tbuckley/cabot-search huggingface dataset:
Nanodefensin-encased hydrogel with dual bactericidal and pro-regenerative functions for advanced wound therapy
Authors: Gan Luo, Yaqi Sun, Jue Zhang, Zhipeng Xu, Wuyuan Lu, Hanbin Wang, Yan Zhang, Hui Li, Zhengwei Mao, Shixin Ye, Baoli Cheng, Xiangming Fang
Journal: Theranostics (2021)

Background: Host defense peptides (HDPs) have emerged as a novel therapeutic paradigm for wound management; however, their clinical applications remain a challenge owing to their poor pharmacological properties and lack of suitable pharmaceutical formulations. Nanodefensin (ND), a nanoengineered human α-defensin 5 (HD5), has shown improved pharmacological properties relative to the parent compound. In this study, we engineered a nanodefensin-encased hydrogel (NDEFgel), investigated the effects of NDEFgel on wound healing, and elucidated underlying mechanisms. Method: ND was chemically synthesized and tested functions by in vitro antimicrobial and scratch assays and western blotting. Different NDEFgels were evaluated by in vitro characterizations including degradation, drug release and antimicrobial activity. In full-thickness excisional murine models, the optimal NDEFgel was directly applied onto wound sites, and the efficacy was assessed. Moreover, the underlying mechanisms of pro-regenerative effect developed by NDEFgel were also explored. Results: Apart from bactericidal effects, ND modulated fibroblast behaviors by promoting migration and differentiation. Among the tested hydrogels, the Pluronic F127 (Plu) hydrogel represented the most desirable carrier for ND delivery owing to its favorable controlled release and compatibility with ND. Local treatment of NDEFgel on the wound bed resulted in accelerated wound regeneration and attenuated bacterial burden. We further demonstrated that NDEFgel therapy significantly upregulated genes related to collagen deposition and fibroblasts, and increased the expression of myofibroblasts and Rac1. We therefore found that Rac1 is a critical factor in the ND-induced modulation of fibroblast behaviors in vitro through a Rac1-dependent cytoskeletal rearrangement. Conclusion: Our results indicate that NDEFgel may be a promising dual-action therapeutic option for advanced wound management in the future.
How Common Is the Rare Charcot Foot in Patients With Diabetes?
Authors: Ole Lander Svendsen, Oliver Christian Rabe, Matilde Winther-Jensen, Kristine Højgaard Allin
Journal: Diabetes Care (2021)

The Charcot foot is a devastating complication to diabetes (1). It manifests as an acute aseptic inflammation of bones and joints in the feet. If not diagnosed and treated in time, it may lead to collapse of bones in the foot, which causes deformity, foot ulcers, amputation, and death (1). The diagnosis of acute Charcot foot is often delayed due to little knowledge of the disease among patients and clinicians, probably because of its rarity. But how rare is it?

To answer this, we have assessed the incidence and prevalence of the Charcot foot among all patients with diabetes in Denmark.

The Danish National Patient Register contains information on all hospitalizations and information on outpatient visits and emergency room contacts from 1995 to present (2). Data about age, sex, and emigrations (temporary or permanent) were retrieved from The Danish Civil Registration System, and dates of death were found in the Death Register, Statistics Denmark (2).

All individuals in the Danish National Patient …
David Oliver: Mistruths and misunderstandings about covid-19 death numbers
Authors: David Oliver
Journal: BMJ (2021)

I want to set the record straight about some serious misinformation surrounding covid-19 death certification and mortality statistics. I will paraphrase some of the claims that I have heard repeatedly in the media:

“People are not dying from, but with, covid-19.” “Deaths classified as from covid-19 result from largely false positive polymerase chain reaction (PCR) test results,” “deaths are mostly from other causes and underlying conditions,” “death numbers are grossly inflated,” “there is no excess mortality compared with other years or months,” and this is “no different from a normal flu season.”

Let’s see, shall we?

According to the Office for National Statistics (ONS), the total number of deaths with covid-19 recorded on the death certificate in England and Wales has now passed 100 000.1 The government’s daily press releases, however, report “deaths within 28 days of a positive test result”—a definition repeated faithfully by broadcast and print journalists and on social media.2 This …
Improved prediction of fracture risk leveraging a genome-wide polygenic risk score
Authors: Tianyuan Lu, Vincenzo Forgetta, Julyan Keller-Baruch, Maria Nethander, Derrick Bennett, Marie Forest, Sahir Bhatnagar, Robin G. Walters, Kuang Lin, Zhengming Chen, Liming Li, Magnus Karlsson, Dan Mellström, Eric Orwoll, Eugene V. McCloskey, John A. Kanis, William D. Leslie, Robert J. Clarke, Claes Ohlsson, Celia M. T. Greenwood, J. Brent Richards
Journal: Genome Medicine (2021)

Abstract Background Accurately quantifying the risk of osteoporotic fracture is important for directing appropriate clinical interventions. While skeletal measures such as heel quantitative speed of sound (SOS) and dual-energy X-ray absorptiometry bone mineral density are able to predict the risk of osteoporotic fracture, the utility of such measurements is subject to the availability of equipment and human resources. Using data from 341,449 individuals of white British ancestry, we previously developed a genome-wide polygenic risk score (PRS), called gSOS, that captured 25.0% of the total variance in SOS. Here, we test whether gSOS can improve fracture risk prediction. Methods We examined the predictive power of gSOS in five genome-wide genotyped cohorts, including 90,172 individuals of European ancestry and 25,034 individuals of Asian ancestry. We calculated gSOS for each individual and tested for the association between gSOS and incident major osteoporotic fracture and hip fracture. We tested whether adding gSOS to the risk prediction models had added value over models using other commonly used clinical risk factors. Results A standard deviation decrease in gSOS was associated with an increased odds of incident major osteoporotic fracture in populations of European ancestry, with odds ratios ranging from 1.35 to 1.46 in four cohorts. It was also associated with a 1.26-fold (95% confidence interval (CI) 1.13–1.41) increased odds of incident major osteoporotic fracture in the Asian population. We demonstrated that gSOS was more predictive of incident major osteoporotic fracture (area under the receiver operating characteristic curve (AUROC) = 0.734; 95% CI 0.727–0.740) and incident hip fracture (AUROC = 0.798; 95% CI 0.791–0.805) than most traditional clinical risk factors, including prior fracture, use of corticosteroids, rheumatoid arthritis, and smoking. We also showed that adding gSOS to the Fracture Risk Assessment Tool (FRAX) could refine the risk prediction with a positive net reclassification index ranging from 0.024 to 0.072. Conclusions We generated and validated a PRS for SOS which was associated with the risk of fracture. This score was more strongly associated with the risk of fracture than many clinical risk factors and provided an improvement in risk prediction. gSOS should be explored as a tool to improve risk stratification to identify individuals at high risk of fracture.
Developmental Perspectives on the Study of Persons with Intellectual Disability
Authors: Jacob A. Burack, David W. Evans, Natalie Russo, Jenilee-Sarah Napoleon, Karen J. Goldman, Grace Iarocci
Journal: Annual Review of Clinical Psychology (2021)

Developmental approaches provide inclusive, universal, and methodologically rigorous frameworks for studying persons with intellectual disability (ID). This is an exceptionally heterogeneous group with regard to etiology, genotype, and phenotype that simply shares the traditional diagnostic criteria, typically a score of two standard deviations below the population mean of 100 on standardized IQ tests and deficits in adaptive behavior. We trace the foundational, conceptual, and methodological roots of developmental approaches and highlight ways that these and more recent iterations continue to be central to advances in the increasingly nuanced study of persons with ID. This work is premised on the consideration of specific etiological groupings and subgroupings across and between different domains of functioning within the context of familial and complex environments throughout the life span. We highlight the potential contributions of advances in behavioral methodologies, genomics, and neuroscience when considered within universal and hierarchic frameworks based on development.
Seroprevalence and risk factors of exposure to COVID-19 in homeless people in Paris, France: a cross-sectional study
Authors: Thomas Roederer, Bastien Mollo, Charline Vincent, Birgit Nikolay, Augusto E Llosa, Robin Nesbitt, Jessica Vanhomwegen, Thierry Rose, Sophie Goyard, François Anna, Corinne Torre, Emilie Fourrey, Erica Simons, William Hennequin, Clair Mills, Francisco J Luquero
Journal: The Lancet Public Health (2021)
The diagnosis of non-life-threatening immediate penicillin allergy should not rest upon low sIgE results between 0.10 kUA/L and 0.35 kUA/L in isolation
Authors: Marie-Line Van Der Poorten, Athina Van Gasse, Margo Hagendorens, Margaretha Faber, Leander De Puysseleyr, Jessy Elst, Christel Mertens, Anca Chiriac, Didier Ebo, Vito Sabato
Journal: Journal of Allergy and Clinical Immunology (2021)
One‐year results of the first‐in‐man study investigating the <scp>Atrial Flow Regulator</scp> for left atrial shunting in symptomatic heart failure patients: the <scp>PRELIEVE</scp> study
Authors: Christina Paitazoglou, Martin W. Bergmann, Ramazan Özdemir, Roman Pfister, Jozef Bartunek, Teoman Kilic, Alexander Lauten, Alexander Schmeisser, Mehdi Zoghi, Stefan D. Anker, Horst Sievert, Felix Mahfoud
Journal: European Journal of Heart Failure (2021)

Attenuating exercise-induced elevated left atrial pressure with an atrial shunt device is under clinical investigation for treatment of symptomatic heart failure (HF).PRELIEVE was a prospective, non-randomised, multicentre, first-in-man study in symptomatic HF patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction and pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg during exercise. Here, we provide follow-up data up to 1 year after implantation of the Atrial Flow Regulator (AFR) device. The AFR was successfully implanted in 53 patients (HFrEF n = 24 and HFpEF n = 29). Two patients were not enrolled due to an unsuccessful transseptal puncture. There was one device embolisation into the left atrium, which required surgical removal. One patient experienced a serious procedure-related adverse event (post-procedural bleeding and syncope). All patients with sufficient echocardiography readout confirmed device patency with left-right shunt both at 3 (n = 47/51, 92%) and 12 (n = 45/49, 92%) months. At 3 months, rest PCWP decreased by 5 (-12, 0) mmHg (P = 0.0003, median Q1, Q3). No patient developed a stroke, worsening of right heart function or significant increase of pulmonary artery pressure. Six (6/53, 11%) patients were hospitalised for worsening of HF and three (3/53, 6%) patients died. We observed improvements in New York Heart Association functional class, 6-min walking distance and quality of life (Kansas City Cardiomyopathy Questionnaire) in certain patients.Implantation of the AFR device in HF patients was feasible. No shunt occlusion, stroke or new right HF was observed during the 1-year follow-up, with clinical improvements in certain patients.
Rapid Adoption of Video Visits and Return-to-Clinic Procedures to Maintain Access to Allergy/Immunology Care Delivery During COVID-19
Authors: Lulu Tsao, Stephanie Anne Villanueva Ferraris, David Pines, Eugene Choo, Michele Pham, Monica Tang, Lorianna Leard, Andrew Gross, Cameron Ashbaugh, Lei Choi, Iris Otani
Journal: Journal of Allergy and Clinical Immunology (2021)
Blood Dendritic Cells, Monocytes and Myeloid-derived Suppressor Cells in Patients with COVID-19 Associated Pneumonia
Authors: Andrei Hancharou, Alena Rynda, Yana Minich, Natalia Antonevich, Oxana Timohina, Alena Halavach, Darya Babrukevich, Marina Dotsenko, Eduard Dotsenko, Lawrence Dubuske
Journal: Journal of Allergy and Clinical Immunology (2021)
Role of nanostructures in allergy: Diagnostics, treatments and safety
Authors: Cristobalina Mayorga, Ezequiel Perez‐Inestrosa, Javier Rojo, Marta Ferrer, Maria Isabel Montañez
Journal: Allergy (2021)

Abstract Nanotechnology is science, engineering and technology conducted at the nanoscale, which is about 1–100 nm. It has led to the development of nanomaterials, which behave very differently from materials with larger scales and can have a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition and functionalization of the system. Nanoparticles, carbon nanotubes, liposomes, polymers, dendrimers and nanogels, among others, can be nanoengineeried for controlling all parameters, including their functionalization with ligands, which provide the desired interaction with the immunological system, that is dendritic cell receptors to activate and/or modulate the response, as well as specific IgE, or effector cell receptors. However, undesired issues related to toxicity and hypersensitivity responses can also happen and would need evaluation. There are wide panels of accessible structures, and controlling their physico‐chemical properties would permit obtaining safer and more efficient compounds for clinical applications goals, either in diagnosis or treatment. The application of dendrimeric antigens, nanoallergens and nanoparticles in allergy diagnosis is very promising since it can improve sensitivity by increasing specific IgE binding, mimicking carrier proteins or enhancing signal detection. Additionally, in the case of immunotherapy, glycodendrimers, liposomes, polymers and nanoparticles have shown interest, behaving as platforms of allergenic structures, adjuvants or protectors of allergen from degradation or having a depot capacity. Taken together, the application of nanotechnology to allergy shows promising facts facing important goals related to the improvement of diagnosis as well as specific immunotherapy.
Pan-Cancer Drivers Are Recurrent Transcriptional Regulatory Heterogeneities in Early-Stage Luminal Breast Cancer
Authors: Shambhavi Singh, Matthew D. Sutcliffe, Kathy Repich, Kristen A. Atkins, Jennifer A. Harvey, Kevin A. Janes
Journal: Cancer Research (2021)

Abstract The heterogeneous composition of solid tumors is known to impact disease progression and response to therapy. Malignant cells coexist in different regulatory states that can be accessed transcriptomically by single-cell RNA sequencing, but these methods have many caveats related to sensitivity, noise, and sample handling. We revised a statistical fluctuation analysis called stochastic profiling to combine with 10-cell RNA sequencing, which was designed for laser-capture microdissection (LCM) and extended here for immuno-LCM. When applied to a cohort of late-onset, early-stage luminal breast cancers, the integrated approach identified thousands of candidate regulatory heterogeneities. Intersecting the candidates from different tumors yielded a relatively stable set of 710 recurrent heterogeneously expressed genes (RHEG), which were significantly variable in &amp;gt;50% of patients. RHEGs were not strongly confounded by dissociation artifacts, cell-cycle oscillations, or driving mutations for breast cancer. Rather, RHEGs were enriched for epithelial-to-mesenchymal transition genes and, unexpectedly, the latest pan-cancer assembly of driver genes across cancer types other than breast. These findings indicate that heterogeneous transcriptional regulation conceivably provides a faster, reversible mechanism for malignant cells to evaluate the effects of potential oncogenes or tumor suppressors on cancer hallmarks. Significance: Profiling intratumor heterogeneity of luminal breast carcinoma cells identifies a recurrent set of genes, suggesting sporadic activation of pathways known to drive other types of cancer. See related articles by Schaff and colleagues, p. 1853 and Sutcliffe and colleagues, p. 1868
Intra-Individual Changes in Immune Marker Concentrations and Multiple Myeloma Risk: A Longitudinal Prospective Study Using Repeated Pre-Diagnostic Plasma Samples
Authors: Florentin Späth, Carl Wibom, Esmeralda J.M. Krop, Ann-Sofie Johansson, Ingvar A. Bergdahl, Roel Vermeulen, Beatrice Melin
Journal: Blood (2017)
Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors
Authors: Jang Hyun Park, Hyun-Jin Kim, Chae Won Kim, Hyeon Cheol Kim, Yujin Jung, Hyun-Soo Lee, Yunah Lee, Young Seok Ju, Ji Eun Oh, Sung-Hong Park, Jeong Ho Lee, Sung Ki Lee, Heung Kyu Lee
Journal: Nature Immunology (2021)
Abstract 18146: Increased Physical Activity is Associated With Lower Risk of Non Alcoholic Fatty Liver Disease Across Spectrum of Cardiometabolic Risk
Authors: Ebenezer T Oni, Ehimen Aneni, Adil Karim, Wasim Mazaik, Theodore Feldman, Michael Blaha, Seth S Martin, Arthur A Agatston, Roger S Blumenthal, Raquel D Conceiçao, Romeu S Meneghelo, Jose A Carvalho, Raul D Santos, Khurram Nasir
Journal: Circulation (2013)

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been linked with increased cardiovascular risk. Its prevalence is associated with increase in obesity and insulin resistance. Although physical activity (PA) and life style modification are often recommended to treat NAFLD, the benefit across metabolic risk spectrum is unclear. We aimed to evaluate the relationship of PA and NAFLD independent of the metabolic syndrome (MS). METHODS: We evaluated 5,743 healthy Brazilian subjects (43±10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. NALFD was ultrasound diagnosed and PA was assessed using the International Physical Activity Questionnaire (IPAQ) scale. MS was classified with the IDF criteria. In hierarchical regression models, we evaluated for an independent association of NAFLD and physical activity (PA). RESULTS: The prevalence of NAFLD was 36% (n=2,075) and 1,152 (20%) had metabolic syndrome. NALFD was significantly higher in those with MS (74%) vs those without MS (26%), p&lt;0.001. Overall 1,304 (23%) individuals were sedentary and 1,987(35%) had minimal activity. The prevalence of NALFD decreased significantly with increasing levels of PA reported (sed: 45%, minimally active: 38%, active= 30%, p&lt;0.001). As shown in table below, after adjusting for confounding variables, higher activity levels was 16-31% less likely associated with NALFD. The benefit appeared to be extend to individuals with and without MS, Conclusions: PA presents a dose response association with hepatic steatosis independent of the MS. The benefits of PA is not only relevant in MS individuals but should also be emphasized in a non-MS population
Searching for the Optimal Exercise Training Regimen in Heart Failure With Preserved Ejection Fraction
Authors: Ambarish Pandey, Dalane W. Kitzman
Journal: JAMA (2021)

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Shorter Dosing Interval Is Associated With Multiple Doses Of Epinephrine Required To Resolve Allergic Reaction At Milk Oral Challenge
Authors: Danbing Ke, Bruce Mazer, Duncan Lejtenyi, Liane Beaudette, Casey Cohen, Eisha Ahmed, Julia Upton, Edmond Chan, Eyal Grunebaum, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2021)
GLS-409, a Synergistic Inhibitor of Both P2Y1 and P2Y12: Efficacy in a Canine Model of Recurrent Coronary Thrombosis and Reversibility of Human Platelet Inhibition
Authors: Elena Smolensky Koganov, Alan D Michelson, Ivan B Yanachkov, Milka I Yanachkova, George E Wright, Karin Przyklenk, Andrew L Frelinger
Journal: Blood (2017)
Real-World Effectiveness of Systemic Therapies for Atopic Dermatitis (AD) in the United States: Analysis of a Retrospective Claims Database
Authors: Marco DiBonaventura, Marie-Helene Lafeuille, Bruno Emond, Mei Sheng Duh, Iman Fakih, Natalie Yin, Daniela Myers, Claire Feeney, Joseph Cappelleri, Jashin Wu
Journal: Journal of Allergy and Clinical Immunology (2021)
Immunosensation: Neuroimmune Cross Talk in the Skin
Authors: Masato Tamari, Aaron M. Ver Heul, Brian S. Kim
Journal: Annual Review of Immunology (2021)

Classically, skin was considered a mere structural barrier protecting organisms from a diversity of environmental insults. In recent decades, the cutaneous immune system has become recognized as a complex immunologic barrier involved in both antimicrobial immunity and homeostatic processes like wound healing. To sense a variety of chemical, mechanical, and thermal stimuli, the skin harbors one of the most sophisticated sensory networks in the body. However, recent studies suggest that the cutaneous nervous system is highly integrated with the immune system to encode specific sensations into evolutionarily conserved protective behaviors. In addition to directly sensing pathogens, neurons employ novel neuroimmune mechanisms to provide host immunity. Therefore, given that sensation underlies various physiologies through increasingly complex reflex arcs, a much more dynamic picture is emerging of the skin as a truly systemic organ with highly coordinated physical, immunologic, and neural functions in barrier immunology.