tbuckley/cabot-search huggingface dataset:
Point-of-care COVID-19 antigen testing in German emergency rooms – a cost-benefit analysis
Authors: R. Diel, A. Nienhaus
Journal: Pulmonology (2021)

The current COVID-19 pandemic is causing significant morbidity and death worldwide and produces significant socio-economic losses. To assess the cost–benefit relation of implementing point-of-care COVID-19 antigen testing (POCT) in emergency rooms (ER) of German hospitals. A deterministic decision-analytic model simulated the incremental costs of using the Sofia® SARS Antigen FIA test compared to those of using clinical judgement alone to confirm or exclude COVID-19 in adult patients in German ER, prior to hospitalization. Direct and indirect costs, with and without subsequent RT-PCR confirmation, were evaluated from the hospital perspective. With respect to ER patients, in base-case analysis, considering a COVID-19 prevalence of 15.6% and a hospitalization rate among COVID-19 suspects of 10.1%, POCT testing reduces average costs of hospitalized patients by €213 per tested patient if nasopharyngeal swabs of patients suspected to have COVID-19 are also sent to external labs for RT-PCR testing. In probabilistic sensitivity analysis, under all reasonable assumptions, implementing the Sofia® SARS Antigen FIA saves on average about €210 as compared to applying the clinical-judgement-only strategy. The major part of cost savings, €159 or 75.9%, is due to the POC test´s high specificity resulting in a 21-fold lower proportion of unnecessary bed blocking at the first day of hospitalization. Using highly specific rapid COVID-19 tests in COVID-19 suspects at German ER, despite of their sub-optimal sensitivity, may significantly reduce hospital expenditure.
Abstract 3019: An ultra-accurate NGS assay reveals great variation in mouse ratios in xenograft tumors by mouse strain and cancer type
Authors: Wubin Qian, Sheng Guo
Journal: Cancer Research (2021)

Abstract Background: Tumors are infiltrated by stromal cells including fibroblasts, myofibroblasts, macrophages, lymphocytes, mast cells, endothelial cells, etc. Heterotypic interactions, such as ligand-receptor signaling, between the two support the growth and metastasis of cancer cells. Xenograft models are useful in studying such interactions because mouse stromal cells quickly replace the human counterparts associated with human tumors implanted in immunocompromised mice, and can be readily detected. There is, however, a lack of accurate and large-scale studies of human/mouse ratios in xenograft tumors, although there are several ways of estimating mouse ratios in xenograft tumors, including RT-PCR, RNA-seq and whole-exome sequencing (WES). None of these methods is accurate due to some systematic bias. For example, RT-PCR compares the expression of one or a few genes, e.g. GAPDH, between human and mouse by using species-specific primers that have inequivalent amplification efficiency and large errors. We have developed a NGS assay to quantify human/mouse ratios in human-mouse mixtures more accurately than the methods currently employed. Methods: Our NGS assay simultaneously amplified 108 human and mouse homologous segments, each with identical flanking sequences in human and mouse, so that a pair of common primers was designed to have equal hybridization efficiency in the two species. A total of 5000 tumors from our patient-derived xenograft (PDX) collection were profiled across 1674 models in 24 cancer types. Results: Several interesting observations were identified. (a) The average mouse content across the collection of PDX models was 23%, but with great variation, ranging from zero to 93%. (b) PDXs have significantly more mouse content in BALB/c than in NOD/SCID mice (31.9% vs 22.1%, p value&amp;lt;2.2e-16). (c) Different cancers have varied mouse content, for example, pancreatic cancer has much higher mouse content than colorectal cancer (37.3±16.6% vs 17.9±12.2%). (d) Different passages of the same PDX model can have very different mouse ratios and this is likely due to randomness in tumor dissection. Conclusions: Our NGS assay and findings will help the study of stroma and the tumor microenvironment of tumors in xenografts models. Citation Format: Wubin Qian, Sheng Guo. An ultra-accurate NGS assay reveals great variation in mouse ratios in xenograft tumors by mouse strain and cancer type [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3019.
Re-Tur + BCG vs. upfront BCG in high-risk non-muscle invasive bladder cancer: Rationale for a feasibility phase of a randomized controlled study
Authors: P. Gontero, F. Soria, M. Burger, E. Comperat, A. Masson-Lecomte, F. Liedberg, H.A. Mostafid, B.W. Van Rhijn, S.F. Shariat, B. Marek, R.J. Sylvester, J. Palou
Journal: European Urology (2021)
Author Correction: Improved reference genome of the arboviral vector Aedes albopictus
Authors: Umberto Palatini, Reem A. Masri, Luciano V. Cosme, Sergey Koren, Françoise Thibaud-Nissen, James K. Biedler, Flavia Krsticevic, J. Spencer Johnston, Rebecca Halbach, Jacob E. Crawford, Igor Antoshechkin, Anna-Bella Failloux, Elisa Pischedda, Michele Marconcini, Jay Ghurye, Arang Rhie, Atashi Sharma, Dmitry A. Karagodin, Jeremy Jenrette, Stephanie Gamez, Pascal Miesen, Patrick Masterson, Adalgisa Caccone, Maria V. Sharakhova, Zhijian Tu, Philippos A. Papathanos, Ronald P. Van Rij, Omar S. Akbari, Jeffrey Powell, Adam M. Phillippy, Mariangela Bonizzoni
Journal: Genome biology (2021)
The ergoreflex: how the skeletal muscle modulates ventilation and cardiovascular function in health and disease
Authors: Alberto Aimo, Luigi Francesco Saccaro, Chiara Borrelli, Iacopo Fabiani, Francesco Gentile, Claudio Passino, Michele Emdin, Massimo Francesco Piepoli, Andrew J.S. Coats, Alberto Giannoni
Journal: European Journal of Heart Failure (2021)

The control of ventilation and cardiovascular function during physical activity is partially regulated by the ergoreflex, a cardiorespiratory reflex activated by physical activity. Two components of the ergoreflex have been identified: the mechanoreflex, which is activated early by muscle contraction and tendon stretch, and the metaboreflex, which responds to the accumulation of metabolites in the exercising muscles. Patients with heart failure (HF) often develop a skeletal myopathy with varying degrees of severity, from a subclinical disease to cardiac cachexia. HF-related myopathy has been associated with increased ergoreflex sensitivity, which is believed to contribute to dyspnoea on effort, fatigue and sympatho-vagal imbalance, which are hallmarks of HF. Ergoreflex sensitivity increases significantly also in patients with neuromuscular disorders. Exercise training is a valuable therapeutic option for both HF and neuromuscular disorders to blunt ergoreflex sensitivity, restore the sympatho-vagal balance, and increase tolerance to physical exercise. A deeper knowledge of the mechanisms mediating ergoreflex sensitivity might enable a drug or device modulation of this reflex when patients cannot exercise because of advanced skeletal myopathy.
Similar Probabilities of Failure to Reach Transplantation and Transplant Outcomes after HLA-Identical Sibling or Unrelated Donor Transplant in Patients with Acute Myeloid Leukemia: A Single Institution Evaluation of a Donor Selection Algorithm
Authors: Eduardo Rodríguez-Arbolí, Francisco J. Márquez-Malaver, Nancy Rodríguez-Torres, Teresa Caballero-Velázquez, Virginia Escamilla Gomez, Cristina Calderón-Cabrera, José F. Falantes, Ildefonso Espigado, José A. Pérez-Simón
Journal: Blood (2017)
Abstract 932: Discovery of D-1553, a novel and selective KRas-G12C Inhibitor with potent anti-tumor activity in a broad spectrum of tumor cell lines and xenograft models
Authors: Zhe Shi, Jifang Weng, Xiaochong Fan, Emma Wang, Qingqing Zhu, Liangshan Tao, Zixing Han, Zhenwu Wang, Haotao Niu, Yueheng Jiang, Ling Zhang, Xing Dai, Yaolin Wang
Journal: Cancer Research (2021)

Abstract KRas mutations are frequently seen in solid tumors such as lung (~25%), colorectal (~40%) and pancreatic (~90%) cancers. The G12C mutation accounts for ~50% of all KRas mutations in lung cancer and to a lower percentage in other tumor types. Recently, selective inhibitors targeting the KRas-G12C mutation through covalent link to the cysteine of the mutated protein have been advanced to early clinical development and exhibited encouraging response in patients with lung cancer. Here, we present a novel small molecule compound that specifically inhibits KRas-G12C in vitro (cell lines) and in vivo (cell line-derived xenograft tumor models). The anti-tumor activity of D-1553 is evaluated across a panel of cancer cell lines including lung, pancreatic and colorectal cancers and shown to be active only in cancer cells with KRas-G12C mutation. In addition, D-1553 is highly potent in vivo in various cell line-derived xenograft tumor models with KRas-G12C mutation as a single agent. When D-1553 is combined with MEK inhibitor, SHP2 inhibitor or cytotoxic agents, further tumor growth inhibition or regression was observed in tumor xenograft models. These data suggest that D-1553 has anti-tumor activity in a broad spectrum of cancers and is suitable for tissue-agnostic clinical development targeting cancers with KRas-G12C mutation. D-1553 is currently in a Phase 1/2 clinical trial evaluating safety, tolerability, PK and efficacy in patients with advanced solid tumors harboring KRasG12C mutation (NCT04585035). Citation Format: Zhe Shi, Jifang Weng, Xiaochong Fan, Emma Wang, Qingqing Zhu, Liangshan Tao, Zixing Han, Zhenwu Wang, Haotao Niu, Yueheng Jiang, Ling Zhang, Xing Dai, Yaolin Wang. Discovery of D-1553, a novel and selective KRas-G12C Inhibitor with potent anti-tumor activity in a broad spectrum of tumor cell lines and xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 932.
Abstract 18353: FOXO3a and Cardiac Remodeling - Modulation of MMP13 Expression
Authors: Jenny Stehr, Franziska Schmidt, Luise Holzhauser, Alexander Jenke, Heinz-Peter Schultheiss, Carsten Skurk
Journal: Circulation (2011)

Objective: Structural alterations of cardiac extracellular matrix occur as a result of pathological processes in the heart, e.g. dilated cardiomyopathy or myocardial infarction. Matrix metalloproteinases (MMPs) are proteolytic enzymes which play a pivotal role in stress induced matrix remodeling. FOXO transcription factors are important stress-activated regulators of cell cycle and size. Therefore, we hypothesized that FOXO3a, a member of the FOXO family known to be expressed in myocardium, modulates the expression of MMPs. Methods: Cardiac myocytes and fibroblasts were transduced with adenoviral vectors encoding either wild-type FOXO3a (WT-FOXO3a), constitutive-active FOXO3a (TM-FOXO3a) or GFP as control. Effects on potential target genes were assessed by QRT-PCR, Western blot/IHC, specific Collagenase assay, CHIP or luciferase promoter assay. Effects of viral myocarditis were studied in WT and FOXO3a-/- mice. Results: Cardiac myocytes and fibroblasts transduced with FOXO3a did not show differences in MMP1, -2, -3, -9 as well as TIMP 1,-2,-4 gene or protein expression when compared with control vector. However, WT-FOXO3a or TM-FOXO3a gene transfer dose-dependently upregulated MMP13 mRNA expression (3.5 ± 1.2 and 22.0 ± 11.0 fold; p &lt; 0.001, WT and TM-FOXO3a vs. GFP, respectively). Furthermore, MMP13 protein levels were also significantly upregulated under these conditions (p &lt; 0.01). Moreover, FOXO3a transduction led to significantly increased Collagenase activity (p &lt; 0.01). Accordingly, FOXO3a-/- mice showed diminished MMP13 mRNA and protein expression. CHIP and luciferase promoter assays revealed binding of FOXO3a to the MMP13 promoter and its transcriptional activation. Finally, viral myocarditis led to FOXO3a activation associated with increased MMP13 mRNA expression that was significantly diminished in FOXO3a-/- mice which demonstrated increased Collagen 1 and 3 protein expression in IHC (p &lt; 0.05). Conclusion: In conclusion our results implicate FOXO3a directly in the regulation of MMP13 expression. FOXO3a might play an important role in controlling extracellular matrix remodeling processes under cardiovascular stress and injury such as inflammation. Thus, targeting FOXO3a might have therapeutic potential.
Adverse pathological findings in deferred radical prostatectomy in men under active surveillance for very low and low risk prostate cancers: Results from GAP3 active surveillance cohorts
Authors: C. Marenghi, Z. Qiu, N. Nicolai, J. Helleman, D. Nieboer, J. Rubio-Briones, P.R. Carroll, J.E. Cowan, L.S. Lee, P.C. Boutros, R. Valdagni
Journal: European Urology (2021)
Summary of Literature on Pediatric Real-world Evidence and Effectiveness
Authors: Ann W. McMahon, Kenneth Quinto, Amy Abernethy, Jacqueline Corrigan-Curay
Journal: JAMA Pediatrics (2021)

of Literature on Pediatric Real-world Evidence and EffectivenessThe US Food and Drug Administration (FDA) has long used clinical real-world data (RWD) and clinical real-world evidence (RWE) to supplement information from traditional randomized clinical trials on the safety of medications in children and adults, but RWD and RWE are not commonly used to demonstrate effectiveness, especially in pediatrics.With the widespread use of electronic health care data, there may be new opportunities for RWE to assess the effectiveness of medical products that are on the market.The 21st Century Cures Act of 2016 provides specific milestones for the FDA to achieve in evaluating potential uses of clinical RWE to support regulatory decision-making.As part of that effort, the FDA published its Framework for FDA's Real-World Evidence Program in 2018 (https://www.fda.gov/media/120060/download).The initial question within the domain of clinical pediatric RWE is: what are the descriptive characteristics of existing clinical pediatric RWE effectiveness studies?This review of clinical pediatric RWE studies assessed studies from ClinicalTrials.gov and other published drug studies that focused on therapeutic effectiveness from 5 subspecialties (ie, psychiatry, cardiology, rheumatology, pulmonology, and oncology), which, based in part on analogous adult studies, could have promising clinical RWE application and could differ from one another in their approach to using clinical RWE to evaluate effectiveness.
Abstract 1065: Concomitant dexamethasone treatment and tumor treating fields induced cell death in glioblastoma
Authors: Abigail Schiesl, Benedikt Linder, Franz Rödel, Stephanie Hehlgans, Ömer Güllülü, Volker Seifert, Donat Koegel, Christian Senft, Daniel Dubinski
Journal: Cancer Research (2021)

Abstract Objective: Patients suffering from Glioblastoma (GBM) usually present with perilesional edema which is the major contributor of neurologic deficit. Dexamethasone (Dex) has become the corticoid of choice due to its fast and effective alleviation of perilesional edema. The impact of concomitant Dex treatment on TTFields efficacy is unexplored to date. Methods: Human GBM cell lines MZ54 and U251 were treated with TTF in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We furthermore investigated the influence of Dex on the cell cycle distribution/cell cycle arrest with and without double thymidine block for synchronisation via flow cytometry in both cell lines. Results: TTF treatment (200 kHz/250 kHz) for 72 h was able to induce massive cell death (70 %) in the cultures of both cell lines. Cell cycle analysis performed after synchronization showed that Dex treatment (65 µM/165 µM) evoked an accumulation of both cell lines in the G0/G1 phase. Concurrent Dex treatment had no significant influence on the extent of apoptosis induced by TTFields. Conclusions: Despite the partial G0/G1 arrest induced by Dex, our results show no interference of Dex with the antitumorous capacity of TTF in vitro. These data support the hypothesis that concomitant therapy with Dex does not negatively interfere with TTF efficacy in primary GBM. Citation Format: Abigail Schiesl, Benedikt Linder, Franz Rödel, Stephanie Hehlgans, Ömer Güllülü, Volker Seifert, Donat Koegel, Christian Senft, Daniel Dubinski. Concomitant dexamethasone treatment and tumor treating fields induced cell death in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1065.
Muc16 carboxyl portion expression alternates PI3K/Akt and EGFR/HER2/ERK signal pathways in human ovarian cells
Authors: Xun Ma, Dhamarao Thapi, Xiujun Yan, Qing-Bai She, Nestor Rosales, David Spriggs
Journal: Cancer Research (2008)

3435  MUC16 (CA125) is a heavily O-glycosylatedtransmembrane mucin family protein and a cell surface marker for ovarian carcinomas and other gynecologic malignancies, distinguished by highly repetitive sequences in the extracellular domain. MUC16 transfection alters tumor growth pattern in xenograft models and in vitro invasion behavior of MUC16-negative ovarian cancer cells. MUC16 expression is also increased cisplatin resistance but the mechanisms and signaling pathwaysof the MUC16 are unclear. We examine the effect of MUC16 on common signal transduction pathways, such as PI3K/Akt and EGFR/HER2/MAPK pathways, which are associated with malignant transformation, invasion and metastasis. We subcloned the truncated MUC16 carboxyl 114 amino acid and 344 amino acid sequences into phrGFP II- C vector and then transfected the MUC16 expression constructs into MUC16-negative ovarian carcinoma cell lines, SKOV3 and A2780, and a transformed human ovarian epithelial cell line, T80. Stable transfectants were selected and enriched by fluorescence activated cell sorting. Western blotting and immunoprecipitation were performed by using cell lysates of cultured transfectants with antibodies against PI3K, Akt, phosphorylated-Akt Ser473, EGFR, HER2, P-HER2/EGFR Tyr1248/Tyr1173, ERK1/2, P-ERK1/2 Thr202/Tyr204, p38 MAPK and P-p38 MAPK Tyr180/Tyr182, GSK3 beta and P-GSK3 beta Ser9, Bad , P-Bad Ser136 and Ser112. Expression of carboxyl MUC16 stimulated phosphrylation of ERK1/2 compared with phrGFP II-C vector transfectants through upregulating phosphorylated HER2/EGFR Tyr1248/Tyr1173, while this effect was inhibited by EGFR tyrosin kinase inhibitor (TKI), gefitinib or MEK inhibitor, U0126. Carboxyl MUC16 also upregulated Akt phosphorylation as well as its downstream GSK3 beta and Bad phosphorylation, and these effects were inhibited by PI3 Kinase inhibitor, LY294002 , but not gefitinib. These results suggest that the expression of carboxyl MUC16 activates MAPK and PI3K/Akt signaling pathways in SKOV3, A2780 and T80 cells in different mechanisms. The phosphorylation inhibition of ERK by gefitinib but not by LY294002 implies that MUC16 induces MAPK signal upregulation through EGFR/HER2/MAPK in an independent manner from the PI3K/Akt pathway. The biological consequences of the PI3K/Akt and EGFR/HER2/MAPK based signal activation by truncated carboxyl MUC16 are under investigation.
Initial Management of Seizure in Adults
Authors: Phil E.M. Smith
Journal: New England Journal of Medicine (2021)

A detailed history taking and an eyewitness account are important in diagnosing a seizure. Antiseizure medication is generally not prescribed after a single seizure, except for patients with a high risk of recurrence. The medication choice varies according to the type of seizure and the patient's coexisting conditions and childbearing potential.
Patients with Myelodysplastic Syndromes, Other Than Del(5)q Syndrome, Exhibiting Del(5)q Alone or Associated with One Additional Chromosomal Abnormality Have Comparable Probability and Duration of Response to Lenalidomide, with Patients Classified As Del(5)q Syndrome
Authors: Argiris Symeonidis, Alexandra Kourakli, Ioannis Kotsianidis, Panagiotis Zikos, Eleftheria Hatzimichael, Theodoros Vassilakopoulos, Aikaterini Palla, Vassiliki Pappa, Evgenia Verigou, Zafeirios Kartasis, Eirini Katodritou, Maria Pagoni, Theodora Assimakopoulou, Charalampos Pontikoglou, Maria Dimou, George Xanthopoulidis, Maria K. Angelopoulou, Maria Kotsopoulou, Dimitra Liapi, Despina Mparmparousi, Evridiki Michali, Anna Kioumi, Nora-Athina Viniou, Achilles Anagnostopoulos, Vassiliki Labropoulou, Maria Dalekou, Michael Voulgarelis, Efthymia Vlachaki, Anna Christoforidou, Ioannis Adamopoulos, Akrivi Kostourou, Petros Laos, Evangelos Terpos, Eleni Kapsali, George Vassilopoulos, Helen A. Papadaki, Panayiotis Panayiotidis, Athanasios Galanopoulos
Journal: Blood (2017)
Is robotic transperitoneal partial nephrectomy safe in the management of cystic renal cell masses? Outcomes of an ERUS multicenter study including 216 patients
Authors: A. Mottrie, B. Challacombe, F. Montorsi, K. Ener, A. Ploumidis, A.E. Canda, A. Larcher, K. Decaestecker, N. De Luyk, N. Buffi, A. Uleri, A. Gallina, G. De Naeyer, G. Guazzoni, A. Fernando, A. Briganti, A. Cestari, Y. Kordan, R. Catterwell, T. Esen, C. Van Praet, M.D. Balbay, U. Capitanio, A. Pappas
Journal: European Urology (2021)
International Classification of Retinopathy of Prematurity, Third Edition
Authors: Michael F. Chiang, Graham E. Quinn, Alistair R. Fielder, Susan R. Ostmo, R.V. Paul Chan, Audina Berrocal, Gil Binenbaum, Michael Blair, J. Peter Campbell, Antonio Capone, Yi Chen, Shuan Dai, Anna Ells, Brian W. Fleck, William V. Good, M. Elizabeth Hartnett, Gerd Holmstrom, Shunji Kusaka, Andrés Kychenthal, Domenico Lepore, Birgit Lorenz, Maria Ana Martinez-Castellanos, Şengül Özdek, Dupe Ademola-Popoola, James D. Reynolds, Parag K. Shah, Michael Shapiro, Andreas Stahl, Cynthia Toth, Anand Vinekar, Linda Visser, David K. Wallace, Wei-Chi Wu, Peiquan Zhao, Andrea Zin
Journal: Ophthalmology (2021)
Response to Erythropoietin in Different Karyotipic Subsets of Myelodysplastic Syndromes (MDS) and MDS with Sideroblasts: Multicentric Real-Life Experience from the Grom-L Cooperative Group
Authors: Roberto Latagliata, Pasquale Niscola, Luana Fianchi, Laura Faglioni, Alessia Campagna, Luca Maurillo, Chiara Sarlo, Annalina Piccioni, Marianna Criscuolo, Ida Carmosino, Alessandro Andriani, Svitlana Gumenyuk, Nicoletta Villivà, Daniela De Benedictis, Roberta Battistini, Susanna Fenu, Massimo Breccia, Stefano Mancini, Maria Teresa Voso, Maria Antonietta Aloe Spiriti, Francesco Buccisano
Journal: Blood (2017)