tbuckley/cabot-search huggingface dataset:
The metabolic phenotypes of non-small cell lung cancer cells in association with clinical treatment strategies
Authors: T.-C. Kuo, T.-H. Hsiao, P.-C. Yang
Journal: Annals of Oncology (2019)

Background: In 2011, metabolic reprogramming was defined as one of the cancer hallmarks, and several drugs targeting cancer metabolism have been developed as anti-cancer drugs. To improve medication efficiency of these anti-metabolic drugs, we tried to sub-classify non-small cell lung cancer (NSCLC) cells by their glycolytic dependency and treat them by targeting different metabolism-related proteins. Methods: We stratified NSCLC cells according to their Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR) measured by the Seahorse XF analyzer. Metformin, an inhibitor of mitochondrial respiratory complex I, was used as an example to measure the sensitivities of NSCLC cells in different metabolic subtypes to drugs targeting oxidative phosphorylation (OXPHOS) pathways. Results: According to the OCR and ECAR, measured by the Seahorse XF analyser, NSCLC cells could be further separated into two metabolic subtypes, OXPHOS-dependent and glycolysis-dependent subtypes. We found that the OXPHOS-dependent subtype was sensitive to metformin, while the glycolysis-dependent subtype was resistant. To target the glycolysis-dependent subtype of NSCLC cells, monocarboxylate transporter 4 (MCT4), a proton-linked lactate transporter, was identified. MCT4 was highly expressed in the glycolysis-dependent subtype of NSCLC cells and its' expression was important for these cells. When we knocked down the expression or blocked the function of MCT4, the proliferation of these cells was significantly inhibited. Conclusions: In this report, we established a method to sub-classify NSCLC cells and predict the sensitivity of these cells to metformin. Besides, we identified MCT4 transporter as a druggable target to inhibit the proliferation of glycolysis-dependent subtype of NSCLC. Legal entity responsible for the study: The authors. Funding: Ministry of Science and Technology in Taiwan. Disclosure: All authors have declared no conflicts of interest.
Abstract 12223: Cardiac Arrest During Pediatric Cardiac Catheterization: A Report From the American Heart Association's Get With the Guidelines-Resuscitation Registry (GWTG-R)
Authors: Javier J Lasa, Alexander Alali, Charles Minard, Shelby Kutty, Dhaval Parekh, Michael Gaies, Tia T Raymond
Journal: Circulation (2017)

Introduction: Pediatric in-hospital cardiac arrest (IHCA) occurs most commonly in intensive care units with overall survival to discharge rates of approximately 35% - 44%. Outcomes for children exp...
The effect of ipilimumab on natural killer cells identifies the subset of advanced melanoma patients with clinical response.
Authors: Ines Esteves Domingues Pires Da Silva, Anne Gallois, Kevin P. Lui, Richard L. Shapiro, Anna C. Pavlick, Nina Bhardwaj, Iman Osman
Journal: Journal of Clinical Oncology (2015)

9065 Background: The concept of immune cell exhaustion in the context of metastatic melanoma has been reinforced by the success of immunotherapies targeting the exhaustion markers CTLA-4 and PD-1. Natural Killer (NK) cell exhaustion, characterized by an up-regulation of inhibitory receptors and loss of function, was described in the context of melanoma. Ipilimumab (IPI - anti-CTLA-4) improves the anti-tumor T cell activity and achieves response rates of 15-20%, however the effect of IPI on NK cells is unknown. In this project, we studied the effect of IPI on the phenotype of NK cells from melanoma patients and how it relates with clinical response. Methods: NK cells were purified from the peripheral blood of 10 advanced melanoma patients treated with IPI. Blood samples were collected at baseline, after the 2nd and 4th cycles of IPI. NK cells were characterized acccording to the expression of activating (NKG2D) and inhibitory (KIRB1) receptors, function (cytotoxicity, IFN-γ production), levels of the IL-2R α chain and response to IL-2 stimulation. We analyzed the effect of IPI on NK cells as it relates to clinical response. Results: IPI induces an upregulation of 50% in the IL-2R α chain levels on NK cells (p = 0.03). There was no significant difference in other receptors or function (p > 0.05). We then checked the phenotype and function of these NK cells after 48 hours of IL-2 stimulation and in 4 patients out of 10 there was an improvement of cytotoxicity and higher levels of IL-2R α chain. Remarkably, this better response to IL-2 was observed in patients with clinical response to IPI (partial/complete response) compared with non-responders, with higher cytotoxicity (p = 0.05) and levels of IL-2R α chain (p = 0.02). Conclusions: CTLA-4 is expressed mainly on T cells, including regulatory T cells, with no expression on NK cells. Nevertheless, we have shown an effect of IPI on the phenotype of NK cells, with an increase of IL-2R expression. More importantly, the effect of IPI on NK cells (better response to IL-2 stimulation and cytotoxicity) is associated with a good clinical response. The mechanism behind this effect is not clear yet, however this may be indirect through the action of IPI on other immune cells.
Aligned Cell‐Laden Yarns: Tendon Tissue Engineering: Effects of Mechanical and Biochemical Stimulation on Stem Cell Alignment on Cell‐Laden Hydrogel Yarns (Adv. Healthcare Mater. 7/2019)
Authors: Chiara Rinoldi, Marco Costantini, Ewa Kijeńska‐Gawrońska, Stefano Testa, Ersilia Fornetti, Marcin Heljak, Monika Ćwiklińska, Robert Buda, Jacopo Baldi, Stefano Cannata, Jan Guzowski, Cesare Gargioli, Ali Khademhosseini, Wojciech Swieszkowski
Journal: Advanced Healthcare Materials (2019)

In articule number 1801218 by Wojciech Swieszkowski and co-workers, highly aligned cell-laden hydrogel yarns are collected on a rotating drum using a novel wet spinning strategy. Cells encapsulated into the hydrogel fibers elongate in the direction of the fiber axis, unraveling the potential of the proposed platform for tendon tissue engineering.
Preying on Prescribers (and Their Patients) — Pharmaceutical Marketing, Iatrogenic Epidemics, and the Sackler Legacy
Authors: Scott H. Podolsky, David Herzberg, Jeremy A. Greene
Journal: New England Journal of Medicine (2019)

Interview with Dr. Scott Podolsky on the revolution in pharmaceutical marketing that set the stage for physician "education" about treating pain with opioids. (08:28)Download Though the Sackler family did not invent the practice of selling drugs to physicians, they were pioneers whose story illustrates the ways marketers developed, naturalized, and monetized the interface between the pharmaceutical industry and prescribing physicians.
Elimination of hepatitis C virus has limited impact on the functional and mitochondrial impairment of HCV-specific CD8+ T cell responses
Authors: Amare Aregay, Solomon Owusu Sekyere, Katja Deterding, Kerstin Port, Julia Dietz, Caterina Berkowski, Christoph Sarrazin, Michael Peter Manns, Markus Cornberg, Heiner Wedemeyer
Journal: Journal of Hepatology (2019)
P041 Immunological characteristics and distribution of cryoglobulins in a cohort of 13000 patients over 6 years
Authors: MN Sarda, P Miossec
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Assistant. <h3>Introduction</h3> Cryoglobulins (CG) are immunoglobulins (Ig) that precipitate <i>in vitro</i> at cold temperature and dissolve at 37°C, they are classified in 3 types. Type I CG are monoclonal Ig of IgM or IgG isotype. Type II and III are mixed CG: type II CG associate a monoclonal with polyclonal Ig, type III CG associate polyclonal Ig. Rheumatoid factor activity (RF) of mixed CG leads to the formation of immune complexes that can precipitate and result in vasculitis. <h3>Objectives</h3> The purpose of this study was to update information on CG biological characteristics in a large population recruited from all clinical departments of a French University Hospital. <h3>Methods</h3> This retrospective study was conducted from January 2010 to December 2016. Patients included had at least one serum sample for CG detection and characterization: CG isotype and clonality, concentration and RF (IgM anti-IgG) in the cryoprecipitate; and serum complement exploration. Associated pathologies were determined by biological markers of gammopathy, viral infection and autoimmunity. <h3>Results</h3> A total of 13439 patients were included, 1675 (12,5%) of whom had positive CG. In case of negative CG detection, 2213 patients were retested and CG was detected on the new sample for 196/2213 patients (8.9%). Type I CG was found in 9.3% (155/1675), type II CG in 47% (788/1675), and type III CG in 43.7% (732/1675) of patients. In type I CG, IgM CG was more frequent than IgG CG, but in lower concentration (p=0.02). For mixed CG, 34.8% of HCV+ tested patients had CG, less than 5% of CG was associated with HBV+ or HIV+ serology. Mixed CG were found in 25.4% of patients with anti dsDNA, anti-SSA60 or anti-CCP autoantibodies (Ab). Mixed CG were positive for 87/333 (26.1%) patients with anti-dsDNA Ab, 74/447 (16.6%) patients with anti-SSA60 Ab, and for 19/155 (12.3%) patients with anti-CCP Ab. Both the cryoprecipitate and the serum were positive for RF in 21.6% of type II CG and 10.1% of type III CG. C3, C4 and/or CH50 decrease was found in 23.6% of serum with CG vs 3.2% of CG-negative serum (p&lt;0.001). <h3>Conclusions</h3> In this largest cohort even studied, with patients from all clinical specialties, CG distribution and characteristics were described with minimal selection bias. Despite strict pre-analytical conditions, negative CG detection must be repeated according to clinical context. Mixed CG are more frequently detected in patients positive for HCV or anti-dsDNA Ab. CG with RF activity form immune complexes that precipitate in vessels and activate complement system, responsible for cryoglobulinemic vasculitis. <h3>Disclosure of Interest</h3> None declared.
Longer term cardiac safety of aldoxorubicin.
Authors: Sant P. Chawla, Kamalesh Sankhala, Scott Wieland, Daniel J. Levitt
Journal: Journal of Clinical Oncology (2015)

10546 Background: Aldoxorubicin (6-maleimidocaproic acid hydrazide) is a novel prodrug of doxorubicin that binds to the thiol group of cysteine-34 amino acid in circulating albumin. The circulating albumin-drug conjugate preferentially accumulates within tumors, bypassing uptake by most normal tissues, including the heart, liver, kidneys and GI tract. Doxorubicin is released in the acidic tumor environment, either intra-or extra-cellularly, thus avoiding the cumulative toxicity that can occur with doxorubicin treatment. Methods: Aldoxorubicin has been investigated in clinical trials since 2011. We reviewed data on the cardiotoxicity of aldoxorubicin from 3 phase I studies and 1 phase IIb study (142 patients). Both MUGA and echocardiograms were administered at baseline then periodically thereafter (usually every 2 months) until either study withdrawal or death. All patients had normal cardiac function at baseline with LVEF > 45% in some studies and 50% in others. Prior exposure up to 225 mg/m2of doxorubicin was permitted. Results: The dose range of aldoxorubicin was 175-350 mg/m2 administered i.v every 3 weeks (equivalent to 130-260 mg/m2 doxorubicin per cycle). There were 126 evaluable patients who received 1-21 cycles of treatment. While 14% of patients demonstrated a ≥ 10% drop in LVEF, 21% had a ≥ increase in LVEF. No patient exhibited a decrease in LVEF that was below 50% of their institution's normal value. Where it was collected, 3.9% of patients exhibited QTc > 500 msec. No patient had a clinically significant increase in troponin concentrations. Patients have received up to 5,439 mg/m2 of doxorubicin equivalents, or 12 times the peak cumulative dose of standard doxorubicin, without any evidence of cardiotoxcity. Conclusions: Despite administering cumulative doses of over 1,500 mg/m2 to the majority of the 126 evaluable patients in these clinical studies, aldoxorubicin has shown no evidence of cardiotoxicty, distinguishing it from doxorubicin itself.
FRI-036-Perception by patients with autoimmune and chronic cholestatic disease of their own health condition: Results of a survey led by the French patient association (ALBI)
Authors: Sara Lemoinne, Philippe Durand, Daniel Leburgue, Angela Leburgue, Gaouar Farid, Christophe Corpechot, Olivier Chazouillères
Journal: Journal of Hepatology (2019)
Naïve regulatory T cells in infancy: Associations with perinatal factors and development of food allergy
Authors: Fiona Collier, Anne‐Louise Ponsonby, Martin O'Hely, Mimi L.K. Tang, Richard Saffery, John Molloy, Lawrence E. Gray, Sarath Ranganathan, David Burgner, Katrina J. Allen, Susanne Brix, Peter J. Vuillermin
Journal: Allergy (2019)

Abstract Background In previous studies, deficits in regulatory T‐cell (Treg) number and function at birth have been linked with subsequent allergic disease. However, longitudinal studies that account for relevant perinatal factors are required. The aim of this study was to investigate the relationship between perinatal factors, naïve Treg (nTreg) over the first postnatal year and development of food allergy. Methods In a birth cohort (n = 1074), the proportion of nTreg in the CD4 + T‐cell compartment was measured by flow cytometry at birth (n = 463), 6 (n = 600) and 12 (n = 675) months. IgE‐mediated food allergy was determined by food challenge at 1 year. Associations between perinatal factors (gestation, labour, sex, birth size), nTreg at each time point and food allergy at 1 year were examined by linear regression. Results A higher proportion of nTreg at birth, larger birth size and male sex was each associated with higher nTreg in infancy. Exposure to labour, as compared to delivery by prelabour Caesarean section, was associated with a transient decrease nTreg. Infants that developed food allergy had decreased nTreg at birth, and the labour‐associated decrease in nTreg at birth was more evident among infants with subsequent food allergy. Mode of birth was not associated with risk of food allergy, and there was no evidence that nTreg at either 6 or 12 months were related to food allergy. Conclusion The proportion of nTreg at birth is a major determinant of the proportion present throughout infancy, highlighting the importance of prenatal immune development. Exposure to the inflammatory stimulus of labour appears to reveal differences in immune function among infants at risk of food allergy.
Effect of Albuterol Premedication vs Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies
Authors: Britta S. von Ungern-Sternberg, David Sommerfield, Lliana Slevin, Thomas F. E. Drake-Brockman, Guicheng Zhang, Graham L. Hall
Journal: JAMA Pediatrics (2019)

Tonsillectomy is a common pediatric procedure for the treatment of sleep-disordered breathing and chronic tonsillitis. Up to half of children having this procedure experience a perioperative respiratory adverse event.To determine whether inhaled albuterol sulfate (salbutamol sulfate) premedication decreases the risk of perioperative respiratory adverse events in children undergoing anesthesia for tonsillectomy.A randomized, triple-blind, placebo-controlled trial (the Reducing Anesthetic Complications in Children Undergoing Tonsillectomies [REACT] trial) was conducted at Perth Children's Hospital (formerly Princess Margaret Hospital for Children), the only tertiary pediatric hospital in Western Australia. Participants included 484 children aged 0 to 8 years who were undergoing anesthesia for tonsillectomy. The study was conducted between July 15, 2014, and May 18, 2017.Participants were randomized to receive either albuterol (2 actuations, 200 μg) or placebo before their surgery.Occurrence of perioperative respiratory adverse events (bronchospasm, laryngospasm, airway obstruction, desaturation, coughing, and stridor) until discharge from the postanesthesia care unit.Of 484 randomized children (median [range] age, 5.6 [1.6-8.9] years; 285 [58.9%] boys), 479 data sets were available for intention-to-treat analysis. Perioperative respiratory adverse events occurred in 67 of 241 children (27.8%) receiving albuterol and 114 of 238 children (47.9%) receiving placebo. After adjusting for age, type of airway device, and severity of obstructive sleep apnea in a binary logistic regression model, the likelihood of perioperative respiratory adverse events remained significantly higher in the placebo group compared with the albuterol group (odds ratio, 2.8; 95% CI, 1.9-4.2; P < .001). Significant differences were seen in children receiving placebo vs albuterol in laryngospasm (28 [11.8%] vs 12 [5.0%]; P = .009), coughing (79 [33.2%] vs 27 [11.2%]; P < .001), and oxygen desaturation (54 [22.7%] vs 36 [14.9%]; P = .03).Albuterol premedication administered before tonsillectomy under general anesthesia in young children resulted in a clinically significant reduction in rates of perioperative respiratory adverse events compared with the rates in children who received placebo. Premedication with albuterol should be considered for children undergoing tonsillectomy.Australian New Zealand Clinical Trials Registry identifier: ACTRN12614000739617.
THU-463-Role of natural killer cells receptors on the development and progression of hepatocellular carcinoma
Authors: Francesco Figorilli, Cristina Manieli, Simona Onali, Michele Casale, Balestrieri Cinzia, Giancarlo Serra, Teresa Zolfino, Lucia Barca, Elena Congeddu, Paola Ragatzu, Roberto Littera, Andrea Perra, Gualtiero Catani, Luchino Chessa
Journal: Journal of Hepatology (2019)
TCTAP A-138 Right Distal Radial Artery Access for Coronary Intervention: Initial Experience in Bangladesh
Authors: Mir Jamal Uddin, Sabina Hashem, Abdul Momen, Sudhakar Sarker, Ashraf Ur Rahman, Mahmudul Hasan, Bishnu Pada Saha, Mizanur Rahman Mozumder, Md Saqif Shahriar
Journal: Journal of the American College of Cardiology (2019)
FRI-212-HBV RNA can be detected more frequently than HBcrAg but decreases during long term treatment with nucleos (t)ide analogues up to 14 years in patients with HBeAg negative chronic hepatitis B
Authors: Florian van Bömmel, Danilo Deichsel, Alessandro Loglio, Floriana Facchetti, Maria Pfefferkorn, Martin Brehm, Thomas Berg, Pietro Lampertico
Journal: Journal of Hepatology (2019)
Detection and recovery of circulating tumor cells in early breast cancer: A connection with vascular invasion.
Authors: Roberta Maltoni, Pietro Fici, Giulia Gallerani, Andrea Rocca, Claudia Cocchi, Lorenzo Cecconetto, Secondo Folli, Emanuela Scarpi, Patrizia Serra, Dino Amadori, Francesco Fabbri
Journal: Journal of Clinical Oncology (2015)

e22028 Background: To date, studies conducted on circulating tumor cells (CTCs) and early breast cancer (EBC) have shown a CTC-positivity rate ranging from 9.4% to 48.6%. Although correlated with worse OS and DFS, CTCs were mainly found to be independent of other cancer features, such as tumor grade and receptor status. Methods: We investigated CTCs in the peripheral blood (PB) of 48 stage I - II EBC patients pre- and one month post-surgery using a new method incorporating a di-electrophoresis-based device (DEPArray). After CTC processing with a nucleus-specific molecule and antibodies directed against CD45, EpCAM and pan-cytokeratins, cells were analyzed and recovered by DEPArray. Study endpoints were method feasibility and the investigation of the correlation between CTCs and primary tumor features. Results: CTCs were found in 13/48 (27.1 %) pre-surgery patients, with one or more CTCs/7.5 ml of PB. Median CTC number was 1.14 cells (range 0 – 11). 9/43 (20.9%) post-surgery patients showed CTC-positivity. CTCs were recovered singly for further molecular characterizations. Pre-surgery, CTC-positive patients were more prone to have negative prognostic features, e.g. vascular invasion, high proliferation, large dimension, lymphnode positivity and negative receptor status. In particular, vascular invasion showed a statistically significant correlation with CTC-positivity. Conclusions: The new procedure proved feasible and capable of recovering epithelial cancer cells present in PB samples from EBC patients. The CTC-positivity percentage was in line with that reported in previous papers in the same clinical setting, was linked to vascular invasion and would appear to be related to other negative prognostic factors. Our results suggest that CTCs detected by DEPArray could be used independently of other standard tumor markers to identify patients who could potentially benefit from additional adjuvant therapy. Clinical features % CTC status Vascular invasion Proliferation (≥ 20%) Tumor size (≥ 20 mm) LN+ Triple negative tumor + 46.2 (6/13)* 46.2 (6/13) 38.5 (5/13) 30.8 (4/13) 23.1 (3/13) - 14.3 (5/35)* 34.3 (12/35) 20.0 (7/35) 20.0 (7/35) 8.6 (3/35) *, p < 0.05
Abstract 17263: Cardiac Myosin Binding Protein-C Phosphorylation Mitigates Pressure-Overload Heart Failure Despite Alterations in Calcium Handling
Authors: Yang Liu, Paola C Rosas, Mohamed I Abdalla, Kevin W Duonge, David T Kidwell, Giuseppina F Dusio, Carl W Tong
Journal: Circulation (2015)

Heart failure with reduced ejection (HFrEF) fraction exhibits both systolic and diastolic dysfunctions; therefore, treatments that improve contractility and lusitropy will be helpful. Cardiac myosin binding protein-C (cMyBP-C), which is a thick filament protein, can increase rate of cross-bridge cycling by its phosphorylation status to enhance contractility and lusitropy. Consequently, we hypothesized that cMyBP-C phosphorylation mitigates HFrEF by preserving systolic and diastolic functions. We tested our idea by challenging WT cMyBP-C(tWT), phosphorylation-deficient cMyBP-C(t3SA):S273A/S282A/S302A, and phosphorylation-mimetic cMyBP-C(t3SD):S273D/S282D/S302D mouse models with trans-aortic constriction (TAC) to induce pressure-overload HFrEF. Survival at 5 weeks showed notable differences (tWT 75.6±6.7% n=41, t3SA 53.4±6.7% n=68, t3SD 92.1±4.4% n=38, p=0.00037). Serial echocardiography showed that cardiac structure and function deteriorated for all mouse models. In comparison to tWT at post-TAC week-5, t3SA demonstrated ventricular dilation and reduced ejection fraction (EF); conversely, t3SD exhibited better preservation of diastolic function (smaller E/Ea, where E=blood flow Doppler and Ea=tissue Doppler of peak myocardial relaxation velocity). Electrically paced intact papillary muscles from t3SA and t3SD demonstrated slower intracellular calcium decay (smaller decay rate constant kCa). Western blotting showed: (1) decreased calcium-ATPase (SERCA2a) expression in t3SA and t3SD, (2) lowest ryanodine receptor (RyR2) expression in t3SD, and (3) decreased calcium calmodulin kinase-2 phosphorylation (pCaMK2) only in t3SD. These calcium handling protein alterations likely prevented stronger rescue by cMyBP-C phosphorylation mimetic. Thus, cMyBP-C phosphorylation mimetic mitigated TAC-induced HFrEF (better survival and preservation of diastolic function) despite depression of calcium handling proteins.
Comment on Mulukutla et al. Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of “A+” Subtypes of Ketosis-Prone Diabetes. Diabetes Care 2018;41:2637–2640
Authors: Petr Heneberg
Journal: Diabetes Care (2019)

I read with great interest the article by Mulukutla et al. (1) demonstrating that antibodies against the luminal (extracellular) domain of phosphatase IA-2, termed IA-2EC (amino acids 26–577), are expressed by patients with ketosis-prone diabetes. Among patients that were negative for other αIA-2 autoantibodies, the αIA-2EC antibodies were reported in 2% of patients with ketosis-prone diabetes without the presence of autoantibodies (1), 6% (2) or 7% (3) of patients with type 1 diabetes, and 5% of patients diagnosed with type 2 diabetes (3). Despite the fact that the mRNA signal of IA-2 is ubiquitous and protein expression is high in various neuroendocrine cells, the data on αIA-2EC autoantibodies from …