anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The GBA (OMIM 606463) gene codes for beta-glucocerebrosidase, a lysosomal enzyme. Disease causing mutations in both alleles of GBA gene cause Gaucher disease (GD) while mutations in one allele lead to Gaucher carrier status. It has been shown recently that patients with GD, even carriers with one mutated GBA gene are at a higher risk for developing Parkinson disease (PD), and at an earlier age, and that the GBA mutations comprise the primary genetic risk factor in the development of PD and other forms of parkinsonism. However, there are no biomarkers to determine the diagnosis of PD, especially in the early and minimally symptomatic or asymptomatic stage. The progression of PD in subjects with a mutation in the GBA gene can currently not be determined. In some cellular and animal models, glucocerebrosidase alterations were shown to impact the metabolism of other proteins implicated in PD pathology. α-Synuclein and Parkin, encoded by SNCA and PARK2 respectively, are implicated in rare genetic forms of parkinsonism. α-Synuclein aggregates are seen in cells of the central and peripheral nervous system and is considered to be the pathological culprit in PD. Mutated glucocerebrosidase has been shown to be present in α-Synuclein aggregates in postmortem brain samples from individuals with GBA mutations and PD. α-Synuclein in addition, is shown to affect the solubility of Parkin in the cells. As an attempt to assess whether GBA alterations would also impact α-Synuclein and Parkin metabolism in humans in easily accessible cell types outside the brain, the expression at both molecular and protein level will be investigated in the peripheral blood mononuclear cells (PBMCs). The study includes three cohorts: 1) Patients and carriers of Gaucher disease with confirmed disease causing mutations in GBA gene who have developed Parkinson's disease symptoms (GD-PD), 2) Patients and carriers of Gaucher disease with no known Parkinson's symptoms (GD-nonPD) and 3) Non-Gaucher disease/healthy controls (HC). PBMCs extracted from 3-5 ml peripheral blood will be used for intracellular staining for α-Synuclein, LRRK2 and Parkin and then acquired on Flow cytometer (BD accuri). Lymphocytes and monocytes will be analyzed for α-Synuclein, LRRK2 and Parkin expression. PBMCs will also be used for RNA extraction and subsequent molecular analysis using qPCR. Since the assay utilizes an easily accessible tissue type i.e., peripheral blood and requires a very small amount (2-3 ml), this assay could be developed as a potential biomarker for diagnosis and a disease progression indicator for Parkinson disease in subjects with GBA gene mutations.
Ten subjects will be randomly assigned in a ratio of 4:1 to receive 5 mg of PA1010 tablets or 5mg of PA1010 placebo tablets. They will be administered a single dose and observed for four days.
Previous research demonstrates the joint association of self-reported physical activity and genotype with coronary artery disease. However, an existing research gap is whether accelerometer-measured overall physical activity or physical activity intensity can offset genetic predisposition to coronary artery disease. This study explores the independent and joint associations of accelerometer-measured physical activity and genetic predisposition with incident coronary artery disease. Incident coronary artery disease based on hospital inpatient records and death register data serves as the outcome of this study. Polygenic risk score and overall physical activity, measured as Euclidean Norm Minus One, and intensity, measured as minutes per day of moderate-to-vigorous intensity physical activity (MVPA), are examined both linearly and by decile. The UK Biobank population-based cohort recruited over 500,000 individuals aged 40 to 69 between 2006 and 2010, with 103,712 volunteers participating in a weeklong wrist-worn accelerometer study from 2013 to 2015. Individuals of White British ancestry (n = 65,079) meeting the genotyping and accelerometer-based inclusion criteria and with no missing covariates were included in the analytic sample. In the sample of 65,079 individuals, the mean (SD) age was 62.51 (7.76) and 61% were female. During a median follow-up of 6.8 years, 1,382 cases of coronary artery disease developed. At the same genetic risk, physical activity intensity had a hazard ratio (HR) of 0.41 (95% CI: 0.29-0.60) at the 90th compared to 10th percentile, equivalent to 31.68 and 120.96 minutes of moderate-to-vigorous physical activity per day, respectively, versus an HR of 0.61 (95% CI: 0.52-0.72) for overall physical activity. The combination of high genetic risk and low physical activity intensity showed the greatest risk, with an individual at the 10th percentile of genetic risk and 90th percentile of intensity facing an HR of 0.14 (95% CI: 0.09-0.21) compared to an individual at the 90th percentile of genetic risk and 10th percentile of intensity. Physical activity, especially physical activity intensity, is associated with an attenuation of some of the risk of coronary artery disease but this pattern does not vary by genetic risk. This accelerometer-based study provides the clearest evidence to date regarding the joint influence of genetics, overall physical activity, and physical activity intensity on coronary artery disease.
Patients with refractory CMV will be given one dose of CMV specific CTLs. HLA matched donors will get Dose 2.5 × 10(4) CD3/kg recipient weight; HLA mismatched will get 0.5x10(4) CD3/kg recipient weight. Additional doses may be given for a total of 5 doses if patients do not have a response to the first dose with a reduction in viral load to normal limits.
OBJECTIVE: Hypertension is a leading preventable cause of mortality, yet high rates of undiagnosed and uncontrolled hypertension continue. The burden falls most heavily on some ethnic minorities and the socially deprived, with the COVID-19 pandemic having further widened inequalities. We sought to determine the prevalence and predictors of unmeasured blood pressure (BP), uncoded elevated BP and uncontrolled hypertension in primary care across 2014-2021.
METHODS: A population-based cohort study using data from all 41 general practices in a socioeconomically diverse inner-city borough. BP measurements, sociodemographic, lifestyle and clinical factors were extracted from anonymized primary care data. Hypertension and BP control were defined using NICE guidelines. Associations between patient characteristics and hypertension outcomes were identified using logistical regression modelling.
RESULTS: Of 549 082 patients, 39.5% had unmeasured BP; predictors included male sex [AOR 2.40, 95% confidence interval (95% CI) 2.26-2.43] and registration in the pandemic years. Of 71 970 adults with elevated BP, 36.0% were uncoded; predictors included obesity (AOR 2.51, 95% CI 2.42-2.60) and increasing age. Of 44 648 adults on the hypertension register, 46.8% had uncontrolled hypertension; predictors included black ethnicity compared to white (AOR 1.54, 95% CI 1.41-1.68) and cardiovascular co-morbidities (AOR 1.23, 95% CI 1.21-1.25). Social deprivation was only weakly or not significantly associated with hypertension outcomes.
CONCLUSION: The burden of uncoded elevated BP and uncontrolled hypertension is high. Obesity and male sex were associated with uncoded elevated BP and uncontrolled hypertension. Black ethnicity was associated with uncontrolled hypertension. Initiatives are needed to optimize hypertension coding and control, with an emphasis on specific population subgroups.
Promethazine HCl, Phenylephrine HCl and Codeine Phosphate Oral Solution, USP contains codeine, an opioid agonist; promethazine, a phenothiazine; and phenylephrine, an alpha-1 adrenergic receptor agonist.

Each 5 mL of Promethazine HCl, Phenylephrine HCl and Codeine Phosphate Oral Solution, USP contains 10 mg of codeine phosphate, 6.25 mg of promethazine hydrochloride, and 5 mg of phenylephrine hydrochloride for oral administration.

Promethazine HCl, Phenylephrine HCl and Codeine Phosphate Oral Solution, USP has a pH between 3.8 and 4.6 and contains alcohol 7%.

Promethazine HCl, Phenylephrine HCl and Codeine Phosphate Oral Solution, USP also contains the following inactive ingredients: Ascorbic acid, citric acid, FD&C Yellow #6, methylparaben, natural tangerine extract, propylene glycol, propylparaben, purified water, sodium benzoate, sodium citrate, and sucrose syrup.

Codeine Phosphate

The chemical name for codeine phosphate is 7,8-Didehydro-4, 5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate. Codeine is one of the naturally occurring phenanthrene alkaloids of opium derived from the opium poppy, it is classified pharmacologically as a narcotic analgesic. The phosphate salt of codeine occurs as white, needle-shaped crystals or white crystalline powder. Codeine phosphate is freely soluble in water and slightly soluble in alcohol. The molecular weight is 406.37. Its molecular formula is C18H21NO3•H3PO4 • ½ H2O, and it has the following chemical structure. 

Promethazine Hydrochloride

The chemical name for promethazine hydrochloride, a phenothiazine derivative, is (±)-10-[2-(Dimethylamino)propyl] phenothiazine monohydrochloride. Promethazine hydrochloride occurs as a white to faint yellow, practically odorless, crystalline powder which slowly oxidizes and turns blue on prolonged exposure to air. It is soluble in water and freely soluble in alcohol. The molecular weight is 320.88. Its molecular formula is C17H20N2S•HCl, and it has the following chemical structure. 

Phenylephrine Hydrochloride

The chemical name for phenylephrine hydrochloride, a sympathomimetic amine salt, is (-)-m-hydroxy-α-[(methyl-amino)methyl] benzyl alcohol hydrochloride. It occurs as white or nearly white crystals, having a bitter taste. It is freely soluble in water and alcohol. Phenylephrine hydrochloride is subject to oxidation and must be protected from light and air. The molecular weight is 203.67. Its molecular formula is C9H13NO2 • HCl, and it has the following chemical structure.
PURPOSE: Microbial dysbiosis is considered as a hallmark of colorectal cancer (CRC). Trimethylamine-N-oxide (TMAO) as a gut microbiota-dependent metabolite has recently been implicated in CRC development. Nevertheless, evidence relating TMAO to intestinal carcinogenesis remains largely unexplored. Herein, we aimed to examine the crucial role of TMAO in CRC progression.
METHODS: Apcmin/+ mice were treated with TMAO or sterile PBS for 14 weeks. Intestinal tissues were isolated to evaluate the effects of TMAO on the malignant transformation of intestinal adenoma. The gut microbiota of mouse feces was detected by 16S rRNA sequencing analysis. HCT-116 cells were used to provide further evidence of TMAO on the progression of CRC.
RESULTS: TMAO administration increased tumor cell and stem cell proliferation, and decreased apoptosis, accompanied by DNA damage and gut barrier impairment. Gut microbiota analysis revealed that TMAO induced changes in the intestinal microbial community structure, manifested as reduced beneficial bacteria. Mechanistically, TMAO bound to farnesoid X receptor (FXR), thereby inhibiting the FXR-fibroblast growth factor 15 (FGF15) axis and activating the Wnt/β-catenin signaling pathway, whereas the FXR agonist GW4064 could blunt TMAO-induced Wnt/β-catenin pathway activation.
CONCLUSION: The microbial metabolite TMAO can enhance intestinal carcinogenesis by inhibiting the FXR-FGF15 pathway.
South American ecosystems host astonishing biodiversity, with potentially great richness in viruses. However, these ecosystems have not yet been the source of any widespread, epidemic viruses. Here we explore a set of putative causes that may explain this apparent paradox. We discuss that human presence in South America is recent, beginning around 14,000 years ago; that few domestications of native species have occurred; and that successive immigration events associated with Old World virus introductions reduced the likelihood of spillovers and adaptation of local viruses into humans. Also, the diversity and ecological characteristics of vertebrate hosts might serve as protective factors. Moreover, although forest areas remained well preserved until recently, current brutal, sudden, and large-scale clear cuts through the forest have resulted in nearly no ecotones, which are essential for creating an adaptive gradient of microbes, hosts, and vectors. This may be temporarily preventing virus emergence. Nevertheless, the mid-term effect of such drastic changes in habitats and landscapes, coupled with explosive urbanization and climate changes, must not be overlooked by health authorities.
Neuropathic pain (NPP) is a devastating and unbearable painful condition. As prevailing treatment strategies have failed to mitigate its complications, there remains a demand for effective therapies. Electroacupuncture (EA) has proved a potent remedial strategy in NPP management in humans and mammals. However, past studies have investigated the underlying mechanism of the analgesic effects of EA on NPP, focusing primarily on adenosine receptors in peripheral tissues. Herein, we elucidate the role of the adenosine (Adora-3) signaling pathway in mediating pain relief through EA in the central nervous system, which is obscure in the literature and needs exploration. Specific pathogen-free (SPF) male adult mice (C57BL/6 J) were utilized to investigate the effect of EA on adenosine metabolism (CD73, ADA) and its receptor activation (Adora-3), as potential mechanisms to mitigate NPP in the central nervous system. NPP was induced via spared nerve injury (SNI). EA treatment was administered seven times post-SNI surgery, and lumber (L4-L6) spinal cord was collected to determine the molecular expression of mRNA and protein levels. In the spinal cord of mice, following EA application, the expression results revealed that EA upregulated (p < 0.05) Adora-3 and CD73 by inhibiting ADA expression. In addition, EA triggered the release of adenosine (ADO), which modulated the nociceptive responses and enhanced neuronal activation. Meanwhile, the interplay between ADO levels and EA-induced antinociception, using an Adora-3 agonist and antagonist, showed that the Adora-3 agonist IB-MECA significantly increased (p < 0.05) nociceptive thresholds and expression levels. In contrast, the antagonist MRS1523 exacerbated neuropathic pain. Furthermore, an upregulated effect of EA on Adora-3 expression was inferred when the Adora-3 antagonist was administered, and the EA treatment increased the fluorescent intensity of Adora-3 in the spinal cord. Taken together, EA effectively modulates NPP by regulating the Adora-3 signaling pathway under induced pain conditions. These findings enhance our understanding of NPP management and offer potential avenues for innovative therapeutic interventions.
Paroxysmal kinesigenic dyskinesia (PKD) is associated with a disturbance of neural circuit and network activities, while its neurophysiological characteristics have not been fully elucidated. This study utilized the high-density electroencephalogram (hd-EEG) signals to detect abnormal brain activity of PKD and provide a neural biomarker for its clinical diagnosis and PKD progression monitoring. The resting hd-EEGs are recorded from two independent datasets and then source-localized for measuring the oscillatory activities and function connectivity (FC) patterns of cortical and subcortical regions. The abnormal elevation of theta oscillation in wildly brain regions represents the most remarkable physiological feature for PKD and these changes returned to healthy control level in remission patients. Another remarkable feature of PKD is the decreased high-gamma FCs in non-remission patients. Subtype analyses report that increased theta oscillations may be related to the emotional factors of PKD, while the decreased high-gamma FCs are related to the motor symptoms. Finally, the authors established connectome-based predictive modelling and successfully identified the remission state in PKD patients in dataset 1 and dataset 2. The findings establish a clinically relevant electroencephalography profile of PKD and indicate that hd-EEG can provide robust neural biomarkers to evaluate the prognosis of PKD.
No interventions will be administered. Retrospective data analysis will be completed to compare health outcomes among patients with a similar baseline health satus who are eligible for both procedures (operative transcatheter AVR patients enrolled in the Transcatheter Valve Therapies (TVT) Registry (Nov 2011-Dec 2013) and surgical AVR patients with STS perioperative risk of mortality whose index procedure is included in the STS Adult Cardiac Surgical DAtabase (ACSD) (Jan 2011-Dec 2013).
Chronic pain is a severely debilitating condition with enormous socioeconomic costs. Current treatment regimens with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or opioids have been largely unsatisfactory with uncertain benefits or severe long-term side effects. This is mainly because chronic pain has a multifactorial aetiology. Although conventional pain medications can alleviate pain by keeping several dysfunctional pathways under control, they can mask other underlying pathological causes, ultimately worsening nerve pathologies and pain outcome. Recent preclinical studies have shown that endoplasmic reticulum (ER) stress could be a central hub for triggering multiple molecular cascades involved in the development of chronic pain. Several ER stress inhibitors and unfolded protein response modulators, which have been tested in randomised clinical trials or apprpoved by the US Food and Drug Administration for other chronic diseases, significantly alleviated hyperalgesia in multiple preclinical pain models. Although the role of ER stress in neurodegenerative disorders, metabolic disorders, and cancer has been well established, research on ER stress and chronic pain is still in its infancy. Here, we critically analyse preclinical studies and explore how ER stress can mechanistically act as a central node to drive development and progression of chronic pain. We also discuss therapeutic prospects, benefits, and pitfalls of using ER stress inhibitors and unfolded protein response modulators for managing intractable chronic pain. In the future, targeting ER stress to impact multiple molecular networks might be an attractive therapeutic strategy against chronic pain refractory to steroids, NSAIDs, or opioids. This novel therapeutic strategy could provide solutions for the opioid crisis and public health challenge.
FIELD: medicine. ^ SUBSTANCE: invention refers to therapeutic agents and concerns a therapeutic agents used for treatment of the patients suffering from diseases caused by monoaminooxidase overactivity and representing polyprenols of formula (1). The content of polyprenols of formula (1) where n=8-20 in the specified agent is 0.1 to 80%. Also there is disclosed method for treatment of the patients suffering from diseases caused by monoaminooxidase overactivity, characterised that a patient takes one or more doses of polyprenols of formula (1) in amount 1 to 150 mg a day (1). ^ EFFECT: invention allows extending range of therapeutic agents for treatment of the patients suffering from diseases caused by monoaminooxidase overactivity. ^ 4 cl, 8 tbl, 12 ex
The recommended starting dose for SAD is 150 mg once daily. After 7 days of dosing, the dose may be increased to the target dose of 300 mg once daily in the morning. Doses above 300 mg of bupropion hydrochloride extended-release were not assessed in the SAD trials.

For the prevention of seasonal MDD episodes associated with SAD, initiate Wellbutrin XL in the autumn, prior to the onset of depressive symptoms. Continue treatment through the winter season. Taper and discontinue Wellbutrin XL in early spring. For patients treated with 300 mg per day, decrease the dose to 150 mg once daily before discontinuing Wellbutrin XL. Individualize the timing of initiation, and duration of treatment should be individualized, based on the patient’s historical pattern of seasonal MDD episodes.
OBJECTIVES: Chronic lung disease is a recognized complication in children with HIV. Acute respiratory exacerbations (ARE) are common among this group and cause significant morbidity. Exhaled nitric oxide (eNO) is a known marker of local airway inflammation. We investigated the association between eNO and ARE, biomarkers of systemic inflammation, and the effect of azithromycin on eNO levels.
METHODS: Individuals aged 6-19 years with HIV-associated chronic lung disease in Harare, Zimbabwe, were enrolled in a placebo-controlled randomized trial investigating the effect of 48-week azithromycin treatment on lung function and ARE. eNO levels and biomarkers were measured at inclusion and after treatment in a consecutively enrolled subset of participants. Linear regression and generalized linear models were used to study associations between eNO and ARE, biomarkers, and the effect of azithromycin on eNO levels.
RESULTS: In total, 172 participants were included in this sub-study, 86 from the placebo group and 86 from the azithromycin group. Participants experiencing at least one ARE during follow-up had significantly higher eNO levels at baseline than participants who did not (geometric mean ratio 1.13, 95% confidence interval [CI] 1.03-1.24, p = 0.015), adjusted for trial arm, age, sex and history of tuberculosis. Matrix metalloproteinase (MMP)-3, -7, and -10 were significantly associated with higher baseline eNO levels. At 48 weeks, azithromycin treatment did not affect eNO levels (geometric mean ratio 0.86, 95% CI 0.72-1.03, p = 0.103).
CONCLUSION: Higher baseline eNO levels were a risk factor for ARE. eNO was associated with proinflammatory biomarkers previously found to contribute to the development of chronic lung disease. The potential use of eNO as a marker of inflammation and risk factor for ARE in HIV-associated chronic lung disease needs further investigation.
Patients with measurable metastatic breast cancer that have been treated in the adjuvant or neo-adjuvant setting with chemotherapy will be considered for this study. Subjects must not have received cytotoxic chemotherapy for locally recurrent/metastatic disease. Patients who fulfil the eligibility criteria, and have signed inform consent for the trial will be centrally randomized by electronic means to one of two ixabepilone treatment arms. Stratification factors will include: time to recurrence from adjuvant treatment, calculated from the date of the last dose of adjuvant treatment to the date of relapse (≤ 1 year vs. \> 1 year); and previous chemotherapy with taxane regimen in the neo-adjuvant or adjuvant setting (yes vs. no). Randomization will be balanced by site.Treatment Protocol· Arm A \[standard once every three weeks schedule\]:Ixabepilone \[BMS-247550\] will be administered on Day 1 (D1) every three weeks as a 3-hour infusion at a dose of 40 mg/m2. · Arm B \[weekly schedule\]:Ixabepilone \[BMS-247550\] will be administered weekly for three weeks as a 3-hour infusion at a dose of 20 mg/m2, followed by one week-off.Treatment can be continued until consent withdrawal by the patient, intolerable toxicity or documented disease progression.
Conventional diet. (50% carbohydrate, 30% lipids, 20% protein). Current dietary recommendations from official guidelines will be reinforced.