anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The underlying mechanisms of asbestos-related autoimmunity are poorly understood. As the size, surface reactivity, and free radical activity of asbestos particles are considered crucial regarding the health effects, this study aims to compare the effects of exposure to pristine amosite (pAmo) or milled amosite (mAmo) particles on lung damage, autoimmunity, and macrophage phenotype. Four months after lung exposure to 0.1 mg of amosite, BAL levels of lactate dehydrogenase, protein, free DNA, CCL2, TGF-β1, TIMP-1, and immunoglobulin A of pAmo-exposed C57Bl/6 mice were increased when compared to fluids from control- and mAmo-exposed mice. Effects in pAmo-exposed mice were associated with lung fibrosis and autoimmunity including anti-double-strand DNA autoantibody production. mAmo or pAmo at 20 µg/cm2 induced a pro-inflammatory phenotype characterized by a significant increase in TNFα and IL-6 secretion on human monocyte-derived macrophages (MDMs). mAmo and pAmo exposure induced a decrease in the efferocytosis capacities of MDMs, whereas macrophage abilities to phagocyte fluorescent beads were unchanged when compared to control MDMs. mAmo induced IL-6 secretion and reduced the percentage of MDMs expressing MHCII and CD86 markers involved in antigen and T-lymphocyte stimulation. By contrast, pAmo but not mAmo activated the NLRP3 inflammasome, as evaluated through quantification of caspase-1 activity and IL-1β secretion. Our results demonstrated that long-term exposure to pAmo may induce significant lung damage and autoimmune effects, probably through an alteration of macrophage phenotype, supporting in vivo the higher toxicity of entire amosite (pAmo) with respect to grinded amosite. However, considering their impact on efferocytosis and co-stimulation markers, mAmo effects should not be neglected. KEY MESSAGES: Lung fibrosis and autoimmunity induced by amosite particles depend on their physicochemical characteristics (size and surface) Inhalation exposure of mice to pristine amosite fibers is associated with lung fibrosis and autoimmunity Anti-dsDNA antibody is a marker of autoimmunity in mice exposed to pristine amosite fibers Activation of lung mucosa-associated lymphoid tissue, characterized by IgA production, after exposure to pristine amosite fibers Pristine and milled amosite particle exposure reduced the efferocytosis capacity of human-derived macrophages.
BACKGROUND: Nearly 20% Patients with cyanotic congenital heart disease (CCHD) are not able to receive surgery. These patients experience a decline in cardiac function as they age, which has been demonstrated to be associated with changes in energy metabolism in cardiomyocytes. Trimetazidine (TMZ), a metabolic regulator, is supposed to alleviate such maladaptation and reserve cardiac function in CCHD patients.
METHODS: This is a randomized, double-blind, placebo-controlled clinical trial. Eighty adult CCHD patients will be recruited and randomized to the TMZ (20 mg TMZ 3 times a day for 3 months) or placebo group (placebo 3 times a day for 3 months). The primary outcome is the difference in cardiac ejection fractions (EF) measured by cardiac magnetic resonance (MRI) between baseline and after 3 months of TMZ treatment. The secondary outcomes include TMZ serum concentration, rate of cardiac events, NYHA grading, fingertip SpO2, NT-proBNP levels, 6-minute walking test (6MWT), KCCQ-CSS questionnaire score, echocardiography, ECG, routine blood examination, liver and kidney function test, blood pressure and heart rate.
DISCUSSION: This trial is designed to explore whether the application of TMZ in adult CCHD patients can improve cardiac function, reduce cardiac events, and improve exercise performance and quality of life. The results will provide targeted drug therapy for CCHD patients with hypoxia and support the application of TMZ in children with CCHD.
Provided are thiol-ene polymer networks which can reduce the ROS species that contribute to delayed bone healing and fusion. Furthermore, patients that suffer from neuropathic comorbidities such as diabetes suffer from a diminished healing capacity. An increase in proinflammatory factors and the high presence of reactive oxygen species (ROS) present in diabetics are linked to lower fusion rates. To this end, there is a need for a clinically relevant bone graft to promote bone fusions in patients with neuropathic comorbidities. Incorporating thiol-ene networks for bone scaffolds has demonstrated increased osteogenic biomarkers over traditional polymeric materials and act as antioxidants. Thiol-ene networks offer improved bone grafts for diabetic patients by reducing the number of hydroxyl radicals associated with neuropathic comorbidities. These networks are particularly well suited in promoting healing in patients with Type II Diabetes or other conditions exacerbated by ROS-mediated damage.
Amiodarone therapy is used frequently for control of ventricular arrhythmias in patients who receive painful shocks from an implantable cardioverter-defibrillator (ICD). Data in post-myocardial infarction (MI) patients and ICD patients suggest that amiodarone is mortality-neutral; it neither confers increased nor decreased mortality. However, these data are derived from patients largely with normal intraventricular conduction, manifesting as a QRS complex duration on the surface ECG \<120 ms. Amiodarone, in addition to potassium-channel blocking effects, is a sodium channel-blocker. Because sodium channels mediate cardiac depolarization, and a QRS complex \>120 ms is indicative of abnormal depolarization, amiodarone may not be benign in patients with such conduction defects. Patients with cardiac resynchronization therapy-defibrillators (CRT-D), who all have abnormal baseline intraventricular conduction, may therefore be adversely affected by amiodarone. Anecdotal clinical data suggest that this may be the case, but the question of amiodarone's cardiac safety profile in CRT patients has never been studied.
In this study, participants will be randomly allocated to a baseline (A) phase that is further divided into two sub-phases, with different durations of either 10 or 21 days. The allocation to different durations of the baseline phase is randomized in order to mitigate threats to internal validity. During the baseline (A) phase, a representative baseline will be established through repeated measurements of the PQRS. Following the baseline phase (A), the 8-week intervention phase (B) is implemented, followed by a second 3-week (A) phase. There is no separate control group in this study, and all participants receive the same intervention during the intervention phase (B).
Febrile seizures (FSs) are defined as seizures occurring in children aged 6 months to 5 years with a background of elevated body temperature. It is one of the most common neurological disorders of childhood, emphasizing the importance of understanding the causes of FSs and their impact on the developing nervous system. However, there are significant limitations to the technologies currently available for studying the etiology and pathophysiology of seizures in humans. It is currently not possible to adequately capture the subtle molecular and structural rearrangements of the nervous system that can occur after seizures in humans. The use of animal models can be invaluable for these purposes. The most commonly used models in modern research are hyperthermic models in rats and mice aged 10-12 days. While these models can reproduce many of the characteristics of FSs, they have certain limitations. This review outlines the key considerations when working with models of FSs, provides an overview of current approaches to producing seizures in different model subjects, and presents a summary of key findings regarding morphological and functional changes in the brain and behavioral alterations that have been identified in studies using animal models of FSs.
The invention relates to a yncD gene knock-out vector for saimonella. The vector comprises a pYG4 plasmid sequence and yncD gene upstream and downstream sequences from which yncD gene sequences are removed and which can ensure that a reading frame is not changed. The invention also provides a preparation method of the yncD gene knock-out vector for the saimonella and a saimonella attenuated vaccine which is prepared by knocking out a yncD gene from the the saimonella by using the yncD gene knock-out vector for the saimonella. Due to the adoption of the yncD gene knock-out vector for the saimonella, the yncD gene can be accurately knocked out from the saimonella, and the toxicity of a knocked-out strain is lowered remarkably and is prevented from restoring. The yncD gene knock-out vector for the saimonella is easy to prepare, and is safe and effective to use. The saimonella attenuated vaccine prepared by knocking out the yncD gene from the saimonella by applying the yncD gene knock-out vector for the saimonella is convenient to use and has high safety.
Temporomandibular disorders (TMDs), collectively representing one of the most common chronic pain conditions, have a substantial genetic component, but genetic variation alone has not fully explained the heritability of TMD risk. Reasoning that the unexplained heritability may be because of DNA methylation, an epigenetic phenomenon, we measured genome-wide DNA methylation using the Illumina MethylationEPIC platform with blood samples from participants in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Associations with chronic TMD used methylation data from 496 chronic painful TMD cases and 452 TMD-free controls. Changes in methylation between enrollment and a 6-month follow-up visit were determined for a separate sample of 62 people with recent-onset painful TMD. More than 750,000 individual CpG sites were examined for association with chronic painful TMD. Six differentially methylated regions were significantly ( P < 5 × 10 -8 ) associated with chronic painful TMD, including loci near genes involved in the regulation of inflammatory and neuronal response. A majority of loci were similarly differentially methylated in acute TMD consistent with observed transience or persistence of symptoms at follow-up. Functional characterization of the identified regions found relationships between methylation at these loci and nearby genetic variation contributing to chronic painful TMD and with gene expression of proximal genes. These findings reveal epigenetic contributions to chronic painful TMD through methylation of the genes FMOD , PM20D1 , ZNF718 , ZFP57 , and RNF39 , following the development of acute painful TMD. Epigenetic regulation of these genes likely contributes to the trajectory of transcriptional events in affected tissues leading to resolution or chronicity of pain.
Cycle 1-Dexamethasone 40mg orally days 1/8/15/22; Lenalidomide 25mg orally days 1-21; Carfilzomib 20mg/m2 days 8/9 then 36mg/m2 venous days 15/16; Daratumumab 16mg/kg venous days 1/8/15/22 (KRd-Dara). Cycle 2 the same except Carfilzomib 36mg/m2 venous days 1/2/8/9/15/16. Cycles 3,4 the same but no Daratumumab Days 8 and 22. Dosage adjusted for last tolerated dose (LTD). Following induction therapy, auto-HCT is done (consolidation 1), then up to two 4-cycle blocks of KRd-Dara consolidation (consolidations 2 and 3). Minimum residual disease (MRD) checked after each phase. Patients with confirmed MRD(-) at or after consolidation 1 will not undergo maintenance and will be actively monitored for resurgence of MRD or clinical relapse. After consolidation if MRD+ patients will undergo standard of care lenalidomide maintenance.
Sham manipulation will be delivered to the cervical spine (segments including occiput-atlas to C7-D1) according to the chiropractors' evaluation during each visit. During each session, one or two segments will receive a sham manipulation applied to the segments with the highest motion restriction, as determined by the chiropractor by static and motion palpation of the cervical spine. The sham manipulation will consist in a identical contact to the real manipulation, except the thrust will be delivered towards the table, away from the target segment and with the intention to lower the cervical drop piece of the table, which will substitute the joint cavitation noise.
The liver has the remarkable capacity to regenerate. In the clinic, regeneration is induced by portal vein embolization, which redirects portal blood flow, resulting in liver hypertrophy in locations with increased blood supply, and atrophy of embolized segments. Here, we apply single-cell and single-nucleus transcriptomics on healthy, hypertrophied, and atrophied patient-derived liver samples to explore cell states in the regenerating liver. Our data unveils pervasive upregulation of genes associated with developmental processes, cellular adhesion, and inflammation in post-portal vein embolization liver, disrupted portal-central hepatocyte zonation, and altered cell subtype composition of endothelial and immune cells. Interlineage crosstalk analysis reveals mesenchymal cells as an interaction hub between immune and endothelial cells, and highlights the importance of extracellular matrix proteins in liver regeneration. Moreover, we establish tissue-scale iterative indirect immunofluorescence imaging for high-dimensional spatial analysis of perivascular microenvironments, uncovering changes to tissue architecture in regenerating liver lobules. Altogether, our data is a rich resource revealing cellular and histological changes in human liver regeneration.
Neuroinflammation, a hallmark of neurodegenerative diseases, is associated with neuronal cell loss and cognitive dysfunction. Monoacylglycerol lipase (MAGL) is involved in neuroinflammation in the brain via the degradation of endocannabinoid 2-arachidonoylglycerol to arachidonic acid, a precursor of some eicosanoids; therefore, MAGL inhibitors are expected to have anti-inflammatory effects. We recently developed a reversible, selective, central nervous system penetrant, and orally available MAGL inhibitor, compound 4f. Compound 4f (1 mg/kg) robustly increased 2-arachidonoylglycerol levels and decreased arachidonic acid levels in the mouse brain. To examine whether compound 4f can suppress neuroinflammation and neuronal cell loss, kainic acid (KA)-injected mice were used as a neuroinflammation model in this study. Compound 4f (1 mg/kg) significantly decreased the cytokine and chemokine expression levels and suppressed neuronal cell loss in the hippocampi of mice. Compound 4f also ameliorated cognitive impairment in KA-injected mice. The cannabinoid receptor 1 antagonist, AM251, and cannabinoid receptor 2 antagonist, AM630, partly blocked the neuroprotective effects of compound 4f in the hippocampi of KA-injected mice. Gene expression profiles and pathway analyses revealed that compound 4f reversed the KA-induced changes in the expression of genes related to inflammation and neurotransmission. These results indicate that the selective and reversible MAGL inhibitor, compound 4f, can be used as a potential therapeutic agent for the treatment of neurodegenerative diseases.
This trial uses an alternative method to demonstrate the analgesic efficacy of NanaBis™ as a monotherapy in cancer participants. Proving analgesic efficacy requires demonstrating that (i) the analgesic is significantly better than placebo and (ii) that the magnitude of the improvement is clinically important. The latter is standardly done by measuring the change in pain levels from a baseline (no analgesia) to the end of a treatment period. A 30% decrease in the Numerical Pain Rating Scale (NPRS) has been correlated with participants reporting a moderate improvement in their pain and this was adopted as the standard method of demonstrating a clinically important magnitude of improvement. In this strategy, the measure of analgesic efficacy is the proportion of participants in the treatment group whose pain is adequately treated (responders). A responder is defined as a patient who completes the treatment phase with an acceptable level of pain (NPRS ≤ 5) and without requiring excessive amounts of rescue (breakthrough analgesia) medication. Unlimited breakthrough analgesia (Oxycodone) is allowed throughout the study; however, excessive use will result in discontinuation. Comparison of the proportion of responders in the NanaBis™ arm and placebo arms will determine if NanaBis™ is significantly better than placebo. Demonstrating that the proportion of responders in the NanaBis™ arm is non-inferior to the Oxycodone controlled release (CR) comparator arm will determine if the magnitude of improvement (provided by NanaBis™) is clinically important because Oxycodone CR has been established as the benchmark analgesic that provides a clinically important effect.
INTRODUCTION: Patients with chronic kidney disease (CKD) are at an alarming risk of fracture compared to age and sex-matched non-CKD individuals. Clinical and preclinical data highlight two key factors in CKD-induced skeletal fragility: cortical porosity and reduced matrix-level properties including bone hydration. Thus, strategies are needed to address these concerns to improve mechanical properties and ultimately lower fracture risk in CKD. We sought to evaluate the singular and combined effects of mechanical and pharmacological interventions on modulating porosity, bone hydration, and mechanical properties in CKD.
METHODS: Sixteen-week-old male C57BL/6J mice underwent a 10-week CKD induction period via a 0.2 % adenine-laced casein-based diet (n = 48) or remained as non-CKD littermate controls (Con, n = 48). Following disease induction (26 weeks of age), n = 7 CKD and n = 7 Con were sacrificed (baseline cohort) to confirm a steady-state CKD state was achieved prior to the initiation of treatment. At 27 weeks of age, all remaining mice underwent right tibial loading to a maximum tensile strain of 2050 μƐ 3× a week for five weeks with the contralateral limb as a non-loaded control. Half of the mice (equal number CKD and Con) received subcutaneous injections of 0.5 mg/kg raloxifene (RAL) 5× a week, and the other half remained untreated (UN). Mice were sacrificed at 31 weeks of age. Serum biochemistries were performed, and bi-lateral tibiae were assessed for microarchitecture, whole bone and tissue level mechanical properties, and composition including bone hydration.
RESULTS: Regardless of intervention, BUN and PTH were higher in CKD animals throughout the study. In CKD, the combined effects of loading and RAL were quantified as lower cortical porosity and improved mechanical, material, and compositional properties, including higher matrix-bound water. Loading was generally responsible for positive impacts in cortical geometry and structural mechanical properties, while RAL treatment improved some trabecular outcomes and material-level mechanical properties and was responsible for improvements in several compositional parameters. While control animals responded positively to loading, their bones were less impacted by the RAL treatment, showing no deformation, toughness, or bound water improvements which were all evident in CKD. Serum PTH levels were negatively correlated with matrix-bound water.
DISCUSSION: An effective treatment program to improve fracture risk in CKD ideally focuses on the cortical bone and considers both cortical porosity and matrix properties. Loading-induced bone formation and mechanical improvements were observed across groups, and in the CKD cohort, this included lower cortical porosity. This study highlights that RAL treatment superimposed on active bone formation may be ideal for reducing skeletal complications in CKD by forming new bone with enhanced matrix properties.
INTRODUCTION: This article presents data on implantable cardioverter-defibrillator implants in Spain in 2023.
METHODS: The registry is based on information provided by centers following device implantation, which is submitted to the Heart Rhythm Association of the Spanish Society of Cardiology via the national online registry platform (Cardiodispositivos). Additional information sources include: a) data transfer from the manufacturing and marketing industry; and b) local databases sent from the implanting centers. Population data from the National Institute of Statistics for the first quarter of 2024 was used to calculate implant rates.
RESULTS: In 2023, 180 hospitals participated in the registry. Data were reported for 8219 units, compared with 8523 reported by Eucomed (European Confederation of Medical Suppliers Associations). The total implant rate was 172 implants per million inhabitants (177 according to Eucomed), representing an increase compared with previous years. However, differences among autonomous communities persisted, and Spain continues to have the lowest implant rate among the European countries participating in Eucomed.
CONCLUSIONS: The data from the 2023 registry reflects 96.4% of the implants performed in Spain. Despite the improvement observed in the implantation rate, Spain's position in Europe remains unchanged, with wide disparities among autonomous communities.
An app-based, "personnel-light" approach to virtual care with a focus on support through group-based interactions with the Trainers, Dietitians and other participants. The patient's personalized 12-week home based exercise program will be enabled in the app after a baseline exercise specialist appointment. The 10-week nutrition program will be enabled at week 3 after a virtual dietitian assessment in week 2 (\~1 hour). The home programs will auto-progress. Participants will also receive a Garmin watch to track their activity over the intervention.