tbuckley/cabot-search huggingface dataset:
Dendrimer- and copolymer-based nanoparticles for magnetic resonance cancer theranostics
Authors: Sayoni Ray, Zhao Li, Chao-Hsiung Hsu, Lian-Pin Hwang, Ying-Chih Lin, Pi-Tai Chou, Yung-Ya Lin
Journal: Theranostics (2018)

Cancer theranostics is one of the most important approaches for detecting and treating patients at an early stage.To develop such a technique, accurate detection, specific targeting, and controlled delivery are the key components.Various kinds of nanoparticles have been proposed and demonstrated as potential nanovehicles for cancer theranostics.Among them, polymer-like dendrimers and copolymer-based core-shell nanoparticles could potentially be the best possible choices.At present, magnetic resonance imaging (MRI) is widely used for clinical purposes and is generally considered the most convenient and noninvasive imaging modality.Superparamagnetic iron oxide (SPIO) and gadolinium (Gd)-based dendrimers are the major nanostructures that are currently being investigated as nanovehicles for cancer theranostics using MRI.These structures are capable of specific targeting of tumors as well as controlled drug or gene delivery to tumor sites using pH, temperature, or alternating magnetic field (AMF)-controlled mechanisms.Recently, Gd-based pseudo-porous polymer-dendrimer supramolecular nanoparticles have shown 4-fold higher T 1 relaxivity along with highly efficient AMF-guided drug release properties.Core-shell copolymer-based nanovehicles are an equally attractive alternative for designing contrast agents and for delivering anti-cancer drugs.Various copolymer materials could be used as core and shell components to provide biostability, modifiable surface properties, and even adjustable imaging contrast enhancement.Recent advances and challenges in MRI cancer theranostics using dendrimerand copolymer-based nanovehicles have been summarized in this review article, along with new unpublished research results from our laboratories.
Diffuse Large B-Cell Lymphoma Recurring as Neurolymphomatosis on FDG PET/CT
Authors: Rueben Ganeshalingam, Paul Roach, Geoffrey Paul Schembri
Journal: Clinical Nuclear Medicine (2018)

Two patients with diffuse large B-cell lymphoma relapsing as neurolymphomatosis diagnosed on FDG PET/CT are presented. Both patients were treated initially with chemotherapy and had a complete metabolic response. Patient 1 represented with lower-limb pain. An FDG PET/CT demonstrated intense uptake throughout the sciatic nerves bilaterally extending distally with relapse confirmed on biopsy. Patient 2 represented to hospital with worsening mobility, neuropathic pain, and facial asymmetry. An FDG PET/CT demonstrated relapse within the spinal cord, left sciatic nerve, and facial nerve branches. Neurolymphomatosis is an uncommon finding on FDG PET/CT and can be the only site of relapse.
New tick seen in nine US states is an emerging disease threat, warns CDC
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

A new tick that can be a vector for human and animal diseases and which has appeared in nine US states “represents a new and emerging disease threat,” the Centers for Disease Control and Prevention (CDC) has warned.1

The agency said that Haemophysalis longicornis , the Asian or longhorned tick, had been detected in the eastern states of Connecticut, New Jersey, New York, North Carolina, Maryland, Pennsylvania, Virginia, and West Virginia, and in the central state of Arkansas.

“Characterisation of the tick’s biology and ecology are needed, and surveillance efforts should include testing for potential indigenous and exotic pathogens,” it …
Safety and Immunogenicity of Early Bacillus Calmette-Guérin Vaccination in Infants Who Are Preterm and/or Have Low Birth Weights
Authors: Shiraz Badurdeen, Andrew Marshall, Hazel Daish, Mark Hatherill, James A. Berkley
Journal: JAMA Pediatrics (2018)

Bacillus Calmette-Guérin (BCG) vaccination is commonly delayed in infants who are preterm and have low birth weights (LBW) despite the association of early vaccination with better vaccination coverage and potentially nonspecific benefits for survival.To determine the safety, immunogenicity, and protective efficacy against tuberculosis (TB) of BCG vaccination given at or before 7 days after birth vs vaccination more than 7 days after birth among infants who are preterm and/or had LBW.Searches of Medline, Embase, and Global Health databases were conducted from inception until August 8, 2017.Clinical trials, cohort studies, and case-control studies that included infants who were preterm and/or had LBW and reported safety, mortality, immunogenicity, proxies of vaccine take, and/or efficacy against TB.Two authors independently extracted data and assessed the quality of the studies. Data extracted included demographics, covariates, sources of bias, and effect estimates. Meta-analysis was performed using a random-effects model.Safety, mortality, immunogenicity, or other proxies of vaccine take, such as tuberculin skin test (TST) conversion and efficacy against tuberculosis.Forty studies were included in a qualitative synthesis; infants who were preterm (born at 26-37 weeks' gestational age) and/or had LBW (0.69-2.5 kg at birth) were included. The BCG vaccine was administered at or before 7 days to 10 568 clinically stable infants who were preterm and/or had LBW; vaccination was administered to 4310 infants at varying times between 8 days and 12 months after birth. Twenty-one studies reporting safety found no cases of BCG-associated death or systemic disease in 8243 infants. Four studies reported no increase in all-cause mortality for infants who had LBW and who received early BCG vaccination compared with infants who had LBW with later vaccination or BCG-vaccinated infants of normal birth weight. Four studies reported lymphadenitis incidence; combined, these reported 0% to 2.9% incidence of vaccination within 7 days and 0% to 4.2% of vaccination after 7 days. Meta-analysis of 7 studies revealed no differences between early and delayed BCG vaccination for scar formation (n = 515; relative risk [RR], 1.01 [95% CI, 0.95-1.07]) or TST conversion (n = 397; RR, 0.97 [95% CI, 0.84-1.13]). Published data were insufficient to assess immunogenicity or protective efficacy against TB disease.Early BCG vaccination in healthy infants who are preterm and/or had LBW has a similar safety profile, reactogenicity, and TST conversion rate as delayed vaccination. Based on current evidence, early BCG vaccination in stable infants who are preterm and/or have LBW to optimize uptake is warranted.
Nonsurgical, Minimally Invasive, and Surgical Methods in Management of Acute Diverticulitis
Authors: Katerina Wells, James Fleshman
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Response to Immune Checkpoint Antibodies: Not All Responses Are Created Equal
Authors: Justine V. Cohen, Keith T. Flaherty
Journal: Clinical Cancer Research (2018)

Early reports from immunotherapy trials conclude durable responses. Long-term data may indicate otherwise. Better delineation of clinical courses of long-term survivors will accelerate the discovery and application of biomarkers. Two pressing issues among those treated with anti-PD-1/PD-L1 are understanding whether responders can have therapy abbreviated and overcoming resistance in nonresponders.See related article by Gauci et al., p. 946.
A comparison of a broad range of EEG acquisition devices – is there any difference for SSVEP BCIs?
Authors: Rosanne Zerafa, Tracey Camilleri, Owen Falzon, Kenneth P. Camilleri
Journal: Brain-Computer Interfaces (2018)

This study compared the signal quality of six commercially available electroencephalography (EEG) signal acquisition systems in order to evaluate their application in a brain-computer interface (BCI). This is one of the largest studies in terms of subjects and systems focusing on comparing different EEG systems, involving the whole variety in terms of amplifier (research grade, consumer grade), electrode type (gel-based, saline-based, dry, active, passive), transmission technique (wired, wireless), and cost. We established an approach to evaluate the signal quality by means of a steady-state visually evoked potentials (SSVEP) experiment. This demonstrated that although high-end traditional EEG equipment may be the best choice for clinical applications, low-end wireless research grade gel-based EEG systems are comparable in terms of signal quality and therefore may be an effective alternative to BCIs developed for real environments. Other factors, such as end user and application, should also be considered when deciding which EEG system is best suited for a BCI.
Abstract P175: Predictors of Long Term Blood Pressure Variability in Young Adulthood Through Middle Age: The Coronary Artery Risk Development in Young Adults Study
Authors: Yacob Tedla, Yuichiro Yano, Mercedes Carnethon, Philip Greenland, Donald Lloyd-Jones
Journal: Circulation (2018)

Introduction: Long-term blood pressure variability (BPV) refers to fluctuation in BP that occur over weeks, months and years. BPV has been identified as a risk factor for the development of subclinical and clinical cardiovascular events independent of mean BP. However, little is known about the factors associated with long-term BPV. We hypothesized that long-term BPV will vary by demographic, behavioral, anthropometric, lab, and clinical factors. Methods: Using data from the CARDIA study – a longitudinal population based cohort study, we investigated whether baseline demographics (age, sex, race, education); behavioral factors (smoking, alcohol intake, physical activity); anthropometric measures (height, weight, body mass index - BMI); lab markers (total cholesterol, high density lipoprotein cholesterol - HDL-C, low density lipoprotein cholesterol – LDL-C, triglycerides, fasting blood glucose, glomerular filtration rate - GFR); and history of asthma are associated with different indictors of long-term BPV. Variability independent of the mean (VIM) and coefficient of variation (CV) of BP were calculated to quantify within-individual long-term BPV from baseline to visit 9 across 30 years. A least absolute shrinkage and selection operator (lasso) linear regression was used to identify variables that may be associated with long-term BPV and multivariate linear regression models were used to assess magnitude of association. Results: Participants were 3,095 individuals who were not taking antihypertensive medication (mean age 24.6 years, 45.5% male and 56.9% white). Mean VIM was 8.5 mmHg (SD=3.7) for systolic and 7.1 mmHg (SD=3.2) for diastolic BP. Age, sex, race, education, physical activity, alcohol intake, pack-years of smoking, height, weight, triglyceride, LDL-C and asthma were potential correlates of VIM or CV of diastolic BP by the lasso model. In addition to those variables, total cholesterol, HDL-C, fasting glucose, and GFR were potential correlates of VIM or CV of systolic BP. Variables that significantly associated with VIM of systolic BP were: age (years) (β=0.11, p&lt;0.001), white race (β= -0.94, p&lt;0.001), female sex (β=1.36, p&lt;0.001), alcohol intake (drinks/wk) (β=0.01, p=0.001), height (cm) (β= -0.03, p=0.001), and history asthma (β=-0.47, p=0.02). Consistent findings were observed when the outcome was CV of systolic BP. VIM of diastolic BP was also significantly associated with age (β= -0.09, p&lt;0.001) white race (β= -0.47, p=0.26), pack-years (β=0.06, p&lt;0.001), height (cm) (β= -0.03, p&lt;0.001), and history asthma (β=-0.47, p=0.01). The same variables were significantly associated with CV of diastolic BP. Conclusion: Identifying factors associated with long-term BPV can be useful to detect individuals who may be at a greater risk for future higher long-term BPV, which in turn is associated with greater cardiovascular risk.
TRANSPLANTATION OF TUMORS.
Authors: L Loeb
Journal: JAMA (1904)

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
Annals Story Slam - About Believing in Santa
Authors: Laveena Munshi
Journal: Annals of Internal Medicine (2018)

Web Exclusives4 December 2018Annals Story Slam - About Believing in SantaFREELaveena Munshi, MDLaveena Munshi, MDUniversity of Toronto and Mt. Sinai Hospital, Toronto, Ontario, Canada (L.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0032 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - About Believing in Santa "About Believing in Santa," by Laveena Munshi, MD (Duration 6:20)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Toronto and Mt. Sinai Hospital, Toronto, Ontario, Canada (L.M.)Current Author Address: Laveena Munshi, MD; e-mail, Laveena.[email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: SS1 ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Ablation of Cancer Stem Cells by Therapeutic Inhibition of the MDM2–p53 Interaction in Mucoepidermoid Carcinoma
Authors: April Andrews, Kristy Warner, Christie Rodriguez-Ramirez, Alexander T. Pearson, Felipe Nör, Zhaocheng Zhang, Samuel Kerk, Aditi Kulkarni, Joseph I. Helman, J. Chad Brenner, Max S. Wicha, Shaomeng Wang, Jacques E. Nör
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Unique cells characterized by multipotency, self-renewal, and high tumorigenic potential have been recently discovered in mucoepidermoid carcinomas. These cells are defined by high aldehyde dehydrogenase activity and high CD44 expression (ALDHhighCD44high) and function as cancer stem cells (CSC). It has been recently shown that p53 regulates cell differentiation, suggesting that induction of p53 by therapeutic blockade of the MDM2–p53 interaction may constitute a novel strategy to ablate CSCs. Here, we evaluated the effect of a small-molecule inhibitor of MDM2–p53 interaction (MI-773) on the fraction of CSCs in mucoepidermoid carcinoma. Experimental Design: Human mucoepidermoid carcinoma cells (UM-HMC-1,-3A,-3B) were used to assess the effect of MI-773 on cell survival, cell cycle, fraction of CSCs, and expression of p53, p21, MDM2, and Bmi-1 (key regulator of self-renewal). Mice bearing xenograft tumors generated with these mucoepidermoid carcinoma cells were treated with MI-773 to determine the effect of MDM2-p53 inhibition on CSCs in vivo. Results: MDM2 is highly expressed in human mucoepidermoid carcinoma tissues. MI-773 induced expression of p53 and its downstream targets p21 and MDM2, caused G1 cell–cycle arrest, and induced mucoepidermoid carcinoma tumor cell apoptosis in vitro. Importantly, a marked decrease in expression of Bmi-1 and in the fraction of ALDHhighCD44high (CSCs) was caused by MI-773 in vitro and in mice harboring mucoepidermoid carcinoma xenografts. Conclusions: Collectively, these data demonstrate that MI-773 reduces the fraction of CSCs, suggesting that patients with mucoepidermoid carcinoma might benefit from therapeutic inhibition of the MDM2–p53 interaction.
Rho-Associated Coiled-Coil Kinase (ROCK) in Molecular Regulation of Angiogenesis
Authors: Jing Liu, Youichiro Wada, Mari Katsura, Hideto Tozawa, Nicholas Erwin, Carolyn M Kapron, Gang Bao, Ju Liu
Journal: Theranostics (2018)

Identified as a major downstream effector of the small GTPase RhoA, Rho-associated coiled-coil kinase (ROCK) is a versatile regulator of multiple cellular processes. Angiogenesis, the process of generating new capillaries from the pre-existing ones, is required for the development of various diseases such as cancer, diabetes and rheumatoid arthritis. Recently, ROCK has attracted attention for its crucial role in angiogenesis, making it a promising target for new therapeutic approaches. In this review, we summarize recent advances in understanding the role of ROCK signaling in regulating the permeability, migration, proliferation and tubulogenesis of endothelial cells (ECs), as well as its functions in non-ECs which constitute the pro-angiogenic microenvironment. The therapeutic potential of ROCK inhibitors in angiogenesis-related diseases is also discussed.
The germline<i>JAK2</i>GGCC (46/1) haplotype and survival among 414 molecularly-annotated patients with primary myelofibrosis
Authors: Ayalew Tefferi, Terra L. Lasho, Mythri Mudireddy, Christy M. Finke, Curtis A. Hanson, Rhett P. Ketterling, Naseema Gangat, Animesh Pardanani
Journal: American Journal of Hematology (2018)

Abstract JAK2 mutations in myeloproliferative neoplasms (MPNs) are associated with the germline GGCC (46/1) haplotype. In 2010, we reported an association between shortened survival in primary myelofibrosis (PMF) and nullizygosity for the JAK2 46/1 haplotype. In the current study, we have increased the number of informative cases from 130 to 414 (median age 63 years; 63% males), in order to revisit with the phenotypic and prognostic relevance of the JAK2 46/1 haplotype in PMF. JAK2 46/1 haplotype was documented in 69% of the study patients, including 25% in homozygous and 44% in heterozygous state. Driver mutation frequency in patients homozygous/heterozygous/nullizygous for the 46/1 haplotype was 78%/60%/56% JAK2 , 10%/20%/18% type 1‐like CALR , 3%/2%/5% type 2‐like CALR , 4%/8%/7% MPL, and 6%/10%/14% triple‐negative ( P = .02). In univariate analysis, nullizygosity for the JAK2 46/1 haplotype was associated with inferior overall survival (HR 1.5, 95% CI 1.1‐1.9), most pronounced in JAK2 ( P &lt;.001), as opposed to CALR / MPL mutated ( P = .48) or triple‐negative cases ( P = .27). Multivariable analysis that included karyotype, driver mutational status and high‐molecular risk mutations confirmed the independent prognostic contribution of nullizygosity for the 46/1 haplotype ( P = .02; HR 1.4, 95% CI 1.1‐1.8). Nullizygosity for 46/1 also remained significant in the context of the genetically‐inspired GIPSS risk model ( P = .04), but not in the context of the integrated genetics‐clinical MIPSS70+ version 2.0 model ( P = .4). Leukemia‐free survival was not affected by the 46/1 haplotype ( P = .6). The current study confirms the association of nullizygosity for the JAK2 GGCC (46/1) haplotype with inferior survival in JAK2 ‐mutated PMF.
Genetic, Epigenetic, and Immunologic Profiling of MMR-Deficient Relapsed Glioblastoma
Authors: Stefano Indraccolo, Giuseppe Lombardi, Matteo Fassan, Lorenza Pasqualini, Silvia Giunco, Raffaella Marcato, Alessandra Gasparini, Cinzia Candiotto, Silvia Nalio, Pasquale Fiduccia, Giuseppe Nicolò Fanelli, Ardi Pambuku, Alessandro Della Puppa, Domenico D'Avella, Laura Bonaldi, Marina Paola Gardiman, Roberta Bertorelle, Anita De Rossi, Vittorina Zagonel
Journal: Clinical Cancer Research (2018)

In-depth characterization of recurrent glioblastoma (rGBM) might contribute to a better understanding of the mechanisms behind tumor progression and enable rGBM treatment with targeted drugs.Experimental Design: In this study, GBM samples were collected at diagnosis and recurrence from adult patients treated with Stupp protocol. Expression of mismatch repair (MMR) proteins was evaluated by IHC, followed by whole exome sequencing (WES) of tumor samples showing loss of MSH6 reactivity. Established genetic, epigenetic, and immunologic markers were assessed by standard methods and correlated with loss of MMR proteins and patient survival.Expression of MMR proteins was partially or completely lost in 25.9% rGBM samples. Specifically, 12 samples showed partial or total MSH6 expression reduction. Conversely, 96.4% of GBM samples at diagnosis expressed MMR markers. WES disclosed lack of variants in MMR genes in primary samples, whereas two MSH6-negative rGBM samples shared a c.3438+1G>A* splicing MSH6 variant with a potential loss of function effect. MSH6-negative rGBM specimens had high tumor mutational burden (TMB), but no microsatellite instability. In contrast, GBM samples with partial loss of MMR proteins disclosed low TMB. MMR-deficient rGBM showed significant telomere shortening and MGMT methylation and are characterized by highly heterogeneous MHC class I expression.Multilevel profiling of MMR-deficient rGBM uncovered hypermutated genotype uncoupled from enriched expression of immune-related markers. Assessment of MHC class I expression and TMB should be included in protocols aiming to identify rGBM patients potentially eligible for treatment with drugs targeting immune-checkpoint inhibitors.