anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
6-Demethyltetracycline antibiotics, e.g. 6-demethyl chlortetracycline are produced by culturing a tetracycline-antibiotic-producing strain of a species of the genus Streptomyces in a nutrient medium containing assimilable carbon and nitrogen sources, a methylation inhibitor being added to the fermentation medium gradually so that the ratio of the amount of nucleic acids and proteins formed related to that of the inhibitor added is maintained substantially constant during the course of the fermentation.  The methylation inhibitor may be a compound of general formula <FORM:1091046/C2/1> where R is a substituted or unsubstituted guanidine, thiazole, pyrimidine or pyrazine radical, e.g. p-aminobenzene sulphonyl guanidine, 2 - (p - aminobenzene sulphonyl) - 4,6-dimethyl pyrimidine, 2-(p-aminobenzene sulphonyl) - 6 - methoxy - pyridazine and 2 - (p-aminobenzene sulphonyl) - 4 - methyl - thiazole. For the production of 6-dimethyl chlorotetracycline or 6-demethylbromotetracycline, the fermentation medium contains chloride or bromide ions respectively in an amount greater than 50g /ml.  If 6-demethyltetracycline is desired, the fermentation medium should contain less than 50 g /ml. of chloride or bromide ions and/or contain chlorination or bromination inhibitors. Preferably, the whole of the methylation inhibitor is added during the first 24 hours of fermentation.
In r-CBT (20 sessions) a naturalistic setting is retained for treatment decisions. Treatment planning follows traditional theories about the effects of the interventions on factors maintaining the disorder, e.g. avoidance and exposure in anxiety disorder or reduced reinforcement of activities and behavioral activation in depression. Interventions are selected on the basis of common treatment manuals related to diagnoses, e.g. CBT for depression. Individual data from the behavioral analysis are used to taylor the techniques to the problem behaviors or dysfunctional thoughts of patients. Treatment process focuses mainly on the implementation of the manualized interventions adapted to the individual patient as recommended in the National guidelines for treatment of depression and anxiety disorders. Concomitant medication is allowed and will be controlled in statistical analyses.
This project will develop and test a low-cost approach to using health information technology (HIT), aimed at improving the effectiveness and cost-effectiveness of care for chronic health conditions that are amenable to home self-monitoring, that is easy to disseminate. In contrast to many other HIT-based interventions, the investigators will utilize commercial, off-the-shelf technology rather than custom, expensive HIT. The investigators are using hypertension control among persons with diabetes as our test case because there is documented need for improving control of hypertension in this high-risk population and studies estimate that improving hypertension control in diabetes is more cost-effective than most other medical interventions and possibly even cost-saving in direct health care dollars. This high-value return on investment is important for encouraging adoption, expansion, and dissemination of HIT innovations. Our intervention will involve recruiting 400 persons with diabetes and uncontrolled hypertension receiving care through Reliant Medical Group (RMG - formerly called Fallon Clinic). MODIFICATION (2/13) - Due smaller than anticipated numbers of eligible persons and low enrollment, we are expanding eligibility to include "prediabetics". Half of them will be randomly assigned to receive an automated blood pressure (BP) monitor capable of uploading readings through a computer, plus instruction on how to connect their monitors at home or in the clinic to upload their information into a popular and free commercial personal health record (PHR) system. These blood pressure data from the PHR will be transferred automatically into RMG's electronic health record (EHR) system and will alert RMG's existing team of care management nurses. Subjects whose blood pressure is uncontrolled will have their medication regimens intensified by these nurses according to protocols. Intervention subjects will receive regular outreach calls from the care management nurses if their blood pressure remains uncontrolled or they are not periodically uploading blood pressure readings. After one year, the investigators will compare outcomes between control and intervention subjects. Our primary outcomes will be change in mean blood pressure and proportion of subjects with controlled blood pressure. The investigators will also measure a range of secondary outcomes including costs of the intervention, medication utilization, and a variety of patient-reported outcomes. Furthermore, the investigators will interview and observe study subjects and care providers to gain a better understanding of factors affecting uptake and use of the intervention. The investigators will examine continued use of the intervention after formal study participation ends and will also measure uptake of the intervention by control subjects offered delayed entry at the end of the formal study. Lastly, the investigators will compare our study and findings to other, recent studies using HIT to improve hypertension control and develop a set of best practices and recommendations for future efforts in this area.
Data on restrictions and aggression events in the department will be collected throughout the two phases, and the participants will undergo an evaluation process. n addition, the subjects who participate in the intervention will wear an Empatica-E4 wristband to monitor autonomous metrics during their stay in the sensory stimulation room and will undergo a brief interview regarding their experience using the room.
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Cymbalta and should counsel them in its appropriate use. A patient Medication Guide About Using Antidepressants in Children and Teenagers is available for Cymbalta. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Cymbalta.
Chromatin remodelers are essential for regulating plant growth, development, and responses to environmental stresses. HIT4 (HEAT-INTOLERANT 4) is a novel stress-induced chromatin remodeling factor that has been less studied in abiotic stress and stress resistance, particularly in cotton. In this study, we conducted a comprehensive analysis of the members of the HIT4 gene family in Gossypium hirsutum using bioinformatics methods, including phylogenetic relationships, gene organization, transcription profiles, phylogenetic connections, selection pressure, and stress response. A total of 18 HIT4 genes were identified in four cotton species, with six HIT4 gene members in upland cotton. Based on the evolutionary relationships shown in the phylogenetic tree, the 18 HIT4 protein sequences were classified into four distinct subgroups. Furthermore, we conducted chromosome mapping to determine the genomic locations of these genes and visually represented the structural characteristics of HIT4 in G. hirsutum. In addition, we predicted the regulatory elements in HIT4 in G. hirsutum and conducted an analysis of repetitive sequences and gene collinearity among HIT4 in four cotton species. Moreover, we calculated the Ka/Ks ratio for homologous genes to assess the selection pressure acting on HIT4. Using RNA-seq, we explored the expression patterns of HIT4 genes in G. hirsutum and Gossypium barbadense. Through weighted gene co-expression network analysis (WGCNA), we found that GHHIT4_4 belonged to the MEblue module, which was mainly enriched in pathways such as DNA replication, phagosome, pentose and glucuronate interconversions, steroid biosynthesis, and starch and sucrose metabolism. This module may regulate the mechanism of upland cotton resistance to Verticillium wilt through DNA replication, phagosome, and various metabolic pathways. In addition, we performed heterologous overexpression of GH_D11G0591 (GHHIT4_4) in tobacco, and the results showed a significant reduction in disease index compared to the wild type, with higher expression levels of disease resistance genes in the transgenic tobacco. After conducting a VIGS (virus-induced gene silencing) experiment in cotton, the results indicated that silencing GHHIT4_4 had a significant impact, the resistance to Verticillium wilt weakened, and the internode length of the plants significantly decreased by 30.7% while the number of true leaves increased by 41.5%. qRT-PCR analysis indicated that GHHIT4_4 mainly enhanced cotton resistance to Verticillium wilt by indirectly regulating the PAL, 4CL, and CHI genes. The subcellular localization results revealed that GHHIT4_4 was predominantly distributed in the mitochondria and nucleus. This study offers preliminary evidence for the involvement of the GHHIT4_4 in cotton resistance to Verticillium wilt and lays the foundation for further research on the disease resistance mechanism of this gene in cotton.
Hypoxic pulmonary hypertension (HPH), a chronic condition affecting the cardiopulmonary system, has high mortality. Echinacoside (ECH) is a phenylethanoid glycoside, which is used to ameliorate pulmonary vascular remodeling and pulmonary vasoconstriction in rats. Accordingly, we aimed to explore the mechanism of ECH in preventing and treating HPH. Sprague Dawley rats were housed in a hypobaric hypoxia chamber for 28 days to obtain the HPH model. The experimental rats were randomly allocated into the following several groups: normoxia group, chronic hypoxia group, and ECH group. The therapeutic results of ECH (10, 20, and 40 mg/kg) showed that ECH reduced mPAP, Hb, Hct, and RVHI in HPH rats. Then this work employed label-free quantitative proteomic analysis, western blotting, and RT-PCR to investigate the mechanism by which ECH prevents HPH. The results found that in the chronic hypoxia group, the levels of ACSL1, COL6A1, COL4A2, COL1A1, and PC increased compared to the normoxia group. However, the opposite effect was observed in the chronic hypoxia group treated with ECH. The study indicates that the administration of ECH may slow the pathological progression of HPH by suppressing the inflammatory response, inhibiting smooth muscle cell proliferation, and minimizing the deposition of extracellular matrix.
This group received follow-up every 2-months for one year. Follow-up included questions about their heart disease progression and how well they had been able to engage in their doctor approved physical activity goal, which was the same as the control arm. Additionally, subjects in this arm were encouraged to use positive affect and self-affirmation techniques to motivate an increased level of participation in their physical activity goal. These subjects also received small token gifts to remind them of their study participation.
Halogenated tetracyclines are prepared by contacting an acid-stable tetracycline, particularly a 6-deoxy- or 6-deoxy-6-demethyl-tetracycline or a corresponding 4-desdimethylamino compound, or a mineral acid salt thereof, in a reaction-inert solvent, with at least a molar equivalent of a halogenating agent selected from perchloryl fluoride, bromine, chlorine, iodochloride, iodobromide, N-chloro, N-iodo and N-bromo lower alkanoic acid amides, hydrocarbon dicarboxylic acid imides and N-(lower alkanoyl) aniline, pyridinium perbromide and perchloride hydrohalides, lower alkyl hypochlorites, and 3-chloro-, 3-bromo-, 3,5-dichloro-and 3,5-dibromo-5,5-dimethyl-hydantoin.  When the tetracycline starting compound contains a 4-dimethylamino substituent, it is preferably reacted with a chlorinating, brominating or iodinating agent in the presence of an acid catalyst.  When perchloryl fluoride is used as fluorinating agent it is preferably used in the presence of an alkali metal lower alkoxide or an alkali or alkaline earth metal hydroxide, bicarbonate or carbonate.  When an equimolar amount of chlorinating, brominating or iodinating agent is employed the principal product is the corresponding 11a-halotetracycline; the desdimethylamino compounds give with a 2 : 1 molar ratio the 7,11a-dihalo compound and with a 3 : 1 molar ratio the 7,9,11a-trihalo compounds; the dimethyl amino compounds give with two moles of a chlorinating agent the corresponding 7,11a-dichlorotetracycline but with a brominating or iodinating agent the corresponding 7-bromo or 7-iodo tetracycline is obtained.  When the starting compound is an 11a-halo tetracycline p treatment with an equimolar amount of halogenating agent gives, when the 11a halogen is bromine or iodine, a 7-monohalo tetracycline and when the 11a-halogen is chlorine or fluorine the product is a 7-halo-11a-chloro- or fluorotetracycline.  Reaction of the starting material with perchloryl fluoride gives an 11a-fluorotetracycline. The 11a-halogen may be removed from the final products by conventional procedures, particularly by hydrogenation.  Products whose preparation is described include 11a-chloro-, 11a-bromo-, 11-fluoro-, 11a-iodo and 7,11a-dichloro-6-deoxy-6-demethyl tetracycline, 11a-bromo-6-deoxytetracycline hydrobromide, 11a - bromo - 6 - deoxy - 5 - oxytetracycline, 7,9,11a-tribromo-, 7,9-dibromo-11a-fluoro-, 7-bromo-11a-fluoro-, and 7,9-diiodo-11a-fluoro-6-deoxy - 6 - demethyl - 4 - desdimethylamino - tetracycline, 7, 9 - dibromo - 11a - fluoro - 6 - deoxy - 4 - desdimethylaminotetracycline, and 11a-bromo-6-deoxy-tetracycline.ALSO:Pharmaceutical preparations comprise an 11a-halogenated acid-stable tetracycline (see Group IV (b)) and a pharmaceutical carrier.  The preparations may be made up as oral suspensions, as tablets or capsules or as solutions suitable for parenteral administration, and may also contain ascorbic acid.
Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an equal volume initial loading dose of 0.9% saline over 10 min after the induction of anaesthesia followed by an equal volume continuous infusion until the end of surgery.
Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia.
The invention belongs to the technical field of anti-tumor medicines made from nano materials and discloses a targeted anti-hepatoma nanoparticle which is high in efficiency, low in toxicity and loaded by nano-selenium and a preparation method and an application thereof in preparing anti-tumor medicines. The nano particle is reduced by a reducing agent to obtain nano-selenium which loads anisomycin and hyaluronic acid. According to the nano particle, anisomycin originated from bacteria is loaded by nano-selenium for the first time, so that the solubility, the stability and the absorption rate are improved, and the use level is reduced. Meanwhile, molecules are selectively targeted to tumors of liver through a polysaccharide framework structure of hyaluronic acid to specifically kill hepatoma carcinoma cells, especially liver cancer stem cells, so that the purpose of specifically killing hepatoma carcinoma cells is realized and the toxic and side effects on normal cells in an effective pharmaceutical dosage range are reduced. The nano particle provided by the invention is simple to prepare, and raw materials are low in cost and easily obtained. No other assistant reagents need to be added in the process, and the product can be directly stored and used.
BACKGROUND: Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS.
METHODS AND RESULTS: Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors.
CONCLUSIONS: OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.
Intervention arm receives a counseling phone call 3 to 4 weeks after enrollment. The call is from a health educator intended to assist with contraception.
Maximal exercise capacity is reduced at altitude or during hypoxia at sea level. It has been suggested that this might reflect increased right ventricular afterload due to hypoxic pulmonary vasoconstriction. We have shown previously that the pulmonary vascular sensitivity to hypoxia is enhanced by sustained isocapnic hypoxia, and inhibited by intravenous iron. In this study, we tested the hypothesis that elevated pulmonary artery pressure contributes to exercise limitation during acute hypoxia. Twelve healthy volunteers performed incremental exercise tests to exhaustion breathing 12% oxygen, before and after sustained (8-h) isocapnic hypoxia at sea level. Intravenous iron sucrose (n = 6) or saline placebo (n = 6) was administered immediately before the sustained hypoxia. In the placebo group, there was a substantial (12.6 ± 1.5 mmHg) rise in systolic pulmonary artery pressure (SPAP) during sustained hypoxia, but no associated fall in maximal exercise capacity breathing 12% oxygen. In the iron group, the rise in SPAP during sustained hypoxia was markedly reduced (3.4 ± 1.0 mmHg). There was a small rise in maximal exercise capacity following sustained hypoxia within the iron group, but no overall effect of iron, compared with saline. These results do not support the hypothesis that elevated SPAP inhibits maximal exercise capacity during acute hypoxia in healthy volunteers.
This study will evaluate a personalized elevated cardiac pacing rate as a treatment for symptomatic heart failure with preserved ejection fraction (LVEF ≥50%). The intervention is designed to improve health status and other signs and symptoms of heart failure in patients with HFpEF. After enrollment, baseline data will be collected, and subjects will then have a pacemaker implanted. Following successful implant, and prior to pre-hospital discharge, subjects will be randomized 1:1 to receive ventricular pacing at a lower rate of 30 bpm (VVI-30; control group) or dual chamber pacing at a personalized elevated cardiac pacing rate determined by their height and baseline LVEF (treatment group). Subjects will complete 2-month and 6-month visits where data will be collected. At the 6-month visit the control group will also be programmed to their personalized elevated cardiac pacing rate. Subjects will complete 8-month and 12-month visits where data will be collected. Following the 12-month visit, additional long-term follow-up visits will occur annually until study completion. The estimated study duration is approximately 3.5 years representing an estimated 30-month enrollment period and 12-month follow-up period.
Subjects received 100 mg multiple dose of BI-409306 (film-coated tablet/s), administered orally once on day 3 to day 9. A wash-out period of 48 hours was included before the second dose (first does of multipled dose segment) was administered. Subjects were considered for both single dose (following first dose) and multiple dose purposes.
Absorption of 3 doses of 9 ug cyano-B12 and 9 ug hydroxo-B12 for two days (the CobaSorb test). No drugs given.