anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Exposure to ambient air pollutants has emerged as a risk for metabolic-dysfunction associated steatotic liver disease (MASLD).
OBJECTIVES: We sought to examine associations between short-term (prior month) and long-term (prior year) ambient air pollution exposure with hepatic fat fraction (HFF) and liver stiffness in Latino youth with obesity. A secondary aim was to investigate effect modification by patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype and liver disease severity.
METHODS: Data was analyzed from 113 Latino youth (age 11-19) with obesity in Southern California. Individual exposure to particulate matter with aerodynamic diameter ≤ 2.5μm (PM2.5), ≤ 10μm (PM10), nitrogen dioxide (NO2), 8-hour maximum ozone (8hrMax-O3), 24-hr O3, and redox-weighted oxidative capacity (Oxwt) were estimated using residential address histories and United States Environmental Protection Agency air quality observations. HFF and liver stiffness were measured using magnetic resonance imaging. Linear models were used to determine associations between short-term and long-term exposure to air pollutants with HFF and liver stiffness. Modification by PNPLA3 and liver disease severity was then examined.
RESULTS: Short-term exposure to 8hrMax-O3 was positively associated with HFF. Relationships between air pollution exposure and HFF were not impacted by PNPLA3 genotype or liver disease severity. Long-term exposure to 8hrMax-O3 and Oxwt were positively associated with liver stiffness. Associations between air pollution exposure and liver stiffness depended on PNPLA3 genotype, such that individuals with GG genotypes exhibited stronger, more positive relationships between short-term exposure to PM10, 8hrMax-O3, 24-hr O3, and Oxwt and liver stiffness than individuals with CC/CG genotypes. In addition, relationships between short-term exposure to NO2 and liver stiffness were stronger in those with severe liver disease.
DISCUSSION: Air pollution exposure may be a risk factor for liver disease among Latino youth with obesity, particularly in those with other preexisting risks for liver damage.
OBJECTIVE: Guidelines suggest considering antiseizure medication (ASM) discontinuation in seizure-free patients with epilepsy. Past work has poorly explored how discontinuation effects vary between patients. We evaluated (1) what factors modify the influence of discontinuation on seizure risk; and (2) the range of seizure risk increase due to discontinuation across low- versus high-risk patients.
METHODS: We pooled three datasets including seizure-free patients who did and did not discontinue ASMs. We conducted time-to-first-seizure analyses. First, we evaluated what individual patient factors modified the relative effect of ASM discontinuation on seizure risk via interaction terms. Then, we assessed the distribution of 2-year risk increase as predicted by our adjusted logistic regressions.
RESULTS: We included 1626 patients, of whom 678 (42%) planned to discontinue all ASMs. The mean predicted 2-year seizure risk was 43% [95% confidence interval (CI) 39%-46%] for discontinuation versus 21% (95% CI 19%-24%) for continuation. The mean 2-year absolute seizure risk increase was 21% (95% CI 18%-26%). No individual interaction term was significant after correcting for multiple comparisons. The median [interquartile range (IQR)] risk increase across patients was 19% (IQR 14%-24%; range 7%-37%). Results were unchanged when restricting analyses to only the two RCTs.
SIGNIFICANCE: No single patient factor significantly modified the influence of discontinuation on seizure risk, although we captured how absolute risk increases change for patients that are at low versus high risk. Patients should likely continue ASMs if even a 7% 2-year increase in the chance of any more seizures would be too much and should likely discontinue ASMs if even a 37% risk increase would be too little. In between these extremes, individualized risk calculation and a careful understanding of patient preferences are critical. Future work will further develop a two-armed individualized seizure risk calculator and contextualize seizure risk thresholds below which to consider discontinuation.
PLAIN LANGUAGE SUMMARY: Understanding how much antiseizure medications (ASMs) decrease seizure risk is an important part of determining which patients with epilepsy should be treated, especially for patients who have not had a seizure in a while. We found that there was a wide range in the amount that ASM discontinuation increases seizure risk-between 7% and 37%. We found that no single patient factor modified that amount. Understanding what a patient's seizure risk might be if they discontinued versus continued ASM treatment is critical to making informed decisions about whether the benefit of treatment outweighs the downsides.
Patients receive verteporfin IV and undergo a biopsy and intratumoral photoradiation over 60-90 minutes using EUS or CT guidance on day 0. Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care oxaliplatin IV over 2-6 hours, leucovorin IV over 15 minutes - 2 hours, irinotecan IV over 90 minutes, and fluorouracil IV on days 3, 15 and 29 of cycle 1 only, then on days 1, 15, and 29 of remaining cycles. Cycles repeat every 42 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo lymph node biopsy on day 2 or 3 of cycle 1. Additionally, patients undergo blood sample collection, CT, PET/CT and optional PET/MRI on study.
BACKGROUND: Synovial calprotectin is a promising biomarker for diagnosing chronic periprosthetic joint infections (PJIs), but its diagnostic value has not been directly compared to synovial leukocyte count and polymorphonuclear neutrophils. This study aimed to: (1) evaluate and compare the diagnostic accuracy between these markers in patients undergoing revision arthroplasty for chronic PJI or aseptic reasons; and (2) determine the best rule-out and rule-in test for PJI.
METHODS: Synovial fluid samples from patients undergoing revision arthroplasty in hip and knee joints were collected and analyzed. Patients diagnosed with an acute PJI, patients treated with antibiotics 2 weeks prior to revision surgery, and/or patients who had active inflammatory joint disease were excluded. Periprosthetic joint infections were diagnosed based on the presence of a sinus tract and/or positive intraoperative cultures according to the European Bone and Joint Infection Society microbiological criteria.
RESULTS: A total of 137 patients were included, of whom 19 (14%) were diagnosed with a PJI. Overall, synovial calprotectin had the highest diagnostic accuracy of all studied markers (area under the curve 96%). Synovial calprotectin, with a cutoff of 50 mg/L, had the highest negative predictive value of 100%. However, PMNs (> 80%) combined with a leukocyte count (> 3,000 cells/μL) showed the highest positive likelihood ratio of an infection (PLR 17).
CONCLUSIONS: Synovial calprotectin is the most accurate biomarker for ruling out a chronic PJI, while the combination of synovial leukocyte count and PMN is most reliable for ruling in a chronic PJI.
BACKGROUND: Published data on whether post-stroke delirium (PSD) is an independent predictor of outcomes in patients with acute stroke are inconsistent and have not yet been synthesized and quantified via meta-analyses.
METHODS: This systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The study protocol involved a search of the PubMed, Embase, PsycINFO, and Medline databases from 1946 to November 1, 2023, of which prospective observational and case-control studies were included. The quality of the included studies was rated using the Newcastle Ottawa Scale. Pooled effect estimates calculated using a random-effects model were expressed as the odds ratios (ORs), hazard ratios (HRs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023472551).
RESULTS: The search yielded 39 eligible articles comprising 3295 and 9643 patients with and without PSD, respectively. Thirty studies were high quality, while 9 had moderate quality. The primary analyses, adequately adjusting for predefined confounders, showed that PSD was significantly associated with mortality risk (average follow-up of 19.50 months; OR, 3.47; 95% CI, 2.35-5.12; I2, 26.0%) and poor neurological function (average follow-up of 21.75 months; OR, 3.62; 95% CI, 2.15-6.09; I2, 0). Secondary analyses, with or without inadequate adjustment, showed that PSD was significantly associated with prolonged hospital length of stay, increased risk of institutionalization, poor cognitive outcomes, and quality of life after discharge.
CONCLUSIONS: This systematic review and meta-analysis provides evidence that PSD was independently associated with mortality and poor neurological function after controlling for pre-specified confounders. The prevention of PSD remains a high clinical and research priority.
Healthy participants will receive a single dose of crovalimab in each dose-escalation cohort of Part 1. Crovalimab will be administered at a starting dose of 75 milligrams (mg) intravenous (IV) infusion. Doses are planned to be escalated up to Cohort 5.
Antimicrobial resistance increasingly complicates neonatal sepsis in a global context. Fosfomycin and amikacin are two agents being tested in an ongoing multicenter neonatal sepsis trial. Although neonatal pharmacokinetics (PKs) have been described for these drugs, the physiological variability within neonatal populations makes population PKs in this group uncertain. Physiologically-based pharmacokinetic (PBPK) models were developed in Simcyp for fosfomycin and amikacin sequentially for adult, pediatric, and neonatal populations, with visual and quantitative validation compared to observed data at each stage. Simulations were performed using the final validated neonatal models to determine drug exposures for each drug across a demographic range, with probability of target attainment (PTA) assessments. Successfully validated neonatal PBPK models were developed for both fosfomycin and amikacin. PTA analysis demonstrated high probability of target attainment for amikacin 15 mg/kg i.v. q24h and fosfomycin 100 mg/kg (in neonates aged 0-7 days) or 150 mg/kg (in neonates aged 7-28 days) i.v. q12h for Enterobacterales with fosfomycin and amikacin minimum inhibitory concentrations at the adult breakpoints. Repeat analysis in premature populations demonstrated the same result. PTA analysis for a proposed combination fosfomycin-amikacin target was also performed. The simulated regimens, tested in a neonatal sepsis trial, are likely to be adequate for neonates across different postnatal ages and gestational age. This work demonstrates a template for determining target attainment for antimicrobials (alone or in combination) in special populations without sufficient available PK data to otherwise assess with traditional pharmacometric methods.
The DNA mismatch repair (MMR) system promotes genome stability and protects humans from certain types of cancer. Its primary function is the correction of DNA polymerase errors. MutLα is an important eukaryotic MMR factor. We have examined the contributions of MutLα to maintaining genome stability. We show here that loss of MutLα in yeast increases the genome-wide mutation rate by ∼130-fold and generates a genome-wide mutation spectrum that consists of small indels and base substitutions. We also show that loss of yeast MutLα leads to error-prone MMR that produces T > C base substitutions in 5'-ATA-3' sequences. In agreement with this finding, our examination of human whole-genome DNA sequencing data has revealed that loss of MutLα in induced pluripotent stem cells triggers error-prone MMR that leads to the formation of T > C mutations in 5'-NTN-3' sequences. Our further analysis has shown that MutLα-independent MMR plays a role in suppressing base substitutions in N3 homopolymeric runs. In addition, we describe that MutLα preferentially protects noncoding DNA from mutations. Our study defines the contributions of MutLα-dependent and independent mechanisms to genome-wide MMR.
AIMS: While observational studies have suggested associations linking aging and mental disorders, the question of causality has remained unclear. This study aimed to explore the causal relationship between aging level and major mental disorders.
METHODS: We utilized Two-Sample Mendelian randomization (2SMR) with mental disorders data and aging indicators information from an extensive genome-wide association study (GWAS) database. The GWAS database is a comprehensive resource that compiles genetic association data, encompassing a sample size of over 450,000 individuals. We employed five methods for 2SMR and single nucleotide polymorphisms were chosen as instrumental variables.
RESULTS: Our analyses consistently supported a bidirectional causal association between the Frailty Index (FI) and Major Depressive Disorder (MDD). Furthermore, our findings indicated potential influences, such as Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BD) affecting GrimAge, and Anxiety Disorder (AD) impacting Left Hand Grip Strength (LHGS). In contrast, we observed no significant correlations for other mental disorders on FI, Telomere Length (TL), GrimAge, Appendicular Lean Mass (ALM), and LHGS. In the reverse direction, FI showed a significant impact on the risk of MDD, AD, and ADHD, while LHGS affected the risk of MDD. Importantly, no significant associations were found between other factors and the risk of MDD, BD, AD, Schizophrenia (SZ), and ADHD.
CONCLUSIONS: This 2SMR analysis has presented evidence for a bidirectional causal relationship between FI and MDD, while the relationship between ADHD, BD, and GrimAge should be more considered. Our study provides genetic evidence supporting a causal link between aging indicators and several mental illnesses.
BACKGROUND: The association between weight and depressive symptoms is well established, but the direction of effects remains unclear. Most studies rely on body mass index (BMI) as the sole weight indicator, with few examining the aetiology of the association between weight indicators and depressive symptoms.
METHODS: We analysed data from the Twins Early Development Study (TEDS) and UK Adult Twin Registry (TwinsUK) (7658 and 2775 twin pairs, respectively). A phenotypic cross-lagged panel model assessed the directionality between BMI and depressive symptoms at ages 12, 16, and 21 years in TEDS. Bivariate correlations tested the phenotypic association between a range of weight indicators and depressive symptoms in TwinsUK. In both samples, structural equation modelling of twin data investigated genetic and environmental influences between weight indicators and depression. Sensitivity analyses included two-wave phenotypic cross-lagged panel models and the exclusion of those with a BMI <18.5.
RESULTS: Within TEDS, the relationship between BMI and depression was bidirectional between ages 12 and 16 with a stronger influence of earlier BMI on later depression. The associations were unidirectional thereafter with depression at 16 influencing BMI at 21. Small genetic correlations were found between BMI and depression at ages 16 and 21, but not at 12. Within TwinsUK, depression was weakly correlated with weight indicators; therefore, it was not possible to generate precise estimates of genetic or environmental correlations.
CONCLUSIONS: The directionality of the relationship between BMI and depression appears to be developmentally sensitive. Further research with larger genetically informative samples is needed to estimate the aetiological influence on these associations.
The present invention presents a unique class of physiological suppressors of cell division and cleavage. In particular, the present invention presents p21-activated protein kinase PAK I, also known as protease activated protein kinase I (with the same abbreviation "PAK I") which has been purified to apparent homogeneity. PAK I is inactive, e.g. as a protein of about 60 kDa (denoted "p60", as determined by polyacrylamide gel electrophoresis) and is active when autophosphorylated, for example, following limited proteolysis, or binding of Cdc42, e.g., as a protein of about 58 kDa (denoted "p58" as determined by polyacrylamide gel electrophoresis). The present invention also presents a fragment of PAK I, a peptide denoted p37, which contains the catalytic domain of PAK I. The purification, characterization, nucleotide and amino acid sequences of PAK I and p37 are also disclosed. Another aspect of the invention discloses the cytostatic activity of PAK I and its fragments. Further disclosed are the uses of these proteins and peptides for diagnosing and treating diseases, especially for cancer.
This is a two arm randomized controlled trial to test the effects of messages communicating the risks of indoor tanning delivered via mobile text messaging as a strategy for promoting cessation among young adult women who meet screening criteria for indoor tanning addiction. Eligible participants are young adult women ages 18 to 30 years who meet screening criteria for indoor tanning addiction and have access to the internet and a personal mobile phone to complete study procedures. Participants will complete baseline measures and then be randomized to the study arms. The text messaging intervention exposure in the intervention arm will last for four weeks. The control arm will be given basic indoor tanning education information and will not receive any intervention. Follow up assessments capturing study outcomes will be administered at 1 month (i.e., immediately post-intervention) and three months post-intervention.
The invention discloses an artemether nanoliposome and a preparation method and application thereof. The artemether nanoliposome is prepared from the following raw materials in parts by weight: 1 part of artemether, 2 parts of cholesterol and 8-10 parts of egg yolk lecithin. The preparation method comprises a film dispersion-ultrasonic-film filtration method and an ethanol injection-ultrasonic method. The application of the artemether nano-liposome is the application of the artemether nano-liposome in preparing artemether targeted preparation medicaments. The encapsulating rate of the artemether nanoliposome is 61.33-63.86%, the average particle size is 161.65-162.73 nm, and the dispersion index PDI is 0.2678-0.4463. The artemether nanoliposome provided by the invention has good storage stability at 4 ℃.
Acute lung injury (ALI) following thoracic surgery remains a major source of morbidity and mortality after lung resection. Despite the advancement in both the surgical techniques and the perioperative management, the incidence of postoperative ALI remains remarkable. Risk factors for postoperative lung injury are evident, including preoperative pulmonary function, type of surgical procedure, intraoperative fluid management, one-lung ventilation, and ventilator settings. One-lung ventilation (OLV) is usually required in thoracic surgery. OLV is also an important predictor of postoperative ALI. Recent laboratory findings suggested that tissue hypoxemia and ischemia / reperfusion injury of the collapsed lungs during OLV is the major cause of lung injury. Exhaled Breath Condensate (EBC), which is the exhalate from breath typically collected by cooling device, contains most molecules found in the airway. EBC analysis has potential applications in lung disease, such as severity of airway inflammation in asthmatic patients. Collecting EBC is simple and non-invasive, in contrast to bronchoscopy for lung biopsy or bronchoalveolar lavage. Metabolomics refers to systematic and scientific study of chemical processes involving metabolites. This study will collect EBC from thoracic surgical patients before, during, and after OLV. The investigators will perform metabolomic analysis and aim to elucidate the biochemical reactions during one-lung ventilation and pathological mechanisms of acute lung injury following thoracic surgery.
Background: Young athletes are thought to be models of peak physical condition, capable of exceptional physical accomplishments. However approximately 64 UK athletes aged 12 to 35 will die each year from a phenomenon known as Sudden Cardiac Death (SCD). SCD can be defined as an unexpected death as a result of abrupt loss of cardiac function within an hour of symptom onset. Undiagnosed heart conditions such as arrhythmias are often found to be the cause of SCD. Advantageous physical attributes found in athletes' hearts can complicate diagnoses as hearts with inherited conditions can appear physiologically similar to hearts adapted to strenuous exercise. Growing research surrounding SCD within sporting populations aims to decrease mortality rates however there is an absence of study specifically into SCD in dance. Within sport, the topic of cardiac screening has generated widespread controversy which is fueled by a lack of empirical evidence. There is currently no international consensus of pre participation cardiac screening methods within dance or sport, potentially leaving many dancers and athletes at risk. Methods: As part of this study, existing material surrounding the topics of SCD and cardiac screening in athletes and dancers was gathered. All existing studies at the time of writing in relation to cardiac screening in athletes and dancers were collected and analysed in order to compare results and evaluate the methodological limitations.This process aimed to identify gaps in current knowledge and research to inform future study. Results: This article aimed to analyze the epidemiology of SCD within sport and dance and to make recommendations for pre-participation screening within dance institutions. The study highlights the need to increase awareness of SCD within the dance community and determine appropriate screening approaches depending on context and setting.