anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The invention provides an anti-lung cancer drug and application thereof. Belongs to the technical field of medicines. The invention adopts the inhibitor YM155 or siRNA to target Survivin, and simultaneously combines with the iron death inducer Erastin to use, thereby promoting the iron death induced by Erastin to a certain extent, inducing apoptosis and having a certain effect on eliminating drug resistance. Apoptosis inhibitor z-VAD-fmk and iron death inhibitor Lip-1 can reverse cytotoxicity induced by Erastin in combination with YM155, while Erastin in combination with YM155 induces activation of autophagy and degradation of GPX4, while lipid peroxidation level and mitochondrial membrane potential increase. Inhibiting Survivin expression promotes autophagic degradation of GPX4, promoting pig death and apoptosis in non-small cell lung cancer cells. By combining YM155 and Erastin, the cytotoxicity of the non-small cell lung cancer cells at the same dosage is obviously enhanced, the two medicines have synergistic effect, and the anti-tumor effect of the medicines is obviously enhanced.
* Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation (see WARNINGS and PRECAUTIONS). 
  * The use of benzodiazepines, including chlordiazepoxide hydrochloride capsules, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing chlordiazepoxide hydrochloride capsules and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (see WARNINGS). 
  * The continued use of benzodiazepines, including chlordiazepoxide hydrochloride capsules, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide hydrochloride capsules after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide hydrochloride capsules or reduce the dosage (see DOSAGE AND ADMINISTRATION and WARNINGS).
Patients will receive 2 cycles of weekly brentuximab vedotin and then undergo evaluation with FDGPET/CT. Patients with normalization of FDG-PET/CT will proceed to ASCT. Patients with persistent abnormalities on FDG-PET/CT will receive 2 cycles of augmented ICE chemotherapy followed by repeat FDG-PET/CT prior to ASCT. Following augmented ICE, patients with negative FDG-PET/CT will proceed to ASCT. Those with persistent abnormalities on FDG-PET/CT will be treated according to their physician's recommendations.
BACKGROUND: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear.
METHODS: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting.
RESULTS: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably.
CONCLUSION: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.
CMAP is a culturally adapted brief problem-focused therapy, based on the principles of CBT which has been adapted with permission from a self-help guide called "Life after self-harm"(Schmidt \& Davidson, 2004). This intervention includes evaluation of the self-harm attempt, crisis skills, problem-solving and basic cognitive techniques to manage emotions, negative thinking and relapse prevention strategies.
Bempedoic acid was negative for mutagenicity in an in vitro Ames assay and negative for clastogenicity in the vitro human lymphocyte chromosome aberration assay. Bempedoic acid was negative in both in vivo mouse micronucleus and in vivo rat bone marrow micronucleus/liver comet assay. In a 2-year rat carcinogenicity study, Wistar rats were given oral doses of bempedoic acid at 3, 10 and 30 mg/kg/day. An increased incidence of liver hepatocellular adenomas and hepatocellular adenomas combined with carcinomas, thyroid gland follicular cell adenoma and follicular cell adenomas combined with carcinomas, and pancreatic islet cell adenomas combined with carcinomas were observed in male rats at the dose of 30 mg/kg/day (exposure equivalent to the maximum recommended human dose (MRHD), based on AUC). In a 2-year mice carcinogenicity study, CD-1 mice were given oral doses of bempedoic acid at 25, 75 and 150 mg/kg/day. Bempedoic acid-related increases in the incidence of liver hepatocellular adenomas, hepatocellular carcinomas and hepatocellular adenomas combined with carcinomas in male mice were observed at 75 and 150 mg/kg/day (exposures equivalent to the MRHD). Observations of liver and thyroid tumors are consistent with PPAR alpha agonism in rodents. The human relevance of pancreatic islet cell tumor findings is unknown.

In fertility and early embryofetal development study in rats, bempedoic acid was given orally to male and female rats at 10, 30 and 60 mg/kg/day. Males were dosed for 28 days prior to mating and females were dosed 14 days prior to mating through gestation day 7. No adverse effects on fertility were observed in females in the absence of maternal toxicity. No effects were observed on male fertility outcomes, but decreases in sperm counts were observed at 60 mg/kg/day (9 times the MRHD).
Infective endocarditis (IE) is an infection of the heart lining, primarily mediated by an endothelial injury causing activation of inflammatory cytokines and cells thus forming a thrombus creating a basis for bacteria adherence. The incidence rate is estimated to 2-10 cases per 100.000 people. In hospital mortality rates have been reported to 14-30%. Hence,it is therefore also worrisome that the incidence of IE has significantly increased in the adult population the last decades. Several reasons for this incline in incidence have been suggested: an increasing elderly population, an increase in the prevalence of prosthetic heart valves and cardiac electronic devices and better diagnostics technique.

Prosthetic valve endocarditis (PVE) is uncommon but severe complication to surgical and transcatheter valve replacement. Early studies have estimated PVE to account for up to 5% of all IE cases, however in recent studies PVE represents an increased proportion of overall infective endocarditis cases -estimated for almost 20%. Staphylococcus aureus is the most common cause of PVE. The mortality rate of PVE patients is significantly higher than native valve endocarditis (NVE) - in hospital mortality is estimated from 22% to 42% for PVE, and one year mortality for PVE is estimated to 21%-80%. The PVE diagnosis is often hard to verify as the symptoms of IE vary broadly.18Fflurodeoxyglukocose positron emission tomography/computed tomography (18F-FDGPET/ CT) is recommended as diagnostic imaging technique, however the sensitivity is 83.5% and specificity is 70.8%. The aim of this trial is to investigate whether 64Cu-DOTATATE will show uptake in the infected vegetations on the prosthetic heart valves and increase the accuracy of the right diagnosis.
PURPOSE: To obtain an easily administable seeded tablet preparation for oral administration easy to handle and purge, composed of an inner seed of easy-to- purge size containing a medicinally active ingredient and a quickly disintegrable compressed coating layer formed around the inner seed. CONSTITUTION: This tablet preparation is made up of a medicinally active ingredient-contg. inner seed miniaturized to 3-7mm in diameter so as to get easy to purge and a quickly disintegrable and/or dissolvable compressed coating layer with a thickness around the seed for compensating for the size of the inner seed. The coating layer, containing a vehicle (e.g. magnesium metasilicate aluminate) and a foamable component (e.g. malic acid), etc., is designed to disintegrate in the oral cavity by drinking water or saliva within one minute (pref. in 5-20s) and leave the inner seed tablet alone. The ratio of the diameter of the coating layer-contg. tablet preparation to the inner seed diameter is set at 1.5-5. This tablet preparation is made by granulation by conventional means into a raw tablet for the inner seed followed by compressive coating.  This tablet preparation can be easily administered by the aged, infants or hard- to-purge subjects.
A thixotropic microemulsion for the treatment of mammalian skin; and methods for the preparation thereof; and skin treatment formulations formed therefrom. The delivery system is an oil-in-water type emulsion that is especially useful as a vehicle for the delivery of hydrophobic and hydroalcoholic plant extracts having anti-irritant and/or anti-oxidant properties. The delivery system is comprised of natural, hydrophobic, chemically-modified type starches and polysaccharaides. Among the oils preferred in this embodiment are: mineral oil, petrolatum jelly and silicone oils, either added singly or in various combinations. Among surfactants employed as emulsifiers are: either a cationic detergent, e.g., benzalkonium chloride, an anionic, e.g., sodium lauryl sulfate, and a non-ionic detergent, e.g., Triton X-100 or combinations of oils and surfactants. The resulting emulsion is a semi-viscous and thixotropic gel, which is stable upon prolonged standing at ambient storage temperature.
Using a pragmatic cluster-randomized trial design, 20 Ontario cancer centres that provide care to patients with breast cancer will be randomly allocated to one of two arms: pro-active telephone toxicity management (intervention), or control (routine care). All patients with early stage (I-III) breast cancer who commence adjuvant or neo-adjuvant chemotherapy at participating institutions during the 6 to 12-month intervention period (will vary between centres depending on the number of incident cases) will be evaluated using Ontario healthcare administrative data. A sub-set of at least 25 patients at each participating institution will participate in a PRO sub-study involving the completion of standardized questionnaires to measure: a) severity of chemotherapy treatment toxicities; b) self-care for management of chemotherapy toxicities; c) self-efficacy (confidence) for managing symptoms; d) quality of life; and e) coordination of care. Patients participating in the PRO sub-study will be asked to provide consent to link their PRO data to Ontario healthcare administrative data so that correlations between the symptom self-assessments and Quality of Life (QoL) measures can be made with the administrative data on ED+H visits and use of supportive care medications. the investigators will compare the use of supportive care medications (i.e. anti-emetics, growth factors) by patients in the intervention and control arms to assess their influence on severity of chemotherapy-related toxicities as part of an exploratory sub-group analysis in patients \>65 years of age as administrative data on supportive care medication use is only available for this age group.
Formation of calcium oxalate (CaOx) crystal, the most common composition in kidney stones, occurs following supersaturation of calcium and oxalate ions in the urine. In addition to endogenous source, another main source of calcium and oxalate ions is dietary intake. In the intestinal lumen, calcium can bind with oxalate to form precipitates to be eliminated with feces. High intake of oxalate-rich foods, inappropriate amount of daily calcium intake, defective intestinal transporters for oxalate secretion and absorption, and gastrointestinal (GI) malabsorption (i.e., from gastric bypass surgery) can enhance intestinal oxalate absorption, thereby increasing urinary oxalate level and risk of kidney stone disease (KSD). The GI microbiome rich with oxalate-degrading bacteria can reduce intestinal oxalate absorption and urinary oxalate level. In addition to the oxalate-degrading ability, the GI microbiome also affects expression of oxalate transporters and net intestinal oxalate transport, cholesterol level, and short-chain fatty acids (SCFAs) production, leading to lower KSD risk. Recent evidence also shows beneficial effects of urinary microbiome in KSD prevention. This review summarizes the current knowledge on the aforementioned aspects. Potential benefits of the GI and urinary microbiomes as probiotics for KSD prevention are emphasized. Finally, challenges and future perspectives of probiotic treatment in KSD are discussed.
The present invention relates to the early treatment, including pre-diagnosis treatment, of sepsis and acute inflammatory syndromes such as systemic inflammatory response syndrome (SIRS) by PLA 2  and metalloprotease inhibitors to improve the performance of antibiotics and outcomes prior to and after confirmation of the diagnosis of sepsis and/or SIRS in a patient or subject. Additional embodiments include methods of treating sepsis, anthrax and severe acute respiratory syndrome coronavirus (SARS and SARS-CoV2) and related inflammatory syndromes and compositions, including pharmaceutical compositions and blood sample compositions. In further embodiments, the present invention is directed to embodiments which evidence that LY315920, LY333013 and related sPLA2 inhibitors are particularly effective COVID-19/cytokine release syndrome therapeutics-prophylactics. In embodiments, the PLA 2  inhibitor is varespladib (LY315920), methyl varespladib (LY333013), AZD2716-(R)-3-(5′-benzyl-2′-carbamoyl-[1,1′-biphenyl-3-yl)-2-methylpropanoic acid—as a racemic mixture or separately, as the “R” enantiomer), AZD Compound 4 (3-(5′-Benzyl-2′-carbamoylbiphenyl-3-yl)propanoic acid) and LY433771 ((9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl) oxyacetic acid), a pharmaceutically acceptable salt thereof or a mixture thereof. In embodiments, the metalloprotease inhibitor is Prinomastat, Batimastat, marimastat or vorinostat dosed alone or in combination with preferred sPLA2 inhibitors for the treatment of infection, inflammatory and wound conditions arising from various causes. Methods and compositions for achieving accelerated. treatment of wounds and burns, anthrax metalloprotease toxin (lethal factor) driven complications, ARDS, neo-natal and pediatric acute respiratory distress syndrome (neo-natal/pediatric ARDS), including, meconium aspiration syndrome are also disclosed.
Colorectal cancer (CRC) is a major cause of cancer-related deaths globally. While treatment advancements have improved survival rates, primarily through targeted therapies based on KRAS, NRAS, and BRAF mutations, personalized treatment strategies for CRC remain limited. Immunotherapy, mainly immune checkpoint blockade, has shown efficacy in various cancers but is effective in only a small subset of patients with CRC with deficient mismatch repair (dMMR) proteins or high microsatellite instability (MSI). Recent research has challenged the notion that CRC is immunologically inert, revealing subsets with high immunogenicity and diverse lymphocytic infiltration. Identifying precise biomarkers beyond dMMR and MSI is crucial to expanding immunotherapy benefits. Hence, exploration has extended to various biomarker sources, such as the tumor microenvironment, genomic markers, and gut microbiota. Recent studies have introduced a novel classification system, consensus molecular subtypes, that aids in identifying patients with CRC with an immunogenic profile. These findings underscore the necessity of moving beyond single biomarkers and toward a comprehensive understanding of the immunological landscape in CRC, facilitating the development of more effective, personalized therapies.
Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice at doses of up to approximately 600 mg/kg/day (53 times the MRHDD when compared on a body surface area basis) or in male and female rats at doses of up to approximately 100 mg/kg/day (18 times the MRHDD when compared on a body surface area basis). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 300 μg/mL, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation. In mice and rats these doses are 9 times and 0.7 times, respectively, the MRHDD when compared on a body surface area basis.
The invention comprises 2-benzyl-2-imidazoline compounds of the formula <FORM:1026778/C2/1> wherein R1 is methyl, R2 and R3 are independently hydrogen or methyl, and R4 is methyl whenever either or both of R2 and R3 are methyl, but otherwise is hydrogen; and acid addition salts thereof.  The imidazolines may be prepared by condensing a compound of the formula <FORM:1026778/C2/2> wherein the symbols R have the meanings stated above, or a suitable functional derivative thereof (e.g. ester, ortho-ester, acid halide, amide or nitrile), with ethylenediamine or a substance or substances which yield ethylenediamine. In an Example 2,5-dimethoxy-4,6-dimethyl - benzyl cyanide is heated with ethylenediamine in the presence of carbon disulphide to form 2-(21,51-dimethoxy-41,61-dimethylbenzyl -2-imidazoline.  The initial cyanide compound is obtained by chloromethylating 1,4-dimethoxy-2,6-dimethyl-benzene and reacting the substituted benzyl chloride so obtained with sodium cyanide.ALSO:Pre-shaving compositions comprise emulsions or solutions containing one or more compounds of the formula <FORM:1026778/A5-A6/1> wherein R1 is methyl, R2 and R3 are independently hydrogen or methyl, and R4 is methyl whenever either or both of R2 and R3 are methyl, but otherwise is hydrogen, or their pharmaceutically acceptable acid addition salts together with one or more of the following: alkylene diols or polyols, esters of fatty acids, alkali metal salts of fatty acids (the fatty acids in either case containing 14 to 18 carbon atoms) and polyvinylpyrrolidone. Besides polyvinylpyrrolidone, propylene glycol and isopropyl myristate are exemplified.  The acid addition salts may be derived from hydrochloric, hydrobromic, sulphuric, citric or succinic acid. Mixtures of water with ethanol or isopropanol are suitable as vehicles for the compositions which may additionally contain an acid such as adipic, citric or tartaric acid or a hydrolysable salt such as zinc chloride or aluminium chloride.  Other optional ingredients include solubilizers such as lactic acid diethylamide, astringents such as hamamelis extract or menthol, antiseptics such as boric acid, camphor, 8-hydroxyquinoline sulphate or p-hydroxybenzoic acid, and perfumes.
We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant.