tbuckley/cabot-search huggingface dataset:
Celecoxib suppresses the HCC development via the cell cycle arrest
Authors: Terence C. M. Tang, Ronnie T. P. Poon, Xin Yuan Guan, Louise W C Chow, Sheung Tat Fan
Journal: Cancer Research (2005)

3018  Liver cancer is the second leading cause of death in males in Hong Kong and the incidence rate of 36 per 100,000 is the second highest in the world. Previous studies have shown increased levels of cyclooxygenase-2 (COX-2) in a variety of human malignancies including hepatocellular carcinoma (HCC), suggesting that abnormal COX-2 expression plays an important role in carcinogenesis. In addition, some evidence suggests that selective COX-2 inhibitors suppress the formation of tumors in experimental models. However, there is no data in the literature on using COX-2 as an inhibitor in HCC. Hence, we performed in vivo studies to investigate the chemopreventive and therapeutic effects of Celecoxib, a selective COX-2 inhibitor, on the development and growth of HCC xenograft in nude mice. To investigate the chemopreventive effect of Celecoxib, the drug was administered at day 0 by post tumor cell injection, while the control group was given vehicle only. To investigate the therapeutic effect of celecoxib on established tumor, the drug was administered at the 100 mm3 while in the control group only vehicle was given. Celecoxib was administered orally at a dose of 250-mg/kg body weight/day. Our results showed that Celecoxib could prolong the latent period (p
P66.01 Characterize the Heterogeneity of the Immunophenotype in Different Neuroendocrine (NE) Subtypes of Small-Cell Lung Cancer (SCLC)
Authors: L. Yang, Y. Guo, L. Liu, J. Dong, J. Zhang, F. Teng, X. Sun, X. Wang, P. Xing, J. Ying, J. Li
Journal: Journal of Thoracic Oncology (2021)
Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients
Authors: Jean Farup, Jesper Just, Frank de Paoli, Lin Lin, Jonas Brorson Jensen, Tine Billeskov, Ines Sanchez Roman, Cagla Cömert, Andreas Buch Møller, Luca Madaro, Elena Groppa, Rikard Göran Fred, Ulla Kampmann, Lars C. Gormsen, Steen B. Pedersen, Peter Bross, Tinna Stevnsner, Nikolaj Eldrup, Tune H. Pers, Fabio M.V. Rossi, Pier Lorenzo Puri, Niels Jessen
Journal: Cell Metabolism (2021)
Optimization of idarubicin and cytarabine induction regimen with homoharringtonine for newly diagnosed acute myeloid leukemia patients based on the peripheral blast clearance rate: A single‐arm, phase 2 trial (<scp>RJ‐AML</scp> 2014)
Authors: Yunxiang Zhang, Xiaoyang Li, Xiangqin Weng, Yang Shen, Yu Chen, Yu Zheng, Huijin Zhao, Jianhua You, Yuanfei Mao, Lining Wang, Min Wu, Yan Sheng, Jing Wu, Jiong Hu, Qiusheng Chen, Junmin Li
Journal: American Journal of Hematology (2021)

Individualized chemotherapy, which is at the forefront of acute myeloid leukemia (AML) treatment, has moderately improved outcomes over the past decade. Monitoring the peripheral blood blast burden during induction by flow cytometry has shown significant value in the evaluation of treatment responses. Our previous study reported the day 5 peripheral blast clearance rate (D5-PBCR) as an indicator of early treatment response, and D5-PBCR (+) patients showed poor outcomes. We performed the present phase 2 trial of early intervention in D5-PBCR (+) patients with homoharringtonine (HHT) introduced in the traditional induction regimen with anthracycline and cytarabine. The primary endpoint was complete remission (CR). This study enrolled 151 patients, 65 patients were D5-PBCR (+) and 55 patients completed induction with HHT addition. The overall CR rate after one course of induction was 84.4%, with 87.5% and 80.0% for the D5-PBCR (-) and D5-PBCR (+) groups, respectively. The incidence of grade 3/4 adverse events was comparable between the two groups. At the median follow-up of 53.1 months, median overall survival (OS) was not reached in the entire cohort, and median event-free survival (EFS) was 42.2 months. Neither the OS nor EFS showed significant differences between the D5-PBCR (-) and D5-PBCR (+) groups. Compared to historical data, significant improvements in both OS (p = .020) and EFS (p = .020) were observed in the D5-PBCR (+) group. In conclusion, optimization of induction chemotherapy with idarubicin and cytarabine according to D5-PBCR is feasible in patients with newly diagnosed AML. The addition of HHT demonstrated a good efficacy and safety profile.
FP04.03 Clinical Benefit of First-Line Cemiplimab in Patients with Locally Advanced NSCLC: Subgroup Analysis from EMPOWER-Lung 1
Authors: I. Bondarenko, A. Sezer, S. Kilickap, M. Gümüş, M. Özgüroğlu, M. Gogishvili, H.M. Turk, I. Cicin, D. Bentsion, O. Gladkov, P. Clingan, V. Sriuranpong, N. Rizvi, J. Mcginniss, J. Pouliot, S. Lee, F. Seebach, I. Lowy, G. Gullo, P. Rietschel
Journal: Journal of Thoracic Oncology (2021)
The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies
Authors: Serdar Durdagi, Timucin Avsar, Muge Didem Orhan, Muge Serhatli, Bertan Koray Balcioglu, Hasan Umit Ozturk, Alisan Kayabolen, Yuksel Cetin, Seyma Aydinlik, Tugba Bagci-Onder, Saban Tekin, Hasan Demirci, Mustafa Guzel, Atilla Akdemir, Seyma Calis, Lalehan Oktay, Ilayda Tolu, Yasar Enes Butun, Ece Erdemoglu, Alpsu Olkan, Nurettin Tokay, Şeyma Işık, Aysenur Ozcan, Elif Acar, Sehriban Buyukkilic, Yesim Yumak
Journal: Molecular Therapy (2021)

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the enzyme (main protease) inhibition-based assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEK293T/hACE2+TMPRSS2, and virus neutralization assay using xCELLigence MP real-time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of montelukast both on the main protease enzyme inhibition and virus entry into the host cell (spike/ACE2). The virus neutralization assay results showed that SARS-CoV-2 virus activity was delayed with montelukast for 20 h on the infected cells. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since 1998, should urgently be completed in clinical phase studies and, if its effect is proved in clinical phase studies, it should be used against coronavirus disease 2019 (COVID-19).
Conjugation of glucosylated polymer chains to checkpoint blockade antibodies augments their efficacy and specificity for glioblastoma
Authors: Tao Yang, Yuki Mochida, Xueying Liu, Hang Zhou, Jinbing Xie, Yasutaka Anraku, Hiroaki Kinoh, Horacio Cabral, Kazunori Kataoka
Journal: Nature Biomedical Engineering (2021)
Assessment of Cognitive Function in Patients After COVID-19 Infection
Authors: Jacqueline H. Becker, Jenny J. Lin, Molly Doernberg, Kimberly Stone, Allison Navis, Joanne R. Festa, Juan P. Wisnivesky
Journal: JAMA Network Open (2021)

People who have survived COVID-19 frequently complain of cognitive dysfunction, which has been described as brain fog. The prevalence of post–COVID-19 cognitive impairment and the association with disease severity are not well characterized. Previous studies on the topic have been limited by small sample sizes and suboptimal measurement of cognitive functioning.1 We investigated rates of cognitive impairment in survivors of COVID-19 who were treated in outpatient, emergency department (ED), or inpatient hospital settings.
Whole-body imaging of tumor vascularture and blood flow using color-coded tumor-host models and laser scanning microscopy
Authors: Meng Yang, Kensuke Yamauchi, Huaiyu Ma, Ping Jiang, Robert Hoffman
Journal: Cancer Research (2007)

2991  We have previously developed a simple yet powerful dual-color fluorescence imaging technique for delineating the morphological events of tumor-induced angiogenesis and other tumor-host interaction. The method clearly images implanted tumors and adjacent stroma, distinguishing unambiguously the host and tumor-specific components of the malignancy. The dual-color fluorescence imaging is effected by using red fluorescent protein (RFP)-expressing tumors growing in GFP-expressing transgenic mice. In order to further visualize tumor angiogenesis and tumor blood flow in live animals, we have developed 3-color whole-body cellular imaging with transgenic GFP-expressing mice implanted in the footpad with dual-color tumor cells having RFP expressed in the cytoplasmand GFP linked to histone H2B expressed in the nucleus. In this model, the host blood vessels are green fluorescent, the tumor cytoplasm is red fluorescent and the GFP-nuclei appear yellow. With the Olympus IV100 Laser Scanning Microscope, tumor angiogenesis and blood flow can be visualized in this model at the subcellular level in live mice by whole-body imaging in real time. This new model system can visualize the efficacy of agents on tumor blood flow kinetics and blood vessel density in real time.
Telerehabilitation for chronic respiratory disease: a randomised controlled equivalence trial
Authors: Narelle S Cox, Christine F McDonald, Ajay Mahal, Jennifer A Alison, Richard Wootton, Catherine J Hill, Paolo Zanaboni, Paul O'Halloran, Janet Bondarenko, Heather Macdonald, Kathryn Barker, Hayley Crute, Christie Mellerick, Bruna Wageck, Helen Boursinos, Aroub Lahham, Amanda Nichols, Pawel Czupryn, Monique Corbett, Emma Handley, Angela T Burge, Anne E Holland
Journal: Thorax (2021)

Pulmonary rehabilitation is an effective treatment for people with chronic respiratory disease but is delivered to <5% of eligible individuals. This study investigated whether home-based telerehabilitation was equivalent to centre-based pulmonary rehabilitation in people with chronic respiratory disease.A multicentre randomised controlled trial with assessor blinding, powered for equivalence was undertaken. Individuals with a chronic respiratory disease referred to pulmonary rehabilitation at four participating sites (one rural) were eligible and randomised using concealed allocation to pulmonary rehabilitation or telerehabilitation. Both programmes were two times per week for 8 weeks. The primary outcome was change in Chronic Respiratory Disease Questionnaire Dyspnoea (CRQ-D) domain at end-rehabilitation, with a prespecified equivalence margin of 2.5 points. Follow-up was at 12 months. Secondary outcomes included exercise capacity, health-related quality of life, symptoms, self-efficacy and psychological well-being.142 participants were randomised to pulmonary rehabilitation or telerehabilitation with 96% and 97% included in the intention-to-treat analysis, respectively. There were no significant differences between groups for any outcome at either time point. Both groups achieved meaningful improvement in dyspnoea and exercise capacity at end-rehabilitation. However, we were unable to confirm equivalence of telerehabilitation for the primary outcome ΔCRQ-D at end-rehabilitation (mean difference (MD) (95% CI) -1 point (-3 to 1)), and inferiority of telerehabilitation could not be excluded at either time point (12-month follow-up: MD -1 point (95% CI -4 to 1)). At end-rehabilitation, telerehabilitation demonstrated equivalence for 6-minute walk distance (MD -6 m, 95% CI -26 to 15) with possibly superiority of telerehabilitation at 12 months (MD 14 m, 95% CI -10 to 38).telerehabilitation may not be equivalent to centre-based pulmonary rehabilitation for all outcomes, but is safe and achieves clinically meaningful benefits. When centre-based pulmonary rehabilitation is not available, telerehabilitation may provide an alternative programme model.ACtelerehabilitationN12616000360415.
Severe herpes simplex and varicella-zoster viral infection in patients with solid organ transplantation: A nationwide population-based cohort study with propensity score matching analysis
Authors: Tung-Min Yu, Kuo-Ting Sun, Shiang-Cheng Kung, Brian K. Lee, Ming-Ju Wu, Cheng-Hsu Chen, Chung-Shu Sun, Ying-Chih Lo, Tsuo-Hung Lan, Chi-Yuan Li, Ting-Fang Chiu, Mei-Chen Lin, Chia-Hung Kao
Journal: Journal of the American Academy of Dermatology (2021)
OA05.01 Impact of an Embedded Palliative Care Clinic on Healthcare Utilization for Patients With an Advanced Thoracic Malignancy
Authors: K. Gast, J. Benedict, M. Grogan, S. Janse, M. Saphire, P. Kumar, E. Bertino, J. Agne, C. Presley
Journal: Journal of Thoracic Oncology (2021)
Identification of novel therapeutic targets for histone 3 mutated children’s brain tumour, using unique tumour cell surface proteomic signatures
Authors: Anya Snary, Richard Grundy, Rob Layfield, Ruman Rahman, Farhana Haque
Journal: Neuro-Oncology (2021)

Abstract Aims Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We hypothesized that the histone 3 mutant tumours will have distinct mutation specific surfactome (cell membrane proteins) signature. Method We therefore analysed the cell surface proteomics of pHGG and DIPG, in order to identify novel targets for therapy. We have at first isolated the cell membrane fractions from a range of patient cells carrying different histone 3 mutations (G34R, G34V), relative to wild type histone 3. A comparative quantitative mass-spectrometry analyses of these cell surface membrane fractions is then performed. Results The results obtained to date demonstrated unique differential cell membrane expression patterns which correlated to specific mutation type. For example, increased expression of Ras-related proteins Rab-3, Rab-3D is detected only in histone H3.3-G34R mutated cell line in comparison. Conclusion Identification and analyses of these unique cell membrane proteins’ association with specific in H3.3 mutation in pHGG, will help to identify precise mutation specific therapeutic targets, benefiting the patients to receive therapy based on tumour’s molecular signature.
LncRNA Snhg1-driven self-reinforcing regulatory network promoted cardiac regeneration and repair after myocardial infarction
Authors: Mengsha Li, Hao Zheng, Yuan Han, Yijin Chen, Bing Li, Guojun Chen, Xiaoqiang Chen, Senlin Huang, Xiang He, Guoquan Wei, Tong Xu, Xiaofei Feng, Wangjun Liao, Yulin Liao, Yanmei Chen, Jianping Bin
Journal: Theranostics (2021)

Rationale: Most current cardiac regeneration approaches result in very limited cell division and little new cardiomyocyte (CM) mass. Positive feedback loops are vital for cell division, but their role in CM regeneration remains unclear. We aimed to determine whether the lncRNA small nucleolar RNA host gene 1 Snhg1 (Snhg1) could form a positive feedback loop with c-Myc to induce cardiac regeneration. Methods: Quantitative PCR and in situ hybridization experiments were performed to determine the Snhg1 expression patterns in fetal and myocardial infarction (MI) hearts. Gain- and Loss-of-function assays were conducted to explore the effect of Snhg1 on cardiomyocyte (CM) proliferation and cardiac repair following MI. We further constructed CM-specific Snhg1 knockout mice to confirm the proliferative effect exerted by Snhg1 using CRISPR/Cas9 technology. RNA sequencing and RNA pulldown were performed to explore how Snhg1 mediated cardiac regeneration. Chromatin immunoprecipitation and luciferase reporter assays were used to demonstrate the positive feedback loop between Snhg1 and c-Myc. Results: Snhg1 expression was increased in human and mouse fetal and myocardial infarction (MI) hearts, particularly in CMs. Overexpression of Snhg1 promoted CM proliferation, angiogenesis, and inhibited CM apoptosis after myocardial infarction, which further improved post-MI cardiac function. Antagonism of Snhg1 in early postnatal mice inhibited CM proliferation and impaired cardiac repair after MI. Mechanistically, Snhg1 directly bound to phosphatase and tensin homolog (PTEN) and induced PTEN degradation, activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway to promote CM proliferation. The c-Myc protein, one of downstream targets of PI3K/AKT signaling, functioned as a transcription factor by binding to the promoter regions of Snhg1. Perturbation of the positive feedback between Snhg1 and c-Myc by mutation of the binding sequence significantly affected Snhg1-induced CM proliferation. Conclusions: Snhg1 effectively elicited CM proliferation and improved cardiac function post-MI by forming a positive feedback loop with c-Myc to sustain PI3K/Akt signaling activation, and thus may be a promising cardiac regeneration strategy in treating heart failure post-MI.
Rapid, dose-dependent and efficient inactivation of surface dried SARS-CoV-2 by 254 nm UV-C irradiation
Authors: Natalia Ruetalo, Ramona Businger, Michael Schindler
Journal: Eurosurveillance (2021)

The COVID-19 pandemic urges for cheap, reliable, and rapid technologies for disinfection and decontamination. One frequently proposed method is ultraviolet (UV)-C irradiation. UV-C doses necessary to achieve inactivation of high-titre SARS-CoV-2 are poorly defined.We investigated whether short exposure of SARS-CoV-2 to UV-C irradiation sufficiently reduces viral infectivity and doses necessary to achieve an at least 6-log reduction in viral titres.Using a box and two handheld systems designed to decontaminate objects and surfaces, we evaluated the efficacy of 254 nm UV-C treatment to inactivate surface dried high-titre SARS-CoV-2.Drying for 2 hours did not have a major impact on the infectivity of SARS-CoV-2, indicating that exhaled virus in droplets or aerosols stays infectious on surfaces for at least a certain amount of time. Short exposure of high titre surface dried virus (3-5*10^6 IU/ml) with UV-C light (16 mJ/cm2) resulted in a total inactivation of SARS-CoV-2. Dose-dependency experiments revealed that 3.5 mJ/cm2 were still effective to achieve a > 6-log reduction in viral titres, whereas 1.75 mJ/cm2 lowered infectivity only by one order of magnitude.SARS-CoV-2 is rapidly inactivated by relatively low doses of UV-C irradiation and the relationship between UV-C dose and log-viral titre reduction of surface residing SARS-CoV-2 is nonlinear. Our findings emphasize that it is necessary to assure sufficient and complete exposure of all relevant areas by integrated UV-C doses of at least 3.5 mJ/cm2 at 254 nm. Altogether, UV-C treatment is an effective non-chemical option to decontaminate surfaces from high-titre infectious SARS-CoV-2.
P28.01 Real-World Experience (RWE) of Consolidation Durvalumab After Concurrent Chemoradiotherapy (CCRT) In Stage III NSCLC
Authors: Y. Huang, J. Zhao, Y.Y. Soon, A. Wong, Y. Ang, Y. Asokumaran, J.L. Low, M. Lee, J. Choo, G. Chan, A. Kee, S.H. Tay, B.C. Goh, R. Soo
Journal: Journal of Thoracic Oncology (2021)
Weighing the Benefits and Unintended Consequences of a 2-Phased Match
Authors: Deborah S. Clements
Journal: JAMA Network Open (2021)

Abigail Ford Winkel, MD, MHPE; Helen K. Morgan, MD; Oluwabukola Akingbola, DO; Keli Santos-Parker, MD, PhD; Erin Nelson, MD; Erika Banks, MD; Nadine T. Katz, MD; Jessica L. Bienstock, MD, MPH; David Marzano, MD; Maya M. Hammoud, MD, MBA
Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem
Authors: Junjie Ren, Jing Zhou, Han Liu, Xiaodan Jiao, Yang Cao, Zhigang Xu, Yuejun Kang, Peng Xue
Journal: Theranostics (2021)

An imbalance in redox homeostasis consistently inhibits tumor cell proliferation and further causes tumor regression. Thus, synchronous glutaminolysis inhibition and intracellular reactive oxygen (ROS) accumulation cause severe redox dyshomeostasis, which may potentially become a new therapeutic strategy to effectively combat cancer.
Evaluation of the Thrombophilic Response to rFVIIa-Induced Hemostasis Activation in Factor V Leiden Carriers By Monitoring of Activated Protein C (APC) In Vivo
Authors: Heiko Rühl, Christina Berens, Franziska Isabelle Winterhagen, Jens Müller, Johannes Oldenburg, Bernd Pötzsch
Journal: Blood (2017)
Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior
Authors: Tamara Markovic, Christian E. Pedersen, Nicolas Massaly, Yvan M. Vachez, Brian Ruyle, Caitlin A. Murphy, Kavitha Abiraman, Jung Hoon Shin, Jeniffer J. Garcia, Hye Jean Yoon, Veronica A. Alvarez, Michael R. Bruchas, Meaghan C. Creed, Jose A. Morón
Journal: Nature Neuroscience (2021)
Bimekizumab for the treatment of moderate‐to‐severe plaque psoriasis: efficacy, safety, pharmacokinetics, pharmacodynamics and transcriptomics from a phase IIa, randomized, double‐blind multicentre study*
Authors: R. Oliver, J.G. Krueger, S. Glatt, P. Vajjah, C. Mistry, M. Page, H. Edwards, S. Garcet, X. Li, B. Dizier, A. Maroof, M. Watling, A. el Baghdady, D. Baeten, L. Ionescu, S. Shaw
Journal: British Journal of Dermatology (2021)

Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which is currently under investigation for treatment of moderate-to-severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL-17 inhibitors for psoriasis.To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies.Forty-nine patients with moderate-to-severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28.At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte-related gene products such as CXCL1 (C-X-C motif chemokine ligand 1), IL-8 (encoded by the CXCL8 gene), CCL20 (C-C motif chemokine 20), IL-36γ and IL-17C were profoundly normalized to levels associated with nonlesional skin.Here, inhibition of IL-17F in addition to IL-17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials.