Tag: pubmed

Ann Hum Genet. 2022 May 18. doi: 10.1111/ahg.12470. Online ahead of print.

ABSTRACT

One of the critical issues in genetic association studies is to evaluate the risk of a disease associated with gene-gene or gene-environment interactions. The commonly employed procedures are derived by assigning a particular set of scores to genotypes. However, the underlying genetic models of inheritance are rarely known in practice. Misspecifying a genetic model may result in power loss. By using some potential genetic variables to separate the genotype coding and genetic model parameter, we construct a model-embedded score test (MEST). Our test is free of assumption of gene-environment independence and allows for covariates in the model. An effective sequential optimization algorithm is developed. Extensive simulations show the proposed MEST is robust and powerful in most of scenarios. Finally, we apply the proposed method to rheumatoid arthritis data from the Genetic Analysis Workshop 16 to further investigate the potential interaction effects.

PMID:35582845 | DOI:10.1111/ahg.12470

Bioconjug Chem. 2022 May 18;33(5):948-955. doi: 10.1021/acs.bioconjchem.2c00159. Epub 2022 May 3.

ABSTRACT

d-Xylonic acid (XA), derived from pentose sugar xylose, is a multifunctional high-value chemical with a wide range of applications in the fields of medicines, food, agriculture and is a valuable chemical reagent for the synthesis of other useful commodity chemicals. In the bacterial system, xylose dehydrogenase (XDH) catalyzes the oxidation of d-xylose into d-xylonolactone, consuming NAD⁺ or NADP⁺ as a cofactor. The d-xylonolactone then undergoes auto-oxidation into d-xylonic acid. Herein, the XDH enzyme overexpressed in Escherichia coli is purified and immobilized on ferromagnetic nanoparticles, effectively converting xylose into xylonic acid. Parameters deciding the bioconversion were statistically optimized and obtained a maximum of 91% conversion rate. Kinetic parameters of immobilized xylose dehydrogenase showed a 2-fold increase in the maximum velocity of the reaction and catalytic efficiency compared to free enzyme. The operational stability test for the enzyme-nanoparticle conjugate retained 93% relative activity after 10 successive experiments, exhibiting the good recyclability of the biocatalyst for XA production.

PMID:35582818 | DOI:10.1021/acs.bioconjchem.2c00159

Stat Med. 2022 May 18. doi: 10.1002/sim.9440. Online ahead of print.

ABSTRACT

Correlated phenotypes often share common genetic determinants. Thus, a multi-trait analysis can potentially increase association power and help in understanding pleiotropic effect. When multiple traits are jointly measured over time, the correlation information between multivariate longitudinal responses can help to gain power in association analysis, and the longitudinal traits can provide insights on the dynamic gene effect over time. In this work, we propose a multivariate partially linear varying coefficients model to identify genetic variants with their effects potentially modified by environmental factors. We derive a testing framework to jointly test the association of genetic factors and illustrated with a bivariate phenotypic trait, while taking the time varying genetic effects into account. We extend the quadratic inference functions to deal with the longitudinal correlations and used penalized splines for the approximation of nonparametric coefficient functions. Theoretical results such as consistency and asymptotic normality of the estimates are established. The performance of the testing procedure is evaluated through Monte Carlo simulation studies. The utility of the method is demonstrated with a real data set from the Twin Study of Hormones and Behavior across the menstrual cycle project, in which single nucleotide polymorphisms associated with emotional eating behavior are identified.

PMID:35582816 | DOI:10.1002/sim.9440

Stat Med. 2022 May 18. doi: 10.1002/sim.9408. Online ahead of print.

ABSTRACT

To strengthen inferences meta-analyses are commonly used to summarize information from a set of independent studies. In some cases, though, the data may not satisfy the assumptions underlying the meta-analysis. Using three Bayesian methods that have a more general structure than the common meta-analytic ones, we can show the extent and nature of the pooling that is justified statistically. In this article, we reanalyze data from several reviews whose objective is to make inference about the COVID-19 asymptomatic infection rate. When it is unlikely that all of the true effect sizes come from a single source researchers should be cautious about pooling the data from all of the studies. Our findings and methodology are applicable to other COVID-19 outcome variables, and more generally.

PMID:35582808 | DOI:10.1002/sim.9408

Proc Biol Sci. 2022 May 25;289(1975):20212535. doi: 10.1098/rspb.2021.2535. Epub 2022 May 18.

ABSTRACT

A clade’s evolutionary history is shaped, in part, by geographical range expansion, sweepstakes dispersal and local extinction. A rigorous understanding of historical biogeography may therefore yield insights into macroevolutionary dynamics such as adaptive radiation. Modern historical biogeographic analyses typically fit statistical models to molecular phylogenies, but it remains unclear whether extant species provide sufficient signal or if well-sampled phylogenies of extinct and extant taxa are necessary to produce meaningful estimates of past ranges. We investigated the historical biogeography of Primates and their euarchontan relatives using a novel meta-analytical phylogeny of over 900 extant (n= 419) and extinct (n = 483) species spanning their entire evolutionary history. Ancestral range estimates for young nodes were largely congruent with those derived from molecular phylogeny. However, node age exerts a significant effect on ancestral range estimate congruence, and the probability of congruent inference dropped below 0.5 for nodes older than the late Eocene, corresponding to the origins of higher-level clades. Discordance was not observed in analyses of extinct taxa alone. Fossils are essential for robust ancestral range inference and biogeographic analyses of extant clades originating in the deep past should be viewed with scepticism without them.

PMID:35582793 | DOI:10.1098/rspb.2021.2535

Am J Psychiatry. 2022 May 18:appiajp20081180. doi: 10.1176/appi.ajp.20081180. Online ahead of print.

ABSTRACT

OBJECTIVE: Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium.

METHODS: iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivity_rw). The main analyses assessed associations of VS connectivity_rw with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations.

RESULTS: Higher right VS connectivity_rw was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivity_rw was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivity_rw and anhedonia emerged in the structural equation model: left VS connectivity_rw was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivity_rw was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivity_rw did not predict low mood at any time point in the structural equation model.

CONCLUSIONS: The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivity_rw in anhedonia but not in low mood.

PMID:35582783 | DOI:10.1176/appi.ajp.20081180

Acta Paediatr. 2022 May 17. doi: 10.1111/apa.16410. Online ahead of print.

ABSTRACT

AIM: To develop and perform an initial validation of a score to measure severity of illness in hospitalized children with severe acute malnutrition (SAM).

METHODS: A prospective study enrolled SAM children aged 6-59 months hospitalized in Borno State, Nigeria. Candidate items associated with inpatient mortality were combined and evaluated as candidate scores. Clinical and statistical methods were used to identify a preferred score.

RESULTS: The 513 children enrolled had a mean age of 15.6 months of whom 48 (9%) died. Seven of the ten evaluated items were significantly associated with mortality. Five different candidate scores were tested. The final score, Responses to Illness Severity Quantification (RISQ), included 7 items: heart rate, respiratory rate, respiratory effort, oxygen saturation, oxygen delivery, temperature and level of consciousness. The mean RISQ score on admission was 2.6 in hospital survivors and 7.3 for children dying <48hr. RISQ scores <24hr before death had an area under the receiver operating characteristic curve (AUROC) of 0.93. The RISQ score performed similarly across differing clinical conditions with AUROCs 0.77-0.98 for all conditions except oedema.

CONCLUSION: The RISQ score can identify high risk malnourished children at and during hospital admission. Clinical application may help prioritize care and potentially improve survival.

PMID:35582782 | DOI:10.1111/apa.16410

Int J Nurs Knowl. 2022 May 17. doi: 10.1111/2047-3095.12372. Online ahead of print.

ABSTRACT

PURPOSE: Nurses are on the forefront of delivering care to patients hospitalized with COVID-19. Nurses’ impact on patient care can be discerned through assessment and documentation strategies, including structured and unstructured narratives, clinical pathways, flowsheets, and problem-based approaches. To date, there are no published reports regarding nursing assessment and documentation during the COVID-19 pandemic using an assessment framework to capture clinical decision making, nursing diagnoses, and key social determinant of health (SDoH) data. Hence, the purpose of this investigation was to conduct an exploratory nursing documentation audit of patients hospitalized with COVID-19 during the first surge to identify types and frequency of nurse-sensitive indicators, including SDoH.

METHOD: This pilot study utilized a retrospective chart review design at a single academic medical center, utilizing Gordon’s Eleven Functional Health Patterns (FHP) framework to extract clinical, social, and nursing assessment data for patients hospitalized with COVID-19. Descriptive statistics were computed for continuous variables and counts/percentages for categorical variables.

FINDINGS: Data from 94 patient records were analyzed. Most patients were male (59.6%), with a mean age of 58 years. Nearly 15% of patients were Black and 12.8% were Hispanic, most residing in four geographic areas. Nine of the 11 FHPs were reflected in nurse-sensitive indicators documented in the electronic health record. SDoH data were inconsistently documented, including race, education, history of neglect/abuse, and occupation.

CONCLUSION: The FHP framework captured many nurse-sensitive indicators during the first COVID-19 surge, although screening for and documenting SDoH data were limited.

IMPLICATIONS FOR NURSING PRACTICE: Findings can influence the development of nursing assessment and documentation during crisis care delivery that are inclusive of distinct sociodemographic factors, in addition to clinical factors, to provide comprehensive, culturally sensitive care. Such documentation will enhance the use of nursing knowledge guided by a nursing framework to make visible the essential contributions of nurses to healthcare delivery.

PMID:35582773 | DOI:10.1111/2047-3095.12372

Cell Prolif. 2022 May 17:e13239. doi: 10.1111/cpr.13239. Online ahead of print.

ABSTRACT

OBJECTIVES: The rapid development of cerebral organoid technology and the gradual maturity of cerebral organoids highlight the necessity of foresighted research on relevant ethical concerns. We employed knowledge graphs and conducted statistical analysis with CiteSpace for a comprehensive analysis of the status quo of the research on the ethical concerns of cerebral organoids from a bibliometric perspective.

MATERIALS AND METHODS: We performed a statistical analysis of published papers on cerebral organoid ethics, keyword co-occurrence graph, literature co-citation and knowledge clustering graph to examine the status of the ethics research, internal relationship between technological development and ethical research, and ethical concerns of the academia. Finally, we used a keyword time zone graph and related statistics to analyze and predict the trends and popular topics of future cerebral organoids ethics research.

RESULTS: We demonstrated that although the ethical concerns of cerebral organoids have long been discussed, it was not until 2017 that the ethical issues began to receive more attention, when cerebral organoids were gradually mimicking the human brain more closely and increasingly being combined with chimera research. The recent key ethical concerns are primarily divided into three categories: concerns that are common in life sciences, specific to cerebral organoids, and present in cross-fields. These increasing ethical concerns are inherently related to the continual development of technology. The analysis pointed out that future research should focus on the ethical concerns of consciousness that are unique to cerebral organoids, ethical concerns of cross-fields, and construction and improvement of legislative and regulatory systems.

CONCLUSIONS: Although research on cerebral organoids can benefit the biomedicine field, the relevant ethical concerns are significant and have received increasing attention, which are inherently related to the continual development of technology. Future studies in ethics regarding cerebral organoid research should focus on the ethical concerns of consciousness, and cross-fields, as well as the improvement of regulatory systems.

PMID:35582763 | DOI:10.1111/cpr.13239

Eur J Dent Educ. 2022 May 17. doi: 10.1111/eje.12827. Online ahead of print.

ABSTRACT

PURPOSE/OBJECTIVES: The purpose of this study was to assess student perception as well as course outcomes (final written examination grades) when using a pilot condensed format in an undergraduate Fixed Prosthodontics course, which was implemented as a response to the global pandemic of covid-19.

METHODS: The course was delivered in a condensed format, with a total of 28 direct contact hours in the Simulation (SIM) Clinic within a 4-day period. Asynchronous remote learning was employed for the didactic portion of the course. Students completed surveys before and after the course, to assess their perception of the condensed format, and written examination grades were compared with previous years’ grades. Data were entered in an Excel database (Microsoft Excel 2016) and analyzed using a statistical analysis software program (IBM SPSS Statistics, v26; IBM Corp). The level of significance was set to α = 0.05.

RESULTS: Overall, student perception about the condensed format was positive. At the beginning of the course female students had less confidence in their skills compared to male students (p < .05). Written examination grades were significantly lower compared to previous years’ grades (p = .04).

CONCLUSIONS: Use of a condensed format can allow a course to be delivered in smaller student cohorts and provides the ability to reduce the total number of direct contact hours allotted to the course, creating space within the curriculum. Student perception of this format was generally positive. However, written examination scores were negatively impacted, indicating possible knowledge gaps resulting from the condensed course format. More studies are needed to assess the effect of the various curricular modifications that have been implemented due to the Covid-19 pandemic.

PMID:35582769 | DOI:10.1111/eje.12827