anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Patients with chronic pain on opioids frequently experience loneliness, which is associated with poorer health outcomes and higher risk for opioid misuse and opioid use disorder. Given that almost half of opioids are prescribed in primary care, a critical need exists for the development and testing of interventions to reduce loneliness in primary care patients at risk for opioid misuse. Cognitive behavioral therapy and social prescribing have been shown to be efficacious in reducing loneliness and improving outcomes in other populations but have not been tested in patients at risk for substance use disorder. The overall objective of our study is to reduce opioid misuse and opioid use disorder by addressing loneliness in patients on long-term opioid therapy in real-world primary care settings.
METHODS: We will conduct a 3-arm pragmatic, randomized controlled trial to compare the effectiveness of two group-based, telehealth-delivered interventions with treatment as usual: (1) cognitive behavioral therapy to address maladaptive thought patterns and behaviors around social connection and (2) a social prescribing intervention to connect participants with social opportunities and develop supportive social networks. Our primary outcome is loneliness as measured by the UCLA Loneliness Scale and our dependent secondary outcome is opioid misuse as measured by the Common Opioid Misuse Measure. We will recruit 102 patients on long-term opioid therapy who screen positive for loneliness from 2 health care systems in Washington State. Implementation outcomes will be assessed using the RE-AIM framework.
DISCUSSION: Our study is innovative because we are targeting loneliness, an under-addressed but critical social risk factor that may prevent opioid misuse and use disorder in the setting where most patients are receiving their opioid prescriptions for chronic pain. If successful, the project will have a positive impact in reducing loneliness, reducing opioid misuse, improving function and preventing substance use disorder.
TRIAL REGISTRATION: NCT06285032, issue date: February 28, 2024, original.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing healthcare problem with limited therapeutic options. Progress in this field depends on the availability of reliable preclinical models. Human precision-cut liver slices (PCLSs) have been employed to replicate the initiation of MASLD, but a comprehensive investigation into MASLD progression is still missing. This study aimed to extend the current incubation time of human PCLSs to examine different stages in MASLD. Healthy human PCLSs were cultured for up to 96 h in a medium enriched with high sugar, high insulin, and high fatty acids to induce MASLD. PCLSs displayed hepatic steatosis, characterized by accumulated intracellular fat. The development of hepatic steatosis appeared to involve a time-dependent impact on lipid metabolism, with an initial increase in fatty acid uptake and storage, and a subsequent down-regulation of lipid oxidation and secretion. PCLSs also demonstrated liver inflammation, including increased pro-inflammatory gene expression and cytokine production. Additionally, liver fibrosis was also observed through the elevated production of pro-collagen 1a1 and tissue inhibitor of metalloproteinase-1 (TIMP1). RNA sequencing showed that the tumor necrosis factor alpha (TNFα) signaling pathway and transforming growth factor beta (TGFβ) signaling pathway were consistently activated, potentially contributing to the development of inflammation and fibrosis. In conclusion, the prolonged incubation of human PCLSs can establish a robust ex vivo model for MASLD, facilitating the identification and evaluation of potential therapeutic interventions.
BACKGROUND: Clinical data demonstrate that chronic use of opioid analgesics increases neuropathic pain in people living with human immunodeficiency virus (HIV). Therefore, it is important to elucidate the molecular mechanisms of HIV-related chronic pain. In this study, we investigated the role of the transcription factor cMyc, epigenetic writer enhancer of zeste homology 2 (EZH2), and sirtuin 3 (Sirt3) pathway in HIV glycoprotein gp120 with morphine (gp120M)-induced neuropathic pain in rats.
METHODS: Neuropathic pain was induced by intrathecal administration of recombinant gp120 with morphine. Mechanical withdrawal threshold was measured using von Frey filaments, and thermal latency using the hotplate test. Spinal expression of cMyc, EZH2, and Sirt3 were measured using Western blots. Antinociceptive effects of intrathecal administration of antisense oligodeoxynucleotide against cMyc, a selective inhibitor of EZH2, or recombinant Sirt3 were tested.
RESULTS: In the spinal dorsal horn, gp120M upregulated expression of cMyc (ratio of gp120M versus control, 1.68 ± 0.08 vs 1.00 ± 0.14, P = .0132) and EZH2 (ratio of gp120M versus control, 1.76 ± 0.05 vs 1.00 ± 0.16, P = .006), and downregulated Sirt3 (ratio of control versus gp120M, 1.00 ± 0.13 vs 0.43 ± 0.10, P = .0069) compared to control. Treatment with intrathecal antisense oligodeoxynucleotide against cMyc, GSK126 (EZH2 selective inhibitor), or recombinant Sirt3 reduced mechanical allodynia and thermal hyperalgesia in this gp120M pain model. Knockdown of cMyc reduced spinal EZH2 expression in gp120M treated rats. Chromatin immunoprecipitation (ChIP) assay showed that enrichment of cMyc binding to the ezh2 gene promoter region was increased in the gp120M-treated rat spinal dorsal horn, and that intrathecal administration of antisense ODN against cMyc (AS-cMyc) reversed the increased enrichment of cMyc. Enrichment of trimethylation of histone 3 on lysine residue 27 (H3K27me3; an epigenetic mark associated with the downregulation of gene expression) binding to the sirt3 gene promoter region was upregulated in the gp120M-treated rat spinal dorsal horn; that intrathecal GSK126 reversed the increased enrichment of H3K27me3 in the sirt3 gene promoter. Luciferase reporter assay demonstrated that cMyc mediated ezh2 gene transcription at the ezh2 gene promoter region, and that H3K27me3 silenced sirt3 gene transcription at the gene promoter region.
CONCLUSION: These results demonstrated that spinal Sirt3 decrease in gp120M-induced neuropathic pain was mediated by cMyc-EZH2/H3K27me3 activity in an epigenetic manner. This study provided new insight into the mechanisms of neuropathic pain in HIV patients with chronic opioids.
Phase 2a expansion cohort for patients with melanoma. Patients will be treated at the maximum tolerated dose discovered in phase I.
Severe acute coronavirus-2 (SARS-CoV-2) infection has been associated with endothelial damage, and impaired nitric oxide production, which results in arterial stiffness and increased risk of cardiovascular disease. Long COVID is a term used to describe the persistence or the development of new symptoms that can occur after an acute infection. Little is known about the association between arterial stiffness and Long COVID. An observational, cross-sectional study in which arterial stiffness was measured with pulse wave velocity (PWV) was carried out in 74 participants between 19 and 40 years old (53 with Long COVID, 21 age and gender-matched controls). Data was collected from participants between 1 and 9 months after acute COVID-19 infection using the Complior analyze unit protocol. The Long COVID group had higher carotid-radial-PWV (crPWV) than controls (10 m/s interquartile range [IQR] 8.5-11.2 m/s) versus 8.8 m/s (IQR 7.7-9.2 m/s) as was their carotid-radial-arterial stiffness index (crASI) (2.26 cm/ms (IQR 1.9-2.56 cm/ms) vs. 2.01 cm/ms (IQR 1.82-2.27 cm/ms); p < 0.05) in both. They also had more type-A waveforms, indicating increased arterial stiffening. Peripheral arterial stiffness was higher in adults with Long COVID than in controls who were never infected with SARS-CoV-2 as noted by the elevated levels of crPWV and crASI among adults with Long COVID.
An impaired intestinal permeability is implicated in the pathophysiology of a number of disorders such as celiac disease, environmental enteropathy, inflammatory bowel disease, obesity, and HIV. Current measurements of intestinal permeability rely on urinary excretion of naturally available, orally ingested, non-absorbable sugars (e.g. lactulose, mannitol). However, dietary intake of these sugars limits interpretation from these assays.

Subjects will have an esophagogastroduodenoscopy (EGD) with biopsies and provide a baseline urine sample. They will be asked to ingest 3 saccharides (12C mannitol 100 mg,13C mannitol 100 mg and lactulose 1 g) in 250 ml of water. Urine samples will be obtained every 30 min. in the Clinical Research and Trials Unit (CRTU) for 0-2 hours. Subjects will collect 2-8 hour sample in provided container. Another container will be provided to collect the 8-24 hour urine which will be returned the following morning. Subjects will undergo an Indomethacin challenge intervention. They will be instructed to take three 25 mg capsules 8 hours before their next visit (just before fasting). They will take 3 additional 25 mg capsules 30 min. before the repeat in vivo permeability testing. Repeat EGD with duodenal biopsies will be done. Long term follow-up will be done within 4-6 weeks of previous testing, where subjects will once again be asked to complete the in vivo permeability testing.
FIELD: medicine, immunology, homeopathy. SUBSTANCE: invention proposes medicinal agent containing supersmall doses of monoclonal, polyclonal or natural antibodies in activated form raised to granulocytic colony-forming factor prepared by multiple successive dilution and external impact being mainly by homeopathic technology. Invention relates also to method of treatment of pathological syndrome caused by hemopoiesis disturbance by administration of indicated medicinal agent. Invention provides the development of effective preparation for treatment and prophylaxis of acute and chronic diseases associated with disturbance of hemopoiesis and eliciting specific pharmacological activity, absence of adverse effects, ecological purity and low cost. Invention can be used for treatment and prophylaxis of acute and chronic diseases associated with disturbance of hemopoiesis being mainly granulocytopoiesis. EFFECT: enhanced effectiveness of agent and treatment, valuable medicinal properties of agent. 4 cl
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a range of motor and non-motor symptoms. Among the motor complaints, freezing of gait (FOG) is a common and disabling phenomenon that episodically hinders patients' ability to produce efficient steps. Concurrently, sleep disorders are prevalent in PD and significantly impact the quality of life of affected individuals. Numerous studies have suggested a bidirectional relationship between FOG and sleep disorders. Therefore, our objective was to systematically review the literature and compare sleep outcomes in PD patients with FOG (PD + FOG) and those without FOG (PD-FOG). By conducting a comprehensive search of the PubMed and Web of Science databases, we identified 20 eligible studies for inclusion in our analysis. Our review revealed that compared to PD-FOG, PD + FOG patients exhibited more severe symptoms of rapid eye movement sleep behavior disorder in nine studies, increased daytime sleepiness in eight studies, decreased sleep quality in four studies, and more frequent and severe sleep disturbances in four studies. These findings indicate that PD + FOG patients generally experience worse sleep quality, higher levels of daytime sleepiness, and more disruptive sleep disturbances compared to those without FOG (PD-FOG). The association between sleep disturbances and FOG highlights the importance of evaluating and monitoring these symptoms in PD patients and open the possibility for future studies to assess the impact of managing sleep disturbances on the severity and occurrence of FOG, and vice versa.
Studies using estimated blood loss show the association of either human papillomavirus (HPV) or cervical intraepithelial neoplasia (CIN) with postpartum hemorrhage (PPH). We study the association of HPV or CIN with either blood loss or PPH as measured by the more precise measure of quantitative blood loss (QBL). We retrospectively studied 2,334 peripartum women with a documented Pap smear prior to de- livery. The main predictor variable had categories for HPV and CIN as compared to normal cytology. Covariates included demographics, medical/surgical history, and pregnancy variables. Model 1 included the whole sample. Model 2 included only those with an operative vaginal delivery or a cesarean delivery. Outcome measures were QBL and PPH measured by QBL. We found in model 1 that those HPV positive and those with CIN were each not significantly associated with QBL. In model 2, those HPV positive were significantly associated with increased QBL (B = 0.11, SE = 0.05, p = 0.047), while CIN was not significantly associated with QBL. In model 1, those HPV positive and those with CIN were each not significantly associated with PPH. In model 2, those HPV positive were significantly associated with increased odds for PPH (OR:11.03, 9% CI:1.77, 68.74, p = 0.01) while CIN was not significantly associated with PPH. In conclusion, the presence of HPV was positively associated with an increase in the QBL and PPH at time of delivery for those with operative vaginal and cesarean deliveries. We suggest that clinicians take HPV results of Pap smears into consideration when considering a patient's risk of PPH.
PROBLEM TO BE SOLVED: To obtain an ophthalmic agent effective to corneal disorder, dry eyes and lacrimation disorder by making the agent contain a compound having an aldose reductase inhibitory action as an active ingredient. SOLUTION: This ophthalmic agent contains a compound of the formula (A, B are each a lower alkylene; X, Y, Z are each a halogen) or its pharmacologically acceptable salt as an active ingredient. As the compound of the formula, [3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4- tetrahydroquinazolin-1-yl] acetic acid is especially preferable. The compound of the formula can be obtained by a known method. The ophthalmic agent is allowed to contain another aldose reductase inhibitor other than the compound of the formula. Further, the ophthalmic agent preferably contains 0.001-10.0 w/v% active ingredient. Thereby, it is possible to provide a treating agent effective for corneal disorder generated by a cause other than diabetes mellitus.
A method and pharmaceutical composition are disclosed for treating, ameliorating and/or preventing one or more myocardial disorders in a mammalian heart caused by a myocardial hypoxic event and/or a loss, reduction or interruption in coronary blood flow such as may happen during or after events such as a heart attack, cardiac surgery including coronary artery bypass graft, or coronary artery or myocardial reperfusion. The myocardial disorders include myocardial arrhythmias, myocardial damage and myocardial cell death, and the subsequent loss of haemodynamic function. The myocardial disorders could be in progress or suspected of being in progress at the time of treatment or could be anticipated disorders being treated prophylactically. The method involves the step of administering an effective amount of the composition. The composition comprises as its active ingredient one or more compounds having myocardial persistent sodium channel blocking activity. A preferred compound is riluzole or a salt or derivative thereof.
Pharmaceutical compsns. contain as essential active component a strain of a 'micropredator' microbe (I) capable of destroying other microbes by its direct action on them. (I) is pref. of the genus Bdellovibrio, specifically B.bacteriovorus CBS 648.73 or 649.73 or its natural or artificial mutants. Used to treat infections and, non-medically, as additives for animal feeds; for treating sewage effluent; purifying water; cleaning soiled linen, Treating soils, walls or hospital waste. Compsns. can be given orally, topically, parenterally etc. depending on the site of infection.
INTRODUCTION: Chronic cough has increasingly been recognized as a distinct clinical entity that affects a significant portion of the global population. Despite advancements in understanding its pathophysiology, treatment options remain limited. Opioid analgesics have long been used for cough, and some have proven clear antitussive potential. However, these have yet to be approved by regulatory authorities for the treatment of chronic cough. Several novel synthetic opioid modulators that demonstrated antitussive effects in early-stage studies also failed to translate into clinical practice.
AREAS COVERED: This mini review aims to summarize the implications of opioid receptors in the development of cough medicines and highlight recent advances in opioid analgesics in cough trials. PUB MED/CINAHL/Web of Science/Scopus was searched (September 2024).
EXPERT OPINION: Our understanding of the precise sites of action and the involvement of peripheral opioid receptors in cough remains limited. Despite these gaps in knowledge, opioids remain a viable option for some patients until more novel effective treatments are available. Due to the frequent opioid side effects, new opioid derivatives with improved properties are needed. The development of tailored or biased delta-opioid receptor ligands and mixed agonists of opioid receptor-like 1/mu receptors may offer hope for new opioid-based drug discovery for chronic cough.
Each participant will undergo one VR session and two control sessions. The VR session will take place in a commercially available VR environment, the Blu, and last 20-30 minutes (VR Blu). The control sessions will include a 2D-tablet based session that mimics the VR content (Tablet Blu) and a content-less placement of the VR headset (VR Blank). The order of these sessions will be randomized across participants are intended to complete all sessions.

Each participant will complete a pre-study questionnaire to elicit their prior experience with the virtual reality as well as measures of gaming addiction/engagement, boredom, and expectancy. These scales will help us determine which patient-level factors predict response to VR. Before and after each session, participants will complete validated scales of pain, nausea, and anxiety.. Pre- and Post-VR opioid use will be recorded. Basic vital signs including heart rate, blood pressure, and respiratory rate, will be recorded before and after each session to monitor autonomic response. Advanced measures of autonomic response will include heart rate variability,,and pupillometry metrics. At the conclusion of all sessions, participants will complete another questionnaire to document their subjective experience of using VR (perceived effectiveness)
FIELD: medicine, phytotherapy. SUBSTANCE: maakia Amur milled core wood is extracted with 96% ethanol at 50-55 C at ratio raw : extract = 1:5 in battery of percolators. Then alcoholic extracts were evaporated and dried under vacuum. The end product can be used in medicine since it shows hepatoprotective effect. EFFECT: improved method of preparing. 3 tbl
On the test days, the participant will be asked to provide a urine sample before taking the supplement, this sample will be used as a baseline and assessed for Vitamin C and creatinine/protein and specific gravity, with the same testing strips as mentioned above. Once collected, the participant will be provided with a drink containing an increasing daily dose of vitamin C (0 - 500 mg). A second urine sample will then be collected approx. 3 - 4 hours later to assess the extent of vitamin C excretion in urine with an increase in vitamin C supplement. Another urine test strip will also be used to determine creatinine concentrations, the presence of albumin/protein, and specific gravity (to determine urine concentration). Up to 3 days will be allowed between daily testing to allow for long weekends, absences, illness, etc. Therefore, the participants are expected to complete the study within 4 weeks.
The invention particularly relates to a traditional Chinese medicine pill for treating pathological fracture and a preparation method thereof. The traditional Chinese medicine pill for treating the pathological fracture contains 46 medicines, such as processed semen strychni, ginseng, scorpio, ephedra, frankincense, myrrh, Yurong powder, stiff silkworm, deer's sinew, notopterygium root, obscured homalomena rhizome, giantleaf ardisia rhizome, cortex acanthopanacis, radix scrophulariae, dried radix rehmanniae, dipsacus root, eucommia ulmoides oliv, taro pulp, morinda officinalis, white paeony root, the root of red-rooted salvia, bighead atractylodes rhizome, schisandra chinensis, fructus ligustri lucidi, fructus alpiniae oxyphyllae, moghania root, garter snake, glue of tortoise plastron, deerhorn glue, degelatinated deer antler, amber and the like. The processed semen strychni is smashed and shaped to obtain the traditional Chinese medicine pill. The traditional Chinese medicine pill for treating pathological fracture can treat various symptoms, such as waist disease, rheumatoid arthritis, hand and foot numbness, various nerve denervation symptoms, bone tumors, osteomyelitis, pathological paralysis, stroke paralysis and the like. The traditional Chinese medicine pill for treating pathological fracture has the advantages of no side effect, and obvious curative effect, and patients do not feel pain. The preparation method for the traditional Chinese medicine pill for treating pathological fracture has a simple technology and is easy to operate.
In the control group, a silent state (a wave file made without sound) is applied via the sound generator and a headset, at the starting of general anesthesia induction. The sound generator volume is set to 60 dB. The sound generator and the headset is assigned after the randomization, and is blinded to the patient and the investigator. This sound is applied during the operation, and at the time of the final skin suture, the sound generator and the headset will be removed from the patient.
The invention discloses a quick-acting bone setting Yi medicine. The Yi medicine comprises capsules and a decoction. The capsules are prepared from, by mass, 50 parts of semen strychni, 20 parts of lilies and 20 parts of cortex acanthopanacis. The decoction is prepared from, by mass, 10 parts of cassia twigs, 10 parts of fructus aurantii, 10 parts of achyranthes roots and 5 parts of liquorice roots. A preparation method comprises the steps that firstly, semen strychni is unhaired and ground into fine powder after being processed; lilies and cortex acanthopanacis are dried and smashed into powder; fine powder of semen strychni, lilies and cortex acanthopanacis is taken in proportion according to the formulation and mixed to be uniform, the mixture is contained in capsules, and the capsules are obtained; cassia twigs, fructus aurantii, achyranthes roots and liquorice roots are taken according to the formulation ratio to be decocted into the decoction, and the decoction is contained in a bottle. The quick-acting bone setting Yi medicine is prominent and fast in medicine effect, and the cure rate reaches 85% or above. After the Yi medicine is used, pain of a patient can be relieved in time within as short as one month and as long as two months, a fracture can be healed fast, action can be fast restored, and the treatment effect is especially remarkable. The Yi medicine is suitable for various fracture patients.