anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Glycosphingolipids (GSLs) are a type of amphipathic lipid molecules consisting of hydrophobic ceramide backbone bound to carbohydrate moiety clustered in the cell surface microdomains named 'lipid rafts' and are known to participate in cell-cell communication as well as intra-cellular signaling, thereby facilitating critical normal cellular processes and functions. Over the past several decades, various GSLs have been reported to be aberrantly expressed in different cancers, many of which have been associated with their prognosis. The wide implication of MAPK signaling in controlling tumor growth, progression, and metastasis through activation of an upstream signaling cascade, often originating in the cell membrane, justifies the rationale for its plausible influence on MAPK signaling. This review highlights the role of GSLs and their metabolites in regulating different signaling pathways towards modulation of tumor cell growth, migration, and adhesion by interacting with various receptors [epidermal growth factor receptor (EGFR), and platelet derived growth factor receptor (PDGFR), and other receptor tyrosine kinases (RTKs)] leading to activation of the MAPK pathway. Furthermore, GSLs can influence the activity and localization of downstream signaling components in the MAPK pathway by regulating the activation state of kinases, which in turn, regulate the activity of MAPKs. Additionally, this review further consolidates the GSL-mediated modulation of MAPK pathway components through the regulation of gene expression. Finally, recent findings on GSL-MAPK crosstalk will be explored in this article for the identification of potential anti-cancer therapeutic targets.
PURPOSE: To characterize the clinical effects of two RP1L1 hotspots in patients with East Asian occult macular dystrophy (OMD).
METHODS: Fifty-one patients diagnosed with OMD harboring monoallelic pathogenic RP1L1 variants (Miyake disease) from Japan, South Korea, and China were enrolled. Patients were classified into two genotype groups: group A, p.R45W, and group B, missense variants located between amino acids (aa) 1196 and 1201. The clinical parameters of the two genotypes were compared, and deep learning based on spectral-domain optical coherence tomographic (SD-OCT) images was used to distinguish the morphologic differences.
RESULTS: Groups A and B included 29 and 22 patients, respectively. The median age of onset in groups A and B was 14.0 and 40.0 years, respectively. The median logMAR visual acuity of groups A and B was 0.70 and 0.51, respectively, and the survival curve analysis revealed a 15-year difference in vision loss (logMAR 0.22). A statistically significant difference was observed in the visual field classification, but no significant difference was found in the multifocal electroretinographic classification. High accuracy (75.4%) was achieved in classifying genotype groups based on SD-OCT images using machine learning.
CONCLUSIONS: Distinct clinical severities and morphologic phenotypes supported by artificial intelligence-based classification were derived from the two investigated RP1L1 hotspots: a more severe phenotype (p.R45W) and a milder phenotype (1196-1201 aa). This newly identified genotype-phenotype association will be valuable for medical care and the design of therapeutic trials.
There is an urgent need for new tools to control human hookworm infection and to reduce its burden of disease in developing countries. This is especially true for children and women of reproductive age who represent populations that are highly vulnerable to the effects of hookworm disease. Up to 65,000 deaths annually have been attributed to human hookworm infection. However, the mortality estimates of hookworm pale in comparison to global disease burden estimates.

The primary approach to hookworm control worldwide has been the frequent and periodic use of benzimidazole anthelminthics for school-age children. However, school-based anthelminthic chemotherapy programs miss populations highly vulnerable to hookworm, including adolescent and adult women. In addition, high rates of hookworm re-infection occur within 4-12 months following anthelminthic chemotherapy, and there is evidence for diminished efficacy of benzimidazoles with frequent and periodic use, possibly because of emerging drug resistance. These concerns have prompted interest in developing alternative tools for hookworm control. Vaccination to prevent high intensity hookworm infection would alleviate the public health deficiencies of drug treatment alone.
BACKGROUND: There is not yet a valid and evidence-based system to classify patients with MDD into more homogeneous subtypes based on their clinical features. This study aims to identify symptom-based subtypes of MDD and investigate whether the treatment outcomes of those subtypes would be different.
METHOD: The cohort was established at 12 densely populated cities of China. A total of 1487 patients were enrolled. All participants were 18-65 years old and diagnosed with MDD. Participants were followed up at baseline, weeks 4, 8, and 12, and months 4 and 6. K-means algorithm was used to cluster patients with MDD according to clinical symptoms. The network analysis was adopted to characterize and compare the symptom patterns in the clusters. We also examined the associations between the clusters and the clinical outcomes.
RESULTS: The optimal number of the clusters was determined to be 2. Each cluster's maximum Jaccard Co-efficient was calculated to be >0.5 (cluster1 = 0.53, cluster 2 = 0.67). The symptom "depressed mood" and some other affective symptoms were the most prominent in cluster 1. Somatic symptoms, such as weight loss and general somatic symptoms, had the greatest expected influence in cluster 2. Compared with the response rates of the patients in the "somatic cluster", those of the patients in the "affective cluster" were significantly higher (P < 0.05).
CONCLUSIONS: Patients with MDD might be classified into two symptom-based subtypes featured with affective symptoms or somatic symptoms. The treatment efficacy and prognosis of the subtype featured with somatic symptoms may be worse.
BACKGROUND: Cotadutide is a dual glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptor agonist peptide. The objective of this analysis was to develop a population pharmacokinetic (popPK) model of cotadutide, and to identify any potential effect on the PK from intrinsic and extrinsic covariates.
METHODS: The popPK analysis utilized a non-linear mixed-effects modeling approach using the data from 10 clinical studies in different participant categories following once-daily subcutaneous dose administration ranging from 20 to 600 μg. Additionally, the covariates affecting cotadutide exposure were quantified, and the model performance was evaluated through the prediction-corrected visual predictive checks.
RESULTS: A one-compartment model with first-order absorption and elimination adequately described the data as confirmed via visual predictive check plots and parameter plausibility. The mean values for cotadutide apparent clearance (CL/F), apparent volume of distribution (V/F), absorption rate constant (Ka), and half-life were 1.05 L/h, 20.0 L, 0.38 h-1, and 13.3 hours, respectively. Covariate modeling identified body weight, alanine transaminase, albumin, anti-drug antibody (ADA) titer values, formulation strength and injection device, and participant categories as significant covariates on PK parameters, where ADAs have been identified to decrease cotadutide clearance. The model demonstrated that a 150-kg participant was estimated to have 30% lower for both AUC and Cmax and a 66 kg participant was estimated to have 35% higher for both AUC and Cmax relative to a reference individual with a median weight of 96 kg.
CONCLUSIONS: A popPK model was developed for cotadutide with cotadutide clinical data, and the impact of the statistically significant covariates identified was not considered clinically meaningful. The popPK model will be used to evaluate exposure-response relationships for cotadutide clinical data.
1,177,650. Alloy pellets for ruminants. MAGNESIUM ELEKTRON Ltd. 11 Dec., 1967 [21 Dec., 1966], No. 57219/66. Heading A5B. [Also in Divisions A2 and C7] A pellet for oral administration to ruminants comprises magnesium or magnesium alloy and particles of iron the term "iron" includes steel within its scope having a coating of refractory material thereon, the proportion of iron being such that the specific gravity is at least 2.2. The coating of refractory material may be iron oxide formed by oxidising the iron particle surfaces by heating in air or by rusting, refractory material applied by coating the particles with a wash thereof or iron phosphate formed by treating the particles with a solution containing a phosphate. The magnesium alloy may contain aluminium and copper.
One nicotinamide 750 mg capsule by mouth twice daily (1500 mg) for 12 months. Two Placebo (for lanthanum carbonate) 500 mg capsules by mouth with each meal (3000 mg) for 12 months.
The COVID-19 pandemic was a major challenge for all health care employees, but it was also difficult for patients to gain access to health care services. Myxedema coma (MC) is an extremely rare but potentially fatal endocrine emergency. The aim of the study was to report an increased incidence of life-threatening myxedema coma that occurred in relation to the COVID-19 pandemic. In this paper, we report a cohort of 11 patients with MC who were treated at the University Hospital in Krakow, Poland, in the period from 2015 to 2023. Only 1 case of MC was recorded in the period from 2015 to 2019, and, in the same area, 10 cases of MC were recorded after the start of COVID-19 pandemic until present. Hypothyroidism was diagnosed de novo in 2 (18%) patients; the remaining patients were severely hypothyroid due to therapy non-compliance. Nine patients had primary hypothyroidism, and 2 had central hypothyroidism. Besides longstanding hypothyroidism, an additional precipitating factor for MC was identified in 4 (36%) of the patients. Due to the inaccessibility of parenteral levothyroxine, patients were treated with oral, mostly liquid, form of levothyroxine. The mortality rate in this cohort was 27.2%. In conclusion, the increase of the incidence of MC, which is a life-threatening complication of inadequately treated hypothyroidism, during the COVID-19 pandemic, when resources were limited, and in the post-pandemic era, underlines the importance of adequate communication with patients and of long-term availability of primary care for patients with thyroid disease.
Round the recommended dosage for patients to the nearest 150 mg dose to provide whole capecitabine tablets.

Swallow capecitabine tablets whole with water within 30 minutes after a meal. Do not chew, cut, or crush capecitabine tablets [see Warnings and Precautions (5.12)].

Take capecitabine tablets at the same time each day approximately 12 hours apart.

Do not take an additional dose after vomiting and continue with the next scheduled dose. Do not take a missed dose and continue with the next scheduled dose.

Capecitabine tablets are a hazardous drug. Follow applicable special handling and disposal procedures.1
Parental ADHD, present in 25-50% of families of children with ADHD and frequently untreated, interferes with effective parenting and predicts poor child developmental and behavioral treatment outcomes. Based on the literature and our own pilot data, the study will randomly assign parents with ADHD and their young at-risk children to one of two conditions: (1) stimulant medication for parents with ADHD followed by a child treatment strategy (CTS) beginning with behavioral parent training (BPT) with the added recommendation of child stimulant treatment if the child remains impaired or (2) a CTS without treatment for parental ADHD. The study will compare treatment effects on child ADHD-related impairment (primary outcome), child ADHD and externalizing symptoms, and time to child stimulant prescription (secondary child outcomes). The study will also examine target mechanisms including improvements in parental ADHD-related impairment and symptomatology (attention, impulsivity, emotional regulation), parenting skills, and BPT engagement, as well as treatment moderators (baseline parental ADHD severity, parental impairment, and parenting skills). Moreover, in an effort to develop a model of treatment that has potential for widespread dissemination while also reducing barriers to receiving care, the study will examine an implementation model involving parent ADHD screening in primary care followed by collaborative care delivered by co-located mental health providers via telehealth. Further, the investigators will develop an implementation plan and associated toolkit using a stakeholder participatory strategy to enhance the ability to move efficiently to adoption of this approach. In addition, the investigators will study the care delivery context, assessing procedures for and rates of screening and participation as well as staffing, workflow, provider- and patient-level acceptability, readiness, and feasibility of implementation approaches. This hybrid effectiveness-implementation project will be achieved via a collaborative R01 across 2 research sites in the US (N = 240 families), with 4-5 primary care partners at each site.
The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus and characterized by the loss of its capability to reproductively replicate in human cell lines. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus. In addition, a method is provided for the administration of a therapeutically effective amount of the virus, or its recombinants, in a vaccinia virus prime/vaccinia virus boost inoculation regimen. The present invention relates to a method of virus amplification in primary cells which are cultivated in a serum free medium. Viruses produced by this method are advantageously free of any infectious agents comprised in animal sera.
Period 1: Participants receive single dose of Islatravir on Day 1. Period 2: Participants receive single dose of MK-8507 on Days 1 and Days 8. Period 3: Participants receive single dose of Islatravir and single dose of MK-8507 on Day 1, 7 days after the Day 8 dose of MK-8507, during Period 2. Participants will receive additional MK-8507 single doses on Days 8, 15, 22, and 29.
In this proposed study, the study will examine treatment-related effects on functional brain circuitry in first episode schizophrenia. Converging lines of evidence suggest a key role for striatal disconnectivity in the pathophysiology of psychosis. The proposed study will utilize resting state functional magnetic resonance imaging (rs-fMRI), as well as fMRI tasks derived from the Research Domain Criteria (RDoC) framework, to: 1) develop and validate a prognostic biomarker to predict antipsychotic treatment response; and 2) to model the underlying neural circuitry changes associated with state changes in psychotic symptomatology. As a prognostic biomarker, a neuroimaging assay of striatal connectivity can potentially provide a clinically useful tool to advance the goal of precision medicine. As a longitudinal index of symptom change, our model can serve as an objective index against which to measure potential efficacy of newly developed antipsychotic treatments.

A large, well-characterized cohort of patients presenting with a first episode active psychosis (regardless of DSM diagnosis) will be recruited, along with matched controls. The study will utilize two well-validated fMRI tasks capturing two portions of the positive valence system: probabilistic category learning and reward responsiveness; these tasks are designed to interrogate dorsal and ventral corticostriatal circuits, respectively. The design will be longitudinal, with two scanning sessions performed for each patient: at baseline, and after 12 weeks of treatment. Treatment will be standardized across all patients to reduce potential confounds, and healthy controls will also be scanned at baseline and 12 weeks in order to control for effects of time and practice. Level of psychotic symptomatology (hallucinations, delusions, and thought disorder) will be measured at regular intervals using a comprehensive battery of rating scales. As secondary measures, electroencephalography (EEG) will be performed coinciding with neuroimaging on a subset of patients who provide consent. We will utilize Kaplan-Meier estimators and hierarchical linear modeling to examine the association of baseline striatal connectivity, and changes in connectivity over time, with clinical response of psychotic symptoms to antipsychotic treatment. Deliverables will include both baseline and longitudinal biomarkers that can subsequently be tested in broader, more heterogeneous populations of patients with psychosis.
The invention relates to a dose measurement system and a method. Embodiments described herein relate generally to devices, systems and methods for measuring a remaining dose in a drug delivery device for delivering a dose to a patient. In some embodiments, a dosimetry system for measuring a volume of liquid in a container comprises a plurality of light sources disposed and configured for emitting electromagnetic radiation toward the container. A plurality of sensors are located in the device, the plurality of sensors being optically couplable to the plurality of light sources and disposed and configured to detect electromagnetic radiation emitted by at least a portion of the light sources. The device also includes a processing unit configured to receive data representing the portion of the detected electromagnetic radiation from each of the plurality of sensors. The processing unit is further operable to convert the received data into a signature representative of the electromagnetic radiation detected by the plurality of sensors.
A method of preparing medical ultrasound coupling gel from a dry base. The method may be performed using a powder that is added to water or other fluid to constitute the gel. The dry gel powder may consist of polysaccharides from plant origin. The gel powder may be packaged enclosed in a dissolvable film, or the powder may be compacted into a tablet. The powder may be packaged in a container with measuring scoop for multiple use. An effervescent agent and/or an anti-caking agent may be included to help prevent clumping. A scent and/or a colouring agent may also be included. Hot or cold water may be used in the method. A shaker bottle or container may be used to facilitate constitution of the gel from fluid and powder, and the shaker bottle may contain a mixer ball. The method may be performed at the location of intended medical use.
Myocardial infarction (MI) is a significant global health issue and the leading cause of death. Myocardial infarction (MI) is characterized by events such as damage to heart cells and stress generated by inflammation. Punicalagin (PCN), a naturally occurring bioactive compound found in pomegranates, exhibits a diverse array of pharmacological effects against many disorders. This study aimed to assess the preventive impact of PCN, with its potential anti-inflammatory and antioxidant properties, on myocardial injury caused by isoproterenol (ISO) in rats and elucidate the possible underlying mechanisms. Experimental rats were randomly categorized into four groups: control group (fed a regular diet for 15 days), PCN group (orally administered PCN at 50 mg/kg body weight (b.w.) for 15 days), ISO group (subcutaneously administered ISO (85 mg/kg b.w.) on days 14 and 15 to induce MI), and PCN+ISO group (orally preadministered PCN (50 mg/kg b.w.) for 15 days and administered ISO (85 mg/kg b.w.) on days 14 and 15). The rat cardiac tissue was then investigated for cardiac marker, oxidative stress marker, and inflammatory marker expression levels. PCN prevented ISO-induced myocardial injury, suppressing the levels of creatine kinase-myocardial band, C-reactive protein, homocysteine, cardiac troponin T, and cardiac troponin I in the rats. Moreover, PCN treatment reversed (P<0.01) the ISO-induced increase in blood pressure, attenuated lipid peroxidation markers, and depleted both enzymatic and nonenzymatic markers in the rats. Additionally, PCN inhibited (P<0.01) ISO-induced overexpression of oxidative stress markers (p-38, p-c-Jun N-terminal kinase, and p-extracellular signal-regulated kinase 1), inflammatory markers (nuclear factor-kappa B, tumor necrosis factor-alpha, and interleukin-6), and matrix metalloproteinases and decreased the levels (P<0.01) of apoptosis proteins in the rats. Nuclear factor erythroid 2-related factor 2/silent information regulator transcript-1 (Nrf2/Sirt1) is a major cellular defense protein that regulates and scavenges oxidative toxic substances through apoptosis. Therefore, overexpression of Nrf2/Sirt1 to inhibit inflammation and oxidative stress is considered a novel target for preventing MI. PCN also significantly enhanced the expression of Nrf2/Sirt1 in ISO-induced rats. Histopathological analyses of cardiac tissue revealed that PCN treatment exhibited a protective effect on the heart tissue, mitigating damage. These findings show that by activating the Nrf2/Sirt1 pathway, PCN regulates oxidative stress, inflammation, and apoptosis, hence providing protection against ISO-induced myocardial ischemia.
PURPOSE: A transgenic plant containing DNA encoding AC1/C1 wild type and mutant sequences that negatively interfere in trans with geminiviral replication during infection is provided which is resistant to viral infection. CONSTITUTION: In the transgenic plant containing DNA encoding AC1 mutants, levels of AC1 expression directly relate to levels of trans-dominance and replication as shown in Fig. 1. According to the figure, replication is observed in inoculations with wild type BGMV-DNA-A plus carrier DNA(A+PBS). No replication is observed in inoculations with a mutant of DNA-A containing double mutations coinoculated with carrier DNA(ADM+PBS). Replication of double mutations is, however, complemented by trans expression of wild type AC1 in transient expression vector(ADM+TAC1). Replication of BGMV-DNA-A in the presence of two different AC1 mutants, treatments A+TDM and A+TD¬262R reduced replication of virus DNA-A compared to the A+PBS treatments. Accordingly, trans expression of AC1 mutants can inhibit replication of BGMV-DNA-A.