bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromelanin magnetic resonance imaging of substantia nigra and locus coeruleus in Parkinson’s disease with freezing of gait
Authors: Wang Shangpei , Wu Tong , Cai Yajie , Yu Yongqiang , Chen Xianwen , Wang Longsheng
Published: February 2023

Background

The downregulation of monoamines, especially dopamine in substantia nigra (SN) and norepinephrine in locus coeruleus (LC), may be responsible for freezing of gait (FOG) pathological basis in Parkinson’s disease (PD).

Methods

Thirty-two Parkinson’s disease patients with freezing of gait (PD-FOG), 32 Parkinson’s disease patients without freezing of gait (PD-NFOG) and 32 healthy controls (HC) underwent neuromelanin magnetic resonance imaging (NM-MRI). The volume, surface area and contrast to noise ratio (CNR) of SN and LC were measured and compared. The correlation analyses were conducted between the measurements of SN and LC with clinical symptoms. We plotted the receiver operating characteristic (ROC) curve and determined the sensitivity and specificity of the CNR of SN and LC for discriminating the PD-FOG from the PD-NFOG.

Results

Both PD-FOG and PD-NFOG showed decreased volume, surface area and CNR of SN compared with HC. The PD-FOG exhibited decreased volume and surface area of LC compared with both PD-NFOG and HC groups, and decreased CNR of LC compared with HC group. The volume, surface area and CNR of SN were negatively correlated with the Unified Parkinson’s Disease Rating Scale part III scores. The illness durations in PD patients were negatively correlated with the volume, surface area of SN, while not the CNR. And the volume and surface area of LC were negatively correlated with new freezing of gait questionnaire scores. ROC analyses indicated that the area under the curve (AUC) was 0.865 and 0.713 in the CNR of SN and LC, respectively, in PD versus HC, whereas it was 0.494 and 0.637 respectively, in PD-FOG versus PD-NFOG. Among these, for discriminating the PD from the HC, the sensitivity and specificity in the CNR of the SN was 90.6 and 71.9%, respectively, when the cut-off value was set at 2.101; the sensitivity and specificity in the CNR of the LC was 90.6 and 50.0%, respectively, when the cut-off value for CNR was set at 1.411.

Conclusion

The dopaminergic changes in the SN were found across both PD-FOG and PD-NFOG, whilst LC noradrenergic neuron reduction was more evident in PD-FOG.
Ventral pallidal regulation of motivated behaviors and reinforcement
Authors: Soares-Cunha Carina , Heinsbroek Jasper A.
Published: February 2023

The interconnected nuclei of the ventral basal ganglia have long been identified as key regulators of motivated behavior, and dysfunction of this circuit is strongly implicated in mood and substance use disorders. The ventral pallidum (VP) is a central node of the ventral basal ganglia, and recent studies have revealed complex VP cellular heterogeneity and cell- and circuit-specific regulation of reward, aversion, motivation, and drug-seeking behaviors. Although the VP is canonically considered a relay and output structure for this circuit, emerging data indicate that the VP is a central hub in an extensive network for reward processing and the regulation of motivation that extends beyond classically defined basal ganglia borders. VP neurons respond temporally faster and show more advanced reward coding and prediction error processing than neurons in the upstream nucleus accumbens, and regulate the activity of the ventral mesencephalon dopamine system. This review will summarize recent findings in the literature and provide an update on the complex cellular heterogeneity and cell- and circuit-specific regulation of motivated behaviors and reinforcement by the VP with a specific focus on mood and substance use disorders. In addition, we will discuss mechanisms by which stress and drug exposure alter the functioning of the VP and produce susceptibility to neuropsychiatric disorders. Lastly, we will outline unanswered questions and identify future directions for studies necessary to further clarify the central role of VP neurons in the regulation of motivated behaviors.

Significance: Research in the last decade has revealed a complex cell- and circuit-specific role for the VP in reward processing and the regulation of motivated behaviors. Novel insights obtained using cell- and circuit-specific interrogation strategies have led to a major shift in our understanding of this region. Here, we provide a comprehensive review of the VP in which we integrate novel findings with the existing literature and highlight the emerging role of the VP as a linchpin of the neural systems that regulate motivation, reward, and aversion. In addition, we discuss the dysfunction of the VP in animal models of neuropsychiatric disorders.
Comprehensive analysis of cuproptosis-related genes in immune infiltration in ischemic stroke
Authors: Fan Xuehui , Chen Hongping , Jiang Fangchao , Xu Chen , Wang Yingju , Wang Haining , Li Meng , Wei Wan , Song Jihe , Zhong Di , Li Guozhong
Published: February 2023

Background

Immune infiltration plays an important role in the course of ischemic stroke (IS) progression. Cuproptosis is a newly discovered form of programmed cell death. To date, no studies on the mechanisms by which cuproptosis-related genes regulate immune infiltration in IS have been reported.

Methods

IS-related microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database and standardized. Immune infiltration was extracted and quantified based on the processed gene expression matrix. The differences between the IS group and the normal group as well as the correlation between the infiltrating immune cells and their functions were analyzed. The cuproptosis-related DEGs most related to immunity were screened out, and the risk model was constructed. Finally, Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and drug target were performed using the Enrichr website database. miRNAs were predicted using FunRich software. Finally, cuproptosis-related differentially expressed genes (DEGs) in IS samples were typed, and Gene Set Variation Analysis (GSVA) was used to analyze the differences in biological functions among the different types.

Results

Seven Cuproptosis-related DEGs were obtained by merging the GSE16561 and GSE37587 datasets. Correlation analysis of the immune cells showed that NLRP3, NFE2L2, ATP7A, LIPT1, GLS, and MTF1 were significantly correlated with immune cells. Subsequently, these six genes were included in the risk study, and the risk prediction model was constructed to calculate the total score to analyze the risk probability of the IS group. KEGG analysis showed that the genes were mainly enriched in the following two pathways: D-glutamine and D-glutamate metabolism; and lipids and atherosclerosis. Drug target prediction found that DMBA CTD 00007046 and Lithocholate TTD 00009000 were predicted to have potential therapeutic effects of candidate molecules. GSVA showed that the TGF-β signaling pathway and autophagy regulation pathways were upregulated in the subgroup with high expression of cuproptosis-related DEGs.

Conclusions

NLRP3, NFE2L2, ATP7A, LIPT1, GLS and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of immune infiltration in IS.
Nerves within bone and their application in tissue engineering of bone regeneration
Authors: Liu Songyang , Liu Shen , Li Shuming , Liang Boran , Han Xiao , Liang Yonghui , Wei Xing
Published: February 2023

Nerves within bone play an irreplaceable role in promoting bone regeneration. Crosstalk between the nerve system and bone has arisen to the attention of researchers in the field of basic medicine, clinical medicine, and biomaterials science. Successful bone regeneration relies on the appropriate participation of neural system components including nerve fibers, signaling molecules, and neural-related cells. Furthermore, more about the mechanisms through which nerves took part in bone regeneration and how these mechanisms could be integrated into tissue engineering scaffolds were under exploration. In the present review, we aimed to systematically elaborate on the structural and functional interrelationship between the nerve system and bone. In particular, peripheral nerves interact with the bone through innervated axons, multiple neurotrophins, and bone resident cells. Also, we aimed to summarize research that took advantage of the neuro-osteogenic network to design tissue engineering scaffolds for bone repair.
Cerebellar functional disruption and compensation in mesial temporal lobe epilepsy
Authors: Peng Yiqian , Wang Kangrun , Liu Chaorong , Tan Langzi , Zhang Min , He Jialinzi , Dai Yuwei , Wang Ge , Liu Xianghe , Xiao Bo , Xie Fangfang , Long Lili
Published: February 2023

Background

Cerebellar functional alterations are common in patients with mesial temporal lobe epilepsy (MTLE), which contribute to cognitive decline. This study aimed to deepen our knowledge of cerebellar functional alterations in patients with MTLE.

Methods

In this study, participants were recruited from an ongoing prospective cohort of 13 patients with left TLE (LTLE), 17 patients with right TLE (RTLE), and 30 healthy controls (HCs). Functional magnetic resonance imaging data were collected during a Chinese verbal fluency task. Group independent component (IC) analysis (group ICA) was applied to segment the cerebellum into six functionally separated networks. Functional connectivity was compared among cerebellar networks, cerebellar activation maps, and the centrality parameters of cerebellar regions. For cerebellar functional profiles with significant differences, we calculated their correlation with clinical features and neuropsychological scores.

Result

Compared to HCs and patients with LTLE, patients with RTLE had higher cerebellar functional connectivity between the default mode network (DMN) and the oculomotor network and lower cerebellar functional connectivity from the frontoparietal network (FPN) to the dorsal attention network (DAN) (p < 0.05, false discovery rate- (FDR-) corrected). Cerebellar degree centrality (DC) of the right lobule III was significantly higher in patients with LTLE compared to HC and patients with RTLE (p < 0.05, FDR-corrected). Higher cerebellar functional connectivity between the DMN and the oculomotor network, as well as lower cerebellar degree centrality of the right lobule III, was correlated with worse information test performance.

Conclusion

Cerebellar functional profiles were altered in MTLE and correlated with long-term memory in patients.
Cannabidiol's neuroprotective properties and potential treatment of traumatic brain injuries
Authors: Aychman Mackenzie M. , Goldman David L. , Kaplan Joshua S.
Published: February 2023

Cannabidiol (CBD) has numerous pharmacological targets that initiate anti-inflammatory, antioxidative, and antiepileptic properties. These neuroprotective benefits have generated interest in CBD's therapeutic potential against the secondary injury cascade from traumatic brain injury (TBI). There are currently no effective broad treatment strategies for combating the damaging mechanisms that follow the primary injury and lead to lasting neurological consequences or death. However, CBD's effects on different neurotransmitter systems, the blood brain barrier, oxidative stress mechanisms, and the inflammatory response provides mechanistic support for CBD's clinical utility in TBI. This review describes the cascades of damage caused by TBI and CBD's neuroprotective mechanisms to counter them. We also present challenges in the clinical treatment of TBI and discuss important future clinical research directions for integrating CBD in treatment protocols. The mechanistic evidence provided by pre-clinical research shows great potential for CBD as a much-needed improvement in the clinical treatment of TBI. Upcoming clinical trials sponsored by major professional sport leagues are the first attempts to test the efficacy of CBD in head injury treatment protocols and highlight the need for further clinical research.
The value of convolutional neural networks-based deep learning model in differential diagnosis of space-occupying brain diseases
Authors: Miao Xiuling , Shao Tianyu , Wang Yaming , Wang Qingjun , Han Jing , Li Xinnan , Li Yuxin , Sun Chenjing , Wen Junhai , Liu Jianguo
Published: February 2023

Objectives

It is still a challenge to differentiate space-occupying brain lesions such as tumefactive demyelinating lesions (TDLs), tumefactive primary angiitis of the central nervous system (TPACNS), primary central nervous system lymphoma (PCNSL), and brain gliomas. Convolutional neural networks (CNNs) have been used to analyze complex medical data and have proven transformative for image-based applications. It can quickly acquire diseases' radiographic features and correct doctors' diagnostic bias to improve diagnostic efficiency and accuracy. The study aimed to assess the value of CNN-based deep learning model in the differential diagnosis of space-occupying brain diseases on MRI.

Methods

We retrospectively analyzed clinical and MRI data from 480 patients with TDLs (n = 116), TPACNS (n = 64), PCNSL (n = 150), and brain gliomas (n = 150). The patients were randomly assigned to training (n = 240), testing (n = 73), calibration (n = 96), and validation (n = 71) groups. And a CNN-implemented deep learning model guided by clinical experts was developed to identify the contrast-enhanced T1-weighted sequence lesions of these four diseases. We utilized accuracy, sensitivity, specificity, and area under the curve (AUC) to evaluate the performance of the CNN model. The model's performance was then compared to the neuroradiologists' diagnosis.

Results

The CNN model had a total accuracy of 87% which was higher than senior neuroradiologists (74%), and the AUC of TDLs, PCNSL, TPACNS and gliomas were 0.92, 0.92, 0.89 and 0.88, respectively.

Conclusion

The CNN model can accurately identify specific radiographic features of TDLs, TPACNS, PCNSL, and gliomas. It has the potential to be an effective auxiliary diagnostic tool in the clinic, assisting inexperienced clinicians in reducing diagnostic bias and improving diagnostic efficiency.
Association between urinary phthalate levels and chronic pain in US adults, 1999–2004: A nationally representative survey
Authors: Jin Guoping , Nie Yaoyao , Fan Jiayao , Yang Ye , Chen Dingwan , Li Yingjun , Ju Li
Published: February 2023

Introduction

Chronic pain is a public health concern throughout the world. Ascertaining and managing its risk factors helps develop well-directed treatment plans and prevention strategies. Phthalates (PAEs) exposure leads to various health problems. The present study aims to explore the potential correlation between urinary PAEs metabolites and chronic pain in adults.

Methods

The study population data were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2004 in the United States. Seven urinary PAEs metabolites were used to assess long-term PAEs exposure. The assessment of chronic pain was determined by a self-report questionnaire. Weighted analyses were conducted to consider the complex sampling design. Models were adjusted by demographic data and lifestyle factors. Urinary PAEs metabolites were assessed as both continuous and categorical variables. Tertile 1 was considered as the reference. Stratified analyses were performed by gender and pain site. All data analyses were conducted with STATA, version 15.1. P < 0.05 was considered with statistical significance.

Results

A total of 4,196 participants were considered in our final analysis. Chronic pain prevalence reached 52.19% (n = 2,138) among the participants, with women accounting for a large proportion (57.75% vs. 42.25%). After multivariable logistic regression analysis, a higher prevalence of chronic pain was observed among participants in the third tertile of mono-(2-ethyl)-hexyl phthalate (MEHP) (OR = 1.23, 95% CI = 1.02–1.48, P = 0.034) and mono-benzyl phthalate (MBzP) (OR = 1.28, 95% CI = 1.04–1.58, P = 0.022) in our adjusted model. The logtransformed concentration of MBzP also showed a significant association with chronic pain prevalence (OR = 1.09, 95% CI = 1.01–1.18, P = 0.036) in the adjusted model. In further analysis, the positive correlations of urinary phthalate metabolites with chronic pain remained robust when stratified by gender and chronic pain site.

Conclusions

Our findings presented a positive correlation between urinary PAEs metabolites and chronic pain among adult participants, and more causal research should be conducted to ascertain the interactions between the two and to expound their underlying mechanisms.
Investigating the involvement of cognitive control processes in innovative and adaptive creativity and their age-related changes
Authors: Nagy Boglárka , Czigler István , Csizmadia Petra , File Domonkos , Fáy Nóra , Gaál Zsófia Anna
Published: February 2023

Introduction

Based on the two-factor model of creativity, two distinct types of creative problem solving can be differentiated: innovative (“do things differently”) and adaptive (“do things better”). Flexible cognitive control is a crucial concept in connection with both general and specific styles of creativity: innovative problem-solving benefits from broader attention and flexible mental set shifting; while adaptive creativity relies on focused attention and persistent goal-oriented processes. We applied an informatively cued task-switching paradigm which is suitable for measuring different cognitive control processes and mechanisms like proactive and reactive control. We hypothesized that adaptive creativity is connected to effective proactive control processes, while innovative creativity is based on reactive task-execution. As we have found no previous evidence how age-related changes in cognitive control affects creative cognition; we also examined the effect of healthy aging on different problem-solving styles in an explorative way.

Methods

Our participants, 37 younger (18–30 years) and 37 older (60–75 years) adults, were divided into innovative and adaptive creative groups according to the Torrance Test of Creative Thinking’s Figural Subtest (Hungarian version).

Results

Our results showed that among younger adults the adaptively creative group had larger cue-locked CNV component (effective preparatory activity connected to proactive control), while the innovatively creative group had a larger target-locked P3b component (effective target evaluation and categorization in line with reactive control) which supports a functional difference in the two creative styles. By contrast, in older adults innovative problem-solving showed larger mixing costs (less effective maintenance and selection of task sets), and the lack of trial type effect on target-locked N2b (target-induced goal reactivation and less effective conflict resolution); while adaptive problem-solving caused them to make fewer errors (accuracy-oriented behavior).

Discussion

All in all, innovative and adaptive creativity is based on distinct cognitive control mechanisms in both age-groups, but their processing level is affected by age-related changes.
Liver’s influence on the brain through the action of bile acids
Authors: Yeo Xin Yi , Tan Li Yang , Chae Woo Ri , Lee Dong-Yup , Lee Yong-An , Wuestefeld Torsten , Jung Sangyong
Published: February 2023

The liver partakes as a sensor and effector of peripheral metabolic changes and a regulator of systemic blood and nutrient circulation. As such, abnormalities arising from liver dysfunction can influence the brain in multiple ways, owing to direct and indirect bilateral communication between the liver and the brain. Interestingly, altered bile acid composition resulting from perturbed liver cholesterol metabolism influences systemic inflammatory responses, blood-brain barrier permeability, and neuron synaptic functions. Furthermore, bile acids produced by specific bacterial species may provide a causal link between dysregulated gut flora and neurodegenerative disease pathology through the gut-brain axis. This review will cover the role of bile acids—an often-overlooked category of active metabolites—in the development of neurological disorders associated with neurodegeneration. Further studies into bile acid signaling in the brain may provide insights into novel treatments against neurological disorders.
Application of diffusion tensor imaging technology in glaucoma diagnosis
Authors: Wang Jiaqi , Zhang Yaqiong , Meng Xueyu , Liu Gang
Published: February 2023

Glaucoma is the first major category of irreversible blinding eye illnesses worldwide. Its leading cause is the death of retinal ganglion cells and their axons, which results in the loss of vision. Research indicates that glaucoma affects the optic nerve and the whole visual pathway. It also reveals that degenerative lesions caused by glaucoma can be found outside the visual pathway. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that can investigate the complete visual system, including alterations in the optic nerve, optic chiasm, optic tract, lateral geniculate nuclear, and optic radiation. In order to provide a more solid foundation for the degenerative characteristics of glaucoma, this paper will discuss the standard diagnostic techniques for glaucoma through a review of the literature, describe the use of DTI technology in glaucoma in humans and animal models, and introduce these techniques. With the advancement of DTI technology and its coupling with artificial intelligence, DTI represents a potential future for MRI technology in glaucoma research.
Exploration of static functional connectivity and dynamic functional connectivity alterations in the primary visual cortex among patients with high myopia via seed-based functional connectivity analysis
Authors: Ji Yu , Huang Shui-qin , Cheng Qi , Fu Wen-wen , Zhong Pei-pei , Chen Xiao-lin , Shu Ben-liang , Wei Bin , Huang Qin-yi , Wu Xiao-rong
Published: February 2023

Aim

This study was conducted to explore differences in static functional connectivity (sFC) and dynamic functional connectivity (dFC) alteration patterns in the primary visual area (V1) among high myopia (HM) patients and healthy controls (HCs) via seed-based functional connectivity (FC) analysis.

Methods

Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 82 HM patients and 59 HCs who were closely matched for age, sex, and weight. Seed-based FC analysis was performed to identify alterations in the sFC and dFC patterns of the V1 in HM patients and HCs. Associations between mean sFC and dFC signal values and clinical symptoms in distinct brain areas among HM patients were identified via correlation analysis. Static and dynamic changes in brain activity in HM patients were investigated by assessments of sFC and dFC via calculation of the total time series mean and sliding-window analysis.

Results

In the left anterior cingulate gyrus (L-ACG)/left superior parietal gyrus (L-SPG) and left V1, sFC values were significantly greater in HM patients than in HCs. In the L-ACG and right V1, sFC values were also significantly greater in HM patients than in HCs [two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05]. In the left calcarine cortex (L-CAL) and left V1, dFC values were significantly lower in HM patients than in HCs. In the right lingual gyrus (R-LING) and right V1, dFC values were also significantly lower in HM patients than in HCs (two-tailed, voxel-level P < 0.01, GRF correction, cluster-level P < 0.05).

Conclusion

Patients with HM exhibited significantly disturbed FC between the V1 and various brain regions, including L-ACG, L-SPG, L-CAL, and R-LING. This disturbance suggests that patients with HM could exhibit impaired cognitive and emotional processing functions, top-down control of visual attention, and visual information processing functions. HM patients and HCs could be distinguished from each other with high accuracy using sFC and dFC variabilities. These findings may help to identify the neural mechanism of decreased visual performance in HM patients.
Satellite glial cells drive the transition from acute to chronic pain in a rat model of hyperalgesic priming
Authors: Du Junying , Yi Min , Xi Danning , Wang Sisi , Liu Boyi , Shao Xiaomei , Liang Yi , He Xiaofen , Fang Jianqiao , Fang Junfan
Published: February 2023

Chronic pain is one of the most common clinical syndromes affecting patients’ quality of life. Regulating the transition from acute to chronic pain is a novel therapeutic strategy for chronic pain that presents a major clinical challenge. However, the mechanism underlying pain transitions remains poorly understood. A rat hyperalgesic priming (HP) model, which mimics pain transition, was established decades ago. Here, this HP model and RNA sequencing (RNA-seq) were used to study the potential role of neuroinflammation in pain transition. In this study, HP model rats developed prolonged hyperalgesia in the hind paw after carrageenan (Car) and PGE2 injection, accompanied by obvious satellite glial cell (SGC) activation in the dorsal root ganglion (DRG), as indicated by upregulation of GFAP. RNA-Seq identified a total of differentially expressed genes in the ipsilateral DRG in HP model rats. The expression of several representative genes was confirmed by real-time quantitative PCR (qPCR). Functional analysis of the differentially expressed genes indicated that genes related to the inflammatory and neuroinflammatory response showed the most significant changes in expression. We further found that the expression of the chemokine CXCL1 was significantly upregulated in the rat DRG. Pharmacological blockade of CXCL1 reduced protein kinase C epsilon overproduction as well as hyperalgesia in HP rats but did not prevent the upregulation of GFAP in the DRG. These results reveal that neuroinflammatory responses are involved in pain transition and may be the source of chronic pain. The chemokine CXCL1 in the DRG is a pivotal contributor to chronic pain and pain transition in HP model rats. Thus, our study provides a putative novel target for the development of effective therapeutics to prevent pain transition.
Single-cell transcriptomic profile of satellite glial cells in trigeminal ganglion
Authors: Chu Yanhao , Jia Shilin , Xu Ke , Liu Qing , Mai Lijia , Liu Jiawei , Fan Wenguo , Huang Fang
Published: February 2023

Satellite glial cells (SGCs) play an important role in regulating the function of trigeminal ganglion (TG) neurons. Multiple mediators are involved in the bidirectional communication between SGCs and neurons in different physiological and pathological states. However, molecular insights into the transcript characteristics of SGCs are limited. Moreover, little is known about the heterogeneity of SGCs in TG, and a more in-depth understanding of the interactions between SGCs and neuron subtypes is needed. Here we show the single-cell RNA sequencing (scRNA-seq) profile of SGCs in TG under physiological conditions. Our results demonstrate TG includes nine types of cell clusters, such as neurons, SGCs, myeloid Schwann cells (mSCs), non-myeloid Schwann cells (nmSCs), immune cells, etc., and the corresponding markers are also presented. We reveal the signature gene expression of SGCs, mSCs and nmSCs in the TG, and analyze the ligand-receptor pairs between neuron subtypes and SGCs in the TG. In the heterogeneity analysis of SGCs, four SGCs subtypes are identified, including subtypes enriched for genes associated with extracellular matrix organization, immediate early genes, interferon beta, and cell adhesion molecules, respectively. Our data suggest the molecular characteristics, heterogeneity of SGCs, and bidirectional interactions between SGCs and neurons, providing a valuable resource for studying SGCs in the TG.
Detection of autism spectrum disorder using graph representation learning algorithms and deep neural network, based on fMRI signals
Authors: Yousefian Ali , Shayegh Farzaneh , Maleki Zeinab
Published: February 2023

Introduction

Can we apply graph representation learning algorithms to identify autism spectrum disorder (ASD) patients within a large brain imaging dataset? ASD is mainly identified by brain functional connectivity patterns. Attempts to unveil the common neural patterns emerged in ASD are the essence of ASD classification. We claim that graph representation learning methods can appropriately extract the connectivity patterns of the brain, in such a way that the method can be generalized to every recording condition, and phenotypical information of subjects. These methods can capture the whole structure of the brain, both local and global properties.

Methods

The investigation is done for the worldwide brain imaging multi-site database known as ABIDE I and II (Autism Brain Imaging Data Exchange). Among different graph representation techniques, we used AWE, Node2vec, Struct2vec, multi node2vec, and Graph2Img. The best approach was Graph2Img, in which after extracting the feature vectors representative of the brain nodes, the PCA algorithm is applied to the matrix of feature vectors. The classifier adapted to the features embedded in graphs is an LeNet deep neural network.

Results and discussion

Although we could not outperform the previous accuracy of 10-fold cross-validation in the identification of ASD versus control patients in this dataset, for leave-one-site-out cross-validation, we could obtain better results (our accuracy: 80%). The result is that graph embedding methods can prepare the connectivity matrix more suitable for applying to a deep network.
Associations of adherence to the DASH diet and the Mediterranean diet with chronic obstructive pulmonary disease among US adults
Authors: Wen Jingli , Gu Shujun , Wang Xinyu , Qi Xu
Published: February 2023

Background

The Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet are associated with reduced cardiovascular, tumor, and diabetes risk, but the effect on chronic obstructive pulmonary disease (COPD) is uncertain.

Objective

To investigate the association of the DASH diet and the Mediterranean diet with the risk of COPD in American adults.

Methods

This cross-sectional study included 28,605 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 survey cycle who had complete dietary and other questionnaire data. The scores of healthy eating patterns (the DASH diet and the Mediterranean diet) were derived from a 24-h dietary recall interview [individual food and total nutrient data from NHANES and food pattern equivalents data from the United States Department of Agriculture (USDA)]. The primary outcome was the prevalence of COPD. COPD was defined based on participants self-reported whether or not a doctor or health professional had diagnosed chronic bronchitis or emphysema. Secondary outcomes were lung function and respiratory symptoms. All analyses were adjusted for demographics and standard COPD risk factors (primary tobacco exposure, secondhand smoke exposure, and asthma).

Results

This study included 2,488 COPD participants and 25,607 non-COPD participants. We found that a higher DASH diet score was associated with a lower risk of COPD [odds ratio (OR): 0.83; 95% confidence interval (CI): 0.71–0.97; P = 0.021]. This association persisted in several subgroups [men (OR: 0.73; 95% CI: 0.58–0.93; P = 0.010), relatively young (OR: 0.74; 95% CI: 0.55–1.01; P = 0.050), and smoker (OR: 0.82; 95% CI: 0.67–0.99; P = 0.038)]. In contrast, the Mediterranean diet score was not significantly associated with COPD prevalence in this large cross-sectional analysis representative of the US adult population (OR: 1.03; 95% CI: 0.88–1.20; P = 0.697). In addition, we found a correlation between DASH diet adherence and lung function [β: −0.01; 95% CI: −0.01–0.00; P = 0.003 (FEV1: FVC)] or respiratory symptoms [OR: 0.80; 95% CI: 0.73–0.89; P < 0.001 (dyspnea); OR: 0.80; 95% CI: 0.70–0.91; P = 0.002 (cough); OR: 0.86; 95% CI: 0.74–0.99; P = 0.042 (expectoration)], especially in non-COPD populations.

Conclusion

A higher DASH diet score was associated with improved COPD prevalence, lung function and respiratory symptoms. This new finding supports the importance of diet in the pathogenesis of COPD and expands the scope of the association of the DASH diet score with major chronic diseases.
Association between coffee intake and frailty among older American adults: A population-based cross-sectional study
Authors: Pang Shuo , Miao Guangrui , Zhou Yuanhang , Duan Mingxuan , Bai Linpeng , Zhao Xiaoyan
Published: February 2023

Objective

We aimed to investigate the association between coffee consumption and frailty in older American adults. We focused on individuals at higher frailty risk, such as women, ethnic minorities, smokers, and those with obesity and insufficient physical activity.

Methods

The data of 8,087 individuals aged over 60 years from the 2007–2018 National Health and Nutrition Examination Surveys were used for this cross-sectional study. The coffee drinks were classified into two categories: caffeinated and decaffeinated. Frailty was measured using the 53-item frailty index. Weighted binary logistic regression was used to evaluate the association between coffee intake and frailty risk. Restricted cubic spline models were used to assess the dose–response relationship between caffeinated coffee intake and frailty.

Results

Among the 8,087 participants, 2,458 (30.4%) had frailty. Compared with those who reported no coffee consumption, the odds ratios [ORs; 95% confidence intervals (CIs)] of total coffee consumption > 498.9 (g/day) were 0.65 (0.52, 0.79) in the fully adjusted model. Compared with those who reported no caffeinated coffee consumption, the ORs (95% CIs) of total coffee consumption > 488.4 (g/day) were 0.68 (0.54, 0.85) in the fully adjusted model. Compared with those who reported no decaffeinated coffee consumption, the ORs (95% CIs) of total coffee consumption > 0 (g/day) were 0.87 (0.71, 1.06) in the fully adjusted model. Nonlinear associations were detected between total coffee and caffeinated coffee consumption and frailty. In the subgroup analyses by smoking status, the association between coffee consumption and the risk of frailty was more pronounced in non-smokers (P for interaction = 0.031).

Conclusion

Caffeinated coffee consumption was independently and nonlinearly associated with frailty, especially in non-smokers. However, decaffeinated coffee consumption was not associated with frailty.
Trends and recent progresses of selenium nanoparticles as novel autophagy regulators for therapeutic development
Authors: Chen Dongsheng , Lu Hongmei , Ma Yuhe , Huang Yuhe , Zhang Tangxin , Fan Shuhao , Lin Wensen , Huang Yifan , Jin Hua , Ruan Yongdui , Xu Jun-Fa , Pi Jiang
Published: February 2023

Autophagy, one of the major intracellular degradation systems, plays an important role in maintaining normal cellular physiological functions and protecting organisms from different diseases. Selenium (Se), an essential trace element, is involved in many metabolic regulatory signaling events and plays a key role in human health. In recent years, selenium nanoparticles (Se NPs) have attracted increasing attentions in biomedical field due to their low toxicity, high bioavailability and high bioactivity. Taking the advantage of their advanced biological activities, Se NPs can be used alone as potential therapeutic agents, or combine with other agents and served as carriers for the development of novel therapeutics. More interestingly, Se NPs have been widely reported to affect autophagy signaling, which therefor allow Se NPs to be used as potential therapeutic agents against different diseases. Here, this review suggested the relationships between Se and autophagy, followed by the trends and recent progresses of Se NPs for autophagy regulation in different diseased conditions. More importantly, this work discussed the roles and potential mechanisms of Se NPs in autophagy regulating, which might enhance our understanding about how Se NPs regulate autophagy for potential disease treatment. This work is expected to promote the potential application of Se NPs as novel autophagy regulators, which might benefit the development of novel autophagy associated therapeutics.
PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway
Authors: Jia Hong-tao , Shao Yan-fei , Zhou Xue-liang , Yang Guang , Huang Ling , Aikemu Batuer , Li Shu-chun , Ding Cheng-sheng , Fan Xiao-dong , Hong Hi-ju , Zhang Sen , Pan Rui-jun , Sun Jing
Published: February 2023

Objective

Colorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into.

Methods

The expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo.

Results

PKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT.

Conclusion

The increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT.
Interim result of phase II, prospective, single-arm trial of long-course chemoradiotherapy combined with concurrent tislelizumab in locally advanced rectal cancer
Authors: Gao Jiale , Zhang Xiao , Yang Zhengyang , Zhang Jie , Bai Zhigang , Deng Wei , Chen Guangyong , Xu Rui , Wei Qi , Liu Yishan , Han Jiagang , Li Ang , Liu Gang , Sun Yi , Kong Dalu , Yao Hongwei , Zhang Zhongtao
Published: February 2023

Background

Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer, with modest benefits on tumor regression and survival. Since chemoradiotherapy combined with immune checkpoint inhibitors has been reported to have synergic effects. This study aims to explore the safety and efficacy of long-course chemoradiotherapy combined with concurrent tislelizumab as a neoadjuvant treatment regimen for patients with locally advanced rectal cancer.

Methods

This manuscript reported the interim result of a prospective, multicenter, single-arm, phase II trial. Patients with mid-to-low locally advanced rectal cancer with clinical stages of cT3-4a N0M0 or cT1-4a N1-2M0 were included. The patients received long-course radiotherapy (50 Gy/25 f, 2 Gy/f, 5 days/week) and three 21-day cycles of capecitabine (1000 mg/m2, bid, day1-14) plus concurrent three 21-day cycles of tislelizumab (200 mg, day8), followed by a radical surgery 6-8 weeks after radiotherapy. The primary endpoint was the pathological complete response rate. (Clinical trial number: NCT04911517)

Results

A total of 26 patients completed the treatment protocol between April 2021 and June 2022. All patients completed chemoradiotherapy, 24 patients received three cycles of tislelizumab, and 2 patients received two cycles. The pathological complete remission (ypT0N0) was achieved in 50% (13/26) of the patients with all proficient mismatch repair tumors. The immune-related adverse event occurred in 19.2% (5/26) of patients. Patients with no CEA elevation or age less than 50 were more likely to benefit from this treatment regimen.

Conclusion

Long-course chemoradiotherapy combined with concurrent tislelizumab in patients with locally advanced low rectal cancer had favorable safety and efficacy, and does not increase the complication rate of surgery. Further study is needed to confirm these results.
Clinical advancement of precision theranostics in prostate cancer
Authors: Tan Yue , Fang Zhihui , Tang Yongxiang , Liu Kai , Zhao Hong
Published: February 2023

Theranostic approaches with positron emission tomography/computed tomography (PET/CT) or PET/magnetic resonance imaging (PET/MRI) molecular imaging probes are being implemented clinically in prostate cancer (PCa) diagnosis and imaging-guided precision surgery. This review article provides a comprehensive summary of the rapidly expanding list of molecular imaging probes in this field, including their applications in early diagnosis of primary prostate lesions; detection of lymph node, skeletal and visceral metastases in biochemical relapsed patients; and intraoperative guidance for tumor margin detection and nerve preservation. Although each imaging probe shows preferred efficacy in some applications and limitations in others, the exploration and research efforts in this field will eventually lead to improved precision theranostics of PCa.
Targeting Staphylococcus aureus dominated skin dysbiosis in actinic keratosis to prevent the onset of cutaneous squamous cell carcinoma: Outlook for future therapies?
Authors: Bromfield Jacoba Isobella , Hugenholtz Philip , Frazer Ian Hector , Khosrotehrani Kiarash , Chandra Janin
Published: February 2023

Cutaneous squamous cell carcinoma (cSCC) and its premalignant precursor, actinic keratosis (AK), present a global health burden that is continuously increasing despite extensive efforts to promote sun safety. Chronic UV exposure is a recognized risk factor for the development of AK and cSCC. However, increasing evidence suggests that AK and cSCC is also associated with skin microbiome dysbiosis and, in particular, an overabundance of the bacterium Staphylococcus aureus (S. aureus). Studies have shown that S. aureus-derived toxins can contribute to DNA damage and lead to chronic upregulation of proinflammatory cytokines that may affect carcinogenesis. Eradication of S. aureus from AK lesions and restoration of a healthy microbiome may therefore represent a therapeutic opportunity to alter disease progression. Whilst antibiotics can reduce the S. aureus load, antibiotic resistant S. aureus pose an increasing global public health threat. The use of specific topically delivered probiotics has been used experimentally in other skin conditions to restore eubiosis, and could therefore also present a non-invasive treatment approach to decrease S. aureus colonization and restore a healthy skin microbiome on AK lesions. This article reviews mechanisms by which S. aureus may contribute to cutaneous carcinogenesis, and discusses hypotheses and theories that explore the therapeutic potential of specific bacterial species which compete with S. aureus in an attempt to restore microbial eubiosis in skin.
Clinicopathologic characteristics and prognostic significance of HER2-low expression in patients with early breast cancer: A systematic review and meta-analysis
Authors: Wei Tong , Wang Dingyuan , Gao Songlin , Wang Xue , Yue Jian , Kang Yikun , Ju Jie , Yang Zixuan , Shuai You , Yuan Peng
Published: February 2023

Background

HER2-low expression breast cancer (BC) accounts for approximately 45%-55% of all BC cases. The purpose of this study was to investigate the prognostic difference between patients with HER2-low expression and HER2-zero BC.

Methods

An electronic search of Pubmed, Embase, Cochrane Library, and Web of Science databases was performed to screen studies that included prognostic comparisons between HER2-zero and HER2-low expression groups. A total of 14 studies involving 52106 patients were included.

Results

Our results indicated that HER2-low expression was associated with a significant benefit in OS among all patients with early BC (HR, 0.83; 95% CI, 0.78–0.88), patients with hormone-receptor positive BC (HR, 0.83; 95% CI, 0.77–0.89), and patients with TNBC (HR, 0.78; 95% CI, 0.70–0.87). HER2-low expression was associated with a significant benefit in DFS among all patients (HR, 0.81; 95% CI, 0.71–0.93), patients with hormone receptor-positive BC (HR, 0.81; 95% CI, 0.72–0.90), but no significant difference in DFS was found in patients with TNBC (HR, 0.87; 95% CI, 0.65–1.17). HER2-low expression was associated with a significant benefit in RFS among all patients (HR, 0.90; 95% CI, 0.85–0.95), patients with hormone receptor-positive BC (HR, 0.90; 95% CI, 0.84–0.96), but no significant difference in RFS was found in patients with TNBC (HR, 0.80; 95% CI, 0.55–1.16).

Conclusions

Among patients with early-stage BC, patients with HER2-low expression BC had better OS in the overall population, hormone receptor-positive and TNBC subgroups. Besides, favorable DFS and RFS were observed in both the overall population and hormone receptor-positive subgroup.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD 42022349458).
Targeting immune-onco-metabolism for precision cancer therapy
Authors: Pajai Sakshi , John Jyoti E. , Tripathi Satyendra Chandra
Published: February 2023

Immune cells play a key role in host defence against infection and cancer. Unlike infection, cancer is a multidimensional disease where cancer cells require continuous activation of certain pathways to sustain their growth and survival. The tumour milieu plays an important role in defining the metabolic reprogramming to support this growth and evasion from the immune system. Cancer and stromal cells modulate each other’s metabolism during cancer progression or regression. The mechanism related to change in the metabolism and its role in the crosstalk between tumour and immune cells is still an area of immense importance. Current treatment modalities can be immensely complemented and benefited by targeting the immuno-oncology metabolism, that can improve patient prognosis. This emerging aspect of immune-oncology metabolism is reviewed here, discussing therapeutic possibilities within various metabolic pathways and their effect on immune and cancer cell metabolism.