tbuckley/cabot-search huggingface dataset:
Calcium Supplement by Tetracycline guided amorphous Calcium Carbonate potentiates Osteoblast promotion for Synergetic Osteoporosis Therapy
Authors: Jianwei Wang, Shan Tao, Xiangyu Jin, Yanqing Song, Wentao Zhou, Haiya Lou, Rui Zhao, Cheng Wang, Fuqiang Hu, Hong Yuan
Journal: Theranostics (2020)

Background: The calcium supplement is a clinically approved approach for osteoporosis therapy but usually requires a large dosage without targetability and with poor outcome. This modality is not fully explored in current osteoporosis therapy due to the lack of proper calcium supplement carrier. Methods: In this study, we constructed a tetracycline (Tc) modified and simvastatin (Sim) loaded phospholipid-amorphous calcium carbonate (ACC) hybrid nanoparticle (Tc/ACC/Sim). Results: The resulted Tc/ACC/Sim was able to enhance its accumulation at the osteoporosis site. Most importantly, the combination of calcium supplement and Sim offered synergetic osteoblast promotion therapy of osteoporosis with advanced performance than non-targeted system or mono therapy. Conclusion: This platform provides an alternative approach to stimulate bone formation by synergetic promotion of osteoblast differentiation using calcium supplement and Sim.
Practical Electricity in Medicine and Surgery.
Journal: JAMA (1890)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Advances in understanding of angioimmunoblastic T-cell lymphoma
Authors: Shigeru Chiba, Mamiko Sakata-Yanagimoto
Journal: Leukemia (2020)

Abstract It has been nearly half a century since angioimmunoblastic T-cell lymphoma (AITL) was characterized in the early 1970’s. Our understanding of the disease has dramatically changed due to multiple discoveries and insights. One of the key features of AITL is aberrant immune activity. Although AITL is now understood to be a neoplastic disease, pathologists appreciated that it was an inflammatory condition. The more we understand AITL at cellular and genetic levels, the more we view it as both a neoplastic and an inflammatory disease. Here, we review recent progress in our understanding of AITL, focusing on as yet unsolved questions.
REPLY:
Authors: Yu Du, Gauri Khandekar, Jessica Llewellyn, William J. Polacheck, Christopher S. Chen, Rebecca G. Wells
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. We appreciate the interest of Xiao et al. in our work. We believe, however, that these researchers have misinterpreted our experimental design and findings. They question our conclusion that the basal surface of cholangiocyte monolayers is more sensitive to the biliary toxin, biliatresone, than the apical surface and raise the possibility that apical and basal biliatresone concentration and flow in our system are different. Our conclusion that biliatresone is more toxic to the basal surface of cholangiocytes than to the apical surface was not meant to imply that biliatresone does not require bile flow for delivery—indeed, we believe strongly that biliatresone is delivered by bile in vivo. Rather, we suggested that damage to the cholangiocyte monolayer through its apical surface results in increased permeability and leakage of bile and toxins such as biliatresone into the duct submucosa, bathing the basal surface of the monolayer, and that increased permeability from apical agents is particularly damaging for this reason. Note that Xiao et al. are not correct in interpreting the results of Lorent et al. as indicating a requirement for bile flow; rather, they indicate a need for the presence of bile in the lumen.(1) While this is synonymous with flow in vivo, culture enables us to separate the two. We used a concentration of biliatresone (2 μg/mL) that has been effective in other in vitro systems.(2) The media flowed freely through the channel and the collagen bulk upon addition to the system. The luminal concentration of biliatresone was either the same as was added to the reservoir or, because of dilution in the collagen bulk, slightly higher (which would suggest that the apical/basal permeability differences were actually greater than observed). Quantitative measurements of permeability were explained in detail.(3) According to the formula Pd=2rI0∂I∂t, permeability is influenced by the lumen radius, initial luminal concentration, and the slope of concentration changes outside the lumen, rather than the gradient over the surface. Flow was not a factor in these experiments; all devices were maintained under static conditions after the addition of toxin. We agree that immunostaining of the cholangiocyte monolayer after biliatresone treatment would be a useful measure of cells. We were most concerned with the impact of biliatresone on the function of the monolayer. In sum, we treated apical and basal surfaces equivalently and cultured cells under no‐flow conditions. Exposure of the susceptible basal surface to bile acids and biliatresone is a potential cause of increased monolayer damage after leakage of luminal contents.
Publisher Correction: Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression
Authors: Jonathan A. Beagan, Elissa D. Pastuzyn, Lindsey R. Fernandez, Michael H. Guo, Kelly Feng, Katelyn R. Titus, Harshini Chandrashekar, Jason D. Shepherd, Jennifer E. Phillips-Cremins
Journal: Nature Neuroscience (2020)
Mansukhlal Chhaganlal Wani, PhD: In Memoriam (1925–2020)
Authors: Rita Ghosh, Arti Patel Varanasi, Debasis Mondal, Meghana Trivedi, Kapil Mehta, Harikrishna Nakshatri, Aniruddha Ganguly
Journal: Cancer Research (2020)

![][1] 

Dr. Mansukhlal Chhaganlal Wani was an esteemed cancer researcher, humanitarian, mentor, and was steadfast in his commitment to train the next generation of cancer researchers. He passed away on April 11, 2020.

Dr. Wani was born in Nandurbar, Maharashtra, India. He obtained his
COVID-19 prediction models should adhere to methodological and reporting standards
Authors: Gary S. Collins, Maarten van Smeden, Richard D. Riley
Journal: European Respiratory Journal (2020)

The coronavirus disease 2019 (COVID-19) pandemic has led to a proliferation of clinical prediction models to aid diagnosis, disease severity assessment and prognosis. A systematic review has identified 66 COVID-19 prediction models: concluding that all, with no exception, are at high risk of bias due to concerns surrounding the data quality, statistical analysis and reporting, and none are recommended for use [1]. Therefore, we read with interest the recent paper by Wu et al. [2] describing the development of a model to identify COVID-19 patients with severe disease on admission to facilitate triage. However, our enthusiasm was dampened by a number of concerns surrounding the design, analysis and reporting of the study which deserve highlighting to readers. COVID-19 prediction models should adhere to methodological and reporting standards <https://bit.ly/3ebnook>
Gold-based Inorganic Nanohybrids for Nanomedicine Applications
Authors: Xianguang Ding, Dan Li, Jiang Jiang
Journal: Theranostics (2020)

Noble metal Au nanoparticles have attracted extensive interests in the past decades, due to their size and morphology dependent localized surface plasmon resonances. Their unique optical property, high chemical stability, good biocompatibility, and easy functionalization make them promising candidates for a variety of biomedical applications, including bioimaging, biosensing, and cancer therapy. With the intention of enhancing their optical response in the near infrared window and endowing them with additional magnetic properties, Au nanoparticles have been integrated with other functional nanomaterials that possess complementary attributes, such as copper chalcogenides and magnetic metal oxides. The as constructed hybrid nanostructures are expected to exhibit unconventional properties compared to their separate building units, due to nanoscale interactions between materials with different physicochemical properties, thus broadening the application scope and enhancing the overall performance of the hybrid nanostructures. In this review, we summarize some recent progresses in the design and synthesis of noble metal Au-based hybrid inorganic nanostructures for nanomedicine applications, and the potential and challenges for their clinical translations.
The role of polygenic susceptibility to obesity among carriers of pathogenic mutations in MC4R in the UK Biobank population
Authors: Nathalie Chami, Michael Preuss, Ryan W. Walker, Arden Moscati, Ruth J. F. Loos
Journal: PLoS Medicine (2020)

Background Melanocortin 4 receptor (MC4R) deficiency, caused by mutations in MC4R, is the most common cause of monogenic forms of obesity. However, these mutations have often been identified in small-scale, case-focused studies. Here, we assess the penetrance of previously reported MC4R mutations at a population level. Furthermore, we examine why some carriers of pathogenic mutations remain of normal weight, to gain insight into the mechanisms that control body weight. Methods and findings We identified 59 known obesity-increasing mutations in MC4R from the Human Gene Mutation Database (HGMD) and Clinvar. We assessed their penetrance and effect on obesity (body mass index [BMI] ≥ 30 kg/m2) in >450,000 individuals (age 40–69 years) of the UK Biobank, a population-based cohort study. Of these 59 mutations, only 11 had moderate-to-high penetrance and increased the odds of obesity by more than 2-fold. We subsequently focused on these 11 mutations and examined differences between carriers of normal weight and carriers with obesity. Twenty-eight of the 182 carriers of these 11 mutations were of normal weight. Body composition of carriers of normal weight was similar to noncarriers of normal weight, whereas among individuals with obesity, carriers had a somewhat higher BMI than noncarriers (1.44 ± 0.07 standard deviation scores [SDSs] ± standard error [SE] versus 1.29 ± 0.001, P = 0.03), because of greater lean mass (1.44 ± 0.09 versus 1.15 ± 0.002, P = 0.002). Carriers of normal weight more often reported that, already at age 10 years, their body size was below average or average (72%) compared with carriers with obesity (48%) (P = 0.01). To assess the polygenic contribution to body weight in carriers of normal weight and carriers with obesity, we calculated a genome-wide polygenic risk score for BMI (PRSBMI). The PRSBMI of carriers of normal weight (PRSBMI = -0.64 ± 0.18) was significantly lower than of carriers with obesity (0.40 ± 0.11; P = 1.7 × 10−6), and tended to be lower than that of noncarriers of normal weight (−0.29 ± 0.003; P = 0.05). Among carriers, those with a low PRSBMI (bottom quartile) have an approximately 5-kg/m2 lower BMI (approximately 14 kg of body weight for a 1.7-m-tall person) than those with a high PRS (top quartile). Because the UK Biobank population is healthier than the general population in the United Kingdom, penetrance may have been somewhat underestimated. Conclusions We showed that large-scale data are needed to validate the impact of mutations observed in small-scale and case-focused studies. Furthermore, we observed that despite the key role of MC4R in obesity, the effects of pathogenic MC4R mutations may be countered, at least in part, by a low polygenic risk potentially representing other innate mechanisms implicated in body weight regulation.
Association of Radioactive Iodine, Antithyroid Drug, and Surgical Treatments With Solid Cancer Mortality in Patients With Hyperthyroidism
Authors: Cari M. Kitahara, Dale L. Preston, Julie Ann Sosa, Amy Berrington de Gonzalez
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The long-term health effects of radioactive iodine (RAI) and antithyroid drug (ATD) treatments compared with surgery for hyperthyroidism remain uncertain. <h3>Objective</h3> To compare solid cancer mortality rates associated with RAI and ATD treatments vs surgical management for hyperthyroidism. <h3>Design, Setting, and Participants</h3> This multicenter cohort study assessed patients treated for hyperthyroidism from January 1, 1946, to December 31, 1964, with follow-up through December 31, 2014. Data analysis was performed from August 1, 2019, to April 23, 2020. <h3>Exposures</h3> Management with RAI, ATDs, surgical intervention, or combinations of these treatments. <h3>Main Outcomes and Measures</h3> Comparisons of solid cancer mortality rates in each treatment group with expected rates from the general population were assessed using standardized mortality ratios (SMRs), and internal comparisons were assessed using hazard ratios (HRs) adjusted for age, sex, and underlying diagnosis (Graves disease or toxic nodular goiter). <h3>Results</h3> Of 31 363 patients (24 894 [79.4%] female; mean [SD] age, 46.9 [14.8] years) included in the study, 28 523 (90.9%) had Graves disease. The median follow-up time was 26.0 years (interquartile range, 12.3-41.9 years). Important differences in patient characteristics existed across treatment groups at study entry. Notably, the drug-only group (3.6% of the cohort) included a higher proportion of patients with prior cancers (7.3% vs 1.9%-4.0%), contributing to an elevated SMR for solid cancer mortality. After excluding prior cancers, solid cancer SMRs were not elevated in any of the treatment groups (SMR for surgery only, 0.82 [95% CI, 0.66-1.00]; SMR for drugs only, 0.90 [95% CI, 0.74-1.09]; SMR for drugs and surgery, 0.88 [95% CI, 0.84-0.94]; SMR for RAI only, 0.90 [95% CI, 0.84-0.96]; SMR for surgery and RAI, 0.66 [95% CI, 0.52-0.85]; SMR for drugs and RAI, 0.94 [95% CI, 0.89-1.00]; and SMR for drugs, surgery, and RAI, 0.85 [95% CI, 0.75-0.96]), and no significant HRs for solid cancer death were observed across treatment groups. Among RAI-treated patients, HRs for solid cancer mortality increased significantly across levels of total administered activity (1.08 per 370 MBq; 95% CI, 1.03-1.13 per 370 MBq); this association was stronger among patients treated with only RAI (HR, 1.19 per 370 MBq; 95% CI, 1.09-1.30 per 370 MBq). <h3>Conclusions and Relevance</h3> After controlling for known sources of confounding, the study found no significant differences in the risk of solid cancer mortality by treatment group. However, among RAI-treated patients, a modest positive association was observed between total administered activity and solid cancer mortality, providing further evidence in support of a dose-dependent association between RAI and solid cancer mortality.
Emerging Treatment Options for the Management of Metastatic Colorectal Cancer
Authors: Dustin A. Deming
Journal: Journal of the National Comprehensive Cancer Network (2020)

An improved understanding of the molecular landscape of metastatic colorectal cancer (CRC) has opened the door for new treatment options. Clinicians should test for molecular alterations that predict resistance to epidermal growth factor receptor (EGFR) inhibitors, such as KRAS and NRAS , and additionally clinically actionable alterations, including BRAF V600 mutations, HER2 amplification, NTRK fusions, and mismatch repair deficiency. Improved outcomes can be achieved with precision treatment strategies for the various CRC subtypes, although clinical features, such as tumor bulk and patient performance status, still help to guide treatment choice. Immune therapies have also produced impressive results in patients with mismatch repair–deficient/microsatellite instability–high tumors. These newer approaches were recently incorporated into the NCCN Guidelines for Colon and Rectal Cancers. In the future, these newer approaches may be used in earlier treatment settings.
OP0329-PARE IN SHORT: EASY-TO-UNDERSTAND INFORMATION FOR VULNERABLE GROUPS
Authors: V. Krafft, E. Rösch
Journal: Annals of the Rheumatic Diseases (2020)

Background: Some 800,000 people in Switzerland have trouble reading (1). For people with reading or learning difficulties, many texts are too complex or simply too long. People with a migrant background likewise often lack access to health information, in their case due to language barriers. Objectives: One of the top priorities set out in Switzerland’s “National Strategy on Musculoskeletal Diseases (2017–2022) is to develop low-threshold services for vulnerable groups. In keeping with this strategy, the Swiss League against Rheumatism (SLR) wants to reach out to people with a migrant background as well as those with reading difficulties by making available to them helpful and readily understandable information material on rheumatic diseases. Methods: During the planning phase, the SLR collaborated with migesplus, the portal for equal health opportunities operated by the Swiss Red Cross. Their input flowed into the conception of the new publication series “kurz &amp; knapp” (in short). The texts for the new series are written in accordance with the rules for Easy Language, with the help of an expert committee from Pro Infirmis, the Swiss professional organisation for people with disabilities ( www.buero-leichte-sprache.ch ). After being evaluated, the final texts then receive a seal of approval. Easy Language is a key component of accessibility, because it makes complex content accessible to a wider audience. For the benefit of people with a migrant background, the SLR has the texts translated not only into the three Swiss national languages German, French and Italian but also into Albanian, Bosnian/Croatian/Montenegrin/Serbian, Portuguese, Spanish and Turkish. Brochures on “Gout” and “Arthrosis” have already been published in the “kurz &amp; knapp” series. In 2020, a publication on the subject of “Back Pain” will follow. In order to make the publications known to the intended target groups, the SLR wrote to various multipliers, such as immigration offices and foreign media. The publications are available free of charge in the online shop. Results: The new series “kurz &amp; knapp” has been commended in particular by migration experts. Within the last ten months, the SLR has already distributed over 1,000 copies. Conclusion: To reach people with reading difficulties or a migrant background – groups that make up a large part of the Swiss population – specially designed communication tools are needed. An interdisciplinary network is indispensable for the development and dissemination of such tools. References: [1]Notter, P. &amp; Arnold, C (2006). Lesen und Rechnen im Alltag: Grundkompetenzen von Erwachsenen in der Schweiz. Swiss Federal Statistical Office (BFS). Accessed on 28 January 2020: https://www.lesen-schreiben-schweiz.ch/myUploadData/files/ALL-StudieD.pdf Disclosure of Interests: Valérie Krafft Grant/research support from: Yes, Menarini AG (for gout brochure), Eva Rösch: None declared
Methylation of HSP70 Orchestrates Its Binding to and Stabilization of BCL2 mRNA and Renders Pancreatic Cancer Cells Resistant to Therapeutics
Authors: Liang Wang, Zhiliang Jia, Dacheng Xie, Tiansuo Zhao, Zhi Tan, Shuxing Zhang, Fanyang Kong, Daoyan Wei, Keping Xie
Journal: Cancer Research (2020)

Pancreatic cancer is a lethal disease owing to its intrinsic and acquired resistance to therapeutic modalities. The altered balance between pro- and antiapoptosis signals within cancer cells is critical to therapeutic resistance. However, the molecular mechanisms underlying increased antiapoptosis signals remain poorly understood. In this study, we report that PRMT1 expression is increased in pancreatic cancer tissues and is associated with higher tumor grade, increased aggressiveness, and worse prognosis. PRMT1 overexpression increased arginine methylation of HSPs of 70 kDa (HSP70); this methylation enhanced HSP70 binding and stabilization of BCL2 mRNA through AU-rich elements in 3'-untranslated region and consequentially increased BCL2 protein expression and protected cancer cells from apoptosis induced by cellular stresses and therapeutics. RNA binding and regulation function of HSP70 was involved in pancreatic cancer drug resistance and was dependent on protein arginine methylation. These findings not only reveal a novel PRMT1-HSP70-BCL2 signaling axis that is crucial to pancreatic cancer cell survival and therapeutic resistance, but they also provide a proof of concept that targeted inhibition of this axis may represent a new therapeutic strategy. SIGNIFICANCE: This study demonstrates that a PRMT1-mediated stabilization of BCL2 mRNA contributes to therapeutic resistance in pancreatic cancer and that targeting this pathway could overcome said resistance.
Emergency General Surgery—To Regionalize, or Not to Regionalize, That Is the Question
Authors: Cindy Y. Teng, Angela M. Ingraham, Brian S. Zuckerbraun
Journal: JAMA Surgery (2020)

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
Clare Gerada: We must not rush back to business as usual
Authors: Clare Gerada
Journal: BMJ (2020)

As we come to the end of the first phase of the covid pandemic it is good to review how this period has affected us, our patients, and our organisations. I have been doing this with respect to my service for doctors with mental illness, NHS Practitioner Health. After an initial dip in referrals, to around half the normal weekly numbers, we are now seeing more doctors presenting than at any time in our 12 year history.

These doctors are not randomly distributed across all specialties, levels of training, or seniority. Staff and associate grade and locum doctors have been more likely to present than consultants. General practitioners still …
Abstract 10801: Postoperative Atrial Fibrillation,The Role of Traditional Risk Factors and C-Reactive Protein Level
Authors: Mohammad Paymard, Lilian Wang, Tony Li, Aadil Rahim, Walter Abhayaratna, Rajeev K Pathak
Journal: Circulation (2018)

Introduction: Post-operative atrial fibrillation (AF) is commonly encountered in clinical practice. Presence of each additional cardiac risk factor increases the risk of postoperative AF proportion...