tbuckley/cabot-search huggingface dataset:
Abstract 11246: Cellular Basis of Progressive Left Ventricle Dysfunction in a Canine Model of Duchenne Muscular Dystrophy: Effects of Cardiomyocyte Contractile Functional Performance, L-Type Calcium Current Response and Beta-Adrenergic Modulation
Authors: Heng-Jie Cheng, Peng Zhou, Chad D Markert, Qun Shao, Dalane Kitzman, David Zhao, Martin K Childers, Che Ping Cheng
Journal: Circulation (2018)

Background: Duchenne muscular dystrophy (DMD) is a common and lethal genetic disease. Cardiomyopathy frequently causes mortality in DMD patients. However, its cardiac pathophysiology is unclear. Wh...
A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy
Authors: Carine El Sissy, Amos Kirilovsky, Marc Van den Eynde, Ana-Maria Muşină, Maria-Gabriela Anitei, Alfredo Romero, Florence Marliot, Audelaure Junca, Jérôme Doyen, Bernhard Mlecnik, Nacilla Haicheur, Tessa Fredriksen, Christine Lagorce, Anne Jouret-Mourin, Daniel Leonard, Frédéric Bibeau, Soledad Iseas, Enrique L. Roca, Ana M. Cabanne, Carlos A. Vaccaro, Juan P. Santino, Eduardo Huertas, David Tougeron, Carlos Carvalho, Nuno Figueiredo, Rodrigo O. Perez, Angelita Habr-Gama, Viorel Scripcariu, Jean-Pierre Gerard, Jérôme Galon, Guy Zeitoun, Franck Pagès
Journal: Clinical Cancer Research (2020)

Abstract Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy (“Watch-and-Wait”). Experimental Design: Biopsies from two independent cohorts (n1 = 131, n2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. Results: ISB positively correlated with the degree of histologic response (P &amp;lt; 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06–0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P &amp;lt; 0.001) and post-nT (P &amp;lt; 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the “Watch-and-Wait” cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). Conclusions: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.
Acute Care Surgery during the COVID-19 pandemic in Spain: Changes in volume, causes and complications. A multicentre retrospective cohort study
Authors: Oscar Cano-Valderrama, Xavier Morales, Carlos J. Ferrigni, Esteban Martín-Antona, Victor Turrado, Alejandro García, Yolanda Cuñarro-López, Leire Zarain-Obrador, Manuel Duran-Poveda, José M. Balibrea, Antonio J. Torres
Journal: International Journal of Surgery (2020)
Associations of Maternal Glycemia in the First Half of Pregnancy With Alterations in Cardiac Structure and Function in Childhood
Authors: Rama J. Wahab, Vincent W.V. Jaddoe, Arno A.W. Roest, Liza Toemen, Romy Gaillard
Journal: Diabetes Care (2020)

Gestational diabetes mellitus has been associated with offspring cardiac congenital malformations, ventricular hypertrophy, and diastolic dysfunction in large observational cohort studies and experimental animal models. We assessed the associations of maternal random glucose concentrations across the full range with childhood cardiac ventricular structure and function.In a population-based prospective cohort among 1,959 women and their offspring, maternal random glucose concentrations were measured at a median 13.1 weeks' gestation (95% range 10.5-16.8 weeks). We obtained offspring cardiac outcomes, relative to body size, through cardiac MRI at 10 years.The mean maternal random glucose concentration was 4.4 mmol/L (SD 0.8). The highest quintile of maternal glucose concentrations, compared with the lowest quintile, was associated with a lower childhood left ventricular mass (-0.19 SD score [SDS]; 95% CI -0.31, -0.07) and left ventricular end-diastolic volume (-0.17 SDS; 95% -0.28, -0.05). Also, higher maternal glucose concentrations across the full range per 1 mmol/L increase were associated with a lower childhood left ventricular mass and left ventricular end-diastolic volume (P values ≤0.05). Adjustment for maternal prepregnancy BMI, gestational age, and weight at birth or childhood BMI and blood pressure did not influence the effect estimates. Maternal glucose concentrations were not significantly associated with childhood right ventricular end-diastolic volume or left and right ventricular ejection fraction.Higher maternal random glucose concentrations in the first half of pregnancy are associated with a lower childhood left ventricular mass and left ventricular end-diastolic volume, with the strongest associations for childhood left ventricular mass. These associations were not explained by maternal, birth, or childhood characteristics. Further studies are needed to replicate these findings using repeated maternal glucose measurements throughout pregnancy and offspring cardiac outcomes throughout childhood and adulthood.
Complete response of metastatic pleomorphic dermal sarcoma to anti‐PD‐1 therapy
Authors: O. Klein, C. McTigue, Z.W. Wong, D.B. Syme, D.J. Hunter‐Smith
Journal: British Journal of Dermatology (2020)

Funding sources: None. Conflicts of interest: The authors declare they have no conflicts of interest. ... Dear Editor, An 87‐year‐old gentleman presented with a scalp nodule. A subsequent biopsy (a) demonstrated pleomorphic dermal sarcoma (PDS). The patient underwent an excision and received adjuvant radiotherapy. He presented 4 months later with two new scalp lesions and an enlarged left parotid gland. A biopsy confirmed metastatic PDS that was heavily infiltrated by T lymphocytes (b). A staging positron emission tomography (PET) scan demonstrated two lung metastases. The patient commenced treatment with the anti‐PD‐1 antibody pembrolizumab, leading to a rapid clinical response. Treatment had to be discontinued after two doses owing to a flare of pre‐existing polymyalgia rheumatica. A PET scan 3 months after commencement of therapy demonstrated a complete response with regression of all sites of metastatic disease (c, d), which is ongoing. This case adds to the evidence that anti‐PD‐1 therapy can be highly effective in patients with advanced PDS.1,2
AcDVP16 Induction Therapy for Acute Myeloid Leukemia
Authors: Michael Richard Grunwald, Amy M. Ellenburg, Michael Keith Allister Zimmerman, Jing Ai, Thomas G. Knight, Lauren M. Bohannon, Danielle Boselli, Jigar Trivedi, Margaret A. Croom, William E. Anderson, James T Symanowski, Edward A Copelan, Dragos Plesca, Jonathan M. Gerber
Journal: Blood (2017)
AB0172 Turner syndrome and pure gonadal dysgenesis: a strong risk factor for osteopenia and osteoporosis
Authors: C Benetti-Pinto, AJ Bedone, L Magna, JF Marques-Neto
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> During the puberal period, the hormonal production is directly associated to bone mass, and related to the development of the peak of bone mass. <h3>Objectives</h3> In order to evaluated the role of Primary Hypoestrogenism as a risk factor for osteopenia, 39 women, aged between 16 and 35 years old, with Pure Gonadal Dysgenesis and Turner Syndrome, were submitted to bone densitometry (DEXA) of lumbar spine and hip. <h3>Methods</h3> Bone densitometry was performed using dual X-ray absorptiometry. T-score values (lumbar spine, femoral neck, Ward triangle and trochanter) were compared to treatment period and to the body mass index. <h3>Results</h3> There were no difference between values of bone mineral density (BMD) in Pure Gonadal Dysgenesis and Turner Syndrome. But from all patients, compared to a normal control group, 90% showed a low BMD in lumbar spine (osteoporosis- 45% and osteopenia- 45%). The mean value of BMD in L2-L4 was 0,92 g/cm<sup>2</sup>. Concerning to the femur BMD, 55% of the patients were affected (osteopenia in 50% and osteoporosis in 5%). The mean value of BMD was 0,83 g/cm<sup>2</sup>. The density of lumbar spine was positively associated to treatment period (R = 0,57) and, in the femur, to the body mass index (R = 0,48). <h3>Conclusion</h3> In conclusion, Primary Hypoestrogenism in the puberal period must be considered an important risk factor for osteopenia. <h3>References</h3> Heaney RP, Recker RR, Saville PD. Menopasal changes in bone remodeling. J Lab Clin Med. 1978;92:953–63 Kleerekoperm KS. Metabolic bone diseases sec IV primer on the metabolic diseases and disorders of mineral metabolism. 4th edn. Philadephia: Lippincott Williams &amp; Wilkins, 1999 Harper KD, Weber TJ. Secondary osteoporosis. Diagnostic considerations. Endocrinol Metabol Clin N Am.1988;27(2):325–47
Next-Generation Bruton Tyrosine Kinase Inhibitors
Authors: Deborah M. Stephens, John C. Byrd
Journal: Journal of Clinical Oncology (2020)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. May 27, 2020 ARTICLE CITATION DOI: 10.1200/JCO.20.01594 Journal of Clinical Oncology - published online before print July 16, 2020 PMID: 32673168 Next-Generation Bruton Tyrosine Kinase Inhibitors Deborah M. Stephens, DO1xDeborah M. StephensSearch for articles by this author and John C. Byrd, MD2xJohn C. ByrdSearch for articles by this author Show More 1University of Utah, Salt Lake City, UT2The Ohio State University, Columbus, OH https://doi.org/10.1200/JCO.20.01594 First Page Full Text PDF Figures and Tables © 2020 by American Society of Clinical Oncology Companion ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
Human Cancers Express TRAILshort, a Dominant Negative TRAIL Splice Variant, Which Impairs Immune Effector Cell Killing of Tumor Cells
Authors: Fatma Aboulnasr, Ashton Krogman, Rondell P. Graham, Nathan W. Cummins, Anisha Misra, Enrique Garcia-Rivera, Jeff R. Anderson, Sekar Natesampillai, Nicole Kogan, Murali Aravamudan, Zilin Nie, Thomas D.Y. Chung, Richard Buick, Andrew L. Feldman, Rebecca L. King, Anne J. Novak, Stephen M. Ansell, Saad Kenderian, Andrew D. Badley
Journal: Clinical Cancer Research (2020)

TNF-related apoptosis inducing ligand (TRAIL) expression by immune cells contributes to antitumor immunity. A naturally occurring splice variant of TRAIL, called TRAILshort, antagonizes TRAIL-dependent cell killing. It is unknown whether tumor cells express TRAILshort and if it impacts antitumor immunity.We used an unbiased informatics approach to identify TRAILshort expression in primary human cancers, and validated those results with IHC and ISH. TRAILshort-specific mAbs were used to determine the effect of TRAILshort on tumor cell sensitivity to TRAIL, and to immune effector cell dependent killing of autologous primary tumors.As many as 40% of primary human tumors express TRAILshort by both RNA sequencing and IHC analysis. By ISH, TRAILshort expression is present in tumor cells and not bystander cells. TRAILshort inhibition enhances cancer cell lines sensitivity to TRAIL-dependent killing both in vitro and in immunodeficient xenograft mouse models. Immune effector cells isolated from patients with B-cell malignancies killed more autologous tumor cells in the presence compared with the absence of TRAILshort antibody (P < 0.05).These results identify TRAILshort in primary human malignancies, and suggest that TRAILshort blockade can augment the effector function of autologous immune effector cells.See related commentary by de Miguel and Pardo, p. 5546.
Therapeutic inhibition of FcγRIIb signaling targets leukemic stem cells in chronic myeloid leukemia
Authors: Oliver Parting, Samantha Langer, Maja Kim Kuepper, Caroline Wessling, Shaoguang Li, Till Braunschweig, Nicolas Chatain, Tiago Maié, Ivan G. Costa, Martina Crysandt, Michael Huber, Tim H. Brümmendorf, Steffen Koschmieder, Mirle Schemionek
Journal: Leukemia (2020)

Despite the successes achieved with molecular targeted inhibition of the oncogenic driver Bcr-Abl in chronic myeloid leukemia (CML), the majority of patients still require lifelong tyrosine kinase inhibitor (TKI) therapy. This is primarily caused by resisting leukemic stem cells (LSCs), which prevent achievement of treatment-free remission in all patients. Here we describe the ITIM (immunoreceptor tyrosine-based inhibition motif)-containing Fc gamma receptor IIb (FcγRIIb, CD32b) for being critical in LSC resistance and show that targeting FcγRIIb downstream signaling, by using a Food and Drug Administration-approved BTK inhibitor, provides a successful therapeutic approach. First, we identified FcγRIIb upregulation in primary CML stem cells. FcγRIIb depletion caused reduced serial re-plaiting efficiency and cell proliferation in malignant cells. FcγRIIb targeting in both a transgenic and retroviral CML mouse model provided in vivo evidence for successful LSC reduction. Subsequently, we identified BTK as a main downstream mediator and targeting the Bcr-Abl-FcγRIIb-BTK axis in primary CML CD34+ cells using ibrutinib, in combination with standard TKI therapy, significantly increased apoptosis in quiescent CML stem cells thereby contributing to the eradication of LSCs.. As a potential curative therapeutic approach, we therefore suggest combining Bcr-Abl TKI therapy along with BTK inhibition.
Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma
Authors: Johannes Gojo, Bernhard Englinger, Li Jiang, Jens M. Hübner, McKenzie L. Shaw, Olivia A. Hack, Sibylle Madlener, Dominik Kirchhofer, Ilon Liu, Jason Pyrdol, Volker Hovestadt, Emanuele Mazzola, Nathan D. Mathewson, Maria Trissal, Daniela Lötsch, Christian Dorfer, Christine Haberler, Angela Halfmann, Lisa Mayr, Andreas Peyrl, Rene Geyeregger, Benjamin Schwalm, Monica Mauermann, Kristian W. Pajtler, Till Milde, Marni E. Shore, Jack E. Geduldig, Kristine Pelton, Thomas Czech, Orr Ashenberg, Kai W. Wucherpfennig, Orit Rozenblatt-Rosen, Sanda Alexandrescu, Keith L. Ligon, Stefan M. Pfister, Aviv Regev, Irene Slavc, Walter Berger, Mario L. Suvà, Marcel Kool, Mariella G. Filbin
Journal: Cancer Cell (2020)
Different guidelines for pre-exposure prophylaxis (PrEP) eligibility estimate HIV risk differently: an incidence study in a cohort of HIV-negative men who have sex with men, Portugal, 2014–2018
Authors: Paula Meireles, Michael Plankey, Miguel Rocha, João Brito, Luís Mendão, Henrique Barros
Journal: Eurosurveillance (2020)

Introduction Guidelines for pre-exposure prophylaxis (PrEP) provide criteria to identify individuals at higher risk of HIV infection. We compared the ability to predict HIV seroconversion of four guidelines: the World Health Organization (WHO), the United States Public Health Service and Centers for Disease Control and Prevention (US CDC), the European AIDS Clinical Society (EACS) and the Portuguese National Health Service (PNHS). Aim We aimed to measure the association between guideline-specific eligibility and HIV seroconversion. Methods We studied 1,254 participants from the Lisbon Cohort of men who have sex with men with at least two evaluations between March 2014 and March 2018, corresponding to 1,724.54 person-years (PY) of follow-up. We calculated incidence rates (IR) according to each guideline eligibility definition and incident rate ratios (IRR) to test the association between eligibility at baseline and HIV seroconversion. Results We found 28 incident cases (IR: 1.62/100 PY; 95% confidence interval (CI) 1.12–2.35). Guidelines’ sensitivity varied from 60.7% (EACS) to 85.7% (PNHS) and specificity varied from 31.8% (US CDC) to 51.5% (EACS). IR was highest among those defined as eligible by the PNHS guideline (2.46/100 PY; IRR = 4.61; 95% CI: 1.60–13.27) and lowest for the WHO guideline (1.89/100 PY; IRR = 1.52; 95% CI: 0.69–3.35). Conclusions Being identified as eligible for PrEP was associated with a higher risk of infection. The magnitude of risk varied according to the guideline used. However, the number of HIV infections identified among ineligible participants highlights the potential for missing people who need PrEP.
Viral CpG Deficiency Provides No Evidence That Dogs Were Intermediate Hosts for SARS-CoV-2
Authors: David D Pollock, Todd A Castoe, Blair W Perry, Spyros Lytras, Kristen J Wade, David L Robertson, Edward C Holmes, Maciej F Boni, Sergei L Kosakovsky Pond, Rhys Parry, Elizabeth J Carlton, James L N Wood, Pleuni S Pennings, Richard A Goldstein
Journal: Molecular Biology and Evolution (2020)

Abstract Due to the scope and impact of the COVID-19 pandemic there exists a strong desire to understand where the SARS-CoV-2 virus came from and how it jumped species boundaries to humans. Molecular evolutionary analyses can trace viral origins by establishing relatedness and divergence times of viruses and identifying past selective pressures. However, we must uphold rigorous standards of inference and interpretation on this topic because of the ramifications of being wrong. Here, we dispute the conclusions of Xia (2020. Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense. Mol Biol Evol. doi:10.1093/molbev/masa095) that dogs are a likely intermediate host of a SARS-CoV-2 ancestor. We highlight major flaws in Xia’s inference process and his analysis of CpG deficiencies, and conclude that there is no direct evidence for the role of dogs as intermediate hosts. Bats and pangolins currently have the greatest support as ancestral hosts of SARS-CoV-2, with the strong caveat that sampling of wildlife species for coronaviruses has been limited.
A nephrotoxicity-free, iron-based contrast agent for magnetic resonance imaging of tumors
Authors: Xiangdong Xue, Ruonan Bo, Haijing Qu, Bei Jia, Wenwu Xiao, Ye Yuan, Natalia Vapniarsky, Aaron Lindstrom, Hao Wu, Dalin Zhang, Longmeng Li, Marina Ricci, Zhao Ma, Zheng Zhu, Tzu-yin Lin, Angelique Y. Louie, Yuanpei Li
Journal: Biomaterials (2020)
All-cause excess mortality observed by age group and regions in the first wave of the COVID-19 pandemic in England
Authors: Mary A Sinnathamby, Heather Whitaker, Laura Coughlan, Jamie Lopez Bernal, Mary Ramsay, Nick Andrews
Journal: Eurosurveillance (2020)

England has experienced one of the highest excess in all-cause mortality in Europe during the current COVID-19 pandemic. As COVID-19 emerged, the excess in all-cause mortality rapidly increased, starting in March 2020. The excess observed during the pandemic was higher than excesses noted in the past 5 years. It concerned all regions and all age groups, except the 0–14 year olds, but was more pronounced in the London region and in those aged ≥ 85 years.
Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease
Authors: Victor Marcos-Garces, Jose Gavara, Jose V. Monmeneu, Maria P. Lopez-Lereu, Maria J. Bosch, Pilar Merlos, Nerea Perez, Cesar Rios-Navarro, Elena De Dios, Clara Bonanad, Paolo Racugno, Alejandro Bellver Navarro, Bruno Ventura Perez, Jose Aguilar Botella, Silvia Ventura, Luis Mainar, Joaquim Canoves, Mauricio Pellicer, David Moratal, Gema Miñana, Julio Nuñez, Francisco J. Chorro, Vicente Bodi
Journal: JACC. Cardiovascular imaging (2020)
Identification of Differential Tumor Subtypes of T1 Bladder Cancer
Authors: A. Gordon Robertson, Clarice S. Groeneveld, Brian Jordan, Xiquo Lin, Kimberly A. McLaughlin, Arighno Das, Leigh Ann Fall, Damiano Fantini, Timothy J. Taxter, Lauren S. Mogil, Sia Viborg Lindskrog, Lars Dyrskjøt, David J. McConkey, Robert S. Svatek, Aurélien de Reyniès, Mauro A.A. Castro, Joshua J. Meeks
Journal: European Urology (2020)
Modeling neoplastic disease with spheroids and organoids
Authors: Michele Zanoni, Michela Cortesi, Alice Zamagni, Chiara Arienti, Sara Pignatta, Anna Tesei
Journal: Journal of Hematology & Oncology (2020)

Abstract Cancer is a complex disease in which both genetic defects and microenvironmental components contribute to the development, progression, and metastasization of disease, representing major hurdles in the identification of more effective and safer treatment regimens for patients. Three-dimensional (3D) models are changing the paradigm of preclinical cancer research as they more closely resemble the complex tissue environment and architecture found in clinical tumors than in bidimensional (2D) cell cultures. Among 3D models, spheroids and organoids represent the most versatile and promising models in that they are capable of recapitulating the heterogeneity and pathophysiology of human cancers and of filling the gap between conventional 2D in vitro testing and animal models. Such 3D systems represent a powerful tool for studying cancer biology, enabling us to model the dynamic evolution of neoplastic disease from the early stages to metastatic dissemination and the interactions with the microenvironment. Spheroids and organoids have recently been used in the field of drug discovery and personalized medicine. The combined use of 3D models could potentially improve the robustness and reliability of preclinical research data, reducing the need for animal testing and favoring their transition to clinical practice. In this review, we summarize the recent advances in the use of these 3D systems for cancer modeling, focusing on their innovative translational applications, looking at future challenges, and comparing them with most widely used animal models.