anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Machine learning (ML) models have made inroads into chemical sciences, with optimization of chemical reactions and prediction of biologically active molecules being prime examples thereof. These models excel where physical experiments are expensive or time-consuming, for example, due to large scales or the need for materials that are difficult to obtain. Studies of natural products suffer from these issues─this class of small molecules is known for its wealth of structural diversity and wide-ranging biological activities, but their investigation is hindered by poor synthetic accessibility and lack of scalability. To facilitate the evaluation of these molecules, we designed ML models that predict which natural products can interact with a particular target or a relevant pathway. Here, we focused on discovering natural products that are capable of modulating the 5-lipoxygenase (5-LO) pathway that plays key roles in lipid signaling and inflammation. These computational approaches led to the identification of nine natural products that either directly inhibit the activity of the 5-LO enzyme or affect the cellular 5-LO pathway. Further investigation of one of these molecules, deltonin, led us to discover a new cell-type-selective mechanism of action. Our ML approach helped deorphanize natural products as well as shed light on their mechanisms and can be broadly applied to other use cases in chemical biology.
BACKGROUND: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.
METHODS: The China Kadoorie Biobank is a prospective cohort study with a baseline survey from 2004 to 2008 and a follow-up period until December 31, 2018. We used the Infinium Methylation EPIC BeadChip to measure the methylation levels of 988 participants' baseline blood leukocyte DNA. Metabolite profiles, including lipoprotein particles, lipid constituents, and various circulating metabolites, were measured using quantitative nuclear magnetic resonance. The pace of DNA methylation age acceleration (AA) was calculated using 5 widely used epigenetic clocks (the first generation: Horvath, Hannum, and Li; the second generation: Grim and Pheno). Incident ASCVD was ascertained through linkage with local death and disease registries and national health insurance databases, supplemented by active follow-up. The frailty index was constructed using medical conditions, symptoms, signs, and physical measurements collected at baseline.
RESULTS: A total of 508 incident cases of ASCVD were documented during a median follow-up of 9.5 years. The first generation of epigenetic clocks was associated with the risk of ASCVD (P<0.05). For each SD increment in LiAA, HorvathAA, and HannumAA, the corresponding hazard ratios for ASCVD risk were 1.16 (1.05-1.28), 1.10 (1.00-1.22), and 1.17 (1.04-1.31), respectively. Only LiAA mediated the association of various metabolites (lipids, fatty acids, histidine, and inflammatory biomarkers) with ASCVD, with the mediating proportion reaching up to 15% for the diameter of low-density lipoprotein (P=1.2×10-2). Regarding general aging, a 1-SD increase in GrimAA was associated with an average increase of 0.10 in the frailty index (P=2.0×10-3), and a 33% and 63% increased risk of prefrailty and frailty at baseline (P=1.5×10-2 and 5.8×10-2), respectively; this association was not observed with other clocks. GrimAA mediated the effect of various lipids, fatty acids, glucose, lactate, and inflammatory biomarkers on the frailty index, with the mediating proportion reaching up to 22% for triglycerides in very small-sized very low-density lipoprotein (P=6.0×10-3).
CONCLUSIONS: These findings suggest that epigenomic mechanisms may play a role in the associations between circulating metabolites and the aging process. Different mechanisms underlie the first and second generations of DNA methylation age in cardiovascular and general aging.
Less than a fourth of ethnic minority teens in the U.S. are a designated donor (DD) on their state-issued driver's license. Asian-American/Pacific Islander (AA/PI) adolescents in Hawaii are even less likely to be a DD or to have talked to their family about becoming an organ donor. Health education interventions for adolescents have demonstrated improvements in knowledge and intentions to be an organ donor; but, AA/PI teens are underrepresented in such studies. Nevertheless, whether changes in knowledge or intentions result in more organ donors is unclear, since previous studies have not included a concrete behavioral outcome such as the teen becoming a donor on their driver's license. This application will test, via a randomized clinical trial, the efficacy of an Interactive Multimedia Intervention (IMI) to increase the number of AA/PI adolescents who are a DD on their state issued driver's license, identification card, or organ donor card/donor registry. Teen groups will be recruited from the community (churches and high schools, n = 40 groups, 530 teens) and randomly assigned to either the intervention or a comparison condition on prevention of underage drinking of alcohol. The theoretically-derived intervention will include culturally sensitive messages and information about being a designated donor that will be delivered via a DVD, Email, text/instant messaging, and websites. The comparison condition includes materials (DVD) previously shown to increase awareness about laws restricting access to alcohol by teens. The primary outcome is objectively validated donor status on a teens' driver's license/state identification card (ID) or donor card after 12 months of intervention. A secondary outcome is the reported rate of family discussions about organ donation and knowledge/intentions about donation. We hypothesize the youth groups assigned to the intervention will have higher rates for family discussions and DD status, compared to groups in the comparison condition. We will also test whether psychosocial and cultural factors act as mediators of any change in teens' knowledge, attitudes \& stages of change to become a DD. After the randomized trial we will disseminate the intervention to Organ Procurement Organizations in Hawaii and other states, and track diffusion outcomes over a year. If IMI methods can increase the number of minority teens who become a DD on their driver's license by 10% this would translate to 500,000 more teenage designated donors in the U.S.
The utility model relates to an anti-colitis capsule which is characterized in that one layer of outer shell made of medical glue is arranged outside a universal capsule for holding medicine with a thin wall. The thickness of the outer shell is equal to 0.5 mm-2.5 mm. The capsule for holding medicine with a thin wall is integrally sealed by the outer shell. After the capsule is taken by a patient, the capsule is dissolved in the colon of the patient. The utility model leads medicine to directly act on the local part of the colon. The anti-colitis capsule can not be destroyed by the environment of stomach intestine. Compared with a conventional oral administration method and an enema medication, the utility model can better treat a colon disease.
Disclosed herein is a delivery composition for administering a hydrophobic active agent. In one embodiment, a delivery composition for local administration of a hydrophobic active agent to a tissue or organ of a patient is disclosed. In one embodiment, the delivery composition includes a cationic delivery agent, a therapeutically effective amount of a hydrophobic active agent and a pharmaceutically acceptable aqueous carrier. In one embodiment, the cationic delivery agent includes polyethyleneimine (PEI). In a more specific embodiment, the cationic delivery agent includes branched PEI. Methods of making the delivery composition, as well as kits and methods of use are also disclosed.
All subjects will receive weekly intravenous infusions of AME-133v. Each subject will receive a total of 4 infusions administered once a week for 3 consecutive weeks.
A dosage form for delivery of a therapeutic agent to a subject is described. The dosage form contains: (a) an outer wall defining an interior compartment; (b) within the interior compartment, a therapeutic agent; (c) at least one exit orifice formed by laser ablation of the outer wall for release of the agent therethrough, and (d) a barrier layer disposed between the outer wall and the interior compartment in at least a region corresponding to the exit orifice. The barrier layer comprises a material that allows the barrier layer to remain intact during laser-formation of the at least one exit orifice in the outer wall. Also disclosed is a method for controlling the depth of laser ablation of a dosage form during laser formation of an exit orifice in an outer wall of the dosage form. The figure depicts dosage form (10), which contains an outer wall (12) that defines an interior compartment (14), visible in the cut-away of the figure. Outer wall (1) is composed of a material that is permeable to the passage of fluid, but is substantially impermeable to the passage of drug or therapeutic agent, e.g., a semipermeable material. Materials suitable for formation of the outer wall include synthetic and naturally occurring semipermeable polymer materials. In one embodiment, the polymer is a thermoplastic polymer. When a thermoplastic polymer is selected as the material for outer wall (12_, outer wall (12) is essentially non-toxic and maintains its physical and chemical integrity during the delivery life of therapeutic agent from the device. Internal compartment (14) of dosage form (10) includes a therapeutic agent (15) intended to be released from the dosage form (10) into the environment of use. The therapeutic agent can be either soluble, insoluble, or combinations thereof in the external fluid imbibed into the dosage form (10).
PURPOSE:To obtain a concentrated extract from a leaf of Sasa albo-marginata industrially in large amounts, by extracting the leaf of the Sasa albo-marginata by easy operation without using a special solvent. CONSTITUTION:A raw leaf of Sasa albo-marginata is dried and finely sheared to give a raw material, which is dipped in water in a pan to leach water-soluble substances. The resultant water-soluble substances are boiled and suitably concentrated, and superheated steam is then jetted into the substances in this state. The resultant leachate having increased boiling point is boiled down to reach within an effective temperature range, e.g. 120-160 deg.C, not reaching 200 deg.C caramelization temperature. The boiled down leachate is further heated in this state continuously for 6-12hr to give the aimed concentrated extract from the leaf of Sasa albo-marginata. Since the solution is concentrated at a high temperature, the concentrating operation is effectively carried out, and bad side effects by solvents are completely removed due to no use of a special solvent. The extracting operation is completely carried out by jetting of the superheated steam, and the concentrated extract can be more effectively mass produced.
Participants undergo a series of 10 education and training sessions over 1 hour every 2 weeks, comprising education on current research, evidence-based health guidelines, application techniques, reference materials specific to extended-stage cancer survivors, and recommendations and personal health goals for survivorship. The guidelines described in class are part of a nutrition intervention and an exercise intervention with personal and group goal setting over the course of the study.
BACKGROUND AND OBJECTIVES: Recurrent isolated pancreatic metastasis from Renal Cell Carcinoma (RCC) after pancreatic resection is rare. The purpose of our study is to describe a series of cases of relapse of pancreatic metastasis from renal cancer in the pancreatic remnant and its surgical treatment with a repeated pancreatic resection, and to analyse the results of both overall and disease-free survival.
METHODS: Multicenter retrospective study of patients undergoing pancreatic resection for RCC pancreatic metastases, from January 2010 to May 2020. Patients were grouped into two groups depending on whether they received a single pancreatic resection (SPS) or iterative pancreatic resection. Data on short and long-term outcome after pancreatic resection were collected.
RESULTS: The study included 131 pancreatic resections performed in 116 patients. Thus, iterative pancreatic surgery (IPS) was performed in 15 patients. The mean length of time between the first pancreatic surgery and the second was 48.9 months (95 % CI: 22.2-56.9). There were no differences in the rate of postoperative complications. The DFS rates at 1, 3 and 5 years were 86 %, 78 % and 78 % vs 75 %, 50 % and 37 % in the IPS and SPS group respectively (p = 0.179). OS rates at 1, 3, 5 and 7 years were 100 %, 100 %, 100 % and 75 % in the IPS group vs 95 %, 85 %, 80 % and 68 % in the SPS group (p = 0.895).
CONCLUSION: Repeated pancreatic resection in case of relapse of pancreatic metastasis of RCC in the pancreatic remnant is justified, since it achieves OS results similar to those obtained after the first resection.
Valvular heart disease constitutes a growing healthcare problem with a general prevalence of 2%-5% and a prevalence of 13% after the age of 75 years Heart valve surgery can be a lifesaving procedure for patients with severe symptomatic heart valve disease. Nevertheless, following the surgery, up to 27% of patients may require readmission within 30 days after discharge. Following heart valve surgery, some patients report anxiety and worries related to readmission and reoperations, postoperative complications, and deconditioning which may prevent or delay return to work and limit activities of daily living.Over the past 30 years, bone-growth stimulators have become a critical component in fracture care. They can be classified into four categories: direct-current (DC) devices, inductive coupling, noninvasive capacitive coupling, and low-intensity ultrasound. Microcurrent electrical stimulation ( MES) is the therapeutic use of constant (DC) and pulsed (interrupted) currents, where the stimulus amplitude is in the micro amperage (millionth of an ampere) range. MES is defined as those of less than 1 mA or 1000 μ, (MES \< 1 mA). This form of electrical stimulation tends to be applied at the suspensory or very low sensory level and they are not designed to stimulate muscle contraction. Generators that produce MES were originally called microcurrent electrical neuromuscular stimulators (MENS). However, the stimulation pathway is not the usual neural pathway, and they are not designed to stimulate muscle contraction. Consequently, this type of generator was subsequently referred to as a microcurrent electrical stimulator (MES). The use of MES may be an adjunctive modality in the treatment of fractures or injury sites, especially fractures prone to nonunion. Fracture healing may be accelerated by passing a monophasic current through the fracture site. Getting the current into the bony area without an invasive technique is difficult.forty subjects will be allocated to two groups; one group will receive micro-current therapy and routine cardiac rehabilitation program both for four weeks and the control group will receive the cardiac rehabilitation program only for four weeks.
The foreign body reaction (FBR) to biomaterials results in fibrous encapsulation. Excessive capsule fibrosis (capsular contracture) is a major challenge to the long-term stability of implants. Clinical data suggests that the tissue type in contact with silicone breast implants alters susceptibility to developing capsular contracture; however, the tissue-specific inflammatory and fibrotic characteristics of capsule have not been well characterized at the cellular and molecular level. In this study, 60 breast implant capsule samples are collected from patients and stratified by the adjacent tissue type including subcutaneous tissue, glandular breast tissue, or muscle tissue. Capsule thickness, collagen organization, immune and fibrotic cellular populations, and expression of inflammatory and fibrotic markers is quantified with histological staining, immunohistochemistry, and real-time PCR. The findings suggest there are significant differences in M1-like macrophages, CD4+ T cells, CD26+ fibroblasts, and expression of IL-1β, IL-6, TGF-β, and collagen type 1 depending on the tissue type abutting the implant. Subglandular breast implant capsule displays a significant increase in inflammatory and fibrotic markers. These findings suggest that the tissue microenvironment contributes uniquely to the FBR. This data could provide new avenues for research and clinical applications to improve the site-specific biocompatibility and longevity of implantable devices.
Participants assigned to Cohort 1b will receive a low dose prime vaccination of AdC6 vector on Day 1. They will not receive a booster vaccination.
BACKGROUND: Olfactory dysfunction has been suggested to be associated with all-cause mortality. Yet, there is a lack of large-scale cohorts to study this relationship.
METHODS: Using data from the Kailuan cohort, we assessed 97 327 Chinese adults for perceived olfactory dysfunction at baseline and gathered mortality data from government records. We used Cox proportional hazards regression models to analyse the risk of all-cause mortality associated with perceived olfactory dysfunction, yielding hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for multiple potential confounders.
RESULTS: Over a median follow-up of 6.4-year, we recorded a total of 3903 deaths. Individuals reporting perceived olfactory dysfunction had a higher risk of mortality (adjusted HR = 1.42; 95% CI = 1.02-2.00) compared to those without the dysfunction. In sensitivity analyses, we found similar results after excluding participants with pre-existing obesity, cardiovascular diseases, those younger than 50 years old, individuals diagnosed with cancer or stroke during follow-up, and those who died within two years of follow-up.
CONCLUSIONS: Perceived olfactory dysfunction was associated with a high risk of all-cause mortality among Chinese adults. Our study is limited by failure to include a national-representative sample and misclassification of exposure assessment due to use of a subjective question to assess olfactory dysfunction. Further studies with objective are warranted to replicate our findings and understand the underlying mechanisms.
Empathy, the capacity to share others' emotional experiences, has been proposed as a key motivation for altruistic behavior in both humans and animals. Sharing another's emotional experience may generate a self-embodied simulation of their emotional state, fostering understanding and promoting prosocial behavior. Vicarious pain responders report sensing physical pain when observing others in pain. Whether this ability extends to emotional experiences remains unexplored. Using both questionnaires and ecologically valid behavioral tasks, we explored whether vicarious pain responders differ from nonresponders in empathic abilities and prosocial behavior. Participants watched video clips of people describing a negative emotional life event. We operationalized several empathic abilities and responses (empathic accuracy, affective synchrony, emotional reaction, and empathic motivation) based on participants' and targets' responses during and after watching the videos. Participants were also engaged in a donation task measuring tendency for prosocial behavior. Findings reveal that compared to nonresponders, vicarious pain responders exhibit enhanced empathic accuracy, intensified emotional reactions to others' emotional pain, and a greater motivation to communicate with the target. This study marks the first behavioral evidence showcasing vicarious pain responders' empathic abilities, reactions, and motivation in response to nonphysical pain of others, expanding our knowledge of this phenomenon and its association with broader empathic abilities.
The inability of surgical biopsy to monitor the dynamic evolution of cancer cells hampers its capacity to reflect real-time tumor heterogeneity. Circulating tumor cells (CTCs), as a crucial target in liquid biopsy, offer a novel approach for accurate monitoring of tumors. However, the rarity and complex phenotype resulting from epithelial-mesenchymal transition pose challenges for conventional methods such as CellSearch and immunohistochemistry, which have insufficient ability for simultaneous phenotyping and enumeration of CTCs. The enumeration of a single phenotype CTCs is insufficient for accurately assessing disease progression. Herein, we propose a strategy to address this issue by fabricating an electrochemiluminescence cytosensor via the integration of dual-target enrichment and nanozymes-catalyzed cascade signal amplification. The graphene oxide@hollow mesoporous Prussian blue/Pt (GO@HMPB/Pt) complex, possessing a large specific surface area and exceptional catalytic activity, is employed for loading a substantial amount of luminol as the signal probe. Dual-target magnetic PPy@Fe3O4/Au-antibody/aptamer is utilized for the magnetic capture of both epithelial and interstitial CTCs. Glutathione (GSH) can disrupt the Au-S bond on aptamer by a thiol exchange reaction and selectively releases a specific subset of phenotypic CTCs, thereby facilitating the efficient capture, accurate classification, and ultrasensitive detection of CTCs in peripheral blood. Using the epithelial MCF-7 and mesenchymal Hela cells as models, the ECL cytosensor demonstrates excellent performance in identifying cells spiked into whole blood. This study presents a novel approach for early detection of metastasis, tracking tumor recurrence, and monitoring therapeutic efficacy.
Bisphenol A (BPA), as a kind of widely exerted environmental hazardous material, brings toxicity to both humans and animals. This study aimed to investigate the role of glutamine (Gln) in intestinal inflammation and microbiota in BPA-challenged piglets. Thirty-two piglets were randomly divided into four groups according to 2 factors including BPA (0 vs. 0.1%) and Gln (0 vs. 1%) supplemented in basal diet for a 42-day feeding experiment. The results showed BPA exposure impaired piglet growth, induced intestinal inflammation and disturbed microbiota balance. However, dietary Gln supplementation improved the growth performance, while decreasing serum pro-inflammatory cytokine levels in BPA-challenged piglets. In addition, Gln attenuated intestinal mucosal damage and inflammation by normalizing the activation of toll-like receptor 4 (TLR4)-p38/MAPK-nuclear factor-kappa B (NF-κB) pathway caused by BPA. Moreover, dietary Gln supplementation decreased the abundance of Actinobacteriota and Proteobacteria, and attenuated the decreased abundance of Roseburia, Prevotella, Romboutsia and Phascolarctobacterium and the content of short-chain fatty acids in cecum contents caused by BPA exposure. Moreover, there exerted potential relevance between the gut microbiota and pro-inflammatory cytokines and cecal short-chain fatty acids. In conclusion, Gln is critical nutrition for attenuating BPA-induced intestinal inflammation, which is partially mediated by regulating microbial balance and suppressing the TLR4/p38 MAPK/NF-κB signaling.