anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
An embodiment of the invention is directed to a microfabricated, silicon-based, Convection Enhanced Delivery (CED) device. The device comprises a silicon shank portion, at least one individual parylene channel disposed along at least a part of an entire length of the shank, wherein the channel has one or more dimensioned fluid exit ports disposed at one or more respective locations of the channel and a fluid (drug) input opening. The fluid input opening may be configured or adapted to be connected to a fluid reservoir and/or a pump and/or a meter and/or a valve or other suitable control device(s) or apparatus that supplies and/or delivers fluid (e.g., a drug) to the microfabricated device. The device may have multiple channels disposed side by side or in different surfaces of the device. The device may be rigid, or flexible, in which case a flexible device can be attached to a bio-degradable support scaffold that provides sufficient structural rigidity for insertion of the device into the target tissue. In certain “functionalized” embodiments of the invention, the CED device is equipped with integrated electrodes and/or a sensor (e.g., glutamate) to detect and convey selective parametric information. Another embodiment of the invention is directed to a CED method for drugs and/or other agents. The method may comprise the delivery of enzymes or other materials to modify tissue permeability and improve drug diffusion. Another embodiment of the invention is directed to a method for making a device for CED of drugs.
Ciclopirox is a broad-spectrum, antifungal agent that inhibits the growth of pathogenic dermatophytes, yeasts, and Malassezia furfur. Ciclopirox exhibits fungicidal activity in vitro against isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, and Candida albicans.

Pharmacokinetic studies in men with radiolabeled ciclopirox solution in polyethylene glycol 400, showed an average of 1.3% absorption of the dose when it was applied topically to 750 cm2 on the back followed by occlusion for 6 hours. 

The biological half-life was 1.7 hours and excretion occurred via the kidney. Two days after application only 0.01% of the dose applied could be found in the urine. Fecal excretion was negligible.

Autoradiographic studies with human cadaver skin showed that ciclopirox penetrates into the hair and through the epidermis and hair follicles into the sebaceous glands and dermis, while a portion of the drug remains in the stratum corneum.

In vitro penetration studies in frozen or fresh excised human cadaver and pig skin indicated that the penetration of ciclopirox olamine topical suspension, 0.77% is equivalent to that of ciclopirox (ciclopirox olamine) cream 0.77%. Therapeutic equivalence of cream and suspension formulations was also indicated by studies of experimentally induced guinea pig and human trichophytosis.
To obtain up-to-date information about the treatment of overdose, a good resource is a certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians' Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient.

No specific information is available on the treatment of overdosage with fosinopril sodium and hydrochlorothiazide tablets; treatment should be symptomatic and supportive. Therapy with fosinopril sodium and hydrochlorothiazide should be discontinued, and the patient should be observed. Dehydration, electrolyte imbalance, and hypotension should be treated by established procedures.

In rats, single oral doses of 2600 mg/kg of fosinopril were associated with significant lethality. In single-dose studies of hydrochlorothiazide, most rats survived doses of up to 2750 mg/kg. Both doses are more than 6000 times (on a mg/kg basis) the maximum recommended daily dose of either fosinopril or hydrochlorothiazide in fosinopril sodium and hydrochlorothiazide tablets.

Data from human overdoses of fosinopril are scanty, but the most common manifestation of human fosinopril overdosage is likely to be hypotension. In human hydrochlorothiazide overdose, the most common signs and symptoms observed have been those of dehydration and electrolyte depletion (hypokalemia, hypochloremia, hyponatremia). If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

Laboratory determinations of serum levels of fosinopril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of fosinopril overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of fosinopril and its metabolites. Fosinoprilat is poorly removed from the body by hemodialysis or peritoneal dialysis.

Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of fosinopril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of fosinopril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat fosinopril overdose by infusion of normal saline solution.
Polycystic ovary syndrome (PCOS) is one of the most widespread endocrinopathy affecting women of reproductive age with detrimental effects on life quality and health. Among several mechanisms involved in its aetiopathogenesis, recent studies have also postulated the involvement of the vaginal and intestinal microbiota in the development of this disorder. In this study, an accurate insight into the microbial changes associated with PCOS was performed through a pooled-analysis highlighting that this syndrome is characterized by intestinal and vaginal dysbiosis with a reduction of beneficial microorganisms and a higher proportion of potential pathogens. Based on this observation, we evaluated the ability of a milk-derived protein exerting positive outcomes in the management of PCOS, that is, α-lactalbumin (α-LA), to recover PCOS-related dysbiosis. In vitro experiments revealed that this protein improved the growth performances of members of two health-promoting bacterial genera, that is, Bifidobacterium and Lactobacillus, depleted in both intestinal and vaginal microbiota of PCOS-affected women. In addition, α-LA modulated the taxonomic composition and growth performances of the microbial players of the complex intestinal and vaginal microbiota. Finally, an in vivo pilot study further corroborated these observations. The oral administration of α-LA for 30 days to women with PCOS revealed that this protein may have a role in favouring the growth of health-promoting bacteria yet limiting the proliferation of potential pathogens. Overall, our results could pave the way to the use of α-LA as a valid compound with 'prebiotic effects' to limit/restore the PCOS-related intestinal and vaginal dysbiosis.
End-stage kidney disease (ESKD) presents a significant public health challenge, with hemodialysis (HD) remaining one of the most prevalent kidney replacement therapies. Ensuring the longevity and functionality of arteriovenous accesses is challenging for HD patients. Blood flow sound, which contains valuable information, has often been neglected in the past. However, machine learning offers a new approach, leveraging data non-invasively and learning autonomously to match the experience of healthcare professionas. This study aimed to devise a model for detecting arteriovenous grafts (AVGs) stenosis. A smartphone stethoscope was used to record the sound of AVG blood flow at the arterial and venous sides, with each recording lasting one minute. The sound recordings were transformed into mel spectrograms, and a 14-layer convolutional neural network (CNN) was employed to detect stenosis. The CNN comprised six convolution blocks with 3x3 kernel mapping, batch normalization, and rectified linear unit activation function. We applied contrastive learning to train the pre-training audio neural networks model with unlabeled data through self-supervised learning, followed by fine-tuning. In total, 27,406 dialysis session blood flow sounds were documented, including 180 stenosis blood flow sounds. Our proposed framework demonstrated a significant improvement (p<0.05) over training from scratch and a popular pre-trained audio neural networks (PANNs) model, achieving an accuracy of 0.9279, precision of 0.8462, and recall of 0.8077, compared to previous values of 0.8649, 0.7391, and 0.6538. This study illustrates how contrastive learning with unlabeled blood flow sound data can enhance convolutional neural networks for detecting AVG stenosis in HD patients.
BACKGROUND: Long-term survival after lung transplantation (LTx) remains limited by chronic lung allograft dysfunction (CLAD), which includes 2 main phenotypes: bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), with possible overlap. We aimed to detail and quantify pathological features of these CLAD sub-types.
METHODS: Peripheral and central paraffin-embedded explanted lung samples were obtained from 20 consecutive patients undergoing a second LTx for CLAD, from 3 lobes. Thirteen lung samples, collected from non-transplant lobectomies or donor lungs, were used as controls. Blinded semi-quantitative grading was performed to assess airway fibrotic changes, parenchymal and pleural fibrosis, and epithelial and vascular abnormalities.
RESULTS: CLAD lung samples had higher scores for all airway- and lung-related parameters compared to controls. There was a notable overlap in histologic scores between BOS and RAS, with a wide range of scores in both conditions. Parenchymal and vascular fibrosis scores were significantly higher in RAS compared to BOS (p = 0.003 for both). We observed a significant positive correlation between the degree of inflammation around each airway, the severity of epithelial changes, and airway fibrosis. Immunofluorescence staining demonstrated a trend toward a lower frequency of club cells in CLAD and a higher frequency of apoptotic club cells in BOS samples (p = 0.01).
CONCLUSIONS: CLAD is a spectrum of airway, parenchymal, and pleural fibrosis, as well as epithelial, vascular, and inflammatory pathologic changes, where BOS and RAS overlap significantly. Our semi-quantitative grading score showed a generally high inter-reader reliability and may be useful for future CLAD histologic assessments.
* See the FDA-approved patient labeling (Instructions for Use).
  * SECUADO transdermal system is applied once daily. Each SECUADO transdermal system should be worn for 24 hours only. Instruct patients to wear only one SECUADO transdermal system at any time.
  * Apply SECUADO to clean, dry, and intact skin at the selected application site. Application sites include: the upper arm, upper back, abdomen, or hip. Apply the transdermal system to a different application site each time a new SECUADO transdermal system is applied.
  * Do not cut open the pouch until ready to apply SECUADO and do not use the transdermal system if the individual pouch seal is broken or if it appears to be damaged. Do not cut SECUADO, the whole transdermal system should be applied.
  * If the SECUADO transdermal system lifts at the edges, reattach SECUADO by pressing firmly and smoothing down the edges of the system. If SECUADO comes off completely, apply a new SECUADO transdermal system. 
  * Discard SECUADO by folding the used transdermal system so that the adhesive side sticks to itself and safely discard.
  * If irritation or a burning sensation occurs while wearing SECUADO, remove the system and apply a new transdermal system to a new application site [see Warnings and Precautions (5.17)].
  * Showering is permitted, but the use of SECUADO during swimming or taking a bath has not been evaluated.
  * Do not apply external heat sources (e.g., heating pad) over the SECUADO transdermal system [see Warnings and Precautions (5.16)]. Prolonged application of heat over a SECUADO transdermal system increases plasma concentrations of asenapine [see Clinical Pharmacology (12.3)].
BACKGROUND AND OBJECTIVES: Available evidence suggests that adults with chronic obstructive pulmonary disease (COPD) performed substantially worse than healthy controls on many balance measures and balance training can improve the balance measures in this population. We conducted this study to determine the effects of incorporating balance training into pulmonary rehabilitation (PR) on the incidence of falls at 12 months follow-up in high fall risk adults with COPD.
METHODS: We conducted a prospective international multi-center randomized controlled trial. Eligible participants were adults with COPD at a high risk of future falls and were randomly assigned (1:1) to the intervention or control group. The intervention included personalized balance training for a targeted total of 90 min per week. Both the intervention and control groups received usual PR (2-3 times per week for 8-12 weeks). The primary outcome was the incidence of falls at 12-month follow-up using monthly fall diary calendars. Negative binomial regression or recurrent events models were used to examine the effects of the intervention on fall events. Multiple imputations were performed to deal with missing values.
RESULTS: Of 258 participants who were enrolled in the trial, 178 provided falls information (intervention group = 91, control group = 87) and were included in the main analysis. Forty-one participants (45%) experienced at least one fall event in the intervention group and 33 (38%) in the control group (p = 0.34). The mean incidence of falls at 12 months was similar between the two groups (128 versus 128 per 100 person-years; mean difference: 0.30, 95% CI: -0.76 to 1.36 per 100 person-years). The results are robust after multiple imputations for missing data (n = 67).
CONCLUSIONS: PR incorporating balance training compared to PR alone did not reduce the incidence of falls over the 12-month period in high fall risk adults with COPD.
TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT02995681) on 14/12/2016.
Previous in vitro and post-mortem studies have reported the role of inflammation in neurodegenerative disorders. However, the association between inflammation and brain structure in vivo and the transcriptome-driven functional basis with relevance to neurodegenerative disorders remains elusive. The aim of the present study is to identify the association among inflammation, brain structure, and neurodegenerative disorders at genetic and transcriptomic levels. Genetic variants associated with inflammatory cytokines were selected from the latest and largest genome-wide association studies of European ancestry. Neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and dementia with Lewy bodies (DLB) and brain structure imaging measures were selected as the outcomes. Two-sample Mendelian randomization analyses were conducted to identify the causal associations. Single-nucleus transcriptome data of the occipitotemporal cortex was further analyzed to identify the differential expressed genes in AD, which were tested for biological processes and protein interaction network. MR analysis indicated that genetically predicted TREM2 and sTREM2 were significantly associated with AD (TREM2: z-score = -9.088, p-value = 1.02 × 10-19; sTREM2: z-score = -7.495, p-value = 6.61 × 10-14). The present study found no evidence to support the causal associations between other inflammatory cytokines and the risks of AD, PD, ALS, or DLB. Genetically predicted TREM2 was significantly associated with the cortical thickness of inferior temporal (z-score = -4.238, p-value = 2.26 × 10-5) and pole temporal (z-score = -4.549, p-value = 5.40 × 10-6). In the occipitotemporal cortex samples, microglia were the main source of TREM2 gene and showed increasing expression of genes associated with inflammation and immunity. The present study has leveraged genetic and transcriptomic data to identify the association among TREM2, temporal lobe, and AD and the underlying cellular and molecular basis, thus providing a new perspective on the role of TREM2 in AD and insights into the complex associations among inflammation, brain structure, and neurodegenerative disorders, particularly AD.
A detergent composition, which may suitably be packaged in a collapsible tube or in a flexible or rigid atomizer, and which is selffoaming at atmospheric temperature and pressure when spread over a surface in a thin layer, comprises an intimate mixture of (a) an aqueous composition capable of foaming when agitated in the presence of air, and (b) an additive containing at least one organic liquid having a maximum solubility below 2 g./100 c.c. in the aqueous composition and a vapour pressure reaching 1 Kg./cm.2 abs. in the range 30-55 DEG C. and which, when mixed with (a), creates a composition having a vapour pressure reaching at least 1 Kg./cm.2 abs. in the range 30-55 DEG C. but being no greater than 2.5 Kg./cm.2 abs. at 60 DEG C.  Composition (a) may contain sodium, potassium, and triethanolamine soaps, sodium lauryl sulphate, stearic acid, glycerol and perfume dissolved in water.  Additive (b) comprises one or more pentanes (including cyclopentane), hexanes, hydrocarbon mixtures rich in pentanes or hexanes, or fluorochlorinated hydrocarbons, e.g. trichlorotrifluoroethane, and several suitable mixtures are listed; such additives are suitably thickened by the incorporation of jellifying agents, such as aluminium octoate, and may also include paraffin oil, lanolin or other fatty esters.  If desired, small quantities of more volatile liquids than additive (b), such as butane or dichlorotetrafluoroethane may be included.  The compositions obtained are suitable for use as shampoos or cleansing creams, and particularly as shaving creams.  French Specification 1,007,282 is referred to.ALSO:A composition which may be used to produce dentifrices, toothpastes and cosmetic cleansing creams suitably packaged in a collapsible tube or in a flexible or rigid atomizer, and which is self-foaming at atmospheric temperature and pressure when spread over a surface in a thin layer, comprises an intimate mixture of (a) an aqueous composition capable of foaming when agitated in the presence of air, and (b) an additive containing at least one organic liquid having a maximum solubility below 2g./100 c.c. in the aqueous composition and a vapour pressure reaching 1 Kg/cm2 abs. in the range 30-55 DEG C. and which, when mixed with (a) creates a composition having a vapour pressure reaching at least 1 Kg./cm2 abs. in the range 30-55 DEG C. but being no greater than 2,5 Kg/cm2. abs. at 60 DEG C.  Additive (b) comprises one or more pentanes (including cyclopentane), hexanes, mixtures rich in pentanes and hexanes, or fluorochlorinated hydrocarbons and several suitable mixtures are listed.  In an example, a self-foaming toothpaste comprises an aqueous mixture of precipitated calcium carbonate, neutral white soap, powdered sugar, talc, glycerol and perfume, with which is mixed an additive comprising pentane, trichlorotrifluoroethane and aluminium octoate; the product is filled into metal tubes.
OBJECTIVES: Caring for pediatric lacerations in the emergency department (ED) is typically painful because of irrigation and suturing. To improve this painful experience, we aimed to increase the use of a topical anesthetic, Eutectic Mixture of Local Anesthetics (EMLA) on eligible pediatric lacerations with an attainable, sustainable, and measurable goal of 60%. The baseline rate of applying topical anesthetic to eligible lacerations was 23% in our ED. We aimed to increase the use of topical anesthetics on eligible pediatric lacerations to a measurable goal of 60% within 3 months of implementing our intervention.
METHODS: We conducted a prospective, single-center, interrupted time series, ED quality improvement project from November 2019 to July 2020. A multidisciplinary team of physicians and nurses performed a cause-and-effect analysis identifying 2 key drivers: early placement of EMLA and physician buy-in on which we built our Plan, Do, Study, and Act (PDSA) cycles. We collected data on number of eligible patients receiving EMLA, as well as patient and physician feedback via phone calls within 2 days after encounter. Balancing measures included ED length of stay (LOS), patient and physician satisfaction with EMLA, and adverse effects of EMLA.
RESULTS: We needed 3 PDSA cycles to reach our goal of 60% in 3 months, which was also maintained for 5 months. The PDSA cycles used educational interventions, direct provider feedback about noncompliance, and patient satisfaction results obtained via phone calls. Balancing measures were minimally impacted: 75% good patient satisfaction, no adverse events but an increase in LOS of patients who received EMLA compared with those who did not (1.79 ± 0.66 vs 1.41 ± 0.83 hours, P < 0.001). The main reasons for dissatisfaction for physicians were the increased LOS and the preference for procedural sedation or intranasal medications.
CONCLUSIONS: With a few simple interventions, our aim of applying EMLA to 60% of eligible pediatric lacerations was attained and maintained.
Some patients treated with NEUPRO exhibited increases in systolic blood pressure (greater than 180 mm Hg) and/or diastolic blood pressure (greater than 105 mm Hg) while supine or standing. In patients with advanced-stage Parkinson's disease, this increased risk for systolic blood pressure greater than 180 mm Hg was 5% for NEUPRO and 3% for placebo and for diastolic blood pressure greater than 105 mm Hg was 4% for NEUPRO and 0% for placebo. In patients with Restless Legs Syndrome, this increased risk for diastolic blood pressure greater than 105 mm Hg was 8% for NEUPRO and 4% for placebo.

Increases in systolic blood pressure (at least 20 mm Hg or more) and in diastolic blood pressure (at least 10 mm Hg or more) occurred more frequently (incidence at least 5% greater than placebo) in all patients (i.e., early- and advanced-stage Parkinson's disease and Restless Legs Syndrome) taking the maximum recommended NEUPRO dose. These increases in systolic and diastolic blood pressure were observed when supine, standing, and changing from supine to standing position. More severe increases in systolic blood pressure (40 mm Hg or more) and in diastolic blood pressure (20 mm Hg or more) also occurred more frequently (incidence at least 2% greater than placebo) in NEUPRO-treated patients with early- and advanced-stage Parkinson's disease and with Restless Legs Syndrome during measurements when supine, standing, and/or changing from supine to standing position.

In the placebo-controlled trials, there was an increased risk for hypertension as an adverse reaction with the maximum recommended NEUPRO dose in patients with advanced-stage Parkinson's disease (NEUPRO 3% vs. placebo 0%) and Restless Legs Syndrome (NEUPRO 4% vs. placebo 0%).

Some patients treated with NEUPRO exhibited increased pulse (greater than 100 beats per minute) while supine and/or standing. In patients with advanced-stage Parkinson's disease, there was an increased risk (at least 2% greater than placebo) of increased pulse for patients taking the maximum recommended NEUPRO dose. In patients with Restless Legs Syndrome, there was an increased risk (at least 5% greater than placebo) of increased pulse for patients taking the maximum recommended NEUPRO dose.

These findings of blood pressure and heart rate elevations should be considered when treating patients with cardiovascular disease.
Apparently healthy, age and sex matched, 100 volunteers, not suffering from any disease or taking any medication. Control subjects with normal kidney functions and liver enzyme levels, absence of any clinical or laboratory evidence of CRC, were recruited during routine checkup examinations for themselves or their relatives or from the Chronic Diseases Screening National Presidential Program.