anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
NEW MATERIAL:The compound of formula I (R1 is H or lower alkyl; R2 is lower alkyl or 2,3-isopropylidene-ribonosyl). EXAMPLE:2,4,7,7,8,8-Hexamethyl-cis-2,4-diazabicyclo[4,2,0]octane-3,5-d ione. USE:Useful as a chemotherapeutic agent for cancer. It has strong differentiation- inducing activity against cancer cell (decarcinogenetic action) and low toxicity and can be used as an excellent carcinostatic agent. PREPARATION:A uracil compound of formula II and 2,3-dimethyl-2-butene(tetramethylethylene) are dissolved in an organic solvent at a molar ratio (the former compound : latter compound) of preferably 1:(10-12). The solution is irradiated with high-pressure mercury lamp under water-cooling in nitrogen atmosphere to effect the addition reaction of the components. After distilling out the solvent, the reaction product is developed with a developing solvent to obtain the objective compound of formula I.
BACKGROUND: Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease. Currently, there is no effective therapy for reducing cardiac I/R injury. Damage-associated molecular patterns are endogenous molecules released after cellular damage to exaggerate tissue inflammation and injury. RIPK3 (receptor-interacting protein kinase 3), a well-established intracellular mediator of cell necroptosis and inflammation, serves as a circulating biomarker of multiple diseases. However, whether extracellular RIPK3 also exerts biological functions in cardiac I/R injury remains totally unknown.
METHODS: Patients with acute myocardial infarction receiving percutaneous coronary intervention (PCI) were recruited independently in the discovery cohort (103 patients) and validation cohort (334 patients), and major adverse cardiovascular events were recorded. Plasma samples were collected before and after PCI (6 and 24 h) for RIPK3 concentration measurement. Cultured neonatal rat ventricular myocytes, macrophages and endothelial cells, and in vivo mouse models with myocardial injury induced by I/R (or hypoxia/reoxygenation) were used to investigate the role and mechanisms of extracellular RIPK3. Another cohort including patients with acute myocardial infarction receiving PCI and healthy volunteers was recruited to further explore the mechanisms of extracellular RIPK3.
RESULTS: In the discovery cohort, elevated plasma RIPK3 levels after PCI are associated with poorer short- and long-term outcomes in patients with acute myocardial infarction, as confirmed in the validation cohort. In both cultured cells and in vivo mouse models, recombinant RIPK3 protein exaggerated myocardial I/R (or hypoxia/reoxygenation) injury, which was alleviated by the RIPK3 antibody. Mechanistically, RIPK3 acted as a damage-associated molecular pattern and bound with RAGE (receptor of advanced glycation end-products), subsequently activating CaMKII (Ca2+/calmodulin-dependent kinase II) to elicit the detrimental effects. The positive correlation between plasma RIPK3 concentrations and CaMKII phosphorylation in human peripheral blood mononuclear cells was confirmed.
CONCLUSIONS: We identified the positive relationship between plasma RIPK3 concentrations and the risk of major adverse cardiovascular events in patients with acute myocardial infarction receiving PCI. As a damage-associated molecular pattern, extracellular RIPK3 plays a causal role in multiple pathological conditions during cardiac I/R injury through RAGE/CaMKII signaling. These findings expand our understanding of the physiological and pathological roles of RIPK3, and also provide a promising therapeutic target for myocardial I/R injury and the associated complications.
To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation, hypervolemia, and hyperkalemia.

Too rapid infusion of hypertonic solutions may cause local pain and, rarely, vein irritation. Rate of administration should be adjusted according to tolerance.

Reactions reported with the use of potassium-containing solutions include nausea, vomiting, abdominal pain and diarrhea. The signs and symptoms of potassium intoxication include paresthesias of the extremities, areflexia, muscular or respiratory paralysis, mental confusion, weakness, hypotension, cardiac arrhythmias, heart block, electrocardiographic abnormalities and cardiac arrest. Potassium deficits result in disruption of neuromuscular function, and intestinal ileus and dilatation.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.
Alzheimer's disease (AD) is the leading cause of dementia and is characterized by a presence of amyloid plaques, composed mostly of the amyloid-β (Aβ) peptides, in the brains of AD patients. The peptides are generated from the amyloid precursor protein (APP), which undergoes a sequence of cleavages, referred as trimming, performed by γ-secretase. Here, we investigated conformational changes in a series of β-amyloid substrates (from less and more amyloidogenic pathways) in the active site of presenilin-1, the catalytic subunit of γ-secretase. The substrates are trimmed every three residues, finally leading to Aβ40 and Aβ42, which are the major components of amyloid plaques. To study conformational changes, we employed all-atom molecular dynamics simulations, while for unfolding, we used steered molecular dynamics simulations in an implicit membrane-water environment to accelerate changes. We have found substantial differences in the flexibility of extended C-terminal parts between more and less amyloidogenic pathway substrates. We also propose that the positively charged residues of presenilin-1 may facilitate the stretching and unfolding of substrates. The calculated forces and work/energy of pulling were exceptionally high for Aβ40, indicating why trimming of this substrate is so infrequent.
The mechanism of the antihypertensive effect of thiazides is unknown. Hydrochlorothiazide does not usually affect normal blood pressure. 

Hydrochlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy. 

Hydrochlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. 

After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours.
The safety and efficacy of CCT301-59 will be evaluated for subjects with ROR2 positive biopsy in a standard 3+3 dose escalation approach. 3 CAR T dosage will be tested in this study: 1×10\^5/kg, 1×10\^6/kg, 1×10\^7/kg CAR+ T cells.
Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are compounds having a DNA damage-binding protein 1 (DDB1) binding moiety. Some such embodiments include a linker. Some such embodiments include a target protein binding moiety. Further provided herein are ligand-DDB1 complexes. Further provided herein are in vivo modified DDB1 proteins.
BACKGROUND: Traumatic brain injury (TBI) is associated with the development of visual system disorders. Visual deficits can present with delay and worsen over time, and may be associated with an ongoing neuroinflammatory response that is known to occur after TBI. Complement system activation is strongly associated with the neuroinflammatory response after TBI, but whether it contributes to vision loss after TBI is unexplored.
METHODS: Acute and chronic neuroinflammatory changes within the dorsal lateral geniculate nucleus (dLGN) and retina were investigated subsequent to a moderate to severe murine unilateral controlled cortical impact. Neuroinflammatory and histopathological outcomes were interpreted in the context of behavioral and visual function data. To investigate the role of complement, cohorts were treated after TBI with the complement inhibitor, CR2-Crry.
RESULTS: At 3 days after TBI, complement component C3 was deposited on retinogeniculate synapses in the dLGN both ipsilateral and contralateral to the lesion, which was reduced in CR2-Crry treated animals. This was associated with microglia morphological changes in both the ipsilateral and contralateral dLGN, with a less ramified phenotype in vehicle compared to CR2-Crry treated animals. Microglia in vehicle treated animals also had a greater internalized VGlut2 + synaptic volume after TBI compared to CR2-Crry treated animals. Microglia morphological changes seen acutely persisted for at least 49 days after injury. Complement inhibition also reduced microglial synaptic internalization in the contralateral dLGN and increased the association between VGLUT2 and PSD95 puncta, indicating preservation of intact synapses. Unexpectedly, there were no changes in the thickness of the inner retina, retinal nerve fiber layer or retinal ganglion layer. Neuropathological changes in the dLGN were accompanied by reduced visual acuity at subacute and chronic time points after TBI, with improvement seen in CR2-Crry treated animals.
CONCLUSION: TBI induces complement activation within the dLGN and promotes microglial activation and synaptic internalization. Complement inhibition after TBI in a clinically relevant paradigm reduces complement activation, maintains a more surveillance-like microglia phenotype, and preserves synaptic density within the dLGN. Together, the data indicate that complement plays a key role in the development of visual deficits after TBI via complement-dependent microglial phagocytosis of synapses within the dLGN.
Studied active product n°1, named VAL070-A, is a dietary supplement in shape of capsule. VAL070-A product contains 4 active plant extracts.
A method and preparations for the treatment of vaginal yeast and other yeast infections is provided for the treatment of infections caused by candida albicans and cryptococcus neoformans. The method and preparations of the invention can also be used for other yeast and fungal infections including systemic, mucosal and cutaneous caused by candida and cryptococcus. The vaginal antiyeast and antifungal preparations include, in addition to suppositories and mouth washes, troches, lotions, creams, tablets and capsules containing gentian preparations as an active ingredient obtained from the, plant Radix gentianae Longdancao other active ingredients which may also be present are American Radix Ginseng, Radix Scutellariae Basica Lensis and Fructus Gardeniae Jasminoidis. For systemic fungal infections gentian preparations from the plant Radix gentianae Longdancao are taken orally in the form of lozenges, tablets, capsules or in solution form for gargling or swallowing. The novel gentian preparations also can be applied topically for cutaneous yeast infections and are administered in the form of suppositories, lozenges and creams to treat mucosal yeast infections. The gentian oral preparations of the invention are capable of passing through the blood brain barrier as demonstrated by the cure of meningitis caused by cryptococcus in AIDS patients. The treatment and novel compositions of the invention are effective in controlling fungal and yeast infections in two days to two weeks and provide a non-toxic treatment of vaginal yeast and other fungal infections caused by cryptococcus and candida.
(57) What have been proposed are methods for the use of various antisense oligonucleotides attached to cell-penetrating peptides as antibacterial agents that target specific bacterial mRNAs and inhibit the bacterial growth of numerous pathogenic bacterial species. The application of these methods can process many antibacterial agents that can accelerate the development of antibacterial drugs. Such drugs can treat current bacterial strains that are resistant to a number of drugs. The antisense chimeric oligonucleotide-oligopeptide molecules created by us and the proposed methods for their use can find application in medicine, pharmacy and so forth, in order to treat and eliminate diseases caused by the aforementioned specific bacteria and improve the quality of life in general. 37 claims, 15 figures A declaration of license readiness has been submitted in accordance with Art. 30 of the Law on Patents and Utility Model Registration.
A series of biomarkers of consensus sequences in a CDR3 sequence of a TCR-β chain and an application thereof. Provided is a set of biomarkers, characterized in that the biomarkers are consensus sequences in the CDR3 sequence of a T cell receptor (TCR) β chain. Preferably, the amino acid sequence of the biomarkers comprises RGG. The biomarkers provided may be used to predict the clinical response effect of PD1/PDL1 pathway immune checkpoint inhibitors to tumors, especially Hodgkin's lymphoma. High-throughput sequencing and statistical analysis are performed on the CDR3 sequence of the TCR-β chain of Hodgkin's lymphoma patients who are given the PD1/PDL1 pathway immune checkpoint inhibitors, and a dominant sequence is determined. By means of the enrichment analysis of the dominant sequence, it is helpful to monitor and predict the response and irAE of the patient after checkpoint immunotherapy.
Reports of COVID-19-related olfactory dysfunction describe a sudden onset of olfactory impairment, which may be in the presence or absence of other symptoms. The possibility that olfactory dysfunction could act as a marker for disease. When COVID-19-related olfactory dysfunction improves spontaneously, specific treatment may not be required. However,when impairment persists beyond 2 weeks, it may be reasonable for treatment to be considered. The efficacy of available treatments for patients with COVID-19-related olfactory dysfunction is unknown. Olfactory training involves repeat and deliberate sniffing of a set of odorants (commonly lemon, rose, cloves, and eucalyptus) for 20 seconds each at least twice a day for at least 3 months (or longer if possible). Studies have demonstrated improved olfaction in patients after olfactory training. Olfactory training can be considered for patients with persistent COVID-19-related olfactory dysfunction. Some evidences shown that corticosteroid treatment would benefit post-COVID-19 olfactory dysfunction but the evidences is not adequate. Until now, the efficacy of oral corticosteroids is controversial. This study investigate the efficacy and the safety of oral corticosteroids and olfactory training as a treatment for patients with COVID-19-related olfactory dysfunction.
Circadian rhythms are timekeeping mechanisms responsible for an array of biological processes. Disruption of such cycles can detrimentally affect animal health. Circadian rhythms are critical in the co-evolution of host–parasite systems, as synchronization of parasite rhythms to the host can influence infection dynamics and transmission potential. This study examines the circadian rhythms in behaviour and activity of a model fish species (Poecilia reticulata) in isolation and in shoals, both when uninfected and infected with an ectoparasite (Gyrodactylus turnbulli). Additionally, the rhythmical variance of parasite activity under different light conditions as well as rhythmical variance in parasite transmissibility was explored. Overall, infection alters the circadian rhythm of fish, causing nocturnal restlessness. Increased activity of gyrodactylids on the host's skin at night could potentially contribute to this elevated host activity. Whilst migration of gyrodactylids across the host's skin may have caused irritation to the host resulting in nocturnal restlessness, the disruption in guppy activity rhythm caused by the expression of host innate immunity cannot be excluded. We discuss the wider repercussions such behavioural responses to infection have for host health, the implications for animal behaviour studies of diurnal species as well as the application of chronotherapeutic approaches to aquaculture.
OBJECTIVE: Genetic variants in the OTOF gene are responsible for non-syndromic hearing loss with an autosomal recessive inheritance pattern. The objective of our work was to evaluate the clinical characteristics of patients with biallelic pathogenic variants in OTOF and their evolution after treatment.
METHODS: A cohort of 124 patients with prelingual hearing loss, studied from 1996 to 2023, was included in this study. A genetic analysis was conducted to identify the type and frequency of variants in the OTOF gene and their relation to the clinical characteristics of the patients.
RESULTS: The homozygous p. Gln829* variant in the OTOF gene was detected in 3 probands (2.4 %) of a group of 124 individuals with prelingual hearing loss. Another 6 family members to a total of 9 individuals were finally included. All presented with severe/profound bilateral sensorineural hearing loss of congenital onset. Three of these individuals were diagnosed with auditory neuropathy spectrum disorder. One individual passed the OAE test during the screening program, and since he did not have risk factors for hearing loss that would warrant ABR testing, this led to a delay in his hearing loss diagnosis. Four individuals underwent cochlear implants (three bilateral) with good functional outcomes in three of them. However, in 17 familial cases with heterozygous variants, either no hearing loss was observed or it was within the expected range for their age.
CONCLUSIONS: Hearing loss secondary to the p.Gln829* variant of the OTOF gene is relatively rare in our medical area. Its presence in homozygosity is the cause of severe/profound bilateral prelingual sensorineural hearing loss, responsible for auditory neuropathy with a good response to cochlear implantation.
Facilitators hold four 15-minute training sessions with the peer group to engage the target child. The facilitator explicitly identifies the "buddy" and asks the children to use four strategies to play with the child during center time: (a) offer your buddy some play options; (b) show and talk about how to play with your buddy; (c) compliment your buddy; and (d) show your buddy how to take turns. At each training session the facilitator will describe one strategy, provide examples, and practice the strategy through role play. After trainings, the facilitator provides ongoing support during center time to implement the strategies over 12 weeks during months 3-6 of the 9 months of study participation.
PURPOSE:To obtain a patch capable of percutaneously absorbing a drug effectively, by forming a tacky agent layer containing a drug, a water absorbing filler and a tacky base on one side of a substrate. CONSTITUTION:0.1-30wt.% drug except eperisone, triperisone and salts thereof is blended with 0.5-20wt.% water absorbing filler (e.g. crosslinked polyvinylpyrrolidone), a tacky base and optionally a compound (e.g. isopropyl myristate) having plasticizing action on the tacky base to form a tacky agent layer. One side of a substrate is coated with the tacky agent layer having about 300-2,000mum thickness to give the objective patch. Since releasing effect of drug is high especially when the patch absorbs water, in the case of skin administration, the patch absorbs water, sweating, etc., vaporizing from the skin surface and the drug is percutaneously absorbed efficiently.
Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of Tripterygium wilfordii, is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH-induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood-induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons. Single-cell nuclear sequencing reveals that the cyclic adenosine monophosphate (cAMP)/cAMP-activated exchange protein-1 (EPAC-1) signaling pathways are impacted by celastrol. Celastrol binds to cNMP (a domain of EPAC-1) to inhibit its interaction with voltage-dependent anion-selective channel protein 1 (VDAC1) and blocks the opening of mitochondrial permeability transition pores. After neuron-specific knockout of EPAC1, the neuroprotective effects of celastrol are diminished. In summary, this study demonstrates that celastrol, through its interaction with EPAC-1, ameliorates mitochondrial dysfunction in neurons, thus potentially improving SBI induced by ICH. These findings suggest that targeting EPAC-1 with celastrol can be a promising therapeutic approach for treating ICH-induced SBI.
PURPOSE:To obtain the title compsn. with improved temp. stability by incorporating a sucrose fatty ester (a), an alkyl glycoside or polyethylene glycol-type surfactant (b), an oily component (c) and water (d) as essential ingredients and using a combination wherein either one of (a) and (b) is lipophilic and another is hydrophilic. CONSTITUTION:A sucrose fatty ester (a) (e.g. sucrose caprylate), an alkyl glycoside e.g. 1-0-hexyl-beta-D-glycopyranoside) or a polyethylene glycol-type surfactant (e.g. polyethylene glycol alkyl ether) (b), an oily component (c) (e.g. heptane) and water (d) are incorporated as essential ingredients and a combination wherein either one of (a) and (b) is lipophilic and another is hydrophilic is used. As the result, stability in the neighborhood of 5-45 deg.C and stability with temp. which have been difficult to realize with the conventional microemulsion can significantly be improved and practical performance on safety and functional side is high.
The invention provides a liquid medicine used for treating bedsore. Raw medicines with following weight part including 25 to 35g of safflower and 1 to 3g of borneol, are sealed and soaked in 500ml ethanol of 50 to 95 percent or over 40 degrees of white spirit. Based on the liquid medicine used for treating the bedsore, the raw medicines with following weight part including 25 to 35g of cowherb seed and 10 to 20g of coptis chinensis, are sealed and soaked in 500ml ethanol of 50 to 95 percent or over 40 degree of white spirit. The liquid medicine used for treating the bedsore has the functions of relieving inflammation, alleviating pain, antibacterial action, removing poisonous substance, healing ulcer and promoting granulation. The compatibility of the liquid medicine is scientific and rational. Drug effect is remarkable. In addition, the liquid medicine used for treating the bedsore has the advantages of little adverse effect, short treatment period, rapid cure, wide application, simple treatment means, convenient dressing change and little treatment suffering. And no scar is left after recovery. If the liquid medicine is taken consistently, the bedsore disease can be completely healed.
Adult Malian males 18 years of age or older with uncomplicated P. falciparum malaria who agree to participate and provide their informed consent will be randomized to receive treatment with either AQ-13 or Coartem. Intervention 'AQ-13 Treatment' Participants randomized to the AQ-13 arm will be treated with two (350 mg) capsules on days 1 and 2 and one (350 mg) AQ-13 capsule on day 3 for a total oral dose of 1750 mg of AQ-13 (5 capsules containing 350 mg apiece) over 3 days.