anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The first-line NAs include entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). All the NAs mentioned above could achieve complete virologic response. NAs mentioned above are sufficient in inhibiting viral replication. However, there may exist difference in long-term prognosis such as HBsAg level decline, resistance development and HCC development. A prospective study performed by our team previously showed that TDF was better than ETV in HBsAg decline. A Korean research showed that TDF therapy was associated with a significantly lower risk of HCC than ETV therapy; the TDF group showed a distinct reduction in HBsAg level after one-year treatment. Also, a Japanese RCT study indicated that the reduction in HBsAg level was significantly greater in the TDF arm than the ETV arm at week 24. The mechanism of HBsAg decline induced by TDF has not been fully elucidated. Patients treated with nucleotide analogues (adefovir, tenofovir) had higher serum IFN-λ3 levels than those treated with nucleoside analogues (lamivudine, entecavir), according to results recently published in Gut. A team from Japan has found that nucleotide analogues inhibit LPS-mediated IL-10 production and induce IL-12p70 and TNF-α production. We speculated that, compared with entecavir, tenofovir could up-regulate IFN-λ3 and reduce the level of HBsAg more significantly.

As known as the second generation of TDF, TAF has a significantly longer half-life than TDF. A phase 3 study displayed that TAF 25 mg was non-inferior to TDF 300 mg in suppressing HBV replication, with a better performance in renal and bone safety. However, there is lack of study evaluating TAF in reducing HBsAg and induces IFN-λ3.The aim of this study was to investigate whether the TAF can achieve a better antiviral therapeutic endpoint, i.e. a greater reduction in HBsAg levels, or even meet the therapeutic expectation of stopping NAS in a larger number of treated patients.

The objective of this clinical study was to observe the changes of HBsAg levels after a sequential 48 weeks-treatment of TAF in ETV experienced CHB patients and to monitor the levels of cytokines such as IFN-λ3, IP-10, IL-12, IL-10, and IL-21.
Participants received 3 grams (g) mycophenolate mofetil (MMF) tablets per os (p.o.) in divided doses (every 12 hours \[q12h\]) adapted to mycophenolic acid (MPA) by area under the curve (AUC) beginning on the day of renal transplant, Day 0, or the day before, Day -1, and continuing through Week 52. In addition, induction by interleukin-2R (IL-2R) was administered at Day 0 per standard of care at the site at the investigator's discretion. At 72 hours post-transplantation, participants received cyclosporine 100-1500 nanograms (ng) per (/) milliliter (mL) from Day 0 to (-) Week 4, 800-1200 ng/mL from Week 4 - Week 12 and 500-800 ng/mL from Week 12 - Week 52. Solumedrol 500 mg intravenously (i.v.) was administered before or after the transplantation, and 0.5 milligrams (mg) per kilogram (kg) p.o. daily from Day 1 - Day 7.
BACKGROUND AND OBJECTIVES: Fibrosis contributes to 45% of deaths in industrialized nations and is characterized by an abnormal accumulation of extracellular matrix (ECM). There are no specific anti-fibrotic treatments for liver fibrosis, and previous unsuccessful attempts at drug development have focused on preventing ECM deposition. Because liver fibrosis is largely acknowledged to be reversible, regulating fibrosis resolution could offer novel therapeutical options. However, little is known about the mechanisms controlling ECM remodeling during resolution. Changes in proteolytic activity are essential for ECM homeostasis and macrophages are an important source of proteases. Herein, in this study we evaluate the role of macrophage-derived cathepsin D (CtsD) during liver fibrosis.
METHODS: CtsD expression and associated pathways were characterized in single-cell RNA sequencing and transcriptomic datasets in human cirrhosis. Liver fibrosis progression, reversion and functional characterization were assessed in novel myeloid-CtsD and hepatocyte-CtsD knock-out mice.
RESULTS: Analysis of single-cell RNA sequencing datasets demonstrated CtsD was expressed in macrophages and hepatocytes in human cirrhosis. Liver fibrosis progression, reversion and functional characterization were assessed in novel myeloid-CtsD (CtsDΔMyel) and hepatocyte-CtsD knock-out mice. CtsD deletion in macrophages, but not in hepatocytes, resulted in enhanced liver fibrosis. Both inflammatory and matrisome proteomic signatures were enriched in fibrotic CtsDΔMyel livers. Besides, CtsDΔMyel liver macrophages displayed functional, phenotypical and secretomic changes, which resulted in a degradomic phenotypical shift, responsible for the defective proteolytic processing of collagen I in vitro and impaired collagen remodeling during fibrosis resolution in vivo. Finally, CtsD-expressing mononuclear phagocytes of cirrhotic human livers were enriched in lysosomal and ECM degradative signaling pathways.
CONCLUSIONS: Our work describes for the first-time CtsD-driven lysosomal activity as a central hub for restorative macrophage function during fibrosis resolution and opens new avenues to explore their degradome landscape to inform drug development.
Antibody inhibitors of the interleukin-6 (IL-6) signaling pathway, such as tocilizumab and sarilumab, have been used to treat rheumatoid arthritis, chimeric antigen receptor T cell-induced cytokine storm, and severe COVID-19 pneumonia. Here, we solve the cryogenic electron microscopy structures of sarilumab and tocilizumab in complex with IL-6R to resolutions of 3.2 and 3.3 Å, respectively. These structures reveal that both tocilizumab and sarilumab bind to the D3 domain of IL-6R. The binding surfaces of the two antibodies largely overlap, but the detailed interactions are different. Functional studies of various mutants show results consistent with our structural analysis of the antibodies and IL-6R interactions. Structural comparisons with the IL-6/IL-6R/gp130 complex indicate that sarilumab and tocilizumab probably inhibit IL-6/IL-6R signaling by competing for the IL-6 binding site. In summary, this work reveals the antibody-blocking mechanism of the IL-6 signaling pathway and paves the way for future antibody discovery.
Methods and systems consistent with the present invention provide a comprehensive assessment and planning system. Methods and systems consistent with the present invention employ a preventive approach to predicting the likelihood of an entity entering a degraded future state by computing a risk value that reflects that likelihood. An embodiment of the present invention applies to a comprehensive healthcare treatment and planning system. This healthcare system employs a preventive approach to healthcare by basing healthcare decisions on a multi-factorial computation of risk. The risk value is computed by evaluation of a function that considers a variety of historic, environmental, and systemic behaviors and conditions. In addition to considering a risk value, a treatment plan developed in accordance with the healthcare system considers symptoms and objectives of the treatment from the perspective of both the patient and the provider. The outcomes associated with treatment and risk assessment are fed back into the healthcare system to increase its accuracy and subsequent effectiveness in computing risk values over time.
PURPOSE:To readily improve the stability of lysozyme without a toxic reagent by combining the lysozyme with a saccharide having reduced terminals and containing no carboxyl group through a peptide. CONSTITUTION:A saccharide (e.g. amylose) having reduced terminals and containing no carboxyl group is reacted with a peptide (e.g. glycyl glycine) having an amino group and a carboxyl group at both the terminals. The reaction product is condensed with N-hydroxysuccinimide in the presence of a condensing agent to prepare an active saccharide. The prepared active saccharide is reacted with lysozyme in a buffer solution having no amino group, followed by separating the resultant saccharide-lysozyme hybrid from the active saccharide with gel chromatography, etc., to provide the saccharide-lysozyme hybrid wherein the saccharide is bonded to the lysozyme through the peptide.
Combination of PVIC and TACE. PVIC started 2 weeks after operation and TACE started 6 weeks after operation. Both PVIC and TACE were repeated at 8 weeks intervals for 3 cycles.
BACKGROUND: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes.
METHODS: Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes.
RESULTS: Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes.
CONCLUSIONS: High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.
Of the patients with MCL who received the 200 mg dose of JAYPIRCA in BRUIN, 93 (78%) were 65 years of age and older and 39 (33%) were 75 years and older [see Clinical Studies (14.1)]. Clinical studies of JAYPIRCA did not include sufficient numbers of patients with MCL who were less than 65 years of age to determine whether older patients respond differently from younger adult patients. Of the patients with CLL/SLL who received the 200 mg once daily dose of JAYPIRCA in BRUIN, 68 (63%) were 65 years of age and older and 21 (19%) were 75 years and older [see Clinical Studies (14.2)]. No overall differences in effectiveness were observed between younger and older patients. 

In the pooled safety population in patients with hematologic malignancies, 401 (68%) were 65 years of age and older, while 154 (26%) were 75 years of age and older. Patients aged 65 years and older experienced higher rates of Grade 3 and higher adverse reactions and serious adverse reactions compared to patients who were less than 65 years of age.
In the experimental group, the acute pain after surgery will be treated with Oliceridine fumarate injection via patient controlled analgesia for 48 hours. Oliceridine 0.4mg/kg will be supplied to 100ml analgesia pump, loading dose for 1-2ml, background infusion dose for 2ml/h, bolus for 2ml/ time, locked for 15min, maximum dose for 12ml/h.
Participants will respond to values clarification writing prompts related to physical exercise once a day over 28 days in addition to a short daily survey. In each session, one writing prompt will be randomly presented from a pool of four categories: hierarchical, conditional, distinction, and perspective-taking. The survey inquires about time spent doing light, moderate, and vigorous exercise the day before, in addition to time spent watching television, using the computer, and sitting. It also includes the 24 item Multidimensional Psychological Flexibility Inventory adapted for ecological momentary assessment and questions asking participants to rate the extent to which they currently feel 8 emotions, their current motivation to exercise, and their stress yesterday. The writing prompt and survey are estimated to take 10 minutes to complete daily. Participants will have the option to review additional educational content about values and their previous written responses.
Breastfeeding reduces the risks of dying from infections and is currently recommended as the most beneficial feeding option for infants born to HIV-infected women in low-resourced settings. This recommendation contradicts previous recommendations to avoid breastfeeding to prevent mother-to-child transmission of HIV. South Africa, a high HIV prevalent country, recently phased out access to free formula milk in the public sector in support of breastfeeding for HIV-infected women. The investigators previously found that few HIV-infected South African women choose breastfeeding and among those who did, many stop breastfeeding early. This study involves text messaging breastfeeding advice encouraging women to exclusively breastfeed, and inquire if they have any breastfeeding related problems, and motivational interviews exploring and supporting woman's commitment to continue breastfeeding.Participants meeting inclusion criteria who consent participation will be enrolled by a research nurse and immediately randomly assigned to text messaging plus motivational interviewing group or usual standard of care group.

The investigators propose a randomized, parallel group, standard of care-controlled pilot trial which will be conducted among HIV-infected women of low socio-economic background, giving birth at a primary healthcare clinic in Cape Town, South Africa. The pilot trial will assess the feasibility of conducting a larger trial on communication and support approaches that may improve HIV-infected woman's adherence to exclusive and continued breastfeeding.
Biotinidase deficiency (BTD) is a treatable, inherited metabolic disorder commonly characterised by alopecia, dermatitis, seizures and developmental delay. It can also manifest as optic neuritis and myelitis; however, these are infrequently described in the literature. We report three cases who presented with quadriplegia and vision loss, initially managed as neuromyelitis optica spectrum disorder (NMOSD), based on neuroimaging findings. Two of them initially responded to immune therapy but relapsed after a few months, while one case showed no clinical improvement with immune therapy. The clinical presentation and neuroimaging findings in all three cases were consistent with NMOSD, leading to a delayed diagnosis of BTD. Antiaquaporin4 and antimyelin oligodendrocyte glycoprotein antibodies were negative in all patients. Urine organic acids reported raised markers of biotinidase or holocarboxylase synthase deficiency. Two of them had a dramatic response to biotin supplementation, showing significant improvement in motor function and vision.
The invention provides an amphipathic polymer with a main chain containing a photosensitive prodrug, as well as a preparation method and a nano-micelle of the amphipathic polymer, and belongs to the technical field of chemical synthetic drugs. The structural formula of the amphipathic polymer is shown in the formula I. The invention further provides the preparation method of the mphipathic polymer. The method comprises the following steps: firstly, preparing a photoactive quadrivalent platinum complex; carrying out a reaction between the obtained photoactive quadrivalent platinum complex and diisocyanate, so as to obtain a first intermediate; finally, carrying out reactions between the first intermediate and methoxy polyethylene glycol of different molecular weights, so as to obtain the amphipathic polymer with the main chain containing the photosensitive prodrug. The invention further provides the nano-micelle of the amphipathic polymer. The amphipathic polymer is relatively low in cytotoxicity but relatively high in antitumor activity.
BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by an excessive host response to infection, manifested by elevated levels of inflammatory cytokines. At present, the use of hemoperfusion to remove inflammatory cytokines from the bloodstream has been expanding. Meanwhile, the pharmacokinetics and pharmacodynamics characteristics of antibiotics in critically ill patients may be impacted by hemoperfusion.
CASE PRESENTATION: The patient was a 69-year-old male with poorly controlled type 2 diabetes. When admitted to the ICU, Multiple Organ Dysfunction Syndrome (MODS) appeared within 48 h, and he was suspected of septic shock due to acute granulocytopenia and significantly increased procalcitonin. Broad-spectrum antibiotics imipenem was administered according to Sepsis 3.0 bundle and hemoperfusion lasting 4 h with a neutron-macroporous resin device (HA-380, Jafron, China) five times was conducted to lower the extremely high value of serum inflammatory factors. Blood samples were collected to measure imipenem plasma concentration to investigate the effect of hemoperfusion quantitatively. This study showed that 4 h of hemoperfusion had a good adsorption ability on inflammatory factors and could remove about 75.2% of imipenem.
CONCLUSIONS: This case demonstrated the high adsorption capacity of hemoperfusion on imipenem in critically ill patients. It implies a timely imipenem supplement is required, especially before hemoperfusion.
Risk Summary 

There are no available data on triheptanoin use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies conducted in pregnant rats and rabbits administered triheptanoin during the period of organogenesis, the primary toxicological effect (reduced body weight gain) was considered to be specific to decreased food consumption related to taste aversion in animals, and therefore is not relevant to clinical use in the intended populations. 

There is a pregnancy safety study for DOJOLVI. If a patient becomes pregnant while receiving DOJOLVI, healthcare providers should report DOJOLVI exposure by calling Ultragenyx Pharmaceutical Inc. at 1-888-756-8657.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Embryofetal developmental studies have been conducted with triheptanoin in rats and rabbits following oral administration of 10% (3.2 g/kg), 30% (9.7 g/kg) and 50% (16 g/kg) DCI in rats and 10% (1.2 g/kg), 20% (2.3 g/kg) and 30% (3.5 g/kg) DCI in rabbits during the period of organogenesis. Reduced body weight gain, associated with decreased food consumption, was observed in pregnant rats and rabbits following administration of triheptanoin food mixture and was attributed to taste aversion. The NOAEL for this maternal toxicity (lack of body weight gain) was 10% DCI for both rats and rabbits. Administration of dietary triheptanoin to pregnant rats at doses approximately 2 times above, and pregnant rabbits approximately equal to the targeted clinical dose of 35% DCI resulted in increased incidence of skeletal malformations and decreased litter weights in both species and reduced number of viable litters in rabbits. The adverse effects on rat and rabbit embryofetal development were associated with the reduced body weight gain observed in pregnant animals. The NOAEL for embryofetal development toxicity was 30% and 20% DCI for rats and rabbits, respectively. In a pre- and postnatal developmental study in rats, reduced birthweights and delayed sexual maturation in pups were observed at 50% DCI and were considered secondary to the reductions in body weight gain in pregnant rats.
Each prefilled DuoDote autoinjector provides a single intramuscular dose of atropine, a cholinergic muscarinic antagonist, and pralidoxime chloride, a cholinesterase reactivator, in a self-contained unit, specifically designed for administration by emergency medical services personnel. 

When activated, each single-dose DuoDote autoinjector delivers the following: 

  * 2.1 mg of atropine in 0.7 mL of sterile, pyrogen-free solution containing 12.47 mg glycerin, not more than 2.8 mg phenol, 3.05 mg sodium citrate dihydrate, 3.5 mg citric acid monohydrate, and Water for Injection. The pH range is 4.0 – 5.0. 
  * 600 mg of pralidoxime chloride equivalent to 476.6 mg of pralidoxime in 2 mL of sterile, pyrogen-free solution containing 40 mg benzyl alcohol, 22.5 mg glycine, and Water for Injection. The pH is adjusted with hydrochloric acid. The pH range is 2.0 to 3.0. 



Atropine occurs as white crystals, usually needle-like, or as a white, crystalline powder. It is slightly soluble in water with a molecular weight of 289.38. Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and l-hyoscyamine, with activity due almost entirely to the levo isomer of the drug. 

Chemically, atropine is designated as 1αH,5αH-Tropan-3α-ol(±)-tropate. Its empirical formula is C17H23NO3 and its structural formula is as follows: 

Pralidoxime chloride is an odorless, white to pale-yellow crystalline powder, freely soluble in water, with a molecular weight of 172.61. Chemically, pralidoxime chloride is designated as 2-formyl-l-methylpyridinium chloride oxime. Its empirical formula is C7H9ClN2O and its structural formula is indicated above.
Sunitinib monotherapy. Participants receive sunitinib 50mg orally once daily for 4 weeks and then are off treatent for 2 weeks, or once daily for 2weeks and then are off treatent for 1 week.
Conventional long-term studies to evaluate the carcinogenic potential of hydroxyurea have not been performed. However, intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6 to 1.2 times the maximum recommended human oral daily dose on a mg/m2 basis) thrice weekly for 6 months to female rats increased the incidence of mammary tumors in rats surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to bacteria, fungi, protozoa, and mammalian cells. Hydroxyurea is clastogenic in vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse micronucleus assay). Hydroxyurea causes the transformation of rodent embryo cells to a tumorigenic phenotype.

Hydroxyurea administered to male rats at 60 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) produced testicular atrophy, decreased spermatogenesis, and significantly reduced their ability to impregnate females.
System 2700 comprising a server 2754 arranged to receive information from a user device 2752 of a user 2750 and to use the received information to process a request for a product to be made available to the user; two or more apparatuses in communication with the server; and the server arranged to determine at least one of the apparatuses to make the product available to the user, and to provide an indication of the selection to the user. The server may determine the at least one apparatus based on location information, which may comprise location information of the user or of the apparatuses. The server may select at least one of the apparatuses based on information of an ability of the user to travel. The apparatuses may comprise a drone 2756 to deliver the product, a machine 2758 such as a vending machine to dispense the product, or a robot 2760 to provide the product. The system may comprise a payment system, which may utilise a proprietary currency. The system is suitable for use in a healthcare ecosystem, for example with pharmaceutical products.