tbuckley/cabot-search huggingface dataset:
CLO19-037: Reducing the Duration, Incidence and Severity of Mucosal Injury Due to Cancer Radiation therapy (RT); Positive Randomized Phase 2b Trial Results With GC4419 (Avasopasem Manganese), a Small Molecule Superoxide (SO) Dismutase (SOD) Mimetic
Authors: Jon T. Holmlund, Carryn M. Anderson, Stephen T. Sonis, Robert Beardsley, Dennis Riley, Jeffrey Mark Brill, Melissa Brookes, Kara Terry, J. Mel Sorensen
Journal: Journal of the National Comprehensive Cancer Network (2019)

Introduction: RT-induced SO contributes to initiation of mucosal injury; eg, oral mucositis (OM) and esophagitis. GC4419 specifically mimics SOD’s dismutation of SO to hydrogen peroxide (H 2 O 2 ), interdicting OM initiation. GC4419 reduced RT-severe OM (SOM) in a hamster cheek pouch model, and protected mucosa and other normal tissues from radiation-induced injury in other animal models. In a published phase 1b/2a open-label trial (Anderson et al, IJROBP, 1 Feb 2018), GC4419 attenuated SOM in patients (Pts) receiving intensity-modulated RT (IMRT) plus concurrent cisplatin (CDDP) for locally advanced head &amp; neck cancer (HNC). Objectives : Determine whether GC4419 reduces duration, incidence, &amp; severity of SOM. Methods: Pts with locally advanced oral cavity or oropharyngeal cancer; definitive or postoperative intensity-modulated (IM)RT (approximately 70 Gy [ &gt; 50 Gy to &gt; 2 oral sites]) plus CDDP (weekly or q3wk) were randomized (stratification: tumor HPV status, CDDP schedule) to 30 or 90 mg of GC4419, or placebo (PBO), 60-minute IV infusion, M–F, ending &lt; 60 minutes before IMRT delivered in 35 fractions over 7 weeks. WHO grade OM was assessed by trained evaluators biw during IMRT &amp; qwk for up to 8 wks after IMRT. Primary endpoint: duration of SOM. Efficacy was tested for each active dose vs PBO (ITT population) by a sequential, conditional approach (2-sided alpha, 0.05). Results: 223 pts (44 sites): 90 mg (n=76), 30 mg (n=73), or PBO (n=74). Baseline patient and tumor characteristics and treatment delivery were balanced. Efficacy: At 90 mg GC4419 vs PBO, duration of SOM was significantly reduced (median, 1.5 vs 19 d; P =.024). SOM incidence (43% vs 65%; P =.009), and grade 4 incidence (16% vs 30%; P =.045) also improved. There were intermediate improvements with 30 mg. Safety was comparable across arms; no significant GC4419-specific toxicity; other known toxicities of IMRT/CDDP were not increased. Conclusions: GC4419 demonstrated a significant, clinically meaningful reduction of SOM duration, and dose-dependent improvements in other SOM parameters, with acceptable safety. A confirmatory phase 3 trial (NCT03689712) is in progress. Clinical trials to reduce RT-related esophagitis are also planned.
Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA
Authors: Franca De Sarno, Alfonso Maria Ponsiglione, Maria Russo, Anna Maria Grimaldi, Ernesto Forte, Paolo Antonio Netti, Enza Torino
Journal: Theranostics (2019)

Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, understanding the MRI enhancement mechanism remains a challenge. Methods: A multidisciplinary approach is used to highlight the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA. Changes in polymer conformation and thermodynamic interactions of CAs and polymers in aqueous solutions are detected by isothermal titration calorimetric (ITC) measurements and later, these interactions are investigated at the molecular level using NMR to better understand the involved phenomena. Water molecular dynamics of these systems is also studied using Differential Scanning Calorimetry (DSC). To observe relaxometric properties variations, we have monitored the MRI enhancement of the examined structures over all the experiments. The study of polymer-CA solutions reveals that thermodynamic interactions between biopolymers and CAs could be used to improve MRI Gd-based CA efficiency. High-Pressure Homogenization is used to obtain nanoparticles. Results: The effect of the hydration of the hydrogel structure on the relaxometric properties, called Hydrodenticity and its application to the nanomedicine field, is exploited. The explanation of this concept takes place through several key aspects underlying biopolymer-CA's interactions mediated by the water. In addition, Hydrodenticity is applied to develop Gadolinium-based polymer nanovectors with size around 200 nm with improved MRI relaxation time (10-times). Conclusions: The experimental results indicate that the entrapment of metal chelates in hydrogel nanostructures offers a versatile platform for developing different high performing CAs for disease diagnosis.
Cardiac Hyaluronan Synthesis Is Critically Involved in the Cardiac Macrophage Response and Promotes Healing After Ischemia Reperfusion Injury
Authors: Anne Petz, Maria Grandoch, Daniel J. Gorski, Marcel Abrams, Marco Piroth, Rebekka Schneckmann, Susanne Homann, Julia Müller, Sonja Hartwig, Stefan Lehr, Yu Yamaguchi, Thomas N. Wight, Simone Gorressen, Zhaoping Ding, Sebastian Kötter, Martina Krüger, Andre Heinen, Malte Kelm, Axel Gödecke, Ulrich Flögel, Jens W. Fischer
Journal: Circulation Research (2019)

Rationale: Immediate changes in the ECM (extracellular matrix) microenvironment occur after myocardial ischemia and reperfusion (I/R) injury. Objective: Aim of this study was to unravel the role of the early hyaluronan (HA)-rich ECM after I/R. Methods and Results: Genetic deletion of Has2 and Has1 was used in a murine model of cardiac I/R. Chemical exchange saturation transfer imaging was adapted to image cardiac ECM post-I/R. Of note, the cardiac chemical exchange saturation transfer signal was severely suppressed by Has2 deletion and pharmacological inhibition of HA synthesis 24 hours after I/R. Has2 KO ( Has2 deficient) mice showed impaired hemodynamic function suggesting a protective role for endogenous HA synthesis. In contrast to Has2 deficiency, Has1 -deficient mice developed no specific phenotype compared with control post-I/R. Importantly, in Has2 KO mice, cardiac macrophages were diminished after I/R as detected by 19 F MRI (magnetic resonance imaging) of perfluorcarbon-labeled immune cells, Mac-2/Galectin-3 immunostaining, and FACS (fluorescence-activated cell sorting) analysis (CD45 + CD11b + Ly6G − CD64 + F4/80 + cells). In contrast to macrophages, cardiac Ly6C high and Ly6C low monocytes were unaffected post-I/R compared with control mice. Mechanistically, inhibition of HA synthesis led to increased macrophage apoptosis in vivo and in vitro. In addition, α-SMA (α-smooth muscle actin)–positive cells were reduced in the infarcted myocardium and in the border zone. In vitro, the myofibroblast response as measured by Acta2 mRNA expression was reduced by inhibition of HA synthesis and of CD44 signaling. Furthermore, Has2 KO fibroblasts were less able to contract collagen gels in vitro. The effects of HA/CD44 on fibroblasts and macrophages post-I/R might also affect intercellular cross talk because cardiac fibroblasts were activated by monocyte/macrophages and, in turn, protected macrophages from apoptosis. Conclusions: Increased HA synthesis contributes to postinfarct healing by supporting macrophage survival and by promoting the myofibroblast response. Additionally, imaging of cardiac HA by chemical exchange saturation transfer post-I/R might have translational value.
Abstract P259: Improvements in Diet Quality Are Associated With Reduced Abdominal Adiposetissue: A Prospective Study
Authors: Rachel Hennein, Jiantao Ma, Michelle Long, Chunyu Liu, Daniel Levy
Journal: Circulation (2018)

Objectives: Visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) are associated with cardiometabolic diseases. The relationship between diet quality and abdominal fat accumulation, however, has not been well studied. We aimed to examine the long-term association of change in diet quality and change in abdominal adipose tissue. Methods: In 1,677 participants who attended two consecutive Framingham Heart Study examinations, we measured the volume of VAT and SAT using multi-detector computed tomography at two time-points (median interval of 6 years). The ratio of VAT/SAT was calculated to reflect the relative abundance of these two fat stores, i.e., abdominal fat distribution. We created two scores to represent overall diet quality, the Mediterranean-style diet score (MDS) and the Alternative Healthy Eating Index (AHEI) score, using food frequency questionnaires at baseline and follow-up exams. We analyzed the association between change in the dietary scores and change in VAT, SAT, and VAT/SAT ratio with adjustment for baseline covariates including sex, age, dietary score, VAT, SAT, or VAT/SAT ratio, BMI, energy intake, smoking status, physical activity score, and change in energy intake, smoking status, and physical activity. Results: For each standard deviation increase in ΔMDS (diet quality improved), VAT volume reduced by 53±19 cm 3 (P=0.005) and SAT volume declined by 52±20 cm 3 (P=0.01). Similarly, for each standard deviation increase in ΔAHEI (diet quality improved), VAT volume declined by 45±18 cm 3 (P=0.01) and SAT volume fell by 57±19 cm 3 (P=0.003). In addition, an increased MDS was associated with a decline in VAT/SAT ratio (P=0.04), but there was no association between ΔAHEI and change in VAT/SAT ratio (P=0.06). We also observed that improved intake of nuts (P=0.04), whole grains (P=0.02), and meat (P=0.005) for MDS and fruits (P=0.02) and meat (P=0.03) for AHEI were associated with a decline in VAT/SAT ratio. Conclusions: The present study demonstrates that longitudinal improvements in diet quality were associated with reduced abdominal fat accumulation, both VAT and SAT. In addition, improved dietary intake of fruits, nuts, whole grains, and meat may affect abdominal fat distribution, i.e., more likely to reduce fat accumulation in VAT relative to SAT.
Residential Exposure to Outdoor Air Pollution and Post-bronchodilator Lung Function Deficits in Mid-Adult Life
Authors: Jennifer L. Perret, Gayan Bowatte, Luke D. Knibbs, David P. Johns, Caroline J. Lodge, Adrian J. Lowe, Dinh S. Bui, Melanie C. Matheson, Bruce R. Thompson, Graham G. Giles, E. Haydn Walters, Michael J. Abramson, Shyamali C. Dharmage
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

The strengths of our study include prospective assessments of pre-ICU frailty and cognition and the availability of highquality, longitudinal data on disability with minimal loss to follow-up.Because frailty and cognitive impairment were assessed every 18 months, it is possible that these factors could have changed between their assessment and ICU admission, although neither would likely have improved.In addition, although we did adjust for mechanical ventilation, shock, and ICU length of stay, severity-of-illness scores were not available.Finally, our participants were drawn from one geographic region, so the results may not be generalizable to other regions.In summary, prehospitalization cognitive impairment and prehospitalization frailty interact to amplify posthospitalization disability among older ICU survivors.Additional research is warranted to confirm these findings and to elucidate the underlying mechanisms.
Computational Modeling of Protein Networks Predicts Treatment Outcomes in Multiple Myeloma (MM)
Authors: Leylah M. Drusbosky, Hemant S. Murthy, Helen L. Leather, Himanshu Grover, Yugandhara Narvekar, Pallavi Kumari, Sirisha Narayanabhatia, Priyanka Bhowmick, Taher Abbasi, Shireen Vali, Qing Zhang, Saad Z Usmani, Christopher R. Cogle
Journal: Blood (2017)
Quality of life and mood of older patients with acute myeloid leukemia (AML) receiving intensive and non-intensive chemotherapy
Authors: Areej El-Jawahri, Gregory A. Abel, Lara Traeger, Lauren Waldman, Netana Markovitz, Harry VanDusen, Amir Fathi, David P. Steensma, Thomas W. LeBlanc, Nora K. Horick, Daniel J. DeAngelo, Martha Wadleigh, Gabriela Hobbs, Julia Foster, Andrew M. Brunner, Philip Amrein, Richard M. Stone, Jennifer S. Temel, Joseph A. Greer
Journal: Leukemia (2019)
Letter to the editor: Prevention of bacterial sexually transmitted infections (STI) in France: why not recommend using condoms and safer sex?
Authors: Eric Caumes
Journal: Eurosurveillance (2019)

Preview this article: Letter to the editor: Prevention of bacterial sexually transmitted infections (STI) in France: why not recommend using condoms and safer sex?, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/24/12/eurosurv-24-12-7-1.gif
Beyond uncertainty: A broader scope for “incentive hope” mechanisms and its implications
Authors: Omer Linkovski, Noam Weinbach, Shimon Edelman, Marcus W. Feldman, Arnon Lotem, Oren Kolodny
Journal: Behavioral and Brain Sciences (2019)

We propose that food-related uncertainty is but one of multiple cues that predicts harsh conditions and may activate "incentive hope." An evolutionarily adaptive response to these would have been to shift to a behavioral-metabolic phenotype geared toward facing hardship. In modernity, this phenotype may lead to pathologies such as obesity and hoarding. Our perspective suggests a novel therapeutic approach.
Supplementing Essential Polyunsaturated Fatty Acids—A Matter of Respecting Fetal Development—Reply
Authors: Sarah A. Keim, Lynette K. Rogers, Mark A. Klebanoff
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 14108: Feasibility and Acceptability of Qigong Exercise in Community-Dwelling Older Adults
Authors: Pei-Shiun Chang, M. Tish Knobf, Byeongsang Oh, Marjorie Funk
Journal: Circulation (2017)

Objectives: Qigong exercise has been shown to improve physical and psychological well-being in Asian adults with chronic conditions, but little is known about the feasibility and acceptability of e...
Controlling genital chlamydial infection
Authors: M J Bolam, T. Stokes, R. Shukla, S. Bhaduri, P. Schober
Journal: BMJ (1997)

Doctors should work towards elimination of all firearms and knivesEditor-With the publication of the Cullen report into the shooting of several children at a school in Scotland 1 and the cross party support in parliament to increase the controls on handguns, the moment is ripe for the medical profession to pursue a new health campaign.Over the past three or four decades the profession has had some success in raising public awareness of the risks of cigarette smoking and through that, probably, in saving lives.The reduction of the suicide rate is an objective of the Health of the Nation for England, yet suicide rates are still rising among young men. 2 Homicide is a major political issue.Weapons, especially firearms and knives, contribute to both these forms of premature death.Elimination of all firearms and knives that are surplus to domestic and industrial requirements would not solve either problem entirely, but it would make an important contribution.We believe that the profession, through the BMA and one or two royal colleges (particularly the Royal College of Psychiatrists), could develop policies about weapons control.The prime minister has already indicated that he would introduce controls on knives if a workable definition for the surplus ones was drawn up.
Patients “increasingly worried” about drug supplies amid Brexit uncertainty, says royal college
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Patients are “increasingly worried” by a lack of information around how drug supplies will be affected by Brexit, despite repeated government reassurances that access will not be impeded, the Royal College of General Practitioners has said.

College chair Helen Stokes-Lampard said that while NHS England and the government had given repeated reassurances that contingency plans were in place, the ongoing uncertainty over Brexit had left patients anxious.

She said the college was concerned that the absence of clear …
RCP adopts neutral stance on assisted dying after poll of members
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The Royal College of Physicians is to remove its opposition to assisted dying and adopt a neutral stance on the issue after announcing the results of a poll of its members.

Of the 6885 doctors who responded to the poll (20% of the RCP’s members and fellows), 43% thought that the college should be opposed to changing the law on assisted dying. This was similar to the 44% when RCP members were last polled in 2014.

But the proportion of respondents wanting the RCP to support a change in the law increased to 32% in 2019, from 25% in 2014. A quarter of respondents (25%) in the latest poll thought that the RCP should be neutral, down from 31% in 2014.

The result means that the college will now adopt a neutral position, which it had pledged to …
Newborn Heart Screening
Authors: Bridget Kuehn
Journal: JAMA (2019)

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
Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters
Authors: Q. Zhong, B.C. Yoon, M. Aryal, J.B. Wang, T. Ilovitsh, M.A. Baikoghli, N. Hosseini-Nassab, A. Karthik, R.H. Cheng, K.W. Ferrara, R.D. Airan
Journal: Biomaterials (2019)
Supplementing Essential Polyunsaturated Fatty Acids—A Matter of Respecting Fetal Development
Authors: Wolfgang Bernhard, Christian F. Poets, Axel R. Franz
Journal: JAMA Pediatrics (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Exosomes from M1-Polarized Macrophages Enhance Paclitaxel Antitumor Activity by Activating Macrophages-Mediated Inflammation
Authors: Piaopiao Wang, Huihui Wang, Qianqian Huang, Can Peng, Liang Yao, Hong Chen, Zhen Qiu, Yifan Wu, Lei Wang, Weidong Chen
Journal: Theranostics (2019)

Exosomes (Exos) are membrane-encased vesicles derived by nearly all cell types for intercellular communication and regulation. They also received attention for their use as natural therapeutic platforms and drug delivery system. Classically activated M1 macrophages suppress tumor growth by releasing pro-inflammatory factors. This study investigated the suitability of M1-exosomes (M1-Exos) as drug carrier and their effect on the NF-κB signal pathway and further detected whether macrophages repolarization can potentiate the antitumor activities of chemotherapeutics.
Anti-tumor effects and potential therapeutic response biomarkers in α-emitting <i>meta</i>-<sup>211</sup>At-astato-benzylguanidine therapy for malignant pheochromocytoma explored by RNA-sequencing
Authors: Yasuhiro Ohshima, Nobuaki Kono, Yuichiro Yokota, Shigeki Watanabe, Ichiro Sasaki, Noriko S. Ishioka, Tetsuya Sakashita, Kazuharu Arakawa
Journal: Theranostics (2019)

Targeted α-particle therapy is a promising option for patients with malignant pheochromocytoma.Recent observations regarding meta-211 At-astato-benzylguanidine ( 211 At-MABG) in a pheochromocytoma mouse model showed a strong anti-tumor effect, though the molecular mechanism remains elusive.Here, we present the first comprehensive RNA-sequencing (RNA-seq) data for pheochromocytoma cells based on in vitro 211 At-MABG administration experiments.Key genes and pathways in the tumor α-particle radiation response are also examined to obtain potential response biomarkers.Methods: We evaluated genome-wide transcriptional alterations in the rat pheochromocytoma cell line PC12 at 3, 6, and 12 h after 211 At-MABG treatment; a control experiment using 60 Co γ-ray irradiation was carried out to highlight 211 At-MABG-specific gene expression.For comparisons, 10% and 80% iso-survival doses (0.8 and 0.1 kBq/mL for 211 At-MABG and 10 and 1 Gy for 60 Co γ-rays) were used.Results: Enrichment analysis of differentially expressed genes (DEGs) and analysis of the gene expression profiles of cell cycle checkpoints revealed similar modes of cell death via the p53-p21 signaling pathway after 211 At-MABG treatment and γ-ray irradiation.The top list of ranked DEGs demonstrated the expression of key genes on the decrease in the survival following 211 At-MABG exposure, and four potential genes (Mien1, Otub1, Vdac1 and Vegfa genes) of 211 At-MABG therapy.Western blot analysis indicated increased expression of TSPO in 211 At-MABG-treated cells, suggesting its potential as a PET imaging probe. Conclusion:Comprehensive RNA-seq revealed contrasting cellular responses to γ-ray and α-particle therapy, leading to the identification of four potential candidate genes that may serve as molecular imaging and 211 At-MABG therapy targets.