tbuckley/cabot-search huggingface dataset:
Factors Associated With Lymphedema in Women With Node-Positive Breast Cancer Treated With Neoadjuvant Chemotherapy and Axillary Dissection
Authors: Jane M. Armer, Karla V. Ballman, Linda McCall, Pamela L. Ostby, Eris Zagar, Henry M. Kuerer, Kelly K. Hunt, Judy C. Boughey
Journal: JAMA Surgery (2019)

Most lymphedema studies include a heterogeneous population and focus on patients treated with adjuvant chemotherapy.To examine factors associated with lymphedema after neoadjuvant chemotherapy (NAC) and axillary lymph node dissection in women with node-positive breast cancer.This cohort study included data from 701 women 18 years or older with cT0-T4N1-2M0 breast cancer with documented axillary nodal metastasis at diagnosis who were enrolled in the American College of Surgeons Oncology Group Z1071 (Alliance for Clinical Trials in Oncology) trial, which took place from January 1, 2009, to December 31, 2012. Data analysis was performed from January 11, 2018, to November 9, 2018.All participants received NAC, breast operation, and axillary lymph node dissection. Participants underwent prospective arm measurements and symptom assessment after NAC completion and at 6-month intervals to 36 months postoperatively.Factors associated with lymphedema were defined as self-reported arm heaviness or swelling (lymphedema symptoms) or an arm volume increase of 10% or more (V10) or 20% or more (V20).A total of 486 patients (mean [SD] age, 50.1 [10.8] years) were included in this study. Median follow-up for the 3 measures was 2.2 to 3.0 years. Cumulative lymphedema incidence at 3 years was 37.8% (95% CI, 33.1%-43.2%) for lymphedema symptoms, 58.4% (95% CI, 53.2%-64.1%) for V10, and 36.9% (95% CI, 31.9%-42.6%) for V20. Increasing body mass index (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06) and NAC for 144 days or longer (HR, 1.48; 95% CI, 1.01-2.17) were associated with lymphedema symptoms. The V20 incidence was higher among patients who received NAC for 144 days or longer (HR, 1.79; 95% CI, 1.19-2.68). The V10 incidence was highest in patients with 30 nodes or more removed (HR, 1.70; 95% CI, 1.15-2.52) and increased with number of positive nodes (HR, 1.03; 95% CI, 1.00-1.06). On multivariable analysis, obesity was significantly associated with lymphedema symptoms (HR, 1.03; 95% CI, 1.01-1.06), and NAC length was significantly associated with V20 (HR, 1.74; 95% CI, 1.15-2.62).In this study, longer NAC duration and obesity were associated with increased lymphedema incidence, suggesting that patients in these groups may benefit from enhanced prospective lymphedema surveillance.
Increased apolipoprotein C3 drives cardiovascular risk in type 1 diabetes
Authors: Jenny E. Kanter, Baohai Shao, Farah Kramer, Shelley Barnhart, Masami Shimizu-Albergine, Tomas Vaisar, Mark J. Graham, Rosanne M. Crooke, Clarence R. Manuel, Rebecca A. Haeusler, Daniel Mar, Karol Bomsztyk, John E. Hokanson, Gregory L. Kinney, Janet K. Snell-Bergeon, Jay W. Heinecke, Karin E. Bornfeldt
Journal: Journal of Clinical Investigation (2019)

Type 1 diabetes mellitus (T1DM) increases the risk of atherosclerotic cardiovascular disease (CVD) in humans by poorly understood mechanisms. Using mouse models of T1DM-accelerated atherosclerosis, we found that relative insulin deficiency rather than hyperglycemia elevated levels of apolipoprotein C3 (APOC3), an apolipoprotein that prevents clearance of triglyceride-rich lipoproteins (TRLs) and their remnants. We then showed that serum APOC3 levels predict incident CVD events in subjects with T1DM in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. To explore underlying mechanisms, we investigated the impact of Apoc3 antisense oligonucleotides (ASOs) on lipoprotein metabolism and atherosclerosis in a mouse model of T1DM. Apoc3 ASO treatment abolished the increased hepatic Apoc3 expression in diabetic mice - resulting in lower levels of TRLs - without improving glycemic control. APOC3 suppression also prevented arterial accumulation of APOC3-containing lipoprotein particles, macrophage foam cell formation, and the accelerated atherosclerosis in diabetic mice. Our observations demonstrate that relative insulin deficiency increases APOC3 and that this results in elevated levels of TRLs and accelerated atherosclerosis in a mouse model of T1DM. Because serum levels of APOC3 predicted incident CVD events in the CACTI study, inhibiting APOC3 might reduce CVD risk in T1DM patients.
Germline Variants in Highly Selected Patients With Prostate Cancer—In Reply
Authors: Oliver Sartor, Piper Nicolosi, Robert L. Nussbaum
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Chemoimmunotherapy for Lymphoma
Authors: Feyza Sancar
Journal: JAMA (2019)

A novel antibody-drug conjugate (ADC) for adults with refractory or relapsing diffuse large B-cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, has received accelerated FDA approval. Up to 40% of patients with DLBCL will relapse.
APE1 Upregulates MMP-14 via Redox-Sensitive ARF6-Mediated Recycling to Promote Cell Invasion of Esophageal Adenocarcinoma
Authors: Heng Lu, Ajaz A. Bhat, Dunfa Peng, Zheng Chen, Shoumin Zhu, Jun Hong, Selma Maacha, Jin Yan, David J. Robbins, M. Kay Washington, Abbes Belkhiri, Wael El-Rifai
Journal: Cancer Research (2019)

Esophageal adenocarcinoma (EAC) is an aggressive malignancy with poor clinical outcome. The incidence of EAC has been rising rapidly in the past three decades. Here, we showed that apurinic/apyrimidinic endonuclease (APE1) is overexpressed in EAC cell lines, and patients' samples of dysplasia and EAC. Downregulation of APE1 or inhibition of its redox function significantly repressed invasion. Overexpression of a redox-defective mutant, C65A, abrogated the proinvasive phenotype of APE1. APE1 regulated invasion via upregulation of matrix metalloproteinase 14 (MMP-14), which subsequently activated MMP-2, leading to degradation of the extracellular matrix in a redox-dependent manner. Downregulation of APE1 or inhibition of its redox function decreased the rate of endocytosis and recycling of MMP-14 protein. APE1 interacted with ARF6, a key regulator of MMP-14 recycling, which maintained ARF6 activity in an APE1-redox-dependent manner, promoting its ability to regulate MMP-14 recycling to the cell surface. In summary, these findings identify a novel redox-sensitive APE1-ARF6-MMP-14 signaling axis that mediates cellular invasion in esophageal carcinogenesis. SIGNIFICANCE: This study demonstrates the association between oxidative stress and the development and metastatic behavior of esophageal adenocarcinoma.
A Compound AC1Q3QWB Selectively Disrupts HOTAIR-Mediated Recruitment of PRC2 and Enhances Cancer Therapy of DZNep
Authors: Yansheng Li, Yu Ren, Yunfei Wang, Yanli Tan, Qixue Wang, Jinquan Cai, Junhu Zhou, Chao Yang, Kai Zhao, Kaikai Yi, Weili Jin, Lin Wang, Mingyang Liu, Jingxuan Yang, Min Li, Chunsheng Kang
Journal: Theranostics (2019)

Over 20% of cancer 'driver' genes encode chromatin regulators. Long noncoding RNAs (lincRNAs), which are dysregulated in various cancers, play a critical role in chromatin dynamics and gene regulation by interacting with key epigenetic regulators. It has been previously reported that the lincRNA HOTAIR mediates recruitment of polycomb repressive complex 2 (PRC2) leading to aberrant transcriptional silencing of tumor suppressor genes in glioma and breast cancer. Thus, lincRNA HOTAIR can serve as a promising therapeutic target. Herein, we identified a small-molecule compound AC1Q3QWB (AQB) as a selective and efficient disruptor of HOTAIR-EZH2 interaction, resulting in blocking of PRC2 recruitment and increasing tumor suppressors expression. Methods: Molecular docking and high-throughput screening were performed to identify the small compound, AQB. RIP and ChIRP assays were carried to assess the selective interference of AQB with the HOTAIR-EZH2 interaction. The effects of AQB on tumor malignancy were evaluated in a variety of cancer cell lines and orthotopic breast cancer models. The combination therapy of AQB and 3-Deazaneplanocin A (DZNep), an inhibitor of the histone methyltransferase EZH2 was used in vitro and in orthotopic breast cancer and glioblastoma patient-derived xenograft (PDX) models. Results: Tumor cells highly expressing HOTAIR and EZH2 were sensitive to AQB. APC2, as one of the target genes, was significantly up-regulated by AQB and led to degradation of β-catenin resulting in suppression of Wnt/β-catenin signaling which may contribute to inhibition of tumor growth and metastasis in vitro and in orthotopic breast cancer models. Remarkably, AQB enhanced the toxicity of DZNep in vitro. In orthotopic breast cancer and glioblastoma patient-derived xenografts (PDX) models, the combination of low doses of AQB and DZNep realized much better killing than DZNep treatment alone. Conclusion: AQB is a HOTAIR-EZH2 inhibitor, which blocks PRC2 recruitment and has great potential as an effective agent for targeted cancer therapy.
Tumor Mutation Burden and Prognosis in Patients with Colorectal Cancer Treated with Adjuvant Fluoropyrimidine and Oxaliplatin
Authors: Dae-Won Lee, Sae-Won Han, Jeong Mo Bae, Hoon Jang, Hyojun Han, Hyoki Kim, Duhee Bang, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Tae-You Kim
Journal: Clinical Cancer Research (2019)

Recent sequencing studies revealed that a subset of colorectal cancer harbors a significantly higher number of somatic mutations. These hypermutated tumors show distinct clinicopathologic features. However, the prognostic impact of the hypermutated tumors is not clearly established.We analyzed tumor mutation burden (TMB) from targeted next-generation sequencing data of 40 major genes in 516 patients with colorectal cancer. TMB was defined as total number of nonsynonymous mutations per tumor. Cutoff value for TMB-high was chosen by which best discriminated relapse-free survival (RFS) using the Contal and O'Quigley method.In the TCGA data, mutation count of the selected 40 genes reflected the whole exome mutation burden (Pearson correlation = 0.873, P < 0.001). In our patient cohort, 8 or more mutations in the 40 genes was defined as TMB-high, which best discriminated RFS. A total of 55 patients (10.7%) had TMB-high. TMB-high tumors were more frequently found in a proximal location (63.6%) and had a higher proportion of N0 disease (30.9%) and MSI-H (49.1%) compared with TMB-low. Most importantly, TMB-high was associated with better 5-year RFS compared with TMB-low (96.3% vs. 79.8%, P = 0.005). Although there was significant overlap between TMB-high and MSI-H, MSI-H status was not significantly associated with RFS. Multivariate analysis revealed TMB-high as an independent positive prognostic factor for RFS [adjusted HR, 0.16 (95% confidence interval, 0.04-0.66), P = 0.011].TMB-high is associated with better prognosis in patients with colorectal cancer treated with curative surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy.
Abstract 10807: Intentional Weight Loss is Associated With a Significant Improvement in Ejection Fraction in Obese Heart Failure
Authors: Jennifer J Rayner, Mark A Peterzan, Ines Abdesselam, William D Watson, Stefan Neubauer, Oliver Rider
Journal: Circulation (2018)

Introduction: Obesity and heart failure with reduced ejection fraction (HFrEF) commonly coexist. However, the parallel observations that obesity is associated with improved survival in HFrEF, and t...
Liver Graft‐Versus‐Host Disease is associated with poor survival among allogeneic hematopoietic stem cell transplant recipients
Authors: Dipenkumar Modi, Jing Christine Ye, Malini Surapaneni, Vijendra Singh, Wei Chen, Hyejeong Jang, Abhinav Deol, Lois Ayash, Asif Alavi, Voravit Ratanatharathorn, Joseph P. Uberti
Journal: American Journal of Hematology (2019)

Abstract Liver Graft‐versus‐host disease (GVHD) is common in patients with post‐transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post‐transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a “non‐liver GVHD” group, which consisted of other etiologies of post‐transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post‐transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the “non‐liver GVHD” group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time‐varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non‐relapse mortality, and adverse relapse‐free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.
University of Nottingham, UK: clinicians and non-clinicians can become a master of sport and exercise medicine (MSc) (continuing professional development series)
Authors: Katherine Rose Marino, James NF Murphy, Adam Geoffrey Culvenor
Journal: British Journal of Sports Medicine (2019)

Individuals who work in elite sport need specialised knowledge and practical skills gained through postgraduate qualifications and clinical experience.1 For doctors, physiotherapists, allied health professionals, academics and non-clinicians interested in furthering their education in SEM, The Universityof Nottingham’s MSc in Sports and Exercise Medicine (SEM) and Applied Sport and Exercise Medicine (ASEM) courses enable students to develop a depth and breadth of knowledge and experience in SEM. There are a number of high level SEM professions, elite performance teams and a diverse range of sports on offer in the East Midlands of England that the course has close links with. On completion of the MSc course, graduates have become involved in a wide range of SEM related jobs ranging from research posts to the provision of on-field medical care for professional athletes and teams.

The Master of Science (MSc) in Sports and Exercise Medicine (SEM) and the MSc in Applied Sport and Exercise Medicine (ASEM) programmes for sport and exercise medicine specialists are based at Queen’s Medical Centre, Nottingham, a large teaching hospital …
Sixty seconds on . . . vitamin drips
Authors: Abi Rimmer
Journal: BMJ (2019)

Vitamin drips. In the latest trend to sweep the “wellness” market, some people are now choosing to get their vitamin hit through “intravenous (IV) drip therapy.” Vitamin injections or “shots” are also available.

The companies offering these drips say that they have a whole host of benefits, ranging from basic hydration to anti-ageing. IV Boost UK, for example, offers …
Abstract 12005: Intracranial Plaque Enhancement From High Resolution MR and Future Stroke Recurrence
Authors: Jeong Min Kim, Keun-Hwa Jung, Chul-Ho Sohn, Jangsup Moon, Moon Hee Han, Jae-Kyu Roh
Journal: Circulation (2013)

Background & Objectives: Intracranial atherosclerosis is associated with frequent ischemic stroke recurrence. High resolution magnetic resonance imaging (HRMR) can provide intracranial atheroma inf...
Putting microbiota-gut-brain research in a systemic developmental context: Focus on breast milk
Authors: Brittany Howell, Antonella Tramacere
Journal: Behavioral and Brain Sciences (2019)

Abstract The microbiota-gut-brain (MGB) field holds huge potential for understanding behavioral development and informing effective early interventions for psychological health. To realize this potential, factors that shape the MGB axis in infancy (i.e., breast milk) must be integrated into a systemic framework that considers salient behavioral outcomes. This is best accomplished applying network analyses in large prospective, longitudinal investigations in humans.
De Novo Mutation Rate Estimation in Wolves of Known Pedigree
Authors: Evan M Koch, Rena M Schweizer, Teia M Schweizer, Daniel R Stahler, Douglas W Smith, Robert K Wayne, John Novembre
Journal: Molecular Biology and Evolution (2019)

Knowledge of mutation rates is crucial for calibrating population genetics models of demographic history in units of years. However, mutation rates remain challenging to estimate because of the need to identify extremely rare events. We estimated the nuclear mutation rate in wolves by identifying de novo mutations in a pedigree of seven wolves. Putative de novo mutations were discovered by whole-genome sequencing and were verified by Sanger sequencing of parents and offspring. Using stringent filters and an estimate of the false negative rate in the remaining observable genome, we obtain an estimate of ∼4.5 × 10-9 per base pair per generation and provide conservative bounds between 2.6 × 10-9 and 7.1 × 10-9. Although our estimate is consistent with recent mutation rate estimates from ancient DNA (4.0 × 10-9 and 3.0-4.5 × 10-9), it suggests a wider possible range. We also examined the consequences of our rate and the accompanying interval for dating several critical events in canid demographic history. For example, applying our full range of rates to coalescent models of dog and wolf demographic history implies a wide set of possible divergence times between the ancestral populations of dogs and extant Eurasian wolves (16,000-64,000 years ago) although our point estimate indicates a date between 25,000 and 33,000 years ago. Aside from one study in mice, ours provides the only direct mammalian mutation rate outside of primates and is likely to be vital to future investigations of mutation rate evolution.
Abstract 15189: Impact of Preoperative Percutaneous Pericardial Drainage on Critical Cardiac Tamponade with Acute Type A Aortic Dissection
Authors: Taro Hayashi, Takuro Tsukube, Tomonori Haraguchi, Ritsu Matsukawa, Shuichi Kozawa, Kyoichi Ogawa, Yutaka Okita
Journal: Circulation (2011)

Objectives: Cardiac tamponade is associated with fatal outcome for the patients with acute type A aortic dissection (AADA), and presence of cardiac tamponade should prompt urgent aortic repair. How...
Intranasal delivery of targeted polyfunctional gold–iron oxide nanoparticles loaded with therapeutic microRNAs for combined theranostic multimodality imaging and presensitization of glioblastoma to temozolomide
Authors: Uday K. Sukumar, Rajendran J.C. Bose, Meenakshi Malhotra, Husam A. Babikir, Rayhaneh Afjei, Elise Robinson, Yitian Zeng, Edwin Chang, Frezghi Habte, Robert Sinclair, Sanjiv S. Gambhir, Tarik F. Massoud, Ramasamy Paulmurugan
Journal: Biomaterials (2019)
Abstract 14190: Optimal Peri-endoscopic Management of Anti-thrombotic Therapy in Chinese Elderly Patients: A Retrospective Study
Authors: Hao Wang, Tao Tao, Hai-jun Wang, Yu-tao Guo, Yu-tang Wang
Journal: Circulation (2015)

Introduction: To investigate optimal timing of cessation and resumption of anti-thrombotic therapy (ATT) during gastrointestinal endoscopy in Chinese elderly patients. Methods: Between January 1st 2008 and December 31st 2014,at Chinese PLA General Hospital, 3747 patients (76.03±10.3 years) hospitalized for elective gastrointestinal endoscopy were retrospectively analyzed. The study population were predominately male(96.1%) and senile(age ≥60, 92.3%).Patients‘ peri-endoscopic management of ATT and adverse events (thromboembolism and bleeding) were recorded. RхC tables were used to compare the differences of peri-endoscopic adverse events among patients with different peri-endoscopic management of ATT. Results: the peri-endoscopic thromboembolic incidence in those with discontinuing ATT ≥7 days before procedure was significantly higher (8.12%). No difference of bleeding incidence was found among different cessation time before procedure. The peri-endoscopic thromboembolic incidence increased as the delaying of resuming ATT after procedure. However, the incidence of peri-endoscopic bleeding in patients with resuming ATT 2-7 days after procedure was lowest (0.63%). The reason why bleeding incidences in patients with resuming ATT &gt;7 days, and those without resuming ATT were much higher than those with resuming ATT 2-7 days was that occurrence of bleeding urged physician to postpone or cancel resumption of ATT. When discontinuing ATT, the differences of peri-endoscopic thromboembolic or bleeding events between patients receiving low-molecular-weight heparin bridging therapy and those without bridging therapy were not significant. Conclusions: Cessation of ATT &lt;7 days before endoscopic procedure and resumption of ATT in 2-7days after procedure were optimal peri-endoscopic ATT management strategy for Chinese elderly patients.Bridging therapy couldn’t protect elderly patients from peri-endoscopic thromboembolic events.