anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Persistent pain following breast surgery for lobular carcinoma in situ (LCIS), ductal carcinoma in situ (DCIS), or invasive breast cancer is increasingly recognized as an important clinical and public health issue due to the large number of women affected, the powerful negative impact that persistent pain has on emotional and physical functioning and its financial costs. Most of the more than a quarter of a million women newly diagnosed with breast cancer in the U.S. this year will undergo surgery as a part of curative treatment. The prevalence of persistent pain following surgical removal of the affected breast (mastectomy) or more limited surgeries (lumpectomy) is high, ranging from 25-60% across studies. Unlike acute post-operative pain, which is a normal response to surgical trauma, persistent pain at or near the surgical site has an uncertain multifaceted etiology, and no satisfactory pharmacological treatment. A critical question is whether key pain-related psychosocial factors are drivers of the continuing burden of persistent pain, and whether they could be ameliorated by non-pharmacological intervention. The research planned under this award will provide a first critical test of the hypothesized driving role of pain catastrophizing in persistent pain after breast surgery. It also will explore the role of two other key psychosocial variables that may contribute to the burden associated with persistent pain after breast cancer surgery: self-efficacy for engaging in valued activities and psychological inflexibility. We have developed, manualized, and pilot tested a pain coping skills training intervention that specifically targets the needs of women with persistent pain following breast cancer surgery (CST-PSP) and aims to reduce pain catastrophizing, increase self-efficacy for engaging in valued activities, and increase psychological flexibility. We propose a multiple-site, randomized clinical trial to evaluate the efficacy of the CST-PSP intervention, as well as a health education intervention. The study will be conducted in diverse oncology clinics affiliated with Duke University/Duke Cancer Network and the University of Pittsburgh/UPMC Hillman Cancer Center. Participants (N=307) will be randomized to either receive: 1) CST-PSP, 2) health education with an interventionist, or 3) self-guided health education . Participants will complete assessments pre-intervention and at 3 months (post-intervention), 6 months follow-up, and 12 months follow-up. Study aims are: Aim 1: Examine the impact of intervention programs on persistent post-surgical pain severity and interference (i.e., PEG score), emotional distress (anxiety and depression), and cancer-specific distress. Aim 2: Investigate the impact of intervention programs on pain catastrophizing, pain self-efficacy, and psychological inflexibility, and evaluate these variables as possible mediators of the intervention benefits. Aim 3: Evaluate the impact of intervention programs on pain sensitivity and central sensitization, and explore whether changes in these variables mediate group differences in pain severity and interference.
The maintenance of genome stability is critical for health, but during individual ontogenesis, different stressors affect DNA integrity, which can lead to functional and/or structural changes in the cells of target organs. In the nervous system, cell genome destabilization is associated with different neurological and psychiatric diseases, but experiments in vivo, where a link between stress and DNA instability has been demonstrated, are relatively rare. Here, we use rat strains selected for the contrast excitability of the tibialis nerve (n. tibialis) and nonselected Wistar rats to investigate the reasons for individual differences in developing post-stress pathologies. Previous research on the behavioral response of these strains to prolonged emotional-painful stress (PEPS) allows us to consider one strain as a model of post-traumatic stress disorder (PTSD) and another strain as a model of compulsive disorder (CD). We study DNA damage in the cells of the prefrontal cortex (PFC), hippocampus, and amygdala, regions involved in stress responses and the formation of post-stress dysfunctions. The evaluation of cell genome integrity via the comet assay shows different responses to PEPS in each brain area analyzed and for all strains used. This could help us to understand the reasons for individual differences in the consequences of stress and the pathophysiology of post-stress disease formation.
BACKGROUND: Hepatocellular carcinoma (HCC) has a high mortality rate, and the mechanisms underlying tumor development and progression remain unclear. However, inactivated tumor suppressor genes might play key roles. DNA methylation is a critical regulatory mechanism for inactivating tumor suppressor genes in HCC. Therefore, this study investigated methylation-related tumor suppressors in HCC to identify potential biomarkers and therapeutic targets.
METHODS: We assessed genome-wide DNA methylation in HCC using whole genome bisulfite sequencing (WGBS) and RNA sequencing, respectively, and identified the differential expression of methylation-related genes, and finally screened phosphodiesterase 7B (PDE7B) for the study. The correlation between PDE7B expression and clinical features was then assessed. We then analyzed the changes of PDE7B expression in HCC cells before and after DNA methyltransferase inhibitor treatment by MassArray nucleic acid mass spectrometry. Furthermore, HCC cell lines overexpressing PDE7B were constructed to investigate its effect on HCC cell function. Finally, GO and KEGG were applied for the enrichment analysis of PDE7B-related pathways, and their effects on the expression of pathway proteins and EMT-related factors in HCC cells were preliminarily explored.
RESULTS: HCC exhibited a genome-wide hypomethylation pattern. We screened 713 hypomethylated and 362 hypermethylated mCG regions in HCC and adjacent normal tissues. GO analysis showed that the main molecular functions of hypermethylation and hypomethylation were "DNA-binding transcriptional activator activity" and "structural component of ribosomes", respectively, whereas KEGG analysis showed that they were enriched in "bile secretion" and "Ras-associated protein-1 (Rap1) signaling pathway", respectively. PDE7B expression was significantly down-regulated in HCC tissues, and this low expression was negatively correlated with recurrence and prognosis of HCC. In addition, DNA methylation regulates PDE7B expression in HCC. On the contrary, overexpression of PDE7B inhibited tumor proliferation and metastasis in vitro. In addition, PDE7B-related genes were mainly enriched in the PI3K/ATK signaling pathway, and PDE7B overexpression inhibited the progression of PI3K/ATK signaling pathway-related proteins and EMT.
CONCLUSION: PDE7B expression in HCC may be regulated by promoter methylation. PDE7B can regulate the EMT process in HCC cells through the PI3K/AKT pathway, which in turn affects HCC metastasis and invasion.
Described herein is an innovative composition that improves sleep quality. This composition includes two important systems: 1) a sleep-inducing system that is being used for the first time in food and beverage products; and 2) a unique stabilizer system that provides a robust rheology and greater stability than other stabilizers. The two systems can be incorporated, individually or in combination, into food and beverage products, including but not limited to protein shakes and powders. Together, they enable this composition to aid in relaxation and optimal sleep quality, better sensory taste experiences than current market products, longer shelf life and robust stability. This disclosure also addresses a relevant need in the art for a beverage composition that promotes calmness and reduces stress by using natural ingredients, more specifically made from milk casein. In summary, the sleep-inducing RTD (ready-to-drink) and RTM (ready-to-mix) compositions described herein include a stabilizer composition that improves shelf-life stability and contributes to enhanced specific sensory attributes without any adverse effects.
MI paste Self-administration of the product by the patient once in the evening. A pea-size amount of the product should be applied per arch, using a dry finger or cotton pellet to distribute it evenly across all teeth and to work it into the interdental spaces. The product was then retained in the mouth for 1-3 min, and manipulated around the teeth using the tongue, before being expectorated and patient should not rinse it until 30 min.
Hearing loss is the most common congenital sensory deficit worldwide and exhibits high genetic heterogeneity, making molecular diagnoses elusive for most individuals. Detecting novel mutations that contribute to hearing loss is crucial to providing accurate personalized diagnoses, tailored interventions, and improving prognosis. Copy number variants (CNVs) are structural mutations that are understudied, potential contributors to hearing loss. Here, we present the Abnormal Wobbly Gait (AWG) mouse, the first documented mutant exhibiting waltzer-like locomotor dysfunction, hyperactivity, circling behaviour, and profound deafness caused by a spontaneous CNV deletion in cadherin 23 (Cdh23). We were unable to identify the causative mutation through a conventional whole-genome sequencing (WGS) and variant detection pipeline, but instead found a linked variant in hexokinase 1 (Hk1) that was insufficient to recapitulate the AWG phenotype when introduced into C57BL/6J mice using CRISPR-Cas9. Investigating nearby deafness-associated genes revealed a pronounced downregulation of Cdh23 mRNA and a complete absence of full-length CDH23 protein, which is critical for the development and maintenance of inner ear hair cells, in whole head extracts from AWG neonates. Manual inspection of WGS read depth plots of the Cdh23 locus revealed a putative 10.4 kb genomic deletion of exons 11 and 12 that was validated by PCR and Sanger sequencing. This study underscores the imperative to refine variant detection strategies to permit identification of pathogenic CNVs easily missed by conventional variant calling to enhance diagnostic precision and ultimately improve clinical outcomes for individuals with genetically heterogenous disorders such as hearing loss.
The systemic levels of albuterol are low after inhalation of recommended doses. A study conducted in 12 healthy male and female subjects using a higher dose (1,080 mcg of albuterol base) showed that mean peak plasma concentrations of approximately 3 ng/mL occurred after dosing when albuterol was delivered using propellant HFA-134a. The mean time to peak concentrations (T ) was delayed after administration of VENTOLIN HFA (T = 0.42 hours) as compared to CFC-propelled albuterol inhaler (T = 0.17 hours). Apparent terminal plasma half-life of albuterol is approximately 4.6 hours. No further pharmacokinetic studies for VENTOLIN HFA were conducted in neonates, children, or elderly subjects. maxmaxmax
Patients receive T-DM1 IV over 30-90 minutes on day 1 and tucatinib PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity.
This study is Randomized controlled trail done at physiotherapy department of Railway General Hospital Rawalpindi. The sample size of 26 individuals calculated using open epi tool. Sampling technique applied was convenience sampling. Randomization in groups by sealed envelope method. The subjects were divided into two groups with 13 patients each. Both groups were treated with Integrated neuromuscular inhibition technique (Muscle energy Technique, sustain pressure, Strain counter-strain) while Kinesio tape was applied after INIT in only experimental group. Study duration was of 6 months. Individuals having age between 20-40 years, upper trapezius active or latent trigger points, limited side bending were included in this study. Tools used in the study were neck disability index (NDI), algometry, numeric pain rating scale (NPRS) and muscle length (side bending through inclinometer). Assessments were taken on 1st day pre and post intervention and on 4th day.
A brain-specific liposome targeting vehicle for transporting neuropharmaceutical agents across the blood-brain barrier (BBB). The targeting vehicle includes a liposome which is sterically stabilized by attaching ligands to the surface of the liposome. The targeting vehicle further includes blood-barrier transport agents which are attached to the tail portion of the stabilizing ligands which extend outward from the liposome surface. The blood-barrier transport agents are capable of transporting the entire liposome targeting vehicle across the blood-brain barrier. Monoclonal antibodies which undergo receptor-mediated transcytosis across the BBB are featured as useful blood-barrier transport agents. The resulting brain-specific immunoliposomes are well-suited for delivering a wide variety of neuropharmaceutical agents across the blood-brain barrier.
Participants will trial the same mask type/variant (full face, nasal, pillows) as the variant they are using as part of their current treatment. Participants in this arm will trial the Menai mask (full face) and Comparison Menai Standard mask (full face) for 7 nights each.
Obesity is associated with one-fifth of cancer deaths, and breast cancer is one of the obesity-related cancers. Triple-negative breast cancer (TNBC) lacks estrogen and progesterone receptors and human epidermal growth factor receptor 2, leading to the absence of these therapeutic targets, followed by poor overall survival. We investigated if obesity could hasten TNBC progression and intermittent fasting (IF) could attenuate the progression of obesity-related TNBC. Our meta-analysis of the TNBC outcomes literature showed that obesity led to poorer overall survival in TNBC patients. Fasting-mimicking media reduced cell proliferation disrupted the cell cycle, and decreased cell migration and invasion. IF decreased body weight in obese mice but no change in normal mice. Obese mice exhibited elevated plasma glucose and cholesterol levels, increased tumor volume and weight, and enhanced macrophage accumulation in tumors. The obesity-exacerbated TNBC progression was attenuated after IF, which decreased cyclin B1 and vimentin levels and reduced the proinflammatory signature in the obesity-associated tumor microenvironment. IF attenuated obesity-induced TNBC progression through reduced obesity and tumor burdens in cell and animal experiments, supporting the potential of a cost-effective adjuvant IF therapy for TNBC through lifestyle change. Further evidence is needed of these IF benefits in TNBC, including from human clinical trials.
The invention discloses an external traditional Chinese medicine composition for treating hyperosteogeny, which belongs to the technical field of traditional Chinese medicine preparations. The external traditional Chinese medicine composition for treating the disease of the hyperosteogeny is characterized by being prepared through processing the following Chinese herbal medicines according to parts by weight: 10 to 18 parts of babylon weeping willow root-bark, 5 to 8 parts of ramulus mori, 6 to 12 parts of peach leaf, 5 to 8 parts of hot pepper stem, 4 to 8 parts of ligusticum wallichii, 4 to 8 parts of radix gentianae macrophyllae, 4 to 8 parts of twotooth achyranthes root, 4 to 8 parts of spatholobus stem and 30 to 50 parts of vinegar. The external traditional Chinese medicine composition for treating the disease of the hyperosteogeny is an ionic penetration agent and is suitable for the auxiliary treatment of the osteoarthritis of knee joints. The external traditional Chinese medicine composition for treating the disease of the hyperosteogeny can be used for enhancing the local medicine concentration of a focus, is quick in acting and is safe in treatment. Moreover, the external traditional Chinese medicine composition for treating the disease of the hyperosteogeny can be used for softening or eliminating bony spurs. Therefore, the external traditional Chinese medicine composition for treating the disease of the hyperosteogeny has good curative effect and has extensive popularization and application prospect.
Schizophrenic patients may develop increased symptoms of psychosis; patients with paranoid symptomatology may have an exaggeration of such symptoms. Depressed patients, particularly those with known manic-depressive illness, may experience a shift to mania or hypomania. In these circumstances the dose of amitriptyline may be reduced or a major tranquilizer such as perphenazine may be administered concurrently.

The possibility of suicide in depressed patients remains until significant remission occurs. Potentially suicidal patients should not have access to large quantities of this drug. Prescriptions should be written for the smallest amount feasible.

Concurrent administration of amitriptyline hydrochloride and electroshock therapy may increase the hazards associated with such therapy. Such treatment should be limited to patients for whom it is essential.

When possible, the drug should be discontinued several days before elective surgery. 

Both elevation and lowering of blood sugar levels have been reported.

Amitriptyline hydrochloride should be used with caution in patients with impaired liver function.
BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a major contributor to mortality worldwide, with delayed cerebral ischaemia (DCI) contributing significantly to morbidity in these patients. There are limited evidence-based therapies for DCI. A 2012 case series first recommended the use of intravenous (IV) milrinone in this patient population, stating the need for formal prospective trials. However, uptake of this therapy into clinical practice has proceeded without adequate studies for efficacy and safety.
METHODS: We sought to determine the effect of IV milrinone on DCI in patients with aSAH in terms of functional outcome through a systematic review using Embase, MEDLINE, and Cochrane Library databases. Quality assessment was performed using MINORS criteria.
RESULTS: A total of 2429 studies were screened, with ten studies included in the review. Of these, no randomized trials were identified. Three observational comparative studies were included, and the remaining seven studies were non-comparative in nature, and mainly retrospective. Overall, the quality of evidence for non-comparative studies was poor.
CONCLUSIONS: This study reveals a paucity of evidence in the literature and highlights the need for high-quality randomized trials to investigate the safety and efficacy of IV milrinone, a commonly utilized treatment in critically ill aSAH patients with DCI. Ultimately, without evidence of efficacy and absence of harm, we caution continued use of intravenous milrinone for the treatment of DCI.
NLRP3 inflammasome plays an important role in autoimmunity and the dysregulation of NLRP3 inflammasome can lead to various human diseases. Natural products are an important source for the discovery of safe and effective inflammatory inhibitors. Chloranthalactone B (CTB), a lindenane sesquiterpenoid (LS) from a common traditional Chinese medicine (TCM) (Sarcandra glabra), could significantly inhibit the level of IL-1β. This study aims to investigate the anti-inflammatory mechanism and target of CTB and its therapeutic effects on inflammatory diseases. CTB significantly inhibited IL-1β secretion induced by different agonists. Co-IP and flow cytometry results showed that CTB inhibited NLRP3-NEK7 interactions, but had no significant effect on upstream events. Pull-down, DARTS, CETSA, biolayer interferometry assay (BLI), and LC/MS/MS results showed that CTB could covalently bind to cysteine 279 (Cys279) in the NACHT domain of NLRP3. The result of the chemical modification indicated that the epoxide motif was the key group of CTB for its anti-inflammatory effect of CTB. Further animal studies showed that CTB significantly reduced the symptoms and inflammation levels of gout, peritonitis, and acute lung injury. However, the protective effect of CTB against peritonitis and gout was abolished in NLRP3-knocked out (NLRP3 KO) mice. Overall, our research revealed that CTB was a specific NLRP3 covalent inhibitor, and epoxide motif was an active pharmacophore that covalently binds to NLRP3, which provided new insights in designing new NLRP3 inhibitors for treating NLRP3-driven diseases.
This Phase 1 study plans to enroll a total of 75 participants.

Three cohorts with two different dose levels will be explored and each cohort will enroll 25 participants. Participants in each cohort will be randomized (4:1) to receive either JCXH-108 (n=20) or placebo (normal saline, n=5). A low dose of JCXH-108 will be explored vs placebo in the 18-45 years of age group first. A high dose will be explored vs placebo in the 18-45 years and ≥ 60 years of age groups once safety data is reviewed for the Sentinel subjects in the low dose cohort. The dose level of JCXH-108 will depend on the time the participant joins the study. Each participant will receive a single dose of JCXH-108 administered intramuscularly (IM) on day 1.
BACKGROUND: Telemedicine remains an underused tool in rural emergency medical servces (EMS) systems. Rural emergency medical technicians (EMT) and paramedics cite concerns that telemedicine could increase Advanced Life Support (ALS) transports, extend on-scene times, and face challenges related to connectivity as barriers to implementation. Our aim in this project was to implement a telemedicine system in a rural EMS setting and assess the impact of telemedicine on EMS management of patients with chest pain while evaluating some of the perceived barriers.
METHODS: This study was a mixed-methods, retrospective review of quality assurance data collected prior to and after implementation of a telemedicine program targeting patients with chest pain. We compared quantitative data from the 12-month pre-implementation phase to data from 15 months post-implementation. Patients were included if they had a chief complaint of chest pain or a 12-lead electrocardiogram had been obtained. The primary outcome was the rate of ALS transport before and after program implementation. Secondary outcomes included EMS call response times and EMS agency performance on quality improvement benchmarks. Qualitative data were also collected after each telemedicine encounter to evaluate paramedic/EMT and EMS physician perception of call quality.
RESULTS: The telemedicine pilot project was implemented in September 2020. Overall, there were 58 successful encounters. For this analysis, we included 38 patients in both the pre-implementation period (September 9, 2019-September 10, 2020) and the post-implementation period (September 11, 2020-December 5, 2021). Among this population, the ALS transport rate was 42% before and 45% after implementation (odds ratio 1.11; 95% confidence interval 0.45-2.76). The EMS median out-of-service times were 47 minutes before, and 33 minutes after (P = 0.07). Overall, 64% of paramedics/EMTs and 89% of EMS physicians rated the telemedicine call quality as "good."
CONCLUSION: In this rural EMS system, a telehealth platform was successfully used to connect paramedics/EMTs to board-certified EMS physicians over a 15-month period. Telemedicine use did not alter rates of ALS transports and did not increase on-scene time. The majority of paramedics/EMTs and EMS physicians rated the quality of the telemedicine connection as "good."