tbuckley/cabot-search huggingface dataset:
Synergistically enhanced colorimetric molecular detection using smart cup: a case for instrument-free HPV-associated cancer screening
Authors: Kun Yin, Vikram Pandian, Karteek Kadimisetty, Carlos Ruiz, Kumarasen Cooper, Jianxin You, Changchun Liu
Journal: Theranostics (2019)

Rationale:Early and accurate detection of disease is crucial for its prevention, identification, and treatment.However, most of disease diagnostics is still limited in clinical laboratories due to the need of complicated instruments and professional personnel.Herein, we reported a smartphone-based synergistically enhanced colorimetric method for molecular diagnostics in our point of care (POC) smart cup platform.Methods: A disposable microfluidic chip was developed for colorimetric loop-mediated isothermal amplification (LAMP) detection of multiple HPV DNA in our POC smart cup platform.The colorimetric detection takes advantage of synergistic effect of PPi 4-and H + ions, two byproducts of LAMP reaction.Color signal of LAMP assay was recorded and analyzed by our custom Android app (dubbed "Hue Analyzer").Results: Our method not only significantly improves colorimetric readout, but also provides a 10-fold increase in detection sensitivity.It has been successfully applied for HPV-associated cancer screening with spiked saliva and clinical swab samples. Conclusion:The proposed POC diagnostic platform is completely compatible with other nucleic acid biomarkers and has great potential for personalized health monitoring and disease prevention.
FRI-028-Spleen stiffness and liver stiffness measurements as surrogate markers of liver fibrosis in patients with autoimmune hepatitis: prospective, single-center study
Authors: Maciej K. Janik, Konrad Kostrzewa, Raszeja-Wyszomirska Joanna, Frank Lammert, Małgorzata Milkiewicz, Piotr Milkiewicz, Marcin Krawczyk
Journal: Journal of Hepatology (2019)
DR4-Ser424<i>O</i>-GlcNAcylation Promotes Sensitization of TRAIL-Tolerant Persisters and TRAIL-Resistant Cancer Cells to Death
Authors: Hyeonjeong Lee, Yumin Oh, Young-Jun Jeon, Song-Yi Lee, Hyunjoo Kim, Ho-June Lee, Yong-Keun Jung
Journal: Cancer Research (2019)

Abstract TNF-related apoptosis-inducing ligand (TRAIL) resistance, including nongenetically acquired tolerance in cancer persister cells, is a major obstacle to translating TRAIL therapy into patients with cancer. However, the underlying mechanisms remain to be elucidated. Here, we show that DR4/TRAIL-R1 is O-GlcNAcylated at Ser424 in its death domain to mediate both apoptosis and necrosis upon TRAIL ligation. We found that DR4–Ser424 mutations, identified from our cell-based functional screen using a cancer patient–derived cDNA expression library and from The Cancer Genome Atlas, caused TRAIL resistance in various human cancer cell lines. Using O-GlcNAc transferase knockdown cells, DR4-preferred versus DR5-preferred cancer cells, and a DR5-neutralizing antibody, we evaluated the essential role of DR4-specific O-GlcNAc modification in TRAIL cytotoxicity. In contrast to DR4, DR5 was not O-GlcNAcylated by TRAIL treatment, discriminating DR4 from DR5-mediated signaling. Apart from genetic changes in DR4-Ser424, we further classified various cancer cell lines originated from stomach, colon, lung, and glioblastoma according to their sensitivity to and receptor preference upon TRAIL death signaling and generated TRAIL-tolerant persister-derived DLD-1PER cells. Among these, we discovered that DR4 was not modified by O-GlcNAc in most of the TRAIL-resistant cancer cells and DLD-1PER cells. Interestingly, promoting DR4 O-GlcNAcylation intentionally using 2-deoxy-d-glucose or a high concentration of glucose sensitized those resistant cancer cells to TRAIL. The O-GlcNAcylation–defective DR4 failed to form DISC/necrosome and could not translocate to aggregated platforms for receptor clustering. Our findings demonstrate that DR4 O-GlcNAcylation is crucial for TRAIL death signaling, providing new opportunities for TRAIL therapy overcoming TRAIL resistance in cancers. Significance: This study reports that a novel posttranslational modification by O-GlcNAcylation of one of the two human TRAIL receptors with a death domain, TRAIL-R1 (DR4), plays a crucial role in enabling both apoptotic and necroptotic cell death induction by TRAIL.
Extragenital Chlamydia and Gonorrhea Among Community Venue–Attending Men Who Have Sex with Men — Five Cities, United States, 2017
Authors: Michelle L. Johnson Jones, Johanna Chapin-Bardales, Destani Bizune, John R. Papp, Christi Phillips, Robert D. Kirkcaldy, Cyprian Wejnert, Kyle T. Bernstein, Salma Khuwaja, Zaida Lopez, Paige Padgett, David Forrest, Willie Nixon, Emma Spencer, Sarah Braunstein, Sidney Carrillo, Alexis Rivera, Theresa Ick, H. Fisher Raymond, Jenevieve Opoku, Irene Kuo
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Sexually transmitted diseases (STDs) disproportionately affect gay, bisexual, and other men who have sex with men (MSM) in the United States (1). Because chlamydia and gonorrhea at extragenital (rectal and pharyngeal) anatomic sites are often asymptomatic, these anatomic sites serve as a reservoir of infection, which might contribute to gonococcal antimicrobial resistance (2) and increased risk for human immunodeficiency virus (HIV) transmission and acquisition (3). To ascertain prevalence of extragenital STDs, MSM attending community venues were recruited in five U.S. cities to provide self-collected swabs for chlamydia and gonorrhea screening as part of National HIV Behavioral Surveillance (NHBS). Overall, 2,075 MSM provided specimens with valid results, and 13.3% of participants were infected with at least one of the two pathogens in at least one of these two extragenital anatomic sites. Approximately one third of participating MSM had not been screened for STDs in the previous 12 months. MSM attending community venues had a high prevalence of asymptomatic extragenital STDs. The findings underscore the importance of sexually active MSM following current recommendations for STD screening at all exposed anatomic sites at least annually (4).
Author Correction: Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signaling
Authors: Martina Rauner, Ulrike Baschant, Antonella Roetto, Rosa Maria Pellegrino, Sandra Rother, Juliane Salbach-Hirsch, Heike Weidner, Vera Hintze, Graeme Campbell, Andreas Petzold, Regis Lemaitre, Ian Henry, Teresita Bellido, Igor Theurl, Sandro Altamura, Silvia Colucci, Martina U. Muckenthaler, Georg Schett, Davide S. K. Komla-Ebri, J. H. Duncan Bassett, Graham R. Williams, Uwe Platzbecker, Lorenz C. Hofbauer
Journal: Nature Metabolism (2019)
TCTAP C-188 Double Layer Stents Technique to Conquer the Severe Recoil Phenomenon After Recanalization of Severe Calcified Chronic Total Occlusion of Left Superficial Femoral Artery
Authors: Chien-wei Chang, Nai-Yu Chi, Tsung-Hsien Lin, Po-Chao Hsu
Journal: Journal of the American College of Cardiology (2019)
PS-054-Quantitative antibodies against hepatitis B core antigen differ in NUC suppressed caucasian HbeAG-negative patients compared to patients who achieved either “NUC induced” or “spontaneous” functional cure of HBV
Authors: Alessandro Loglio, Floriana Facchetti, Corinna Orsini, Alberto Perego, Riccardo Perbellini, Sara Colonia Uceda Renteria, Simone Segato, Giovanna Lunghi, Ferruccio Ceriotti, Pietro Lampertico
Journal: Journal of Hepatology (2019)
SAT-314-Liver fibrosis by FibroScan is highly prevalent in type 2 diabetic patients with NAFLD and fairly normal liver enzymes but increased uric acid
Authors: Rosa Lombardi, Lorena Airaghi, Giovanni Targher, Gaetano Serviddio, Gabriele Maffi, Alessandro Mantovani, Claudio Maffeis, Antonio Colecchia, Rosanna Villani, Luca Rinaldi, Emanuela Orsi, Silvia Fargion, Anna Ludovica Fracanzani
Journal: Journal of Hepatology (2019)
High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma
Authors: Sarah Wang, Elizabeth E. Hwang, Rajarshi Guha, Allison F. O'Neill, Nicole Melong, Chansey J. Veinotte, Amy Conway Saur, Kellsey Wuerthele, Min Shen, Crystal McKnight, Gabriela Alexe, Madeleine E. Lemieux, Amy Wang, Emma Hughes, Xin Xu, Matthew B. Boxer, Matthew D. Hall, Andrew Kung, Jason N. Berman, Mindy I. Davis, Kimberly Stegmaier, Brian D. Crompton
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Ewing sarcoma is an aggressive solid tumor malignancy of childhood. Although current treatment regimens cure approximately 70% of patients with localized disease, they are ineffective for most patients with metastases or relapse. New treatment combinations are necessary for these patients. Experimental Design: Ewing sarcoma cells are dependent on focal adhesion kinase (FAK) for growth. To identify candidate treatment combinations for Ewing sarcoma, we performed a small-molecule library screen to identify compounds synergistic with FAK inhibitors in impairing Ewing cell growth. The activity of a top-scoring class of compounds was then validated across multiple Ewing cell lines in vitro and in multiple xenograft models of Ewing sarcoma. Results: Numerous Aurora kinase inhibitors scored as synergistic with FAK inhibition in this screen. We found that Aurora kinase B inhibitors were synergistic across a larger range of concentrations than Aurora kinase A inhibitors when combined with FAK inhibitors in multiple Ewing cell lines. The combination of AZD-1152, an Aurora kinase B–selective inhibitor, and PF-562271 or VS-4718, FAK-selective inhibitors, induced apoptosis in Ewing sarcoma cells at concentrations that had minimal effects on survival when cells were treated with either drug alone. We also found that the combination significantly impaired tumor progression in multiple xenograft models of Ewing sarcoma. Conclusions: FAK and Aurora kinase B inhibitors synergistically impair Ewing sarcoma cell viability and significantly inhibit tumor progression. This study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma.
SAT-487-Reliability of a single biopsy in evaluating immune tumor microenvironment of hepatocellular carcinoma
Authors: Ying-Chun Shen, Chia-Lang Hsu, Yung-Ming Jeng, Ming-Chih Ho, Cheng-Maw Ho, Ching-Ping Yeh, Chia-Yu Yeh, Meng-Chi Hsu, Ray-Heng Hu, Ann-Lii Cheng
Journal: Journal of Hepatology (2019)
Abstract P011: Predictive Ability of 35 Frailty Scores for Cardiovascular Events in the General Population
Authors: Gloria A Aguayo, Anna Schritz, Anne-Françoise Donneau, Michel T Vaillant, Saverio Stranges, Laurent Malissoux, Michèle Guillaume, Majon Muller, Daniel R Witte
Journal: Circulation (2017)

Introduction: Frailty is a state of vulnerability in elderly people linked to higher mortality risk. Cardiovascular disease (CVD) is highly prevalent in aged populations and associated with frailty. Thus, frailty state could predict higher risk of CVD. Many frailty scores (FS) have been developed, but none of them is considered the gold standard. We aimed to compare predictive and discriminative ability of an extensive list of FS with regard to incidence of CVD in a sample of the general elderly population in England. We assessed the hypothesis that some FS will have better predictive ability than others, depending on their characteristics. Methods: We performed a prospective analysis of the association between 35 FS in participants free of CVD at baseline wave 2 of the English Longitudinal Study of Ageing (2004-2005), and incident CVD assessed until February 2012. The sample consisted of 4,177 participants (43.0 % men). Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated for each FS using Cox proportional hazards model, adjusted for demographic, lifestyle and comorbidity variables. FS were analyzed on a continuous scale and using original cutoffs. The added predictive ability of FS beyond a basic model consisting of sex and age was studied using Harrel’s C statistic (the higher the better). Results: The median follow-up was 5.8 years, the incidence rate of CVD events was 301.2 /10,000 person-years and CVD represented 28% of the total cause of death. The mean age was 70.5 (SD: ±7.8) years. In fully-adjusted models with demographics, lifestyles and comorbidity, HRs ranged from: 1.0 (0.7; 1.6) to 12.7 (5.5; 29.3). Using cutoffs, HRs ranged from 0.7 (0.2; 1.9) to 1.8 (1.3; 2.5). Adjusted for sex and age, delta Harrel’s C statistic ranged from -0.8 (-3.4; 1.8) to 3.0 (-0.4; 6.4). The best CVD predictive ability was found for the Frailty Index with 70 variables and the Comprehensive Geriatric Assessment screening FS for continuous and cutoff analyses respectively. In conclusion, there is high variability in the association between different published FS and incident CVD. FS have better predictive ability used as continuous variable. Although most of the analyzed FS have good predictive ability with regard to incident CVD, they do not significantly improve on the discriminative capacity of a basic model. Our results will help to guide clinicians, researchers and public health practitioners in choosing the most informative frailty assessment tool.
The Landscape of Actionable Molecular Alterations in Immunomarker-Defined Large-Cell Carcinoma of the Lung
Authors: Anthony W. Chan, Shuk L. Chau, Joanna H. Tong, Chit Chow, Johnny S.H. Kwan, Lau Y. Chung, Raymond W. Lung, Carol Y. Tong, Edith K. Tin, Peggy P. Law, Wai T. Law, Calvin S.H. Ng, Innes Y.P. Wan, Tony S.K. Mok, Ka Fai To
Journal: Journal of Thoracic Oncology (2019)
Abstract P176: Pedometer Feedback - Superior for Increasing Daily Physical Activity in Cardiac Rehabilitation Patients
Authors: Leonard Kaminsky, Cemal Ozemek, Katrina Riggin, Wonwoo Byun, Scott Strath
Journal: Circulation (2013)

Introduction: Although cardiac patients obtain favorable cardiovascular outcomes and reduced risk of mortality when participating in cardiac rehabilitation (CR), it is well established that most do not typically achieve recommended amounts of daily physical activity (PA) solely through participation in CR. Therefore, the purpose of this study was to examine the relative effectiveness of three different individually tailored interventions designed to increase PA in cardiac patients attending CR. Hypothesis: We assessed the hypothesis that cardiac patients attending long-term CR who receive pedometer feedback (PF) or motivational messaging (MM) will achieve higher levels of PA than patients who receive usual care (UC) recommendations. Methods: A total of 99 (77 men and 22 women, 61.5±10.6 years, BMI 30.6 ± 5.1 kg/m2) patients entering a long-term CR program completed a 12-week PA intervention. Patients were randomized to: UC (time-based recommendation), PF, MM, or PF with individualized MM (PF+MM). Both PF groups were given a goal of increasing step counts/day by 10% of the individual’s baseline value each week. If the goal for the week was not reached, the same goal was used for the next week. PA was assessed for 7 days with Kenz Lifecorder PLUS monitors (Suzukan, Co, LTD, Nagoya, Japan) prior to beginning CR and on the 12 th week of the intervention. Criteria for acceptable PA data were daily wear time &gt; 10 hours on a minimum of 4 days (including at least 1 weekend day) with daily PA &gt; 1000 steps. Results: A two-way ANOVA for change in PA from baseline to 12 th week of the intervention for the 4 groups revealed a significant time and group interaction. Post-hoc testing showed significant increases for both PF and PF+MM, however, no significant change for UC or MM. Conclusion: The findings from this study demonstrate that using PF feedback is superior to the usual time-based recommendations patients are given in CR. CR programs can assist patients in increasing their daily PA by encouraging pedometer use with individualized step goals.
Information for lung cancer patients and their caregivers: A systematic analysis of the online landscape
Authors: P. Naish, E. Purdy
Journal: Annals of Oncology (2019)

Background: A lung cancer patient may turn to the internet for information on their disease, or on terms that their doctor has used. Anecdotal evidence suggests that such information may be outdated or incomplete. This research analyses the information available on lung cancer, aiming to support the identification of areas for improvement to ensure patients can be well-informed. Methods: Researchers in 11 countries entered 22 search terms related to lung cancer into Google. Websites that appeared on the first page of search results were analysed to identify the content they included, the owners of the websites that provided the information, and the intended purpose of the information. Websites were reviewed in detail to determine the depth of information provided and how helpful, factual and current it was. Results: 885 unique websites were mapped (982 total; 97 duplicates removed). Sources of information differed between countries, with news sources as the leading type of website (375[42%]), followed by healthcare providers (115[13%]), online health resources (104[12%]), professional organisations (104[12%]), pharmaceutical companies (95[11%]), patient groups (72[8%]) and Wikipedia (20[2%]). 65% [573] of sources provided information on differences between non-small cell and small cell lung cancer and 29% [254] explained staging. 35% [310] of information sources covered point mutations (e.g. EGFR, ALK) and 19% [164] noted the availability of testing for point mutations. 23% [202] of information sources mentioned IO biomarkers (e.g. PD-1, PD-L1) and 11% [94] cited potential testing options for these. Chemotherapy was the most common treatment mentioned (58%[514]), followed by radiation therapy (44%[393]), surgery (40%[358]), immuno-oncology therapies (38%[336]) and targeted therapies (33%[288]). Conclusions: Online lung cancer information was not always up-to-date or easily accessible. Information on treatment options was often either too complex or too high-level and incomplete. Websites that provided more up-to-date information were often not search optimised, therefore more difficult to find. Results varied considerably between countries but gaps in information were identified across all countries and these should be addressed. Editorial acknowledgement: Writing assistance provided by GCI Health. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: P. Naish: Employee and shareholder: AstraZeneca. E. Purdy: Employee: GCI Health.
Utility of <sup>18</sup>F-FDG PET and CT to assess response to neoadjuvant chemotherapy.
Authors: Jamie E. Chaft, Jarushka Naidoo, Mark Dunphy, Kaitlin Woo, Camelia S. Sima, Robert J. Downey, William D. Travis, Mark G. Kris
Journal: Journal of Clinical Oncology (2015)

7548 Background: Perioperative chemotherapy improves survival in resected NSCLCs. Neoadjuvant administration allows for in vivo assessment of efficacy. Major pathologic response (MPR), defined as <10% viable tumor tissue in the surgical resection specimen, strongly correlates with clinical outcomes in lung cancers. (Hellmann, Lancet Oncol 2014) Unfortunately, it is a minority of tumors that demonstrate MPR after standard induction chemotherapy and adaptive strategies are needed. The understanding of the clinical utility of non-invasive mid-and post-treatment PET and CT scans is essential for adaptive trial design. Methods: This analysis is derived from a completed phase 2 trial of PET response-adaptive therapy that treated 40 pts with clinical stage IB-IIIA NSCLCs (primary >2 cm & SUVmax≥4.5). Pts received 2 cycles of cis- or carboplatin + gemcitabine (squamous) or pemetrexed (adenocarcinoma/other), followed by repeat PET + CT. Pts with suboptimal response (<35% decrease in SUV) were switched to vinorelbine + docetaxel q2 wks. This analysis utilizes non-parametric tests to assess the correlation of % change in SUV of the primary tumor (PERCIST) and the % change in size on CT (RECIST) with MPR after 2 cycles and at completion of induction therapy. Results: 40 pts were treated. 15 pts has <35% decrease in SUV, of whom 13 were switched to vinorelbine/docetaxel, and 2 to definitive radiotherapy only. 27 pts had R0resections. 6 tumors demonstrated MPR. In all settings, PET response correlated with MPR and CT response did not (see Table). Conclusions: 18F-FDG PET response, but not CT response, in the primary tumor after 2 and 4 cycles of chemotherapy correlates with major pathologic response, a surrogate for survival. The use of early PET response to offer alternative therapies to pts who are not benefiting should be considered. NCT01443078 was supported in part by Eli Lilly. Clinical trial information: NCT01443078. % decrease, median (range) p-value MPR no MPR All pts after 2 cycles PET CT 71 (23 – 87) 31 (0 – 43) 49 (+51 – 86) 21 (+6 – 38) 0.016 0.19 Pts not assigned to switch after 2 cycles PET CT 75 (65 – 87) 33 (0 – 43) 54 (36 – 86) 24 (2 – 38) 0.007 0.094 All pts after 4 cycles PET CT 76 (67 – 94) 44 (16 – 51) 64 (+24 – 87) 38 (+6 – 64) 0.034 0.26
“Navigate-dock-activate” anti-tumor strategy: Tumor micromilieu charge-switchable, hierarchically activated nanoplatform with ultrarapid tumor-tropic accumulation for trackable photothermal/chemotherapy
Authors: Kondareddy Cherukula, Saji Uthaman, In-Kyu Park
Journal: Theranostics (2019)

The delivery of therapeutics into tumors remains a challenge in nanoparticle-mediated drug delivery. However, effective therapies such as photothermal therapy (PTT) are limited by quick systemic clearance and non-specific biodistribution. Anti-tumor strategies tailored to accommodate both tumor accumulation/retention and cellular internalization under a single platform would be a promising strategy. This work demonstrates a hierarchical activating strategy that would exhibit enhanced circulation and rapid tumor-tropism as well as facilitate tumor penetration, followed by tumor-specific drug release to realize trackable photothermal/chemotherapy. Methods: We engineered a lithocholic acid-conjugated disulfide-linked polyethyleneimine micelle (LAPMi) loaded with paclitaxel (LAPMi-PTX, L), followed by the electrostatic adsorption of indocyanine green (ICG, I) on LAPMI-PTX and subsequently coated them with thermosensitive DPPC and DSPE-PEG-NH2 lipids (L), producing Lipid/ICG/LAPMi-PTX (LIL-PTX) nanoparticles (NPs). The characteristics of NPs, including physicochemical characterization, photothermal & pH responsiveness, cell uptake, tumor spheroid penetration, anti-tumor efficacy and hierarchical activation of LIL-PTX NPs were investigated in vitro and in vivo by using CT26 cell line. The anti-metastatic potential of LIL-PTX NPs were demonstrated using 4T1 orthotopic tumor model. Results: The NPs synthesized possessed charge switchability in the mildly acidic pH, and were laser- and pH-responsive. Dual stimuli-responsive nature of LIL-PTX NPs improved the disposition of therapeutics to the tumor, reflected by enhanced intracellular uptake, tumor spheroid penetration and in vitro cytotoxicity studies. LIL-PTX NPs readily switched its surface charge from neutral to positive upon reaching the tumor milieu, thus resulting in rapid tumor tropism and accumulation. Under near-infrared laser irradiation, the thermosensitive lipids on LIL-PTX NPs were deshielded, and the tumor-penetrating LAPMi-PTX was subsequently exposed to the tumor milieu, thus resulting in enhanced intracellular internalization. Next, LAPMi-PTX evaded the endo-lysosomes, thereby releasing the PTX through the degradation of LAPMi mediated by intracellular GSH in the tumor. LIL-PTX NPs significantly improved the therapy by eradicating primary tumors completely and suppressing their subsequent lung metastasis. Conclusion: The improved therapeutic index is due to enhanced passive targeting by rapid tumor-tropic accumulation and tumor penetration by laser-driven exposure of LAPMi, thereby improving the therapeutic delivery for image-guided photothermal/chemotherapy.