tbuckley/cabot-search huggingface dataset:
Beyond Cholinesterase Inhibition: Developmental Neurotoxicity of Organophosphate Ester Flame Retardants and Plasticizers
Authors: Heather B. Patisaul, Mamta Behl, Linda S. Birnbaum, Arlene Blum, Miriam L. Diamond, Seth Rojello Fernández, Helena T. Hogberg, Carol F. Kwiatkowski, Jamie D. Page, Anna Soehl, Heather M. Stapleton
Journal: Environmental Health Perspectives (2021)

Background: To date, the toxicity of organophosphate esters has primarily been studied regarding their use as pesticides and their effects on the neurotransmitter acetylcholinesterase (AChE). Currently, flame retardants and plasticizers are the two largest market segments for organophosphate esters and they are found in a wide variety of products, including electronics, building materials, vehicles, furniture, car seats, plastics, and textiles. As a result, organophosphate esters and their metabolites are routinely found in human urine, blood, placental tissue, and breast milk across the globe. It has been asserted that their neurological effects are minimal given that they do not act on AChE in precisely the same way as organophosphate ester pesticides. Objectives: This commentary describes research on the non-AChE neurodevelopmental toxicity of organophosphate esters used as flame retardants and plasticizers (OPEs). Studies in humans, mammalian, nonmammalian, and in vitro models are presented, and relevant neurodevelopmental pathways, including adverse outcome pathways, are described. By highlighting this scientific evidence, we hope to elevate the level of concern for widespread human exposure to these OPEs and to provide recommendations for how to better protect public health. Discussion: Collectively, the findings presented demonstrate that OPEs can alter neurodevelopmental processes by interfering with noncholinergic pathways at environmentally relevant doses. Application of a pathways framework indicates several specific mechanisms of action, including perturbation of glutamate and gamma-aminobutyric acid and disruption of the endocrine system. The effects may have implications for the development of cognitive and social skills in children. Our conclusion is that concern is warranted for the developmental neurotoxicity of OPE exposure. We thus describe important considerations for reducing harm and to provide recommendations for government and industry decision makers. https://doi.org/10.1289/EHP9285
A Biofilm Microenvironment‐Activated Single‐Atom Iron Nanozyme with NIR‐Controllable Nanocatalytic Activities for Synergetic Bacteria‐Infected Wound Therapy
Authors: Qiqi Xu, Yusheng Hua, Yuetong Zhang, Mingzhu Lv, Huan Wang, Yang Pi, Jiani Xie, Chengyan Wang, Yuan Yong
Journal: Advanced Healthcare Materials (2021)

Abstract Biofilm microenvironment (BME)‐activated antimicrobial agents display great potential for improved biofilm‐related infection therapy because of their superior specificities and sensitivities, effective eliminations, and minimal side effects. Herein, BME‐activated Fe‐doped polydiaminopyridine nanofusiform‐mediated single‐atom nanozyme (FePN SAzyme) is presented for photothermal/chemodynamic synergetic bacteria‐infected wound therapy. The photothermal therapy (PTT) function of SAzyme can be specifically initiated by the high level of H 2 O 2 and further accelerated through mild acid within the inflammatory environment through “two‐step rocket launching‐like” process. Additionally, the enhanced chemodynamic therapy (CDT) for the FePN SAzyme can also be endowed by producing hydroxyl radicals through reacting with H 2 O 2 and consuming glutathione (GSH) of the BME, thereby contributing to more efficient synergistic therapeutic effect. Meanwhile, FePN SAzyme could catalyze biofilm‐overexpressed H 2 O 2 decomposing into O 2 and overcome the hypoxia of biofilm, which significantly enhances the susceptibility of biofilm and increases the synergistic efficacy. Most importantly, the synergistic therapy of bacterial‐induced infection diseases can be switched on by the internal and external stimuli simultaneously, resulting in minimal nonspecific damage to healthy tissue. These remarkable characteristics of FePN SAzyme not only develop an innovative strategy for the BME‐activated combination therapy but also open a new avenue to explore other nanozyme‐involved nanoplatforms for bacterial biofilm infections.
Dissecting Genomic Determinants of Positive Selection with an Evolution-Guided Regression Model
Authors: Yi-Fei Huang
Journal: Molecular Biology and Evolution (2021)

In evolutionary genomics, it is fundamentally important to understand how characteristics of genomic sequences, such as gene expression level, determine the rate of adaptive evolution. While numerous statistical methods, such as the McDonald-Kreitman (MK) test, are available to examine the association between genomic features and the rate of adaptation, we currently lack a statistical approach to disentangle the independent effect of a genomic feature from the effects of other correlated genomic features. To address this problem, I present a novel statistical model, the MK regression, which augments the MK test with a generalized linear model. Analogous to the classical multiple regression model, the MK regression can analyze multiple genomic features simultaneously to infer the independent effect of a genomic feature, holding constant all other genomic features. Using the MK regression, I identify numerous genomic features driving positive selection in chimpanzees. These features include well-known ones, such as local mutation rate, residue exposure level, tissue specificity, and immune genes, as well as new features not previously reported, such as gene expression level and metabolic genes. In particular, I show that highly expressed genes may have a higher adaptation rate than their weakly expressed counterparts, even though a higher expression level may impose stronger negative selection. Also, I show that metabolic genes may have a higher adaptation rate than their nonmetabolic counterparts, possibly due to recent changes in diet in primate evolution. Overall, the MK regression is a powerful approach to elucidate the genomic basis of adaptation.
895P Disproportional enrichment of FoxP3+CD4+ regulatory T-cells shapes a suppressive tumor microenvironment and provokes anti–PD-1 resistance in head and neck squamous cell carcinoma
Authors: C.G. Kim, S. Park, D.H. Kim, M.H. Hong, E.C. Choi, S.H. Kim, Y.M. Park, J. Kim, S.O. Yoon, G. Kim, S. Shin, Y.W. Koh, S-J. Ha, H.R. Kim
Journal: Annals of Oncology (2021)
1646TiP Efficacy of SARS-CoV-2 vaccination in cancer patients during treatment: A prospective observational study (ANTICOV trial)
Authors: R. Passalacqua, M. Ratti, A. Pan, S. Testa, A. Molteni, S. Tonoli, A. Faliva, E. Mainardi, J. Saleri, A. Gobbi, N. Nanni, N. Bacciocchini, G. Donati, R. Marchi, M. Cattaneo, N. Gnocchi, G. Grizzi, M. Brighenti, G. Maglietta, C. Caminiti
Journal: Annals of Oncology (2021)
525P Efficacy, safety, pharmacokinetic (PK) and pharmacodynamic (PD) data from phase I dose escalation of a novel therapeutic peptide, ST101, targeting the oncogenic transcription factor C/EBPβ, in patients (pts) with advanced and metastatic solid tumors
Authors: M.A. Mckean, N.J. Lakhani, H-T. Arkenau, S. Symeonides, T.R.J. Evans, E.A. Lim, E. Fontana, M. Bupathi, A. Mclaren, S.R. Chandana, T-E. Ding, J. Rotolo, G. Capiaux, R. Michel, S. Kaesshaefer, A. Bexon, G.S. Falchook
Journal: Annals of Oncology (2021)
Methodological challenges of performing meta-analyses to compare the risk of hepatocellular carcinoma between chronic hepatitis B treatments
Authors: Won-Mook Choi, Terry Cheuk-Fung Yip, Young-Suk Lim, Grace Lai-Hung Wong, W. Ray Kim
Journal: Journal of Hepatology (2021)

Despite several recent meta-analyses on the topic, the comparative risk of hepatocellular carcinoma in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) remains controversial. The controversy partly results from the arbitrary nature of significance levels leading to contradictory conclusions from very similar datasets. However, the use of observational data, which is prone to both within- and between-study heterogeneity of patient characteristics, also lends additional uncertainty. The asynchronous introduction of ETV and TDF in East Asia, where the majority of these studies have been conducted, further complicates analyses, as does the ensuing difference in follow-up time between ETV and TDF cohorts. Researchers conducting meta-analyses in this area must make many methodological decisions to mitigate bias but are ultimately limited to the methodologies of the included studies. It is therefore important for researchers, as well as the audience of published meta-analyses, to be aware of the quality of observational studies and meta-analyses in terms of patient characteristics, study design and statistical methodologies. In this review, we aim to help clinicians navigate the published meta-analyses on this topic and to provide researchers with recommendations for future work.
1382P Phase Ib/II open-label, randomised evaluation of second-line atezolizumab (atezo) + linagliptin (lina) vs ramucirumab (ram) + paclitaxel (pac) in MORPHEUS-gastric cancer
Authors: J. Lee, J.A. Ajani, H.C. Chung, Y-K. Kang, S. Iqbal, S. Allen, N. Al-Sakaff, J. Decalf, S. Li, J. Pintoffl, P. Sayyed, Y-J. Bang
Journal: Annals of Oncology (2021)
646TiP A randomized phase III, factorial design, of cabazitaxel and pelvic radiotherapy in patients with localized prostate cancer and high-risk features of relapse: The PEACE 2 trial from Unicancer
Authors: P. Blanchard, S. Foulon, X. Artignan, J. Carles, P. Ronchin, M. Gizzi, S. Villa Freixa, R. Valdagni, P. Sargos, L.A. Marques Da Costa, T. Duberge, A. Guillot, I. Latorzeff, E. Gallardo, M.I. Sáez, S. Abadie-Lacourtoisie, M. Bennamoun, A. Hasbini, F. Tantot, K. Fizazi
Journal: Annals of Oncology (2021)
958O Coordinated activation of antitumor responses of g9d2 and CD8 T-cells by targeting BTN3A with ICT01 in patients with solid tumors: EVICTION trial
Authors: A. Marabelle, M. Wermke, C. Jungels, J. de Bono, N. Vey, E. Garralda, P. Lorusso, D. Olive, P.A. Frohna
Journal: Annals of Oncology (2021)
532P Phase Ib study evaluating BI 836880 (VEGF/Ang2 nanobody) in combination with ezabenlimab (BI 754091; anti-PD-1 antibody) in patients with solid tumours
Authors: N. Girard, M. Wermke, E. Ledin, D-W. Kim, F. Ghiringhelli, J. Bennouna, T. Lesimple, E. Felip, D. Berz, J-S. Lee, A. Jeanson, C. Mascaux, M. Voskoboynik, P. Serwatowski, M.C. Burger, H.T. Landsteiner, V. Chen, G. Jayadeva, J. Alt, B. Hackanson
Journal: Annals of Oncology (2021)
1295P Prognostic impact of baseline tumor size (BTS) on survival outcomes in patients (pts) with untreated advanced non-small cell lung cancer (NSCLC), PD-L1 ≥50%, treated with pembrolizumab alone
Authors: M. Bureau, T. Chatelier, T. Perennec, T. Goronflot, C. Greilsamer, A-L. Chene, R. Affi, J. Bennouna, E. Pons-Tostivint
Journal: Annals of Oncology (2021)
Abstract 12983: Advanced Lipid Testing Uncovers Residual Coronary Heart Disease Risk
Authors: Eveline O Stock, Ernst J Schaefer, Creasy T Kate, Lihong He, Margaret R Diffenderfer, Bela F Asztalos, John P Kane
Journal: Circulation (2019)

Hypothesis: Advanced testing parameters improve the C index in 10-year coronary heart disease (CHD) risk prediction, compared with the recommended pooled cohort equation (PCE) based on age, gender,...
間葉系幹細胞由来細胞外小胞に基づく治療は脳卒中における中枢神経系と血管系の結合変性から保護する【JST・京大機械翻訳】
Authors: Rahmani Abolfazl, Saleki Kiarash, Javanmehr Nima, Khodaparast Javad, Saadat Payam, Nouri Hamid Reza
Journal: Ageing Research Reviews (2020)
1226P Efficacy and safety of Anti-EGFR TKIs combined with bevacizumab or ramucirumab in the first-line treatment of non-small cell lung cancer: Meta-analysis of randomized controlled trials
Authors: Y. Ergün, G. Uçar, Y. Açıkgöz, M. Dirikoç, S. Aktürk Esen, M. Bardakçı, D. Uncu
Journal: Annals of Oncology (2021)
Multi-country collaboration in responding to global infectious disease threats: lessons for Europe from the COVID-19 pandemic
Authors: Mark Jit, Aparna Ananthakrishnan, Martin McKee, Olivier J. Wouters, Philippe Beutels, Yot Teerawattananon
Journal: The Lancet Regional Health - Europe (2021)

Since 2005, the world has faced several public health emergencies of international concern arising from infectious disease outbreaks. Of these, the COVID-19 pandemic has had by far the greatest health and economic consequences. During these emergencies, responses taken by one country often have an impact on other countries. The implication is that coordination between countries is likely to achieve better outcomes, individually and collectively, than each country independently pursuing its own self-interest. During the COVID-19 pandemic, gaps in multilateral cooperation on research and information sharing, vaccine development and deployment, and travel policies have hampered the speed and equity of global recovery. In this Health Policy article, we explore how multilateral collaboration between countries is crucial to successful responses to public health emergencies linked to infectious disease outbreaks. Responding to future global infectious disease threats and other health emergencies will require the creation of stronger mechanisms for multilateral collaboration before they arise. A change to the governance of multilateral institutions is a logical next step, with a focus on providing equal ownership and leadership opportunities to all member countries. Europe can be an example and advocate for stronger and better governed multilateral institutions.
524P A phase I, open-label, dose-escalation trial of BI 1701963 in patients (pts) with KRAS mutated solid tumours: A snapshot analysis
Authors: M.L. Johnson, E. Gort, S. Pant, M.P. Lolkema, M. Sebastian, M. Scheffler, J. Hwang, U. Dünzinger, K. Riemann, T. Kitzing, P.A. Jänne
Journal: Annals of Oncology (2021)
ABC of hypertension: Blood pressure measurement
Authors: E. O'Brien
Journal: BMJ (2001)

In recent years, the accuracy of the conventional Riva-Rocci/Korotkoff technique of blood pressure measurement has been questioned and efforts have been made to improve the technique with automated devices. In the same period, recognition of the phenomenon of white coat hypertension, whereby some subjects with apparent elevation of blood pressure have normal, or reduced, blood pressures when measurement is repeated away from the medical environment, has focused attention on methods of measurement that provide profiles of blood pressure behaviour rather than relying on isolated measurements under circumstances that may in themselves influence the level of blood pressure recorded. This article has been adapted from the newly published 4th edition of ABC of Hypertension . The book is available from the BMJ bookshop and at http://www.bmjbooks.com/ These methodologies have included repeated measurements of blood pressure using the traditional technique, self measurement of blood pressure in the home or workplace, and ambulatory blood pressure measurement (ABPM) using innovative automated devices.1 #### Essential messages ### Which monitor to buy? A large variety of ambulatory blood pressure measurement devices are now available on the market, and the number will increase as the technique of ambulatory blood pressure measurement becomes more widespread. A number of factors should influence this choice, among which the most important is to ensure that the device has been validated independently according to either the protocol of the British Hypertension Society (BHS),2 and/or that of the Association for the Advancement of Medical Instrumentation (AAMI).3 #### Which monitor to choose
Nonalcoholic Steatohepatitis — Opportunities and Challenges
Authors: Guadalupe Garcia-Tsao
Journal: New England Journal of Medicine (2021)

Nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease, has superseded hepatitis C as the main cause of cirrhosis and the main reason for liver transplantation.1 Contrary to hepatitis C, a liver-specific disorder caused by a single etiologic agent, NASH is a multifactorial, complex metabolic disorder that forms part of a systemic disease. Therefore, finding therapies (other than weight loss), identifying the target population, and defining response to therapy represent important challenges in NASH. The diagnosis of NASH is established through a liver-biopsy sample that shows steatosis, lobular inflammation, and hepatocellular ballooning. NASH is classified into 5 stages . . .
P05.04 Retrospective Study on the Correlation of Central Tumour and Central Structures and the Effect on Survival for Patients Receiving Lung SABR
Authors: N.A. Mokhtar, C. Lee, M. Hatton, W. Mok, T. Das, P. Fisher, E. Bates, T. Mathew
Journal: Journal of Thoracic Oncology (2021)
P51.01 Tepotinib Plus an EGFR TKI in Patients with EGFR-mutant NSCLC and Resistance to EGFR TKIs Due to MET Amplification (METamp)
Authors: C.K. Liam, A. Rozila Ahmad, T. Hsia, J.Y. Li, X. Le, J. Heymach, J.C. Yang, R. Soo, Y. Zhang, S. Kim, S.W. Shin, A. Johne, N. Karachaliou, R. Bruns, B. Ellers-Lenz, Y. Wu
Journal: Journal of Thoracic Oncology (2021)
PTEN and HER2 regulate self-renewal and invasion of human mammary stem cells.
Authors: Hasan Korkaya, Flora Iovino, Max Wicha
Journal: Cancer Research (2007)

1287  There is increasing evidence in breast cancers as well as other malignancies that tumorigenesis is driven by a cell population that retains stem cell properties. The key property of stem cells is their ability to self-renew. Thus, the elucidation of pathways which regulate stem cell self-renewal is important in understanding mammary carcinogenesis and of developing agents which can target the tumor stem cell pool. Two genes frequently deregulated in human breast cancers are HER2 and PTEN. HER2 is amplified in approximately 20-25% of human breast carcinomas and is associated with a poor clinical outcome. The lipid phosphatase PTEN is deregulated in approximately 40% of human breast carcinomas and is associated with increased Akt activation and poor clinical outcome. Patients with a combined loss of PTEN and HER2 amplification have a worse prognosis than either molecular defect alone. In order to study the effect of deregulation of these pathways we utilized both MCF7 human mammary carcinoma cells as well as normal human mammary epithelium isolated from reduction mammoplasties. Knockdown of PTEN expression in MCF7 cells utilizing a lenti-viral siRNA increased tumor formation in NOD-SCID mice 4 fold compared to GFP transfected cells. HER2 overexpression by lenti-viral infection in these cells increased their tumorigenicity 6 fold whereas the combination of HER2 overexpression and PTEN knockdown increased tumorigenicity 10 fold compared to GFP transfected controls. In order to determine whether these effects on tumorigenicity resulted from changes in stem cell populations, we utilized both mammosphere formation assay as well as the expression of the stem cell marker ALDH1. Deletion of PTEN and overexpression of HER2 increased the proportion of cells expressing the stem cell marker ALDH1 by 2-4 fold whereas the combination of PTEN deletion and HER2 overexpression placed the stem cell population up to 8 fold. Similar effects were observed when these genes genes were deregulated in normal human mammary epithelial cells. In order to determine whether this increase in stem cell populations produced changes in tumor characteristics we examined the ability of transfected MCF7 cells to invade utilizing the matrigell Boyden Chamber assay. PTEN deletion or HER2 overexpression led to an increase of up to 2-4 fold in the number of cells invading the matrix, with cells with combined PTEN knockdown and HER2 overexpression increasing their invasion up to 10 fold compared to MCF7 GFP cells. Furthermore, cells invading the matrix expressed the stem cell marker ALDH1. These experiments suggest that two genes commonly deregulated in sporadic breast cancer and associated with poor clinical outcome. HER2 and PTEN modulate stem cell function leading to increased invasion and tumorigenicity.
P30.01 Extended Resections for Advanced Stages T3/T4 NSCLC After Neoadjuvant Treatment: Conclusions of SAKK Pooled Analysis (16/96, 16/00, 16/01)
Authors: K. Furrer, W. Weder, E. Eboulet, D. Betticher, M. Pless, R. Stupp, T. Krueger, J.Y. Perentes, R. Schmid, D. Lardinois, M. Furrer, M. Fruh, S. Peters, A. Curioni-Fontecedro, R. Stahel, S. Rothschild, S. Hayoz, S. Thierstein, C. Biaggi, I. Opitz
Journal: Journal of Thoracic Oncology (2021)
Proteomic analysis of lung cancer cells reveals a critical role of BCAT1 in cancer cell metastasis
Authors: Lin Mao, Jin Chen, Xue Lu, Canlin Yang, Yi Ding, Mingming Wang, Yunpeng Zhang, Yuying Tian, Xing Li, Yunyun Fu, Yueying Yang, Yunyun Gu, Fei Gao, Junxing Huang, Lujian Liao
Journal: Theranostics (2021)

Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis thus holds promise for identifying new therapeutic strategies that may enhance survival. Methods: We applied quantitative mass spectrometry to compare protein expression profiles between primary and metastatic lung cancer cells whilst investigating metastasis-related molecular features. Results: We discovered that BCAT1, the key enzyme in branched-chain amino acid metabolism, is overexpressed at the protein level in metastatic lung cancer cells, as well as in metastatic tissues from lung cancer patients. Analysis of transcriptomic data available in the TCGA database revealed that increased BCAT1 transcription is associated with poor overall survival of lung cancer patients. In accord with a critical role in metastasis, shRNA-mediated knockdown of BCAT1 expression reduced migration of metastatic cells in vitro and the metastasis of these cells to distal organs in nude mice. Mechanistically, high levels of BCAT1 depleted α-ketoglutarate (α-KG) and promoted expression of SOX2, a transcription factor regulating cancer cell stemness and metastasis. Conclusion: Our findings suggest that BCAT1 plays an important role in promoting lung cancer cell metastasis, and may define a novel pathway to target as an anti-metastatic therapy.
COVID-19 vaccination in patients receiving dialysis
Authors: Benjamin Wilde, Johannes Korth, Michael Jahn, Andreas Kribben
Journal: Nature Reviews Nephrology (2021)

Patients receiving dialysis are at high risk of contracting SARS-CoV-2 and developing severe COVID-19. Established SARS-CoV-2 vaccination schemes might lack efficacy in these patients and a personalized approach is therefore necessary. Importantly, given the enhanced infection risks associated with dialysis, current vaccines do not replace non-pharmacological measures to prevent infection.
P16.06 Comparison of Clinical Outcomes of Patients With Advanced NSCLC In Clinical Trials and in the Real World Received PD-1/PD-L1 Inhibitor
Authors: H. Wang, C. Wei, G.W. Zhang, M. Zhang, X. Yan, X. Zhang, Y.Y. Niu, J. Yang, Z. Ma
Journal: Journal of Thoracic Oncology (2021)