tbuckley/cabot-search huggingface dataset:
Brief family history questionnaire for identification of Lynch syndrome in women with newly diagnosed endometrial cancer.
Authors: Sarah E Ferguson, Blaise Clarke, Golnessa Mojtahedi, Amit M. Oza, Steve Gallinger, Aaron Pollett, Helen Mackay, Marcus Bernardini, Melyssa Aronson
Journal: Journal of Clinical Oncology (2012)

5026 Background: Endometrial cancer (EC) is often the sentinel cancer for women with Lynch syndrome (LS); however, it is underappreciated in this population. The Brief Family History Questionnaire (bFHQ) was developed to identify women with EC who have family histories suggestive of LS. The objective of our study was to evaluate the bFHQ compared to an extended family history (eFHQ) and medical record in identifying women with EC who may benefit from genetic cancer risk assessment. Methods: All women with newly diagnosed EC from July 2010 to June 2011 were asked to participate in a prospective screening protocol for LS which included completing two family history questionnaires; the bFHQ which is a 4-item self-report measure and the 37-item eFHQ administered by a research assistant. Family history was also extracted from the medical record. Using the bFHQ women were flagged as requiring additional investigation for LS based on predetermined criteria and the predictive ability of the flag was evaluated treating eFHQ as the gold standard. Comparisons were made between the bFHQ, eFHQ and medical record for families meeting Amsterdam II, Society Gynecologic Oncologist (SGO) 20-25% or the Ontario Ministry of Health (MOH) testing criteria for LS, using generalized estimating equation logistic regression models. Results: 119 (N = 182, 65%) consented to the study and 106 (89%) completed the bFHQ. The median age was 61 (26-91). The number of women who met testing criteria by the eFHQ was 17 (16%) and 33 (31%) were flagged by the bFHQ. The sensitivity, specificity, PPV and NPV of the bFHQ was 88.2%, 79.8%, 45.5% and 97.3%. There was no significant difference in the number of women who met Amsterdam II or SGO 20-25% testing criteria between the bFHQ, eFHQ and medical record (P &gt; 0.05). The numbers of women meeting MOH criteria using the bFHQ (N=16, 15%) and the eFHQ were similar (N=17, 16%) (P = 0.7); however, more women met MOH criteria using the bFHQ and the eFHQ compared to the medical record (N=8, 7.6%) (P = 0.011; P = 0.006). Conclusions: The patient-administered bFHQ is a highly effective tool in identifying women who meet MOH testing criteria for LS and is a good screening tool to identify women with EC for further genetic assessment.
The Efficacy of Omega-3 Fatty Acids for Depressive Symptoms among Pregnant Women in Japan and Taiwan: A Randomized, Double-Blind, Placebo-Controlled Trial (SYNCHRO; NCT01948596)
Authors: Daisuke Nishi, Kuan-Pin Su, Kentaro Usuda, Jane Pei-Chen Chang, Yi-Ju Chiang, Hui-ting Chen, Yu-Chuan Chien, Tai-Wei Guu, Emi Okazaki, Kei Hamazaki, Ryoko Susukida, Naoki Nakaya, Toshimasa Sone, Yo Sano, Hiroe Ito, Keiichi Isaka, Yoshiyuki Tachibana, Shinji Tanigaki, Tomo Suzuki, Kenji Hashimoto, Tomohito Hamazaki, Yutaka J. Matsuoka
Journal: Psychotherapy and Psychosomatics (2018)
Six-Month Safety and Efficacy of the Intelligent Retinal Implant System II Device in Retinitis Pigmentosa
Authors: Mahiul M.K. Muqit, Michaela Velikay-Parel, Michel Weber, Gerard Dupeyron, Didier Audemard, Borja Corcostegui, José Sahel, Yannick Le Mer
Journal: Ophthalmology (2018)
Abstract 17944: Pulmonary Vascular Reserve and Right Ventricular Contractile Reserve in Patients With Chronic Thromboembolic Disease Without Pulmonary Hypertension at Rest: An Exercise Cardiac Magnetic Resonance Study
Authors: Mathias Claeys, Guido Claessen, Rik Willems, Thibault Petit, Catharina Belge, Andre La Gerche, Jan Bogaert, Marion Delcroix, Piet Claus
Journal: Circulation (2016)

Background: A significant number of patients with incomplete thrombus resolution after pulmonary embolism have marked exercise limitation despite normal resting hemodynamics. Hypothesis: We investigated whether reduced exercise capacity in patients with chronic thromboembolic disease (CTED) can be explained by a reduced right ventricular (RV) contractile reserve and abnormal pulmonary vascular reserve. Methods: Nine CTED patients, 18 patients with chronic thromboembolic pulmonary hypertension (CTEPH) and 9 controls underwent cardiopulmonary exercise testing and exercise cardiac magnetic resonance with simultaneous registration of invasive pulmonary pressures. Abnormal pulmonary vascular reserve was defined as an increase in mean pulmonary artery pressure to cardiac output (mPAP/CO slope) >3 mmHg/L/min and abnormal RV contractile reserve as a ratio of peak-exercise to resting RV end-systolic pressure/volume relationship (RVESPVR ratio) <2. Results: Exercise capacity was reduced in CTEPH and CTED patients a...
Abstract #3255: Tetrameric erythropoietin anchored on IgG with improved biological activity.
Authors: Diane Nordstrom, David Goldenberg, Thomas Cardillo, Edmund Rossi, Chien-Hsing Chang
Journal: Cancer Research (2009)

Introduction: Erythropoietin (EPO) is a hematopoietic growth factor that stimulates the proliferation and differentiation of erythrocytes into mature red blood cells. Several recombinant human EPOs (rhEPO) are currently used for the treatment of anemia, predominantly associated with chronic renal failure and post cancer chemotherapy. However, the short half-life (4-13 hours) of rhEPO necessitates frequent dosing and, therefore, increasing the serum half-life of EPO to allow less frequent dosing is highly desirable and has been an important goal for developing next-generation EPO. Here we describe a novel approach to generate multimeric hEPO with improved pharmacokinetics and potency by the Dock-and-Lock (DNL) method. Methods: The modular DNL method has been used to make a variety of multivalent and multifunctional bioactive molecules by using a pair of distinct protein domains involved in the natural binding between protein kinase A (PKA) and A-kinase anchoring proteins (AKAP), whereby the dimerization-and-docking domain (DDD) of PKA and the anchoring domain of an interactive AKAP are each fused to bioactive molecules. We have selectively combined recombinant DDD-modules comprising hEPO with recombinant AD-modules derived from a humanized monoclonal antibody to generate complexes comprising four copies of hEPO site-specifically linked to IgG. Results: The IgG-AD2 and hEPO-DDD2 modules were purified from separate myeloma cell cultures by protein A and immobilized metal affinity chromatography, respectively. Combining an IgG-AD2 module with slightly more than two molar equivalents of hEPO-DDD2 module under mild redox conditions resulted in the formation of a covalent complex comprising one IgG and 4 hEPO via the docking of each of the two AD2 domains on IgG with a dimer of hEPO-DDD2, and subsequent formation of disulfide bonds (locking) between DDD2 and AD2. IgG-hEPO, which was purified by Protein A, was detected by non-reducing SDS-PAGE and size-exclusion HPLC, where it was resolved as a single predominant protein peak with a retention time consistent with a 255-kDa protein. IgG-hEPO maintained biological activity, as demonstrated by its stimulation of increased proliferation of the growth factor-dependent TF1 cell line with similar potency to rhEPO. In vivo activity was confirmed in normal mice, since as a single i.v. administration of IgG-hEPO showed a significant increase in hematocrit levels. Conclusions: The DNL method has successfully tethered multimeric hEPO onto an IgG, which is expected to display improved pharmacokinetics and other advantages characteristic of an antibody.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3255.
Focusing PI and IMiD Resistance in Multiple Myeloma: Impact of DNA Methylation
Authors: Larissa Haertle, Max Bittrich, Ramya Potabattula, Matteo Claudio Da Via', Umair Munawar, Yanira Ruiz-Heredia, Cornelia Vogt, Torsten Steinbrunn, Andoni Garitano-Trojaola, Thorsten Stuehmer, Joaquin Martinez Lopez, Hermann Einsele, Thomas Haaf, K. Martin Kortüm, Santiago Barrio Garcia
Journal: Blood (2018)
Abstract 11: Lamin A/C Mutations Epigenetically Dysregulate Scn5a Gene Expression, Perturbing Action Potential Properties in IPSC-derived Cardiomyocytes
Authors: Silvia Crasto, Nicolò Salvarani, Michele Miragoli, Marianna Paulis, Paolo Kunderfranco, Pierluigi Carullo, Alberto Forni, Giuseppe Faggian, Gianluigi Condorelli, Elisa Di Pasquale
Journal: Circulation Research (2017)

Mutations of the LMNA gene, encoding the nuclear lamina proteins Lamin A/C, are a common cause of dilated cardiomyopathy, typically manifesting in association with cardiac conduction defects. LaminA/C regulate various nuclear activities, including maintenance of the nuclear structure, gene transcription and chromatin organization. Most studies on the consequences of Lamin A/C defects were conducted on fibroblasts, while studies on human cardiomyocytes (CMs) are scarce. We therefore generated a cardiac model of laminopathy obtained by differentiation of CMs from induced pluripotent stem cells (iPSCs) of patients carrying the K219T Lamin A/C mutation. In vitro, these cells recapitulate the morphological features of dilated cardiomyopathy, specifically sarcomeric disorganization and increased size. Using this model, we performed a comprehensive analysis of the electrophysiological properties of LMNA-CMs both at single cell level and in a multi-cellular setting. Using patch-clamp technique, results revealed significant changes in maximal upstroke velocity (dV/dt max ), action potential amplitude (APA) and overshoot (OV) in LMNA-CMs compared to those obtained from family-matched healthy controls (CNTR); these defects were associated with a reduction of the peak sodium currents and a diminished conduction velocity, measured in strands of electrically-coupled CMs. Biochemical studies showed a significant reduction of both the sodium channel Nav1.5 protein and its transcript in LMNA-CMs, accompanied by an increased binding of LaminA/C to the promoter of its coding gene, SCN5A. Binding of the Polycomb group protein SUZ12 and of the H3K27me3 histone repressive mark was also increased. Consistently, 3D-FISH experiments also indicated a preferential localization of SCN5A genomic loci at the nuclear periphery in LMNA-CMs. As a whole, our findings support a model in which mutated Lamin A/C perturb SCN5A gene expression by favouring PRC2 (Polycomb Repressive Complex 2) binding to its promoter, leading to decreased sodium current peak and slower conduction velocity. This mechanism may eventually sustain the conduction abnormalities inevitably occurring in patients with LMNA-cardiomyopathy.
The Butterfly Effect in the Economic Gender Gap in Academia
Authors: Sophia Frangou
Journal: JAMA Network Open (2018)

Avani D. Rao, MD; Sarah E. Nicholas, MD; Bartlomiej Kachniarz, MD, MBA; Chen Hu, MS, PhD; Kristin J. Redmond, MD, MPH; Curtiland Deville, MD; Jean L. Wright, MD; Brandi R. Page, MD; Stephanie Terezakis, MD; Akila N. Viswanathan, MD, MPH; Theodore L. DeWeese, MD; Barbara A. Fivush, MD; Sara R. Alcorn, MD, MPH
The Latitudinal Diversity Gradient: Novel Understanding through Mechanistic Eco-evolutionary Models
Authors: Mikael Pontarp, Lynsey Bunnefeld, Juliano Sarmento Cabral, Rampal S. Etienne, Susanne A. Fritz, Rosemary Gillespie, Catherine H. Graham, Oskar Hagen, Florian Hartig, Shan Huang, Roland Jansson, Odile Maliet, Tamara Münkemüller, Loïc Pellissier, Thiago F. Rangel, David Storch, Thorsten Wiegand, Allen H. Hurlbert
Journal: Trends in Ecology & Evolution (2018)
Anti-BCMA BiTE® AMG 701 Potently Induces Specific T Cell Lysis of Human Multiple Myeloma (MM) Cells and Immunomodulation in the Bone Marrow Microenvironment
Authors: Shih-Feng Cho, Liang Lin, Lijie Xing, Jiye Liu, Tengteng Yu, Kenneth Wen, Phillip Hsieh, Nikhil Munshi, Kenneth Anderson, Yu-Tzu Tai
Journal: Blood (2018)
Bayesian Adaptive Randomization in Dose-Finding Trials
Authors: Steffen Ventz, Brian M. Alexander, Lorenzo Trippa
Journal: JAMA Network Open (2018)

Alan E. Jones, MD; Michael A. Puskarich, MD, MS; Nathan I. Shapiro, MD, MPH; Faheem W. Guirgis, MD; Michael Runyon, MD, MPH; Jason Y. Adams, MD; Robert Sherwin, MD; Ryan Arnold, MD; Brian W. Roberts, MD, MSc; Michael C. Kurz, MD, MS; Henry E. Wang, MD, MS; Jeffrey A. Kline, MD; D. Mark Courtney, MD; Stephen Trzeciak, MD, MPH; Sarah A. Sterling, MD; Utsav Nandi, MD; Deepti Patki, MS; Kert Viele, PhD
Pevonedistat, a Neuronal Precursor Cell‐Expressed Developmentally Down‐Regulated Protein 8–Activating Enzyme Inhibitor, Is a Potent Inhibitor of Hepatitis B Virus
Authors: Kazuma Sekiba, Motoyuki Otsuka, Motoko Ohno, Mari Yamagami, Takahiro Kishikawa, Takahiro Seimiya, Tatsunori Suzuki, Eri Tanaka, Rei Ishibashi, Kazuyoshi Funato, Kazuhiko Koike
Journal: Hepatology (2018)

Hepatitis B virus (HBV) infection is a major health concern worldwide. To prevent HBV-related mortality, elimination of viral proteins is considered the ultimate goal of HBV treatment; however, currently available nucleos(t)ide analogs rarely achieve this goal, as viral transcription from episomal viral covalently closed circular DNA (cccDNA) is not prevented. HBV regulatory protein X was recently found to target the protein structural maintenance of chromosomes 5/6 (Smc5/6) for ubiquitination and degradation by DDB1-CUL4-ROC1 E3 ligase, resulting in enhanced viral transcription from cccDNA. This ubiquitin-dependent proteasomal pathway requires an additional ubiquitin-like protein for activation, neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8). Here, we show that pevonedistat, a NEDD8-activating enzyme inhibitor, works efficiently as an antiviral agent. Pevonedistat significantly restored Smc5/6 protein levels and suppressed viral transcription and protein production in the HBV minicircle system in in vitro HBV replication models and in human primary hepatocytes infected naturally with HBV. Conclusion: These results indicate that pevonedistat is a promising compound to treat chronic HBV infection.
Prognostic significance of sentinel lymph node biopsies (SLNB) in melanoma.
Authors: Diwakar Davar, Melissa Saul, Kerry Trent, Matthew Peter Holtzman, Howard Edington, Hussein Abdul-Hassan Tawbi, Ahmad A. Tarhini, John M. Kirkwood
Journal: Journal of Clinical Oncology (2014)

e20029 Background: The risk of lymph node involvement for cutaneous melanoma increases with tumor thickness - 5% for Breslow thickness ≤1mm and 34% for T4 or ulcerated lesions. SLNB is standard of care for cutaneous melanoma of Breslow thickness >1mm. Positive SLNB is followed by completion lymph node dissection (CLND) of the affected nodal basin. SLNB has a high negative predictive value (NPV) but false negative (FN) rates vary widely (3-12.5%). Methods: Data were collected on 3,600 patients (pts) who underwent SLNB for cutaneous melanoma from 1996 to 2012 using the UPCI Cancer Registry. Cancer registry records were reviewed for primary tumor characteristics, demographic details, and outcomes. The influence of baseline characteristics on SLNB positivity was assessed using Cox proportional hazards analysis. Results: 3,600 SLNB performed from 1996 to 2012 of which 969 SLNB (969 pts) reviewed as a pilot. Primary tumor characteristics and demographic details obtained. SLN metastases were detected in 169 pts (17.4%). 134 CLND were performed with 31 pts not having CLND secondary to refusal or early distant metastatic disease. Following CLND, 48 recurrences were observed: recurrence pattern was predominantly cutaneous (19/48 pts, 39.6%), although ipsilateral recurrences in the prior CLND bed were noted (14/48 pts, 29.2%). Visceral recurrences comprised the remainder [non-pulmonary 7/48 pts (14.6%), pulmonary 5/48 pts (10.4%) and CNS 2/48 pts (4.2%)]. Most CLNDs followed by ipsilateral regional nodal recurrences were performed outside tertiary care centers. PFS and OS were significantly worse with increasing stage and SLNB status. Conclusions: AJCC, ASCO and SSO guidelines recommend SLN biopsy for intermediate-thickness melanomas (1-4mm Breslow) to optimize staging accuracy. Incidence of regional recurrence after CLND has been estimated at 30-35%. In this large and uniformly treated series of patients at a major melanoma referral center, SLN were involved in 17.2% and median PFS after CLND was 22mos. Biomarkers associated with SLNB and CLND positivity are currently being evaluated in prospectively banked specimens from patients (07-133) and under the aegis of the SPORE in Skin Cancer (P50CA121973).
Community based distribution of oral HIV self-testing kits in Zambia: a cluster-randomised trial nested in four HPTN 071 (PopART) intervention communities
Authors: Chama Mulubwa, Bernadette Hensen, Mwelwa M Phiri, Kwame Shanaube, Albertus J Schaap, Sian Floyd, Comfort R Phiri, Chiti Bwalya, Virginia Bond, Musonda Simwinga, Lawrence Mwenge, Sarah Fidler, Richard Hayes, Alwyn Mwinga, Helen Ayles
Journal: The Lancet HIV (2018)

The HPTN 071 (PopART) cluster-randomised trial provided door-to-door HIV testing services to a large proportion of individuals residing in 21 intervention communities in Zambia and South Africa from 2014 to 2017 and reached the UNAIDS first 90 target among women in Zambia, yet gaps remained among men and young adults. This cluster-randomised study nested in the HPTN 071 (PopART) trial sought to increase knowledge of HIV status across all groups by offering the choice of oral HIV self-testing in addition to routine door-to-door HIV testing services.
Management of Small Lung Nodules in the Era of Lung Cancer Screening
Authors: Kathleen S. Berfield, Oluwatobi A. Afolayan, Douglas E. Wood
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
Exploring the emotional and behavioural reactions to receiving personalized melanoma genomic risk information: a qualitative study
Authors: G.L. Fenton, A.K. Smit, L. Keogh, A.E. Cust
Journal: British Journal of Dermatology (2018)

There is a need for greater understanding of the spectrum of emotional and behavioural reactions that individuals in the general population may experience in response to genomic testing for melanoma risk. To explore how individuals in the general population respond to receiving personalized genomic risk of melanoma. Semistructured interviews were undertaken with 30 participants (aged 24–69 years, 50% female, 12 low risk, eight average risk, 10 high risk) recruited from a pilot trial in which they received personalized melanoma genomic risk information. We explored participants’ emotional and behavioural responses to receiving their melanoma genomic risk information. The qualitative data were analysed thematically. Many participants reported a positive response to receiving their melanoma genomic risk, including feelings of happiness, reassurance and gaining new knowledge to help manage their melanoma risk. Some participants reported short‐term negative emotional reactions that dissipated over time. Most individuals, particularly those who received average or high‐risk results, reported making positive behaviour changes to reduce their melanoma risk. Emotional and behavioural responses were linked to participants’ expectations for their risk result, their pre‐existing perception of their own melanoma risk, their existing melanoma preventive behaviours and their genomic risk category. Personalized melanoma genomic risk information alongside education and lifestyle counselling is favourably received by people without a personal history and unselected for a family history of melanoma. Participants described increased knowledge and awareness around managing skin cancer risk and improved sun protection and skin examination behaviours. Any initial feelings of distress usually dissipated over time.
Monitoring ESAM Expression Levels Reveals Autonomous Fluctuation of Leukemia Stem Cells By Autocrine/Paracrine Cytokine Signaling
Authors: Yasuhiro Shingai, Takafumi Yokota, Takayuki Ozawa, Tomoaki Ueda, Yukiko Doi, Tomohiko Ishibashi, Akira Tanimura, Michiko Ichii, Hirohiko Shibayama, Yuzuru Kanakura
Journal: Blood (2018)
Impact of MYD88L265P mutation Status on Histological Transformation of Waldenstrom Macroglobulinemia
Authors: Saurabh Zanwar, Jithma Prasad Abeykoon, Stephen M. Ansell, Rebecca L King, Rong He, Morie A. Gertz, Patricia Greipp, Robert A. Kyle, Thomas M. Habermann, David Dingli, Anne J Novak, David J Inwards, Francis K. Buadi, Grzegorz S. Nowakowski, Carrie A. Thompson, Patrick Johnston, Gita Thanarajasingam, Nora N Bennani, Thomas E. Witzig, Ivana Micallef, Luis Porrata, Jose C Villasboas, Angela Dispenzieri, Martha Q. Lacy, Ronald S. Go, Eli Muchtar, Taxiarchis Kourelis, Wilson I Gonsalves, Yi Lin, S. Vincent Rajkumar, Shaji K. Kumar, Prashant Kapoor
Journal: Blood (2018)