anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
COPD is a disease in which the lung airways are partly damaged and obstructed, making it difficult to breathe. COPD is the fourth leading cause of death in the United States. Symptoms include coughing, excess mucus production, shortness of breath, wheezing, and chest tightness. Treatment usually includes inhaled bronchodilator or steroid medications that work by relaxing the muscles around the lung airways and reducing inflammation. Zileuton, a medication that is used to prevent asthma symptoms, may be beneficial in treating people who experience COPD exacerbations. Zileuton works by blocking the formation of substances that cause inflammation, fluid retention, and constriction in the lungs. The purpose of this study is to evaluate the effectiveness of zileuton at reducing the length of a hospital stay for adults who are hospitalized for a COPD exacerbation.

This study will enroll adults who are admitted to the hospital due to severe COPD symptoms. Participants will be randomly assigned to receive either zileuton or placebo four times a day for up to 14 days. While in the hospital, lung function testing and urine collection will occur. Study visits will occur at Days 14 and 30, and will include lung function testing, a medical history review, and a study drug adverse effects review.
Chronic alcohol consumption, an important risk factor for diseases and deaths, can cause intestinal microbiota dysbiosis and increase the infection of some opportunistic pathogens. However, the current studies on the effects of alcohol-induced intestinal microbiota dysbiosis on gut colonization of Klebsiella pneumoniae are still scarce. In the present study, we established a binge-on-chronic alcohol model in mice to identify the characteristics of alcohol-induced intestinal microbiome and metabolite dysbiosis using multi-omics and explored the effects and potential mechanisms of these dysbioses on the intestinal colonization of K. pneumoniae. The results show that chronic alcohol consumption alters the diversity and composition of gut microbiota (including bacteria and fungi), decreases the complexity of the interaction between intestinal bacteria and fungi, disturbs the gut metabolites, and promotes the colonization of K. pneumoniae on the gut of mice. The relevance analyses find that alcohol-induced gut microbiome dysbiosis has a strong correlation with the alteration of secondary bile acids. In vitro results suggest that the high concentration of lithocholic acid, a secondary bile acid, could significantly inhibit the proliferation of K. pneumoniae, and the adhesion of K. pneumoniae to Caco-2 cells. Our results indicate that alcohol-induced microbiome dysbiosis contributes to decreased levels of secondary bile acids, which was one of the main reasons affecting the colonization of K. pneumoniae in mice's intestines. Some secondary bile acids (e.g., lithocholic acid) might be a potential drug to prevent the colonization and spread of K. pneumoniae.IMPORTANCEAlcohol is one of the most commonly misused substances in our lives. However, long-term heavy drinking will increase the colonization of some opportunistic pathogens (e.g., Klebsiella pneumoniae) in the body. Here, we revealed that binge-on-chronic alcohol consumption disrupted the balance between gut bacteria and fungi, induced the gut microbiome and metabolites dysbiosis, and promoted the colonization of K. pneumoniae in the intestine of mice. In particular, alcohol-taking disrupted intestinal bile acid metabolism and reduced the lithocholic acid concentration. However, a high concentration of lithocholic acid can protect against intestinal colonization of K. pneumoniae by inhabiting the bacterial growth and adhesion to the host cell. Hence, regulating the balance of gut microbiota and intestinal bile acid metabolism may be a potential strategy for reducing the risk of K. pneumoniae infection and spread.
FIELD: organic chemistry, medicine, pharmacy. SUBSTANCE: invention relates to novel compounds with structure associated with 1,3-propanediol that are able to penetrate across lipid barriers. Invention proposes compound of the formula (I)   wherein R 1  means acyl group or saturated alcohol group as derivative of C 12-30 ,-fatty acid but preferably C 16-30 -fatty acid and desirable with two or more double bonds at cis- or trans-position; R 2  means hydrogen atom, acyl group or saturated alcohol group that similar or distinct from that indicated for R 1 , either is a biologically active residue distinct from niacin residue being its chemical structure allows binding with 1,3-propanediol through available carboxyl, alcoholic or amino-group. Compounds with structure associated with 1,3-propanediol that are able to penetrate through lipid barriers relate to the formula (I) wherein R 1  means acyl group or saturated alcohol group as derivative from C 12-30 ,-fatty acid but preferably C 16-30 -fatty acid being desirable with two or more double bonds at cis- or trans-position and R 2  means hydrogen atom, acyl group or saturated alcohol group that is similar or distinct from that indicated for R 1 , either is biologically active residue distinct from niacin being its chemical structure allows binding with 1,3-propanediol through available carboxyl, alcoholic or amino- group wherein phosphate, succinate or other bifunctional acid group is added between group R 1  and/or R 2  and residue of 1,3-propanediol, in part, when R 2  is a biologically active residue with hydroxyl- or amino- functional groups. Invention relates also to medicinal preparation used for therapy and delivery of medicinal agent or other active substance through lipid membranes in body or showing additional or complementary, or synergistic effect in common with R 1  and comprising compound of the formula (I) as an active agent. Invention provides preparing novel compounds eliciting ability to penetrate through lipid barriers. EFFECT: valuable biological and medicinal properties of substances. 15 cl, 51 ex
This study is a multicenter (more than 1 site), placebo-controlled (compared to placebo), randomized (participants assigned study drug by chance), double-blind (neither the participant nor the physician know the assigned study drug), parallel-group comparison (comparison for each group at the same time) study. The study period consists of 4 phases: the observation phase, double-blind phase, exit period and follow-up period. After the double-blind phase, the participants will be transferred to the continuous treatment study. The observation phase which is started after informed consent consists of the washout period (non-treatment period with migraine preventive medication: at least 2 weeks) and baseline determination period (at least 4 weeks). The participants who complete the observation phase and meet the inclusion criteria will be randomly assigned to the topiramate 50 milligram (mg) group, topiramate 100-mg group or placebo group after registration. The double-blind phase consists of the titration period (dose-escalation, 4 weeks) and fixed-dose period (18 weeks). In the titration period, starting from 1 topiramate 25-mg tablet or 1 topiramate 25-mg placebo tablet once daily (1 tablet in the evening), the dose will be increased by 1 tablet every week up to twice daily (2 tablets in the morning, 2 tablets in the evening). After that, the twice-daily treatment (2 tablets in the morning, 2 tablets in the evening) will be continued for 7 days from Day 22 to Day 28. In the fixed-dose period, the topiramate 25-mg tablets or topiramate 25-mg placebo tablets at the same dose as that in the final treatment in titration period will be continued. The participants who are not transferred to the continuous treatment study after completion of the double-blind phase or after discontinuation during the double-blind phase will be transferred to the exit period (up to 1 week).The participants who complete the exit period will be transferred to the follow-up period, and a follow-up of the participant's safety and headache symptoms such as the migraine period rate will be conducted for 4 weeks after the completion of investigational treatment. Meanwhile, the participants who complete the double-blind phase or those who discontinue the study at Week 4 or later in the fixed-dose period during the double-blind phase due to lack of efficacy and give consent to transfer to the continuous treatment study will be transferred to the transfer period (up to 3 weeks) under blind conditions.
PURPOSE:To improve the degree of freedom for formation of a system by securing the star LAN connection among plural display devices which contain the frame memories that store once the image information in an image process controller and the means which display the images as the visibel ones. CONSTITUTION:The medical image information stored in a filing device 12 are fetched to an image process controller 10 via a transmission line of the comparatively low capacity. Then the image information are stored in a memory of the comparatively small capacity of the controller 10 and undergoes a prescribed image process. These processed image information are displayed as the visible images via the display means DPM1-DPMn which are radially arranged at the places compartively distant from each other. Thus it is possible to improve the degree of freedom and the economy related to a transmission circuit line for forming a medical image information system which stores and then retrieves and displays the medical image information. At the same time, many display means can be arranged and many pieces of image information can be retrieved and displayed at one time.
Participants to brush with 1.5 g of NaF/KNO3 toothpaste containing 1450 ppm F - EU level as NaF. All study treatments contain 5% w/w KNO3.
1. A method for treating a patient suffering from or susceptible to treatment resistant major depression, comprising administering to said patient an effective amount of a first component, which is olanzapine or a pharmaceutically acceptable salt thereof in combination with an effective amount of a second component, which is fluoxetine or a pharmaceutically acceptable salt thereof. 2. A method for treating a patient suffering from or susceptible to treatment resistant major depression comprising administering to said patient an effective amount of a first component, which is olanzapine in combination with an effective amount of a second component, which is hydrochloride fluoxetine. 3. A method of claim 1, where administration of the compounds is oral. 4. A method of claim 1, wherein the ratio of olanzapine to fluoxetine by weight is selected from the group consisting of 1/5, 6/25, 12.5/25, 25/50, 17.5/50 and 25/75. 5. A method for treating a patient partially responding to treatment of major depression comprising administering to said patient an effective amount of a first component, which is olanzapine or a pharmaceutically acceptable salt thereof in combination with an effective amount of a second component, which is fluoxetine or a pharmaceutically acceptable salt thereof. 6. A method for treating a patient partially responding to treatment of major depression comprising administering to said patient an effective amount of a first component, which is olanzapine in combination with an effective amount of a second component, which is hydrochloride fluoxetine. 7. A method of claim 5, where administration of the compounds is oral. 8. A method of claim 5, wherein the ratio of olanzapine to fluoxetine by weight is selected from the group consisting of 1/5, 6/25, 12.5/25, 25/50, 17.5/50 and 25/75. 9. A method for attenuating the adverse events associated with treating a patient suffering from or susceptible to treatment resistant major depression, or partially responding to treatment of major depression, comprising administering to said patient an effective amount of a first component, which is olanzapine in combination with an effective amount of a second component, which is fluoxetine. 10. A method of claim 9, where administration of the compounds is oral. 11. A method of claim 9, wherein the ratio of olanzapine to fluoxetine by weight is selected from the group consisting of 1/5, 6/25, 12.5/25, 25/50, 17.5/50 and 25/75.
BACKGROUND/AIM: Exosome exchange between cancer cells or between cancer and stromal cells is involved in cancer metastasis. We have previously developed in vivo color-coded labeling of cancer cells and stromal cells with spectrally-distinct fluorescent genetic reporters to demonstrate the role of exosomes in metastasis. In the present study, we studied exosome transfer between different pancreatic-cancer cell lines in vivo and in vitro and its potential role in metastasis.
MATERIALS AND METHODS: Human pancreatic-cancer cell lines AsPC-1 and MiaPaCa-2 were used in the present study. AsPC-1 cells contain a genetic exosome reporter gene labeled with green fluorescent protein (pCT-CD63-GFP) and MiaPaCa-2 cells express red fluorescent protein (RFP). Both cell lines were co-injected into the spleen of nude mice (n=5) to further study the role of exosome exchange in metastasis. Three weeks later mice were sacrificed and tumors at the primary and metastatic sites were cultured and observed by confocal fluorescence microscopy for exosome transfer.
RESULTS: The primary tumor formed in the spleen and metastasized to the liver, as observed macroscopically. Cells were cultured from the spleen, liver, lung, bone marrow and ascites. Transfer of exosomes from AsPC-1 to MiaPaCa-2 was demonstrated in the cultured cells by confocal fluorescence microscopy. Moreover, cell fusion was also observed along with exosome transfer. Exosome transfer did not occur during in vitro co-culture between the two pancreatic-cancer cell lines, suggesting a role of the tumor microenvironment (TME) in exosome transfer.
CONCLUSION: The transfer of exosomes between different pancreatic-cancer cell lines was observed during primary-tumor and metastatic growth in nude mice. This cell-cell communication might be a trigger of cell fusion and promotion of cancer metastasis. Exosome transfer between the two pancreatic-cancer cell lines appears to be facilitated by the TME, as it did not occur during in vitro co-culture.
The present invention synthetically solves a medical compound scattering problem of a conventional technology which requires a lot of manpower and consumes a lot of chemical solutions since a medical compound scattering work is cumbersome and is periodically performed. As an antifungal non-woven fabric sheet for disease prevention and pest control in which a continuous medical compound is impregnated having a maximized effective pest control period and efficiency of sterilization or killing insects, etc. as a layered structure. In the layered structure, a medical compound coating layer is bonded using upper and lower water soluble adhesive layers between non-woven fabric sheets. The non-woven fabric sheets are formed of an outer skin based on a permeable non-woven fabric with gas-permeable properties on one side to be touched with the outside and an inner skin based on a waterproof film coating layer on the other side. The medical compound coating layer is obtained by mixing and impregnating a medical compound for disease prevention and pest control such as disinfectant or the like and absorbent resins. The adhesive layers comprise long and width directional binding wires in a grid structure. The antifungal non-woven fabric sheet for the disease prevention and pest control in which the continuous medical compound is impregnated can be easily mounted on a pen or the like by using length and width directional binding wires in a grid structure. Accordingly, the antifungal non-woven fabric sheet can perform disease prevention and pest control with indirect scattering of the medical compound in an enclosed space or an opened space without a separate disinfection device and the direct scattering of the medical compound when being widely used such as a cover sheet for disease prevention, a disinfection mat, a tree trunk protective guard, and the like, wherein the cover sheet for disease prevention prevents a bacteria such as a virus or the like from being entered from the outside by covering the external side of the pen where cows, pigs, and the like are raised or a plastic greenhouse, and the like, and disinfecting the same; the disinfection mat prevents a bacteria on the bottom of shoes of people who enter the pen or the like from being entering a farm; and the tree trunk protective guard performs disease prevention and pest control for trees.
he primary objective of the dose escalation part is to determine the MTD and/or RP2D of selumetinib in combination with gefinitib. Once MTD and/or RP2D has been determined in the phase Ib dose escalation phase, study drug selumetinib with combination of 250mg QD dose of gefitinib will be further evaluated in a phase II dose expansion phase of the study. The purpose of the dose expansion phase is to evaluate the efficacy of selumetinib in combination of gefitinib and to further characterize the safety, and tolerability of the combination.

20 patients will be required in the phase II period. In the expansion phase, 10 patients with T790M and 10 patients without T790M will be enrolled. It is assumed that 20% response rate is the target of clinical interest. If the true response rate is 20%, the probability of observing no responses in a random sample of 10 patients is 0.107. The false negative rate for detecting a true 20% response rate in each cohort is approximately 10%. Each cohort will be enrolled 10 patients to evaluate the efficacy; therefore 20 patients will be enrolled in dose expansion part. Patients treated at the MTD and/or RP2D during the phase Ib will be considered as part of the required number of patients in the phase II. Patients at the MTD or RP2D cannot contribute to the 20 patients require for phase II part.
The popularity and usage of synthetic cannabinoids (SCs) are increasing due to their easy accessibility and psychoactive effects worldwide. Studies on cannabinoids on leukemic stem cells (LSC) and hematopoietic stem cells (HSCs), which are the precursors of leukemia cells, generally depend on the natural cannabinoid delta-9-THC. As there is only a limited number of studies focusing on the results of SC applications, the reflections upon LSCs have to be clarified. In this study, biological responses and antileukemic effects of JWH-018-one of the first produced and widely used SCs-were evaluated upon leukemia cells. Whether JWH-018 exhibited a preventive effect on both leukemic and HSCs was evaluated by presenting a therapeutic approach for the first time in the literature. Cells were analyzed in case of cell proliferation, apoptosis, and transcriptional expression profiling of some significant JAK/STAT and AKT/mTOR pathways, apoptotic, cell cycle regulation, and epigenetic chromatin remodeling-related genes following JWH-018 treatment. In conclusion, however, further studies are still needed upon both HSCs and LSCs to illuminate the effects of SCs on leukemogenesis on chronic myeloid leukemia (CML) more clearly; we consider that the JWH-018 can provide a therapeutic effect on the pathogenesis of leukemia and particularly upon LSCs and SCs might have therapeutic potential in addition to current therapy.
* Pregnancy Test: 



\- Female patients of childbearing potential must have had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial Zenatane prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for Zenatane. The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the two tests must be at least 19 days. 

\- For patients with regular menstrual cycles, the second pregnancy test must be done during the first 5 days of the menstrual period immediately preceding the beginning of Zenatane therapy and after the patient has used 2 forms of contraception for 1 month. 

\- For patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding, the second pregnancy test must be done immediately preceding the beginning of Zenatane therapy and after the patient has used 2 forms of contraception for 1 month. 

\- Each month of therapy, patients must have a negative result from a urine or serum pregnancy test. A pregnancy test must be repeated each month, in a CLIA-certified laboratory, prior to the female patient receiving each prescription.

  * Lipids: Pretreatment and follow-up blood lipids should be obtained under fasting conditions. After consumption of alcohol, at least 36 hours should elapse before these determinations are made. It is recommended that these tests be performed at weekly or biweekly intervals until the lipid response to Zenatane is established. The incidence of hypertriglyceridemia is one patient in four on Zenatane therapy (see WARNINGS: Lipids). 
  * Liver Function Tests: Since elevations of liver enzymes have been observed during clinical trials, and hepatitis has been reported, pretreatment and follow-up liver function tests should be performed at weekly or biweekly intervals until the response to Zenatane has been established (see WARNINGS: Hepatotoxicity). 
  * Glucose: Some patients receiving Zenatane have experienced problems in the control of their blood sugar. In addition, new cases of diabetes have been diagnosed during Zenatane therapy, although no causal relationship has been established. 
  * CPK: Some patients undergoing vigorous physical activity while on Zenatane therapy have experienced elevated CPK levels; however, the clinical significance is unknown. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity. In a clinical trial of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne, transient elevations in CPK were observed in 12% of patients, including those undergoing strenuous physical activity in association with reported musculoskeletal adverse events such as back pain, arthralgia, limb injury, or muscle sprain. In these patients, approximately half of the CPK elevations returned to normal within 2 weeks and half returned to normal within 4 weeks. No cases of rhabdomyolysis were reported in this trial.
The control group will be treated with the same post-operative protocol, but with 0.9% saline instead of DMSO. On the seventh post-operative day, the patient will be guided to set 10 cc 0.9% saline soaked gauze compresses on the breast, twice a day for 20 minutes, for the term of 6 weeks. This treatment will be holed for 24 hours on tissue expander inflation dates. A repeated course of compresses will be taken after adjuvant radiotherapy, starting 24 hours after the last therapy.
Patients aged 18 to 40 in good physical condition Eastern Cooperative Oncology Group (ECOG) scale 0-1, who are set to receive neoadjuvant chemotherapy will be selected. Criteria for entry into the study include proper liver, kidney and bone marrow function as well as heart ejection fraction of ≥ 50%. Treatment will be carried out according to 4 x AC regimen (doxorubicin 60 mg/ m2 cyclophosphamide 600 mg/ m2 i.v. every 21 or every 14 days + pegfilgastrim) followed by 12 x paclitaxel 80 mg/ m2 every 7 days and in the case of HER2 positive tumors trastuzumab ± pertuzumab (according to SPC).