tbuckley/cabot-search huggingface dataset:
Transmission modelling of environmentally persistent zoonotic diseases: a systematic review
Authors: Eleanor M Rees, Amanda Minter, W John Edmunds, Colleen L Lau, Adam J Kucharski, Rachel Lowe
Journal: The Lancet Planetary Health (2021)

Transmission of many infectious diseases depends on interactions between humans, animals, and the environment. Incorporating these complex processes in transmission dynamic models can help inform policy and disease control interventions. We identified 20 diseases involving environmentally persistent pathogens (ie, pathogens that survive for more than 48 h in the environment and can cause subsequent human infections), of which indirect transmission can occur from animals to humans via the environment. Using a systematic approach, we critically appraised dynamic transmission models for environmentally persistent zoonotic diseases to quantify traits of models across diseases. 210 transmission modelling studies were identified and most studies considered diseases of domestic animals or high-income settings, or both. We found that less than half of studies validated their models to real-world data, and environmental data on pathogen persistence was rarely incorporated. Model structures varied, with few studies considering the animal–human–environment interface of transmission in the context of a One Health framework. This Review highlights the need for more data-driven modelling of these diseases and a holistic One Health approach to model these pathogens to inform disease prevention and control strategies.
Abstract 3127: A transcriptional lineage tracing approach to unravel crucial gene expression patterns in breast cancer progression
Authors: Niccolò Roda, Roman Hillje, Stefano Cheloni, Valentina Gambino, Giada Blandano, Paolo Falvo, Francesco Bertolini, Pier Giuseppe Pelicci
Journal: Cancer Research (2021)

Abstract Breast cancer represents a major clinical hurdle, with intra-tumor heterogeneity and metastatic outcome accounting for poor prognosis. Traditionally, its poly-clonal structure was investigated through the genetic barcoding of cells followed by the tracing of the offspring. However, this analysis does not allow a solid investigation of the transcriptional profile associated to clones throughout tumor progression. In this work, we exploited a recently published library of expressed barcodes to perform both clonal and transcriptional tracing in breast cancer by single-cell RNA sequencing. To this aim, human breast cancer cell line MDA-MB-231 was transduced with the above mentioned library and orthotopically transplanted in immune-deficient mice. To analyze our data we generated a pipeline aimed at identifying the barcodes at single-cell level and subsequently sequenced more than 20000 cells in six independent primary tumors. Our clonal distribution analysis strongly suggested that clones within the same tumor possess different growth potential. Furthermore, we found that breast tumors show a transcriptional heterogeneity characterized by two major transcriptional patterns: highly proliferating cells on one side, and stressed and dormant cells on the other. Notably, breast cancer clones were shown to belong to one of these two patterns, therefore suggesting that primary tumors are composed of both proliferative and non-proliferative clones. Interestingly, although the non-proliferative clones outnumbered the proliferative ones, the two different transcriptional patterns do not differ in terms of absolute number of cells. Analyses of breast cancer metastases to lungs and liver revealed that the clones that spread metastases belong to both the transcriptional patterns identified in the primary tumor. Interestingly, the metastatic clones were found to be rare in the primary tumors and shared between the two colonized organs. In addition, metastases recapitulated the same transcriptional heterogeneity of primary tumors, despite being composed of a much lower number of clones. Altogether, these findings represent an intriguing launching pad for the identification of the transcriptional markers whose inhibition may counter the metastatic outcome. Citation Format: Niccolò Roda, Roman Hillje, Stefano Cheloni, Valentina Gambino, Giada Blandano, Paolo Falvo, Francesco Bertolini, Pier Giuseppe Pelicci. A transcriptional lineage tracing approach to unravel crucial gene expression patterns in breast cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3127.
Additively manufactured biodegradable porous magnesium implants for elimination of implant-related infections: An in vitro and in vivo study
Authors: Kai Xie, Nanqing Wang, Yu Guo, Shuang Zhao, Jia Tan, Lei Wang, Guoyuan Li, Junxiang Wu, Yangzi Yang, Wenyu Xu, Juan Chen, Wenbo Jiang, Penghuai Fu, Yongqiang Hao
Journal: Bioactive Materials (2021)

Magnesium (Mg) alloys that have both antibacterial and osteogenic properties are suitable candidates for orthopedic implants. However, the fabrication of ideal Mg implants suitable for bone repair remains challenging because it requires implants with interconnected pore structures and personalized geometric shapes. In this study, we fabricated a porous 3D-printed Mg-Nd-Zn-Zr (denoted as JDBM) implant with suitable mechanical properties using selective laser melting technology. The 3D-printed JDBM implant exhibited cytocompatibility in MC3T3-E1 and RAW267.4 cells and excellent osteoinductivity in vitro. Furthermore, the implant demonstrated excellent antibacterial ratios of 90.0% and 92.1% for methicillin-resistant S. aureus (MRSA) and Escherichia coli, respectively. The 3D-printed JDBM implant prevented MRSA-induced implant-related infection in a rabbit model and showed good in vivo biocompatibility based on the results of histological evaluation, blood tests, and Mg2+ deposition detection. In addition, enhanced inflammatory response and TNF-α secretion were observed at the bone-implant interface of the 3D-printed JDBM implants during the early implantation stage. The high Mg2+ environment produced by the degradation of 3D-printed JDBM implants could promote M1 phenotype of macrophages (Tnf, iNOS, Ccl3, Ccl4, Ccl5, Cxcl10, and Cxcl2), and enhance the phagocytic ability of macrophages. The enhanced immunoregulatory effect generated by relatively fast Mg2+ release and implant degradation during the early implantation stage is a potential antibacterial mechanism of Mg-based implant. Our findings indicate that 3D-printed porous JDBM implants, having both antibacterial property and osteoinductivity, hold potential for future orthopedic applications.
Evolving Respiratory Care of the Preterm Infant
Authors: Sara B. DeMauro, Erik A. Jensen
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 14659: Novel Metabolic Regulations by Adrenomedullin-RAMP2 System
Authors: Akiko Kamiyoshi, Takayuki Sakurai, Yuka Shindo, Teruhide Koyama, Takahiro Yoshizawa, Ryuichi Uetake, Lei Yang, Akihiro Yamauchi, Megumu Tanaka, Hisaka Kawate, Tsuyoshi Nakanishi, Takayuki Shindo
Journal: Circulation (2011)

Various humoral factors are involved in the physiological and pathological conditions in both vascular and metabolic system. Adrenomedullin (AM), originally identified as a vasodilatory peptide, is...
Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma
Authors: Nicole M. Anderson, Xiaodan Qin, Jennifer M. Finan, Andrew Lam, Jacob Athoe, Rindert Missiaen, Nicolas Skuli, Annie Kennedy, Amandeep S. Saini, Ting Tao, Shizhen Zhu, Itzhak Nissim, A. Thomas Look, Guoliang Qing, M. Celeste Simon, Hui Feng
Journal: Cancer Research (2021)

Abstract High-risk neuroblastoma remains therapeutically challenging to treat, and the mechanisms promoting disease aggression are poorly understood. Here, we show that elevated expression of dihydrolipoamide S-succinyltransferase (DLST) predicts poor treatment outcome and aggressive disease in patients with neuroblastoma. DLST is an E2 component of the α-ketoglutarate (αKG) dehydrogenase complex, which governs the entry of glutamine into the tricarboxylic acid cycle (TCA) for oxidative decarboxylation. During this irreversible step, αKG is converted into succinyl-CoA, producing NADH for oxidative phosphorylation (OXPHOS). Utilizing a zebrafish model of MYCN-driven neuroblastoma, we demonstrate that even modest increases in DLST expression promote tumor aggression, while monoallelic dlst loss impedes disease initiation and progression. DLST depletion in human MYCN-amplified neuroblastoma cells minimally affected glutamine anaplerosis and did not alter TCA cycle metabolites other than αKG. However, DLST loss significantly suppressed NADH production and impaired OXPHOS, leading to growth arrest and apoptosis of neuroblastoma cells. In addition, multiple inhibitors targeting the electron transport chain, including the potent IACS-010759 that is currently in clinical testing for other cancers, efficiently reduced neuroblastoma proliferation in vitro. IACS-010759 also suppressed tumor growth in zebrafish and mouse xenograft models of high-risk neuroblastoma. Together, these results demonstrate that DLST promotes neuroblastoma aggression and unveils OXPHOS as an essential contributor to high-risk neuroblastoma. Significance: These findings demonstrate a novel role for DLST in neuroblastoma aggression and identify the OXPHOS inhibitor IACS-010759 as a potential therapeutic strategy for this deadly disease.
Тактика ведения пациенток с синдромом доброкачественных узловых образований молочной железы на фоне беременности (обзор литературы с собственными клиническими наблюдениями)
Authors: N. V. Klimova, L. D. Belotserkovtseva, А. А. Kuznetsov
Journal: Radiology - Practice (2021)

The paper presents data on the nodular formations during pregnancy and diagnosis principles of the mammary glands nodular formations during pregnancy. The data of 53 women survey with mammary glands benign tumors that appeared at different pregnancy stages after the assisted reproductive technology protocols use are presented. The tactics of these patients management are proposed. Unresolved issues that require further discussion are identified.
Abstract 1154: Site-specific gene editing with ABBIE for T-cell therapy
Authors: Jihyun Park, Xiaohong Wang, Leonardo Mirandola, Maurizio Chiriva-Internati
Journal: Cancer Research (2021)

Abstract Therapeutic T-cell engineering using viral vectors has been extensively explored as the most promising therapeutic purpose. However, virus-mediated gene delivery carries many challenges and limitations, such as random insertion of transgene into chromosome, posing risk of oncogenic transformation of the host cells, and complexity in the manufacturing process.We are developing a gene-editing tool, ABBIE (A Binding-Based Integrase Enzyme) which combines the specificity of Cas9 with the non-destructive DNA integration conferred by HIV integrase. Unlike endonucleases, HIV integrase can efficiently insert LTR-flanked DNA without causing dsDNA breaks. In our system, by use of fusing protein of enzymatically dead Cas9 (Cas9DN) to integrase of HIV-1 or its mutants, we were able to perform the gene knock-out (KO) and knock-in (KI) in one step at the target genome loci. For proof of concept, we generated the ABBIE proteins and donor DNA containing fluorescent gene with LTR sequence and tested the ABBIE mediated knock-in with conversion of fluorescent proteins. The integration of fluorescent donor DNA into genome was observed in the 293 T-cells transfected with both WT and Mut ABBIE proteins. Higher integration rate was observed in the cells expressing Mut ABBIE protein. Further, we applied this strategy to deliver the donor fluorescent DNA or chimeric antigen receptors (CARs) via electroporation into the HPRT1 locus for specific insertion using primary human T cells. We observed an average of ~30% and ~16% knock-in efficiency as measured by flow cytometry of GFP+ and CD34+ expression, respectively. The site-specific transgene integration was tested by treating the cells with 6- thioguanine (6-TG). We will further optimize the electroporation condition to maximize editing efficiency. This novel therapeutic toolkit will provide a modular platform for inserting therapeutic genes safely and efficiently into the target genome, further accelerate the offshore immunotherapy development. Citation Format: Jihyun Park, Xiaohong Wang, Leonardo Mirandola, Maurizio Chiriva-Internati. Site-specific gene editing with ABBIE for T-cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1154.
Abstract 2050: Comprehensive genomic instability characteristics analysis in Chinese patients with osteosarcoma
Authors: Yonggang Wang, Hongtao Li, Jing Xia, Shiqing Chen, Yuezong Bai
Journal: Cancer Research (2021)

Abstract Background: Previous study indicated that &amp;gt;80% of osteosarcomas (OSs) have genomic instability characteristics similar to BRCA1/2-deficient cancers. Such BRCA-like traits could manifest a deficiency in the DNA damage repair (DDR) pathway. Patients with alterations in DDR pathway was reported sensitive to platinum-based chemotherapy and PARP inhibitors. In order to seek more precision therapeutic opportunities, we explored the molecular profile of Chinese OS patients to identify whether the analogous phenomena exists as reported. Material and Methods: 44 archival Chinese OS patients from 3D Medicines and a public dataset including 35 OS patients (download from cBioPortal), were collected and analyzed next-generation sequencing (NGS) results on tumor tissues for gene mutations, copy number alterations (CNAs) and fusions in 33 cancer-associated DDR genes. Simultaneously, 44 Chinese OS patients' tumor analysis generated homologous recombination deficiency (HRD) scores (defined as the unweighted sum of LOH, TAI and LST scores) through the 733 gene panel sequencing. Results: Among 44 Chinese OS patients, 18 (40.9%) of OS had DDR pathway gene somatic alterations, and TP53 (31.8%) were the most frequently mapped gene. Other DDR somatic alterations were identified in BRCA2 (6.8%), BARD1 (4.5%), BRCA1 (2.3%), PMS2 (2.3%), FANCA (2.3%) and CHEK1 (2.3%). It was worth mention that all gene alterations were copy number reduction except TP53. Collectively, the frequencies of HRR and mismatch repair (MMR) alterations were 15.9% and 2.3%, respectively. HRD score were available in 18 patients, the median was 40.5 (range, 0-81). As to public dataset, 6 (17.1%) patients harbored somatic alterations in DDR genes. The variations were BRCA2 (5.7%), ATR (2.9%), BARD1 (2.9%), FANCC (2.9%), MLH1 (2.9%), MSH6 (2.9%) and PMS2 (2.9%). The HRR mutations frequency was 11% and MMR was 8.6%. Conclusions: This is the first large-scale comprehensive genomic instability characteristics analysis for Chinese patients with OS. Chinese patients and public dataset patients covers many common features. The DDR gene alteration frequency and HRD score are higher in OS patients, the association of variations in DDR genes and HRD score could be considered substitutable in predicting platinum-based therapy and PARP inhibitor response in clinical practice. Citation Format: Yonggang Wang, Hongtao Li, Jing Xia, Shiqing Chen, Yuezong Bai. Comprehensive genomic instability characteristics analysis in Chinese patients with osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2050.
Association of sex with oncologic outcomes in pTa bladder cancer
Authors: I. Lysenko, D. D’andrea, M. Moschini, F. Soria, A. Heidenreich, P.I. Karakiewicz, F. Quhal, M. Abufaraj, N. Fossati, A. Briganti, F. Janisch, M. Rink, S.F. Shariat
Journal: European Urology (2021)
Optimal Interval of Serial Coronary Computed Tomography Angiography to Detect Coronary Artery Plaque Progression
Authors: Ito Hajime, Motoyama Sadako, Sarai Masayoshi, Kawai Hideki, Harigaya Hiroto, Kan Shino, Naruse Hiroyuki, Takahashi Hiroshi, Ishii Junichi, Ozaki Yukio
Journal: Circulation (2013)
Abstract LB215: Transglutaminase 2 maintains hepatocyte growth factor signaling to enhance the epidermal cancer stem cell phenotype
Authors: Xi Chen, Gautam Adhikary, Suruchi Shrestha, Wen Xu, Richard Eckert
Journal: Cancer Research (2021)

Abstract Epidermal squamous cell carcinoma (SCC) is one of the most common cancers. Ultraviolet radiation exposure leads to DNA damage in keratinocyte stem cells leading to transformation. Epidermal cancer stem cells (ECS cells) display aggressive spheroid formation, invasion, and migration, and form rapidly growing and highly vascularized tumors. The transglutaminase 2 (TG2) cancer stem cell maintenance proteins is present at high levels in ECS cells and is required for maintenance of the ECS cell phenotype. Identifying how TG2 maintains the ECS cell phenotype is an important goal. RNA transcriptomic analysis, comparing gene expression in wild-type and TG2 knockout cells, reveals that hepatocyte growth factor (HGF) signaling is markedly reduced in TG2 knockout cells, a finding that was confirmed by showing that TG2 knockdown/knockout reduces HGF and MET mRNA and protein. HGF/MET signaling appears to play an important role in maintaining the cancer phenotype, as inhibition of HGF/MET reduces ECS cell spheroid formation, invasion and migration. Stem cell and EMT marker expression and MEK1/2 and ERK1/2 activity are also reduced. These changes phenocopy the response to TG2 knockdown. Treatment with MEK1/2 and ERK1/2 inhibitors suppresses the ECS cell phenotype indicating that MAPK signaling is a major HGF/MET target, and MET knockout reduces ECS cell tumor formation which is associated with reduced MEK1/2 and ERK1/2 activity. These findings suggest that TG2 maintains HGF/MET signaling which stimulates MEK1.2 and ERK1/2 activity to enhance the aggressive ECS cell cancer phenotype and drive tumor formation. Citation Format: Xi Chen, Gautam Adhikary, Suruchi Shrestha, Wen Xu, Richard Eckert. Transglutaminase 2 maintains hepatocyte growth factor signaling to enhance the epidermal cancer stem cell phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB215.
Language training for oral and written naming impairment in primary progressive aphasia: a review
Authors: Ilaria Pagnoni, Elena Gobbi, Enrico Premi, Barbara Borroni, Giuliano Binetti, Maria Cotelli, Rosa Manenti
Journal: Translational Neurodegeneration (2021)

Abstract Background Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by a gradual, insidious and progressive loss of language abilities, with naming difficulties being an early and persistent impairment common to all three variants. In the absence of effective pharmacological treatments and given the progressive nature of the disorder, in the past few decades, many studies have investigated the effectiveness of language training to minimize the functional impact of word-finding difficulties in daily life. Main body We review language treatments most commonly used in clinical practice among patients with different variants of PPA, with a focus on the enhancement of spoken and written naming abilities. Generalization of gains to the ability to name untrained stimuli or to other language abilities and the maintenance of these results over time are also discussed. Forty-eight studies were included in this literature review, identifying four main types of language treatment: a) lexical retrieval treatment, b) phonological and/or orthographic treatment, c) semantic treatment, and d) a multimodality approach treatment. Overall, language training is able to induce immediate improvements of naming abilities in all variants of PPA. Moreover, despite the large variability among results, generalization and long-term effects can be recorded after the training. The reviewed studies also suggest that one factor that determines the choice of a particular approach is the compromised components of the lexical/semantic processing system. Conclusion The majority of studies have demonstrated improvements of naming abilities following language treatments. Given the progressive nature of PPA, it is essential to apply language treatment in the early stages of the disease.
Abstract 454: The landscape of PD-L1 expression in lung cancer harboring driver oncogene mutations except EGFR mutations
Authors: Ningbo Liu, Fuyu Gong
Journal: Cancer Research (2021)

Abstract Background: Results from previous studies indicated that lung cancer patients harboring EGFR sensitizing mutations may receive unfavorable outcomes from immunotherapy. The present study aims to investigate the landscape of PD-L1 expression in lung cancer harboring driver oncogene mutations except EGFR mutations. Methods: Tissue samples were subjected to NGS in a College of American Pathologists-certified and Clinical Laboratory Improvement Amendments-accredited lab for driver oncogene mutations and PD-L1 expression. Results: A total of 22143 lung cancer patients were selected, there are 2120 patients have the driver oncogene mutation, including 1115 (5.04%) ALK positive cases,498 (2.25%) MET positive cases,239(1.08%) RET positive cases,182(0.82%) BRAF positive cases, 72 (0.33%) ROS1 positive cases and 14 (0.03%) NTRK positive cases. Among all the driver oncogene mutation patients, 481 patients have been collected tumor tissue, and the PD-L1 expression have been tested by FDA-approved 22C3 antibodies. Among all the driver oncogene mutation cases assessed PD-L1 expression (n=481), low PD-L1 expression levels (&amp;lt;1%) were 33.3% (n=160), PD-L1 expression level of 1%-49% accounted for 38.3% (n=184), PD-L1 expression level of 50%-79% accounted for 19.5% (n=94), PD-L1 expression level of 80%-89% accounted for 4.2% (n=20), and PD-L1 expression level higher than 90% accounted for 4.8% (n=23). Conclusion: Our study supported that NSCLC patients harboring sensitizing oncogenic mutations may potentially benefit from anti-PD-1/L1 especially for those with positive indicators of immunotherapy with strong positive PD-L1 expression. Citation Format: Ningbo Liu, Fuyu Gong. The landscape of PD-L1 expression in lung cancer harboring driver oncogene mutations except EGFR mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 454.