tbuckley/cabot-search huggingface dataset:
Modeling Nanocarrier Transport across a 3D In Vitro Human Blood‐Brain–Barrier Microvasculature
Authors: Sharon Wei Ling Lee, Marco Campisi, Tatsuya Osaki, Luca Possenti, Clara Mattu, Giulia Adriani, Roger Dale Kamm, Valeria Chiono
Journal: Advanced Healthcare Materials (2020)

Polymer nanoparticles (NPs), due to their small size and surface functionalization potential have demonstrated effective drug transport across the blood-brain-barrier (BBB). Currently, the lack of in vitro BBB models that closely recapitulate complex human brain microenvironments contributes to high failure rates of neuropharmaceutical clinical trials. In this work, a previously established microfluidic 3D in vitro human BBB model, formed by the self-assembly of human-induced pluripotent stem cell-derived endothelial cells, primary brain pericytes, and astrocytes in triculture within a 3D fibrin hydrogel is exploited to quantify polymer NP permeability, as a function of size and surface chemistry. Microvasculature are perfused with commercially available 100-400 nm fluorescent polystyrene (PS) NPs, and newly synthesized 100 nm rhodamine-labeled polyurethane (PU) NPs. Confocal images are taken at different timepoints and computationally analyzed to quantify fluorescence intensity inside/outside the microvasculature, to determine NP spatial distribution and permeability in 3D. Results show similar permeability of PS and PU NPs, which increases after surface-functionalization with brain-associated ligand holo-transferrin. Compared to conventional transwell models, the method enables rapid analysis of NP permeability in a physiologically relevant human BBB set-up. Therefore, this work demonstrates a new methodology to preclinically assess NP ability to cross the human BBB.
Abstract P313: Self-reported Sleep Disturbance is Associated With Poor Hypertension Self-management in Latinos
Authors: Billy A Caceres, Niurka Suero-Tejada, Leah Estrada, Suzanne Bakken
Journal: Circulation (2020)

Background: Antihypertensive medication adherence is an important determinant of hypertension control. Although Latinos have high rates of uncontrolled hypertension, factors associated with anti-hypertensive medication adherence in this population are poorly understood. Self-reported sleep disturbance is associated with impaired chronic disease self-management in the general population. To date, no study has examined the association of sleep disturbance with hypertension self-management among Latinos. Hypothesis: Sleep disturbances will be associated with poor anti-hypertensive medication adherence and higher rates of uncontrolled hypertension in Latinos. Methods: We used cross-sectional data from the Washington Heights/Inwood Comparative Effectiveness Research (WICER) Project to assess the link between sleep disturbance with anti-hypertensive medication adherence and uncontrolled hypertension among Latinos with hypertension. The 8-item Morisky Medication Adherence Scale (MMAS) was used to assess medication adherence (alpha 0.75; range 0-8). The 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance measure was used (alpha 0.75; range 4-20). Uncontrolled hypertension was defined as a systolic blood pressure ≥130 mm Hg and/or diastolic blood pressure ≥80 mm Hg. Multiple logistic regression models were used to examine the associations of self-reported sleep disturbance with low medication adherence (MMAS &lt;6). In addition, we examined whether sleep disturbance was associated with uncontrolled hypertension. Models were adjusted for age, sex, education, preferred language, insurance status, comorbid conditions, and anxiety. Results: The final sample consisted of 1,116 Latino participants with hypertension (mean age 63.2, 76.8% were female, and 69.5% had completed less than a high school education). The mean MMAS and PROMIS sleep disturbance scores were 1.9 and 10.1, respectively. A total of 341 (30.4%) participants were classified as having low medication adherence. Participants with low medication adherence were more likely to be younger (p &lt;0.001), single (p &lt;0.001), and have lower educational attainment (p &lt;0.01). After covariate adjustment, a one-point increase in sleep disturbance was associated with higher odds of low medication adherence (AOR 1.05, 95% CI [1.01-1.09]). Sleep disturbance was also associated with higher odds of uncontrolled hypertension (AOR 1.04, 95% CI [1.01-1.07]). Conclusions: Reducing sleep disturbance in Latinos may be an important target for improving hypertension self-management. It remains unclear whether sleep disturbances are a cause of poor hypertension self-management in these patients. Additional research that incorporates longitudinal designs is needed to examine associations between sleep disturbance and hypertension self-management among Latinos.
<i>Vibrio vulnificus</i> Infections From a Previously Nonendemic Area
Authors: Yasuo Oshima, Tetsuya Tanimoto, Koichiro Yuji
Journal: Annals of Internal Medicine (2020)

Letters3 March 2020Vibrio vulnificus Infections From a Previously Nonendemic AreaYasuo Oshima, MD, PhD, Tetsuya Tanimoto, MD, and Koichiro Yuji, MD, PhDYasuo Oshima, MD, PhDCancer Institute Hospital of Japanese Foundation for Cancer Research and The University of Tokyo, Tokyo, Japan (Y.O.)Search for more papers by this author, Tetsuya Tanimoto, MDJyoban Hospital of Tokiwa Foundation, Fukushima, Japan (T.T.)Search for more papers by this author, and Koichiro Yuji, MD, PhDThe University of Tokyo, Tokyo, Japan (K.Y.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0757 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We read King and colleagues' case report (1) involving 5 cases affected by V vulnificus with interest and were curious about the opportunities for exposure to this pathogen in patients 2 through 5. Although patient 1 denied exposure to crabs or the Delaware Bay, he had the potential for multiple exposures to these pathogenic bacteria in his daily job at a seafood restaurant. Patients 2 through 5 did have exposure to crabs and the Delaware Bay, but whether these were 1-time opportunities or they had potentially repeated exposures in their daily life is unclear.Reference1. King M, Rose L, Fraimow H, et al. Vibrio vulnificus infections from a previously nonendemic area. Ann Intern Med. 2019;171:520-1. [PMID: 31207614]. doi:10.7326/L19-0133 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Cancer Institute Hospital of Japanese Foundation for Cancer Research and The University of Tokyo, Tokyo, Japan (Y.O.)Jyoban Hospital of Tokiwa Foundation, Fukushima, Japan (T.T.)The University of Tokyo, Tokyo, Japan (K.Y.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0757. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoVibrio vulnificus Infections From a Previously Nonendemic Area Madeline King , Lucia Rose , Henry Fraimow , Maria Nagori , Mobeen Danish , and Katherine Doktor Vibrio vulnificus Infections From a Previously Nonendemic Area Katherine Doktor and Henry Fraimow Vibrio vulnificus Infections From a Previously Nonendemic Area Homan Wai and Samantha Ahdoot Metrics Cited byPathogenicity Factors of Vibrio Vulnificus: A Review 3 March 2020Volume 172, Issue 5Page: 367KeywordsBacteriaBacterial pathogensCrabsDisclosureLife expectancyPathogensVibrio ePublished: 3 March 2020 Issue Published: 3 March 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Limited Evidence for Selection at the FADS Locus in Native American Populations
Authors: Iain Mathieson
Journal: Molecular Biology and Evolution (2020)

Abstract The FADS locus contains the genes FADS1 and FADS2 that encode enzymes involved in the synthesis of long-chain polyunsaturated fatty acids. This locus appears to have been a repeated target of selection in human evolution, likely because dietary input of long-chain polyunsaturated fatty acids varied over time depending on environment and subsistence strategy. Several recent studies have identified selection at the FADS locus in Native American populations, interpreted as evidence for adaptation during or subsequent to the passage through Beringia. Here, we show that these signals are confounded by independent selection—postdating the split from Native Americans—in the European and, possibly, the East Asian populations used in the population branch statistic test. This is supported by direct evidence from ancient DNA that one of the putatively selected haplotypes was already common in Northern Eurasia at the time of the separation of Native American ancestors. An explanation for the present-day distribution of the haplotype that is more consistent with the data is that Native Americans retain the ancestral state of Paleolithic Eurasians. Another haplotype at the locus may reflect a secondary selection signal, although its functional impact is unknown.
Abstract P431: ASSOCIATION OF LIPOPROTEIN(A) WITH CARDIOVASCULAR EVENTS IN YOUNG NON-FAMILIAL HYPERCHOLESTEROLEMIA
Authors: Pao-Hsien Chu
Journal: Circulation (2020)

Background and aims: Elevated lipoprotein(a) is an independent risk factor for atherosclerotic cardiovascular disease especially in familial hypercholesterolemia. The association of elevated lipoprotein(a) within non-familial hypercholesterolemia or healthy population however, is not known. Therefore, we investigated the associations between elevated lipoprotein(a) and the risk of cardiovascular disease in a non-familial hypercholesterolemia clinically healthy young age cohort. Methods: In this retrospective cohort study, we reviewed medical records of 3,427 participants with lipoprotein(a) levels from a tertiary healthcare center in Taiwan. We further classified lipoprotein(a) level into four groups and analyzed cardiovascular events. Results: Our study population had a mean age 46 years old that were 78% male. Mean total cholesterol and low-density lipoprotein level were 195 mg/dL and 118 mg/dL respectively. Overall, 12.9% of the participants had an elevated lipoprotein(a) level (&gt;30 mg/dL), and 2.7% had a very high level (&gt;70 mg/dL). Thirty-three events including 6 participants with stroke and 27 with coronary artery disease were identified. A lipoprotein(a) level &gt;70 mg/dL was associated with a higher risk of coronary artery disease events in Kaplan-Meier analysis. Aging was associated with a higher lipoprotein(a) value in the male participants but not in the female participants. However, the severity of fatty liver was not positively associated with lipoprotein(a) value. Conclusions: Elevated lipoprotein(a) was associated with coronary events but not the severity of fatty liver disease in non-familial hypercholesterolemia clinically healthy population. Aging may be associated with a higher lipoprotein(a) level in males but not females.
Nasopharyngeal carcinoma: Comparison of concomitant chemoradiotherapy with neoadjuvant chemotherapy in the caucasian population
Authors: A. Sancho, I. Rubio, I. Diaz de Corcuera, A. Munoz, A. Martinez-Bueno, J. M. Mane, A. Ruiz de Lobera, R. Fernandez-Rodriguez, A. Gil-Negrete, S. Carrera
Journal: Journal of Clinical Oncology (2007)

16532 Background: Nowadays, concomitant chemoradiotherapy (CT-RT) is the standard treatment for nasopharyngeal carcinoma (NPC). Neoadyuvant chemotherapy (CT) has been investigated without definitive conclusions. The aim of this study is to compare results of patients(pts) treated with neoadyuvant CT with those treated with concurrent CT-RT. Methods: 38 pts with histologically proven NPC stage II-IVb (PS 0–2) were treated. 27 pts (71.1%) (Group A) (June 1994-May 2000) received Cisplatin (P) 100 mg/m2, Epirrubicin (E) 70 mg/m2, Bleomicin (B) 15 mg D1 and B 12 mg/m2 continous infusion (c.i) for 5 days every 3 week with sequential RT. The other 11 pts (28.9%) (Group B) (June 2002-August 2006) received P 100 mg/m2 D1, D22 and D43 concurrent with RT followed by adyuvant CT P 80 mg/m2 and 5-Fluorouracil 1,000mg/m2/d D1-D4 c.i every 28 day for 3 cycles. Results: 38 pts: 30 male(79%), 8 female(21%). Median age: 53(range 15–75). Stages:II:7, III:11, IVA:12, IVB:8(AJCC 2002). Histology:WHO I-II:11, WHO III:27. Overall response rate: Group A: 25/27 (92.5%), Group B: 10/11 (90.9%) p=0.65. Group A: CR: 17/27 (62.9%); PR: 8/27 (29.6%); PD: 1/27( 3.7%). Group B: CR: 8/11(72.7%); RP: 2/11 (18.1%). 1 pts of each group was not evaluated. Median overall survival (OS) was 34 months (m) in Group A and has not been reached in Group B. Estimated 3 years OS was 48% in GroupA and 80% in GroupB. Median progression free survival (PFS) was 42 m in Group A and 45 m in Group B p=0.72. Estimated 3 years PFS was 50.6% and 66.7% respectively. In the multivariate analysis concurrent CT-RT (HR=5.94 p=0.03) and stage (HR=0.17 p=0.01) were associated with OS. There was 2 toxic death in Group A. The most common toxicities was; Group A: bone marrow suppresion, nausea; Group B: mucositis. Conclusions: These data suggest that P based concomitant CT-RT improves OS and PFS compared with neoadyuvant CT (BEC) followed by RT. No significant financial relationships to disclose.
CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer
Authors: Haiyang Zhang, Ting Deng, Rui Liu, Tao Ning, Haiou Yang, Dongying Liu, Qiumo Zhang, Dan Lin, Shaohua Ge, Ming Bai, Xinyi Wang, Le Zhang, Hongli Li, Yuchong Yang, Zhi Ji, Hailong Wang, Guoguang Ying, Yi Ba
Journal: Molecular Cancer (2020)

Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic.Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential.Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity.The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC.
MIR22HG acts as a tumor suppressor via TGFβ/SMAD signaling and facilitates immunotherapy in colorectal cancer
Authors: Juan Xu, Tingting Shao, Mingxu Song, Yunjin Xie, Jialiang Zhou, Jiaqi Yin, Na Ding, Haozhe Zou, Yongsheng Li, Jiwei Zhang
Journal: Molecular Cancer (2020)

Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. However, we are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC).Differentially expressed lncRNAs in CRC were identified by bioinformatics screen and the level of MIR22HG in CRC and control tissues were determined by qRT-PCR. Cell viability and migration capacities were examined by MTT and transwell assay. Mouse model was used to examine the function and rational immunotherapy of MIR22HG in vivo.We systematically investigated the expression pattern of lncRNAs and revealed MIR22HG acts as a tumor suppressor in CRC. The expression of MIR22HG was significantly decreased in CRC, which was mainly driven by copy number deletion. Reduced expression of MIR22HG was significantly associated with poor overall survival. Silencing of MIR22HG promoted cell survival, proliferation and tumor metastasis in vitro and in vivo. Mechanistically, MIR22HG exerts its tumor suppressive activity by competitively interacting with SMAD2 and modulating the activity of TGFβ pathway. Decreased MIR22HG promoted the epithelial-mesenchymal transition in CRC. Importantly, we found that MIR22HG expression is significantly correlated with CD8A and overexpression of MIR22HG triggers T cell infiltration, enhancing the clinical benefits of immunotherapy.MIR22HG acts as a tumor suppressor in CRC. Our data provide mechanistic insights into the regulation of MIR22HG in TGFβ pathway and facilitates immunotherapy in cancer.
Implementation of targeted screening for lung cancer in a high-risk population within routine NHS practice using low-dose computed tomography
Authors: Helen Grover, Thomas Ross, Elizabeth Fuller
Journal: Thorax (2020)

We report a primary care-based lung cancer targeted screening programme using low-dose CT (LDCT) in South Tyneside and Sunderland. Ever smokers with ≥10 pack-years aged 55–74 years were identified at annual COPD review. 925 individuals attended for LDCT. 2% (n=19/925) had lung cancer diagnosed. 66.7% (n=14/21) had early stage disease and 78.9% (n=15/19) were offered treatment with curative intent. 79.3% of individuals attending for LDCT were ranked in the lowest deprivation quintiles. This approach has been successfully established in routine NHS practice; it is effective with improvements in stage of disease and engages individuals in deprived areas.
Abstract P475: Dementia and Heart Failure a Community Study
Authors: Sheila M Manemann, David Knopman, Jennifer St. Sauver, Suzette J Bielinski, Alanna M Chamberlain, Susan A Weston, Ruoxiang Jiang, Veronique L Roger
Journal: Circulation (2020)

Background: The effective self-management of heart failure (HF) is highly dependent on cognitive function. Dementia frequently coexists with HF, but its exact prevalence and impact on health care utilization and death is not well understood. Methods: Residents from 7 southeast Minnesota counties with a first-ever code for HF (ICD-9 428 and ICD-10 I50) between 1/1/2012 and 12/31/2017 were identified. Dementia before and after the HF diagnosis was ascertained with codes recommended by the US Department of Health and Human Services. Patients were followed through 12/31/2018 for death and hospitalizations. Cox and Andersen-Gill models were used to examine associations between dementia (prior and post HF) and death and hospitalizations, respectively. Dementia after HF was analyzed as a time-dependent variable. Results: Among 6,312 patients with HF (mean age 75 years, 49% female), 636 (10%) had a prior diagnosis of dementia. After a mean (SD) follow-up of 3.1 (1.8) years, 601 (9.5%) patients were diagnosed with dementia post HF. The median time from HF to dementia was 1.3 years, with 43% of dementia cases occurring within 1 year and 64% within 2 years post HF. During follow-up, 2,678 deaths and 15,095 hospitalizations occurred. After adjustment, patients with dementia before HF had nearly a 2-times increased risk of death and 10% increased risk of hospitalization compared to those that did not have dementia (Table). Dementia after HF was associated with a 78% increased risk of death and 63% increased risk of hospitalization compared to those that did not have dementia. Conclusions: Approximately 10% of patients had dementia prior to HF and 10% develop dementia shortly after HF diagnosis. Patients with HF and dementia have an increased risk of death and hospitalization compared to dementia-free counterparts. These data underscore the importance of recognizing the presence and impact of dementia on outcomes in HF to optimize care delivery.
Erratum: Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor–neutralizing therapy in patients with inflammatory bowel disease
Authors: Nathaniel R West, Ahmed N Hegazy, Benjamin M J Owens, Samuel J Bullers, Bryan Linggi, Sofia Buonocore, Margherita Coccia, Dieter Görtz, Sébastien This, Krista Stockenhuber, Johanna Pott, Matthias Friedrich, Grigory Ryzhakov, Frédéric Baribaud, Carrie Brodmerkel, Constanze Cieluch, Nahid Rahman, Gerhard Müller-Newen, Raymond J Owens, Anja A Kühl, Kevin J Maloy, Scott E Plevy, Satish Keshav, Simon P L Travis, Fiona Powrie
Journal: Nature Medicine (2017)
Functional imaging by DCE-US as a surrogate for response in phase I/II of different targeted therapies by DCE-US: Which quantitative parameter and which timing
Authors: N. Lassau, S. Koscielny, L. Chami, A. Roche, J. Soria, A. le Cesne, V. Boige, J. Armand
Journal: Journal of Clinical Oncology (2007)

14093 Background: The early evaluation of targeted treatments is a major challenge in oncology. Functional approaches based on the measure of tumoral vascularization have been developed using different modalities of imaging (CT, MRI, US). We analyzed the response of tumors in three studies using different targeted treatments with dynamic contrast enhanced-ultrasonography (DCE-US). Seven parameters characterizing tumor perfusion were estimated. The objective of the study was to determine which parameter is the most appropriate and when to use it to confirm earlier the efficacy of treatment. Methods: A total of 157 DCE-US were performed in 30 responding patients (PFS&gt;3 months) selected from 3 following studies (multikinase inhibitor targeting angiogenic-receptor with a cytotoxic, thyrosine-kinase inhibitor targeted angiogenic-receptor and C-kit, VEGF monoclonal antibody). Each DCE-US was performed using contrast agent (Sonovue,Bracco) with perfusion and quantification softwares (Toshiba) from raw linear data. Seven quantitative parameters of perfusion were estimated: peak intensity (PI) and area under the curve (AUC), area under the wash-in (AUWI), area under the wash-out (AUWO), time to PI, mean transit time (MTT), wash-in slope. DCE-US were performed before treatment and after during 5 periods (P) : 1–12 days(P1), 13–22 days(P2), 23–43 days(P3), 44–110 days (P4), &gt; 111 days(P5). Results: 1099 parameters have benefited a statistical analysis. Significant modifications (P&lt;0.05) of 4 parameters (PI, AUC, AUWI, AUWO) were observed for the 3 treatments. The earliest significant modifications were observed during the 3 rd period for the first 2 studies and during the 4 th period for the 3 rd study. Conclusions: DCE-US is a sensitive tool to evaluate early tumor response to targeted drugs. Four functional parameters were significantly modified patients responding to treatment: PI, AUC, AUWI, AUWO. Those modifications appear earlier for the multikinase inhibitor targeting angiogenic receptor and the thyrosine-kinase inhibitor targeted angiogenic receptor and C-kit ( (23–43 d) compared to VEGF monoclonal antibody (44 -110 d). DCE- US represent a key add value to early evaluation of targeted therapies. No significant financial relationships to disclose.