Tag: statistics

Nucleic Acids Res. 2023 May 24:gkad373. doi: 10.1093/nar/gkad373. Online ahead of print.

ABSTRACT

Polygenic risk scores (PRSs) are expected to play a critical role in precision medicine. Currently, PRS predictors are generally based on linear models using summary statistics, and more recently individual-level data. However, these predictors mainly capture additive relationships and are limited in data modalities they can use. We developed a deep learning framework (EIR) for PRS prediction which includes a model, genome-local-net (GLN), specifically designed for large-scale genomics data. The framework supports multi-task learning, automatic integration of other clinical and biochemical data, and model explainability. When applied to individual-level data from the UK Biobank, the GLN model demonstrated a competitive performance compared to established neural network architectures, particularly for certain traits, showcasing its potential in modeling complex genetic relationships. Furthermore, the GLN model outperformed linear PRS methods for Type 1 Diabetes, likely due to modeling non-additive genetic effects and epistasis. This was supported by our identification of widespread non-additive genetic effects and epistasis in the context of T1D. Finally, we constructed PRS models that integrated genotype, blood, urine, and anthropometric data and found that this improved performance for 93% of the 290 diseases and disorders considered. EIR is available at https://github.com/arnor-sigurdsson/EIR.

PMID:37224538 | DOI:10.1093/nar/gkad373

Nucleic Acids Res. 2023 May 24:gkad445. doi: 10.1093/nar/gkad445. Online ahead of print.

ABSTRACT

We present GePI, a novel Web server for large-scale text mining of molecular interactions from the scientific biomedical literature. GePI leverages natural language processing techniques to identify genes and related entities, interactions between those entities and biomolecular events involving them. GePI supports rapid retrieval of interactions based on powerful search options to contextualize queries targeting (lists of) genes of interest. Contextualization is enabled by full-text filters constraining the search for interactions to either sentences or paragraphs, with or without pre-defined gene lists. Our knowledge graph is updated several times a week ensuring the most recent information to be available at all times. The result page provides an overview of the outcome of a search, with accompanying interaction statistics and visualizations. A table (downloadable in Excel format) gives direct access to the retrieved interaction pairs, together with information about the molecular entities, the factual certainty of the interactions (as verbatim expressed by the authors), and a text snippet from the original document that verbalizes each interaction. In summary, our Web application offers free, easy-to-use, and up-to-date monitoring of gene and protein interaction information, in company with flexible query formulation and filtering options. GePI is available at https://gepi.coling.uni-jena.de/.

PMID:37224532 | DOI:10.1093/nar/gkad445

J Gerontol B Psychol Sci Soc Sci. 2023 May 24:gbad077. doi: 10.1093/geronb/gbad077. Online ahead of print.

ABSTRACT

OBJECTIVE: A meta-analytic review was conducted to assess the effects of healthy aging, amnestic Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) on naturalistic autobiographical memory using the Autobiographical Interview, a widely used, standardized assessment that derives measures of internal (episodic) and external (non-episodic) details from freely recalled autobiographical narratives.

METHOD: A comprehensive literature search identified 21 aging, 6 MCI, and 7 AD studies (total N =1556 participants). Summary statistics for internal and external details for each comparison (younger vs. older or MCI/AD vs. age-matched comparison groups) and effect size statistics were extracted and summarized using Hedges’ g (random effects model) and adjusted for the presence of publication bias.

RESULTS: The pattern of reduced internal and elevated external details in aging was robust and consistent across nearly all 21 studies. MCI and – to a greater extent – AD were associated with reduced internal details, whereas the external detail elevation faded with MCI and AD. Although there was evidence of publication bias on reporting of internal detail effects, these effects remained robust after correction.

DISCUSSION: The canonical changes to episodic memory observed in aging and neurodegenerative disease are mirrored in the free recall of real-life events. Our findings indicate that the onset of neuropathology overwhelms the capacity of older adults to draw upon distributed neural systems to elaborate on past experiences, including both episodic details specific to identified events and non-episodic content characteristic of healthy older adults’ autobiographical narratives.

PMID:37224530 | DOI:10.1093/geronb/gbad077

J Clin Endocrinol Metab. 2023 May 24:dgad287. doi: 10.1210/clinem/dgad287. Online ahead of print.

ABSTRACT

OBJECTIVE: Two-way relationship between periodontitis and diabetes was advocated. However, bidirectional epidemiological observation is still limited and inconsistent. Using the National Health Insurance Research Database of Taiwan (covering over 99% of the entire population), we estimate the development of diabetes in periodontitis patients or that of periodontitis in patients with type 2 diabetes mellitus (T2DM), respectively.

METHODS: A total of 11,011 patients with severe periodontitis were recruited from 2000 to 2015. After matching by age, sex, and index date, 11,011 patients with mild periodontitis and 11,011 non-periodontitis controls were registered. Conversely, 157,798 patients with T2DM and 157,798 non-T2DM controls were enrolled, whereas the development of periodontitis was traced. Cox proportional hazards model was performed.

RESULTS: Periodontitis patients tended to have a statistically high risk of having T2DM. Adjusted hazard ratio (aHR) was 1.94 (95% CI 1.49-2.63, p < 0.01) and 1.72 (95% CI 1.24-2.52, p < 0.01) for severe and mild periodontitis groups, respectively. Besides, the patients in severe periodontitis had a high risk of having T2DM compared to that in mild periodontitis [1.17 (95% CI 1.04-1.26, p < 0.001)]. Conversely, the risk of periodontitis increased significantly in patients with T2DM [1.99 (95% CI,1.42-2.48, p < 0.01)]. However, the high risk was observed for the outcome of severe periodontitis [2.08 (95% CI, 1.50-2.66, p < 0.001)], not for that of mild periodontitis [0.97 (95% CI,0.38-1.57, p = 0.462)].

CONCLUSIONS: We suggested the bi-direction is between T2DM and severe periodontitis, but not in mild type.

PMID:37224522 | DOI:10.1210/clinem/dgad287

Eur J Endocrinol. 2023 May 24:lvad052. doi: 10.1093/ejendo/lvad052. Online ahead of print.

ABSTRACT

OBJECTIVE: Interpreting laboratory results for transgender individuals who started hormone therapy requires careful consideration, specifically for analytes that have sex-specific reference intervals. In literature, conflicting data exist on the effect of hormone therapy on laboratory parameters. By studying a large cohort, we aim to define what reference category (male or female) is most appropriate to use for the transgender population over the course of gender-affirming therapy.

METHODS: A total of 2201 people (1178 transgender women and 1023 transgender men) were included in this study. We analyzed hemoglobin (Hb), hematocrit (Ht), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), creatinine, and prolactin, at three different time points: pretreatment, during hormone therapy, and after gonadectomy.

RESULTS: For transgender women, Hb and Ht levels decrease after initiation of hormone therapy. The concentration of liver enzymes ALT, AST, and ALP decrease whereas the levels of GGT do not change statistically significantly. Creatinine levels decrease whereas prolactin levels rise in transgender women during gender-affirming therapy. For transgender men Hb and Ht values increase after starting hormone therapy. Liver enzymes and creatinine levels increase statistically significant as well upon hormone therapy while prolactin concentrations decrease. Overall, reference intervals in transgender people after 1 year on hormone therapy resembled those of their affirmed gender.

CONCLUSIONS: Generating transgender-specific reference intervals is not essential to correctly interpret laboratory results. As a practical approach, we recommend to use the reference intervals of the affirmed gender from 1 year onwards after starting hormone therapy.

PMID:37224509 | DOI:10.1093/ejendo/lvad052

J Chromatogr Sci. 2023 May 23:bmad036. doi: 10.1093/chromsci/bmad036. Online ahead of print.

ABSTRACT

Mayonnaise is an emulsion of oil that is susceptible to lipid oxidation, which can cause spoilage and the formation of harmful compounds. This study aims to evaluate the impact of Syrian apple and grape vinegar on the oxidative stability of mayonnaise and compare the use of natural antioxidants to synthetic ones such as butylated hydroxyanisole and butylated hydroxytoluene. The study measured total phenol content, radical scavenging activity, and identified some phenolic compounds by High Performance Liquid Chromatography (HPLC). The rancidity of mayonnaise was examined using peroxide value and thiobarbituric acid number. The fatty acids content in the mayonnaise samples was examined using gas chromatography. Vinegar samples containing high concentrations of phenolic antioxidants showed high ability to scavenge free radicals. The antioxidants in vinegar protected the mayonnaise samples from primary and secondary oxidation, and there was no statistically significant difference between the ratio of unsaturated fatty acids in the samples containing vinegar at the beginning and at the end of the storage period. The study shows the significance of using vinegar to protect mayonnaise from deterioration and increase its shelf life, in addition to its role as a dressing.

PMID:37224456 | DOI:10.1093/chromsci/bmad036

Int J Inj Contr Saf Promot. 2023 May 24:1-9. doi: 10.1080/17457300.2023.2214887. Online ahead of print.

ABSTRACT

Despite statistics indicating that China has the world’s largest taxi industry, there exists limited research about the relationship between workplace health hazards and taxi driver occupational crashes. In this paper, a cross-sectional survey of taxi drivers in four typical Chinese cities was conducted, and data on their self-reported job stress, health status, and daily risky driving behaviours, together with crash involvement experience in the two years before the survey was collected. Three hypotheses were then developed, and they were verified via multivariate analysis of variance (MANOVA) that the seriousness of drivers’ health problems and the frequency of their daily risky driving behaviours could be the accurate predictor of their crash risk of taxi drivers. These factors were subsequently substituted in a bivariate negative binomial (BNB) distribution model to determine the joint rate of at-fault taxi drivers’ involvement in property-damage-only (PDO) and personal-injury (PI) crashes. The results offer some useful advice for policy development to decrease and prevent professional taxi drivers from causing severe traffic crashes.

PMID:37224451 | DOI:10.1080/17457300.2023.2214887

J Am Geriatr Soc. 2023 May 24. doi: 10.1111/jgs.18396. Online ahead of print.

ABSTRACT

BACKGROUND: To determine the potential mediating role of loneliness in the relationship between hearing ability and dementia.

METHODS: Design: Longitudinal observational study.

SETTING: English Longitudinal Study of Ageing (ELSA).

PARTICIPANTS: Individuals aged 50 and older (N = 4232).

MEASUREMENTS: Self-reported hearing ability and loneliness were assessed from Wave 2 (2004-2005) to Wave 7 (2014-2015) of ELSA. Dementia cases were ascertained via self- or carer-report or dementia medication at these waves. The medeff command in Stata version 17 was used to do cross-section mediation analysis between hearing ability, loneliness, and dementia (Waves 3-7). Path-specific effects proportional (cause-specific) hazard models were then used to investigate longitudinal mediation (Waves 2-7).

RESULTS: In cross-sectional analyses in Wave 7 alone, loneliness only mediated 5.4% of the total effects of limited hearing on dementia (indirect effects = increased risk of 0.06%; 95% CI: 0.002%-0.15%) under limited hearing and 0.04% (95% CI: 0.001%-0.11%) under normal hearing). In longitudinal analyses, there was no statistical evidence of a mediating role for loneliness in explaining the relationship between hearing ability and time-to-dementia (indirect effect estimate hazard ratio = 1.01 (95% CI: 0.99-1.05).

CONCLUSION: In this community-dwelling sample of English adults, there is a lack of evidence that loneliness mediates the relationship between hearing ability and dementia in both cross-sectional and longitudinal analyses. However, as the number of dementia cases in this cohort was low, replication in other cohorts with larger sample sizes is required to confirm the absence of a mediated effect via loneliness.

PMID:37224416 | DOI:10.1111/jgs.18396

J Spec Oper Med. 2023 May 24:MB9O-LXOB. doi: 10.55460/MB9O-LXOB. Online ahead of print.

ABSTRACT

BACKGROUND: Our objective was to optimize a novel damage control resuscitation (DCR) cocktail composed of hydroxyethyl starch, vasopressin, and fibrinogen concentrate for the polytraumatized casualty. We hypothesized that slow intravenous infusion of the DCR cocktail in a pig polytrauma model would decrease internal hemorrhage and improve survival compared with bolus administration.

METHODS: We induced polytrauma, including traumatic brain injury (TBI), femoral fracture, hemorrhagic shock, and free bleeding from aortic tear injury, in 18 farm pigs. The DCR cocktail consisted of 6% hydroxyethyl starch in Ringer’s lactate solution (14mL/kg), vasopressin (0.8U/kg), and fibrinogen concentrate (100mg/kg) in a total fluid volume of 20mL/kg that was either divided in half and given as two boluses separated by 30 minutes as control or given as a continuous slow infusion over 60 minutes. Nine animals were studied per group and monitored for up to 3 hours. Outcomes included internal blood loss, survival, hemodynamics, lactate concentration, and organ blood flow obtained by colored microsphere injection.

RESULTS: Mean internal blood loss was significantly decreased by 11.1mL/kg with infusion compared with the bolus group (p = .038). Survival to 3 hours was 80% with infusion and 40% with bolus, which was not statistically different (Kaplan Meier log-rank test, p = .17). Overall blood pressure was increased (p < .001), and blood lactate concentration was decreased (p < .001) with infusion compared with bolus. There were no differences in organ blood flow (p > .09).

CONCLUSION: Controlled infusion of a novel DCR cocktail decreased hemorrhage and improved resuscitation in this polytrauma model compared with bolus. The rate of infusion of intravenous fluids should be considered as an important aspect of DCR.

PMID:37224392 | DOI:10.55460/MB9O-LXOB

Int J Prosthodont. 2023 Marhc, Apr;36(2):161-171. doi: 10.11607/ijp.7518.

ABSTRACT

PURPOSE: To investigate and analyze the effects of different prosthetic protocols under different loading and occlusal conditions on the survival rates of single implants immediately placed into fresh extraction sockets of maxillary or mandibular premolars with single-stage surgery.

MATERIALS AND METHODS: Patients needing replacement of a single premolar in the maxilla or mandible were included and randomly divided into three groups based on the different loading protocols: group 1 = healing abutment; group 2 = provisional crown left out of occlusion without functional loading; and group 3 = provisional crown in functional occlusion in maximum intercuspation without contact in excursions. The hypothesis was that single implants inserted into fresh extraction sockets and immediately connected to a temporary crown under functional loading would demonstrate survival rates comparable to single implants placed in the same conditions connected to a healing abutment or to an immediate temporary crown left out of occlusion.

RESULTS: A total of 112 patients were treated, and 126 implants were placed (92 in the maxilla and 34 in the mandible). After a mean follow-up of 2.5 years (range 1 to 5 years), there were no failures in groups 1 or 2. Two implants failed in group 3 (one in the maxilla, one in the mandible). The cumulative survival rate was 98.5% across all groups, with 100% in groups 1 and 2 and 95% in group 3. Statistical analysis showed that group 3 displayed a survival rate comparable to groups 1 and 2 (P = .08).

CONCLUSION: Within the limitations of this study, no significant differences were found in terms of implant survival rates between implants inserted into fresh extraction sockets without loading vs with immediate nonfunctional or functional loading. Int J Prosthodont 2023;36:161-171. doi: 10.11607/ijp.7518.

PMID:37224307 | DOI:10.11607/ijp.7518