tbuckley/cabot-search huggingface dataset:
Comparison of non-parametric T2 relaxometry methods for myelin water quantification
Authors: Erick Jorge Canales-Rodríguez, Marco Pizzolato, Gian Franco Piredda, Tom Hilbert, Nicolas Kunz, Caroline Pot, Thomas Yu, Raymond Salvador, Edith Pomarol-Clotet, Tobias Kober, Jean-Philippe Thiran, Alessandro Daducci
Journal: Medical Image Analysis (2021)

Multi-component T2 relaxometry allows probing tissue microstructure by assessing compartment-specific T2 relaxation times and water fractions, including the myelin water fraction. Non-negative least squares (NNLS) with zero-order Tikhonov regularization is the conventional method for estimating smooth T2 distributions. Despite the improved estimation provided by this method compared to non-regularized NNLS, the solution is still sensitive to the underlying noise and the regularization weight. This is especially relevant for clinically achievable signal-to-noise ratios. In the literature of inverse problems, various well-established approaches to promote smooth solutions, including first-order and second-order Tikhonov regularization, and different criteria for estimating the regularization weight have been proposed, such as L-curve, Generalized Cross-Validation, and Chi-square residual fitting. However, quantitative comparisons between the available reconstruction methods for computing the T2 distribution, and between different approaches for selecting the optimal regularization weight, are lacking. In this study, we implemented and evaluated ten reconstruction algorithms, resulting from the individual combinations of three penalty terms with three criteria to estimate the regularization weight, plus non-regularized NNLS. Their performance was evaluated both in simulated data and real brain MRI data acquired from healthy volunteers through a scan-rescan repeatability analysis. Our findings demonstrate the need for regularization. As a result of this work, we provide a list of recommendations for selecting the optimal reconstruction algorithms based on the acquired data. Moreover, the implemented methods were packaged in a freely distributed toolbox to promote reproducible research, and to facilitate further research and the use of this promising quantitative technique in clinical practice.
Abstract 13347: Effect of Severe Anemia (hemoglobin &lt; 10g/dl) on Short- and Long-term Outcome in Acute Coronary Syndrome: Insights of a Terciary Centre
Authors: Isabel Campos, Cátia Oliveira, Paulo Medeiros, Carla Marques Pires, Rui Flores, Fernando Mané, Carlos Braga, António Gaspar, Regina Pereira, Catarina Vieira
Journal: Circulation (2020)

Introduction: Although invasive strategies are the generalized approach in the management of ACS pts, their benefits in pts with significant anemia are unclear, as anemia is strongly associated with increased risk of morbidity and mortality. Aim: To determine the incidence and the impact of severe anemia (hemoglobin&lt;10g/dL) on short- and long-term outcome in pts hospitalized with ACS. Methods: We analyzed retrospectively 2905 ACSpts admitted for 6 years in our CCU. Pts were divided into two groups: group 1-pts with severe anemia(hemoglobin &lt; 10g/dL) (n=257,8.8%); group 2-pts without severe anemia (hemoglobin &gt;=10g/dL) (n=2648,91.2%). Primary endpoint was the occurrence of a composite of death and adverse cardiovascular events (stroke, reinfarction, and rehospitalization of cardiovascular etiology) at 6 months; FU was completed in 96%pts. Results: The sample consisted in 77.9% men and 22.1% women, with mean age of 64±13 years. The incidence of severe anemia was 8.8%. Group1 pts were older (p&lt;0.001), had a higher proportion of women (p&lt;0.001), diabetes (p&lt;0.001), CKD (p&lt;0.001) and AF (p&lt;0.001). During hospitalization, group 1 had more HF (p&lt;0.001), angor (p&lt;0.001), refarction (p=0.006), bleeding (p&lt;0.001) and transfusion (p&lt;0.001). Group 1 had a higher proportion of NSTEMI (p=0.009) as opposed to group2 which had more STEMI (p=0.031). During hospitalization, group 2 pts were more likely to undergo revascularization (p&lt;0.001). A multivariate analysis identified age [OR 1.06, 95%CI 1.04 to 1.07; p&lt;0.001] and feminine sex [OR 2.61, 95%CI 1.89 to 3.61; p&lt;0.001] as independent predictors of severe anemia during hospitalization. Pts with severe anemia had higher 6-month mortality (32.1%vs6.9%;p&lt;0.001). In multivariate analysis and after adjusting for different baseline characteristics, pts with severe anemia had higher occurrence of a composite of death and MACE at 6months [OR5.04,95%CI 1.21 to 21.04;p=0.026]. Conclusion: Severe anemia was strongly associated with increased risk of morbidity and mortality in ACS pts. However, pts with severe anemia who were double antiaggregated had no worse outcomes than those who had simple antiaggregation after 6months. Therefore, there was no significant difference regarding revascularization in these pts.
Reperfusion Injury: Putting the Genie Back in the Bottle?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Nathaniel Reichek, Kambiz Parcham-Azad
Journal: Journal of the American College of Cardiology (2010)
Shedding Light on High-Density Lipoprotein Cholesterol: The Post-ILLUMINATE Era⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Carl J. Lavie, Richard V. Milani
Journal: Journal of the American College of Cardiology (2008)
Large-scale genome sequencing reveals the driving forces of viruses in microalgal evolution
Authors: David R. Nelson, Khaled M. Hazzouri, Kyle J. Lauersen, Ashish Jaiswal, Amphun Chaiboonchoe, Alexandra Mystikou, Weiqi Fu, Sarah Daakour, Bushra Dohai, Amnah Alzahmi, David Nobles, Mark Hurd, Julie Sexton, Michael J. Preston, Joan Blanchette, Michael W. Lomas, Khaled M.A. Amiri, Kourosh Salehi-Ashtiani
Journal: Cell Host & Microbe (2021)
A Procarcinogenic Colon Microbe Promotes Breast Tumorigenesis and Metastatic Progression and Concomitantly Activates Notch and β-Catenin Axes
Authors: Sheetal Parida, Shaoguang Wu, Sumit Siddharth, Guannan Wang, Nethaji Muniraj, Arumugam Nagalingam, Christina Hum, Panagiotis Mistriotis, Haiping Hao, C. Conover Talbot, Konstantinos Konstantopoulos, Kathleen L. Gabrielson, Cynthia L. Sears, Dipali Sharma
Journal: Cancer Discovery (2021)

The existence of distinct breast microbiota has been recently established, but their biological impact in breast cancer remains elusive. Focusing on the shift in microbial community composition in diseased breast compared with normal breast, we identified the presence of Bacteroides fragilis in cancerous breast. Mammary gland as well as gut colonization with enterotoxigenic Bacteroides fragilis (ETBF), which secretes B. fragilis toxin (BFT), rapidly induces epithelial hyperplasia in the mammary gland. Breast cancer cells exposed to BFT exhibit "BFT memory" from the initial exposure. Intriguingly, gut or breast duct colonization with ETBF strongly induces growth and metastatic progression of tumor cells implanted in mammary ducts, in contrast to nontoxigenic Bacteroides fragilis. This work sheds light on the oncogenic impact of a procarcinogenic colon bacterium ETBF on breast cancer progression, implicates the β-catenin and Notch1 axis as its functional mediators, and proposes the concept of "BFT memory" that can have far-reaching biological implications after initial exposure to ETBF. SIGNIFICANCE: B. fragilis is an inhabitant of breast tissue, and gut or mammary duct colonization with ETBF triggers epithelial hyperplasia and augments breast cancer growth and metastasis. Short-term exposure to BFT elicits a "BFT memory" with long-term implications, functionally mediated by the β-catenin and Notch1 pathways.This article is highlighted in the In This Issue feature, p. 995.
Lovastatin enhances the cytotoxic effect of gemcitabine in breast cancer cells
Authors: Sejal Dave, Catherine Lobocki, Anibal Drelichman
Journal: Cancer Research (2008)

4029  Lovastatin, an inhibitor of cholesterol biosynthesis, exerts its anti-neoplastic activity by interfering with isoprenylation of mutated G-proteins such as Ras and Rho, impeding signal transduction which results in impaired cellular proliferation and shortened survival. Other anti-tumor mechanisms include G1 and G2/M growth arrest, reduced expression of matrix metalloproteinase-9, and inhibition of TNF-alpha. Gemcitabine is a nucleoside analog that exerts its effect primarily by killing cells during the S-phase of the cell cycle. The purpose of this study was to evaluate the cytotoxic and apoptotic effects of lovastatin in combination with the chemotherapeutic agent gemcitabine on breast cancer cells. Three breast carcinoma cell lines with varied sensitivities to lovastatin were studied: T47D (IC50 = 30 μM), MDA-MB231 (IC50 = 1.2 μM), and SKBR3 (IC50 = 10 μM). The growth inhibitory effect of lovastatin, using the IC50 dose for each cell line, was tested with increasing doses of gemcitabine (0.001 - 1 μM) using the MTT colorimetric assay. Apoptosis was evaluated by quantitating Caspase-3 levels and cytosolic Cytochrome C expression after 48 hrs of treatment. A dose-dependent growth inhibition was demonstrated with either drug alone, as well as the combination. After 3 days of treatment a significant antiproliferative effect was seen with the combination compared to single agents in all three cell lines (p
Abstract 14167: Incidence and Predictors of Anemia Complicating Heart Failure: The RBC HEART Study
Authors: Alan S Go, Grace H Tabada, Thomas K Leong, Jerry Gurwitz, Andrew Artz, Stanley Schrier, Sunil V Rao, Huiman Barnhart, Kristi Reynolds, David H Smith, Pamela N Peterson, Sue Hee Sung, Harvey J Cohen
Journal: Circulation (2017)

Introduction: Limited contemporary data exist about the incidence and factors associated with developing anemia in diverse heart failure (HF) populations. We characterized the incidence of anemia i...
A Prospective Randomized Study With No Clinically Important Differences in Closed vs Open Treatment for Distal Radius Fracture in Elderly Individuals
Authors: E. Gene Deune
Journal: JAMA Surgery (2021)

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 2022 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
Kinase–substrate Edge Biomarkers Provide A More Accurate Prognostic Prediction in ER-negative Breast Cancer
Authors: Yidi Sun, Chen Li, Shichao Pang, Qianlan Yao, Luonan Chen, Yixue Li, Rong Zeng
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract The estrogen receptor (ER)-negative breast cancer subtype is aggressive with few treatment options available. To identify specific prognostic factors for ER-negative breast cancer, this study included 705,729 and 1034 breast invasive cancer patients from the Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas (TCGA) databases, respectively. To identify key differential kinase–substrate node and edge biomarkers between ER-negative and ER-positive breast cancer patients, we adopted a network-based method using correlation coefficients between molecular pairs in the kinase regulatory network. Integrated analysis of the clinical and molecular data revealed the significant prognostic power of kinase–substrate node and edge features for both subtypes of breast cancer. Two promising kinase–substrate edge features, CSNK1A1–NFATC3 and SRC–OCLN, were identified for more accurate prognostic prediction in ER-negative breast cancer patients.
Comparison of Biologically Assigned HLA-Identical Versus Haploidentical Related Donor Hematopoietic Stem Cell Transplantation
Authors: Mohammad Junaid Hussain, Jigar Trivedi, Jiaxian He, Nilanjan Ghosh, Emily S Reese, Taylor Brown, Michael Richard Grunwald, Saad Z Usmani, Jonathan M. Gerber, Thomas G. Knight, Jing Ai, Ryan Jacobs, Peter M. Voorhees, Manisha Bhutani, Emiliano Mugnaini, Aleksander L. Chojecki, Danyu Sun, Sarah Lestrange, Annah Pfeiffer, Srinivasa Reddy Sanikommu, James T Symanowski, Belinda Rene Avalos, Edward A Copelan
Journal: Blood (2017)
Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors
Authors: Matthew D. Hellmann, Nicoletta Bivi, Boris Calderon, Toshio Shimizu, Brant Delafontaine, Zhuqing Tina Liu, Anna M. Szpurka, Victoria Copeland, F. Stephen Hodi, Sylvie Rottey, Philippe Aftimos, Yongzhe Piao, Leena Gandhi, Violeta Regnier Galvao, Ching Ching Leow, Toshihiko Doi
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Investigate the safety and efficacy of LY3415244, a TIM-3/PD-L1 bispecific antibody that blocks TIM-3 and PD-L1 in patients with advanced solid tumors. Patients and Methods: A phase I, multicenter, open-label study was conducted in patients with advanced solid tumors. Patients were dosed every 2 weeks intravenously with flat doses of LY3415244 escalating from 3 to 70 mg. The primary endpoints were safety, tolerability, and identification of the recommended phase II dose. Results: Between November 2018 and October 2019, 12 patients were enrolled into four cohorts and received at least one dose of LY3415244. Two patients (16.7%) developed clinically significant anaphylactic infusion-related reactions and all patients developed treatment-emergent antidrug antibodies (TE-ADA). ADA titers were sometimes very high and negatively impacted soluble TIM-3 target engagement in most patients. ADA epitope specificity was against both TIM-3 and PD-L1 arms of the bispecific antibody; most TE-ADAs initially targeted the TIM-3 arm after the first dose. Preexisting ADAs against LY3415244 were also detected in normal (unexposed) human serum samples. One patient with PD-1 refractory non–small cell lung cancer had a near partial response (−29.6%). Conclusions: This TIM-3 and PD-L1 bispecific format was associated with unexpected immunogenicity targeting both arms of the bispecific antibody, resulting in early study termination. Epitope specificity analysis revealed an initial response toward the TIM-3 arm and presence of preexisting ADAs to the bispecific molecule in the general population. This experience emphasizes the importance of thorough analyses for preexisting ADAs as part of immunogenicity risk assessment of novel antibodies. See related commentary by de Spéville and Moreno, p. 2669
Abstract 14898: Prognostic Value of Tissue Doppler Imaging for Predicting Ventricular Arrhythmias and Cardiovascular Mortality in Ischemic Cardiomyopathy
Authors: Tor Biering-Sørensen, Flemming J Olsen, Katrine Storm, Thomas Fritz-Hansen, Niels T Olsen, Christian Jøns, Peter Søgaard, Niels Risum
Journal: Circulation (2015)

Background: Only 30% of patients receiving an implantable cardioverter defibrillator (ICD) for primary prevention respond appropriately to this therapy. The purpose of this study was to investigate the value of Tissue Doppler Imaging (TDI) Echocardiography at predicting appropriate ICD therapy and cardiovascular mortality (CVD) in patients with primary prevention ICD. Methods: In total, 151 ICD patients meeting primary prevention criteria, with no history of ventricular arrhythmias were included. All participants were examined by conventional 2D echocardiography and TDI echocardiography. Longitudinal systolic (s’), early diastolic (e’), and late diastolic (a’) myocardial velocities were measured using TDI at six mitral annular sites and averaged to provide global estimates. Results: Forty patients experienced the combined endpoint of ventricular tachycardia (VT), fibrillation (VF) or CVD during a median follow-up of 2.3 years. Neither left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), E/e’, global s’ nor global e’ were significantly impaired in patients who developed VT/VF/CVD (LVEF: 31 vs. 28 %, p=0.06; GLS: 9 vs. 9 %, p=0.85; E/e’: 16 vs. 16, p=0.80; s’: 3.8 vs. 3.7 cm/s, p=0.68; e’: 4.5 vs. 4.6 cm/s, p=0.61). In contrast, global a’ was significantly lower in patients with an unfavorable outcome compared to those without (5.7±1.8 vs. 4.8±2.0 cm/s, p=0.020). Global a’ remained an independent predictor of VT/VF/CVD after multivariable adjustment for age, gender, beta blocker therapy and deceleration time (HR=1.25 [1.02; 1.54], p=0.032). Regional analysis revealed that a depressed a’ in the inferior wall drives the predictive capability of a’ (Figure). Conclusion: Late diastolic velocity by TDI seems to be a superior echocardiographic predictor of VT/VF/CVD in ischemic cardiomyopathy. Additionally, impaired late diastolic velocity in the inferior myocardial wall seems to be a paramount marker of future VT/VF/CVD.
Exosome-based <i>Ldlr</i> gene therapy for familial hypercholesterolemia in a mouse model
Authors: Zhelong Li, Ping Zhao, Yajun Zhang, Jia Wang, Chen Wang, Yunnan Liu, Guodong Yang, Lijun Yuan
Journal: Theranostics (2021)

Familial hypercholesterolemia (FH), with high LDL (low-density lipoprotein) cholesterol levels, is due to inherited mutations in genes, such as low-density lipoprotein receptor (LDLR). Development of therapeutic strategies for FH, which causes atherosclerosis and cardiovascular disease, is urgently needed. Methods: Mice with low-density lipoprotein receptor (Ldlr) deletion (Ldlr-/- mice) were used as an FH model. Ldlr mRNA was encapsulated into exosomes by forced expression of Ldlr in the donor AML12 (alpha mouse liver) cells, and the resultant exosomes were denoted as ExoLdlr. In vivo distribution of exosomes was analyzed by fluorescence labeling and imaging. The delivery efficiency of Ldlr mRNA was analyzed by qPCR and Western blotting. Therapeutic effects of ExoLdlr were examined in Ldlr-/- mice by blood lipids and Oil Red O staining. Results: The encapsulated mRNA was stable and could be translated into functional protein in the recipient cells. Following tail vein injection, exosomes were mainly delivered into the liver, producing abundant LDLR protein, resembling the endogenous expression profile in the wild-type mouse. Compared with control exosomes, ExoLdlr treatment significantly decreased lipid deposition in the liver and lowered the serum LDL-cholesterol level. Significantly, the number and size of atherosclerotic plaques and inflammation were reduced in the ExoLdlr-treated mice. Conclusions: We have shown that exosome-mediated Ldlr mRNA delivery effectively restored receptor expression, treating the disorders in the Ldlr-/- mouse. Our study provided a new therapeutic approach for the treatment of FH patients and managing atherosclerosis.
Efficacy of Pembrolizumab Monotherapy for Advanced Gastric/Gastroesophageal Junction Cancer with Programmed Death Ligand 1 Combined Positive Score ≥10
Authors: Zev A. Wainberg, Charles S. Fuchs, Josep Tabernero, Kohei Shitara, Kei Muro, Eric Van Cutsem, Yung-Jue Bang, Hyun Cheol Chung, Kensei Yamaguchi, Eniko Varga, Jen-Shi Chen, Daniel Hochhauser, Peter Thuss-Patience, Salah-Eddin Al-Batran, Marcelo Garrido, Uma Kher, Chie-Schin Shih, Sukrut Shah, Pooja Bhagia, Joseph Chao
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Pembrolizumab demonstrated efficacy in PD-L1–positive [combined positive score (CPS) ≥1] advanced gastric/gastroesophageal junction (G/GEJ) cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively. To better delineate the specificity of CPS as a predictor of clinical outcomes, we analyzed pembrolizumab efficacy in patients with CPS ≥ 10 in these trials. Patients and Methods: Included were patients with CPS ≥ 10 tumors from KEYNOTE-059 cohort 1 (pembrolizumab, n = 46; post hoc), KEYNOTE-061 (pembrolizumab, n = 53; chemotherapy, n = 55; post hoc), and KEYNOTE-062 (pembrolizumab, n = 92; chemotherapy, n = 90; primary). Efficacy outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Results: In KEYNOTE-059, median follow-up was 6 months, median OS was 8 months [95% confidence interval (CI), 5.8–11.1], ORR was 17%, and median (range) DOR was 21 months (3+ to 35+). In KEYNOTE-061, median follow-up was 9 months, median OS (pembrolizumab vs. chemotherapy) was 10 versus 8 months (HR, 0.64; 95% CI, 0.41–1.02), median PFS was 3 months versus 3 months (HR, 0.86; 95% CI, 0.56–1.33), ORR was 25% versus 9%, and median (range) DOR was not reached (4 to 26+ months) versus 7 months (3–7). In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs. chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49–0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79–1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+ to 34+) versus 7 months (2+ to 30+). Conclusions: This comprehensive analysis showed consistent improvements toward more favorable clinical outcomes with pembrolizumab across lines of therapy in patients with CPS ≥ 10 G/GEJ cancer.
Add-on azithromycin reduces sputum cytokines in non-eosinophilic asthma: an AMAZES substudy
Authors: Shakti D Shukla, Steven L Taylor, Peter G Gibson, Daniel Barker, John W Upham, Ian A Yang, Paul N Reynolds, Sandra Hodge, Alan L James, Geraint B Rogers, Jodie L Simpson
Journal: Thorax (2021)

Add-on azithromycin (AZM) significantly reduces exacerbations in poorly controlled asthma irrespective of disease phenotype. In a predefined substudy of the original AMAZES protocol (500 mg, three times a week for 48 weeks), we report that AZM treatment reduces key sputum inflammatory proteins (interleukin (IL)-6, IL-1β and extracellular DNA), which is more evident in non-eosinophilic asthma (NEA). Moreover, AZM reduced Haemophilus influenzae load only in NEA. Our data support the anti-inflammatory effects of AZM in poorly controlled asthma. Prospective studies are required to identify patients that derive greatest benefit from AZM add-on therapy.
IVUS「所見」ガイドでpseudo lumenからtrue lumenへのガイドワイヤー復帰に成功したCTOの1例
Authors: 榊原雅義, 宮澤拓也, 平野周太, 香山大輔, 奥野友信, 松尾晴海, 朝田淳, 森井健, 清水陽一
Journal: Circulation (2007)
フォーカルアドヒージョンキナーゼ(FAK)をFAK関連非キナーゼドメインに関するマイクロエレクトロポレーションで破損させると,ループ形成した心筒の膨化を引き起こす
Authors: Shiraishi I, Hamaoka K
Journal: Circulation (2002)
Nano-herb medicine and PDT induced synergistic immunotherapy for colon cancer treatment
Authors: Xiaoli Wu, Han Yang, Xingmeng Chen, Junxiao Gao, Yue Duan, Daohe Wei, Jinchao Zhang, Kun Ge, Xing-Jie Liang, Yuanyu Huang, Sizhou Feng, Rongli Zhang, Xi Chen, Jin Chang
Journal: Biomaterials (2021)