Simple and efficient methods for local structural analysis in polydisperse hard disk systems.

In nonequilibrium statistical physics, quantifying the nearest (and higher-order) neighbors and free volumes of particles in many-body systems is crucial to elucidating the origin of macroscopic collective phenomena, such as glass/granular jamming transitions and various aspects of the behavior of active matter. However, conventional techniques (based on a fixed-distance cutoff or the Voronoi construction) have mainly been applied to equilibrated, homogeneous, and monodisperse particle systems. In this paper, we implement simple and efficient methods for local structure analysis in nonequilibrium, inhomogeneous, and polydisperse hard disk systems. We show how these novel methods can overcome the difficulties encountered by conventional techniques as well as demonstrate some applications.

Analysis of risk factors for fatal renal complications after allogeneic hematopoietic cell transplantation.

Various complications can influence hematopoietic cell transplantation (HCT) outcomes. Renal complications can occur during the early to late phases of HCT along with various factors. However, studies focusing on fatal renal complications (FRCs) are scarce. Herein, we analyzed 36,596 first allogeneic HCT recipients retrospectively. Overall, 782 patients died of FRCs at a median of 108 (range, 0-3,440) days after HCT. The cumulative incidence of FRCs was 1.7% and 2.2% at one and five years, respectively. FRCs were associated with older age, male sex, non-complete remission (non-CR), lower performance status (PS), and HCT comorbidity index (HCT-CI) associated with renal comorbidity in multivariate analysis. The risk factors within 100 days included older age, multiple myeloma, PS, and HCT-CI comorbidities (psychiatric disturbance, hepatic disease, obesity, and renal disease). Older age and male sex were risk factors between 100 days and one year. After one year, HCT-CI was associated with the presence of diabetes and prior solid tumor; total body irradiation was identified as a risk factor. Non-CR was a common risk factor in all three phases. Furthermore, acute and chronic graft-versus-host disease, reactivation of cytomegalovirus, and relapse of underlying disease also affected FRCs. Systematic follow-up may be necessary based on the patients' risk factors and post-HCT events.

MR imaging features to predict the type of bone metastasis in prostate cancer.

Bone metastases (BMs) of prostate cancer (PCa) have been considered predominantly osteoblastic, but non-osteoblastic (osteolytic or mixed osteoblastic and osteolytic) BMs can occur. We investigated the differences in prostate MRI and clinical findings between patients with osteoblastic and non-osteoblastic BMs. Between 2014 and 2021, patients with pathologically proven PCa without a history of other malignancies were included in this study. Age, Gleason score, prostate-specific antigen (PSA) density, normalized mean apparent diffusion coefficient and normalized T2 signal intensity (nT2SI) of PCa, and Prostate Imaging Reporting and Data System category on MRI were compared between groups. A multivariate logistic regression analysis using factors with P-values < 0.2 was performed to detect the independent parameters for predicting non-osteoblastic BM group. Twenty-five (mean 73 ± 6.6 years) and seven (69 ± 13.1 years) patients were classified into the osteoblastic and non-osteoblastic groups, respectively. PSA density and nT2SI were significantly higher in the non-osteoblastic group than in the osteoblastic group. nT2SI was an independent predictive factor for non-osteoblastic BMs in the multivariate logistic regression analysis. These results indicated that PCa patients with high nT2SI and PSA density should be examined for osteolytic BMs.

Osteolytic or mixed bone metastasis is not uncommon in patients with high-risk prostate cancer.

PURPOSE: Osteolytic or mixed bone metastases (BMs) are considered rare in prostate cancer (PCa). However, we hypothesized that they are not uncommon in high-risk PCa. This study aimed to compare the clinical and CT imaging characteristics of PCa by focusing on BMs among patients with Gleason score (GS) ≥ 8 (high-risk group) and those with GS ≤ 7 (intermediate-low-risk group). METHODS: Between 2014 and 2021, patients with pathologically proven PCa and no history of other malignancies were included. Clinical findings including age and prostate-specific antigen (PSA) were collected. CT imaging findings, including the types of BM and other metastases, were evaluated by two radiologists. The clinical and CT imaging findings were compared between the high- and intermediate-low-risk groups. RESULTS: Patients were classified into high-risk (n = 527) and intermediate-low-risk (n = 973) groups. Age at diagnosis (median: 71 [44-91] vs 69 [35-86] years, p < 0.0001), PSA (8.7 [0.01-15314.5] vs 5.8 [0.01-163.2] ng/mL, p < 0.0001), frequencies of BMs (osteoblastic: 47/527 [8.7%] vs 3/973 [0.3%]), osteolytic or mixed BM (19/527 [3.6%] vs 2/973 [0.2%]), lymph node metastases (76/527 [14.4%] vs 3/973 [0.3%]), and lung metastases (13/527 [2.5%] vs 0%) were significantly higher in the high-risk group than in the intermediate-low-risk group (all p < 0.0001). CONCLUSIONS: Age, PSA, and the frequencies of osteolytic or mixed BMs were significantly higher in the high-risk group than in the intermediate-low-risk group. This study highlights the importance of high-risk PCa in the differential diagnoses of osteolytic or mixed BMs.

Localization of the central sulcus using the distinctive high signal intensity of the paracentral lobule on T1-weighted images.

PURPOSE: The central sulcus is an important landmark in the brain. This study aimed to investigate the distinctive signal of the paracentral lobule (PL) on T1-weighted images (T1WIs; the white PL sign) and evaluate its usefulness as a new method of identifying the central sulcus. METHODS: T1WIs of the brain of 96 participants (age, 58.9 ± 17.9 years; range, 8-87 years) scanned at 3-T MR system were retrospectively reviewed. First, we qualitatively analyzed the signal of the cortex of the PL by comparing it with that of the ipsilateral superior frontal gyrus on a 4-point grading score. Second, we compared the cortical signal intensity and gray/white-matter contrast between the PL and superior frontal gyrus. Third, we evaluated the usefulness of the PL signal for identifying the central sulcus. RESULTS: The PL cortex was either mildly hyperintense (grade 2) or definitely hyperintense (grade 3) in comparison with that of superior frontal cortex in all participants. The signal intensity of the PL cortex was significantly higher than that of the superior frontal cortex (p < 0.001), whereas the gray/white-matter contrast of the PL was weaker than that of the superior frontal gyrus (p < 0.001). The central sulci were identified with 94.3% accuracy (181/192) using the new method. CONCLUSION: The white PL sign may be helpful in identifying the central sulcus, and this approach can be recognized as a new method for identification of the central sulcus.

Differential diagnosis of thymic epithelial neoplasms on computed tomography using the diameter of the thymic vein.

ABSTRACT: Although differentiating benign and malignant thymic epithelial lesions is important to avoid unnecessary treatment and predict prognosis, it is challenging because of overlaps in the chest computed tomography (CT) findings. In this study, we investigated whether the diameter of the thymic vein and other CT findings could differentiate between benign (thymoma and thymic cysts) and malignant (thymic carcinoma, [TCa]) lesions.We conducted a retrospective study across two tertiary referral hospitals in Japan between November 2009 and June 2018. We included 12 patients with TCa, 34 patients with thymomas, and 17 patients with thymic cysts. We analyzed the receiver operating characteristic (ROC) curve to determine the best cut-off values and performed univariate and multivariate analyses of CT findings to distinguish TCa from other benign lesions. Post-hoc analysis was performed for the maximum short axis of the thymic vein using the Mann-Whitney U test, and the number of the maximum short axis of the thymic vein ≥ the cutoff was determined using the Fisher exact test with a family-wise error-correction using Bonferroni's method.ROC analysis showed that a maximum short axis of the thymic vein ≥2 mm was considerably more frequent in TCa than in the other lesions (P < .001 for both), with 83% sensitivity and 86% specificity. Univariate and multivariate analyses revealed the association with TCa of the number of the maximum short axis of the thymic vein ≥2 mm (P = .005, multivariate generalized linear model analysis), ill-defined margin (P = .001), and mediastinal lymphadenopathy (P < .001). Thymic vein diameter was in descendimg order of TCa > thymoma > thymic cysts with statistically significant differences between the groups (Ps < .05).Thymic vein diameter was significantly longer in TCa than in thymoma and thymic cysts. Measurement of the maximum short axis of the thymic vein could be a powerful diagnostic tool to differentiate TCa from thymoma and thymic cysts.

Distinctive Regulation of Emotional Behaviors and Fear-Related Gene Expression Responses in Two Extended Amygdala Subnuclei With Similar Molecular Profiles.

The central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus of the stria terminalis (BNST) are the two major nuclei of the central extended amygdala that plays essential roles in threat processing, responsible for emotional states such as fear and anxiety. While some studies suggested functional differences between these nuclei, others showed anatomical and neurochemical similarities. Despite their complex subnuclear organization, subnuclei-specific functional impact on behavior and their underlying molecular profiles remain obscure. We here constitutively inhibited neurotransmission of protein kinase C-δ-positive (PKCδ+) neurons-a major cell type of the lateral subdivision of the CeA (CeL) and the oval nucleus of the BNST (BNSTov)-and found striking subnuclei-specific effects on fear- and anxiety-related behaviors, respectively. To obtain molecular clues for this dissociation, we conducted RNA sequencing in subnuclei-targeted micropunch samples. The CeL and the BNSTov displayed similar gene expression profiles at the basal level; however, both displayed differential gene expression when animals were exposed to fear-related stimuli, with a more robust expression change in the CeL. These findings provide novel insights into the molecular makeup and differential engagement of distinct subnuclei of the extended amygdala, critical for regulation of threat processing.

Physiological 2-deoxy-2-[fluorine-18] fluoro-D-glucose accumulation in the thenar eminence in adults: a single-center retrospective study.

OBJECTIVE: This study evaluated the frequency, and effect of physiological 2-deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) tracer injection and its association with the penetration rates of mobile devices. METHODS: This retrospective analysis included 213 patients (mean age ± standard deviation, 66.2 ± 14.1 years; range 23-93 years; 125 men) who underwent FDG-positron emission tomography examination. Elevated FDG activity in the thenar eminence with maximum standardized uptake value (SUVmax) ≥ 2.5 was considered positive. Differences according to age, sex, laterality, and tracer injection side were evaluated using Fisher's exact test. Associations were assessed using Pearson's correlation coefficient. RESULTS: Twenty-three percent (49/213) of the patients had elevated FDG activity in the thenar eminence (mean SUVmax, 3.50 ± 1.04; range 2.5-6.3), including 18 with bilateral findings. No significant difference existed according to age (< 50 years vs. 50-69 years vs. ≥ 70 years), sex, laterality, or tracer injection side. No significant correlation existed between penetration rates of mobile devices and the findings (p = 0.08). CONCLUSION: Elevated FDG activity in the thenar eminence occurs in adults, regardless of age, sex, laterality, or tracer injection side. This should be considered a common physiological change that does not warrant any further investigation.

Peptidoglycan recognition protein genes and their roles in the innate immune pathways of the red flour beetle, Tribolium castaneum.

We have previously demonstrated that the functional Toll and IMD innate immune pathways indeed exist in the model beetle, Tribolium castaneum while the beetle's pathways have broader specificity in terms of microbial activation than that of Drosophila. To elucidate the molecular basis of this broad microbial activation, we here focused on potential upstream sensors of the T. castaneum innate immune pathways, peptidoglycan recognition proteins (PGRPs). Our phenotype analyses utilizing RNA interference-based comprehensive gene knockdown followed by bacterial challenge suggested: PGRP-LA functions as a pivotal sensor of the IMD pathway for both Gram-negative and Gram-positive bacteria; PGRP-LC acts as an IMD pathway-associated sensor mainly for Gram-negative bacteria; PGRP-LE also has some roles in Gram-negative bacterial recognition of the IMD pathway. On the other hand, we did not obtain clear phenotype changes by gene knockdown of short-type PGRP genes, probably because of highly inducible nature of these genes. Our results may collectively account for the promiscuous bacterial activation of the T. castaneum innate immune pathways at least in part.

Identification of novel Arabidopsis thaliana upstream open reading frames that control expression of the main coding sequences in a peptide sequence-dependent manner.

Upstream open reading frames (uORFs) are often found in the 5'-leader regions of eukaryotic mRNAs and can negatively modulate the translational efficiency of the downstream main ORF. Although the effects of most uORFs are thought to be independent of their encoded peptide sequences, certain uORFs control translation of the main ORF in a peptide sequence-dependent manner. For genome-wide identification of such peptide sequence-dependent regulatory uORFs, exhaustive searches for uORFs with conserved amino acid sequences have been conducted using bioinformatic analyses. However, whether the conserved uORFs identified by these bioinformatic approaches encode regulatory peptides has not been experimentally determined. Here we analyzed 16 recently identified Arabidopsis thaliana conserved uORFs for the effects of their amino acid sequences on the expression of the main ORF using a transient expression assay. We identified five novel uORFs that repress main ORF expression in a peptide sequence-dependent manner. Mutational analysis revealed that, in four of them, the C-terminal region of the uORF-encoded peptide is critical for the repression of main ORF expression. Intriguingly, we also identified one exceptional sequence-dependent regulatory uORF, in which the stop codon position is not conserved and the C-terminal region is not important for the repression of main ORF expression.

Involvement of NF-κB transcription factors in antimicrobial peptide gene induction in the red flour beetle, Tribolium castaneum.

We previously demonstrated that Tribolium castaneum antimicrobical peptide (AMP) genes can be classified to IMD-dependent group I, Toll-dependent group III and co-dependent group II genes besides non-inducible group IV. Here, we focused on NF-κB transcription factor genes, Dif1, Dif2 and Rel, and examined their functions in AMP gene induction as well as linkages to the Toll or IMD pathway. IMD-dependent group I and Toll-dependent group III genes were revealed to be Rel- and Dif-dependent respectively through knockdown experiments, indicating that the pathway specificity of NF-κB classes found in Drosophila is also conserved in T. castaneum. The Toll-Dif and IMD-Rel pathways of T. castaneum were activated concomitantly by single microbe species, which may represent a distinctive feature of its immune responses. In addition, Rel knockdown impaired host defense against two model bacterial pathogens. Finally, potential κB motifs were searched in the regulatory regions of AMP genes, and relevance to respective NF-κB transcription factors was discussed.

Antimicrobial peptide gene induction, involvement of Toll and IMD pathways and defense against bacteria in the red flour beetle, Tribolium castaneum.

Using Tribolium castaneum, we quantitatively investigated the induction of nine antimicrobial peptide (AMP) genes by live gram-negative bacteria (Escherichia coli and Enterobacter cloacae), gram-positive bacteria (Micrococcus luteus and Bacillus subtilis) and the budding yeast (Saccharomyces cerevisiae). Then, five representative AMP genes were selected, and the involvement of the Toll and IMD pathways in their induction by E. coli, M. luteus and S. cerevisiae was examined by utilizing RNA interference of either MyD88 or IMD. Results indicated: Robust and acute induction of three genes by the two bacterial species was mediated mainly by the IMD pathway; slow and sustained induction of one gene by the two bacteria was mediated mainly by the Toll pathway; induction of the remaining one gene by the two bacteria was mediated by both pathways; induction of the five genes by the yeast was mediated by the Toll and/or IMD pathways depending on respective genes. These results suggest that more promiscuous activation and usage of the two pathways may occur in T. castaneum than in Drosophila melanogaster. In addition, the IMD pathway was revealed to dominantly contribute to defense against two bacterial species, gram-negative E. cloacae and gram-positive B. subtilis that possesses DAP-type peptidoglycan.