tbuckley/cabot-search huggingface dataset:
Research progress of in-situ gelling ophthalmic drug delivery system
Authors: Yumei Wu, Yuanyuan Liu, Xinyue Li, Dereje Kebebe, Bing Zhang, Jing Ren, Jun Lu, Jiawei Li, Shouying Du, Zhidong Liu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Blindness and vision impairment are the most devastating global health problems resulting in a substantial economic and social burden. Delivery of drug to particular parts of the anterior or posterior segment has been a major challenge due to various protective barriers and elimination mechanisms associated with the unique anatomical and physiological nature of the ocular system. Drug administration to the eye by conventional delivery systems results in poor ocular bioavailability (<5%). The designing of a novel approach for a safe, simple, and effective ocular drug delivery is a major concern and requires innovative strategies to combat the problem. Over the past decades, several novel approaches involving different strategies have been developed to improve the ocular delivery system. Among these, the ophthalmic in-situ gel has attained a great attention over the past few years. This review discussed and summarized the recent and the promising research progress of in-situ gelling in ocular drug delivery system.
Impact of adyuvant chemotherapy treatment according to tumor primary location in colorectal cancer: Experience at University Hospital Ramon y Cajal (HURyC) Madrid.
Authors: Arantzazu Martínez Barquín García, Olga Martinez Saez, Elena Corral de la Fuente, Juan José Serrano Domingo, Roberto Martín Huertas, Maria Villamayor Delgado, Cristina Saavedra Serrano, Mercedes Rodríguez Garrote, Vanesa Pachón Olmos, Pablo Reguera Puertas, FEDERICO LONGO, Carmen Guillen, Alfredo Carrato, REYES Ferreiro
Journal: Journal of Clinical Oncology (2018)

655 Background: Adyuvant chemotherapy is a unified therapeutic principle in colon cancer (CC). However, many prognostic factors are arising to determine who really benefits from adyuvant chemotherapy in order to avoid overtreatment. Primary tumor location of CC is emerging as an important prognostic factor owing to distinct biological features. However, there is hardly any evidence showing the benefit of treatment according to primary tumor location. Methods: We retrospectively included patients with stage II and III CC that underwent surgical resection between 2009 and 2014 HURyC. We performed a multivariable Cox model analysis to estimate the benefit of chemotherapy according to tumor location in terms of DFS and OS. The model was further adjusted by including the following confounders: ECOG-PS, number of removed nodes ( &lt; 12 or ≥ 12), use of adyuvant chemotherapy and age. A covariate was considered a confounder factor if the difference between the adjusted and unadjusted coefficient of chemotherapy varied &gt; 10%. Stata 13.1 was used to analyze the data. Results: 564 patients were identified (267 left sided and 297 right sided). The median follow-up of the entire cohort was 49 months. Globally, chemotherapy did not improve DFS neither in right sided or left sided CC (HR: 0.81, p: 0.58; HR 1.31, p: 0.4, respectively). As for OS, it was improved when adding chemotherapy in both sides (right sided CC HR 0.51, p: 0.061 and left sided CC HR 0.42, p: 0.009). By stages, chemotherapy did not improve DFS or OS according to tumor localization in stage II. In right sided stage III, there was a trend to improve both DFS and OS (HR: 0.54, p: 0.14; HR: 0.39, p: 0.1, respectively). In left sided stage III, there was a trend to improve DFS (HR: 0.66, p: 0.36) and there was an improvement in OS (HR: 0.23, p &lt; 0.001). Conclusions: The multivariable analysis showed benefit of chemotherapy in both right and left sided CC in terms of OS, exhibiting more benefit those patients with left sided CC.
Nature engineered diatom biosilica as drug delivery systems
Authors: U.T. Uthappa, Varsha Brahmkhatri, G. Sriram, Ho-Young Jung, Jingxian Yu, Nikita Kurkuri, Tejraj M. Aminabhavi, Tariq Altalhi, Gururaj M. Neelgund, Mahaveer D. Kurkuri
Journal: Journal of Controlled Release (2018)
Abstract B44: Lysyl oxidases suppress pancreatic cancer progression and inhibit FAK and ERK signaling
Authors: Mario Shields, Pascal Maguin, Christopher Giuliano, Sarah Dallas, John Erby Wilkinson, Mikala Egeblad
Journal: Cancer Research (2018)

Abstract Pancreatic cancer carries a dismal prognosis, as most patients present with locally advanced and metastatic disease at time of diagnosis. High levels of type I collagen extracellular matrix in pancreatic tumor specimens are associated with poor survival and resistance to therapy. Furthermore, the expression of lysyl oxidases (LOXs), enzymes that mediate cross-linking and linearization of collagen type I, correlate with poor prognosis in breast and pancreatic cancer. However, a clinical trial targeting LOX-like (LOXL) 2 in pancreatic cancer did not show any survival benefits, pointing to a limited understanding of the context in which these enzymes function in cancer progression. To understand how collagen structure influences cancer cell behavior, we used host mice that expressed GFPtopaz fused to collagen type I and performed intravital microscopy after orthotopic injection of fluorescently labeled cancer cells (derived from the KPC mouse models of pancreatic cancer). Strikingly, we observed that invasive cancer cells migrated out of the tumors on linear type I collagen. Surprisingly, inhibition of LOX and LOXL2, using a pharmacologic inhibitor or shRNA-mediated knockdown, had the opposite results of what we expected with increased metastasis, collagen linearization, and focal adhesion kinase (FAK) activity. Indicating a mechanism independently of collagen crosslinking, LOX inhibition promoted invasion and increased FAK and Ras/ERK-MAPK signaling in vitro, when cells were grown on plastic. We demonstrated that the FAK activity was required for the increased metastasis induced by LOX inhibition, using a clinical stage pharmacologic inhibitor. Our data highlight that LOXs in pancreatic cancer play an important role in suppression of the ERK and FAK signaling pathways, and metastasis. Indeed, the earliest report of lysyl oxidase function in cancer was as a tumor suppressor in Ras transformed cells. Citation Format: Mario Shields, Pascal Maguin, Christopher Giuliano, Sarah Dallas, John Erby Wilkinson, Mikala Egeblad. Lysyl oxidases suppress pancreatic cancer progression and inhibit FAK and ERK signaling [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B44.
Comparison and optimization of CRISPR/dCas9/gRNA genome-labeling systems for live cell imaging
Authors: Yu Hong, Guangqing Lu, Jinzhi Duan, Wenjing Liu, Yu Zhang
Journal: Genome biology (2018)

CRISPR/dCas9 binds precisely to defined genomic sequences through targeting of guide RNA (gRNA) sequences. In vivo imaging of genomic loci can be achieved by recruiting fluorescent proteins using either dCas9 or gRNA. We thoroughly validate and compare the effectiveness and specificity of several dCas9/gRNA genome labeling systems. Surprisingly, we discover that in the gRNA-labeling strategies, accumulation of tagged gRNA transcripts leads to non-specific labeling foci. Furthermore, we develop novel bimolecular fluorescence complementation (BIFC) methods that combine the advantages of both dCas9-labeling and gRNA-labeling strategies. The BIFC-dCas9/gRNA methods demonstrate high signal-to-noise ratios and have no non-specific foci.
Redox signal-mediated TRPM2 promotes Ang II-induced adipocyte insulin resistance via Ca2+-dependent CaMKII/JNK cascade
Authors: Min Gao, Yu Du, Jing-Wen Xie, Jing Xue, Yi-Ting Wang, Li Qin, Ming-Ming Ma, Yong-Bo Tang, Xiao-Yan Li
Journal: Metabolism (2018)
Correction to: Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017
Authors: Djillali Annane, Stephen M. Pastores, Bram Rochwerg, Wiebke Arlt, Robert A. Balk, Albertus Beishuizen, Josef Briegel, Joseph Carcillo, Mirjam Christ-Crain, Mark S. Cooper, Paul E. Marik, Gianfranco Umberto Meduri, Keith M. Olsen, Sophia Rodgers, James A. Russell, Greet Van den Berghe
Journal: Intensive Care Medicine (2018)
Abstract IA09: Metabolic recycling in cancer
Authors: Marcia Haigis
Journal: Cancer Research (2018)

Abstract Metabolic reprogramming is a hallmark of cancer that supports the rapid proliferation and survival of tumor cells. While many studies have focused on identifying pathways involved in increased fuel usage, such as glucose and glutamine uptake and metabolism, the fate of metabolic waste products has been little investigated. Ammonia is a ubiquitous by-product of cellular metabolism, long thought to be a toxic waste product. Here we will discuss ammonia recycling to support cellular biomass and proliferation in breast cancer. Citation Format: Marcia Haigis. Metabolic recycling in cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA09.
Temporal and long‐term gut microbiota variation in allergic disease: A prospective study from infancy to school age
Authors: K. Simonyté Sjödin, M.‐L. Hammarström, P. Rydén, A. Sjödin, O. Hernell, L. Engstrand, C. E. West
Journal: Allergy (2018)

Abstract Background Compositional changes in the early‐life gut microbiota have been implicated in IgE‐associated allergic diseases, but there is lack of longitudinal studies. We examined gut microbiota development from infancy to school age in relation to onset of IgE‐associated allergic diseases. At 8 years of age, we also examined the relationship between gut microbiota and T‐cell regulation, estimated as responses to polyclonal T‐cell activation. Methods Stool samples were collected from 93 children at 4, 6, 13 months, and 8 years of age. The gut microbiota was profiled using 16S rRNA gene sequencing. Peripheral blood was drawn from all children, and mononuclear cells were polyclonally activated. Levels of IL ‐10 and FOXP 3 mRNA copies were determined using real‐time quantitative reverse transcriptase‐PCR. Results At 8 years of age, 21 children were diagnosed with IgE‐associated allergic disease and 90% displayed allergic comorbidity. Seventy‐two children were nonallergic and nonsensitized. Statistical tests with multiple testing corrections demonstrated temporal underrepresentation of Ruminococcus and consistent underrepresentation of Bacteroides, Prevotella, and Coprococcus in allergic compared to nonallergic children from infancy to school age. The gut microbiota of the allergic 8‐year‐olds was enriched in Bifidobacterium and depleted of Lactobacillus, Enterococcus, and Lachnospira . In allergic 8‐year‐olds, Faecalibacterium correlated with IL ‐10 mRNA levels ( r s = 0.49 , P adj = 0.02) with the same trend for FOXP 3 ( r s = 0.39 , P adj = 0.08). Conclusions We identified both temporal and long‐term variation in the differential abundance of specific bacterial genera in children developing IgE‐associated allergic disease. Improved dietary interventions aiming at expanding immune‐modulatory taxa could be studied for prevention of allergic disease.
<i>GFPT2</i>-Expressing Cancer-Associated Fibroblasts Mediate Metabolic Reprogramming in Human Lung Adenocarcinoma
Authors: Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B. Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J. Gentles, Maximilian Diehn, Andrew Quon, Robert B. West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K. Plevritis
Journal: Cancer Research (2018)

Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-PET scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma and cell growth in squamous cell carcinoma (SCC). Next, we identified genes correlated to glucose uptake that were predominately overexpressed in a single cell-type comprising the tumor microenvironment. For SCC, most of these genes were expressed by malignant cells, whereas in adenocarcinoma, they were predominately expressed by stromal cells, particularly cancer-associated fibroblasts (CAF). Among these adenocarcinoma genes correlated to glucose uptake, we focused on glutamine-fructose-6-phosphate transaminase 2 (GFPT2), which codes for the glutamine-fructose-6-phosphate aminotransferase 2 (GFAT2), a rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which is responsible for glycosylation. GFPT2 was predictive of glucose uptake independent of GLUT1, the primary glucose transporter, and was prognostically significant at both gene and protein level. We confirmed that normal fibroblasts transformed to CAF-like cells, following TGFβ treatment, upregulated HBP genes, including GFPT2, with less change in genes driving glycolysis, pentose phosphate pathway, and TCA cycle. Our work provides new evidence of histology-specific tumor stromal properties associated with glucose uptake in NSCLC and identifies GFPT2 as a critical regulator of tumor metabolic reprogramming in adenocarcinoma.Significance: These findings implicate the hexosamine biosynthesis pathway as a potential new therapeutic target in lung adenocarcinoma. Cancer Res; 78(13); 3445-57. ©2018 AACR.
Accuracy of Pediatric Trauma Field Triage
Authors: Rogier van der Sluijs, Eveline A. J. van Rein, Joep G. J. Wijnand, Luke P. H. Leenen, Mark van Heijl
Journal: JAMA Surgery (2018)

Field triage of pediatric patients with trauma is critical for transporting the right patient to the right hospital. Mortality and lifelong disabilities are potentially attributable to erroneously transporting a patient in need of specialized care to a lower-level trauma center.To quantify the accuracy of field triage and associated diagnostic protocols used to identify children in need of specialized trauma care.MEDLINE, Embase, PsycINFO, and Cochrane Register of Controlled Trials were searched from database inception to November 6, 2017, for studies describing the accuracy of diagnostic tests to identify children in need of specialized trauma care in a prehospital setting. Identified articles with a study population including patients not transported by emergency medical services were excluded. Quality assessment was performed using a modified version of the Quality Assessment of Diagnostic Accuracy Studies-2.After deduplication, 1430 relevant articles were assessed, a full-text review of 38 articles was conducted, and 5 of those articles were included. All studies were observational, published between 1996 and 2017, and conducted in the United States, and data collection was prospective in 1 study. Three different protocols were studied that analyzed a combined total of 1222 children in need of specialized trauma care. One protocol was specifically developed for a pediatric out-of-hospital cohort. The percentage of pediatric patients requiring specialized trauma care in each study varied between 2.6% (110 of 4197) and 54.7% (58 of 106). The sensitivity of the prehospital triage tools ranged from 49.1% to 87.3%, and the specificity ranged from 41.7% to 84.8%. No prehospital triage protocol alone complied with the international standard of 95% or greater sensitivity. Undertriage and overtriage rates, representative of the quality of the full diagnostic strategy to transport a patient to the right hospital, were not reported for inclusive trauma systems or emergency medical services regions.It is crucial to transport the right patient to the right hospital. Yet the quality of the full diagnostic strategy to determine the optimal receiving hospital is unknown. None of the investigated field triage protocols complied with current sensitivity targets. Improved efforts are needed to develop accurate child-specific tools to prevent undertriage and its potential life-threatening consequences.
Abstract 13147: The Prognostic Value of Coronary CTA in Young versus Older Patients Depends on the Outcome
Authors: Marcio Bittencourt, Edward Hulten, Brian Gohshhajra, Michael Cheezum, Udo Hoffmann, Suhny Abbara, Marcelo Di Carli, Paulo A Lotufo, Ron Blankstein
Journal: Circulation (2015)

Introduction: Considerable debate exists on the optimal outcome in cardiovascular (CV) prognostic studies, particularly across different age groups. Objective: We sought to compare the use of all-cause death and CV events (CV death or MI) among patients undergoing coronary computed tomography angiography (CCTA) across different age groups. Methods: We included all consecutive patients with no known coronary artery disease (CAD) referred for CCTA. Severity of CAD was categorized as non-obstructive (normal or &lt;50% stenosis) in 1525 (77%) patients or obstructive (≥50% stenosis) in 717 (23% ) of the patients. Age was categorized as young (&lt; 60 years-old) in 2008 (62%) patients or old (≥60 years old) in 1234 (38%). Blinded event adjudication was performed for all-cause death, CV death or myocardial infarction (MI). Results: Among 3242 patients (58% males, 56±13 years), 92 (2.8%) CV events and 144 (4.4%) all-cause deaths occurred over a median follow up of 3.6 years (IQ: 2.1 - 5.0). While the presence of obstructive CAD was equally associated with CV death or MI in younger and older individuals, the association between obstructive CAD and all-cause death was only significant for younger individuals both in the crude analysis and after adjustment for the pretest probability of disease (figure). Conclusions: While the association of CAD with CV events is equal for younger and older individuals, the association of CAD with all-cause death was attenuated by age in our study.These suggests that the use of all-cause death among older patients referred for coronary CTA may be less representative of cardiovascular events and it may attenuate potentially significant differences in patient outcomes.
Abstract 17671: The Critical Role of Sterol Regulatory Element-binding Protein-1c in Hypertriglyceridemia Caused by Apolipoprotein A5 Deficiency
Authors: Hiroaki Okazaki, Mikio Takanashi, Takeshi Kimura, Satoru Takase, Ako Matsuhashi, Hiroki Yoshida, Yoshino Taira, Pengfei Xu, Chengcheng Li, Sachiko Okazaki, Yoko Iizuka, Takashi Kadowaki, Guosheng Liang
Journal: Circulation (2016)

Introduction: The pivotal role of apolipoprotein A5 (apoA5) in hypertriglyceridemia (HTG) is evident from the fact that APOA5 deficiency predisposes to massive HTG (ca. 1,000 - 8,000 mg/dl) and tha...
Treatment of paediatric narcolepsy with sodium oxybate: a double-blind, placebo-controlled, randomised-withdrawal multicentre study and open-label investigation
Authors: Giuseppe Plazzi, Chad Ruoff, Michel Lecendreux, Yves Dauvilliers, Carol L Rosen, Jed Black, Rupa Parvataneni, Diane Guinta, Youyu Grace Wang, Emmanuel Mignot
Journal: The Lancet Child & Adolescent Health (2018)
Endoscopic mucosa-sparing lateral dissection for treatment of gastric submucosal tumors: a prospective cohort study
Authors: Yue Li, Qiang Zhang, Chaojun Zhu, Yuchen Luo, Zelong Han, Haitao Qing, Jianqun Cai, Ling Li, Ying Huang, Side Liu
Journal: Endoscopy (2018)

In our previous work, we developed a modified method for the removal of gastric submucosal tumors (SMTs), called endoscopic mucosa-sparing lateral dissection (EMSLD). This prospective study aimed to evaluate the efficacy and postoperative outcomes of EMSLD.We prospectively enrolled 25 consecutive patients with gastric SMTs, who received EMSLD treatment. Clinicopathological characteristics and operation-related outcomes were analyzed.The mean age of patients was 49.3 ± 9.7 years, and the mean tumor size was 14.6 ± 6.1 mm. En bloc resection was achieved in all cases. The mean procedure time was 47.3 ± 25.9 minutes, and the estimated blood loss was 4.8 ± 3.5 mL. Endoscopic full-thickness resection was performed in six patients (24 %) because the tumors originated from the deep muscularis propria layer. All perforations and resection defects were successfully closed by the retained mucosa and endoclips. No serious complications related to EMSLD were encountered during or after the procedure.EMSLD was reliable and effective for the removal of gastric SMTs. However, large-scale randomized controlled trials are needed.
<i>Notes from the Field:</i> Vaccine Administration Errors Involving Recombinant Zoster Vaccine — United States, 2017–2018
Authors: Tom T. Shimabukuro, Elaine R. Miller, Raymond A. Strikas, Beth F. Hibbs, Kathleen Dooling, Ravi Goud, Maria V. Cano
Journal: MMWR Morbidity and Mortality Weekly Report (2018)
Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in <i>ALK</i>-Rearranged NSCLC
Authors: Ka-Won Noh, Insuk Sohn, Ji-Young Song, Hyun-Tae Shin, Yu-Jin Kim, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Se-Hoon Lee, Mi-Sook Lee, Yoon-La Choi
Journal: Clinical Cancer Research (2018)

Purpose: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small-molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication.Experimental Design: We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization and then conducted multiplex gene expression analysis. We also performed a clinicopathologic analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed.Results: Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P < 0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity in vitro and in vivo (both P < 0.05).Conclusions: We discovered a positive correlation between ALK and integrin β3 expression levels in ALK-rearranged NSCLC. Our findings suggest that high integrin β3 expression in ALK-rearranged NSCLC is associated with tumor progression and a worse prognosis. This finding demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with ALK-rearranged NSCLC. Clin Cancer Res; 24(17); 4162-74. ©2018 AACR.