Markerless Lung Tumor Trajectory Estimation from Rotating Cone Beam Computed Tomography Projections

Respiration introduces large tumor motion in the thoracic region which influences treatment outcome for lung cancer patients. Tumor motion management techniques require characterization of temporal tumor motions because tumor motion varies patient to patient, day to day and cycle to cycle. This work develops a markerless algorithm to estimate 3 dimensional (3D) lung-tumor trajectories on free breathing cone beam computed tomography (CBCT) projections, which are 2 dimensional (2D) sequential images rotating about an axis and are used to reconstruct 3D CBCT images. A gold standard tumor trajectory is required to guide the algorithm development and estimate the tumor detection accuracy for markerless tracking algorithms. However, a sufficient strategy to validate markerless tracking algorithms is lacking. A validation framework is developed based on fiducial markers. Markers are segmented and marker trajectories are xiv obtained. The displacement of the tumor to the marker is calculated and added to the segmented marker trajectory to generate reference tumor trajectory. Markerless tumor trajectory estimation (MLTM) algorithm is developed and improved to acquire tumor trajectory with clinical acceptable accuracy for locally advanced lung tumors. The development is separate into two parts. The first part considers none tumor deformation. It investigates shape and appearance of the template, moreover, a constraint method is introduced to narrow down the template matching searching region for more precise matching results. The second part is to accommodate tumor deformation near the end of the treatment. The accuracy of MLTM is calculated and compared against 4D CBCT, which is the current standard of care. In summary, a validation framework based on fiducial markers is successfully built. MLTM is successfully developed with or without the consideration of tumor deformation with promising accuracy. MLTM outperforms 4D CBCT in temporal tumor trajectory estimation

Audio-Visual Spatiotemporal Perceptual Training Enhances the P300 Component in Healthy Older Adults

In older adults, cognitive abilities, such as those associated with vision and hearing, generally decrease with age. According to several studies, audio-visual perceptual training can improve perceived competence regarding visual and auditory stimuli, suggesting that perceptual training is effective and beneficial. However, whether audio-visual perceptual training can induce far-transfer effects in other forms of untrained cognitive processing that are not directly trained in older adults remains unclear. In this study, the classic P300 component, a neurophysiological indicator of cognitive processing of a stimulus, was selected as an evaluation index of the training effect. We trained both young and older adults on the ability to judge the temporal and spatial consistency of visual and auditory stimuli. P300 amplitudes were significantly greater in the posttraining session than in the pretraining session in older adults (P = 0.001). However, perceptual training had no significant effect (P = 0.949) on the P300 component in young adults. Our results illustrate that audio-visual perceptual training can lead to far-transfer effects in healthy older adults. These findings highlight the robust malleability of the aging brain, and further provide evidence to motivate exploration to improve cognitive abilities in older adults

Clades of huge phages from across Earth's ecosystems.

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems

Closely related Lak megaphages replicate in the microbiomes of diverse animals.

Lak phages with alternatively coded ∼540 kbp genomes were recently reported to replicate in Prevotella in microbiomes of humans that consume a non-Western diet, baboons, and pigs. Here, we explore Lak phage diversity and broader distribution using diagnostic polymerase chain reaction and genome-resolved metagenomics. Lak phages were detected in 13 animal types, including reptiles, and are particularly prevalent in pigs. Tracking Lak through the pig gastrointestinal tract revealed significant enrichment in the hindgut compared to the foregut. We reconstructed 34 new Lak genomes, including six curated complete genomes, all of which are alternatively coded. An anomalously large (∼660 kbp) complete genome reconstructed for the most deeply branched Lak from a horse microbiome is also alternatively coded. From the Lak genomes, we identified proteins associated with specific animal species; notably, most have no functional predictions. The presence of closely related Lak phages in diverse animals indicates facile distribution coupled to host-specific adaptation

The causal effect of educational attainment on stress urinary incontinence: a two-sample mendelian randomization study

Abstract Background Stress urinary incontinence (SUI) is characterized by involuntary urine leakage in response to increased abdominal pressure, such as coughing, laughing, or sneezing. It significantly affects women’s quality of life and imposes a substantial disease burden. While pregnancy and childbirth have been previously identified as risk factors for SUI, educational attainment may also play a role. Therefore, this paper investigates the causal relationship between educational attainment and SUI using two-sample Mendelian randomization (TSMR) analysis, years of schooling (YOS), and college or university degree (CUD) as proxies. Methods Summary statistics of YOS, CUD, and SUI were obtained from genome-wide association studies (GWAS), and TSMR analysis was applied to explore potential causal relationships between them. Causal effects were mainly estimated using the standard inverse variance weighting (IVW) method, and complementary and sensitivity analyses were also performed using multiple methods. Results The results indicate that both YOS (OR = 0.994, 95% CI: 0.992–0.996; P = 7.764E-10) and CUD (OR = 0.987, 95% CI: 0.983–0.991; P = 1.217E-09) may have a negative causal effect on SUI. Conclusions Improving educational attainment may go some way towards reducing the risk of SUI. Therefore, it is important to increase efforts to improve the imbalance in educational development and safeguard women’s health

Grief reactions of couples to perinatal loss : a one-year prospective follow-up

Aims and objectives: To explore couples’ perceptions of the effects of perinatal loss on their marital relationship, social support and grief 1 year postloss, and analyse what factors changed the severity of their grief. Background: Perinatal losses are traumatic events in the lives of families and can have serious long-term consequences for the psychological health of parents and any subsequent children. Design: A prospective follow-up study. Methods: We recruited, at a teaching hospital in southern Taiwan, a convenience sample of 30 couples whose babies either miscarried or were stillborn. At 1 month (T1), 3 months (T2), 6 months (T3) and 1 year (T4) after the pregnancy loss, all participants completed four questionnaires. To analyse the changing status of their grief and its related factors, we used a generalised estimating equation (GEE) to account for correlations between repeated observations. Results: Postbereavement grief levels fell over the four time-points. Mothers reported feeling more grief than did the fathers. Couples with a history of infertility, no religious beliefs or no living children before the loss felt more grief from a perinatal miscarriage or stillbirth. Furthermore, couples reported more grief if their marital satisfaction level was low, if their socioemotional support from husband's parents was low or if they had never participated in a ritual for their deceased baby. Conclusions: Six months postloss is the crucial period for bereaved parents after a perinatal loss. Being a mother, having no previous living children and low-level socioemotional support from the husband's parents are significant high-risk factors for a high level of grief 1 year after perinatal death. Relevance to clinical practice: We recommend that health professionals increase their ability to identify the factors that psychologically affect postloss grief. Active postloss follow-up programmes should focus on these factors to offer specific support and counselling

A survey of tagging techniques for music, speech and environmental sound

Sound tagging has been studied for years. Among all sound types, music, speech, and environmental sound are three hottest research areas. This survey aims to provide an overview about the state-of-the-art development in these areas.We discuss about the meaning of tagging in different sound areas at the beginning of the journey. Some examples of sound tagging applications are introduced in order to illustrate the significance of this research. Typical tagging techniques include manual, automatic, and semi-automatic approaches.After reviewing work in music, speech and environmental sound tagging, we compare them and state the research progress to date. Research gaps are identified for each research area and the common features and discriminations between three areas are discovered as well. Published datasets, tools used by researchers, and evaluation measures frequently applied in the analysis are listed. In the end, we summarise the worldwide distribution of countries dedicated to sound tagging research for years

Assessment of reproductive toxicity in adult zebrafish (Danio rerio) following sublethal exposure to penthiopyrad

Penthiopyrad (PO), a succinate dehydrogenase inhibitor (SDHI) fungicide, poses a potential risk to fish. Here, we investigated the adverse effects of PO on endocrine regulation and reproductive capacity in zebrafish during a 21-d sublethal exposure to PO concentrations ranging from 0.02 to 2.00 mg/L. Following exposure to PO (0.20 and 2.00 mg/L), female-specific effects including follicle necrosis, structural disturbance of the yolk follicle, fusion of cortical follicles appeared in ovarian tissue of adult females, which led to a significant reduction in fertility. Correspondingly, 0.20 and 2.00 mg/L PO led to a marked reduction in the GSI values of females, and 2.00 mg/L PO caused a 31% decline in the proportion of perinucleolar oocytes (PCO) in oocytes. In addition, testosterone (T) level was obviously suppressed and 17β-estradiol (E2) level was increased in females after exposure to 2.00 mg/L PO. Male zebrafish treated with 0.20 and 2.00 mg/L of PO exhibited significant interstitial enlargement, edema in the testes, and reduced diameter of seminiferous tubules, along with a thinner basement membrane. The effects of PO on males were associated with significant increase in E2 level, suggesting that PO has an estrogenic effect on male fish. Greater E2 levels in serum were further supported by increased transcription levels of genes linked to the hypothalamic-pituitary-gonad-liver (HPGL) axis. Notably, transcription levels of cyp19a, er2b, era, and cyp19b was remarkably increased, exhibiting a clear link with variations in E2 levels. Overall, the present study demonstrates that PO induces reproductive impairment in zebrafish by promoting steroidogenesis

Perilipin5 protects against non-alcoholic steatohepatitis by increasing 11-Dodecenoic acid and inhibiting the occurrence of ferroptosis

Abstract Background Non-alcoholic steatohepatitis (NASH) is a major contributor to liver cirrhosis and hepatocellular carcinoma. There remains no effective pharmacological therapy. The hepatic lipid metabolism and fatty acid β-oxidation are regulated by Perilipin5 (Plin5). However, it is yet unknown how Plin5 affects NASH and the molecular process. Methods High-fat, high-cholesterol and high-fructose (HFHC) diets were used to mimic the progression of NASH in wild type (WT) mice and Plin5 knockout (Plin5 KO) mice. The degree of ferroptosis was measured by detecting the expression of key genes of ferroptosis and the level of lipid peroxide. The degree of NASH was judged by observing the morphology of the liver, detecting the expression of inflammation and fibrosis related genes of liver damage. Plin5 was overexpressed in the liver of mice by tail vein injection of adenovirus, and the process of NASH was simulated by methionine choline deficiency (MCD) diet. The occurrence of ferroptosis and NASH was detected by the same detection method. Targeted lipidomics sequencing was used to detect the difference in free fatty acid expression in the WT Plin5 KO group. Finally, it was verified in cell experiments to further study the effect of free fatty acids on ferroptosis of hepatocytes. Results In various NASH models, hepatic Plin5 was dramatically reduced. Plin5 knockout (KO) worsened NASH-associated characteristics in mice given a high-fat/high-cholesterol (HFHC) diet, such as lipid accumulation, inflammation and hepatic fibrosis. It has been shown that ferroptosis is involved in NASH progression. We revealed that Plin5 KO in mice aggravated the degree of ferroptosis in NASH models. Conversely, overexpression of Plin5 significantly alleviated ferroptosis and further ameliorated progression of MCD-induced NASH. Analysis of livers obtained from HFHC diet-fed mice by targeted lipidomics revealed that 11-Dodecenoic acid was significantly decreased in Plin5 KO mice. Addition of 11-Dodecenoia acid to Plin5 knockdown hepatocytes effectively prevented ferroptosis. Conclusion Our study demonstrates that Plin5 protects against NASH progression by increasing 11-Dodecenoic acid level and further inhibiting ferroptosis, suggesting that Plin5 has therapeutic potential as a target for the management of NASH