anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The dysregulation of circadian rhythm oscillation is a prominent feature of various solid tumors. Thus, clarifying the molecular mechanisms that maintain the circadian clock is important. In the present study, we revealed that the transcription factor forkhead box FOXK1 functions as an oncogene in breast cancer. We showed that FOXK1 recruits multiple transcription corepressor complexes, including NCoR/SMRT, SIN3A, NuRD, and REST/CoREST. Among them, the FOXK1/NCoR/SIN3A complex transcriptionally regulates a cohort of genes, including CLOCK, PER2, and CRY2, that are critically involved in the circadian rhythm. The complex promoted the proliferation of breast cancer cells by disturbing the circadian rhythm oscillation. Notably, the nuclear expression of FOXK1 was positively correlated with tumor grade. Insulin resistance gradually became more severe with tumor progression and was accompanied by the increased expression of OGT, which caused the nuclear translocation and increased expression of FOXK1. Additionally, we found that metformin downregulates FOXK1 and exports it from the nucleus, while HDAC inhibitors (HDACi) inhibit the FOXK1-related enzymatic activity. Combined treatment enhanced the expression of circadian clock genes through the regulation of FOXK1, thereby exerting an antitumor effect, indicating that highly nuclear FOXK1-expressing breast cancers are potential candidates for the combined application of metformin and HDACi.
Wnt signaling plays a crucial role in embryonic development and homeostasis maintenance. Delicate and sensitive fine-tuning of Wnt signaling based on the proper timings and positions is required to balance cell proliferation and differentiation and maintain individual health. Therefore, homeostasis is broken by tissue hypoplasia or tumor formation once Wnt signal dysregulation disturbs the balance of cell proliferation. The well-known regulatory mechanism of Wnt signaling is the molecular reaction associated with the cytoplasmic accumulation of effector β-catenin. In addition to β-catenin, most Wnt effector proteins are also regulated by ubiquitin-dependent modification, both qualitatively and quantitatively. This review will explain the regulation of the whole Wnt signal in four regulatory phases, as well as the different ubiquitin ligases and the function of deubiquitinating enzymes in each phase. Along with the recent results, the mechanism by which RNF43 negatively regulates the surface expression of Wnt receptors, which has recently been well understood, will be detailed. Many RNF43 mutations have been identified in pancreatic and gastrointestinal cancers and examined for their functional alteration in Wnt signaling. Several mutations facilitate or activate the Wnt signal, reversing the RNF43 tumor suppressor function into an oncogene. RNF43 may simultaneously play different roles in classical multistep tumorigenesis, as both wild-type and mutant RNF43 suppress the p53 pathway. We hope that the knowledge obtained from further research in RNF43 will be applied to cancer treatment in the future despite the fully unclear function of RNF43.
QuilliChew ER has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Warnings and Precautions (5.1)].   
QuilliChew ER can be diverted for non-medical use into illicit channels or distribution.

Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.

Misuse and abuse of methylphenidate may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including QuilliChew ER, can result in overdose and death [see Overdosage (10)], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
TAVR will be performed according to standard institutional practice under local or general anesthesia by the transfemoral approach. The investigational device will be advanced and deployed across the aortic arch covering the ostia of the 3 great vessels (innominate, left carotid, and left-subclavian arteries) at the initiation of the procedure and withdrawn at the completion of the TAVR procedure.
Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which act as intracellular second messengers for signal transduction pathways and modulate various processes in the central nervous system. Recent discoveries that mutations in genes encoding different PDEs, including PDE10A, are responsible for rare forms of chorea in children led to the recognition of an emerging role of PDEs in the field of pediatric movement disorders. A comprehensive literature review of all reported cases of PDE10A mutations in PubMed and Web of Science was performed in English. We included eight studies, describing 31 patients harboring a PDE10A mutation and exhibiting a hyperkinetic movement disorder with onset in infancy or childhood. Mutations in both GAF-A, GAF-B regulatory domains and outside the GAF domains of the PDE10A gene have been reported to cause hyperkinetic movement disorders. In general, patients with homozygous mutations in either GAF-A domain of PDE10A present with a more severe phenotype and at an earlier age but without any extensive abnormalities of the striata compared with patients with dominant variants in GAF-B domain, indicating that dominant and recessive mutations have different pathogenic mechanisms. PDE10A plays a key role in regulating control of striato-cortical movement. Comprehension of the molecular mechanisms within the cAMP and cGMP signaling systems caused by PDE10A mutations may inform novel therapeutic strategies that could alleviate symptoms in young patients affected by these rare movement disorders.
Teratogenic Effects: Pregnancy Category C   
Glyburide has been shown to affect the maturation of the long bones (humerus and femur) in rat pups when given in doses 6250 times the maximum recommended human dose. These effects, which were seen during the period of lactation and not during organogenesis, are a shortening of the bones with effects to various structures of the long bones, especially in humerus and femur. 

There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, glyburide should be used during pregnancy only if the potential benefit justifies the risk to the fetus. Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.

Nonteratogenic Effects: Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. If glyburide tablets are used during pregnancy, it should be discontinued at least two weeks before the expected delivery date.
Infusion of eptifibatide into baboons caused a dose-dependent inhibition of ex vivo platelet aggregation, with complete inhibition of aggregation achieved at infusion rates greater than 5 mcg/kg/min. In a baboon model that is refractory to aspirin and heparin, doses of eptifibatide that inhibit aggregation prevented acute thrombosis with only a modest prolongation (2- to 3-fold) of the bleeding time. Platelet aggregation in dogs was also inhibited by infusions of eptifibatide, with complete inhibition at 2 mcg/kg/min. This infusion dose completely inhibited canine coronary thrombosis induced by coronary artery injury (Folts model).

Human pharmacodynamic data were obtained in healthy subjects and in patients presenting with UA or NSTEMI and/or undergoing percutaneous coronary intervention. Studies in healthy subjects enrolled only males; patient studies enrolled approximately one-third women. In these studies, eptifibatide inhibited ex vivo platelet aggregation induced by adenosine diphosphate (ADP) and other agonists in a dose- and concentration-dependent manner. The effect of eptifibatide was observed immediately after administration of a 180-mcg/kg intravenous bolus. Table 4 shows the effects of dosing regimens of eptifibatide used in the IMPACT II and PURSUIT studies on ex vivo platelet aggregation induced by 20 µM ADP in PPACK-anticoagulated platelet-rich plasma and on bleeding time. The effects of the dosing regimen used in ESPRIT on platelet aggregation have not been studied.

The eptifibatide dosing regimen used in the ESPRIT study included two 180-mcg/kg bolus doses given 10 minutes apart combined with a continuous 2-mcg/kg/min infusion.

When administered alone, eptifibatide has no measurable effect on PT or aPTT.

There were no important differences between men and women or between age groups in the pharmacodynamic properties of eptifibatide. Differences among ethnic groups have not been assessed.
Patients without EGFR ectodomain, KRAS, NRAS, or BRAF mutation receive panitumumab as in Cohort 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Cohort 2.
Dynamic Splinting utilizes the protocols of Low-Load, Prolonged-Duration Stretch (LLPS) with calibrated, adjustable tension to increase the Total End Range Time (TERT) to reduce contracture. This unit is worn at night while sleeping (6-8 hours).
Percutaneous coronary intervention is increasingly guided by coronary physiology and optimized using intravascular imaging. Pressure-based measurements determine the significance of a stenosis using hyperemic or nonhyperemic pressure ratios (eg, the instantaneous wave-free ratio). Intravascular ultrasound and optical coherence tomography provide cross-sectional and longitudinal detail regarding plaque composition and vessel characteristics. These facilitate lesion preparation and optimization of stent sizing and positioning. This review explores the evidence-base and practical aspects of coregistering pressure gradient assessment and intravascular imaging with angiography. We then discuss gaps in the evidence and what is needed to help integrate these techniques into clinical practice.
The LDC program consists of 6 monthly sessions of approx. 1 hour each. Each LDC session is led by a transplant physician or clinical coordinator. LDC sessions incorporate formal didactics, active-participant learning, personal stories, moderated group discussions, role-playing, and other skill-building exercises. LDC sessions are as follows: 1) education about ESRD, KT, and LDKT 2) communication skills building 3) Exploring social networks 4) sharing successful donor and recipient stories 5) encouraging candidate self-efficacy. At session 3, the the Facebook app will be incorporated and given to candidates. The Facebook app provides step-by-step instructions for creating a Facebook post that details each waitlist candidate's struggle with ESRD and their need for a live donor. The post is then uploaded to Facebook so it can be shared with the candidate's Facebook social network.
Phytonadione is a vitamin K replacement, which is a clear, yellow to amber, viscous, and nearly odorless liquid. It is insoluble in water, soluble in chloroform and slightly soluble in ethanol. It has a molecular weight of 450.7.

Phytonadione is 2-methyl-3-phytyl-1, 4-naphthoquinone. Its empirical formula is C31H46O2 and its structural formula is:

Phytonadione tablets, USP for oral administration contain 5 mg of phytonadione, USP and are yellow round shaped scored tablets, debossed with “AP” on top and “5” on bottom of the score-line and plain on the other side. Inactive ingredients are microcrystalline cellulose, lactose monohydrate, pregelatinized starch, colloidal silicon dioxide, and magnesium stearate.
PURPOSE: Electrical stimulation (ES) is a widely used technique in the medical field for various purposes. The effect of ES on several skin properties has been investigated; however, its effect on skin vulnerability to irritants remains unknown. This study aimed to investigate the effects of ES application on skin vulnerability to external irritants.
MATERIALS AND METHODS: An experimental study on 12 healthy male subjects (Mean ± SD, 22.9 ± 3.6 years) who completed the study. The subjects were free of skin abnormalities in the volar aspect of both forearms. Three areas were allocated to each forearm and marked as areas 1, 2, and A in the treated forearm, and areas 3, 4, and B in the control forearm. ES was applied to the volar aspect of the treated forearm for 30 min three times a week, for 2 weeks. The effect of ES on skin vulnerability was investigated using 5% and 0.5% sodium lauryl sulfate (SLS) patches applied to both treated and control forearms. The skin response to irritants was evaluated using transepidermal water loss (TEWL) and a visual erythema score 24 h after patch removal.
RESULTS: Compared to the control forearm, ES increased skin permeability and erythema in response to external irritants (SLS), as measured by the visual analog score (Z = 2.75, p = 0.006) and TEWL (p < 0.05), respectively.
CONCLUSIONS: ES escalates skin reactions to low concentrations of irritant substances, such as SLS, in the area between the two electrodes. This emphasizes the use of this substance, and similar irritants should be avoided in areas treated with ES.
Participants with 50-95% forced vital capacity (FVC), and normal or impaired amyotrophic lateral sclerosis functional rating scale (ALSFRS) scores. Participants in this group will receive standard of care NIPPV therapy but will also undergo detailed analysis of nutritional status.
ETHNOPHARMACOLOGICAL RELEVANCE: Dalitong Granules (DLT), a potent Traditional Chinese Medicine known for its ability to promote gastrointestinal motility, is widely used in clinical practice for the treatment of Functional Dyspepsia (FD). Despite the remarkable clinical efficacy of DLT, the specific components responsible for its effectiveness remains unclear.
AIM OF THE STUDY: The study aimed to identify potential active ingredients of DLT for treating FD through spectrum-effect relationship analysis, multivariate statistical analysis and network pharmacology analysis. The efficacy of these identified compounds was subsequently validated using the zebrafish intestinal peristalsis model.
MATERIALS AND METHODS: The fingerprints of various solvent-extracted DLT were analyzed using high performance liquid chromatography coupled with tandem high-resolution mass spectrometry. The intestinal motility-promoting activities of DLT extracted by different solvents were evaluated through an intestinal propulsion test in mice. Potential therapeutic substances in DLT for treating FD were screened via chemometric analysis based on spectrum-effect relationship analysis. The correlation between the intensity of common peaks in the total ion chromatogram and the pharmacodynamic indices was assessed using multivariate statistical analysis. Additionally, given the complexity of Traditional Chinese Medicine, which comprises multiple components and targets, a network pharmacology analysis was performed to investigate the potential active ingredients in DLT. Finally, the pharmacological effects of these compounds in DLT were validated using a zebrafish intestinal motility model.
RESULTS: Through spectral-effect relationships analysis and network pharmacology analysis, it was determined that ten ingredients in DLT contribute to the promotion of intestinal motility. In a zebrafish intestinal motility model, it was observed that eight chemicals (excluding tetrahydropalmatine) demonstrate favorable activity of promoting gastrointestinal motility. These findings suggest that these ingredients may serve as potential therapeutic agents for improving gastric motility disorders.
CONCLUSIONS: This study employed spectral-effect relationship and network pharmacology analysis to identify the active ingredients in DLT. The findings were then validated using a zebrafish intestinal peristalsis model. These results provide a scientific foundation for the clinical application of DLT as a key traditional herbal formula for managing FD.
Participants will receive golimumab 50 mg as subcutaneous (SC) (under the skin) injections administered every 4 weeks for up to 48 weeks. In addition, participants will receive a stable dose of MTX.
Daily administration of 400mg vorinostat on 28 days (one therapy cycle). Seven days of therapy break between two consecutive cycles.
FIELD: cosmetics, dyes. SUBSTANCE: invention relates to a composite for oxidative staining of keratine fibers, in part, human keratine fibers, for example, hair. The composite comprises at least one the first oxidizing base taken among pyrazol[1,5-a] pyrimidines and N, N-bis-(β-hydroxy-ethyl)-p- phenylenediamine as the second oxidizing base and at least one dye-forming component taken among m- aminophenols and m-phenylenediamines in medium suitable for staining. Invention relates to also a method of staining where this composite and set for staining are used. Invention ensure to obtain novel dyes providing intensive, slow selective and very resistant to different aggressive effects hair staining. EFFECT: improved properties of composite. 11 cl, 1 tbl, 2 ex
INTRODUCTION AND HYPOTHESIS: The aim is to compare the effects of the progressive training program (PTP), a new protocol, with two different hybrid telerehabilitation methods, on the parameters related to urinary incontinence in women with urinary incontinence.
METHODS: A total of 50 participants with stress or mixed urinary incontinence participated in this two-arm, parallel-group, randomized, non-inferiority trial. Individual hybrid training (IHT) or group hybrid training (GHT) was given to women for 8 weeks. The Power, Endurance, Repetitions, Fast contractions, and Every Contraction Timed (PERFECT) scheme and surface electromyography were used to assess pelvic floor muscle function, whereas quality of life, exercise adherence, and symptoms were assessed by questionnaires and a 3-day bladder diary. An intention-to-treat analysis was performed. Linear mixed model analysis with the factors "time" and "group" was used to determine the effects of IHT and GHT.
RESULTS: The primary outcome was changes in pelvic floor muscle function as evaluated using the PERFECT scheme and surface electromyography at the 4th and 8th weeks relative to baseline. No statistical difference was found between the groups except for "power" of the PERFECT scheme and "nocturnal urination frequency" (p > 0.05). The GHT showed significant improvement in P and nocturnal urination frequency at the end of the 8th week (p < 0.05). From baseline to week 8, the effect size for the P value was found to be small (Cohen's d = 0.33).
CONCLUSION: Eight weeks of PTP did not lead to different results in incontinence-related parameters in either of the training methods. It may be better to conduct GHT in terms of implementing PTP in incontinence and training programs in terms of time, staff workload, and applicability.
Investigators will enroll \~100 counseling Maternal-Fetal Medicine (MFM) specialists and 100 counseling Neonatologists (total \~200 providers), who provided counseling to the enrolled pregnant women between 22 0/7-25 6/7 weeks' estimated gestation for anticipated extremely preterm delivery. This assumes 1 counseling provider from MFM and 1 from Neonatology per pregnant woman, although there could be more if a consult is performed by both an attending physician and a training fellow or practitioner, or less, if a counseling provider declines to participate in the study. There will be anticipated repetition of counseling providers, accounted for in the statistical analysis. Providers will be asked to complete educational interventions to improve counseling at extreme prematurity.
A seizure or convulsion is a time-limited, paroxysmal, change in motor activity and or behavior that results from electrical activity in the brain that is abnormal.1 The emergency department of a hospital is usually the place where children with seizures receive first treatment and medical support. Seizures make up about 1% of all emergency department visits for pediatric patients, and at least 5% of pediatric patients will have a seizure by the time they are 16 years old. Children younger than one year of age are commonly affected by new and unprovoked seizures.2 Seizures can result in continuous muscular activity, which leads to tissue breakdown because of anaerobic metabolism as well as decreasing oxygen and glucose to the brain causing brain ischemia and neuronal death. So, the seizures must be controlled rapidly to decrease the systemic as well as brain damage.3,4 First-line anticonvulsants for the treatment of acute seizures are benzodiazepines. Diazepam is frequently used for the treatment of seizures because it can be delivered either intravenously or rectally. It is lipophilic so does not have proper intramuscular absorption. Precious time is spent in getting intravenous access or per rectal catheterization. While midazolam, is a lipid-soluble benzodiazepine, rapidly absorbed after intramuscular (IM) injection.5,6 For managing seizure, the drug should be sufficiently potent to allow small volume and an administration that is quick, easy, and safe with quick action and little monitoring.7 Intramuscular midazolam meets these criteria and may be useful for the treatment of seizures, but more trials are needed to see the safety and efficacy of this therapy in the pediatric population.8 A major chunk of the seizures may occur out of the hospital. For the parents its frightening to see their kid in fits. Usually these parents immediately take their child to the nearby hospital or clinic. But it's not possible for all the parents, because in many areas health facilities are not present. Hence these patients are at increased risk for sustaining post ictal brain damage. There is a long-awaited wish that how to prevent this brain damage. A lot of options are tried nowadays and also in the past, like rectal diazepam, sublingual midazolam, but unfortunately most such options are not without risks.

The objective of this study was to compare the time taken by intramuscular midazolam to stop the seizure as compared to intravenous diazepam in emergency cases in the pediatric age group.