Identifying Predictors of Functional Limitations Associated with Depression, Anxiety, and Emotional Problems in US Adults

Depressive disorders are characterized as sharing affected mood, and somatic (e.g. sleep pattern, appetite, and unintentional changes in weight) and cognitive alterations from previous normal daily functioning that are clinically significant. Anxiety disorders are characterized by excessive fear, general or specific anxiety, and related behavioral disturbances that are also clinically significant. This project attempts to identify risk factors that may predict what groups are most likely to be affected by depression and/or anxiety. Sponsored by the CDC, the National Health Interview Survey collects general health information for non-institutionalized individuals living in the US. Variables for use in logistic regression model construction were selected from the all-inclusive pool of data measurements taken during the 2014 NHIS person data module, using the literature as a guide. The sample was limited to adult respondents at least 18 years of age. Odds ratios were calculated for each level of potential predictor variables comparing the two levels of the dependent variable: those with a self-reported depression, anxiety, or emotional problem (DAE) related functional limitation and those without. These were used as initial inclusion criteria for logistic regression modeling, which resulted in two final models. Each model contained eight variables accounting for age, marital status, education level, financial factors, and other functional limitations. The nine predictor model also included sex as a predictor (c=0.763), while the eight predictor did not (c=0.790). Different effects were observed in each model. These models were designed for use as a tool for selecting groups for targeted public health intervention, not for use in a clinical setting, and could likely help distinguish groups that would be prime for investigating the prevalence and effects of DAE-related functional limitations. There were several limitations worth addressing in future research into this topic

Effect of Refrigerated Storage on Meat Quality

Maintaining meat quality during cold temperature storage is an important goal for increasing consumer satisfaction and reducing food waste. Following a literature review on the importance of cold meat storage, a study was conducted as a part of Electrolux refrigerator research and development. Chicken breast and beef sirloin filets were stored at -2°C, -5°C, and -18°C and monitored for quality changes over a 7-day period. Temperature fluctuations and relative humidity data were monitored automatically by sensors. Meat quality was evaluated by measuring water activity, moisture content, pH, colorimetry, sensory, and drip loss. Microbial plate counts were used to monitor the safety of the samples. Further experimentation based on initial quality results included observing the impact of different cooking methods as measured by cook loss and sensory evaluation. Trends in acceptability were difficult to correlate with storage temperatures and cooking method due to a limited sensory group size. Storing meat at -2°C was the best at preserving quality for both chicken breasts and beef sirloin for both phases of experimentation

Artificial intelligence and precision health through lenses of ethics and social determinants of health: Protocol for a state-of-the-art literature review

Background: Precision health is a rapidly developing field, largely driven by the development of artificial intelligence (AI)–related solutions. AI facilitates complex analysis of numerous health data risk assessment, early detection of disease, and initiation of timely preventative health interventions that can be highly tailored to the individual. Despite such promise, ethical concerns arising from the rapid development and use of AI-related technologies have led to development of national and international frameworks to address responsible use of AI. Objective: We aimed to address research gaps and provide new knowledge regarding (1) examples of existing AI applications and what role they play regarding precision health, (2) what salient features can be used to categorize them, (3) what evidence exists for their effects on precision health outcomes, (4) how do these AI applications comply with established ethical and responsible framework, and (5) how these AI applications address equity and social determinants of health (SDOH). Methods: This protocol delineates a state-of-the-art literature review of novel AI-based applications in precision health. Published and unpublished studies were retrieved from 6 electronic databases. Articles included in this study were from the inception of the databases to January 2023. The review will encompass applications that use AI as a primary or supporting system or method when primarily applied for precision health purposes in human populations. It includes any geographical location or setting, including the internet, community-based, and acute or clinical settings, reporting clinical, behavioral, and psychosocial outcomes, including detection-, diagnosis-, promotion-, prevention-, management-, and treatment-related outcomes. Results: This is step 1 toward a full state-of-the-art literature review with data analyses, results, and discussion of findings, which will also be published. The anticipated consequences on equity from the perspective of SDOH will be analyzed. Keyword cluster relationships and analyses will be visualized to indicate which research foci are leading the development of the field and where research gaps exist. Results will be presented based on the data analysis plan that includes primary analyses, visualization of sources, and secondary analyses. Implications for future research and person-centered public health will be discussed. Conclusions: Results from the review will potentially guide the continued development of AI applications, future research in reducing the knowledge gaps, and improvement of practice related to precision health. New insights regarding examples of existing AI applications, their salient features, their role regarding precision health, and the existing evidence that exists for their effects on precision health outcomes will be demonstrated. Additionally, a demonstration of how existing AI applications address equity and SDOH and comply with established ethical and responsible frameworks will be provided

Enhanced Protein Homeostasis Mechanisms in Naked Mole Rats Cells

Phylogenic studies suggest that cells from long-lived species are more resistant to a variety of stressors than short-lived species. However, there is little information on the cellular mechanisms that give rise to increased resistance to stress. Our previous studies have shown that liver proteins from a long-lived species have lower levels of protein ubiquitination which is associated with increased proteasome activity, suggesting that mechanisms of protein quality control could play a critical role in assuring longevity of long-lived species. In this study, we evaluated whether autophagy and heat shock chaperones proteins (HSPs) are associated with longevity in rodents using skin fibroblasts isolated from mice and naked mole rats (NMR); two species that are similar in body size but differ almost 10 fold in longevity. Our results indicate that macroautophagy induced by serum-starvation is significantly enhanced in NMR compared to mouse which correlates with an inhibition of the mTOR pathway and increased LC3 conversion. We also found that several HSPs (e.g., Hsp90, Hsp70, Hsp40, Hsp 27) were significantly higher at both basal and after heat shock conditions. These observations suggest that NMR, a long-lived species, has increased mechanisms to ensure protein quality (autophagy and HSPs) and support the idea that protein homeostasis could play an important role in promoting longevity

RESOLVE and ECO: Finding Low-metallicity z ∼ 0 Dwarf AGN Candidates Using Optimized Emission-line Diagnostics

Existing star-forming vs. active galactic nucleus (AGN) classification schemes using optical emission-line diagnostics mostly fail for low-metallicity and/or highly star-forming galaxies, missing AGN in typical z ∼ 0 dwarfs. To recover AGN in dwarfs with strong emission lines (SELs), we present a classification scheme optimizing the use of existing optical diagnostics. We use Sloan Digital Sky Survey emission-line catalogs overlapping the volume- and mass-limited REsolved Spectroscopy Of a Local VolumE (RESOLVE) and Environmental COntex (ECO) surveys to determine the AGN percentage in SEL dwarfs. Our photoionization grids show that the [O iii]/Hβ versus [S ii]/Hα diagram (S ii plot) and [O iii]/Hβ versus [O i]/Hα diagram (O i plot) are less metallicity sensitive and more successful in identifying dwarf AGN than the popular [O iii]/Hβ versus [N ii]/Hα diagnostic (N ii plot or “BPT diagram”). We identify a new category of “star-forming AGN” (SF-AGN) classified as star-forming by the N ii plot but as AGN by the S ii and/or O i plots. Including SF-AGN, we find the z ∼ 0 AGN percentage in dwarfs with SELs to be ∼3%–16%, far exceeding most previous optical estimates (∼1%). The large range in our dwarf AGN percentage reflects differences in spectral fitting methodologies between catalogs. The highly complete nature of RESOLVE and ECO allows us to normalize strong emission-line galaxy statistics to the full galaxy population, reducing the dwarf AGN percentage to ∼0.6%–3.0%. The newly identified SF-AGN are mostly gas-rich dwarfs with halo mass <1011.5 M ⊙, where highly efficient cosmic gas accretion is expected. Almost all SF-AGN also have low metallicities (Z ≲ 0.4 Z ⊙), demonstrating the advantage of our method

Sleep, stress and compensatory behaviors in Australian nurses and midwives

OBJECTIVE: To describe sleep, stress and compensatory behaviors in nurses and midwives. METHODS: The study included 41 midwives and 21 nurses working in Australian hospitals between 2005 and 2009. Participation was voluntary. All participants recorded on a daily basis their work and sleep hours, levels of stress and exhaustion, caffeine intake and use of sleep aids for a month (1,736 days, 1,002 work shifts). RESULTS: Participants reported moderate to high levels of stress and exhaustion on 20-40% of work days; experienced sleep disruption on more than 50% of work days; struggled to remain awake on 27% of work days; and suffered extreme drowsiness or experienced a near accident while travelling home on 9% of workdays. Age, perceived sleep duration and work hours were significant predictors of caffeine intake. About 60% of participants reported using sleep aids (about 20% reported taking prescription medications and 44% of nurses and 9% of midwives reported alcohol use as a sleep aid at least once during the study). Stress and workdays were significant predictors of sedative use. Overall, 22% reported being indifferent or mildly dissatisfied with their job. CONCLUSIONS: Sleep problems, high levels of stress and exhaustion and low job satisfaction are prevalent among nurses and midwives. The use of alcohol and sleeping pills as sleep aids, and the use of caffeine to help maintain alertness is also common. Nurses and midwives may use caffeine to compensate for reduced sleep, especially on workdays, and sleeping pills to cope with their daily work-related stress

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population