tbuckley/cabot-search huggingface dataset:
Improving the Effectiveness of Psychological Interventions for Depression and Anxiety in Cardiac Rehabilitation: PATHWAY—A Single-Blind, Parallel, Randomized, Controlled Trial of Group Metacognitive Therapy
Authors: Adrian Wells, David Reeves, Lora Capobianco, Calvin Heal, Linda Davies, Anthony Heagerty, Patrick Doherty, Peter Fisher
Journal: Circulation (2021)

Depression and anxiety in cardiovascular disease are significant, contributing to poor prognosis. Unfortunately, current psychological treatments offer mixed, usually small improvements in these symptoms. The present trial tested for the first time the effects of group metacognitive therapy (MCT; 6 sessions) on anxiety and depressive symptoms when delivered alongside cardiac rehabilitation (CR).
Ximpact of chronic obstructive pulmonary disease and/or emphysema on outcomes of hospitalized patients with COVID-19 pneumonia
Authors: R. M. Marron, M. Zheng, G. A. Fernandez Romero, H. Zhao, R. Patel, I. Leopold, A. Thomas, T. Standiford, M. Kumaran, N. Patlakh, J. I. Stewart, G. J. Criner
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Background: Comorbid disease was identified early during the COVID-19 pandemic as a risk factor for severe infection, however, initial rates of chronic obstructive pulmonary disease (COPD) in case series were low and severity of COVID-19 in COPD patients was variable. Methods: We performed a retrospective study of patients admitted with COVID-19 and evaluated outcomes in those with and without COPD and/or emphysema. Patients were identified as having COPD if they had a diagnosis in the medical record and a history of airflow-obstruction on spirometry, or a history of tobacco use and prescribed long-acting bronchodilator(s). Computed tomography scans were evaluated by radiologists. Propensity matching was performed for age, body-mass index (BMI), and serologic data correlated with severity of COVID-19 disease (D-dimer, C-reactive protein, ferritin, fibrinogen, absolute lymphocyte count, lymphocyte percentage, and lactate dehydrogenase).Results: Of 577 patients admitted with COVID-19, 103 had a diagnosis of COPD and/or emphysema. The COPD and/or emphysema cohort was older (67 years vs 58 years, p<0.0001) than the other cohort and had a lower BMI (28.3 kg/m2 vs 31.1 kg/m2, p<0.01). Among unmatched cohorts those with COPD and/or emphysema had higher rates of intensive care unit (ICU) admission (35% vs 24.9%, p=0.036) and maximal respiratory support requirements (p=0.007), with more frequent invasive mechanical ventilation (21.4% vs 11.8%), and a trend towards higher mortality (12.6% vs 8.2%) that was not statistically significant (p=0.158). After propensity-matching there was no difference in rates of ICU admission, maximal respiratory support requirements, or mortality. The propensity-matched group with COPD and/or emphysema had higher median pack-years of tobacco use (35.0 vs 17.5, p=0.046) and rates of active smoking (28.2% vs 9.7%, p<0.01). Propensity matching was not performed for rates of comorbid disease such as coronary artery disease but the propensity-matched groups had no significant differences in cardiac comorbidities.DiscussionOur propensity-matched retrospective cohort study suggests that patients hospitalized with COVID-19 that have COPD and/or emphysema may not have worse outcomes than those without these comorbid conditions.
Abstract 130: Arginine Methylation of Smad6 Defines Bone-morphogenetic-protein (BMP) Signaling Duration and Intensity
Authors: JIAN WU, Olan Jackson-Weaver, Tingwei Zhang, Yongchao Gou, Jian Xu
Journal: Circulation Research (2016)

Bone-morphogenetic-protein (BMP)/Smads signaling pathway plays crucial role during heart development and vessel angiogenesis. BMP signaling is induced by the binding of BMP ligands (eg. BMP4) to their receptors, which recruit and phosphorylate receptor-Smads (R-Smads, eg. Smad1, Smad5) that form nuclear-transporting complexes with Smad4 for transcriptional regulation. Smad6 is an inhibitory Smad expresses predominantly in atria-ventricular cushion and outflow tract of the developing mouse heart, and expands to valves and great vessels. At the cell surface level, Smad6 binds to BMP type I receptor to block R-Smads recruitment to the receptor. At cytosolic level, Smad6 block Smad1/Smad4 complex formation. In the nucleus, Smad6 represses transcription. How these three levels of regulation are coordinated to inhibit BMP signaling is not known. We previously showed that BMP ligand induces an acute Smad6 methylation at arginine 74 (R74) at the cell surface level by a methyltransferase PRMT1, and methyl-Smad6 dissociates from receptor to allow receptor-induced Smad1/5 phosphorylation and activation. We further identified a delayed methylation on arginine 81 (R81) of Smad6 in the cytosol by PRMT1. We found that R81 methylation is required for BMP signaling-induced recruitment of Smad6 to phosphor-Smad1; it is also required for Smad6 to disrupt phosphor-Smad1/Smad4 complex formation and the following nuclear transportation, as well as for Smad6 to suppress Smad1 targeting gene transactivation. Previous findings indicate that Smad6 binds to type I receptor and Smad1 through its C-terminal region. We examined how arginine methylation in the N-terminal region, regulates the binding properties of C-terminal Smad6. We found that N-terminal Smad6 stabilizes the interaction between C-terminal Smad6 and Smad1 and enhances Smad6 inhibitory function. Disruption of R81 methylation results in loss of inhibitory function because of an increase in binding between N-term and C-term Smad6 that results in a "closed" conformation. In summary, R81 methylation controls Smad6 activity and R81 methylation of Smad6 defines the duration and intensity of BMP-induced Smad1/5 signaling.
Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma
Authors: Hong Yang, Hui Liu, Yuping Chen, Chengchu Zhu, Wentao Fang, Zhentao Yu, Weimin Mao, Jiaqing Xiang, Yongtao Han, Zhijian Chen, Haihua Yang, Jiaming Wang, Qingsong Pang, Xiao Zheng, Huanjun Yang, Tao Li, Xu Zhang, Qun Li, Geng Wang, Baofu Chen, Teng Mao, Min Kong, Xufeng Guo, Ting Lin, Mengzhong Liu, Jianhua Fu
Journal: JAMA Surgery (2021)

The prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival.To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC.The Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020.Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization.The primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival.A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively.In this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC.ClinicalTrials.gov Identifier: NCT01216527.
Intestinal MYC modulates obesity-related metabolic dysfunction
Authors: Yuhong Luo, Shoumei Yang, Xuan Wu, Shogo Takahashi, Lulu Sun, Jie Cai, Kristopher W. Krausz, Xiaozhen Guo, Henrique B. Dias, Oksana Gavrilova, Cen Xie, Changtao Jiang, Weiwei Liu, Frank J. Gonzalez
Journal: Nature Metabolism (2021)
Ultrasound and microbubbles to beat barriers in tumors: Improving delivery of nanomedicine
Authors: Sofie Snipstad, Krister Vikedal, Matilde Maardalen, Anna Kurbatskaya, Einar Sulheim, Catharina de Lange Davies
Journal: Advanced Drug Delivery Reviews (2021)

Successful delivery of drugs and nanomedicine to tumors requires a functional vascular network, extravasation across the capillary wall, penetration through the extracellular matrix, and cellular uptake. Nanomedicine has many merits, but penetration deep into the tumor interstitium remains a challenge. Failure of cancer treatment can be caused by insufficient delivery of the therapeutic agents. After intravenous administration, nanomedicines are often found in off-target organs and the tumor extracellular matrix close to the capillary wall. With circulating microbubbles, ultrasound exposure focused toward the tumor shows great promise in improving the delivery of therapeutic agents. In this review, we address the impact of focused ultrasound and microbubbles to overcome barriers for drug delivery such as perfusion, extravasation, and transport through the extracellular matrix. Furthermore, we discuss the induction of an immune response with ultrasound and delivery of immunotherapeutics. The review discusses mainly preclinical results and ends with a summary of ongoing clinical trials.
Abstract 341: Effect of Guideline Changes on Drug Administration in Pediatric In-Hospital Cardiac Arrest
Authors: Catherine E Ross, Ari Moskowitz, Tuyen Yankama, Mathias Johan J Holmberg, Lars Andersen, Anne V Grossestreuer, Amanda O’Halloran, Monica E Kleinman, Michael Donnino
Journal: Circulation (2019)

Introduction: Updates to PALS include modifications to recommendations and pictorial algorithms surrounding intra-arrest drug administration. These include: bicarbonate, which had been an option for prolonged arrests, was changed in 2010 to recommend against routine use; lidocaine was removed from the pictorial algorithm in 2010 and reintroduced in 2015, at which time the recommendation changed from it being 2 nd -line to being equivalent to amiodarone as 1 st line; and atropine for which text was added in 2010 stating there was insufficient evidence to support or refute routine use in pulseless cardiac arrest. Understanding the effects of these changes may be important in future guideline development. Hypotheses: We hypothesized that use of bicarbonate, lidocaine and atropine would decrease after 2010, and use of lidocaine would increase after 2015. Methods: Index pulseless IHCA in children ≤18 years of age in the GWTG-R pediatric database between 2001 and 2017 were included. We performed interrupted time series analyses using segmented linear regression with GEE for each medication. Atropine was analyzed post-hoc . Results: A total of 4,806 index cases (698 shockable, 4108 non-shockable) were included. After 2010, bicarbonate had no changes in the intercept (-3.1% (95% CI, -7.5, 1.3%; p = 0.17) or slope (0.7% (95% CI, -1.0, 2.3%; p = 0.41). For lidocaine in shockable arrests there was no change in the intercept (-7.7%, 95% CI, -21.6, 6.1%; p = 0.27) or slope (-2.7%, (95% CI, -7.2, 1.8%; p = 0.24) in 2010 nor in 2015 (intercept: -0.2%; 95% CI, -32.1, 31.8%; p = 0.99; slope: -3.6%; 95% CI; -7.8, 15.0%; p = 0.53). For atropine, there was a 9.3% downward step change in the intercept (95% CI, 3.3-15.2%; p &lt; 0.01) for all arrests and 11.7% (95% CI, 5.3-18.2%; p &lt; 0.001) for initial PEA/asystole. Conclusion: Recommendation changes in the PALS text correlated with decreased use of atropine but not bicarbonate. This is especially interesting considering atropine had not previously been part of the PALS cardiac arrest algorithm. However, this update coincides with the removal of atropine from the ACLS PEA/asystole algorithm in 2010, which may have influenced some providers. Lidocaine use was not affected by changes to the pictorial algorithm nor by changes in the text.
The Clinical Implication and Prognostic Impact of Dynamic Molecular Evolution in Acute Myeloid Leukemia
Authors: Jui-Che Chen, Cheng-Hong Tsai, Jih-Luh Tang, Yuan-Yeh Kuo, Chien-Chin Lin, Mei-Hsuan Tseng, Ming Yao, Chi-Cheng Li, Shang-Yi Huang, Bor-Sheng Ko, Szu-Chun Hsu, Chien-Ting Lin, Shang-Ju Wu, Chien-Yuan Chen, Woei Tsai, Wen-Chien Chou, Hsin-An Hou, Hwei-Fang Tien
Journal: Blood (2017)
Measures of physical performance in COVID-19 patients: a mapping review
Authors: Carla Simonelli, Mara Paneroni, Michele Vitacca, Nicolino Ambrosino
Journal: Pulmonology (2021)

There is evidence of short- and long-term impairment of physical performance in patients with COVID-19 infection, but a verification of measures of physical impairment in this condition is lacking. We reviewed the measures used to assess physical performance in these patients. Secondary targets were measures of exercise or daily life activities induced symptoms.Medline, CINAHL, and Pedro databases were searched from January 2020 to February 2021 for articles in the English language. Two investigators independently conducted the search, screened all titles and/or abstracts based on the inclusion criteria and independently scored the studies. The quality of the studies was evaluated by two reviewers according to the NIH quality assessment tool for observational cohort and cross-sectional studies. Discrepancies were resolved through consensus.Out of 156 potentially relevant articles, 31 observational studies (8 cross-sectional), 1 randomized controlled trial, and 1 protocol were included. The quality of most of the 31 evaluable studies was judged as low (11 studies) or fair (14 studies). Sample sizes of the studies ranged from 14 to 20,889 patients. among the 28 reported measures, Barthel Index (42.4% of studies), Six-Minute Walking Distance Test (36.4%), Short Physical Performance Battery (21.2%) and 1-Minute Sit-to-Stand (12.1%) were the most used. Fifteen% and 36% of studies reported exercise induced desaturation and dyspnoea when performing the assessments, respectively. Other exercise induced symptoms were fatigue and pain. Studies reported wide ranges of impairment in physical performance as compared to "reference" values (range of mean or median reported values vs "reference values": 11-77 vs 100 points for Barthel Index; 11-22 vs 22-37 repetitions/min for 1m-STS; 0.5-7.9 vs 11.4 ± 1.3 points for SPPB; and 45-223 vs 380-782 m for 6MWT respectively).This review found that a wide variety of functional status tests have been used, making comparisons difficult between studies. These measures show impairment in physical performance in COVID-19 patients. However, the quality of most of the studies was judged as low or fair.
INTERBIO-21st Phenotypes—Additional Considerations
Authors: Mudita Tiwari, Claire Mowry, Habib Bhurawala
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
The clear cell sarcoma functional genomic landscape
Authors: Emanuele Panza, Benjamin B. Ozenberger, Krystal M. Straessler, Jared J. Barrott, Li Li, Yanliang Wang, Mingchao Xie, Anne Boulet, Simon W.A. Titen, Clinton C. Mason, Alexander J. Lazar, Li Ding, Mario R. Capecchi, Kevin B. Jones
Journal: Journal of Clinical Investigation (2021)

Clear cell sarcoma (CCS) is a deadly malignancy affecting adolescents and young adults. It is characterized by reciprocal translocations resulting in expression of the chimeric EWSR1-ATF1 or EWSR1-CREB1 fusion proteins, driving sarcomagenesis. Besides these characteristics, CCS has remained genomically uncharacterized. Copy number analysis of human CCSs showed frequent amplifications of the MITF locus and chromosomes 7 and 8. Few alterations were shared with Ewing sarcoma or desmoplastic, small round cell tumors, which are other EWSR1-rearranged tumors. Exome sequencing in mouse tumors generated by expression of EWSR1-ATF1 from the Rosa26 locus demonstrated no other repeated pathogenic variants. Additionally, we generated a new CCS mouse by Cre-loxP–induced chromosomal translocation between Ewsr1 and Atf1, resulting in copy number loss of chromosome 6 and chromosome 15 instability, including amplification of a portion syntenic to human chromosome 8, surrounding Myc. Additional experiments in the Rosa26 conditional model demonstrated that Mitf or Myc can contribute to sarcomagenesis. Copy number observations in human tumors and genetic experiments in mice rendered, for the first time to our knowledge, a functional landscape of the CCS genome. These data advance efforts to understand the biology of CCS using innovative models that will eventually allow us to validate preclinical therapies necessary to achieve longer and better survival for young patients with this disease.
Abstract 103: MCL-1 <sub>Matrix</sub> Promotes Mitochondrial Fusion and Protects Against Mitophagy
Authors: Leonardo J Leon, Alexandra G Moyzis, Asa B Gustafsson
Journal: Circulation Research (2016)

MCL-1 is a less well characterized anti-apoptotic BCL-2 protein which is highly expressed in the myocardium. We recently discovered that loss of MCL-1 in cardiac myocytes leads to rapid mitochondrial dysfunction and development of heart failure. MCL-1 exists both in the outer mitochondrial membrane (MCL-1 OM ) and in the mitochondrial matrix (MCL-1 Matrix ). Because the Mcl-1 -/- knockout mice are missing both MCL-1 Matrix and MCL-1 OM , the functional importance of each form is still unknown. While studies have implicated MCL-1 OM in regulating apoptosis, very little is known about the functional role of MCL-1 Matrix . Here, we examined whether cardiac MCL-1 levels were altered in response to fasting. Our data show that the MCL-1 Matrix /MCL-1 OM protein ratio was significantly increased in mouse hearts after 24 and 48 h of fasting. This was mainly due to a decrease in MCL-1 OM , while MCL-1 Matrix levels were unchanged. We also confirmed that the reduction in MCL-1 OM did not lead to a significant activation of apoptosis. Mitochondria are responsive to alterations in cellular metabolism and culturing cells in “oxidative” media containing galactose or acetoacetate led to a significant increase in the MCL-1 Matrix /MCL-1 OM ratio due to a reduction in MCL-1 OM protein and to elongation of mitochondria. We also confirmed that the reduced MCL-1 OM levels did not result in activation of apoptosis. This suggests that the MCL-1 Matrix /MCL-1 OM ratio is altered in response to changes in metabolism and energy demand without activating apoptosis. We have started dissecting how altering the MCL-1 Matrix /MCL-1 OM ratio affects mitochondrial morphology and turnover. We confirmed that MCL-1 Matrix overexpression led to more fused mitochondria under baseline conditions. Interestingly, we also found that the elongated mitochondria were also more protected against FCCP-induced fission as well as degradation by autophagosomes. Thus, we propose that MCL-1 Matrix protects mitochondria from unnecessary mitophagy to preserve the bioenergetic capacity when nutrients are limited. We are currently evaluating how cardiac restricted overexpression of MCL-1 Matrix (αMHC-MCL-1 Matrix ) affects mitochondrial morphology, mitophagy and bioenergetics during fasting.
Safety and Efficacy of Upadacitinib in Patients With Active Ankylosing Spondylitis and an Inadequate Response to Nonsteroidal Antiinflammatory Drug Therapy: One‐Year Results of a Double‐Blind, Placebo‐Controlled Study and Open‐Label Extension
Authors: Atul Deodhar, Désirée van der Heijde, Joachim Sieper, Filip Van den Bosch, Walter P. Maksymowych, Tae‐Hwan Kim, Mitsumasa Kishimoto, Andrew Ostor, Bernard Combe, Yunxia Sui, Alvina D. Chu, In‐Ho Song
Journal: Arthritis & Rheumatology (2021)

To report the efficacy and safety of upadacitinib through 1 year in patients with ankylosing spondylitis (AS).
Widespread implementation of a low-cost telehealth service in the delivery of antenatal care during the COVID-19 pandemic: an interrupted time-series analysis
Authors: Kirsten R Palmer, Michael Tanner, Miranda Davies-Tuck, Andrea Rindt, Kerrie Papacostas, Michelle L Giles, Kate Brown, Helen Diamandis, Rebecca Fradkin, Alice E Stewart, Daniel L Rolnik, Andrew Stripp, Euan M Wallace, Ben W Mol, Ryan J Hodges
Journal: The Lancet (2021)