anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: The pathogenesis of brain ischemic/reperfusion (I/R) insult is characterized by neuronal loss due to excessive oxidative stress responses. Ferroptosis, a form of oxidative cell death, can be triggered when the balance between antioxidants and pro-oxidants in cells is disrupted. Ozone, a natural bioactive molecule with antioxidant/anti-apoptotic and pro-autophagic properties, has been shown to enhance the antioxidant system's capacity and ameliorate oxidative stress. However, its role in neuronal ferroptosis remains unclear. Therefore, we investigated the functions and possible mechanisms of ozone in cerebral I/R-induced ferroptotic neuronal death.
METHODS: A cerebral ischemia-reperfusion injury model was induced in Sprague-Dawley (SD) rats pre-treated with ozone. Intraperitoneal administration of the NRF2 inhibitor ML385, the SLC7A11 inhibitor Erastin, and the GPX4 inhibitor RSL3 was performed one hour prior to model establishment.
RESULTS: Our results showed that ozone preconditioning mitigated neuronal damage caused by cerebral I/R, reduced the severity of neurological deficits, lowered cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats, and decreased the volume of cerebral infarcts. Transmission electron microscopy, immunofluorescence, and Western blotting indicated ferroptosis following MCAO-induced brain damage. MCAO resulted in morphological damage to neuronal mitochondria, increased lipid peroxidation accumulation, and elevated malondialdehyde (MDA) production. Furthermore, MCAO decreased levels of FTH1 and GPX4 (negative regulators of ferroptosis) and increased ACSL4 levels (a positive regulator of ferroptosis). Ozone preconditioning demonstrated a neuroprotective effect by increasing NRF2 nuclear translocation and the expression of SLC7A11 and GPX4. Treatment with ML385, Erastin, and RSL3 significantly reversed ozone preconditioning's protective effect on neuronal ferroptosis.
CONCLUSION: Our findings demonstrated that ozone treatment attenuates ferroptosis in a cerebral ischemia/reperfusion injury rat model via the NRF2/SLC7A11/GPX4 pathway, providing a theoretical basis for ozone's potential use as a therapy to prevent ischemic stroke.
A nasal drug delivery device for delivering a plume derived from a propellant and a drug compound. The drug compound is in an intranasal dosage form in the form of powder, suspension, dispersion, or liquid. The propelled intranasal dosage form is deposited within the upper nasal cavity such as the olfactory region. The drug deposited within the olfactory region is delivered to the brain avoiding the blood-brain-barrier. Hydrofluoroalkane propellant from a pressurized canister is channeled to a diffuser and drug-containing channel where the intranasal dosage form is aerosolized. The aerosolized intranasal dosage form passes through a nozzle thus delivering a plume to the user’s upper nasal cavity. Prior art problems include not adequately propelling the drug from the device, inconsistent propulsion of drug due to inconsistent user actuation and some drug products not readily mixing and / or staying suspended with propellants. A device for delivering a compound to an upper nasal cavity comprising a housing body comprising an actuator configured to move relative to the housing body. The actuation of the actuator is configured to actuate a canister thereby releasing a contained propellant. The device also comprises a stem protruding from the housing body. The stem comprising a mating interface that is configured to mate with a nozzle containing the compound. The device also comprises a release button positioned within the housing body and configured to move relative to the housing body. The release button directly connected to a securing mechanism that is configured to couple the nozzle to the mating interface. The actuation of the release button is configured to decouple the nozzle from the mating interface. The mating interface comprises an opening, and the securing mechanism comprises a securing latch that is configured to protrude through the opening of the mating interface.
Love, Sex, and Choices (LSC) is an engaging 12-episode video series to reduce HIV risk in young, adult predominately Black women. A peer video guide was added to the end of LSC episodes to provoke viewers to question their own sex scripts and consider their own need for change. Investigators propose to conduct a two-arm clinical trial of guide enhanced LSC impact on reducing unprotected sex with high risk partners and increasing HIV testing in Black women in high HIV prevalence neighborhoods.
BACKGROUND: Imeglimin is a new anti-diabetic drug which promotes insulin secretion from pancreatic β-cells and reduces insulin resistance in insulin target tissues. However, there have been no reports examining the possible anti-atherosclerotic effects of imeglimin. In this study, we investigated the possible anti-atherosclerotic effects of imeglimin using atherosclerosis model ApoE KO mice treated with streptozotocin (STZ).
METHODS: ApoE KO mice were divided into three groups: the first group was a normoglycemic group without injecting STZ (non-DM group, n = 10). In the second group, mice were injected with STZ and treated with 0.5% carboxymethyl cellulose (CMC) (control group, n = 12). In the third group, mice were injected with STZ and treated with imeglimin (200 mg/kg, twice daily oral gavage, n = 12). We observed the mice in the three groups from 10 to 18 weeks of age. Plaque formation in aortic arch and expression levels of various vascular factors in abdominal aorta were evaluated for each group.
RESULTS: Imeglimin showed favorable effects on the development of plaque formation in the aortic arch in STZ-induced hyperglycemic ApoE KO mice which was independent of glycemic and lipid control. Migration and proliferation of vascular smooth muscle cells and infiltration of macrophage were observed in atherosclerotic lesions in STZ-induced hyperglycemic ApoE KO mice, however, which were markedly reduced by imeglimin treatment. In addition, imeglimin reduced oxidative stress, inflammation and inflammasome in hyperglycemic ApoE KO mice. Expression levels of macrophage makers were also significantly reduced by imeglimin treatment.
CONCLUSIONS: Imeglimin exerts favorable effects on the development of plaque formation and progression of atherosclerosis.
BACKGROUND: Magnesium sulfate (MgSO4) is a potential neuroprotective agent for patients with aneurysmal subarachnoid hemorrhage (SAH). We analyzed the effect of early application of intraoperative intravenous MgSO4 and compared cerebral vasospasm (CV), delayed cerebral ischemia (DCI), and neurological outcome in 2 patient cohorts.
METHODS: A retrospective matched-pair analysis from patients at a single center in Germany was performed without (group A) and with (group B) MgSO4 application <24 hours after diagnosis. Pairs were matched according to the known risk factors for DCI and CV (age, Fisher grade, smoking, severity of SAH). Incidence of CV and DCI and neurological outcome using the modified Rankin Scale score 3 and 12 months after SAH were recorded.
RESULTS: The inclusion criteria were met by 196 patients. After risk stratification, 48 patients were included in the final analysis (age 54.2 ± 8.1 years; 30 women and 18 men) and were assigned to group A (n = 24) or group B (n = 24). CV occurred less frequently in group B (33%) than in group A (46%). Likewise, DCI was present in 13% in group B compared with 42% in group A. After 12 months, 22 patients in group B had a favorable functional outcome (modified Rankin Scale score 0-3) compared with 15 patients in group A.
CONCLUSIONS: In this study, the incidence of CV and DCI was lower in patients receiving intravenous MgSO4 within 24 hours after aneurysmal SAH onset. Favorable functional outcome was more likely in the MgSO4 group after 12 months of follow-up.
The present invention relates to assessing and measuring endothelial functions. A vasodilating stimulant is provided to a patient to stimulate hemodynamic activity in a selected region of the patient's body. In an embodiment, endothelial function may then be assessed by monitoring a change in a hemodynamic parameter at the selected region and assessing the patient's endothelial function based upon that monitoring. In a further embodiment, endothelial function may then be measured by monitoring a change in blood oxygen content at the selected region and assessing the patient's endothelial function based upon that monitoring. In yet a further embodiment, endothelial function may then be measured by monitoring a change in blood flow rate at the selected region and assessing the patient's endothelial function based upon said monitoring. It is emphasized that this abstract is provided to comply with the rules requiring an abstract which will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.
Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases inflammation in lupus mouse models. In this study, sex- and age-matched wild-type (WT) and HDAC6-/- mice on the C57BL/6 background were administered 0.5 ml of pristane or PBS i.p. at 8-12 wk of age and were euthanized 10 d later. At sacrifice, body weight and spleen weight were measured, sera were collected, and splenocytes and peritoneal cells were harvested for flow cytometry. We found pristane administration increased the spleen weight with no difference between WT and HDAC6-/- mice. Pristane administration promoted the population of CD11b+Ly6C++ inflammatory monocytes and CD11b+Ly6G+ neutrophils. Peritoneal recruitment of these inflammatory monocytes and neutrophils was significantly decreased in HDAC6-/- mice compared with the WT mice. Flow cytometry results showed that the number of CD69+ T and B cells was increased in HDAC6-/- mice. Pristane administration also induced the IFN signature genes as determined by RT-qPCR. Furthermore, IFN signature genes were not affected in HDAC6-/- mice compared with the WT mice. In vitro studies in J774A.1 cells revealed that the selective HDAC6 inhibitor (ACY-738) increased acetylation of NF-κB while increasing Stat1 phosphorylation, which resulted in inducible NO synthase production in LPS/IFN-γ-stimulated cells. Taken together, these results demonstrate that although HDAC6 inhibition may inhibit some inflammatory pathways, others remain unaffected.
Participants in the wait-list group will not receive OLP pills until the end of the 45-day monitoring period. Therefore, the 45 days without OLP will serve as an no intervention comparators relative to the OLP group.
This study explores the molecular underpinnings of neuropathic pain (NPP) and neuroinflammation, focusing on the role of TRIM28 in the regulation of autophagy and microglia ferroptosis. Leveraging transcriptomic data associated with NPP, we identified TRIM28 as a critical regulator of ferroptosis. Through comprehensive analysis, including Gene Ontology enrichment and protein-protein interaction network assessments, we unveiled GSK3B as a downstream target of TRIM28. Experimental validation confirmed the capacity of TRIM28 to suppress GSK3B expression and attenuate autophagic processes in microglia. We probed the consequences of autophagy and ferroptosis on microglia physiology, iron homeostasis, oxidative stress, and the release of proinflammatory cytokines. In a murine model, we validated the pivotal role of TRIM28 in NPP and neuroinflammation. Our analysis identified 20 ferroptosis regulatory factors associated with NPP, with TRIM28 emerging as a central orchestrator. Experimental evidence affirmed that TRIM28 governs microglial iron homeostasis and cell fate by downregulating GSK3B expression and modulating autophagy. Notably, autophagy was found to influence oxidative stress and proinflammatory cytokine release through the iron metabolism pathway, ultimately fueling neuroinflammation. In vivo experiments provided conclusive evidence of TRIM28-mediated pathways contributing to heightened pain sensitivity in neuroinflammatory states. The effect of TRIM28 on autophagy and microglia ferroptosis drives NPP and neuroinflammation. These findings offer promising avenues for identifying novel therapeutic targets to manage NPP and neuroinflammation.
Smart phone application MyNetDiary will be used to track calories and exercise log. The intervention period would last for 3 months.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that involves functional and structural defects in selective central nervous system (CNS) regions, harming the individual capability to process and respond to external stimuli, including impaired verbal and non-verbal communications. Etiological causes of ASD have not been fully clarified; however, prenatal activation of the innate immune system by external stimuli might infiltrate peripheral immune cells into the fetal CNS and activate cytokine secretion by microglia and astrocytes. For instance, genomic and postmortem histological analysis has identified proinflammatory gene signatures, microglia-related expressed genes, and neuroinflammatory markers in the brain during ASD diagnosis. Active neuroinflammation might also occur during the developmental stage, promoting the establishment of a defective brain connectome and increasing susceptibility to ASD after birth. While still under investigation, we tested the hypothesis whether the monocyte chemoattractant protein-1 (MCP-1) signaling is prenatally programmed to favor peripheral immune cell infiltration and activate microglia into the fetal CNS, setting susceptibility to autism-like behavior. In this review, we will comprehensively provide the current understanding of the prenatal activation of MCP-1 signaling by external stimuli during the developmental stage as a new selective node to promote neuroinflammation, brain structural alterations, and behavioral defects associated to ASD diagnosis.
This was a prospective, multicenter, randomized, open-label, 3-arm, phase II study with a single-stage design in each arm. The purpose of this study was to test the effectiveness and safety of Everolimus or Pasireotide LAR alone or in combination in adult patients with advanced (unresectable or metastatic) neuroendocrine carcinoma (typical and atypical) of the lung and thymus. It was expected that a total of 120 patients with 40 patients in each arm were to be enrolled into this study. Patients were seen weekly for one month and monthly thereafter. Radiological and biochemical response assessments were performed every 3 months.

Patients with disease control (stable disease or better) in the combination arm or monotherapy with pasireotide LAR and everolimus who had not experienced unacceptable toxicity were permitted to continue treatment in the extension phase of the study and were seen every 3 months. Patients could remain in the extension phase as long as they continued to have clinical benefit and had not fulfilled any of the study discontinuation criteria. All patients had a safety follow-up visit 56 days after last treatment dose.
A wireless location system has at least one wireless tag to be located by the wireless location system, wherein the at least one wireless tag transmits two wireless signals having a known time relationship and having different bandwidths. A plurality of receivers is provided wherein a first receiver receives and processes a first of the two wireless signals and estimates a time to arrive (TOA) of the first wireless signal, and a second receiver receives and processes a second of the two wireless signals and estimates a TOA of the second wireless signal at the second transceiver. The plurality of receivers is time synchronized based on a common timing signal. A location server is coupled to each of the plurality of receivers. The location server receives the TOA of the first wireless signal from the first receiver and the TOA of the second wireless signal from the second receiver. The location server calculating a TDOA of the two wireless signals and estimates a position of the at least one wireless tag based on the TDOA.
Patients in this group will receive DNB in right hand. DNB will be performed by injecting 2 ml of 0.25% bupivacaine at the base of medial and lateral sides of the finger attached to the sensor (1 ml on each side of the base).
The invention discloses an orally-administrable oxybuprocaine hydrochloride gastroscope lubricating liquid and a preparation method thereof, wherein the lubricating liquid is prepared from the following raw materials: glycerin, dimeticone, oxybuprocaine hydrochloride, sodium alginate and purified water. The invention has the following advantages: 1. contains no bitter component, and has sweet glycerol taste, and can improve discomfort such as nausea and emesis. 2. Has outstanding defoaming performance and clear visual field in gastroscopy. 3. The lubricating function is excellent, and the mechanical damage to the upper digestive tract in the process of inserting the endoscope is reduced. 4. No additional bacteriostatic and antibacterial agent is needed. 5. The lubricant has synergistic effect in lubrication, thickening and anesthesia, and clinical data show that the lubricant effect of the invention is improved by 12.5 percentage points compared with oxybuprocaine hydrochloride gel, the defoaming effect is improved by 50 percentage points, while the anesthesia and pain relieving effect is improved by 6.9 percentage points under the condition that the using amount of oxybuprocaine hydrochloride is less than 33% of oxybuprocaine hydrochloride gel, and the palatability is improved by 52.8 percentage points.
The process of personal identification differs according to the state of preservation of the corpse, becoming more complicated when dealing with remains altered by taphonomic variables. Since 2015, the staff of the Laboratory of Forensic Anthropology and Odontology (LABANOF) of the University of Milan has been engaged in recovering the skeletons of 36 unknown people from the cemeteries of the city of Milan, to redraw their biological profiles and give them back the possibility of being identified. Of the 36 starting skeletons, 7 have been identified and therefore are not the object of this study, 25 individuals were previously subjected to an autopsy examination and 4 skeletons were studied for the first time in the present work. The post-mortem data of all the individuals who had previously undergone autopsy and had not yet been identified (n = 25) have been retrieved from the archives of the Institute of Forensic Medicine in Milan and allowed for a comparison with those obtained from the new anthropological study of each exhumed skeleton. The authors aim to present the three most interesting cases to better highlight the results that emerged from the comparison. The autopsy information alone lacked important details. In all cases, the anthropological examination proved to be capable of detailing the biological profile of the unknowns even after a long period of inhumation (even more than 20 years). The limitations of instrumental investigations in achieving the goal single-handedly and the importance of recovering the unknown skeletons from cemeteries for identification purposes are discussed.
Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both. Numerous topical and systemic therapies are available for the treatment of psoriasis. Treatment modalities are chosen on the basis of disease severity, relevant comorbidities, patient preference. For moderate to severe psoriasis, phototherapy, systemic therapy and biologic immune modifying agents are recommended, but all of them have some drawbacks or limitations. Until now, no curative treatment is available. Therefore, it is important to find new treatment for psoriasis.

Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can differentiate into bone, cartilage and adipose cells. Adipos-derived Mesenchymal Stem Cells(AD-MSCs) were isolated from fat tissues and were reported to treat moderate to severe psoriasis vulgaris and psoriasis arthritis successfully by case reports. For the mechanism of the disease, involvement of the immune system in psoriasis is now widely accepted. Mesenchymal stem cells (MSCs) are found to have the function of immunomodulation, migration to skin lesions, limitation of autoimmunity. Therefore, investigators supposed that the injection of AD-MSCs could be beneficial for treatment of moderate to severe psoriasis.
One IPX066 95 mg LD was given TID on days 1-3. One IPX066 145 mg LD was given TID on days 4-7. One IPX066 195 mg LD was given TID on days 8-14. One IPX066 245 mg LD was given TID on days 15-21. One IPX066 245 mg LD and one placebo capsule were given TID on days 22 till end of study (week 30).
The peptide having the amino acid sequence SEQ ID NO:1, and optionally this peptide in mixture with one or more peptides SEQ ID NO:3 - 11, is described.  All these peptides correspond to regions of the genomic TT virus sequence.  Further, monospecific antibodies binding to the TT virus are disclosed. The peptides may be coupled to a carrier and/or label, or immobilized on a solid phase. The peptide or peptide mixture, or the monospecific antibody may be used in a medicament or in diagnostic kits. The peptide or peptide mixture may also be used for immunization of a non-human mammal to produce monospecific antibodies directed against TT virus.
The comparator will be administered as a single dose oral Moxifloxacin Hydrochloride tablet (open-label), with a total of 240 mL of water. There will be a minimum washout of 3 days between each study drug administration.
Minimally invasive micro-osteoperforation (PROPEL™) procedure used to achieve rapid orthodontic tooth movement. Topical or local anesthetic will be delivered in the area to be treated in accordance with standard practice. Prior to intervention subject will swish 5cc of chlorhexidine for one minute, twice, will take place. Following procedure Chlorhexidine rinses are to begin twice a day for a week.
Patients in the group K arm will receive a loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached. After 48 hours of burst suppression the ketamine dosage will be reduced by 2mg/kg/hr in a stepwise fashion to evaluated for EEG or clinical evidence of seizure recurrence.