tbuckley/cabot-search huggingface dataset:
Association of Emotional Intelligence With Malpractice Claims
Authors: Daniel Shouhed, Catherine Beni, Nicholas Manguso, Waguih William IsHak, Bruce L. Gewertz
Journal: JAMA Surgery (2019)

Approximately 8% of physicians experience a malpractice claim annually. Most malpractice claims are a result of adverse events, which may or may not be a result of medical errors. However, not all medicolegal cases are the result of medical errors or negligence, but rather, may be associated with the individual nature of the patient-physician relationship. The strength of this relationship may be partially determined by a physician's emotional intelligence (EI), or his or her ability to monitor and regulate his or her emotions as well as the emotions of others. This review evaluates the role of EI in developing the patient-physician relationship and how EI may influence patient decisions to pursue medicolegal action.Several physician characteristics are associated with increased medicolegal risk. Some of these traits, such as sex, age, level of experience, and specialty, are inherent. Other characteristics, such as patient interaction, patient satisfaction, and prior legal history, appear to be related to physicians themselves, yet they are modifiable if such physicians can be identified. Numerous tools exist that provide general measures of different aspects of EI. Furthermore, identification of those with lower EI and intervention with specific training has been shown to improve both EI and patient satisfaction.The study and effect of EI within medicine offers great opportunity to investigate how physician characteristics may influence one's EI, as well as medicolegal risk. This review suggests an indirect negative correlation between a physician's level of EI and his or her risk of litigation. Studies directly linking physicians with low EI to a higher risk of litigation are lacking and may provide valuable insight. Demonstrating such a correlation should prompt the development of interventions that may enhance a physician's level of EI early in his or her career and may limit future legal action.
Phase I/II Trial of Multi-Target Chimeric Antigen Receptor Modified T Cells (4SCAR2.0) Against Relapsed or Refractory Lymphomas
Authors: Lung-Ji Chang, Yuhua Li, Sanfang Tu, Xun Lai, Rui Huang, Shih-Ting Tsao, Yu-Chen Liu, Rui Zhang, Lan Deng, Xuan Zhou, Hongyu Zhang, Wenli Zhang, Yuchen Li
Journal: Blood (2018)
Novel SPECC1L-MET Fusion Detected in Circulating Tumor DNA in a Patient with Lung Adenocarcinoma following Treatment with Erlotinib and Osimertinib
Authors: Annie W. Nelson, Alexa B. Schrock, Dean C. Pavlick, Siraj M. Ali, Emily C. Atkinson, Abraham Chachoua
Journal: Journal of Thoracic Oncology (2019)
Abstract 16820: Impaired KCNQ1/KCNE1 Channel Activation by Alpha-Adrenergic Receptor is Associated with Emotion/Arousal Triggered Events in Long QT Syndrome Type 1
Authors: Jin O-Uchi, John J Rice, Ilan Goldenberg, Arthur J Moss, Coeli M Lopes
Journal: Circulation (2011)

Background: Stimulation of the cardiac K + channel IKs (KCNQ1/KCNE1) is crucial in mediating the QT shortening at high adrenergic stimulation states, with mutations in the KCNQ1 subunit being linked to a high risk of cardiac events triggered by adrenergic stimulation. IKs is strongly regulated by β-adrenergic receptor (AR) stimulation, but little is known about the role of α 1 -AR-mediated regulation and relation to the LQT1 phenotype. Methods: We co-expressed wild-type and mutant KCNQ1/KCNE1 subunits together in HEK293T cells. A single cardiomyocyte model adapted from the Flaim-Giles-McCulloch model was used to simulate the effect of α 1 -AR and β-AR activation in action potential duration (APD). Mutation specific adrenergic-effects on APD were correlated to the cumulative rate for exercise and stress-triggered cardiac events (syncope, sudden death and aborted cardiac arrest) by age 40 for patients carrying the mutation. Results: Acute α 1 -AR activation strongly facilitated voltage dependence of IKs activation independently of β-AR stimulation (V 1/2 shift @ - 20 mV) via activation of cPKC. We measured the effect of β-AR-PKA and α 1 -AR-cPKC activation for 8 LQT1 associated mutations. For each mutant we introduced the current activation measured in a single cardiomyocyte model to simulate the overall effect of (α 1 + β1) AR stimulation. Mutant specific α 1 - and β- AR-mediated APD showed stronger correlation to the cumulative rate of emotion/arousal triggered cardiac events than β-AR alone (α+β: R 2 =0.94, β: R 2 =0.58), while β-AR activation alone showed a better correlation with exercised triggered event rate (α+β: R 2 =0.34, β: R 2 =0.74) for patients carrying these mutations. Conclusion: Our study suggests that acute α 1 -AR regulation of the voltage activation of IKs may be important for QT shortening in response to strong adrenergic stimulation in the flight and fight response. In addition, impaired α 1 -AR regulation may be linked to increased risk of sudden emotion/arousal triggered cardiac events in LQT1patients.
Implementation of the 2017 Addendum Guidelines for Peanut Allergy Prevention Among AAAAI Allergists and Immunologists
Authors: Jacqueline Johnson, Ruchi S. Gupta, Lucy A. Bilaver, Jack W. Hu, Jennifer Martin, Jialing Jiang, Alexandria Bozen, Matthew M. Davis, Jamie Reese, Susan Cooper, Alkis Togias, Samuel J. Arbes
Journal: Journal of Allergy and Clinical Immunology (2019)
Effect of Glucose Improvement on Spirometric Maneuvers in Patients With Type 2 Diabetes: The Sweet Breath Study
Authors: Liliana Gutiérrez-Carrasquilla, Enric Sánchez, Ferran Barbé, Mireia Dalmases, Carolina López-Cano, Marta Hernández, Ferran Rius, Paola Carmona, Cristina Hernández, Rafael Simó, Albert Lecube
Journal: Diabetes Care (2019)

Type 2 diabetes exerts a deleterious effect on lung function. However, it is unknown whether an improvement in glycemic control ameliorates pulmonary function.Prospective interventional study with 60 patients with type 2 diabetes and forced expiratory volume in 1 s (FEV1) ≤90% of predicted. Spirometric maneuvers were evaluated at baseline and after a 3-month period in which antidiabetic therapy was intensified. Those with an HbA1c reduction of ≥0.5% were considered to be good responders (n = 35).Good responders exhibited a significant improvement in spirometric values between baseline and the end of the study (forced vital capacity [FVC]: 78.5 ± 12.6% vs. 83.3 ± 14.7%, P = 0.029]; FEV1: 75.6 ± 15.3% vs. 80.9 ± 15.4%, P = 0.010; and peak expiratory flow [PEF]: 80.4 ± 21.6% vs. 89.2 ± 21.0%, P = 0.007). However, no changes were observed in the group of nonresponders when the same parameters were evaluated (P = 0.586, P = 0.987, and P = 0.413, respectively). Similarly, the initial percentage of patients with a nonobstructive ventilatory defect and with an abnormal FEV1 decreased significantly only among good responders. In addition, the absolute change in HbA1c inversely correlated to increases in FEV1 (r = -0.370, P = 0.029) and PEF (r = -0.471, P = 0.004) in the responders group. Finally, stepwise multivariate regression analysis showed that the absolute change in HbA1c independently predicted increased FEV1 (R2 = 0.175) and PEF (R2 = 0.323). In contrast, the known duration of type 2 diabetes, but not the amelioration of HbA1c, was related to changes in forced expiratory flow between 25% and 75% of the FVC.In type 2 diabetes, spirometric measurements reflecting central airway obstruction and explosive muscle strength exhibit significant amelioration after a short improvement in glycemic control.
Protease-Activatable Adeno-Associated Virus Vector for Gene Delivery to Damaged Heart Tissue
Authors: Caitlin M. Guenther, Mitchell J. Brun, Antonette D. Bennett, Michelle L. Ho, Weitong Chen, Banghe Zhu, Michael Lam, Momona Yamagami, Sunkuk Kwon, Nilakshee Bhattacharya, Duncan Sousa, Annicka C. Evans, Julie Voss, Eva M. Sevick-Muraca, Mavis Agbandje-McKenna, Junghae Suh
Journal: Molecular Therapy (2019)

Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, and low immunogenicity compared to other viruses. However, its adoption as a safe and effective delivery vector for certain diseases relies on altering its tropism to deliver transgenes to desired cell populations. To this end, we have developed a protease-activatable AAV vector, named provector, that responds to elevated extracellular protease activity commonly found in diseased tissue microenvironments. The AAV9-based provector is initially inactive, but then it can be switched on by matrix metalloproteinases (MMP)-2 and -9. Cryo-electron microscopy and image reconstruction reveal that the provector capsid is structurally similar to that of AAV9, with a flexible peptide insertion at the top of the 3-fold protrusions. In an in vivo model of myocardial infarction (MI), the provector is able to deliver transgenes site specifically to high-MMP-activity regions of the damaged heart, with concomitant decreased delivery to many off-target organs, including the liver. The AAV provector may be useful in the future for enhanced delivery of transgenes to sites of cardiac damage.
Imaging findings of patients undergoing SBRT for HCC after prior TACE.
Authors: Aneliya Maleeva, Tarita Thomas, Joseph H Yacoub
Journal: Journal of Clinical Oncology (2019)

252 Background: Our purpose is to assess the treatment response using follow up MRI or CT in lesions treated with stereotactic body radiation therapy (SBRT) after transarterial chemoembolization (TACE). Methods: Twenty-six patients treated with liver SBRT at our institution in the period between 2015 and 2017. Of these we included patients who had lesions diagnosed as HCC (LR-5) or probable HCC (LR-4), and who had prior TACE with a residual/recurrent enhancing component on the pre SBRT images with adequate post SBRT imaging. One radiologist (5 year experience) evaluated all pre and post SBRT imaging and measured the lesion size and the size of the largest enhancing component. Lesion decrease or increased in size was assessed based on the mRECIST criteria. Explant pathology results were collected for patients who received transplant. Necrosis &gt; 90% on explant was considered full response to treatment. AFP (alpha-fetoprotien) values before and after SBRT were collected. Results: Eight patients with 9 lesions meet our inclusion criteria, 3 of which were LR-5 and 6 LR-4 prior to the TACE. At 3 month, 2 lesions had no residual enhancing component, 2 lesions decreased in size, 2 lesions increased in size, 3 lesions remain unchanged. After maximum available follow-up (ranging from 3 to 8 months), 3 lesions had no residual enhancing component, 2 decreased, 2 lesions increased in size, 2 lesions remain unchanged. Of the 3 lesions that were definitive HCC (LR-5): 1 lesion decreased in size, 2 lesions increased in size. 4 of 8 patients (4 lesions) underwent transplant, 3 of them showed only 50% necrosis on explant. 1 of 3 lesions showed no change in size by imaging, the other 2 lesions had no residual enhancing component. Only 1 lesion had full response on the transplant. This lesion was unchanged on 3 and 6 months follow up. The AFP was not helpful since the majority of the patient had low pre-treatment AFP. Conclusions: Patient with viable disease on imaging after TACE subsequently treated with SBRT demonstrated variable behavior on imaging. Close to half demonstrated resolution of the enhancing component, however, in the few that had explant follow up there was no correlation between imaging findings and pathology.
Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibres on intestinal inflammation
Authors: Vishal Singh, Beng San Yeoh, Rachel E Walker, Xia Xiao, Piu Saha, Rachel M Golonka, Jingwei Cai, Alexis Charles Andre Bretin, Xi Cheng, Qing Liu, Michael D Flythe, Benoit Chassaing, Gregory C Shearer, Andrew D Patterson, Andrew T Gewirtz, Matam Vijay-Kumar
Journal: Gut (2019)

Diets rich in fermentable fibres provide an array of health benefits; however, many patients with IBD report poor tolerance to fermentable fibre-rich foods. Intervention studies with dietary fibres in murine models of colonic inflammation have yielded conflicting results on whether fibres ameliorate or exacerbate IBD. Herein, we examined how replacing the insoluble fibre, cellulose, with the fermentable fibres, inulin or pectin, impacted murine colitis resulting from immune dysregulation via inhibition of interleukin (IL)-10 signalling and/or innate immune deficiency (Tlr5KO).Mice were fed with diet containing either cellulose, inulin or pectin and subjected to weekly injections of an IL-10 receptor (αIL-10R) neutralising antibody. Colitis development was examined by serological, biochemical, histological and immunological parameters.Inulin potentiated the severity of αIL10R-induced colitis, while pectin ameliorated the disease. Such exacerbation of colitis following inulin feeding was associated with enrichment of butyrate-producing bacteria and elevated levels of caecal butyrate. Blockade of butyrate production by either metronidazole or hops β-acids ameliorated colitis severity in inulin-fed mice, whereas augmenting caecal butyrate via tributyrin increased colitis severity in cellulose containing diet-fed mice. Elevated butyrate levels were associated with increased IL-1β activity, while inhibition of the NOD-like receptor protein 3 by genetic, pharmacologic or dietary means markedly reduced colitis.These results not only support the notion that fermentable fibres have the potential to ameliorate colitis but also caution that, in some contexts, prebiotic fibres can lead to gut dysbiosis and surfeit colonic butyrate that might exacerbate IBD.
Abstract #4561: Preclinical studies of CG200745, novel histone deacetylase inhibitor discovered using structure-based drug discovery technologies
Authors: Young-Lan Hyun, Hyun Ji Kim, Yong Eun Kim, Jun Hee Lee, Cheol Hae Lee, Hee Jung Jung, Jae Hak Kim, Eunha Choi, Dong-Kyu Shin, Myung Guan Park, Sun Nam Kim, Ho-Jin Chang, Jong-Ryoo Choi, Joong Myung Cho, Seonggu Ro
Journal: Cancer Research (2009)

Histone acetylation and deacetylation play essential roles in modifying chromatin structure and regulating gene expression in eukaryotes. Histone deacetylase (HDACs) regulate histone acetylation by catalyzing the removal of acetyl groups on the side chain of lysine of core nucleosomal histones. This posttranslational modification of core histone is involved in the regulation of the transcriptional activity of certain genes. It has been known that aberrant recruitment of HDAC activity is associated with the development of certain human cancers. In this study, we have discovered series of HDAC inhibitors by using the structure-based drug discovery technologies. The optimized compounds were evaluated by various enzyme inhibitory assays, anti-proliferation assays against cancer cell lines, FACS analysis and measurement of acetylated histone accumulation. We also carried out in vitro ADME studies including metabolic stability, CYP inhibition assays, and in vivo PK studies. The anti-tumor efficacy was also tested in the various xenograft tumor model. Many of them showed clear anti-tumor effects. Among them, CG200745 showed promising anti-tumor profiles. CG200745 inhibits histone deacetylase activity in low range nM of IC50 against class 1 and class II HDACs. The CG200745 exhibited a broad spectrum of anti-proliferative activity against various cancer cell lines at sub micromolar EC50. Mechanistically, the CG200745 induced dose -dependent increase in the accumulation of acetylated histone H4 and in apoptosis supported by annexin-V analysis in various tumor cell lines. CG200745 also showed potent antitumor effect in various xenograft tumor model. In addition, the preclinical safety studies of CG200745 were performed in rodent and non-rodent systems for dose determination of first in human trial. In conclusion, CG200745, novel HDAC inhibitors that are discovered through the structure based drug discovery, showed potent anti-tumor activity in cell-based assays and animal studies. Currently, further PK/PD studies and preclinical safety studies of CG200745 are in progress.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4561.
Adjuvant therapy is associated with improved survival in pT1N1 gastric cancer in a heterogeneous western patient population.
Authors: Matthew R. Porembka, Caitlin Hester, Mathew M Augustine, John C. Mansour, Patricio Polanco, Adam Charles Yopp, Herbert Zeh, Sam C. Wang
Journal: Journal of Clinical Oncology (2019)

36 Background: Two recent South Korean studies showed adjuvant therapy (AT) was not associated with improved survival in pT1N1 gastric adenocarcinoma (GAC). We aimed to establish the prognostic utility of lymph node status, determine the pattern of use of AT, and compare survival stratified by type of AT in pT1N1 GAC in a Western patient population. Methods: We identified patients with pT1N0 and pT1N1 GAC using the National Cancer Database from 2004 to 2012. Clinicopathologic variables, treatment regimens, and overall survival (OS) were compared. Results: We compared 4,516 (86.6%) pT1N0 to 696 (13.4%) pT1N1 patients. pT1N1 tumors were larger (median size 2.5 vs. 1.8 cm, p &lt; 0.001), more often poorly differentiated (56.2% vs. 39.6%, p &lt; 0.001), and had higher median retrieved lymph nodes (RLN) (14 vs. 12, p &lt; 0.001) compared to pT1N0. pT1N1 was associated with worse median OS (6.9 years vs. 9.9 years for pT1N0, p &lt; 0.001). pN1 was independently associated with worse OS (HR 2.17 95% CI 1.84-2.56). Increased RLN was associated with improved OS (HR 0.73, 95% CI 0.65-0.83). Among pT1N1 patients, 330 (47.4%) had observation (OBS), 77 (11.1%) received adjuvant chemotherapy (ACT), 68 (9.8%) received adjuvant radiation therapy (ART), and 221 (31.8%) received adjuvant chemoradiation therapy (ACRT). ACT and ACRT were independently associated with improved OS (HR 0.37, 95% CI 0.22-0.65 and HR 0.40, 95% CI 0.28-0.57). Conclusions: pN1 was associated with worse survival and RLN ≥ 15 was associated with improved survival in pT1 GAC. ACT and ACRT were independently associated with improved survival in pT1N1 gastric cancer suggesting a valuable role in Western patients.
Splenic Hemangioma as a Potential Pitfall on PSMA-Targeted 18F-DCFPyL PET/CT
Authors: Guillaume Chaussé, Jerome Laufer, Gad Abikhzer, Stephan Probst
Journal: Clinical Nuclear Medicine (2019)

Abstract A 69-year-old man with biochemical recurrence after radical prostatectomy underwent 6 months of androgen deprivation therapy. Upon discontinuation of androgen deprivation therapy, serum prostate-specific antigen rose again to 0.69 ng/mL, and 18 F-DCFPyL PET/CT was performed to identify the site of recurrence. However, only an intense focus of uptake in the spleen could be found. Subsequent contrast-enhanced MRI findings were pathognomonic for splenic hemangioma.
Abstract 11966: Rhythm Changes Following Defibrillation During Resuscitation in Out-of-hospital Cardiac Arrest
Authors: Yongqin Li, Yushun Gong, Mi He, Weilun Quan
Journal: Circulation (2015)

Introduction: In the treatment of cardiac arrest, immediate resumption of chest compressions is recommended after delivery of defibrillation. However, it is unclear what the optimal timing is to determine presence of an organized rhythm after shock delivery. The purpose of this study was to investigate the dynamic rhythm changes after defibrillation during resuscitation. Methods: A total of 581 shocks from 264 out-of-hospital cardiac arrest patients with ventricular fibrillation (VF) as the first recorded rhythm were included in this study. Post shock rhythms were analyzed every10 seconds after each shock up to 120 seconds. We determined the presence of VF, asystole (AS) and organized rhythm (OR) at each time point. Results: Ten seconds after shock delivery, VF had been terminated in 70.4% cases (N=409). However, 53.5% of these non-VF rhythms were AS (N=219). Rhythm changes occurred in half of all cases (N=274, 47.2%) during the 2 minutes after shock delivery (Figure 1) and 88.3% of these changes occurred within 60 seconds. Of those initially in AS, 62 (28.3%) evolved into OR within 32.4±24.6 seconds and 117 (53.4%) returned to VF after 31.3±19.9 seconds. Of those with OR (N=190), 89 (46.8%) returned to VF 40.2±28.2 seconds later and 6 degenerated to AS (3.2%) after 48.3±41.7 seconds. VF was recurred in 50.4% (N=206) non-VF rhythms but there were no post-shock rhythm changes in patients remaining in VF (N=172) after shock delivery. Conclusion: Post-shock rhythms are very volatile in the first minute after shock delivery. Given the large percentage of post-shock rhythm changes, chest compressions should resume for at least 60 seconds immediately after a shock before rhythm and pulse are checked. Technology displaying cardiac rhythm during chest compressions could help to decide whether chest compressions should be stopped for a pulse check at that time.
Human megakaryocytes possess intrinsic antiviral immunity through regulated induction of IFITM3
Authors: Robert A. Campbell, Hansjorg Schwertz, Eugenio D. Hottz, Jesse W. Rowley, Bhanu Kanth Manne, A. Valance Washington, Robert Hunter-Mellado, Neal D. Tolley, Miles Christensen, Alicia S. Eustes, Emilie Montenont, Seema Bhatlekar, Cassandra H. Ventrone, Beth D. Kirkpatrick, Kristen K. Pierce, Stephen S. Whitehead, Sean A. Diehl, Paul F. Bray, Guy A. Zimmerman, Yasuhiro Kosaka, Patricia T. Bozza, Fernando A. Bozza, Andrew S. Weyrich, Matthew T. Rondina
Journal: Blood (2019)
An Orally Active Galectin-3 Antagonist Inhibits Lung Adenocarcinoma Growth and Augments Response to PD-L1 Blockade
Authors: Lynda Vuong, Eleni Kouverianou, Claire M. Rooney, Brian J. McHugh, Sarah E.M. Howie, Christopher D. Gregory, Stuart J. Forbes, Neil C. Henderson, Fredrik R. Zetterberg, Ulf J. Nilsson, Hakon Leffler, Paul Ford, Anders Pedersen, Lise Gravelle, Susan Tantawi, Hans Schambye, Tariq Sethi, Alison C. MacKinnon
Journal: Cancer Research (2019)

Abstract A combination therapy approach is required to improve tumor immune infiltration and patient response to immune checkpoint inhibitors that target negative regulatory receptors. Galectin-3 is a β-galactoside-binding lectin that is highly expressed within the tumor microenvironment of aggressive cancers and whose expression correlates with poor survival particularly in patients with non–small cell lung cancer (NSCLC). To examine the role of galectin-3 inhibition in NSCLC, we tested the effects of galectin-3 depletion using genetic and pharmacologic approaches on syngeneic mouse lung adenocarcinoma and human lung adenocarcinoma xenografts. Galectin-3−/− mice developed significantly smaller and fewer tumors and metastases than syngeneic C57/Bl6 wild-type mice. Macrophage ablation retarded tumor growth, whereas reconstitution with galectin-3-positive bone marrow restored tumor growth in galectin-3−/− mice, indicating that macrophages were a major driver of the antitumor response. Oral administration of a novel small molecule galectin-3 inhibitor GB1107 reduced human and mouse lung adenocarcinoma growth and blocked metastasis in the syngeneic model. Treatment with GB1107 increased tumor M1 macrophage polarization and CD8+ T-cell infiltration. Moreover, GB1107 potentiated the effects of a PD-L1 immune checkpoint inhibitor to increase expression of cytotoxic (IFNγ, granzyme B, perforin-1, Fas ligand) and apoptotic (cleaved caspase-3) effector molecules. In summary, galectin-3 is an important regulator of lung adenocarcinoma progression. The novel galectin-3 inhibitor presented could provide an effective, nontoxic monotherapy or be used in combination with immune checkpoint inhibitors to boost immune infiltration and responses in lung adenocarcinoma and potentially other aggressive cancers. Significance: A novel and orally active galectin-3 antagonist inhibits lung adenocarcinoma growth and metastasis and augments response to PD-L1 blockade.