bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of three-dimension movie visual fatigue on cognitive performance and brain activity
Authors: Akagi Ryota , Sato Hiroki , Hirayama Tatsuya , Hirata Kosuke , Kokubu Masahiro , Ando Soichi
Published: October 2022

To further develop three-dimensional (3D) applications, it is important to elucidate the negative effects of 3D applications on the human body and mind. Thus, this study investigated differences in the effects of visual fatigue on cognition and brain activity using visual and auditory tasks induced by watching a 1-h movie in two dimensions (2D) and 3D. Eighteen young men participated in this study. Two conditions were randomly performed for each participant on different days, namely, watching the 1-h movie on television in 2D (control condition) and 3D (3D condition). Before and after watching the 1-h movie on television, critical flicker fusion frequency (CFF: an index of visual fatigue), and response accuracy and reaction time for the cognitive tasks were determined. Brain activity during the cognitive tasks was evaluated using a multi-channel near-infrared spectroscopy system. In contrast to the control condition, the decreased CFF, and the lengthened reaction time and the decreased activity around the right primary somatosensory cortex during Go/NoGo blocks in the visual task at post-viewing in the 3D condition were significant, with significant repeated measures correlations among them. Meanwhile, in the auditory task, the changes in cognitive performance and brain activity during the Go/NoGo blocks were not significant in the 3D condition. These results suggest that the failure or delay in the transmission of visual information to the primary somatosensory cortex due to visual fatigue induced by watching a 3D movie reduced the brain activity around the primary somatosensory cortex, resulting in poor cognitive performance for the visual task. This suggests that performing tasks that require visual information, such as running in the dark or driving a car, immediately after using a 3D application, may create unexpected risks in our lives. Thus, the findings of this study will help outlining precautions for the use of 3D applications.
A separable convolutional neural network-based fast recognition method for AR-P300
Authors: He Chunzhao , Du Yulin , Zhao Xincan
Published: October 2022

Augmented reality-based brain–computer interface (AR–BCI) has a low signal-to-noise ratio (SNR) and high real-time requirements. Classical machine learning algorithms that improve the recognition accuracy through multiple averaging significantly affect the information transfer rate (ITR) of the AR–SSVEP system. In this study, a fast recognition method based on a separable convolutional neural network (SepCNN) was developed for an AR-based P300 component (AR–P300). SepCNN achieved single extraction of AR–P300 features and improved the recognition speed. A nine-target AR–P300 single-stimulus paradigm was designed to be administered with AR holographic glasses to verify the effectiveness of SepCNN. Compared with four classical algorithms, SepCNN significantly improved the average target recognition accuracy (81.1%) and information transmission rate (57.90 bits/min) of AR–P300 single extraction. SepCNN with single extraction also attained better results than classical algorithms with multiple averaging.
Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults
Authors: Scheel Norman , Keller Jeffrey N. , Binder Ellen F. , Vidoni Eric D. , Burns Jeffrey M. , Thomas Binu P. , Stowe Ann M. , Hynan Linda S. , Kerwin Diana R. , Vongpatanasin Wanpen , Rossetti Heidi , Cullum C. Munro , Zhang Rong , Zhu David C.
Published: October 2022

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the “Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts” (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer’s Disease (rrAD) trial included hypertensive older adults (60–84 years old) at elevated risk of developing Alzheimer’s Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults.
The use of attention-deficit hyperactivity disorder medications in cardiac disease
Authors: Topriceanu Constantin-Cristian , Moon James C. , Captur Gabriella , Perera Bhathika
Published: October 2022

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset usually in childhood characterized by inattention, impulsivity, and hyperactivity causing a functional impairment. Untreated ADHD, or treatment delay is associated with adverse outcomes and poor quality of life. Although conservative management strategies such as behavioral and psychological interventions are important, pharmacological treatment has a strong evidence base with improved outcomes. ADHD medications are broadly divided into stimulant and non-stimulant medications. Stimulant medications are generally more effective than non-stimulants. Cardiovascular safety of ADHD medication has been a matter of debate for decades. Treatment guidelines advise the careful consideration of risks and benefits in people with cardiovascular diseases such as congenital heart disease or cardiomyopathy. Although stimulants can increase systemic blood pressure and heart rate, no significant associations were found between their use and serious cardiovascular events. Concerns regarding QT effects and attendant sudden cardiac death risks deter clinicians from initiating much-needed ADHD medications in patients with heart disease. This overly cautious approach is potentially depriving low-risk individuals from significant benefits associated with timely ADHD drug treatment. This review discusses the cardiovascular risks reportedly associated with ADHD medications, the evidence base for their safe usage in persons with established cardiovascular disease, and highlights future research directions.
Axial resolution and imaging contrast enhancement in inverted light-sheet microscopy by natural illumination modulation
Authors: Wang Zhi , Qiao Wei , Jiang Tao , Chen Siqi , Lu Bolin , Ning Kefu , Jin Rui , Gong Hui , Yuan Jing
Published: October 2022

Inverted light-sheet microscopy (ILSM) is widely employed for fast large-volume imaging of biological tissue. However, the scattering especially in an uncleared sample, and the divergent propagation of the illumination beam lead to a trade-off between axial resolution and imaging depth. Herein, we propose naturally modulated ILSM (NM-ILSM) as a technique to improve axial resolution while simultaneously maintaining the wide field-of-view (FOV), and enhancing imaging contrast via background suppression. Theoretical derivations, simulations, and experimental imaging demonstrate 15% axial resolution increases, and fivefold greater image contrast compared with conventional ILSM. Therefore, NM-ILSM allows convenient imaging quality improvement for uncleared tissue and could extend the biological application scope of ILSM.
Functional changes in the auditory cortex and associated regions caused by different acoustic stimuli in patients with presbycusis and tinnitus
Authors: Fuksa Jakub , Profant Oliver , Tintěra Jaroslav , Svobodová Veronika , Tóthová Diana , Škoch Antonin , Syka Josef
Published: October 2022

Presbycusis and tinnitus are the two most common hearing related pathologies. Although both of these conditions presumably originate in the inner ear, there are several reports concerning their central components. Interestingly, the onset of presbycusis coincides with the highest occurrence of tinnitus. The aim of this study was to identify age, hearing loss, and tinnitus related functional changes, within the auditory system and its associated structures. Seventy-eight participants were selected for the study based on their age, hearing, and tinnitus, and they were divided into six groups: young controls (Y-NH-NT), subjects with mild presbycusis (O-NH-NT) or expressed presbycusis (O-HL-NT), young subjects with tinnitus (Y-NH-T), subjects with mild presbycusis and tinnitus (O-NH-T), and subjects with expressed presbycusis and tinnitus (O-HL-T). An MRI functional study was performed with a 3T MRI system, using an event related design (different types of acoustic and visual stimulations and their combinations). The amount of activation of the auditory cortices (ACs) was dependent on the complexity of the stimuli; higher complexity resulted in a larger area of the activated cortex. Auditory stimulation produced a slightly greater activation in the elderly, with a negative effect of hearing loss (lower activation). The congruent audiovisual stimulation led to an increased activity within the default mode network, whereas incongruent stimulation led to increased activation of the visual cortex. The presence of tinnitus increased activation of the AC, specifically in the aged population, with a slight prevalence in the left AC. The occurrence of tinnitus was accompanied by increased activity within the insula and hippocampus bilaterally. Overall, we can conclude that expressed presbycusis leads to a lower activation of the AC, compared to the elderly with normal hearing; aging itself leads to increased activity in the right AC. The complexity of acoustic stimuli plays a major role in the activation of the AC, its support by visual stimulation leads to minimal changes within the AC. Tinnitus causes changes in the activity of the limbic system, as well as in the auditory AC, where it is bound to the left hemisphere.
The outcome of severely injured patients following traumatic brain injury is affected by gender—A retrospective, multicenter, matched-pair analysis utilizing data of the TraumaRegister DGU®
Authors: Mair Olivia , Greve Frederik , Lefering Rolf , Biberthaler Peter , Hanschen Marc ,   the TraumaRegister DGU
Published: October 2022

Introduction

Traumatic brain injury (TBI) causes a major health-concern globally. Gender-dependent differences in mortality outcome after TBI have been controversially discussed.

Materials and methods

We conducted a retrospective, multicenter, matched-pair analysis using data collected by the TraumaRegister DGU® of the German Trauma Society between 2009 and 2020. All patients after severe trauma with the leading injury of TBI (AIS ≥ 3), above 18 years of age were included. Thereby, 42,034 cases were identified. We used 12 different matching criteria to ensure highly accurate matching and were able to match 11,738 pairs of one female and one male patient.

Results

Average age at injury was 67.5 ± 19.6 years in women and 66.7 ± 19.1 years in men. Mean Injury Severity Score (ISS) was 21.3 ± 8.1 in women and 21.6 ± 8.2 in men. While women were more likely to die within the first week after trauma, the mortality was significantly higher in men overall (30.8 vs. 29.2%, p < 0.002). Women were less likely to suffer from multi organ failure (MOF) (27.5 vs. 33.0%) or sepsis (4.5 vs. 7.1%). When comparing younger (≤ 45-years) and older (> 45 years) patients, overall mortality was lower in men (13.1% men vs. 13.4% women) in the younger age group, but in the older group mortality was lower in women (33.8% men vs. 31.8% women).

Discussion

Gender-specific differences in the clinical outcome of severely injured patients with leading TBI could be detected. While women are overall characterized by an advantage in survival, this feature is not equally reproducible in premenopausal women. Therefore, the exact pathophysiological reasons for the described survival advantages of women will have to be explored in further prospective clinical studies.
The neural coding of tonal working memory load: An functional magnetic resonance imaging study
Authors: Li Qiang , Gong Dinghong , Tang Huiyi , Tian Jing
Published: October 2022

Tonal working memory load refers to the number of pitches held in working memory. It has been found that different verbal working memory loads have different neural coding (local neural activity pattern). However, whether there exists a comparable phenomenon for tonal working memory load remains unclear. In this study, we used a delayed match-to-sample paradigm to evoke tonal working memory. Neural coding of different tonal working memory loads was studied with a surface space and convolution neural network (CNN)-based multivariate pattern analysis (SC-MVPA) method. We found that first, neural coding of tonal working memory was significantly different from that of the control condition in the bilateral superior temporal gyrus (STG), supplement motor area (SMA), and precentral gyrus (PCG). Second, neural coding of nonadjacent tonal working memory loads was distinguishable in the bilateral STG and PCG. Third, neural coding is gradually enhanced as the memory load increases. Finally, neural coding of tonal working memory was encoded in the bilateral STG in the encoding phase and shored in the bilateral PCG and SMA in the maintenance phase.
Probiotics Bacillus cereus and B. subtilis reshape the intestinal microbiota of Pengze crucian carp (Carassius auratus var. Pengze) fed with high plant protein diets
Authors: Li Jiamin , Fang Peng , Yi Xinwen , Kumar Vikas , Peng Mo
Published: October 2022

The intestinal dysfunction induced by high plant protein diets is frequently observed in farmed fish, and probiotics of Bacillus genus were documented to benefit the intestinal health through the modulation of intestinal microbiota without clearness in its underlying mechanism yet. Fusobacteria, Proteobacteria, and Firmicutes were observed to be the dominate phyla, but their proportion differentiated in the intestinal bacterial community of Pengze crucian carp (Carassius auratus var. Pengze) fed different diets in this study. Dietary supplementation of B. cereus and B. subtilis could reshape the intestinal bacterial community altered by high plant protein diets through a notable reduction in opportunistic pathogen Aeromonas together with an increase in Romboutsia and/or Clostridium_sensu_stricto from Firmicutes. Due to the alteration in the composition of bacterial community, Pengze crucian carp exhibited characteristic ecological networks dominated by cooperative interactions. Nevertheless, the increase in Aeromonas intensified the competition within bacterial communities and reduced the number of specialists within ecological network, contributing to the microbial dysbiosis induced by high plant protein diets. Two probiotics diets promoted the cooperation within the intestinal bacterial community and increased the number of specialists preferred to module hubs, and then further improved the homeostasis of the intestinal microbiota. Microbial dysbiosis lead to microbial dysfunction, and microbial lipopolysaccharide biosynthesis was observed to be elevated in high plant protein diets due to the increase in Aeromonas, gram-negative microbe. Probiotics B. cereus and B. subtilis restored the microbial function by elevating their amino acid and carbohydrate metabolism together with the promotion in the synthesis of primary and secondary bile acids. These results suggested that dietary supplementation of probiotics B. cereus and B. subtilis could restore the homeostasis and functions of intestinal microbiota in Pengze crucian carp fed high plant protein diets.
Litchi flower essential oil balanced lipid metabolism through the regulation of DAF-2/IIS, MDT-15/SBP-1, and MDT-15/NHR-49 pathway
Authors: Chen Yun , Qin Qiao , Luo Jingrui , Dong Yusi , Lin Chunxiu , Chen Houbin , Cao Yong , Chen Yunjiao , Su Zuanxian
Published: October 2022

Many litchi flowers are discarded in China every year. The litchi flower is rich in volatile compounds and exhibits strong anti-obesity activity. Litchi flower essential oil (LFEO) was extracted by the continuous phase transformation device (CPTD) independently developed by our research group to recycle the precious material resources in litchi flowers. However, its fat-reducing effect and mechanism remain unclear. Employing Caenorhabditis elegans as a model, we found that LFEO significantly reduced fat storage and triglyceride (TG) content in normal, glucose-feeding, and high-fat conditions. LFEO significantly reduced body width in worms and significantly decreased both the size and number of lipid droplets in ZXW618. LFEO treatment did not affect energy intake but increased energy consumption by enhancing the average speed of worms. Further, LFEO might balance the fat metabolism in worms by regulating the DAF-2/IIS, sbp-1/mdt-15, and nhr-49/mdt-15 pathways. Moreover, LFEO might inhibit the expression of the acs-2 gene through nhr-49 and reduce β-oxidation activity. Our study presents new insights into the role of LFEO in alleviating fat accumulation and provides references for the large-scale production of LFEO to promote the development of the litchi circular economy.
Producing natural functional and low-carbon milk by regulating the diet of the cattle—The fatty acid associated rumen fermentation, biohydrogenation, and microorganism response
Authors: Sun Xiaoge , Wang Yue , Ma Xiaoyan , Li Shengli , Wang Wei
Published: October 2022

Conjugated linoleic acid (CLA) has drawn significant attention in the last two decades for its various potent beneficial effects on human health, such as anticarcinogenic and antidiabetic properties. CLA could be generally found in ruminant products, such as milk. The amount of CLA in ruminant products mainly depends on the diet of the animals. In general, the fat content in the ruminant diet is low, and dietary fat supplementation can be provided to improve rumen activity and the fatty acid (FA) profile of meat and milk. Especially, dietary 18-carbon polyunsaturated FA (C18 PUFA), the dominant fat source for ruminants, can modify the milk FA profile and other components by regulating the ruminal microbial ecosystem. In particular, it can improve the CLA in milk, intensify the competition for metabolic hydrogen for propionate producing pathways and decrease methane formation in the rumen. Therefore, lipid supplementation appears to be a promising strategy to naturally increase the additional nutritional value of milk and contribute to lower methane emissions. Meanwhile, it is equally important to reveal the effects of dietary fat supplementation on rumen fermentation, biohydrogenation (BH) process, feed digestion, and microorganisms. Moreover, several bacterial species and strains have been considered to be affected by C18 PUFA or being involved in the process of lipolysis, BH, CLA, or methane emissions. However, no review so far has thoroughly summarized the effects of C18 PUFA supplementation on milk CLA concentration and methane emission from dairy cows and meanwhile taken into consideration the processes such as the microorganisms, digestibility, rumen fermentation, and BH of dairy cattle. Therefore, this review aims to provide an overview of existing knowledge of how dietary fat affects rumen microbiota and several metabolic processes, such as fermentation and BH, and therefore contributes to functional and low-carbon milk production.
New insights into the role of ribonuclease P protein subunit p30 from tumor to internal reference
Authors: Wu Junchao , Yu Sijie , Wang Yalan , Zhu Jie , Zhang Zhenhua
Published: October 2022

Ribonuclease P protein subunit p30 (RPP30) is a highly conserved housekeeping gene that exists in many species and tissues throughout the three life kingdoms (archaea, bacteria, and eukaryotes). RPP30 is closely related to a few types of tumors in human diseases but has a very stable transcription level in most cases. Based on this feature, increasing number of studies have used RPP30 as an internal reference gene. Here, the structure and basic functions of RPP30 are summarized and the likely relationship between RPP30 and various diseases in plants and human is outlined. Finally, the current application of RPP30 as an internal reference gene and its advantages over traditional internal reference genes are reviewed. RPP30 characteristics suggest that it has a good prospect of being selected as an internal reference; more work is needed to develop this research avenue.
Eradication of tumors and development of anti-cancer immunity using STINGa targeted by pHLIP
Authors: Moshnikova Anna , DuPont Michael , Visca Hannah , Engelman Donald M. , Andreev Oleg A. , Reshetnyak Yana K.
Published: October 2022

Despite significant progress in the development of novel STING agonists (STINGa), applications appear to be challenged by the low efficiency and poor selectivity of these agents. A pH Low Insertion Peptide (pHLIP) extends the lifetime of a STINGa in the blood and targets it to acidic cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid derived suppressor cells (mMDSCs) and dendritic cells (DCs). CAFs constitute 25% of all live cells within CT26 tumors, and M2-type TAMs and mMDSCs are the most abundant among the immune cells. The resulting activation of cytokines within the tumor microenvironment (TME) triggers the eradication of small (100 mm3) and large (400-700 mm3) CT26 tumors in mice after a single dose of pHLIP-STINGa. The tumor stroma was destroyed (the number of CAFs was reduced by 98%), intratumoral hemorrhage developed, and the level of acidity within the TME was reduced. Further, no tumors developed in 20 out of 25 tumor-free mice re-challenged by an additional injection of cancer cells. The therapeutic effect on CT26 tumors was insignificant in nude mice, lacking T-cells. Thus, targeted delivery of STINGa to tumor stroma and TAMs induces activation of signaling, potentially resulting in the recruitment and infiltration of T-cells, which gain access to the tumor core. The cytotoxic activity of T-cells is not impaired by an acidic environment and immune memory is developed.
Bispecific antibodies in multiple myeloma treatment: A journey in progress
Authors: Cho Shih-Feng , Yeh Tsung-Jang , Anderson Kenneth C. , Tai Yu-Tzu
Published: October 2022

The incorporation of novel agents and monoclonal antibody-based therapies into the treatment of multiple myeloma (MM) has significantly improved long-term patient survival. However, the disease is still largely incurable, with high-risk patients suffering shorter survival times, partly due to weakened immune systems. Bispecific molecules, including bispecific antibodies (BisAbs) and bispecific T-cell engagers (BiTEs), encourage immune cells to lyse MM cells by simultaneously binding antigens on MM cells and immune effector cells, bringing those cells into close proximity. BisAbs that target B-cell maturation antigen (BCMA) and GPRC5D have shown impressive clinical activity, and the results of early-phase clinical trials targeting FcRH5 in patients with relapsed/refractory MM (RRMM) are also promising. Furthermore, the safety profile of these agents is favorable, including mainly low-grade cytokine release syndrome (CRS). These off-the-shelf bispecific molecules will likely become an essential part of the MM treatment paradigm. Here, we summarize and highlight various bispecific immunotherapies under development in MM treatment, as well as the utility of combining them with current standard-of-care treatments and new strategies. With the advancement of novel combination treatment approaches, these bispecific molecules may lead the way to a cure for MM.
Systematic analysis of the effects of genetic variants on chromatin accessibility to decipher functional variants in non-coding regions
Authors: Wang Dongyang , Wu Xiaohong , Jiang Guanghui , Yang Jianye , Yu Zhanhui , Yang Yanbo , Yang Wenqian , Niu Xiaohui , Tang Ke , Gong Jing
Published: October 2022

Genome-wide association study (GWAS) has identified thousands of single nucleotide polymorphisms (SNPs) associated with complex diseases and traits. However, deciphering the functions of these SNPs still faces challenges. Recent studies have shown that SNPs could alter chromatin accessibility and result in differences in tumor susceptibility between individuals. Therefore, systematically analyzing the effects of SNPs on chromatin accessibility could help decipher the functions of SNPs, especially those in non-coding regions. Using data from The Cancer Genome Atlas (TCGA), chromatin accessibility quantitative trait locus (caQTL) analysis was conducted to estimate the associations between genetic variants and chromatin accessibility. We analyzed caQTLs in 23 human cancer types and identified 9,478 caQTLs in breast carcinoma (BRCA). In BRCA, these caQTLs tend to alter the binding affinity of transcription factors, and open chromatin regions regulated by these caQTLs are enriched in regulatory elements. By integrating with eQTL data, we identified 141 caQTLs showing a strong signal for colocalization with eQTLs. We also identified 173 caQTLs in genome-wide association studies (GWAS) loci and inferred several possible target genes of these caQTLs. By performing survival analysis, we found that ~10% caQTLs potentially influence the prognosis of patients. To facilitate access to relevant data, we developed a user-friendly data portal, BCaQTL (http://gong_lab.hzau.edu.cn/caqtl_database), for data searching and downloading. Our work may facilitate fine-map regulatory mechanisms underlying risk loci of cancer and discover the biomarkers or therapeutic targets for cancer prognosis. The BCaQTL database will be an important resource for genetic and epigenetic studies.
Small area disease mapping of cancer incidence in British Columbia using Bayesian spatial models and the smallareamapp R Package
Authors: Simkin Jonathan , Dummer Trevor J. B. , Erickson Anders C. , Otterstatter Michael C. , Woods Ryan R. , Ogilvie Gina
Published: October 2022

Introduction

There is an increasing interest in small area analyses in cancer surveillance; however, technical capacity is limited and accessible analytical approaches remain to be determined. This study demonstrates an accessible approach for small area cancer risk estimation using Bayesian hierarchical models and data visualization through the smallareamapp R package.

Materials and methods

Incident lung (N = 26,448), female breast (N = 28,466), cervical (N = 1,478), and colorectal (N = 25,457) cancers diagnosed among British Columbia (BC) residents between 2011 and 2018 were obtained from the BC Cancer Registry. Indirect age-standardization was used to derive age-adjusted expected counts and standardized incidence ratios (SIRs) relative to provincial rates. Moran’s I was used to assess the strength and direction of spatial autocorrelation. A modified Besag, York and Mollie model (BYM2) was used for model incidence counts to calculate posterior median relative risks (RR) by Community Health Service Areas (CHSA; N = 218), adjusting for spatial dependencies. Integrated Nested Laplace Approximation (INLA) was used for Bayesian model implementation. Areas with exceedance probabilities (above a threshold RR = 1.1) greater or equal to 80% were considered to have an elevated risk. The posterior median and 95% credible intervals (CrI) for the spatially structured effect were reported. Predictive posterior checks were conducted through predictive integral transformation values and observed versus fitted values.

Results

The proportion of variance in the RR explained by a spatial effect ranged from 4.4% (male colorectal) to 19.2% (female breast). Lung cancer showed the greatest number of CHSAs with elevated risk (Nwomen = 50/218, Nmen = 44/218), representing 2357 total excess cases. The largest lung cancer RRs were 1.67 (95% CrI = 1.06–2.50; exceedance probability = 96%; cases = 13) among women and 2.49 (95% CrI = 2.14–2.88; exceedance probability = 100%; cases = 174) among men. Areas with small population sizes and extreme SIRs were generally smoothed towards the null (RR = 1.0).

Discussion

We present a ready-to-use approach for small area cancer risk estimation and disease mapping using BYM2 and exceedance probabilities. We developed the smallareamapp R package, which provides a user-friendly interface through an R-Shiny application, for epidemiologists and surveillance experts to examine geographic variation in risk. These methods and tools can be used to estimate risk, generate hypotheses, and examine ecologic associations while adjusting for spatial dependency.
A new approach to delineating clinical target volume for radiotherapy of glioblastoma: A phase II trial
Authors: Huang Yong , Ding Haixia , Luo Min , Li Zhiqiang , Li Sirui , Xie Conghua , Zhong Yahua
Published: October 2022

Purpose

No consensus has currently been reached regarding the optimal radiation volume for radiotherapy of glioblastoma. Here, we have proposed a new delineation approach to delineating clinical target volume based on the relationship between the growth patterns of glioblastoma and neural pathways. Its safety and efficacy were evaluated in a phase II clinical trial.

Methods

A total of 69 patients with histologically confirmed glioblastoma were enrolled. All patients underwent tumor resection, followed by focal radiotherapy and concomitant temozolomide (TMZ), and then received six cycles of adjuvant TMZ. The gross tumor volume (GTV) was defined as the surgical resection cavity plus any residual enhancing tumor, on contrast enhanced T1-weighted MRI. The clinical target volume (CTV) was delineated through our new approach.

Results

The median recurrence-free survival (RFS) and overall survival (OS) were 11.4 months and 18.2 months, which were better than the previous reports. Relapse was found in 47 patients, of whom 41 patients (87.2%) failed in central, two patients (4.3%) failed in field, and four patients (8.5%) failed in distance. No marginal recurrence was found. Our regimen showed a trend of lower rates of marginal recurrence, and the brain volume of high-dose radiation fields in our regimen was similar to that of EORTC (p = 0.257).

Conclusions

We have proposed a novel method for the delineation of clinical target volume by referencing the nerve fiber bundles for radiotherapy of glioblastoma. The results of the present phase II clinical trial suggest that this approach may be feasible and effective.
Diagnostic performance of the Bosniak classification, version 2019 for cystic renal masses: A systematic review and meta-analysis
Authors: Zhang Qing , Dai Xiaoli , Li Wei
Published: October 2022

Purpose

To systematically assess the diagnostic performance of the Bosniak classification, version 2019 for risk stratification of cystic renal masses.

Methods

We conducted an electronic literature search on Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar to identify relevant articles between June 1, 2019 and March 31, 2022 that used the Bosniak classification, version 2019 for risk stratification of cystic renal masses. Summary estimates of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), and diagnostic odds ratio (DOR) were pooled with the bivariate model and hierarchical summary receiver operating characteristic (HSROC) model. The quality of the included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool.

Results

A total of eight studies comprising 720 patients were included. The pooled sensitivity and specificity were 0.85 (95% CI 0.79–0.90) and 0.68 (95% CI 0.58–0.76), respectively, for the class III/IV threshold, with a calculated area under the HSROC curve of 0.84 (95% CI 0.81–0.87). The pooled LR+, LR−, and DOR were 2.62 (95% CI 2.0–3.44), 0.22 (95% CI 0.16–0.32), and 11.7 (95% CI 6.8–20.0), respectively. The Higgins I2 statistics demonstrated substantial heterogeneity across studies, with an I2 of 57.8% for sensitivity and an I2 of 74.6% for specificity. In subgroup analyses, the pooled sensitivity and specificity for CT were 0.86 and 0.71, respectively, and those for MRI were 0.87 and 0.67, respectively. In five studies providing a head-to-head comparison between the two versions of the Bosniak classification, the 2019 version demonstrated significantly higher specificity (0.62 vs. 0.41, p < 0.001); however, it came at the cost of a significant decrease in sensitivity (0.88 vs. 0.94, p = 0.001).

Conclusions

The Bosniak classification, version 2019 demonstrated moderate sensitivity and specificity, and there was no difference in diagnostic accuracy between CT and MRI. Compared to version 2005, the Bosniak classification, version 2019 has the potential to significantly reduce overtreatment, but at the cost of a substantial decline in sensitivity.
Irradiation enhances the malignancy-promoting behaviors of cancer-associated fibroblasts
Authors: Zhang Ziyue , Dong Yi , Wu Bin , Li Yingge , Liu Zehui , Liu Zheming , Gao Yanjun , Gao Likun , Song Qibin , Zheng Zhongliang , Yao Yi
Published: October 2022

Background

Cancer-associated fibroblasts (CAFs) are the important component of the tumor microenvironment (TME). Previous studies have found that some pro-malignant CAFs participate in the resistance to radiotherapy as well as the initiation and progression of tumor recurrence. However, the exact mechanism of how radiation affects CAFs remains unclear. This study aimed to explore the effect and possible mechanism of radiation-activated CAFs, and its influence on lung cancer.

Methods

CAFs were isolated from surgical specimens in situ and irradiated with 8Gy x-rays. The changes in cell morphology and subcellular structure were observed. CAFs marker proteins such as FAP and α-SMA were detected by Western Blotting. Cell counting kit-8 (CCK8) assay, flow cytometry, wound healing assay, and transwell chamber assay was used to detect the activation of cell viability and migration ability. A nude mouse xenograft model was established to observe the tumorigenicity of irradiated CAFs in vivo. The genomic changes of CAFs after radiation activation were analyzed by transcriptome sequencing technology, and the possible mechanisms were analyzed.

Results

The CAFs showed a disorderly growth pattern after X-ray irradiation. Subcellular observations suggested that metabolism-related organelles exhibited more activity. The expression level of CAFs-related signature molecules was also increased. The CAFs irradiated by 8Gy had good proliferative activity. In the (indirect) co-culture system, CAFs showed radiation protection and migration induction to lung cancer cell lines, and this influence was more obvious in radiation-activated CAFs. The radiation protection was decreased after exosome inhibitors were applied. Vivo study also showed that radiation-activated CAFs have stronger tumorigenesis. Transcriptome analysis showed that genes were enriched in several pro-cancer signaling pathways in radiation-activated CAFs.

Conclusions

Our study confirmed that CAFs could be activated by ionizing radiation. Irradiation-activated CAFs could promote cancer cell proliferation, migration, radiotherapy tolerance, and tumorigenesis. These results suggested that irradiation-activated CAFs might participate in the recurrence of lung cancer after radiotherapy, and the inhibition of CAFs activation may be an important way to improve clinical radiotherapy efficacy.
Liver metastases and the efficacy of immune checkpoint inhibitors in advanced lung cancer: A systematic review and meta-analysis
Authors: Xia Handai , Zhang Wengang , Zhang Yuqing , Shang Xiaoling , Liu Yanguo , Wang Xiuwen
Published: October 2022

Background

Liver metastasis is the most common type of lung cancer metastasis, and is a significant prognostic factor in lung cancer. However, the effect of liver metastases on the efficacy of immune checkpoint inhibitors (ICIs) remains inconsistent and controversial. The aim of this study was to explore the relationship between liver metastases and ICI efficacy in patients with advanced lung cancer based on data from randomized controlled trials (RCTs) and observational studies.

Methods

PubMed, EMBASE, Cochrane Library databases, conference proceedings, as well as grey literature websites were searched for eligible studies without language restrict ion. Study quality was assessed using Cochrane tools and the Newcastle–Ottawa Quality Assessment Scale (NOS). Outcomes of interest were overall survival (OS) and progression-free survival (PFS). The difference in efficacy between patients with and without liver metastases was calculated by pooling ratios of hazard ratios (HR), as calculated using the deft approach.

Results

A total of 16 RCTs and 14 observational trials were included. Analyses of RCTs revealed a survival benefit for ICI treatment (i.e., ICI monotherapy, ICI + Chemotherapy, dual ICI therapy and dual ICI + Chemotherapy) versus standard therapies among non-small cell lung cancer (NSCLC) patients with liver metastases (PFS HR, 0.77; 95%CI, 0.61–0.97; OS HR, 0.78; 95%CI, 0.68–0.90). NSCLC patients with liver metastases achieved less PFS benefit and comparable OS benefit from ICI treatment compared with those without liver metastases (ratios of PFS–HRs, 1.19; 95%CI, 1.02–1.39; P=0.029; Ratios of OS–HRs, 1.10; 95%CI, 0.94–1.29; P=0.24). For patients with small cell lung cancer (SCLC), ICI treatment achieved a marginal effect on patients with liver metastases as compared with standard therapies (OS HR, 0.94; 95%CI, 0.73–1.23). SCLC patients with liver metastases benefited less from ICI treatment than patients without liver metastases (ratio of OS–HRs, 1.22; 95%CI, 1.01–1.46; P=0.036). In real-world data analysis, liver metastasis could be used as an independent prognostic risk factor, increasing the risk of death by 21% in lung cancer patients receiving ICI treatment compared with those without liver metastases (OS HR, 1.21; 95%CI, 1.17–1.27; P<0.0001). Subgroup analysis confirmed that this association was not modified by race (Asian vs. Western) or number of treatment lines.

Conclusions

The presence of liver metastases does not significantly influence the OS benefit of ICIs in patients with NSCLC. However, a small amount of data shows that liver metastasis restrains the magnitude of OS benefit in patients with SCLC. Liver metastasis has potential as an independent prognostic risk factor for lung cancer patients receiving ICI treatment in clinical practice.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022306449).
Why responses to immune checkpoint inhibitors are heterogeneous in head and neck cancers: Contributions from tumor-intrinsic and host-intrinsic factors
Authors: Chen Zhangguo , John Jessy , Wang Jing H.
Published: October 2022

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment including in head and neck squamous cell carcinomas (HNSCCs); however, only a fraction of HNSCC patients respond to ICI, whereas the majority fail to do so. The mechanisms underlying such variable responses remain incompletely understood. A better understanding of such mechanisms may broaden the spectrum of responding patients and enhance the rate of ICI response. HNSCCs exhibit a high level of genetic heterogeneity, manifested as mutations or amplifications of oncogenes (e.g., PIK3CA) and mutations of tumor suppressor genes (e.g., TP53). The immune tumor microenvironment (TME) of HNSCCs also varies significantly in composition and in relative abundance of distinct immune subsets such as CD8 tumor-infiltrating lymphocytes (TILs) or tumor-associated macrophages (TAMs), which represents a high degree of immunological heterogeneity. Here, we briefly discuss how heterogeneous ICI responses may be attributed to tumor-intrinsic factors, including genetic, transcriptional, and functional variations in tumor cells, and host-intrinsic factors, including cellular composition of the TME (e.g., CD8 TILs and TAMs), and host-intrinsic differences in the T cell receptor (TCR) repertoire of CD8 TILs. We also discuss the potential impact of these factors on designing strategies for personalized immunotherapy of HNSCCs.
A novel mutation in ryanodine receptor 2 (RYR2) genes at c.12670G>T associated with focal epilepsy in a 3-year-old child
Authors: Hu Junji , Gao Xueping , Chen Longchang , Zhou Tianshu , Du Zhaoli , Jiang Jinghan , Wei Lei , Zhang Zhijun
Published: October 2022

Background

Ryanodine receptor 2 (RYR2) encodes a component of a calcium channel. RYR2 variants were well-reported to be associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), but rarely reported in epilepsy cases. Here, we present a novel heterozygous mutation of RYR2 in a child with focal epilepsy.

Methods

At the age of 2 years and 7 months, the patient experienced seizures, such as eye closure, tooth clenching, clonic jerking and hemifacial spasm, as well as abnormal electroencephalogram (EEG). Then, he was analyzed by whole-exome sequencing (WES). The mutations of both the proband and his parents were further confirmed by Sanger sequencing. The pathogenicity of the variant was further assessed by population-based variant frequency screening, evolutionary conservation comparison, and American Association for Medical Genetics and Genomics (ACMG) scoring.

Results

WES sequencing revealed a novel heterozygous truncating mutation [c.12670G > T, p.(Glu4224*), NM_001035.3] in RYR2 gene of the proband. Sanger sequencing confirmed that this mutation was inherited from his mother. This novel variant was predicted to be damaging by different bioinformatics methods. Cardiac investigation showed that the proband had no structural abnormalities, but sinus tachycardia.

Conclusion

We proposed that RYR2 is a potential candidate gene for focal epilepsy, and epilepsy patients carried with RYR2 variants should be given more attention, even if they do not show cardiac abnormalities
Intervention effects of traditional Chinese medicine on stem cell therapy of myocardial infarction
Authors: Wang Yu , Xue Yuezhen , Guo Hai-dong
Published: October 2022

Cardiovascular diseases are the leading cause of global mortality, in which myocardial infarction accounts for 46% of total deaths. Although good progress has been achieved in medication and interventional techniques, a proven method to repair the damaged myocardium has not yet been determined. Stem cell therapy for damaged myocardial repair has evolved into a promising treatment for ischemic heart disease. However, low retention and poor survival of the injected stem cells are the major obstacles to achieving the intended therapeutic effects. Chinese botanical and other natural drug substances are a rich source of effective treatment for various diseases. As such, numerous studies have revealed the role of Chinese medicine in stem cell therapy for myocardial infarction treatment, including promoting proliferation, survival, migration, angiogenesis, and differentiation of stem cells. Here, we discuss the potential and limitations of stem cell therapy, as well as the regulatory mechanism of Chinese medicines underlying stem cell therapy. We focus on the evidence from pre-clinical trials and clinical practices, and based on traditional Chinese medicine theories, we further summarize the mechanisms of Chinese medicine treatment in stem cell therapy by the commonly used prescriptions. Despite the pre-clinical evidence showing that traditional Chinese medicine is helpful in stem cell therapy, there are still some limitations of traditional Chinese medicine therapy. We also systematically assess the detailed experimental design and reliability of included pharmacological research in our review. Strictly controlled animal models with multi-perspective pharmacokinetic profiles and high-grade clinical evidence with multi-disciplinary efforts are highly demanded in the future.
Systematic review of Lonicerae Japonicae Flos: A significant food and traditional Chinese medicine
Authors: Zheng Senwang , Liu Songtao , Hou Ajiao , Wang Song , Na Yexin , Hu Jianhua , Jiang Hai , Yang Liu
Published: October 2022

Lonicerae Japonicae Flos has been used as a tea and medicine for more than 1,500 years. It has the functions of clearing heat, detoxification, and is often used to treat carbuncle, furuncle, throat arthralgia, erysipelas, heat-toxic blood dysentery, febrile fever. This paper summarizes the botany, ethnopharmacology, chemical composition and pharmacological action of Lonicerae Japonicae Flos from 1986 to 2022, and looks forward to the future research direction of Lonicerae Japonicae Flos. At present, the components isolated from Lonicerae Japonicae Flos include essential oils, organic acids, flavonoids, iridoids, saponins and other compounds. It has the effects of anti-inflammation, anti-virus, anti-bacteria, anti-oxidation, anti-tumor, protect liver and galltesticles, hypotensive, hypolipidemic, anti-thrombosis, anti-allergy, immune regulation and so on. It is often used in clinical treatment of diarrhea, hematochezia, febrile disease, exogenous wind-heat, and cold, swelling and toxin of carbuncle, sore throat and so on. The comprehensive evaluation of the quality of Lonicerae Japonicae Flos and the understanding of multi-target network pharmacology also need to be studied. As a kind of health food with high value, LJF is worthy of further promotion and development.