anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as RAS, BRAF, and microsatellite instability (MSI). Novel genomic changes, including ERBB2 amplifications, mutations, and gene fusions, are now recognized as potential targets for precision therapy. This study aims to explore the genomic landscape of a Chinese cohort with mCRC to identify potentially targetable genetic alterations for personalized treatment strategies.
METHODS: A total of 500 mCRC patients in China were enrolled, based on which genomic profiling was performed using capture-based targeted sequencing across a panel of 520 genes on tumor tissues to identify prevalent genomic alterations. The mutations were analyzed by optimized proprietary algorithms. MSI and mismatch repair deficiency status were analyzed using the read-count-distribution approach. Besides, the overall survival (OS) related to these molecular changes was estimated.
RESULTS: The cohort's genomic profiling revealed TP53 mutations in 78%, APC in 60%, and KRAS in 47% of the patients. MSI-High status was confirmed in 5.8% of cases via a next-generation sequencing (NGS)-based algorithm. ERBB2/HER2 amplifications were found in 12% (60/500) of patients, with potential therapeutic implications for those without concurrent KRAS mutations. A subset of patients (1.2%; 6/500) showed fusions and DNA damage response (DDR) gene mutations (except TP53) that could be targeted therapeutically. The KRAS (G12C) variant was detected in 14 patients (2.8%), and 61 (12.2%) had a BRAF V600E mutation. Notably, survival analysis showed no significant differences in OS between KRAS mutant loci and NRAS mutations (p = 0.436). However, BRAF V600E mutations were associated with a poorer prognosis than BRAF wild-type and non-V600E mutations (16.3 months vs. 29.5 and 31.1 months, respectively; p < 0.001).
CONCLUSIONS: This study validates the feasibility of using NGS to detect prognostic and therapeutically actionable genetic variants in Chinese mCRC patients, contributing to understanding the genomic variation within this population and highlighting the potential for personalized medicine in managing mCRC.
Subjects randomized to this study arm used either the 4mm PN or the 8mm PN for 3 weeks, then switched to the alternate PN for another 3 weeks. Order of PN use was randomly determined.
The study will enroll 20 healthy subjects between the ages of 18 to 65 years old. Individuals will be recruited from multiple locations. Exclusion criteria include: any boney or tendinous foot/ankle operative procedure, diagnosis of neuromuscular disorder, any previous ankle fracture or degenerative changes that would limit dorsiflexion range of motion. Participants must have no obvious gait asymmetries demonstrated through observation. In addition, participants who are pregnant will be excluded from participation in the study.
Disclosed is an adjuvant for improving the bioavailability of bioactive compositions. The adjuvant is prepared from a byproduct of mint flavor production. In vitro and in vivo testing confirms effectiveness. The adjuvant contains a mixture of compounds which is effective to improve the oral bioavailability of a bioactive composition normally having limited absorptivity, and it comprises a mixture of nonpolar compounds and compounds with some polar characteristics. In preferred form the nonpolar compounds comprise compounds selected from a group that includes terpene hydrocarbons and terpene derivatives and the compounds with some polar characteristics comprise compounds selected from a group that includes aldehydes, alcohols and ketones. The preferred compositions will have a ratio of nonpolar compounds and compounds with some polar characteristics is within the range of from 5:1 to 20:1. The adjuvants can enhance delivery of CoQ10 and other bioactive compositions, such as carotenoids (e.g., β-carotene), curcuminoids, lycopene, resveratrol, flavonoids and other phenolic compounds, organosulfur compounds, saponins, sterols, stanols, and mixtures of at least two of these, to the interior cellular environment, including organelles, such as the mitochondria.
The overall prognosis of pancreatic cancer is poor. For resectable patients, adjuvant chemotherapy is performed after surgery, which has become the standard and standard treatment recommended by various guidelines. Preoperative neoadjuvant therapy is proved to improve the R0 resection rate and reduce the lymph node metastasis rate, thus prolonging the postoperative recurrence-free survival time and increasing the survival benefit of patients. But despite adequate preoperative and postoperative treatment, the patient benefit remains limited. In pancreatic cancer surgery, improving the R0 resection rate, increasing the positive lymph node resection rate, and accurately identifying small metastases to accurately stage, can improve the prognosis of patients to a certain extent. Therefore, this study intends to design the prospective, exploratory, single center clinical study, using targeted EGFR fluorescence imaging agent (anti-EGFR-IR800CW) and fluorescent navigation technology, in its lymph node tracing, intraoperative tumor localization, accurate determination of resection margin, and explore its clinical significance in radical surgical resection of pancreatic cancer.
In the invention it is described application of xenon or gaseous xenon-containing mixtures for treatment of neurointoxications. In particular, the present invention relates to the application of xenon in those cases when neurointoxication is caused by an excess of neuromediators. The xenon can reduce release of neuromediators, firstly of dopamine, which is conditioned by the reasons of hypoxia, such as apoplexy or craniocerebral trauma. It is also proposed a preparation for treatment of neurointoxications, containing xenon or gaseous xenon mixture and a process for obtaining the said preparation. The xenon-containing preparation can also be applied in the capacity of therapeutic agent for treatment of depressions, schizophrenia and Parkinson's disease, wherein it also troubled the neuromediator balance.Claims: 19Fig.: 2
PURPOSE:To obtain the title powder excellent in dispersibility and useful as a material to be incorporated into a cosmetic, a paint, resin, etc., by partially modifying raw material comprising, e.g. an animal dermis or tendon in the presence of water, followed by a specified processing. CONSTITUTION:Raw material comprising an animal dermis or tendon, or a raw hide, i.e., a by-product of the leather industry, and/or a split after liming is partially modified in the presence of water. The modified portion is removed by dissolution by the action of a protease (e.g. trypsin). A dispersion of insoluble fine collagen fibers comprising the obtained unmodified portion is washed and, if necessary, dried.
This multicenter randomized, non-blinded clinical trial compared two parallel groups of patients with bullous pemphigoid treated with oral methylprednisolone in combination with either azathioprine or mycophenolate mofetil. Patients were randomly assigned, irrespective of severity of disease, to receive either 0.5 mg per kg body weight (BW) methylprednisolone (Urbason®, Aventis Pharma, Bad Soden, Germany) with 2 mg per kg BW azathioprine sodium (Imurek®, GlaxoSmithKline, Munich, Germany) once daily or 0.5 mg per kg BW methylprednisolone once daily and 1,000 mg mycophenolate mofetil (CellCept® provided by Hoffmann-La Roche AG, Grenzach-Wyhlen, Germany), given twice daily (2 g/d). The initial dose was maintained until blister formation ceased, crusts as well as erosions disappeared, and re-epithelialization of previous lesions started. The corticosteroid dose was then sequentially reduced by 10 mg every two weeks until a dose of 20 mg per day was reached followed by a reduction in 5 mg-steps every two weeks until 10 mg per day. Afterwards, corticosteroid reduction was performed in 2.5 mg-steps every two weeks until zero. After discontinuation of corticosteroids azathioprine or mycophenolate mofetil doses were maintained at the initial dosage as monotherapy for an additional 4 weeks. Subsequently, azathioprine was reduced by 0.5 mg per kg BW every four weeks to a dose of 100 mg per day. Thereafter, azathioprine was tapered in 25 mg-steps every four weeks until discontinuation of treatment. Mycophenolate mofetil was reduced in 500 mg/d-steps every four weeks to 1,000 mg per day. From then on the mycophenolate mofetil dosage was decreased in 250 mg-steps every four weeks until discontinuation of treatment.
Pemetrexed (Alimta, Eli Lilly and Company) is administrated by intrathecal injection, plus dexamethasone 5 mg, twice per week for 2 weeks, followed by once per week for 4 weeks. The initial dose of intrathecal pemetrexed is 15 mg, escalated to 20 mg, and then 25 mg.... A minimum of three patients and a maximum of six are enrolled in each cohort. Folic acid 200-400 μg is administered orally once daily, prior to the first intrathecal pemetrexed, until 21 days after the last intrathecal pemetrexed. A single dose of vitamin B12 1000 μg is administered by intramuscular injection before the first intrathecal pemetrexed, once per 3 weeks.
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of DEMEROL Injection, the risk is greatest during the initiation of therapy or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of DEMEROL Injection are essential [see Dosage and Administration (2.3)]. Overestimating the DEMEROL Injection dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.2)].
Participants will receive a higher dose of ASP2802 on Day 0 of cycle 1. Each participant will then receive up to 2 doses of MA-20 booster in each 28-day cycle, with dose level(s) selected from Group B.
The influence of metabolic and bariatric surgery (MBS) on taste preferences and the pleasurable aspects of appetite may be mediated through its effects on gut hormones, potentially affecting weight loss results. Research indicates that the nature of the MBS performed significantly impacts food cravings in the year following the procedure, with no clear relationship to psychological factors or pre-surgery eating behaviors. During the period from August 2021 to August 2022, a group of adult patients with a body mass index (BMI) of 40 kg/m2 or above, or 35 kg/m2 or above with obesity-related medical complications, underwent Roux-en-Y gastric bypass (RYGB), one-anastomosis gastric bypass (OAGB), or sleeve gastrectomy (SG) at a tertiary academic center focused on MBS. This research included 294 patients who completed the Taste Desire and Enjoyment Change Questionnaire (TDECQ) one year after their surgical procedures, which were primary RYGB, OAGB, or SG. Most participants noted changes in their taste perception, cravings, and enjoyment of flavors after undergoing SG, RYGB, and OAGB. The study's findings suggest that the type of MBS significantly affects taste preferences. Additionally, RYGB and OAGB were associated with a more substantial decrease in the craving for sweet and fatty flavors relative to SG.
This pilot feasibility randomized controlled study will determine the feasibility, acceptability and preliminary efficacy of the ENACT Group Visit intervention compared to a comparison arm.

The ENACT Group Visit intervention aims to engage patients in an interactive discussion of key ACP concepts and support patient-initiated ACP actions (i.e. choosing decision-maker(s), deciding on preferences during serious illness, discussing preferences with decision-makers and healthcare providers, and documenting advance directives). The group visits involve two 2-hour sessions, one month apart, facilitated by a geriatrician and a social worker. The ENACT Group Visit is based on an intervention manual that guides the structure, facilitator considerations, session format, and documentation and billing details. The discussions include sharing experiences related to ACP, considering values related to serious illness, choosing a surrogate decision-maker(s), flexibility in decision making, and having conversations with decision-makers and healthcare providers. The facilitators support an interactive discussion that promotes opportunities for patients to learn from others' experiences.
A serous effusion is common event in metastatic carcinoma, but it also can be associated with other benign medical conditions. Current standard method for detecting malignancy is by cytological examination. However, cytological examination is often low sensitive, often due to the large amount of fluid with relatively sparse tumor cells present and the presence of many normal cells such as mesothelial cell. The investigators have developed a new method, malignant cell enrichment with immunomagnetic beads capture followed by Pap staining and NGS, to identify target malignant cells in body fluids.

McAb NJ001 is developed for malignant cell isolation with immunomagnetic beads capture technique. This is a prospective, multi-center, double-blind, statistically powered clinical trial that will enroll patients scheduled to undergo a procedure for removal of fluid from a serous effusion with or without clinical diagnosis of caner. The purpose of the current study is to compare the novel serous effusion detection assay using NJ001 coated immunomagnetic beads capture followed by Pap staining and NGS analysis with traditional cytologic evaluation.
BACKGROUND: Berberine (BBR), the main active component of Coptis chinensis Franch., has a variety of pharmacological effects, notably anti-inflammatory, which make it a potential treatment for ulcerative colitis (UC). Nevertheless, the specific target and the mode of action of BBR against UC are still unclear.
PURPOSE: Here, we aim to identify BBR's anti-inflammatory target and its mode of action in UC treatment.
METHODS: The therapeutic effects of BBR and Coptis chinensis Franch. extract were first assessed in UC mice. Then, stable isotope labeling using amino acids in cell culture-activity-based protein profiling (SILAC-ABPP) was applied to identify the anti-inflammatory target proteins of BBR in an inflammation model of RAW264.7 cells stimulated by LPS. Molecular docking, drug affinity responsive target stability (DARTS), molecular dynamics simulation, cellular thermal shift assay (CETSA), and biological layer interference (BLI) measurement were employed to study the interaction between BBR and its targets. Lentiviral transfection was used to knock down the target protein and investigate BBR's anti-inflammatory mechanism.
RESULTS: BBR and Coptis chinensis Franch. extracts both significantly alleviated UC in mice. SILAC-ABPP identified IRGM1 as BBR's anti-inflammatory target, with its overexpression reduced by BBR treatment in both RAW264.7 cell inflammation models stimulated by LPS and UC mice. BBR significantly reduced inflammatory cytokines in LPS-induced RAW264.7 cells by blocking the PI3K/AKT/mTOR pathway. Knockdown of IRGM1 weakened BBR's effects on cytokine expression and pathway regulation.
CONCLUSION: For the first time, IRGM1 was identified as the direct anti-inflammatory target of BBR. BBR has the potential to inhibit IRGM1 expression in vitro as well as in vivo. The molecular mechanism of BBR's anti-inflammatory activity was inhibiting the PI3K/AKT/mTOR pathway by targeting IRGM1.
Maternal and child health is of great concern globally. Early life phase of a fetus and infant is a critical period for the development of health and disease in the whole life. Exposure of negative environmental, nutritional and lifestyle factors in pregnant women during this period can have adverse effects on fetal and infant. In addition, for mothers, complications during pregnancy could also have a negative effect on long-term health of mothers, such as diabetes, hypertension. Thus, the Peking University Birth Cohort in Weifang is primarily aimed to investigate the short-term and long-term effects of pre-pregnant and prenatal exposure on maternal and child health. Data are collected regarding environmental, nutritional and lifestyle exposures as well as short-term and long-term health outcomes of mothers, husbands and their children from birth to before 18 years old. Biological samples including peripheral blood, urine, placenta, umbilical cord, cord blood, and faeces samples are also collected.
To explore the feasibility and preliminary efficacy of Evolutionary Systems Therapy, the present study includes three actions. In the first action investigators enroll 6 adolescents (16-19 years) with personality disorders, in the second 15 young adults (20-25 years) with personality disorders. All participants receive 6 months of psychotherapy. The two subsamples of patients (adolescents and young adults) are assessed based on the conceptualization model of Evolutionary Systems Therapy which envisages three macro-organizations of personality (consistently with dimensional and hierarchical models such as Hierarchical Taxonomy of Psychopathology): internalizing, externalizing, schizotypal. Investigators plan to recruit patients until the size of the sub-samples is reached (15 young adults divided into 3 groups of 5 patients, each for each of the three interpersonal patterns; 6 adolescents divided into 3 groups of 2 patients, each for each of the three patterns interpersonal). In the third action, an ecological momentary assessment study will investigate the consistency over time between the conceptualization model and the experiences of the young adult patients enrolled: investigators will explore whether the hypothesized conceptualization will be confirmed by collected data on the patients' interpersonal styles.
The method of the present invention is to label living cells so as to render them detectable in MRI. The invention relates to the use of magnetic resonance (MR) sensitive agents to render treated living cells identifiable and distinguishable in MR Imaging (MRI). MR sensitive agents can be bound to a targeting compound such as a protein or antibody. The targeting compound reacts with living cells in a way that the MR sensitive agent is incorporated into the or onto the cell surface. The MR sensitive agents can also be coated with agents that render the magnetic resonance sensitive agent able to bind to or be internalized by cells. The treated cells of the invention can be applied to patient for any therapeutic, diagnostic, or experimental purpose. The invention also encompasses imaging the host with MRI to locate MR labeled cells, to track their migration or bio-distribution non-invasively, and to establish to survival characteristics of such cells.
On-site weekly group visits using small change approach to improve physical activity and diet. Initial treatment of 3 months, followed by 21 months of follow-up phone support (phone-only ASPIRE-VA).
The invention provides a reagent for preparing universal CAR-T cells, the reagent comprising: (i) a sgRNA targeting a class I Human LeukocyTe AnTigen (Human leukocy AnTigen-I, HLA-I) or an expression vector for expressing the sgRNA, the sgRNA being one or more nucleotide sequences selected from the group consisting of: HLA-A, HLA-B, HLA-C, HLA-E, HLA-F targeting the alpha chain, and/or HLA-G transposon SEQ ID NO. 1-250, SEQ ID NO. 251-481, SEQ ID NO. 482-726, SEQ ID NO. 727-956, SEQ ID NO. 957-1226, and SEQ ID NO. 1227-1447, and (ii) an expression cassette which does not express or expresses the Cas9 protein or which expresses the Cas9 protein. The sgRNA of the invention can knock out 6 transposon genes of HLA-1 efficiently, specifically and stably without off-target and mutual interference, thereby greatly improving the gene knockout efficiency. In addition, the invention also provides universal CAR-T cells engineered with the sgrnas. The invention can effectively reduce the risk of graft-versus-host disease and immune rejection.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

A 104-week dietary carcinogenicity study with ezetimibe was conducted in rats at doses up to 1500 mg/kg/day (males) and 500 mg/kg/day (females) (~20 × the human exposure at 10 mg daily based on AUC0–24hr for total ezetimibe). A 104-week dietary carcinogenicity study with ezetimibe was also conducted in mice at doses up to 500 mg/kg/day (>150 × the human exposure at 10 mg daily based on AUC0–24hr for total ezetimibe). There were no statistically significant increases in tumor incidences in drug-treated rats or mice. 

No evidence of mutagenicity was observed in vitro in a microbial mutagenicity (Ames) test with Salmonella typhimurium and Escherichia coli with or without metabolic activation. No evidence of clastogenicity was observed in vitro in a chromosomal aberration assay in human peripheral blood lymphocytes with or without metabolic activation. In addition, there was no evidence of genotoxicity in the in vivo mouse micronucleus test.

In oral (gavage) fertility studies of ezetimibe conducted in rats, there was no evidence of reproductive toxicity at doses up to 1000 mg/kg/day in male or female rats (~7 × the human exposure at 10 mg daily based on AUC0–24hr for total ezetimibe).

13.2 Animal Toxicology and/or Pharmacology

The hypocholesterolemic effect of ezetimibe was evaluated in cholesterol-fed Rhesus monkeys, dogs, rats, and mouse models of human cholesterol metabolism. Ezetimibe was found to have an ED50 value of 0.5 µg/kg/day for inhibiting the rise in plasma cholesterol levels in monkeys. The ED50 values in dogs, rats, and mice were 7, 30, and 700 µg/kg/day, respectively. These results are consistent with ZETIA being a potent cholesterol absorption inhibitor.

In a rat model, where the glucuronide metabolite of ezetimibe (SCH 60663) was administered intraduodenally, the metabolite was as potent as the parent compound (SCH 58235) in inhibiting the absorption of cholesterol, suggesting that the glucuronide metabolite had activity similar to the parent drug.

In 1-month studies in dogs given ezetimibe (0.03 to 300 mg/kg/day), the concentration of cholesterol in gallbladder bile increased ~2- to 4-fold. However, a dose of 300 mg/kg/day administered to dogs for one year did not result in gallstone formation or any other adverse hepatobiliary effects. In a 14-day study in mice given ezetimibe (0.3 to 5 mg/kg/day) and fed a low-fat or cholesterol-rich diet, the concentration of cholesterol in gallbladder bile was either unaffected or reduced to normal levels, respectively.

A series of acute preclinical studies was performed to determine the selectivity of ZETIA for inhibiting cholesterol absorption. Ezetimibe inhibited the absorption of 14C-cholesterol with no effect on the absorption of triglycerides, fatty acids, bile acids, progesterone, ethinyl estradiol, or the fat-soluble vitamins A and D.

In 4- to 12-week toxicity studies in mice, ezetimibe did not induce cytochrome P450 drug metabolizing enzymes. In toxicity studies, a pharmacokinetic interaction of ezetimibe with statins (parents or their active hydroxy acid metabolites) was seen in rats, dogs, and rabbits.