anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Strategies to prolong brachial plexus nerve blocks analgesia beyond the pharmacological duration of the local anaesthetic used include placement of indwelling perineural catheters to allow prolonged infusion or the co-administration of adjuvants such as epinephrine, a2 agonists (i.e. clonidine and dexmedetomidine), midazolam, or the corticosteroid dexamethasone.

The investigators will use calcium channel blocker as adjuvant to bupivacaine in supraclavicular block. Calcium plays an important role in analgesia produced by local anesthetics. The activation of N-methyl-D-aspartate receptors may lead to calcium entry into cells and potentiation of spinal cord and plays a role in pain formation. Hence, calcium channel blockers may prevent central sensitization and provide better sensory motor block characteristics. Verapamil, a calcium channel blocker can potentiate analgesic action of local anesthetics and reduce postoperative pain and analgesic consumption. Few studies were there using 2.5 mg of verapamil, showing no effect on onset and duration of sensory motor block. Hence, the investigators have used 5 mg of verapamil as adjuvant to bupivacaine. The primary aim of the study was to know whether verapamil (5 mg) as adjuvant to bupivacaine in supraclavicular brachial plexus block would delay the need of rescue analgesia.
Mutations in ADNP result in Helsmoortel-Van der Aa syndrome. Here, we describe the first de novo intronic deletion, affecting the splice-acceptor site of the first coding ADNP exon in a five-year-old girl with developmental delay and autism. Whereas exome sequencing failed to detect the non-coding deletion, genome-wide CpG methylation analysis revealed an episignature suggestive of a Helsmoortel-Van der Aa syndrome diagnosis. This diagnosis was further supported by PhenoScore, a novel facial recognition software package. Subsequent whole-genome sequencing resolved the three-base pair ADNP deletion c.[-5-1_-4del] with transcriptome sequencing showing this deletion leads to skipping of exon 4. An N-terminal truncated protein could not be detected in transfection experiments with a mutant expression vector in HEK293T cells, strongly suggesting this is a first confirmed diagnosis exclusively due to haploinsufficiency of the ADNP gene. Pathway analysis of the methylome indicated differentially methylated genes involved in brain development, the cytoskeleton, locomotion, behavior, and muscle development. Along the same line, transcriptome analysis identified most of the differentially expressed genes as upregulated, in line with the hypomethylated CpG episignature and confirmed the involvement of the cytoskeleton and muscle development pathways that are also affected in patient cell lines and animal models. In conclusion, this novel mutation for the first time demonstrates that Helsmoortel-Van der Aa syndrome can be caused by a loss-of-function mutation. Moreover, our study elegantly illustrates the use of EpiSignatures, WGS and Phenoscore as novel complementary diagnostic tools in case a of negative WES result.
FIELD: organic chemistry, chemical technology, pharmacy. SUBSTANCE: invention relates to a novel method of synthesis of acridine carboxamide of the formula (I)   where R 1 ,R 2 ,R 5 ,R 6 , x, Y are indicated in the invention claim. Method of synthesis involves cyclization of compound of the formula (II)   by treatment with boron trifluoride or suitable complex based on its in a suitable solvent to yield tetrafluoroborate salt of the formula (IIIa)   followed by treatment of this salt with inorganic base in EtOAc or CH 2 Cl 2  medium to form compound of the formula (III)   and treatment of: (i) compound of the formula (III) with primary alkyl amine of the formula (IV) NH 2 (CH 2 ) x Y  (IV) or (ii) carboxylic acid obtained by hydrolysis of compound of the formula (III) at alkaline conditions with primary alkyl amine of the formula (IV) in the presence of a suitable binding agent to yield compound (I) or if necessary the conversion of one compound of the formula (I) to other compound of the formula (I) and/or to its pharmaceutically acceptable salt. Invention provides to synthesize the useful compound which is an antitumor medicinal agent, easy separation and further processing tetrafluoroborate salt. EFFECT: new improved method of synthesis, simplified process in industrial scale, increased productivity of process, valuable antitumor properties of compound. 8 cl, 12 ex
Iron deficiency is prevalent in patients with heart failure. Iron deficiency is associated with a worse prognosis, and randomised controlled trials have shown that correction of iron deficiency with intravenous iron therapy improves functional capacity, quality of life, and 6-minute walk distance. Current guidelines therefore recommend intravenous iron substitution in patients with heart failure with reduced ejection fraction and iron deficiency. Intravenous iron is more effective, better tolerated, and improves quality of life to a greater extent than oral iron supplements. In the IRONOUT HF trial, in which 225 patients with systolic heart failure were randomised to oral iron supplement or placebo, there was no effect on oxygen uptake, 6-minute walk distance, or quality of life. The authors attributed the negative results to the minimal effect on iron stores, suggesting that oral iron does not adequately replenish iron stores in patients with heart failure.

Cardiac allograft recipients resemble patients with heart failure in many respects. Prior to transplantation, and in some instances after heart transplantation, they have had overt heart failure. Moreover, due to the immunologic challenge posed by the allograft, and their susceptibility to infection due to immunosuppressive treatment, cardiac allograft recipients have low-grade inflammation. This low-grade inflammation makes it difficult to interpret iron stores, and results in dysregulated iron metabolism.

There have been no studies to assess the effect of intravenous iron therapy in heart transplant recipients who have iron deficiency. There is reason to believe that a liberal definition of iron deficiency should be used in cardiac allograft recipients, and the investigators have elected to use the well-established definition used in patients with heart failure: serum ferritin \< 100 µg/l or ferritin between 100 and 300 µg/l in combination with a transferrin saturation \< 20 %. Because oral iron supplement is less effective then intravenous iron in general, and in patients with heart failure in particular, the investigators assume that oral iron supplement is inadequate in heart transplant recipients. the investigators have designed the IronIC trial to assess the effect of intravenous iron isomaltoside on exercise capacity, muscle strength, cognition and quality of life in iron-deficient heart transplant recipients.
Mental health services are less available and accessible in rural and northern communities than in urban areas. These issues are concerning as extended time on wait lists can exacerbate symptoms, prolong symptoms, prolong distress, and increase the risk for suicide, self-harm, and the need for hospitalization. Moreover, delayed access to mental health services negatively impacts treatment engagement, with non-attendance, decreased motivation, and reduced satisfaction with services frequently reported following prolonged wait times. A particularly vulnerable group in this context is adolescent youth, for whom research suggests mental health symptoms such as anxiety and depression and related hospital visits have increased in recent decades. Given the imminent need for and reduced access to accessible mental health services for youth in Northwestern Ontario, innovative solutions are needed. In partnership with St. Joseph Care Group and Thunder Bay Counselling Centre, the investigators are evaluating the impact of a mental health app (JoyPop) as a tool for youth who are waiting for mental health services. The JoyPop app was developed to support improved emotion regulation - an ability still undergoing development during adolescence and which can present as a key difficulty for youth with mental health challenges. Mobile mental health applications have the potential to increase accessible mental health support for youth in Northwestern Ontario. Despite this promise of mobile mental health apps, significant gaps exist between the growing number of apps available in the public domain and empirical evidence of the beneficial impacts of apps for users. In particular, most apps that focus on emotion regulation have not been evaluated, are narrow in scope, or have only been evaluated among adult populations. The JoyPop app includes a broader focus, and this research is unique given its focus on rigorously evaluating the JoyPop app as a tool for youth aged 12-17 in Northwestern Ontario, a population that has previously expressed interest in using the JoyPop in a pilot study.

Using a randomized controlled trial (RCT) design, the primary objective is to determine the effectiveness of the JoyPop app in improving emotion regulation among youth (12-17) who are waiting for mental health services as compared to usual practice (UP; monitoring those on the wait-list). The secondary objectives are to: (1) Assess change in mental health difficulties and treatment readiness between youth in each condition to better understand the app's broader impact as a wait-list tool; (2) Conduct an economic analysis to determine whether receiving the app while waiting for mental health services reduces other health service use and associated costs; (3) Define the Minimal Clinically Important Difference (MCID) for the primary outcome measure; and (4) Assess youth perspectives on the quality of the JoyPop app.
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of ULTOMIRIS or other ravulizumab-cwvz products.

The immunogenicity of ravulizumab-cwvz has been evaluated using an enzyme-linked immunosorbent assay (ELISA) for the detection of binding anti-ravulizumab-cwvz antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies.

In clinical studies with ULTOMIRIS, treatment-emergent antibodies to ravulizumab-cwvz were detected in 1 of 219 (0.5%) patients with PNH [see Clinical Studies (14.1)] and 1 of 71 (1.4%) patients with aHUS [see Clinical Studies (14.2)]. In these 2 patient populations, the observed ADA were non-neutralizing with no apparent impact on PK, safety, or efficacy. In the gMG study (N=86) and NMOSD study (N=58), no treatment-emergent antibodies to ravulizumab-cwvz were detected [see Clinical Studies (14.3 & 14.4)].

However, the assay used to measure anti-drug antibodies (ADA) is subject to interference by serum ravulizumab-cwvz, possibly resulting in an underestimation of the incidence of antibody formation. Due to the limitation of the assay conditions, the potential clinical impact of antibodies to ravulizumab-cwvz is not known.
INTRODUCTION: The original description of tubularized incised plate urethroplasty (TIPU) was provided by Snodgrass in 1994. The results were significantly improved by several modifications. To decrease the incidence of complications, interposing a vascularized flap after tubularization of the neourethra is recommended. The extent to which the type of interposed tissue has a direct effect on the rate of complications and cosmetic outcomes after TIPU repair is considered the answer to the main hypothesis of this study.
MATERIALS AND METHODS: This prospective controlled randomized trial was conducted in the Department of Pediatric Surgery, Al-Azhar University, Cairo, Egypt, between May 2019 and May 2023. A total of 220 patients were included in this study. Patients were randomly assigned to either group A or group B. Group A included 110 patients who underwent TIPU with spongioplasty-dartosoraphy reinforcement. The other 110 patients (group B) underwent TIPU with dorsal dartos flap interposition, without spongioplasty.
RESULTS: Complications developed in 34 of 220 patients (15.4%). In group A, complications developed in 11 of 110 patients (10.0%). In group B, complications occurred in 23 of 110 patients (20.9%). Although the fistula rate, glanular dehiscence, disruption, and meatal stenosis were not significantly different between the study groups, the skin necrosis rate was significantly lower in group A than in group B. The overall complication rate was significantly lower in group A than in group B. Also, the difference in the mean Hypospadias Objective Scoring Evaluation between the two groups was statistically significant.
CONCLUSION: TIPU with spongioplasty-dartosoraphy reinforcement is an effective modification of conventional TIPU. This modification appears to reduce the rate of complications and yield better cosmetic outcomes.
BACKGROUND: This study aims to investigate the role of endoplasmic reticulum stress (ER stress) in human dermal lymphatic endothelial cells (HDLECs) and lymphatic malformations (LMs) and its relationship with aerobic glycolysis and inflammation.
METHODS: The proliferation and apoptosis of HDLECs were examined with lipopolysaccharide (LPS) treatment. ER stress-associated proteins and glycolysis-related markers were detected by western blot. Glycolysis indexes were detected by seahorse analysis and lactic acid production assay kits. Immunohistochemistry was used to reveal the ER stress state of lymphatic endothelial cells (LECs) in LMs.
RESULTS: LPS induced ER stress in HDLECs but did not trigger detectable apoptosis. Intriguingly, LPS-treated HDLECs also showed increased glycolysis flux. Knockdown of Hexokinase 2, a key enzyme for aerobic glycolysis, significantly inhibited the ability of HDLECs to resist ER stress-induced apoptosis. Moreover, compared to normal skin, glucose-regulated protein 78 (GRP78/BIP), and phosphorylation protein kinase R-like kinase (p-PERK), two key ER stress-associated markers, were upregulated in LECs of LMs, which was correlated with the inflected state. In addition, excessively activated ER stress inhibited the progression of LMs in rat models.
CONCLUSIONS: These data indicate that glycolysis could rescue activated ER stress in HDLECs, which is required for the accelerated development of LMs.
IMPACT: Inflammation enhances both ER stress and glycolysis in LECs while glycolysis is required to attenuate the pro-apoptotic effect of ER stress. Endoplasmic reticulum (ER) stress is activated in lymphatic endothelial cells (LECs) of LMs, especially in inflammatory condition. The expression of ER stress-related proteins is increased in LMs and correlated with Hexokinase 2 expression. Pharmacological activation of ER stress suppresses the formation of LM lesions in the rat model. ER stress may be a promising and effective therapeutic target for the treatment of LMs.
The recommended initial dosage of metyrosine capsules for adults and children 12 years of age and older is 250 mg orally four times daily. This may be increased by 250 mg to 500 mg every day to a maximum of 4 g/day in divided doses. When used for preoperative preparation, the optimally effective dosage of metyrosine capsules should be given for at least five to seven days.

Optimally effective dosages of metyrosine capsules usually are between 2 g/day and 3 g/day, and the dose should be titrated by monitoring clinical symptoms and catecholamine excretion. In patients who are hypertensive, dosage should be titrated to achieve normalization of blood pressure and control of clinical symptoms. In patients who are usually normotensive, dosage should be titrated to the amount that will reduce urinary metanephrines and/or vanillylmandelic acid by 50% or more.

If patients are not adequately controlled by the use of metyrosine capsules, an alpha-adrenergic blocking agent (phenoxybenzamine) should be added.

Use of metyrosine capsules in children under 12 years of age has been limited and a dosage schedule for this age group cannot be given.
The Diabetes Staging System (DSS) is a novel type 2 diabetes (DM2) staging system patterned after Tumor Node Metastasis (TNM) cancer staging that uses the number of macrovascular and microvascular complications and most recent A1C and glomerular filtration rate (GFR) to determine DSS stage which reflects disease severity. The DSS stage is then linked to specific evidence-based clinical interventions that decrease morbidity and mortality. One of the most important clinical interventions of the DSS is recommending a SGLT2i/GLP-1 agonist in DM2 patients with CVD which helps address the inequity of low overall SGLT2i/GLP-1 use. The DSS has been adapted into a CPRS-DSS template available to all PACT providers within the Durham VA system which could address the racial differences in SGLT2i/GLP-1 agonist use. DSS offers a systematic approach to DM2 care (Stage DM2 -determine medical therapy based on DM2 stage) that has the potential to address inequities related to SGLT2i/GLP-1 overall use and racial differences in use. Primary Care Aligned Teams (PACT) are best positioned to use the DSS because they treat the vast majority of Veteran DM2 patients. This pilot proposal will seek to address inequities in SGLT2i/GLP-1 agonist use within in the VA by examining the feasibility and acceptability of the DSS among 12 different PACT teams within the Durham VA Medical System by measuring its ability to increase SGLT2i/GLP-1 agonist after 6 months of DSS implementation.
OBJECTIVES: The Gothenburg Trismus Questionnaire (GTQ) is a comprehensive scale for screening and assessing trismus in head and neck (H&N) cancer and temporomandibular joint disorders (TMD) patients. This study aimed to translate and cross-culturally adapt the GTQ in China, and to test its measurement invariance.
METHODS: This study comprised 278 H&N cancer, 245 TMD, and 507 control patients. Internal consistency and test-retest reliability were tested to assess the GTQ's reliability. The validity was evaluated through composite reliability (CR), average variance extracted (AVE), and correlation tests. Multi-group confirmatory factor analysis (CFA) was used to investigate the GTQ's measurement invariance across clinical status and gender. T tests were employed to compare score differences across clinical status and gender.
RESULTS: The Chinese version of GTQ scale shows excellent internal consistency and test-retest reliability. The CR, AVE, and correlation values demonstrate the good validity of GTQ. The multi-group CFA supported configural invariance across clinical status but not metric invariance, while it supported strict invariance across gender. Additionally, t tests revealed that patients with H&N cancer and TMD scored higher than the control group, while males scored higher than females.
CONCLUSIONS: The Chinese version of GTQ serves as an effective tool for screening and assessing trismus.
The invention belongs to the technical field of biological medicines, and particularly relates to application of hsa_circ_0000512 (circRPPH 1) gene in glioma diagnosis, treatment and prognosis. A biomarker for glioma, said marker being the hsa_circ_0000512 (circRPPH 1) gene. Use of hsa_circ_0000512 (circRPPH 1) gene in glioma diagnosis and prognosis related kit. Use of an inhibitor of the hsa_circ_0000512 (circRPPH 1) gene capable of specifically inhibiting the function of the hsa_circ_0000512 (circRPPH 1) gene for the preparation of a targeted medicament for the treatment of glioma. Experiments prove that the expression of the hsa_circ_0000512 (circRPPH 1) gene in the glioma tissue in vivo is obviously up-regulated compared with that in the normal brain tissue, so that the hsa_circ_0000512 (circRPPH 1) gene becomes a tumor auxiliary diagnosis marker and has feasibility. The invention provides a new theoretical basis and a brand new stability target for diagnosis and treatment of glioma and also provides a strategy for prognosis judgment of glioma.
Patients will receive pregabalin 150 mg oral (PO) twice per day (BID), and sham transcranial direct current stimulation (sham tDCS) five times per week during 2 weeks, and then twice per week until week 8th. The sham tDCS consists of the same montage of the active tDCS, but the device is turned off 30 seconds after initiating stimulation (without letting the patient notice it). Rest of the montage is kept identical as the active one during the 30 minutes that the session lasts.
This study aimed to explore the impact of clinical nursing pathway applied to acute appendicitis surgery on patients' postoperative wound infections and complications. A computerised search of PubMed, Cochrane Library, Web of Science, EMBASE, Wanfang, Chinese Biomedical Literature Database and China National Knowledge Infrastructure was conducted and supplemented by a manual search, from database inception to October 2023, to collect randomised controlled trials (RCTs) on the application of clinical nursing pathways to acute appendicitis surgery. Literature screening, data extraction and quality assessment of the included literature were carried out independently by two researchers. RevMan 5.4 software was applied for data analysis. Twenty-one RCTs with a total of 2408 patients were finally included. The analysis revealed the implementation of clinical nursing pathway could effectively reduce the incidence of wound infection (OR = 0.26, 95% CI: 0.15-0.46, p < 0.001) and postoperative complications (OR = 0.20, 95% CI: 0.15-0.27, p < 0.001), as well as shorten the hospital length of stay (MD = -3.26, 95% CI: -3.74 to -2.79, p < 0.001) and accelerated the time to first ventilations (MD = -14.85, 95% CI: -21.56 to -8.13, p < 0.001), as well as significantly improved patient satisfaction (OR = 5.52, 95% CI: 3.52-8.65, p < 0.001) in patients undergoing surgery for acute appendicitis. The application of clinical nursing pathway in acute appendicitis surgery can significantly reduce postoperative wound infection and complications, and at the same time can shorten the hospital length of stay as well as improve the satisfaction of patients.