tbuckley/cabot-search huggingface dataset:
The Effects of Vitamin D and Marine Omega‐3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial
Authors: Lindsey A. MacFarlane, Nancy R. Cook, Eunjung Kim, I‐Min Lee, Maura D. Iversen, David Gordon, Julie E. Buring, Jeffrey N. Katz, JoAnn E. Manson, Karen H. Costenbader
Journal: Arthritis & Rheumatology (2020)

Knee pain from osteoarthritis is frequent in the adult population. Prior trials have had conflicting results concerning the therapeutic effects of vitamin D on knee pain, and few trials have investigated marine Omega-3 fatty acids (n-3 FA).
Evaluation of the Merits and Limitations of Evidence-Based Medicine
Authors: Emily Y. Chu, Jennifer A. Stein, Michael E. Ming
Journal: JAMA Dermatology (2020)

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Spatiotemporal PET Imaging Reveals Differences in CAR-T Tumor Retention in Triple-Negative Breast Cancer Models
Authors: Alessia Volpe, Cameron Lang, Lindsay Lim, Francis Man, Ewelina Kurtys, Candice Ashmore-Harris, Preeth Johnson, Elena Skourti, Rafael T.M. de Rosales, Gilbert O. Fruhwirth
Journal: Molecular Therapy (2020)

Chimeric antigen receptor T cell therapy (CAR-T) has been rolled out as a new treatment for hematological malignancies. For solid tumor treatment, CAR-T has been disappointing so far. Challenges include the quantification of CAR-T trafficking, expansion and retention in tumors, activity at target sites, toxicities, and long-term CAR-T survival. Non-invasive serial in vivo imaging of CAR-T using reporter genes can address several of these challenges. For clinical use, a non-immunogenic reporter that is detectable with exquisite sensitivity by positron emission tomography (PET) using a clinically available non-toxic radiotracer would be beneficial. Here, we employed the human sodium iodide symporter to non-invasively quantify tumor retention of pan-ErbB family targeted CAR-T by PET. We generated and characterized traceable CAR T cells and examined potential negative effects of radionuclide reporter use. We applied our platform to two different triple-negative breast cancer (TNBC) models and unexpectedly observed pronounced differences in CAR-T tumor retention by PET/CT (computed tomography) and confirmed data ex vivo. CAR-T tumor retention inversely correlated with immune checkpoint expression in the TNBC models. Our platform enables highly sensitive non-invasive PET tracking of CAR-T thereby addressing a fundamental unmet need in CAR-T development and offering to provide missing information needed for future clinical CAR-T imaging.
Assessment of Physician Prescribing of Muscle Relaxants in the United States, 2005-2016
Authors: Samantha E. Soprano, Sean Hennessy, Warren B. Bilker, Charles E. Leonard
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Little is known to date about national trends in the prescribing of skeletal muscle relaxants (SMRs), the use of which is associated with important safety concerns, especially in older adults and in those who use concomitant opioids. <h3>Objective</h3> To measure national trends in SMR prescribing over a 12-year period. <h3>Design, Setting, and Participants</h3> This cross-sectional study used data from the National Ambulatory Medical Care Survey from January 2005 to December 2016. Data were analyzed from August 21, 2018, to July 18, 2019. The study included patients with ambulatory care visits who had encounters with non–federally funded, office-based physicians in the United States. <h3>Exposures</h3> SMR use, categorized as newly prescribed or continued therapy at the office visit. <h3>Main Outcomes and Measures</h3> Ambulatory care visits—overall and stratified by calendar year, geographic region, and patient age, sex, and race—in which an SMR was newly prescribed or continued were quantified. Among office visits in which an SMR was newly prescribed, diagnoses were assessed. Concomitant medications were quantified for all office visits, stratified by new or continued therapy. Survey visit weights were used to estimate nationally representative measures, and age-standardized rates were generated by geographic region using US Census data. <h3>Results</h3> This study included a total of 314 970 308 office visits (mean [SD] age, 53.5 [15.2] years; 194 621 102 [61.8%] men and 120 349 206 [38.2%] women). In 2016, there were 30 730 262 (95% CI, 30 626 464-30 834 060) US ambulatory care visits in which an SMR was either newly prescribed or continued as ongoing therapy. Patients in these visits were most frequently female (58.2% [95% CI, 57.9%-58.6%]), white (53.7% [95% CI, 53.4%-54.0%]), and aged 45 to 64 years (48.5% [95% CI, 48.2%-48.9%]). During the study period, office visits with a prescribed SMR nearly doubled from 15.5 million (95% CI, 15.4-15.6 million) in 2005 to 30.7 million (95% CI, 30.6-30.8 million) in 2016. Although visits for new SMR prescriptions remained stable, office visits with continued SMR drug therapy tripled from 8.5 million (95% CI, 8.4-8.5 million) visits in 2005 to 24.7 million (95% CI, 24.6-24.8 million) visits in 2016. Older adults accounted for 22.2% (95% CI, 21.8%-22.6%) of visits with an SMR prescription. Concomitant use of an opioid was recorded in 67.2% (95% CI, 62.0%-72.5%) of all visits with a continuing SMR prescription. <h3>Conclusions and Relevance</h3> This study found that SMR use increased rapidly between 2005 and 2016, which is a concern given the prominent adverse effects and limited long-term efficacy data associated with their use. These findings suggest that approaches are needed to limit the long-term use of SMRs, especially in older adults, similar to approaches to limit long-term use of opioids and benzodiazepines.
Characterization of the Inflammatory Response to Severe COVID-19 Illness
Authors: Oliver J. McElvaney, Natalie L. McEvoy, Oisín F. McElvaney, Tomás P. Carroll, Mark P. Murphy, Danielle M. Dunlea, Orna Ní Choileáin, Jennifer Clarke, Eoin O’Connor, Grace Hogan, Daniel Ryan, Imran Sulaiman, Cedric Gunaratnam, Peter Branagan, Michael E. O’Brien, Ross K. Morgan, Richard W. Costello, Killian Hurley, Seán Walsh, Eoghan de Barra, Cora McNally, Samuel McConkey, Fiona Boland, Sinead Galvin, Fiona Kiernan, James O’Rourke, Rory Dwyer, Michael Power, Pierce Geoghegan, Caroline Larkin, Ruth Aoibheann O’Leary, James Freeman, Alan Gaffney, Brian Marsh, Gerard F. Curley, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1β, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1β, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.
Low dose computed tomography of the lung for detection and grading of interstitial lung disease: A systematic simulation study
Authors: S. Ley, L. Fidler, H. Schenk, M. Durand, T. Marras, N. Paul, S. Shapera, S. Mittoo
Journal: Pulmonology (2020)

HRCT is the preferred imaging technique to evaluate Interstitial-Lung-Disease. Optimal Low-Dose-Computed-Tomography protocol for monitoring ILD with lowest radiation dose and optimal diagnostic accuracy and image quality unknown.28 Patients underwent HRCT. Image reconstructions with varying combinations of tube current (50mA, 20mA, 15 mA, 10mA) and image-thickness/increment (1/1mm, 2/2mm, 3/2.4mm, 5/4mm) were simulated from raw data. 448 CTs evaluated by 2 readers on image quality and ILD-specific features (ground glass opacification (ggo), honeycombing (hc), reticulation (ret)).Reduced dose settings with 20 mA did not show any significant difference to standard dose settings for all parameters in reader 1, while results were significantly altered in reader 2. Slice thickness did not significantly influence rating of typical ILD features like ggo, hc, ret or total disease extent. The correct differentiation between UIP and NSIP could be made on all dose settings and with all slice thickness. It was even found, that an increased slice thickness can compensate for the noise associated image quality degradation. Overall, for ggo detection a combination of 20 mA and 3 or 5 mm slice thickness was not different to the original evaluation.Assessment of ILD specific CT features down to 20 mA and a slice thickness of 3 or 5 mm is feasible.
Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient mice
Authors: Klytaimnistra Kiouptsi, Giulia Pontarollo, Hristo Todorov, Johannes Braun, Sven Jäckel, Thomas Koeck, Franziska Bayer, Cornelia Karwot, Angelica Karpi, Susanne Gerber, Yvonne Jansen, Philipp Wild, Wolfram Ruf, Andreas Daiber, Emiel Van Der Vorst, Christian Weber, Yvonne Döring, Christoph Reinhardt
Journal: Gut Microbes (2020)

The microbiota has been linked to the development of atherosclerosis, but the functional impact of these resident bacteria on the lesion size and cellular composition of atherosclerotic plaques in the aorta has never been experimentally addressed with the germ-free low-density lipoprotein receptor-deficient (Ldlr-/- ) mouse atherosclerosis model. Here, we report that 16 weeks of high-fat diet (HFD) feeding of hypercholesterolemic Ldlr-/- mice at germ-free (GF) housing conditions did not impact relative aortic root plaque size, macrophage content, and necrotic core area. Likewise, we did not find changes in the relative aortic arch lesion size. However, late atherosclerotic GF Ldlr-/- mice had altered inflammatory plasma protein markers and reduced smooth muscle cell content in their atherosclerotic root plaques relative to CONV-R Ldlr-/- mice. Neither absolute nor relative aortic root or aortic arch plaque size correlated with age. Our analyses on GF Ldlr-/- mice did not reveal a significant contribution of the microbiota in late aortic atherosclerosis.
Single-cell transcriptome and antigen-immunoglobin analysis reveals the diversity of B cells in non-small cell lung cancer
Authors: Jian Chen, Yun Tan, Fenghuan Sun, Likun Hou, Chi Zhang, Tao Ge, Huansha Yu, Chunxiao Wu, Yuming Zhu, Liang Duan, Liang Wu, Nan Song, Liping Zhang, Wei Zhang, Di Wang, Chang Chen, Chunyan Wu, Gening Jiang, Peng Zhang
Journal: Genome biology (2020)

Malignant transformation and progression of cancer are driven by the co-evolution of cancer cells and their dysregulated tumor microenvironment (TME). Recent studies on immunotherapy demonstrate the efficacy in reverting the anti-tumoral function of T cells, highlighting the therapeutic potential in targeting certain cell types in TME. However, the functions of other immune cell types remain largely unexplored.We conduct a single-cell RNA-seq analysis of cells isolated from tumor tissue samples of non-small cell lung cancer (NSCLC) patients, and identify subtypes of tumor-infiltrated B cells and their diverse functions in the progression of NSCLC. Flow cytometry and immunohistochemistry experiments on two independent cohorts confirm the co-existence of the two major subtypes of B cells, namely the naïve-like and plasma-like B cells. The naïve-like B cells are decreased in advanced NSCLC, and their lower level is associated with poor prognosis. Co-culture of isolated naïve-like B cells from NSCLC patients with two lung cancer cell lines demonstrate that the naïve-like B cells suppress the growth of lung cancer cells by secreting four factors negatively regulating the cell growth. We also demonstrate that the plasma-like B cells inhibit cancer cell growth in the early stage of NSCLC, but promote cell growth in the advanced stage of NSCLC. The roles of the plasma-like B cell produced immunoglobulins, and their interacting proteins in the progression of NSCLC are further validated by proteomics data.Our analysis reveals versatile functions of tumor-infiltrating B cells and their potential clinical implications in NSCLC.
Cognitive Bias and Public Health Policy During the COVID-19 Pandemic
Authors: Scott D. Halpern, Robert D. Truog, Franklin G. Miller
Journal: JAMA (2020)

This Viewpoint reviews common cognitive biases that led health centers and the public to favor patient- over population health–oriented policy responses to the initial COVID-19 pandemic, and proposes messaging to better articulate the rationale for more effective population health responses.
Bioresorbable, Wireless, Passive Sensors as Temporary Implants for Monitoring Regional Body Temperature
Authors: Di Lu, Ying Yan, Raudel Avila, Irawati Kandela, Iwona Stepien, Min‐Ho Seo, Wubin Bai, Quansan Yang, Chenhang Li, Chad R. Haney, Emily A. Waters, Matthew R. MacEwan, Yonggang Huang, Wilson Z. Ray, John A. Rogers
Journal: Advanced Healthcare Materials (2020)

Measurements of regional internal body temperatures can yield important information in the diagnosis of immune response-related anomalies, for precisely managing the effects of hyperthermia and hypothermia therapies and monitoring other transient body processes such as those associated with wound healing. Current approaches rely on permanent implants that require extraction surgeries after the measurements are no longer needed. Emerging classes of bioresorbable sensors eliminate the requirements for extraction, but their use of percutaneous wires for data acquisition leads to risks for infection at the suture site. As an alternative, a battery-free, wireless implantable device is reported here, which is constructed entirely with bioresorbable materials for monitoring regional internal body temperatures over clinically relevant timeframes. Ultimately, these devices disappear completely in the body through natural processes. In vivo demonstrations indicate stable operation as subcutaneous and intracranial implants in rat models for up to 4 days. Potential applications include monitoring of healing cascades associated with surgical wounds, recovery processes following internal injuries, and the progression of thermal therapies for various conditions.
Covid-19: scientific advisers must do more than just voice their concerns behind closed doors
Authors: Minesh Khashu
Journal: BMJ (2020)

Abbasi raises the important issue of conscience and duty for scientific advisers in the covid-19 pandemic.1

We expect all people in public office to abide by the Nolan principles,2 but time and again, we have found many falling short. The yardstick is even more stringent for scientific and medical advisers, who …
Alginate‐based complex fibers with the Janus morphology for controlled release of co‐delivered drugs
Authors: Wing-Fu Lai, Eric Huang, Kwok-Ho Lui
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Hydrogels are soft materials consisting of a three-dimensional network of polymer chains. Over the years, hydrogels with different compositions have been developed as drug carriers for diverse biomedical applications, ranging from cancer therapy and wound care to the treatment of neurodegenerative and inflammatory diseases. Most of these carriers, however, are designed only to deliver single agents. Carriers based on hydrogels for co-delivery of multiple agents, with the release rate of each of the co-delivered agents tunable, are lacking. This study reports a one-pot method of fabricating alginate-based complex fibers with the Janus morphology, with carboxymethyl cellulose sodium functioning as a polymeric modifier of the properties of each of the fiber compartments. By using malachite green and minocycline hydrochloride as model drugs, the generated fibers demonstrate the capacity of enabling the release profile of each of the co-delivered drugs to be precisely controlled. Along with their negligible toxicity and the retention of the activity of the loaded drugs, the complex fibers reported in this study warrant further development and optimization for applications that involve co-delivery of multiple agents.
Genetic analyses support the contribution of mRNA N6-methyladenosine (m6A) modification to human disease heritability
Authors: Zijie Zhang, Kaixuan Luo, Zhongyu Zou, Maguanyun Qiu, Jiakun Tian, Laura Sieh, Hailing Shi, Yuxin Zou, Gao Wang, Jean Morrison, Allen C. Zhu, Min Qiao, Zhongshan Li, Matthew Stephens, Xin He, Chuan He
Journal: Nature Genetics (2020)
Do Nicotinic Receptors Modulate High-Order Cognitive Processing?
Authors: Fani Koukouli, Jean-Pierre Changeux
Journal: Trends in Neurosciences (2020)

Recent studies provided strong evidence that deficits in cholinergic signaling cause disorders of cognition and affect conscious processing. Technical advances that combine molecular approaches, in vivo recordings in awake behaving animals, human brain imaging, and genetics have strengthened our understanding of the roles of nicotinic acetylcholine receptors (nAChRs) in the modulation of cognitive behavior and network dynamics. Here, we review the emergent role of nAChRs in high-order cognitive processes and discuss recent work implicating cholinergic circuits in cognitive control, including conscious processing.
Bisphosphonate-based nanocomposite hydrogels for biomedical applications
Authors: Weihao Yuan, Zhuo Li, Xian Xie, Zhi-Yong Zhang, Liming Bian
Journal: Bioactive Materials (2020)

Nanocomposite hydrogels consist of polymeric network embedded with functional nanoparticles or nanostructures, which not only contribute to the enhanced mechanical properties but also exhibit the bioactivities for regulating cell behavior. Bisphosphonates (BPs) are capable of coordinating with various metal ions and modulating bone homeostasis. Thanks to the inherent dynamic properties of metal-ligand coordination bonds, BP-based nanocomposite hydrogels possess tunable mechanical properties, highly dynamic structures, and the capability to mediate controlled release of encapsulated therapeutic agents, thereby making them highly versatile for various biomedical applications. This review presents the comprehensive overview of recent developments in BP-based nanocomposite hydrogels with an emphasis on the properties of embedded nanoparticles (NPs) and interactions between hydrogel network and NPs. Furthermore, various challenges in the biomedical applications of these hydrogels are discussed to provide an outlook of potential clinical translation.
Personal Protective Equipment and Covid-19
Authors: Ala Nozari, Rafael Ortega, Mauricio Gonzalez
Journal: New England Journal of Medicine (2020)

To the Editor: The video by Ortega et al. (published on May 19 at NEJM.org) 1 is practical.However, we think that some of the details in the video do not meet the strict requirements for epidemic prevention or at least should be improved.The routes of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), include direct contact and indirect contact.More importantly, SARS-CoV-2 may maintain its biologic stability in aerosol and on different surfaces for hours to days. 2 In the care of patients with infectious viruses such as Ebola, a principle of protection for staff wearing personal protective equipment (PPE) is to not expose their skin. 3 This principle should also apply to the care of patients with SARS-CoV-2.We think that staff should place a hood over the head, ensuring that it overlaps the gown and covers the head and neck fully.In addition, a study showed that SARS-CoV-2 was widely distributed on floors and in trash cans in hospital wards. 4 Another study showed that SARS-CoV-2 RNA in aerosol was detected in protective-apparel removal rooms. 5 These studies suggest that to minimize the risk of infection, staff should wear disposable shoe covers in wards, use covered waste receptacles, and disinfect PPE before taking it off.
Abstract 11146: AZD3366-an Optimized Recombinant Human Apyrase Combining Anti Platelet, Anti Inflammatory and Tissue Protective Actions With Low Bleeding Risk for Potential Mitigation of Thromboembolic Complications
Authors: Susanne Pehrsson, Bengt Kull, Daniel Hovdal, Marie Elebring, Carl Whatling, Ola Fjellstrom, Leif Carlsson
Journal: Circulation (2019)

Antithrombotic therapies reduce cardiovascular events after acute myocardial infarction but are associated with increased bleeding. AZD3366 (APT102) is an engineered, optimized version of recombina...