tbuckley/cabot-search huggingface dataset:
Potential use of a novel telemetric sensor capsule in patients with suspected gastrointestinal bleeding during the COVID-19 pandemic
Authors: Ismaeil Elsayed, Benjamin Meier, Karel Caca, Andreas Wannhoff
Journal: Endoscopy (2021)

Upper gastrointestinal endoscopy during the COVID-19 pandemic carries a risk of disease transmission [1] [2]. The HemoPill (Ovesco Endoscopy, Tübingen, Germany) is composed of an orally administered telemetric sensor capsule that is capable of detecting blood and hematin, and a wireless receiver for data display [3] [4] [5]. Results are expressed as the HemoPill indicator (HI). A HI value ≥ 0.8 during the first 10 minutes of the examination or ≥ 1.0 thereafter denotes a positive test result. We evaluated this sensor capsule in patients with confirmed or suspected COVID-19.
Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial
Authors: Helga Blauw, A. Joannet Onvlee, Michel Klaassen, Arianne C. van Bon, J. Hans DeVries
Journal: Diabetes Care (2021)

OBJECTIVE To demonstrate the performance and safety of a bihormonal (insulin and glucagon) artificial pancreas (AP) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS In this outpatient, randomized, crossover trial, 2-week fully closed loop glucose control (AP therapy) was compared with 2-week open loop control (patient’s normal insulin pump therapy with a glucose sensor if they had one). RESULTS A total of 23 patients were included in the analysis. Time in range (70–180 mg/dL [3.9–10 mmol/L]) was significantly higher during closed loop (median 86.6% of time [interquartile range 84.9–88.5]) compared with open loop (53.9% [49.7–67.2]; P &amp;lt; 0.0001). CONCLUSIONS Compared with insulin pump therapy, the bihormonal AP provided superior glucose control, without meal or exercise announcements, and was safe in adults with type 1 diabetes.
Screening Tools for Identifying Older Adults With Cancer Who May Benefit From a Geriatric Assessment
Authors: Maja V. Garcia, Meera R. Agar, Wee-Kheng Soo, Timothy To, Jane L. Phillips
Journal: JAMA Oncology (2021)

<h3>Importance</h3> Older adults with cancer are at risk of overtreatment or undertreatment when decision-making is based solely on chronological age. Although a geriatric assessment is recommended to inform care, the time and expertise required limit its feasibility for all patients. Screening tools offer the potential to identify those who will benefit most from a geriatric assessment. Consensus about the optimal tool to use is lacking. <h3>Objective</h3> To appraise the evidence on screening tools used for older adults with cancer and identify an optimal screening tool for older adults with cancer who may benefit from geriatric assessment. <h3>Evidence Review</h3> Systematic review of 4 databases (MEDLINE, Embase, CINAHL [Cumulative Index to Nursing and Allied Health Literature], and PubMed) with narrative synthesis from January 1, 2000, to March 14, 2019. Studies reporting on the diagnostic accuracy and use of validated screening tools to identify older adults with cancer who need a geriatric assessment were eligible for inclusion. Data were analyzed from March 14, 2019, to March 23, 2020. <h3>Findings</h3> Seventeen unique studies were included, reporting on the use of 12 screening tools. Most studies were prospective cohort studies (n = 11) with only 1 randomized clinical trial. Not all studies reported time taken to administer the screening tools. The Geriatric-8 (G8) (n = 12) and the Vulnerable Elders Survey-13 (VES-13) (n = 9) were the most frequently evaluated screening tools. The G8 scored better in sensitivity and the VES-13 in specificity. Other screening tools evaluated include the Groningen Frailty Index, abbreviated comprehensive geriatric assessment, and Physical Performance Test in 2 studies each. All other screening tools were evaluated in 1 study each. <h3>Conclusions and Relevance</h3> To date, the G8 and VES-13 have the most evidence to recommend their use to inform the need for geriatric assessment. When choosing a screening tool, clinicians will need to weigh the tradeoffs between sensitivity and specificity. Future research needs to further validate or improve current screening tools and explore other factors that can influence their use, such as ease of use and resourcing.
Abstract 14847: Genetic Variation at the Coronary Artery Disease Risk Locus GUCY1A3 Modifies Cardiovascular Disease Prevention Effects of Aspirin
Authors: Kathryn T Hall, Thorsten Kessler, Julie Buring, Dani Passow, Howard Sesso, Robert Zee, Paul Ridker, Daniel Chasman, Heribert Schunkert
Journal: Circulation (2018)

Introduction: Efficacy of aspirin in primary prevention of cardiovascular disease (CVD) may be influenced by a common allele at GUCY1A3, shown to modify platelet function and increase CVD risk. Hyp...
A cross-platform approach identifies genetic regulators of human metabolism and health
Authors: Luca A. Lotta, Maik Pietzner, Isobel D. Stewart, Laura B. L. Wittemans, Chen Li, Roberto Bonelli, Johannes Raffler, Emma K. Biggs, Clare Oliver-Williams, Victoria P. W. Auyeung, Jian’an Luan, Eleanor Wheeler, Ellie Paige, Praveen Surendran, Gregory A. Michelotti, Robert A. Scott, Stephen Burgess, Verena Zuber, Eleanor Sanderson, Albert Koulman, Fumiaki Imamura, Nita G. Forouhi, Kay-Tee Khaw, Julian L. Griffin, Angela M. Wood, Gabi Kastenmüller, John Danesh, Adam S. Butterworth, Fiona M. Gribble, Frank Reimann, Melanie Bahlo, Eric Fauman, Nicholas J. Wareham, Claudia Langenberg
Journal: Nature Genetics (2021)
Therapeutic targets and potential agents for the treatment of COVID‐19
Authors: Yinuo Wu, Zhe Li, Yun‐Song Zhao, Yi‐You Huang, Mei‐Yan Jiang, Hai‐Bin Luo
Journal: Medicinal Research Reviews (2021)

Abstract The outbreak of coronavirus disease 2019 (COVID‐19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, has become a global crisis. As of November 9, COVID‐19 has already spread to more than 190 countries with 50,000,000 infections and 1,250,000 deaths. Effective therapeutics and drugs are in high demand. The structure of SARS‐CoV‐2 is highly conserved with those of SARS‐CoV and Middle East respiratory syndrome‐CoV. Enzymes, including RdRp, M pro /3CL pro , and PL pro , which play important roles in viral transcription and replication, have been regarded as key targets for therapies against coronaviruses, including SARS‐CoV‐2. The identification of readily available drugs for repositioning in COVID‐19 therapy is a relatively rapid approach for clinical treatment, and a series of approved or candidate drugs have been proven to be efficient against COVID‐19 in preclinical or clinical studies. This review summarizes recent progress in the development of drugs against SARS‐CoV‐2 and the targets involved.
Abstract 16497: Intensive Cardiac Rehabilitation and Traditional Cardiac Rehabilitation are Markedly Underutilized: Results From a Medicare Sample Analysis
Authors: Mustafa Husaini, Elena Deych, Susan B RACETTE, Michael W Rich, Karen E Joynt Maddox, Linda R Peterson
Journal: Circulation (2020)

Introduction: Cardiac rehabilitation (CR) is proven to improve cardiovascular outcomes in patients with heart disease. Intensive cardiac rehabilitation (ICR) was developed to enhance CR by adding sessions focused on nutrition, education, and stress management. ICR improves adiposity, lipid profiles, and exercise capacity vs. CR and has been Medicare-approved since 2010. Little is known about national utilization rates of ICR in the Medicare population or baseline characteristics associated with its use. Methods: A 5% sample of Medicare claims data from 2012 to 2015 was used to identify beneficiaries with a qualifying indication for CR/ICR (MI, CABG, valve surgery, PCI, heart transplant, heart failure, stable angina) and to quantify utilization of CR or ICR within 1 year of the index qualifying diagnosis. Results: From 2012-2015, there were 111,432 qualifying events in 107,261 Medicare beneficiaries. On average in this 5% sample, 15.6% of eligible beneficiaries (n = 17,422) completed at least 1 session of CR and only 0.1% (n = 108) completed at least 1 session of ICR. Rates of CR and ICR use (combined) increased by 2.95% to only 17.55% (Figure). The number of ICR centers (14 to 29 centers) increased over these 3 years. Those who attended CR or ICR were younger, more likely to be male and white, and have higher median income compared with eligible beneficiaries who did not attend. While participants that attended CR lived closer to the center (CR 5.5 miles; ICR 7.2 miles; p=0.01), there were no differences between CR and ICR enrollees with respect to age, sex, race, discharge location, median income, dual enrollment (Medicare + Medicaid), or number of comorbidities. Conclusions: Although the number of ICR centers has increased, CR and ICR remain markedly underutilized and ICR is not yet widely available. Continued research is needed to understand the barriers to program development, patient participation.
Aberrations of biochemical indicators in amyotrophic lateral sclerosis: a systematic review and meta-analysis
Authors: Yangfan Cheng, Yongping Chen, Huifang Shang
Journal: Translational Neurodegeneration (2021)

Accumulating evidence has suggested that the pathological changes in amyotrophic lateral sclerosis (ALS) are not only confined to the central nervous system but also occur in the peripheral circulating system. Here, we performed a meta-analysis based on the PubMed, EMBASE, EBSCO, and CNKI databases, to find out biochemical indicators associated with energy metabolism, iron homeostasis, and muscle injury that are altered in ALS patients and their correlations with ALS phenotypes. Forty-six studies covering 17 biochemical indicators, representing 5454 ALS patients and 7986 control subjects, were included in this meta-analysis. Four indicators, including fasting blood glucose level (weighted mean difference [WMD] = 0.13, 95% CI [0.06-0.21], p = 0.001), serum ferritin level (WMD = 63.42, 95% CI [48.12-78.73], p < 0.001), transferrin saturation coefficient level (WMD = 2.79, 95% CI [1.52-4.05], p < 0.001), and creatine kinase level (WMD = 80.29, 95% CI [32.90-127.67], p < 0.001), were significantly higher in the ALS patients, whereas the total iron-binding capacity (WMD = - 2.42, 95% CI [- 3.93, - 0.90], p = 0.002) was significantly lower in ALS patients than in the control subjects. In contrast, the other 12 candidates did not show significant differences between ALS patients and controls. Moreover, pooled hazard ratios (HR) showed significantly reduced survival (HR = 1.38, 95% CI [1.02-1.88], p = 0.039) of ALS patients with elevated serum ferritin levels. These findings suggest that abnormalities in energy metabolism and disruption of iron homeostasis are involved in the pathogenesis of ALS. In addition, the serum ferritin level is negatively associated with the overall survival of ALS patients.
Abstract 14153: Cardiovascular Disease Risk Factor Knowledge Among Monolingual Hispanics
Authors: Maria O Gore, Stephanie Coronel-Mockler, Raymond Estacio, Mori J Krantz
Journal: Circulation (2019)

Introduction: Hispanics have worse cardiovascular disease (CVD) risk factor profiles compared with non-Hispanic Whites, and although CVD mortality is relatively lower (“the Hispanic paradox”), CVD ...
Abstract 15336: Real-world Diagnostic Performance of Single-lead Handheld Electrocardiograms for Atrial Fibrillation Screening: The Vital-af Trial
Authors: Shaan Khurshid, Yuchiao Chang, Wyliena Guan, Ana Lipsanopoulos, Leila H Borowsky, Patrick T Ellinor, David D McManus, Steven Atlas, Daniel Singer, Jeffrey M Ashburner, Steven Lubitz
Journal: Circulation (2020)

Introduction: AF screening can detect undiagnosed AF, but concerns exist regarding false positives and downstream consequences. AF screening using single-lead handheld electrocardiograms (1L ECGs) is feasible, but diagnostic performance in a pragmatic screening setting is not well-understood. Methods: VITAL-AF is a cluster-randomized trial (NCT035115057) of population-based AF screening with 30-second 1L ECGs. Individuals aged ≥65 years receiving primary care in a study practice were eligible, with practices randomized to screening (n=8) or usual care (n=8). Screening was performed with the AliveCor Kardia 1L ECG (AliveCor US) administered by medical assistants. In addition to the AliveCor interpretation, all 1L ECGs were overread by cardiologists. We assessed the distribution of automated interpretations and predictive values using cardiologist 1L ECG overread as the gold standard. Results: Screening generated 38,190 tracings representing 16,496 individuals read by 13 cardiologists (median time to read: 10h, quartile 1: 5, quartile 3: 19). We removed 1,554 tracings overread as uninterpretable, resulting in 36,636 tracings in the analysis. A total of 27,251 (74.4%) tracings had an AliveCor interpretation of normal, 6,223 (17.0%) unclassified, 2,420 (6.6%) possible AF, and 742 (2.0%) no interpretation. The positive predictive value (PPV) of possible AF by AliveCor was 76.2% (95% CI 74.5-77.9, Figure ). The negative predictive values (NPVs) were 99.7% (95% CI 99.6-99.8) for normal, 92.3% (95% CI 91.6-92.9) for unclassified, and 87.1% (95% CI 84.4-89.4) for no interpretation. Of 2,502 tracings overread as AF, 482 (19.3%) were unclassified by AliveCor. Conclusions: In an elderly primary care population, the PPV of possible AF by AliveCor algorithm was modest, whereas the NPV of a normal interpretation was very high. Unclassified tracings were common and enriched for AF. Abnormal findings, including unclassified 1L ECG tracings, merit follow-up testing.
Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease
Authors: Aaron Waxman, Ricardo Restrepo-Jaramillo, Thenappan Thenappan, Ashwin Ravichandran, Peter Engel, Abubakr Bajwa, Roblee Allen, Jeremy Feldman, Rahul Argula, Peter Smith, Kristan Rollins, Chunqin Deng, Leigh Peterson, Heidi Bell, Victor Tapson, Steven D. Nathan
Journal: New England Journal of Medicine (2021)

No therapies are currently approved for the treatment of pulmonary hypertension in patients with interstitial lung disease. The safety and efficacy of inhaled treprostinil for patients with this condition are unclear.We enrolled patients with interstitial lung disease and pulmonary hypertension (documented by right heart catheterization) in a multicenter, randomized, double-blind, placebo-controlled, 16-week trial. Patients were assigned in a 1:1 ratio to receive inhaled treprostinil, administered by means of an ultrasonic, pulsed-delivery nebulizer in up to 12 breaths (total, 72 μg) four times daily, or placebo. The primary efficacy end point was the difference between the two groups in the change in peak 6-minute walk distance from baseline to week 16. Secondary end points included the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level at week 16 and the time to clinical worsening.A total of 326 patients underwent randomization, with 163 assigned to inhaled treprostinil and 163 to placebo. Baseline characteristics were similar in the two groups. At week 16, the least-squares mean difference between the treprostinil group and the placebo group in the change from baseline in the 6-minute walk distance was 31.12 m (95% confidence interval [CI], 16.85 to 45.39; P<0.001). There was a reduction of 15% in NT-proBNP levels from baseline with inhaled treprostinil as compared with an increase of 46% with placebo (treatment ratio, 0.58; 95% CI, 0.47 to 0.72; P<0.001). Clinical worsening occurred in 37 patients (22.7%) in the treprostinil group as compared with 54 patients (33.1%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40 to 0.92; P = 0.04 by the log-rank test). The most frequently reported adverse events were cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea.In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline, assessed with the use of a 6-minute walk test, as compared with placebo. (Funded by United Therapeutics; INCREASE ClinicalTrials.gov number, NCT02630316.).
ROR1 targeting with the antibody-drug conjugate VLS-101 is effective in Richter syndrome patient–derived xenograft mouse models
Authors: Tiziana Vaisitti, Francesca Arruga, Nicoletta Vitale, Thanh-Trang Lee, Mira Ko, Amy Chadburn, Esteban Braggio, Arianna Di Napoli, Andrea Iannello, John N. Allan, Langdon L. Miller, Brian J. Lannutti, Richard R. Furman, Katti A. Jessen, Silvia Deaglio
Journal: Blood (2021)
MO01.09 Phase 2 Basket Trial of Lurbinectedin in Small-Cell Lung Cancer (SCLC): Analysis of Efficacy by Baseline Characteristics
Authors: J. Sands, L. Paz-Ares, B. Besse, S. Peters, M.A. Sala, J.A. López-Vilariño, C. Fernández, C. Kahatt, A. Zeaiter, A. Nieto, M. Siguero, K. Zaman, J. Arrondeau, J.-P. Delord, M. Martínez, A. Antón, A. Awada, R. Kristeleit, M.E. Olmedo, M.J. Rubio, J. Sarantopoulos, J. Mosquera-Martinez, M. D’Arcangelo, A. Santoro, José M. Trigo, V. Subbiah, J. Arrondeau
Journal: Journal of Thoracic Oncology (2021)
OFP01.05 Circulating Ensembles of Tumor Associated Cells Facilitate Efficient Triaging of Asymptomatic Individuals for Low Dose Computed Tomography
Authors: D. Akolkar, D. Patil, S. Limaye, P. Fulmali, P. Fulmali, A. Adhav, S. Apurwa, S. Pawar, S. Patel, R. Chougule, V. Ranjan, P. Shejwalkar, S. Khan, R. Dhasarathan, V. Datta, S. Schuster, P. Kumar, C. Sims, P. Devhare, A. Srinivasan, R. Datar
Journal: Journal of Thoracic Oncology (2021)
Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice
Authors: Sikai Ling, Shiqi Yang, Xinde Hu, Di Yin, Yao Dai, Xiaoqing Qian, Dawei Wang, Xiaoyong Pan, Jiaxu Hong, Xiaodong Sun, Hui Yang, Soren Riis Paludan, Yujia Cai
Journal: Nature Biomedical Engineering (2021)
Co-delivery of 5-fluorouracil and miRNA-34a mimics by host-guest self-assembly nanocarriers for efficacious targeted therapy in colorectal cancer patient-derived tumor xenografts
Authors: Jianbin Xu, Guolin Zhang, Xin Luo, Di Wang, Wei Zhou, Yan Zhang, Wei Zhang, Jiaxin Chen, Qing Meng, Engeng Chen, Heng Chen, Zhangfa Song
Journal: Theranostics (2021)

Rationale: A co-delivery system that can transport chemotherapeutic drugs and nucleotide drugs to distinct targets in tumors is an attractive strategy for cancer therapy. In this study, well-defined targeted quantum dot (QD)-based multifunctional nanocarriers were developed through self-assembly driven by host-guest interactions. 5-fluorouracil (5-FU) and microRNA-34a mimics (miR-34a(m)) were co-administered to achieve synergistic effects for colorectal cancer (CRC) therapy for the first time. Furthermore, the CRC patient-derived tumor xenograft (PDX) model, which closely mimics human CRC tumor pathological properties, was used for evaluating the therapeutic effect in this research. Methods: Multiple β-cyclodextrin (CD)-attached QD nanoparticles were used as host molecules. An adamantane (ADA)-modified TCP1 peptide-targeting ligand (TCP1) was used as the guest molecule. 5-FU and miR-34a(m) were loaded into TCP1-CD-QD nanocarriers, which were used to treat CRC in vitro and in vivo. In addition, the CRC PDX model was used to evaluate the treatment efficacy of this co-delivery system. Results: 5-FU and miR-34a(m) can be efficiently encapsulated into TCP1-CD-QD nanocarriers and delivered into CRC cells, which led to the inhibition of the proliferation and migration of CRC cells in vitro and suppression of tumor growth in a CRC cell-derived tumor xenograft model. The obtained data further suggested that co-delivery of 5-FU and miR-34a(m) could achieve synergistic effects for CRC therapy. Notably, targeted therapy via the co-delivery of 5-FU and miR-34a(m) by TCP1-CD-QD nanocarriers significantly inhibited the growth of PDX tumors. Conclusions: These studies strongly indicate that such a nanocarrier-based co-delivery system is a promising combined therapeutic strategy that utilizes chemotherapeutic drugs and nucleotide drugs for enhancing colorectal cancer targeting and synergistic therapy.
Methotrexate impacts conserved pathways in diverse human gut bacteria leading to decreased host immune activation
Authors: Renuka R. Nayak, Margaret Alexander, Ishani Deshpande, Kye Stapleton-Gray, Bipin Rimal, Andrew D. Patterson, Carles Ubeda, Jose U. Scher, Peter J. Turnbaugh
Journal: Cell Host & Microbe (2021)
Targeting the IRAK1–S100A9 Axis Overcomes Resistance to Paclitaxel in Nasopharyngeal Carcinoma
Authors: Lizhen Liu, Sailan Liu, Peng Deng, Yujing Liang, Rong Xiao, Lin-Quan Tang, Jinghong Chen, Qiu-Yan Chen, Peiyong Guan, Shu-Mei Yan, Xiangliang Huang, Jing Han Hong, Jianfeng Chen, Yichen Sun, Bin Tean Teh, Qiang Yu, Hai-Qiang Mai, Jing Tan
Journal: Cancer Research (2021)

Abstract Novel strategies to treat late-stage nasopharyngeal carcinoma that often develop resistance to chemotherapy remains an unmet clinical demand. In this study, we identify the multi-kinase inhibitor pacritinib as capable of resensitizing the response to paclitaxel in an acquired resistance model. Transcriptome analysis of paclitaxel-sensitive and -resistant cell lines, as well as chemorefractory clinical samples, identified S100A9 as the top candidate gene suppressed by pacritinib and whose overexpression was significantly associated with paclitaxel resistance and poor clinical outcome. Moreover, both paclitaxel-resistant nasopharyngeal carcinoma cells and relapsed/metastatic clinical samples exhibited increased IRAK1 phosphorylation and demonstrated that pacritinib could abolish the IRAK1 phosphorylation to suppress S100A9 expression. Functional studies in both in vitro and in vivo models showed that genetic or pharmacologic blockade of IRAK1 overcame the resistance to paclitaxel, and combined treatment of pacritinib with paclitaxel exhibited superior antitumor effect. Together, these findings demonstrate an important role for the IRAK1–S100A9 axis in mediating resistance to paclitaxel. Furthermore, targeting of IRAK1 by pacritinib may provide a novel therapeutic strategy to overcome chemoresistance in nasopharyngeal carcinoma. Significance: Deregulation of the IRAK1–S100A9 axis correlates with poor prognosis, contributes to chemoresistance in nasopharyngeal carcinoma, and can be targeted by pacritinib to overcome chemoresistance in nasopharyngeal carcinoma.