tbuckley/cabot-search huggingface dataset:
Examining the Developmental Trajectory of an <i>in Vitro</i> Model of Mouse Primordial Germ Cells following Exposure to Environmentally Relevant Bisphenol A Levels
Authors: Steen K.T. Ooi, Hui Jiang, Yanyuan Kang, Patrick Allard
Journal: Environmental Health Perspectives (2021)

Animal-based studies indicate that bisphenol A (BPA) exposure is detrimental to reproductive health, but its impact on the earliest stages of germ cell development remains poorly defined.Using a murine in vitro model of early germ cell specification and differentiation, we sought to assess whether exposure to low levels of BPA prior to formation of primordial germ cells (PGCs) alters their differentiation trajectory and unique molecular program.We used an established method of in vitro differentiation of mouse embryonic stem cells (ESCs) into epiblast-like cells (EpiLCs) followed by PGC-like cells (PGCLCs), which together recapitulate defined stages of early germ cell development. Cellular consequences were determined using hemocytometer-based cell counting, fixation, and intracellular staining, followed by flow cytometry/fluorescence-activated cell sorting (FACS) of cells exposed to increasing concentrations (range: 1 nM-10 μM) of BPA. To interrogate and characterize gene expression differences resulting from BPA exposure, we also generated RNA-seq libraries from RNA extracted from FACS-purified PGCLCs and performed transcriptome analysis using bioinformatics-based approaches.Exposure of EpiLCs to BPA resulted in higher numbers of cells that were associated with a higher proportion of cells in S-phase as well as a lower proportion undergoing apoptosis; this difference occurred in a concentration-dependent manner. Exposure also resulted in a greater fraction of EpiLCs showing signs of DNA damage. Remarkably, EpiLC exposure did not negatively affect PGC specification and resulted in a concentration-dependent effect on PGCLC proliferation in XX but not XY cells. PGCLC transcriptome analysis revealed an aberrant program with significant deregulation of X-linked genes and retrotransposon expression. Differential gene expression analysis also revealed the deregulation of genes associated with lipid metabolism as well as deregulated expression of genes associated with later stages of gametogenesis.To the best of our knowledge our findings represent the first characterization of the consequences of early BPA exposure on a model of mammalian PGC development, highlighting altered cell behavior, altered underlying pathways, and altered molecular processes. https://doi.org/10.1289/EHP8196.
1O Harnessing innate immunity in cancer therapies: The example of natural killer cell engagers
Authors: E. Vivier, M. Vetizou, A. Blanchard Alvarez, G. Habif, C. Bonnafous, A. Represa, B. Rossi, S.L. Cornen, A. Morel, I. Perrot, Y. Morel, L. Gauthier, O. Demaria
Journal: Annals of Oncology (2021)
1239P ORCHARD osimertinib + savolitinib interim analysis: A biomarker-directed phase II platform study in patients (pts) with advanced non-small cell lung cancer (NSCLC) whose disease has progressed on first-line (1L) osimertinib
Authors: H.A. Yu, H. Ambrose, C. Baik, B.C. Cho, E. Cocco, S.B. Goldberg, J.W. Goldman, S. Kraljevic, A.J. de Langen, I. Okamoto, Z. Piotrowska, M. Pluta, S. Powar, N. Reguart Aransay, J.W. Riess, X. Le
Journal: Annals of Oncology (2021)
1025TiP SOLTI-1904: Efficacy of spartalizumab across multiple cancer-types in patients with PD1-high mRNA expressing tumors defined by a single and pre-specified cutoff (ACROPOLI)
Authors: A. Prat, L. Paz-Ares, M. Juan, E. Felip, E. Garralda, B. González-Farré, A.M. Arance Fernandez, J. Martin-Liberal, J. Gavilá, A. López González, J.M. Cejalvo, Y. Izarzugaza, K. Amillano, J. Garcia-Corbacho, C. Saura Manich, F. Salvador, T. Pascual, R. Mesía, A. Cervantes, J. Tabernero
Journal: Annals of Oncology (2021)
Enzymatically releasable polyethylene glycol – host defense peptide conjugates with improved activity and biocompatibility
Authors: Matthew Drayton, Morgan A. Alford, Daniel Pletzer, Evan F. Haney, Yoan Machado, Haiming D. Luo, Christopher M. Overall, Jayachandran N. Kizhakkedathu, Robert E.W. Hancock, Suzana K. Straus
Journal: Journal of Controlled Release (2021)
Abstract 13108: Disturbance in Cardiac Th1/th2 Cytokine Balance Plays the Pivotal Role in the Transition from Left Ventricular Hypertrophy to Diastolic Heart Failure In Salt-Sensitive Hypertensive Rats
Authors: Hiroaki Kusaka, Eiichiro Yamamoto, Yoshihiro Hirata, Tetsuharu Katayama, Jun-ichi Matsubara, Seigo Sugiyama, Shokei Kim-Mitsuyama, Hisao Ogawa
Journal: Circulation (2012)

Background: Although cardiac inflammation and fibrosis are closely associated with the progression of cardiac remodeling, little is known about the relative role of inflammation and fibrosis-relate...
833O A phase Ib study result of HMPL-689, a PI3Kδ inhibitor, in Chinese patients with relapsed/refractory lymphoma
Authors: J. Cao, Z. Li, J. Zhou, Q. Zhang, Y. Chen, Z. Zhu, L. Li, R. Feng, F. Li, B. Xu, W. Yang, Z. Zhai, X. Zhang, Q. Wen, H. Xue, X. Duan, S. Fan, Y. Cai, W. Su
Journal: Annals of Oncology (2021)
1059P 18F-FDG-PET/CT response assessment in patients with advanced melanoma treated with combination of low-dose ipilimumab and anti-PD1: A real-world experience
Authors: C.D. De Liz, M. Teixeira, L.B. Mendes Gomes, J.A. Rinck, J.P.S. Lima, M.C. Tavares, D. Garcia, T.B. Oliveira, M.B. Silva
Journal: Annals of Oncology (2021)
Exploring New Approaches for Locally Advanced Gastroesophageal Adenocarcinomas: TNT, Irinotecan, and ctDNA
Authors: Daniel V.T. Catenacci
Journal: Clinical Cancer Research (2021)

Abstract The authors of a recent pilot study incorporated novel concepts including total neoadjuvant therapy with induction triplet FOLFIRINOX then chemoradiotherapy before surgery, along with ctDNA minimal residual disease analyses demonstrating both feasibility of this approach as well as confirming prognostic value of ctDNA analysis before and after surgery. See related article by Wo et al., p. 6343
Cellular regeneration as a potential strategy to treat cardiac conduction disorders
Authors: Satadru K. Lahiri, Mohit M. Hulsurkar, Xander H.T. Wehrens
Journal: Journal of Clinical Investigation (2021)

Loss of atrioventricular conduction system (AVCS) cells due to either inherited or acquired deficits leads to conduction diseases, which can deteriorate into fatal cardiac arrhythmias and sudden death. In this issue of the JCI, Wang et al. constructed a mouse model of atrioventricular block (AVB) by inducing AVCS cell-specific injury using the Cx30.2 enhancer to drive expression of diphtheria toxin fragment A. AVCS cell ablation in adult mice led to irreversible AVB. jkjkIn contrast, AVCS cell injury in neonatal mice was followed by spontaneous recovery in a subset of mice, revealing a limited postnatal time window during which the regeneration of AVCS cells can occur as a result of cellular plasticity. This exciting study paves the way for future research into biological or cellular treatment approaches for cardiac conduction diseases by exploiting the regenerative potential of AVCS cells.
Prehospital management of exertional heat stroke at sports competitions for Paralympic athletes
Authors: Yuri Hosokawa, Paolo Emilio Adami, Ben Thomas Stephenson, Cheri Blauwet, Stephane Bermon, Nick Webborn, Sebastien Racinais, Wayne Derman, Victoria L Goosey-Tolfrey
Journal: British Journal of Sports Medicine (2021)

Objectives To adapt key components of exertional heat stroke (EHS) prehospital management proposed by the Intenational Olympic Committee Adverse Weather Impact Expert Working Group for the Olympic Games Tokyo 2020 so that it is applicable for the Paralympic athletes. Methods An expert working group representing members with research, clinical and lived sports experience from a Para sports perspective reviewed and revised the IOC consensus document of current best practice regarding the prehospital management of EHS. Results Similar to Olympic competitions, Paralympic competitions are also scheduled under high environmental heat stress; thus, policies and procedures for EHS prehospital management should also be established and followed. For Olympic athletes, the basic principles of EHS prehospital care are: early recognition, early diagnosis, rapid, on-site cooling and advanced clinical care. Although these principles also apply for Paralympic athletes, slight differences related to athlete physiology (eg, autonomic dysfunction) and mechanisms for hands-on management (eg, transferring the collapsed athlete or techniques for whole-body cooling) may require adaptation for care of the Paralympic athlete. Conclusions Prehospital management of EHS in the Paralympic setting employs the same procedures as for Olympic athletes with some important alterations.
1075P Regression tree analysis to identify factors associated with relapse-free survival (RFS) in patients with resected stage III BRAF V600E/K–mutant melanoma
Authors: C. Robert, M.A. Davies, R. Dummer, J.J. Grob, A. Hauschild, J.M. Kirkwood, G.V. Long, M. Mandalà, P.D. Nathan, H. Banerjee, B.G. Sahoo, M. Lau, K. Biette, A.D. Boran, D. Schadendorf
Journal: Annals of Oncology (2021)
1004P Initial results from a phase I study of Nous-209, an off-the-shelf viral vectored immunotherapy encoding 209 shared frame shift peptide neoantigens, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability
Authors: M.J. Overman, G. Leoni, A.M. D'Alise, G. Cotugno, F. Langone, S. Capone, M. Del Sorbo, M. Fakih, D.T. Le, A.F. Shields, K.S. Pedersen, M.A. Shah, S. Mukherjee, P. Delaite, T. Faivre, E. Scarselli
Journal: Annals of Oncology (2021)
Firefighters for the Wrong Type of Inflammation in Tumors
Authors: Ignacio Melero, Alvaro Teijeira, Fernando Aranda, Pedro Berraondo
Journal: Cancer Discovery (2021)

Abstract Summary: In this issue of Cancer Discovery, Pelly and colleagues show that inhibition of prostaglandin E2 synthesis or its activity on EP2 and EP4 receptors synergizes with anti–PD-1 immunotherapy and triggers a potent intratumoral IFNγ response in mouse models and in fresh surgical human tumor explants. This therapeutic strategy is in line with other interventions that aim at fostering immunotherapy by means of quenching protumor inflammation. See related article by Pelly et al., p. 2602.
1320TiP The efficacy and safety of stereotactic body radiation therapy (SBRT) plus toripalimab with or without bevacizumab as second-line treatment for advanced non-small cell lung cancer (NSCLC): A prospective, multicenter, open-label, phase II study
Authors: J. Sun, L. Xie, Y. Feng, S. Qin
Journal: Annals of Oncology (2021)
Characteristics of diarrheagenic Escherichia coli among patients with acute diarrhea in China, 2009‒2018
Authors: Shi-Xia Zhou, Li-Ping Wang, Meng-Yang Liu, Hai-Yang Zhang, Qing-Bin Lu, Lu-Sha Shi, Xiang Ren, Yi-Fei Wang, Sheng-Hong Lin, Cui-Hong Zhang, Meng-Jie Geng, Xiao-Ai Zhang, Yu-Liang Zhu, Zhong-Jie Li, Li-Qun Fang, Wei Liu, Wei-Zhong Yang
Journal: Journal of Infection (2021)

Objectives To investigate the epidemiological features of diarrheagenic Escherichia coli (DEC) in patients with acute diarrhea in China. Methods An active sentinel surveillance was performed in all-age patients with acute diarrhea in China, 2009‒2018. DEC was isolated and identified by serological assay and PCR from stool samples. Results DEC was determined in 6.68% (6,119/91,651) of the patients, with higher positive rates among females than among males (6.97% vs. 6.46%) and among 18‒59 years patients (7.88%) than among other age groups. Five pathotypes were identified, the most prevalent was enteroaggregative E. coli (EAEC), followed by enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC). Pediatric patients <5 years had higher positive rate of EAEC (2.07%), followed by EPEC (1.81%), and enterohemorrhagic E. coli (EHEC) (0.31%), while the 18‒59 years patients had higher infection of ETEC (2.36%). ETEC and EPEC were more frequently identified in urban than rural areas, with age and gender adjusted positive rate of 1.68% vs. 1.14% respectively, and 1.77% vs. 1.55%, while EIEC and EHEC were more frequently identified in rural areas. Conclusions These findings highlight the epidemiology features of DEC and underscores the need for conducting DEC surveillance.
1238P AUTOMAN: A phase Ib/IIa study of osimertinib combined with anlotinib in EGFRm, treatment-naive advanced NSCLC patients
Authors: B. Han, B. Yan, A. Gu, T. Chu, W. Zhang, H. Wang, H. Zhong, C. SHI, X. Zhang
Journal: Annals of Oncology (2021)
Abstract MP051: A Novel Genetic Locus for Coronary Heart Disease in Type 2 Diabetes
Authors: Lu Qi, Qibin Qi, Christine Mendonca, Sabrina Prudente, Francesco Andreozzi, Ernest Gervino, Thomas Hauser, Giorgio Sesti, Vincenzo Trischitta, Frank Hu, Alessandro Doria
Journal: Circulation (2012)

Genetic susceptibility to cardiovascular disease in type 2 diabetes is influenced by abnormal metabolic status in the affected diabetic patients; and the implicated genes may differ from those in the non-diabetic populations. We conducted 3-stage genome-wide association analysis to detect the genetic factors for coronary heart disease (CHD) in existing type 2 diabetes. We analyzed 2.4 million SNPs in 1,249 diabetic women from the Nurses’ Health Study (273 CHD cases and 976 controls) and 984 diabetic men from the Health Professionals’ Follow-up Study (319 CHD cases and 665 controls), all of European ancestry. The first-stage replication was performed in Joslin Heart Study (420 CHD cases and 431 controls); and the second-stage replication was performed in Gargano Heart Study (314 CHD cases and 384 controls), and Catanzaro study (114 CHD cases and 215 controls). All the replication samples were of European ancestry and also affected by type 2 diabetes. We observed associations of genome-wide significance (the best p=2.04 * 10 -8 ) between CHD and SNPs on chromosome 1, between genes ZNF648 ( zinc finger protein 648; 1q25 .3) and GLUL (glutamate-ammonia ligase; 1q31). eQTL analysis indicates suggestive association between the associated SNPs and a potential CHD gene PPAP2B on chromosome 1 with marginal significance (p=1 * 10 -5 ). The identified SNP showed a significant association with the plasma levels of vascular cell adhesion molecule 1 ( VCAM1 ) in patients with type 2 diabetes but not in non-diabetic healthy controls. Our findings indicate that specific genetic predisposition may determine cardiovascular risk in patients with type 2 diabetes. The findings may inform the development of novel therapies for reduction of cardiovascular complications in diabetes.
120MO Prognostic value of immune gene-expression signatures (iGES) vs tumor-infiltrating lymphocytes (TILs) in early-stage HER2+ breast cancer: A combined analysis of CALGB 40601 (C40601) and PAMELA trials
Authors: A. Fernandez-Martinez, T. Pascual, B. Singh, P. Nuciforo, K.A. Hoadley, N.U. Rashid, P.A. Spears, N. Chic, I. Krop, D. Hillman, A. Partridge, A. Prat, L.A. Carey, C.M. Perou
Journal: Annals of Oncology (2021)
<scp>VEXAS</scp> Syndrome: A Case Series From a <scp>Single‐Center</scp> Cohort of Italian Patients With Vasculitis
Authors: Francesco Muratore, Chiara Marvisi, Paola Castrignanò, Davide Nicoli, Enrico Farnetti, Orsola Bonanno, Rosina Longo, Piera Zaldini, Elena Galli, Nicholas Balanda, David B. Beck, Peter C. Grayson, Nicolò Pipitone, Luigi Boiardi, Carlo Salvarani
Journal: Arthritis & Rheumatology (2021)

To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) from a single-center cohort of Italian patients with vasculitis, using a clinically oriented phenotype-first approach.We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment-resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin-activating enzyme E1 (UBA-1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue.Seven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA-1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients.To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA-associated vasculitis reported herein warrants further investigation.
Targeting the opioid pathway for the treatment of chronic kidney disease‐associated pruritus: a systematic review and meta‐analysis of randomized controlled trials
Authors: A.M.J. Bailey, H.O.‐Y. Li, K. Burns, W. Cheng, D. Collister, E.P. Westby, K.S. Purdy, M. Walsh, K.K. Tennankore
Journal: British Journal of Dermatology (2021)
MALT1 expression in normal and neoplastic lymphoid tissues: Strong expression characterizes t(14;18)(q32;q21) of MALT lymphoma.
Authors: HT Ye, HX Liu, S Shirali, A Chott, B Streubel, R Siebert, S Gesk, JA Radford, S Banerjee, PG Isaacson, A Dogan, MQ Du
Journal: Blood (2003)
1231P Characterization and management of mobocertinib (TAK-788) induced skin toxicity in patients with EGFR exon 20 insertion+ (ex20ins+) non-small cell lung cancer (NSCLC) who previously received platinum chemotherapy
Authors: J.C-H. Yang, S.S. Ramalingam, T.M. Kim, S-W. Kim, G.J. Riely, T. Mekhail, D. Nguyen, M.R. Garcia Campelo, E. Felip, L. Bazhenova, S. Jin, C. Griffin, V. Bunn, J. Lin, E.N. Churchill, M. Mehta, P.A. Janne, C. Zhou
Journal: Annals of Oncology (2021)
Macrophage nuclear factor erythroid 2‐related factor 2 deficiency promotes innate immune activation by tissue inhibitor of metalloproteinase 3–mediated RhoA/ROCK pathway in the ischemic liver
Authors: Jianhua Rao, Jiannan Qiu, Ming Ni, Hao Wang, Peng Wang, Lei Zhang, Zeng Wang, Mu Liu, Feng Cheng, Xuehao Wang, Ling Lu
Journal: Hepatology (2021)

Abstract Background and Aims Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a master regulator of reactive oxygen species (ROS) and inflammation and has been implicated in both human and murine inflammatory disease models. We aimed to characterize the roles of macrophage‐specific Nrf2 in liver ischemia/reperfusion injury (IRI). Approach and Results First, macrophage Nrf2 expression and liver injury in patients undergoing OLT or ischemia‐related hepatectomy were analyzed. Subsequently, we created a myeloid‐specific Nrf2‐knockout (Nrf2 M‐KO ) strain to study the function and mechanism of macrophage Nrf2 in a murine liver IRI model. In human specimens, macrophage Nrf2 expression was significantly increased in liver tissues after transplantation or hepatectomy. Interestingly, lower Nrf2 expressions correlated with more severe liver injury postoperatively. In a mouse model, we found Nrf2 M‐KO mice showed worse hepatocellular damage than Nrf2‐proficient controls based on serum biochemistry, pathology, ROS, and inflammation. In vitro, Nrf2 deficiency promoted innate immune activation and migration in macrophages on toll‐like receptor (TLR) 4 stimulation. Microarray profiling showed Nrf2 deletion caused markedly lower transcriptional levels of tissue inhibitor of metalloproteinase 3 (Timp3). ChIP‐seq, PCR, and luciferase reporter assay further demonstrated Nrf2 bound to the promoter region of Timp3. Moreover, a disintegrin and metalloproteinase (ADAM) 10/ROCK1 was specifically increased in Nrf2‐deficient macrophages. Increasing Timp3 expression effectively inhibited ADAM10/ROCK1 expression and rescued the Nrf2 M‐KO ‐mediated inflammatory response on TLR4 stimulation in vitro. Importantly, Timp3 overexpression, recombinant Timp3 protein, or ROCK1 knockdown rescued Nrf2 M‐KO ‐related liver IRI by inhibiting macrophage activation. Conclusions In conclusion, macrophage Nrf2 mediates innate proinflammatory responses, attenuates liver IRI by binding to Timp3, and inhibits the RhoA/ROCK pathway, which provides a therapeutic target for clinical organ IRI.
Mucins, gut microbiota, and postbiotics role in colorectal cancer
Authors: Ramesh Pothuraju, Sanjib Chaudhary, Satyanarayana Rachagani, Sukhwinder Kaur, Hemant K. Roy, Michael Bouvet, Surinder K. Batra
Journal: Gut Microbes (2021)

An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host and gut microbiota via different dietary patterns (prebiotics and probiotics) is needed to maintain mucus composition, mucin synthesis, and regulation. Here, we review how the interactions between diet and gut microbiota and bacterial metabolites (postbiotics) regulate mucus layer functionalities and mucin expression in human health and disease.