tbuckley/cabot-search huggingface dataset:
Abstract PS16-32: Obg-like ATPase 1 enhances chemoresistance of breast cancer <i>via</i> activation of TGF-β/Smad axis cascades
Authors: Gary Xiao, Jianzhou Liu, Xiaoyu Miao
Journal: Cancer Research (2021)

Abstract Background: Understanding the molecular mechanism of drug resistance helps identify aneffective target for therapy of breast cancer. We investigated in this study the regulatory role ofObg-like ATPase 1 playing in multiple drug resistance of breast cancer.Methods: Paclitaxel resistant cell line (MCF-7-PTR) was developed by a continuous increasingpaclitaxel concentration. MTT assay was used to validate either acquired resistant or OLA1modified cell lines. qRT-PCR, immunoblot, apoptosis and cell cycle assays were performed toassess expression of genes and proteins in cell lines. A series of in vitro assays was performed inthe cells with RNAi-mediated knockdown to elucidate the regulatory role of OLA1 in breast cancer.Findings: We demonstrated that OLA1 was highly correlated with either acquired or intrinsicresistance of breast cancer. Further study showed that escalated expression of OLA1 promotedEMT process in tumor cells through TGF-β/Smad signaling cascades, resulting in the enhancedexpression of anti-apoptosis-related proteins (cleaved caspase3, Bax, Bcl-2) and the strengthendepolymerization of microtubules in tumor cells. Our findings revealed that OLA1 enhanced theanti-apoptotic ability and elucidated a regulatory role of OLA1 in promoting drug resistance ofbreast cancer.Interpretation: OLA1 is highly correlated with drug resistance of breast cancer. Chemo-sensitivity of the disease can be thus enhanced significantly by knocked down OLA1,which ledto inactivation of the TGF-β/Smad signaling cascades, polymerized microtubules, and promotedcell apoptosis. Our data suggest that OLA1 may be developed as a potential target to improvechemotherapy of patients with breast cancer.Keywords: breast cancer; Obg-like ATPase 1; multidrug resistance; γ-tubulin; paclitaxel Citation Format: Gary Xiao, Jianzhou Liu, Xiaoyu Miao. Obg-like ATPase 1 enhances chemoresistance of breast cancer via activation of TGF-β/Smad axis cascades [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-32.
Comment on Herring et al. Metabolic Effects of an SGLT2 Inhibitor (Dapagliflozin) During a Period of Acute Insulin Withdrawal and Development of Ketoacidosis in People With Type 1 Diabetes. Diabetes Care 2020;43:2128–2136
Authors: Geremia B. Bolli, Francesca Porcellati, Paola Lucidi, Carmine G. Fanelli
Journal: Diabetes Care (2021)

The recent article by Herring et al. (1) is an interesting attempt to establish the mechanisms of diabetic ketoacidosis (DKA) associated with use of SGLT inhibitors (SGLT-i) in type 1 diabetes (T1D). The unmet needs of T1D treated with either multiple daily insulin injections (MDII) or continuous subcutaneous insulin infusion (CSII) have stimulated interest in using “adjunct therapy” (2). SGLT-i are popular in T2D and appear attractive also in T1D (2). However, because of the greater risk of DKA, the use of SGLT-i in T1D is, at present, controversial.

Herring et al. (1) treated a small group of people with T1D on CSII for 7 days with SGLT2-i or placebo, then switched them from s.c. to i.v. insulin for at least 2 h, after which they acutely withdrew insulin and studied glucose and lipid metabolism over a period of 10 h fasting. As expected, acute insulin deficiency resulted in lower increase in plasma glucose (PG) with SGLT2-i despite higher endogenous glucose …
It's a matter of (executive) load: Separation as a load-dependent resetting procedure
Authors: Giorgia Ponsi, Vanessa Era, Chiara Fini, Ilenia Falcinelli
Journal: Behavioral and Brain Sciences (2021)

Abstract Lee and Schwarz made considerable theoretical advances in the psychology of cleansing by proposing that cleaning actions might serve as separation procedures between two psychological entities. Here, we propose that the effectiveness of the separation process may be modulated by the available amount of executive resources, and that separation may operate as a load-dependent resetting procedure.
Abstract 14837: Social Determinants of Health and Outcomes in Patients With Advanced Heart Failure: Findings From PAL-HF
Authors: Vanessa Blumer, Joseph G Rogers, Christopher OConnor, Robert M Clare, Daniel B Mark, Mona Fiuzat, Bradi B Granger, Chetan B Patel, Marc D Samsky, Kimberly Johnson, James Tulsky, Robert J Mentz
Journal: Circulation (2020)

Background: Social determinants of health (SDH) are associated with cardiovascular disease outcomes, but the overall influence of SDH on end-stage heart failure has not been well-described. Methods: In the Palliative Care in Heart Failure (PAL-HF) study, 150 advanced HF patients were randomized to usual care or usual care plus palliative care intervention. In the present analysis, quality of life (QoL) metrics [Kansas City Cardiomyopathy Questionnaire (KCCQ) and Functional Assessment of Chronic Illness Therapy (FACIT) Palliative care (PAL)], anxiety and depression (Hospital Anxiety and Depression Scale; HADS Depression, HADS Anxiety) and clinical outcomes (mortality, rehospitalization) were examined based on SDH (marital status, employment status, economic security, education level). For statistical analyses, patients were grouped per independent variable of interest in dichotomous categories (partner vs. no partner, employed/retired vs. unemployed, patient-reported economic constraints vs. no constraints, education beyond high school (HS) vs. less than HS). Repeated measures models were used to compare QoL metrics between SDH groups and Cox models for clinical outcomes. Results: At 6-month follow-up, having a partner, being employed, education beyond HS, and having economic security were not associated with better QoL or anxiety/depression metrics in advanced HF patients. Unemployment and education less than HS were associated with increased 6-month rehospitalization (both p=0.03). SDH measures were not associated with mortality (all p&gt;0.05) (Table). Conclusions: In this analysis of PAL-HF patients, SDH were not associated with improved QoL or anxiety/depression metrics over 6 months. However, being employed and education beyond HS were associated with reduced rehospitalization. Further studies accounting for SDH are needed to better determine how these factors should be incorporated into palliative care interventions in advanced HF.
Organ Donation After Euthanasia Starting at Home Is Feasible
Authors: Johan P. C. Sonneveld, Johannes Mulder
Journal: JAMA Surgery (2021)

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Abstract PS9-55: Subcutaneous fixed-dose combination of pertuzumab and trastuzumab for the treatment of metastatic breast cancer in Canada - a budget impact analysis
Authors: Kaushik Sripada, Siddhi Manjrekar, Kristoph Klein-Panneton, Megan Coombes, Cristiano Ferrario
Journal: Cancer Research (2021)

Abstract Background: Recently, the FeDeriCa trial investigated a fixed-dose combination (FDC) of Perjeta and Herceptin (PH), administered by subcutaneous (SC) injection, and demonstrated non-inferior pharmacokinetics of serum Perjeta and Herceptin levels compared to PH IV, along with a similar efficacy and safety profile to the intravenous (IV) administration of PH. In Canada, the standard of care for first-line HER2-positive metastatic breast cancer (mBC) is PH plus taxane chemotherapy with PH until disease progression. Currently, PH are administered as sequential IV infusions. SC administration of PH FDC has the potential to relieve pressure on the healthcare system, decrease treatment burden, and improve the patient experience. Objective: To estimate the incremental costs/savings, including time savings, associated with the use of PH FDC SC for the treatment of HER2+ mBC, if reimbursed with the same provincial funding criteria as PH IV in Ontario and Quebec, Canada. Methods: An Excel-based budget impact model was developed to determine the economic impact of PH FDC SC in comparison to PH IV in Ontario and Quebec. Direct medical costs in the analysis included drug acquisition, drug preparation and administration, and systemic therapy infusion chair/suite costs. Nurse and pharmacist wages were obtained from the Government of Canada’s Job Bank. Systemic therapy infusion chair/suite costs were derived from literature. Data related to time associated with preparation and administration of PH FDC SC and PH IV were collected through a survey completed by nurses and pharmacists involved in the FeDeriCa clinical trial in Canada. Results: HER2+ mBC patients treated with PH FDC SC generate net cost savings to the health system compared to treatment with PH IV. These cost savings to the health system are generated due to fewer costs associated with drug acquisition, pharmacist and nurse wages directed towards drug preparation and administration respectively, as well as fewer overhead costs associated with the infusion chair/suite for PH FDC SC compared to PH IV. The use of PH FDC SC provides the healthcare payer with the opportunity to optimize drug and medical resources appropriately while offering a therapy that is aligned with patient and clinician preferences. Citation Format: Kaushik Sripada, Siddhi Manjrekar, Kristoph Klein-Panneton, Megan Coombes, Cristiano Ferrario. Subcutaneous fixed-dose combination of pertuzumab and trastuzumab for the treatment of metastatic breast cancer in Canada - a budget impact analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-55.
NK/ILC1 cells mediate neuroinflammation and brain pathology following congenital CMV infection
Authors: Daria Kveštak, Vanda Juranić Lisnić, Berislav Lisnić, Jelena Tomac, Mijo Golemac, Ilija Brizić, Daniela Indenbirken, Maja Cokarić Brdovčak, Giovanni Bernardini, Fran Krstanović, Carmen Rožmanić, Adam Grundhoff, Astrid Krmpotić, William J. Britt, Stipan Jonjić
Journal: The Journal of Experimental Medicine (2021)

Congenital human cytomegalovirus (cHCMV) infection of the brain is associated with a wide range of neurocognitive sequelae. Using infection of newborn mice with mouse cytomegalovirus (MCMV) as a reliable model that recapitulates many aspects of cHCMV infection, including disseminated infection, CNS infection, altered neurodevelopment, and sensorineural hearing loss, we have previously shown that mitigation of inflammation prevented alterations in cerebellar development, suggesting that host inflammatory factors are key drivers of neurodevelopmental defects. Here, we show that MCMV infection causes a dramatic increase in the expression of the microglia-derived chemokines CXCL9/CXCL10, which recruit NK and ILC1 cells into the brain in a CXCR3-dependent manner. Surprisingly, brain-infiltrating innate immune cells not only were unable to control virus infection in the brain but also orchestrated pathological inflammatory responses, which lead to delays in cerebellar morphogenesis. Our results identify NK and ILC1 cells as the major mediators of immunopathology in response to virus infection in the developing CNS, which can be prevented by anti–IFN-γ antibodies.
Retraction: KSHV vFLIP Is Essential for the Survival of Infected Lymphoma Cells
Authors: Ilaria Guasparri, Shannon A. Keller, Ethel Cesarman
Journal: The Journal of Experimental Medicine (2021)

Primary effusion lymphomas (PELs) associated with infection by the Kaposi's sarcoma–associated herpesvirus (KSHV/HHV-8) have constitutive nuclear factor (NF)–κB activity that is essential for their survival, but the source of this activity is unknown. We report that viral FADD-like interleukin-1-β–converting enzyme [FLICE/caspase 8]-inhibitory protein (FLIP) activates NF-κB more potently than cellular FLIP in B cells and that it is largely responsible for NF-κB activation in latently infected PEL cells. Elimination of vFLIP production in PEL cells by RNA interference results in significantly decreased NF-κB activity, down-regulation of essential NF-κB–regulated cellular prosurvival factors, induction of apoptosis, and enhanced sensitivity to external apoptotic stimuli. vFLIP is the first virally encoded gene shown to be essential for the survival of naturally infected tumor cells.
Abstract 13377: Benefit and Risk of Antithrombotic Therapy in Patients With Atrial Fibrillation -A Report From the CHART-2 Study-
Authors: Takashi Shiroto, Yasuhiko Sakata, Kotaro Nochioka, Ruri Abe, Takuya Oikawa, Shintaro Kasahara, Masayuki Sato, Hajime Aoyanagi, Shinsuke Yamanaka, Takahide Fujihashi, Masanobu Miura, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2018)

Background: Antithrombotic agents, especially anticoagulants (ACs), are widely used for patients with atrial fibrillation (AF) to prevent thromboembolic events including stroke. However, the effica...
Abstract 13194: Relationship Between Left Ventricular Diastolic Intra-Ventricular Pressure Gradient Just After Aortic Valve Closure Using Vector Flow Mapping and Left Ventricular Diastolic Suction in Humans
Authors: Takeshi Hozumi, Yuki Nozawa, Kazushi Takemoto, Suwako Fujita, Wada Teruaki, Manabu Kashiwagi, Kunihiro Shimamura, Yasutsugu Shiono, Akio Kuroi, Yoshiki Matsuo, Yasushi Ino, Takashi Kubo, Atsushi Tanaka, Takashi Akasaka
Journal: Circulation (2019)

Introduction: Left ventricular (LV) early diastolic (ED) suction is an important determinant of LV diastolic function. Previous studiesusing color M-mode echocardiography have shown ED LV untwistin...
Promoting Ethical Payments in Human Challenge Studies Conducted in LMICs: Are We Asking the Right Questions?
Authors: Paul Ndebele, Adnan A. Hyder
Journal: The American Journal of Bioethics (2021)

The paper by Lynch et al. (2021) raises interesting ethical questions regarding whether and how much SARS-CoV-2 Human Challenge Studies (HCS) participants should be paid. We appreciate the timely e...
Abstract 145: Efficacy of ECG Waveform to Predict Outcome in Patients With Out-of-Hospital Cardiac Arrest
Authors: Ryozo Yoshioka, Chihiro Narita, Koichi Haruta, Kyuhei Miyakawa, Nobuyuki Maki, Akihiro Miyake, Naoki Tosaka, Hiroshi Yoshida, Hiroshi Nonogi
Journal: Circulation (2018)

Introduction: Neurological intact survival of pulseless electrical activity (PEA) has extremely poor outcome when compared with ventricular fibrillation. In Japan, the all patients with out-of-hospital cardiac arrest received CPR is transferred to emergency hospitals. To determine termination of resuscitation, it is necessary to predict their outcome. Therefore, we analyzed the relationship between ECG changes during prehospital resuscitation and outcome. Method: This study is a retrospective observational study for out-of-hospital PEA in April 2012 - April 2017 which was transported to the emergency medical center in Shizuoka General Hospital. We examined consecutive PEA cases where recorded by emergency medical services. The QRS width and RR interval were measured in ECG recording in the initial check pulse phase and arrival hospital. The primary outcome was survival admission and the secondary outcome was good neurologic outcome defined as cerebral performance score (CPC) of 1, 2. ECG changes determined as QRS width and RR interval in initial rhythm minus those at hospital arrival. Results: Eighty-four patients were analyzed and the average age was 77.3 years old, male 52.0%. There were 44 cases (52%) with survival admission (ROSC cases) and 7 (8%) with CPC 1-2. ROSC cases showed significantly narrower QRS width than non-ROSC cases in the initial waveform (139.1±61.9 vs 165.5±57.5msec, P&lt;0.05). Regarding ECG waveform changes, RR interval was significantly shortened in ROSC cases(-356.0±1256.0 vs 386.8±1258.6msec, P&lt;0.01). Comparing CPC1-2 cases and CPC3-5 cases, QRS width is significantly narrower in CPC1-2 cases(108.6±44.51 vs 155.6±60msec, P&lt;0.05), and there were no significant differences in ECG waveform changes. Multivariate analysis revealed that Initial QRS width and RR interval change are the independent factors associated with survival admission. Conclusion: Those findings suggested that analyzing QRS width and change of RR intervals during prehospital resuscitation predict survival admission in PEA cases.
Impact of hydroxytyrosol on stroke: tracking therapy response on neuroinflammation and cerebrovascular parameters using PET-MR imaging and on functional outcomes
Authors: Cristina Barca, Maximilian Wiesmann, Jesús Calahorra, Lydia Wachsmuth, Christian Döring, Claudia Foray, Ali Heiradi, Sven Hermann, Maria Ángeles Peinado, Eva Siles, Cornelius Faber, Michael Schäfers, Amanda J Kiliaan, Andreas H. Jacobs, Bastian Zinnhardt
Journal: Theranostics (2021)

Immune cells have been implicated in influencing stroke outcomes depending on their temporal dynamics, number, and spatial distribution after ischemia.Depending on their activation status, immune cells can have detrimental and beneficial properties on tissue outcome after stroke, highlighting the need to modulate inflammation towards beneficial and restorative immune responses.Novel dietary therapies may promote modulation of pro-and anti-inflammatory immune cell functions.Among the dietary interventions inspired by the Mediterranean diet, hydroxytyrosol (HT), the main phenolic component of the extra virgin olive oil (EVOO), has been suggested to have antioxidant and anti-inflammatory properties in vitro.However, immunomodulatory effects of HT have not yet been studied in vivo after stroke.The aim of this project is therefore to monitor the therapeutic effect of a HT-enriched diet in an experimental stroke model using non-invasive in vivo multimodal imaging, behavioural phenotyping and cross-correlation with ex vivo parameters.Methods: A total of N = 22 male C57BL/6 mice were fed with either a standard chow (n = 11) or a HT enriched diet (n = 11) for 35 days, following a 30 min transient middle cerebral artery occlusion (tMCAo).T2-weighted (lesion) and perfusion (cerebral blood flow)-/diffusion (cellular density)-weighted MR images were acquired at days 1, 3, 7, 14, 21 and 30 post ischemia.[ 18 F]DPA-714 (TSPO, neuroinflammation marker) PET-CT scans were acquired at days 7, 14, 21 and 30 post ischemia.Infarct volume (mm 3 ), cerebral blood flow (mL/100g/min), apparent diffusion coefficient (10 -4 •mm 2 /s) and percentage of injected tracer dose (%ID/mL) were assessed.Behavioural tests (grip test, rotarod, open field, pole test) were performed prior and after ischemia to access therapy effects on sensorimotor functions. Ivyspring International
Abstract PS18-22: Association of molecular biomarkers heterogeneity and treatment pattern, disease outcomes in multifocal or multicentric breast cancer patients
Authors: Shuai Li, Jiayi Wu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Xiaosong Chen, Kunwei Shen
Journal: Cancer Research (2021)

Abstract Background: To evaluate the rates of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 heterogeneity in multifocal or multicentric breast cancer (MMBC) and its association with treatment pattern and disease outcomes.Methods: MMBC patients with ER, PR, HER2, and Ki67 results for each tumor focus were retrospectively analyzed. Patients with concordant ER, PR, HER2, and Ki67 status among all invasive tumor foci were categorized into the Homo group, while the rest were defined as the Hetero group. Chi-square or Fisher test were performed to compare the treatment options between the Hetero and Homo groups. Disease-free survival (DFS) and overall survival (OS) rates were estimated from Kaplan-Meier curves and compared between two groups.Results: A total of 330 patients were included. Concordance rates of ER, PR, HER2, Ki67, and molecular subtype were 97.0%, 93.9%, 96.5%, 91.2%, and 88.2%, respectively (all P values &amp;lt; 0.001). There were 53 (16.1%) and 287 (83.9%) patients classified into the Hetero and Homo groups. Adjuvant endocrine therapy was more frequently assigned for patients in the Hetero group than in the Homo group (84.9% vs. 71.7%, P = 0.046). There was no difference in terms of adjuvant anti-HER2 therapy (28.3% vs. 19.6%, P = 0.196) and chemotherapy (69.9% vs. 69.8%, P = 0.987) usage between two groups. At a median follow-up of 36 months, DFS rates were 81.2% for the Hetero group and 96.5% for the Homo group (HR = 2.81, 95% CI: 1.00-7.88, P = 0.041). The estimated 3-year OS rates for these two groups were 95.8% and 99.5%, respectively (HR = 4.31, 95% CI: 0.83-22.46, P = 0.059).Conclusion: Heterogeneity of ER, PR, HER2, or Ki67 was present in 16.1% patients with MMBC. Biomarkers heterogeneity influenced adjuvant endocrine therapy usage and was associated with worse disease outcomes, indicating further clinical evaluation. Citation Format: Shuai Li, Jiayi Wu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Xiaosong Chen, Kunwei Shen. Association of molecular biomarkers heterogeneity and treatment pattern, disease outcomes in multifocal or multicentric breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-22.