tbuckley/cabot-search huggingface dataset:
Meteorin-like/Meteorin-β protects heart against cardiac dysfunction
Authors: Celia Rupérez, Gemma Ferrer-Curriu, Aina Cervera-Barea, Laura Florit, Mariona Guitart-Mampel, Gloria Garrabou, Mònica Zamora, Fàtima Crispi, Joaquim Fernandez-Solà, Josep Lupón, Antoni Bayes-Genis, Francesc Villarroya, Anna Planavila
Journal: The Journal of Experimental Medicine (2021)

Meteorin-like/Meteorin-β (Metrnl/Metrnβ) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrnβ in cardiac disease is completely unknown. Here, we show that Metrnβ-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus–mediated specific overexpression of Metrnβ in the heart prevents the development of cardiac remodeling. Furthermore, Metrnβ inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrnβ in cardiomyocyte cell cultures indicated an autocrine action of Metrnβ on the heart, in addition to an endocrine action. Moreover, Metrnβ is highly produced in the heart, and analysis of circulating Metrnβ concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value.
Electrocardiographic QRS Amplitude Predicts Mortality in Hospitalized Patients With CoViD-19
Authors: J. Lampert, J. Halperin, G. Giustino, C. Oates, K. Nelson, J. Feinman, M. Pulaski, D. Musikantow, M. Turagam, M. Miller, M. N. Langan, J. S. Koruth, S. Dukkipati, W. Whang, M. Goldman, V. Fuster, V. Y. Reddy
Journal: Circulation (2020)
Predicting future cognitive decline with hyperbolic stochastic coding
Authors: Jie Zhang, Qunxi Dong, Jie Shi, Qingyang Li, Cynthia M. Stonnington, Boris A. Gutman, Kewei Chen, Eric M. Reiman, Richard J. Caselli, Paul M. Thompson, Jieping Ye, Yalin Wang
Journal: Medical Image Analysis (2021)
Prion protein oligomers cause neuronal cytoskeletal damage in rapidly progressive Alzheimer’s disease
Authors: Mohsin Shafiq, Saima Zafar, Neelam Younas, Aneeqa Noor, Berta Puig, Hermann Clemens Altmeppen, Matthias Schmitz, Jakob Matschke, Isidre Ferrer, Markus Glatzel, Inga Zerr
Journal: Molecular Neurodegeneration (2021)

Abstract Background High-density oligomers of the prion protein (HDPs) have previously been identified in brain tissues of patients with rapidly progressive Alzheimer’s disease (rpAD). The current investigation aims at identifying interacting partners of HDPs in the rpAD brains to unravel the pathological involvement of HDPs in the rapid progression. Methods HDPs from the frontal cortex tissues of rpAD brains were isolated using sucrose density gradient centrifugation. Proteins interacting with HDPs were identified by co-immunoprecipitation coupled with mass spectrometry. Further verifications were carried out using proteomic tools, immunoblotting, and confocal laser scanning microscopy. Results We identified rpAD-specific HDP-interactors, including the growth arrest specific 2-like 2 protein (G2L2). Intriguingly, rpAD-specific disturbances were found in the localization of G2L2 and its associated proteins i.e., the end binding protein 1, α-tubulin, and β-actin. Discussion The results show the involvement of HDPs in the destabilization of the neuronal actin/tubulin infrastructure. We consider this disturbance to be a contributing factor for the rapid progression in rpAD.
Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial
Authors: Geltrude Mingrone, Annieke CG van Baar, Jacques Devière, David Hopkins, Eduardo Moura, Cintia Cercato, Harith Rajagopalan, Juan Carlos Lopez-Talavera, Kelly White, Vijeta Bhambhani, Guido Costamagna, Rehan Haidry, Eduardo Grecco, Manoel Galvao Neto, Guruprasad Aithal, Alessandro Repici, Bu'Hussain Hayee, Amyn Haji, A John Morris, Raf Bisschops, Manil D Chouhan, Naomi S Sakai, Deepak L Bhatt, Arun J Sanyal, J J G H M Bergman
Journal: Gut (2021)

Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D).Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m2, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks.Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient.DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG.NCT02879383.
Abstract 5944: Neural Crest Stem Cells Supply Intrinsic Cardiac Adrenergic Cells and Contribute to Reinnervation After Cardiac Transplantation in Mice
Authors: Yuichi Tamura, Hiroshi Nakamura, Masaki Ieda, Hideaki Kanazawa, Kensuke Kimura, Keisuke Matsumura, Yuichi Tomita, Takahiko Nishiyama, Motoaki Sano, Masunori Matsuzaki, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2009)
When should the UK lift its lockdown?
Authors: Tony Kirby
Journal: The Lancet Respiratory Medicine (2021)

By any reasonable measure, the UK has been one of the countries hardest hit by the COVID-19 pandemic. As of Feb 15, 2021, there have been more than 117 000 deaths and more than 4 million confirmed infections. The country is in the dark depths of a third national lockdown, which began on Jan 4, 2021, after a new SARS-CoV-2 variant (B1.1.7, also known as the UK or Kent variant) caused infections to soar nationwide.
Abstract PS13-36: Prevention of chemotherapy-induced alopecia: A prospective study in breast and ovarian cancer patients
Authors: Lia A Papadopoulos, Susan Chua, Geraldine Goss, Jane Johnson, Aaron Ling, Bianca Devitt
Journal: Cancer Research (2021)

Abstract Background: Scalp cooling minimises chemotherapy-induced alopecia (CIA) which may reduce distress, improve quality of life and body image. This study assesses scalp-cooling efficacy in women receiving chemotherapy for early and advanced breast and ovarian cancer. Methods: Women with breast or ovarian cancer undergoing chemotherapy and scalp cooling at two intuitions were enrolled prospectively. Data collected included demographics, chemotherapy agent(s), hair loss and reasons for discontinuing scalp cooling. Successful hair preservation (SHP) was defined as Dean’s scale grade 0-2 (&amp;lt;!–=50%) hair loss without desire for head-cover use at the completion of chemotherapy. Results were analysed using descriptive statistics. Results: 188 patients were enrolled, mean age 54 [28-83] . 90 women (48%) achieved SHP. 120 (64%) completed scalp cooling. Reasons for discontinuation included: intolerance 34 (49%), perceived loss of hair in 28 (41%) and extra chair time in 6 (9%). 14% continued scalp cooling despite significant hair loss (&amp;gt;50%) SHP was significantly higher in non-anthracycline regimens; 62% (70/112) compared with anthracycline-containing regimens; 24% (18/74), p&amp;lt;0.0001. Single-agent taxane regimen achieved highest SHP in 70% (31/44)and in carboplatin/Paclitaxel regimen; 80% (16 of 20). SHP was lower in Docetaxel-Cyclophosphamide; 48% (21/44), in FEC-D; 27% (20/74) and in AC-T; 26% (16 of 62). SHP rates did not differ between ethnicities; 47% (15/32) in Asian and 47% (75/156) of non-Asian ethnicities, p=0.90. In non-anthracycline regimens SHP was numerically, but non-significantly higher in younger age (&amp;lt;65) 65% (52/81) compared with older age (&amp;gt;/=65) 57% (17/29). Conclusion: Among women receiving chemotherapy for early or advanced breast and ovarian cancer, scalp cooling offers a chance to prevent CIA with most success in taxane +/- carboplatin regimens. Further study is warranted into patients views on the trade-off of benefits and costs in this limited, resource intensive intervention. Citation Format: Lia A Papadopoulos, Susan Chua, Geraldine Goss, Jane Johnson, Aaron Ling, Bianca Devitt. Prevention of chemotherapy-induced alopecia: A prospective study in breast and ovarian cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-36.
COVID-19 mRNA Vaccination–Induced Lymphadenopathy Mimics Lymphoma Progression on FDG PET/CT
Authors: Guofan Xu, Yang Lu
Journal: Clinical Nuclear Medicine (2021)

We present here a 72-year-old man with mantle cell lymphoma who has completed chemotherapy and achieved complete metabolic response to the therapy 10 months ago. Series follow-up FDG PET/CT scans have been negative for lymphoma. Current FDG PET/CT scan showed a new cluster of subcentimeter left axillary lymphadenopathy with avid FDG uptake. There was also focal FDG uptake in the left upper arm deltoid muscle and adjacent subcutaneous soft tissue, with no other abnormal FDG-avid lesion or suspicious CT image findings. The medical history revealed that the patient received COVID-19 mRNA vaccine 2 days before the FDG PET/CT examination.
Detection of B.1.351 SARS-CoV-2 Variant Strain — Zambia, December 2020
Authors: Mulenga Mwenda, Ngonda Saasa, Nyambe Sinyange, George Busby, Peter J. Chipimo, Jason Hendry, Otridah Kapona, Samuel Yingst, Jonas Z. Hines, Peter Minchella, Edgar Simulundu, Katendi Changula, King Shimumbo Nalubamba, Hirofumi Sawa, Masahiro Kajihara, Junya Yamagishi, Muzala Kapin’a, Nathan Kapata, Sombo Fwoloshi, Paul Zulu, Lloyd B. Mulenga, Simon Agolory, Victor Mukonka, Daniel J. Bridges
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

The first laboratory-confirmed cases of coronavirus disease 2019 (COVID-19), the illness caused by SARS-CoV-2, in Zambia were detected in March 2020 (1). Beginning in July, the number of confirmed cases began to increase rapidly, first peaking during July-August, and then declining in September and October (Figure). After 3 months of relatively low case counts, COVID-19 cases began rapidly rising throughout the country in mid-December. On December 18, 2020, South Africa published the genome of a SARS-CoV-2 variant strain with several mutations that affect the spike protein (2). The variant included a mutation (N501Y) associated with increased transmissibility.†,§ SARS-CoV-2 lineages with this mutation have rapidly expanded geographically.¶,** The variant strain (PANGO [Phylogenetic Assignment of Named Global Outbreak] lineage B.1.351††) was first detected in the Eastern Cape Province of South Africa from specimens collected in early August, spread within South Africa, and appears to have displaced the majority of other SARS-CoV-2 lineages circulating in that country (2). As of January 10, 2021, eight countries had reported cases with the B.1.351 variant. In Zambia, the average number of daily confirmed COVID-19 cases increased 16-fold, from 44 cases during December 1-10 to 700 during January 1-10, after detection of the B.1.351 variant in specimens collected during December 16-23. Zambia is a southern African country that shares substantial commerce and tourism linkages with South Africa, which might have contributed to the transmission of the B.1.351 variant between the two countries.
Association of Germline BRCA Pathogenic Variants With Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data
Authors: Volkan Turan, Matteo Lambertini, Dong-Yun Lee, Erica Wang, Florian Clatot, Beth Y. Karlan, Isabelle Demeestere, Heejung Bang, Kutluk Oktay
Journal: Journal of Clinical Oncology (2021)

To determine whether germline
Abstract 13703: Initial Stress Echocardiography is Superior for the Prediction of Coronary Artery Disease and Outcome and is More Cost-Effective than Initial Exercise Electrocardiography in Patients With Suspected Angina and no Known Coronary Artery Disease
Authors: Kostas Zacharias, Shahram Ahmadvazir, Benoy N Shah, Jatinder Pabla, Roxy Senior
Journal: Circulation (2013)

Background: Exercise ECG (ExECG) is recommended as the initial test in patients with suspected coronary artery disease (CAD). Stress echocardiography (SE) is however more accurate, for the assessme...
First-Level Systematic Echocardiographic Evaluation in a COVID-19 Lombardy Hospital
Authors: Giuseppe Ciconte
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Coronavirus Disease 2019 (COVID-19) is a global pandemic. Although cardiovascular (CV) morbidity has been associated to the clinical course of the disease, systematic data regarding CV implications during COVID19 are still lacking. The aim of this study is to report the echocardiographic features of COVID19 patients undergoing first-level echocardiographic screening in a COVID Hospital in Lombardy. In this retrospective study, 70 consecutive patients admitted to our Hospital with confirmed COVID-19 diagnosis, underwent a first-level echocardiographic screening. Of the 70 patients, 8 (11.4%) patients died; survivors had lower sPAP levels as compared to deceased subjects (25.4±9.4 vs 34.8±5.9 mmHg, p=0.008) and splitting the patients in four quartiles based on sPAP, mortality rate was significantly higher among patients with more elevated sPAP compared to the other groups (Q4 29.4% vs Q3 12.5% vs Q2 6.25% vs Q1 0%, p=0.026). A first-level echocardiographic screening might be helpful in the management of Covid-19 patients by identifying those at higher risk of fatal outcome.
Rescuing the Last-Line Polymyxins: Achievements and Challenges
Authors: Sue C. Nang, Mohammad A. K. Azad, Tony Velkov, Qi (Tony) Zhou, Jian Li
Journal: Pharmacological Reviews (2021)

Antibiotic resistance is a major global health challenge and, worryingly, several key Gram negative pathogens can become resistant to most currently available antibiotics. Polymyxins have been revived as a last-line therapeutic option for the treatment of infections caused by multidrug-resistant Gram negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacterales. Polymyxins were first discovered in the late 1940s but were abandoned soon after their approval in the late 1950s as a result of toxicities (e.g., nephrotoxicity) and the availability of "safer" antibiotics approved at that time. Therefore, knowledge on polymyxins had been scarce until recently, when enormous efforts have been made by several research teams around the world to elucidate the chemical, microbiological, pharmacokinetic/pharmacodynamic, and toxicological properties of polymyxins. One of the major achievements is the development of the first scientifically based dosage regimens for colistin that are crucial to ensure its safe and effective use in patients. Although the guideline has not been developed for polymyxin B, a large clinical trial is currently being conducted to optimize its clinical use. Importantly, several novel, safer polymyxin-like lipopeptides are developed to overcome the nephrotoxicity, poor efficacy against pulmonary infections, and narrow therapeutic windows of the currently used polymyxin B and colistin. This review discusses the latest achievements on polymyxins and highlights the major challenges ahead in optimizing their clinical use and discovering new-generation polymyxins. To save lives from the deadly infections caused by Gram negative "superbugs," every effort must be made to improve the clinical utility of the last-line polymyxins. SIGNIFICANCE STATEMENT: Antimicrobial resistance poses a significant threat to global health. The increasing prevalence of multidrug-resistant (MDR) bacterial infections has been highlighted by leading global health organizations and authorities. Polymyxins are a last-line defense against difficult-to-treat MDR Gram negative pathogens. Unfortunately, the pharmacological information on polymyxins was very limited until recently. This review provides a comprehensive overview on the major achievements and challenges in polymyxin pharmacology and clinical use and how the recent findings have been employed to improve clinical practice worldwide.
CD8+ T cells fail to limit SIV reactivation following ART withdrawal until after viral amplification
Authors: Afam A. Okoye, Derick D. Duell, Yoshinori Fukazawa, Benjamin Varco-Merth, Alejandra Marenco, Hannah Behrens, Morgan Chaunzwa, Andrea N. Selseth, Roxanne M. Gilbride, Jason Shao, Paul T. Edlefsen, Romas Geleziunas, Mykola Pinkevych, Miles P. Davenport, Kathleen Busman-Sahay, Michael Nekorchuk, Haesun Park, Jeremy Smedley, Michael K. Axthelm, Jacob D. Estes, Scott G. Hansen, Brandon F. Keele, Jeffery D. Lifson, Louis J. Picker
Journal: Journal of Clinical Investigation (2021)

To define the contribution of CD8+ T cell responses to control of SIV reactivation during and following antiretroviral therapy (ART), we determined the effect of long-term CD8+ T cell depletion using a rhesusized anti-CD8β monoclonal antibody on barcoded SIVmac239 dynamics on stable ART and after ART cessation in rhesus macaques (RMs). Among the RMs with full CD8+ T cell depletion in both blood and tissue, there were no significant differences in the frequency of viral blips in plasma, the number of SIV RNA+ cells and the average number of RNA copies/infected cell in tissue, and levels of cell-associated SIV RNA and DNA in blood and tissue relative to control-treated RMs during ART. Upon ART cessation, both CD8+ T cell–depleted and control RMs rebounded in fewer than 12 days, with no difference in the time to viral rebound or in either the number or growth rate of rebounding SIVmac239M barcode clonotypes. However, effectively CD8+ T cell–depleted RMs showed a stable, approximately 2-log increase in post-ART plasma viremia relative to controls. These results indicate that while potent antiviral CD8+ T cell responses can develop during ART-suppressed SIV infection, these responses effectively intercept post-ART SIV rebound only after systemic viral replication, too late to limit reactivation frequency or the early spread of reactivating SIV reservoirs.
Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study
Authors: Amy Langdon, Drew J. Schwartz, Christopher Bulow, Xiaoqing Sun, Tiffany Hink, Kimberly A. Reske, Courtney Jones, Carey-Ann D. Burnham, Erik R. Dubberke, Gautam Dantas
Journal: Genome Medicine (2021)

Abstract Background Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non- C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI. Methods An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one ( N = 16) or two doses of RBX2660 ( N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms. Results Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted. Conclusions Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others. Trial registration ClinicalTrials.gov, NCT01925417 ; registered on August 19, 2013.
The patient tells it! The importance of patient's quality of life perception in pulmonary arterial hypertension risk assessment
Authors: Silvia Ulrich, Ekkehard Grunig
Journal: European Respiratory Journal (2021)

<b>Assessment of quality of life in pulmonary hypertension is important to identify additional therapeutic needs, and patients with good QoL have better prognosis. QoL assessment in PH care can be done with validated short questionnaires, such as emPHasis-10.</b>https://bit.ly/3s5jF3U