anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for tinnitus, although outcomes are highly variable. We previously described a multilocus sequential rTMS treatment protocol for tinnitus involving stimulation of both prefrontal and auditory targets. In this study, we report results using this approach in an open-label treatment study of tinnitus with and without comorbid major depressive disorder (MDD).
MATERIALS AND METHODS: Forty patients with chronic tinnitus (mean age 56 years, ten female) and with (n = 17) or without (n = 23) MDD received multilocus rTMS administered sequentially to 1) left dorsolateral prefrontal cortex, followed by 2) auditory cortex (Heschel's gyrus). Patients completed weekly self-report ratings using the Tinnitus Functional Index (TFI) and Tinnitus Handicap Inventory, and patients with MDD completed the Inventory of Depressive Symptomatology Self-Report 30-item.
RESULTS: Patients showed significant mean improvement in tinnitus at sessions 5 (mean TFI improvement 6.8 points ± 12.2, p = 0.002) and 10 (mean improvement 9.2 points ± 14.1, p = 0.002), with 48% of patients responding within ten treatment sessions. Responders were significantly older than nonresponders (61.5 ± 15 years vs 51.3 ± 16 years), and there was a trend toward decreased likelihood of response in subjects with comorbid MDD compared with subjects without comorbidity (odds ratio = 0.28, p = 0.06). Patients with comorbid MDD reported significantly less improvement after ten sessions than did those with tinnitus alone (4.3 ± 10.3 vs 14.7 ± 15.0 points, p = 0.04). Post hoc analyses suggested that the comorbid group achieved improvement comparable to that of the tinnitus-only group after 30 treatments.
CONCLUSIONS: Patients showed significant improvement in tinnitus from multilocus sequential rTMS treatment, and those with tinnitus alone improved more quickly. Those with depression who continued rTMS through a full 30-session course further improved, indicating that tinnitus with comorbid MDD may respond with extended treatment.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age and is characterized by menstrual irregularities, metabolic imbalances and infertility. The pathogenesis of PCOS is complex and not fully understood, and chronic inflammation and insulin resistance are implicated in its progression. In this study, we investigated the role of m6A methylation, an important epigenetic modification, in the pathogenesis of PCOS. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq), we mapped the m6A methylation profile in granulosa cells from patients with PCOS and identified a significant regulatory effect on gene expression. CD36 is a novel m6A-regulated gene that may facilitate the progression of PCOS. We demonstrated that METTL3, an m6A methyltransferase, modulated CD36 expression and influenced glucose metabolism and inflammatory responses in PCOS. Employing KGN cells as a model of insulin resistance, we observed that CD36 knockdown ameliorated the impaired glucose uptake and significantly reduced the production of pro-inflammatory cytokines. These findings are consistent with the results of CD36 inhibition in a mouse model of PCOS, indicating a role of CD36 in modulating the disease phenotype. Our study delineates a previously unrecognized epigenetic mechanism involving m6A methylation in PCOS, highlighting the potential of targeting the METTL3-CD36 axis as a therapeutic strategy for managing ovarian inflammation and metabolic dysregulation in patients with PCOS.
Fatalities caused by infectious diseases (i.e., diseases caused by parasite, bacteria, and viruses) have become reinstated as a major public health threat globally. Factors such as antimicrobial resistance and viral complications are the key contributors to the death numbers. As a result, new compounds with structural diversity classes are critical for controlling the virulence of pathogens that are multi-drug resistant. Derivatization of bio-active organic molecules with organometallic synthons is a promising strategy for modifying the inherent and enhanced properties of biomolecules. Due to their redox chemistry, bioactivity, and structural diversity, organometallic moieties make excellent candidates for lead structures in drug development. Furthermore, organometallic compounds open an array of potential in therapy that existing organic molecules lack, i.e., their ability to fulfill drug availability and resolve the frequent succumbing of organic molecules to drug resistance. Additionally, metal complexes have the potential towards metal-specific modes of action, preventing bacteria from developing resistance mechanisms. This review's main contribution is to provide a thorough account of the biological efficacy (in vitro and in vitro) of metal-based complexes against infectious diseases. This resource can also be utilized in conjunction with corresponding journals on metal-based complexes investigated against infectious diseases.
The entrance to and walls of a woman's vaginal tract are normally in a constricted state. The fact that air cannot readily enter the vagina and circulate within is at the root of or complicates the treatment of many, common female diseases. For example, many of the disease organisms which attack the vagina are anaerobic which means they cannot thrive or survive in oxygen. Studies show that most die almost at once if exposed to air. Accordingly, it is an object of this invention to insert a highly porous, cylindrical device into the vagina in order to expand the vaginal opening and canal within. After air is allowed to freely enter the vaginal canal, anaerobic organisms are rapidly destroyed.
This is a pivotal trial in members of the same family carrying the V282M nutation in the Gardos channel (KCNN4) and other patients with V282 mutations with demonstrated in-vitro sensitivity to senicapoc. These mutations lead to hyperactivation of the channel and red cell dehydration. Up to 6 patients are eligible to enroll in this study, which will assess effectiveness based on individual changes of primary endpoints over individually established baselines.
PURPOSE: To obtain a radiation sensitive mixture capable of satisfactory image differentiation by using specified multifunctional α-diazo-β-keto-ester as an optically active component. CONSTITUTION: This radiation sensitive mixture contains multifunctional α- diazo-β-keto-ester represented by formula I as an optically active component and a binder insoluble in water but soluble or swellable in an alkaline aq. soln. In the formula I, R<1> is 4-20C aliphatic, alicyclic, arom.-aliphatic or arom. group, X is 2-22C aliphatic, alicyclic, carbocyclic, heterocyclic or arom.-aliphatic group, O, S or -O-C(O)-O- may be substd. for each CH2 group, (m) is an integer of 2-10 and (n) is an integer of 0-2. This mixture enables satisfactory differentiation between the exposed and unexposed parts of a layer.
No formal pharmacokinetic study of either propoxyphene alone or in combination with acetaminophen has been conducted in patients with mild, moderate or severe hepatic impairment. 

After oral administration of propoxyphene in patients with cirrhosis, plasma concentrations of propoxyphene were considerably higher and norpropoxyphene concentrations were much lower than in control patients. This is presumably because of a decreased first-pass metabolism of orally administered propoxyphene in these patients. The AUC ratio of norpropoxyphene: propoxyphene was significantly lower in patients with cirrhosis (0.5 to 0.9) than in controls (2.5 to 4). 

Compared to healthy subjects, acetaminophen had a lower total clearance and longer half-life in patients with liver disease. Decreased metabolite formation clearance (8-42%) was observed in subjects with liver disease compared to healthy subjects after both single and multiple-doses (at steady state). In addition, there is an increase in the amount of acetaminophen excreted unchanged in the urine (4.7% vs. 2.5%) in patients with liver disease compared to healthy subjects after repeat doses, suggesting that more acetaminophen was excreted by renal elimination in the liver disease state.
It is intended to provide a protein complex and a production process whereby the protein complex can be efficiently produced without lowering its function. It is also intended to provide use of the protein complex in a biosensor, an immobilized enzyme and so on. A protein complex comprising a polyhedral protein having an insect virus encapsulated therein and a target protein having a restricted region of a capsid protein VP3 of cytoplasmic polyhedrosis virus, more specifically, a region which is either a region from the N-terminus to the 40th amino acid residue or a region from the 41st amino acid residue to the 79th amino acid residue as an embedding signal for polyhedron, and a process for producing the same. The polyhedral protein has an effect on improvement in the stability of the target protein, protection thereof or improvement in the preservation properties thereof, or a combination of any of these. The target protein is at least one member selected from the group consisting of fluorescent or light-emitting proteins, enzymes, antigens, antibodies, cytokines, receptors and bioactive proteins. A biosensor characterized in that the above-described protein complex is arranged in dots or lines on a substrate and immobilized thereon.
Nicotine acts as an angiogenic factor by stimulating endogenous cholinergic pathways. Several subtypes of nicotinic acetylcholine receptors (nAChRs) have been demonstrated to be closely correlated to the formation and progression of different types of cancers. Recently, several studies have found that nicotinic acetylcholine receptors α9 (α9-nAChRs) are highly expressed in breast tumors, especially in tumors derived from patients diagnosed at advanced stages. In vitro studies have demonstrated that activation of α9-nAChRs is associated with increased proliferation and migration of breast cancer. To study the tumor-promoting role of α9-nAChRs in breast cancers, we generated a novel anti-α9-nAChR and methoxy-polyethylene glycol (mPEG) bispecific antibody (α9 BsAb) for dissecting the molecular mechanism on α9-nAChR-mediated tumor progression. Unexpectedly, we discovered the angiogenic role of α9-nAChR in nicotine-induced neovascularization of tumors. It revealed α9 BsAbs reduced nicotine-induced endothelial cell tube formation, blood vessel development in Matrigel plug assay and angiogenesis in microtube array membrane murine model (MTAMs). To unbraid the molecular mechanism of α9-nAChR in nicotine-mediated angiogenesis, the α9 BsAbs were applied and revealed the inhibitory roles in nicotine-induced production of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor A (VEGF-A), phosphorylated vascular endothelial growth factor receptor 2 (p-VEGFR2), vascular endothelial growth factor receptor 2 (VEGFR2) and matrix metalloproteinase-9 (MMP9) from triple-negative breast cancer cells (MDA-MB-231), suggesting α9-nAChRs played an important role in nicotine-induced angiogenesis. To confirm our results, the shRNA targeting α9-nAChRs was designed and used to silence α9-nAChR expression and then evaluated the angiogenic role of α9-nAChRs. The results showed α9 shRNA also played an inhibitory effect in blocking the nicotine-induced angiogenic signaling. Taken together, α9-nAChR played a critical role in nicotine-induced angiogenesis and this bispecific antibody (α9 BsAb) may serve as a potential therapeutic candidate for treatments of the α9 positive cancers.
Absorption and Bioavailability: Pharmacokinetic studies of orally inhaled zanamivir indicate that approximately 4% to 17% of the inhaled dose is systemically absorbed. The peak serum concentrations ranged from 17 to 142 ng/mL within 1 to 2 hours following a 10 mg dose. The area under the serum concentration versus time curve (AUC∞) ranged from 111 to 1,364 ng•hr/mL.

Distribution: Zanamivir has limited plasma protein binding (<10%).

Metabolism: Zanamivir is renally excreted as unchanged drug. No metabolites have been detected in humans.

Elimination: The serum half-life of zanamivir following administration by oral inhalation ranges from 2.5 to 5.1 hours. It is excreted unchanged in the urine with excretion of a single dose completed within 24 hours. Total clearance ranges from 2.5 to 10.9 L/hr. Unabsorbed drug is excreted in the feces.

Impaired Hepatic Function: The pharmacokinetics of zanamivir have not been studied in patients with impaired hepatic function.

Impaired Renal Function: After a single intravenous dose of 4 mg or 2 mg of zanamivir in volunteers with mild/moderate or severe renal impairment, respectively, significant decreases in renal clearance (and hence total clearance: normals 5.3 L/hr, mild/moderate 2.7 L/hr, and severe 0.8 L/hr; median values) and significant increases in half-life (normals 3.1 hr, mild/moderate 4.7 hr, and severe 18.5 hr; median values) and systemic exposure were observed. Safety and efficacy have not been documented in the presence of severe renal insufficiency. Due to the low systemic bioavailability of zanamivir following oral inhalation, no dosage adjustments are necessary in patients with renal impairment. However, the potential for drug accumulation should be considered.

Pediatric Patients: The pharmacokinetics of zanamivir were evaluated in pediatric patients with signs and symptoms of respiratory illness. Sixteen patients, 6 to 12 years of age, received a single dose of 10 mg zanamivir dry powder via DISKHALER. Five patients had either undetectable zanamivir serum concentrations or had low drug concentrations (8.32 to 10.38 ng/mL) that were not detectable after 1.5 hours. Eleven patients had Cmax median values of 43 ng/mL (range 15 to 74) and AUC∞ median values of 167 ng•hr/mL (range 58 to 279). Low or undetectable serum concentrations were related to lack of measurable PIFR in individual patients [see Use in Specific Populations (8.4), Clinical Studies (14.1)].

Geriatric Patients: The pharmacokinetics of zanamivir have not been studied in patients over 65 years of age [see Use in Specific Populations (8.5)].

Gender, Race, and Weight: In a population pharmacokinetic analysis in patient studies, no clinically significant differences in serum concentrations and/or pharmacokinetic parameters (V/F, CL/F, ka, AUC0-3, Cmax, Tmax, CLr, and % excreted in urine) were observed when demographic variables (gender, age, race, and weight) and indices of infection (laboratory evidence of infection, overall symptoms, symptoms of upper respiratory illness, and viral titers) were considered. There were no significant correlations between measures of systemic exposure and safety parameters.
<P>PROBLEM TO BE SOLVED: To provide a creamy preparation for external use having improved retainability of an antimycotic agent in the horny layer of skin and exhibiting improved curing effect.  <P>SOLUTION: This creamy preparation for external use at least contains an oil phase component, a drug as an active component and a water phase component. The oil phase component is composed of a 1st oil component exhibiting solid or semisolid state at normal temperature and a 2nd oil component exhibiting liquid state at normal temperature. The content of the oil phase component is ≤20 mass% based on the creamy preparation for external use and the amount of the 2nd oil component is 40-150 pts. mass based on 100 pts. mass of the 1st oil component.  <P>COPYRIGHT: (C)2005,JPO&NCIPI
Concept Foundation, an international nonprofit organization based in Bangkok, Thailand, was given the commercial rights to Cyclofem® by the World Health Organization (WHO) for use internationally. The brand names that the Concept Foundation has registered internationally include Cyclofem®, and Novafem® (Pharmacia Pharmaceuticals, Peapack NJ, formerly (Pharmacia and Upjohn of Kalamazoo, Michigan). The company launched its product under license from Concept Foundation with their own brand name, Lunelle™ in the US market. Lunelle™ was approved by the Food and Drug Administration (FDA) in October, 2000 following which approximately 350,000 women had used the product. However, following the acquisition of Pharmacia and Upjohn by Pfizer and due to several production problems, Pfizer withdrew Lunelle™ from the United States (US) market. Concept Foundation has licensed Sun Pharmaceutical Industries Ltd, Mumbai, India to manufacture and market Cyclofem® in India and other developing countries. United States Food and Drug Administration (US FDA) approval of Cyclofem® is pivotal to the ultimate acceptance of such products in many countries because of the rigorous standards applied by the Food and Drug Administration (FDA) for drug safety and efficacy. This initial pharmacokinetic (PK) study is the first step on the road to Food and Drug Administration (FDA) approval with the ultimate goal to expand the access and range of methods available to women in the public sector. Approval of Cyclofem® by the United States Food and Drug Administration (US FDA) would also allow the reintroduction of CICs to the United States (US) market.
This is a multicentre study conducted in two periods. Subjects will first be enrolled to enter the double blind (DB) period Cycle 1. Subjects who are eligible for retreatment will then be offered to enter open label (OL) Cycles 2 to 5 as DB roll-over subjects. Once recruitment of the DB period is complete, the study will enrol additional BTX-naïve subjects (hereafter referred to as OL de novo subjects) into the OL period Cycle 1. All OL de novo subjects who are eligible for retreatment will also be offered to enter OL Cycles 2 to 5. A total of 580 subjects (180 subjects randomised in the DB period and an additional 400 de novo subjects in the OL period) are planned to complete the study.
FIELD: medicine. SUBSTANCE: invention relates to anxiolytic, antialcoholic, cerebroprotective drug. Agent is a gelatinous capsule containing mexidol and potato starch, polyvinylpyrrolidone, magnesium stearate, microcrystalline cellulose, lactose as accessory substances. Agent is recommended for prophylaxis and treatment of neurotic and neurosis-like states of different genesis, stress, alcoholism and narcomania, for memory improvement, for treatment of acute and chronic disorders of cerebral circulation, dyscirculatory encephalopathy, vegeto-vascular dystonia, atherosclerotic disorders of the brain functions. EFFECT: increased bioavailability, insignificant adverse effects, low toxicity of drug. 2 cl, 8 tbl
PURPOSE: Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing.
EXPERIMENTAL DESIGN: We collected a 105-patient case-control cohort of stage I EEC comprising 45 patients who experienced recurrence less than 6 years after excision, and 60 Fédération Internationale de Gynécologie et d'Obstétrique grade-matched controls without recurrence. We first utilized two RNA-based, previously validated machine learning approaches, namely, EcoTyper and Complexity Index in Sarcoma (CINSARC). We developed Endometrioid Endometrial RNA Index (EERI), which uses RNA expression data from 46 genes to generate a personalized risk score for each patient. EERI was trained on our 105-patient cohort and tested on a publicly available cohort of 263 patients with stage I EEC.
RESULTS: EERI was able to predict recurrences with 94% accuracy in the training set and 81% accuracy in the test set. In the test set, patients assigned as EERI high-risk were significantly more likely to experience recurrence (30%) than the EERI low-risk group (1%) with a hazard ratio of 9.9 (95% CI, 4.1-23.8; P < 0.001).
CONCLUSIONS: Tumors with high-risk genetic features may require additional treatment or closer monitoring and are not readily identified using traditional clinicopathologic and molecular features. EERI performs with high sensitivity and modest specificity, which may benefit from further optimization and validation in larger independent cohorts.
1. A compound of the formula   and the individual optical isomers thereof, or a pharmaceutically acceptable derivative thereof. 2. An isolated and purified compound of Claim 1 substantially free of other metabolic products of montelukast sodium. 3. A pharmaceutical composition comprising a thereapeutically effective amount of a compound of Claim 1 and a pharmaceutically acceptable carrier. 4. A method of preventing the actions of leukotriene in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of Claim 1. 5. A method for the treatment or prevention of asthma, allergies or inflammation in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of Claim 1. 6. A process for the preparation of a compound of Claim 1 which comprises: a) reacting a compound of formula 1   wherein R is lower alkyl with dimethylsulfoxide and an electrophile to provide a compound of formula 2   b) reacting a compound of formula 2 with silver nitrate and a base to provide the compound of Claim 1. 7. A process for the preparation of the individual diastereomers of a compound of Claim 1 which comprises: (a) separating a diastereomeric mixture of a compound of formula 7:   wherein R* is 8-phenylmenthyl; (b) reacting an individual diastereomer with methanesulfonylchloride to provide the corresponding mesylate; (c) reacting the mesylate from step (b) with the dianion of 1-mercaptomethylcyclopropaneacetic acid to provide a compound of formula 8:   (d) removing the 8-phenylmenthyl group to provide a compound of Claim 1.
Nasal Potential Difference (NPD) measurements will be conducted on participants. The NPD measurement, is a bioelectric assay of CFTR-dependent ion transport that has been used in a variety of protocols designed to detect CFTR function. A 4-Step protocol will be utilized. The nasal cavities will be perfused in a step-wise fashion with the following solutions: 1) Ringer's solution, 2) Ringer's solution + amiloride 100μM, 3) Low-Cl--containing solution, and 4) Low-Cl- + isoproterenol (10 µM). The potential difference will be monitored in nasal epithelium in comparison to an agar filled reference butterfly electrode placed in the volar aspect of the forearm, and connected via a calomel cell to a high impedance voltmeter.

Following placement of the subcutaneous reference bridge, the nasal probe will be secured 1-3 cm within the inferior meatus and secured in position at the most polarizing position. Each nare will then be sequentially perfused with Ringer solution. All nasal potential difference tracings will be scored independently by a single reviewer.

The investigator and an internal committee comprised of Gregory Fleming James Associate Scientists will oversee the safety of the study. Our internal committee is a multidisciplinary group consisting of physician and subspecialists who, collectively, have experience in treatment patients with cystic fibrosis and other airway disease in the conduct of randomized clinical trials. The primary responsibility of this committee is to protect the safety and welfare of subjects consenting to the investigator's procurement of remnant tissue during endoscopic sinus procedure. Members are responsible for reviewing procedural conduct, including acquisition of consents and materials, to protect patient well-being. An interim data safety review will be conducted on a yearly basis. The committee will consist of at least 3 members with clinical trials experience in airway diseases. During annual review, issues relating to the safety and process for acquiring human tissues will be reviewed. Summary reports from each annual meeting will be prepared and will address concerns about the procurement of tissue or any other information deemed pertinent to the review.