tbuckley/cabot-search huggingface dataset:
Micelles: Multifunctional Polymeric Micelles for Combining Chelation and Detection of Iron in Living Cells (Adv. Healthcare Mater. 17/2017)
Authors: Zhi Liu, Max Purro, Jing Qiao, May P. Xiong
Journal: Advanced Healthcare Materials (2017)

May P. Xiong and co-workers construct multifunctional Pluronics F127 micelles for iron chelation and fluorescence detection by introducing tetraphenylethene and the chelating drug deferoxamine into self-assembling polymeric micelles in article 1700162. Deferoxamine can simultaneously be used to chelate iron(III) and quench the fluorescence emission of tetraphenylethene. This fluorescence “turn-off” process can be used to monitor the iron chelation process in an iron overload cell model.
Zinc-finger domains in metazoans: evolution gone wild
Authors: M. Mar Albà
Journal: Genome biology (2017)

A new study uncovers a potential mechanism that may allow zinc-finger domains in metazoans to recognize and bind virtually any DNA sequence.The human genome encodes about 700 proteins with Cys2-His2 zinc finger (C2H2-ZF) domains, the majority of which are likely to bind to DNA and regulate transcription.This makes C2H2-ZF the largest transcription factor (TF) family in our species [1], and the same is true in many other metazoans.By contrast, the genomes of more distant species, such as fungi and plants, encode a much more limited number of C2H2-ZFs.A combination of evolutionary processes has resulted in a diverse range of C2H2-ZF proteins that show affinity for different DNA targets in metazoans [2].In fact, human zinc-fingers may recognize a larger number of DNA sequences than all other human TFs combined [3].This implies that zinc-fingers can potentially impact many diverse cellular processes.C2H2-ZF domains are short sequences that contain a beta-hairpin and an alpha-helix stabilized by a zinc ion, with only two cysteines and two histidines that are invariable.The rest of the amino acids can have almost any identity.Structural studies have shown that there are four positions in the alpha-helix that make direct contact with three or four bases in the DNA.In a recent study published in Genome Biology, Najafabadi and colleagues [4] revealed why the C2H2-ZF protein domain is so frequent and diverse in metazoans but not in other eukaryotes, and how it is able to recognize so many different DNA targets, considering that only four residues directly contact the bases in DNA.By analyzing experimental data for thousands of zincfinger domain sequences, they discovered that it is the contribution of residues that do not make direct contact with the bases that does the trick.
Arsenic and Obesity: A Comparison of Urine Dilution Adjustment Methods
Authors: Catherine M. Bulka, Sithembile L. Mabila, James P. Lash, Mary E. Turyk, Maria Argos
Journal: Environmental Health Perspectives (2017)

Introduction: A commonly used approach to adjust for urine dilution in analyses of biomarkers is to adjust for urinary creatinine. However, creatinine is a product of muscle mass and is therefore associated with body mass. In studies of urinary analytes and obesity or obesity-related outcomes, controlling for creatinine could induce collider stratification bias. We illustrate this phenomenon with an analysis of urinary arsenic. Objective: We aimed to evaluate various approaches of adjustment for urinary dilution on the associations between urinary arsenic concentration and measures of obesity. Methods: Using data from the National Health and Nutrition Examination Survey, we regressed body mass index (BMI) and waist-to-height ratios on urinary arsenic concentrations. We compared eight approaches to account for urine dilution, including standardization by urinary creatinine, osmolality, and flow rates, and inclusion of these metrics as independent covariates. We also used a recently proposed method known as covariate-adjusted standardization. Results: Inverse associations between urinary arsenic concentration with BMI and waist-to-height ratio were observed when either creatinine or osmolality were used to standardize or as covariates. Not adjusting for dilution, standardizing or adjusting for urinary flow rate, and using covariate-adjusted standardization resulted in null associations observed between arsenic concentration in relation to BMI and waist-to-height ratio. Conclusions: Our findings suggest that arsenic exposure is not associated with obesity, and that urinary creatinine and osmolality may be colliders on the causal pathway from arsenic exposure to obesity, as common descendants of hydration and body composition. In studies of urinary biomarkers and obesity or obesity-related outcomes, alternative metrics such as urinary flow rate or analytic strategies such as covariate-adjusted standardization should be considered. https://doi.org/10.1289/EHP1202
NCCN Guidelines Insights: Acute Lymphoblastic Leukemia, Version 1.2017
Authors: Patrick A. Brown, Bijal Shah, Amir Fathi, Matthew Wieduwilt, Anjali Advani, Patricia Aoun, Stefan K. Barta, Michael W. Boyer, Teresa Bryan, Patrick W. Burke, Ryan Cassaday, Peter F. Coccia, Steven E. Coutre, Lloyd E. Damon, Daniel J. DeAngelo, Olga Frankfurt, John P. Greer, Hagop M. Kantarjian, Rebecca B. Klisovic, Gary Kupfer, Mark Litzow, Arthur Liu, Ryan Mattison, Jae Park, Jeffrey Rubnitz, Ayman Saad, Geoffrey L. Uy, Eunice S. Wang, Kristina M. Gregory, Ndiya Ogba
Journal: Journal of the National Comprehensive Cancer Network (2017)

The prognosis for patients with newly diagnosed acute lymphoblastic leukemia (ALL) has improved with the use of more intensive chemotherapy regimens, tyrosine kinase inhibitors, targeted agents, and allogeneic hematopoietic cell transplantation. However, the management of relapsed or refractory (R/R) ALL remains challenging and prognosis is poor. The NCCN Guidelines for ALL provide recommendations on standard treatment approaches based on current evidence. These NCCN Guidelines Insights summarize treatment recommendations for R/R ALL and highlight important updates, and provide a summary of the panel's discussion and underlying data supporting the most recent recommendations for R/R ALL management.
Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart
Authors: Michael Rubart, Wen Tao, Xiao-Long Lu, Simon J Conway, Sean P Reuter, Shien-Fong Lin, Mark H Soonpaa
Journal: Cardiovascular Research (2017)

Recent studies have demonstrated electrotonic coupling between scar tissue and the surrounding myocardium in cryoinjured hearts. However, the electrical dynamics occurring at the myocyte-nonmyocyte interface in the fibrotic heart remain undefined. Here, we sought to develop an assay to interrogate the nonmyocyte cell type contributing to heterocellular coupling and to characterize, on a cellular scale, its voltage response in the infarct border zone of living hearts.We used two-photon laser scanning microscopy in conjunction with a voltage-sensitive dye to record transmembrane voltage changes simultaneously from cardiomyocytes and adjoined nonmyocytes in Langendorff-perfused mouse hearts with healing myocardial infarction. Transgenic mice with cardiomyocyte-restricted expression of a green fluorescent reporter protein underwent permanent coronary artery ligation and their hearts were subjected to voltage imaging 7-10 days later. Reporter-negative cells, i.e. nonmyocytes, in the infarct border zone exhibited depolarizing transients at a 1:1 coupling ratio with action potentials recorded simultaneously from adjacent, reporter-positive ventricular myocytes. The electrotonic responses in the nonmyocytes exhibited slower rates of de- and repolarization compared to the action potential waveform of juxtaposed myocytes. Voltage imaging in infarcted hearts expressing a fluorescent reporter specifically in myofibroblasts revealed that the latter were electrically coupled to border zone myocytes. Their voltage transient properties were indistinguishable from those of nonmyocytes in hearts with cardiomyocyte-restricted reporter expression. The density of connexin43 expression at myofibroblast-cardiomyocyte junctions was ∼5% of that in the intercalated disc regions of paired ventricular myocytes in the remote, uninjured myocardium, whereas the ratio of connexin45 to connexin43 expression levels at heterocellular contacts was ∼1%.Myofibroblasts contribute to the population of electrically coupled nonmyocytes in the infarct border zone. The slower kinetics of myofibroblast voltage responses may reflect low electrical conductivity across heterocellular junctions, in accordance with the paucity of connexin expression at myofibroblast-cardiomyocyte contacts.
What priorities should be considered for Iranian veterans with ankle-foot injuries? A health needs assessment study, 25 years post-conflict
Authors: Mostafa Allami, Mohammadreza Soroush
Journal: Military Medical Research (2017)

Despite the passage of time, a large number of veterans are still affected by injuries acquired during Iran-Iraq war. In addition to their primary injuries, the majority of veterans also experience difficulty with long-term, secondary effects. Studies have shown that the most common of these include a range of disabilities, pain, and dramatic decline in mental health and quality of life. Improving living conditions and providing rehabilitation services to veterans has always been a main priority of authorities. The goal of this study was to explain the methods and materials with which these priorities were explored.
Adefovir-induced Fanconi syndrome associated with osteomalacia
Authors: Samel Park, Woo-Il Kim, Dai-Hyun Cho, Yeo-Joo Kim, Hong-Soo Kim, Ji-Hee Kim, Seung-Kuy Cha, Kyu-Sang Park, Ji-Hye Lee, Sang Mi Lee, Eun Young Lee
Journal: Clinical and Molecular Hepatology (2017)

Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia. Keywords: Adefovir; Fanconi syndrome; Mitochondria; Proximal tubules; Osteomalacia
Missed therapeutic and prevention opportunities in women with BRCA‐mutated epithelial ovarian cancer and their families due to low referral rates for genetic counseling and BRCA testing: A review of the literature
Authors: Paul J. Hoskins, Walter H. Gotlieb
Journal: CA A Cancer Journal for Clinicians (2017)

Abstract Answer questions and earn CME/CNE Fifteen percent of women with epithelial ovarian cancer have inherited mutations in the BRCA breast cancer susceptibility genes. Knowledge of her BRCA status has value both for the woman and for her family. A therapeutic benefit exists for the woman with cancer, because a new family of oral drugs, the poly ADP‐ribose polymerase (PARP) inhibitors, has recently been approved, and these drugs have the greatest efficacy in women who carry the mutation. For her family, there is the potential to prevent ovarian cancer in those carrying the mutation by using risk‐reducing surgery. Such surgery significantly reduces the chance of developing this, for the most part, incurable cancer. Despite these potential benefits, referral rates for genetic counseling and subsequent BRCA testing are low, ranging from 10% to 30%, indicating that these therapeutic and prevention opportunities are being missed. The authors have reviewed the relevant available literature. Topics discussed are BRCA and its relation to ovarian cancer, the rates of referral for genetic counseling/ BRCA testing, reasons for these low rates, potential strategies to improve on those rates, lack of effectiveness of current screening strategies, the pros and cons of risk‐reducing surgery, other prevention options, and the role and value of PARP inhibitors. CA Cancer J Clin 2017;67:493‐506. © 2017 American Cancer Society.
Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas
Authors: De-Chen Lin, Huy Q Dinh, Jian-Jun Xie, Anand Mayakonda, Tiago Chedraoui Silva, Yan-Yi Jiang, Ling-Wen Ding, Jian-Zhong He, Xiu-E Xu, Jia-Jie Hao, Ming-Rong Wang, Chunquan Li, Li-Yan Xu, En-Min Li, Benjamin P Berman, H Phillip Koeffler
Journal: Gut (2017)

Oesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) are distinct cancers in terms of a number of clinical and epidemiological characteristics, complicating the design of clinical trials and biomarker developments. We analysed 1048 oesophageal tumour-germline pairs from both subtypes, to characterise their genomic features, and biological and clinical significance.
Effect of high-dose corticosteroids on CD4+ or CD8+ lymphocyte proliferation or IL-2 production after stimulation with pembrolizumab.
Authors: John WT Walker, Lai Xu, Michael Smylie, Shokrollah Elahi
Journal: Journal of Clinical Oncology (2017)

e14587 Background: Immune checkpoint inhibitor (ICI) therapy has improved survival of patients with melanoma and other types of cancers. The effect of immunosuppresive corticosteroids on ICI efficacy is unknown, however treatment of immune-related adverse events with high-dose steroid therapy impairs neither efficacy nor time to failure of ICI. In certain clinical circumstances (for instance in the treatment of patients with symptomatic brain metastases) it may be advantageous to begin ICI therapy despite a requirement for steroid therapy. This study examined the effect of high-dose steroid therapy on lymphocyte proliferation/functionality after stimulation with anti-CD3 in the presence of pembrolizumab (PD-1 inhibitor) ex vivo. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from patients with either chronic hepatitis C infection or active malignant melanoma. CD4+ and CD8+ T cells were isolated and subjected to flow cytometry stating for the expression of PD-1. Isolated PBMCs were then pre-treated with prednisone (1 nM - 1 mM) before anti-CD3 stimulation. Anti-CD3-stimulated cells were then incubated with pembrolizumab (5 µg/mL) and their proliferative capacity and IL-2 secretion ability were measured by carboxyfluorescein succinimidyl ester (CFSE) staining and ELISA, respectively. Results: A dose-dependent inhibition of both lymphocyte proliferation and IL-2 production was observed, but at physiologically relevant nanomolar prednisone concentration the steroid effect was negligible. Millimolar prednisone concentrations resulted in &gt; 50% relative reduction in lymphocyte proliferation, however even at this steroid concentration treatment with pembrolizumab was able to further stimulate proliferation and IL-2 secretion versus anti-CD 3 stimulation alone. Conclusions: Despite heavily immunosuppressive treatment, CD 4+ and CD 8+ lymphocytes demonstrate proliferative capacity and immunological activity following treatment with pembrolizumab. This suggests that treatment with pembrolizumab may be efficacious despite a requirement for steroid therapy, a scenario often encountered in patients with brain metastases.
FRI0323 Comparison of biopsy proven giant cell arteritis in north america and southern europe: a population-based study
Authors: F Muratore, CS Crowson, L Boiardi, MJ Koster, G Restuccia, TA Kermani, EL Matteson, C Salvarani, KJ Warrington
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To compare clinical characteristics, treatment, long-term follow-up and prognosis of two population-based cohorts of patients with biopsy-proven giant cell arteritis (GCA) from Olmsted County, Minnesota, USA (Olmsted cohort) and the Reggio Emilia area, Northern Italy (Reggio cohort). <h3>Methods</h3> All patients residing in Olmsted County and the Reggio Emilia area with a new diagnosis of biopsy-proven GCA in 1986–2007 were retrospectively identified. Patients were followed from GCA diagnosis to death, migration or September 2011. Comparisons were performed using Chi-square and rank sum tests, Kaplan-Meier methods and Cox models. <h3>Results</h3> The study included 110 patients in the Olmsted and 144 in the Reggio cohort. Compared with the Olmsted cohort, patients from the Reggio cohort were younger (mean±SD age 74.6±7.4 years vs 77.8±7.6, p=0.002), more likely to have cranial symptoms (93% vs 86%, p=0.048), temporal artery abnormalities at physical examination (68% vs 42%, p&lt;0.001), partial or complete unilateral or bilateral permanent vision loss (21% vs 6%, p=0.001), systemic symptoms (67% vs 46%, p=0.001) and polymyalgia rheumatica at or before GCA diagnosis (47% vs 26%, p&lt;0.001). Scalp tenderness was less common in the Reggio cohort (36% vs 49%, p=0.033). ESR and CRP were higher (mean 88±29 mm/h vs 73±77, p&lt;0.001 and mean 89.0±60.2 mg/L vs 35.2±43.4, p&lt;0.001 respectively) and hemoglobin lower (mean 11.2±1.4 g/dl vs 11.8±1.4, p=0.004) in Reggio than in the Olmsted cohort. Patients from the Olmsted cohort received a higher initial prednisone dose (mean 53.6±15.3 mg/day vs 49.5±12.8, p=0.001). There were no differences in relapse rates, cumulative glucocorticoid (GC) dosages at 1, 2 and 5 years, and time to first GC discontinuation. However, the Reggio cohort reached a prednisone dose &lt;10 mg/day sooner (median 4.9 months vs 7.9, p=0.012) and had a first relapse later (median 13.6 months vs 7.9, p=0.003) than the Olmsted cohort. Patients from the Reggio cohort had a significantly higher mortality compared to those from the Olmsted cohort (HR 1.72, 95% CI 1.12–2.65 adjusted for age and sex). <h3>Conclusions</h3> Genetic and/or environmental factors may contribute to the differences in clinical characteristics and disease outcomes observed in this study comparing patients with GCA from North America and Southern Europe. <h3>Disclosure of Interest</h3> None declared
Preparation of glutinous rice starch/polyvinyl alcohol copolymer electrospun fibers for using as a drug delivery carrier
Authors: Patthanakorn Jaiturong, Busaban Sirithunyalug, Sukum Eitsayeam, Chawalinee Asawahame, Pratchaya Tipduangta, Jakkapan Sirithunyalug
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Glutinous rice starch (GRS) is commonly produced in the Northeast of Thailand. GRS is a biopolymer which is widely used in the food industry but not yet commonly applied within the pharmaceutical industry as an alternative resource. GRS exhibits a branch chain structure which is not feasible to fabricate as nanofiber. Therefore, combining GRS with polyvinyl alcohol (PVA) in hybrid form can be a potential platform to produce GRS-PVA nanofibers. Smooth nanofibers of 2% (w/v) GRS combined with 8% (w/v) PVA were fabricated by an electrospinning process. A scanning electron microscope (SEM) revealed an average diameter size of the GRS-PVA nanofibers equal to 191 ± 25 nm. A highly water soluble model drug, Chlorpheniramine maleate (CPM), was incorporated into the GRS-PVA electrospun fibers to prove a drug delivery carrier concept and drug release control of the nanofibers. The GRS-PVA nanofibers exhibited a biphasic CPM release in which approximately 60% of the drug immediately released in 10 min, and it reached 90% drug release in 120 min. This study demonstrated a potential application of GRS combining with PVA as an oral drug delivery carrier. Therefore, it can be a promised step that expands the application GRS in pharmaceuticals and related areas.
Types of Shade Vary in Protection Just Like Sunscreens—Reply
Authors: Hao Ou-Yang, Aaron S. Farberg, Darrell S. Rigel
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
Secondary Mitral Regurgitation and Survival in Patients With Left Ventricular Dysfunction
Authors: Robert O. Bonow, Patrick T. O’Gara
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal