anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Tumor cells can survive when detached from the extracellular matrix or lose cell-to-cell connections, leading to a phenomenon known as anoikis resistance (AR). AR is closely associated with the metastasis and proliferation of tumor cells, enabling them to disseminate, migrate, and invade after detachment. Here, we have investigated a novel composite nanoenzyme comprising mesoporous silica/nano-cerium oxide (MSN-Ce@SP/PEG). This nanoenzyme exhibited satisfactory catalase (CAT) activity, efficiently converting high levels of H2O2 within tumor cells into O2, effectively alleviating tumor hypoxia. Furthermore, MSN-Ce@SP/PEG nanoenzyme demonstrated high peroxidase (POD) activity, elevating reactive oxygen species (ROS) levels and attenuating AR in hepatocellular carcinoma (HCC) cells. The MSN-Ce@SP/PEG nanoenzyme exhibited satisfactory dual bioactivity in CAT and POD and was significantly enhanced under favorable photothermal conditions. Through the synergistic effects of these capabilities, the nanoenzyme disrupted the epithelial-mesenchymal transition (EMT) process in detached HCC cells, ultimately inhibiting the recurrence and metastasis potential of anoikis-resistant HCC cells. This study represents the first report of a novel nanoenzyme based on mesoporous silica/nano-cerium oxide for treating AR in HCC cells, thereby suppressing HCC recurrence and metastasis. The findings of this work offer a pioneering perspective for the development of innovative strategies to prevent the recurrence and metastasis of HCC.
Intermittent hypoxia (IH), a major pathophysiologic alteration in obstructive sleep apnea syndrome (OSAS), is an important contributor to cognitive impairment. Increasing research suggests that melatonin has anti-inflammatory properties and improves functions related to synaptic plasticity. However, it is unclear whether melatonin has a protective effect against OSAS-induced cognitive dysfunction in aged individuals and the involved mechanisms are also unclear. Therefore, in the study, the effects of exposure to IH alone and IH in combination with daily melatonin treatment were investigated in C57BL/6 J mice aged 18 months. Assessment of the cognitive ability of mice in a Morris water maze showed that melatonin attenuated IH-induced impairment of learning and memory in aged mice. Enzyme-linked immunosorbent assay, polymerase chain reaction, and western blotting molecular techniques showed that melatonin treatment reduced the levels of the proinflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, decreased the levels of NOD-like receptor thermal protein domain associated protein 3 and nuclear factor kappa-B, lowered the levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and increased the levels of the synaptic proteins, activity-regulated cytoskeleton-associated protein, growth-associated protein-43, postsynaptic density protein 95, and synaptophysin in IH-exposed mice. Moreover, electrophysiological results showed that melatonin ameliorated the decline in long-term potentiation induced by IH. The results suggest that melatonin can ameliorate IH-induced cognitive deficits by inhibiting neuroinflammation and improving synaptic plasticity in aged mice.
The focus of this work is a proposed novel artificial intelligence (AI) system to self-adapt control policy in powered exoskeletons to aid deployment systems that personalize to individual patient gait. The investigators hypothesize that walking speed will improve with the use of the self-adaptive control policy system. Individuals post stroke have a broad range of mobility challenges including asymmetric gait, substantially decreased SSWS, and reduced stability, and therefore have greatly impaired overall mobility independence in the community. The investigators expect the proposed novel controller, capable of personalization to such variable and asymmetric gait patterns, will have significant benefits towards increasing community independence and mobility for patients post stroke. 12 patients post stroke will be fit with the hip exoskeleton and proceed to walk at varying speeds and inclines on a Motek CAREN system while the investigators measure self-selected walking speed. The self-adaptive system will be compared directly to a best-on-average control policy (non-adaptive) as well as to a 'standard of care' baseline. This baseline will be walking with no exoskeleton plus any clinically prescribed passive orthoses. The investigators expect the self-adaptive system to learn the control policy that best matches the patient's gait patterns, thus yielding advantages in walking speed.
Significance of the Study. Based on the Fear-Avoidance model, the fear comes from the pain perception which increases level of disability (Leeuw et al., 2007). Thus, to break the fear cycle, we need first to reduce the pain intensity. This can be done by a virtual environment into a Head Mounted Displays (HMDs) that provides a fully immersive experience to engage the patients in a virtual environment and distract them from the pain while performing their exercises. Moreover, based on recent clinical guidelines for LBP rehabilitation, exercises are one of the most effective treatments for LBP. Therefore, we believe that a fully immersive based exercise game integrated with physical exercises that include a series of trunk movements such as moving forward, backward, sideways, and rotation. This solution will enhance the rehabilitation outcome since the patients who are suffering from CLBP with fear of movement and high level of disability can use the system at their home and train more for long period of time using a low-cost virtual reality device.
Creatinine-based estimated glomerular filtration rate (eGFR) is imprecise at individual level, due to non-GFR-related serum creatinine determinants, including atypical muscle mass. Cystatin C has the advantage of being independent of muscle mass, a feature that led to the development of race- and sex-free equations. Yet, cystatin C-based equations do not perform better than creatinine-based equations for estimating GFR unless both variables are included together. The new race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation had slight opposite biases between Black and non-Black subjects in the USA, but has poorer performance than that the previous version in European populations. The European Kidney Function Consortium (EKFC) equation developed in 2021 can be used in both children and adults, is more accurate in young and old adults, and is applicable to non-white European populations, by rescaling the Q factor, i.e. population median creatinine, in a potentially universal way. A sex- and race-free cystatin C-based EKFC, with the same mathematical design, has also be defined. New developments in the field of GFR estimation would be standardization of cystatin C assays, development of creatinine-based eGFR equations that incorporate muscle mass data, implementation of new endogenous biomarkers and the use of artificial intelligence. Standardization of different GFR measurement methods would also be a future challenge, as well as new technologies for measuring GFR. Future research is also needed into discrepancies between cystatin C and creatinine, which is associated with high risk of adverse events: we need to standardize the definition of discrepancy and understand its determinants.
Itch, a common somatic sensation, serves as a crucial protective system. Recent studies have unraveled the neural mechanisms of itch at peripheral, spinal cord as well as cerebral levels. However, a comprehensive understanding of the central mechanism governing itch transmission and regulation remains elusive. Here, we report the role of the medial septum (MS), an integral component of the basal forebrain, in modulating the acute itch processing. The increases in c-Fos+ neurons and calcium signals within the MS during acute itch processing were observed. Pharmacogenetic activation manipulation of global MS neurons suppressed the scratching behaviors induced by chloroquine or compound 48/80. Microinjection of GABA into the MS or pharmacogenetic inhibition of non-GABAergic neurons markedly suppressed chloroquine-induced scratching behaviors. Pharmacogenetic activation of the MS-ACC GABAergic pathway attenuated chloroquine-induced acute itch. Hence, our findings reveal that MS has a regulatory role in the chloroquine-induced acute itch through local increased GABA to inhibit non-GABAergic neurons and the activation of MS-ACC GABAergic pathway.
New 3-oxopiperazinium derivatives agonists of Nerve Growth Factor and it use as medicaments. Neurotrophin binding to its specific receptor Trk A leads to the activation of multiple signalling cascades, culminating in neuroregenerative effects, including neuronal survival and neurite outgrowth. Neurotrophic factors have been used for the treatment of several neurodegenerative diseases. However, their use is limited by their inability to cross the blood-brain barrier, their short half life and their side effects. Small molecule neurotrophin peptidomimetics may be beneficial in treating a number of neurodegenerative disorders. The present invention shows the capacity of nerve growth factor agonist molecules derived from the 3-oxopiperazinium scaffold to induce differentiation in PC12 cells and, therefore, that these small molecules with NGF agonist activity may be beneficial for treatment of neurodegenerative diseases, due to their neuroregenerative effects.
Healthy individuals that were not born premature. Individuals are ages 18-35. Subjects will undergo Pulmonary Function Testing, Electrocardiogram, Positron Emission Tomography, and Magnetic Resonance Imaging.
Sansulin® Log-G is an insulin glargine biosimilar. For a biosimilar, its efficacy, safety, and immunogenicity should be compared head-to-head with its reference product in at least non-inferiority study. Immunogenicity assessment should always be done because it is influenced by so many factors, from nature of the drug substance until patient and disease related factors. Moreover its consequences also vary considerably, from clinically irrelevant to serious and life-threatening. Immunogenicity of a biosimilar should always be investigated in humans, since animal data are usually not predictive of the immune response in humans.

Since blinding of study participants is likely unfeasible, at least anti-drug antibodies should be determined in a blinded fashion. Since anti-insulin antibodies develop early, then 6 months duration of study is adequate.
A next-best-action system includes real-time operation and off-line training and processes. During off-line training databases of medical conditions and associated diagnostic factors, tests and treatments are used to create models used for later natural language processing of input electronic text. Diagnostic factors are ranked according to the probability that they indicate conditions and are stored in a matrix. Treatments corresponding to conditions are also stored in a matrix. During real-time operation electronic text is received from patient history of an EHR system, from a transcribed conversation between a physician and a patient, or from input that the physician makes in the EHR system or in an overlaid diagnostic user interface. The electronic text is processed by an NLP pipeline that derives clinical diagnostic factors and test results for the patient. The factors and test results are matched against the matrix of factors to produce a list of likely conditions, along with an ordered list of factors and tests that are either unknown or not yet performed for that patient.
Myocarditis is an inflammatory condition of cardiac tissue presenting significant variability in clinical manifestations and outcomes. Its etiology is diverse, encompassing infectious agents (primarily viruses, but also bacteria, protozoa, and helminths) and non-infectious factors (autoimmune responses, toxins, and drugs), though often the specific cause remains unidentified. Recent research has highlighted the potential role of genetic susceptibility in the development of myocarditis (and in some cases the development of inflammatory dilated cardiomyopathy, i.e., the condition in which there is chronic inflammation (>3 months) and left ventricular dysfunction\dilatation), with several studies indicating a correlation between myocarditis and genetic backgrounds. Notably, pathogenic genetic variants linked to dilated or arrhythmic cardiomyopathy are found in 8-16% of myocarditis patients. Genetic predispositions can lead to recurrent myocarditis and a higher incidence of ventricular arrhythmias and heart failure. Moreover, the presence of DSP mutations has been associated with distinct pathological patterns and clinical outcomes in arrhythmogenic cardiomyopathy (hot phases). The interplay between genetic factors and environmental triggers, such as viral infections and physical stress, is crucial in understanding the pathogenesis of myocarditis. Identifying these genetic markers can improve the diagnosis, risk stratification, and management of patients with myocarditis, potentially guiding tailored therapeutic interventions. This review aims to synthesize current knowledge on the genetic underpinnings of myocarditis, with an emphasis on desmoplakin-related arrhythmogenic cardiomyopathy, to enhance clinical understanding and inform future research directions.
When adaptive phenotypic variation or quantitative trait loci map within an inverted segment of a chromosome, researchers often despair because the suppression of crossing over will prevent the discovery of selective target genes that established the rearrangement. If an inversion polymorphism is old enough, then the accumulation of gene conversion tracts offers the promise that quantitative trait loci or selected loci within inversions can be mapped. The inversion polymorphism of Drosophila pseudoobscura is a model system to show that gene conversion analysis is a useful tool for mapping selected loci within inversions. D. pseudoobscura has over 30 different chromosomal arrangements on the third chromosome (Muller C) in natural populations and their frequencies vary with changes in environmental habitats. Statistical tests of five D. pseudoobscura gene arrangements identified outlier genes within inverted regions that had potentially heritable variation, either fixed amino acid differences or differential expression patterns. We use genome sequences of the inverted third chromosome (Muller C) to infer 98,443 gene conversion tracts for a total coverage of 142 Mb or 7.2× coverage of the 19.7 Mb chromosome. We estimated gene conversion tract coverage in the 2,668 genes on Muller C and tested whether gene conversion coverage was similar among arrangements for outlier vs non-outlier loci. Outlier genes had lower gene conversion tract coverage among arrangements than the non-outlier genes suggesting that selection removes exchanged DNA in the outlier genes. These data support the hypothesis that the third chromosome in D. pseudoobscura captured locally adapted combinations of alleles prior to inversion mutation events.
In patients with congenital hypothyroidism, assess the adequacy of replacement therapy by measuring both serum TSH and total or free-T4. Monitor TSH and total or free-T4 in children as follows: 2 and 4 weeks after the initiation of treatment, 2 weeks after any change in dosage, and then every 3 to 12 months thereafter following dose stabilization until growth is completed. Poor compliance or abnormal values may necessitate more frequent monitoring. Perform routine clinical examination, including assessment of development, mental and physical growth, and bone maturation, at regular intervals. 

While the general aim of therapy is to normalize the serum TSH level, TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of levothyroxine sodium tablets therapy and/or of the serum TSH to decrease below 20 IU per liter within 4 weeks may indicate the child is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of levothyroxine sodium tablets [see Warnings and Precautions (5.1)and Use in Specific Populations (8.4)].
Fibromyalgia is a pain syndrome characterized by central sensitization, and hypersensitivity to nociceptive stimuli. In people with fibromyalgia, objective measures of sensory perception are often impaired. For example, somatosensory temporal discrimination thresholds are elevated, and this correlates with increased widespread pain and severity of other symptoms including fatigue, sleep quality, cognitive symptoms, somatic symptoms and decreased functional status. Sensory-Cognitive training may reduce symptoms by improving attentional modulation of somatosensory signals, improving precision of sensory discrimination, and altering affective processing of somatosensation. The objective of this study is to evaluate the feasibility of the TrainPain program as a somatosensory therapy for people with fibromyalgia.. This study plans to enroll 30 participants between the ages of 18 and 65 who are diagnosed with fibromyalgia and have been experiencing chronic pain with an NRS rating of 4/10 for at least 3 months. All participants who agree to participate in this study will answer a set of baseline questionnaires (PEG, FAS) about their symptoms at the time of inclusion. Participants will also receive the device, and view a demonstration of how to use the technology. The technology consists of two components; (1) an application downloaded to the participants' smartphone and (2) two vibrational devices to be placed on the body of the participant, connected to the application via bluetooth. Participants will use this technology once daily for 28 days. Participants will complete a 15 minute sensory training session using the provided technology; additionally, participants will receive daily text messages to promote pain self-management, and program adherence. Participants will also complete the PEG questionnaire once weekly. After 28 days study team members will conduct a virtual follow-up visit. In that visit, participants will complete the same questionnaires as at baseline (PEG, FAS), as well as a question on their perception of clinical change (PGIC). Participants will also be asked to complete the system usability scale and provide a net promoter score. Finally, participants will complete a subjective feedback questionnaire where they will rate whether participating in this program was time well spent and enjoyable. The primary aim is to determine the feasibility of at-home somatosensorial training for people with fibromyalgia. The secondary aim is to survey participants' subjective report of clinical change after this.
Diabetic cardiomyopathy (DCM) contributes significantly to the heightened mortality rate observed among diabetic patients, with myocardial fibrosis (MF) being a pivotal element in the disease's progression. Hydrogen sulfide (H2S) has been shown to mitigate MF, but the specific underlying mechanisms have yet to be thoroughly understood. A connection has been established between the evolution of DCM and the incidence of cardiomyocyte pyroptosis. Our research offers insights into H2S protective impact and its probable mode of action against DCM, analyzed through the lens of MF. In this study, a diabetic rat model was developed using intraperitoneal injections of streptozotocin (STZ), and hyperglycemia-stimulated cardiomyocytes were employed to replicate the cellular environment of DCM. There was a marked decline in the expression of cystathionine γ-lyase (CSE), a catalyst for H2S synthesis, in both the STZ-induced diabetic rats and hyperglycemia-stimulated cardiomyocytes. Experimental results in vivo indicated that H2S ameliorates MF and enhances cardiac functionality in diabetic rats by mitigating cardiomyocyte pyroptosis. In vitro assessments highlighted the induction of cardiomyocyte pyroptosis and the subsequent decline in cell viability under hyperglycemic conditions. However, the administration of sodium hydrosulfide (NaHS) curtailed cardiomyocyte pyroptosis and augmented cell viability. In contrast, propargylglycine (PAG), a CSE inhibitor, reversed the effects rendered by NaHS administration. Additional exploration indicated that the mitigating effect of H2S on cardiomyocyte pyroptosis is modulated through the ROS/NLRP3 pathway. In essence, our findings corroborate the potential of H2S in alleviating MF in diabetic subjects. This therapeutic effect is likely attributable to the regulation of cardiomyocyte pyroptosis via the ROS/NLRP3 pathway. This discovery furnishes a prospective therapeutic target for the amelioration and management of MF associated with diabetes.
BACKGROUND: Previous systematic reviews have identified the benefits of exercise for chronic neck pain on subjective reports of pain, but not with objective measures such as quantitative sensory testing (QST). A systematic review was conducted to identify the effects of neck specific exercise on QST measures in adults with chronic neck pain to synthesise existing literature and provide clinical recommendations.
METHODS: The study protocol was registered prospectively with PROSPERO (PROSPERO CRD42021297383). For both randomised and non-randomised trials, the following databases and trial registries were searched: AMED, CINAHL, Embase, Google Scholar, Medline, PEDro, PubMed, Scopus, SPORTDiscus, Science Citation Index and Social Science Citation Index from Web of Science Core Collection, clinicaltrials.gov, GreyOpen, and ISRCTN registry. These searches were conducted from inception to February 2022 and were updated until September 2023. Reference lists of eligible studies were screened. Study selection was performed independently by two reviewers, with data extraction and quality appraisal completed by one reviewer and independently ratified by a second reviewer. Due to high heterogeneity, narrative synthesis was performed with results grouped by exercise type.
FINDINGS: Three trials were included. Risk of bias was rated as moderate and the certainty of evidence as low or moderate for all studies. All exercise groups demonstrated statistically significant improvement at an intermediate-term follow-up, with progressive resistance training combined with graded physical training demonstrating the highest certainty of evidence. Fixed resistance training demonstrated statistically significant improvement in QST measures at a short-term assessment.
INTERPRETATION: Fixed resistance training is effective for short-term changes in pain sensitivity based on low-quality evidence, whilst moderate-quality evidence supports progressive resistance training combined with graded physical training for intermediate-term changes in pain sensitivity.
In Part A of the study, subjects were split into two cohorts whereby enrollment of the second cohort depended on the safety profile of the first cohort. In Part A, subjects received three oral doses of ACE527 at 0, 1, and 2 months. For Part B of the study, eligible subjects who expressed interest of the study were administered H10407 challenge strain 5-7 months after the three-dose vaccination series.