Tag: pubmed

Res Sq. 2023 Aug 17:rs.3.rs-3242375. doi: 10.21203/rs.3.rs-3242375/v1. Preprint.

ABSTRACT

In this note, we present an innovative approach called “homologous hypothesis tests” that focuses on cross-sectional comparisons of average tumor volumes at different time-points. By leveraging the correlation structure between time-points, our method enables highly efficient per time-point comparisons, providing inferences that are highly efficient as compared to those obtained from a standard two-sample $t$-test. The key advantage of this approach lies in its user-friendliness and accessibility, as it can be easily employed by the broader scientific community through standard statistical software packages.

PMID:37645958 | PMC:PMC10462185 | DOI:10.21203/rs.3.rs-3242375/v1

bioRxiv. 2023 Aug 16:2023.03.20.532813. doi: 10.1101/2023.03.20.532813. Preprint.

ABSTRACT

The D. melanogaster protein coding gene bag of marbles ( bam ) plays a key role in early male and female reproduction by forming complexes with partner proteins to promote differentiation in gametogenesis. Like another germline gene, Sex lethal , bam genetically interacts with the endosymbiont Wolbachia , as Wolbachia rescues the reduced fertility of a bam hypomorphic mutant. Here, we explored the specificity of the bam-Wolbachia interaction by generating 22 new bam mutants, with ten mutants displaying fertility defects. Nine of these mutants trend towards rescue by the w Mel Wolbachia variant, with eight statistically significant at the fertility and/or cytological level. In some cases, fertility was increased a striking 20-fold. There is no specificity between the rescue and the known binding regions of bam , suggesting w Mel does not interact with one singular bam partner to rescue the reproductive phenotype. We further tested if w Mel interacts with bam in a non-specific way, by increasing bam transcript levels or acting upstream in germline stem cells. A fertility assessment of a bam RNAi knockdown mutant reveals that w Mel rescue is specific to functionally mutant bam alleles and we find no obvious evidence of w Mel interaction with germline stem cells in bam mutants.

AUTHOR SUMMARY: Reproduction in the Drosophila melanogaster fruit fly is dependent on the bag of marbles ( bam ) gene, which acts early in the process of generating eggs and sperm. Mutations to this gene negatively impact the fertility of the fly, causing it to be sterile or have fewer progeny. Interestingly, we find that the bacteria Wolbachia , which resides within reproductive cells across a wide range of insects, partially restores the fertility and ovary phenotype of several bam mutants of which the resultant Bam protein is altered from wildtype. The protein function of Bam is further suggested to be important by the lack of rescue for a fly that has a fertility defect due to low expression of a non-mutated bam gene. Previous work makes similar conclusions about Wolbachia with another reproductive gene, Sex lethal ( Sxl ), highlighting the potential for rescue of fertility mutants to occur in a similar way across different genes. An understanding of the ways in which Wolbachia can affect host reproduction provides us with context with which to frame Wolbachia ‘s impact on host genes, such as bam and Sxl, and consider the evolutionary implications of Wolbachia ‘s infection in D. melanogaster fruit flies.

PMID:37645949 | PMC:PMC10461928 | DOI:10.1101/2023.03.20.532813

bioRxiv. 2023 Aug 14:2023.08.11.551770. doi: 10.1101/2023.08.11.551770. Preprint.

ABSTRACT

The nervous system needs to balance the stability of neural representations with plasticity. It is unclear what is the representational stability of simple actions, particularly those that are well-rehearsed in humans, and how it changes in new contexts. Using an electrocorticography brain-computer interface (BCI), we found that the mesoscale manifold and relative representational distances for a repertoire of simple imagined movements were remarkably stable. Interestingly, however, the manifold’s absolute location demonstrated day-to-day drift. Strikingly, representational statistics, especially variance, could be flexibly regulated to increase discernability during BCI control without somatotopic changes. Discernability strengthened with practice and was specific to the BCI, demonstrating remarkable contextual specificity. Accounting for drift, and leveraging the flexibility of representations, allowed neuroprosthetic control of a robotic arm and hand for over 7 months without recalibration. Our study offers insight into how electrocorticography can both track representational statistics across long periods and allow long-term complex neuroprosthetic control.

PMID:37645922 | PMC:PMC10462094 | DOI:10.1101/2023.08.11.551770

bioRxiv. 2023 Aug 21:2023.06.21.545365. doi: 10.1101/2023.06.21.545365. Preprint.

ABSTRACT

Cancerous tumors may contain billions of cells including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections. By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones, which are not observed in normal human brain samples. Importantly, by genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations identified from bulk tumor sections, we show that existing strategies for inferring malignancy from single-cell transcriptomes may be inaccurate. Furthermore, we identify a core set of genes that is consistently expressed by the truncal clone, including AKR1C3 , whose expression is associated with poor outcomes in several types of cancer. This work establishes a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity in clinical specimens and clarifying the molecular profiles of distinct cellular populations in any kind of solid tumor.

PMID:37645893 | PMC:PMC10461981 | DOI:10.1101/2023.06.21.545365

bioRxiv. 2023 Aug 17:2023.08.15.553308. doi: 10.1101/2023.08.15.553308. Preprint.

ABSTRACT

Improvements in nanopore sequencing necessitate efficient classification methods, including pre-filtering and adaptive sampling algorithms that enrich for reads of interest. Signal-based approaches circumvent the computational bottleneck of basecalling. But past methods for signal-based classification do not scale efficiently to large, repetitive references like pangenomes, limiting their utility to partial references or individual genomes. We introduce Sigmoni: a rapid, multiclass classification method based on the r -index that scales to references of hundreds of Gbps. Sigmoni quantizes nanopore signal into a discrete alphabet of picoamp ranges. It performs rapid, approximate matching using matching statistics, classifying reads based on distributions of picoamp matching statistics and co-linearity statistics. Sigmoni is 10-100 × faster than previous methods for adaptive sampling in host depletion experiments with improved accuracy, and can query reads against large microbial or human pangenomes.

PMID:37645873 | PMC:PMC10462034 | DOI:10.1101/2023.08.15.553308

medRxiv. 2023 Aug 16:2023.08.15.23294141. doi: 10.1101/2023.08.15.23294141. Preprint.

ABSTRACT

OBJECTIVE OR PURPOSE: Primary open-angle glaucoma (POAG) is a highly heritable disease with 127 identified risk loci. Polygenic risks score (PRS) offers a measure of aggregate genetic burden. In this study, we assess whether PRS improves risk stratification in patients with ocular hypertension.

DESIGN: A post-hoc analysis of the Ocular Hypertension Treatment Study (OHTS) data.

SETTING PARTICIPANTS AND/OR CONTROLS: 1636 participants were followed from 1994 to 2020 across 22 sites. The PRS was computed for 1009 OHTS participants using summary statistics from largest cross-ancestry POAG metanalysis with weights trained using 8,813,496 variants from 488,395 participants in the UK Biobank.

METHODS INTERVENTIONS OR TESTING: Survival regression analysis, with endpoint as development of POAG, predicted disease onset from PRS incorporating baseline covariates.

MAIN OUTCOMES AND MEASURES: Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent AUC were used to compare the predictive performance of multivariable Cox-Proportional Hazards models.

RESULTS: Mean PRS was significantly higher for POAG-converters (0.24 ± 0.95) than for non-converters (- 0.12 ± 1.00) (p < 0.01). POAG risk increased 1.36% with each higher PRS decile, with conversion ranging from 9.5% in the lowest PRS decile to 21.8% in the highest decile. Comparison of low-and high-risk PRS tertiles showed a 1.8-fold increase in 20-year POAG risk for participants of European and African ancestries (p<0.01). In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year decrease in age at diagnosis, (p=0.05). No significant linear relationship between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C-index = 0.77) compared to OHTS baseline model (C-index=0.75) (p<0.01). One standard deviation higher PRS conferred a mean hazard ratio of 1.25 (CI=[1.13, 1.44]) for POAG onset.

CONCLUSIONS: Higher PRS is associated with increased risk for, and earlier development of POAG in patients with ocular hypertension. Early treatment may mitigate the risk from high genetic burden, delaying clinically detectable disease by up to 5.2 years. The inclusion of a PRS improves the prediction of POAG onset.

PMID:37645858 | PMC:PMC10462203 | DOI:10.1101/2023.08.15.23294141

Diabet Med. 2023 Aug 29:e15201. doi: 10.1111/dme.15201. Online ahead of print.

ABSTRACT

AIMS: Gestational diabetes treatment requires several outpatient consultations from diagnosis until delivery, in order to prevent hyperglycaemia, which is associated with maternal and foetal complications. There is limited evidence in the literature about telemedicine superiority in improving pregnancy outcomes of women with gestational diabetes. The primary aim of the study was to evaluate the maternal and foetal outcomes, while the secondary aim was to estimate the degree of satisfaction in gestational diabetes treatment, comparing telemedicine versus outpatient care.

METHODS: This observational cohort study involved 60 consecutive women with gestational diabetes treated at the Diabetology Unit of Ferrara: 27 were followed-up through a weekly remote control method (telemedicine group) and 33 in ambulatory clinics every two or three weeks (conventional group). After giving birth, 56 women replied to the modified Oxford Maternity Diabetes Treatment Satisfaction Questionnaire, to assess their satisfaction with diabetes care.

RESULTS: No statistically significant differences were found in most of the maternal and neonatal parameters evaluated in both groups. The questionnaire scores were positive in all areas investigated. Telemedicine follow-up made women feel more controlled (p = 0.045) and fit better with their lifestyle (p = 0.005). It also emerged that almost all women treated with telemedicine would recommend this method to a relative or a friend.

CONCLUSIONS: Telemedicine follow-up proved to be safe both in terms of metabolic control and pregnancy outcomes; furthermore, it significantly decreased the need for outpatient consultations and increased women’s satisfaction. Studying the impact of telemedicine is also necessary, considering the current difficulties associated with the Sars-COV-2 pandemic.

PMID:37643876 | DOI:10.1111/dme.15201

Respir Care. 2023 Aug 29:respcare.11225. doi: 10.4187/respcare.11225. Online ahead of print.

ABSTRACT

BACKGROUND: Perceived organizational support has been linked to employee commitment and job satisfaction. Understanding the effects of perceived organizational support on employees allows leaders to improve employees’ performance and the success of their organizations. The purpose of this study was to identify the perceived organizational support across different respiratory care education programs in the United States.

METHODS: All chairs and program directors of bachelor’s of science and master’s of science degree respiratory care education programs in the United States were surveyed (N = 97). The Survey of Perceived Organizational Support was modified after written approval, and the final instrument included 31 items with a Likert scale (1 = strongly disagree, 7 = strongly agree). Descriptive statistics, multiple regression, and topic modeling were used for data analysis (P < .05).

RESULTS: A total of 67 respondents responded to the perceived organizational support survey; a 69% response rate. They were satisfied with their job and committed to their institutions. They also reported that faculty salaries were equitable relative to the national average, and their institutions encouraged teamwork among faculty. The respondents’ titles, total years of administrative experience, students’ scores on the national credentialing therapist multiple choice examination (TMC), and institutions that offer both bachelor’s of science and master’s of science degree programs had a direct relationship with perceived organizational support in respiratory care education programs. Age and sex were inversely related to perceived organizational support. A topic modeling analysis based on the respondents’ opinions about perceived organizational support showed that the respondents frequently mentioned the words support, institution, budget, year, nursing, and experience. The respondents emphasized the importance of support, institution marketing, their years of experience, and the program budget. They also mentioned that nursing programs overshadowed respiratory care education programs at their institutions.

CONCLUSIONS: Age, sex, job title, years of administrative experience, students’ TMC scores, and the type of programs offered impacted perceived organizational support by respiratory care directors. Student-, program- and participant-related factors can be used to improve perceived organizational support in respiratory care education.

PMID:37643868 | DOI:10.4187/respcare.11225

BMJ Open. 2023 Aug 29;13(8):e069018. doi: 10.1136/bmjopen-2022-069018.

ABSTRACT

OBJECTIVES: To compare the prediction effects of six models based on machine learning theories, which can provide a methodological reference for predicting the risk of type 2 diabetes mellitus (T2DM).

SETTING AND PARTICIPANTS: This study was based on the monitoring data of chronic disease risk factors in Dongguan residents from 2016 to 2018. The multistage cluster random sampling method was adopted at each monitoring site, and 4157 people were finally selected. In the initial population, we excluded individuals with more than 20% missing data and eventually included 4106 subjects.

DESIGN: K nearest neighbour algorithm and synthetic minority oversampling technique were used to process the data. Single factor analysis was used for preliminary selection of variables. The 10-fold cross-validation was used to optimise the parameters of some models. The accuracy, precision, recall and area under receiver operating characteristic curve (AUC) were used to evaluate the prediction effect of models, and Delong test was used to analyse the differences of AUC values of each model.

RESULTS: After balancing data, the sample size increased to 8013, of which 4023 are patients with T2DM and 3990 in control group. The comparison results of the six models showed that back propagation neural network model has the best prediction effect with 93.7% accuracy, 94.6% accuracy, 92.8% recall and the AUC value of 0.977, followed by logistic model, support vector machine model, CART decision tree model and C4.5 decision tree model. Deep neural network has the worst prediction performance, with 84.5% accuracy, 86.1% precision, 82.9% recall and the AUC value of 0.845.

CONCLUSIONS: In this study, six types of risk prediction models for T2DM were constructed, and the predictive effects of these models were compared based on various indicators. The results showed that back propagation neural network based on the selected data set had the best prediction effect.

PMID:37643856 | DOI:10.1136/bmjopen-2022-069018

BMJ Open. 2023 Aug 29;13(8):e071213. doi: 10.1136/bmjopen-2022-071213.

ABSTRACT

OBJECTIVES: The hypertriglyceridaemic waist (HTGW) phenotype, an indicator to assess metabolic syndrome, could be a useful predictive marker for the risk of acute pancreatitis. This study aimed to evaluate the association between the HTGW phenotype and the risk of acute pancreatitis with a nationwide population-based cohort.

DESIGN: A retrospective, nationwide cohort study.

SETTING: Registry of health check-up result from Korean National Health Insurance Service.

PARTICIPANTS: A total of 3 912 551 adults who underwent health checkups under the National Health Insurance Service in 2009 were enrolled in this study.

INTERVENTIONS: Subjects with both increased waist circumference (WC) and elevated blood triglyceride concentrations were defined as the HTGW phenotype. The participants were divided into four groups, classified as NWNT (normal WC-normal triglycerides), EWNT (elevated WC-normal triglycerides), NWET (normal WC-elevated triglycerides) and HTGW. The WC triglyceride index (WTI) is a quantitative indicator of the HTGW phenotype which is calculated by multiplying WC (cm) by triglyceride levels (mmol/L).

PRIMARY OUTCOME MEASURE: The subjects were followed until 31 December 2018. The adjusted HRs of acute pancreatitis in each group were estimated.

RESULTS: During the follow-up, there were a total of 8933 of acute pancreatitis occurrences. The incidence of acute pancreatitis in all subjects was 0.278 per 1000 person-year. The HTGW group had the highest incidence (0.444), followed by the NWET (0.381), and EWNT (0.316) groups. The HTGW group had a significant higher incidence of acute pancreatitis than the NWNT groups (HR 1.364 (95% CI 1.279 to 1.454)). The risk of acute pancreatitis steadily increased as the WTI increased (HR 1.847 (95% CI 1.657 to 2.058) in 10th decile).

CONCLUSIONS: The HTGW phenotype is confirmed to be an independent risk factor that increases the risk of acute pancreatitis.

PMID:37643853 | DOI:10.1136/bmjopen-2022-071213