tbuckley/cabot-search huggingface dataset:
Complete Responses in the TEMPI Syndrome after Treatment with Daratumumab
Authors: David B Sykes, Wilfried Schroyens
Journal: New England Journal of Medicine (2018)

Daratumumab in the TEMPI Syndrome Patients with the TEMPI syndrome often have a response to bortezomib or autologous hematopoietic stem-cell transplantation. In two patients with disease that relap...
Training for our digital future: a human-centered design approach to graduate medical education for aspiring clinician-innovators
Authors: Jocelyn Carter, Yanik J. Bababekov, Maulik D. Majmudar
Journal: npj Digital Medicine (2018)

In the current era of value-based healthcare with increasing emphasis on delivering higher quality care at lower costs, US healthcare innovation as a metric is at a premium. However, an implementation gap exists between technology-enabled innovations and patient-centered care secondary to a lack of formal training rooted in implementation science, healthcare operations, and clinical informatics for healthcare providers. We illustrate the application of human-centered design principles with focus on medical trainees as the end-user in a unique approach to developing clinician-innovators best suited to bridge the implementation gap.
Therapeutic interleukin-6 blockade reverses transforming growth factor-beta pathway activation in dermal fibroblasts: insights from the faSScinate clinical trial in systemic sclerosis
Authors: Christopher P Denton, Voon H Ong, Shiwen Xu, Haiyin Chen-Harris, Zora Modrusan, Robert Lafyatis, Dinesh Khanna, Angelika Jahreis, Jeffrey Siegel, Thierry Sornasse
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Skin fibrosis mediated by activated dermal fibroblasts is a hallmark of systemic sclerosis (SSc), especially in the subset of patients with diffuse disease. Transforming growth factor-beta (TGFβ) and interleukin-6 (IL-6) are key candidate mediators in SSc. Our aim was to elucidate the specific effect of IL-6 pathway blockade on the biology of SSc fibroblasts in vivo by using samples from a unique clinical experiment—the faSScinate study—in which patients with SSc were treated for 24 weeks with tocilizumab (TCZ), an IL-6 receptor-α inhibitor. Methods We analysed the molecular, functional and genomic characteristics of explant fibroblasts cultured from matched skin biopsy samples collected at baseline and at week 24 from 12 patients receiving placebo (n=6) or TCZ (n=6) and compared these with matched healthy control fibroblast strains. Results The hallmark functional and molecular-activated phenotype was defined in SSc samples and was stable over 24 weeks in placebo-treated cases. RNA sequencing analysis robustly defined key dysregulated pathways likely to drive SSc fibroblast activation in vivo. Treatment with TCZ for 24 weeks profoundly altered the biological characteristics of explant dermal fibroblasts by normalising functional properties and reversing gene expression profiles dominated by TGFβ-regulated genes and molecular pathways. Conclusions We demonstrated the exceptional value of using explant dermal fibroblast cultures from a well-designed trial in SSc to provide a molecular framework linking IL-6 to key profibrotic pathways. The profound impact of IL-6R blockade on the activated fibroblast phenotype highlights the potential of IL-6 as a therapeutic target in SSc and other fibrotic diseases. Trial registration number NCT01532869 ; Post-results.
Complex roles of the old drug aspirin in cancer chemoprevention and therapy
Authors: Hui Hua, Hongying Zhang, Qingbin Kong, Jiao Wang, Yangfu Jiang
Journal: Medicinal Research Reviews (2018)

Abstract The nonsteroidal anti‐inflammatory agent aspirin is widely used for preventing and treating cardiovascular and cerebrovascular diseases. In addition, epidemiologic evidences reveal that aspirin may prevent a variety of human cancers, while data on the association between aspirin and some kinds of cancer are conflicting. Preclinical studies and clinical trials also reveal the therapeutic effect of aspirin on cancer. Although cyclooxygenase is a well‐known target of aspirin, recent studies uncover other targets of aspirin and its metabolites, such as AMP‐activated protein kinase, cyclin‐dependent kinase, heparanase, and histone. Accumulating evidence demonstrate that aspirin may act in different cell types, such as epithelial cell, tumor cell, endothelial cell, platelet, and immune cell. Therefore, aspirin acts on diverse hallmarks of cancer, such as sustained tumor growth, metastasis, angiogenesis, inflammation, and immune evasion. In this review, we focus on recent progress in the use of aspirin for cancer chemoprevention and therapy, and integratively analyze the mechanisms underlying the anticancer effects of aspirin and its metabolites. We also discuss mechanisms of aspirin resistance and describe some derivatives of aspirin, which aim to overcome the adverse effects of aspirin.
DNA repair processes are critical mediators of p53-dependent tumor suppression
Authors: Ana Janic, Liz J. Valente, Matthew J. Wakefield, Leon Di Stefano, Liz Milla, Stephen Wilcox, Haoyu Yang, Lin Tai, Cassandra J. Vandenberg, Andrew J. Kueh, Shinsuke Mizutani, Margs S. Brennan, Robyn L. Schenk, Lisa M. Lindqvist, Anthony T. Papenfuss, Liam O’Connor, Andreas Strasser, Marco J. Herold
Journal: Nature Medicine (2018)
Returning to school: Parent preferences, perceptions, and preparedness.
Authors: Kathy Ruble, Juliana Pare-Blagoev, Lisa Jacobson, Allison Martin, Stacy Cooper
Journal: Journal of Clinical Oncology (2018)

72 Background: Neurocognitive late-effects (LE) are among the most pervasive complications of childhood cancer and can impact academic success. Successful transition back to school can be challenging and requires parents to be knowledgeable of potential LE and procedures necessary to secure support services. It can be unclear which oncology provider has responsibility for ensuring parents have such knowledge. Further, little is known about parent preferences, perceptions, or preparedness regarding neurocognitive LE and available supports. Methods: As part of a PCORI-funded engagement award, an online parent survey was developed and disseminated about neurocognitive LE and school-related challenges after treatment. Survey items were informed by qualitative analysis of parent interviews and stakeholder input. Parents were recruited nationally via stakeholder social media, and foundation emails and websites. Results: Of the 202 parents responding, 53% reported receiving information on possible treatment related cognitive or school problems from their healthcare team, while 55% reported needing to seek information independently. Information was most often provided by the oncologist (32%), nurse/social worker (26%), or psychologist/neuropsychologist (17%). Parent preferences for topics included information on learning difficulties, physical/health problems that could impact school, and resources for neurocognitive LE. Approximately half (55%) thought their healthcare team understood the issues facing survivors returning to school, although 47% reported that the team did not inquire about school issues or only asked general questions during follow up visits. A large proportion of parents (49%) reported feeling generally underprepared for their childs return to school. Additional information on parent preferences as well as implications for program development, advocacy, and transition procedures will be discussed. Conclusions: Oncology providers are on the frontline of educating and preparing parents to meet the challenges of childrens return to school after childhood cancer. Improved multidisciplinary services and coordination of care to ensure successful transition back to school are needed.
Expanded base editing in rice and wheat using a Cas9-adenosine deaminase fusion
Authors: Chao Li, Yuan Zong, Yanpeng Wang, Shuai Jin, Dingbo Zhang, Qianna Song, Rui Zhang, Caixia Gao
Journal: Genome biology (2018)

Nucleotide base editors in plants have been limited to conversion of cytosine to thymine. Here, we describe a new plant adenine base editor based on an evolved tRNA adenosine deaminase fused to the nickase CRISPR/Cas9, enabling A•T to G•C conversion at frequencies up to 7.5% in protoplasts and 59.1% in regenerated rice and wheat plants. An endogenous gene is also successfully modified through introducing a gain-of-function point mutation to directly produce an herbicide-tolerant rice plant. With this new adenine base editing system, it is now possible to precisely edit all base pairs, thus expanding the toolset for precise editing in plants.
An epsilon wave on electrocardiogram
Authors: Daniel B Petrov
Journal: BMJ (2018)

A 39 year old man with no history of heart disease was admitted with symptoms of palpitations and weakness lasting for several hours. An electrocardiogram (ECG) showed a wide complex tachycardia with left bundle branch block morphology, consistent with sustained ventricular tachycardia of right ventricular origin. Because of continuing haemodynamic instability, the patient was cardioverted to sinus rhythm with a single 200 J shock. The post-cardioversion ECG (fig 1) showed inverted T-waves in leads V1-V3, with QRS complex duration of 112 ms, and prolonged S-waves upstroke of 55 ms. Increased amplitude ECG showed waves with a small spike upward in lead V …
PTH-128 Low fodmaps diet in ibs is more effective for constipation than other symptoms in joint hyperombiolty syndrome
Authors: KC Fragkos, A Cox, J Barragry, J Eady, K Keetarut, N Zarate-Lopez, A Emmanuel
Journal: Gut (2017)

Introduction  A low FODMAPs diet is now an established strategy for the management of irritable bowel syndrome (IBS). Patients with joint hypermobility syndrome (JHS), a non-inflammatory connective tissue disorder, frequently report functional gut symptoms, often fulfilling criteria for IBS. A low FODMAPs diet effect is known to reduce bowel distension and gas generation secondary to modified food fermentation, impacting on visceral hypersensitivity, and hence potentially improving pain in IBS.  Method  Consecutive patients fulfilling the Rome III criteria for IBS referred to a dedicated dietician clinic for implementation of the low FODMAP diet were included in the study. Patients who completed low FODMAPs dietary education therapy were analysed. Symptoms were assessed at baseline and follow up (median 63 days post-treatment) via self-administered questionnaire. The primary endpoint was a symptom severity score (scale 0–5) based on pain, bloating, constipation and diarrhoea. Patients with a positive diagnosis of JHS made by an experienced rheumatologist were identified.  Results  170 patients (135 F, age 43±14 years) were included in the analysis of whom 35 (34 F) had JHS. This female preponderance of comorbid JHS and IBS was statistically significant (p=0.003). A disproportionately larger proportion of patients with both JHS and IBS had constipation-predominant IBS than other subtypes (p  Conclusion  In this cohort, there is a difference in IBS subtypes between patients with and without JHS, with IBS-C being especially prevalent in JHS patients. A low FODMAPs diet is effective in improving symptoms in patients with IBS and JHS. In particular, pain and constipation are especially improved in patients with JHS.  Disclosure of Interest  None Declared
Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis
Authors: Carla Winter, Carlos Silvestre-Roig, Almudena Ortega-Gomez, Patricia Lemnitzer, Hessel Poelman, Ariane Schumski, Janine Winter, Maik Drechsler, Renske de Jong, Roland Immler, Markus Sperandio, Michael Hristov, Tanja Zeller, Gerry A.F. Nicolaes, Christian Weber, Joana R. Viola, Andres Hidalgo, Christoph Scheiermann, Oliver Soehnlein
Journal: Cell Metabolism (2018)
Molecular subtype assay to reveal anti-EGFR response sub-clones in colorectal cancer (CRC).
Authors: Elisa Fontana, Gift Nyamundanda, David Cunningham, Chanthirika Ragulan, Francesco Sclafani, Katherine Eason, Maria Antonietta Bali, Ines Vendrell, Yatish Patil, Sanna Hulkki Wilson, Jenkev Samantha Sing Yu Moorcraft, Ruwaida Begum, Ian Chau, Naureen Starling, Anguraj Sadanandam
Journal: Journal of Clinical Oncology (2018)

658 Background: We previously stratified CRC into five intrinsic gene expression subtypes (CRCAssigner) and four consensus molecular subtypes (CMS1-4) using expensive and time-consuming microarray/RNAseq platforms. Recently, we developed a low-cost (NanoCRC) assay using nCounter platform (NanoString Technology) and robust gene signatures to classify individual samples into both CRCAssigner and CMS subtypes. Here, we tested the assays using formalin-fixed paraffin-embedded (FFPE) patient samples from Royal Marsden Hospital. Given increased sensitivity to cetuximab in one of our CRCAssigner subtypes transit-amplifying (TA) that represents partly CMS2 subtype, we associated anti-EGFR response to the presence of TA sub-clones. Methods: FFPE from resected and biopsy CRC samples were profiled for our NanoCRC assay. Along with our single-sample subtyping method, we developed a tool to identify sub-clones of TA within individual samples. RAS/BRAF wild-type patients treated with single agent anti-EGFR therapy were statistically associated with sub-clonal molecular profiles, sidedness and single gene expression. Results: NanoCRC assay was highly reproducible with &gt; 0.9 correlation coefficient. Among 76 samples (from 64 patients), all the five CRCAssigner, four CMS subtypes (including the mixed samples) and their associations with RAS/BRAF mutations were successfully identified. Subtype-mutational associations were similar to our previous publications. Among 15 KRAS/BRAF wild-type (wt) patients with single agent anti-EGFR therapy response data, TA sub-clone was identified in 7/9 with clinical benefit and 1/6 with no benefit (p &lt; 0.05). The other sub-clones, sidedness and individual genes within the panels were not significantly associated. This TA sub-clone association was further confirmed using a publicly available cetuximab response data (39 KRAS wt; Khambata-Ford data; p=0.02). Conclusions: Overall, we developed a robust NanoCRC assay to classify CRC FFPE samples in to molecular subtypes. With caveat of small numbers, the presence of TA sub-clones is significantly associated with cetuximab response. Extensive validation is warranted.
Despite Educational Campaigns, US Infants Are Still Dying Due to Unsafe Sleep Conditions
Authors: Rita Rubin
Journal: JAMA (2018)

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
Serotonin Transporter Gene Association Between Anxiety and Long-Term Cardiac Outcomes in Acute Coronary Syndromes
Authors: Jae-Min Kim, Robert Stewart, Ju-Wan Kim, Hee-Ju Kang, Kyung-Yeol Bae, Sung-Wan Kim, Young Joon Hong, Youngkeun Ahn, Myung Ho Jeong, Jin-Sang Yoon
Journal: Journal of the American College of Cardiology (2018)

Anxiety is common in acute coronary syndromes (ACS), but its influence on long-term cardiac prognosis is unclear, as is the influence of genetic susceptibility [(1)][1]. The serotonin transporter (5-HTT) gene has potential effects on both anxiety and ACS, influencing both the central nervous and
Seeing results: Outcomes from offering breast cancer survivorship care for more than 10 years.
Authors: Andrew Joseph Ward, Jillian Lloyd, Emily Pospiech, Cystal Wheelon, Amila Orucevic, John Lawrence Bell
Journal: Journal of Clinical Oncology (2018)

32 Background: The University of Tennessee Medical Center (UTMCK), Knoxville Tennessee is the region’s sole academic medical center. Annually, 3000 new patients are seen within the Cancer Institute (CI) of UTMCK, and over 13% are breast cancer patients. Under the leadership of our director, Surgical Oncologist Dr. John L. Bell, survivorship care has been offered to these patients for almost twenty years. This combination has created a unique opportunity for us to look at long term results of offering disease-specific survivorship care, and what effect it has made upon detection of recurrence. Methods: Tumor registry data was utilized to examine the influence of survivorship care upon detection of recurrence. All patients treated from 1999 – 2015 with a diagnosis of recurrent breast cancer were selected out of the tumor registry. These patients were then stratified by time to recurrence, and mean, median, and range were calculated in time to recurrence (TR) by month. Results: A total of 223 patients with recurrent breast cancer were identified in our tumor registry out of 4422 total breast cancer patients treated by UTMCK from 1999 – 2015, recurrence rate of 5.04%. The mean TR for this cohort was 43.9 months. The median TR was 33 months, and the range of TR varied from 4 months to 166 months. All patients were followed for a minimum of five years following their diagnosis, and by 60 months, 73.99% of all recurrences were identified. Conclusions: Offering disease specific survivorship care to breast cancer patients is beneficial to both patients and our institution. When recurrence is diagnosed, survivorship care is valuable by helping to identify these cases as early as possible, to get patients back into active treatment sooner in the disease process. We have demonstrated that this is not a recent phenomenon reflective of current practice changes and accreditation requirements, and have validated this with our institution’s long history of providing survivorship care services for breast cancer patients dating back to the last century.
Twist1 Regulates Vimentin through Cul2 Circular RNA to Promote EMT in Hepatocellular Carcinoma
Authors: Jing Meng, Shuang Chen, Jing-Xia Han, Baoxin Qian, Xiao-Rui Wang, Wei-Long Zhong, Yuan Qin, Heng Zhang, Wan-Feng Gao, Yue-Yang Lei, Wei Yang, Lan Yang, Chao Zhang, Hui-Juan Liu, Yan-Rong Liu, Hong-Gang Zhou, Tao Sun, Cheng Yang
Journal: Cancer Research (2018)

Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1 in vitro and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.Significance: A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg Cancer Res; 78(15); 4150-62. ©2018 AACR.
Breast cancer stem cell autoantibodies to identify women with advanced breast cancer.
Authors: Sasha E. Stanton, Denise L Cecil, Megan Marie O'Meara, Jennifer S Childs, Mary L. Disis
Journal: Journal of Clinical Oncology (2018)

1079 Background: Cancer stem cells have properties of self-renewal, inducing drug resistance, and metastases. Breast cancer stem cells (BCSC) are associated with epithelial to mesenchymal transformation (EMT), increased invasiveness, and metastases. We identified a panel of BCSC proteins involved in EMT that predicted aggressive disease and could be targets for breast cancer vaccines. A therapeutic vaccine of five of the BCSC antigens is currently in a phase 1 clinical trial (NCT02157051) in breast cancer patients. We now demonstrate that autoantibodies of eight BCSC proteins (CDC25b, YB1, CD105, SOX2, CDH3, HIF1alpha, Survivin, and MDM2) identify women with increasing disease in breast cancer and may be a marker of progression of disease. Methods: Autoantibodies were evaluated by ELISA from sera of 253 individuals, 100 individuals with no breast atypia, 124 individuals with stage I and II invasive breast cancer (IBC), and 29 individuals with stage III and IV IBC. A positive autoantibody response was greater than 2 standard deviations above the mean of individuals with no IBC (control). Results: The percentage of individuals with a positive autoantibody response increased between control and stage I/II IBC and/or stage III/IV in 6 of the 8 autoantibodies. For example with CDC25b, there was 2% positive autoantibody response in control individuals, 13.7% in individuals with stage I/II IBC (p = 0.0014), and 17.2% of individuals with stage III/IV breast cancer (p = 0.0064). There were no differences in mean autoantibodies between breast cancer subtypes except increased autoantibodies to HIF1 alpha in ER+ HER2- disease as compared to HER2+ disease (p = 0.01). The panel of 8 autoantibodies predicted patients with stage I/II IBC from control individuals with AUC of 0.66 (95% CI 0.589 to 0.732, p < 0.0001). The panel could predict patients with III/IV IBC from control individuals with AUC of 0.84 (95% CI 0.0.753 to 0.931, p < 0.0001). Conclusions: These data demonstrate an increasing humoral immune response against 8 BCSC proteins at higher stages of breast cancer and suggests that these autoantibodies indicate more aggressive disease. Future studies will prospectively evaluate the antibody panel as a biomarker for breast cancer progression.