anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The invention comprises compounds of the formula X-CH2-NH-NHCH3 and acid (including ascorbic acid) addition salts thereof, wherein X represents a mononuclear or polynuclear oxygen-, nitrogen- and/or sulphur containing heterocyclic residue which may contain one or more alkyl, trifluoromethyl, cyano, mercapto alkylthio, amino, acylamino, ureido, alkylsulphonylamino, guanidino, amidino, aminoalkyl, carbamoyl, allophanoyl, sulphamoyl, nitro, 2-methylhydrazinomethyl, acyl and phenyl groups or halogen atoms, the preparation thereof by either reacting methylhydrazine, or a methylhydrazine in which hydrazine group is partially substituted by protecting groups such as acyl, alkoxycarbonyl, benzyloxycarbonyl, or benzyl, with an agent which yields the moiety X1-CH2-, wherein X1 has the meaning as X or is convertible into X, or methylating a hydrazine which contains such a moiety as a substituent, or such a substituted hydrazine which is partially further substituted by protecting groups such as acyl, alkoxycarbonyl, benzyloxycarbonyl or benzyl, and, in either case if necessary converting the moiety X1 in the product into X and, also if necessary, splitting off any protecting groups present and, if desired, converting the base into its acid addition salt.  In a variation the agent in the above process may be substituted for an appropriate aldehyde and the resulting hydrazone catalytically hydrogenated.  In a further variation 1,2-di(alkoxycarbonyl) - hydrazine is methylated and then reacted with the agent which yields the residue X1-CH2- and the alkoxycarbonyl groups split off from the products.  The conversion of X1 to X may be effected at any point. Carbamoyl compounds may be prepared from the carboxylic acids either by direct condensation or through the acid halide or anhydride, or from the nitriles; acylamino compounds from the amines derived in turn by reduction of nitro or azo compounds, ureido compounds from cyanates and isocyanates; guanidino compounds from cyanamides and amidino compounds from the nitriles through the imido ethers or imido halides.  5 - [(2 - Methyl - 1,2 - di(benzyloxycarbonyl)-hydrazino) - methyl] thiophene - (2) - carboxylic acid chloride was prepared from the free acid, in turn prepared from the methyl ester, in turn prepared from 1-methyl-1,2-di(benzyloxycarbonyl) - hydrazine and 5 - (chloro - methyl)-thiophene - (2) - carboxylic acid methyl ester. The above acid chloride was also converted into the acyl isothiocyanate. Pharmaceutical compositions comprise the compounds of the invention and an inert carrier and may be in the form of tablets, dragees, suppositories, capsules, suspensions or emulsions. The compounds are cystostatic agents.
PURPOSE OF REVIEW: This review aims to summarize recent studies that highlight the complex relationship between nutrition, carbohydrate, insulin provision and glycaemic control in the critically ill patient population.
RECENT FINDINGS: Results of observational studies concur to support early hypoglycaemia and persisting hyperglycaemia as life-threatening events. In contrast, interventional studies indicate that early macronutrient restriction appears to reduce the benefits related to insulin therapy. This restriction is however associated with improved outcomes in itself. The potential role of modified enteral solutions as an adjunctive treatment to attenuate hyperglycaemia warrants further research. The selection of a therapeutic modality may also differ according to the characteristics of the setting, such as the nurse-to-patient ratio, the type and accuracy of meters, including near-continuous glucose monitoring and the availability of computer-guided protocols.
SUMMARY: There appears to be significant interplay between nutrition, including carbohydrate provision, blood glucose control and clinical outcomes. Individualized care is probably needed to define the optimal glucose target and nutritional intervention. This can differ according to the preexistence of chronic hyperglycaemia, the timing from the onset of critical illness and the clinical condition itself.
Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who have advanced liver disease (decompensated cirrhosis by Child-Pugh score and no known cause of hepatitis other than HBV), a HBV viral load of at least 1 million copies/mL blood, and at least one year of therapy with lamivudine will be treated with open-label adefovir dipivoxil 10 mg daily and lamivudine 150 mg bid to evaluate the safety and efficacy of this regimen in this patient group and to obtain specimens for studies of immune responses to HBV in HIV-infected patients. Additionally the kinetics of viral load response to adefovir will be assessed. Specimens will be stored for possible use in evaluating HBV and HIV resistance to adefovir. L-carnitine supplementation will be used only if low serum carnitine levels are documented. Patients will be followed for HBV viral load response to adefovir for 48 weeks with possible extension. The primary study endpoints will be HBV viral load at week 24 (per-protocol patients) and DAVG at week 24 (intent-to-treat patients). Adefovir will be discontinued for toxicity; there will be no dose reduction. Up to 30 subjects will be enrolled.
For predominantly enhanced tumors with volume of 8 cc or less, only 1 Cleveland Multiport Catheter (CMC) will be placed and convection-enhanced delivery (CED) will be performed over a 4-hour period within an MRI scanner, with the goal of complete tumor coverage (as evidenced by tracer distribution on MRI). The initial rate will be 1.20 ml/hour (5.0 microliters/minute/microcatheter) and infusion will be monitored by intermittent MRI imaging. The rate may be adjusted upwards during the infusion, in the event of incomplete tumor coverage, or downwards, if new mass effect is apparent. Following completion of the 4-hour infusion, the CMC will be removed. The initial rate for each subsequent patient may be adjusted upwards in increments of up to 5 microliters/minute/microcatheter based upon the tumor coverage and safety characteristics of the previously treated patients.
Like many bacteria, yeast species can form biofilms on several surfaces. The properties and way of life in these communities are distinct from those of free-swimming populations. Candida albicans colonizes the surfaces of catheters, prostheses and epithelia, developing biofilms that are extremely resistant to antifungal drugs. Here, we show that different biofilm populations of C.  albicans display very similar transcript profiles. Biofilm and planktonic cultures produced under different conditions of nutrient flow, aerobiosis or carbon-source concentration were compared by overall gene-expression correlation.  Correlation was much higher between biofilms than planktonic populations irrespective of growth conditions. A cluster of 325 differentially expressed genes was identified. In agreement with the over-representation of amino acid biosynthetic pathways in this cluster, Gcn4p, a regulator of amino acid starvation responses, is required for normal biofilm growth. In an effort to identify biofilm-related genes that are independent of mycelial development, we studied the transcriptome of hyphae switched and un-switched biofilms produced by wild-type and cph1/cph1 efg1/efg1 strains, respectively. Biofilm versus planktonic comparisons in both strains yielded a set of 442 differentially expressed genes, of which 317 were expressed independently of hyphae formation. This subset reveals activation of the sulfur-amino acid biosynthesis pathway as a biofilm-related feature. Our work shows not only that expression of some cell attributes, e.g. amino acid metabolism, change during biofilm growth, but also that the overall transcriptome moves to characteristic expression values. Together, the data suggest transcriptome invariance in different environments as a salient property of C. albicans biofilm populations.
Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include (i) proinflammatory effectors of the innate immune system, (ii) coagulation factors, and (iii) targets specifically associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, wherein the targets included in group (iii) are neither a proinflammatory effector of the immune system nor a coagulation factor. When the multispecific antagonist reacts specifically with a target associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, it also binds specifically with at least one proinflammatory effector of the immune system or at least one coagulation factor. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system, such as a receptor or antigen of B cells, T cells, neutrophils, monocytes and macrophages, and dendritic cells, a modulator of coagulation, or a proinflammatory cytokine. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system or coagulation factors. Such diseases more particularly include acute and chronic inflammatory disorders, autoimmune diseases, giant cell arteritis, septicemia and septic shock, coagulopathies (including diffuse intravascular coagulation), neuropathies, graft versus host disease, infectious diseases, acute respiratory distress syndrome, granulomatous diseases, transplant rejection, asthma, cachexia, myocardial ischemia, and atherosclerosis. Other diseases also responsive to these therapies include cancers and conditions with pathological angiogenesis.
Ulcerative colitis is a chronic disease with colonic mucosa injury. Nitazoxanide is an antiprotozoal drug in clinic. Nitazoxanide and its metabolite tizoxanide have been demonstrated to activate AMPK and inhibit inflammation, therefore, the aim of the present study is to investigate the effect of nitazoxanide on dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. Oral administration of nitazoxanide ameliorated the symptoms of mice with DSS-induced colitis, as evidenced by improving the increased disease activity index (DAI), the decreased body weight, and the shortened colon length. Oral administration of nitazoxanide ameliorated DSS-induced intestinal barrier dysfunction and reduced IL-6 and IL-17 expression in colon tissues. Mechanistically, nitazoxanide and its metabolite tizoxanide treatment activated AMPK and inhibited JAK2/STAT3 signals. Nitazoxanide and tizoxanide treatment increased caudal type homeobox 2 (CDX2) expression, increased alkaline phosphatase (ALP) activity and promoted tight junctions in Caco-2 cells. Nitazoxanide and tizoxanide treatment restored the decreased zonula occludens-1(ZO-1) and occludin protein levels induced by LPS or IL-6 in Caco-2 cells. On the other hand, nitazoxanide and tizoxanide regulated macrophage bias toward M2 polarization, as evidenced by the increased arginase-1expression in bone marrow-derived macrophages (BMDM). Nitazoxanide and tizoxanide reduced the increased IL-6, iNOS and CCL2 pro-inflammatory gene expressions and inhibited JAK2/STAT3 activation in BMDM induced by LPS. In conclusion, nitazoxanide protects against DSS-induced ulcerative colitis in mice through improving intestinal barrier and inhibiting inflammation and the underlying mechanism involves AMPK activation and JAK2/STAT3 inhibition.
This is a randomized, double-blind, placebo-controlled, multicenter study. The main purpose of the study is to evaluate the clinical efficacy and safety of nimotuzumab combined with trifluridine/tipiracil in third-line and beyond for the treatment of metastatic colorectal cancer (mCRC). This study planned to be divided into two parts: Part A and Part B. Part A is a dose escalation study, and two dose levels are set up in terms of the dose of nimotuzumab (dose level 1: nimotuzumab 400 mg weekly; dose level 2: nimotuzumab 600 mg weekly), while the dose of trifluridine/tipiracil remains unchanged. The aim of this part is to investigate the safety of combination therapy and ensure the dose of nimotuzumab in Part B. After completed the safety-run-in of Part A, Part B can be started. In Part B (main study), a prospective, randomized, double-blind, placebo-controlled design is proposed. Patients of this part will be stratified by tumor site (left half of colorectal vs right half of colon), age (less than 65 years old vs 65 years old or older) and number of metastases (\<3 vs ≥3) and randomly divided into experimental group (nimotuzumab plus trifluridine/tipiracil) and control group (placebo plus trifluridine/tipiracil) at a ratio of 2:1. Treatment will continue until disease progression or intolerable toxicity or withdrawal of consent. In part B, the primary endpoint is overall survival (OS); the secondary endpoint included: Progression free survival (PFS), time to progress (TTP), overall response rate (ORR), disease control rate (DCR), duration of response (DoR), quality of life (QoL), etc.
Controlled release penicillin prepns. for oral application contain as one of the active ingredients the dienyl-ethylene-diamine-salt of phenoxy-methyl-penicillin. This penicillin salt has useful adhesive properties and takes part in the formation of the matrix, together with the indifferent solid polymers, allowing a reduction in the quantity of release retarding additives. - The structure of the matrix and hence the rate of release of the penicillin can be controlled by varying the pressure used in making the tablets, and the ratio of solid polymer to the phenoxy-methyl-penicillin -dibenzyl-ethylene-diamine salt. - A single tablet contg. 600.000 i.u. maintains a curative penicillin level in the blood stream for 12 hours.
Each patient will have atrial pacing 10% higher than the sinus rate or atrial pacing at a rate of 60 bpm if significant sinus bradycardia is present. Each patient will have six ECGs and echocardiographic sequences performed in the same session. In addition six electrical activation evaluations by the Medtronic ECG belt will be done as well. The first study will always be with no ventricular pacing. One study will be echocardiography-optimized BIV pacing and four studies for echocardiography-optimized (?) adaptive RV-only pacing with different AV intervals. A random-sequence will be performed to determine the order for the rest of the studies.
Unilateral spatial neglect (neglect) post stroke is characterized by a lack of attention to one side of the body or one side of the environment. Individuals with neglect experience significant disability and are often unaware of their neglect symptoms which can make it even more difficult to treat. There are a lack of effective treatments for neglect and new interventions are needed to help reduce disability for these individuals. Metacognitive strategy training (strategy training) is an intervention that has the potential to reduce neglect-related disability and improve individuals' awareness of their neglect. Strategy training teaches individuals to develop personalized goals, self-assess their performance of daily activities, and develop and evaluate strategies designed to overcome barriers and improve their performance of daily activities. While strategy training shows promise for individuals with neglect, no studies have tailored the intervention for this group of individuals or examined the effects of strategy training for individuals with neglect. This study examines whether strategy training facilitates reductions in disability and neglect and improves self-awareness after acute stroke.
Zolpidem Tartrate Capsules are only available in a 7.5 mg strength. Use another zolpidem tartrate immediate-release product for the 5 mg or 10 mg dose of zolpidem tartrate immediate-release. Refer to the Prescribing Information of other zolpidem tartrate immediate-release products for the recommended dosage for those products.

  * Zolpidem Tartrate Capsules are not indicated in geriatric patients. Avoid use of Zolpidem Tartrate Capsules in geriatric patients because the recommended dosage in these patients cannot be achieved with the Zolpidem Tartrate Capsules 7.5 mg strength [see Use in Specific Populations (8.5)]. Use another zolpidem tartrate product for geriatric patients.
  * The recommended starting dosage for females is different than males because zolpidem clearance is lower in females [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Do not use Zolpidem Tartrate Capsules to initiate zolpidem tartrate treatment in females because the recommended starting dosage in females cannot be achieved with the Zolpidem Tartrate Capsules 7.5 mg strength. Use another zolpidem tartrate immediate-release product to initiate treatment in females [see Dosage and Administration (2.2)].
  * Avoid Zolpidem Tartrate Capsules in patients with mild or moderate hepatic impairment because the recommended dosage in such patients cannot be achieved with the Zolpidem Tartrate Capsules 7.5 mg strength [see Warnings and Precautions (5.8), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
  * Avoid any zolpidem tartrate use in patients with severe hepatic impairment because its use may contribute to encephalopathy [see Warnings and Precautions (5.8), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
Using an antisense nucleotide, a ribozyme, a maxyzine or an RNAi constructed based on the base sequence of exon 1.beta. of a PDGF receptor .alpha. gene, which is expressed in specific cancer cells, or a polypeptide fragment thereof, the translation of an mRNA transcribed from the exon 1.beta. of the PDGF receptor .alpha. gene is inhibited. An expression inhibitor having as the active ingredient a substance inhibiting expression (for example, the antisense nucleotide, ribozyme, maxyzine or an RNAi as described above) is efficacious as a remedy for cancer.
Long-term in vivo animal studies designed to evaluate the carcinogenic potential of amantadine have not been performed. In several in vitro assays for gene mutation, amantadine did not increase the number of spontaneously observed mutations in four strains of Salmonella typhimurium (Ames Test) or in a mammalian cell line (Chinese Hamster Ovary cells) when incubations were performed either with or without a liver metabolic activation extract. Further, there was no evidence of chromosome damage observed in an in vitro test using freshly derived and stimulated human peripheral blood lymphocytes (with and without metabolic activation) or in an in vivo mouse bone marrow micronucleus test (140 to 550 mg/kg; estimated human equivalent doses of 11.7 to 45.8 mg/kg based on body surface area conversion). 

Impairment of Fertility   
The effect of amantadine on fertility has not been adequately tested, that is, in a study conducted under Good Laboratory Practice (GLP) and according to current recommended methodology. In a three litter, non-GLP, reproduction study in rats, amantadine at a dose of 32 mg/kg/day (equal to the maximum recommended human dose on a mg/m 2 basis) administered to both males and females slightly impaired fertility. There were no effects on fertility at a dose level of 10 mg/kg/day (or 0.3 times the maximum recommended human dose on a mg/m 2 basis); intermediate doses were not tested. 

Failed fertility has been reported during human in vitro fertilization (IVF) when the sperm donor ingested amantadine 2 weeks prior to, and during the IVF cycle.
Piperine, an active plant alkaloid from black pepper (Piper nigrum), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential and cytokine, protein and gene expression were investigated in head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified morphology and inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in the G2/M and S phases. A decrease in cell migration was also observed, and there was decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IFN-γ and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anticancer effects on tumor cells by regulating signaling pathways associated with head and neck cancer.
This investigation will evaluate corneal staining and epithelial barrier function after eight hours of contact lens wear, which is past the peak staining time and more typical of daily lens wear time. A silicone hydrogel lens and multipurpose solution combination shown to induce significant corneal staining ( e.g. equivalent Grade 3 out of Grade 4 scale) will be used to evaluate potential corneal compromise. The study will be a prospective, single-center, double-masked, contralateral, daily wear investigation in adapted soft contact lens wearers. After a three day washout period (without lens wear, lenses will then be worn on one day for eight hours. Corneal staining and barrier function will be determined for a regimen and a saline control situation for each subject. Staining will be graded using the Efron Grading Scale, and permeability data will be estimated as the fluorescein penetration rate, Pdc in nm/sec for the test and control condition.
Teratogenic Effect: Pregnancy Category C.

When pramipexole was given to female rats throughout pregnancy, implantation was inhibited at a dose of 2.5 mg/kg/day (5 times the MRHD on a mg/m2 basis). Administration of 1.5 mg/kg/day of pramipexole to pregnant rats during the period of organogenesis (gestation days 7 through 16) resulted in a high incidence of total resorption of embryos. The plasma AUC in rats at this dose was 4 times the AUC in humans at the MRHD. These findings are thought to be due to the prolactin-lowering effect of pramipexole, since prolactin is necessary for implantation and maintenance of early pregnancy in rats (but not rabbits or humans). Because of pregnancy disruption and early embryonic loss in these studies, the teratogenic potential of pramipexole could not be adequately evaluated. There was no evidence of adverse effects on embryo-fetal development following administration of up to 10 mg/kg/day to pregnant rabbits during organogenesis (plasma AUC was 71 times that in humans at the MRHD). Postnatal growth was inhibited in the offspring of rats treated with 0.5 mg/kg/day (approximately equivalent to the MRHD on a mg/m2 basis) or greater during the latter part of pregnancy and throughout lactation. 

There are no studies of pramipexole in human pregnancy. Because animal reproduction studies are not always predictive of human response, pramipexole should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.