tbuckley/cabot-search huggingface dataset:
Artificial intelligence and colonoscopy experience: lessons from two randomised trials
Authors: Alessandro Repici, Marco Spadaccini, Giulio Antonelli, Loredana Correale, Roberta Maselli, Piera Alessia Galtieri, Gaia Pellegatta, Antonio Capogreco, Sebastian Manuel Milluzzo, Gianluca Lollo, Dhanai Di Paolo, Matteo Badalamenti, Elisa Ferrara, Alessandro Fugazza, Silvia Carrara, Andrea Anderloni, Emanuele Rondonotti, Arnaldo Amato, Andrea De Gottardi, Cristiano Spada, Franco Radaelli, Victor Savevski, Michael B Wallace, Prateek Sharma, Thomas Rösch, Cesare Hassan
Journal: Gut (2021)

Background and aims Artificial intelligence has been shown to increase adenoma detection rate (ADR) as the main surrogate outcome parameter of colonoscopy quality. To which extent this effect may be related to physician experience is not known. We performed a randomised trial with colonoscopists in their qualification period (AID-2) and compared these data with a previously published randomised trial in expert endoscopists (AID-1). Methods In this prospective, randomised controlled non-inferiority trial (AID-2), 10 non-expert endoscopists (&lt;2000 colonoscopies) performed screening/surveillance/diagnostic colonoscopies in consecutive 40–80 year-old subjects using high-definition colonoscopy with or without a real-time deep-learning computer-aided detection (CADe) (GI Genius, Medtronic). The primary outcome was ADR in both groups with histology of resected lesions as reference. In a post-hoc analysis, data from this randomised controlled trial (RCT) were compared with data from the previous AID-1 RCT involving six experienced endoscopists in an otherwise similar setting. Results In 660 patients (62.3±10 years; men/women: 330/330) with equal distribution of study parameters, overall ADR was higher in the CADe than in the control group (53.3% vs 44.5%; relative risk (RR): 1.22; 95% CI: 1.04 to 1.40; p&lt;0.01 for non-inferiority and p=0.02 for superiority). Similar increases were seen in adenoma numbers per colonoscopy and in small and distal lesions. No differences were observed with regards to detection of non-neoplastic lesions. When pooling these data with those from the AID-1 study, use of CADe (RR 1.29; 95% CI: 1.16 to 1.42) and colonoscopy indication, but not the level of examiner experience (RR 1.02; 95% CI: 0.89 to 1.16) were associated with ADR differences in a multivariate analysis. Conclusions In less experienced examiners, CADe assistance during colonoscopy increased ADR and a number of related polyp parameters as compared with the control group. Experience appears to play a minor role as determining factor for ADR. Trial registration number NCT:04260321.
A large-scale nanoscopy and biochemistry analysis of postsynaptic dendritic spines
Authors: Martin S. Helm, Tal M. Dankovich, Sunit Mandad, Burkhard Rammner, Sebastian Jähne, Vanessa Salimi, Christina Koerbs, Richard Leibrandt, Henning Urlaub, Thomas Schikorski, Silvio O. Rizzoli
Journal: Nature Neuroscience (2021)
Nanoparticle and Biomolecule Surface Modification Synergistically Increases Neural Electrode Recording Yield and Minimizes Inflammatory Host Response
Authors: Kevin M. Woeppel, Xinyan Tracy Cui
Journal: Advanced Healthcare Materials (2021)

Abstract Due to their ability to interface with neural tissues, neural electrodes are the key tool used for neurophysiological studies, electrochemical detection, brain computer interfacing, and countless neuromodulation therapies and diagnostic procedures. However, the long‐term applications of neural electrodes are limited by the inflammatory host tissue response, decreasing detectable electrical signals, and insulating the device from the native environment. Surface modification methods are proposed to limit these detrimental responses but each has their own limitations. Here, a combinatorial approach is presented toward creating a stable interface between the electrode and host tissues. First, a thiolated nanoparticle (TNP) coating is utilized to increase the surface area and roughness. Next, the neural adhesion molecule L1 is immobilized to the nanoparticle modified substrate. In vitro, the combined nanotopographical and bioactive modifications (TNP+L1) elevate the bioactivity of L1, which is maintained for 28 d. In vivo, TNP+L1 modification improves the recording performance of the neural electrode arrays compared to TNP or L1 modification alone. Postmortem histology reveals greater neural cell density around the TNP+L1 coating while eliminating any inflammatory microglial encapsulation after 4 weeks. These results demonstrate that nanotopographical and bioactive modifications synergistically produce a seamless neural tissue interface for chronic neural implants.
<i>In Utero</i> Exposure to Heavy Metals and Trace Elements and Childhood Blood Pressure in a U.S. Urban, Low-Income, Minority Birth Cohort
Authors: Mingyu Zhang, Tiange Liu, Guoying Wang, Jessie P. Buckley, Eliseo Guallar, Xiumei Hong, Mei-Cheng Wang, Marsha Wills-Karp, Xiaobin Wang, Noel T. Mueller
Journal: Environmental Health Perspectives (2021)

In utero exposure to heavy metals lead (Pb), mercury (Hg), and cadmium (Cd) may be associated with higher childhood blood pressure (BP), whereas trace elements selenium (Se) and manganese (Mn) may have protective antioxidant effects that modify metal-BP associations. We examined the individual and joint effects of in utero exposure to Pb, Hg, Cd, Se, and Mn on childhood BP. We used data from the Boston Birth Cohort (enrolled 2002-2013). We measured heavy metals and trace elements in maternal red blood cells collected 24-72 h after delivery. We calculated child BP percentile per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We used linear regression models to estimate the association of each metal, and Bayesian kernel machine regression (BKMR) to examine metal coexposures, with child BP between 3 to 15 years of age. Our analytic sample comprised 1,194 mother-infant pairs (61% non-Hispanic Black, 20% Hispanic). Hg and Pb were not associated with child systolic BP (SBP). Se and Mn were inversely associated with child SBP percentiles, which, on average, were 6.23 points lower with a doubling of Se (95% CI: -11.51, -0.96) and 2.62 points lower with a doubling of Mn (95% CI: -5.20, -0.04). BKMR models showed similar results. Although Cd was not associated with child SBP overall, the inverse association between Mn and child SBP was stronger at higher levels of Cd (p-interaction=0.04). Consistent with this finding, in utero exposure to cigarette smoke modified the Mn-child SBP association. Among children whose mothers smoked during pregnancy, a doubling of Mn was associated with a 10.09-point reduction in SBP percentile (95% CI: -18.03, -2.15), compared with a 1.49-point reduction (95% CI: -4.21, 1.24) in children whose mothers did not smoke during pregnancy (p-interaction=0.08). Se and Mn concentrations in maternal red blood cells collected 24-72 h after delivery were associated with lower child SBP at 3 to 15 years of age. There was an interaction between Mn and Cd on child SBP, whereby the protective association of Mn on child SBP was stronger among mothers who had higher Cd. The association of Mn and child SBP was also modified by maternal cigarette smoking-a source of Cd-during pregnancy. Optimizing in utero Se levels, as well as Mn levels in women who had high Cd or smoked during pregnancy, may protect offspring from developing high BP during childhood. https://doi.org/10.1289/EHP8325.
Effects of Exercise on Cancer Treatment Efficacy: A Systematic Review of Preclinical and Clinical Studies
Authors: Lin Yang, Andria R. Morielli, Emily Heer, Amy A. Kirkham, Winson Y. Cheung, Nawaid Usmani, Christine M. Friedenreich, Kerry S. Courneya
Journal: Cancer Research (2021)

Abstract We systematically reviewed and synthesized evidence on the impact of physical activity/exercise on cancer treatment efficacy. We included six preclinical and seven clinical studies. Exercise significantly enhanced the efficacy of chemotherapy and tamoxifen in seven of eight rodent models in either an additive, sensitizing, or synergistic manner. In clinical studies, preliminary evidence indicates that exercise during neoadjuvant, primary, and adjuvant treatment may enhance efficacy of cancer therapies; however, no clinical study was designed for this purpose. Here we discuss the biological mechanisms of exercise-associated enhancement of therapeutic efficacy and propose future research directions to definitively examine the effects of exercise on cancer treatment and patient outcomes.
Circulating Thrombospondin-2 as a Novel Fibrosis Biomarker of Nonalcoholic Fatty Liver Disease in Type 2 Diabetes
Authors: Chi-Ho Lee, Wai-Kay Seto, David Tak-Wai Lui, Carol Ho-Yi Fong, Helen Yilin Wan, Chloe Yu-Yan Cheung, Wing-Sun Chow, Yu-Cho Woo, Man-Fung Yuen, Aimin Xu, Karen Siu-Ling Lam
Journal: Diabetes Care (2021)

OBJECTIVE Preclinical studies have suggested that thrombospondin-2 (TSP2) is implicated in liver fibrosis. However, the clinical relevance of TSP2 in nonalcoholic fatty liver disease (NAFLD) remains undefined. Here, we investigated the cross-sectional and longitudinal associations of circulating TSP2 levels with advanced fibrosis (F3 or greater [≥FE] fibrosis) in NAFLD. RESEARCH DESIGN AND METHODS Serum TSP2 levels were measured in 820 patients with type 2 diabetes and NAFLD. All participants received vibration-controlled transient elastography (VCTE) at baseline to evaluate their hepatic steatosis and fibrosis using controlled attenuation parameter (CAP) and liver stiffness (LS) measurements, respectively. Among those without advanced fibrosis at baseline, reassessment VCTE was performed to determine whether ≥F3 fibrosis had developed over time. Multivariable logistic regression analysis was used to evaluate the cross-sectional and longitudinal associations of serum TSP2 level with ≥F3 fibrosis. RESULTS Baseline serum TSP2 level was independently associated with the presence of ≥F3 fibrosis (odds ratio [OR] 5.13, P &amp;lt; 0.001). The inclusion of serum TSP2 level significantly improved the identification of ≥F3 fibrosis by clinical risk factors. Over a median follow-up of 1.5 years, 8.8% developed ≥F3 fibrosis. Baseline serum TSP2 level was significantly associated with incident ≥F3 fibrosis (OR 2.82, P = 0.005), independent of other significant clinical risk factors of fibrosis progression, including BMI, platelet count, and CAP at baseline. CONCLUSIONS Circulating TSP2 level was associated with both the presence and the development of advanced fibrosis and might be a potentially useful prognostic biomarker for the development and progression of liver fibrosis in patients with type 2 diabetes and NAFLD.
Integration of Functional Ex Vivo Drug Testing and Molecular Profiling Reveals Novel Vulnerabilities in CMML
Authors: Tea Pemovska, Gregory Ian Vladimer, Vitaly Sedlyarov, Emir Hadzijusufovic, Karoline Veronika Gleixner, Alexandra Keller, Berend Snijder, Nikolaus Krall, Oscar Lopez de la Fuente, Mathias A Schneeweiss, Wolfgang R. Sperr, Paul Knöbl, Klaus Geissler, Philipp Bernhard Staber, Ulrich Jaeger, Peter Valent, Giulio Superti Furga
Journal: Blood (2017)
Abstract 212: Aggregation of Child Cardiac Progenitor Cells into 3D Spheres Improves Endothelial Lineage Commitment
Authors: David Q Trac, Chunhui Xu, Michael E. Davis
Journal: Circulation Research (2016)

Congenital heart disease is rarely cured by surgery and can lead to life-threatening, intractable right ventricular heart failure (HF). In particular, children with hypoplastic left heart syndrome have a 10 year transplant-free survival rate of 50-75% despite palliative surgical repair. Currently, no effective stem-cell based treatments are available for pediatric HF. Recent stem-cell based clinical trials have been limited by poor differentiation rates and low cell retention. Additionally, we have shown that human cardiac progenitor cells (hCPCs) have reduced regenerative potential as they age, starting as early as 1 year old. We propose the aggregation of CPCs into scaffold-free spheres to improve the differentiation of child CPCs into mature cardiac phenotypes by enhancing intercellular Notch signaling. Notch signaling activity has been implicated in the regulation of CPC fate decisions and prior research in our lab has shown that intramyocardial delivery of Notch-ligand containing hydrogels improves cardiac function. Child CPC spheres were produced at a size of 1500 cells per sphere using a microwell array and cultured in suspension. Using immunohistochemistry, we showed that aggregation of CPCs increased Notch1 expression compared to parallel monolayer cultures. This effect is not limited to CPCs and was recapitulated in spheres of Chinese hamster ovarian cells transfected with Notch1-YFP. Additionally, Notch signaling pathway gene array data showed increased expression of the Notch-cleaving metalloprotease ADAM10 (3.6-fold) and Notch ligand DLL1 (25.0-fold) in CPC spheres by 3 days in culture compared to monolayer cultures. By 14 days in culture, we showed that aggregation of CPCs robustly increases the expression of the GATA4, a cardiac transcription factor associated with angiogenesis, and VEGFR1, an early marker of endothelial lineage commitment. Based on our results, we hypothesize that aggregation of CPCs into spheroids increases endothelial differentiation via a Notch-dependent mechanism. Transplantation of CPC spheres may improve cardiac function in vivo compared to transplantation of single CPCs. The results from our project will facilitate the development of autologous stem-cell based therapies for pediatric HF.
Symptoms, complications and management of long COVID: a review
Authors: Olalekan Lee Aiyegbusi, Sarah E Hughes, Grace Turner, Samantha Cruz Rivera, Christel McMullan, Joht Singh Chandan, Shamil Haroon, Gary Price, Elin Haf Davies, Krishnarajah Nirantharakumar, Elizabeth Sapey, Melanie J Calvert
Journal: Journal of the Royal Society of Medicine (2021)

Globally, there are now over 160 million confirmed cases of COVID-19 and more than 3 million deaths. While the majority of infected individuals recover, a significant proportion continue to experience symptoms and complications after their acute illness. Patients with 'long COVID' experience a wide range of physical and mental/psychological symptoms. Pooled prevalence data showed the 10 most prevalent reported symptoms were fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhoea. Other common symptoms were cognitive impairment, memory loss, anxiety and sleep disorders. Beyond symptoms and complications, people with long COVID often reported impaired quality of life, mental health and employment issues. These individuals may require multidisciplinary care involving the long-term monitoring of symptoms, to identify potential complications, physical rehabilitation, mental health and social services support. Resilient healthcare systems are needed to ensure efficient and effective responses to future health challenges.
Zemstvo doctor Vasyl Leontovych— the father of the dynasty of scientists
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2021)

The article describes the life and professional activity of zemstvo doctor, a descendant of the Zaporozhian Cossacks Vasyl Fedorovych Leontovych (1842–1888). The young man was a graduate of the Yekaterynoslav Classical Gymnasium in 1862. The doctor managed to start a dynasty of outstanding domestic scientists. His son Oleksandr became a physiologist, academician. His grandson Mykhailo is a physicist and academician; granddaughter Tatiana and great-granddaughter Natalia are doctors of medical sciences. The Leontovych family is an example of the medical dynasty of Cossacks.
AZD1222-induced neutralising antibody activity against SARS-CoV-2 Delta VOC
Authors: Emma C Wall, Mary Wu, Ruth Harvey, Gavin Kelly, Scott Warchal, Chelsea Sawyer, Rodney Daniels, Lorin Adams, Philip Hobson, Emine Hatipoglu, Yenting Ngai, Saira Hussain, Karen Ambrose, Steve Hindmarsh, Rupert Beale, Andrew Riddell, Steve Gamblin, Michael Howell, George Kassiotis, Vincenzo Libri, Bryan Williams, Charles Swanton, Sonia Gandhi, David LV Bauer
Journal: The Lancet (2021)
Sleep quality after COVID-19 infection
Authors: V. Badami, B. Hackett, S. Sharma, R. C. Stansbury
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Introduction: As the COVID-19 pandemic continues to worsen our understanding of the disease remains in its infancy, and the repercussions of acute COVID-19 infection are yet to be fully appreciated. Of the various morbidities suffered by survivors of this acute illness, the effects on mental health, quality of life, and changes in cognition have been of recent interest. These changes have long been associated with sleep fragmentation and disruption;moreover, significant cytokine storm and inflammatory response is a hallmark of acute COVID-19 infection, and previous studies have linked inflammatory pathways with the sleep dysregulation. We examined the change in sleep quality after severe acute COVID-19 infections requiring hospitalization. Methods: We performed a retrospective, single-center follow-up study of 20 patients with acute COVID-19 infection confirmed by PCR testing who had previously required hospital admission and deemed to have moderate to severe infection. Patients with a previous history of any diagnosed sleep disorder, including OSA, or those hospitalized within the last 30 days were excluded. Eligible patients were called and completed a telephone survey of the Pittsburgh Sleep Quality Index (PSQI) prior to and one month after COVID infection, with a score of 5 or above indicative of poor sleep quality. Secondary data from EMR including demographics, comorbid medical conditions, inflammatory markers, disease severity, measures of hypoxia and oxygenation and hospital length of stay were collected. ResultsThe mean PSQI prior to COVID-19 infection was 6.1, worsening to 10.3 one month after acute infection, denoting a delta-PSQI of 4.2 (p = 0.0004) as shown in Figure 1A. There were 6 out of 20 patients in whom sleep quality either improved or remained completely unchanged following COVID infection;these patients had poorer initial sleep quality (indicated by PSQI >5) than the 14 patients whose PSQI worsened (pre-infection PSQI 9.67 vs 4.57, p = 0.009). In the 14 patients whose sleep worsened after infection, on average they did not have sleep disturbances prior to COVID infection, and had a statistically significant increase in PSQI postinfection from 4.57 to 10.93 (p < 0.001) [Figure 1B]. There were no difference between groups in age, sex, BMI, hospital length of stay, mean PaO2/FiO2 ratio, rates of intubation, or inflammatory markers. Conclusions: In our study of patients with moderate-severe COVID-19 infections, those who had poor baseline sleep quality remained poor sleepers, while those without previous sleep disturbances had a significant worsening of sleep quality.
Inhibition of lysine methyltransferase G9a/GLP reinstates long-term synaptic plasticity and synaptic tagging/capture by facilitating protein synthesis in the hippocampal CA1 area of APP/PS1 mouse model of Alzheimer’s disease
Authors: Javan Lee Tze Han, Karen Ka Lam Pang, Sheila Rui Xia Ang, Mahima Sharma, Sreedharan Sajikumar
Journal: Translational Neurodegeneration (2021)
Lack of predictive tools for conventional and targeted cancer therapy: Barriers to biomarker development and clinical translation
Authors: Nikolaos Batis, Jill M. Brooks, Karl Payne, Neil Sharma, Paul Nankivell, Hisham Mehanna
Journal: Advanced Drug Delivery Reviews (2021)

Predictive tools, utilising biomarkers, aim to objectively assessthe potentialresponse toa particular clinical intervention in order to direct treatment.Conventional cancer therapy remains poorly served by predictive biomarkers, despite being the mainstay of treatment for most patients. In contrast, targeted therapy benefits from a clearly defined protein target for potential biomarker assessment. We discuss potential data sources of predictive biomarkers for conventional and targeted therapy, including patient clinical data andmulti-omicbiomarkers (genomic, transcriptomic and protein expression).Key examples, either clinically adopted or demonstrating promise for clinical translation, are highlighted. Following this, we provide an outline of potential barriers to predictive biomarker development; broadly discussing themes of approaches to translational research and study/trial design, and the impact of cellular and molecular tumor heterogeneity. Future avenues of research are also highlighted.
ANXA7 Regulates Platelet Lipid Metabolism and Ca <sup>2+</sup> Release in Arterial Thrombosis
Authors: Mailin-Christin Manke, Sascha Geue, Cristina Coman, Bing Peng, Ferdinand Kollotzek, Patrick Münzer, Britta Walker, Stephan M. Huber, Dominik Rath, Albert Sickmann, David Stegner, Daniel Duerschmied, Florian Lang, Bernhard Nieswandt, Meinrad Gawaz, Robert Ahrends, Oliver Borst
Journal: Circulation Research (2021)

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Abstract 14598: Ivabradine Induces Cardiac Protection by Preventing Inflammatory Response Through Inhibition of Cyclophilin-A Secretion After Myocardial Ischemia/Reperfusion Injury
Authors: Ignacio Hernandez Navarro, Rafael Ramirez-Carracedo, Laura Tesoro, Javier Diez Mata, Ricardo Garcia De la P, Paula Reventun, Jose L Zamorano, Marta Saura, Carlos Zaragoza
Journal: Circulation (2019)

Introduction: Inflammation and extracellular matrix proteolysis contribute with abnormal cardiac remodeling after ischemia/reperfusion injury. The binding of secreted Cyclophilin-A (CypA) with its ...
Midlife Wealth Mobility and Long-term Cardiovascular Health
Authors: Sara Machado, Andrew Sumarsono, Muthiah Vaduganathan
Journal: JAMA Cardiology (2021)

The association of socioeconomic status and cardiovascular outcomes has been well described, but little is known about whether longitudinal changes in wealth are associated with cardiovascular health status.To evaluate the association between midlife wealth mobility and risk of cardiovascular events.This longitudinal, retrospective cohort study included US adults 50 years or older who participated in the Health and Retirement Study. Participants in the primary analysis had no history of cardiovascular disease and had observations in at least two of three 5-year age intervals (50-54, 55-59, and 60-64 years) and follow-up after 65 years of age. Data were collected from January 1, 1992, to December 31, 2016, and analyzed from November 10, 2020, to April 26, 2021.Quintiles of wealth (reflecting total nonhousing assets) were defined within each of 4 birth cohorts (1931-1935, 1936-1940, 1941-1945, and 1946-1950). Wealth mobility was defined as an increase or a decrease of 1 or more wealth quintiles and was compared with wealth stability (same quintile over time) using covariate-adjusted Cox proportional hazards regression models.Composite outcome of nonfatal cardiovascular event (myocardial infarction, heart failure, cardiac arrhythmia, or stroke) or cardiovascular death.A total of 5579 participants were included in the primary analysis (mean [SD] age, 54.2 [2.6] years; 3078 women [55.2%]). During a mean (SD) follow-up of 16.9 (5.8) years, 1336 participants (24.0%) experienced a primary end point of nonfatal cardiovascular event or cardiovascular death (14.4 [95% CI, 13.6-15.2] per 1000 patient-years). Higher initial wealth (per quintile) was associated with lower cardiovascular risk (adjusted hazard ratio [aHR] per quintile, 0.89 [95% CI, 0.84-0.95]; P = .001). When compared with stable wealth, participants who experienced upward wealth mobility (by at least 1 quintile) had independently lower hazards of a subsequent nonfatal cardiovascular event or cardiovascular death (aHR, 0.84 [95% CI, 0.73-0.97]; P = .02), and participants who experienced downward wealth mobility had higher risks (aHR, 1.15 [95% CI, 1.00-1.32]; P = .046).These findings suggest that upward wealth mobility relative to peers in late middle age is associated with lower risks of cardiovascular events or death after 65 years of age.