tbuckley/cabot-search huggingface dataset:
Annals Story Slam - Innovations: Practices That Build Trust - Transparency and Public Reporting
Authors: Christopher Queram
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Innovations: Practices That Build Trust - Transparency and Public ReportingFREEChristopher QueramChristopher QueramWCHQ, Madison, Wisconsin (C.Q.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0005 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Innovations: Practices That Build Trust - Transparency and Public Reporting "Innovations: Practices That Build Trust - Transparency and Public Reporting," by Christopher Queram (Duration 4:13)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: WCHQ, Madison, Wisconsin (C.Q.)Current Author Address: Christopher Queram, WCHQ, 301 Westfield Road, Madison, WI 53717; e-mail, [email protected]org PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1 ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
Dll4 Suppresses Transcytosis for Arterial Blood-Retinal Barrier Homeostasis
Authors: Jee Myung Yang, Chan Soon Park, Soo Hyun Kim, Tae Wook Noh, Ju-Hee Kim, Seongyeol Park, Jingu Lee, Jang Ryul Park, Dohyun Yoo, Hyun Ho Jung, Hiroshi Takase, David T. Shima, Markus Schwaninger, Seungjoo Lee, Il-Kug Kim, Junyeop Lee, Yong-Sok Ji, Sangyong Jon, Wang-Yuhl Oh, Pilhan Kim, Akiyoshi Uemura, Young Seok Ju, Injune Kim
Journal: Circulation Research (2020)

Rationale: Central nervous system has low vascular permeability by organizing tight junction (TJ) and limiting endothelial transcytosis. While TJ has long been considered to be responsible for vascular barrier in central nervous system, suppressed transcytosis in endothelial cells is now emerging as a complementary mechanism. Whether transcytosis regulation is independent of TJ and its dysregulation dominantly causes diseases associated with edema remain elusive. Dll4 signaling is important for various vascular contexts, but its role in the maintenance of vascular barrier in central nervous system remains unknown. Objective: To find a TJ-independent regulatory mechanism selective for transcytosis and identify its dysregulation as a cause of pathological leakage. Methods and Results: We studied transcytosis in the adult mouse retina with low vascular permeability and employed a hypertension-induced retinal edema model for its pathological implication. Both antibody-based and genetic inactivation of Dll4 or Notch1 induce hyperpermeability by increasing transcytosis without junctional destabilization in arterial endothelial cells, leading to nonhemorrhagic leakage predominantly in the superficial retinal layer. Endothelial Sox17 deletion represses Dll4 in retinal arteries, phenocopying Dll4 blocking-driven vascular leakage. Ang II (angiotensin II)–induced hypertension represses arterial Sox17 and Dll4, followed by transcytosis-driven retinal edema, which is rescued by a gain of Notch activity. Transcriptomic profiling of retinal endothelial cells suggests that Dll4 blocking activates SREBP1 (sterol regulatory element-binding protein 1)-mediated lipogenic transcription and enriches gene sets favorable for caveolae formation. Profiling also predicts the activation of VEGF (vascular endothelial growth factor) signaling by Dll4 blockade. Inhibition of SREBP1 or VEGF-VEGFR2 (VEGF receptor 2) signaling attenuates both Dll4 blockade–driven and hypertension-induced retinal leakage. Conclusions: In the retina, Sox17-Dll4-SREBP1 signaling axis controls transcytosis independently of TJ in superficial arteries among heterogeneous regulations for the whole vessels. Uncontrolled transcytosis via dysregulated Dll4 underlies pathological leakage in hypertensive retina and could be a therapeutic target for treating hypertension-associated retinal edema.
Autophagy Modulated by Inorganic Nanomaterials
Authors: Lingling Guo, Nongyue He, Yongxiang Zhao, Tonghua Liu, Yan Deng
Journal: Theranostics (2020)

With the rapid development of nanotechnology, inorganic nanomaterials (NMs) have been widely applied in modern society.As human exposure to inorganic NMs is inevitable, comprehensive assessment of the safety of inorganic NMs is required.It is well known that autophagy plays dual roles in cell survival and cell death.Moreover, inorganic NMs have been proven to induce autophagy perturbation in cells.Therefore, an in-depth understanding of inorganic NMs-modulated autophagy is required for the safety assessment of inorganic NMs.This review presents an overview of a set of inorganic NMs, consisting of iron oxide NMs, silver NMs, gold NMs, carbon-based NMs, silica NMs, quantum dots, rare earth oxide NMs, zinc oxide NMs, alumina NMs, and titanium dioxide NMs, as well as how each modulates autophagy.This review emphasizes the potential mechanisms underlying NMs-induced autophagy perturbation, as well as the role of autophagy perturbation in cell fate determination.Furthermore, we also briefly review the potential roles of inorganic NMs-modulated autophagy in diagnosis and treatment of disease.
Risk stratification in pediatric low-grade glioma and glioneuronal tumor treated with radiation therapy: an integrated clinicopathologic and molecular analysis
Authors: Sahaja Acharya, Jo-Fen Liu, Ruth G Tatevossian, Jason Chiang, Ibrahim Qaddoumi, Amar Gajjar, David Walker, Julie H Harreld, Thomas E Merchant, David W Ellison
Journal: Neuro-Oncology (2020)

Management of unresectable pediatric low-grade glioma and glioneuronal tumor (LGG/LGGNT) is controversial. There are no validated prognostic features to guide use of radiation therapy (RT). Our study aimed to identify negative prognostic features in patients treated with RT using clinicopathologic and molecular data and validate these findings in an external dataset.Children with non-metastatic, biopsy-proven unresectable LGG/LGGNT treated with RT at a single institution between 1997 and 2017 were identified. Recursive partitioning analysis (RPA) was used to stratify patients into low- and high-risk prognostic groups based on overall survival (OS). CNS9702 data were used for validation.One hundred and fifty patients met inclusion criteria. Median follow-up was 11.4 years. RPA yielded low- and high-risk groups with 10-year OS of 95.6% versus 76.4% (95% CI: 88.7%-98.4% vs 59.3%-87.1%, P = 0.003), respectively. These risk groups were validated using CNS9702 dataset (n = 48) (4-year OS: low-risk vs high-risk: 100% vs 64%, P < 0.001). High-risk tumors included diffuse astrocytoma or location within thalamus/midbrain. Low-risk tumors included pilocytic astrocytoma/ganglioglioma located outside of the thalamus/midbrain. In the subgroup with known BRAF status (n = 49), risk stratification remained prognostic independently of BRAF alteration (V600E or fusion). Within the high-risk group, delayed RT, defined as RT after at least one line of chemotherapy, was associated with a further decrement in overall survival (P = 0.021).A high-risk subgroup of patients, defined by diffuse astrocytoma histology or midbrain/thalamus tumor location, have suboptimal long-term survival and might benefit from timely use of RT. These results require validation.
Abstract P3-07-09: The preoperative systemic inflammatory response as a strong prognostic factor in breast cancer patients
Authors: Nami Yamashita, Sayuri Akiyoshi, Eiki Sano, Tomoko Shigechi, Yuichi Hisamatsu, Eriko Tokunaga, Eiji Oki, Masaki Mori
Journal: Cancer Research (2020)

Abstract Background: Recent reports show that the preoperative systemic inflammatory response status correlate with the survival rate in cancer patients. The Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT), Neutrophil Lymphocyte Ratio (NLR) and Platelet Lymphocyte Ratio (PLR) score are used as screening tools for immunonutritional status and reported to be a predictor of postoperative recurrence in patients with various gastrointestinal cancers. However, the clinical importance of these scoring in breast cancer has not been fully elucidated. The aim of this study is to investigate the clinical impact of preoperative systemic inflammatory response on long-term survival of breast cancer patients. Patients and Methods: We retrospectively analyzed 653 consecutive stage I-III breast cancer patients who were treated from January 2002 to December 2013. The PNI score was calculated as 10 x serum albumin (g/dl) + 0.005 x total lymphocyte count (per mm3). The CONUT score is calculated from three parameters, serum albumin, cholesterol, and total lymphocytes count. The patients were divided into two groups according to each value. The uni- and multivariate Cox regression analyses were performed to evaluate the prognositic value of the systemic inflammatory response in breast cancer. Results: The malnutritional or high SIR status was observed in 170 (26%),131 (20%), 119 (18%) and 226 (35%) patients as low-PNI, high-CONUT, elevated NLR and PLR, respectively. The relapse-free survival (RFS) and overall survival (OS) rates were significantly lower in the low-PNI group (RFS: p&amp;lt;0.0001, OS: p&amp;lt;0.0001) and high-CONUT group (RFS: p=0.0009, OS: p=0.0018). No significant association was found between NLR, PLR and prognosis. In the multivariate analysis, low-PNI was the independent prognostic factors for OS (HR4.71, p=0.0023). In the subset analysis, the low-PNI group showed poor prognosis especially in the postmenopausal, hormone receptor negative patients. The low-PNI also had poorer prognosis in post-recurrence survival. Conclusions: The preoperative systemic inflammatory response, especially PNI, is a strong independent predictor of long-term survival among breast cancer patients. Citation Format: Nami Yamashita, Sayuri Akiyoshi, Eiki Sano, Tomoko Shigechi, Yuichi Hisamatsu, Eriko Tokunaga, Eiji Oki, Masaki Mori. The preoperative systemic inflammatory response as a strong prognostic factor in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-07-09.
Combination Therapy for Methicillin-Resistant <i>Staphylococcus aureus</i> Bacteremia
Authors: Tejal N. Gandhi, Preeti N. Malani
Journal: JAMA (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 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
Exome-Based Case-Control Analysis Highlights the Pathogenic Role of Ciliary Genes in Transposition of the Great Arteries
Authors: Xuanyu Liu, Wen Chen, Wenke Li, James R. Priest, Yuanyuan Fu, Kunjing Pang, Baihui Ma, Bianmei Han, Xuewen Liu, Shengshou Hu, Zhou Zhou
Journal: Circulation Research (2020)

Rationale: Transposition of the great arteries (TGA) is one of the most severe types of congenital heart diseases. Understanding the clinical characteristics and pathogenesis of TGA is, therefore, urgently needed for patient management of this severe disease. However, the clinical characteristics and genetic cause underlying TGA remain largely unexplored. Objective: We sought to systematically examine the clinical characteristics and genetic cause for isolated nonsyndromic TGA. Methods and Results: We recruited 249 patients with TGA (66 family trios) and performed whole-exome sequencing. The incidence of patent ductus arteriosus in dextro-TGA (52.7%) and dextrocardia/mesocardia in congenitally corrected TGA (32.8%) were significantly higher than that in other subtypes. A high prevalence of bicuspid pulmonic valve (9.6%) was observed in patients with TGA. Similar results were observed in a replication group of TGA (n=132). Through a series of bioinformatics filtering steps, we obtained 82 candidate genes harboring potentially damaging de novo, loss of function, compound heterozygous, or X-linked recessive variants. Established congenital heart disease–causing genes, such as FOXH1 , were found among the list of candidate genes. A total of 19 ciliary genes harboring rare potentially damaging variants were also found; for example, DYNC2LI1 with a de novo putatively damaging variant. The enrichment of ciliary genes supports the roles of cilia in the pathogenesis of TGA. In total, 33% of the TGA probands had &gt;1 candidate gene hit by putatively deleterious variants, suggesting that a portion of the TGA cases were probably affected by oligogenic or polygenic inheritance. Conclusions: The findings of clinical characteristic analyses have important implications for TGA patient stratification. The results of genetic analyses highlight the pathogenic role of ciliary genes and a complex genetic architecture underlying TGA.
Abstract P5-12-10: Tamoxifen versus anastrozole as adjuvant therapy in early stage breast cancer in premenopausal women on ovarian function suppression: A meta-analysis of randomized clinical trials
Authors: Shima Sidahmed, Ahmed Abdalla, Babikir Kheiri, Ghassan Bachuwa
Journal: Cancer Research (2020)

Abstract Introduction: Different strategies have been studied in adjuvant treatment for hormone positive early stage breast cancer. The addition of ovarian function suppression (OFS) therapy to Tamoxifen in premenopausal women was proven to prolong disease-free survival and overall survival compared with Tamoxifen alone. However, trials that examined the use of anastrozole inhibitor (AI) in the presence of OFS in comparison to Tamoxifen with OFS showed contradicting results. Therefore, we conducted this meta-analysis of randomized clinical trials (RCTs) comparing these two approaches. Methods: A comprehensive search of the electronic database (PubMed) from inception to July 2019 was conducted to identify all RCTs that compared OFS with Tamoxifen versus OFS with AI in premenopausal females with breast cancer. The primary endpoint was event-free survival, defined as females without events (local or distant recurrence, cancer in the contralateral breast, secondary non-breast malignancy, or death) at the longest follow-up duration. The secondary endpoints were death, the incidence of distant metastasis, and the incidence of contralateral breast cancer. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for all dichotomous data. Heterogeneity was explored by the Cochran Q statistic and I-squared (I2) statistic. P-values &amp;lt;0.05 were considered statistically significant. Results: We included 4 RCTs with 7,202 total patients (mean age 43.8). At baseline, T1 disease represented 53.5% and nodal positive disease was 44.5%. After a median follow-up period of 78 months, there was a non-significant reduction of event-free survival with the AI group compared with the Tamoxifen group (OR=1.13; 95% CI=0.87-1.47; P=0.37). In addition, there were no significant differences between both groups with regard to deaths (OR=1.11; 95% CI=0.50-2.47; P=0.8). The incidence of distant metastasis did not differ between both groups (OR=1.02; 95% CI=0.82-1.26; P=0.86). Similarly, there were no differences in the incidence of contralateral breast cancer between both groups (OR=1.30; 95% CI=0.86-1.96; P=0.21). Conclusions: Among premenopausal women with early breast cancer, the use of AI plus OFS versus Tamoxifen plus OFS was not associated with significantly reduced event-free survival. Given the limited number of RCTs and low events, further, adequately powered trials are needed to validate this finding. Citation Format: Shima Sidahmed, Ahmed Abdalla, Babikir Kheiri, Ghassan Bachuwa. Tamoxifen versus anastrozole as adjuvant therapy in early stage breast cancer in premenopausal women on ovarian function suppression: A meta-analysis of randomized clinical trials [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-10.
Circular RNA-ZBTB44 regulates the development of choroidal neovascularization
Authors: Rong-mei Zhou, Lian-jun Shi, Kun Shan, Ya-nan Sun, Shan-shan Wang, Shu-jie Zhang, Xiu-miao Li, Qin Jiang, Biao Yan, Chen Zhao
Journal: Theranostics (2020)

Rationale: Choroidal neovascularization (CNV) is a major cause of severe vision loss and occurs in many ocular diseases, especially neovascular age-related macular degeneration (nAMD).Circular RNAs (circRNAs) are emerging as a new class of endogenous noncoding RNAs, which have been implicated in the regulation of endothelial cell dysfunction in diabetes mellitus and cancer.In this study, we aimed to determine the role of circRNA-ZBTB44 (cZBTB44) in the pathogenesis of CNV.Methods: Quantitative polymerase chain reaction was conducted to detect cZBTB44 expression pattern during CNV development.Isolectin B4 staining, hematoxylin and eosin (HE) staining, and choroidal sprouting assay ex vivo were conducted to evaluate the role of cZBTB44 in the development of CNV.Endothelial cell proliferation, migration and tube formation assays were conducted to determine the role of cZBTB44 in angiogenic effect in vitro.Bioinformatics analysis, RNA immunoprecipitation assay, luciferase assay, and in vitro studies were conducted to investigate the mechanism of cZBTB44-mediated CNV development.Results: cZBTB44 expression was significantly up-regulated in a laser-induced CNV mouse model in vivo and in endothelial cells upon hypoxia stress in vitro.cZBTB44 silencing retarded CNV development, while overexpression of cZBTB44 showed the opposite effects.The role of cZBTB44 in CNV development was confirmed in choroidal sprouting assay ex vivo.cZBTB44 silencing reduced endothelial cell viability, proliferation, migration and tube formation in vitro.cZBTB44 acted as miR-578 sponge to sequester and inhibit miR-578 activity, which led to increased expression of vascular endothelial growth factor A (VEGFA) and vascular cell adhesion molecule-1 (VCAM1).Overexpression of miR-578 mimicked cZBTB44 silencing-mediated anti-angiogenic effects in vivo and in vitro.Furthermore, dysregulated cZBTB44 expression was detected in the clinical samples of nAMD patients.Conclusions: This study provided novel insights into the molecular pathogenesis of CNV.The cZBTB44-miR-578-VEGFA/VCAM1 axis might be a potential source of novel therapeutic targets for neovascularization-related diseases.
Time for second-generation artificial intelligence in medical imaging
Authors: Fons van der Sommen
Journal: Endoscopy (2019)

After decades of modest successes and setbacks, it is safe to say that artificial intelligence (AI) is here to stay. Although most of the basic concepts of modern AI technology date back to the second half of the previous century, the enormous increment in data and computational power over the past decade has enabled it to demonstrate its full potential. A branch of AI known as machine learning has been responsible for most of the progress, with remarkable results: from generating hyper-realistic fake images [1] to the detection of lymph node metastases in women with breast cancer [2].
Physician Orders for Life-Sustaining Treatment and Limiting Overtreatment at the End of Life
Authors: Robert D. Truog, Terri R. Fried
Journal: JAMA (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 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
<i>N6</i>-methyladenosine-induced ERRγ triggers chemoresistance of cancer cells through upregulation of ABCB1 and metabolic reprogramming
Authors: Zhuojia Chen, Long Wu, Jiawang Zhou, Xinyao Lin, Yanxi Peng, Lichen Ge, Cheng-Ming Chiang, Hui Huang, Hongsheng Wang, Weiling He
Journal: Theranostics (2020)

Background: Drug resistance severely reduces treatment efficiency of chemotherapy and leads to poor prognosis. However, regulatory factors of chemoresistant cancer cells are largely unknown. Methods: The expression of estrogen receptor related receptors (ERRs) in chemoresistant cancer cells are checked. The roles of ERRγ in chemoresistance are confirmed by in vitro and in vivo studies. The mechanisms responsible for ERRγ-regulated expression of ABCB1 and CPT1B are investigated. Results: The expression of ERRγ is upregulated in chemoresistant cancer cells. Targeted inhibition of ERRγ restores the chemosensitivity. ERRγ can directly bind to the promoter of ABCB1 to increase its transcription. An elevated interaction between ERRγ and p65 in chemoresistant cells further strengthens transcription of ABCB1. Further, ERRγ can increase the fatty acid oxidation (FAO) in chemoresistant cells via regulation of CPT1B, the rate-limiting enzyme of FAO. The upregulated ERRγ in chemoresistant cancer cells might be due to increased levels of N6-methyladenosine (m6A) can trigger the splicing of precursor ESRRG mRNA. Conclusions: m6A induced ERRγ confers chemoresistance of cancer cells through upregulation of ABCB1 and CPT1B.
Colorectal cancer in Crohn's disease: a Scandinavian population-based cohort study
Authors: Ola Olén, Rune Erichsen, Michael C Sachs, Lars Pedersen, Jonas Halfvarson, Johan Askling, Anders Ekbom, Henrik Toft Sørensen, Jonas F Ludvigsson
Journal: The Lancet. Gastroenterology & hepatology (2020)