tbuckley/cabot-search huggingface dataset:
Phosphorylation promotes activation-induced cytidine deaminase activity at the Myc oncogene
Authors: Yunxiang Mu, Monika A. Zelazowska, Kevin M. McBride
Journal: The Journal of Experimental Medicine (2017)

Activation-induced cytidine deaminase (AID) is a mutator enzyme that targets immunoglobulin (Ig) genes to initiate antibody somatic hypermutation (SHM) and class switch recombination (CSR). Off-target AID association also occurs, which causes oncogenic mutations and chromosome rearrangements. However, AID occupancy does not directly correlate with DNA damage, suggesting that factors beyond AID association contribute to mutation targeting. CSR and SHM are regulated by phosphorylation on AID serine38 (pS38), but the role of pS38 in off-target activity has not been evaluated. We determined that lithium, a clinically used therapeutic, induced high AID pS38 levels. Using lithium and an AID-S38 phospho mutant, we compared the role of pS38 in AID activity at the Ig switch region and off-target Myc gene. We found that deficient pS38 abated AID chromatin association and CSR but not mutation at Myc. Enhanced pS38 elevated Myc translocation and mutation frequency but not CSR or Ig switch region mutation. Thus, AID activity can be differentially targeted by phosphorylation to induce oncogenic lesions.
Benefits and Risks of Machine Learning Decision Support Systems
Authors: Eta S. Berner, Bunyamin Ozaydin
Journal: JAMA (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 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
Rewiring to Regain Function in Patients with Spastic Hemiplegia
Authors: Robert J. Spinner, Alexander Y. Shin, Allen T. Bishop
Journal: New England Journal of Medicine (2017)

Spastic hemiplegia results from several relatively common disorders, including stroke, traumatic brain injury, and cerebral palsy. Frequently, upper-limb function is impaired. In this issue of the Journal, Zheng et al.1 report a new approach to the treatment of this condition: the use of a contralateral C7 nerve transfer from the nonparalyzed side to the paralyzed side in order to engage the unimpaired cerebral hemisphere. Nerve transfers have long been performed as treatment for lesions affecting the lower motor neurons, mostly involving the brachial plexus. Gu and colleagues at Huashan Hospital, Fudan University, in Shanghai have pioneered nerve transfers, particularly those . . .
Mutations in the X-linked <i>ATP6AP2</i> cause a glycosylation disorder with autophagic defects
Authors: Maria A. Rujano, Magda Cannata Serio, Ganna Panasyuk, Romain Péanne, Janine Reunert, Daisy Rymen, Virginie Hauser, Julien H. Park, Peter Freisinger, Erika Souche, Maria Clara Guida, Esther M. Maier, Yoshinao Wada, Stefanie Jäger, Nevan J. Krogan, Oliver Kretz, Susana Nobre, Paula Garcia, Dulce Quelhas, Thomas D. Bird, Wendy H. Raskind, Michael Schwake, Sandrine Duvet, Francois Foulquier, Gert Matthijs, Thorsten Marquardt, Matias Simons
Journal: The Journal of Experimental Medicine (2017)

The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects. The introduction of one of the missense mutations into Drosophila led to reduced survival and altered lipid metabolism. We further demonstrate that in the liver-like fat body, the autophagic dysregulation was associated with defects in lysosomal acidification and mammalian target of rapamycin (mTOR) signaling. Finally, both ATP6AP2 mutations impaired protein stability and the interaction with ATP6AP1, a member of the V0 assembly complex. Collectively, our data suggest that the missense mutations in ATP6AP2 lead to impaired V-ATPase assembly and subsequent defects in glycosylation and autophagy.
Stenting Does Not Relieve Stable Angina Symptoms
Authors: Anita Slomski
Journal: JAMA (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 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
Baseline peripheral blood biomarkers predict clinical outcome ofadvanced melanoma patients treated with ipilimumab: singleinstitution real-life data experience
Authors: Lenka Gescheidtová, Alexandr Poprach, Radek Lakomý, Iveta Selingerová, Pilatova K, Valik D, Katarína Petráková, Rostislav Vyzula, L Zdrazilova-Dubska, Kozakova S, Demlova R
Journal: Journal for ImmunoTherapy of Cancer (2016)
A Low-Fat Dietary Pattern and Diabetes: A Secondary Analysis From the Women’s Health Initiative Dietary Modification Trial
Authors: Barbara V. Howard, Aaron K. Aragaki, Lesley F. Tinker, Matthew Allison, Melanie D. Hingle, Karen C. Johnson, JoAnn E. Manson, Aladdin H. Shadyab, James M. Shikany, Linda G. Snetselaar, Cynthia A. Thomson, Oleg Zaslavsky, Ross L. Prentice
Journal: Diabetes Care (2017)

OBJECTIVE We performed a secondary analysis to evaluate the effect of the Women’s Health Initiative dietary intervention on incident diabetes and diabetes treatment in postmenopausal women. RESEARCH DESIGN AND METHODS A total of 48,835 women were randomized to a comparison group or an intervention group that underwent a behavioral/nutritional modification program to decrease fat and increase vegetable, fruit, and grain intake for an average of 8.1 years. Ninety-three percent of participants completed the intervention, and 71% participated in active follow-up through 30 September 2015 (median 17.3 years). We measured time to development of treated diabetes and progression from oral antihyperglycemic agents to insulin. Serum glucose and insulin were measured in a subsample of women (N = 2,324) at baseline and years 1, 3, and 6. RESULTS During the trial, intervention group women had lower rates of initiation of insulin therapy (hazard ratio [HR] 0.74 [95% CI 0.59, 0.94]; P = 0.01). Moreover, women with baseline waist circumference ≥88 cm (P interaction = 0.01) and worse metabolic syndrome scores (P interaction = 0.02) had the greatest reduction in risk of initiating insulin therapy. The decreased risk from the intervention was present during the cumulative follow-up (HR 0.88 [95% CI 0.78, 0.99]; P = 0.04). In participants with measured biomarkers (5.8% subsample) who had baseline glucose &amp;lt;100 mg/dL, the intervention reduced the risk of developing glucose ≥100 mg/dL by 25% (odds ratio 0.75 [95% CI 0.61, 0.93]; P = 0.008). Adjustment for weight change did not alter the results. CONCLUSIONS In this secondary analysis, a dietary intervention in postmenopausal women aimed at reducing fat and increasing intake of vegetables, fruits, and grains did not increase risk of diabetes and may have slowed progression.
The Promise of Intranasal Esketamine as a Novel and Effective Antidepressant
Authors: Daniel S. Quintana, Nils Eiel Steen, Ole A. Andreassen
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Clinical Dosing Regimen of Selinexor Maintains Normal Immune Homeostasis and T Cell Effector Function in Mice: Implications for Combination with Immunotherapy
Authors: Paul M Tyler, Mariah M Servos, Boris Klebanov, Trinayan Kashyap, Sharon Shacham, Yosef Landesman, Michael Dougan, Stephanie K Dougan
Journal: Blood (2016)
The ER membrane adaptor ERAdP senses the bacterial second messenger c-di-AMP and initiates anti-bacterial immunity
Authors: Pengyan Xia, Shuo Wang, Zhen Xiong, Xiaoxiao Zhu, Buqing Ye, Ying Du, Shu Meng, Yuan Qu, Jing Liu, Guangxia Gao, Yong Tian, Zusen Fan
Journal: Nature Immunology (2017)
Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections From a<i>Diabetes Care</i>Editors’ Expert Forum
Authors: William T Cefalu, Sanjay Kaul, Hertzel C Gerstein, Rury R Holman, Bernard Zinman, Jay S Skyler, Jennifer B Green, John B Buse, Silvio E Inzucchi, Lawrence A Leiter, Itamar Raz, Julio Rosenstock, Matthew C Riddle
Journal: Diabetes Care (2017)

In December 2008, the U.S. Food and Drug Administration issued guidance to the pharmaceutical industry setting new expectations for the development of antidiabetes drugs for type 2 diabetes. This guidance expanded the scope and cost of research necessary for approval of such drugs by mandating long-term cardiovascular outcomes trials (CVOTs) for safety. Since 2008, 9 CVOTs have been reported, 13 are under way, and 4 have been terminated. Reassuringly, each of the completed trials demonstrated the noninferiority of their respective drugs to placebo for their primary cardiovascular (CV) composite end point. Notably, four additionally provided evidence of CV benefit in the form of significant decreases in the primary CV composite end point, two suggested reductions in CV death, and three suggested reductions in all-cause mortality. Although these trials have yielded much valuable information, whether that information justifies the investment of time and resources is controversial. In June 2016, a
Daily intake of sulforaphane-rich broccoli sprouts prevents progression of high salt diet-induced gastric atrophy in H.pylori-infected C57/BL6 mice in vivo
Authors: Akinori Yanaka, Songhua Zhang, Masafumi Tauchi, Hideo Suzuki, Akira Nakahara, Naomi Tanaka, Masayuki Yamamoto
Journal: Cancer Research (2005)

5170   Background: Sulforaphane, shown to be abundantly present in broccoli sprouts, possesses anticarcinogenic activity, since it strongly induces nrf-2 (NF-E2 p45-related factor-2) gene-dependant antioxidant (or phase 2) enzymes, such as glutathione-S- transferase (GSH) and NADPH:quinone reductase(QR), which exert as free radical scavengers, thereby protecting cells from oxidative injury (PNAS, 94:10367, 1997). It has been reported that nrf-2 is strongly expressed in gastric mucosa (Cancer Res 61:3299,2001). Recent studies have also shown that sulforaphane has strong bactericidal activity against  Helicobacter pylori (Hp)  in vitro  (PNAS 99:7610, 2002). We have previously shown that high salt diet accelerates progression of gastric atrophy in Hp-infected mice  in vivo  by enhancing oxidative stress and by exacerbating Hp-induced gastritis. (Gastroenterology 122: A1, 2002). Based on these backgrounds, we examined if 1) sulforaphane inhibits Hp colonization  in vivo , and if 2) sulforaphane prevents progression of high salt diet-induced gastric atrophy in Hp-infected gastric mucosa via activation of nrf-2 dependent antioxidant ezymes. Methods: C57BL/6 wild type (nrf-2+/+) or nrf-2 gene kockout (nrf-2-/-) female mice were inoculated with Hp Sydney Strain; SS1. Mice were daily fed with high salt diet (7.5% NaCl), supplemented with or without 2.5 mmol sulforaphane or homogenate of broccoli sprouts, which contains 2.5 mmol sulforaphane. Mice were sacrificed at 8 wks after starting the treatment. Degree of gastritis and atrophy was evaluated by updated Sydney system. DNA damage was estimated by measuring mucosal level of 8-OHdG. Expressions of TNF-a, IL-1b, MIP-2, and COX-2 were analyzed by real time PCR. Results: 1. Treatment with either sulforaphane or broccoli sprouts enhanced activities of GSH and quinone reductase in gastric mucosa in nrf2+/+, but not in nrf-2-/- mice  in vivo . 2. Treatment with sulforaphane or broccoli sprouts attenuated mucosal expressions of TNF-a, IL-1b, MIP-2, and COX-2, mitigated gastritis and DNA damage, and prevented progression of high salt diet-induced gastric atrophy in nrf2+/+, but not in nrf-2-/- mice. 3. Treatment with either sulforaphane or broccoli sprouts decreased Hp colonization in gastric mucosa, but failed to induce complete eradication of Hp in both nrf2+/+ nrf-2-/- mice  in vivo .Conclusions: Daily intake of sulforaphane-rich broccoli-sprouts attenuates gastritis and prevents progression of gastric atrophy in Hp-infected mice fed with high salt diet, effects appear to be mediated in part by enhancing activities of nrf-2 gene dependent anti-oxidant enzymes against oxidative stress induced by Hp infection, and in part by suppressing Hp colonization.
Reversible Conformational Conversion of α-Synuclein into Toxic Assemblies by Glucosylceramide
Authors: Friederike Zunke, Alexandra C. Moise, Nandkishore R. Belur, Eilrayna Gelyana, Iva Stojkovska, Haris Dzaferbegovic, Nicholas J. Toker, Sohee Jeon, Kristina Fredriksen, Joseph R. Mazzulli
Journal: Neuron (2017)
Measurable residual disease detection by high-throughput sequencing improves risk stratification for pediatric B-ALL
Authors: Brent Wood, David Wu, Beryl Crossley, Yunfeng Dai, David Williamson, Charles Gawad, Michael J. Borowitz, Meenakshi Devidas, Kelly W. Maloney, Eric Larsen, Naomi Winick, Elizabeth Raetz, William L. Carroll, Stephen P. Hunger, Mignon L. Loh, Harlan Robins, Ilan Kirsch
Journal: Blood (2017)
Prevalence of Work-Related Musculoskeletal Disorders Among Surgeons and Interventionalists
Authors: Sherise Epstein, Emily H. Sparer, Bao N. Tran, Qing Z. Ruan, Jack T. Dennerlein, Dhruv Singhal, Bernard T. Lee
Journal: JAMA Surgery (2017)

Physicians in procedural specialties are at high risk for work-related musculoskeletal disorders (MSDs). This has been called "an impending epidemic" in the context of the looming workforce shortage; however, prevalence estimates vary by study.To estimate the prevalence of work-related MSDs among at-risk physicians and to evaluate the scope of preventive efforts.Systematic search in MEDLINE (Ovid), Embase (Elsevier), Web of Science, PubMed (National Center for Biotechnology Information), and 2 clinical trial registries, without language restriction, for studies reporting on the prevalence and prevention of work-related MSDs among at-risk physicians published until December 2016. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for meta-analyses and systematic reviews of observational studies were used. At-risk physicians were defined as surgeons and medical interventionalists. Studies reporting on specific disorders or pain assessed with validated instruments were included.Study characteristics; disease prevalence for the neck, shoulder, back, and upper extremity; and measures of resulting disability were recorded. Study estimates were pooled using random-effects meta-analytic models.Career prevalence of injuries and 12-month prevalence of pain.Among 21 articles (5828 physicians [mean age, 46.0 years; 78.5% male; 12.8 years in practice; 14.4 hours performing procedures per week]) included in this systematic review and meta-analysis, pooled crude prevalence estimates of the most common work-related MSDs were degenerative cervical spine disease in 17% (457 of 2406 physicians) (95% CI, 12%-25%), rotator cuff pathology in 18% (300 of 1513 physicians) (95% CI, 13%-25%), degenerative lumbar spine disease in 19% (544 of 2449 physicians) (95% CI, 5%-16%), and carpal tunnel syndrome in 9% (256 of 2449 physicians) (95% CI, 5%-16%). From 1997 to 2015, the prevalence of degenerative cervical spine disease and degenerative lumbar spine disease increased by 18.3% and 27%, respectively. Pooled prevalence estimates for pain ranged from 35% to 60% and differed by assessment instrument. Of those with a work-related MSD, 12% (277 of 2319 physicians) (95% CI, 7%-18%) required a leave of absence, practice restriction or modification, or early retirement. Heterogeneity was considerable for all crude analyses (mean I2 = 93.5%) but was lower for sensitivity analyses (mean I2 = 72.3%). Interventions focused on products and behaviors. Twelve at-risk specialties described a gross lack of awareness and an unmet need for ergonomics education.Prevalence estimates of work-related MSDs among at-risk physicians appear to be high. Further research is needed to develop and validate an evidence-based applied ergonomics program aimed at preventing these disorders in this population.
Periosteum Extracellular‐Matrix‐Mediated Acellular Mineralization during Bone Formation
Authors: Xianfeng Lin, Chenchen Zhao, Peizhi Zhu, Jiaxin Chen, Huaguang Yu, Yin Cai, Qi Zhang, An Qin, Shunwu Fan
Journal: Advanced Healthcare Materials (2017)

Abstract Cell‐mediated mineralization is essential for bone formation and regeneration. In this study, it is proven that extracellular matrix (ECM) of decellularized periosteum can play an initiative and independent role in bone‐like apatite formation. Using decellularized periosteum scaffold, it is revealed that ECM scaffold itself can promote critical bone defect regeneration and nude mouse ectopic ossification. The natural collagen matrix of decellularized periosteum can serve as a 3D structural template for Ca–P nuclei initiation, controlling the size and orientation of bone‐like mineral crystals. The naturally cross‐linked and highly ordered 3D fibrillar network of decellularized periosteum not only provides a model for mimicking mineralization in vitro and in vivo to elucidate the important functions of ECM in bone formation and regeneration, but also can be a promising biomaterial for bone tissue engineering and clinical application.
Whole-Brain Radiotherapy for Brain Metastases: Evolution or Revolution?
Authors: Paul D. Brown, Manmeet S. Ahluwalia, Osaama H. Khan, Anthony L. Asher, Jeffrey S. Wefel, Vinai Gondi
Journal: Journal of Clinical Oncology (2017)

An estimated 20% of patients with cancer will develop brain metastases. Approximately 200,000 individuals in the United States alone receive whole-brain radiotherapy (WBRT) each year to treat brain metastases. Historically, the prognosis of patients with brain metastases has been poor; however, with new therapies, this is changing. Because patients are living longer following the diagnosis and treatment of brain metastases, there has been rising concern about treatment-related toxicities associated with WBRT, including neurocognitive toxicity. In addition, recent clinical trials have raised questions about the use of WBRT. To better understand this rapidly changing landscape, this review outlines the treatment roles and toxicities of WBRT and alternative therapies for the management of brain metastases.
Gadolinium-chelate functionalized bismuth nanotheranostic agent for in vivo MRI/CT/PAI imaging-guided photothermal cancer therapy
Authors: Bo Wu, Shu-Ting Lu, Hui Yu, Ru-Fang Liao, Huan Li, B.V. Lucie Zafitatsimo, Yu-Shuang Li, Ying Zhang, Xiao-Lei Zhu, Hong-Guang Liu, Hai-Bo Xu, Shi-Wen Huang, Zhen Cheng
Journal: Biomaterials (2017)
Fluorination Enhances Serum Stability of Bioreducible Poly(amido amine) Polyplexes and Enables Efficient Intravenous siRNA Delivery
Authors: Gang Chen, Kaikai Wang, Yixin Wang, Pengkai Wu, Minjie Sun, David Oupický
Journal: Advanced Healthcare Materials (2017)

Abstract The use of small interfering RNA (siRNA) in cancer treatment has been limited by the lack of effective systemic delivery methods. Although synthetic polycations have been widely explored in siRNA delivery, polycation/siRNA polyplexes often suffer from insufficient stability in vivo. Here, rationally designed siRNA delivery systems that meet the requirements for systemic siRNA delivery to distant tumors are reported. The hypothesis that modular design of delivery systems based on poly(amido amine)s that combine fluorination for systemic stability with bioreducibility for easy intracellular siRNA release, and PEGylation for improved safety and colloidal stability will overcome problems with contradicting siRNA delivery demands is tested. PEGylated, fluorinated, and bioreducible copolymers (PEG‐PCD‐F) with different degree of fluorination are thus synthesized. The fluorinated copolymers readily formed polyplexes with siRNA and achieved greatly improved gene silencing efficacy in multiple cell lines in vitro when compared with nonfluorinated controls. The results show fluorination‐induced enhancement of stability, cellular uptake, and endosomal escape of the polyplexes, while exhibiting efficient siRNA release in reducing intracellular environment. PEG‐PCD‐F polyplexes with siRNA against Bcl2 inhibit breast tumor growth following systemic intravenous administration. The results provide strong evidence of successful combination of bioreducibility with fluorination and PEGylation to achieve systemic siRNA polyplex delivery.