tbuckley/cabot-search huggingface dataset:
Abstract 11: Early Magnetic Resonance Imaging to Quantify Ischemic Brain Insult Early Following Cardiac Arrest in a Swine Model
Authors: Miriam Peckham, Adam DeHavenon, Matthew D Alexander, Jeffrey Anderson, Scott McNally, Stephen H McKellar, Joseph Tonna, Ka-ho Wong, Jacob Steenblik, Scott T Youngquist
Journal: Circulation (2019)

Introduction: Hypoxic ischemic brain injury (HIBI) results from loss of oxygen or perfusion during cardiac arrest and is the most common cause of death/disability in patients surviving to admission. Diagnostic tests are crucial to identify irreversible injury thresholds for neuroprognostication. MRI DTI can detect cellular injury in response to HIBI, but imaging timing and severity of hypoxia vary widely. Hypothesis: We hypothesized that a model with fixed periods of ischemia followed by both standardized reperfusion and time to image acquisition would demonstrate a reliable gradient of injury. Such a model would allow neuroprotective strategies to be tested using early imaging biomarkers to quantify effects on cytoarchitecture. Methods: Eleven healthy swine (49 + 5 kg) under isoflurane anesthesia underwent control MRI with DTI at b2000/20 directions. Two animals each were then randomized to sham, 10, 15, 20, and one to 30-minutes of arrest. For reperfusion, extracorporeal membrane oxygenation (ECMO) catheters were placed in the distal aorta and right atrium, after which ventricular fibrillation was induced by a bipolar pacing catheter. Following the fixed period of ischemia, animals were reperfused at 2.8-3.5 L/min with unblended oxygenated blood. After 4 minutes they were defibrillated. Over two hours they were weaned from pump and decannulated with epinephrine and fluid boluses for hemodynamic support. Animals were re-imaged within two hours post-resuscitation using the same pre-arrest protocol. Whole brain ADC measurements were performed in the gray and white matter. Results: Baseline hemodynamic parameters: BP, Heart Rate, End-Tidal CO2, and SpO2 were similar between animals. When comparing pre- to post-arrest MRI, there was a strong linear correlation between percent gray matter ADC change (r=-0.87, p&lt;0.001) and white matter ADC change (r=-0.79, p&lt;0.001) with ischemia duration. Conclusion: MRI DTI changes observed following fixed periods of ischemia with ADC in gray and white matter correlated well with ischemia duration in the first few hours post arrest. These findings support the feasibility of MRI for measuring severity of insult in HIBI and an animal model that might serve as translational endpoint for neuroprotectant strategies.
ATHENA (GOG-3020/ENGOT-ov45): A randomised, double-blind, placebo-controlled phase III study of the poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib + the PD-1 inhibitor nivolumab following frontline platinum-based chemotherapy in ovarian cancer
Authors: K. Fujiwara, H.-H. Chou, J.-W. Kim, D.S. Tan, K. Tamura, N. Katsumata, K. Harano, K. Hasegawa, S. Hume, E. Jones, S. Goble, L. Sullivan, D. Shih, R.L. Coleman, I. McNeish, B. Monk, R. Kristeleit
Journal: Annals of Oncology (2019)
Postablation Modulation after Single High-Dose Radiation Therapy Improves Tumor Control via Enhanced Immunomodulation
Authors: Talicia Savage, Sanjay Pandey, Chandan Guha
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Radiotherapy (RT) is frequently used for local control of solid tumors using equal dose per fraction. Recently, single high-dose radiation has been used for ablation of solid tumors. In this report, we provide a novel immunological basis for radiation dose fractionation consisting of a single high-dose radiotherapy, followed by postablation modulation (PAM) with four daily low-dose fractions (22 Gy + 0.5 Gy × 4) to reprogram the tumor microenvironment by diminishing immune suppression, enabling infiltration of effector cells and increasing efficacy of tumor control. Experimental Design: Palpable 3LL and 4T1 tumors in C57Bl/6 and Balb/c mice were irradiated with the Small-Animal Radiation Research Platform irradiator, and tumor growth and survival were monitored. Immunomodulation of tumor and immune cells in vitro and in vivo characterization of tumor-infiltrating immune effector cells were performed by FACS. For systemic application of PAM-RT, whole-lung irradiation was administered in 4T1-bearing Balb/c mice. Results: We report significant tumor growth delays and increased survival in 3LL tumor–bearing mice with PAM. Primary tumor PAM-RT increased infiltration of immune effector cells and decreased Treg in irradiated tumors and secondary lymphoid organs. In a model of murine metastatic breast cancer (4T1), we demonstrated that systemic PAM-RT to the whole lung, 12 days after primary tumor ablative radiotherapy, increased survival with suppression of pulmonary metastases. Conclusions: We provide a novel immunologic basis for radiation dose fractionation consisting of a single high dose of radiotherapy followed by daily low-dose PAM-RT fractionation to improve the immunogenic potential of ablative radiotherapy.
Patient-reported symptom profiles: A tool to direct palliative care referral.
Authors: Tara L. Kaufmann, Jesse Y. Hsu, Kelly D. Getz, Arif Kamal, Angela DeMichele
Journal: Journal of Clinical Oncology (2019)

93 Background: Both routine PRO monitoring and specialty palliative care are associated with a survival benefit in advanced cancer patients, yet the integration of these efforts has not been described. As PRO collection becomes standard of care, there is a need to understand how PROs may be leveraged to identify patients who could benefit from palliative care referral. Methods: We applied latent profile analysis (LPA) to PROs from a national palliative care registry collected from 2008 – 2017 on 745 solid tumor patients at the time of initial outpatient palliative care visit. LPA is an established method to identify unobserved groups from variables of interest. We used patients’ responses to 11 questions across 4 palliative care domains (9 ESAS items and 2 items for social and existential distress) to generate “PRO profiles” and examined their clinical and demographic correlates using multinomial logistic regression. Results: Four PRO profiles were identified using 9 ESAS items (Table). Young age, metastatic disease, and tumor type (including breast, GYN, GI) differed across PRO profiles compared to lung. Patients with PPS &lt; 70% were 4.5 times more likely to be in the High vs. Low symptom profile compared to those with PPS &gt; 70%. Subgroup analyses showed correlation of social and existential distress PROs with Mood and High profiles. Conclusions: Cancer patients referred to outpatient palliative care can be differentiated into clinically meaningful PRO profiles using brief, routinely collected data in the real-world setting. PRO profiles provide richer data on patient needs compared to prognosis estimates or cancer stage, and synthesize big data for use in clinical practice and epidemiologic research. PRO profiles should include comprehensive palliative domains and be tested as screening thresholds for palliative care referral. [Table: see text]
Overall Survival, Adverse Events, and Economic Burden in Medicare-Insured Patients with Mantle Cell Lymphoma Receiving Cancer-Directed Therapy
Authors: Shaum M Kabadi, Ravi K Goyal, Saurabh P Nagar, Keith L Davis, Hannah Le, Xianglin L Du, Preetesh Jain, Michael L. Wang, Jorge Enrique Romaguera, James A Kaye
Journal: Blood (2019)
Detection of collagens by multispectral optoacoustic tomography as an imaging biomarker for Duchenne muscular dystrophy
Authors: Adrian P. Regensburger, Lina M. Fonteyne, Jörg Jüngert, Alexandra L. Wagner, Teresa Gerhalter, Armin M. Nagel, Rafael Heiss, Florian Flenkenthaler, Matthias Qurashi, Markus F. Neurath, Nikolai Klymiuk, Elisabeth Kemter, Thomas Fröhlich, Michael Uder, Joachim Woelfle, Wolfgang Rascher, Regina Trollmann, Eckhard Wolf, Maximilian J. Waldner, Ferdinand Knieling
Journal: Nature Medicine (2019)
Use of liposome encapsulated doxorubicin citrate (LEDC) as a valid drug in patients affected by ovarian cancer suffering from chemotherapy side-effects.
Authors: Michela Angelucci, Francesco Plotti, Ludovico Muzii, Corrado Terranova, Carlo De Cicco Nardone, Roberto Montera, Patrizio Damiani, Ester Valentina Cafà , Nella Dugo, Federica Guzzo, Roberto Ricciardi, Alessia Aloisi, Daniela Luvero, Andrea Miranda, Stella Capriglione, Salvatore Lopez, Giuseppe Scaletta, Francesca Linciano, Pierluigi Benedetti Panici, Roberto Angioli
Journal: Journal of Clinical Oncology (2012)

e15547 Background: Doxorubicin had a wide spectrum of cytotoxic activity in gynecological cancer. Moreover, this drug is associated with chronic cardiac toxicity, often irreversible, which limits lifetime dose. A new liposomal formulations has been developed in the past decades to limite side-effects of doxorubicin: liposome encapsulated doxorubicin citrate (LEDC). In this study we report our experience with LEDC in patients affected by advanced/recurrent gynaecological cancer, suffering from chemotherapy side effects. Methods: From 2000 to December 2008, 43 patients who showed palmoplantar erythrodysesthesia (PPE) during adjuvant or palliative setting treatment of metastatic/recurrent epithelial ovarian cancer. All patients enrolled in the study were treated with liposomal encapsulated doxorubicin citrate (LEDC), administered at the dose of 50 mg/mq every 3 weeks until disease progression or adverse effects. Results: We have enrolled 43 patients who suspended previously chemotherapy treatment for severe PPE. A total of 32 patients completed planned 6 cycles of chemotherapy. After 6 cycles of chemotherapy 3 out of 43 patients (6%) continued to show a complete response, 9 patients (20%) maintained partial response, 16 patients (37%) showed stable disease and 4 patients (9%) suffered disease progression. No severe G3–G4 hematologic toxicity was showed, but neutropenia and anemia continued to be the most common side effects. No cutaneous toxicity were reported. Conclusions: LEDC is a well tolerated drug and a valid alternative in patients affected by ovarian cancer suffering from cutaneous toxicity by other drugs.
Glutaminase Inhibition Overcomes Acquired Resistance to Mitochondrial Complex I in NOTCH1-Driven T-Cell Acute Lymphoblastic Leukemias (T-ALL) Via Block of Glutamine Driven Reductive Metabolism
Authors: Natalia Baran, Alessia Lodi, Shannon Renee Sweeney, Vinitha Mary Kuruvilla, Antonio Cavazos, Daniel Herranz, Anna Skwarska, Marc Warmoes, Eric Davis, Karine Harutyunyan, Ningping Feng, Jason P Gay, Marcin Kaminski, Sergej Konoplev, Elias Jabbour, Adolfo A. Ferrando, Maria E Di Francesco, Philip Lorenzi, Joseph R Marszalek, Stefano Tiziani, Marina Y Konopleva, Pandey Renu
Journal: Blood (2019)
Adjuvant axitinib in Asian vs non-Asian patients with metastatic renal cell carcinoma (mRCC): ATLAS trial subgroup analysis
Authors: C.F. Ng, T.G. Kwon, M. Eto, H. Miyake, S.I. Seo, S.-S. Byun, J.L. Lee, B. Rosbrook, E. Grande, M. Gross-Goupil, D.I. Quinn
Journal: Annals of Oncology (2019)
Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial
Authors: Sandra Demaria, Emanuela Romano, Muriel Brackstone, Silvia C. Formenti
Journal: Journal for ImmunoTherapy of Cancer (2019)

Programmed cell death protein 1 (PD-1) blockade is only effective in a minority of patients, prompting the search for combinatorial therapies that increase responses. Identifying effective combinations requires lengthy testing and so far has shown few successes. To accelerate progress Voorwerk and colleagues (Nat Med. 25(6):920-8, 2019) used an adaptive trial design to compare 4 short-course therapies (radiotherapy, cyclophosphamide, cisplatin and doxorubicin) for their ability to improve the tumor immune microenvironment and enhance responses to subsequent PD-1 blockade in women with metastatic triple negative breast cancer, a disease with low response rate to PD-1 blockade. They reported the first phase of the trial that enrolled 12 to 17 patients per arm to "pick the winner" induction treatment. Higher objective response rates (ORR) compared to no induction were observed only in the arm containing doxorubicin, which proceeded to phase II. These results raise a number of questions about testing local versus systemic induction treatments and whether sequencing with PD-1 blockade is appropriate in light of evidence supporting concomitant treatment, at least for radiotherapy. Small imbalances in baseline characteristics can also influence results obtained with limited numbers of patients per arm. We hope that these considerations will help future adaptive, signal-finding combination immunotherapy studies.
M1dG and O6-CoMedG DNA adducts are present in human exfoliated colonocytes
Authors: Nina Bailey, Tanya Bandaletova, David Shuker, Sheila Bingham
Journal: Cancer Research (2004)

1971  Aim: Westernisation and the consumption of a high fat/high red meat diet, have been associated with an increased risk for colon cancer. Malondialdehyde is the mutagenic and carcinogenic end product of lipid peroxidation associated with polyunsaturated fat intake capable of reacting with DNA to form adducts such as the malondialdehyde-deoxyguanosine adduct M1dG. High red meat diets have been associated with colorectal cancer risk due to the increased formation of alkylating agents such as N-nitroso compounds (NOC’s), some of which are known to be potent carcinogens. The aim of this study was to investigate the reliability of exfoliated cells as a source of biomarkers of diet related DNA damage within the colon. Methods: Exfoliated colonocytes from stools from individuals consuming a normal Western diet were isolated using a non-invasive immunomagnetic bead technique (Bandaletova et al., 2002). These exfoliated colonocytes were then stained using the avidin-biotin method for the presence of the adducts M1dG and 06-carboxymethylguanine (O6-CoMedG). The colon carcinoma cell line HT-29 exposed to 1,1,3,3 tetraethoxypropane to induce the M1dG adduct, and potassium diazoacetate to induce the O6-CoMedG adduct in vitro was used as a positive control. Results: HT-29 cells were shown to stain for M1dG and O6-CoMedG adducts after treatment with 20mM 1,1,3,3-tetraethoxypropane and 1mM potassium diazoacetate respectively. Exfoliated cells were consistently extracted from faecal samples and were shown to stain positively for M1dG and O6-CoMedG adducts in stool samples from individuals consuming a normal Western diet. Conclusion: In this study, we have shown that exfoliated colonocytes can be reliably extracted from stool and that the M1dG and O6-CoMedG adducts can be visually detected in exfoliated colonocytes from humans consuming a normal Western diet. HT-29 cells treated with the adduct inducing compounds 1,1,3,3 tetraethoxypropane and potassium diazoacetate provided reliable positive controls. The presence of the M1dG and O6-CoMedG adducts in exfoliated colonocytes are indicators of DNA damage as a result of diet related genotoxic compounds. Bandaletova,T, Bailey N, Bingham S, Loktionov A. (2002). Isolation of exfoliated colonocytes from the human stool as a new technique for colonic cytology. APIMS 110 239-46.
Association of Increasing Use of Spinal Anesthesia in Hip Fracture Repair With Treating an Aging Patient Population
Authors: Bryan G. Maxwell, Warren Spitz, Jeremy Porter
Journal: JAMA Surgery (2019)

describing an association between ASA and mortality after emergency colectomy. 6 This finding, along with the association between lower preoperative hematocrit and mortality, underscores the importance of obtaining early surgical consultation to ensure patients who need surgery receive it in a timely fashion.This study has limitations.Preoperative interventions are not documented in the database, so we could not describe associations between postoperative mortality and interventions, such as colonoscopy.Functional outcomes, while important, are also not available in the database.That laparoscopic approach was associated with a lower odds of mortality likely represents confounding by indication.This study provides a robust estimate of the risk of mortality for patients undergoing emergency surgery for acute LGIB in the contemporary context.This prognostic information will better equip surgeons to provide goal-concordant care.
Costimulation Blockade in Kidney Transplant Recipients
Authors: Marieke van der Zwan, Dennis A. Hesselink, Martijn W. F. van den Hoogen, Carla C. Baan
Journal: Drugs (2019)

Costimulation between T cells and antigen-presenting cells is essential for the regulation of an effective alloimmune response and is not targeted with the conventional immunosuppressive therapy after kidney transplantation. Costimulation blockade therapy with biologicals allows precise targeting of the immune response but without non-immune adverse events. Multiple costimulation blockade approaches have been developed that inhibit the alloimmune response in kidney transplant recipients with varying degrees of success. Belatacept, an immunosuppressive drug that selectively targets the CD28-CD80/CD86 pathway, is the only costimulation blockade therapy that is currently approved for kidney transplant recipients. In the last decade, belatacept therapy has been shown to be a promising therapy in subgroups of kidney transplant recipients; however, the widespread use of belatacept has been tempered by an increased risk of acute kidney transplant rejection. The purpose of this review is to provide an overview of the costimulation blockade therapies that are currently in use or being developed for kidney transplant indications.
High Accuracy, Low-Cost Transcriptional Diagnostic to Transform Lymphoma Care in Low- and Middle-Income Countries
Authors: Edward Briercheck, Fabiola Valvert, Elizabeth Solorzano, Oscar Silva, Maneka Puligandla, Marcos Mauricio Siliézar Tala, Timothy Guyon, Samuel L. Dixon, Robert Terbrueggen, Yasodha Natkunam, Kristen E. Stevenson, David M Weinstock
Journal: Blood (2019)
Drug deaths: Scottish minister vows to tackle “public health emergency”
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The number of people dying from drug use in Scotland is a “public health emergency” that the government is determined to fix, the country’s public health minister has vowed.

Speaking at the Faculty of Public Health’s annual conference in Dunblane on 28 November, Joe Fitzpatrick said he would support any measures to reduce the “devastating impact of substance misuse.”

Scotland has the highest number of drug related deaths in Europe and possibly the world.1

Fitzpatrick said that the government would …
‘If they didn’t support me, I most likely wouldn’t be here’: Transgender young people and their parents negotiating medical treatment in Australia
Authors: Damien W. Riggs, Clare Bartholomaeus, Annie Pullen Sansfaçon
Journal: International Journal of Transgender Health (2019)

Background: It is increasingly recognized that transgender young people require affirming medical care, however the provision of such care may be mitigated by the availability of services and the views of parents.Aims: This study aimed to explore the views of Australian transgender young people (aged 11–17) and their parents with regards to medical treatment.Methods: Ten qualitative interviews were conducted with parent-child dyads in two Australian states. Thematic analysis was undertaken on responses to interview questions related to family relationships, views about medical treatment (specifically hormone blockers and hormones), and the relationship between medical treatment and sense of self.Results: Themes developed focused on the importance of strong supportive parent-child relationships, the meaning of and access to hormone blockers, and the meaning of and access to hormones.Discussion: The paper concludes by discussing the implications of the findings for clinical services, particularly in relation to supporting parents to be affirming of a transgender child, the need to prepare transgender young people and their parents for the passage of time in regards to medical treatment, and the need to focus on expectations in regards to sense of self in relation to medical treatment.
Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)
Authors: Seema Aceves, Margaret H. Collins, Marc E. Rothenberg, Glenn T. Furuta, Nirmala Gonsalves, J. Pablo Abonia, Seema Aceves, Samuel Almonte, Rachel Andrews, Ashley Arrington, Nicoleta Arva, Fred Atkins, Dominique Bailey, Alexis Berry, Bridget Besl, Scott Bolton, Peter Bonis, Wendy Book, Kimberly Bray, Teresa Brown, Cassandra Burger, Deirdre Burke, Jonathon Cahoon, Kelley Capocelli, Mirna Chehade, Margaret Collins, Carla Davis, Evan Dellon, Maureen DeMarshall, Lauren DiTommaso, Ranjan Dohil, Michael Eby, Gary Falk, David Fleischer, Heather Foote, Kelci Foss, Joel Friedlander, Patricia Fulkerson, Glenn Furuta, Debra Geno, Nirmala Gonsalves, Thomas Greuter, Sandeep Gupta, Frank Hamilton, Kirk Harris, Jennifer Harris, Ikuo Hirano, Girish Hiremath, Nicole Holland-Thomas, Lea Jacinto, Amir Kagalwalla, Timothy Kaseta, David Katzka, Kaitlin Keeley, Emad Khosh-Hemmat, Paneez Khoury, Eileen King, Kara Kliewer, Amy Klion, Jennifer Knowles, Kendra Kocher, Ellyn Kodroff, Jeffrey Krischer, Shay Kyle, John Leung, Meredith Levy, Chris Liacouras, Denise Mack, Lisa Martin, Ellen Martin, Talaya McCright-Gill, Paul Menard-Katcher, Calies Menard-Katcher, Gabriela Mendoza, Melissa Mingler, Mike Minnicozzi, Amanda Muir, Vincent Mukkada, Cristin MurrayPetzold, Robert Newbury, Quan Nhu, Oghenekpaobor (Joel) Oyibo, Allisa Paliana, Zhaoxing Pan, Robbie Pesek, Kathryn Peterson, Heidi Poppendeck, Philip Putnam, Fabian Rivera, Marc Rothenberg, Amanda Rudman-Spergel, Kathleen Sable, Alain Schoepfer, Melissa Scott, Rachel Sheridan, Selma Sinanovic, Jonathan Spergel, MaryJo Strobel, Kiki Sun, Amy Tasco, Crystal Tholen, Katherine Thompson, Tiffany Tomkinson, Daisy Tran, Alexandra Tylicki, Tiina Urv, Mei-Lun Wang, Joshua Wechsler, Barry Wershil, Lisa Wheatley, Leah Wilkey, Guang-Yu Yang, Angelika Zalewski, Amy Zicarelli
Journal: Journal of Allergy and Clinical Immunology (2019)
Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF
Authors: Richard Moreau, Joan Clària, Ferran Aguilar, François Fenaille, Juan José Lozano, Christophe Junot, Benoit Colsch, Paolo Caraceni, Jonel Trebicka, Marco Pavesi, Carlo Alessandria, Frederik Nevens, Faouzi Saliba, Tania M. Welzel, Agustin Albillos, Thierry Gustot, Javier Fernández, Christophe Moreno, Maurizio Baldassarre, Giacomo Zaccherini, Salvatore Piano, Sara Montagnese, Victor Vargas, Joan Genescà, Elsa Solà, William Bernal, Noémie Butin, Thaïs Hautbergue, Sophie Cholet, Florence Castelli, Christian Jansen, Christian Steib, Daniela Campion, Raj Mookerjee, Miguel Rodríguez-Gandía, German Soriano, François Durand, Daniel Benten, Rafael Bañares, Rudolf E. Stauber, Henning Gronbaek, Minneke J. Coenraad, Pere Ginès, Alexander Gerbes, Rajiv Jalan, Mauro Bernardi, Vicente Arroyo, Paolo Angeli
Journal: Journal of Hepatology (2019)
A needed amendment that explains too much and resolves little
Authors: Slavisa Tasic, Zeljka Buturovic
Journal: Behavioral and Brain Sciences (2019)

Abstract Baumard's application of Life History Theory to explain the origins of economic growth is a needed amendment to incentive-based explanations of modern economics. However, even though it is grounded in evolution, the theory does not do enough to specify the relevant evolutionary mechanisms. As such, it accommodates too many alternative historic scenarios, yet remains unable to explain divergent regional patterns of economic growth.
Subgroup analysis of IMpassion130: Atezolizumab + nab-paclitaxel (nab-P) in patients (pts) with advanced triple-negative breast cancer (TNBC) in Asian countries
Authors: H. Iwata, S.-A. Im, J. Sohn, K.H. Jung, Y.-H. Im, K.S. Lee, K. Inoue, K. Tamura, A. Wong, L.A. Emens, C.H. Barrios, S. Adams, A. Schneeweiss, V. Diéras, E.P. Winer, S.Y. Chui, V. Henschel, H.S. Rugo, S. Loi, P. Schmid
Journal: Annals of Oncology (2019)