Noise power spectrum properties of deep learning-based reconstruction and iterative reconstruction algorithms: Phantom and clinical study.

PURPOSE: To compare the noise power spectrum (NPS) properties and perform a qualitative analysis of hybrid iterative reconstruction (IR), model-based IR (MBIR), and deep learning-based reconstruction (DLR) at a similar noise level in clinical study and compare these outcomes with those in phantom study. METHODS: A Catphan phantom with an external body ring was used in the phantom study. In the clinical study, computed tomography (CT) examination data of 34 patients were reviewed. NPS was calculated from DLR, hybrid IR, and MBIR images. The noise magnitude ratio (NMR) and the central frequency ratio (CFR) were calculated from DLR, hybrid IR, and MBIR images relative to filtered back-projection images using NPS. Clinical images were independently reviewed by two radiologists. RESULTS: In the phantom study, DLR with a mild level had a similar noise level as hybrid IR and MBIR with strong levels. In the clinical study, DLR with a mild level had a similar noise level as hybrid IR with standard and MBIR with strong levels. The NMR and CFR were 0.40 and 0.76 for DLR, 0.42 and 0.55 for hybrid IR, and 0.48 and 0.62 for MBIR. The visual inspection of the clinical DLR image was superior to that of the hybrid IR and MBIR images. CONCLUSION: Deep learning-based reconstruction improves overall image quality with substantial noise reduction while maintaining image noise texture compared with the CT reconstruction techniques.

Determination of lower radiation dose limit for automatic measurement of adipose tissue.

The purpose of this study was to determine the lower limit of radiation dose required to measure visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes when a fat quantification and noise reduction techniques (NRTs) are combined. For this purpose, we utilized CT colonography (CTC) images taken at low doses and manually segmented VAT and SAT fat volumes as ground truth. In order to derive the acceptable precision of the measurements needed to estimate the lower limit of radiation dose, we estimated the effect of different positioning during CT scanning on fat measurements using manually segmented VAT and SAT against normal dose. As a result, the acceptable accuracy of SAT and VAT was found to be 94.5% and 85.2%, respectively. Using these thresholds, the lower radiation dose limit required to accurately measure SAT using 5.25-mm slice-thick images was 1.5 mGy of size-specific dose estimates (SSDE), while the lower radiation dose limit required to accurately measure VAT was 0.4 mGy of SSDE. The lower dose limit for SAT and VAT combined was 1.5 mGy, which was equivalent to an estimated effective dose of 0.38 mSv. Alternatively, without noise reduction, SAT could not achieve acceptable accuracy even for images with a slice thickness of 5.25 mm, while VAT required noise reduction for images with a slice thickness of 1.25 mm, but could achieve acceptable accuracy without noise reduction for images with a slice thickness of 5.25 mm.

Computational approach to evaluate scRNA-seq data quality and gene body coverage with SkewC.

SkewC is a single-cell RNA sequencing (scRNA-seq) data quality evaluation tool. The approach is based on determining gene body coverage, and its skewness, as a quality metric for each individual cell. SkewC distinguishes between two types of single cells: typical cells with prototypical gene body coverage profiles and skewed cells with skewed gene body coverage profiles. SkewC can be used on any scRNA-seq data as it is independent from the underlying technology used to generate the data. For complete details on the use and execution of this protocol, please refer to Abugessaisa et al. (2022).1.

Do people who highly value happiness tend to ruminate?

Previous studies have suggested that an extremely strong desire for happiness might ironically reduce a person's well-being, particularly among Western people. According to the goal progress theory and the theory of valuing happiness, rumination might explain the relationship between valuing happiness and well-being. Based on these theoretical rationales, this study examined the following hypotheses: (1) valuing happiness is significantly associated with rumination, (2) people who experience low life stress have a stronger association between valuing happiness and rumination, and (3) people with more interdependent self-construal have a weaker association between valuing happiness and rumination. University students in Japan participated in a cross-sectional study (N = 350; Study 1) and a 4-weeks longitudinal study (N = 329; Study 2). They responded to a packet of questionnaires assessing valuing happiness, trait rumination, depressive symptoms, negative events, and interdependent self-construal. Consistent with our hypothesis, valuing happiness was concurrently and longitudinally associated with increased rumination after controlling for depressive symptoms. However, negative events did not moderate the association between valuing happiness and rumination. Furthermore, Study 1, but not Study 2, indicated that the association between valuing happiness and rumination was stronger among students with highly interdependent self-construal than those with less interdependent self-construal. The preset findings indicated that valuing happiness might be a factor that perpetuates rumination. More sophisticated evidence on the influence of valuing happiness on rumination can lead to effective psychotherapies for decreasing rumination and depression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04131-6.

Antisense-oligonucleotide-mediated perturbation of long non-coding RNA reveals functional features in stem cells and across cell types.

Within the scope of the FANTOM6 consortium, we perform a large-scale knockdown of 200 long non-coding RNAs (lncRNAs) in human induced pluripotent stem cells (iPSCs) and systematically characterize their roles in self-renewal and pluripotency. We find 36 lncRNAs (18%) exhibiting cell growth inhibition. From the knockdown of 123 lncRNAs with transcriptome profiling, 36 lncRNAs (29.3%) show molecular phenotypes. Integrating the molecular phenotypes with chromatin-interaction assays further reveals cis- and trans-interacting partners as potential primary targets. Additionally, cell-type enrichment analysis identifies lncRNAs associated with pluripotency, while the knockdown of LINC02595, CATG00000090305.1, and RP11-148B6.2 modulates colony formation of iPSCs. We compare our results with previously published fibroblasts phenotyping data and find that 2.9% of the lncRNAs exhibit a consistent cell growth phenotype, whereas we observe 58.3% agreement in molecular phenotypes. This highlights that molecular phenotyping is more comprehensive in revealing affected pathways.

Preliminary validation of the self-report measure assessing experiences of negative independent and dependent event frequency in Japanese university students.

Background: In the past, different stress generation studies have used self-report measures comprising different items to assess each category of negative events. Moreover, the validity of these scales has not been adequately investigated. Therefore, we developed a self-report measure dedicated to assessing experiences of negative interpersonal dependent events, negative non-interpersonal dependent events, and negative independent events in university students, which was named the Negative Independent/Dependent Events Scale. Methods: Japanese undergraduate students (N = 247; mean age = 19.18 years, SD = 3.08) responded to the Negative Independent/Dependent Events Scale, which had items selected for adequate content validity. They also responded to self-report measures of depressive symptoms, reassurance-seeking behaviors, inattention, and lack of perseverance. Results: All the negative events subscales had moderate positive correlations with depressive symptoms. In addition, the negative interpersonal dependent events subscale showed a moderate positive correlation with reassurance-seeking behaviors, and the negative non-interpersonal dependent events subscale showed a strong positive correlation with inattention. Furthermore, the negative non-interpersonal dependent events subscale was more strongly correlated with inattention than the other two negative events subscales. In contrast, the negative interpersonal dependent events subscale was more strongly correlated with reassurance-seeking behaviors than with the negative independent events subscale but not more strongly than with the negative non-interpersonal dependent events subscale. Conclusions: These findings indicated the acceptable construct validity of the Negative Independent/Dependent Events Scale. However, further research is necessary to establish the discriminant validity of the negative interpersonal dependent events subscale and the negative non-interpersonal dependent events subscale.

U-Net-based image segmentation of the whole heart and four chambers on pediatric X-ray computed tomography.

This study aimed to determine whether a U-Net-based segmentation method could be used to automatically extract regions of the whole heart and atrioventricular regions from pediatric cardiac computed tomography images with high accuracy. Pediatric cardiac contrast computed tomography images with no abnormalities (n = 20; patient age, 0-13 years; mean 5 years) were used for segmentation of the whole heart and each atrioventricular region using U-Net. Segmentation accuracy was evaluated using the Dice similarity coefficient. The mean Dice similarity coefficient for the whole-heart segmentation was high at 0.95. There were no significant differences between age categories. The median Dice similarity coefficients for segmentation of the atria and ventricles were good (> 0.86). There were significant differences between age categories at some sites. Differences in the Dice similarity coefficient may have occurred because the target diseases and examination procedures differed according to subject age. There was no clear tendency for similar values between subjects of school age, close to adulthood, and newborns; good agreement was obtained in all age categories. These results suggest that U-Net-based segmentation may be useful for automatic extraction of the whole heart and atrioventricular regions from pediatric computed tomography images.

A tin filter's dose reduction effect revisited: Using the detectability index in low-dose computed tomography for the chest.

PURPOSE: To reevaluate a tin filter's (TF) dose reduction effect in computed tomography (CT) using a combination of an anthropomorphic chest phantom and a rod-shaped phantom. METHODS AND MATERIALS: A third-generation dual-source CT system equipped with a built-in TF was employed. A chest phantom was scanned under low-dose conditions of 0.2 to 1.0 mGy with the TF at 100 kV (TF100kV) and without it at 100 kV and 120 kV (NF100kV and NF120kV). To eliminate effects other than that of the TF, only filtered back projection (FBP) was used for image reconstruction. On the images of the rod phantom placed inside the lung field, the CT number and the spatial resolution using the modulation transfer function (MTF) were measured. Using these indices plus the noise power spectrum (NPS) that was also measured, the detectability index based on the non-prewhitening model observer (d'NPW) was calculated. RESULTS: The CT numbers and MTFs were almost identical across the three conditions. The area under the NPS curve was decreased by 13-17% with the TF compared with non-TF conditions. NPS increases at low frequencies of < 0.06 mm-1 observed in NF120kV and NF100kV were eliminated by TF100kV. The potential dose reduction by the TF, estimated using the d'NPW values, turned out to be 22 to 25%. CONCLUSION: Based on the analysis of the FBP images of a chest phantom, the dose reduction attributable only to the TF was estimated at 22-25%, notably lower than those reported in previous studies.

Impact of pixel value truncation on image quality of low dose chest CT.

PURPOSE: In some noisy low dose CT lung cancer screening images, we noticed that the CT density values of air were increased and the visibility of emphysema was distinctly decreased. By examining histograms of these images, we found that the CT density values were truncated at -1024 HU. The purpose of this study was to investigate the effect of pixel value truncation on the visibility of emphysema using mathematical models. METHODS AND MATERIALS: Assuming CT noise follows a normal distribution, we derived the relationship between the mean CT density value and the standard deviation (SD) when the pixel values below -1024 HU are truncated and replaced by -1024 HU. To validate our mathematical model, 20 untruncated phantom CT images were truncated by simulation, and the mean CT density values and SD of air in the images were measured and compared with the theoretical values. In addition, the mean CT density values and SD of air were measured in 100 cases of real clinical images obtained by GE, Siemens, and Philips scanners, respectively, and the agreement with the theoretical values was examined. Next, the contrast-to-noise ratio (CNR) between air (-1000 HU) and lung parenchyma (-850 HU) was derived from the mathematical model in the presence and absence of truncation as a measure of the visibility of emphysema. In addition, the radiation dose ratios required to obtain the same CNR in the case with and without truncation were also calculated. RESULTS: The mathematical model revealed that when the pixel values are truncated, the mean CT density values are proportional to the noise magnitude when the magnitude exceeds a certain level. The mean CT density values and SD measured in the images with pixel values truncated by simulation and in the real clinical images acquired by GE and Philips scanners agreed well with the theoretical values from our mathematical model. In the Siemens images, the measured and theoretical values agreed well when a portion of the truncated values were replaced by random values instead of simply replacing by -1024 HU. The CNR of air and lung parenchyma was lowered by truncating CT density values compared to that of no truncation. Furthermore, it was found that higher radiation dose was required to obtain the same CNR with truncation as without. As an example, when the noise SD was 60 HU, the radiation dose required for the GE and Philips truncation method was about 1.2 times higher than that without truncation, and that for the Siemens truncation method was about 1.4 times higher. CONCLUSIONS: It was demonstrated mathematically that pixel value truncation causes a brightening of the mean CT density value and decreases the CNR of emphysema. Our results indicate that it is advisable to turn off truncation at -1024 HU, especially when scanning at low and ultra-low radiation doses in the thorax.

SkewC: Identifying cells with skewed gene body coverage in single-cell RNA sequencing data.

The analysis and interpretation of single-cell RNA sequencing (scRNA-seq) experiments are compromised by the presence of poor-quality cells. For meaningful analyses, such poor-quality cells should be excluded as they introduce noise in the data. We introduce SkewC, a quality-assessment tool, to identify skewed cells in scRNA-seq experiments. The tool's methodology is based on the assessment of gene coverage for each cell, and its skewness as a quality measure; the gene body coverage is a unique characteristic for each protocol, and different protocols yield highly different coverage profiles. This tool is designed to avoid misclustering or false clusters by identifying, isolating, and removing cells with skewed gene body coverage profiles. SkewC is capable of processing any type of scRNA-seq dataset, regardless of the protocol. We envision SkewC as a distinctive QC method to be incorporated into scRNA-seq QC processing to preclude the possibility of scRNA-seq data misinterpretation.

Causes and consequences of stress generation: Longitudinal associations of negative events, aggressive behaviors, rumination, and depressive symptoms.

The present study examined the causes and consequences of stress generation in university students in Japan. A two-wave longitudinal study with an 8- or 9-week interval was conducted in the fall of 2020. Undergraduate and graduate students at four universities in Japan (N = 201) completed self-report measures assessing experiences of negative interpersonal dependent events, negative non-interpersonal events, and negative independent events at two times. At the same time, they also responded to measures of aggressive behaviors, trait rumination, and depressive symptoms. Path analyses revealed that baseline aggressive behaviors were positively associated with an increase in subsequent negative interpersonal dependent events, even after controlling for the influences of negative interpersonal dependent events, rumination, and depressive symptoms at baseline. However, aggressive behaviors were not significantly associated with subsequent negative non-interpersonal dependent events or negative independent events. These findings suggest that aggressive behaviors may have been a factor leading to interpersonal stress generation. Furthermore, all categories of negative event experiences predicted an increase in subsequent depressive symptoms, but not subsequent rumination, and rumination was not significantly associated with subsequent depressive symptoms. This research extends previous studies on the causes and consequences of stress generation conducted in the US by using specific measures of aggressive behaviors and including a non-restricted sample of university students in Japan. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-022-02859-9.

Correlation between sensitization to house dust mite major allergens, age, and symptoms in Japanese house dust mite allergic subjects.

Der p 23 has recently been recognized as a new house dust mite (HDM) major allergen that may be linked to the development of asthma in HDM allergic patients. This study aimed to investigate the frequency of sensitization to HDM major allergen components including Der p 23 and to examine the correlation between HDM-sensitization and AR symptom score in Japanese HDM allergic rhinitis (AR) patients without allergic asthma. Serum samples (n = 120) collected from Japanese HDM AR patients (12 to 64 years) without asthma were assessed for allergen-specific IgE (s-IgE) by ImmunoCAP (Dermatophagoides pteronyssinus (D. pteronyssinus; Der p) extract, Der p 23) or immunosolid-phase allergen chip (Der p 1, Der p 2). Japanese HDM AR patients without asthma showed a high prevalence of allergic sensitization to the HDM major allergens Der p 1 (94.2%), Der p 2 (97.5%) and Der p 23 (71.7%). No difference in the prevalence was detected for Der p 1 and Der p 2 s-IgE among three age groups. However, the prevalence of Der p 23 s-IgE was significantly higher in the younger group compared to the elderly group. No significant correlation was found between AR symptom scores and concentration of s-IgE towards Der p extract and any of the three HDM major allergens. Although the prevalence of sensitization towards D. pteronyssinus major allergens is high in Japanese AR patients without asthma, there was no correlation between allergen specific IgE including IgE towards Der p 23 and AR symptom in this population.

Inducing human retinal pigment epithelium-like cells from somatic tissue.

Regenerative medicine relies on basic research outcomes that are only practical when cost effective. The human eyeball requires the retinal pigment epithelium (RPE) to interface the neural retina and the choroid at large. Millions of people suffer from age-related macular degeneration (AMD), a blinding multifactor genetic disease among RPE degradation pathologies. Recently, autologous pluripotent stem-cell-derived RPE cells were prohibitively expensive due to time; therefore, we developed a faster reprogramming system. We stably induced RPE-like cells (iRPE) from human fibroblasts (Fibs) by conditional overexpression of both broad plasticity and lineage-specific transcription factors (TFs). iRPE cells displayed critical RPE benchmarks and significant in vivo integration in transplanted retinas. Herein, we detail the iRPE system with comprehensive single-cell RNA sequencing (scRNA-seq) profiling to interpret and characterize its best cells. We anticipate that our system may enable robust retinal cell induction for basic research and affordable autologous human RPE tissue for regenerative cell therapy.

Response inhibition deficits are positively associated with trait rumination, but attentional inhibition deficits are not: aggressive behaviors and interpersonal stressors as mediators.

Previous findings on relationships between inhibition that is a core executive function, and trait rumination have been inconsistent. This inconsistency could be overcome by investigating the association between rumination and the two subcomponents of inhibition: response inhibition and attentional inhibition. This study examined whether and how response inhibition and attentional inhibition were related to rumination as well as worry. University students in Japan (N = 213) conducted the Go/No-Go Task and the Modified Stroop Task. They also completed self-report measures of depression, trait rumination, trait worry, stressors, and aggressive behaviors. Results indicated that response inhibition deficits were positively associated with trait rumination, and this association was mediated by increases in aggressive behaviors and interpersonal stressors. The associations between these variables remained significant even after controlling for depression level. There were no significant direct or indirect associations between attentional inhibition deficits and rumination. These results suggest that response inhibition deficits, among the subcomponents of inhibition, have an indirect positive association with rumination through interpersonal processes. Results also showed nonsignificant differences between rumination and worry in the magnitude of correlation coefficients with the two subcomponents of inhibition. Therefore, it remains unclear whether the positive association with response inhibition is unique to rumination.

Noise reduction profile: A new method for evaluation of noise reduction techniques in CT.

PURPOSE: Noise power spectrum (NPS) is a commonly used performance metric to evaluate noise-reduction techniques (NRT) in imaging systems. The images reconstructed with and without an NRT can be compared via their NPS to better understand the NRT's effects on image noise. However, when comparing NPSs, simple visual assessments or a comparison of NPS peaks or medians are often used. These assessments make it difficult to objectively evaluate the effect of noise reduction across all spatial frequencies. In this work, we propose a new noise reduction profile (NRP) to facilitate a more complete and objective evaluation of NPSs for a range of NRTs used specifically in computed tomography (CT). METHODS AND MATERIALS: The homogeneous section of the ACR or Catphan phantoms was scanned on different CT scanners equipped with the following NRTs: AIDR3D, AiCE, ASiR, ASiR-V, TrueFidelity, iDose, SAFIRE, and ADMIRE. The images were then reconstructed with all strengths of each NRT in reference to the baseline filtered back projection (FBP) images. One set of the baseline FBP images was also processed with PixelShine, an NRT based on artificial intelligence. The NPSs of the images before and after noise reduction were calculated in both the xy-plane and along the z-direction. The difference in the logarithmic scale between each NPS (baseline FBP and NRT) was then calculated and deemed the NRP. Furthermore, the relationship between the NRP and NPS peak positions was mathematically analyzed. RESULTS: Each NRT has its own unique NRP. By comparing the NPS and NRP for each NRT, it was found that NRP is related to the peak shift of NPS. Additionally, under the assumption that the NPS has one peak and is differentiable, a relationship was mathematically derived between the slope of the NRP at the peak position of the NPS before noise reduction and the shift of the NPS peak position after noise reduction. CONCLUSIONS: A new metric, NRP, was proposed based on NPS to objectively evaluate and compare methods for noise reduction in CT. The NRP can be used to compare the effects of various NRTs on image noise in both the xy-plane and z-direction. It also enables unbiased assessment of the detailed noise reduction properties of each NRT over all relevant spatial frequencies.

Genetic Mapping of the HLA1 Locus Causing Hybrid Lethality in Nicotiana Interspecific Hybrids.

Hybrid lethality, a postzygotic mechanism of reproductive isolation, is a phenomenon that causes the death of F1 hybrid seedlings. Hybrid lethality is generally caused by the epistatic interaction of two or more loci. In the genus Nicotiana, N. debneyi has the dominant allele Hla1-1 at the HLA1 locus that causes hybrid lethality in F1 hybrid seedlings by interaction with N. tabacum allele(s). Here, we mapped the HLA1 locus using the F2 population segregating for the Hla1-1 allele derived from the interspecific cross between N. debneyi and N. fragrans. To map HLA1, several DNA markers including random amplified polymorphic DNA, amplified fragment length polymorphism, and simple sequence repeat markers, were used. Additionally, DNA markers were developed based on disease resistance gene homologs identified from the genome sequence of N. benthamiana. Linkage analysis revealed that HLA1 was located between two cleaved amplified polymorphic sequence markers Nb14-CAPS and NbRGH1-CAPS at a distance of 10.8 and 10.9 cM, respectively. The distance between these markers was equivalent to a 682 kb interval in the genome sequence of N. benthamiana.

The choice of negative control antisense oligonucleotides dramatically impacts downstream analysis depending on the cellular background.

BACKGROUND: The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism's physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner. RESULTS: To investigate the potential roles of lncRNAs in vascular biology, we performed antisense oligonucleotide (ASO) knockdowns of lncRNA candidates specifically expressed either in human lymphatic or blood vascular endothelial cells (LECs or BECs) followed by Cap Analysis of Gene Expression (CAGE-Seq). Here, we describe the quality control steps adopted in our analysis pipeline before determining the knockdown effects of three ASOs per lncRNA target on the LEC or BEC transcriptomes. In this regard, we especially observed that the choice of negative control ASOs can dramatically impact the conclusions drawn from the analysis depending on the cellular background. CONCLUSION: In conclusion, the comparison of negative control ASO effects on the targeted cell type transcriptomes highlights the essential need to select a proper control set of multiple negative control ASO based on the investigated cell types.

Two Nicotiana occidentalis accessions enable gene identification for Type II hybrid lethality by the cross to N. sylvestris.

Hybrid lethality, meaning the death of F1 hybrid seedlings, has been observed in many plant species, including Nicotiana. Previously, we have revealed that hybrids of the selected Nicotiana occidentalis accession and N. tabacum, an allotetraploid with S and T genomes, exhibited lethality characterized by the fading of shoot color. The lethality was suggested to be controlled by alleles of loci on the S and T genomes derived from N. sylvestris and N. tomentosiformis, respectively. Here, we extended the analysis of hybrid lethality using other two accessions of N. occidentalis identified from the five tested accessions. The two accessions were crossed with N. tabacum and its two progenitors, N. sylvestris and N. tomentosiformis. After crosses with N. tabacum, the two N. occidentalis accessions yielded inviable hybrid seedlings whose lethality was characterized by the fading of shoot color, but only the T genome of N. tabacum was responsible for hybrid lethality. Genetic analysis indicated that first-mentioned N. occidentalis accession carries a single gene causing hybrid lethality by allelic interaction with the S genome.