anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
UNLABELLED: SF3B1 is the most recurrently mutated RNA splicing gene in cancer. However, research of its pathogenic role has been hindered by a lack of disease-relevant cell line models. Here, our study compared four genome engineering platforms to establish SF3B1 mutant cell lines: CRISPR-Cas9 editing, AAV homology-directed repair editing, base editing (ABEmax, ABE8e), and prime editing (PE2, PE3, PE5max). We showed that prime editing via PE5max achieved the most efficient SF3B1 K700E editing across a wide range of cell lines. Our approach was further refined by coupling prime editing with a fluorescent reporter that leverages a SF3B1 mutation-responsive synthetic intron to mark successfully edited cells. By applying this approach, called prime editing coupled intron-assisted selection (PRECIS), we introduced the K700E hotspot mutation into two chronic lymphocytic leukemia cell lines, HG-3 and MEC-1. We demonstrated that our PRECIS-engineered cells faithfully recapitulate known mutant SF3B1 phenotypes, including altered splicing, copy number variations, and cell-growth defect. Moreover, we discovered that the SF3B1 mutation can cause the loss of Y chromosome in chronic lymphocytic leukemia. Our results showcase that PRECIS is an efficient and generalizable method for engineering genetically faithful SF3B1 mutant models. Our approach provides new insights on the role of SF3B1 mutation in cancer and enables the generation of SF3B1 mutant cell lines in relevant cellular context.
SIGNIFICANCE: This study developed an approach that can reliably and efficiently engineer SF3B1 mutation into different cellular contexts, thereby revealing novel roles of SF3B1 mutation in driving aberrant splicing, clonal evolution, and genome instability.
Early gene therapy clinical trials for the treatment of Haemophilia B have been instrumental to our global understanding of gene therapy and have significantly contributed to the rapid expansion of the field. The use of adeno-associated viruses (AAVs) as vectors for gene transfer has successfully led to therapeutic expression of coagulation factor IX (FIX) in severe haemophilia B patients. Expression of FIX has remained stable following a single administration of vector for up to 8 years at levels that are clinically relevant to reduce the incidence of spontaneous bleeds and have permitted a significant change in the disease management with reduction or elimination of the need for coagulation factor concentrates. These trials have also shed light on several concerns around AAV-mediated gene transfer such as the high prevalence of pre-existing immunity against the vector capsid as well as the elevation of liver transaminases that is associated with a loss of FIX transgene expression in some patients. However, this field is advancing very rapidly with the development of increasingly more efficient strategies to overcome some of these obstacles and importantly raise the possibility of a functional cure, which has been long sought after. This review overviews the evolution of gene therapy for haemophilia B over the last two decades.
OBJECTIVES: Sleep disorders impact at least 10 % of children, pose risks to overall wellbeing, and are key targets of preventive interventions. The objectives of this study were to describe the prevalence of pediatric sleep disorder diagnoses across sociodemographic characteristics and co-occurring conditions, and to explore potential sociodemographic disparities.
METHODS: Cross-sectional analysis of 12,394,902 children (0-17 years; 50.9 % Medicaid-insured) in the 2017 MarketScan database. Prevalence was assessed utilizing ICD-10 codes, with multivariate logistic regressions examining disparities (insurance coverage; race and ethnicity in Medicaid-insured) for diagnoses in ≥0.10 % of children.
RESULTS: The prevalence of sleep disorder diagnoses was 2.36 %. The most common diagnoses were obstructive sleep disordered breathing (oSDB, 1.17 %), unspecified sleep disorders (0.64 %), insomnia (0.52 %), and other SDB (0.10 %), with <0.10 % for all other diagnoses. Insomnia and parasomnias diagnoses were much lower than diagnostic estimates. Sleep diagnoses were more prevalent in Medicaid versus commercially insured youth, 2-5-year-olds, and in children with co-occurring medical, neurodevelopmental, or behavioral health conditions. Girls and boys were generally equally likely to be diagnosed with any sleep disorder. In Medicaid-insured children, white children were more likely to have any sleep diagnosis compared to all other racial and ethnic groups. Black/African American children were more likely than white children to have oSDB.
CONCLUSIONS: Compared to diagnostic estimates, claims data suggest sleep disorders are under-diagnosed, with notable sociodemographic disparities. Findings suggest a need for clinical resources to identify and address sleep disorders and to understand biases potentially driving disparities, given that sleep is a modifiable determinant of child wellbeing.
BACKGROUND AND AIM: While several predictive models for the development of hepatocellular carcinoma (HCC) have been proposed, including those for patients with chronic hepatitis C virus (HCV) infection who have achieved sustained virologic response (SVR), the best model may differ between regions. We compared the ability of six reported models to stratify the risk of post-SVR HCC in Japan, where rigorous surveillance and early detection of HCC is common.
METHODS: A total of 6048 patients with no history of HCC who achieved SVR by oral direct-acting antiviral drugs were enrolled in this nationwide study. Patients continued HCC surveillance every 6 months after SVR. The incidence of post-SVR HCC was compared between risk groups using the aMAP score, FIB-4 index, Tahata model, GAF4 criteria, GES score, and ADRES score.
RESULTS: During the observation period with a median duration of 4.0 years after SVR, post-SVR HCC developed in 332 patients (5.5%). All six models performed significantly at stratifying the incidence of HCC. However, Harrell's C-index was below 0.8 for all models (range, 0.660-0.748), indicating insufficient stratification ability.
CONCLUSION: Although all six proposed models demonstrated a good ability to predict the development of post-SVR HCC, their ability to stratify the risk of post-SVRHCC was unsatisfactory. Further studies are necessary to identify the best model for assessing the risk of post-SVR HCC in regions where early detection of HCC is common.
The invention relates to protein conjugates, methods, vectors, proteins and DNA for producing them, their use, and medicaments and vaccines containing a certain quantity of said protein conjugates. According to the invention, supramolecular particles are produced that represent one or more different, randomly selectable structural units in a large number on the surface of an individual, approximately spherical protein molecule. Icosahedral lumazine synthases are used as carrier proteins for peptides or proteins. A DNA fragment that encodes a peptide molecule is fused with a DNA fragment that encodes an icosahedral lumazine synthase by molecular-biological methods. Said DNA fragment is inserted into a cloning vector and transformed with an appropriate host strain. A polypeptide is expressed by gene expression. If certain peptide structures are used as the fusion partners, a post-translational change of said structures can be observed in the host strain. The chimeric peptide is purified and chemically modified if necessary. It is possible to produce icosahedral molecules that contain up to 120 different peptide motifs on their surfaces by mixing. The compounds produced lend themselves as auxiliary agents for carrying out analytical methods (ELISA, biosensors) or for producing vaccines.
Participants received propanolol for 7 weeks. On Day -1 of Period 1 (Study Visit 6), single dose MK0893 was added and propanolol was continued. After Period 1, participants underwent a 3-week wash-out while continuing to receive propanolol. Following the washout, participants were treated with a single dose of MK0893-matched placebo on Day 21 (Visit 8).
The gut physiology of pediatric and adult persons with cystic fibrosis (pwCF) is altered relative to healthy persons. The CF gut is characterized, in part, as having excess mucus, increased fat content, acidic pH, increased inflammation, increased antibiotic perturbation, and the potential for increased oxygen availability. These physiological differences shift nutritional availability and the local environment for intestinal microbes, thus likely driving significant changes in microbial metabolism, colonization, and competition with other microbes. The impact of any specific change in this physiological landscape is difficult to parse using human or animal studies. Thus, we have developed a novel culture medium representative of the CF gut environment, inclusive of all the aforementioned features. This medium, called CF-MiPro, maintains CF gut microbiome communities, while significantly shifting nonCF gut microbiome communities toward a CF-like microbial profile, characterized by low Bacteroidetes and high Proteobacteria abundance. This medium is able to maintain this culture composition for up to 5 days of passage. Additionally, microbial communities passaged in CF-MiPro produce significantly less immunomodulatory short-chain fatty acids (SCFA), including propionate and butyrate, than communities passaged in MiPro, a culture medium representative of healthy gut physiology, confirming not only a shift in microbial composition but also altered community function. Our results support the potential for this in vitro culture medium as a new tool for the study of CF gut dysbiosis. IMPORTANCE Cystic fibrosis is an autosomal recessive disease that disrupts ion transport at mucosal surfaces, leading to mucus accumulation and altered physiology of both the lungs and the intestines, among other organs, with the resulting altered environment contributing to an imbalance of microbial communities. Culture media representative of the CF airway have been developed and validated; however, no such medium exists for modeling the CF intestine. Here, we develop and validate a first-generation culture medium inclusive of features that are altered in the CF colon. Our findings suggest this novel medium, called CF-MiPro, as a maintenance medium for CF gut microbiome samples and a flexible tool for studying key drivers of CF-associated gut dysbiosis.
The present invention discloses a Diacylglycerol (DAG) composition derived from the fruits of  Emblica officinalis . DAG is a form of Alpha-linolenic acid (ALA) and, in the composition the DAG form of ALA and Triacylglycerol (TAG) form of ALA is in the range ratio of 4:1 to 15:1. The DAG has been enriched in the  Emblica officinalis  fruit extract to achieve such ratio. DAG derived from the fruit of  Emblica officinalis  has been identified to have medicinal property and is used to make medicinal composition that can be used for the treatment of dyslipidaemia, especially for the reduction of visceral fat and also modulating Thyroid Stimulating Hormones (TSH). The DAG form of ALA is combined with polyphenols, oil and other plant extracts to obtain the medicinal composition. The composition is also formed into different medicinal forms for oral administration purpose. The method of enriching DAG and preparation of a DAG composition is also disclosed.
Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver. Here, we investigated the metabolism activity of CYP1A2, CYP3A1/2 and CYP2C6/11 during PXR activation-induced liver enlargement and regeneration in rats after cocktail dosing of CYP probe drugs. For PCN-induced hepatomegaly, a notable increase in the metabolic activity of CYP3A1/2 and CYP2C6/11, as evidenced by the plasma exposure of probe substrates and the AUC ratios of the characteristic metabolites to its corresponding probe substrates. The metabolic activity of CYP1A2, CYP3A1/2 and CYP2C6/11 decreased significantly after PHx. However, PCN treatment obviously enhanced the metabolic activity of CYP2C6/11 and CYP3A1/2 in PHx rats. Furthermore, the protein expression levels of CYP3A1/2 and CYP2C6/11 in liver were up-regulated. Taken together, this study demonstrates that PXR activation not only induces hepatomegaly and liver regeneration in rats, but also promotes the protein expression and metabolic activity of the PXR downstream metabolizing enzymes such as CYP3A1/2 and CYP2C6/11 in the body.
False-Positive Drug Test Results

Lamotrigine has been reported to interfere with the assay used in some rapid urine drug screens, which can result in false-positive readings, particularly for phencyclidine (PCP). A more specific analytical method should be used to confirm a positive result. 

Plasma Concentrations of Lamotrigine

The value of monitoring plasma concentrations of lamotrigine in patients treated with lamotrigine has not been established. Because of the possible pharmacokinetic interactions between lamotrigine and other drugs including AEDs (see Table 13), monitoring of the plasma levels of lamotrigine and concomitant drugs may be indicated, particularly during dosage adjustments. In general, clinical judgment should be exercised regarding monitoring of plasma levels of lamotrigine and other drugs and whether or not dosage adjustments are necessary.The value of monitoring plasma concentrations of lamotrigine in patients treated with lamotrigine has not been established. Because of the possible pharmacokinetic interactions between lamotrigine and other drugs including AEDs (see Table 13), monitoring of the plasma levels of lamotrigine and concomitant drugs may be indicated, particularly during dosage adjustments. In general, clinical judgment should be exercised regarding monitoring of plasma levels of lamotrigine and other drugs and whether or not dosage adjustments are necessary.
1. Use of component B which is a protein having the following amino acid sequence SEQ ID No: 1:     for obtaining medical preparations applicable as cicatrizant. 2. The use as claimed in claim 1, characterized in that said medical preparation is administered for treatment of wounds, ulcers and other traumatic lesions to any of the tissues in the body. 3. A pharmaceutical composition in an applicable form comprising Component B which is a protein having the following amino acid sequence SEQ ID No: 1:   as an active ingredient together with a pharmaceutically acceptable excipient. 4. A method for treating of wounds, ulcers and other traumatic lesions to any of the tissues in the body, comprising administering administering an effective amount of Component B, which is a protein having the following amino acid sequence SEQ ID No: 1:   together with a pharmaceutically acceptable carrier.
Participants in the Screening Wizard 2.0 + SOVA group will have a symptoms scores report of results and treatment preferences, barriers, and recommendations sent to their provider based on their Screening Wizard responses. This group will also receive access to the SOVA website aimed at addressing perceptions about mental health providing support to teens through peer interaction.
For patients randomized to the UC referral arm, the patient's HIV provider will receive an electronic alert of the patient's positive screen for a Mental Health and Substance Use Disorder. The patient will not be contacted by the P-CM. The provider, at their discretion, will initiate referral to the psychiatry service available onsite. For patients with Substance Use Disorder, providers refer to the in-clinic Substance Use Disorder treatment program that is managed by a nurse practitioner with Substance Use Disorder care experience. Once referred, the patient is seen by the nurse practitioner (separate from the HIV provider) who manages prescription of and assessment of adherence to buprenorphine, including monitoring of urine toxicology results with support from an addiction counselor. The Bartlett Clinic runs 2 substance use groups weekly and has processes for referral to a higher level of Substance Use Disorder care at offsite Substance Use Disorder treatment programs.
Naphthoquinone derivatives of Lawsone have been found to be effective against  Staphylococcus aureus  and methicillin-resistant  Staphylococcus aureus  (MRSA). Such compounds generally contain a substituent group at the 3-position of a specific naphthoquinone compound, i.e. 2-hydroxy-1,4-naphthoquinone. One of these derivatives referred to as compound 6c in the series exhibits potent antimicrobial activity that is comparable to that of the two commercial antibiotics  ofloxacin  and  ciprofloxacin  against the two strains of methicillin sensitive  Staphylococcus aureus  (MSSA; ATCC 29213 and ATCC 6538). In the case of two strains of MRSA (ATCC BAA-44 and ATCC BAA-1717) that have developed drug resistance to both ofloxacin and ciprofloxacin, the antimicrobial activity of 6c can almost rival that of vancomycin and daptomycin. Furthermore, 6c is also effective against vancomycin-intermediate and daptomycin non-susceptible strain of MRSA (ATCC 700699). Besides the efficacy, 6c has a much improved drug resistance profile in comparison with the conventional antibiotics.
Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.

Normosol-R pH 7.4 does not contain calcium to avoid precipitation of calcium salts that may occur when certain drugs are added. Solutions which contain calcium in amounts exceeding the normal plasma concentration may enhance clotting on contact with citrated blood. Hence, Normosol-R pH 7.4 can be used for starting a blood transfusion.
For 4 weeks participants will be encouraged to adopt the UK dietary guidelines (Eatwell Guide). In combination with these guidelines, an intermittent fasting regime involving two days of the week will be implemented. The regime will encourage individuals to consume of 500kcal per day for women and 625kcal per day for men, resulting in 75% daily caloric restriction during each of these two days.
X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3-AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X-NDI. Here we demonstrate that the β3-AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X-NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow-release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X-NDI mice. Taken together, these data suggest that human β3-AR agonists might represent an effective possible treatment strategy for X-NDI.
PROBLEM TO BE SOLVED: To obtain a lipase inhibitor capable of preventing and treating diseases caused by lipase, especially pimple by including an extract of Eriobotorya japonica Lindl., as an active ingredient. SOLUTION: This inhibitor comprises an extract of Eriobotorya japonica Lindl., of the family Rosaceae as active ingredient. The amount of the active ingredient is 0.001-10 wt.%, preferably 0.01-10 wt.% in the case of using the inhibitor as an external preparation for skin. The inhibitor is properly mixed with an oil, surfactant, humectant, thickening agent, perfume, coloring matter, etc., and prepared into a state applicable to skin such as cream, lotion, ointment, etc. The extract is obtained by extraction-treating leaf, fruit, bark or dried rhizome of Eriobotorya japonica Lindl., with a solvent such as ethanol. The lipase inhibitor suppresses lipase powerfully and effectively and does not provide skin with irritation and hormone-like action. The inhibitor can effectively prevent dandruff by application to scalp.
INTRODUCTION: The purpose of this retrospective registry-based study is to assess survival and causes of failure of cementless stem implants used in total hip arthroplasty (THAs), to ascertain if there are differences when these are categorized according to the six types described by Mont.
METHODS: Data collected from the regional registry regarding all primary THAs performed from 2000 to 2019 were analyzed. Femoral prosthetic stems were divided into the six types of Mont classification. For each stem type, number of implants, survival and causes of failure were evaluated and compared.
RESULTS: The most frequently implanted stem type was the 3c type (53.4%). Type 1 had the lowest stem failure rate (1.6%), and type 6 showed the highest (3.9%). Periprosthetic fracture was the most frequent complication in type 6, accounting for 34.5% of failures. Aseptic loosening was the main complication in type 2 stems, accounting for 36.4% of failures. Pairwise comparisons showed significant higher survival of type 1 compared to type 3c (p = 0.000026) and type 6 (p = 0.000076), and between type 3a compared to type 3c (p = 0.03) and type 6 (p = 0.026).
CONCLUSION: Significant variations in implant survival rates were found among the six Mont-types of cementless stems. These findings emphasize the paramount importance of stem design and fixation area in determining long-term survival, providing a guidance for orthopedic surgeons in the selection of the most appropriate stem for primary THA, contributing to our understanding of cementless stem performance, presenting invaluable insights to further improve patient outcomes in THA surgery.
PURPOSE: To obtain a torpent for alcoholic irritation, containing a glucose derivative and capable of reducing an irritant smell and irritation to the skin or oral cavity due to a lower alcohol in a short time. CONSTITUTION: This torpent for alcoholic irritation contains a glucose derivative of the formula (R is a benzyl alcohol, a phenylethyl alcohol, a cinnamyl alcohol, a eugenol, a vanillin, a sesamol derivative residue, etc.) as an active ingredient. The torpent for the alcoholic irritation comprising the glucose derivative is added to a lower alcohol and water to provide an aqueous solution of the alcohol useful for a cosmetic and a food and drink. The aqueous solution of the alcohol contains 0.1-15wt.% compound of the formula, 10-85 wt.% alcohol and 10-85wt.% water based on the total amount of the aqueous solution of the alcohol. The blending ratio of the compound of the formula to the lower alcohol is (1:1) to (1:50).  The resultant torpent is used for antisepticizing and flavoring a cosmetic such as a perfume or toilet lotion, a distilled liquor, a brewed liquor or a marine fish-paste product such as boiled fish paste or fish meat ham, uncooked noodles, confectioneries, etc.