tbuckley/cabot-search huggingface dataset:
Cellular Uptake of A Taurine-Modified, Ester Bond-Decorated D-Peptide Derivative via Dynamin-Based Endocytosis and Macropinocytosis
Authors: Jie Zhou, Xuewen Du, Cristina Berciu, Steven J. Del Signore, Xiaoyi Chen, Natsuko Yamagata, Avital A. Rodal, Daniela Nicastro, Bing Xu
Journal: Molecular Therapy (2018)

Most of the peptides used for promoting cellular uptake bear positive charges. In our previous study, we reported an example of taurine (bearing negative charges in physiological conditions) promoting cellular uptake of D-peptides. Taurine, conjugated to a small D-peptide via an ester bond, promotes the cellular uptake of this D-peptide. Particularly, intracellular carboxylesterase (CES) instructs the D-peptide to self-assemble and to form nanofibers, which largely disfavors efflux and further enhances the intracellular accumulation of the D-peptide, as supported by that the addition of CES inhibitors partially impaired cellular uptake of this molecule in mammalian cell lines. Using dynamin 1, 2, and 3 triple knockout (TKO) mouse fibroblasts, we demonstrated that cells took up this molecule via macropinocytosis and dynamin-dependent endocytosis. Imaging of Drosophila larval blood cells derived from endocytic mutants confirmed the involvement of multiple endocytosis pathways. Electron microscopy (EM) indicated that the precursors can form aggregates on the cell surface to facilitate the cellular uptake via macropinocytosis. EM also revealed significantly increased numbers of vesicles in the cytosol. This work provides new insights into the cellular uptake of taurine derivative for intracellular delivery and self-assembly of D-peptides. Most of the peptides used for promoting cellular uptake bear positive charges. In our previous study, we reported an example of taurine (bearing negative charges in physiological conditions) promoting cellular uptake of D-peptides. Taurine, conjugated to a small D-peptide via an ester bond, promotes the cellular uptake of this D-peptide. Particularly, intracellular carboxylesterase (CES) instructs the D-peptide to self-assemble and to form nanofibers, which largely disfavors efflux and further enhances the intracellular accumulation of the D-peptide, as supported by that the addition of CES inhibitors partially impaired cellular uptake of this molecule in mammalian cell lines. Using dynamin 1, 2, and 3 triple knockout (TKO) mouse fibroblasts, we demonstrated that cells took up this molecule via macropinocytosis and dynamin-dependent endocytosis. Imaging of Drosophila larval blood cells derived from endocytic mutants confirmed the involvement of multiple endocytosis pathways. Electron microscopy (EM) indicated that the precursors can form aggregates on the cell surface to facilitate the cellular uptake via macropinocytosis. EM also revealed significantly increased numbers of vesicles in the cytosol. This work provides new insights into the cellular uptake of taurine derivative for intracellular delivery and self-assembly of D-peptides.
ADXS11-001 <i>Lm</i>-LLO Immunotherapy, Mitomycin, 5-fluorouracil (5-FU) and Intensity-modulated radiation therapy (IMRT) for Anal Cancer.
Authors: Howard Safran, Kara Lynne Leonard, Thomas A. DiPetrillo, Adam Klipfel, Steven Schechter, Nicholas Oldenburg, Matthew Vrees, Leslie Roth, Nishit Shah, Kalyan C. Mantripragada, Kayla Rosati, Lakshmi Rajdev
Journal: Journal of Clinical Oncology (2017)

e15072 Background: Human papillomavirus (HPV) DNA is present in the majority of anal cancer. ADXS11-001 Lm-LLO immunotherapy is a live attenuated Listeria monocytogenes ( Lm) bioengineered to secrete a HPV-16-E7 fusion protein targeting HPV transformed cells. The Lmvector is phagocytosed by antigen presenting cells where it cross presents, stimulating MHC class 1 and 2 pathways resulting in specific T-cell immunity. The objective of this study was to determine the safety of ADXS11-001 with mitomycin, 5-FU and IMRT (chemoradiation therapy, CRT) and obtain preliminary data on progression free survival (PFS) in locally advanced anal cancer. Methods: Eligibility included patients (pts) with anal squamous cell cancer and stages T1N2-N3; T2( &lt; 4 cm)N1-N3; T2(≥4cm)N0-N3, T3N0-3, T4N0-3; without evidence of metastases. Pts received standard 54 Gy IMRT with 2 cycles of mitomycin and 5-FU. ADXS11-001, 1x10 9 colony forming units IV, was given x 1 dose before CRT then x 3 additional monthly doses after CRT. Results: The study enrolled the first pt in April 2013. Ten patients were treated (median age 62.5, range 37-71) including 5 with pelvic adenopathy. Two patients had grade 3 toxicities related to the vaccine including chills/rigors (n = 2), back pain (n = 1), hyponatremia (n = 1). All toxicities were within 24 hours of the vaccine and resolved successfully with standard care. There was no exacerbation of CRT toxicities or myelosuppression. One patient had a grade 5 cardiopulmonary event shortly after beginning 5-FU treatment which was judged to be unlikely related to ADXS11-001and possibly related to CRT. Eight patients treated on the study had a complete response at six-month sigmoidoscopy. One additional patient who did not undergo six-month sigmoidoscopy had complete response on sigmoidoscopy performed at approximately one year. Eight of 9 patients (89%) are disease-free at a median follow-up of 34 months. Conclusions: ADXS11-001 can be safely administered with CRT for anal cancer. Promising PFS was observed in patients with locally advanced disease. Clinical trial information: NCT01671488.
Abstract 20214: Lipoprotein Lipase Hydrolysis Products Differentially Regulate Gene Expression in Human THP-1 Macrophages
Authors: Narmadaa Thyagarajan, Sherri L Christian, Robert J Brown
Journal: Circulation (2016)

Introduction: Lipoprotein lipase (LPL) expression in the aorta is associated with atherosclerosis, and the free fatty acid (FFA) component of LPL hydrolysis products detrimentally affects genes ass...
Risk-Targeted Lung Cancer Screening
Authors: Vaibhav Kumar, Joshua T. Cohen, David van Klaveren, Djøra I. Soeteman, John B. Wong, Peter J. Neumann, David M. Kent
Journal: Annals of Internal Medicine (2018)

Background: Targeting low-dose computed tomography (LDCT) for lung cancer screening to persons at highest risk for lung cancer mortality has been suggested to improve screening efficiency. Objective: To quantify the value of risk-targeted selection for lung cancer screening compared with National Lung Screening Trial (NLST) eligibility criteria. Design: Cost-effectiveness analysis using a multistate prediction model. Data Sources: NLST. Target Population: Current and former smokers eligible for lung cancer screening. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Risk-targeted versus NLST-based screening. Outcome Measures: Incremental 7-year mortality, life expectancy, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of screening with LDCT versus chest radiography at each decile of lung cancer mortality risk. Results of Base-Case Analysis: Participants at greater risk for lung cancer mortality were older and had more comorbid conditions and higher screening-related costs. The incremental lung cancer mortality benefits during the first 7 years ranged from 1.2 to 9.5 lung cancer deaths prevented per 10 000 person-years for the lowest to highest risk deciles, respectively (extreme decile ratio, 7.9). The gradient of benefits across risk groups, however, was attenuated in terms of life-years (extreme decile ratio, 3.6) and QALYs (extreme decile ratio, 2.4). The incremental cost-effectiveness ratios (ICERs) were similar across risk deciles ($75 000 per QALY in the lowest risk decile to $53 000 per QALY in the highest risk decile). Payers willing to pay $100 000 per QALY would pay for LDCT screening for all decile groups. Results of Sensitivity Analysis: Alternative assumptions did not substantially alter our findings. Limitation: Our model did not account for all correlated differences between lung cancer mortality risk and quality of life. Conclusions: Although risk targeting may improve screening efficiency in terms of early lung cancer mortality per person screened, the gains in efficiency are attenuated and modest in terms of life-years, QALYs, and cost-effectiveness. Primary Funding Source: National Institutes of Health (U01NS086294).
A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial
Authors: Steven K. Malin, Emily L. Kullman, Amanda R. Scelsi, Jacob M. Haus, Julianne Filion, Mangesh R. Pagadala, Jean-Philippe Godin, Sunil Kochhar, Alastair B. Ross, John P. Kirwan
Journal: Metabolism (2018)
Safety of Addition of Inotuzumab Ozogamicin (CMC 544) to Bendamustine, Fludarabine, and Rituximab (BFR) Allogeneic Conditioning for Lymphoid Malignancies
Authors: Issa F. Khouri, Alison M. Gulbis, Denái R. Milton, Martin Korbling, Celina Ledesma, Sairah Ahmed, Amin M. Alousi, Betul Oran, Paolo Anderlini, Stefan O. Ciurea, Roland L. Bassett, Elias J. Jabbour
Journal: Blood (2017)
Effect of Standardized Handoff Curriculum on Improved Clinician Preparedness in the Intensive Care Unit
Authors: Brodie Parent, Lacey N. LaGrone, Mohamed T. Albirair, Peter T. Serina, Jonathan M. Keller, Joseph Cuschieri, Erin J. Addison, Lapio Choe, Genecelle B. Delossantos, Cameron E. Gaskill, Sarah D. Moon, Jestine T. MacDonald, Matthew J. Stolzberg, Erik G. Van Eaton, Jennifer M. Zech, Patricia A. Kritek
Journal: JAMA Surgery (2018)

Clinician miscommunication contributes to an estimated 250 000 deaths in US hospitals per year. Efforts to standardize handoff communication may reduce errors and improve patient safety.To determine the effect of a standardized handoff curriculum, UW-IPASS, on interclinician communication and patient outcomes.This cluster randomized stepped-wedge randomized clinical trial was conducted from October 2015 to May 2016 at 8 medical and surgical intensive care units at 2 hospital systems within an academic tertiary referral center. Participants included residents, fellows, advance-practice clinicians, and attending physicians (n = 106 clinicians, with 1488 handoff events over 8 months) and data were collected from daily text message-based surveys and patient medical records.The UW-IPASS standardized handoff curriculum.The primary aim was to assess the effect of the UW-IPASS handoff curriculum on perceived adequacy of interclinician communication. Patient days of mechanical ventilation, intensive care unit length of stay, reintubations within 24 hours, and order workflow patterns were also analyzed. Mixed-effects logistic regression was used to compute odds ratios and confidence intervals with adjustment for location, time period, and clinician.A total of 63 residents and advance practice clinicians, 13 fellows, and 30 attending physicians participated in the study. During the control period, clinicians reported being unprepared for their shift because of a poor-quality handoff in 35 of 343 handoffs (10.2%), while UW-IPASS-period residents reported being unprepared in 53 of 740 handoffs (7.2%) (odds ratio, 0.19; 95% CI, 0.03-0.74; P = .03). Compared with the control phase, the perceived duration of handoffs among clinicians using UW-IPASS was unchanged (+5.5 minutes; 95% CI, 0.34-9.39; P = .30). Early morning order entry decreased from 106 per 100 patient-days in the control phase to 78 per 100 patient-days in the intervention period (-28 orders; 95% CI, -55 to -4; P = .04). Overall, UW-IPASS was not associated with any changes in intensive care unit length of stay, duration of mechanical ventilation, or the number of reintubations.The UW-IPASS standardized handoff curriculum was perceived to improve intensive care provider preparedness and workflow. IPASS-based curricula represent an important step forward in communication standardization efforts and may help reduce communication errors and omissions.isrctn.org Identifier: ISRCTN14209509.
3D Bioprinting of Self‐Standing Silk‐Based Bioink
Authors: Zhaozhu Zheng, Jianbing Wu, Meng Liu, Heng Wang, Chunmei Li, María J. Rodriguez, Gang Li, Xiaoqin Wang, David L. Kaplan
Journal: Advanced Healthcare Materials (2018)

Abstract Silk/polyethylene glycol (PEG) hydrogels are studied as self‐standing bioinks for 3D printing for tissue engineering. The two components of the bioink, silk fibroin protein (silk) and PEG, are both Food and Drug Administration approved materials in drug and medical device products. Mixing PEG with silk induces silk β‐sheet structure formation and thus gelation and water insolubility due to physical crosslinking. A variety of constructs with high resolution, high shape fidelity, and homogeneous gel matrices are printed. When human bone marrow mesenchymal stem cells are premixed with the silk solution prior to printing and the constructs are cultured in this medium, the cell‐loaded constructs maintain their shape over at least 12 weeks. Interestingly, the cells grow faster in the higher silk concentration (10%, w/v) gel than in lower ones (7.5 and 5%, w/v), likely due to the difference in material stiffness and the amount of residual PEG remaining in the gel related to material hydrophobicity. Subcutaneous implantation of 7.5% (w/v) bioink gels with and without printed fibroblast cells in mice reveals that the cells survive and proliferate in the gel matrix for at least 6 week postimplantation. The results suggest that these silk/PEG bioink gels may provide suitable scaffold environments for cell printing and function.
The Nuremberg Code and Informed Consent for Research
Authors: Jon F. Merz
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The fibrotic tumor stroma
Authors: Mitsuo Yamauchi, Thomas H. Barker, Don L. Gibbons, Jonathan M. Kurie
Journal: Journal of Clinical Investigation (2018)

Intratumoral fibrosis results from the deposition of a cross-linked collagen matrix by cancer-associated fibroblasts (CAFs). This type of fibrosis has been shown to exert mechanical forces and create a biochemical milieu that, together, shape intratumoral immunity and influence tumor cell metastatic behavior. In this Review, we present recent evidence that CAFs and tumor cells are regulated by provisional matrix molecules, that metastasis results from a change in the type of stromal collagen cross-link, and that fibrosis and inflammation perpetuate each other through proteolytic and chemotactic mediators released into the tumor stroma. We also discuss aspects of the emerging biology that have potential therapeutic value.
Concealed complete response in melanoma patients under therapy with immune checkpoint inhibitors: two case reports
Authors: Stefan Schliep, Abbas Agaimy, Alexander Cavallaro, Franklin Kiesewetter, Gerold Schuler, Lucie Heinzerling
Journal: Journal for ImmunoTherapy of Cancer (2018)

The assessment of tumor size by RECIST using CT scans and MRIs is considered to be standard of care for staging cancer patients. Despite radiologic evidence of widespread disease, we document for the first time that patients were completely free of viable tumor.Two patients with metastatic melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab) and progressive metastases were detected on CT-scans performed shortly before histologic examinations. In both patients histologic assessment revealed a complete response with necrotic and scarred lesions free of tumor. One of the patients had started immunotherapy 20 months before with an initial partial response.This phenomenon of a concealed complete response can lead to overtreatment or unnecessary change in treatment. Thus, it is essential to raise awareness for it. Correct identification of responders to immune checkpoint inhibitor therapy is crucial to spare patients immune-mediated side effects and unnecessary as well as expensive treatment. Regression of metastases without decline in size, in these cases manifesting as complete responses, are probably more common than expected and identified to date. Until such responses can be readily identified by new imaging techniques, we recommend liberal biopsies for histologic assessment of progressive metastases in patients during and/or after immune checkpoint inhibitor therapy.
Ofatumumab for TTP in a Patient with Anaphylaxis Associated with Rituximab
Authors: Maeve P. Crowley, Vickie McDonald, Marie Scully
Journal: New England Journal of Medicine (2018)

Ofatumumab in Rituximab-Allergic TTP A patient with refractory thrombotic thrombocytopenic purpura had anaphylaxis associated with rituximab that was mediated by human antichimeric antibodies. The patient was successfully treated with ofatumumab, with restoration of ADAMTS13 levels.
Promising Results of a Phase 1/2 Clinical Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia
Authors: Eric Padron, Amy E. DeZern, Sandrine Niyongere, Markus Christian Ball, Maria Balasis, Hanadi Ramadan, Jeffrey E. Lancet, Alan F List, Ruben A Mesa, Gail J. Roboz, David P. Steensma, Mikkael A. Sekeres, Rami S. Komrokji
Journal: Blood (2017)
Comparison of Accessibility, Cost, and Quality of Elective Coronary Revascularization Between Veterans Affairs and Community Care Hospitals
Authors: Paul G. Barnett, Juliette S. Hong, Evan Carey, Gary K. Grunwald, Karen Joynt Maddox, Thomas M. Maddox
Journal: JAMA Cardiology (2018)

The Veterans Affairs (VA) Community Care (CC) Program supplements VA care with community-based medical services. However, access gains and value provided by CC have not been well described.To compare the access, cost, and quality of elective coronary revascularization procedures between VA and CC hospitals and to evaluate if procedural volume or publicly reported quality data can be used to identify high-value care.Observational cohort study of veterans younger than 65 years undergoing an elective coronary revascularization, controlling for differences in risk factors using propensity adjustment. The setting was VA and CC hospitals. Participants were veterans undergoing elective percutaneous coronary intervention (PCI) and veterans undergoing coronary artery bypass graft (CABG) procedures between October 1, 2008, and September 30, 2011. The analysis was conducted between July 2014 and July 2017.Receipt of an elective coronary revascularization at a VA vs CC facility.Access to care as measured by travel distance, 30-day mortality, and costs.In the 3 years ending on September 30, 2011, a total of 13 237 elective PCIs (79.1% at the VA) and 5818 elective CABG procedures (83.6% at the VA) were performed in VA or CC hospitals among veterans meeting study inclusion criteria. On average, use of CC was associated with reduced net travel by 53.6 miles for PCI and by 73.3 miles for CABG surgery compared with VA-only care. Adjusted 30-day mortality after PCI was higher in CC compared with VA (1.54% for CC vs 0.65% for VA, P < .001) but was similar after CABG surgery (1.33% for CC vs 1.51% for VA, P = .74). There were no differences in adjusted 30-day readmission rates for PCI (7.04% for CC vs 7.73% for VA, P = .66) or CABG surgery (8.13% for CC vs 7.00% for VA, P = .28). The mean adjusted PCI cost was higher in CC ($22 025 for CC vs $15 683 for VA, P < .001). The mean adjusted CABG cost was lower in CC ($55 526 for CC vs $63 144 for VA, P < .01). Neither procedural volume nor publicly reported mortality data identified hospitals that provided higher-value care with the exception that CABG mortality was lower in small-volume CC hospitals.In this veteran cohort, PCIs performed in CC hospitals were associated with shorter travel distance but with higher mortality, higher costs, and minimal travel savings compared with VA hospitals. The CABG procedures performed in CC hospitals were associated with shorter travel distance, similar mortality, and lower costs. As the VA considers expansion of the CC program, ongoing assessments of value and access gains are essential to optimize veteran outcomes and VA spending.
Daily home BNP monitoring in heart failure for prediction of impending clinical deterioration: results from the HOME HF study
Authors: Kenneth McDonald, Richard Troughton, Ulf Dahlström, Henry Dargie, Henry Krum, Peter van der Meer, Theresa McDonagh, John J. Atherton, Ken Kupfer, Richard C. San George, Mark Richards, Robert Doughty
Journal: European Journal of Heart Failure (2018)
The perivascular origin of pathological fibroblasts
Authors: Selene E. Di Carlo, Lucie Peduto
Journal: Journal of Clinical Investigation (2018)

The ability to repair tissues is essential for the survival of organisms. In chronic settings, the failure of the repair process to terminate results in overproduction of collagen, a pathology known as fibrosis, which compromises organ recovery and impairs function. The origin of the collagen-overproducing cell has been debated for years. Here we review recent insights gained from the use of lineage tracing approaches in several organs. The resulting evidence points toward specific subsets of tissue-resident mesenchymal cells, mainly localized in a perivascular position, as the major source for collagen-producing cells after injury. We discuss these findings in view of the functional heterogeneity of mesenchymal cells of the perivascular niche, which have essential vascular, immune, and regenerative functions that need to be preserved for efficient repair.
What Exactly Is an “SNF-ist?”—Reply
Authors: Joan M. Teno, Amal N. Trivedi, Pedro Gozalo
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal