Efficacy and indications of gamma knife radiosurgery for recurrent low-and high-grade glioma.

PURPOSE: To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma. METHODS: This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on. RESULTS: The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS. CONCLUSION: GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects.

Deep learning algorithm performance in contouring head and neck organs at risk: a systematic review and single-arm meta-analysis.

PURPOSE: The contouring of organs at risk (OARs) in head and neck cancer radiation treatment planning is a crucial, yet repetitive and time-consuming process. Recent studies have applied deep learning (DL) algorithms to automatically contour head and neck OARs. This study aims to conduct a systematic review and meta-analysis to summarize and analyze the performance of DL algorithms in contouring head and neck OARs. The objective is to assess the advantages and limitations of DL algorithms in contour planning of head and neck OARs. METHODS: This study conducted a literature search of Pubmed, Embase and Cochrane Library databases, to include studies related to DL contouring head and neck OARs, and the dice similarity coefficient (DSC) of four categories of OARs from the results of each study are selected as effect sizes for meta-analysis. Furthermore, this study conducted a subgroup analysis of OARs characterized by image modality and image type. RESULTS: 149 articles were retrieved, and 22 studies were included in the meta-analysis after excluding duplicate literature, primary screening, and re-screening. The combined effect sizes of DSC for brainstem, spinal cord, mandible, left eye, right eye, left optic nerve, right optic nerve, optic chiasm, left parotid, right parotid, left submandibular, and right submandibular are 0.87, 0.83, 0.92, 0.90, 0.90, 0.71, 0.74, 0.62, 0.85, 0.85, 0.82, and 0.82, respectively. For subgroup analysis, the combined effect sizes for segmentation of the brainstem, mandible, left optic nerve, and left parotid gland using CT and MRI images are 0.86/0.92, 0.92/0.90, 0.71/0.73, and 0.84/0.87, respectively. Pooled effect sizes using 2D and 3D images of the brainstem, mandible, left optic nerve, and left parotid gland for contouring are 0.88/0.87, 0.92/0.92, 0.75/0.71 and 0.87/0.85. CONCLUSIONS: The use of automated contouring technology based on DL algorithms is an essential tool for contouring head and neck OARs, achieving high accuracy, reducing the workload of clinical radiation oncologists, and providing individualized, standardized, and refined treatment plans for implementing "precision radiotherapy". Improving DL performance requires the construction of high-quality data sets and enhancing algorithm optimization and innovation.

Genome-wide DNA methylation profiles and small noncoding RNA signatures in sperm with a high DNA fragmentation index.

BACKGROUND: A growing number of studies have reported that sperm DNA fragmentation (SDF) is associated with male infertility. However, no studies have compared genome-wide DNA methylation profiles and sncRNA signatures between sperm with high and low sperm DNA fragmentation indices (DFIs). METHODS: Whole-genome bisulfite sequencing (WGBS) was performed on sperm samples from a weak group (DFI ≥ 30%, n = 6) and normal group (DFI ≤ 15%, n = 7). Small noncoding RNA (sncRNA) deep sequencing was conducted for sperm samples from the weak (DFI ≥ 30%, n = 13) and normal (DFI ≤ 15%, n = 17) groups. RESULTS: A total of 4939 differentially methylated regions (DMRs) were identified in the weak group sperm samples relative to normal group sperm samples, with 2072 (41.95%) of them located in promoter regions. The percentages of hypermethylated DMRs were higher than those of hypomethylated DMRs in all seven examined gene annotation groups. Hypermethylated DMRs were significantly enriched in terms associated with neurons and microtubules. Compared with the normal group, the global DNA methylation level of the weak group sperm showed a downward trend, with lower correlation for methylation in the weak group sperm; therefore, the chromosomes of high-DFI sperm may be loose. On average, 40.5% of sncRNAs were annotated as rsRNAs, 19.3% as tsRNAs, 10.4% as yRNAs, and 7.1% as miRNAs. A total of 27 miRNAs, 151 tsRNAs, and 70 rsRNAs were differentially expressed between the two groups of sperm samples. Finally, 7 sncRNAs were identified as candidate sperm quality biomarkers, and the target genes of the differentially expressed miRNAs are involved in nervous system development. CONCLUSION: Our findings suggest that genome-wide DNA methylation profiles and sncRNA signatures are significantly altered in high-DFI sperm. Our study provides potential biomarkers for sperm quality.

Matrix hardness regulates the cancer cell malignant progression through cytoskeletal network.

The tumor microenvironment is a complex microenvironment that combines the biochemical and biophysical factors. When the cells are exposed to the microenvironment, the direct biophysical factor is the matrix hardness. As an auxiliary indicator of clinical disease diagnosis, it is still not clear how the matrix hardness induces cell malignant changes and the regulation mechanisms. In this study, we identified that hard matrix significantly promoted cancer cell migratory behaviors. Cell shape was closely associated with cancer cell malignancy, the high malignant cells were associated with high ratios of length/width and low circularity. F-actin networks were also linked with extracellular matrix, it was not regularly distributed when cells were in non-malignant tumor phases or under F-actin inhibition. F-actin might play the key role that transmitted the signal from extracellular matrix to the intracellular organelles. Further study confirmed that active YAP was translocated to nucleus on hard matrix. Cells on hard matrix with cytochalasin D reversed the cancer cell malignancy, meanwhile F-actin re-distributed to the membrane and YAP nucleus translocations were hindered. This work confirmed that F-actin and YAP were upstream-downstream cascade for the cellular and nucleus outside-in signal transductions. The above results demonstrated that hard matrix promoted breast cancer cell malignant behaviors through F-actin network and YAP activation. These results not only described the signal transductions from extracellular to intracellular that was initiated by the biophysical tumor microenvironment, but provided clinical intervention ideas for cancer treatments.

Determination of local chromatin interactions using a combined CRISPR and peroxidase APEX2 system.

The architecture and function of chromatin are largely regulated by local interacting molecules, such as transcription factors and noncoding RNAs. However, our understanding of these regulatory molecules at a given locus is limited because of technical difficulties. Here, we describe the use of Clustered Regularly Interspaced Short Palindromic Repeats and an engineered ascorbate peroxidase 2 (APEX2) system to investigate local chromatin interactions (CAPLOCUS). We showed that with specific small-guide RNA targets, CAPLOCUS could efficiently identify both repetitive genomic regions and single-copy genomic locus with high resolution. Genome-wide sequencing revealed known and potential long-range chromatin interactions for a specific single-copy locus. CAPLOCUS also identified telomere-associated RNAs. CAPLOCUS, followed by mass spectrometry, identified both known and novel telomere-associated proteins in their native states. Thus, CAPLOCUS may be a useful approach for studying local interacting molecules at any given chromosomal location.

CELF1 contributes to aberrant alternative splicing patterns in the type 1 diabetic heart.

Dysregulated alternative splicing (AS) that contributes to diabetes pathogenesis has been identified, but little is known about the RNA binding proteins (RBPs) involved. We have previously found that the RBP CELF1 is upregulated in the diabetic heart; however, it is unclear if CELF1 contributes to diabetes-induced AS changes. Utilizing genome wide approaches, we identified extensive changes in AS patterns in Type 1 diabetic (T1D) mouse hearts. We discovered that many aberrantly spliced genes in T1D hearts have CELF1 binding sites. CELF1-regulated AS affects key genes within signaling pathways relevant to diabetes pathogenesis. Disruption of CELF1 binding sites impairs AS regulation by CELF1. In sum, our results indicate that CELF1 target RNAs are aberrantly spliced in the T1D heart leading to abnormal gene expression. These discoveries pave the way for targeting RBPs and their RNA networks as novel therapies for cardiac complications of diabetes.

[Impacts of Climate Change and Human Activities on NDVI Change in Eastern Coastal Areas of China].

Based on the datasets of normalized difference vegetation index (NDVI), temperature, precipitation, and solar radiation and the methods of trend, partial correlation, and residual analyses, this study explored the spatiotemporal variation in NDVI and its response to climate change from 1982 to 2019 in eastern coastal areas of China. Then, the effects of climate change and non-climatic factors (e.g., human activities) on NDVI trends were analyzed. The results showed that:① the NDVI trend varied greatly in different regions, stages, and seasons. On average, the growing season NDVI increased faster during 1982-2000 (stage I) than that during 2001-2019 (stage Ⅱ) in the study area. Moreover, NDVI in spring showed a more rapid increase than that in other seasons in both stages. ② For a given stage, the relationships between NDVI and each climatic factor varied in different seasons. For a given season, the major climatic factors associated with NDVI change were different between the two stages. The relationships between NDVI and each climatic factor showed great spatial differences in the study period. In general, the increase in growing season NDVI in the study area from 1982 to 2019 was closely related to the rapid warming. The increase in precipitation and solar radiation in stage Ⅱ also played a positive role. ③ In the past 38 years, climate change played a greater role in the change in growing season NDVI than non-climatic factors, including human activities. Whereas non-climatic factors dominated the increase in growing season NDVI during stage I, climate change played a major role during stage Ⅱ. We suggest that more attention should be paid to the impacts of various factors on vegetation cover variation during different periods to promote the understanding of terrestrial ecosystem changes.

Effects of ownership expressed by the first-person possessive pronoun.

The present study examined the behavioral effects of the first-person possessive pronoun. In each trial, a noun (e.g. cup or bread) was presented to participants after visual presentation of a possessive pronoun "wo de" (Chinese for "my") or "ta de" (Chinese for "his"), which formed ownership. Half participants were assigned to contextual encoding (CE) condition in which they were required to judge whether they liked the item expressed by a noun from the first or third-person perspective. The rest were assigned to perceptual encoding (PE) condition in which they were asked to judge what color the noun was. A subsequent recall test was performed. The results showed that there were significant memory and response advantages for nouns in "my" ownership under both conditions. The results were discussed with reference to self-specificity and other effects in the current study.

Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis.

BACKGROUND: Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis. RESULTS: Ascending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96). CONCLUSIONS: These findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.

DNA hypomethylation of a transcription factor binding site within the promoter of a gout risk gene NRBP1 upregulates its expression by inhibition of TFAP2A binding.

BACKGROUND: Genome-wide association studies (GWASs) have identified dozens of loci associated with gout, but for most cases, the risk genes and the underlying molecular mechanisms contributing to these associations are unknown. This study sought to understand the molecular mechanism of a common genetic variant, rs780093, in the development of gout, both in vitro and in vivo. RESULTS: Nuclear receptor binding protein 1 (NRBP1), as a gout risk gene, and its regulatory region, 72 bp upstream of the transcription start site, designated as B1, were identified through integrative analyses of genome-wide genotype and DNA methylation data. We observed elevated NRBP1 expression in human peripheral blood mononuclear cells (PBMCs) from gout patients. In vitro luciferase reporter and protein pulldown assay results showed that DNA methylation could increase the binding of the transcription factor TFAP2A to B1, leading to suppressed gene expression. There results were further confirmed by in vivo bisulfite pyrosequencing showing that hypomethylation on B1 is associated with increased NRBP1 expression in gout patients. CONCLUSIONS: Hypomethylation at the promoter region of NRBP1 reduces the binding of TFAP2A and thus leads to elevated NRBP1 expression, which might contribute to the development of gout.

Worrying Thoughts Limit Working Memory Capacity in Math Anxiety.

Sixty-one high-math-anxious persons and sixty-one low-math-anxious persons completed a modified working memory capacity task, designed to measure working memory capacity under a dysfunctional math-related context and working memory capacity under a valence-neutral context. Participants were required to perform simple tasks with emotionally benign material (i.e., lists of letters) over short intervals while simultaneously reading and making judgments about sentences describing dysfunctional math-related thoughts or sentences describing emotionally-neutral facts about the world. Working memory capacity for letters under the dysfunctional math-related context, relative to working memory capacity performance under the valence-neutral context, was poorer overall in the high-math-anxious group compared with the low-math-anxious group. The findings show a particular difficulty employing working memory in math-related contexts in high-math-anxious participants. Theories that can provide reasonable interpretations for these findings and interventions that can reduce anxiety-induced worrying intrusive thoughts or improve working memory capacity for math anxiety are discussed.

Selective enrichment and desalting of hydrophilic peptides using graphene oxide.

The wide variety and low abundance of peptides in tissue brought great difficulties to the separation and identification of peptides, which is not in favor of the development of peptidomics. RP-HPLC, which could purify small molecules based on their hydrophobicity, has been widely used in the separation and enrichment of peptide due to its fast, good reproducibility and high resolution. However, RP-HPLC requires the instrument and expensive C18 column and its sample capacity is also limited. Recently, graphene oxide has been applied to the adsorption of amino acids. However, the enrichment efficiency and selectivity of graphene oxide for peptides remain unclear. In this study, the adsorption efficiency and selectivity of graphene oxide and RP-C18 matrix were compared on trypsinized α-actin and also on tissue extracts from pituitary gland and hippocampus. For α-actin, there exhibit similar elution peaks for total trypsinized products and those adsorpted by GO and C18 matrix. But peptides adsorbed by GO showed the higher hydrophilic peaks than which adsorbed by C18 matrix. The resulted RP-HPLC profile showed that most of peptides enriched by graphene oxide were eluted at low concentration of organic solvent, while peptides adsorbed by RP-C18 matrix were mostly eluted at relatively high concentration. Moreover, mass spectrometry analysis suggested that, in pituitary sample, there were 495 peptides enriched by graphene oxide, 447 peptides enriched by RP-C18 matrix while in hippocampus sample 333 and 243 peptides respectively. The GRAVY value analysis suggested that the graphene oxide has a stronger adsorption for highly hydrophilic peptides compared to the RP-C18 matrix. Furthermore, the combination of these two methods could notably increase the number of identification peptides but also the number of predicted protein precursors. Our study provided a new thought to the role of graphene oxide during the enrichment of peptides from tissue which should be useful for peptidomics study.

An EEG study on the effect of self-relevant possessive pronoun: self-referential content and first-person perspective.

The present study aimed at examining the brain mechanism of the effect of self-relevant possessive pronoun (SRPP). Eighteen participants observed the following stimuli: "wo de" (Chinese for "my"/"mine"), "ta de" (Chinese for "his"), "wo" (Chinese for "I"/"me"), "ta" (Chinese for "he"/"him"), small circle and big circle. Relative to "ta de", "wo" and "ta", "wo de" elicited a significantly larger P300 amplitude, i.e. the effect of SRPP. The results showed that the effect was not due to the difference between the characters that comprise "wo de" and the characters that comprise "ta de". Low-resolution brain electromagnetic tomography (LORETA) was also conducted, which showed activities in medial prefrontal cortex (MPFC), anterior cingulate and postcentral cortex. Two representations of SRPP, self-referential content (SRC) and first-person perspective (FPP), are discussed.

An ERP study on the effect of self-relevant possessive pronoun.

The present study examined the electrophysiological correlates of the psychological processing of possessive pronouns such as "wo de" (Chinese for "my"/"mine") and "ta de" (Chinese for "his") using a three-stimulus oddball paradigm. Sixteen participants were visually presented the stimuli (possessive pronouns, small circle and big circle). The results showed that, relative to non-self-relevant possessive pronoun "ta de", self-relevant possessive pronoun "wo de" elicited a significantly larger P300 amplitude independently. The present study suggested that the self-relevant possessive pronoun was psychologically important to human beings.