Tag: statistics

Nat Neurosci. 2022 Apr 5. doi: 10.1038/s41593-022-01042-4. Online ahead of print.

ABSTRACT

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

PMID:35383335 | DOI:10.1038/s41593-022-01042-4

ISME J. 2022 Apr 5. doi: 10.1038/s41396-022-01230-x. Online ahead of print.

ABSTRACT

The salinity gradient separating marine and freshwater environments represents a major ecological divide for microbiota, yet the mechanisms by which marine microbes have adapted to and ultimately diversified in freshwater environments are poorly understood. Here, we take advantage of a natural evolutionary experiment: the colonization of the brackish Baltic Sea by the ancestrally marine diatom Skeletonema marinoi. To understand how diatoms respond to low salinity, we characterized transcriptomic responses of acclimated S. marinoi grown in a common garden. Our experiment included eight strains from source populations spanning the Baltic Sea salinity cline. Gene expression analysis revealed that low salinities induced changes in the cellular metabolism of S. marinoi, including upregulation of photosynthesis and storage compound biosynthesis, increased nutrient demand, and a complex response to oxidative stress. However, the strain effect overshadowed the salinity effect, as strains differed significantly in their response, both regarding the strength and the strategy (direction of gene expression) of their response. The high degree of intraspecific variation in gene expression observed here highlights an important but often overlooked source of biological variation associated with how diatoms respond to environmental change.

PMID:35383290 | DOI:10.1038/s41396-022-01230-x

Sci Rep. 2022 Apr 5;12(1):5671. doi: 10.1038/s41598-022-09987-z.

ABSTRACT

Studies exploring mediators of socioeconomic inequalities in excess weight gain in early-life and subsequent overweight/obesity (OW/OB) among youth are limited. Thus, this study examined the mediating role of prenatal and early postnatal factors and child energy balance-related behaviours (EBRB) in the effects of parental education on (i) excess weight gain from birth to 2 years and (ii) OW/OB at 5, 8 and 14 years. The Norwegian Mother, Father and Child Cohort Study was used to include participants at the ages of 2 (n = 59,597), 5 (n = 27,134), 8 (n = 28,285) and 14 (n = 11,278) years. Causal mediation analyses using the inverse odds weighting approach were conducted. Children of low-educated parents had a higher conditional excess weight gain at 2 years compared to children of high-educated parents (total effect, RR^TE = 1.06; 95% CI 1.01, 1.10). The joint mediation effects of the prenatal and early postnatal factors explained most of the total effect of low education on conditional excess weight gain at 2 years. Children of low-educated parents had a higher risk of OW/OB at 5, 8 and 14 years compared to children of high-educated parents. The mediators jointly explained 63.7%, 67% and 88.9% of the total effect of parental education on OW/OB among 5, 8 and 14 year-old-children, respectively. Of the total mediated effects at 5, 8 and 14 years, the prenatal and early postnatal mediators explained 59.2%, 61.7% and 73.7%, whereas the child EBRB explained 10.3%, 15.8.0%% and 34.8%. The mediators included were found to have a considerable mediating effect in the associations explored, in particular the prenatal and early postnatal factors. If truly causal, the findings could indicate potential targets for interventions to tackle socioeconomic inequalities in OW/OB from birth to adolescence.

PMID:35383270 | DOI:10.1038/s41598-022-09987-z

Sci Rep. 2022 Apr 5;12(1):5708. doi: 10.1038/s41598-022-09764-y.

ABSTRACT

This meta-analysis aims to compare Apert syndrome (AS) patients with non-AS populations (not clinically or genetically diagnosed) on craniofacial cephalometric characteristics (CCC) to combine publicly available scientific information while also improving the validity of primary study findings. A comprehensive search was performed in the following databases: PubMed, Google Scholar, Scopus, Medline, and Web of Science, an article published between 1st January 2000 to October 17th, 2021. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to carry out this systematic review. We used the PECO system to classify people with AS based on whether or not they had distinctive CCC compared to the non-AS population. Following are some examples of how PECO has been used: People with AS are labeled P; clinical or genetic diagnosis of AS is labeled E; individuals without AS are labeled C; CCC of AS are labeled O. Using the Newcastle-Ottawa Quality-Assessment-Scale, independent reviewers assessed the articles’ methodological quality and extracted data. 13 studies were included in the systematic review. 8 out of 13 studies were score 7-8 in NOS scale, which indicated that most of the studies were medium to high qualities. Six case-control studies were analyzed for meta-analysis. Due to the wide range of variability in CCC, we were only able to include data from at least three previous studies. There was a statistically significant difference in N-S-PP (I²: 76.56%; P = 0.014; CI 1.27 to – 0.28) and Greater wing angle (I²: 79.07%; P = 0.008; CI 3.07-1.17) between AS and control subjects. Cleft palate, anterior open bite, crowding in the upper jaw, and hypodontia occurred more frequently among AS patients. Significant shortening of the mandibular width, height and length is the most reported feature in AS patients. CT scans can help patients with AS decide whether to pursue orthodontic treatment alone or to have their mouth surgically expanded. The role of well-informed orthodontic and maxillofacial practitioners is critical in preventing and rehabilitating oral health issues.

PMID:35383244 | DOI:10.1038/s41598-022-09764-y

Sci Rep. 2022 Apr 5;12(1):5692. doi: 10.1038/s41598-022-09704-w.

ABSTRACT

To improve the reliability of the quantitative scorings of the synovial biopsies, we evaluate whether diameter of arthroscopic forceps influences histological quality of synovial tissue and/or histological scores and we compare the intra- and inter-observer performances of the main histological scoring systems. Synovial biopsies were retrieved in the same part of the joint using 1, 2 and 4 mm diameters grasping forceps. After standard staining and immunohistochemistry with anti-CD68 antibody, slides were scored blindly by 2 independent experienced operators for tissue quality and with Krenn score, de Bois-Tak score and CD68 semi-quantitative score. Four samples did not pass quality control. No difference other than a higher number of vessels in the 4 mm versus 2 mm forceps (p = 0.01) was found among the 3 groups. CD68 score was significantly higher in the 2 versus 4 mm forceps (p = 0.009). So we concluded that only vessels quantification and CD68 semi-quantitative score seemed affected by the forceps size. The intra-reader agreement was variable across observers and features: 0.78 (0.66-0.87) for the Krenn scoring system, 0.89 (0.78-0.97) for the de Bois-Tak score and 0.93 (0.81-1.00) for the CD68 score. Interobserver reliabilities of Krenn score, de Bois-Tak score and CD68 scores were satisfactory: 0.95 (0.92-0.99) for Krenn, 0.98 (0.96-0.99) for de Bois-Tak and 0.80 (0.71-0.89) for CD68.

PMID:35383240 | DOI:10.1038/s41598-022-09704-w

Sci Rep. 2022 Apr 5;12(1):5657. doi: 10.1038/s41598-022-09462-9.

ABSTRACT

New recommendations on evaluation of peritoneal membrane function suggest ruling out catheter dysfunction when evaluating patients with low ultrafiltration capacity. We introduce the use of a combination of parameters obtained from the cycler software PD Link with HomeChoicePro (Baxter International Inc., Illinois, United States) cyclers for predicting catheter dysfunction in automated peritoneal dialysis patients (APD). Out of 117 patients treated at the Medical University of Vienna between 2015 and 2021, we retrospectively identified all patients with verified catheter dysfunction (n = 14) and compared them to controls without clinical evidence of mechanical catheter problems and a recent X-ray confirming PD catheter tip in the rectovesical/rectouterine space (n = 19). All patients had a coiled single-cuff PD catheter, performed tidal PD, and received neutral pH bicarbonate/lactate-buffered PD fluids with low-glucose degradation products on APD. Icodextrin-containing PD fluids were used for daytime dwells. We retrieved cycler data for seven days each and tested parameters’ predictive capability of catheter dysfunction. Total number of alarms/week > 7 as single predictive parameter of catheter dislocation identified 85.7% (sensitivity) of patients with dislocated catheter, whereas 31.6% (1-specificity) of control patients were false positive. A combination of parameters (number of alarms/week > 7, total drain time > 22 min, ultrafiltration of last fill < 150 mL) where at least two of three parameters appeared identified the same proportion of patients with catheter dislocation, but was more accurate in identifying controls (21.1% false positive). In contrast to yearly PET measurements, an easily applicable combination of daily cycler readout parameters, also available in new APD systems connected to remote monitoring platforms shows potential for diagnosis of catheter dysfunction during routine follow-up.

PMID:35383211 | DOI:10.1038/s41598-022-09462-9

Sci Rep. 2022 Apr 5;12(1):5716. doi: 10.1038/s41598-022-09644-5.

ABSTRACT

Blood pressure (BP) shows a seasonal variation with higher levels at lower temperatures. Many hypertensives, however, report on BP disturbances rather in association with acutely changing weather conditions than with absolute temperatures. To date, the impact of changing meteorological parameters on hypertensive episodes remains elusive. We performed a retrospective time series regression analysis on 203,703 patients in three hospitals in Germany between 2010 and 2018, of whom 7362 patients were admitted for hypertensive disease. Numbers of daily admissions for hypertension were associated with metereological data obtained from three nearby weather stations. Data comprised temperature (mean, maximal, minimal and range within 24 h), athmospheric pressure, and precipitation. Changes of these parameters were calculated over a two and three day period. There was an inverse correlation between maximal daily temperature and the number of admissions for hypertensive disease, which remained significant both after adjustment for seasonality and week day in a spline model and in a constrained distributed lag model. A decrease of maximal temperature by 5 °C was associated with a 3% increase of risk for admission for hypertension and vice versa. There were no significant effects of precipitation and athmospheric pressure on the number of admissions. With regard to all observed metereological parameters, neither the change within two, nor within three days was consistently associated with the number of daily admissions. High temperatures are associated with lower numbers of hypertensive episodes requiring hospital admission. In contrast to the subjective perception of many hypertensive patients, however, acutely changing weather conditions are not associated with a higher risk of hypertensive emergency.

PMID:35383236 | DOI:10.1038/s41598-022-09644-5

Nat Commun. 2022 Apr 5;13(1):1828. doi: 10.1038/s41467-022-29497-w.

ABSTRACT

Alternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. However, the extent to which alternative isoforms establish co-expression networks that may be relevant in cellular function has not been explored yet. Here, we present acorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships. To achieve this, we develop and validate percentile correlations, an innovative approach that overcomes data sparsity and yields accurate co-expression estimates from single-cell data. Next, acorde uses correlations to cluster co-expressed isoforms into a network, unraveling cell type-specific alternative isoform usage patterns. By selecting same-gene isoforms between these clusters, we subsequently detect and characterize genes with co-differential isoform usage (coDIU) across cell types. Finally, we predict functional elements from long read-defined isoforms and provide insight into biological processes, motifs, and domains potentially controlled by the coordination of post-transcriptional regulation. The code for acorde is available at https://github.com/ConesaLab/acorde .

PMID:35383181 | DOI:10.1038/s41467-022-29497-w

Nat Commun. 2022 Apr 5;13(1):1829. doi: 10.1038/s41467-022-29457-4.

ABSTRACT

The transformation of sensory input to motor output is often conceived as a decoder operating on neural representations. We seek a mechanistic understanding of sensory decoding by mimicking neural circuitry in the decoder’s design. The results of a simple experiment shape our approach. Changing the size of a target for smooth pursuit eye movements changes the relationship between the variance and mean of the evoked behavior in a way that contradicts the regime of “signal-dependent noise” and defies traditional decoding approaches. A theoretical analysis leads us to propose a circuit for pursuit that includes multiple parallel pathways and multiple sources of variation. Behavioral and neural responses with biomimetic statistics emerge from a biologically-motivated circuit model with noise in the pathway that is dedicated to flexibly adjusting the strength of visual-motor transmission. Our results demonstrate the power of re-imagining decoding as processing through the parallel pathways of neural systems.

PMID:35383170 | DOI:10.1038/s41467-022-29457-4

Nat Commun. 2022 Apr 5;13(1):1824. doi: 10.1038/s41467-022-29367-5.

ABSTRACT

The acute stress response mobilizes energy to meet situational demands and re-establish homeostasis. However, the underlying molecular cascades are unclear. Here, we use a brief swim exposure to trigger an acute stress response in mice, which transiently increases anxiety, without leading to lasting maladaptive changes. Using multiomic profiling, such as proteomics, phospho-proteomics, bulk mRNA-, single-nuclei mRNA-, small RNA-, and TRAP-sequencing, we characterize the acute stress-induced molecular events in the mouse hippocampus over time. Our results show the complexity and specificity of the response to acute stress, highlighting both the widespread changes in protein phosphorylation and gene transcription, and tightly regulated protein translation. The observed molecular events resolve efficiently within four hours after initiation of stress. We include an interactive app to explore the data, providing a molecular resource that can help us understand how acute stress impacts brain function in response to stress.

PMID:35383160 | DOI:10.1038/s41467-022-29367-5