tbuckley/cabot-search huggingface dataset:
Sulforaphane Inhibits the Acquisition of Tobacco Smoke-Induced Lung Cancer Stem Cell-Like Properties <i>via</i> the IL-6/ΔNp63α/Notch Axis
Authors: Chunfeng Xie, Jianyun Zhu, Ye Jiang, Jiaqi Chen, Xueqi Wang, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Xiaoting Li, Zili Meng
Journal: Theranostics (2019)

Background: Tobacco smoke (TS) critically contributes to the development of lung cancer; however, the underlying molecular mechanisms remain unclear.The induction of cancer stem cells (CSCs) by TS represents an early event in tumor initiation.The lung cancer-related gene ΔNp63α is highly expressed in epithelial tissues and drives tumor formation and cancer stem cell properties.This study investigated the role of ΔNp63α in the long-term acquisition of TS-induced lung CSC-like properties. Methods:The expression levels of ΔNp63α, lung CSC markers, and interleukin (IL)-6 in lung carcinoma specimens were determined by western blotting and enzyme linked immunosorbent assays.Human bronchial epithelial (HBE) cells were chronically exposed to 2 % cigarette smoke extract for 55 passages, following which colony formation capacity, expression of proteins associated with malignant transformation, lung CSC markers, and tumor incidence were investigated.The effects of ΔNp63α on long-term TS exposure-induced lung CSC-like properties and Notch activation were analyzed using tumorsphere formation ability, immunofluorescence assays, luciferase reporter assays, and western blotting.The roles of IL-6 on chronic TS exposure-induced lung CSC-like properties and ΔNp63α expression were also examined.Moreover, the effects of sulforaphane (SFN) on TS-transformed lung CSC-like properties, IL-6 and ΔNp63α expression, and Notch signaling were investigated in vitro and in vivo.Results: Higher levels of ΔNp63α were observed in the lung cancer tissues of smokers than in those of non-smokers, whereas ΔNp63α was positively correlated with CD133 and Oct4 expression in lung cancer tissues.Data from the in vivo and in vitro experiments demonstrated that long-term TS exposure-transformed HBE (THBE) cells acquired lung CSC-like properties.Furthermore, ΔNp63α transcriptionally activated the Notch signaling pathway to promote the acquisition of CSC-like properties by the THBE cells.TS upregulated IL-6, which increased ΔNp63α expression in THBE sphere-forming cells.Finally, SFN inhibited the TS-induced CSC-like properties of THBE cells via the IL-6/ΔNp63α/Notch axis. Conclusion:Our data suggest that the IL-6/ΔNp63α/Notch axis plays an important role in the long-term TS exposure-induced acquisition of lung CSC-like properties and SFN intervention.
SPED Statement: Colorectal cancer screening in Portugal
Authors: M Dinis-Ribeiro, M Areia, A Dias-Pereira
Journal: Endoscopy (2019)

The Portuguese Society of Digestive Endoscopy (SPED) throughout its history has always been focused on colorectal cancer (CRC) and the promotion of its population-based screening. CRC is a major health problem due to its high incidence and mortality [1]. In 2018 in Portugal about 10 000 people were diagnosed with this disease (1st place in incidence, surpassing breast and prostate cancer) with a mortality around 45 % (1st cause of cancer death, representing 16 % of deaths due to neoplasia). In reality, there are 11 Portuguese who die every day from this disease, potentially avoidable by screening [2] [3] [4] [5]!
Association of an Emergency Department–Based Intensive Care Unit With Survival and Inpatient Intensive Care Unit Admissions
Authors: Kyle J. Gunnerson, Benjamin S. Bassin, Renee A. Havey, Nathan L. Haas, Cemal B. Sozener, Richard P. Medlin, Jennifer A. Gegenheimer-Holmes, Stephanie L. Laurinec, Caryn Boyd, James A. Cranford, Sage P. Whitmore, Cindy H. Hsu, Reham Khan, Neha N. Vazirani, Stephen G. Maxwell, Robert W. Neumar
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Increased patient acuity, decreased intensive care unit (ICU) bed availability, and a shortage of intensivist physicians have led to strained ICU capacity. The resulting increase in emergency department (ED) boarding time for patients requiring ICU-level care has been associated with worse outcomes. <h3>Objective</h3> To determine the association of a novel ED-based ICU, the Emergency Critical Care Center (EC3), with 30-day mortality and inpatient ICU admission. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used electronic health records of all ED visits between September 1, 2012, and July 31, 2017, with a documented clinician encounter at a large academic medical center in the United States with approximately 75 000 adult ED visits per year. The pre-EC3 cohort included ED patients from September 2, 2012, to February 15, 2015, when the EC3 opened, and the post-EC3 cohort included ED patients from February 16, 2015, to July 31, 2017. Data analyses were conducted from March 2, 2018, to May 28, 2019. <h3>Exposures</h3> Implementation of EC3, an ED-based ICU designed to provide rapid initiation of ICU-level care in the ED setting and seamless transition to inpatient ICUs. <h3>Main Outcomes and Measures</h3> The main outcomes were 30-day mortality among ED patients and rate of ED to ICU admission. <h3>Results</h3> A total of 349 310 visits from a consecutive sample of ED patients (mean [SD] age, 48.5 [19.7] years; 189 709 [54.3%] women) were examined; the pre-EC3 cohort included 168 877 visits and the post-EC3 cohort included 180 433 visits. Implementation of EC3 was associated with a statistically significant reduction in risk-adjusted 30-day mortality among all ED patients (pre-EC3, 2.13%; post-EC3, 1.83%; adjusted odds ratio, 0.85; 95% CI, 0.80-0.90; number needed to treat, 333 patient encounters; 95% CI, 256-476). The risk-adjusted rate of ED admission to ICU decreased with implementation of EC3 (pre-EC3, 3.2%; post-EC3, 2.7%; adjusted odds ratio, 0.80; 95% CI, 0.76-0.83; number needed to treat, 179 patient encounters; 95% CI, 149-217). <h3>Conclusions and Relevance</h3> Implementation of a novel ED-based ICU was associated with improved 30-day survival and reduced inpatient ICU admission. Additional research is warranted to further explore the value of this novel care delivery model in various health care systems.
Association of Region and Hospital and Patient Characteristics With Use of High-Intensity Statins After Myocardial Infarction Among Medicare Beneficiaries
Authors: Vera Bittner, Lisandro D. Colantonio, Yuling Dai, Mark Woodward, Matthew T. Mefford, Robert S. Rosenson, Paul Muntner, Keri L. Monda, Meredith L. Kilgore, Byron C. Jaeger, Emily B. Levitan
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> High-intensity statin use after myocardial infarction (MI) varies by patient characteristics, but little is known about differences in use by hospital or region. <h3>Objective</h3> To explore the relative strength of associations of region and hospital and patient characteristics with high-intensity statin use after MI. <h3>Design, Setting, and Participants</h3> This retrospective cohort analysis used Medicare administrative claims and enrollment data to evaluate fee-for-service Medicare beneficiaries 66 years or older who were hospitalized for MI from January 1, 2011, through June 30, 2015, with a statin prescription claim within 30 days of discharge. Data were analyzed from January 4, 2017, through May 12, 2019. <h3>Exposures</h3> Beneficiary characteristics were abstracted from Medicare data. Hospital characteristics were obtained from the 2014 American Hospital Association Survey and Hospital Compare quality metrics. Nine regions were defined according to the US Census. <h3>Main Outcomes and Measures</h3> Intensity of the first statin claim after discharge characterized as high (atorvastatin calcium, 40-80 mg, or rosuvastatin calcium, 20-40 mg/d) vs low to moderate (all other statin types and doses). Trends in high-intensity statins were examined from 2011 through 2015. Associations of region and beneficiary and hospital characteristics with high-intensity statin use from January 1, 2014, to June 15, 2015, were examined using Poisson distribution mixed models. <h3>Results</h3> Among the 139 643 fee-for-service beneficiaries included (69 968 men [50.1%] and 69 675 women [49.9%]; mean [SD] age, 76.7 [7.5] years), high-intensity statin use overall increased from 23.4% in 2011 to 55.6% in 2015, but treatment gaps persisted across regions. In models considering region and beneficiary and hospital characteristics, region was the strongest correlate of high-intensity statin use, with 66% higher use in New England than in the West South Central region (risk ratio [RR], 1.66; 95% CI, 1.47-1.87). Hospital size of at least 500 beds (RR, 1.15; 95% CI, 1.07-1.23), medical school affiliation (RR, 1.11; 95% CI, 1.05-1.17), male sex (RR, 1.10; 95% CI, 1.07-1.13), and patient receipt of a stent (RR, 1.35; 95% CI, 1.31-1.39) were associated with greater high-intensity statin use. For-profit hospital ownership, patient age older than 75 years, prior coronary disease, and other comorbidities were associated with lower use. <h3>Conclusions and Relevance</h3> This study's findings suggest that geographic region is the strongest correlate of high-intensity statin use after MI, leading to large treatment disparities.
Investing in global health will “improve our NHS,” says England’s CMO
Authors: Nigel Hawkes
Journal: BMJ (2019)

The determinants of health respect no national boundaries, says Sally Davies in her final report as chief medical officer for England,1 urging the need to invest in global health as a proper use of international aid and as a process with benefits that cut both ways.

She suggests that the UK aid budget, set at 0.7% of GDP, could be used to support medical and nursing schools in the UK that are willing to collaborate with universities in low and middle income countries to raise the quality of their graduates. Aid money could also be used for study grants and scholarships for students and graduates from such countries.

These need not be restricted to medicine, she adds, but could include a broad range of disciplines that can improve health, such as digital techniques, computing, engineering, philosophy, ethics, anthropology, and architecture. …
Antibiotic Delivery: In Vitro and In Vivo Antimicrobial Activity of Antibiotic‐Conjugated Carriers with Rapid pH‐Responsive Release Kinetics (Adv. Healthcare Mater. 14/2019)
Authors: Sunyoung Kang, Gee Ho Park, Seulah Kim, Jungah Kim, Yoonhwa Choi, Yan Huang, Yan Lee, Tae Hyun Choi
Journal: Advanced Healthcare Materials (2019)

In article number 1900247 by Yan Lee, Tae Hyun Choi, and co-workers, a pH-responsive antibiotic drug conjugate system is developed using a maleic acid amide-based linker. The conjugate system can rapidly release the antibiotics and induce antimicrobial activities against S. aureus at weakly acidic environments in abscesses or inflammatory tissues.
Safety and Benefit of Using Liver Grafts From Older Donors
Authors: Brian K. P. Goh
Journal: JAMA Surgery (2019)

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
Hydroxyurea Shows Clinical Benefit without Alteration of Fetal Hemoglobin, MCV, or Hemoglobin in Unselected Adult and Pediatric Patients with Sickle Cell Anemia
Authors: Crawford John Strunk, Biree Andemariam, Fredericka Sey, Fatimah Farooq, Rebekah Urbonya, Charles Antwi-Boasiako, Adetola A. Kassim, Onike Rodrigues, Connie M. Piccone, Angela Rivers, Deepa Manwani, Imma Tartaglione, Laura Sainati, Raffaella Colombatti, Andrew D. Campbell
Journal: Blood (2015)
Ethics in Practice: Managed Care and the Changing Health Care Environment
Authors: Gail J. Povar, Helen Blumen, John Daniel, Suzanne Daub, Lois Evans, Richard P. Holm, Natalie Levkovich, Alice O. McCarter, James Sabin, Lois Snyder, Daniel Sulmasy, Peter Vaughan, Laurence D. Wellikson, Amy Campbell
Journal: Annals of Internal Medicine (2004)

This statement offers guidance on preserving the patient–physician relationship; patient rights and responsibilities; confidentiality and privacy; resource allocation and stewardship; the obligatio...
Comment on Braffett et al. Association of Insulin Dose, Cardiometabolic Risk Factors, and Cardiovascular Disease in Type 1 Diabetes During 30 Years of Follow-up in the DCCT/EDIC Study. Diabetes Care 2019;42:657–664
Authors: Jennifer R. Snaith, Deborah J. Holmes-Walker, Jerry R. Greenfield
Journal: Diabetes Care (2019)

We read with great interest that Braffett et al. (1) report an association between insulin dose and adverse cardiometabolic profiles using 30 years of follow-up data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Intensive diabetes treatment necessitating increased insulin doses became the accepted standard of care in type 1 diabetes after the DCCT/EDIC trial demonstrated cardiovascular risk benefit (mean ± SD 0.71 ± 0.21 vs. 0.65 ± 0.21 units/kg/day in the intensive vs. conventional treatment group; P = 0.0001). We support the authors’ emphasis that this association is somewhat driven by insulin-related weight gain, especially in males. The report …
Does Socioeconomic Status Influence the Risk of Subclinical Atherosclerosis?
Authors: Lidia Redondo-Bravo, Juan Miguel Fernández-Alvira, Juan Górriz, José María Mendiguren, Javier Sanz, Leticia Fernández-Friera, José Manuel García-Ruiz, Antonio Fernández-Ortiz, Borja Ibáñez, Héctor Bueno, Valentín Fuster
Journal: Journal of the American College of Cardiology (2019)

Socioeconomic status (SES)—education, income level, and occupation—is associated with cardiovascular risk. This study aimed to investigate the association between SES and subclinical atherosclerosis and the potential mechanisms involved. SES, lifestyle habits (smoking, dietary patterns, physical activity, and hours of sleep), traditional risk factors, and subclinical atherosclerosis extent were prospectively assessed in 4,025 individuals aged 40 to 54 years without known cardiovascular disease enrolled in the PESA (Progression of Early Subclinical Atherosclerosis) study. After factors associated with atherosclerosis were identified, a multiple mediation model was created to quantify the effect of SES on subclinical atherosclerosis as explained by lifestyle behaviors. Although education level was significantly associated with the presence of atherosclerosis, no differences were found according to income level in this population. Participants with lower education presented with a higher risk of generalized atherosclerosis than those with higher education (odds ratio: 1.46; 95% confidence interval: 1.15 to 1.85; p = 0.002). Lifestyle behaviors associated with both education level and atherosclerosis extent were: smoking status, number of cigarettes/day, and dietary pattern, which explained 70.5% of the effect of SES on atherosclerosis. Of these, tobacco habit (smoking status 35% and number of cigarettes/day 32%) accounted for most of the explained differences between groups, whereas dietary pattern did not remain a significant mediator in the multiple mediation model. Despite the relative economic homogeneity of the cohort, lower education level is associated with increased subclinical atherosclerosis, mainly mediated by the higher and more frequent tobacco consumption. Smoking cessation programs are still needed, particularly in populations with lower education level.
Innate immune cell–epithelial crosstalk during wound repair
Authors: Jennifer C. Brazil, Miguel Quiros, Asma Nusrat, Charles A. Parkos
Journal: Journal of Clinical Investigation (2019)

Skin and intestinal epithelial barriers play a pivotal role in protecting underlying tissues from harsh external environments. The protective role of these epithelia is, in part, dependent on a remarkable capacity to restore barrier function and tissue homeostasis after injury. In response to damage, epithelial wounds repair by a series of events that integrate epithelial responses with those of resident and infiltrating immune cells including neutrophils and monocytes/macrophages. Compromise of this complex interplay predisposes to development of chronic nonhealing wounds, contributing to morbidity and mortality of many diseases. Improved understanding of crosstalk between epithelial and immune cells during wound repair is necessary for development of better pro-resolving strategies to treat debilitating complications of disorders ranging from inflammatory bowel disease to diabetes. In this Review we focus on epithelial and innate immune cell interactions that mediate wound healing and restoration of tissue homeostasis in the skin and intestine.
The loneliness of me: The assumption of social disinterest and its worrying consequences in autism
Authors: Rachel Louise Moseley, Jie Sui
Journal: Behavioral and Brain Sciences (2019)

Abstract We share Jaswal &amp; Akhtar's concerns about the unintended repercussions of assumed social disinterest in autism. We expand consideration of these consequences with discussion of the literature and our own work on loneliness, mental ill-health, and self-representation, which is a cornerstone to social and emotional health. Further study is needed with expansive, mixed methodologies and involvement of the autistic community.
Identification of intermediate-sized deletions and inference of their impact on gene expression in a human population
Authors: Jing Hao Wong, Daichi Shigemizu, Yukiko Yoshii, Shintaro Akiyama, Azusa Tanaka, Hidewaki Nakagawa, Shu Narumiya, Akihiro Fujimoto
Journal: Genome Medicine (2019)

Next-generation sequencing has allowed for the identification of different genetic variations, which are known to contribute to diseases. Of these, insertions and deletions are the second most abundant type of variations in the genome, but their biological importance or disease association is not well-studied, especially for deletions of intermediate sizes. We identified intermediate-sized deletions from whole-genome sequencing (WGS) data of Japanese samples (n = 174) with a novel deletion calling method which considered multiple samples. These deletions were used to construct a reference panel for use in imputation. Imputation was then conducted using the reference panel and data from 82 publically available Japanese samples with gene expression data. The accuracy of the deletion calling and imputation was examined with Nanopore long-read sequencing technology. We also conducted an expression quantitative trait loci (eQTL) association analysis using the deletions to infer their functional impacts on genes, before characterizing the deletions causal for gene expression level changes. We obtained a set of polymorphic 4378 high-confidence deletions and constructed a reference panel. The deletions were successfully imputed into the Japanese samples with high accuracy (97.3%). The eQTL analysis identified 181 deletions (4.1%) suggested as causal for gene expression level changes. The causal deletion candidates were significantly enriched in promoters, super-enhancers, and transcription elongation chromatin states. Generation of deletions in a cell line with the CRISPR-Cas9 system confirmed that they were indeed causative variants for gene expression change. Furthermore, one of the deletions was observed to affect the gene expression levels of a gene it was not located in. This paper reports an accurate deletion calling method for genotype imputation at the whole genome level and shows the importance of intermediate-sized deletions in the human population.
Improved techniques to localize foci of carcinoma within the prostate using high-resolution transrectal gamma imaging (TRGI) of monoclonal antibody directed at prostate specific membrane antigen (PSMA).
Authors: Benjamin L. Franc, Yonggang Cui, Seth A Rosenthal, Tammie Johnston, Uday Poonamallee, Jason B Wiesner, Kristen MN Vandewalker, Youngho Seo, Terrance Lall, Ralph James
Journal: Journal of Clinical Oncology (2012)

e21026 Background: As many as 40% of prostate cancers may be missed on biopsy, necessitating novel methods for biopsy guidance. There is also interest in mapping primary prostate cancers for treatment. The presented work evaluated the ability of a transrectal gamma-imaging (TRGI) device to detect and localize a prostate-specific membrane antigen (PSMA) - specific radiopharmaceutical in the prostate. Methods: The IRB approved this exploratory proof-of-concept study. Male patients with untreated, biopsy-proven prostatic adenocarcinoma received 5±0.5 mCi In-111 capromab pendetide (Prostascint, a PSMA-specific agent) i.v. and were imaged 4 days later using single photon emission computed tomography (SPECT-CT). A commercially available cadmium zinc telluride (CZT)-based endorectal gamma camera (ProxiScan TM , Hybridyne Imaging Technologies, Inc.) determined the radiopharmaceutical’s planar distribution (1.5x4 cm FOV; 5 min acquisition) in four prostatic quadrants. Safety assessments occurred day 1 and 7. MRI was acquired within 14 days. Pathology from TRUS biopsy or following prostatectomy identified prostatic quadrants containing adenocarcinoma. Results: Of 8 patients recruited, 6 completed imaging, all without adverse event. Subsequent treatment included prostatectomy (n=3) and radiation (n=3). Twenty-three prostatic quadrants were evaluated. In detecting a cancer-containing quadrant, TRGI, SPECT, and MRI had sensitivities of 100%, 75%, and 33%, respectively, and similar accuracy (61-70%). Target-to-background signal ratio of TRGI was independent of serum PSA level and not significantly different than SPECT. TRGI identified a greater number of foci in each quadrant when compared with SPECT (p&lt;0.001). Lesion sizes on TRGI were smaller (p=0.04) and correlated with cancer size on pathology in patients treated surgically (r=0.69), identifying tracer uptake associated with tumors ≥ 5 mm. Conclusions: TRGI provides improved localization of prostate carcinoma compared with conventional SPECT with potential implications for the diagnosis and treatment of prostate cancer.