anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Macrophage-driven inflammation critically involves in cardiac injury and repair following myocardial infarction (MI). However, the intrinsic mechanisms that halt the immune response of macrophages, which is critical to preserve homeostasis and effective infarct repair, remain to be fully defined. Here, we aimed to determine the ubiquitination-mediated regulatory effects on averting exaggerated inflammatory responses in cardiac macrophages.
METHODS: We used transcriptome analysis of mouse cardiac macrophages and bone marrow-derived macrophages to identify the E3 ubiquitin ligase RNF149 (ring finger protein 149) as a modulator of macrophage response to MI. Employing loss-of-function methodologies, bone marrow transplantation approaches, and adenovirus-mediated RNF149 overexpression in macrophages, we elucidated the functional role of RNF149 in MI. We explored the underlying mechanisms through flow cytometry, transcriptome analysis, immunoprecipitation/mass spectrometry analysis, and functional experiments. RNF149 expression was measured in the cardiac tissues of patients with acute MI and healthy controls.
RESULTS: RNF149 was highly expressed in murine and human cardiac macrophages at the early phase of MI. Knockout of RNF149, transplantation of Rnf149-/- bone marrow, and bone marrow macrophage-specific RNF149-knockdown markedly exacerbated cardiac dysfunction in murine MI models. Conversely, overexpression of RNF149 in macrophages attenuated the ischemia-induced decline in cardiac contractile function. RNF149 deletion increased infiltration of proinflammatory monocytes/macrophages, accompanied by a hastened decline in reparative subsets, leading to aggravation of myocardial apoptosis and impairment of infarct healing. Our data revealed that RNF149 in infiltrated macrophages restricted inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1 (interferon gamma receptor 1). Loss of IFNGR1 rescued deleterious effects of RNF149 deficiency on MI. We further demonstrated that STAT1 (signal transducer and activator of transcription 1) activation induced Rnf149 transcription, which, in turn, destabilized the IFNGR1 protein to counteract type-II IFN (interferon) signaling, creating a feedback control mechanism to fine-tune macrophage-driven inflammation.
CONCLUSIONS: These findings highlight the significance of RNF149 as a molecular brake on macrophage response to MI and uncover a macrophage-intrinsic posttranslational mechanism essential for maintaining immune homeostasis and facilitating cardiac repair following MI.
An isolated peptidic fragment of apolipoprotein E comprises at least 3 contiguous amino acids, Including glycosylated threonine 194, threonine 289, serine 94, or serine 76 of SEQ ID NO.: 1, or any combination of those. An antibody capable of binding to the isolated peptidic fragment. A method of detecting a naturally-occurring circulating atherogenic low-density lipoprotein in a plasma sample from an individual, comprising qualitatively and/or quantitatively detecting in a low-density lipoprotein that binds to the antibody. A method of assessing an individual's risk of ischemic heart disease and/or atherosclerosis comprises quantifying in a plasma sample from the individual an amount of apolipoprotein E comprising glycosylated threonine 194, threonine 289, serine 94 or serine 76 of SEQ ID NO.: 1, or any combination of those.
The broad objective of this proposal is to identify functional neuroanatomical correlates of changes in brain functional connectivity during smoking abstinence. The investigators will measure changes in regional blood oxygenation levels using fMRI while adult smokers and non-smokers lie in the scanner with their eyes closed. Smokers will be scanned when they are abstinent from smoking for 24 hrs and shortly after smoking. Our primary hypothesis is that smoking abstinence will alter resting state brain activity (or resting state functional connectivity; RSFC) across widely distributed neural networks and that high-resolution fMRI will help in resolving the exact nature of such changes. Data will be analyzed using methods developed in our laboratory and applied to other resting state datasets. All of the procedures used in the study are well validated and introduce only minor risk to participants (e.g. blood draw; MRI).
Preoperative anxiety is common and can adversely affect a patient's perioperative course by elevating stress markers, promoting fluctuations in hemodynamics and negatively impacting on postoperative recovery. Preoperative anxiety is routinely treated with pharmacologic agents such as midazolam, a benzodiazepine, which has known, undesirable side effects including respiratory depression, hemodynamic perturbations, and paradoxical effects such as hostility, aggression, and psychomotor agitation. The use of sedative medications requires continuous vital sign monitoring of patients by either anesthesia or nursing personnel and there is a question of whether midazolam helps reduce pre-procedural anxiety compared with placebo. Music is a non-pharmacologic intervention that has been shown to significantly decrease preoperative anxiety. This intervention can be used as an adjunct or even replace pharmacologic agents to help with preoperative anxiety. Music is a modality that is virtually harm-free and relatively cheap in cost. Patients who are unable to tolerate pharmacologic agents to treat preoperative anxiety can greatly benefit from non-pharmacologic options such as music.

Regional anesthesia procedures such as an ultrasound guided, peripheral nerve block is a common bedside procedure done preoperatively. Patients may have some anxiety prior to the administration of this nerve block procedure and may receive sedation for it. However, it is imperative not to over sedate them as constant feedback from the patient is necessary during the procedure. Commonly, midazolam is used to reduce this anxiety, but non-pharmacologic therapies can also reduce anxiety. In our recent published study, we evaluated the use of research-selected, relaxing music, to reduce anxiety before the nerve block is administered. In this study, we used noise-canceling headphones and played research-selected music as our anxiolytic music modality and compared this with midazolam. The findings showed no difference between both groups in the change in anxiety scores from after to before the nerve block, however patients had better satisfaction in the midazolam group and increased difficulty in communication in the music group. We attributed this to not allowing patients to choose their own selection of music and the use of noise-canceling headphones.

Therefore, in this follow-up study, we aim to evaluate the use of patient-selected music via non-noise canceling headphones as a preoperative anxiolytic prior to the administration of a bedside, peripheral nerve block procedure. This study will be conducted at an ambulatory surgical center in a university setting.
A substance encapsulation system capable of being apertured under a tensioning force comprises a first web and a second web. A powdered, granular, particulate, or gel substance can be disposed between the first and second webs. Upon application of a sufficient force having a vector component parallel to the transverse axis, the bond site fractures to form a corresponding aperture to facilitate exposure of the substance. Alternatively, a central layer may be disposed between at least a portion of the first and second webs. The central layer may carry a substance to be exposed or the central layer may be a dissimilar material from the first and second webs. In a preferred embodiment, the system has a plurality of bond sites.
The trial includes two 32-week treatment periods in a cross-over design. Total trial duration for the individual subjects will be up to 67 weeks.
Semi-solid biological substances which are viable e.g. viruses, bacteria, fungi and tissue organs such as heart, kidney and liver cells, are reduced in size by surrounding the substance with a chemically inert cryogenic liquid having a boiling point of -130 DEG C. at normal atmospheric pressure thereby cooling the substance to a temperature below the recrystallization temperature of ice i.e. about -130 DEG C. and grinding or milling at said temperature.  Specified cryogenic liquids are nitrogen (preferred), helium, neon, argon and krypton.  Comminution may be by grinding, crushing or cutting, in batch, continuous or closed circuit operation.  Examples relate to comminution of bones, calf liver, rat tissues, rabbit kidney cells, Neurospora crassa (nitrate reductase), Penicillium notatum (glucose oxidase), aspergillus niger (catalase), pancreas (insulin), pituitary glands (ACTH), Pneumococcus pertussis, Hemophilus pertussis, Staphylococcus epidermidis and Staphylococcus aureus var. albus.ALSO:Semi-solid biological substances which are viable e.g. viruses, bacteria, fungi and tissue organs such as heart, kidney and liver cells, are reduced in size by surrounding the substance with a chemically inert cryogenic liquid having a boiling point - 130 DEG C. at normal atmospheric pressure thereby cooling the substance to a temperature below the recrystallization temperature of ice i.e. about - 130 DEG  C. and grinding or milling at said temperature. Specified cryogenic liquids are nitrogen (preferred), helium, neon, argon and krypton.  Comminution may be by grinding, crushing or cutting, in batch, continuous or closed circuit operation.  Examples relate to comminution of bones, calf liver, rat tissues, rabbit kidney cells, eurospora erassa (nitrate reductase) Penicillium notatum (glucose oxidase), Aspergillus niger (catalase), pancreas (insulin), pituitary glands (ACTH), Pneumococcus pertussis, Hemophilus pertussis, Staphylococcus epidermidis and Staphylococcus aureus var. albus.ALSO:Semi-solid biological substances which are viable, e.g viruses, bacteria, fungi and tissue organs such as heart, kidney and liver cells, are reduced in size by surrounding the substance with a chemically inert cryogenic liquid having a boiling point of -130  DEG C. at normal atmospheric pressure thereby cooling the substance to a temperature below the recrystallization temperature of ice, i.e. about -130  DEG C. and grinding or milling at said temperature. Specified cryogenic liquids are nitrogen (preferred), helium, neon, argon and krypton.  Comminution may be by grinding, crushing or cutting, in batch, continuous or closed circuit operation.  Examples relate to the comminution of bones, calf liver, rat tissues, rabbit kidney cells, Neurospora crassa (nitrate reductase) Penicillium notatum (glucose oxidase), Aspergillus niger (catalase), pancreas (insulin), pituitary glands (ACTH), Pneumococcus pertussis, Hemophilus pertussis, Staphylococcus epidermidis and Staphylococcus var albus.
BACKGROUND & AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery.
METHODS: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry.
RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, Egerthella lenta, Adlercreutzia equalofaciens, and Gordonibacter pamelaeae were lower in abundance among patients with prior surgery in both cohorts.
CONCLUSIONS: In 2 different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria and secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.
Part 1: This study will include 50 patients with MDD (MDD group) and 50 HC participants (HC group). PTG and IRT, respectively, will be adopted to assess 2 kinds of biological specificity of MDD-related acupoints: pain sensitivity specificity and thermal specificity. Based on the results of the PTG and IRT tests, the potentially superior acupoints for the treatment of MDD will be selected separately. After statistical analysis of the data from PTG and IRT tests, 4 pressure pain threshold strong response acupoints (PSA) and 4 temperature strong response acupoints (TSA) will be selected, respectively.

Part 2: A total of 160 participants with MDD who meet the inclusion criteria will be included in the study. Patients with MDD who met the criteria will be randomly divided 1:1:1:1 into 4 groups: waiting treatment (WT) group, clinical common acupoint (CCA) group, TSA group, and PSA group. All participants received basic therapeutic medication for the use of one or more antidepressants. Dosing and dosage will be adjusted by a specialist. The Patient Health Questionnare-9 (PHQ-9) and the MOS item short form health survey (SF-36) will be used as clinical efficacy outcome indicators, and each group's incidence of adverse effects will be observed. This study will investigate the effectiveness and safety of IA based on changes in the biological specificity of acupoints for MDD.
Atherosclerosis is the most common cause of myocardial infarction, stroke and peripheral arterial disease. Research has clearly demonstrated that inflammation plays a key role in the initiation, progression and manifestations of atherosclerosis. Atherosclerotic lesions begin as an accumulation of lipid-laden cells (primarily macrophages) beneath the endothelium, and progress with the further accumulation of cells, connective-tissue elements, lipids and debris through immunological and inflammatory activation. Neutrophils and other inflammatory cells have been shown to invade culprit atherosclerotic lesions in acute coronary syndromes. It is likely that the inflammatory process is responsible for the high rate of cardiovascular events despite significant advances in the treatment of risk factors such as hypercholesterolemia and hypertension. It is vital to improve our understanding of the inflammatory nature of atherosclerotic disease and modify the inflammatory process with targeted therapies. Prospective cohort studies have consistently shown that high sensitivity C-reactive protein (hs-CRP) and several other biomarkers of inflammation are independently associated with increasing risk of future cardiovascular events in different populations. This together with animal models showing that reduced inflammation has anti-atherosclerotic effects, create the impetus to test the hypothesis that treatment of the underlying inflammatory process will contribute to improved cardiovascular clinical outcomes. Colchicine is an inexpensive, yet potent, anti-inflammatory drug approved for acute use in patients with gout and chronic use in patients with Familial Mediterranean Fever. The mechanism of action is through the inhibition of tubulin polymerization and potentially also through effects on cellular adhesion molecules and inflammatory chemokines. Colchicine may also have direct anti-inflammatory effects by inhibiting key inflammatory signaling networks known as the inflammasome and pro-inflammatory cytokines. Through the disruption of the cytoskeleton, colchicine is believed to suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. Considerable work has highlighted the potential of colchicine in the treatment of cardiovascular diseases mediated by pro-inflammatory processes. More recently colchicine has been evaluated for its effect on cardiovascular events in patients with coronary artery disease (CAD).
This invention is directed to a process for the prevention or treatment of inflammation or other cyclooxygenase-2 mediated disorders. This process comprises administering a conjugated fatty acid to an organism in an amount effective to prevent or treat the cyclooxygenase-2 mediated disorder by inhibiting cyclooxygenase -2. In one embodiment, the process comprises administering a fatty acid compound having formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 is hydrogen, hydrocarbyl, or substituted hydrocarbyl; m is from 6 to 11; and the sum of n and m is from 13 to 16. In another embodiment, the process comprises administering a fatty acid compound having formula (VI) or a pharmaceutically acceptable salt thereof, wherein R6 is hydrogen, hydrocarbyl, or substituted hydrocarbyl; R7 is -OH, -SO¿3?H, -SH, -NH2, -PO3H2, or halogen; v is from 7 to 11; and the sum of v and w is from 11 to 15. This invention is also directed to a process for preparing a fatty acid compound. The process comprises combining a ylide with an aldehyde.
BACKGROUND: Mitochondria have emerged as a promising target for ischemic disease. A previous study reported the application of mitochondrial transplantation in focal cerebral ischemia/reperfusion injury, but it is unclear whether exogenous mitochondrial transplantation could be a therapeutic strategy for global ischemia/reperfusion injury induced by cardiac arrest.
METHODS: We hypothesized that transplantation of autologous mitochondria would rescue hippocampal cells and alleviate neurological impairment after cardiac arrest. In this study, we employed a rat cardiac arrest-global cerebral ischemia injury model (CA-GCII) and transplanted isolated mitochondria intravenously. Behavior test was applied to assess neurological deficit. Apoptosis and mitochondria permeability transition pore opening in hippocampus was determined using immunoblotting and swelling assay, respectively.
RESULTS: Transplanted mitochondria distributed throughout hippocampal cells and reduced oxidative stress. An improved neurological outcome was observed in rats receiving autologous mitochondria. In the hippocampus, mitophagy was enhanced while cell apoptosis was induced by ischemia/reperfusion insult was downregulated by mitochondrial transplantation. Mitochondrial permeability transition pore (MPTP) opening in surviving hippocampal cells was also suppressed.
CONCLUSIONS: These results indicated that transplantation of autologous mitochondria rescued hippocampal cells from ischemia/reperfusion injury and ameliorated neurological impairment caused by cardiac arrest.
The concept of an "immunological continuum model," introduced by McGonagle and McDermott in 2006, redefines the traditional dichotomy between autoimmunity and autoinflammation, proposing a spectrum where innate and adaptive immune dysregulation can co-occur, reflecting a more nuanced understanding of immune disorders. Systemic lupus erythematosus (SLE) exemplifies the complexity of this continuum, often displaying manifestations of autoimmunity, autoinflammation, and immunodeficiency. The interplay between genetic, epigenetic, hormonal, psychological, and environmental factors contributes to its distinctive immunopathological signatures. Historically recognized as a systemic disease with diverse clinical manifestations, SLE is primarily a polygenic autoimmune condition but can, however, present in monogenic forms. Examining SLE through the lens of the immunological continuum model allows for emphasis on the contributions of both innate and adaptive immunity. SLE and primary immunodeficiencies share genetic susceptibilities and clinical manifestations. Additionally, autoinflammatory mechanisms, such as inflammasome activation and interferonopathies, can play a role in SLE pathogenesis, illustrating the disease's position at the crossroads of immune dysregulation. Recognizing the diverse clinical expressions of SLE and its mimickers is critical for accurate diagnosis and targeted therapy. In conclusion, the immunological continuum model provides a comprehensive framework for understanding SLE, acknowledging its multifaceted nature and guiding future research and clinical practice toward more effective and individualized treatments. After the Mosaic of Autoimmunity, it is now the time to focus and attempt to solve the intricate mosaic of SLE.
This is a retrospective cohort study of Thai octogenarians with NVAF. Patients who were prescribed with apixaban, dabigatran, edoxaban, rivaroxaban or warfarin from January 1, 2013, to December 31, 2018 were recruited. The primary efficacy was recurrent ischemic stroke or TIA in 90 days after initiating OACs. The secondary efficacy were recurrent ischemic stroke or TIA in 180 days after initiating OACs. While any bleeding complications were defied as primary safety outcomes. Continuous variables were compared using independent t test and MannWhitney U test, and categorical variables were compared using chi-square test or Fisher's exact test.
The invention relates to methods and pharmaceutical compositions for the treatment of BAP1 deficient cancer. The inventors investigate the role of BET (Bromodomain and Extra-Terminal motif proteins) in BAP1 deficient cancer and screened isogenic cells (BAP1 WT vs KO) with libraries of chemical compounds. The inventors demonstrated that BET inhibitors showed more anti -proliferative activity against cells KO for BAP1. The inventors demonstrated using isogenic cell lines and uveal melanoma PDX derived cell lines with different status of expression for BAP1 a highest dose response to a BET inhibitors (OTX015 and B1894999) in BAP1 KO isogenic cells compared to WT cells and an enhanced dose response to OTX015 in a BAP1 mutated uveal melanoma (UM) derived cells compared to UM cells expressing BAP1. Altogether, the present invention highlights the role of BET inhibitors in BAP1 deficient cancer, and the use of BET inhibitors in the treatment of BAP1 deficient cancer, particularly BAP1 deficient Uveal Melanoma, clear cell Renal Carcinoma, cholangiocarcinoma and mesothelioma. In the present invention, the inventors provide in vitro evidences towards a direct role of BET in BAP1 deficient cancer carcinogenesis and metastatic progression. Thus, the present invention relates to BET inhibitor for use in the treatment of BAP1 deficient cancer, particularly, BAP1 deficient uveal melanoma.
GH stimulation

Maximum GH levels are observed between 30 to 90 minutes after administration of MACRILEN. 

Cardiac electrophysiology

The effects of macimorelin on ECG parameters were investigated in a dedicated Thorough QT study that investigated in a 3-way cross-over design with 60 healthy subjects the effects of a supra-therapeutic dose of macimorelin (2 mg/kg) (4 times the recommended dosage) in comparison with placebo and with moxifloxacin. This study showed a mean baseline- and placebo-adjusted change (upper single-sided 95% confidence interval) in QTcF of 9.6 msec (11.4 msec) at 4 h post-dose, which occurred after the mean maximum macimorelin plasma concentration (0.5 h). A similar increase in the QTcF interval was also observed in a single-ascending dose study, which included three dose levels (0.5 mg/kg, and 1 mg/kg and 2 mg/kg (2 times and 4 times the recommended dosage, respectively). All three dose levels studied showed a similar magnitude of QTcF prolongation in the Thorough QT study, suggesting an absence of dose dependent changes. The mechanism for the observed QTcF prolongation is unknown [see Warnings and Precautions (5.1)].