anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Early-onset pre-eclampsia is believed to arise from defective placentation in the first trimester, leading to placental ischaemia/reperfusion (I/R) and oxidative stress. However, our current understanding of the effects of I/R and oxidative stress on trophoblast function is ambiguous in part due to studies exposing trophoblasts to hypoxia instead of I/R, and which report conflicting results. Here, we present a model of simulated ischaemia/reperfusion (SI/R) to recapitulate the pathophysiological events of early-onset pre-eclampsia (PE), by exposing first trimester cytotrophoblast HTR-8/SVneo cells to a simulated ischaemia buffer followed by reperfusion. We examined different ischaemia and reperfusion times and observed that 1 h ischaemia and 24 h reperfusion induced an increase in reactive oxygen species (ROS) production (P<0.0001) and oxygen consumption rate (P<0.01). SI/R-exposed trophoblast cells exhibited deficits in migration, proliferation, and invasion (P<0.01). While the deficits in migration and proliferation were rescued by antioxidants, suggesting an ROS-dependent mechanism, the loss of invasion was not affected by antioxidants, which suggests a divergent ROS-independent pathway. In line with this, we observed a decrease in MMP-9, the key regulatory enzyme necessary for trophoblast invasion (P<0.01), which was similarly unaffected by antioxidants, and pharmacological inhibition of MMP-9 replicated the phenotype of deficient invasion (P<0.01). Collectively, these data demonstrate that I/R impairs trophoblast migration and proliferation via a ROS-dependent mechanism, and invasion via an ROS-independent loss of MMP-9, disambiguating the role of oxidative stress and providing insights into the response of trophoblasts to I/R in the context of early-onset PE.
The present invention provides novel compounds of formula (I) wherein R is selected from the group consisting of R2, R2NH-, or H2N-R3- wherein R2 is selected from the group consisting of C1-C8 alkyl and formula (II), wherein Z is selected from the group consisting of phenyl, heterocycle and cycloalkyl, each R4 is independently hydrogen or C1-C4 alkyl, and n is an integer 1-8; wherein each C1-C8 alkyl and Z is optionally substituted with 1 to 3 substituents, which may be the same or different, selected from the group consisting of Hal, OH, and C1-C4 alkyl; R3 is C1-C8 alkylene; and R1 is selected from the group consisting of cyclopentyl and isopropyl, and the pharmaceutically acceptable salts, optical isomers, and hydrates thereof. In addition, the present invention provides a method of inhibiting cell cycle progression. More specifically, the present invention provides a method of inhibiting cyclin dependent kinases, particularly cdk-2. The present invention also provides a method of preventing apoptosis in neuronal cells and a method of inhibiting the development of neoplasms. In addition, the present invention provides a composition comprising an assayable amount of a compound of formula (I) in admixture or otherwise in association with an inert carrier. The present invention also provides a pharmaceutical composition comprising an effective inhibitory amount of a compound of formula (I) in admixture or otherwise in association with one or more pharmaceutically acceptable carriers or excipients.
The invention discloses industrialized production of a liposome combination medicine by molecular dispersion method, and quality control technology. The liposome combination medicine comprises following raw materials, by molar ratio, 0.03 to 0.15 portion of an active ingredient, 0.40 to 2.20 portions of phospholipid, 0.01 to 0.06 portion of an antioxygen, 1.05 to 2.60 portions of a phospholipid dispersing agent, 1.20 to 3.70 portions of a liposome drug carrier dispersing agent which can be called as excipient, and 0.10 to 0.55 portion of a surfactant. A preparation method of the liposome combination medicine comprises steps of dissolving, ultrafiltration, spray drying, boiling coating, ingredient preparation and freeze drying. The invention also provides the production quality control technology, and a matched equipment combination of the production method. The equipment combination comprises a dissolving tank, an ultrafiltration column, a spray drier, a boiling coating machine, an ingredient preparation tank and a freezer dryer. 20 embodiments of preparation of the liposome combination medicine are also provided.
The invention discloses a 3D printing vaccine containing cell membrane vesicles, a preparation method and application thereof. The 3D printing vaccine is prepared by 3D printing for carrying the target vaccine on the biological ink. The bio-ink comprises PD1 cell membrane vesicles and GelMA hydrogel. By applying the technical scheme of the invention, the PD1 cell membrane vesicles extracted from methacrylic anhydride modified gelatin (GelMA), target vaccine (e.g. dendritic cells) and gene editing cells are printed into the 3D printing vaccine by a 3D printing technology. The GelMA hydrogel porous scaffold has good biocompatibility and provides a growing microenvironment for a target vaccine. The pores of the scaffold promote substance exchange, further improving survival of the vaccine of interest.
To address the previously unanswered question of whether theoretically-driven caregiver education and coaching in nonpharmacologic approaches to reduce care resistant behaviors as a trigger of behavioral and psychiatric symptoms of dementia (BPSD) and neuropsychiatric symptoms after Traumatic Brain Injury (NPTBI) will improve caregiver burden, quality of life (QOL), and related outcomes of patients with these conditions and their family members. The intervention of interest is the Neurobehavioral Non-Pharmacologic Supportive Strategies for Family Caregivers of Persons with Dementia or TBI (NeuroNS-Care). Behavioral symptoms in dementia and following TBI vary considerably over time, with a tendency toward spontaneous regression to the mean. Additionally, caregivers often develop idiosyncratic strategies in response to adverse behaviors that might be either adaptive or maladaptive. In order to separate the effects of time alone from the effects of the coaching intervention, one group will be randomized to delayed intervention following a 6 week wait time. This will allow the investigative team the opportunity to compare the natural history of the outcome variables in an "untrained" portion of the sample to the effects of training over a similar time period.
DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.
An exercise bar is provided. The exercise bar includes a handle tube with a longitudinal interior bore. The handle tube has a first end and a second end. A center shaft has an outer surface. The center shaft is fitted through the longitudinal interior bore exposing a first end portion of the center shaft at the first end of the handle tube and exposing a second end portion of the center shaft at the second end of the handle tube. A sensor is disposed on a mounting section of the outer surface of the center shaft between the first and second portion of the center shaft. A processor is disposed in an interior of the exercise bar. The sensor is in electronic communication with the processor in the exercise bar.
Use of SPY AGENT GREEN for visualization of vessels, blood flow and tissue perfusion has been established in pediatric patients aged 1 month and older. Pediatric use is supported by published data in 49 pediatric patients who received indocyanine green for assessment of blood flow and tissue perfusion in cardiovascular, vascular, plastic, micro- and reconstructive surgical procedures, and by clinical trials in adults. No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [See Dosage and Administration (2.1)]. The use of SPY AGENT GREEN for visualization of vessels, blood flow and tissue perfusion has not been established in pediatric patients aged less than 1 month.

Use of SPY AGENT GREEN for visualization of extrahepatic biliary ducts has been established in pediatric patients aged 12 years and older. Pediatric use is supported by clinical trials in adults in addition to clinical use in pediatric patients. No overall differences in safety or effectiveness have been observed between pediatric patients and adults. The dose range was similar to the effective dose range in adults [See Dosage and Administration (2.2)]. The use of SPY AGENT GREEN for visualization of extrahepatic biliary ducts has not been established in pediatric patients aged less than 12 years.

The safety and efficacy of SPY AGENT GREEN for visualization of lymph nodes and lymphatic vessels during lymphatic mapping for cervical and uterine cancer and breast cancer have not been established in pediatric patients.
Men receiving the control condition will be comprised of standard of care counseling from the clinic plus a variety of free condoms and water-based lubricants. They will also provide a specimen for STD testing, and receive text message questions for 12 weeks. The text messaging system will be used to collect self-reported dependent variables from men on a weekly basis. Texting will also serve as a constant method of contact between the PD and the enrolled men to remind them of follow-up assessments. In addition, the participants will complete the ACASI questionnaire to assess their sexual behavior, as well as demonstrate their condom application ability.
ABC \[abacavir\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO 3TC \[lamivudine\]: syrup or tablet, dosed twice-daily according to weight-bands following WHO non-nucleoside reverse transcriptase inhibitor (NNRTI): either nevirapine or efavirenz based on availability (provided by national ART programmes in Uganda/Zimbabwe). Nevirapine syrup or tablet dosed twice-daily according to weight-bands following WHO. Efavirenz tablets dosed once-daily according to weight-bands following WHO.
All patients treated with pulmonary artery strapping between 2005 and 2016 at the Queen Fabiola Children Hospital. Patients benefiting from an uni-ventricular reparation.
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT 1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue sumatriptan tablets if a cerebrovascular event occurs.

Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, exclude other potentially serious neurological conditions. Sumatriptan tablets are contraindicated in patients with a history of stroke or TIA.
Obstetrical hemorrhage is a leading cause of maternal morbidity and mortality worldwide with a significantly higher frequency and severity following cesarean delivery. In 2020, 31.9 percent of pregnant women in the United States underwent cesarean delivery, making it the second most common operation performed. Though multiple complications can occur following cesarean delivery, hemorrhage morbidities are among the most common with significant cardiovascular implications. Twin gestations are at particularly higher risk for postpartum hemorrhage due to impaired myometrial contractility and atony following overdistention; increased maternal blood volume; and increased uterine blood flow compared to singletons, yet the management of obstetrical bleeding following twin delivery remains identical to singleton delivery. Current strategies to address intrapartum hemorrhage have relied on pharmacological and mechanical treatments after intraoperative identification. However, there is extensive work on prophylactic therapies administered intraoperatively to prevent obstetrical hemorrhage. Recent evidence has emerged about the utility of prophylactic Methylergonovine for the prevention of obstetrical hemorrhage. Methylergonovine, a semisynthetic ergot alkaloid, acts primarily on alpha adrenergic receptors of uterine and vascular smooth muscle, increasing uterine tone and promoting vasoconstriction. In a randomized trial of 80 women undergoing intrapartum cesarean delivery found that fewer patients who were allocated to the methylergonovine group received additional uterotonic agents (20% vs 55%, relative risk (RR) 0.4, 95% confidence interval (CI) 0.2-0.6). Participants receiving methylergonovine were more likely to have satisfactory uterine tone (80% vs 41%, RR 1.9, 95% CI 1.5-2.6), lower incidence of postpartum hemorrhage (35% vs 59%, RR 0.6, 95% CI 0.4-0.9), lower mean quantitative blood loss (967 mL vs 1,315 mL; mean difference 348, 95% CI 124-572), and a lower frequency of blood transfusion (5% vs 23%, RR 0.2, 95% CI 0.1-0.6). Investigators concluded that the administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents. In a prospective study of 1210 participants found that intraoperative, prophylactic methylergonovine decreased post-operative blood loss with no adverse side effects. Randomized trials of Methylergonovine as prophylaxis to prevent hemorrhage in cesarean delivery have exclude twin gestations. Currently, there remains a paucity of research regarding prophylactic procedures for twin cesarean delivery. There is an opportunity to prophylactically address hemorrhage in high-risk groups. Therefore, the investigators propose a prospective randomized controlled trial which will compare maternal blood loss associated with prophylactic methylergonovine during cesarean delivery among patients with twin.
Incomplete understanding of patient-specific factors that determine whether someone will respond well to language therapy after stroke limits the development of methods to target or account for sources of variability. There is a strong likelihood that genetics play a role in language recovery after stroke, but very little research has been dedicated to investigating this link. The long-term goal of this line of work is to maximize response to aphasia therapy by incorporating patient-specific factors into decisions related to treatment planning. The overall objective of this application is to identify patterns of patient-specific factors including two candidate genes and cognitive skills that show a relationship with treatment outcomes. The central hypothesis is that there will be a relationship between ApoE and BDNF genotypes, and working memory on stimulus generalization. The rationale for the proposed project is that the identification of factors that impact treatment responsiveness will allow for better estimation of prognosis, improved triage of individuals into appropriate therapy regimens and direct targeting of cognitive factors to maximize behavioral gains. The two specific aims of the project are to determine the degree to which (1) ApoE and BDNF genotypes influence how individuals with aphasia respond to therapy, and (2) working memory abilities are related to stimulus acquisition and stimulus generalization after anomia therapy. Individuals with chronic post-stroke aphasia will undergo cognitive and language assessment, and provide a saliva sample for genetic analysis prior to participating in a cued picture-naming therapy for anomia. The expected outcomes are to integrate cognitive scores and genotypes for BDNF and ApoE into formulating probabilities of individual patient responsiveness to restorative therapy. Improvement in word retrieval abilities will be evaluated using the percentage of pictures named correctly. This contribution is expected to be significant because it will allow for more informed clinical decision making and better allocation of resources to appropriate treatments, thereby making advances in the field toward more personalized medicine, as opposed to a one-size-fits-all clinical approach.

The investigators will determine genotypes for BDNF and ApoE, which will yield four separate groups. At least 20 participants will be enrolled for each genotype group.
Cognitive Behavioral Therapy for Insomnia (CBTI) is the evidence-based first line treatment for chronic insomnia. Randomized controlled trials and meta-analyses have established that CBTI is efficacious and effective. Despite the strong evidence for CBTI, chronic insomnia remains under-treated among Veterans because of several barriers that limit access to behavioral treatments. In recent years, the VA has taken substantial measures to train more clinicians to provide insomnia treatment; however, a deficit in treatment availability remains. In 2011, the VA began to train clinicians in CBTI as part of the VA's Evidence Based Psychotherapy (EBP) training program, with a goal to train 1000 clinicians. Even with 1000 VA clinicians trained in CBTI, a shortage of clinicians will likely remain due to the high prevalence of insomnia. High prevalence and a shortage of clinicians prevent the VA from meeting the care demand of Veterans with insomnia. While the CBTI roll-out is a significant investment from the VA, additional mechanisms, such as dissemination and implementation of other evidence-based treatments for insomnia with fewer implementation barriers, must be considered to address the high prevalence of insomnia.

The in-person delivery and length of treatment for CBTI may be one of barriers to accessing care. Briefer protocols that use multiple delivery modalities have recently been developed and may help to increase session attendance and treatment completion. These shorter insomnia treatments are often referred to as Brief Behavioral Treatment for Insomnia (BBTI) and consist of ≤4 sessions. Besides fewer and briefer sessions, and utilizing both in-person and phone delivery of treatment, BBTI also emphasizes the behavioral components of CBTI (i.e., stimulus control and sleep restriction) rather than a combined approach focusing on both behavioral and cognitive components. BBTI is efficacious in adults-studies with older adults and Veterans found BBTI resulted in a significant decrease in insomnia severity with Cohen's d effect sizes in the moderate to large range. Like CBTI, BBTI significantly improves insomnia severity and may also help to improve secondary outcomes like depression and anxiety.

Integration of newer insomnia treatments, like BBTI, will first depend on establishing its evidence directly compared to CBTI. Effectiveness trials of BBTI, especially those conducted with military Veterans in typical VA settings, have yet to be conducted. Before BBTI can be broadly implemented and integrated into the VA, it needs to be established as a clinically effective treatment for insomnia among Veterans and a statistically non-inferior treatment (not necessarily better or worse) for Veterans compared to CBTI.
Study investigators propose to enroll 60 children with SCA and an elevated TCD measurement between 5 and 12 years of age in this one arm feasibility study of hydroxyurea therapy, with follow-up of at least 12 months per subject. The study intervention will include HU to begin at \~ 20 mg/kg/day(range 17.5 - 26 mg/kg/day). No dose escalation will occur. Given the success of the first year of enrollment and the favorable response of TCD measurement after 3 months on HU therapy, the study investigators have participants as an internal pilot. The definitive phase III trial will now compare low dose HU therapy to the result of no treatment arm from the STOP Trial.
In medical studies, repeated measurements of biomarkers and time-to-event data are often collected during the follow-up period. To assess the association between these two outcomes, joint models are frequently considered. The most common approach uses a linear mixed model for the longitudinal part and a proportional hazard model for the survival part. The latter assumes a linear relationship between the survival covariates and the log hazard. In this work, we propose an extension allowing the inclusion of nonlinear covariate effects in the survival model using Bayesian penalized B-splines. Our model is valid for non-Gaussian longitudinal responses since we use a generalized linear mixed model for the longitudinal process. A simulation study shows that our method gives good statistical performance and highlights the importance of taking into account the possible nonlinear effects of certain survival covariates. Data from patients with a first progression of glioblastoma are analysed to illustrate the method.
In the first step, the stimuli that led the individuals in the experimental group to drink alcohol were assessed, and the conceptual-theoretical-experimental (CTE) framework of the study was created. The personal behaviors that could be related to recurrence (physiological, self-concept, role function, and mutual commitment) and the stimuli that caused recurrence (focal and affecting) were assessed, objectives were determined, and nursing interventions were carried out in line with these objectives. The interventions planned for diagnosing ineffective coping were selected according to the patients' needs among the "support coping" interventions under the title of the behavioral area in the Nursing Intervention Classification (NIC). A total of 10 individual interviews were made twice a week for about 45 to 60 minutes. The interviews were evaluated by determining the area specific Nursing outcome classification (NOC) (self respect, social support, mood management, role performance).