tbuckley/cabot-search huggingface dataset:
Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials
Authors: Keisuke Koroki, Sadahisa Ogasawara, Yoshihiko Ooka, Hiroaki Kanzaki, Kengo Kanayama, Susumu Maruta, Takahiro Maeda, Masayuki Yokoyama, Toru Wakamatsu, Masanori Inoue, Kazufumi Kobayashi, Soichiro Kiyono, Masato Nakamura, Naoya Kanogawa, Tomoko Saito, Takayuki Kondo, Eiichiro Suzuki, Shingo Nakamoto, Shin Yasui, Akinobu Tawada, Tetsuhiro Chiba, Makoto Arai, Tatsuo Kanda, Hitoshi Maruyama, Jun Kato, Satoshi Kuboki, Masayuki Ohtsuka, Masaru Miyazaki, Osamu Yokosuka, Naoya Kato
Journal: Liver Cancer (2020)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden. &lt;b&gt;&lt;i&gt;Aims:&lt;/i&gt;&lt;/b&gt; The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
In vitro studies of bidentate pyridyl phosphine gold(I) and silver(I) complexes as potential antitumour agents in ovarian tumor cell lines and isolated hepatocytes
Authors: Johnson J. Liu, Peter Galettis, Li Ding, Alistair Farr, Lenushka Maharaj, Gabi Haddad, Hasitha Samarasinha, Adam C. McGechan, Bruce C. Baguley, Susan J. Berners-Price, Mark J. McKeage
Journal: Cancer Research (2005)

628  Gold(I) phosphine derivatives have previously attracted interest as potential antitumour agents but hepatotoxicity was encountered during preclinical development. A series of bidentate pyridyl phosphine gold(I) and silver(I) complexes were synthesised covering a range of lipophilic/hydrophilic properties. Previously we reported that their lipophilicity greatly affects cellular uptake and cytotoxicity in a CH1 cell line. Herein we examined their in vitro uptake and cytotoxicity in a panel of human ovarian tumor cell lines and isolated hepatocytes. Sulforhodamine B assay and lactate dehydrogenase release assay were used to determine tumor cell growth inhibition and hepatocyte viability. Gold content was analyzed by inductively coupled plasma mass spectrometry. The in vitro cytotoxicity of bidentate pyridyl phosphine complexes to isolated hepatocytes and ovarian tumor cell lines correlated with their lipophilicity and rate of gold uptake. The 3- and 4-pyridyl derivatives showed less hepatotoxicity, slower cellular uptake and marked cytotoxicity to 2-deoxy-D-glucose-sensitive tumor cell lines. The cellular uptake of the 2-pyridyl gold(I) phosphine complex was partially inhibited by the membrane potential inhibitor valinomycin, and was higher in mitochondria relative to cytosolic and nuclear fractions. Unlike the phenyl phosphine gold(I) complex, the 2- and 4-pyridyl derivatives did not induce hepatotoxicity in vivo and showed lower gold accumulation in liver relative to tumor. In conclusion, the in vitro cytotoxicity of bidentate pyridyl phosphine gold(I) and silver(I) complexes to isolated hepatocytes and tumor cell lines correlated with their lipophilic/hydrophilic properties and cellular uptake. Their hepatotoxicity and antitumour activity may be due to their direct cytotoxicity, interference with energy metabolism and preferential accumulation in mitochondria. The Auckland Medical Research Foundation, the Wellcome Trust, and the Auckland Division of the Cancer Society of New Zealand supported the work.
The world should establish an early warning system for new viral infectious diseases by space‐weather monitoring
Authors: Jiangwen Qu, N.Chandra Wickramasinghe
Journal: MedComm (2020)

With the emergence of several new epidemics of viral infections - SARS, MERS, EBOLA, ZIKA, Influenza A (H1N1) pandemic,Covid-2019 - over the past 3 decades we suggest that a world-wide programme of stratospheric surveillance and space weather monitoring should be urgently put in place without further delay.
New Rules for the Pandemic Era
Authors: David Cutler
Journal: JAMA (2020)

oronavirus disease 2019 is not the world's first pandemic, and it is unlikely to be the last.In recent years, there have been actual or potential pandemics in 2002 (severe acute respiratory syndrome coronavirus), 2009 (H1N1 influenza), 2012 (Middle East respiratory syndrome coronavirus), and 2014 (Ebola).The new normal seems to be an actual or potential epidemic every 2 to 3 years.Loss of life is one devastating effect of regular pandemics and economic damage is another.Consider what happens to the economy if pandemics occur regularly.Close association of individuals with different perspectives is a key to productivity.Large, dense cities are the most innovative areas, and the most innovative companies are those that bring disparate people together.If cities become ground zero for pandemics, fewer people will probably choose to live in them.And with that will come a decline in national vitality.Preventing recurrent pandemics is a major public health challenge.To meet this challenge, society will need to act domestically and globally.
Long Term Echocardiographic Follow-Up as Predictor of Ventricular Arrhythmias in Super-Responders to Cardiac Resynchronization Therapy
Authors: A.C. van der Heijden, U. Hoke, C.J. Borleffs, I. Thijssen, R. Wolterbeek, E.T. van der Velde, M.J. Schaiij, L. van Erven
Journal: Circulation (2013)
Oxygen carrier in core-shell fibers synthesized by coaxial electrospinning enhances Schwann cell survival and nerve regeneration
Authors: Teng Ma, Yafeng Yang, Xin Quan, Lei Lu, Bing Xia, Jianbo Gao, Fengyu Qi, Shengyou Li, Laihe Zhao, Liangwei Mei, Yi Zheng, Yanbing Shen, Zhuojing Luo, Yan Jin, Jinghui Huang
Journal: Theranostics (2020)

Rationale: Local hypoxia is a challenge for fabrication of cellular grafts and treatment of peripheral nerve injury. In our previous studies, we demonstrated that perfluorotributylamine (PFTBA) could provide short term oxygen supply to Schwann cells (SCs) and counteract the detrimental effects of hypoxia on SCs during the early stages of nerve injury. However, the quick release of oxygen in PFTBA compromised its ability to counteract hypoxia over an extended time, limiting its performance in peripheral nerve injury. Methods: In this study, PFTBA-based oxygen carrier systems were prepared through coaxial electrospinning to prolong the time course of oxygen release. Core-shell structures were fabricated, optimized, and the oxygen kinetics of PFTBA-enriched core-shell fibers evaluated. The effect of core-shells on the survival and function of SCs was examined in both 2D and 3D systems as well as in vivo. The system was used to bridge large sciatic nerve defects in rats. Results: PFTBA core-shell fibers provided high levels of oxygen to SCs in vitro, enhancing their survival, and increasing NGF, BDNF, and VEGF expression in 2D and 3D culture systems under hypoxic condition. In vivo analysis showed that the majority of GFP-expressing SCs in the PFTBA conduit remained viable 14 days post-implantation. We found that axons in PFTBA oxygen carrier scaffold improved axonal regeneration, remyelination, and recovery. Conclusion: A synthetic oxygen carrier in core-shell fibers was fabricated by the coaxial electrospinning technique and was capable of enhancing SC survival and nerve regeneration by prolonged oxygen supply. These findings provide a new strategy for fabricating cellular scaffolds to achieve regeneration in peripheral nerve injury treatment and other aerobic tissue injuries.
Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: a phase 1 pharmacokinetic study
Authors: Catherine A Chappell, Kimberly K Scarsi, Brian J Kirby, Vithika Suri, Anuj Gaggar, Debra L Bogen, Ingrid S Macio, Leslie A Meyn, Katherine E Bunge, Elizabeth E Krans, Sharon L Hillier
Journal: The Lancet Microbe (2020)

Hepatitis C virus (HCV) infection is increasing among pregnant women because of the opioid epidemic, yet there are no interventions to reduce perinatal HCV transmission or to treat HCV during pregnancy. Physiological changes in pregnancy alter the pharmacokinetics of some medications; thus, our aim was to compare the pharmacokinetic parameters of ledipasvir 90 mg plus sofosbuvir 400 mg during pregnancy with non-pregnant women.This was an open-label, phase 1 study of pregnant women with genotype 1 HCV infection and their infants. A reference group of women who had participated in pharmacokinetic studies of ledipasvir-sofosbuvir during phase 2 and 3 trials was used. Participants were enrolled at Magee-Womens Hospital (Pittsburgh, PA, USA) between 23 and 24 weeks' gestation and had a 12-week course of oral ledipasvir-sofosbuvir (daily 90 mg ledipasvir plus 400 mg sofosbuvir). Three 12-h intensive pharmacokinetic visits were done at 25-26, 29-30, and 33-34 weeks' gestation and individual pharmacokinetics were summarised by geometric mean across the three visits. The primary outcome, analysed in all participants without suspected dosing errors, was the ledipasvir-sofosbuvir area under the concentration-time curve of the dosing interval (AUCtau) during pregnancy compared with the reference group by geometric mean ratio. This study is registered with ClinicalTrials.gov, NCT02683005.From Oct 1, 2016, to Sept 30, 2018, 29 pregnant women were screened and nine (31%) were enrolled. Eight (89%) women were included in the primary analysis. Ledipasvir and sofosbuvir exposures were similar in the pregnant women versus the non-pregnant reference group (geometric mean ratio of AUCtau ledipasvir 89·3% [90% CI 68·7-116·1]; sofosbuvir 91·1% [78·0-106·3]).Ledipasvir-sofosbuvir was safe and effective without clinically meaningful differences in drug exposure among pregnant versus non-pregnant women.National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health/Office of Research on Women's Health, and Gilead Sciences.
Narrow-band imaging versus Lugol chromoendoscopy for esophageal squamous cell cancer screening in normal endoscopic practice: randomized controlled trial
Authors: Mélissa Gruner, Angélique Denis, Claude Masliah, Morgane Amil, Elodie Metivier-Cesbron, Dominique Luet, Medhi Kaasis, Emmanuel Coron, Marc Le Rhun, Stéphane Lecleire, Michel Antonietti, Jean-Louis Legoux, Laurent Lefrou, Pascal Renkes, Anne-Laure Tarreirias, Philippe Balian, Philippe Rey, Bénédicte Prost, Christophe Cellier, Gabriel Rahmi, Elia Samaha, Serge Fratte, Béatrice Guerrier, Verena Landel, Sandrine Touzet, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2020)

Abstract Background Narrow-band imaging (NBI) is as sensitive as Lugol chromoendoscopy to detect esophageal squamous cell carcinoma (SCC) but its specificity, which appears higher than that of Lugol chromoendoscopy in expert centers, remains to be established in general practice. This study aimed to prove the superiority of NBI specificity over Lugol chromoendoscopy in the detection of esophageal SCC and high grade dysplasia (HGD) in current general practice (including tertiary care centers, local hospitals, and private clinics). Methods This prospective randomized multicenter trial included consecutive patients with previous or current SCC of the upper aerodigestive tract who were scheduled for gastroscopy. Patients were randomly allocated to either the Lugol or NBI group. In the Lugol group, examination with white light and Lugol chromoendoscopy were successively performed. In the NBI group, NBI examination was performed after white-light endoscopy. We compared the diagnostic characteristics of NBI and Lugol chromoendoscopy in a per-patient analysis. Results 334 patients with history of SCC were included and analyzed (intention-to-treat) from 15 French institutions between March 2011 and December 2015. In per-patient analysis, sensitivity, specificity, positive and negative likelihood values were 100 %, 66.0 %, 21.2 %, and 100 %, respectively, for Lugol chromoendoscopy vs. 100 %, 79.9 %, 37.5 %, and 100 %, respectively, for NBI. Specificity was greater with NBI than with Lugol (P = 0.002). Conclusions As previously demonstrated in expert centers, NBI was more specific than Lugol in current gastroenterology practice for the detection of early SCC, but combined approaches with both NBI and Lugol could improve the detection of squamous neoplasia.
Clinical benefit of baseline imaging in Merkel cell carcinoma: Analysis of 584 patients
Authors: Neha Singh, Nora A Alexander, Kristina Lachance, Christopher W Lewis, Aubriana McEvoy, Gensuke Akaike, David Byrd, Sanaz Behnia, Shailender Bhatia, Kelly G Paulson, Paul Nghiem
Journal: Journal of the American Academy of Dermatology (2020)
Surface Immobilized Nucleic Acid–Transcription Factor Quantum Dots for Biosensing
Authors: Mingfu Chen, Thuy T. Nguyen, Nitinun Varongchayakul, Chloé Grazon, Margaret Chern, R. C. Baer, Sébastien Lecommandoux, Catherine M. Klapperich, James E. Galagan, Allison M. Dennis, Mark W. Grinstaff
Journal: Advanced Healthcare Materials (2020)

Abstract Immobilization of biosensors on surfaces is a key step toward development of devices for real‐world applications. Here the preparation, characterization, and evaluation of a surface‐bound transcription factor–nucleic acid complex for analyte detection as an alternative to conventional systems employing aptamers or antibodies are described. The sensor consists of a gold surface modified with thiolated Cy5 fluorophore‐labeled DNA and an allosteric transcription factor (TetR) linked to a quantum dot (QD). Upon addition of anhydrotetracycline (aTc)—the analyte—the TetR‐QDs release from the surface‐bound DNA, resulting in loss of the Förster resonance energy transfer signal. The sensor responds in a dose‐dependent manner over the relevant range of 0–200 µ m aTc with a limit of detection of 80 n m . The fabrication of the sensor and the subsequent real‐time quantitative measurements establish a framework for the design of future surface‐bound, affinity‐based biosensors using allosteric transcription factors for molecular recognition.
Some glucose-lowering drugs reduce risk for major adverse cardiac events
Authors: Aris Liakos, Apostolos Tsapas, Eleni Bekiari
Journal: Annals of Internal Medicine (2020)

Source Citation Zhu J, Yu X, Zheng Y, et al. Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map. Lancet Diabetes Endocrinol. 2020;8:192-205. 32006518
Cardiovascular and Bleeding Risks Associated With Nonsteroidal Anti-Inflammatory Drugs After Myocardial Infarction
Authors: Dong Oh Kang, Hyonggin An, Geun U Park, Yunjin Yum, Eun Jin Park, Yoonjee Park, Won Young Jang, Woohyeun Kim, Jah Yeon Choi, Seung-Young Roh, Jin Oh Na, Jin Won Kim, Eung Ju Kim, Seung-Woon Rha, Chang Gyu Park, Hong Seog Seo, Cheol Ung Choi
Journal: Journal of the American College of Cardiology (2020)
HP0036 Multidisciplinary care in outpatient clinics: the clinical nurse specialist’s input
Authors: JG Deenen, JT Alberts-Pijnenborg, PL Van Riel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Rationale</h3> In The Netherlands multidisciplinary care for inpatients with rheumatic diseases is quite common. It is generally recognised that this kind of care is necessary to fulfil the treatment goals. Within the University Medical Centre Nijmegen the multidisciplinary meetings are not only scheduled for inpatients, but also for outpatients. This way the continuity of treatment and care will be positively influenced. <h3>Objective</h3> In order to propagate and let more patients benefit from this kind of care, we will describe the role and input of the nurse practitioner in the multidisciplinary team. <h3>Patients and methods</h3> At our outpatient clinic the multidisciplinary meetings are scheduled once a month. The team consists of rheumatologists, social workers, occupational therapists, and the clinical nurse specialists. All team members have the possibility to add their case (s) to the agenda for discussion. Generally these are patients with more complex problems, necessitating optimal co-ordination of treatment and care. The discussion and decision making process take place on the 'base of equality'. In our team, each member's knowledge and experience are respected and applied. This equality of disciplines is required to guarantee optimal quality of the multidisciplinary care. The role of the clinical nurse specialist consists of: representing the patients by clearly explaining their questions and problems input of her expert opinion to the multidisciplinary treatment approach advising the colleagues in the clinic as well as the primary health care making a working schedule and point out priorities, based on the planned treatment approach. <h3>Conclusion</h3> The clinical nurse specialist is more and more an expert with a crucial role in patient care. Within the multidisciplinary team, an open relationship between physicians and health professionals is an important condition for good quality of the decision making process.
RNA Sequencing Illustrates the Genetic Backgrounds of Pediatric Acute Myeloid Leukemia
Authors: Norio Shiba, Kenichi Yoshida, Yusuke Hara, Genki Yamato, Masashi Sanada, Yuichi Shiraishi, Kentaro Ohki, Jun Okubo, Myoung-JA Park, Daisuke Tomizawa, Tomohiko Taki, Manabu Sotomatsu, Keizo Horibe, Takashi Taga, Souichi Adachi, Akio Tawa, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
Journal: Blood (2017)
THU0035 Cytokine production by cd3<sup>+</sup>t cell in synovial fluid from patients affected by psoriatic arthritis and rheumatoid arthritis
Authors: L Riente, F Pratesi, S Frigelli, A Delle Sedie, M Scavuzzo, D Chimenti, P Migliorini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with psoriasis, characterised by synovitis which often leeds to destruction of cartilage and bone. The mechanism of joint damage is unclear, but it's likely that cytokines play critical roles. In PsA cytokines have been previously measured by enzyme-linked immunoassays; however, these molecules are not very stable in inflammatory fluids and are detectable only when produced in large amount. <h3>Objectives</h3> The aim of our study was to analyse the cytokines production in synovial fluids of patients affected by psoriatic arthritis. <h3>Methods</h3> We analysed cytokines production <i>ex vivo</i> by single cell analysis in flow cytometry in synovial fluids of 9 patients affected by PsA. As control group we used synovial fluids from 8 patients affected by Rheumatoid Arthritis (RA). Synovial fluid leukocytes isolated on Ficoll gradients were stimulated with phorbol-myristate-acetate and ionomycin, treated with brefeldin, permeabilized and stained with anti-CD3, anti-IL4 and anti-IFNg. <h3>Results</h3> In 9 patients affected by PsA, IFNg-producing cells were the vast majority (43%, 46%, 75%, 55%, 51%, 42%, 38%, 32%, 20% of CD3<sup>+</sup> cells). A similar predominance was observed in 8 patients with rheumatoid arthritis (64%, 36%, 35%, 75%, 38%, 29%, 46%, 26%). <h3>Conclusion</h3> IFNg is the typical cytokine produced by TH1 T cells, thus the results of our study suggest that TH1 T cell selectively home to synovial tissue in PsA, as already shown in RA. A better understanding of cytokine production in psoriatic arthritis synovium in a larger number of patients may help to clarify the pathogenesis of the disease and lead to the development of more specific and effective therapeutic agents. <h3>Reference</h3> Nuti S, Rosa D, Valiante NM, Saletti G, Caratozzolo M, Dellabona P, Barnaba V, Abrignani S. Dynamics of intra-hepatic lymphocytes in chronic hepatitis C: enrichment for Va24+ Tcells and rapid elimination of effector cells by apoptosis. Eur J Immunol. 1998;28:3448–56
Identification of FGFR2 as a novel melanoma oncogene
Authors: Michael G. Gartside, Amy Curtis, Laura Yudt, Ursula Harper, Ana Bengston, Sandra Pavey, Ralph Tuthill, Boris Bastian, Paul S. Meltzer, Pamela M. Pollock
Journal: Cancer Research (2005)

2588  Melanoma is the eighth most common malignancy in the United States, and its incidence has been increasing over the last two decades. One of the hallmarks of melanocytic transformation is a change from paracrine growth factor stimulation via ectopic expression of growth factors and/or receptors by melanoma cells. FGF signaling has been implicated in melanoma progression for many years through evidence of an autocrine loop involving FGF2 and FGFR1. In normal skin, melanocytes do not express FGF2; it is provided by the keratinocytes. However the majority of melanomas do express FGF2, with expression levels increasing with tumor progression. In vitro skin models have implicated FGF2 in mediating proliferation, survival and migration in the dermis. Although FGF2 has been shown to bind to all four FGFRs, the only FGFR that has been extensively studied regarding its role in melanoma progression is FGFR1. Abrogation of FGFR1 expression either by antisense oligonucleotides or the use of dominant negative expression constructs in both melanocytes and melanomas has been shown to result in inhibition of growth and induction of apoptosis in both in vitro and in vivo model systems. Based on these and other data implicating FGF signaling in melanoma progression, we sequenced all four FGFRs in a panel of 47 melanoma cell lines as part of a candidate gene mutation screen to identify novel RTKs mutated in melanoma. Somewhat surprisingly, we identified mutations in FGFR2, but not FGFR1, in 12% of melanoma cell lines. This mutation analysis has now been expanded, and over 20 novel FGFR2 mutations have been identified in 14/113 (12%) cell lines and 3/26 (12%) metastatic tumors. In addition, approximately 80% of the FGFR2 coding sequence has been assessed in a panel of 83 primary tumors and to date, mutations have been identified in 7/83 (8%) tumors. These mutations occur predominantly in the IgII, IgIII and kinase domains of FGFR2. Mutation data from the cell line panel shows that FGFR2 and PTEN mutations demonstrate mutual exclusivity, suggesting that the PI3K/AKT pathway as an important downstream signaling pathway. Analysis by IHC of FGFR1 and FGFR2 has been performed on two melanoma progression arrays, and shows that expression of FGFR2 clearly increases with disease progression. The novel FGFR2 mutations we have identified are predicted to result in receptor activation via several mechanisms, including ligand-independent receptor dimerization and kinase activation, and data on the functional significance of these mutations will be presented.