tbuckley/cabot-search huggingface dataset:
RE: Presence of Circulating Tumor Cells in High-Risk Early Breast Cancer During Follow-Up and Prognosis
Authors: Serenai Di Cosimo, Valter Torri, Luca Porcu
Journal: JNCI Journal of the National Cancer Institute (2019)

As determined at 2 years after the end of chemotherapy.CI ¼ confidence interval; CTC ¼ circulating tumor cell; DFS ¼ disease-free survival; NPV ¼ negative predictive value (ie, probability to be declared alive and disease-free at 40 months, after 2 years from end of chemotherapy); PPV ¼ positive predictive value (ie, probability to be declared relapsed or dead at 40 months, after 2 years from end of chemotherapy).
PB2192 GLOBAL COAGULATION CAPACITY OF ESSENTIAL THROMBOCYTHEMIA PATIENTS BY ROTEM ANALYSIS ADJUSTED FOR PLATELET COUNT CORRELATES WITH THROMBOTIC RISK CLASS
Authors: C. Giaccherini, M. Marchetti, C. Verzeroli, S. Gamba, L. Russo, G. Finazzi, A. Rambaldi, A. Falanga
Journal: HemaSphere (2019)

Background: Essential Thrombocythemia (ET) is characterized by hypercoagulability and increased risk of arterial and venous thrombosis. The thromboelastometry profile by ROTEM, a point of care system for assessment of global coagulation in whole blood, has never been investigated in these patients, who have abnormalities in blood cell counts. This approach is attractive in that the test reflects the activity of both soluble and cellular components of hemostasis. Furthermore, the test is rapid, does not require blood sample centrifugation and may be useful in prospective studies of thrombotic risk assessment in ET patients. Aims: To evaluate the global clotting process in ET patients by thromboelastometry with ROTEM and establish whether and to what extent elevated platelet count and mutational status affect the global hemostasis evaluation. Methods Analysis was performed in 52 ET patients using INTEM and EXTEM reagents, to evaluate the intrinsic and extrinsic pathway, respectively. Maximum clot firmness (MCF, [mm]), which reflects the maximum tensile strength of the thrombus, clotting formation time (CFT [sec]), namely the time that clot takes to increase from 2 mm to 20 mm above baseline, and clotting time (CT [sec]), the time to clot initiation, were recorded. Patient thrombotic risk was classified as, i.e.: very low risk (age≤60 yrs, no thrombosis history, JAK2/MPL − ), low risk (age≤60 yrs, no thrombosis history, JAK2/MPL + ), intermediate risk (age &gt; 60 yrs, no thrombosis history, JAK2/MPL − ), and high risk (thrombosis history or age &gt;60 yrs with JAK2/MPL + ). Results: ROTEM analysis with both EXTEM and INTEM reagents showed that ET patients had a hypercoagulable profile, characterized by significant (p &lt; 0.01) short CFT and high MCF values compared to healthy subjects. None of the ROTEM parameters per se correlated with classes of thrombotic risk. However, a strong correlation (p &lt; 0.01) was present between platelet count and CFT or MCF (both with EXTEM and INTEM reagents). Therefore, the parameters were adjusted for platelet count. After adjustment, corrected CFT (cCFT) significantly correlated with the patient thrombotic risk category (p &lt; 0.05). Furthermore, corrected MCF (cMCF) was significantly increased in JAK2V617F + /MPL + compared to CalR + subjects (p &lt; 0.01). Summary/Conclusion: This study confirms the occurrence of a hypercoagulable state in ET patients and shows that ROTEM parameters are significantly influenced by platelet count. Correction of CFT and MCF values allows a better understanding of global coagulation of ET patients and may potentially better reflect the thrombotic risk in these patients.
OP0004 IS DUAL-ENERGY COMPUTED TOMOGRAPHY ABLE TO IDENTIFY EARLY-STAGE CALCIUM CRYSTAL DEPOSITION IN VIVO? INITIAL CLINICAL EXPERIENCE IN 132 PATIENTS WITH AND WITHOUT KNEE CHONDROCALCINOSIS
Authors: Tristan Pascart, Claire Marzin, Laurène Norberciak, Julie Legrand, Fabio Becce, Jean-François Budzik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Calcium crystals are below the spatial resolution limit of currently available imaging techniques, and only aggregates can be identified in vivo at more advanced stages of the disease. Although dual-energy computed tomography (DECT) has the potential to discriminate the various calcium crystal types owing to its biochemical signature assessment capabilities, it remains to be seen whether this technique would be able to identify early-stage calcium crystal deposition in vivo. <h3>Objectives</h3> We aimed to assess whether DECT was able to identify calcium crystal deposition in the knee prior to the onset of chondrocalcinosis (CC), more specifically if DECT attenuation properties differed between patients with CC and controls without CC on DECT. <h3>Methods</h3> Consecutive patients with clinical suspicion of crystal arthritis and knee DECT scans were retrospectively reviewed and assigned to either CPPD (n=50) or control (n=82) groups depending on the presence/absence of CC on DECT. Regions of interest (ROI) were drawn in the following knee zones on a specific coronal DECT image: hyaline cartilage of the patellofemoral and medial and lateral tibiofemoral joint spaces, as well as medial and lateral menisci. The presence or absence of CC in these predefined ROIs were noted. Five DECT parameters were obtained: CT numbers (HU) at 80 and 140 kV, dual-energy index (DEI), electron density (ρe), and effective atomic number (Zeff). Knee zones were compared between groups using mixed linear models adjusting for age and the presence of osteoarthritis. A subgroup analysis was performed excluding zones were calcifications were visible on DECT images. <h3>Results</h3> Menisci from CPPD patients and controls had a mean Zeff of 7.9±0.4 and 7.6±0.2 (p&lt;0.0001), mean ρe of 85±23 and 74±14 (p&lt;0.0001) and mean DEI of 0.0036±0.0046 and -0.0001±0.0042 (p&lt;0.001), respectively. DEI values differed significantly between patients and controls in tibiofemoral cartilage (0.0026±0.0041 in CPPD and 0.0023±0.0045)(p=0.013) but not in patellofemoral cartilage (p=0.57). When considering only the various regions from CPPD patients without CC in the selected ROIs, the ρe in menisci (n=79/185) did not differ between groups and differences in Zeff (p=0.15) and DEI (p=0.09) did not reach statistical significance after adjustment for age and osteoarthritis. <h3>Conclusion</h3> DECT has the potential to discriminate between meniscal fibrocartilage and articular cartilage of CPPD patients and controls in predefined regions of interest. DECT's ability to improve the sensitivity of conventional CT to identify invisible CPP deposits remains unclear as the trend did not reach statistical significance. <h3>Disclosure of Interests</h3> None declared
A Stem-Cell-Derived Platform Enables Complete Cryptosporidium Development In Vitro and Genetic Tractability
Authors: Georgia Wilke, Lisa J. Funkhouser-Jones, Yi Wang, Soumya Ravindran, Qiuling Wang, Wandy L. Beatty, Megan T. Baldridge, Kelli L. VanDussen, Bang Shen, Mark S. Kuhlenschmidt, Theresa B. Kuhlenschmidt, William H. Witola, Thaddeus S. Stappenbeck, L. David Sibley
Journal: Cell Host & Microbe (2019)

Despite being a frequent cause of severe diarrheal disease in infants and an opportunistic infection in immunocompromised patients, Cryptosporidium research has lagged due to a lack of facile experimental methods. Here, we describe a platform for complete life cycle development and long-term growth of C. parvum in vitro using "air-liquid interface" (ALI) cultures derived from intestinal epithelial stem cells. Transcriptomic profiling revealed that differentiating epithelial cells grown under ALI conditions undergo profound changes in metabolism and development that enable completion of the parasite life cycle in vitro. ALI cultures support parasite expansion > 100-fold and generate viable oocysts that are transmissible in vitro and to mice, causing infection and animal death. Transgenic parasite lines created using CRISPR/Cas9 were used to complete a genetic cross in vitro, demonstrating Mendelian segregation of chromosomes during meiosis. ALI culture provides an accessible model that will enable innovative studies into Cryptosporidium biology and host interactions.
Risk factors and diagnostic markers of bacteremia in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cohort study of 176 patients
Authors: Hui Kai Koh, Zi Teng Chai, Hui Wen Tay, Stephanie Fook-Chong, Karen J.L. Choo, Choon Chiat Oh, Yi Wei Yeo, Hong Yi Koh, Shiu Ming Pang, Haur Yueh Lee
Journal: Journal of the American Academy of Dermatology (2019)
RUNX1 Deficiency and SRSF2 Mutation Cooperate to Promote Myelodysplastic Syndrome Development
Authors: Yi-Jou Huang, Ming Yan, Eunhee Kim, Amanda G Davis, Takahiro Shima, Sayuri Miyauchi, Xiang-Dong Fu, Omar Abdel-Wahab, Dong-Er Zhang
Journal: Blood (2017)
Association of Disease Definition, Comorbidity Burden, and Prognosis With Hip Fracture Probability Among Late-Life Women
Authors: Kristine E. Ensrud, Allyson M. Kats, Cynthia M. Boyd, Susan J. Diem, John T. Schousboe, Brent C. Taylor, Douglas C. Bauer, Katie L. Stone, Lisa Langsetmo
Journal: JAMA Internal Medicine (2019)

Advanced age is associated with lower use of drug treatment to prevent fractures, but concerns about comorbidities and prognosis increase the complexity of managing osteoporosis in this age group.To determine the association of disease definition, number of comorbidities, and prognosis with 5-year hip fracture probabilities among women who are 80 years and older.This prospective cohort study (4 US sites) included 1528 community-dwelling women identified as potential candidates for initiation of osteoporosis drug treatment.Women were contacted every 4 months to ascertain vital status and hip fracture. Five-year hip fracture probability was calculated accounting for competing mortality risk. Participants were classified into 2 distinct groups based on disease definition criteria proposed by the National Bone Health Alliance: with osteoporosis (n = 761) and without osteoporosis but at high fracture risk (n = 767). Comorbid conditions were assessed by self-report. Prognosis was estimated using a mortality prediction index. All analysis was performed between March 2018 and January 2019.The study had 1528 participants, all of whom were women, with a mean (SD) age of 84.1 (3.4) years. During follow-up, 125 (8.0%) women experienced a hip fracture and 287 (18.8%) died before experiencing this event. Five-year mortality probability was 24.9% (95% CI, 21.8-28.1) among women with osteoporosis and 19.4% (95% CI, 16.6-22.3) among women without osteoporosis but at high fracture risk. In both groups, mortality probability similarly increased with more comorbidities and poorer prognosis. In contrast, 5-year hip fracture probability was 13.0% (95% CI, 10.7-15.5) among women with osteoporosis and 4.0% (95% CI, 2.8-5.6) among women without osteoporosis but at high fracture risk. The difference was most pronounced among women with more comorbidities or worse prognosis. For example, among women with 3 or more comorbid conditions, hip fracture probability was 18.1% (95% CI, 12.3-24.9) among women with osteoporosis vs 2.5% (95% CI, 1.3-4.2) among women without osteoporosis but at high fracture risk.Women 80 years and older who have osteoporosis, including those with more comorbidities or poorer prognosis, have a high 5-year probability of hip fracture despite accounting for competing mortality risk. In contrast, among women without osteoporosis but at high fracture risk, competing mortality risk far outweighs hip fracture probability, especially among those with more comorbidities or worse prognosis.
Expanded Access to Obinutuzumab from Cost-Savings Generated By Biosimilar Filgrastim-Sndz in the Prophylaxis of Chemotherapy-Induced (Febrile) Neutropenia: US Simulation Study
Authors: Ali McBride, Kim Campbell, Mohan Bikkina, Karen MacDonald, Ivo Abraham, Sanjeev Balu
Journal: Blood (2017)
The epigenetic regulator ATF7ip inhibits <i>Il2</i> expression, regulating Th17 responses
Authors: Jun Hyung Sin, Cassandra Zuckerman, Jessica T. Cortez, Walter L. Eckalbar, David J. Erle, Mark S. Anderson, Michael R. Waterfield
Journal: The Journal of Experimental Medicine (2019)

T helper 17 cells (Th17) are critical for fighting infections at mucosal surfaces; however, they have also been found to contribute to the pathogenesis of multiple autoimmune diseases and have been targeted therapeutically. Due to the role of Th17 cells in autoimmune pathogenesis, it is important to understand the factors that control Th17 development. Here we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of Th17 differentiation. Mice with T cell–specific deletion of Atf7ip have impaired Th17 differentiation secondary to the aberrant overproduction of IL-2 with T cell receptor (TCR) stimulation and are resistant to colitis in vivo. ChIP-seq studies identified ATF7ip as an inhibitor of Il2 gene expression through the deposition of the repressive histone mark H3K9me3 in the Il2-Il21 intergenic region. These results demonstrate a new epigenetic pathway by which IL-2 production is constrained, and this may open up new avenues for modulating its production.
Girl Meets Tumor
Authors: Chloe Y. Li
Journal: Annals of Internal Medicine (2019)

On Being a Doctor18 June 2019Girl Meets TumorChloe Y. Li, BAChloe Y. Li, BAHarvard Medical School, Boston, Massachusetts, and Northwestern University Center for Bioethics and Medical Humanities, Chicago, Illinois (C.Y.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0032 Audio Reading - “Girl Meets Tumor” Audio. Virginia Hood, MD, reads “Girl Meets Tumor” by Chloe Y. Li, BA Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail On Wednesday afternoons in my first year of medical school, we practiced the physical examination in groups of about 10 students. On one especially humid afternoon, we learned the head and neck examination. Then, my classmates and I learned I had a tumor.The doctor meant to teach my examination partner how to palpate the temporomandibular joint and used my jaw as a model. His fingers, which had been lightly examining the right side of my face, turned insistent and probing. He asked whether I'd had that checked.“Oh, that's just a bump.”He shook his head definitively. “That is ... Author, Article, and Disclosure InformationAffiliations: Harvard Medical School, Boston, Massachusetts, and Northwestern University Center for Bioethics and Medical Humanities, Chicago, Illinois (C.Y.L.)Current Author Address: Chloe Y. Li, BA, 25 Shattuck Street, Boston, MA 02115; e-mail, [email protected]harvard.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Girl Meets Tumor” Audio. Virginia Hood, MD, reads “Girl Meets Tumor” by Chloe Y. Li, BA Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 18 June 2019Volume 170, Issue 12Page: 895-896KeywordsBiopsyFacial nerveFearHead and neck tumorsHearingMedical educationMouthScarsSurgeryTemporomandibular joint ePublished: 18 June 2019 Issue Published: 18 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 273: Pressure Overload Induces Cardiac Insulin Resistance in an Angiotensin II-Independent Manner
Authors: Ning Zhou, Yong Ye, Hongyang Shu, Jingjing Fan, Yunzeng Zou, Dao Wen Wang
Journal: Circulation Research (2017)

Aims: Pressure overload is able to provoke the cardiac insulin resistance via angiotensin II (AngII). However, the direct effect of pressure overload on the myocardial insulin sensitivity was poorly understood. This study was aimed to explore whether and how pressure overload impairs myocardial insulin sensitivity independent of AngII. Methods and Results: To mimic cardiac pressure overload, C57BL/6 mice were subjected to transverse aortic constriction (TAC) for 2 weeks in vivo . Cultured neonatal rat cardiomyocytes (NRCMs) were imposed with mechanical stretch for 24 hours in vitro . Although pressure overload dramatically restrained the glucose uptake and expression of glucose transporter 4 (GLUT4) in the myocardial membrane, it didn’t increase the local expression of AngII in TAC mouse hearts and mechanically-stretched NRCMs. C57BL/6 mice were treated with Enalapril and then subjected to TAC for 2 weeks. The glucose uptake and expression of GLUT4 in the myocardial membrane were dramatically restrained in the left ventricles (LVs) of 2 week TAC mice, which were preserved in mice treated with Enalapril. Angiotensinogen knock out ( ATG -/- ) mice were subjected to TAC for 2 weeks. Angiotensin converting enzyme (ACE)-deficient NRCMs were mechanically stretched. Insulin sensitivity was significantly impaired by TAC in ATG -/- mouse hearts and mechanical stretch in NRCMs evidenced by a notably decreased glucose uptake and expression of GLUT4 in myocardial membrane. Pressure overload impaired the myocardial insulin signals including decreased phosphorylation of insulin receptor, insulin receptor substrate 1 and Akt. Candesartan, an AngII receptor 1 (AT1R) blocker, partly attenuated the myocardial insulin resistance induced by mechanical stress in vivo and in vitro . Conclusion: In conclusion, we unraveled that pressure overload is able to provoke myocardial insulin resistance independent of AngII which was partly mediated by AT1R.
Clinical Epidemiological Research on Suicide-Related Behaviors—Where We Are and Where We Need to Go
Authors: Ronald C. Kessler
Journal: JAMA Psychiatry (2019)

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Abstract 223: Surgical Resolution of Coronary Artery Obstruction in Incomplete Kawasaki Disease
Authors: Andres N Rodriguez, Maria Del Rocio Maldonado, Enrique Faugier, Javier E Tomala, Angel D Flores, Diego Salinas, Fernando Garcia, Paola B Lara
Journal: Circulation (2015)

Case Report 8 months old male, who presented with 7 days fever, hematuria, conjunctival injection and limb edema; treated as a post infectious glomerulonephritis. Twenty days later, desquamation at the tip of the fingers and in palms and soles plus thrombocytosis were found. Considering Kawasaki disease (KD), an echocardiogram was performed, finding a 5mm aneurysm in right coronary artery and 4mm ectasia in the left coronary artery. The patient was on the subacute therefore IVIG was not administered; aspirin however in antiplatelet dose range was begun. He continued on surveillance by Cardiology Department without signs of cardiac malfunction. At two years follow up a new echocardiogram was performed, showing a left coronary aneurism of 6mm and a right coronary artery of 2.0mm which was difficult to identify. Left ventricular function was preserved with an ejection fraction of 72%. Four years later, posterior myocardial necrosis, without acute ischemia on electrocardiography was found. A perfusion myocardial scan showed an uptake defect in apical region, both during stress and rest phase, suggesting an old apical infarction. Cardiac catheterization reported a tortuous right coronary artery with diffuse obstruction and left coronary artery aneurysm of 6.1mm. Due to findings above, heart transplant was considered. On a second perfusion scan a large perfusion defect on the inferior and septal wall, which improved during the rest phase was seen. The finding above correlates with inferior and septal myocardial infarction and residual ischemia. The PET-CT scan showed viable tissue in the left ventricle wall. Recently, the patient underwent revascularization surgery of right coronary artery with coronary artery bypass graft. Postsurgical echocardiogram reported a left coronary giant aneurysm of 8mm, ejection fraction of 40%, and a compromised posterior and inferior left ventricular wall function. We report the first case of surgical resolution of a coronary artery obstruction due to KD in our medical center. Because of patient’s age and coronary arteries abnormalities, a surgically intervention was the best approach in order to preserve patient’s life, cardiac function, improve the prognosis and mainly to gain time for future treatment decisions.