tbuckley/cabot-search huggingface dataset:
The osteogenic niche-targeted arsenic nanoparticles prevent colonization of disseminated breast tumor cells in the bone
Authors: Cong Liu, Anzhi Hu, Huijuan Chen, Jing Liang, Mancang Gu, Yang Xiong, Chao-Feng Mu
Journal: Acta Pharmaceutica Sinica B (2021)

Up to 70% of patients with late-stage breast cancer have bone metastasis. Current treatment regimens for breast cancer bone metastasis are palliative with no therapeutic cure. Disseminated tumor cells (DTCs) colonize inside the osteogenic niches in the early stage of bone metastasis. Drug delivery into osteogenic niches to inhibit DTC colonization can prevent bone metastasis from entering its late stage and therefore cure bone metastasis. Here, we constructed a 50% DSS6 peptide conjugated nanoparticle to target the osteogenic niche. The osteogenic niche was always located at the endosteum with immature hydroxyapatite. Arsenic-manganese nanocrystals (around 14 nm) were loaded in osteogenic niche-targeted PEG-PLGA nanoparticles with an acidic environment-triggered arsenic release. Arsenic formulations greatly reduced 4T1 cell adhesion to mesenchymal stem cells (MSCs)/preosteoblasts (pre-OBs) and osteogenic differentiation of osteoblastic cells. Arsenic formulations also prevented tumor cell colonization and dormancy via altering the direct interaction between 4T1 cells and MSCs/pre-OBs. The chemotactic migration of 4T1 cells toward osteogenic cells was blocked by arsenic in mimic 3D osteogenic niche. Systemic administration of osteogenic niche-targeted arsenic nanoparticles significantly extended the survival of mice with 4T1 syngeneic bone metastasis. Our findings provide an effective approach for osteogenic niche-specific drug delivery and suggest that bone metastasis can be effectively inhibited by blockage of tumor cell colonization in the bone microenvironment.
Circulating bacterial signature is linked to metabolic disease and shifts with metabolic alleviation after bariatric surgery
Authors: Rima M. Chakaroun, Lucas Massier, Anna Heintz-Buschart, Nedal Said, Joerg Fallmann, Alyce Crane, Tatjana Schütz, Arne Dietrich, Matthias Blüher, Michael Stumvoll, Niculina Musat, Peter Kovacs
Journal: Genome Medicine (2021)

The microbiome has emerged as an environmental factor contributing to obesity and type 2 diabetes (T2D). Increasing evidence suggests links between circulating bacterial components (i.e., bacterial DNA), cardiometabolic disease, and blunted response to metabolic interventions. In this aspect, thorough next-generation sequencing-based and contaminant-aware approaches are lacking. To address this, we tested whether bacterial DNA could be amplified in the blood of subjects with obesity and high metabolic risk under strict experimental and analytical control and whether a putative bacterial signature is related to metabolic improvement after bariatric surgery.Subjects undergoing bariatric surgery were recruited into sex- and BMI-matched subgroups with (n = 24) or without T2D (n = 24). Bacterial DNA in the blood was quantified and prokaryotic 16S rRNA gene amplicons were sequenced. A contaminant-aware approach was applied to derive a compositional microbial signature from bacterial sequences in all subjects at baseline and at 3 and 12 months after surgery. We modeled associations between bacterial load and composition with host metabolic and anthropometric markers. We further tested whether compositional shifts were related to weight loss response and T2D remission. Lastly, bacteria were visualized in blood samples using catalyzed reporter deposition (CARD)-fluorescence in situ hybridization (FISH).The contaminant-aware blood bacterial signature was associated with metabolic health. Based on bacterial phyla and genera detected in the blood samples, a metabolic syndrome classification index score was derived and shown to robustly classify subjects along their actual clinical group. T2D was characterized by decreased bacterial richness and loss of genera associated with improved metabolic health. Weight loss and metabolic improvement following bariatric surgery were associated with an early and stable increase of these genera in parallel with improvements in key cardiometabolic risk parameters. CARD-FISH allowed the detection of living bacteria in blood samples in obesity.We show that the circulating bacterial signature reflects metabolic disease and its improvement after bariatric surgery. Our work provides contaminant-aware evidence for the presence of living bacteria in the blood and suggests a putative crosstalk between components of the blood and metabolism in metabolic health regulation.
Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration in relation to apoE-linked mechanisms
Authors: Yang Shi, Prabhakar Sairam Andhey, Christina Ising, Kairuo Wang, Lisa L. Snipes, Kevin Boyer, Stephanie Lawson, Kaoru Yamada, Wei Qin, Melissa Manis, Javier Remolina Serrano, Bruno A. Benitez, Robert E. Schmidt, Maxim Artyomov, Jason D. Ulrich, David M. Holtzman
Journal: Neuron (2021)
Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease
Authors: John W. Eikelboom, Deepak L. Bhatt, Keith A.A. Fox, Jacqueline Bosch, Stuart J. Connolly, Sonia S. Anand, Alvaro Avezum, Scott D. Berkowitz, Kelley R.H. Branch, Gilles R. Dagenais, Camilo Félix, Tomasz J. Guzik, Robert G. Hart, Aldo P. Maggioni, Eva Muehlhofer, Mukul Sharma, Olga Shestakovska, Salim Yusuf
Journal: Journal of the American College of Cardiology (2021)
Endoscopic Treatment of a Total Ileorectal Anastomosis Stenosis using Magnets
Authors: Guilherme Francisco Gomes, Rafael William Noda, Thienes Maria da Costa Lima, Eduardo Carboni da Silva, Leandro Yoshimi Kashiwagui, Thaisa Sami Nakadomari, Marciano Anghinoni
Journal: Endoscopy (2021)

The use of magnets in endoscopy has been described for more than 20 years [1]. Magnetic compression anastomosis has been described in experimental animal models as well in clinical use [2]. Chopita and colleagues demonstrated the results of magnetic endoscopic gastroenteric anastomosis in humans with a success rate of 86.6 % [3]. Other authors have used magnets to treat refractory strictures of the esophagus and total stenosis of the biliary tract [4]. Trials with compression anastomosis involving the rectum have already been reported in swine models. A few cases have also been described [5].
Return to Play After COVID-19 Infection in Children
Authors: Lindsay A. Thompson, Maria N. Kelly
Journal: JAMA Pediatrics (2021)

Return to Play After COVID-19 Infection in ChildrenAs the pandemic continues, children may experience long-term effects from COVID-19 infections.Because children may become "long haulers" or develop multisystem inflammatory syndrome in children (MIS-C), close monitoring after a COVID-19 diagnosis is important.In addition, children who are athletes require a separate return-to-play evaluation before they return to competitive sports or physical activities. Children Who Test Positive for COVID-19 InfectionMore than 3 million children have been diagnosed with COVID-19 since the pandemic began.Children have been tested after close exposures, during times of illness, or because they needed clearance for travel or procedures.During a COVID-19 infection, children can experience fever, cough, difficulty breathing, muscle aches, headache, or diarrhea, but many others have no symptoms.Unfortunately, as children get older and/or if they are Hispanic, Black, or American Indian or Alaska Native, they are at a higher risk for severe disease and death from a COVID-19 infection.In addition, any of these children can develop long-term effects.
The protein landscape of chronic lymphocytic leukemia
Authors: Fabienne Meier-Abt, Junyan Lu, Ester Cannizzaro, Marcel F. Pohly, Sandra Kummer, Sibylle Pfammatter, Laura Kunz, Ben C. Collins, Ferran Nadeu, Kwang Seok Lee, Peng Xue, Myriam Gwerder, Michael Roiss, Jennifer Hüllein, Sebastian Scheinost, Sascha Dietrich, Elias Campo, Wolfgang Huber, Ruedi Aebersold, Thorsten Zenz
Journal: Blood (2021)
Brian Hall Smith
Authors: Frank C T Smith
Journal: BMJ (2021)

Brian Hall Smith (also known as “BH”) was born in Wellington, Shropshire, on 31 December 1924. His parents were both headteachers and imbued him with curiosity for science and biology, interest in literature, and lifelong love for botany, photography, and mountains, which he combined, photographing wild orchids in the hills.

Brian gained a scholarship to Bablake Grammar School, Coventry. Evacuated to Lincolnshire during the blitz, he was admitted to Birmingham Medical School in 1942. In his second year he took leave to join the Royal Navy for the D-Day landings. As a member of the Royal Observer Corps, he was deployed as an aircraft spotter, sole British representative on a US Liberty ship. His first view of foreign …
Names of doctors who advised withdrawing treatment from babies should not be disclosed, says judge
Authors: Clare Dyer
Journal: BMJ (2021)

Two sets of parents who fought court battles to try to stop doctors withdrawing life prolonging treatment from their severely ill children have lost their bid to lift reporting restriction orders protecting the identities of the clinicians who treated them.1

The parents of Zainab Abbasi and Isaac Haastrup told the High Court that they wanted to be free to tell their stories about their children’s treatment and identify the doctors involved.

The president of the High Court’s family division, Andrew McFarlane, had to weigh up two rights guaranteed by the European Convention on Human Rights: the parents’ right to freedom of expression under article 10 against the clinicians’ right to privacy under article 8. He decided that the evidence led …
Versatile Nanodrugs Containing Glutathione and Heme Oxygenase 1 Inhibitors Enable Suppression of Antioxidant Defense System in a Two‐Pronged Manner for Enhanced Photodynamic Therapy
Authors: Hao Zhong, Pei‐Ying Huang, Ping Yan, Pei‐Ling Chen, Qun‐Yin Shi, Ze‐An Zhao, Jing‐Xuan Chen, Xian Shu, Ping Wang, Bin Yang, Zheng‐Zheng Zhou, Jian‐Jun Chen, Jian‐Xin Pang, Ying‐Feng Tu, Li‐Han Liu, Xian‐Zheng Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract The antioxidant defense system in malignant cells, which involves antioxidant enzymes and antioxidant molecules, is an innate barrier to photodynamic therapy (PDT). Because of the complexity of the endogenous antioxidant mechanisms of these cells, simply inhibiting individual antioxidant pathways has a limited effect on improving the lethality of ROS. To enhance the efficacy of PDT for tumor treatment, a versatile nanoparticle (NP)‐based drug is developed, which the authors call PZB NP, containing the glutathione inhibitor l ‐buthionine sulfoximine (BSO) and the heme oxygenase 1 (HO‐1) inhibitor protoporphyrin zinc(II) (ZnPP) to suppress the innate antioxidant defense system of cancer cells in a two‐pronged manner. BSO reduces intracellular glutathione levels to minimize ROS elimination and protein protection during PDT, and ZnPP inhibits the ROS‐stimulated upregulation of the antioxidant HO‐1, thus preventing ROS removal by cells after PDT. Thus, BSO and ZnPP synergistically suppress the antioxidant defense systems of cancer cells both during and after protoporphyrin‐IX‐mediated PDT in a two‐pronged manner, resulting in tumor cell death through excess oxidative pressure. The results demonstrate that the construction of nanodrugs having dual antioxidation defense suppression properties is a promising route for the development of highly efficient ROS‐based therapies.
Constrictive bronchiolitis postinfection sars cov2
Authors: S. M. Restrepo, M. I. Garcia-Moya, L. C. Rodriguez-Monasterios, O. P. Panqueva, L. F. Uriza
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Introduction Bronchiolitis obliterans (BO) is a chronic obstructive lung disease with irreversible histological changes, in pediatric patients it is often under diagnosed because of its unusual presentation, however in bronchial obstructive episodes with atypical or severe evolution it should be considered. Bronchiolitis obliterans (BO) can be present in two histopathological forms: constrictive (CB), which is more frequent in pediatrics and proliferative.Case summaryWe present the case of a 2 month-old male who was born full-term, with history of hospitalization for bronchiolitis by SARS CoV2 at 16 days of age. He received management with supplemental oxygen by nasal cannula, without the requirement of invasive ventilatory support, second-line antibiotic management was given due to suspicion of late neonatal sepsis with negative infectious profile studies. He is discharged after 8 days with supplemental oxygen. He was readmitted 3 weeks after for exacerbation of respiratory symptoms and hypoxemia, presenting signs of respiratory distress with intercostal and subcostal retractions and pulmonary auscultation with wheezing. CXR: Interstitial peribronchial opacities (Image A). Due to stationary clinical evolution with signs of respiratory distress and bronchial obstruction, a control CXR showed: Thickening of the axial interstitium (Image B), and echocardiogram was normal. Due to atypical evolution with persistent oxygen requirements and respiratory distress, CB is suspected. A high resolution chest CT showed: Thickening of central bronchial walls with signs of air trapping with small airway compromise and 'ground glass' opacities in the lower lobes (Images C, D). The diagnosis of CB was made and treatment with systemic corticosteroids, macrolide and esteroid inhaled was given.The patient improves and is discharged with oxygen by nasal cannula 0.25L/min.Discussion:The diagnosis of CB is made by a score according to clinical and radiological criteria (High resolution computed tomography of the chest) and clinical criteria. BO score >7 points predicts the diagnosis of BO with high precision. BO it is a chronic inflammatory disease mediated by immune response, the treatment is aimed at suppressing the inflammatory response to avoid lung damage due to irreversible changes, however, once the disease is established, treatment will be symptomatic with strict follow-up of the disease.
Loss of regulatory capacity in Treg cells following rhinovirus infection
Authors: Kirstin Jansen, Oliver F. Wirz, Willem van de Veen, Ge Tan, David Mirer, Milena Sokolowska, Pattraporn Satitsuksanoa, Simon D. Message, Tatiana Kebadze, Nicholas Glanville, Patrick Mallia, Roman Skiepko, Andrzej Eljaszewicz, Marcin Moniuszko, Carlos Cardoso, James E. Gern, Nikolaos G. Papadopoulos, Cezmi A. Akdis, Sebastian L. Johnston, Kari C. Nadeau, Mübeccel Akdis
Journal: Journal of Allergy and Clinical Immunology (2021)
Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a single-arm, open-label, proof-of-concept study
Authors: Lisa Christ, Luca Seitz, Godehard Scholz, Adela-Cristina Sarbu, Jennifer Amsler, Lukas Bütikofer, Christoph Tappeiner, Florian Kollert, Stephan Reichenbach, Peter M Villiger
Journal: The Lancet Rheumatology (2021)
Circulating microRNAs predispose to takotsubo syndrome following high-dose adrenaline exposure
Authors: Liam S Couch, Jan Fiedler, Giles Chick, Rory Clayton, Eef Dries, Laura M Wienecke, Lu Fu, Jerome Fourre, Pragati Pandey, Anselm A Derda, Brian X Wang, Richard Jabbour, Mayooran Shanmuganathan, Peter Wright, Alexander R Lyon, Cesare M Terracciano, Thomas Thum, Sian E Harding
Journal: Cardiovascular Research (2021)

Abstract Aims Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and in the absence of culprit coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. Methods and results miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal), cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavβ subunit), RGS4 (regulator of G-protein signalling 4), and G-protein subunit Gβ (GNB1) as underlying these effects. Conclusion miR-16 and miR-26a sensitize the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future.
Mosaic <i>NEK9</i> mutation, fibrous dysplasia and premature puberty in naevus comedonicus syndrome
Authors: V. Carmignac, G. Salomon, M. Severino‐Freire, Y. Duffourd, M. Chevarin, P. Vabres, J. Mazereeuw‐Hautier
Journal: British Journal of Dermatology (2021)
Early Lung Disease Exhibits Bacteria-Dependent and -Independent Abnormalities in Cystic Fibrosis Pigs
Authors: Drake C. Bouzek, Mahmoud H. Abou Alaiwa, Ryan J. Adam, Alejandro A. Pezzulo, Leah R. Reznikov, Daniel P. Cook, Maria I. Aguilar Pescozo, Patrick Ten Eyck, Chaorong Wu, Thomas J. Gross, Douglas B. Hornick, Eric A. Hoffman, David K. Meyerholz, David A. Stoltz
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Although it is clear that cystic fibrosis (CF) airway disease begins at a very young age, the early and subsequent steps in disease pathogenesis and the relative contribution of infection, mucus, and inflammation are not well understood. Objectives: As one approach to assessing the early contribution of infection, we tested the hypothesis that early and continuous antibiotics would decrease the airway bacterial burden. We believed that, if they do, this might reveal aspects of the disease that are more or less sensitive to decreasing infection. Methods: Three groups of pigs were studied from birth until ∼3 weeks of age: 1) wild-type, 2) CF, and 3) CF pigs treated continuously with broad-spectrum antibiotics from birth until study completion. Disease was assessed with chest computed tomography, histopathology, microbiology, and BAL. Measurements and Main Results: Disease was present by 3 weeks of age in CF pigs. Continuous antibiotics from birth improved chest computed tomography imaging abnormalities and airway mucus accumulation but not airway inflammation in the CF pig model. However, reducing bacterial infection did not improve two disease features already present at birth in CF pigs: air trapping and submucosal gland duct plugging. In the CF sinuses, antibiotics did not prevent the development of infection or disease or the number of bacteria but did alter the bacterial species. Conclusions: These findings suggest that CF airway disease begins immediately after birth and that early and continuous antibiotics impact some, but not all, aspects of CF lung disease development.
Serum Magnesium Is Inversely Associated With Heart Failure, Atrial Fibrillation, and Microvascular Complications in Type 2 Diabetes
Authors: Lynette J. Oost, Amber A.W.A. van der Heijden, Emma A. Vermeulen, Caro Bos, Petra J.M. Elders, Roderick C. Slieker, Steef Kurstjens, Miranda van Berkel, Joost G.J. Hoenderop, Cees J. Tack, Joline W.J. Beulens, Jeroen H.F. de Baaij
Journal: Diabetes Care (2021)

OBJECTIVE We investigated whether serum magnesium (Mg2+) was prospectively associated with macro- or microvascular complications and mediated by glycemic control (hemoglobin A1c [HbA1c]), in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We analyzed in 4,348 participants the association of serum Mg2+ with macrovascular disease and mortality (acute myocardial infarction [AMI], coronary heart disease [CHD], heart failure [HF], cerebrovascular accident [CVA], and peripheral arterial disease [PAD]), atrial fibrillation (AF), and microvascular complications (chronic kidney disease [CKD], diabetic retinopathy, and diabetic foot) using Cox regression, adjusted for confounders. Mediation analysis was performed to assess whether HbA1c mediated these associations. RESULTS The average baseline serum Mg2+ concentration was 0.80 ± 0.08 mmol/L. During 6.1 years of follow-up, serum Mg2+ was inversely associated with major macrovascular, 0.87 (95% CI 0.76; 1.00); HF, 0.76 (95% CI 0.62; 0.93); and AF, 0.59 (95% CI 0.49; 0.72). Serum Mg2+ was not associated with AMI, CHD, CVA, and PAD. During 5.1 years of follow-up, serum Mg2+ was inversely associated with overall microvascular events, 0.85 (95% CI 0.78; 0.91); 0.89 (95% CI 0.82; 0.96) for CKD, 0.77 (95% CI 0.61; 0.98) for diabetic retinopathy, and 0.85 (95% CI 0.78; 0.92) for diabetic foot. HbA1c mediated the associations of serum Mg2+ with HF, overall microvascular events, diabetic retinopathy, and diabetic foot. CONCLUSIONS Serum Mg2+ concentration is inversely associated with the risk to develop HF and AF and with the occurrence of CKD, diabetic retinopathy, and foot complications in T2D. Glycemic control partially mediated the association of serum Mg2+ with HF and microvascular complications.