anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
A total of 510 subjects currently on chronic opioid therapy entered an open-label conversion and titration phase (up to 6 weeks) with ZOHYDRO ER dosed every 12 hours at an approximated equianalgesic dose of their pre-study opioid medication. For inadequately controlled pain, ZOHYDRO ER was increased by 10 mg per 12-hour dose, once every 3–7 days until a stabilized dose was identified, or a maximum dosage of 100 mg every 12 hours. There were 302 subjects (59%) randomized at a ratio of 1:1 into a 12-week double-blind treatment phase with their fixed stabilized dose of ZOHYDRO ER (40–200 mg daily taken as 20–100 mg, every 12 hours) or a matching placebo. Subjects randomized to placebo were given a blinded taper of ZOHYDRO ER according to a pre-specified tapering schedule. During the treatment phase, subjects were allowed to use rescue medication (hydrocodone 5 mg/500 mg acetaminophen) up to 2 doses (2 tablets) per day. There were 124 treated subjects (82%) that completed the 12-week treatment with ZOHYDRO ER and 59 subjects (39%) with placebo.

ZOHYDRO ER provided greater analgesia compared to placebo. There was a significant difference in the mean changes from Baseline to Week 12 in average weekly pain intensity Numeric Rating Scale (NRS) scores between the two groups. 

The percentage of subjects in each group who demonstrated improvement in their NRS pain score at End-of-Study, as compared to Screening is shown in the figure below. The figure is cumulative, so subjects whose change from Screening is, for example, 30%, are also included at every level of improvement below 30%. Subjects who did not complete the study were classified as non-responders. Treatment with ZOHYDRO ER produced a greater number of responders, defined as subjects with at least a 30% improvement, as compared to placebo (67.5% vs. 31.1%).
The subjects will be given 1 month supply of Pioglitazone pills. Pioglitazone is a class of anti-diabetic drugs called thiazolidinediones that are primarily used in the treatment of type 2 diabetes. The aim of the study is to determine if Pioglitazone also reduces ADMA and sympathetic nerve activity in CKD patients. This drug will be taken orally as a pill or capsule for one month. The dosage is 15 mg/day. This is on the lower dosage side for pioglitazone with the maximum dosage being 45mg/day. The research subjects are not responsible for the cost of the drug or for drug administration costs. The subjects will be verbally instructed to take 1 pill everyday by mouth, for 1 month. In addition, the pill bottle will be labeled with the same instructions.
The potential for supine and sitting hypertension should be evaluated at the beginning of midodrine hydrochloride therapy. Supine hypertension can often be controlled by preventing the patient from becoming fully supine, i.e., sleeping with the head of the bed elevated. The patient should be cautioned to report symptoms of supine hypertension immediately. Symptoms may include cardiac awareness, pounding in the ears, headache, blurred vision, etc.

The patient should be advised to discontinue the medication immediately if supine hypertension persists. Blood pressure should be monitored carefully when midodrine hydrochloride is used concomitantly with other agents that cause vasoconstriction, such as phenylephrine, ephedrine, dihydroergotamine, phenylpropanolamine or pseudoephedrine.

A slight slowing of the heart rate may occur after administration of midodrine hydrochloride, primarily due to vagal reflex. Caution should be exercised when midodrine hydrochloride is used concomitantly with cardiac glycosides (such as digitalis), psychopharmacologic agents, beta blockers or other agents that directly or indirectly reduce heart rate. Patients who experience any signs or symptoms suggesting bradycardia (pulse slowing, increased dizziness, syncope, cardiac awareness) should be advised to discontinue midodrine hydrochloride and should be re-evaluated.

Midodrine hydrochloride should be used cautiously in patients with urinary retention problems, as desglymidodrine acts on the alpha-adrenergic receptors of the bladder neck.

Midodrine hydrochloride should be used with caution in orthostatic hypotensive patients who are also diabetic, as well as those with a history of visual problems who are also taking fludrocortisone acetate, which is known to cause an increase in intraocular pressure and glaucoma.

Midodrine hydrochloride use has not been studied in patients with renal impairment. Because desglymidodrine is eliminated via the kidneys and higher blood levels would be expected in such patients, midodrine hydrochloride should be used with caution in patients with renal impairment, with a starting dose of 2.5 mg (see DOSAGE AND ADMINISTRATION). Renal function should be assessed prior to initial use of midodrine hydrochloride.

Midodrine hydrochloride use has not been studied in patients with hepatic impairment. Midodrine hydrochloride should be used with caution in patients with hepatic impairment, as the liver has a role in the metabolism of midodrine.
Guanfacine is a selective central alpha 2A -adrenergic receptor agonist in that it has a 15 to 20 times higher affinity for this receptor subtype than for the alpha 2B or alpha 2C subtypes. 

Guanfacine is a known antihypertensive agent. By stimulating central alpha 2A -adrenergic receptors, guanfacine reduces sympathetic nerve impulses from the vasomotor center to the heart and blood vessels. This results in a decrease in peripheral vascular resistance and a reduction in heart rate. 

In a thorough QT study, the administration of two dose levels of immediate-release guanfacine (4 mg and 8 mg) produced concentrations approximately 2 to 4 times the concentrations observed with the maximum recommended dose of guanfacine extended-release tablets of 0.12 mg/kg. Guanfacine was not shown to prolong the QTc interval to any clinically relevant extent.
BACKGROUND: Gait deficits are very common after stroke and therefore an important aspect in poststroke rehabilitation. A currently little used method in gait rehabilitation after stroke is the activation of the flexor reflex (FR) by electrical stimulation of the sole of foot while walking. The aim of this study was to investigate the effect of FR stimulation on gait performance and gait parameters in participants with stroke within a single session of flexor reflex stimulation using Incedo™.
METHODS: Twenty-five participants with subacute (n = 14) and chronic (n = 11) stroke were enrolled in the study. Motor functions were tested with a 10-m walk test (10mWT), a 2-min walk test (2minWT), and a gait analysis. These tests were performed with and without Incedo™ within a single session in randomized order.
RESULTS: In the 10mWT, a significant difference was found between walking with Incedo™ (15.0 ± 8.5 s) versus without Incedo™ (17.0 ± 11.4 s, p = 0.01). Similarly, the 2minWT showed a significant improvement with Incedo™ use (90.0 ± 36.4 m) compared to without Incedo™ (86.3 ± 36.8 m, p = 0.03). These results indicate that while the improvements are statistically significant, they are modest and should be considered in the context of their clinical relevance. The gait parameters remained unchanged except for the step length. A subgroup analysis indicated that participants with subacute and chronic stroke responded similarly to the stimulation. There was a correlation between the degree of response to electrostimulation while walking and degree of improvement in 2minWT (r = 0.50, p = 0.01).
CONCLUSIONS: This study is the first to examine FR activation effects in chronic stroke patients and suggests that stimulation effects are independent of the time since stroke. A larger controlled clinical trial is warranted that addresses issues as the necessary number of therapeutical sessions and for how long stimulation-induced improvements outlast the treatment period.
TRIAL REGISTRATION: The trial was retrospectively registered in German Clinical Trials Register.
CLINICAL TRIAL REGISTRATION NUMBER: DRKS00021457. Date of registration: 29 June 2020.
This study is an observational study performed in adult patients undergoing propofol based TIVA for clipping of unruptured cerebral aneurysm. We will collect data regarding recovery after stopping propofol infusion (time for eye opening and extubation), propofol requirement during anesthesia maintenance, and propofol effect site concentration to achieve bispectral index 40 during anesthesia induction, without doing any interventions. Data collection will be established with just observing and recording values displayed in screens of monitoring devices, and reviewing patient charts.
BACKGROUND: Ulcerative proctitis (UP) and ulcerative proctosigmoiditis (UPS) are special forms of ulcerative colitis. The disease burdens of UP and UPS are increasing. However, the natural history and prognosis of patients with mild-to-moderate UP or UPS have been poorly studied.
AIMS: The aim of this study is to evaluate the characteristics, short-term and long-term outcomes of patients with mild-to-moderate UP or UPS followed at a single center over a period of 3 years.
METHODS: A retrospective study of patients with UP and UPS followed at a single center from 2021 to 2023 was performed. After scanning for inclusion and exclusion criteria, patient demographics and clinical data were collected. Disease severity was accessed by Myao endoscopy scores and ulcerative colitis endoscopic index of severity. Endoscopic improvement was defined as decreased scores at the last follow-up. Disease extension was defined as endoscopic evidence of a greater extent of disease at the last follow-up.
RESULTS: A total of 414 patients were included for evaluation, of which 292 patients (70.53%) were at mild disease stage, and 122 patients (29.47%) had moderate diseases. At the last follow-up, 315 patients (76.09%) showed endoscopic improvement, and 247 patients (59.66%) showed endoscopic remission. An overall extension rate of 11.11% was observed at the last follow-up. Subgroup analysis revealed a better prognosis in younger patients. The disease extension rate was higher in moderate group and symptomatic patients.
CONCLUSION: Promising outcomes were observed in patients with mild-to-moderate ulcerative proctitis or ulcerative proctosigmoiditis. Disease severity and symptoms are correlated with the risk of extension.
Deletion of the rsk2 gene in mice results in reduced body weight, reduced body fat and reduced sensitivity to diet-induced weight gain, as well as lower levels of leptin in the serum of rsk2 deficient mice and lower levels of oxygen consumption, as compared to wild type littermates. Thus, altering RSK2 activity provides a means for modulating RSK2-mediated signaling and therefore modulating the above described physiological parameters. The present invention encompasses methods and compositions for altering, or modulating in a mammal, body weight, fat content, leptin levels by altering, or modulating, RSK2 activity. Specifically encompassed in the present invention are methods and compositions to alter activity of the RSK2. The present invention is drawn to a model for the study of Coffin-Lowry syndrome as well as an in vivo model to screen and test therapeutic agents for the treatment of Coffin-Lowry syndrome. The present invention is further drawn to use of the rsk2 knockout mouse as a model to study and treatment of lipodystrophy and impaired glucose tolerance in mammals.
Patients fulfilling the inclusion criteria will be divided into 2 groups i.e. Group A and Group B. Patients in Group A will receive thrust manipulation technique and Group B will receive pelvic stabilization exercises, heating pad will be given to both groups. Patients will be treated 3 times per week for 4 consecutive weeks. Patient will be evaluated at baseline, midline and at end of 4th week. Pain, functional status and disability will be evaluated after every 3 sessions.
Patients with sleep disordered breathing (SDB) experience nighttime sleep fragmentation and often become hypoxic during the night. The fragmentation and hypoxemia can frequently result in daytime impairments including impairments in cognitive functioning. The state-of-the-art treatment for SDB is Continuous Positive Airway Pressure (CPAP). Many SDB patients who are successfully treated with CPAP show improvement in memory and other cognitive functions. Data have shown that there is a strong relationship between SDB and dementia with patients with Alzheimer's Disease (AD) having a high rate of SDB. This proposal will examine whether treating SDB with CPAP in patients with AD will result in improvement in cognitive functioning. The specific aims are to assess whether patients with mild AD and SDB will tolerate CPAP and be compliant with treatment; to examine the effect of CPAP treatment on SDB in patients with mild AD and SDB; to examine the effect of CPAP treatment on cognitive functioning in patients with mild AD and SDB; to examine whether improvement is greater after six weeks of CPAP treatment than after three weeks of treatment. Since caregivers are often disturbed by the patients poor sleep, we will also evaluate the effect of the patients' treatment on their caregivers. Specifically, the secondary aims are to evaluate whether caregivers feel that CPAP improves the patient's sleep and to evaluate whether caregivers feel that their own sleep improves as the patient's sleep improves. Patient identified as having mild AD and SDB will have an extensive neuropsychological battery. Half will be randomized to CPAP treatment and the other half to shamCPAP. After three weeks neuropsychological tests will be repeated. The shamCPAP will be switched to CPAP and the CPAP group will remain on CPAP for an additional three weeks. Neuropsychological tests will again be repeated. The long-term goal of this line of research is to find a new approach that might improve the quality of life, delay the dementing process, postpone institutionalization and save millions of dollars in nursing care costs.
A highly engaging and interactive 60-minute, in-person communication skills training program will be developed as part of this project. Participating transplant providers will complete a brief online survey before (pre) and after (post) participating in the training.
Migraine causes a tremendous disease burden around the world. Migraine is one of the most prevalent neurological disorders and is reported by the WHO as the second leading cause of disease-related disabilities globally (No. 1 in the population under the 50s). There has been no much change in the ranking of disability for migraine for the past two decades, reflecting an unmet need for better treatment options. Even with the recently available calcitonin-gene related peptide (CGRP)-based treatment, the treatment response versus placebo is still disappointing (6.4-17.6% in acute treatment, 10.2-23.7% in preventive treatment). There is an urgent need to push further the current understanding of the pathophysiology of migraine, based on which novel treatment strategies can be developed. The lack of appropriate research tools hinders the acceleration of migraine research. As a neurological disorder, many neuroimaging studies have been focused on brain alterations; however, the majority focused on the cerebrum. Limited by the currently available neuroimaging and electrophysiological technologies, the deep brain structures especially the brainstem involved in the sensory and nociceptive neurotransmission in migraine, such as the trigeminal nucleus, could only be investigated to a limited extent. Obviously, there is an unmet need for novel technologies that can be used to delineate structural or functional alterations in the brainstem. Elucidation of the role of these deep brain structures may fill the gap in the current understanding of migraine pathophysiology, and pave the way to precise and efficient treatment. Studies restricted to single methodologies are insufficient for the complexity of migraine. Migraine is a complex and dynamic disorder. However, most prior studies were limited to single methodologies and provided limited insights into such a multifaceted disorder. Studies with an integrated approach are lacking. An exhaustive examination of the discrete components of a phenotype, i.e., 'deep phenotyping', can help understand different aspects of its clinical manifestations, and facilitate patient classification. Coupled with neuroimaging and electrophysiological research methodologies, a multi-modal decoding approach would help identify a constellation of migraine-specific biosignatures, rather than just one. This can not only provide clues to decipher migraine pathophysiology in various dimensions but also serve as the basis of the development of a prediction algorithm that can be applied in clinical practice. To pursue the overall goal, the present project schemes as a composition of the following 5 aims:

Aim 1: Deep phenotyping for sensory processing in patients with migraine Aim 2: Brainstem-based functional and structural connectomics in migraine Aim 3: Capturing brainstem electro-neurosignature in migraine Aim 4: Constructing a data fusion platform and developing an EEG cap with a built-in analytic chip Aim 5: Exploring brainstem-based connectome sequencing in migraine animal model
The invention discloses a medicine paste for treating sudden facial paralysis. The medicine paste comprises a paste strap (1). The four edges of the paste strap body (1) are each provided with a set of intermittent paste strips (4). A cataplasm (2) for sticking medicine cakes is arranged on the cloth face of the paste strip body (1). The four edges of the cataplasm (2) are each provided with a piece of preset paper (3) for containing medicine cakes conveniently. Frame strips of the cataplasm with no preset paper (3) can be used for being stuck to skin, wherein a medicine cake prepared from radix angelicae, geranium wilfordii, nandina roots, Chingma Abutilon seeds, Celtis sinensis root tengyuch euonymus bark, fructus polygoni orientalis, solarium xanthocarpum and Ardisia Crenata Sims on the basis of the ratio being 3:2:2:2:1:1:1:1 is arranged on the cataplasm (2). The effect of preventing irritability of the adhesion position can be achieved through the preset paper (3) and the intermittent paste strips (4) on the paste strap body (1). The medicine paste is pure Chinese herbal medicine powder and has the advantages of being proper in external application sticking, low in manufacturing cost, rapid in using effect and good in treatment effect.
A new synergistic flame retardant named Bisiminopropyl trimethoxysilane-1,3,5-triazine-O-bicyclic pentaerythritol phosphate (BTPODE) was synthesized, which is a type of Si/P/N flame retardant. This was accomplished by grafting aminopropyl trimethoxysilane and bicyclic pentaerythritol phosphate onto a triazine ring structure, serving as an intermediate. The structure of BTPODE was determined using nuclear magnetic resonance (1H NMR, 13C NMR, and 31P NMR) and Fourier transform infrared spectroscopy (FT-IR). SEM was used to detect the surface morphology of cotton fabrics, which suggested that BTPODE had been resoundingly stick to cotton fabrics. The flame retardant properties of cotton fabrics were evaluated by measuring the limiting oxygen index (LOI) and conducting vertical flammability experiments. Cotton fabrics with a weight gain of 20.73 % achieved an LOI value of 32.5 %. Thermogravimetric (TG) experiments demonstrated the samples' good thermostability. Furthermore, under nitrogen conditions, the char residue of cotton fabric with a weight gain of 20.73 % was 36.85 %. The cone calorimetry test (CONE) showed a significant reduction in the TSP value, indicating a certain level of smoke suppression performance. Finally, based on the obtained experimental results, the fire-retardant mechanism principle of the flame retardant was deduced.
Genome-wide Association Studies (GWAS) methods have identified individual single-nucleotide polymorphisms (SNPs) significantly associated with specific phenotypes. Nonetheless, many complex diseases are polygenic and are controlled by multiple genetic variants that are usually non-linearly dependent. These genetic variants are marginally less effective and remain undetected in GWAS analysis. Kernel-based tests (KBT), which evaluate the joint effect of a group of genetic variants, are therefore critical for complex disease analysis. However, choosing different kernel functions in KBT can significantly influence the type I error control and power, and selecting the optimal kernel remains a statistically challenging task. A few existing methods suffer from inflated type 1 errors, limited scalability, inferior power or issues of ambiguous conclusions. Here, we present a new Bayesian framework, BayesKAT (https://github.com/wangjr03/BayesKAT), which overcomes these kernel specification issues by selecting the optimal composite kernel adaptively from the data while testing genetic associations simultaneously. Furthermore, BayesKAT implements a scalable computational strategy to boost its applicability, especially for high-dimensional cases where other methods become less effective. Based on a series of performance comparisons using both simulated and real large-scale genetics data, BayesKAT outperforms the available methods in detecting complex group-level associations and controlling type I errors simultaneously. Applied on a variety of groups of functionally related genetic variants based on biological pathways, co-expression gene modules and protein complexes, BayesKAT deciphers the complex genetic basis and provides mechanistic insights into human diseases.
BACKGROUND: Intervertebral disc (IVD) degeneration is a multifactorial pathological process resulting in the dysregulation of IVD cell activity. The catabolic shift observed in IVD cells during degeneration leads to increased inflammation, extracellular matrix (ECM) degradation, aberrant intracellular signaling and cell loss. Importantly, these pathological processes are known to be interconnected and to collectively contribute to the progression of the disease. MicroRNAs (miRNAs) are known as strong post-transcriptional regulators, targeting multiple genes simultaneously and regulating numerous intracellular pathways. Specifically, miR-155-5p has been of particular interest since it is known as a pro-inflammatory mediator and contributing factor to diseases like cancer and osteoarthritis. This study investigated the role of miR-155-5p in IVD degeneration with a specific focus on inflammation and mechanosensing.
METHODS: Gain- and loss-of-function studies were performed through transfection of human Nucleus pulposus (NP) and Annulus fibrosus (AF) cells isolated from degenerated IVDs with miR-155-5p mimics, inhibitors or their corresponding non-targeting control. Transfected cells were then subjected to an inflammatory environment or mechanical loading. Conditioned media and cell lysates were collected for phosphorylation and cytokine secretion arrays as well as gene expression analysis.
RESULTS: Increased expression of miR-155-5p in AF cells resulted in significant upregulation of interleukin (IL)-8 cytokine secretion during cyclic stretching and a similar trend in IL-6 secretion during inflammation. Furthermore, miR-155-5p mimics increased the expression of the brain-derived neurotrophic factor (BDNF) in AF cells undergoing cyclic stretching. In NP cells, miR-155-5p gain-of-function resulted in the activation of the mitogen-activated protein kinase (MAPK) signaling pathway through increased phosphorylation of p38 and p53. Lastly, miR-155-5p inhibition caused a significant increase in the anti-inflammatory cytokine IL-10 in AF cells and the tissue inhibitor of metalloproteinases (TIMP)-4 in NP cells respectively.
CONCLUSION: Overall, these results show that miR-155-5p contributes to IVD degeneration by enhancing inflammation through pro-inflammatory cytokines and MAPK signaling, as well as by promoting the catabolic shift of AF cells during mechanical loading. The inhibition of miR-155-5p may constitute a potential therapeutic approach for IVD degeneration and low back pain.