tbuckley/cabot-search huggingface dataset:
YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis
Authors: Hyunsoo Cho, Jaeryung Kim, Ji Hoon Ahn, Young-Kwon Hong, Taija Mäkinen, Dae-Sik Lim, Gou Young Koh
Journal: Circulation Research (2019)

The Hippo pathway governs cellular differentiation, morphogenesis, and homeostasis, but how it regulates these processes in lymphatic vessels is unknown.We aimed to reveal the role of the final effectors of the Hippo pathway, YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), in lymphatic endothelial cell (LEC) differentiation, morphogenesis, and homeostasis.During mouse embryonic development, LEC-specific depletion of Yap/Taz disturbed both plexus patterning and valve initiation with upregulated Prox1 (prospero homeobox 1). Conversely, LEC-specific YAP/TAZ hyperactivation impaired lymphatic specification and restricted lymphatic sprouting with profoundly downregulated Prox1. Notably, lymphatic YAP/TAZ depletion or hyperactivation aggravated or attenuated pathological lymphangiogenesis in mouse cornea. Mechanistically, VEGF (vascular endothelial growth factor)-C activated canonical Hippo signaling pathway in LECs. Indeed, repression of PROX1 transcription by YAP/TAZ hyperactivation was mediated by recruitment of NuRD (nucleosome remodeling and histone deacetylase) complex and endogenous binding activity of TEAD (TEA domain family members) to the PROX1 promoter. Furthermore, YAP/TAZ hyperactivation enhanced MYC signaling and inhibited CDKN1C, leading to cell cycle dysregulation and aberrant proliferation.We find that YAP and TAZ play promoting roles in remodeling lymphatic plexus patterning and postnatal lymphatic valve maintenance by negatively regulating Prox1 expression. We further show that YAP and TAZ act as plastic regulators of lymphatic identity and define the Hippo signaling-mediated PROX1 transcriptional programing as a novel dynamic checkpoint underlying LEC plasticity and pathophysiology.
Misinterpretation of Study Data
Authors: Christopher Power, Jon D. Laman, William Branton
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Sit Back and Listen — The Relevance of Patients’ Stories to Trauma-Informed Care
Authors: Dorothy R. Novick
Journal: New England Journal of Medicine (2018)

Interview with Dr. Eve Rittenberg on providing patient-centered and compassionate care for people who have experienced trauma. (11:30)Download Patients reveal their most personal and painful life experiences when we build trusting relationships and encourage open dialogue. But how can we encourage the dialogue required for trauma-informed care in today's health care climate?
Ovulation: Parallels With Inflammatory Processes
Authors: Diane M Duffy, CheMyong Ko, Misung Jo, Mats Brannstrom, Thomas E Curry
Journal: Endocrine Reviews (2018)

Abstract The midcycle surge of LH sets in motion interconnected networks of signaling cascades to bring about rupture of the follicle and release of the oocyte during ovulation. Many mediators of these LH-induced signaling cascades are associated with inflammation, leading to the postulate that ovulation is similar to an inflammatory response. First responders to the LH surge are granulosa and theca cells, which produce steroids, prostaglandins, chemokines, and cytokines, which are also mediators of inflammatory processes. These mediators, in turn, activate both nonimmune ovarian cells as well as resident immune cells within the ovary; additional immune cells are also attracted to the ovary. Collectively, these cells regulate proteolytic pathways to reorganize the follicular stroma, disrupt the granulosa cell basal lamina, and facilitate invasion of vascular endothelial cells. LH-induced mediators initiate cumulus expansion and cumulus oocyte complex detachment, whereas the follicular apex undergoes extensive extracellular matrix remodeling and a loss of the surface epithelium. The remainder of the follicle undergoes rapid angiogenesis and functional differentiation of granulosa and theca cells. Ultimately, these functional and structural changes culminate in follicular rupture and oocyte release. Throughout the ovulatory process, the importance of inflammatory responses is highlighted by the commonalities and similarities between many of these events associated with ovulation and inflammation. However, ovulation includes processes that are distinct from inflammation, such as regulation of steroid action, oocyte maturation, and the eventual release of the oocyte. This review focuses on the commonalities between inflammatory responses and the process of ovulation.
Pleural Mesothelioma Detects by 18F-Choline PET/CT in a Patient With Biochemical Recurrence of Prostate Cancer
Authors: Marco Rensi, Guido Ferretti, Fernando Di Gregorio, Laura Evangelista
Journal: Clinical Nuclear Medicine (2018)

A 73-year-old man with a prostate cancer treated by radical prostatectomy in 2006. For a biochemical recurrence of disease (prostate-specific antigen level, 0.1 ng/mL) during hormonal therapy, patient underwent F-choline PET/CT that showed a significant uptake in a diffuse right pleural thickening. The patient was sent to pleurectomy decortication showing an epithelioid pleural mesothelioma. This case highlighted that a histopathological evaluation is mandatory in case of a significant radiolabeled choline uptake in pleural lesions.
Development of a Group Judgment Process for Forecasts of Health Care Innovations
Authors: Paul G. Shekelle, Dana P. Goldman
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Health care costs have increased substantially over the past few decades, in part owing to the development and diffusion of new medical treatments. Forecasting potential future technologic innovations can allow for more informed planning. <h3>Objective</h3> To assess the predictive validity of a structured formal method for forecasting future technologic innovations in health care. <h3>Design, Setting, and Participants</h3> This pilot study combined an untested, unvalidated combination of a consensus process and group judgment process to evaluate forecasts made in 2001 for technologic innovations by 2021 in Alzheimer disease (AD) and cardiovascular disease (CVD). Six experts in AD and 7 experts in CVD composed the judgment group. The study was conducted in 2017-2018. <h3>Main Outcomes and Measures</h3> Year 2001 forecasts for 2021 that were judged by experts as being close to correct, directionally correct, or not correct, as well as innovations that occurred since 2001 that were not predicted. <h3>Results</h3> Four forecasts of innovations in AD, each considered to be between 30% and 40% likely to be achieved by 2021, were judged to be close to correct. One forecast was considered to be directionally correct, with a likelihood of occurrence of 40%, in that it was overoptimistic. One innovation that occurred was missed: new imaging techniques (amyloid β plaque and tau tangle positron emission tomographic imaging). Five forecasts of CVD innovations were considered to be at least 50% likely to occur by 2021, and of these, 2 were judged to be close to correct, 1 was judged as being directionally correct, and 2 were judged as being not correct (although in one of these forecasts, the overarching innovation has been achieved but with a different noninvasive imaging modality). Of 7 additional forecasts considered to be less likely to be achieved by 2021, 4 were judged to be close to correct and 3 were judged as being directionally correct. Two innovations occurred but were missed: transcatheter aortic valve replacement and cardiac resynchronization therapy. Across both conditions, 15 of 17 innovations forecasted were judged to be close to correct or directionally correct, 2 were judged to be incorrect, and there were 3 missed innovations. <h3>Conclusions and Relevance</h3> Expert elicitation provided a useful, but not fully accurate, lens into future innovation.
Associations between black tea and coffee consumption and risk of lung cancer among current and former smokers.
Authors: Julie A. Baker, Susan E. McCann, Mary E. Reid, Kirsten B. Moysich
Journal: Cancer Research (2004)

3718  Although cigarette smoking is a clear risk factor for lung cancer, the other determinants of lung cancer risk among smokers are less clear. Tea and coffee contain many phytochemicals, including catechins and flavonoids, which have been shown to exhibit anti-carcinogenic properties. The current study investigated the effects of regular consumption of black tea and coffee on lung cancer risk among 993 current and former smokers with primary, incident lung cancer and 986 age, sex, and smoking matched hospital controls with non-neoplastic conditions. All participants received medical services at Roswell Park Cancer Institute and agreed to complete a comprehensive epidemiologic questionnaire. Results indicated that lung cancer risk was not different for those with the highest black tea consumption (≥2 cups/day) compared to non-drinkers of tea [adjusted odds ratio (aOR) 0.92, 95% confidence interval (CI) 0.67–1.26]. However, elevated lung cancer risk was observed for participants who consumed 2–3 cups of regular coffee daily (aOR 1.31, 95% CI 0.97–1.77) or ≥4 cups of regular coffee daily (aOR 1.42, 95% CI 1.06–1.91). When analyses were stratified by histology, the elevated risk for coffee drinking persisted in all subtypes except adenocarcinoma. These results do not suggest that black tea consumption is involved in the chemoprevention of lung cancer. The observed increase in risk among individuals with the highest coffee consumption may be the result of uncontrolled residual confounding by smoking.
Abstract 14717: Identifying Predictors of Red Cell Distribution Width at Admission and Changes in RDW During Heart Failure Hospitalization
Authors: Benjamin D Horne, Joseph B Muhlestein, Deborah Budge, Donald L Lappé, Joseph B Muhlestein, Sterling T Bennett, José Benuzillo, Alejandra Bradshaw, Heidi T May, Tami L Bair, Jeffrey L Anderson
Journal: Circulation (2015)

Introduction: The causes of risk-associated elevations in red cell distribution width (RDW) are unknown, but RDW strongly predicts adverse outcomes in heart failure (HF) patients. Initial RDW level and the change in RDW (ΔRDW) were previously shown to predict hospital length of stay, 30-day readmission, and 30-day mortality. Hypothesis: Risk factors and diagnoses predict initial RDW and in-hospital ΔRDW of HF patients. Methods: Patients (N=6,414) were studied if they had an inpatient stay for the primary diagnosis of HF during 2004-2013, had RDW measured within 24 hours after admission, and had a second RDW tested within 24 hours prior to discharge. ΔRDW was calculated as the difference between the two RDW measurements. All patients were aged 65 years or older and were discharged alive and not to hospice. Results: In linear regression, predictors of initial RDW included age, being ever diagnosed with 15 comorbidities (Table), and diagnosis in the prior month with 8 comorbidities. Those 24 factors explained 10.5% of the variation in RDW (model F-statistic= 33.3, p&lt;0.001). In contrast, predictors of ΔRDW were sex, length of stay, initial red blood cell count, mean corpuscular volume, RDW, mean corpuscular hemoglobin concentration, sodium, calcium, potassium, medications administered in-hospital (e.g., ACE-I, inotropes, and vasopressors), and diagnosis ever or within the last month of various comorbidities (Table). Those factors explained 13.9% of the variation in ΔRDW (model F-statistic= 35.9, p&lt;0.001). Conclusions: Predictors of initial RDW and ΔRDW in HF patients clustered among diagnoses of cardiovascular, pulmonary, renal, and psychological diseases, and (as expected) hematological/bleeding conditions. These findings may aid in determining the cause of RDW elevations and in personalizing medical care using common, inexpensive, electronic laboratory data. With most variance in RDW and ΔRDW still unexplained, discovery of other predictors is needed.
Emergency department visits among patients with advanced solid tumors at a cancer center in Mexico City.
Authors: Miguel Araujo, Mirza Alcalde Castro, Enrique Soto Perez De Celis, Andrea De la O, Rafael Reyes, Yanin Chavarri Guerra
Journal: Journal of Clinical Oncology (2018)

52 Background: Emergency department (ED) visits are a distressing event for patients with advanced cancer, and identifying planned, unplanned and avoidable ED visits is important for providing better cancer care. We studied the causes for ED visits, as well as potentially avoidable ED visits during palliative chemotherapy, among patients with advanced cancer treated at a public cancer center in Mexico City. Methods: Consecutive patients with newly diagnosed advanced solid tumors treated at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from 10/2015 to 03/2016 were screened. Patients who visited the ED during that period were included, and their demographic and clinical characteristics recorded. Number and reasons for ED visits were obtained from medical records. Among patients who received chemotherapy within the previous 30 days, the following reasons for ED visits were classified as avoidable: anemia, nausea, dehydration, neutropenia, diarrhea, pain, emesis, pneumonia, fever or sepsis (according to Centers for Medicare and Medicare Services Hospital Outpatient Quality Reporting Program). Results: 77 patients were diagnosed with advanced solid tumors during the study period, of which 53 (69%) had at least one ED visit. Median age was 63 years (range, 19-88), and 47% were men (n = 25). 51% had gastrointestinal, 21% genitourinary and 28% other tumors. Median follow-up was 360 days. 95 ED visits were identified; with a median number of ED visits per patient of 1 (range 1-5). The most common causes of ED visits were: infections (n = 20; 21%), gastrointestinal disorders (n = 18; 19%), pain (n = 15; 16%), ascites (n = 14; 15%), anemia (n = 4; 4%), catheter dysfunction (n = 4; 4%), and other causes (n = 20; 21%). 57% of ED visits among patients who received chemotherapy within the previous 30 days were classified as potentially avoidable. Conclusions: Over two thirds of patients with newly diagnosed metastatic cancer had ED visits in the first year after diagnosis. Furthermore, more than a half of ED visits among patients receiving palliative chemotherapy were potentially avoidable. Strategies aimed at reducing ED visits are needed to improve quality of care for patients with advanced cancer.
Cancer sites and/or histologies with increasing incidence in elderly.
Authors: Jigisha P. Thakkar, Bridget J. McCarthy, John L. Villano
Journal: Journal of Clinical Oncology (2012)

e12036 Background: In the US, from 2004-2008, approximately 7.8% of all cancers were diagnosed and 15.2% of cancer deaths occurred in those age 85 and older. Due to the aging of the US population, a focus on the incidence of cancer in the elderly population is needed to advance knowledge on the prevention, diagnosis, and treatment of cancer in this age group. Methods: Data was retrieved from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review and from the SEER website. Data from seventeen SEER registries for the years 2000-2008 were included. Cancer sites/histologies included invasive cases only, unless otherwise noted, and rates were per 100,000. Age-specific incidence rates for meningioma were obtained from Central Brain Tumor Registry of the United States (CBTRUS) Statistical Report: NPCR (National Program of Cancer Registries) and SEER (2004-2007). Results: The overall cancer incidence rate decreases in the elderly age group. The age-specific (crude) SEER incidence rate for all cancer sites combined for those aged 85+ is 2299.65/100,000. Elderly males have a higher incidence rate as compared to elderly females (3220.7 versus 1884.9). Despite the overall decline in the incidence rate in the oldest age group, the cancer sites and/or histologies with continued increasing incidence rates after 85 years of age are: colon, bones and joints, gall bladder, Kaposi’s sarcoma, leukemia, myelodysplastic syndromes, pancreas, soft tissue including heart, vulva, vagina, and meningioma. Conclusions: Among cancer sites with increasing incidence after age 85; colon cancer has the highest incidence rate. Screening and early diagnosis for cancer in the elderly should be critically considered for colorectal cancers.
Advances in multiple omics of natural-killer/T cell lymphoma
Authors: Jie Xiong, Wei-Li Zhao
Journal: Journal of Hematology & Oncology (2018)

Natural-killer/T cell lymphoma (NKTCL) represents the most common subtype of extranodal lymphoma with aggressive clinical behavior. Prevalent in Asians and South Americans, the pathogenesis of NKTCL remains to be fully elucidated. Using system biology techniques including genomics, transcriptomics, epigenomics, and metabolomics, novel biomarkers and therapeutic targets have been revealed in NKTCL. Whole-exome sequencing studies identify recurrent somatic gene mutations, involving RNA helicases, tumor suppressors, JAK-STAT pathway molecules, and epigenetic modifiers. Another genome-wide association study reports that single nucleotide polymorphisms mapping to the class II MHC region on chromosome 6 contribute to lymphomagenesis. Alterations of oncogenic signaling pathways janus kinase-signal transducer and activator of transcription (JAK-STAT), nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), WNT, and NOTCH, as well as epigenetic dysregulation of microRNA and long non-coding RNAs, are also frequently observed in NKTCL. As for metabolomic profiling, abnormal amino acids metabolism plays an important role on disease progression of NKTCL. Of note, through targeting multiple omics aberrations, clinical outcome of NKTCL patients has been significantly improved by asparaginase-based regimens, immune checkpoints inhibitors, and histone deacetylation inhibitors. Future investigations will be emphasized on molecular classification of NKTCL using integrated analysis of system biology, so as to optimize targeted therapeutic strategies of NKTCL in the era of precision medicine.
TIRED: A randomised controlled trial evaluating efficacy of cognitive behavior therapy and graded exercise therapy in severely fatigue patients with advanced cancer.
Authors: Hanneke Poort, Marlies Peters, Winette T.A. Van Der Graaf, Pythia Nieuwkerk, Agnes W Van de Wouw, Maria Nijhuis-van der Sanden, Gijs Bleijenberg, Stans Verhagen, Hans Knoop
Journal: Journal of Clinical Oncology (2018)

183 Background: Patients with advanced, metastatic cancer frequently suffer from severe fatigue. We assessed the effect of cognitive behavioral therapy (CBT) and graded exercise therapy (GET) on fatigue during cancer treatment with palliative intent. Methods: This randomized study took place between Jan 1, 2013 and Sep 1, 2017 at Radboud University Medical Center (Nijmegen, Netherlands). We enrolled adult patients from nine medical oncology clinics. Eligible patients had advanced cancer and reported severe fatigue (Checklist Individual Strength, subscale fatigue severity [CIS fatigue] ≥ 35) during cancer treatment. Participants were randomized to CBT, GET, or usual care (1:1:1 ratio, using a computer-generated sequence, stratified by study site and minimized for sex). We measured fatigue (CIS fatigue and European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30 [EORTC-QLQ-C30] fatigue), quality of life, emotional functioning, physical functioning (all by EORTC-QLQ-C30), and functional impairments (Sickness Impact Profile [SIP8]) at baseline, 14, 18, and 26 weeks. The primary outcome was CIS fatigue at 14 weeks; secondary outcomes included scores for the aforementioned scales. We registered the trial with TrialRegister.nl (NTR3812). Results: 134 participants completed baseline measures (46 CBT, 42 GET, 46 usual care); 126 completed assessment at 14 weeks. There was a significant difference in CIS fatigue scores between CBT and usual care (-7.22, 97.5% CI -12.73 to -1.72; p = .003, d= 0.72), but no significant difference between GET and usual care (-4.70, -10.24 to 0.85, p = .057, d= 0.44). Secondary outcomes showed significant differences for EORTC-QLQ-C30 fatigue (-13.05 [95% CI -22.12 to -3.97]; p = 0.005), quality of life (10.15 [2.37 to 17.93]; p = 0.11), and physical functioning (7.10 [0.48 to 13.72]; p = 0.036), but not for emotional functioning or SIP8 functional impairments (p's &gt; 0.05). There were no significant differences in secondary outcomes between GET and usual care. Conclusions: The findings support CBT for severe fatigue in patients with advanced cancer during treatment. Clinical trial information: NTR3812.
Utility of Bladder-Sparing Therapy vs Radical Cystectomy for Muscle-Invasive Bladder Cancer
Authors: Jason A. Efstathiou, Ananya Choudhury, Anne E. Kiltie
Journal: JAMA Surgery (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 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