tbuckley/cabot-search huggingface dataset:
Inhaled and intranasal ciclesonide for the treatment of covid-19 in adult outpatients: CONTAIN phase II randomised controlled trial
Authors: Nicole Ezer, Sara Belga, Nick Daneman, Adrienne Chan, Benjamin M Smith, Shay-Anne Daniels, Kristen Moran, Charlotte Besson, Louisa Y Smyth, Susan J Bartlett, Andrea Benedetti, James G Martin, Todd C Lee, Emily G McDonald
Journal: BMJ (2021)

Abstract Objective To determine if inhaled and intranasal ciclesonide are superior to placebo at decreasing respiratory symptoms in adult outpatients with covid-19. Design Randomised, double blind, placebo controlled trial. Setting Three Canadian provinces (Quebec, Ontario, and British Columbia). Participants 203 adults aged 18 years and older with polymerase chain reaction confirmed covid-19, presenting with fever, cough, or dyspnoea. Intervention Participants were randomised to receive either inhaled ciclesonide (600 μg twice daily) and intranasal ciclesonide (200 μg daily) or metered dose inhaler and nasal saline placebos for 14 days. Main outcome measures The primary outcome was symptom resolution at day 7. Analyses were conducted on the modified intention-to-treat population (participants who took at least one dose of study drug and completed one follow-up survey) and adjusted for stratified randomisation by sex. Results The modified intention-to-treat population included 203 participants: 105 were randomly assigned to ciclesonide (excluding two dropouts and one loss to follow-up) and 98 to placebo (excluding three dropouts and six losses to follow-up). The median age was 35 years (interquartile range 27-47 years) and 54% were women. The proportion of participants with resolution of symptoms by day 7 did not differ significantly between the intervention group (42/105, 40%) and control group (34/98, 35%); absolute adjusted risk difference 5.5% (95% confidence interval −7.8% to 18.8%). Results might be limited to the population studied, which mainly included younger adults without comorbidities. The trial was stopped early, therefore could have been underpowered. Conclusion Compared with placebo, the combination of inhaled and intranasal ciclesonide did not show a statistically significant increase in resolution of symptoms among healthier young adults with covid-19 presenting with prominent respiratory symptoms. As evidence is insufficient to determine the benefit of inhaled and intranasal corticosteroids in the treatment of covid-19, further research is needed. Trial registration ClinicalTrials.gov NCT04435795 .
ST-Segment Depression in V<sub>2</sub> With Precordial Hyperacute T-Waves Is an Anterior ST-Segment Elevation Myocardial Infarction (STEMI) Equivalent—Reply
Authors: Anish Kapil, Abhishek Thakur, Satyavir Yadav
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Relationships of Changes in Physical Activity and Sedentary Behavior With Changes in Physical Fitness and Cardiometabolic Risk Profile in Individuals With Type 2 Diabetes: The Italian Diabetes and Exercise Study 2 (IDES_2)
Authors: Stefano Balducci, Jonida Haxhi, Massimo Sacchetti, Giorgio Orlando, Patrizia Cardelli, Martina Vitale, Lorenza Mattia, Carla Iacobini, Lucilla Bollanti, Francesco Conti, Silvano Zanuso, Antonio Nicolucci, Giuseppe Pugliese
Journal: Diabetes Care (2021)

OBJECTIVE In the Italian Diabetes and Exercise Study_2 (IDES_2), behavioral counseling promoted a sustained increase in physical activity (PA) volume (+3.3 MET h ⋅ week−1), moderate- to vigorous-intensity PA (MVPA) (+6.4 min ⋅ day−1), and light-intensity PA (LPA) (+0.8 h ⋅ day−1) and decrease in sedentary time (SED-time) (−0.8 h ⋅ day−1). Here, we investigated the relationships of changes in PA/SED-time with changes in physical fitness and cardiometabolic risk profile in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In this 3-year randomized clinical trial, 300 physically inactive and sedentary patients were randomized 1:1 to receive 1-month theoretical and practical counseling once a year or standard care. Changes in physical fitness and cardiovascular risk factors/scores according to quartiles of accelerometer-measured changes in PA/SED-time were assessed, together with univariate and multivariable associations between these parameters, in the whole cohort and by study arm. RESULTS Physical fitness increased and HbA1c and coronary heart disease 10-year risk scores decreased with quartiles of MVPA and SED-time change. In quartile IV of MVPA increase and SED-time decrease, cardiorespiratory fitness increased by 5.23 and 4.49 mL ⋅ min−1 ⋅ kg−1 and HbA1c decreased by 0.73 and 0.85%, respectively. Univariate correlations confirmed these relationships, and mean changes in both MPVA and SED-time predicted changes in physical fitness and cardiovascular risk factors/scores independently of one another and of other confounders. Similar findings were observed with LPA and PA volume and in each group separately. CONCLUSIONS Even modest increments in MVPA may have a clinically meaningful impact, and reallocating SED-time to LPA may also contribute to improved outcomes, possibly by increasing total energy expenditure.
Ticagrelor versus Clopidogrel in <i>CYP2C19</i> Loss-of-Function Carriers with Stroke or TIA
Authors: Yongjun Wang, Xia Meng, Anxin Wang, Xuewei Xie, Yuesong Pan, S. Claiborne Johnston, Hao Li, Philip M. Bath, Qiang Dong, Anding Xu, Jing Jing, Jinxi Lin, Siying Niu, Yilong Wang, Xingquan Zhao, Zixiao Li, Yong Jiang, Wei Li, Liping Liu, Jie Xu, Liguo Chang, Lihua Wang, Xianbo Zhuang, Jinguo Zhao, Yefang Feng, Honghao Man, Guozhong Li, Baojun Wang
Journal: New England Journal of Medicine (2021)

Comparisons between ticagrelor and clopidogrel for the secondary prevention of stroke in CYP2C19 loss-of-function carriers have not been extensively performed.
TCT-6 Impact of Diabetes Mellitus on the Effectiveness of Aspirin Versus Clopidogrel as a Chronic Maintenance Antiplatelet Monotherapy After Percutaneous Coronary Intervention: Results From the HOST-EXAM Trial
Authors: Tae-Min Rhee, Jeehoon Kang, Kyung Woo (KW) Park, Han-Mo Yang, Ki-Bum Won, Seung-Woon Rha, Jang Whan Bae, Nam Ho Lee, Seung-Ho Hur, Junghan Yoon, Tae-Ho Park, Bum Soo Kim, Sang wook Lim, Yoon Haeng Cho, Dong Woon Jeon, Sang-Hyun Kim, Kyoo-Rok Han, Keon-Woong Moon, Seok-Kyu Oh, Ung Kim, Moo-Yong Rhee, Doo-Il Kim, Song-Yi Kim, Sungyun Lee, Seung Uk Lee, Sang-Wook Kim, Seok-Yeon Kim, Hui-Kyung Jeon, Kwang Soo Cha, Sang-Ho Jo, Jae Kean Ryu, Il-Woo Suh, Hyun Hee Choi, Seoung-Il Woo, In-Ho Chae, Won-Yong Shin, Dae-Kyeong Kim, Ju Hyeon Oh, Myung Ho Jeong, Yong Hoon Kim, Jung-Kyu Han, Eun-Seok Shin, Bon-Kwon Koo, Hyo-Soo Kim
Journal: Journal of the American College of Cardiology (2021)
Population Genomics of Wall Lizards Reflects the Dynamic History of the Mediterranean Basin
Authors: Weizhao Yang, Nathalie Feiner, Daniele Salvi, Hanna Laakkonen, Daniel Jablonski, Catarina Pinho, Miguel A Carretero, Roberto Sacchi, Marco A L Zuffi, Stefano Scali, Konstantinos Plavos, Panayiotis Pafilis, Nikos Poulakakis, Petros Lymberakis, David Jandzik, Ulrich Schulte, Fabien Aubret, Arnaud Badiane, Guillem Perez i de Lanuza, Javier Abalos, Geoffrey M While, Tobias Uller
Journal: Molecular Biology and Evolution (2021)

Abstract The Mediterranean Basin has experienced extensive change in geology and climate over the past six million years. Yet, the relative importance of key geological events for the distribution and genetic structure of the Mediterranean fauna remains poorly understood. Here, we use population genomic and phylogenomic analyses to establish the evolutionary history and genetic structure of common wall lizards (Podarcis muralis). This species is particularly informative because, in contrast to other Mediterranean lizards, it is widespread across the Iberian, Italian, and Balkan Peninsulas, and in extra-Mediterranean regions. We found strong support for six major lineages within P. muralis, which were largely discordant with the phylogenetic relationship of mitochondrial DNA. The most recent common ancestor of extant P. muralis was likely distributed in the Italian Peninsula, and experienced an “Out-of-Italy” expansion following the Messinian salinity crisis (∼5 Mya), resulting in the differentiation into the extant lineages on the Iberian, Italian, and Balkan Peninsulas. Introgression analysis revealed that both inter- and intraspecific gene flows have been pervasive throughout the evolutionary history of P. muralis. For example, the Southern Italy lineage has a hybrid origin, formed through admixture between the Central Italy lineage and an ancient lineage that was the sister to all other P. muralis. More recent genetic differentiation is associated with the onset of the Quaternary glaciations, which influenced population dynamics and genetic diversity of contemporary lineages. These results demonstrate the pervasive role of Mediterranean geology and climate for the evolutionary history and population genetic structure of extant species.
The Association of <i>ERBB2</i>-Low Expression With the Efficacy of Cyclin-Dependent Kinase 4/6 Inhibitor in Hormone Receptor–Positive, <i>ERBB2</i>-Negative Metastatic Breast Cancer
Authors: Kelvin K. H. Bao, Leone Sutanto, Shirley S. W. Tse, Ka Man Cheung, Jeffrey C. H. Chan
Journal: JAMA Network Open (2021)

This cohort study investigates the association between low levels of ERBB2 expression and progression-free survival among patients with HR+/ERBB2− metastatic breast cancer treated with CDK4/6 inhibitors.
The cortical connectome of primate lateral prefrontal cortex
Authors: Rui Xu, Narcisse P. Bichot, Atsushi Takahashi, Robert Desimone
Journal: Neuron (2021)

The lateral prefrontal cortex (LPFC) of primates plays an important role in executive control, but how it interacts with the rest of the cortex remains unclear. To address this, we densely mapped the cortical connectome of LPFC, using electrical microstimulation combined with functional MRI (EM-fMRI). We found isomorphic mappings between LPFC and five major processing domains composing most of the cerebral cortex except early sensory and motor areas. An LPFC grid of ∼200 stimulation sites topographically mapped to separate grids of activation sites in the five domains, coarsely resembling how the visual cortex maps the retina. The temporal and parietal maps largely overlapped in LPFC, suggesting topographically organized convergence of the ventral and dorsal streams, and the other maps overlapped at least partially. Thus, the LPFC contains overlapping, millimeter-scale maps that mirror the organization of major cortical processing domains, supporting LPFC's role in coordinating activity within and across these domains.
Viscous Fingering as a Rapid 3D Pattering Technique for Engineering Cell‐Laden Vascular‐Like Constructs
Authors: Min‐Chun Tsai, Shih‐Yen Wei, Ling Fang, Ying‐Chieh Chen
Journal: Advanced Healthcare Materials (2021)

Tissues are much larger than the diffusion limit distance, so rapidly providing blood vessels to supply embedded cells inside tissues with sufficient nutrients and oxygen is regarded as a major strategy for the success of bioengineered large and thick tissue constructs. Here, a patterning technique, viscous fingering, is developed to bioengineer vascularized-like tissues within a few minutes. By controlling viscosity, flow rate, and the volume of photo-cross-linkable prepolymer, macro- and microscale vascular network structures can be precisely engineered using the Hele-Shaw cell that is designed in this study. After cross-linking, a vascular-like gel with fingering structures is formed between the bottom and top base gels, creating a sandwich-like structure. Cells can be incorporated into the fingers, bases, or both gels. The spreading and growth direction of the embedded cells are successfully controlled and guided by manipulating the physical properties of the fingering and base gels individually. Moreover, fingering is generated, connected, and surrounded prepared cell-laden microgels in base prepolymers to form prevascularized tissue-like constructs. Taken together, the 3D cell patterning technique extends the potential for modeling and fabricating large and stackable vascularized tissue-like constructs for both ex vivo and in vivo applications.
Acc/aha/esc guidelines for the management of patients with atrialfibrillation: executive summary a report of the american college ofcardiology/american heart association task force on practice guideli
Authors: Fuster, R Westerling
Journal: Circulation (2001)

Acc/aha/esc guidelines for the management of patients with atrialfibrillation: executive summary a report of the american college ofcardiology/american heart association task force on practice guideli
Burden of anemia and its underlying causes in 204 countries and territories, 1990–2019: results from the Global Burden of Disease Study 2019
Authors: Saeid Safiri, Ali-Asghar Kolahi, Maryam Noori, Seyed Aria Nejadghaderi, Nahid Karamzad, Nicola Luigi Bragazzi, Mark J. M. Sullman, Morteza Abdollahi, Gary S. Collins, Jay S. Kaufman, Jessica A. Grieger
Journal: Journal of Hematology & Oncology (2021)

Abstract Background Anemia is a common disease which affects around 40% of children and 30% of reproductive age women and can have major health consequences. The present study reports the global, regional and national burden of anemia and its underlying causes between 1990 and 2019, by age, sex and socio-demographic index (SDI). Methods Publicly available data on the point prevalence and years lived with disability (YLDs) were retrieved from the global burden of disease (GBD) 2019 study for 204 countries and territories between 1990 and 2019. The point prevalence, YLD counts and rates per 100,000 population were presented, along with their corresponding 95% uncertainty intervals. Results In 2019, the global age-standardized point prevalence and YLD rates for anemia were 23,176.2 (22,943.5–23,418.6) and 672.4 (447.2–981.5) per 100,000 population, respectively. Moreover, the global age-standardized point prevalence and YLD rate decreased by 13.4% (12.1–14.5%) and 18.8% (16.9–20.8%), respectively, over the period 1990–2019. The highest national point prevalences of anemia were found in Zambia [49327.1 (95% UI: 46,838.5–51,700.1)], Mali [46890.1 (95% UI: 44,301.1–49,389.8)], and Burkina Faso [46117.2 (95% UI: 43,640.7–48,319.2)]. In 2019, the global point prevalence of anemia was highest in the 15–19 and 95+ age groups in females and males, respectively. Also, the burden of anemia was lower in regions with higher socio-economic development. Globally, most of the prevalent cases were attributable to dietary iron deficiency, as well as hemoglobinopathies and hemolytic anemias. Conclusions Anemia remains a major health problem, especially among females in less developed countries. The implementation of preventive programs with a focus on improving access to iron supplements, early diagnosis and the treatment of hemoglobinopathies should be taken into consideration.
Intrafascicular peripheral nerve stimulation produces fine functional hand movements in primates
Authors: Marion Badi, Sophie Wurth, Ilaria Scarpato, Evgenia Roussinova, Elena Losanno, Andrew Bogaard, Maude Delacombaz, Simon Borgognon, Paul C̆vanc̆ara, Florian Fallegger, David K. Su, Eric Schmidlin, Grégoire Courtine, Jocelyne Bloch, Stéphanie P. Lacour, Thomas Stieglitz, Eric M. Rouiller, Marco Capogrosso, Silvestro Micera
Journal: Science Translational Medicine (2021)

Intrafascicular stimulation evokes precise and functional hand movements in monkeys, suggesting clinical opportunities for people with hand paralysis.
TCT-219 Same-Day Discharge After Transcatheter Aortic Valve Implantation: Insights From the National Readmissions Database for 2016-2018
Authors: Salman Zahid, Muhammad Khan, Waqas Ullah, Devesh Rai, Mian Tanveer Ud Din, Sakina Abbas, Aamer Ubaid, Muhammad Khan, Sammarthkumar Thakkar, Fnu Salman, Muhammad Atif Khan, Amr Salama, Mohamad Alkhouli, Sudarshan Balla, Jeremiah Depta
Journal: Journal of the American College of Cardiology (2021)
COVID-19-Induced P-ANCA-Associated Nephritic Syndrome in a Woman Without Respiratory Involvement
Authors: Jan P. Rosaly, Elizabeth Pabon-Vazquez, Bryan L. Pagan rivera
Journal: Journal of the American Society of Nephrology (2021)

Journal of the American Society of Nephrology 32(10S):p 93, October 2021. | DOI: 10.1681/ASN.20213210S193b
CHI3L1 regulates PD-L1 and anti–CHI3L1–PD-1 antibody elicits synergistic antitumor responses
Authors: Bing Ma, Bedia Akosman, Suchitra Kamle, Chang-Min Lee, Chuan Hua He, Ja Seok Koo, Chun Geun Lee, Jack A. Elias
Journal: Journal of Clinical Investigation (2021)

Evasion of the immune response is a hallmark of cancer, and programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) are major mediators of this immunosuppression. Chitinase 3-like 1 (CHI3L1) is induced in many cancers, where it portends a poor prognosis and contributes to tumor metastasis and spread. However, the mechanism(s) that CHI3L1 uses in metastasis have not been defined. Here we demonstrate that CHI3L1 regulates the expression of PD-L1, PD-L2, PD-1, LAG3, and TIM3 and plays a critical role in melanoma progression and lymphatic spread. CHI3L1 also contributed to IFN-γ-stimulated macrophage PD-L1 expression, and RIG-like helicase innate immunity suppressed CHI3L1, PD-L1, and melanoma progression. Individual antibodies against CHI3L1 or PD-1 had discrete antitumor effects and additive antitumor responses in metastasis models and T cell-tumor cell cocultures when administered simultaneously. Synergistic cytotoxic tumor cell death was seen in T cell-tumor cell cocultures, and significantly enhanced antitumor responses were seen in in vivo tumor models treated with bispecific antibodies that simultaneously target CHI3L1 and PD-1. CHI3L1 contributes to tumor progression by stimulating the PD-1/PD-L1 axis and other checkpoint molecules. The simultaneous targeting of CHI3L1 and the PD-1/PD-L1 axis with individual and, more powerfully, with bispecific antibodies represents a promising therapy for pulmonary metastasis and progression.
Host Genetics But Not Commensal Microbiota Determines the Initial Development of Systemic Autoimmune Disease in <scp>BXD2</scp> Mice
Authors: Huixian Hong, Fatima Alduraibi, David Ponder, Wayne L. Duck, Casey D. Morrow, Jeremy B. Foote, Trenton R. Schoeb, Huma Fatima, Charles O. Elson, Hui‐Chen Hsu, John D. Mountz
Journal: Arthritis & Rheumatology (2021)

To determine the extent to which the gut microbiome influences systemic autoimmunity in a mouse model of lupus.We generated germ-free (GF) lupus-prone BXD2 mice, which under normal conditions develop spontaneous germinal centers (GCs) and high titers of serum autoantibodies. GF status was confirmed by gut bacterial culture. The autoimmune phenotypes of 6- and 12-month-old gnotobiotic GF BXD2 mice and specific pathogen-free (SPF) BXD2 mice were compared. Serum levels of autoantibodies were measured by enzyme-linked immunosorbent assay. Histologic sections of the mouse kidney and joints were evaluated. Flow cytometry was used to analyze GCs and age-associated B cells. CD4+ T cells were analyzed for PD-1+ICOS+ activated T cells, T follicular regulatory (Tfr) cells (Foxp3+CD25+ PD-1+CXCR5+), and PD-1+ICOS+ T cells expressing interleukin-17A (IL-17A) or interferon-γ (IFNγ) after stimulation with phorbol myristate acetate (PMA)/ionomycin.In 6-month-old mice, GF status did not affect splenomegaly, GC B cells, age-associated B cells, or serum autoantibody levels, except for IgG antihistone. GF BXD2 mice exhibited a significantly higher percentage of Tfr cells compared to their SPF counterparts (P < 0.05). At 12 months of age, however, GF BXD2 mice had significantly diminished IgG autoantibody levels and a lower percentage of GC B cells and age-associated B cells (P < 0.05). Following stimulation with PMA/ionomycin, PD-1+ICOS+ CD4+ T cells expressed significantly lower IL-17A, but not IFNγ, levels in GF BXD2 mice compared to SPF BXD2 mice (P < 0.01). SPF BXD2 mice and GF BXD2 mice developed equivalent renal and joint disease with no significant differences in severity.Our results suggest a model in which genetics plays a dominant role in determining the initial development of autoimmunity. In contrast, gut microbiomes may regulate the persistence of certain aspects of systemic autoimmunity.
TCT-351 Predictors and Outcomes of Cardiac Amyloidosis Patients With Concomitant Atrial Fibrillation
Authors: Sundeep Kumar, Ziad SayedAhmad, Ruthvik Srinivasamurthy, Ali Ghani, Hiren Patel, Sarika Kumari, Akhil Mogalapalli, Sayed Hussain, Ammar Nasir, Philip Mar, Deana Mikhalkova
Journal: Journal of the American College of Cardiology (2021)
Osteoblast-derived EGFL6 couples angiogenesis to osteogenesis during bone repair
Authors: Kai Chen, Shijie Liao, Yicheng Li, Haibo Jiang, Yun Liu, Chao Wang, Vincent Kuek, Jacob Kenny, Boxiang Li, Qian Huang, Jianxin Hong, Yan Huang, Shek Man Chim, Jennifer Tickner, Nathan J Pavlos, Jinmin Zhao, Qian Liu, An Qin, Jiake Xu
Journal: Theranostics (2021)

Rationale: Angiogenesis and osteogenesis are highly coupled processes which are indispensable to bone repair. However, the underlying mechanism(s) remain elusive. To bridge the gap in understanding the coupling process is crucial to develop corresponding solutions to abnormal bone healing. Epidermal growth factor-like protein 6 (EGFL6) is an angiogenic factor specifically and distinctively up-regulated during osteoblast differentiation. In contrast with most currently known osteoblast-derived coupling factors, EGFL6 is highlighted with little or low expression in other cells and tissues. Methods: In this study, primary bone marrow mesenchymal stem cells (MSCs) and osteoblastic cell line (MC3T3-E1) were transduced with lentiviral silencing or overexpression constructs targeting EGFL6. Cells were induced by osteogenic medium, followed by the evaluation of mineralization as well as related gene and protein expression. Global and conditional knockout mice were established to examine the bone phenotype under physiological condition. Furthermore, bone defect models were created to investigate the outcome of bone repair in mice lacking EGFL6 expression. Results: We show that overexpression of EGFL6 markedly enhances osteogenic capacity in vitro by augmenting bone morphogenic protein (BMP)-Smad and MAPK signaling, whereas downregulation of EGFL6 diminishes osteoblastic mineralization. Interestingly, osteoblast differentiation was not affected by the exogenous addition of EGFL6 protein, thereby indicating that EGFL6 may regulate osteoblastic function in an intracrine manner. Mice with osteoblast-specific and global knockout of EGFL6 surprisingly exhibit a normal bone phenotype under physiological conditions. However, EGFL6-deficiency leads to compromised bone repair in a bone defect model which is characterized by decreased formation of type H vessels as well as osteoblast lineage cells. Conclusions: Together, these data demonstrate that EGFL6 serves as an essential regulator to couple osteogenesis to angiogenesis during bone repair.