anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This is an exploratory translational research study to obtain research biopsies of RAS mutant metastatic colorectal cancer (mCRC) tumour tissue prior to commencement of regorafenib multi-tyrosine kinase inhibitor (MKI) treatment targeting vascular endothelial growth factor receptor (VEGFR), tumour microenvironment and oncogenic driver alterations, and again at development of resistance. Candidate markers of resistance will be identified in tissue biopsies through genetic and other molecular analysis and parallel collection of serial blood specimens will facilitate the identification of resistance markers and the tracking of resistance evolution in circulating nucleic acids. Early dynamic contrast enhanced MRI (DCE-MRI) along with diffusion weighted (DW)-MRI imaging at the beginning, and on day 15+/-7 post treatment will be performed. Additionally, dual contrast enhanced CT (DECT) will be performed according to routine clinical evaluation time points before drug administration and at 8 weeks after drug administration. Disease will be monitored with serial CT scans of the chest abdomen and pelvis (CT-CAP) every eight weeks, until progression. The aim of the study is to identify novel predictive biomarkers of resistance and response to this targeted therapy in mCRC previously treated with oxaliplatin, fluoropyrimidines and irinotecan, using genetic, epigenetic, transcriptomics, proteomic and live tissue culture methods. These molecular analyses will be performed on metastatic tumour tissue samples taken firstly before commencement of regorafenib, and secondly on progression of disease, and thirdly from archival primary or metastatic tumour tissue. There is an additional biopsy at 8 weeks in patients with response or stable disease, as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.
Hypersensitivity/infusion reactions, including hypotension, pyrexia, tremor, chills, urticaria, rash, and pruritus may occur with 3% and 5% Sodium Chloride Injection, USP.

Stop the infusion immediately if signs or symptoms of a hypersensitivity reaction develop, such as tachycardia, chest pain, dyspnea and flushing. Appropriate therapeutic countermeasures must be instituted as clinically indicated. 

Depending on the volume and rate of infusion, the intravenous administration of 3% and 5% Sodium Chloride Injection, USP can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration/hypervolemia, congested states, pulmonary edema, or acid-base imbalance. The risk of dilutive states is inversely proportional to the electrolyte concentration of the injection. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the electrolyte concentrations of the injection.

Monitor changes in fluid balance, electrolyte concentrations, and acid base balance during prolonged parenteral therapy or whenever the condition of the patient or the rate of administration warrants such evaluation.

Administer 3% and 5% Sodium Chloride Injection, USP with particular caution to patients with or at risk for hypernatremia, hyperchloremia, hypervolemia or with conditions that may cause sodium retention, fluid overload and edema; such as patients with primary hyperaldosteronism, or secondary hyperaldosteronism (for example, associated with hypertension, congestive heart failure, liver disease (including cirrhosis), renal disease (including renal artery stenosis, nephrosclerosis) or pre-eclampsia). Certain medications may increase risk of sodium and fluid retention, see DRUG INTERACTIONS.

Administer 3% and 5% Sodium Chloride Injection, USP with particular caution to patients with severe renal impairment. In such patients administration of Sodium Chloride Injection, USP may result in sodium retention.
The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin tablets USP and should continue on this diet during treatment with lovastatin tablets USP (see NCEP Treatment Guidelines for details on dietary therapy). Lovastatin tablets USP should be given with meals. 

Adult Patients 

The usual recommended starting dose is 20 mg once a day given with the evening meal. The recommended dosing range of lovastatin is 10 to 80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day. Doses should be individualized according to the recommended goal of therapy (see Error! Hyperlink reference not valid. and CLINICAL PHARMACOLOGY). Patients requiring reductions in LDL-C of 20% or more to achieve their goal (see INDICATIONS AND USAGE) should be started on 20 mg/day of lovastatin tablets. A starting dose of 10 mg of lovastatin may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more. 

Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of lovastatin tablets if cholesterol levels fall significantly below the targeted range. 

Dosage in Patients taking Danazol, Diltiazem, Dronedarone or Verapamil 

In patients taking danazol, diltiazem, dronedarone or verapamil concomitantly with lovastatin, therapy should begin with 10 mg of lovastatin and should not exceed 20 mg/day (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Error! Hyperlink reference not valid., Error! Hyperlink reference not valid., Error! Hyperlink reference not valid.). 

Dosage in Patients taking Amiodarone 

In patients taking amiodarone concomitantly with lovastatin, the dose should not exceed 40 mg/day (see Error! Hyperlink reference not valid. and Error! Hyperlink reference not valid., Error! Hyperlink reference not valid.).

Adolescent Patients (10 to 17 years of age) with Heterozygous Familial Hypercholesterolemia 

The recommended dosing range of lovastatin is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy (see Error! Hyperlink reference not valid. 4, CLINICAL PHARMACOLOGY, and INDICATIONS AND USAGE). Patients requiring reductions in LDL-C of 20% or more to achieve their goal should be started on 20 mg/day of lovastatin. A starting dose of 10 mg of lovastatin may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more. 

Concomitant Lipid-Lowering Therapy 

Lovastatin tablets USP are effective alone or when used concomitantly with bile-acid sequestrants (see Error! Hyperlink reference not valid. and Error! Hyperlink reference not valid.). 

Dosage in Patients with Renal Insufficiency 

In patients with severe renal insufficiency (creatinine clearance <30 mL/min), dosage increases above 20 mg/day should be carefully considered and, if deemed necessary, implemented cautiously (see CLINICAL PHARMACOLOGY and Error! Hyperlink reference not valid.).
The invention discloses a capsule which can restore deficiency and promote longevity and the preparation method, belonging to the technical field of the traditional Chinese medicine. The invention in particular relates to a deficiency-restoring and longevity-promoting capsule for treating insomnia and energy deficiency. The invention is composed of rehmanniae radix, schisandra chinensis, worm grass, ganoerma lucidum, lily, helix alga and fresh royal jelly. Worm grass, helix alga and the dried royal jelly are crushed for standby; the rehmanniae radix, schisandra chinensis, ganoerma lucidum and lily are decoct with water three times; the herbal liquors are combined and filtered, concentrated into ointment, alcohol-added, mixed, placed quietly; the supernatant fluid is taken to callback alcohol and then the fluid is concentrated continuously to be ointment; the medical powder is mixed evenly, dried and crushed before being put into O-sized capsules. The medicine has the nerve-soothing and sleep-benefiting effect; deficiency-restoring and strength-improving effect; good energy-recovery effect for the cancer-patient after the chemo-treatment and the radiation treatment; the curative effect for diabetics; the curative effect for climacteric syndrome; the depressurization and pressure-raising effect. The invention is free of side effect for long-term administration.
Autoimmune and inflammatory diseases are polygenic disorders of the immune system. Many genomic loci harbor risk alleles for several diseases, but the limited resolution of genetic mapping prevents determining whether the same allele is responsible, indicating a shared underlying mechanism. Here, using a collection of 129,058 cases and controls across 6 diseases, we show that ~40% of overlapping associations are due to the same allele. We improve fine-mapping resolution for shared alleles twofold by combining cases and controls across diseases, allowing us to identify more expression quantitative trait loci driven by the shared alleles. The patterns indicate widespread sharing of pathogenic mechanisms but not a single global autoimmune mechanism. Our approach can be applied to any set of traits and is particularly valuable as sample collections become depleted.
As genetic testing becomes increasingly accessible and affordable, the uniform and accurate interpretation of genetic variants becomes essential. The ACMG/AMP joint guidelines provide the basis for systematic and uniform interpretation of pathogenicity of genetic variants. However, the application of these in routine clinical interpretation at-scale has largely been limited by the lack of resources providing harmonized data especially at a population-scale. Here we describe BRCAIndica, a resource for BRCA1 and BRCA2 variants conforming to the ACMG & AMP joint guidelines to aid uniform clinical interpretation of genetic tests with a specific focus on variants reported in the Indian population. We collected and harmonized variants from across several resources including population-scale datasets, literature survey and other variant datasets. We then classified them according to the ACMG/AMP guidelines.We have collected a total of 10,490 unique variants, of which 2261 Pathogenic and 43 Likely Pathogenic variants belong to BRCA1 and 2694 Pathogenic and 20 Likely Pathogenic variants to BRCA2 respectively. BRCAIndica can be accessed at:https://clingen.igib.res.in/brcaindica/ . In conclusion, BRCAIndica is a powerful resource that offers researchers and clinicians with ACMG/AMP annotated BRCA variants.
PROBLEM TO BE SOLVED: To provide a new antiallergic agent, and a medicine, food and drink, or cosmetic containing the same. SOLUTION: An antiallergic agent containing naringenin chalcone or its derivative as an active ingredient. A histamine release-suppressing agent or leukotriene release-suppressing agent containing naringenin chalcone or its derivative as an active ingredient. Further, a medicine, food and drink, and cosmetic each containing one of the above agents. The antiallergic agent is useful as a preventing or treating agent for various allergic diseases, or a histamine release-suppressing agent. The antiallergic agent is useful as a preventive or treating agent for various allergic diseases, an antiinflammatory agent or a histamine release-inhibiting agent.  The antiallergic agent is useful for preventing or treating atopic dermatitis, allergic rhinitis, pollinosis, allergic asthma and the like, which are attributable to I-type allergic reaction since the antiallergic agent inhibits the histamine release from mast cells in the I-type allergic reaction.
Pulmonary fibrosis (PF) is a chronic, progressive, and fatal lung disease with a high mortality rate. Nintedanib, as a multi-tyrosine kinase inhibitor, is widely used as the first line drug for PF patients. However, only nintedanib oral formulations are used currently in clinic and show a low drug selectivity, significant first-pass effect and low bioavailability with 4.7%, thus limiting the clinical outcome of nintedanib. In this study, nintedanib was prepared in the form of nintedanib nanocrystalline (Nib-NC) and then encapsulated with hyaluronic acid (HA) to construct a nanocrystalline-in-adhesive delivery system Nib-NC@HA with high drug loading efficacy and pulmonary bio-adhesive properties, which could avoid the first-pass effects, increase the bioavailability and reduce the systemic side effects of nintedanib. After inhalation administration of Nib-NC@HA, due to the bio-adhesive properties of HA, Nib-NC@HA could prolong the retention time of drug in the lungs and inhibit the expression of inflammation associated factors such as IL-6, IL-1β and TNF-α in lung tissue, reduce the release of pro-fibrotic growth factor, and improve the lung function, thus showing enhanced anti-fibrotic effect than Nib-NC. The results suggested that Nib-NC@HA is an efficient and optimal targeted bio-adhesive delivery system for the lungs to treat pulmonary fibrosis.
A method for the preparation of magnetic nanoparticles coated with a noble metal is described. The method includes providing a first mixture containing a first non-polar organic solvent and uncoated magnetic nanoparticles. The first mixture is mixed with a second mixture containing a second non-polar organic solvent and ions comprising the noble metal to form a third mixture. The third mixture is mixed with an organic ligand or a fourth mixture containing an organic ligand to form a fifth mixture. The fifth mixture is reacted with a sixth mixture containing a reducing agent to form a seventh mixture containing the monodispersed magnetic nanoparticles coated with the noble metal. The monodispersed magnetic coated nanoparticles may be separated from the seventh mixture by adding a polar organic solvent or a mixture of polar organic solvents in which the nanoparticles are insoluble.
Mentors will attend one 6-7 hour virtual training session. Study expectations and logistics will be reviewed with each potential mentor prior to the training session via phone. Informed consent process will take place online via REDCap prior to the training session. Baseline data will be collected via online surveys. Next, mentors will receive training regarding topics including active listening, mentoring, goal-and boundary-setting, an overview of LBD, risk factors for hospitalization, impact on caregiver, practical approaches to symptom management, and caregiving issues. The study team will present the PERSEVERE curriculum and accompanying handbook. The team will solicit questions and lead roleplay conversations. Finally mentors will complete post-training assessments. Once all caregiver mentees (Arm 3) are recruited, the mentors will contact their mentees once weekly by phone for 16 weeks to deliver the PERSEVERE curriculum.
Correlations between histologic disease activity and other assessments of clinical disease activity are not well established despite a good correlation being found between endoscopy and histology, especially during active ulcerative colitis (1,2). Endoscopic healing induced by infliximab in Crohn's disease patients was associated with a significant reduction in surgeries and hospitalizations (3). Histological recovery in ulcerative colitis is often incomplete and some studies have shown that microscopic evidence of inflammation is common even in patients with clinically and quiescent colitis assessed by sigmoidoscopy (4,5). Although this fact has not yet been completely elucidated, it is suggested that some patients with residual microscopic acute inflammation may be more prone to relapse (2). The prognostic importance of microscopic inflammation is unknown. Given that the rectum is always involved in ulcerative colitis and inflammatory activity is diffuse and restricted to the mucosa, the collection of samples from the rectal and sigmoid mucosa are potentially useful tools for evaluating disease severity. In addition, there is a strong correlation between the levels of calprotectin and the degree of inflammation as assessed by endoscopic and histologic criteria (6). Therefore, the measurement of faecal calprotectin and lactoferrin may also provide as valuable non-invasive tools to assess disease activity and optimize the treatment in UC patients.

Histologically, active disease is defined by the presence of neutrophils in conjunction with epithelial cell damage. Analysis generally relies on the examination of H \& E-stained sections. Two samples are suggested as more appropriated because it is well-known that treatment may induce variations in the expression of inflammation intensity. Several histological scores were proposed, however, Geboes index (7) has been validated and tested for reproducibility and has 5 domains: structural change, chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils in epithelium, crypt destruction and erosion or ulceration. The Geboes index has a more elaborated grading of crypt lesions and surface epithelial damage than other proposed indexes. The aim of this study is to assess the relationship between microscopic Geboes index of inflammation and clinical course of ulcerative colitis in patients treated with infliximab. The investigators propose to test the hypothesis if infliximab is able to induce histological remission and then change the clinical course of ulcerative colitis
BACKGROUND: Sepsis is a heterogeneous syndrome, and enrollment of more homogeneous patients is essential to improve the efficiency of clinical trials. Artificial intelligence (AI) has facilitated the identification of homogeneous subgroups, but how to estimate the uncertainty of the model outputs when applying AI to clinical decision-making remains unknown.
OBJECTIVE: We aimed to design an AI-based model for purposeful patient enrollment, ensuring that a patient with sepsis recruited into a trial would still be persistently ill by the time the proposed therapy could impact patient outcome. We also expected that the model could provide interpretable factors and estimate the uncertainty of the model outputs at a customized confidence level.
METHODS: In this retrospective study, 9135 patients with sepsis requiring vasopressor treatment within 24 hours after sepsis onset were enrolled from Beth Israel Deaconess Medical Center. This cohort was used for model development, and 10-fold cross-validation with 50 repeats was used for internal validation. In total, 3743 patients with sepsis from the eICU Collaborative Research Database were used as the external validation cohort. All included patients with sepsis were stratified based on disease progression trajectories: rapid death, recovery, and persistent ill. A total of 148 variables were selected for predicting the 3 trajectories. Four machine learning algorithms with 3 different setups were used. We estimated the uncertainty of the model outputs using conformal prediction (CP). The Shapley Additive Explanations method was used to explain the model.
RESULTS: The multiclass gradient boosting machine was identified as the best-performing model with good discrimination and calibration performance in both validation cohorts. The mean area under the receiver operating characteristic curve with SD was 0.906 (0.018) for rapid death, 0.843 (0.008) for recovery, and 0.807 (0.010) for persistent ill in the internal validation cohort. In the external validation cohort, the mean area under the receiver operating characteristic curve (SD) was 0.878 (0.003) for rapid death, 0.764 (0.008) for recovery, and 0.696 (0.007) for persistent ill. The maximum norepinephrine equivalence, total urine output, Acute Physiology Score III, mean systolic blood pressure, and the coefficient of variation of oxygen saturation contributed the most. Compared to the model without CP, using the model with CP at a mixed confidence approach reduced overall prediction errors by 27.6% (n=62) and 30.7% (n=412) in the internal and external validation cohorts, respectively, as well as enabled the identification of more potentially persistent ill patients.
CONCLUSIONS: The implementation of our model has the potential to reduce heterogeneity and enroll more homogeneous patients in sepsis clinical trials. The use of CP for estimating the uncertainty of the model outputs allows for a more comprehensive understanding of the model's reliability and assists in making informed decisions based on the predicted outcomes.
Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by loss-of-function mutation in the SACS gene, which encodes sacsin, a putative HSP70-HSP90 co-chaperone. Previous studies with Sacs knock-out (KO) mice and patient-derived fibroblasts suggested that SACSIN mutations inhibit the function of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). This in turn resulted in mitochondrial hyperfusion and dysfunction. We experimentally tested this hypothesis by genetically manipulating the mitochondrial fission/fusion equilibrium, creating double KO (DKO) mice that also lack positive (PP2A/Bβ2) and negative (PKA/AKAP1) regulators of Drp1. Neither promoting mitochondrial fusion (Bβ2 KO) nor fission (Akap1 KO) influenced progression of motor symptoms in Sacs KO mice. However, our studies identified profound learning and memory deficits in aged Sacs KO mice. Moreover, this cognitive impairment was rescued in a gene dose-dependent manner by deletion of the Drp1 inhibitor PKA/Akap1. Our results are inconsistent with mitochondrial dysfunction as a primary pathogenic mechanism in ARSACS. Instead, they imply that promoting mitochondrial fission may be beneficial at later stages of the disease when pathology extends to brain regions subserving learning and memory.
PURPOSE: This study aimed to assess the prevalence and factors of physical, psychological, and social frailty among older adults in the emergency department, comparing these data with community population to understand emergency setting manifestations.
METHODS: Conducted at the Emergency Department of National Taiwan University BioMedical Park Hospital, this prospective observational cohort study enrolled older adult patients over a three-month period. Frailty assessments included the Study of Osteoporotic Fractures scale for physical frailty, the Tilburg Frailty Indicator for psychological frailty, and the Makizako Social Frailty Index for social frailty. Data analysis involved a multivariable logistic model to determine the risk factors associated with each frailty type.
RESULTS: Out of 991 older adult individuals seeking medical care, 207 participated in the study. The study found high prevalence rates of frailty: 46.38% for physical, 41.06% for psychological, and 48.79% for social frailty. Risk factors for frailty included older age and a history of falls. Interestingly, the prevalence of social frailty was notably higher than physical and psychological frailty. Gender and polypharmacy showed no significant association with any frailty type.
CONCLUSION: This research reveals high physical, psychological, and social frailty among older ED patients, especially noting social frailty's prevalence. It highlights the importance for emergency care to adopt holistic care strategies that address older adults' multifaceted health challenges, suggesting a paradigm shift in current healthcare practices to better cater to the multifaceted needs of this vulnerable population.
Blood glucose levels in a patient are determined after oral administration of an aq. maltose soln. By taking blood samples at various intervals after administration of the maltose, and analysing the glucose content of the samples in order to determine the glucose level-time relationship, the patient's tolerance to sugar may be determined. Method is used for diagnosis of diabetes. In prior art, tolerance to sugar is usually determined after administration of glucose. By replacing this with maltose a similar accuracy is obtained but side effects (nausea, diarrhoea, abdominal pain, etc.) are eliminated.