tbuckley/cabot-search huggingface dataset:
Advances in Controlling Differentiation of Adult Stem Cells for Peripheral Nerve Regeneration
Authors: Metin Uz, Suprem R. Das, Shaowei Ding, Donald S. Sakaguchi, Jonathan C. Claussen, Surya K. Mallapragada
Journal: Advanced Healthcare Materials (2018)

Adult stems cells, possessing the ability to grow, migrate, proliferate, and transdifferentiate into various specific phenotypes, constitute a great asset for peripheral nerve regeneration. Adult stem cells' ability to undergo transdifferentiation is sensitive to various cell-to-cell interactions and external stimuli involving interactions with physical, mechanical, and chemical cues within their microenvironment. Various studies have employed different techniques for transdifferentiating adult stem cells from distinct sources into specific lineages (e.g., glial cells and neurons). These techniques include chemical and/or electrical induction as well as cell-to-cell interactions via co-culture along with the use of various 3D conduit/scaffold designs. Such scaffolds consist of unique materials that possess controllable physical/mechanical properties mimicking cells' natural extracellular matrix. However, current limitations regarding non-scalable transdifferentiation protocols, fate commitment of transdifferentiated stem cells, and conduit/scaffold design have required new strategies for effective stem cells transdifferentiation and implantation. In this progress report, a comprehensive review of recent advances in the transdifferentiation of adult stem cells via different approaches along with multifunctional conduit/scaffolds designs is presented for peripheral nerve regeneration. Potential cellular mechanisms and signaling pathways associated with differentiation are also included. The discussion with current challenges in the field and an outlook toward future research directions is concluded.
Rising infant mortality rates in England and Wales—we need to understand gestation specific mortality
Authors: Peter J Davis, Alan C Fenton, Christopher J Stutchfield, Elizabeth S Draper
Journal: BMJ (2018)

The BMJ has covered the many legitimate concerns regarding the state of child health in the United Kingdom,12 but the reported rise in infant mortality rates from 2015 onwards3 requires a more detailed analysis before being included in this overall picture.

Infant mortality rates are calculated by combining neonatal (0 to 28 days) and postneonatal (4 weeks to 1 year) mortality rates. The …
2-Arachidonoylglycerol: A signaling lipid with manifold actions in the brain
Authors: Marc P. Baggelaar, Mauro Maccarrone, Mario van der Stelt
Journal: Progress in Lipid Research (2018)

2-Arachidonoylglycerol (2-AG) is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that activates the cannabinoid CB1 receptor. It is involved in a wide array of (patho)physiological functions, such as emotion, cognition, energy balance, pain sensation and neuroinflammation. In this review, we describe the biosynthetic and metabolic pathways of 2-AG and how chemical and genetic perturbation of these pathways has led to insight in the biological role of this signaling lipid. Finally, we discuss the potential therapeutic benefits of modulating 2-AG levels in the brain.
Precision Profiling of the Cardiovascular Post-Translationally Modified Proteome
Authors: Justyna Fert-Bober, Christopher I. Murray, Sarah J. Parker, Jennifer E. Van Eyk
Journal: Circulation Research (2018)

There is an exponential increase in biological complexity as initial gene transcripts are spliced, translated into amino acid sequence, and post-translationally modified. Each protein can exist as multiple chemical or sequence-specific proteoforms, and each has the potential to be a critical mediator of a physiological or pathophysiological signaling cascade. Here, we provide an overview of how different proteoforms come about in biological systems and how they are most commonly measured using mass spectrometry-based proteomics and bioinformatics. Our goal is to present this information at a level accessible to every scientist interested in mass spectrometry and its application to proteome profiling. We will specifically discuss recent data linking various protein post-translational modifications to cardiovascular disease and conclude with a discussion for enablement and democratization of proteomics across the cardiovascular and scientific community. The aim is to inform and inspire the readership to explore a larger breadth of proteoform, particularity post-translational modifications, related to their particular areas of expertise in cardiovascular physiology.
Combining precision radiotherapy with molecular targeting and immunomodulatory agents: a guideline by the American Society for Radiation Oncology
Authors: Robert G Bristow, Brian Alexander, Michael Baumann, Scott V Bratman, J Martin Brown, Kevin Camphausen, Peter Choyke, Deborah Citrin, Joseph N Contessa, Adam Dicker, David G Kirsch, Mechthild Krause, Quynh-Thu Le, Michael Milosevic, Zachary S Morris, Jann N Sarkaria, Paul M Sondel, Phuoc T Tran, George D Wilson, Henning Willers, Rebecca K S Wong, Paul M Harari
Journal: The Lancet Oncology (2018)
<i>Notes from the Field:</i><i>Salmonella</i> Oranienburg Infection Linked to Consumption of Rattlesnake Pills — Kansas and Texas, 2017
Authors: Lyndsay Bottichio, Lindsey Martin Webb, Greg Leos, Beth Tolar, Natasha Dowell, Colin Basler
Journal: MMWR Morbidity and Mortality Weekly Report (2018)
P257Duchenne muscular dystrophy leads to compromised genomic stability in stem cells and depletion of cardiac progenitors in failing heart
Authors: S Jelinkova, P Fojtik, A Kohutova, A Finan-Marchi, Y Sleiman, F Aimond, A Vilotic, G Carnac, A Meli, V Rotrekl
Journal: Cardiovascular Research (2018)

Background/Introduction: Telomeres are dynamic chromosome-end structures that protect DNA in our genome from deterioration.Throughout life, telomere lengths (TLs) become shorter, and the rate of this process has been associated with lifestyle and the onset of age-related diseases.Moreover, the aging-associated factor growth differentiation factor 11 (GDF11) has been suggested as a rejuvenating factor.Together, the interplay of these aspects that possibly modulate the aging process is of interest to explore.Purpose: To investigate the associations between leukocyte TLs (LTLs) and chronological age, comorbidities and clinical outcome in patients with coronary artery disease (CAD).Potential covariations between LTL and GDF11 were further assessed.Methods: 300 patients with stable CAD, 20% female, age range 36-81 yrs, were included.Within 2 years, a composite of new clinical events (unstable angina pectoris, myocardial infarction (MI), stroke and deaths) was recorded.DNA and RNA were isolated from whole blood for the analysis of LTLs and GDF11 gene expression, respectively.LTLs were measured by PCR using telomerespecific primers and determined relatively to a single copy gene (36B4).The amount of GDF11 was measured as relative quantification using PCR and the house-keeping gene b2M.Results: We observed that patients with previously suffered MI presented with 20% shorter LTLs vs. patients without (p ¼ 0.015), however, only in men (p ¼ 0.009, n ¼ 115).To further explore this association, LTLs were divided into quartiles (Qs) and further dichotomized at the distinctive cut-off level between Q3 and Q4.LTLs in the upper Q were associated with 60% lower frequency of having suffered a previous MI (p ¼ 0.008, adjusted for age, treated hypertension, body mass index (BMI), triglycerides, HDL and fasting glucose).LTLs were not differently distributed according to sex or the presence of treated hypertension (52%), diabetes type 2 (25%), metabolic syndrome (35%) and clinical outcome (12%).In the total cohort, LTLs were further inversely correlated to age (r ¼ -0.17, p ¼ 0.007), however, only in women (r ¼ -0.37, p ¼ 0.006).In all subjects, GDF11 gene-expression was weakly and inversely correlated to age (r ¼ -0.16, p ¼ 0.010).Overall, no correlation was observed between LTLs and gene-expression of GDF11.However, when dividing into subgroups, a strong correlation was observed in overweight women (BMI > 25), (r ¼ 0.40, p ¼ 0.028).Conclusions: Although no association between LTLs and clinical outcome was observed, LTLs correlated to the severity of CAD in men, in this case previously suffered MI.In women, LTLs seem to be more associated with age.The results may indicate gender-related differences in regulatory mechanisms of TLs and a possible metabolically influenced association between LTLs and GDF11.
In older patients with UTIs, trimethoprim vs amoxicillin was linked to higher risk for AKI at 14 d
Authors: Monica Guzman-Limon, Donald Molony
Journal: Annals of Internal Medicine (2018)

ACP Journal Club15 May 2018In older patients with UTIs, trimethoprim vs amoxicillin was linked to higher risk for AKI at 14 dMonica Guzman-Limon, MD, Donald Molony, MDMonica Guzman-Limon, MDMcGovern Medical School, University of Texas HSC Houston, Houston, Texas, USA (M.G., D.M.)Search for more papers by this author, Donald Molony, MDMcGovern Medical School, University of Texas HSC Houston, Houston, Texas, USA (M.G., D.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-168-10-058 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationCrellin E, Mansfield KE, Leyrat C, et al. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study. BMJ. 2018;360:k341. https://pubmed.ncbi.nlm.nih.gov/29438980Clinical Impact RatingsGIM/FP/GP: Geriatrics: Nephrology: References1 Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int. 2012;81:442-8. [PMID: 22113526] Google Scholar2 Bird ST, Etminan M, Brophy JM, Hartzema AG, Delaney JA. Risk of acute kidney injury associated with the use of fluoroquinolones. CMAJ. 2013;185:E475-82. [PMID: 23734036] Google Scholar3 Rowe TA, Juthani-Mehta M. Diagnosis and management of urinary tract infection in older adults. Infect Dis Clin North Am. 2014;28:75-89. [PMID: 24484576] Google Scholar Author, Article, and Disclosure InformationAffiliations: McGovern Medical School, University of Texas HSC Houston, Houston, Texas, USA (M.G., D.M.)This article was published at Annals.org on 1 May 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 2018Volume 168, Issue 10Page: JC58KeywordsAcute kidney injuryAntibioticsCohort studiesDrugsInformation storage and retrievalInternational classification of diseases tenth revisionMortalityRenal diseasesRenal failure ePublished: 15 May 2018 Issue Published: 15 May 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Study of Intraventricular Cerliponase Alfa for CLN2 Disease
Authors: Angela Schulz, Temitayo Ajayi, Nicola Specchio, Emily de Los Reyes, Paul Gissen, Douglas Ballon, Jonathan P. Dyke, Heather Cahan, Peter Slasor, David Jacoby, Alfried Kohlschütter
Journal: New England Journal of Medicine (2018)

Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.
Efficacy and Safety of Peginterferon Alfa‐2a (40KD) in Children With Chronic Hepatitis B: The PEG‐B‐ACTIVE Study
Authors: Stefan Wirth, Hongfei Zhang, Winita Hardikar, Kathleen B. Schwarz, Etienne Sokal, Weibo Yang, Huimin Fan, Vyacheslav Morozov, Qing Mao, Hong Deng, Yang Huang, Lei Yang, Nicolas Frey, Clare Nasmyth‐Miller, Vedran Pavlovic, Cynthia Wat
Journal: Hepatology (2018)

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 μg/1.73 m2 . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.
TCTAP A-077 Prognostic Significance of Extracellular Volume Evaluated by Cardiac Magnetic Resonance Imaging for Patients with Acute Myocardial Infarction
Authors: Masaki Ishiyama, Tairo Kurita, Kaoru Dohi, Taku Omori, Naoki Fujimoto, Masaki Ishida, Kakuya Kitagawa, Hajime Sakuma, Masaaki Ito
Journal: Journal of the American College of Cardiology (2018)
Another Nail in the Coffin for Fish Oil Supplements
Authors: Jennifer Abbasi
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of Uterosacral Ligament Suspension vs Sacrospinous Ligament Fixation With or Without Perioperative Behavioral Therapy for Pelvic Organ Vaginal Prolapse on Surgical Outcomes and Prolapse Symptoms at 5 Years in the OPTIMAL Randomized Clinical Trial
Authors: J. Eric Jelovsek, Matthew D. Barber, Linda Brubaker, Peggy Norton, Marie Gantz, Holly E. Richter, Alison Weidner, Shawn Menefee, Joseph Schaffer, Norma Pugh, Susan Meikle
Journal: JAMA (2018)

<h3>Importance</h3> Uterosacral ligament suspension (ULS) and sacrospinous ligament fixation (SSLF) are commonly performed pelvic organ prolapse procedures despite a lack of long-term efficacy data. <h3>Objective</h3> To compare outcomes in women randomized to (1) ULS or SSLF and (2) usual care or perioperative behavioral therapy and pelvic floor muscle training (BPMT) for vaginal apical prolapse. <h3>Design, Setting, and Participants</h3> This 2 × 2 factorial randomized clinical trial was conducted at 9 US medical centers. Eligible participants who completed the Operations and Pelvic Muscle Training in the Management of Apical Support Loss Trial enrolled between January 2008 and March 2011 and were followed up 5 years after their index surgery from April 2011 through June 2016. <h3>Interventions</h3> Two randomizations: (1) BPMT (n = 186) or usual care (n = 188) and (2) surgical intervention (ULS: n = 188 or SSLF: n = 186). <h3>Main Outcomes and Measures</h3> The primary surgical outcome was time to surgical failure. Surgical failure was defined as (1) apical descent greater than one-third of total vaginal length or anterior or posterior vaginal wall beyond the hymen or retreatment for prolapse (anatomic failure), or (2) bothersome bulge symptoms. The primary behavioral outcomes were time to anatomic failure and Pelvic Organ Prolapse Distress Inventory scores (range, 0-300). <h3>Results</h3> The original study randomized 374 patients, of whom 309 were eligible for this extended trial. For this study, 285 enrolled (mean age, 57.2 years), of whom 244 (86%) completed the extended trial. By year 5, the estimated surgical failure rate was 61.5% in the ULS group and 70.3% in the SSLF group (adjusted difference, −8.8% [95% CI, −24.2 to 6.6]). The estimated anatomic failure rate was 45.6% in the BPMT group and 47.2% in the usual care group (adjusted difference, −1.6% [95% CI, −21.2 to 17.9]). Improvements in Pelvic Organ Prolapse Distress Inventory scores were −59.4 in the BPMT group and −61.8 in the usual care group (adjusted mean difference, 2.4 [95% CI, −13.7 to 18.4]). <h3>Conclusions and Relevance</h3> Among women who had undergone vaginal surgery for apical pelvic organ vaginal prolapse, there was no significant difference between ULS and SSLF in rates of surgical failure and no significant difference between perioperative behavioral muscle training and usual care on rates of anatomic success and symptom scores at 5 years. Compared with outcomes at 2 years, rates of surgical failure increased during the follow-up period, although prolapse symptom scores remained improved. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01166373
Endoscopic Killian–Jamieson diverticulotomy using a scissor-type electrosurgical knife
Authors: Dennis Yang, Peter Draganov
Journal: Endoscopy (2018)

Killian–Jamieson diverticulum (KJD) is a rare, true esophageal diverticulum. Unlike the more common Zenker's diverticulum that arises on the posterior wall above the cricopharyngeus muscle, a KJD originates on the anterolateral wall of the cervical esophagus below the cricopharyngeal muscle [1]. The literature on endoscopic therapy for symptomatic KJD is limited [2] [3] [4].
A phase 1/2, randomized, placebo controlled and open label extension studies of Givosiran and investigational RNA interference therapeutic, in patients with acute intermittent porphyria
Authors: E. Sardh, M. Balwani, P. Harper, P. Stein, D. Rees, J. Bloomer, D.M. Bissell, C. Parket, J. Phillips, H. Bonkovsky, R. Desnick, N. Al-Tawil, S. Rock, C. Penz, A. Chan, W. Querbes, A. Simon, K. Anderson
Journal: Journal of Hepatology (2018)
Prevalence and predictive factors of hepatic nodules in patients with fontan surgery: the VALDIG fonliver study
Authors: E. Rodríguez-Santiago, L. Téllez, E. Garrido, A. Baiges, V.L. Mura, E. Garrido-Lestache, R. Romera, J. Martinez, D. Rincón, A. Clemente, L. Aguilera, A. Olavarría, E. Llop, I. Sánchez, F. Gea, M.A. Fuente, D.M.J. del Cerro, R. Bañares, G.P.J. Carlos, A. Albillos
Journal: Journal of Hepatology (2018)
Abstract 20438: Rescuing an Acquired Cardiac Retinoic Acid Deficiency Prevents Hypertrophy and Sudden Cardiac Death in a Pressure-Overload/Chronic Catecholamine Model of Hypertrophy and Heart Failure
Authors: Ni Yang, Ting Liu, Robert O’Meally, Kai Kammers, Djahida Bedja, C. Conover Talbot, Robert N Cole, David A Kass, Maureen Kane, Brian O’Rourke, D. Brian Foster
Journal: Circulation (2016)

Introduction:  Recently, we have investigated a pressure-overload/chronic catecholamine guinea pig model (ACi) of cardiac hypertrophy (HYP) and HF with the unique features of acquired long QT syndrome and sudden cardiac death (SCD) by quantitative global-scale proteomics using isobaric tags for relative and absolute quantitation.   Hypothesis:  By compiling proteins altered significantly both compensated HYP and HF, it may be possible to identify novel early contributors to pressure overload- induced HF pathogenesis.   Results:  Pathway mapping of proteins differentially regulated in HYP that were also changed in HF (p   Conclusion:  The data support a causal role for ATRA deficiency in the pathogenesis of pressure overload-induced HF and susceptibility to SCD.
Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation
Authors: Julio Pascual, Stefan P. Berger, Oliver Witzke, Helio Tedesco, Shamkant Mulgaonkar, Yasir Qazi, Steven Chadban, Federico Oppenheimer, Claudia Sommerer, Rainer Oberbauer, Yoshihiko Watarai, Christophe Legendre, Franco Citterio, Mitchell Henry, Titte R. Srinivas, Wen-Lin Luo, AnaMaria Marti, Peter Bernhardt, Flavio Vincenti
Journal: Journal of the American Society of Nephrology (2018)

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin.Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.