anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Conditioning regimens and the choice of immunosuppression have substantial impact on immune reconstitution after allogeneic hematopoietic stem cell transplantation (aHSCT). The pivotal mechanism to maintain remission is the induction of the graft-versus-tumor effect. Relapse as well as graft versus host disease remain common. Classic immunosuppressive strategies implementing calcineurin inhibitors (CNI) have significant toxicities, hamper the immune recovery, and reduce the anti-cancer immune response.
METHODS: We designed a phase II clinical trial for patients with relapsed and refractory lymphoid malignancies undergoing aHSCT using a CNI-free approach consisting of post-transplant cyclophosphamide (PTCy) and short-term Everolimus after reduced-intensity conditioning and matched peripheral blood stem cell transplantation. The results of the 19 planned patients are presented. Primary endpoint is the cumulative incidence and severity of acute GvHD.
RESULTS: Overall incidence of acute GvHD was 53% with no grade III or IV. Cumulative incidence of NRM at 1, 2, and 4 years was 11%, 11%, and 16%, respectively, with a median follow-up of 43 months. Cumulative incidence of relapse was 32%, 32%, and 42% at 1, 2, and 4 years after transplant, respectively. Four out of six early relapses were multiple myeloma patients. Overall survival was 79%, 74%, and 62% at 1, 2, and 4 years. GvHD-relapse-free-survival was 47% after 3 years.
CONCLUSIONS: Using PTCy and short-term Everolimus is safe with low rates of aGvHD and no severe aGvHD or cGvHD translating into a low rate of non-relapse mortality. Our results in this difficult to treat patient population are encouraging and warrant further studies.
AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs.
METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up.
CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.
FIELD: organic chemistry, medicine, biochemistry, pharmacy. SUBSTANCE: invention relates to novel cyclic compounds of diamine of the formula (I)   where   represents optionally substituted bivalent residue of benzene where substituents are taken among unsubstituted lower alkyl group, unsubstituted lower alkoxy-group, unsubstituted lower acyl-group, acyl group, lower alkylthio-group, lower alkylsulfonyl group, halogen atom and so on, or unsubstituted pyridine; Ar represents phenyl group that can be substituted with from one to fourth groups taken among unsubstituted lower alkyl group, unsubstituted alkoxy-group, lower alkylthio-group, lower alkylsulfonyl group and so on, optionally substituted amino- group, alkylenedioxy-group; X represents NH-, oxygen or sulfur atom; Y represents sulfur atom, sulfoxide or sulfone; Z represents ordinary linkage or -NR 2 -; R 2  represents hydrogen atom or unsubstituted lower alkyl group; l is a whole number 2 or 3; m is a whole number 2 or 3; n is a whole number from 1 to 3. Invention relates also to their salts or solvates. Invention relates also to pharmaceutical composition showing ACAT-inhibitory effect comprising compound of the formula (I) or its salt taken in the effective dose and pharmaceutically acceptable carrier. Invention relates also to method of treatment or prophylaxis of hyperlipemia, arteriosclerosis, cerebrovascular disturbances, ischemic cardiopathy, ischemic enteropathy or aortic aneurysm by administration of effective dose of compound of the formula (I) or its salt or solvate in patient suffering with hyperlipemia, arteriosclerosis, cerebrovascular disturbances, ischemic cardiopathy, ischemic enteropathy or aortic aneurysm. Invention provides preparing novel cyclic compounds of diamine showing ACAT-inhibitory effect. EFFECT: valuable medicinal properties of compound. 11 cl, 22 tbl, 116 ex _
Study TDE-PH-310 is an international, multicenter, randomized (1:1 oral treprostinil (UT-15C): placebo), double-blind, placebo-controlled study in subjects with pulmonary arterial hypertension (PAH) who are receiving background oral monotherapy for PAH for at least 30 days at randomization. Subjects are randomly allocated to receive oral treprostinil extended-release tablets or placebo by a stratified randomization by type of background therapy (Strata 1: phosphodiesterase type 5 inhibitor \[PDE5-I\] or soluble guanylate cyclase \[sGC\] stimulator; Strata 2: endothelin receptor antagonist \[ERA\]. Subjects are also stratified by baseline 6-minute walk distance (6MWD) less than or equal to 350 m or greater than 350 m. Subjects receive their first dose of study drug (0.125 mg) or matching placebo on the day of randomization. Oral dosing of study drug is continued at 0.125 mg 3 times daily (TID; every 6 to 8 hours) with food. The dose (or matching placebo) is titrated throughout the study up to a maximum dose of 12 mg TID to reach and maintain a tolerated dosing regimen that provided optimal clinical benefit. Once randomized, subjects return for study visits every 4 weeks for the first 12 weeks, then every 12 weeks for the duration of the study. Subjects continue in the study until experiencing clinical worsening, the number of adjudicated events necessary for study closure occurr, or prematurely discontinue participation in the study for any reason other than protocol-specified clinical worsening. At each scheduled visit, subjects undergo efficacy assessments for clinical worsening, exercise capacity (6MWD and Borg dyspnea score), WHO functional class (FC), and plasma N-Terminal pro-brain natriuretic peptide (NT-proBNP). Subjects could participate in an optional hemodynamic sub-study (assessed by RHC). Safety assessments consist of adverse events (AEs), physical examinations, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory parameters. Patients who complete all required assessments are eligible to enter a long-term, open-label, extension study (TDE-PH-311).
The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults including trauma, stroke, infections, and long seizures (status epilepticus, SE) increase the nuclear expression and chromatin binding of the neuron-restrictive silencing factor/RE-1 silencing transcription factor (NRSF/REST). REST/NRSF orchestrates major disruption of the expression of key neuronal genes, including ion channels and neurotransmitter receptors, potentially contributing to epileptogenesis. Accordingly, transient interference with REST/NRSF chromatin binding after an epilepsy-provoking SE suppressed spontaneous seizures for the 12 d duration of a prior study. However, whether the onset of epileptogenesis was suppressed or only delayed has remained unresolved. The current experiments determined if transient interference with REST/NRSF chromatin binding prevented epileptogenesis enduringly or, alternatively, slowed epilepsy onset. Epileptogenesis was elicited in adult male rats via systemic kainic acid-induced SE (KA-SE). We then determined if decoy, NRSF-binding-motif oligodeoxynucleotides (NRSE-ODNs), given twice following KA-SE (1) prevented REST/NRSF binding to chromatin, using chromatin immunoprecipitation, or (2) prevented the onset of spontaneous seizures, measured with chronic digital video-electroencephalogram. Blocking NRSF function transiently after KA-SE significantly lengthened the latent period to a first spontaneous seizure. Whereas this intervention did not influence the duration and severity of spontaneous seizures, total seizure number and seizure burden were lower in the NRSE-ODN compared with scrambled-ODN cohorts. Transient interference with REST/NRSF function after KA-SE delays and moderately attenuates insult-related hippocampal epilepsy, but does not abolish it. Thus, the anticonvulsant and antiepileptogenic actions of NRSF are but one of the multifactorial mechanisms generating epilepsy in the adult brain.
PURPOSE:To produce a new peptide having an elastase inhibitory activity and useful, e.g. as a medicine for improving diseases induced by elastase, by partly modifying the amino acid structure of a peptide existing in the C terminal of human urin trypsin inhibitor and having a trypsin inhibitory activity. CONSTITUTION:A clone having a DNA coding human urine trypsin inhibitor (UTI) is selected by using human cDNA library and carrying out screening by a probe. The DNA is isolated and a necessary modification is introduced into this DNA according to the sitespecific modification introduction method. Further, the modified DNA is treated with a restriction enzyme and subsequently bonded to a suitable manifestation vector to prepare a partly modified recombinant DNA coding the C-terminal side region containing the trypsin inhibitory part of UTI. This partly modified recombinant DNA is transferred to a host cell to transform it. The resultant transformant is cultured, thus producing the objective new peptide having an amino acid sequence of the formula (X11 is Arg, Glu; X15 is Ile, Leu, etc.; X18 is Ile, Phe; X46 is Tyr, Gln) and exhibiting an elastase inhibitory activity.
Mesenchymal stem cells (MSCs) exert their anti-inflammatory and anti-fibrotic effects by secreting various humoral factors. Interferon-gamma (IFN-γ) can enhance these effects of MSCs, and enhancement of regulatory T (Treg) cell induction is thought to be an underlying mechanism. However, the extent to which Treg cell induction by MSCs pretreated with IFN-γ (IFN-γ MSCs) ameliorates renal fibrosis remains unknown. In this study, we investigated the effects of Treg cell induction by IFN-γ MSCs on renal inflammation and fibrosis using an siRNA knockdown system. Administration of IFN-γ MSCs induced Treg cells and inhibited infiltration of inflammatory cells in ischemia reperfusion injury (IRI) rats more drastically than control MSCs without IFN-γ pretreatment. In addition, administration of IFN-γ MSCs more significantly attenuated renal fibrosis compared with control MSCs. Indoleamine 2,3-dioxygenase (IDO) expression levels in conditioned medium from MSCs were enhanced by IFN-γ pretreatment. Moreover, IDO1 knockdown in IFN-γ MSCs reduced their anti-inflammatory and anti-fibrotic effects in IRI rats by reducing Treg cell induction. Our findings suggest that the increase of Treg cells induced by enhanced secretion of IDO by IFN-γ MSCs played a pivotal role in their anti-fibrotic effects. Administration of IFN-γ MSCs may potentially be a useful therapy to prevent renal fibrosis progression.
During the initial treatment of patients with pernicious anemia, serum potassium must be observed closely the first 48 hours and potassium replaced if necessary.

Hematocrit, reticulocyte count, vitamin B12, folate and iron levels should be obtained prior to treatment. Hematocrit and reticulocyte counts should be repeated daily from the fifth to seventh days of therapy and then frequently until the hematocrit is normal. If folate levels are low, folic acid should also be administered. If reticulocytes have not increased after treatment or if reticulocyte counts do not continue at least twice normal as long as the hematocrit is less than 35%, diagnosis or treatment should be reevaluated. Repeat determinations of iron and folic acid may reveal a complicating illness that might inhibit the response of the marrow.

Patients with pernicious anemia have about 3 times the incidence of carcinoma of the stomach as the general population, so appropriate tests for this condition should be carried out when indicated.
The laryngeal mask airway (LMA) provides a useful alternative for airway management during general anaesthesia. Inflation of the LMA cuff produces a low-pressure seal around the larynx, enabling positive pressure ventilation (PPV). The use of LMA as an airway management technique is common in the pediatric anesthesia because of its less irritating effect on the airways due to its location in the upper larynx. Now, the use of laryngeal mask instead of tracheal intubation for airway management has been achieved in day surgery, therefore, how to perform a respiratory management with a laryngeal mask is particularly important. In addition, mechanical ventilation is also a commonly used method of airway management in clinical practice. the ventilator will deliver a constant pressure by decelerating the flow. However, the ventilation volume varies according to the patient's respiratory mechanics . Pressure-controlled ventilation-volume guaranteed (PCV-VG) combines the advantages of both VCV and PCV, which delivers a stable ventilation volume using a decelerating flow pattern.
The invention discloses an extracellular vesicle carrying active proteins, a preparation method and application thereof, and particularly relates to the technical field of pharmaceutical preparations. The extracellular vesicles carrying the active proteins are prepared by constructing an extracellular vesicle bionic nano system carrying the active proteins and derived from grapes. The invention designs and prepares the grape-derived extracellular vesicles carrying the polypeptide macromolecular drugs, and avoids the reduction of the drug activity caused by complex preparation processes, materials and organic solvents. The material source is natural edible grape, and compared with a nanometer drug delivery system prepared by using a synthetic polymer material, the grape-derived extracellular vesicle oral administration has better safety. The grape-derived extracellular vesicles have good stability in the gastrointestinal tract and can promote intestinal absorption of drugs. Can improve the trans-intestinal transfer efficiency of macromolecular drugs. The grape-derived extracellular vesicles have better oral absorption effects than the milk-derived extracellular vesicles.
The human microbiome has a crucial role in the homeostasis and health of the host. These microorganisms along with their genes are involved in various processes, among these are neurological signaling, the maturation of the immune system, and the inhibition of opportunistic pathogens. In this sense, it has been shown that a healthy ocular microbiota acts as a barrier against the entry of pathogens, contributing to the prevention of infections. In recent years, a relationship has been suggested between microbiota dysbiosis and the development of neurodegenerative diseases. In patients with glaucoma, it has been observed that the microbiota of the ocular surface, intraocular cavity, oral cavity, stomach, and gut differ from those observed in healthy patients, which may suggest a role in pathology development, although the evidence remains limited. The mechanisms involved in the relationship of the human microbiome and this neurodegenerative disease remain largely unknown. For this reason, the present review aims to show a broad overview of the influence of the structure and composition of the human oral and gut microbiota and relate its dysbiosis to neurodegenerative diseases, especially glaucoma.
Provided is an anticancer agent that has a novel function based on a novel mechanism. Also provided is a novel anticancer agent that has a function of suppressing cancer stem cell properties and/or a function of suppressing cancer cell proliferation. Also provided is a method for screening a novel anticancer agent. The anticancer agent comprises as an active ingredient a substance having an anti-adipsin function. The anticancer agent according to the present invention, which comprises as an active ingredient a substance having an anti-adipsin function, has functions of suppressing cancer stem cell properties and suppressing cancer cell proliferation. The antitumor function based on the suppression of adipsin is a novel mechanism. Therefore, a novel anticancer agent can be screened by focusing on this function mechanism. Thus, a more efficacious anticancer agent capable of suppressing cancer stem cell properties can be acquired.
Mexican American adolescents are at an increased risk for interrelated problems of poor mental health and school dropout. Unfortunately, there is a lack of interventions specifically designed to address this risk. This study will evaluate a preventive intervention for low-income Mexican American adolescents.

Participants are randomly assigned to either a multi-component intervention called the Bridges to High School Program or a Low Dose Workshop. The 11-week multi-component intervention takes place during the fall semester of seventh grade and consists of an adolescent group, a parenting group, a combined (parent-adolescent) family group, and a school liaison. This intervention focuses on adolescent coping skills, parenting practices, family cohesion, and parental support for education. The Low-Dose Workshop consists of a 3-hour workshop in which adolescents and parents are given information and resources to facilitate school engagement. Participants are assessed prior to and immediately following the intervention and again in eighth and ninth grade. Academic and mental health outcomes are measured with questionnaire-based interviews given to caregivers and adolescents. Teachers are asked to complete questionnaires; archival school data are also collected. Diagnostic interviews are conducted at the ninth grade assessment.
Orientation discrimination task, which is a cognitive task. Patients were trained for 1 hour per day, 15 days in total.
Breast cancer (BC) is the most abundant and aggressive cancer that impacts millions of women with poorly understood mechanisms. Here, we aimed to investigate the function of LINC01806 in BC development. Human BC tissues and nearby normal specimens were taken from diagnosed BC patients. The expression levels of LINC01806, miR-1286, ZEB1, and EMT-related markers were evaluated by qRT-PCR and western blotting. FISH was used to visualize the subcellular localization of LINC01806. The viability, proliferation, migration and invasion capacities of BC cells were assessed by MTT, colony formation, and transwell assays. Interactions among LINC01806, miR-1286 and ZEB1 were validated by dual luciferase assay. The unpaired Student t-test (for two groups) or one-way ANOVA following with Tukey post-hoc test (for more than three groups) was employed for statistical analysis. LINC01806 level was elevated in BC tissues. Knockdown of LINC01806 suppressed EMT process and BC cell proliferation, migration, and invasion. LINC01806 co-localized and directly bound with miR-1286 in the cytoplasm. MiR-1286 inhibitor blocked the effects of LINC01806 knockdown on BC cell EMT, proliferation and migration. MiR-1286 targeted ZEB1 and overexpression of ZEB1 blocked the regulatory functions of miR-1286 mimics in BC. LINC01806 facilitates EMT and accelerates BC cell proliferation, migration, and invasion via acting as miR-1286 sponge to disinhibit ZEB1 expression.
Romberg test and single leg standing test will be used in balance assessment. The presence of vestibular dysfunction will be evaluated with the Utenberger test. Under the name of visual-spatial perception, spatial memory will be evaluated with the mobile application called Corsi Block Tapping, and navigation performance will be evaluated with the triangle completion task. In addition, X-ray images taken during routine follow-ups will be used to determine the location, type of curvature and Cobb angle of the scoliosis. The degree of rotation will be measured with a mobile application called Scoliodetector. Quality of life is planned to be evaluated with the Scoliosis Research Society-22 questionnaire.
Most patients receiving morphine sulfate extended-release will experience initial drowsiness. This usually disappears within 3 to 5 days and is not a cause of concern unless it is excessive, or accompanied by unsteadiness or confusion. Dizziness and unsteadiness may be associated with postural hypotension, particularly in elderly or debilitated patients, and has been associated with syncope and falls in non-tolerant patients started on opioids.

Excessive or persistent sedation should be investigated. Factors to be considered should include: concurrent sedative medications, the presence of hepatic or renal insufficiency, hypoxia or hypercapnia due to exacerbated respiratory failure, intolerance to the dose used (especially in older patients), disease severity and the patient's general condition.

The dosage should be adjusted according to individual needs, but additional care should be used in the selection of initial doses for the elderly patient, the cachectic or gravely ill patient, or in patients not already familiar with opioid analgesic medications to prevent excessive sedation at the onset of treatment.
PURPOSE:The titled carcinostatic agent obtained by supporting 4-carbamoyl- imidazolium-5-oleate(SM-108), its salt or its hydrate on a specific carrier decomposable in organism. CONSTITUTION:A compound shown by the formula, its salt or its hydrate is blended with a solution containing a carrier decomposable in organism, selected from collagen and gelatin, with stirring, the blend is concentrated, subjected to spray drying, or lyophilized. In the operation, a stabilizer, antispetic, soothing agent, dissolution auxiliary, etc. or an addition agent to adjust moldability and sustained release may be optionally added to the solution. The prepared substance is properly processed depending upon purposes, to give a sustained release carcinostatic agent. Each process is carried out sterilely with respect to characteristics as injection or an embedded agent, and it can be pharmaceutically manufactured into a long acting oral agent, external preparation, suppository, etc. depending upon its purpose.
Participants in this arm will receive a total of three doses of study vaccine: the first dose at Day 0, the second dose at Day 28 (plus or minus 7 days), and the third dose at Day 56 (plus or minus 7 days). Each dose will consist of a 1-mL injection (dose strength 4 mg/mL) and will be administered by IM injection in the deltoid muscle.
FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to transplantology, and can be used for prevention of cadaver kidney rejection. That is ensured by examining a recipient in genetic HLA typing at high resolution. Then alloepitopes HLA of recipient and donor are compared. Detecting alloepitopes, present in donor, but absent in recipient. For prevention, basic three-component immunosuppressive therapy is used. If observing less than 10 mismatches of alloepitopes, additionally monoclonal antibodies blocking the alpha-chain of the interleukin-2 receptor molecule are introduced. If observing 10–24 misclosures of alloepitopes, photophoresis is additionally performed. If more than 24 mismatches of alloepitopes are detected, photopheresis and an induction therapy with antithymocyte globulin infusion are additionally prescribed. In all cases, pulse therapy with methylprednisolone is performed.EFFECT: method provides more effective prevention of graft kidney graft rejection by reducing side effects of the preparations and preserving graft life.3 cl, 3 ex