28232 research outputs found
Sort by
Heat shock factor 1 directly regulates transsulfuration pathway to promote prostate cancer proliferation and survival
No full textAbstractThere are limited therapeutic options for patients with advanced prostate cancer (PCa). We previously found that heat shock factor 1 (HSF1) expression is increased in PCa and is an actionable target. In this manuscript, we identify that HSF1 regulates the conversion of homocysteine to cystathionine in the transsulfuration pathway by altering levels of cystathionine-β-synthase (CBS). We find that HSF1 directly binds the CBS gene and upregulates CBS mRNA levels. Targeting CBS decreases PCa growth and induces tumor cell death while benign prostate cells are largely unaffected. Combined inhibition of HSF1 and CBS results in more pronounced inhibition of PCa cell proliferation and reduction of transsulfuration pathway metabolites. Combination of HSF1 and CBS knockout decreases tumor size for a small cell PCa xenograft mouse model. Our study thus provides new insights into the molecular mechanism of HSF1 function and an effective therapeutic strategy against advanced PCa.</jats:p
Integrating frame-level boundary detection and deepfake detection for locating manipulated regions in partially spoofed audio forgery attacks
No full textDomestic Polarization and International Rivalry: How Adversaries Respond to America’s Partisan Politics
No full textWhat predicts the best 24-month outcomes following surgery for cervical spondylotic myelopathy? A QOD prospective registry study.
No full textThe aim of this study was to identify predictors of the best 24-month improvements in patients undergoing surgery for cervical spondylotic myelopathy (CSM). For this purpose, the authors leveraged a large prospective cohort of surgically treated patients with CSM to identify factors predicting the best outcomes for disability, quality of life, and functional status following surgery. This was a retrospective analysis of prospectively collected data. The Quality Outcomes Database (QOD) CSM dataset (1141 patients) at 14 top enrolling sites was used. Baseline and surgical characteristics were compared for those reporting the top and bottom 20th percentile 24-month Neck Disability Index (NDI), EuroQol-5D (EQ-5D), and modified Japanese Orthopaedic Association (mJOA) change scores. A multivariable logistic model was constructed and included candidate variables reaching p ≤ 0.20 on univariate analyses. Least important variables were removed in a stepwise manner to determine the significant predictors of the best outcomes (top 20th percentile) for 24-month NDI, EQ-5D, and mJOA change. A total of 948 (83.1%) patients with 24-month follow-up were included in this study. For NDI, 204 (17.9%) had the best NDI outcome and 200 (17.5%) had the worst NDI outcome. Factors predicting the best NDI outcomes included symptom duration less than 12 months (OR 1.5, 95% CI 1.1-1.9; p = 0.01); procedure other than posterior fusion (OR 1.5, 95% CI 1.03-2.1; p = 0.03); higher preoperative visual analog scale neck pain score (OR 1.2, 95% CI 1.1-1.3; p < 0.001); and higher baseline NDI (OR 1.06, 95% CI 1.05-1.07; p < 0.001). For EQ-5D, 163 (14.3%) had the best EQ-5D outcome and 169 (14.8%) had the worst EQ-5D outcome. Factors predicting the best EQ-5D outcomes included arm pain-only complaints (compared to neck pain) (OR 1.9, 95% CI 1.3-2.9; p = 0.002) and lower baseline EQ-5D (OR 167.7 per unit lower, 95% CI 85.0-339.4; p < 0.001). For mJOA, 222 (19.5%) had the best mJOA outcome and 238 (20.9%) had the worst mJOA outcome. Factors predicting the best mJOA outcomes included lower BMI (OR 1.03 per unit lower, 95% CI 1.004-1.05; p = 0.02; cutoff value of ≤ 29.5 kg/m2); arm pain-only complaints (compared to neck pain) (OR 1.7, 95% CI 1.1-2.5; p = 0.02); and lower baseline mJOA (OR 1.6 per unit lower, 95% CI 1.5-1.7; p < 0.001). Compared to the worst outcomes for EQ-5D, the best outcomes were associated with patients with arm pain-only complaints. For mJOA, lower BMI and arm pain-only complaints portended the best outcomes. For NDI, those with the best outcomes had shorter symptom durations, higher preoperative neck pain scores, and less often underwent posterior spinal fusions. Given the positive impact of shorter symptom duration on outcomes, these data suggest that early surgery may be beneficial for patients with CSM
Multimorbidity clusters in adults 50 years or older with and without a history of cancer: National Health Interview Survey, 2018
No full textAbstract
Background
Multimorbidity is increasing among adults in the United States. Yet limited research has examined multimorbidity clusters in persons aged 50 years and older with and without a history of cancer. An increased understanding of multimorbidity clusters may improve the cancer survivorship experience for survivors with multimorbidity.
Methods
We identified 7580 adults aged 50 years and older with 2 or more diseases—including 811 adults with a history of primary breast, colorectal, cervical, prostate, or lung cancer—from the 2018 National Health Interview Survey. Exploratory factor analysis identified clusters of multimorbidity among cancer survivors and individuals without a history of cancer (controls). Frequency tables and chi-square tests were performed to determine overall differences in sociodemographic characteristics, health-related characteristics, and multimorbidity between groups.
Results
Cancer survivors reported a higher prevalence of having 4 or more diseases compared to controls (57% and 38%, respectively). Our analysis identified 6 clusters for cancer survivors and 4 clusters for controls. Three clusters (pulmonary, cardiac, and liver) included the same diseases for cancer survivors and controls.
Conclusions
Diseases clustered differently across adults ≥ 50 years of age with and without a history of cancer. Findings from this study may be used to inform clinical care, increase the development and dissemination of multilevel public health interventions, escalate system improvements, and initiate innovative policy reform.
</jats:sec
Patient Characteristics Associated with Telemedicine Use for Diabetes Mellitus Care: Experience of a University Health System.
No full textObjectivesThe objective was to understand the characteristics of patients who used telemedicine for diabetes management to inform future implementation of telemedicine.MethodsWe examined patient characteristics associated with telemedicine use for diabetes mellitus (DM) care between March 1, 2020 and April 1, 2021 (the coronavirus disease 2019 pandemic period) in a large university health system when telemedicine visits increased rapidly. Logistic regression models assessed patient characteristics associated with telemedicine visits and delays in DM process measures (hemoglobin A1c checks, nephropathy, and retinopathy evaluations) during the pandemic period after adjusting for potential confounders and corresponding values before the pandemic period (March 1, 2019-February 29, 2020).ResultsA total of 45,159 patients were seen from 987,791 visits during the pandemic period. The number of visits averaged one visit less during the pandemic period than before the pandemic period. Approximately 5.4% of patients used telemedicine during the pandemic period from 42,750 visits. The mean (standard deviation) telemedicine visit was 1.28 (0.91). Men, Asian, Black, and other race (vs White), having Medicare or uninsured (vs private insurance), were less likely to use telemedicine. Patients with more visits before the pandemic period were more likely to use telemedicine and less likely to experience a delay in DM process measures during the pandemic period. Telemedicine users were 18% less likely to experience a delay in nephropathy visits than nonusers, but without difference for other process measures.ConclusionsRace, sex, insurance, and prepandemic in-person visits were associated with telemedicine use for DM management in a large health system. Telemedicine use was not associated with delays in hemoglobin A1c testing, nephropathy, and retinopathy assessments. Understanding reasons for not using telemedicine is important to be able to deliver equitable DM care
Physiological Differences Between Low Versus High Skeletal Muscle Hypertrophic Responders to Resistance Exercise Training: Current Perspectives and Future Research Directions
No full textFinding a common definition of heparin resistance in adult cardiac surgery: Communication from the ISTH SSC Subcommittee on Perioperative and Critical Care Thrombosis and Hemostasis.
No full textSkeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities
No full textSkeletal muscle adaptations to resistance and endurance training include increased ribosome and mitochondrial biogenesis, respectively. Such adaptations are believed to contribute to the notable increases in hypertrophy and aerobic capacity observed with each exercise mode. Data from multiple studies suggest the existence of a competition between ribosome and mitochondrial biogenesis, in which the first adaptation is prioritized with resistance training while the latter is prioritized with endurance training. In addition, reports have shown an interference effect when both exercise modes are performed concurrently. This prioritization/interference may be due to the interplay between the 5’ AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) signaling cascades and/or the high skeletal muscle energy requirements for the synthesis and maintenance of cellular organelles. Negative associations between ribosomal DNA and mitochondrial DNA copy number in human blood cells also provide evidence of potential competition in skeletal muscle. However, several lines of evidence suggest that ribosome and mitochondrial biogenesis can occur simultaneously in response to different types of exercise and that the AMPK-mTORC1 interaction is more complex than initially thought. The purpose of this review is to provide in-depth discussions of these topics. We discuss whether a curious competition between mitochondrial and ribosome biogenesis exists and show the available evidence both in favor and against it. Finally, we provide future research avenues in this area of exercise physiology.</jats:p
