bone derived stem cells (CBSCs) are known to have improved growth kinetics and myocardial repair properties that are superior to other known stem cell types used. Salutary effects of CBSCs in large are mediated by paracrine secretion. Since exosomes represent an active component of released factors we tested if CBSC derived exosomes (CBSCs-Exo) can recapitulate the beneficial reparative effects of CBSCs. Objective: Determine CBSCs derived exosomes and their contents for myocardial repair. Methods and Results: Exosomes were isolated from murine CBSCs by ultracentrifugation and had typical size (30-100nm), as validated by electron microscopy and dynamic light scattering. To determine cardiac therapeutic value, CBSCs- Exo (60μg) were injected into the border zone of the mouse heart after myocardial infarction (MI). Animals injected with CBSCs-Exo had reduced infarct size and increased myocyte survival after MI injury. Interestingly, serum levels of pro-inflammatory cytokines were significantly reduced along with decreased expression of CD68+ cells in animals receiving CBSCs-Exo versus control animals. Long term analysis of CBSC-Exo animals showed improved cardiac function and contractility compared to saline treated animals concurrent with enhanced angiogenesis 6 weeks after MI. Salutary effects of CBSC-Exo were confirmed in vitro. CBSCs-Exo increased cardiac protection in NRVMs after hypoxic challenge and enhanced tube formation in HUVECs. Simultaneously, treatment of bone marrow-derived macrophages stimulated with lipopolysaccharide (LPS) and treated with CBSCs-Exo showed increased polarization towards the M2 phenotype, demonstrating an immunomodulatory capacity of CBSCs-Exo. The underlying mechanism for beneficial effects was linked to increased packaging of cardioprotective miRs including miR125, miR20 and miR18a in CBSCs-Exo confirmed by MiRNA array analysis. Conclusion: Exosomes derived from CBSCs provide a cell free system that retains the reparative power of CBSC. CBSCs-Exo augment cardiac function after myocardial injury recapitulating earlier findings with CBSCs. The packaging of cardioprotective and immune-modulatory miRs in CBSCs-Exo appears to enhance their reparative effects after MI.
Maternal Anti-αIIb Antibodies Target Fetal Hematopoietic Stem Cells and May Lead to Pancytopenia and Miscarriage in Fnait
Authors: Jade Sullivan, Brigitta Elaine Oswald, Brian Vadasz, June Li, Pingguo Chen, Mortimer Poncz, John J. Freedman, Heyu Ni
Journal: Blood (2017)
Abstract 12892: The Effect of Elevated Body Mass Index on Atrial Fibrillation Recurrence After Ablation: A Systematic Review and Meta-Analysis
Authors: Pablo Paz, Wasawat Vutthikraivit, Mohamed Elmassry, Rubayat Rahman, Saif El Nawaa, Barbara Mantilla, Pattara Rattanawong, Prapaipan Putthapiban, Mohamed Zitun, Mohammad Ansari, Scott W Shurmur
Journal: Circulation (2019)

Background: Catheter ablation (CA) has been widely used as an effective therapy for symptomatic patients with drug-refractory atrial fibrillation (AF), but a number of factors can influence ablatio...
Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity
Authors: Colin Hutton, Felix Heider, Adrian Blanco-Gomez, Antonia Banyard, Alexander Kononov, Xiaohong Zhang, Saadia Karim, Viola Paulus-Hock, Dale Watt, Nina Steele, Samantha Kemp, Elizabeth K.J. Hogg, Joanna Kelly, Rene-Filip Jackstadt, Filipa Lopes, Matteo Menotti, Luke Chisholm, Angela Lamarca, Juan Valle, Owen J. Sansom, Caroline Springer, Angeliki Malliri, Richard Marais, Marina Pasca di Magliano, Santiago Zelenay, Jennifer P. Morton, Claus Jørgensen
Journal: Cancer Cell (2021)

Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition of 18 murine tissues and 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals extensive stromal heterogeneity across tissues and tumors, and identifies coordinated relationships between mesenchymal and immune cell subsets in pancreatic ductal adenocarcinoma. Expression of CD105 demarks two stable and functionally distinct pancreatic fibroblast lineages, which are also identified in murine and human healthy tissues and tumors. Whereas CD105-positive pancreatic fibroblasts are permissive for tumor growth in vivo, CD105-negative fibroblasts are highly tumor suppressive. This restrictive effect is entirely dependent on functional adaptive immunity. Collectively, these results reveal two functionally distinct pancreatic fibroblast lineages and highlight the importance of mesenchymal and immune cell interactions in restricting tumor growth.
Author Correction: Accelerated antimicrobial discovery via deep generative models and molecular dynamics simulations
Authors: Payel Das, Tom Sercu, Kahini Wadhawan, Inkit Padhi, Sebastian Gehrmann, Flaviu Cipcigan, Vijil Chenthamarakshan, Hendrik Strobelt, Cicero dos Santos, Pin-Yu Chen, Yi Yan Yang, Jeremy P. K. Tan, James Hedrick, Jason Crain, Aleksandra Mojsilovic
Journal: Nature Biomedical Engineering (2021)
Additive Manufacturing of Multi‐Scale Porous Soft Tissue Implants That Encourage Vascularization and Tissue Ingrowth
Authors: Fergal B. Coulter, Ruth E. Levey, Scott T. Robinson, Eimear B. Dolan, Stefano Deotti, Michael Monaghan, Peter Dockery, Brian S. Coulter, Liam P. Burke, Aoife J. Lowery, Rachel Beatty, Ryan Paetzold, James J. Prendergast, Gabriella Bellavia, Stefania Straino, Francesca Cianfarani, Monica Salamone, Carmelo M. Bruno, Kevin M. Moerman, Giulio Ghersi, Garry P. Duffy, Eoin D. O'Cearbhaill
Journal: Advanced Healthcare Materials (2021)

Abstract Medical devices, such as silicone‐based prostheses designed for soft tissue implantation, often induce a suboptimal foreign‐body response which results in a hardened avascular fibrotic capsule around the device, often leading to patient discomfort or implant failure. Here, it is proposed that additive manufacturing techniques can be used to deposit durable coatings with multiscale porosity on soft tissue implant surfaces to promote optimal tissue integration. Specifically, the “liquid rope coil effect”, is exploited via direct ink writing, to create a controlled macro open‐pore architecture, including over highly curved surfaces, while adapting atomizing spray deposition of a silicone ink to create a microporous texture. The potential to tailor the degree of tissue integration and vascularization using these fabrication techniques is demonstrated through subdermal and submuscular implantation studies in rodent and porcine models respectively, illustrating the implant coating's potential applications in both traditional soft tissue prosthetics and active drug‐eluting devices.
Generation of osteoarthritic mesenchymal stromal cell lines.
Authors: María Piñeiro-Ramil, Rocío Castro Viñuelas, Clara Sanjurjo-Rodríguez, Silvia Rodríguez-Fernández, Tamara Hermida Gómez, Francisco Javier de Toro Santos, Francisco J Blanco García, Isaac Manuel Fuentes Boquete, Silvia Díaz Prado
Journal: Annals of the Rheumatic Diseases (2019)
Precision Methylome and <i>in Vivo</i> Methylation Kinetics Characterization of <i>Klebsiella Pneumoniae</i>
Authors: Jing Fu, Ju Zhang, Li Yang, Nan Ding, Liya Yue, Xiangli Zhang, Dandan Lu, Xinmiao Jia, Cuidan Li, Chongye Guo, Zhe Yin, Xiaoyuan Jiang, Yongliang Zhao, Fei Chen, Dongsheng Zhou
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Klebsiella pneumoniae (K. pneumoniae) is an important pathogen that can cause severe hospital- and community-acquired infections. To systematically investigate its methylation features, we determined the whole-genome sequences of 14 K. pneumoniae strains covering varying serotypes, multilocus sequence types, clonal groups, viscosity/virulence, and drug resistance. Their methylomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies. We identified 15 methylation motifs [13 N6-methyladenine (6 mA) and two 5-methylcytosine (5mC) motifs], among which eight were novel. Their corresponding DNA methyltransferases were also validated. Additionally, we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains, and identified differential distribution patterns of some hemi-/un-methylated GATC motifs, which tend to be located within intergenic regions (IGRs). Specifically, we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation. The slow methylation of the GATC motifs in the replication origin (oriC) regions and IGRs implicates the epigenetic regulation of replication initiation and transcription. Our findings illustrate the first comprehensive dynamic methylome map of K. pneumoniae at single-base resolution, and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.
Abstract 60: Double Hit Mutations in Thoracic Aortic Aneurysm Disease That Have Variable Impact on Phenotype
Authors: Brett D Hambly, Elizabeth Robertson, Stefanie Portelli, Yaxin Lu, Murat Kekic, Richmond Jeremy
Journal: Circulation Research (2016)

Multiple genes are associated with thoracic aortic aneurysm (TAA) formation, including FBN1, TGFBR1&amp;2, COL3A1 &amp; 5A2, and MYH11. Given the population incidence of mutations in these genes we hypothesise that it is likely that ‘double hit’ mutations occur, which may result in an altered clinical phenotype when compared with the single gene mutation. Genomic DNA analysis of 19 genes implicated in TAA was performed on 12 patients with inherited TAA disease. Of the patients analysed, one patient (P1) was identified as having a mutation in both MYH11 (c.2517G.C (pW839C)) and FBN1 (splice donor site c.4210+1G&gt;A). Another patient (P2) was identified as having both COL5A2 (c.3794A&gt;G (pD1265G)) and FBN1 (c.5861T&gt;G (p.F1954C)). All mutations were predicted by PolyPhen to be deleterious. P1 has Marfan Syndrome (MFS), caused by the FBN1 mutation, and has severe aortic dilatation while his mother (M1), who also has MFS but does not have the MHY11 mutation, developed mild aortic dilatation, suggesting that the MHY11 mutation in P1 has resulted in a more aggressive phenotype. P2, siblings S1 and S2 and father (F2) all have relatively less severe MFS with progressive moderate dilatation of the aorta. Thus, the phenotype of pedigree 2 is similar for all affected members, but only P2 has a double hit mutation, suggesting that the presence of the COL5A2 mutation in P2 has not altered the clinical phenotype. This is the first instance where double hit mutations have been described in inherited thoracic aortic aneurysm but the effect of multiple mutations on phenotype appears to be variable. Mutation analysis for individuals with inherited thoracic aortic aneurysm should consider the possibility of multiple gene culprits.
Functional Evaluation and Clinical Implications of FLT3 J uxtamembrane Domain Short Variants in Pediatric AML
Authors: Katherine Tarlock, Todd A Alonzo, Yi-Cheng Wang, Robert B Gerbing, Tiffany Hylkema, Rhonda E. Ries, M. Eva Hansen, Edward A Kolb, Alan S Gamis, Soheil Meshinchi
Journal: Blood (2017)
Response to: ‘Correspondence on ‘Efficacy and safety of brodalumab, an anti-IL17RA monoclonal antibody, in patients with axial spondyloarthritis: 16-week results from a randomised, placebo-controlled, phase 3 trial’’ by Zhao and Huang
Authors: James Cheng-Chung Wei, Tae-Hwan Kim, Mitsumasa Kishimoto, Naoki Ogusu, Haeyoun Jeong, Shigeto Kobayashi
Journal: Annals of the Rheumatic Diseases (2021)

We thank Dr Zhao and Dr Huang for their interest in our article.1 2

The approved dosage of brodalumab for plaque psoriasis includes a loading treatment of 210 mg every week at weeks 0, 1 and 2 followed by a dose of 210 mg every 2 weeks thereafter.3 The brodalumab dosage administered in patients with axial spondyloarthritis (axSpA) in our study1 was the same as that approved for plaque psoriasis. Therefore, the rapid improvement in Assessment of SpondyloArthritis International Society 40/20 as early as week 2 in patients with axSpA in our study and similar to the improvement observed in Psoriasis Area and Severity Index in patients with plaque psoriasis4 could be attributed to the loading treatment. However, the study5 that Zhao et al have referred to in their correspondence2 was conducted in patients with psoriatic arthritis and not in those with plaque psoriasis and included a loading treatment of brodalumab 210 mg every week at weeks 0, 1 and 2.

With regard to the comment on safety, we believe that the short study period of 16 weeks …
The Whole Exome Analysis and Clinical Relevance in Patients with Atypical Hemolytic Uremic Syndrome
Authors: Mustafa Nuri Yenerel, Yasar Caliskan, Alaattin Yildiz, Sedat Karadeniz, Aydin Turkmen, Mehmet Seit Kayacan, Tufan Tukek, Murat Köse, Melih Aktan, Meliha Nalcaci
Journal: Blood (2017)
Helen Salisbury: Should I stay or should I go?
Authors: Helen Salisbury
Journal: BMJ (2021)

Whenever two or three GPs of a certain age are gathered together, the subject of early retirement will arise. Last month a BMA survey reported that growing numbers were considering hanging up their stethoscopes for good because work had become too stressful to be worth the personal cost of continuing.12 I have no retirement plans at present, but these conversations inevitably make me think about what keeps me working.

After many years in the role I still have the capacity to be surprised—even excited—by the challenge of diagnosis when some unusual constellation of symptoms and signs sets me …
Clinical Impact of Sarcopenia and Skeletal Muscle Mass Change during Chemotherapy on Outcomes of Diffuse Large B-Cell Lymphoma
Authors: Hiroshi Teranaka, Shin Fujisawa, Takayuki Sakuma, Haruka Teshigawara, Ayako Matsumura, Taiki Ando, Taisei Suzuki, Akiko Negoro, Eriko Ogusa, Jun Aoki, Kazuho Miyashita, Yoshimi Ishii, Hiroyuki Takahashi, Yuki Nakajima, Takuya Miyazaki, Maki Hagihara, Kenji Matsumoto, Etsuko Yamazaki, Hideaki Nakajima
Journal: Blood (2017)