tbuckley/cabot-search huggingface dataset:
Polymorphisms in eicosanoid‐related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti‐inflammatory drug hypersensitivity
Authors: R. Jurado‐Escobar, I. Doña, J.R. Perkins, J.J. Laguna, R. Muñoz‐Cano, A. García‐Sánchez, P. Ayuso, M.J. Torres, C. Mayorga, J.A. Cornejo‐García
Journal: British Journal of Dermatology (2021)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug hypersensitivity, with NSAID-induced acute urticaria/angioedema (NIUA) the most frequent phenotype. NSAID hypersensitivity is caused by cyclooxygenase 1 inhibition, which leads to an imbalance in prostaglandin (PG) and cysteinyl leukotriene (CysLT) synthesis. As only susceptible individuals develop NSAID hypersensitivity, genetic factors are believed to be involved; however, no study has assessed the overall genetic variability of key enzymes in PG and CysLT synthesis in NSAID hypersensitivity.To evaluate simultaneously variants in the main genes involved in PG and CysLT biosynthesis in NIUA.Two independent cohorts of patients were recruited in Spain, alongside NSAID-tolerant controls. The discovery cohort included only patients with NIUA; the replication cohort included patients with NSAID-exacerbated respiratory disease (NERD). A set of tagging single-nucleotide polymorphisms (tagSNPs) in PTGS1, PTGS2, ALOX5 and LTC4S was genotyped using mass spectrometry coupled with endpoint polymerase chain reaction.The study included 1272 individuals. Thirty-five tagSNPs were successfully genotyped in the discovery cohort, with three being significantly associated after Bonferroni correction (rs10306194 and rs1330344 in PTGS1; rs28395868 in ALOX5). These polymorphisms were genotyped in the replication cohort: rs10306194 and rs28395868 remained associated with NIUA, and rs28395868 was marginally associated with NERD. Odds ratios (ORs) in the combined analysis (discovery and replication NIUA populations) were 1·7 for rs10306194 [95% confidence interval (CI) 1·34-2·14; Pcorrected = 2·83 × 10-4 ) and 2·19 for rs28395868 (95% CI 1·43-3·36; Pcorrected = 0·002).Variants of PTGS1 and ALOX5 may play a role in NIUA and NERD, supporting the proposed mechanisms of NSAID-hypersensitivity and shedding light on their genetic basis.
Lower-Limb Medical and Rehabilitation Exoskeletons: A Review of the Current Designs
Authors: Alberto Plaza, Mar Hernandez, Gonzalo Puyuelo, Elena Garces, Elena Garcia
Journal: IEEE Reviews in Biomedical Engineering (2021)

Medical and rehabilitation exoskeletons are being increasingly considered by therapists when choosing a treatment for individuals affected by lower limb impairments. Although all such exoskeletons seem to provide similar features and performance, there are, in practice, significant differences among them in terms of maximum walking speed, maximum torque, weight, autonomy, interaction with the user, or even the way to use it. In this review, the state of the art of the main commercial exoskeletons is described, while analyzing their properties, advantages, and disadvantages. Three groups are considered: complete exoskeletons, partial exoskeletons and open lines of research. A comparative analysis between them is performed while considering the main scientific and technical aspects to be improved. In conclusion to this analysis, the balance between feasibility and innovation in exoskeletons development is a design challenge. Commercial exoskeletons must fulfil standards whilst ensuring their safety and robustness. However, achieving a new generation of exoskeletons means a need to implement new hardware paradigms, and to enhance control strategies focused on assist-as-needed scheme. Finally, some aspects to improve current designs of the exoskeleton are presented.
ECHO IN THE TIME OF COVID: USE OF ULTRASOUND ENHANCING AGENTS SAVES TIME AND REDUCES EXPOSURE RISK
Authors: Ashton Lai, Solomon Bienstock, Connor Oates, Rajeev Samtani, Frans Beerkens, Dylan Sperling, Madison Edens, Mohanchandran Satish, Nikola Kocovic, Matthew Pulaski, Stamatios Lerakis, Samantha Buckley, Martin Goldman, Lori Croft
Journal: Journal of the American College of Cardiology (2021)
THE FEASIBILITY, SAFETY AND CLINICAL BENEFITS FOR CHRONIC TOTAL OCCLUSION (CTO) PCI IN PATIENTS WITH REDUCED EJECTION FRACTIONS (EF) COMPARED TO NORMAL EF
Authors: Mohamad Firas Barbour, Akhil Rasim Reddy, Annie Dong, William Grigg, Neil Patel, Kathleen Brown, Adam Strunk
Journal: Journal of the American College of Cardiology (2021)
A genome‐wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans
Authors: Y. Chen, M. André, K. Adhikari, M. Blin, B. Bonfante, J. Mendoza‐Revilla, M. Fuentes‐Guajardo, S. Palmal, J.C. Chacón‐Duque, M. Hurtado, V. Villegas, V. Granja, C. Jaramillo, W. Arias, R.B. Lozano, P. Everardo‐Martínez, J. Gómez‐Valdés, H. Villamil‐Ramírez, C.C.S. Cerqueira, T. Hünemeier, V. Ramallo, R. Gonzalez‐José, L. Schüler‐Faccini, M.‐C. Bortolini, V. Acuña‐Alonzo, S. Canizales‐Quinteros, C. Gallo, G. Poletti, G. Bedoya, F. Rothhammer, D. Balding, D.J. Tobin, S. Wang, P. Faux, A. Ruiz‐Linares
Journal: British Journal of Dermatology (2021)

Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans.To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America.Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome.Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing.We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.
Maximizing and evaluating the impact of test-trace-isolate programs: A modeling study
Authors: Kyra H. Grantz, Elizabeth C. Lee, Lucy D’Agostino McGowan, Kyu Han Lee, C. Jessica E. Metcalf, Emily S. Gurley, Justin Lessler
Journal: PLoS Medicine (2021)

Background Test-trace-isolate programs are an essential part of coronavirus disease 2019 (COVID-19) control that offer a more targeted approach than many other nonpharmaceutical interventions. Effective use of such programs requires methods to estimate their current and anticipated impact. Methods and findings We present a mathematical modeling framework to evaluate the expected reductions in the reproductive number, R , from test-trace-isolate programs. This framework is implemented in a publicly available R package and an online application. We evaluated the effects of completeness in case detection and contact tracing and speed of isolation and quarantine using parameters consistent with COVID-19 transmission ( R 0 : 2.5, generation time: 6.5 days). We show that R is most sensitive to changes in the proportion of cases detected in almost all scenarios, and other metrics have a reduced impact when case detection levels are low (&lt;30%). Although test-trace-isolate programs can contribute substantially to reducing R , exceptional performance across all metrics is needed to bring R below one through test-trace-isolate alone, highlighting the need for comprehensive control strategies. Results from this model also indicate that metrics used to evaluate performance of test-trace-isolate, such as the proportion of identified infections among traced contacts, may be misleading. While estimates of the impact of test-trace-isolate are sensitive to assumptions about COVID-19 natural history and adherence to isolation and quarantine, our qualitative findings are robust across numerous sensitivity analyses. Conclusions Effective test-trace-isolate programs first need to be strong in the “test” component, as case detection underlies all other program activities. Even moderately effective test-trace-isolate programs are an important tool for controlling the COVID-19 pandemic and can alleviate the need for more restrictive social distancing measures.
Inhibitory Synapses Are Repeatedly Assembled and Removed at Persistent Sites In Vivo
Authors: Katherine L. Villa, Kalen P. Berry, Jaichandar Subramanian, Jae Won Cha, Won Chan Oh, Hyung-Bae Kwon, Yoshiyuki Kubota, Peter T.C. So, Elly Nedivi
Journal: Neuron (2016)
3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration
Authors: Mamatali Rahman, Xue-Liang Peng, Xiao-Hong Zhao, Hai-Lun Gong, Xiao-Dan Sun, Qiong Wu, Dai-Xu Wei
Journal: Bioactive Materials (2021)

Hydrophilic bone morphogenetic protein 2 (BMP2) is easily degraded and difficult to load onto hydrophobic carrier materials, which limits the application of polyester materials in bone tissue engineering. Based on soybean-lecithin as an adjuvant biosurfactant, we designed a novel cell-free-scaffold of polymer of poly(ε-caprolactone) and poly(lactide-co-glycolide)-co-polyetherimide with abundant entrapped and continuously released BMP2 for in vivo stem cell-capture and in situ osteogenic induction, avoiding the use of exogenous cells. The optimized bioactive osteo-polyester scaffold (BOPSC), i.e. SBMP-10SC, had a high BMP2 entrapment efficiency of 95.35%. Due to its higher porosity of 83.42%, higher water uptake ratio of 850%, and sustained BMP2 release with polymer degradation, BOPSCs were demonstrated to support excellent in vitro capture, proliferation, migration and osteogenic differentiation of mouse adipose derived mesenchymal stem cells (mADSCs), and performed much better than traditional BMP-10SCs with unmodified BMP2 and single polyester scaffolds (10SCs). Furthermore, in vivo capture and migration of stem cells and differentiation into osteoblasts was observed in mice implanted with BOPSCs without exogenous cells, which enabled allogeneic bone formation with a high bone mineral density and ratios of new bone volume to existing tissue volume after 6 months. The BOPSC is an advanced 3D cell-free platform with sustained BMP2 supply for in situ stem cell capture and osteoinduction in bone tissue engineering with potential for clinical translation.
Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets
Authors: Jaehwan Kim, Jongmi Lee, Hyun Je Kim, Naoya Kameyama, Roya Nazarian, Evan Der, Steven Cohen, Emma Guttman-Yassky, Chaim Putterman, James G. Krueger
Journal: Journal of Allergy and Clinical Immunology (2021)
Safety and efficacy of faecal microbiota transplantation for active peripheral psoriatic arthritis: an exploratory randomised placebo-controlled trial
Authors: Maja Skov Kragsnaes, Jens Kjeldsen, Hans Christian Horn, Heidi Lausten Munk, Jens Kristian Pedersen, Søren Andreas Just, Palle Ahlquist, Finn Moeller Pedersen, Maarten de Wit, Sören Möller, Vibeke Andersen, Karsten Kristiansen, Dorte Kinggaard Holm, Hanne Marie Holt, Robin Christensen, Torkell Ellingsen
Journal: Annals of the Rheumatic Diseases (2021)

Objectives Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA). Methods In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26. Results Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)). Conclusions In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA. Trial registration number NCT03058900 .
Editor's Note: Epigenetic Modifications of <i>RASSF1A</i> Gene through Chromatin Remodeling in Prostate Cancer
Authors: Ken Kawamoto, Steven T. Okino, Robert F. Place, Shinji Urakami, Hiroshi Hirata, Nobuyuki Kikuno, Toshifumi Kawakami, Yuichiro Tanaka, Deepa Pookot, Zhong Chen, Shahana Majid, Hideki Enokida, Masayuki Nakagawa, Rajvir Dahiya
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about this article (1): following an institutional review by the Veterans Affairs Medical Center, San Francisco and the University of California, San Francisco, the primary affiliations for several of the authors, it was determined that blank panels were used to represent negative results for AcH4 modification of the RASSF1A gene in LNCaP cells in Fig. 5A and AcH4 modification of the RASSF1A gene in cells untreated for 5-aza-dC and TSA in Fig. 6.
GENDER DIFFERENCES AND OUTCOMES IN ACUTE CORONARY SYNDROMES ADMITTED TO AN EMERGENCY DEPARTMENT IN LATIN AMERICA
Authors: Cynthia Jackson-Pedroza, Hector Gonzalez-Pacheco, Rodrigo Gopar-Nieto, Leticia Gallardo Grajeda, Carlos Dattoli-Garcia, Oscar Garcia-Padron, Diego Araiza Garaygordobil, Alexandra Arias-Mendoza
Journal: Journal of the American College of Cardiology (2021)
Effects of sodium–glucose co‐transporter 2 inhibition with empagliflozin on potassium handling in patients with acute heart failure
Authors: Joost C. Beusekamp, Jasper Tromp, Eva M. Boorsma, Hiddo J.L. Heerspink, Kevin Damman, Adriaan A. Voors, Peter van der Meer
Journal: European Journal of Heart Failure (2021)
Establishment of a new human prostate cancer cell line, IGR-CaP1, from a localized epithelial prostate cancer.
Authors: Anne Chauchereau, Sylvestre Le Moulec, Gaelle Fromont, Catherine Gaudin, Pierre Validire, Nadine Beron-Gaillard, Anne Plantade, Christophe Massard, Renaud de Crevoisier, Jean Benard, Karim Fizazi
Journal: Cancer Research (2007)

3880  Introduction: Around 10 human prostate cancer cell lines are available to-date and thereof only five are currently used. Most of these models have been obtained from prostate tumor metastases or have been artificially established in vitro. Therefore it is still a challenge to obtain new cancer models that may better reflect the mechanisms of local and distant tumor progression.  Methods: Taking advantage of the natural extra cellular matrix we recently developed, one new cell line (IGR-CaP1) was obtained from 3 processed samples derived from patients with clinically localized prostate cancer. Extensive characterization of this cell line was performed using immunoblotting and immunofluorescence analysis, quantitative real-time PCR, cytogenetic analysis and tumorigenicity in mice.  Results: IGR-CaP1 cells were cultured for at least 35 passages. They showed epithelial-like morphology although CK8, CK19, EpCAM were expressed at low levels. Immunoblotting studies showed that IGR-Cap1 cells have lost expression of epithelial cell adhesion molecule E-Cadherin and possess high levels of the mesenchymal protein vimentin suggesting that the cells are already engaged in the tumor invasion process. Further, these cells showed a tetraploid karyotype, a high expression of p53 protein expression, and a high telomerase activity. They express neither PSA nor androgen receptor. However, the tight-junction protein ZO-1 was mainly localized at the membrane and the cells do not exhibit mesenchymal markers such as STRO-1, CD105 and CD73. In vivo study reveals that subcutaneous injection of IGR-CaP1 cells in immune-deprived nude mice induce tumor formation after 3 weeks. The effect of orthotopic injections of IGR-CaP1 cells on metastases is currently studied.  Conclusion: The IGR-CaP1 cell line is one of the only in vitro and in vivo models obtained from localized prostate cancer. In contrast to previously established models from metastases tissue, IGR-CaP1 may be a suitable model to study molecular pathways implicated in the early steps of the oncogenic development of prostate cancer. Furthermore, its high tumorigenic properties make a potential model for both tumor progression and drug assessment in animals.
IS ROUTINE CORONARY ARTERY CALCIUM SCREENING FOR PRIMARY CARDIOVASCULAR RISK ASSESSMENT COST-EFFECTIVE? INSIGHT FROM THE RANDOMIZED CORCAL TRIAL
Authors: Jeffrey L. Anderson, Kirk Knowlton, Viet Le, Donald Lappe, Heidi May, David Min, Kevin Johnson, Shanelle T. Cripps, Lesley H. Schwab, Shelbi B. Braun, Tami Bair, J. Muhlestein
Journal: Journal of the American College of Cardiology (2021)
High PDGFRb Expression Predicts Resistance to Radiotherapy in DCIS within the SweDCIS Randomized Trial
Authors: Carina Strell, Dick Folkvaljon, Erik Holmberg, Aglaia Schiza, Viktoria Thurfjell, Per Karlsson, Jonas Bergh, Troy Bremer, Lars A. Akslen, Fredrik Wärnberg, Arne Östman
Journal: Clinical Cancer Research (2021)

Abstract Purpose: This study analyzes the potential of stromal platelet-derived growth factor receptor-beta (PDGFRb) expression as biomarker for radiotherapy (RT) benefit on ipsilateral breast events (IBE) in ductal carcinoma in situ (DCIS). Improved identification of DCIS patients refractory to adjuvant whole-breast RT is needed. Predictive biomarker studies in DCIS have focused on tumor cell features rather than the tumor-associated stroma, despite growing evidence of its influence on therapy efficiency. Experimental Design: Samples from the Swedish randomized radiotherapy DCIS trial (SweDCIS) were subjected to IHC analysis for stromal PDGFRb expression. IBE incidence at 10 years after breast-conserving surgery was the primary endpoint. Interactions between marker and treatment were analyzed. Results: PDGFRb score was predictive for RT benefit with regard to IBE (Pinteraction = 0.002 and Pinteraction = 0.008 adjusted multivariably). Patients of the PDGFRblow group had a strong benefit from RT regarding IBE risk [HR, 0.23; 95% confidence interval (CI), 0.12–0.45; P &amp;lt; 0.001] with an absolute risk reduction of 21% (cumulative risk 7% vs. 28%) at 10 years. No significant risk reduction by RT was observed for patients of the PDGFRbhigh group (HR, 0.83; 0.51–1.34; P = 0.444; cumulative risk 22% vs. 25%). The RT response–predictive effect of stromal PDGFRb was equally strong in analyses for in situ and invasive IBE when analyzed separately (in situ IBE: P = 0.029; invasive IBE: P = 0.044). Conclusions: Results suggest high stromal PDGFRb expression as a novel biomarker identifying DCIS patients who are refractory to standard whole-breast adjuvant RT. The data imply previously unrecognized fibroblast-mediated modulation of radiosensitivity of DCIS, which should be further explored from mechanistic and targeting perspectives.
NON-ALCOHOLIC FATTY LIVER DISEASE AND TYPE 2 DIABETES ARE MUTUALLY INDEPENDENT PREDICTORS OF CARDIOVASCULAR EVENTS IN PATIENTS WITH ESTABLISHED CARDIOVASCULAR DISEASE
Authors: Christoph H. Saely, Alexander Vonbank, Maximilian Maechler, Barbara Larcher, Lukas Sprenger, Arthur Mader, Beatrix Mutschlechner, Daniela Zanolin-Purin, Margaretha Klement, Andreas Leiherer, Axel Muendlein, Heinz Drexel
Journal: Journal of the American College of Cardiology (2021)
UTILIZATION AND OUTCOMES ASSOCIATED WITH INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY IN 1.3 MILLION PATIENTS UNDERGOING CABG: AN ANALYSIS OF THE SOCIETY OF THORACIC SURGEONS ADULT CARDIAC SURGERY DATABASE
Authors: Thomas S. Metkus, Dylan Thibault, Michael Grant, Vinay Badhwar, Jeffrey Jacobs, Jennifer Lawton, Sean O’Brien, Vinod Thourani, Zachary Wegermann, Brittany Zwischenberger, Robert Higgins
Journal: Journal of the American College of Cardiology (2021)
Views on mobile health apps for skin cancer screening in the general population: an in‐depth qualitative exploration of perceived barriers and facilitators*
Authors: T.E. Sangers, M. Wakkee, E.C. Kramer‐Noels, T. Nijsten, M. Lugtenberg
Journal: British Journal of Dermatology (2021)

Background Mobile health (mHealth) applications (apps) incorporating artificial intelligence for skin cancer screening are increasingly reimbursed by health insurers. However, an in-depth exploration of the general public's views towards these apps is lacking. Objectives To explore the perceived barriers and facilitators towards mHealth apps for skin cancer screening among the Dutch general population. Methods A qualitative study consisting of four focus groups with 27 participants was conducted. A two-stage purposive sampling method was used to include information-rich participants from the Dutch general population with varying experience of mHealth. A topic guide was used to structure the sessions. All focus group meetings were transcribed verbatim and analysed in thematic content analysis by two researchers using several coding phases, resulting in an overview of themes and subthemes, categorized as (sub-)barriers and (sub)facilitators. Results Main barriers to using mHealth apps included a perceived lack of value, perception of untrustworthiness, preference for a doctor, privacy concerns, a complex user interface, and high costs. The main factors facilitating the use of mHealth among the general population were a high perceived value, a transparent and trustworthy identity of app developers, endorsement by healthcare providers and government regulating bodies, and ease and low costs of use. Conclusions To increase successful adoption in skin cancer screening apps, developers should create a transparent identity and build trustworthy apps. Collaboration between app developers, general practitioners and dermatologists is advocated to improve mHealth integration with skin cancer care. Special attention should be given to the development of low-cost, privacy-friendly, easy-to-use apps.