anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Mitochondrial dysfunction is a primary driver of cardiac contractile failure; yet, the cross talk between mitochondrial energetics and signaling regulation remains obscure. Ponatinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia, is among the most cardiotoxic tyrosine kinase inhibitors and causes mitochondrial dysfunction. Whether ponatinib-induced mitochondrial dysfunction triggers the integrated stress response (ISR) to induce ponatinib-induced cardiotoxicity remains to be determined.
METHODS: Using human induced pluripotent stem cells-derived cardiomyocytes and a recently developed mouse model of ponatinib-induced cardiotoxicity, we performed proteomic analysis, molecular and biochemical assays to investigate the relationship between ponatinib-induced mitochondrial stress and ISR and their role in promoting ponatinib-induced cardiotoxicity.
RESULTS: Proteomic analysis revealed that ponatinib activated the ISR in cardiac cells. We identified GCN2 (general control nonderepressible 2) as the eIF2α (eukaryotic translation initiation factor 2α) kinase responsible for relaying mitochondrial stress signals to trigger the primary ISR effector-ATF4 (activating transcription factor 4), upon ponatinib exposure. Mechanistically, ponatinib treatment exerted inhibitory effects on ATP synthase activity and reduced its expression levels resulting in ATP deficits. Perturbed mitochondrial function resulting in ATP deficits then acts as a trigger of GCN2-mediated ISR activation, effects that were negated by nicotinamide mononucleotide, an NAD+ precursor, supplementation. Genetic inhibition of ATP synthase also activated GCN2. Interestingly, we showed that the decreased abundance of ATP also facilitated direct binding of ponatinib to GCN2, unexpectedly causing its activation most likely because of a conformational change in its structure. Importantly, administering an ISR inhibitor protected human induced pluripotent stem cell-derived cardiomyocytes against ponatinib. Ponatinib-treated mice also exhibited reduced cardiac function, effects that were attenuated upon systemic ISRIB administration. Importantly, ISRIB does not affect the antitumor effects of ponatinib in vitro.
CONCLUSIONS: Neutralizing ISR hyperactivation could prevent or reverse ponatinib-induced cardiotoxicity. The findings that compromised ATP production potentiates GCN2-mediated ISR activation have broad implications across various cardiac diseases. Our results also highlight an unanticipated role of ponatinib in causing direct activation of a kinase target despite its role as an ATP-competitive kinase inhibitor.
BACKGROUND: Atrial fibrosis is one of the main causes of the onset and recurrence of atrial fibrillation (AF), for which there is no effective treatment. The aim of this study was to investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on AF in rats.
METHODS: The rat model of AF was established by rapid pacing induction after angiotensin-II (Ang-II) induced atrial fibrosis to verify the relationship between atrial fibrosis and the AF. The expression levels of TGF-β/Smad3 pathway molecules and lysyl oxidase (LOX) in AF were detected. Subsequently, EGCG was used to intervene Ang-II-induced atrial fibrosis to explore the role of EGCG in the treatment of AF and its inhibitory mechanism on fibrosis. It was further verified that EGCG inhibited the production of collagen and the expression of LOX through the TGF-β/Smad3 pathway at the cellular level.
RESULTS: The results showed that the induction rate and maintenance time of AF in rats increased with the increase of the degree of atrial fibrosis. Meanwhile, the expressions of Col I, Col III, molecules related to TGF-β/Smad3 pathway, and LOX increased significantly in the atrial tissues of rats in the Ang-II induced group. EGCG could reduce the occurrence and maintenance time of AF by inhibiting the degree of Ang-induced rat atrial fibrosis. Cell experiments confirmed that EGCG could reduce the synthesis of collagen and the expression of LOX in cardiac fibroblast induced by Ang-II. The possible mechanism is to down-regulate the expression of genes and proteins related to the TGF-β/Smad3 pathway.
CONCLUSION: EGCG could downregulate the expression levels of collagen and LOX by inhibiting the TGF-β/Smad3 signaling pathway, alleviating Ang-II-induced atrial fibrosis, which in turn inhibited the occurrence and curtailed the duration of AF.
Colorectal cancer (CRC) is the third most common cancer in men and women in the United States with an estimated 147,000 new cases and more than 56,000 deaths each year. Early detection of colon cancer and removal of precancerous adenomatous polyps have been shown to reduce its morbidity, mortality and incidence. There are several recommended CRC screening tests, including fecal occult blood test (FOBT), flexible sigmoidoscopy, air-contrast barium enema, and colonoscopy. In the VA, FOBT is the predominant screening test for CRC. Numerous randomized controlled trials have established the efficacy of FOBT in CRC screening. Its advantages include privacy, noninvasiveness, and cost-effectiveness. Use of guaiac-based testing, however, is hampered by low patient compliance, sensitivity, specificity, and positive predictive value. The poor patient compliance, and low specificity and positive predictive value, may be related to the testing procedure. For example, dietary and medication restrictions are recommended to decrease false-negative and false-positive tests. Such restrictions may impede patient compliance. Recently, several studies have evaluated the effectiveness immunochemical-based testing as a potential alternative, with reportedly better compliance, sensitivity, and specificity than guaiac-based tests. The purpose of our study is to evaluate the diagnostic validity of a new IFOBT (Teco Diagnostics) in U.S. veterans and to compare it with the guaiac based FOBT.
The patients aged 6-12 with a diagnose of ADHD of this group is deficient or insufficient in vitamin A and vitamin D. They will receive placebo once a day in addition to methylphenidate for 8 weeks. After the study, the placebo group will be prescribed with vitamin A and vitamin D supplementation on the grounds of retinol and 25 (OH)D concentration.
FIELD: medicine, pharmacology. SUBSTANCE: method of synthesis involves the successive chain splicing from C-end of molecule using strategy of maximal blocking functional groups. Pentapeptide is synthesized from glycine tert. -butyl ester using a method of activated esters and a method of mixed anhydrides and using carbobenzoxy- and tert. -butylhydroxycarbonylamino acids. Final deblocking is carried out in acid medium and the end product is purified by ion-exchange chromatography. Peptide can be used in clinics, veterinary science and experimental investigations. EFFECT: improved method of synthesis. 8 dwg
A mobile unit with a memory is temporarily connected to a medical technology apparatus is temporarily connected to a central storage device for data transmission. When the mobile unit is connected to the medical technology apparatus, a real configuration of the medical technology apparatus is compared with a local virtual image of the configuration of the medical technology apparatus held in the memory of the mobile unit. Depending on this comparison, the local configuration and/or the real configuration are updated. When the mobile unit is connected to the central storage device, the local configuration is compared with a central virtual image of the configuration of the medical technology apparatus. Depending on this comparison, the central configuration and/or the local configuration are updated. Via the indirect route of the local configuration this enables the real configuration and the central configuration to be mutually updated.
BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment.
METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened.
RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts].
CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.
Type 2 diabetes mellitus has a worldwide prevalence of 10.5% in the adult population (20-79 years), and by 2045, the prevalence is expected to keep rising to one in eight adults living with diabetes. Mild cognitive impairment has a global prevalence of 19.7% in adults aged 50 years. Both conditions have shown a concerning increase in prevalence rates over the past 10 years, highlighting a growing public health challenge. Future forecasts indicate that the prevalence of dementia (no estimations done for individuals with mild cognitive impairment) is expected to nearly triple by 2050. Type 2 diabetes mellitus is a risk factor for the development of cognitive impairment, and such impairment increase the likelihood of poor glycemic/metabolic control. High phytate intake has been shown to be a protective factor against the development of cognitive impairment in observational studies. Diary phytate intake might reduce the micro- and macrovascular complications of patients with type 2 diabetes mellitus through different mechanisms. We describe the protocol of the first trial (the PHYND trial) that evaluate the effect of daily phytate supplementation over 56 weeks with a two-arm double-blind placebo-controlled study on the progression of mild cognitive impairment, cerebral iron deposition, and retinal involvement in patients with type 2 diabetes mellitus. Our hypothesis proposes that phytate, by inhibiting advanced glycation end product formation and chelating transition metals, will improve cognitive function and attenuate the progression from Mild Cognitive Impairment to dementia in individuals with type 2 diabetes mellitus and mild cognitive impairment. Additionally, we predict that phytate will reduce iron accumulation in the central nervous system, mitigate neurodegenerative changes in both the central nervous system and retina, and induce alterations in biochemical markers associated with neurodegeneration.
Subjects in the first group ("Life Completion") completed a psychosocial intervention which consisted of meeting with the facilitator three times for 45-60 minutes each. In the first session, subjects were asked to discuss issues related to life review. In session two, participants spoke about issues of regret and forgiveness. In the final session, subjects focused on heritage and legacy.
BACKGROUND: Early allograft dysfunction (EAD) is a common complication after liver transplantation (LT) and is associated with poor prognosis. Graft itself plays a major role in the development of EAD. We aimed to reveal the EAD-specific molecular profiles to assess graft quality and establish EAD predictive models.
METHODS: A total of 223 patients who underwent LT were enrolled and divided into training ( n =73) and validation ( n =150) sets. In the training set, proteomics was performed on graft biopsies, together with metabolomics on paired perfusates. Differential expression, enrichment analysis, and protein-protein interaction network were used to identify the key molecules and pathways involved. EAD predictive models were constructed using machine learning and verified in the validation set.
RESULTS: A total of 335 proteins were differentially expressed between the EAD and non-EAD groups. These proteins were significantly enriched in triglyceride and glycerophospholipid metabolism, neutrophil degranulation, and the MET-related signaling pathway. The top 12 graft proteins involved in the aforementioned processes were identified, including GPAT1, LPIN3, TGFB1, CD59, and SOS1. Moreover, downstream metabolic products, such as lactate dehydrogenase, interleukin-8, triglycerides, and the phosphatidylcholine/phosphorylethanolamine ratio in the paired perfusate displayed a close relationship with the graft proteins. To predict the occurrence of EAD, an integrated model using perfusate metabolic products and clinical parameters showed areas under the curve of 0.915 and 0.833 for the training and validation sets, respectively. It displayed superior predictive efficacy than that of currently existing models, including donor risk index and D-MELD scores.
CONCLUSIONS: We identified novel biomarkers in both grafts and perfusates that could be used to assess graft quality and provide new insights into the etiology of EAD. Herein, we also offer a valid tool for the early prediction of EAD.
The invention relates to the field of traditional Chinese medicines, in particular to a medicine for treating burns, scalds and trauma. The medicinal effective components are prepared from the following raw material medicines in parts by weight: dragon's blood 180-. Treating burn, scald, electric injury, bedsore, explosion injury, abrasion, contusion, knife wound, mechanical injury, various open skin wounds, various high-temperature impact wounds, and various external applications after external operations. The raw materials only adopt three medicines of dragon's blood, garden burnet and cuttlebone, and the formula is simple, the process is simple, the cost is low and the toxic and side effects are small. Clinical verification shows that the traditional Chinese medicine composition has an obvious curative effect, the cure rate is 100%, and the traditional Chinese medicine composition is worthy of popularization. Through clinical treatment observation of 30 patients by an authoritative department, the traditional Chinese medicine burn cream has the effects of clearing away heat and toxic materials, promoting blood circulation to remove blood stasis, relieving swelling and pain, removing necrotic tissue and promoting granulation, promotes rapid growth of skin epidermis, obviously shortens the treatment course, has no toxic or side effect, and is safe and reliable.
BACKGROUND: The neuroprotective effect of magnesium has been widely discussed, and its effectiveness has been confirmed by animal and clinical trials. However, there are still difficulties in clinical translation in diseases such as cerebral ischemia and subarachnoid hemorrhage. Therefore, it is necessary to analyze the literatures about neuroprotection of magnesium to reveal a more comprehensive knowledge framework, research hotspots and trends in the future.
METHODS: Original articles and reviews related to neuroprotective effects of magnesium from 1999 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The bibliometrics CiteSpace 6.2.R4 software was used to conduct co-occurrence/co-citation network analysis and plot knowledge visualization maps.
RESULTS: A total of 762 articles from 216 institutions in 64 countries were included in this study. The United States had the largest number of publications, followed by China and Canada. The University of California, UDICE-French Research Universities, and the University of Adelaide were the top three institutions in publication volume. Crowther Caroline A was the most published and cited author. Among the top 10 cited articles, there were seven articles on neuroprotection in preterm infants and three on acute stroke. Keyword cluster analysis obtained 11 clusters, showing that current research hotspots focused on magnesium therapy in neurovascular diseases such as cerebral ischemia, spinal cord injury, subarachnoid hemorrhage, and emerging treatment strategies.
CONCLUSION: The neuroprotective effects of magnesium in preterm infants have been extensively studied and adequately confirmed. The therapeutic effects of magnesium on cerebral ischemia and subarachnoid hemorrhage have been demonstrated in animal models. However, the results of clinical studies were not satisfactory, and exploring new therapeutic strategies may be the solution. Recently, the combination of magnesium and hypothermia had great potential in neuroprotective therapy and may become a development trend and hotspot in the future.
It is well-known that interpersonal traumatic events can impact the physical and mental health of those indirectly exposed to the events. Less studied are populations of loved ones who have been indirectly exposed to interpersonal trauma. We conducted a scoping review to synthesize literature related to potential consequences of indirect interpersonal trauma exposure, specifically vicarious traumatization (VT) and vicarious posttraumatic growth (VPTG). We used the Joanna Briggs Institute methodology. Inclusion criteria included: (1) participants were indirectly exposed to the interpersonal trauma of a loved one in adulthood, (2) discussion of VT, VPTG, or related terms, (3) published peer-reviewed empirical journal articles, and (4) available in English. We used a three-step search strategy to find relevant articles. Keywords found from the first two steps were entered into PsycINFO, PsycArticles, PubMed, Scopus, and Web of Science databases. Reference lists of the included articles were also examined. The identified articles were then screened using the inclusion and exclusion criteria. Twenty-eight articles met inclusion and exclusion criteria. Twenty-six articles referenced VT or related terms, one referenced VPTG, and one referenced vicarious trauma keywords. Results of this scoping review are summarized by definitions, measures, key findings, and knowledge gaps. Future research should focus on vocabulary management, diverse samples, and VPTG in this population, including the identification or creation of appropriate measures.
BACKGROUND: Family factors, sleep, and physical activity have previously been associated with risk of sick leave and disability benefits due to musculoskeletal disorders. However, how these factors act during adolescence and young adulthood is unclear. The aim of this study was to (i) examine if chronic pain, disability benefits and education in parents influence the risk of long-term sick leave due to musculoskeletal disorders in young adulthood, and (ii) to explore if offspring sleep problems and physical activity modify these effects.
METHODS: A population-based prospective study of 18,552 adolescents and young adults (≤ 30 years) in the Norwegian HUNT Study. Survey data was linked to national registry data on sick leave, disability benefits, family relations and educational attainment. We used Cox regression to estimate hazard ratio (HR) with 95% confidence interval (CI) for long-term (≥ 31 days) sick leave due to a musculoskeletal disorder in offspring associated with parental factors and the joint effect of parental factors and offspring lifestyle factors.
RESULTS: Parental chronic pain (HR 1.36, 95% CI 1.27-1.45), disability benefits (HR 1.41, 95% CI 1.33-1.48) and low educational attainment (HR 1.78, 95% CI 1.67-1.90) increased the risk of long-term sick leave due to musculoskeletal disorders among offspring. There was no strong evidence that sleep and physical activity modified these effects.
CONCLUSION: Chronic pain, disability benefit and low education in parents increased the risk of long-term sick leave due to musculoskeletal disorders among offspring, but these effects were not modified by offspring sleep problems or physical activity level. The findings suggest that efforts beyond individual lifestyle factors might be important as preventive measures.
PURPOSE: Animal models of ocular hypertension (OH) have been developed to understand the pathogenesis of glaucoma and facilitate drug discovery. However, many of these models are fraught with issues, including severe intraocular inflammation and technical challenges. Lysophosphatidic acid (LPA) is implicated in trabecular meshwork fibrosis and increased resistance of aqueous outflow, factors that contribute to high intraocular pressure (IOP) in human open-angle glaucoma. We aimed to elevate IOP by increasing expression of the LPA-producing enzyme autotaxin (ATX) in mouse eyes.
METHODS: Tamoxifen-inducible ATX transgenic mice were developed. Tamoxifen was administered to six- to eight-week-old mice via eye drops to achieve ATX overexpression in the eye. IOP and retinal thickness were measured over time, and retinal flat-mount were evaluated to count retinal ganglion cells (RGCs) loss after three months.
RESULTS: Persistent elevation of ATX expression in mouse eyes was confirmed through immunohistochemistry and LysoPLD activity measurement. ATX Tg mice exhibited significantly increased IOP for nearly two months following tamoxifen treatment, with no anterior segment changes or inflammation. Immunohistochemical analysis revealed enhanced expression of extracellular matrix near the angle after two weeks and three months of ATX induction. This correlated with reduced outflow facility, indicating that sustained ATX overexpression induces angle fibrosis, elevating IOP. Although inner retinal layer thickness remained stable, peripheral retina showed a notable reduction in RGC cell count.
CONCLUSIONS: These findings confirm the successful creation of an open-angle OH mouse model, in which ATX expression in the eye prompts fibrosis near the angle and maintains elevated IOP over extended periods.
The first group consists of nine general practitioners having received a brief training on the use of ultrasound scanners in general practice. The general practitioner includes all adult patients who are consulting for one of the 8 medical conditions studied and perform an ultrasound scan. Two weeks later, he/she calls each patient to collect the necessary data.
Atherosclerosis, which currently contributes to 31% of deaths globally, is of critical cardiovascular concern. Current diagnostic tools and biomarkers are limited, emphasizing the need for early detection. Lifestyle modifications and medications form the basis of treatment, and emerging therapies such as photodynamic therapy are being developed. Photodynamic therapy involves a photosensitizer selectively targeting components of atherosclerotic plaques. When activated by specific light wavelengths, it induces localized oxidative stress aiming to stabilize plaques and reduce inflammation. The key advantage lies in its selective targeting, sparing healthy tissues. While preclinical studies are encouraging, ongoing research and clinical trials are crucial for optimizing protocols and ensuring long-term safety and efficacy. The potential combination with other therapies makes photodynamic therapy a versatile and promising avenue for addressing atherosclerosis and associated cardiovascular disease. The investigations underscore the possibility of utilizing photodynamic therapy as a valuable treatment choice for atherosclerosis. As advancements in research continue, photodynamic therapy might become more seamlessly incorporated into clinical approaches for managing atherosclerosis, providing a blend of efficacy and limited invasiveness.