tbuckley/cabot-search huggingface dataset:
Protein‐Engineered Functional Materials
Authors: Yao Wang, Priya Katyal, Jin Kim Montclare
Journal: Advanced Healthcare Materials (2019)

Abstract Proteins are versatile macromolecules that can perform a variety of functions. In the past three decades, they have been commonly used as building blocks to generate a range of biomaterials. Owing to their flexibility, proteins can either be used alone or in combination with other functional molecules. Advances in synthetic and chemical biology have enabled new protein fusions as well as the integration of new functional groups leading to biomaterials with emergent properties. This review discusses protein‐engineered materials from the perspectives of domain‐based designs as well as physical and chemical approaches for crosslinked materials, with special emphasis on the creation of hydrogels. Engineered proteins that organize or template metal ions, bear noncanonical amino acids (NCAAs), and their potential applications, are also reviewed.
Abstract 20117: Exosomes From Hypoxia-Preconditioned Adipose-Derived Stem Cells Play a Novel Pro-Angiogenic Role via Angiogenic MicroRNAs
Authors: Lina Zhao, Takerra Johnson, Ting Kang, Dong Liu
Journal: Circulation (2016)

Adipose-derived stem cells (ASCs) have been reported to be beneficial in therapeutic angiogenesis and myocardial repair. However, as all other stem cells, the application of ASCs in the treatment o...
Abstract 16892: Prenatal Diagnosis Influences Preoperative Status in Neonates With Congenital Heart Disease: an Analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD)
Authors: Michael Quartermain, Kevin D Hill, David J Goldberg, Jeffery J Jacobs, Marshall L Jacobs, Sara K Pasquali, George R Verghese, Amelia Wallace, Ross M Ungerleider
Journal: Circulation (2016)

Background: The early postnatal course for a newborn with critical congenital heart disease (CHD) can be negatively impacted if diagnosis is delayed. Despite this, there continues to be inconsistent evidence regarding the benefits of prenatal diagnosis (PND) in neonates undergoing cardiac surgery. To isolate the impact of a PND on pre-operative morbidity and overcome limitations of previous studies we utilized a large clinical database to assess the effects of PND of CHD on pre-operative status. Methods: Neonates (<30 days) undergoing heart surgery from 2010-2014 and recorded in the STS-CHSD were included. Multivariable logistic regression was used to evaluate association between PND and a composite measure including nine major preoperative risk factors. Covariates were included to adjust for important patient characteristics (e.g., weight-for-age z-score, genetic syndromes, prematurity), case complexity, and center effects. Centers and patients with excess missing data for relevant covariates were exclud...
Abstract 16355: Stroke Public Awareness Campaign are Associated With Improved Ambulance Use for Stroke and Tia in Victoria, Australia
Authors: Janet Bray, Judith Finn, Peter Cameron, Karen Smith, Lahn Straney, Ziad Nehme, Christopher Bladin
Journal: Circulation (2017)

Introduction: International guidelines recommend suspected stroke patients are assessed and transported to hospital by ambulance. Since 2004, the Stroke Foundation have run public awareness campaig...
Prehospital Care of the 13 Hypothermic, Anesthetized Patients in the Thailand Cave Rescue
Authors: Chanrit Lawthaweesawat, Richard Harris, Wutichai Isara, Krit Pongpirul
Journal: New England Journal of Medicine (2019)

Prehospital Management in the Thailand Cave Rescue The dramatic rescue of a youth soccer team from Tham Luang cave in 2018 offered important lessons in the care of patients with hypothermia.
Combined MAPK Pathway and HDAC Inhibition Breaks Melanoma
Authors: David B. Lombard, Tomasz Cierpicki, Jolanta Grembecka
Journal: Cancer Discovery (2019)

Abstract Summary: In this issue, Maertens and colleagues demonstrate that HDAC3 inhibition potentiates the effects of MAPK pathway inhibitors in melanoma, including difficult-to-treat NRAS- and NF1-driven tumors, with MGMT expression serving as a biomarker for responsiveness to the BRAF/MEK/HDAC inhibitor combination. Mechanistically, this triple cocktail suppresses expression of genes involved in DNA repair, leading to enhanced killing of melanoma cells. See related article by Maertens et al., p. 526.
The Importance of Predefined Rules and Prespecified Statistical Analyses
Authors: John P. A. Ioannidis
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
Organs from Hepatitis C Virus–Positive Donors
Authors: Emily A. Blumberg
Journal: New England Journal of Medicine (2019)

Organs that are suitable for donation to the more than 113,000 persons who are waiting for transplants in the United States are in short supply; in 2018, only 36,500 persons received transplants.1 Many potential recipients die before transplantation, and in 2018, a total of 12,225 persons were removed from the waiting list because of death or progressive illness that rendered them too sick to undergo transplantation. Given these dismal outcomes, substantial efforts have been made to find new approaches to expand the pool of donor organs that were previously considered to be unacceptable. This expansion includes the use of organs . . .
Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis
Authors: Nathalie Sermondade, Stéphanie Huberlant, Vanessa Bourhis-Lefebvre, Elisangela Arbo, Vanessa Gallot, Marina Colombani, Thomas Fréour
Journal: Human Reproduction Update (2019)

Obesity is a well-established risk factor for infertility. Consequentially, women living with obesity may require fertility treatment to support them to conceive. Due to evidence suggesting obesity is also linked with poorer outcomes following in vitro fertilisation (IVF), local commissioning guidelines on assisted conception recommend a BMI of <30kg/m
Abstract 18024: Tissue Transglutaminase-Mediated AT1 Receptor Posttranslational Modification Underlies Inflammatory Cytokine-Induced Hypertension and Cardiac Dysfunction
Authors: Chen Liu, Renna Luo, Wei Wang, Zhangzhe Peng, Rodney Kellems, Yang Xia
Journal: Circulation (2017)

Hypertension is a severe cardiovascular complication with elevated inflammation. Encoded by a gene whose transcription is activated by inflammatory cytokines, tissue transglutaminase (TG2) is known to stabilize the angII receptor AT1 and contribute to pathogenesis of preeclampsia. We hypothesize that TG2 is an essential effector of inflammation-induced hypertension and cardiac dysfunction by stabilizing AT1 receptors. To test this, we applied the TG2-specific inhibitor ERW1041E (0.125mg/day) to a hypertension mouse model established by 14-day introduction of inflammatory cytokine LIGHT/TNFSF14 (4ng/day). Hypertensive features including blood pressure increase (PBS=106±4, LIGHT=145±5 vs LIGHT+ERW1041E=105±12mmHg), proteinuria (PBS=0.02±0.01, LIGHT=0.17±0.05 vs LIGHT+ERW1041E=0.03±0.01mg albumin/mg creatinine), AT1-AA production (PBS=1.6±0.3, LIGHT=19.6±3.7 vs LIGHT+ERW1041E=9.4±1.7U/ml), elevation of plasma transglutaminase activity (PBS=3.8±1.1, LIGHT=16.7±0.5 vs LIGHT+ERW1041E=8.7±0.6mU/ml), and echocard...
Impaired Retinal Vessel Dilation Predicts Mortality in End-Stage Renal Disease
Authors: Roman Günthner, Henner Hanssen, Christine Hauser, Susanne Angermann, Georg Lorenz, Stephan Kemmner, Julia Matschkal, Matthias C. Braunisch, Claudius Küchle, Lutz Renders, Philipp Moog, Siegfried Wassertheurer, Marcus Baumann, Hans-Peter Hammes, Christopher C. Mayer, Bernhard Haller, Sarah Stryeck, Tobias Madl, Javier Carbajo-Lozoya, Uwe Heemann, Konstantin Kotliar, Christoph Schmaderer
Journal: Circulation Research (2019)

Rationale : Patients with end-stage renal disease are characterized by increased cardiovascular and all-cause mortality because of advanced remodeling of the macrovascular and microvascular beds. Objective : The aim of this study was to determine whether retinal microvascular function can predict all-cause and cardiovascular mortality in patients with end-stage renal disease. Methods and Results : In the multicenter prospective observational ISAR study (Risk Stratification in End-Stage Renal Disease), data on dynamic retinal vessel analysis were available in a subcohort of 214 dialysis patients (mean age, 62.6±15.0; 32% women). Microvascular dysfunction was quantified by measuring maximum arteriolar dilation and maximum venular dilation (vMax) of retinal vessels in response to flicker light stimulation. During a mean follow-up of 44 months, 55 patients died, including 25 cardiovascular and 30 noncardiovascular fatal events. vMax emerged as a strong independent predictor for all-cause mortality. In the Kaplan-Meier analysis, individuals within the lowest tertile of vMax showed significantly shorter 3-year survival rates than those within the highest tertile (66.9±5.8% versus 92.4±3.3%). Univariate and multivariate hazard ratios for all-cause mortality per SD increase of vMax were 0.62 (0.47–0.82) and 0.65 (0.47–0.91), respectively. Maximum arteriolar dilation and vMax were able to significantly predict nonfatal and fatal cardiovascular events (hazard ratio, 0.74 [0.57–0.97] and 0.78 [0.61–0.99], respectively). Conclusions : Our results provide the first evidence that impaired retinal venular dilation is a strong and independent predictor of all-cause mortality in hemodialyzed end-stage renal disease patients. Dynamic retinal vessel analysis provides added value for prediction of all-cause mortality and may be a novel diagnostic tool to optimize cardiovascular risk stratification in end-stage renal disease and other high-risk cardiovascular cohorts. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01152892.
Conjugated Polymers in Bioelectronics: Addressing the Interface Challenge
Authors: Kristina Fidanovski, Damia Mawad
Journal: Advanced Healthcare Materials (2019)

Abstract Conjugated polymers are the material of choice for organic bioelectronic interfaces as they combine mechanical flexibility with electric and ionic conductivity. Their attractive properties are largely demonstrated in vitro, while the in vivo applications are limited to the coating of inorganic electrodes, where they are used to improve the intimate electronic contact between the device and the tissue. However, there has not been a commensurate rise in the in vivo applications of entirely organic implantable electronic devices based on conjugated polymers. To date, there is no comprehensive understanding of how these devices will interface with real biological systems. With the push toward increasingly thinner and more flexible next generation medical implants, this limitation remains a major detractor in the translation of conjugated polymers toward biological applications. This research news article examines the few reported in vivo studies and attempts to establish why there is such a dearth in the literature.
Exosomal miRNA Cargo as Mediator of Immune Escape Mechanisms in Neuroblastoma
Authors: Thomas D. Schmittgen
Journal: Cancer Research (2019)

Both natural killer (NK) cells and exosomes released from these cells induce tumor cell cytotoxicity by way of the cell killing proteins perforin and granzyme. TGFβ1 protein in the tumor microenvironment generates an immune escape mechanism rendering NK cells inactive. The tumor-suppressive miR-186 that is downregulated in neuroblastoma and in TGFβ-treated NK cells represses oncogenic proteins in neuroblastoma (MYCN and AURKA) and components of the TGFβ pathway. Restoration of miR-186 levels in neuroblastoma through NK cell-derived exosomes or by nanoparticle delivery reduces tumor burden, promotes survival, and restores the cell-killing abilities of NK cells, demonstrating the therapeutic potential of tumor-suppressive miRNAs in neuroblastoma.See related article by Neviani and colleagues; Cancer Res 79(6):1151-64.
Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
Authors: Jakob Wirbel, Paul Theodor Pyl, Ece Kartal, Konrad Zych, Alireza Kashani, Alessio Milanese, Jonas S. Fleck, Anita Y. Voigt, Albert Palleja, Ruby Ponnudurai, Shinichi Sunagawa, Luis Pedro Coelho, Petra Schrotz-King, Emily Vogtmann, Nina Habermann, Emma Niméus, Andrew M. Thomas, Paolo Manghi, Sara Gandini, Davide Serrano, Sayaka Mizutani, Hirotsugu Shiroma, Satoshi Shiba, Tatsuhiro Shibata, Shinichi Yachida, Takuji Yamada, Levi Waldron, Alessio Naccarati, Nicola Segata, Rashmi Sinha, Cornelia M. Ulrich, Hermann Brenner, Manimozhiyan Arumugam, Peer Bork, Georg Zeller
Journal: Nature Medicine (2019)
Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy
Authors: Jeannie Chew, Casey Cook, Tania F. Gendron, Karen Jansen-West, Giulia del Rosso, Lillian M. Daughrity, Monica Castanedes-Casey, Aishe Kurti, Jeannette N. Stankowski, Matthew D. Disney, Jeffrey D. Rothstein, Dennis W. Dickson, John D. Fryer, Yong-Jie Zhang, Leonard Petrucelli
Journal: Molecular Neurodegeneration (2019)

A G4C2 hexanucleotide repeat expansion in the noncoding region of C9orf72 is the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). Putative disease mechanisms underlying c9FTD/ALS include toxicity from sense G4C2 and antisense G2C4 repeat-containing RNA, and from dipeptide repeat (DPR) proteins unconventionally translated from these RNA products. Intracerebroventricular injections with adeno-associated virus (AAV) encoding 2 or 149 G4C2 repeats were performed on postnatal day 0, followed by assessment of behavioral and neuropathological phenotypes. Relative to control mice, gliosis and neurodegeneration accompanied by cognitive and motor deficits were observed in (G4C2)149 mice by 6 months of age. Recapitulating key pathological hallmarks, we also demonstrate that sense and antisense RNA foci, inclusions of poly(GA), poly(GP), poly(GR), poly(PR), and poly(PA) DPR proteins, and inclusions of endogenous phosphorylated TDP-43 (pTDP-43) developed in (G4C2)149 mice but not control (G4C2)2 mice. Notably, proteins that play a role in the regulation of stress granules – RNA-protein assemblies that form in response to translational inhibition and that have been implicated in c9FTD/ALS pathogenesis – were mislocalized in (G4C2)149 mice as early as 3 months of age. Specifically, we observed the abnormal deposition of stress granule components within inclusions immunopositive for poly(GR) and pTDP-43, as well as evidence of nucleocytoplasmic transport defects. Our in vivo model of c9FTD/ALS is the first to robustly recapitulate hallmark features derived from both sense and antisense C9orf72 repeat-associated transcripts complete with neurodegeneration and behavioral impairments. More importantly, the early appearance of persistent pathological stress granules prior to significant pTDP-43 deposition implicates an aberrant stress granule response as a key disease mechanism driving TDP-43 proteinopathy in c9FTD/ALS.
Mutation and gene copy number of KRAS, BRAF, HER2 and PIK3CA in colorectal cancer
Authors: Naoki Okumura, Takao Takahashi, Hiromasa Yamamoto, Mitsuo Sato, Junichi Soh, Eugene Frenkel, Adi Gazdar
Journal: Cancer Research (2008)

1686  Background: Colorectal cancer is a multistep disease requiring various mutations as well as increased gene copy number of several genes for its progression. In colon cancer, Ras-Raf-Mek and PIK3CA-Akt signaling pathways are activated through multiple mechanisms. The aim of this study is to analyze the occurrence of mutations and abnormal gene copy number of KRAS, BRAF, HER2 and PIK3CA that are related to those pathways.  Methods: We analyzed the mutation status of KRAS (codon 12, 13 and 61), BRAF (exon 11 and 15), HER2 (exon 19 and 20) and PIK3CA (exon 9 and 20) in 19 colon cancer cell lines and 171 resected colorectal tumors from patients in the United States (60) and Japan (111). We also examined the same samples for gene copy number using quantitative real time PCR. Gene copy number more than 4.0 in cell lines and 3.5 in clinical samples were considered as increased copy number. For the functional analysis, we established stable knockdown of KRAS and PIK3CA in cell lines (HCT116 and HCT15) that have mutations of both KRAS and PIK3CA. Furthermore, we performed colony formation assay using these cell lines.  Results: We identified mutations of KRAS (52.6%, 42.7%), BRAF (15.7%, 6.4%), HER2 (5.3%, 0%) and PIK3CA (15.7%, 8.2%) in colon cancer cell lines and resected colorectal tumors, respectively. We could not find any mutations in codon 61 of KRAS, exon 11 of BRAF and HER2 in resected tumors. We found that mutations of KRAS and BRAF were mutually exclusive. Two cell lines and 7 resected tumors had mutations in both KRAS and PIK3CA. We detected increased gene copy number of KRAS (36.8%, 9.4%), BRAF (31.6%, 8.8%), HER2 (21.0%, 5.8%) and PIK3CA (31.6%, 1.8%) in cell lines and resected tumors, respectively. Increased gene copy number of all genes was not found in any T1 tumor and only one resected tumor less than 2 cm had increased gene copy number of BRAF. Frequencies of increased copy number of HER2 were 1.7% and 8.1% from the United States and Japan, respectively (P=0.086). High gene copy number more than 10 from resected tumors were found in KRAS (1 of 171) and HER2 (3 of 171) and all of them were located in left colon. Individually knocking down of KRAS and PIK3CA by shRNA expression plasmid resulted in absent expression of phosphorylated Mek and phosphorylated Akt, respectively, and inhibited cell growth of KRAS and PIK3CA mutant cells.  Conclusion: Mutations and increased gene copy number of KRAS, BRAF, HER2 and PIK3CA are present in a subset of colon cancers; especially KRAS and PIK3CA mutations. Knockdown of KRAS or PIK3CA led to inhibition of growth of KRAS or PIK3CA mutant cells, suggesting that KRAS and PIK3CA may be a candidate for targeting therapy in colon cancer.
Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma
Authors: Thomas Martin, Stephen Strickland, Martha Glenn, Eric Charpentier, Hélène Guillemin, Karl Hsu, Joseph Mikhael
Journal: Blood Cancer Journal (2019)

Abstract This phase I dose-escalation/expansion study evaluated isatuximab (anti-CD38 monoclonal antibody) monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Patients progressing on or after standard therapy received intravenous isatuximab (weekly [QW] or every 2 weeks [Q2W]). The primary objective was to determine the maximum tolerated dose (MTD) of isatuximab. Overall, 84 patients received ≥ 1 dose of isatuximab. The MTD was not reached; no cumulative adverse reactions were noted. The most frequent adverse events were infusion reactions (IRs), occurring in 37/73 patients (51%) following introduction of mandatory prophylaxis. IRs were mostly grade 1/2, occurred predominantly during Cycle 1, and led to treatment discontinuation in two patients. CD38 receptor occupancy reached a plateau of 80% with isatuximab 20 mg/kg (highest dose tested) and was associated with clinical response. In patients receiving isatuximab ≥ 10 mg/kg, overall response rate (ORR) was 23.8% (15/63), including one complete response. In high-risk patients treated with isatuximab 10 mg/kg (QW or Q2W), ORR was 16.7% (3/18). Median (range) duration of response at doses ≥ 10 mg/kg was 25 (8–30) weeks among high-risk patients versus 36 (6–85) weeks for other patients. In conclusion, isatuximab demonstrated a manageable safety profile and clinical activity in patients with RRMM.
Supportive interpersonal relationships: a key component to high-performance sport
Authors: Lauren Burns, Juanita Ruth Weissensteiner, Marc Cohen
Journal: British Journal of Sports Medicine (2019)

Social health determinants, including human social connections, are critical to sustain health and well-being1 and are central to elite sporting performance. Athletes live in high-pressure environments, and supportive relationships with coaches, support staff and/or others are vital to both athletic performance and well-being. Our study of World, Olympic and Paralympic champions revealed that while interpersonal relationships are a key contributor to high performance, they are not easily prescribed.2 

Quality relationships can induce positive physiological changes that improve adaption to stress and enhance performance.3 The ability of relationships to mitigate stressful experiences is highlighted by Coan et al who found that access to social resources altered physiological and neuronal responses to a threat or stress.3 This study, which used functional MRI scans to document neuronal responses of women confronted with the threat of electrical shock, found that high-quality relationships reduced threat-related brain activation. This is consistent with research that suggests quality relationships attenuate physiological responses such as cardiovascular arousal, cortisol and glucocorticoid levels, reduce threat-related brain activity and enhance general health and longevity.1 4 

An athlete’s progression and transition from novice to expert is greatly influenced by their social environment including peer interaction and culture.5 Like the general population, athletes have innate needs when it comes to building relationships, and interpersonal relationships can shape developmental experiences and perspectives for either better or worse. The stress associated with the highs and lows of competition, negative chance events (ie, injury, illness and so on), and the typical demands of high-performance sport (travel, funding, juggling a dual-career,6 non-selection, self-perceived poor performance, losses, relegation and the impact of social media) can be alleviated by a strong social scaffold. In contrast, non-accidental violence and maltreatment in sport, which includes psychological (bullying, harassment and ostracism), sexual and physical violence, is more prevalent in elite athletes and …