anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Achondroplasia is the most common form of dwarfism and is characterized by short limbs with the thighs and upper arms being the most affected. Achondroplasia is also associated with a narrowing of the foramen magnum and spinal stenosis. Hypochondroplasia is a related, but less severe form of dwarfism that does not have the neurologic problems. Achondroplasia and hypochondroplasia are caused by mutations in the fibroblast growth factor receptor-3 (FGFR-3) gene that causes constitutive activation of the receptor. FGFR-3 signals primarily through the MAP kinase pathway, which is overactivated in growth plate chondrocytes in achondroplasia. C-type natriuretic peptide (CNP) is a hormone that is produced and acts in the growth plate as a potent positive regulator of linear growth. CNP signals through natriuretic peptide receptor-B (NPR-B), generating cGMP. Studies in mice show that activation of the MAP kinase pathway inhibits signaling through NPR-B. Hence the achondroplasia phenotype may be due in part to inhibition of CNP signaling. Conversely, CNP intracellular signaling inhibits the MAP kinase pathway and CNP analogs are being studied as a potential specific therapy for achondroplasia. The objective of this project is to define the state of the CNP system in children and adults with achondroplasia or hypochondroplasia. Our hypotheses are 1) blood levels of CNP and its aminoterminal propeptide (NTproCNP) are elevated and blood levels of cGMP are reduced in children with achondroplasia or hypochondroplasia, due to inhibition of NPR-B; 2) CNP and NTproCNP levels are normal in adults with achondroplasia and hypochondroplasia, due to their lack of growth plate cartilage; and 3) as in healthy children, NTproCNP levels predict height velocity in children with achondroplasia or hypochondroplasia. These hypotheses will be addressed with two specific aims. Specific aim 1 is to determine plasma levels of CNP, NTproCNP, and cGMP in children and adults with achondroplasia or hypochondroplasia. Specific aim 2 is to determine if NTproCNP levels correlate with height velocity in children with achondroplasia or hypochondroplasia.

The study is an observational, cross-sectional/partially longitudinal study of children and adults with achondroplasia or hypochondroplasia. Children will be seen as part of routine clinic visits. Children seen more than once during the study period will provide longitudinal data. Adult subjects with achondroplasia or hypochondroplasia will be studied a single time. Data collected will include anthropometrics, information on neurologic complications of achondroplasia, and blood levels of CNP, NTproCNP, and cGMP. We anticipate 100 subjects will be recruited, with about 20 being studied as many as three times during the course of the study.

By studying the potential role of the CNP system in achondroplasia and hypochondroplasia, not only will we provide further insight into the pathophysiology of these common syndromes, we will also provide greater insight into the regulation of normal linear growth.
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses.
The Sentinel Safety Cohort of the Parent Study will enroll 56 healthy adults, 18 to 55 years of age, who will be randomized to receive AZD5156 (40 participants) or placebo (16 participants). Participants will be randomized to receive study intervention IM either in the gluteal or the anterolateral thigh. Dosing within the Sentinel Safety Cohort will be staggered, with participants allocated sequentially to 4 subcohorts (1a, 1b, 2a, and 2b).
Although Parkinson's disease (PD) has been mainly viewed as a movement disorder, the pathophysiology of declined motor function incorporates impairments of multiple systems, including sensory, motor and cognitive pathways. Specifically, it has been demonstrated that cognitive function may play an essential role in motor function for individuals with PD. Cognitive dysfunction involving set-shifting and attentional control has been found to be associated with movement slowness in performing a finger sequence task and freezing of gait. Furthermore, a recent rodent model indicates that cognitive dysfunction may occur prior to the onset of motor symptoms. Similarly human studies show that 25-30% individuals with PD exhibit cognitive impairments at the time of diagnosis. The overall evidence suggests that cognitive dysfunction may contribute to degraded motor function in PD. Interestingly, several studies demonstrate that aerobic exercise and resistance training can improve cognitive function in individuals with PD, indicating a tight interplay between motor and cognitive function. Targeting cognitive function by incorporating cognitive training into physical rehabilitation may be important for people with PD. Although there is mounting evidence for the benefits of physical exercise in PD, few studies investigate whether combining cognitive training with physical exercise can provide additional benefits than physical exercise alone. Thus, the purpose of this pilot study is to investigate the effect of SMARTfit training, a novel technology that provides an opportunity to combine physical training with cognitive training, in individuals with PD. The hypothesis is that SMARTfit training will promote greater motor and cognition improvements than conventional physical training. To test the above hypothesis, ten individuals with mild PD will receive both SMARTfit training and conventional physical training in a counterbalanced order with a washout period. For each training program, participants will receive a 1-hour training session 3 times per week for 8 weeks. The changes in disease biomarkers before and after training will also be explored.
FIELD: medicine. ^ SUBSTANCE: leuko-platelet mass, isolated from anticoagulated blood, contains platelets and leukocytes in their individual concentration, exceeding their concentration in blood, at least, 2 times. Medication consists of described above leuko-platelet mass and platelet activator. Treatment by impact of leuko-platelet mass and based on it medication lies in increase of content of factors of new vessel growth and factors which contribute to tissue regeneration. ^ EFFECT: leuko-platelet mass and based on it medication make it possible to reduce term of treatment and increase its quality. ^ 14 cl
The pharmacokinetics of carisoprodol and its metabolite meprobamate were studied in a crossover study of 24 healthy subjects (12 male and 12 female) who received single doses of 250 mg and 350 mg carisoprodol (see Table 2). The exposure of carisoprodol and meprobamate was dose proportional between the 250 mg and 350 mg doses. The Cmax of meprobamate was 2.5 ± 0.5 μg/mL (mean ± SD) after administration of a single 350 mg dose of carisoprodol, which is approximately 30% of the Cmax of meprobamate (approximately 8 μg/mL) after administration of a single 400 mg dose of meprobamate.

Absorption: Absolute bioavailability of carisoprodol has not been determined. The mean time to peak plasma concentrations (Tmax) of carisoprodol was approximately 1.5 to 2 hours. Co-administration of a high-fat meal with carisoprodol (350 mg tablet) had no effect on the pharmacokinetics of carisoprodol. Therefore, carisoprodol may be administered with or without food.

Metabolism: The major pathway of carisoprodol metabolism is via the liver by cytochrome enzyme CYP2C19 to form meprobamate. This enzyme exhibits genetic polymorphism (see Patients with Reduced CYP2C19 Activity below).

Elimination: Carisoprodol is eliminated by both renal and non-renal routes with a terminal elimination half-life of approximately 2 hours. The half-life of meprobamate is approximately 10 hours.

Gender: Exposure of carisoprodol is higher in female than in male subjects (approximately 30 to 50% on a weight adjusted basis). Overall exposure of meprobamate is comparable between female and male subjects.

Patients with Reduced CYP2C19 Activity: Carisoprodol should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3 to 5% and in Asians is approximately 15 to 20%.
PURPOSE: This comprehensive investigation delved into the intricate causal interplay existing between cardiovascular-related plasma proteins and the susceptibility to colorectal cancer, leveraging the robust framework of Mendelian randomization, and employed expression profiling and survival analysis to unravel the latent clinical worth embedded within pertinent gene expressions.
METHODS: Protein quantitative trait loci (pQTLs) of 85 cardiovascular proteins were employed as instrumental variables to investigate the causal relationship between proteins and CRC risk using a Mendelian randomization approach. Causal inferences were graded as strong, intermediate or weak based on statistical checks. Drug-target MR examined VEGF receptors for their potential as therapeutic targets for colorectal cancer. Differential expression analysis, diagnostic ROC curves, and survival analyses were performed for identified proteins using RNA-seq data from The Cancer Genome Atlas (TCGA) colorectal cancer cohort.
RESULTS: Using cis-pQTLs, LOX-1, VEGF-A and OPG were associated with increased CRC risk (strong evidence), while PTX3, TNF-R2 and MMP-7 were protective (strong evidence). Pan-pQTL analysis found MMP-10 increased risk (intermediate evidence) and ADM increased risk (weak evidence). Drug-target MR found VEGF R1 may be promising therapeutic targets. Differential expression analysis revealed seven genes encoding the identified proteins were dysregulated in tumors. ROC analysis showed five gene expression had high diagnostic accuracy. KM analysis showed four genes had prognostic value.
CONCLUSIONS: This large-scale MR study implicates several cardiovascular proteins in CRC susceptibility and progression. Findings highlight roles for VEGF signaling and extracellular matrix regulation. Results nominate specific proteins as potential diagnostic biomarkers or therapeutic targets warranting further investigation.
The invention relates to an anti-HIV genetic engineering divalent antibody and a preparation method thereof, and an anti-HIV genetic engineering medicine. The anti-HIV genetic engineering divalent antibody comprises a human antibody constant region and CD4 and CCR5 connected with the human antibody constant region. The preparation method of the anti-HIV genetic engineering antibody comprises the steps that: human antibody constant region gene, CD4 gene, and CCR5 gene are obtained; expression plasmids comprising the three genes are constructed; the expression plasmids are transfected into cell lines and are cultured; and the divalent antibody is obtained after separation and purification. The divalent antibody provided by the invention has both CD4 and CCR5 which can be specifically bound with CD4 and CCR5 loci on HIV virus, specific binding effect is substantially improved, and HIV-infected host cell dual inhibition can be realized. The preparation method provided by the invention is simple and feasible. The anti-HIV genetic engineering medicine with the divalent antibody can effectively act upon HIV virus, and assists in effectively preventing and treating HIV virus infections.
Mast cells (MCs) are tissue-resident immune cells, well-positioned at the host-environment interface for detecting external antigens and playing a critical role in mobilizing innate and adaptive immune responses. Sensory neurons are afferent neurons innervating most areas of the body but especially in the periphery, where they sense external and internal signals and relay information to the brain. The significance of MC-sensory neuron communication is now increasingly becoming recognized, especially because both cell types are in close physical proximity at the host-environment interface and around major organs of the body and produce specific mediators that can activate each other. In this review, we explore the roles of MC-sensory neuron crosstalk in allergic diseases, shedding light on how activated MCs trigger sensory neurons to initiate signaling in pruritus, shock, and potentially abdominal pain in allergy, and how activated sensory neurons regulate MCs in homeostasis and atopic dermatitis associated with contact hypersensitivity and type 2 inflammation. Throughout the review, we also discuss how these 2 sentinel cell types signal each other, potentially resulting in a positive feedback loop that can sustain inflammation. Unraveling the mysteries of MC-sensory neuron crosstalk is likely to unveil their critical roles in various disease conditions and enable the development of new therapeutic approaches to combat these maladies.
Participants will receive mycophenolate mofetil (MMF) for up to 96 weeks, in addition to their background Standard of Care medication for systemic sclerosis related symptoms. They will receive 500mg twice daily over the first 4 weeks following their randomisation, and if tolerated the dose will be increased to a target dose of 1g twice daily starting from week 5 until their Final visit.
BACKGROUND: Antithrombotic treatment (ATT) post-left atrial appendage occlusion (LAAO) remains controversial. Furthermore, most of the patients undergoing LAAO are at a very high bleeding risk.
AIMS: This study aimed to compare a simplified versus conventional ATT after LAAO in very high bleeding risk patients.
METHODS: This is a multicentre, retrospective study including very high bleeding risk patients, according to the Bleeding Academic Research Consortium (BARC) definition, who underwent LAAO. These included patients at >4% risk of BARC 3 to 5 bleeding or >1% risk of intracranial bleeding after the procedure. Two groups were established based on the discharge ATT. The simplified group included single antiplatelet treatment or no treatment, and the conventional group comprised dual antiplatelet treatment or anticoagulation (combined or not with antiplatelet therapy).
RESULTS: A total of 1,135 patients were included. The mean CHA2DS2-VASc and HAS-BLED scores were 4.5±1.5 and 3.7±1.0, respectively. There were no differences in the composite endpoint (death, stroke, transient ischaemic attack, device-related thrombus or major bleeding) between the 2 groups (hazard ratio [HR] 0.81, 95% confidence interval [CI]: 0.59-1.11; p=0.188). Although the rate of major bleeding during the first year was numerically lower in the simplified group, it did not reach statistical significance (HR 0.67, 95% CI: 0.41-1.10; p=0.104). Nonetheless, patients with previous major bleeding presented a significantly lower rate of major bleeding when using the simplified treatment (HR 0.61, 95% CI: 0.36-0.99; p=0.049).
CONCLUSIONS: In patients with very high bleeding risk, a simplified ATT after LAAO seems to be as effective as conventional protocols. Furthermore, patients with a history of major bleeding experienced a lower risk of major bleeding with the simplified ATT.
PROBLEM TO BE SOLVED: To make a water-insoluble mutan water-soluble by carboxymethylating mutan. SOLUTION: A carboxymethylated mutan is represented by the formula (wherein R is H or -CH2COOH provided at least one R is -CH2COOH; and n is an integer of 0-10,000). Na, K, Ca, and amine salts are examples of a salt of carboxymethylated mutan. A carboxymethylated mutan can be prepared by any method for carboxymethylating saccharides; for example, by reacting mutan with monochloroacetic acid under an alkaline condition, if necessary, in the presence of an organic solvent. Mutan such as one prepared by a general fermentation method or one prepared while dextranase is being added to a fermentation solution can be used. When an organic solvent is used, 2-propanol is preferable. A reaction in the presence of an alkaline solution without using a solvent can also be conducted.
ICT programs that include health information learning by disease and self-management based on Smart Management Strategy for Health (SMASH) are provided. After that, subjects will conduct self-management health care for 12 weeks. After 3 months, they finish self-management ICT programs, and then they fill out the questionnaire.
Patients assigned to IPT will receive 12 sessions of individual therapy of approximately 50 minutes duration. Therapy will be manualized and slightly adapted to meet the needs of patients with Parkinson's Disease. Therapy focuses on one of four interpersonal events that are linked with onset or maintenance of depression (role transition, role disputes, unresolved grief, and interpersonal deficits).
Aneurysmal recurrence after successful flow-diversion embolization is exceptionally rare. The rarity of recurrence has called into question the yield of interval surveillance imaging. Here we report the case of a recurrent intracranial aneurysm despite complete angiographic resolution after flow-diversion therapy with a Pipeline embolization device (PED). Given the absence of poor wall apposition, endoleak, and device migration, how this aneurysm recurred remains unclear, particularly given the recurrence was at a timepoint at which complete reendothelialization of the device would be expected. The patient ultimately underwent interval treatment with a second device placed across the neck of the aneurysm. Although rare, reports of aneurysmal recurrences support the use of interval non-invasive imaging surveillance to ensure successful embolization in this patient population.
Part B will explore doses to refine the dose-response curve of GSK2018682 on lymphocyte suppression, as allowed by stopping criteria, in 1 or 2 cohorts of up to 15 subjects (Cohort 2 and Cohort 3). In Part B, up to six single ascending doses of GSK2018682 and one dose of placebo will be investigated in up to 8 sessions.
PURPOSE:To provide an eye lotion composition effective to prevent the degradation of acid mucopolysaccharide an useful for the remedy of cataract, etc., by compounding a group composed of an acid mucopolysaccharide, ascorbic acid and their salt and a group composed of tryptophan, histidine, uric acid, etc. CONSTITUTION:The objective composition contains (A) 0.01-5 wt% one or more compounds selected from acid mucopolysaccharide, ascorbic acid and their salts and (B) 0.001-1 wt% one or more compounds selected form tryptophan, histidine, uric acid and their salts. The depolymerization of acid mucopolysaccharide can be prevented even in the presence of a depolymerization acceleration factor such as ascorbic acid, metallic ion, etc., by the use of tryptophan, histidine, uric acid and their salts. Accordingly, the composition is effective for the remedy and prevention of eye diseases (e.g. catalact, glaucoma, etc.) caused by the chemical change in the acid mucopolysaccharide in the lens. It can be applied also as a preservation liquid for surgical operation of eye diseases.
PURPOSE: The aim of this study was to assess the agreement of multiplanar reconstruction (MPR) and semiautomated central lumen line (CLL) analysis of abdominal aortic aneurysms (AAA), with 3 different software workstations (WS1, WS2, WS3) and 2 experienced practitioners as well as to analyze its eventual impact in graft selection.
MATERIALS AND METHODS: Twenty computed tomography (CT) angiography data sets were randomly chosen from a series of 100 consecutive studies. Measurements were performed twice by each reader, in random order, and included 8 parameters (5 diameters and 3 lengths). Each observer performed a complete set of 60 studies. Intra-observer and interobserver variability for every WS was assessed. Measurements were evaluated using Bland-Altman analysis, correlation coefficients (r), and concordance correlation coefficients (CCC [95% confidence interval (CI)]).
RESULTS: A high overall agreement between repeated measurements for both observers was obtained (r=0.989; CCC=0.988 [0.982-0.992] and r=0.998; CCC=0.996 [0.994-0.997], for observers 1 and 2, respectively). However, reproducibility for individual parameters was excellent for observer 2 and only moderate for observer 1. A high overall agreement was obtained for interobserver concordance (r=0.987; CCC=0.986 [0.982-0.989]). When analyzing for individual parameters, greatest interobserver differences were found at CLL measurement of the diameter of aortic neck (WS2) and bifurcation (WS1 and WS2) as well as iliac diameter in all 3 WS for both CLL and MPR. Similar differences were observed in paired comparison between WS when involving these parameters. Careful inspection of Bland-Altman charts revealed some cases of disagreement between WS and observers that would affect decision making on graft selection, changing the neck diameter to a different size, in 2 cases when measuring with WS1, and iliac diameter in 4 cases (2 of them with WS1 and 2 with WS2). Greatest discordance was observed regarding ipsilateral iliac length affecting 7 measurements that would lead to change the length of the selected limb graft (2 with WS1, 3 with WS2, and 2 with WS3).
CONCLUSIONS: Although a high agreement between different observers using different WS for AAA measurements is to be expected, small differences may lead to the selection of a different graft size. The use of a single software by experienced users, and double check by a different one, may be advisable.
CLINICAL IMPACT: Influence of inter and intraobserver variability in CT measurements during planning of endovascular aneurysm repair (EVAR) has been extensively reviewed. However, its impact in graft selection (final choose of diameter and lengths) has been scarcely analyzed. The results of this study suggest that, although a high agreement between different observers using different workstations for AAA measurements is to be expected, small differences may lead to the selection of a different graft size. The use of a single software by experienced users, and double check by a different one, may be advisable.
Among patients who were confirmed as COVID-19 and admitted to the COVID-19 management ward of Daegu Catholic University Hospital, patients who were consulted by the Department of psychiatry was selected as participants. Socio-demographic information, medical severity (oxygen saturation, chest x-ray readings, medication being administered), clinical psychological scale (PHQ-9, GAD-7, PC-PTSD-5, AIS, P4, SF-36, SCL-90-R). were collected from participants. It evaluates whether there is a difference in the psychological scale according to the difference in participants' sociodemographic status and medical severity, and evaluates the effectiveness of psychiatric counseling by comparing clinical psychological measures before and after referral to department of psychiatry.