anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Absorption: After oral administration, repaglinide is rapidly and completely absorbed from the gastrointestinal tract. After single and multiple oral doses in healthy subjects or in patients, peak plasma drug levels (Cmax) occur within 1 hour (Tmax). Repaglinide is rapidly eliminated from the blood stream with a half-life of approximately 1 hour. The mean absolute bioavailability is 56%. When repaglinide was given with food, the mean Tmax was not changed, but the mean Cmax and AUC (area under the time/plasma concentration curve) were decreased 20% and 12.4%, respectively.

Distribution: After intravenous (IV) dosing in healthy subjects, the volume of distribution at steady state (Vss) was 31 L, and the total body clearance (CL) was 38 L/h. Protein binding and binding to human serum albumin was greater than 98%.

Metabolism: Repaglinide is completely metabolized by oxidative biotransformation and direct conjugation with glucuronic acid after either an IV or oral dose. The major metabolites are an oxidized dicarboxylic acid (M2), the aromatic amine (M1), and the acyl glucuronide (M7). The cytochrome P-450 enzyme system, specifically 2C8 and 3A4, have been shown to be involved in the N-dealkylation of repaglinide to M2 and the further oxidation to M1. Metabolites do not contribute to the glucose-lowering effect of repaglinide.

Repaglinide appears to be a substrate for active hepatic uptake transporter (organic anion transporting protein OATP1B1).

Excretion: Within 96 hours after dosing with 14C-repaglinide as a single, oral dose, approximately 90% of the radiolabel was recovered in the feces and approximately 8% in the urine. Only 0.1% of the dose is cleared in the urine as parent compound. The major metabolite (M2) accounted for 60% of the administered dose. Less than 2% of parent drug was recovered in feces.

Pharmacokinetic Parameters: The pharmacokinetic parameters of repaglinide obtained from a single-dose, crossover study in healthy subjects and from a multiple-dose, parallel, dose-proportionality (0.5, 1, 2 and 4 mg) study in patients with type 2 diabetes are summarized in the following table:

These data indicate that repaglinide did not accumulate in serum. Clearance of oral repaglinide did not change over the 0.5 - 4 mg dose range, indicating a linear relationship between dose and plasma drug levels.

Variability of Exposure: Repaglinide AUC after multiple doses of 0.25 to 4 mg with each meal varies over a wide range. The intra-individual and inter-individual coefficients of variation were 36% and 69%, respectively. AUC over the therapeutic dose range included 69 to 1005 ng/mL*hr, but AUC exposure up to 5417 ng/mL*hr was reached in dose escalation studies without apparent adverse consequences.
Ingrown toenails are common among adolescents and young adults with the big toe being the most commonly affected. The exact incidence is unknown. An ingrown toenail occurs when the nail traumatizes the surrounding skin, resulting in swelling, infection, and the generation of granulation tissue. This cycle causes the nail to embed itself even further into the surrounding tissues, leading to additional swelling and infection.

Many treatments have been proposed for this condition. Non-surgical options include soaking, wearing loose shoes, antibiotics, and specialized braces. While these treatments often provide short-term symptomatic relief, many people with ingrown toenails eventually need surgery. The most common surgical treatment is a wedge excision (removal of the ingrown part of the nail). Most clinicians perform a partial matricectomy at the same time (destruction of part of the underlying nailbed with chemicals or surgical instruments). This prevents recurrence (where the toenail becomes ingrown again). The rate of recurrence with the wedge excision and matricectomy is reported to be 12-50%.

An alternative surgical technique is the Vandenbos procedure, where the skinfold is excised and allowed to heal by secondary intention over a period of approximately 6 weeks. This approach theoretically involves more pain, a higher risk of post-operative bleeding (because it is initially an open wound), and a longer recovery time. Proponents of this technique argue that these short-term morbidities are justified given the low rate of recurrence and excellent long-term results.

The original case series published by Vandenbos in 1959 found a recurrence rate of 0%. Two recent case series published by doctors from Ontario reported the same finding, but it was unclear how many patients in their series were lost to follow-up. Other studies have reported positive results but with a recurrence rate of 7-20%. Thus, the true effectiveness of this procedure remains unclear. Furthermore, there is no high quality evidence to support one technique over the other. Even a recent Cochrane review of 24 randomized controlled trials could not reach any definitive conclusions as to which procedure (among other surgical options) is the most effective. Previous trials show significant heterogeneity and none have assessed the Vandenbos procedure specifically. As a result, many clinicians continue to use the wedge excision and matricectomy.
Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have occurred during BORUZU therapy, including reports in patients with no risk factors for decreased left ventricular ejection fraction [see Adverse Reactions (6.1)]. Patients with risk factors for, or existing heart disease should be frequently monitored. In the relapsed multiple myeloma study of BORUZU vs dexamethasone, the incidence of any treatment-related cardiac disorder was 8% and 5% in the BORUZU and dexamethasone groups, respectively. The incidence of adverse reactions suggestive of heart failure (acute pulmonary edema, pulmonary edema, cardiac failure, congestive cardiac failure, cardiogenic shock) was ≤ 1% for each individual reaction in the BORUZU group. In the dexamethasone group the incidence was ≤ 1% for cardiac failure and congestive cardiac failure; there were no reported reactions of acute pulmonary edema, pulmonary edema, or cardiogenic shock. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.
The study is prospective. Subjects will be implanted with an iTotal® PS Knee Replacement System. The study will include a minimum of 100 subjects across up to 10 sites. The patients enrolled in this study may represent the first cases of the iTotal PS KRS implanted at a particular site; data collected for the first 15 patients at each site will be analyzed separately from the rest of the enrolled population. This will provide visibility towards determining if there exists a learning curve in the implantation process of the iTotal PS KRS. The study sites will be located in the United States.
Inhibition of the proximal B cell receptor (BCR) signaling pathway by BTK inhibitors is highly effective in the treatment of CLL, but drug resistance or intolerance occurs. Here, we investigated c-Jun N-terminal protein kinase 1 (JNK1) as an alternative drug target in the distal BCR pathway. JNK1 was preferentially overexpressed and activated in poor prognostic CLL with unmutated IGHV. Proximal BCR inhibition (BTK, PI3K, or SYK inhibitors) or SYK knockdown efficiently dephosphorylated JNK1, identifying JNK1 as a critical BCR downstream kinase in CLL. JNK1 inhibition induced apoptosis in primary CLL cells, resulting in the downregulation of BCL2, MCL1, and c-JUN. JNK1 inhibition in patient-derived CLL xenografted mice and Eµ-TCL1-tg mice prevented CLL progression, reduced splenic infiltration, and restored T cell function and normal hematopoiesis. JNK1 inhibitors even remained effective in ibrutinib refractory CLL. In conclusion, our study revealed JNK1 as a promising drug target in CLL downstream of the BCR, overcoming ibrutinib resistance, blocking the protective microenvironment, and improving CLL-specific immunosuppressive mechanisms.
Fibroblast activation protein (FAP) is a serine protease that belongs to the dipeptidyl peptidase-IV (DPP-IV) family located in fibroblast membranes. FAP is overexpressed in the cancer-associated fibroblasts (CAFs) of 90% epithelial carcinomas, including primary and metastatic liver cancer. Therefore, FAP-targeted radiopharmaceuticals can be considered a promising approach for the visualization of CAFs. CAFs are crucial component of tumor stroma, promote the growth of cancer cells and are associated with poor prognosis. Currently, Gallium 68 (68Ga)-fibroblast activation protein inhibitor (FAPI) has shown promising diagnostic value in many types of tumors, including lung cancer, gastric carcinomas, peritoneal carcinomas. However, there are currently no studies on head-to-head comparison of diagnosis value of various types of cancer in 18F-FAPI and 18F-FDG PET/CT. Therefore, we conducted a prospective study to investigate the value of 18F-FAPI PET/CT in various types of cancer, and compare it with 18F-FDG PET/CT.
The invention provides a beta-hairpin antibacterial peptide WLF with cross-chain interaction of tryptophan and leucine and a preparation method thereof. The sequence of the antibacterial peptide WLF is shown as SEQ ID No. 1. The preparation method takes tryptophan and leucine cross-chain interaction and PG as corner units, and the template of the antibacterial peptide is XWRYRPGRWRYX-NH  2  Wherein X is a hydrophobic amino acid, Y is leucine, and when x= F, Y =l, the antimicrobial peptide is named WLF. The antibacterial peptide WLF has better treatment effect on bacterial infectious diseases caused by gram-negative bacteria and/or gram-positive bacteria. The antibacterial peptide still has good stability on the premise of replacing disulfide bonds, has low hemolytic activity on the premise of keeping good antibacterial activity, and has a therapeutic index as high as 137.27. The antimicrobial peptide WLF is believed to have potential as an antibiotic replacement.
BACKGROUND: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA.
METHODS: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently.
RESULTS: Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 μmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 μmol/L increase in glutamine.
CONCLUSIONS: This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.
Avoid contact with eyes, eyelids, lips and mucous membranes. If accidental contact occurs, rinse with water. Patients should discontinue the use of Sodium Sulfacetamide Medicated Pads if the condition becomes worse, or if a rash develops in the area being treated or elsewhere. Sodium Sulfacetamide Medicated Pads also should be discontinued promptly and the physician notified if any arthritis, fever, or sores in the mouth develop. 

Drug Interactions: Sodium Sulfacetamide Medicated Pads are incompatible with silver preparations. 

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term animal studies for carcinogenic potential have not been performed on Sodium Sulfacetamide Medicated Pads. 

Pregnancy Category C: Animal reproduction studies have not been conducted with Sodium Sulfacetamide Medicated Pads. It also is not known whether Sodium Sulfacetamide Medicated Pads can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium Sulfacetamide Medicated Pads should be used by a pregnant woman only if clearly needed. 

Nursing Mothers: It is not known whether this drug is excreted in human milk following topical use of Sodium Sulfacetamide Medicated Pads. Because many drugs are excreted in human milk, caution should be exercised when Sodium Sulfacetamide Medicated Pads are administered to a nursing woman. 

Pediatric Use: Safety and effectiveness in children below the age of 12 years have not been established.
The study will consist of a double blind randomized controlled trial of HBMT (versus placebo) with subsequent pre-, during, and post-deployment surveys to assess the effectiveness of HBMT to influence relevant unit- and Soldier-level outcomes. Soldiers will be Command directed to participate. As such, all data will be used for briefing to unit leadership, however, participants will be asked to consent whether they allow their data to be used for research purposes. Subordinate units within the BN will be randomly assigned to complete either an active training or placebo version of the task. The individual briefing the Soldiers during training sessions will not know which version of the training the Soldiers are completing on the computer. Up to 40 Soldiers will complete HBMT at a time on individual study computers. Brief surveys will follow each training. There will also be a survey shortly before deployment, during deployment and shortly after deployment. See Appendix Q for tentative study timeline. For details on procedure see Section 9.8. Surveys completed during same day as HBMT training sessions will be completed on experimenter provided laptops, whereas surveys completed independent of an HBMT training session will be completed in pencil and paper format. See section 219.8 for details. The current protocol provides details for the first time point (initial HBMT training session). Additional amendments will be used to provide details and obtain approval for subsequent time points as these are coordinated with the unit. However, general information for follow-on time points is provided in this version of the protocol.
As highlighted by NCI, low HPV vaccination rates represent a major lost opportunity for population-wide cancer prevention. Pediatric primary care office visits are the main site for HPV vaccination, yet many missed opportunities (MOs) for vaccination occur in primary care and contribute to low vaccination rates. MOs are office visits during which a patient is eligible for a vaccine, but does not receive it. Many factors cause MOs - provider factors (e.g., time-constrained visits, lack of communication skills, and giving vaccinations only at preventive visits) and parent factors (e.g., vaccine hesitancy). This cluster randomized clinical trial will test the effectiveness (and cost-effectiveness) of training providers in HPV vaccine communication to reduce MOs and increase HPV vaccination rates. This training will be done through online educational modules (sent via text or email), weekly mini lessons and live office practice sessions.
Pap smear and colposcopy were done at 6 months and 12 months. HPV testing was repeated again at 12 months.
The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence.
PURPOSE:An antiallergic drug having both inhibitory effects on immediate-type allergy and inhibitory effects on delayed-type allergy, containing zedoary or an extract of zedoary with a solvent as an active ingredient. CONSTITUTION:Zedoary is extracted with one or more solvents of n-hexane, petroleum ether, ethanol, water, etc. Prepared extract with the solvent or zedoary is used as an active ingredient, to give an antiallergic drug. A dose is 0.1-10 g/person/day, especially 0.5-3g/person/day in the case of zedoary and 0.005-2 g/person/day, especially 0.01-0.5g/person/day in the case of the extract of zedoary with the solvent. The active ingredient has high safety. Tabelt, capsule, soft capsule, granule, etc., for internal use are used as dosage form. It has inhibitory effects on immediate-type allergy based on prominent inhibition of arachidonate 5-lipoxygenase taking charge of biosynthesis of SRS-A as well as inhibitory effects on delayed-type allergy.
An ischemic stroke (IS) is caused due to the lack of blood flow to cerebral tissue. Most of the studies have focused on how stroke affects the localized tissue, but it has been observed that a stroke can cause secondary complications in distant organs, such as Bone Marrow (BM). Our study focused on the effect of ischemic strokes on the bone marrow microenvironment. Bone marrow (BM) is a vital organ that maintains inflammatory homeostasis and aids in the repair of damaged tissue after injury/IS. We used the middle cerebral artery occlusion (MCAO) model of ischemic stroke on adult mice (6 months) and investigated the changes in the BM environment. BM cells were used for western blot and RT-PCR, and the BM supernatant was used for cytokine analysis and extracellular vesicle (EVs) isolation. We observed a significant increase in the total cell number within the BM and an increase in TNF-alpha and MCP-1, which are known for inducing a pro-inflammatory environment. Western blots analysis on the whole BM cell lysate demonstrated elevated levels of inflammatory factors (IL-6, TNF-alpha, and TLR-4) and senescence markers (p21 p16). EVs isolated from the BM supernatant showed no change in size or concentration; however, we found that the EVs carried increased miRNA-141-3p and miRNA-34a. Proteomic analysis on BM-derived EVs showed an alteration in the protein cargo of IS. We observed an increase in FgB, C3, Fn1, and Tra2b levels. The signaling pathway analysis showed mitochondrial function is most affected within the bone marrow. Our study demonstrated that IS induces changes in the BM environment and EVs secreted in the BM.
Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors antidepressants, inhibit the NLR pyrin domain-containing protein 3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by international classification of diseases revision 9-CM or international classification of diseases revision 10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR = 0.62, 95% CI = (0.41-0.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.
Tissue blocks from CALGB-9344 and CALGB-9741 are utilized to purify RNA to be tested in the PAM50 assay (a 50-gene quantitative PCR assay, that provides an intrinsic breast cancer subtype diagnosis) and generate risk of relapse (ROR) scores. For more information, see Details section.
Rifampin is contraindicated in patients with a history of hypersensitivity to rifampin or any of the components, or to any of the rifamycins. (See WARNINGS.)

Rifampin is contraindicated in patients who are also receiving ritonavir-boosted saquinavir due to an increased risk of severe hepatocellular toxicity. (See PRECAUTIONS, Drug Interactions.) 

Rifampin is contraindicated in patients who are also receiving atazanavir, darunavir, fosamprenavir, saquinavir, or tipranavir due to the potential of rifampin to substantially decrease plasma concentrations of these antiviral drugs, which may result in loss of antiviral efficacy and/or development of viral resistance. 

Rifampin is contraindicated in patients receiving praziquantel since therapeutically effective blood levels of praziquantel may not be achieved. In patients receiving rifampin who need immediate treatment with praziquantel alternative agents should be considered. However, if treatment with praziquantel is necessary, rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment with rifampin can then be restarted one day after completion of praziquantel treatment.
Gastric cancer (GC) remains one of the most common causes of cancer-related mortality worldwide. Surgery has always been considered as the most effective treatment for GC. Peritoneal metastasis is the common pattern of postoperative recurrence, especially patients with T4 stage or serosal invasion. What is worse, patients with peritoneal metastasis have a poor prognosis. However, it is often difficult to diagnose peritoneal metastasis at an early stage. As we know, the implantation of peritoneal free cancer cells exfoliating from serosa-invasive tumors is main reason of peritoneal seeding. Cytological examination of peritoneal lavage fluid is always performed to predict peritoneal micrometastases. However, more than half of patients with negative cytological results develop peritoneal recurrence. Low sensitivity and poor negative predictive value of this method have heralded the development of advanced techniques in detecting peritoneal free cancer cells.

In this study, novel genetic techniques will be used to detect mutated DNA of shed cancer cells in abdominal cavity. The present clinical trial aims to find a better tool to detect abdominal micrometastasis in GC patients, which may become a valid clinical index to predict postoperative relapse and direct treatment.