bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll-like receptor 4 deficiency in mice impairs venous thrombus resolution
Authors: Yuan Haixin , Huang Xiaoxi , Ding Jie
Published: May 2023

Objective: Toll-like receptor 4 (TLR4) is crucial to the development of sterile inflammatory responses. The deep venous thrombosis resolution (DVT) is similar to sterile inflammation, so we hypothesize that TLR4 is involved.

Methods and Results: We evaluated the effects of TLR4 deficiency on thrombus lysis in vivo, and explored the mechanisms in vitro. DVT mouse model was established by inferior vena cava (IVC) ligation. After the IVC ligation (1, 3, and 7 d), the mice were euthanized to collect the venous thrombus. The Tlr4−/− mice had significantly elevated weight/length ratios of thrombi at 3 and 7 d and increased collagen content at 3 d after IVC ligation, in addition to significantly lesser intrathrombus infiltration of neutrophils and macrophages, lower monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) expression in thrombus tissue sections and homogenates, and lower pro-MMP-9 activity at 3 d after IVC ligation than wild-type mice. After 7 days of IVC ligation, VEGF, IFNβ, and MCP-5 protein expression were decreased in venous thrombus from Tlr4−/− mice. 2 ml of 3% thioglycolate was injected intraperitoneally and peritoneal exudate was collected 3 days later from Tlr4−/− and wild type mice respectively. The intraperitoneal macrophages were isolated from adherent culture after centrifugation. Lipopolysaccharide (LPS) can activate TLR4/NF-κB signalling pathway in a concentration-dependent manner, initiated p65 nuclear translocation, IκBα phosphorylation and degradation, MMP-9 and MCP-1 transcription in WT intraperitoneal macrophages but not in Tlr4−/− intraperitoneal macrophages.

Conclusion: TLR4 is involved in venous thrombosis resolution through NF-κB pathway. Loss of TLR4 in mice impairs the process.
The relationship between protein modified folding molecular network and Alzheimer’s disease pathogenesis based on BAG2-HSC70-STUB1-MAPT expression patterns analysis
Authors: Yang Xiaolong , Guo Wenbo , Yang Lin , Li Xuehui , Zhang Zhengkun , Pang Xinping , Liu Ji , Pang Chaoyang
Published: May 2023

Background

Alzheimer’s disease (AD) is the most common cause of dementia and cognitive decline, while its pathological mechanism remains unclear. Tauopathies is one of the most widely accepted hypotheses. In this study, the molecular network was established and the expression pattern of the core gene was analyzed, confirming that the dysfunction of protein folding and degradation is one of the critical factors for AD.

Methods

This study analyzed 9 normal people and 22 AD patients’ microarray data obtained from GSE1297 in Gene Expression Omnibus (GEO) database. The matrix decomposition analysis was used to identify the correlation between the molecular network and AD. The mathematics of the relationship between the Mini-Mental State Examination (MMSE) and the expression level of the genes involved in the molecular network was found by Neural Network (NN). Furthermore, the Support Vector Machine (SVM) model was for classification according to the expression value of genes.

Results

The difference of eigenvalues is small in first three stages and increases dramatically in the severe stage. For example, the maximum eigenvalue changed to 0.79 in the severe group from 0.56 in the normal group. The sign of the elements in the eigenvectors of biggest eigenvalue reversed. The linear function of the relationship between clinical MMSE and gene expression values was observed. Then, the model of Neural Network (NN) is designed to predict the value of MMSE based on the linear function, and the predicted accuracy is up to 0.93. For the SVM classification, the accuracy of the model is 0.72.

Conclusion

This study shows that the molecular network of protein folding and degradation represented by “BAG2-HSC70-STUB1-MAPT” has a strong relationship with the occurrence and progression of AD, and this degree of correlation of the four genes gradually weakens with the progression of AD. The mathematical mapping of the relationship between gene expression and clinical MMSE was found, and it can be used in predicting MMSE or classification with high accuracy. These genes are expected to be potential biomarkers for early diagnosis and treatment of AD.
Mendelian randomization analyses of smoking and Alzheimer’s disease in Chinese and Japanese populations
Authors: Zhu Yuan , Guan Ying , Xiao Xuewen , Jiao Bin , Liao Xinxin , Zhou Hui , Liu Xixi , Qi Feiyan , Peng Qiyuan , Zhou Lu , Xu Tianyan , Yang Qijie , Zhang Sizhe , Li Meng , Zhu Zhouhai , Lu Sheming , Li Jinchen , Tang Beisha , Shen Lu , Yao Jianhua , Zhou Yafang
Published: May 2023

Background

Previous epidemiological studies have reported controversial results on the relationship between smoking and Alzheimer’s disease (AD). Therefore, we sought to assess the association using Mendelian randomization (MR) analysis.

Methods

We used single nucleotide polymorphisms (SNPs) associated with smoking quantity (cigarettes per day, CPD) from genome-wide association studies (GWAS) of Japanese population as instrumental variables, then we performed two-sample MR analysis to investigate the association between smoking and AD in a Chinese cohort (1,000 AD cases and 500 controls) and a Japanese cohort (3,962 AD cases and 4,074 controls), respectively.

Results

Genetically higher smoking quantity showed no statistical causal association with AD risk (the inverse variance weighted (IVW) estimate in the Chinese cohort: odds ratio (OR) = 0.510, 95% confidence interval (CI) = 0.149–1.744, p = 0.284; IVW estimate in the Japanese cohort: OR = 1.170, 95% confidence interval CI = 0.790–1.734, p = 0.434).

Conclusion

This MR study, for the first time in Chinese and Japanese populations, found no significant association between smoking and AD.
Biomarkers of delirium risk in older adults: a systematic review and meta-analysis
Authors: Lozano-Vicario Lucía , García-Hermoso Antonio , Cedeno-Veloz Bernardo Abel , Fernández-Irigoyen Joaquín , Santamaría Enrique , Romero-Ortuno Román , Zambom-Ferraresi Fabricio , Sáez de Asteasu Mikel L. , Muñoz-Vázquez Ángel Javier , Izquierdo Mikel , Martínez-Velilla Nicolás
Published: May 2023

Delirium is a neuropsychiatric syndrome associated with increased morbidity and mortality in older patients. The aim of this study was to review predictive biomarkers of delirium in older patients to gain insights into the pathophysiology of this syndrome and provide guidance for future studies. Two authors independently and systematically searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus databases up to August 2021. A total of 32 studies were included. Only 6 studies were eligible for the meta-analysis, pooled results showed a significant increase in some serum biomarkers (C-reactive protein [CRP], tumour necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) among patients with delirium (odds ratio = 1.88, 95% CI 1.01 to 1.637; I2 = 76.75%). Although current evidence does not favour the use of any particular biomarker, serum CRP, TNF-α, and IL-6 were the most consistent biomarkers of delirium in older patients.
Impaired rich-club connectivity in childhood absence epilepsy
Authors: Yu Yadong , Qiu Mengdi , Zou Wenwei , Zhao Ying , Tang Yan , Tian Jisha , Chen Xiaoyu , Qiu Wenchao
Published: May 2023

Introduction

Childhood absence epilepsy (CAE) is a well-known pediatric epilepsy syndrome. Recent evidence has shown the presence of a disrupted structural brain network in CAE. However, little is known about the rich-club topology. This study aimed to explore the rich-club alterations in CAE and their association with clinical characteristics.

Methods

Diffusion tensor imaging (DTI) datasets were acquired in a sample of 30 CAE patients and 31 healthy controls. A structural network was derived from DTI data for each participant using probabilistic tractography. Then, the rich-club organization was examined, and the network connections were divided into rich-club connections, feeder connections, and local connections.

Results

Our results confirmed a less dense whole-brain structural network in CAE with lower network strength and global efficiency. In addition, the optimal organization of small-worldness was also damaged. A small number of highly connected and central brain regions were identified to form the rich-club organization in both patients and controls. However, patients exhibited a significantly reduced rich-club connectivity, while the other class of feeder and local connections was relatively spared. Moreover, the lower levels of rich-club connectivity strength were statistically correlated with disease duration.

Discussion

Our reports suggest that CAE is characterized by abnormal connectivity concentrated to rich-club organizations and might contribute to understanding the pathophysiological mechanism of CAE.
A novel sleep aid device to reduce sleep latency using air–CO2 mixed gas
Authors: Han Hyewon , Kim Dongsin , Kim Jin Seok , Kwac Lee Ku , Hyeon Janghun , Oh Junhyoung
Published: May 2023

Introduction

Sleep is an indispensable component of human life. However, in modern times, the number of people suffering from sleep disorders, such as insomnia and sleep deprivation, has increased significantly. Therefore, to alleviate the discomfort to the patient due to lack of sleep, sleeping pills and various sleep aids are being introduced and used. However, sleeping drugs are prescribed only to a limited extent due to the side effects posed by them and resistance to such drugs developed by patients in the long term, and the majority of sleep aids are scientifically groundless products. This study aimed to develop a device that induced sleep by spraying a mixed gas of carbon dioxide and air to create an environment that could induce sleep, similar to the inside of a sealed vehicle, to control oxygen saturation in the body.

Methods

Based on the stipulated safety standards and the human tidal volume, the target concentration of carbon dioxide was determined to be of three types: 15,000, 20,000, and 25,000 ppm. After analyzing diverse structures for safely mixing gases, the most appropriate shape, the reserve tank, was selected as the best suited structure. Various variables, such as spraying angle and distance, flow rate, atmospheric temperature, and nozzle length, were comprehensively measured and tested. Furthermore based on this aspect, diffusion simulation of carbon dioxide concentration and actual experiments were conducted. To secure the stability and reliability of the developed product, an accredited test was performed to investigate the error rate of carbon dioxide concentration. Furthermore, clinical trials comprising polysomnography and questionnaires confirmed the effectiveness of the developed product not only in reducing sleep latency but also in enhancing the overall sleep quality.

Results

When the developed device was put to use in reality, sleep latency was decreased by 29.01%, on average, for those with a sleep latency of 5 min or more, compared to when the device was not in use. Moreover, the total sleep time was increased by 29.19 min, WASO was decreased by 13.17%, and sleep efficiency was increased by 5.48%. We also affirmed that the ODI and 90% ODI did not decrease when the device was used. Although different questions may be raised about the safety of using a gas such as carbon dioxide (CO2), the result that tODI was not reduced shows that sleep aids using CO2 mixtures do not adversely affect human health.

Discussion

The results of this study suggest a new method that can be used to treat sleep disorders including insomnia.
Art therapy as a comprehensive complementary treatment for Parkinson’s disease
Authors: Ettinger Tom , Berberian Marygrace , Acosta Ikuko , Cucca Alberto , Feigin Andrew , Genovese Danilo , Pollen Travis , Rieders Julianne , Kilachand Rohita , Gomez Clara , Kaimal Girija , Biagioni Milton , Di Rocco Alessandro , Ghilardi Felice M. , Rizzo John-Ross
Published: May 2023

Introduction

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. Complementary and alternative therapies are increasingly utilized to address its complex multisystem symptomatology. Art therapy involves motoric action and visuospatial processing while promoting broad biopsychosocial wellness. The process involves hedonic absorption, which provides an escape from otherwise persistent and cumulative PD symptoms, refreshing internal resources. It involves the expression in nonverbal form of multilayered psychological and somatic phenomena; once these are externalized in a symbolic arts medium, they can be explored, understood, integrated, and reorganized through verbal dialogue, effecting relief and positive change.

Methods

42 participants with mild to moderate PD were treated with 20 sessions of group art therapy. They were assessed before and after therapy with a novel arts-based instrument developed to match the treatment modality for maximum sensitivity. The House-Tree-Person PD Scale (HTP-PDS) assesses motoric and visuospatial processing–core PD symptoms–as well as cognition (thought and logic), affect/mood, motivation, self (including body-image, self-image, and self- efficacy), interpersonal functioning, creativity, and overall level of functioning. It was hypothesized that art therapy will ameliorate core PD symptoms and that this will correlate with improvements in all other variables.

Results

HTP-PDS scores across all symptoms and variables improved significantly, though causality among variables was indeterminate.

Discussion

Art therapy is a clinically efficacious complementary treatment for PD. Further research is warranted to disentangle causal pathways among the aforementioned variables, and additionally, to isolate and examine the multiple, discrete healing mechanisms believed to operate simultaneously in art therapy.
Neurophysiological correlates of tactile width discrimination in humans
Authors: Pais-Vieira Carla , Allahdad Mehrab K. , Perrotta André , Peres André S. , Kunicki Carolina , Aguiar Mafalda , Oliveira Manuel , Pais-Vieira Miguel
Published: May 2023

Introduction

Tactile information processing requires the integration of sensory, motor, and cognitive information. Width discrimination has been extensively studied in rodents, but not in humans.

Methods

Here, we describe Electroencephalography (EEG) signals in humans performing a tactile width discrimination task. The first goal of this study was to describe changes in neural activity occurring during the discrimination and the response periods. The second goal was to relate specific changes in neural activity to the performance in the task.

Results

Comparison of changes in power between two different periods of the task, corresponding to the discrimination of the tactile stimulus and the motor response, revealed the engagement of an asymmetrical network associated with fronto-temporo-parieto-occipital electrodes and across multiple frequency bands. Analysis of ratios of higher [Ratio 1: (0.5–20 Hz)/(0.5–45 Hz)] or lower frequencies [Ratio 2: (0.5–4.5 Hz)/(0.5–9 Hz)], during the discrimination period revealed that activity recorded from frontal-parietal electrodes was correlated to tactile width discrimination performance between-subjects, independently of task difficulty. Meanwhile, the dynamics in parieto-occipital electrodes were correlated to the changes in performance within-subjects (i.e., between the first and the second blocks) independently of task difficulty. In addition, analysis of information transfer, using Granger causality, further demonstrated that improvements in performance between blocks were characterized by an overall reduction in information transfer to the ipsilateral parietal electrode (P4) and an increase in information transfer to the contralateral parietal electrode (P3).

Discussion

The main finding of this study is that fronto-parietal electrodes encoded between-subjects’ performances while parieto-occipital electrodes encoded within-subjects’ performances, supporting the notion that tactile width discrimination processing is associated with a complex asymmetrical network involving fronto-parieto-occipital electrodes.
Exoskeleton gait training with spinal cord neuromodulation
Authors: Ivanenko Yury , Shapkova Elena Y. , Petrova Daria A. , Kleeva Daria F. , Lebedev Mikhail A.
Published: May 2023

Neuromodulating the locomotor network through spinal cord electrical stimulation (SCES) is effective for restoring function in individuals with gait deficits. However, SCES alone has limited effectiveness without concurrent locomotor function training that enhances activity-dependent plasticity of spinal neuronal networks by sensory feedback. This mini review discusses recent developments in using combined interventions, such as SCES added to exoskeleton gait training (EGT). To develop personalized therapies, it is crucial to assess the state of spinal circuitry through a physiologically relevant approach that identifies individual characteristics of spinal cord function to develop person-specific SCES and EGT. The existing literature suggests that combining SCES and EGT to activate the locomotor network can have a synergistic rehabilitative effect on restoring walking abilities, somatic sensation, and cardiovascular and bladder function in paralyzed individuals.
EMG-EMG coherence during voluntary control of human standing tasks: a systematic scoping review
Authors: Yamanaka Eiji , Horiuchi Yuki , Nojima Ippei
Published: May 2023

Background

Intra- or inter-muscular (EMG-EMG) coherence is a simple and non-invasive method for estimating central nervous system control during human standing tasks. Although this research area has developed, no systematic literature review has been conducted.

Objectives

We aimed to map the current literature on EMG-EMG coherence during various standing tasks to identify the research gaps and summarize previous studies comparing EMG-EMG coherence between healthy young and elderly adults.

Methods

Electronic databases (PubMed, Cochrane Library, and CINAHL) were searched for articles published from inception to December 2021. We incorporated studies that analyzed EMG-EMG coherence of the postural muscles in various standing tasks.

Results

Finally, 25 articles fulfilled the inclusion criteria and involved 509 participants. Most participants were healthy young adults, while only one study included participants with medical conditions. There was some evidence that EMG-EMG coherence could identify differences in standing control between healthy young and elderly adults, although the methodology was highly heterogeneous.

Conclusion

The present review indicates that EMG-EMG coherence may help elucidate changes in standing control with age. In future studies, this method should be used in participants with central nervous system disorders to understand better the characteristics of standing balance disabilities.
A randomised sham-controlled study evaluating rTMS analgesic efficacy for postherpetic neuralgia
Authors: Wang Huan , Hu Yuzhong , Deng Jiayi , Ye Yang , Huang Manli , Che Xianwei , Yu Liang
Published: May 2023

Context

Postherpetic neuralgia (PHN) is a refractory neuropathic pain condition in which new treatment options are being developed. Repetitive transcranial magnetic stimulation (rTMS) may have the potential to reduce pain sensations in patients with postherpetic neuralgia.

Objectives

This study investigated the efficacy on postherpetic neuralgia by stimulating two potential targets, the motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC).

Methods

This is a double-blind, randomised, sham-controlled study. Potential participants were recruited from Hangzhou First People’s Hospital. Patients were randomly assigned to either the M1, DLPFC or Sham group. Patients received ten daily sessions of 10-Hz rTMS in 2 consecutive weeks. The primary outcome measure was visual analogue scale (VAS) assessed at baseline, first week of treatment (week 1), post-treatment (week 2), 1-week (week 4), 1-month (week 6) and 3-month (week 14) follow-up.

Results

Of sixty patients enrolled, 51 received treatment and completed all outcome assessments. M1 stimulation resulted in a larger analgesia during and after treatment compared to the Sham (week 2 – week 14, p < 0.005), as well as to the DLPFC stimulation (week 1 – week 14, p < 0.05). In addition to pain, sleep disturbance was significantly improved and relieved by targeting either the M1 or the DLPFC (M1: week 4 – week 14, p < 0.01; DLPFC: week 4 – week 14, p < 0.01). Moreover, pain sensations following M1 stimulation uniquely predicted improvement in sleep quality.

Conclusion

M1 rTMS is superior to DLPFC stimulation in treating PHN with excellent pain response and long-term analgesia. Meanwhile, M1 and DLPFC stimulation were equally effective in improving sleep quality in PHN.

Clinical trial registration

https://www.chictr.org.cn/, identifier ChiCTR2100051963.
Glutamatergic neurons and GABAergic neurons of medial prefrontal cortex control hoarding-like behavior
Authors: Xiong Yujie , Wang Beining , Shang Yunxia , Liu Huan , Zhan Zihao , Xu Qi , Wang Kai , Zhang Zhi , Sun Tingting
Published: May 2023

Hoarding disorder (HD) is a chronic disease that begins early in life and does not remission unless timely treated. A large number of factors affect the presentation of HD symptoms, including a strong possessive psychology of objects and neurocognitive functioning. However, the underlying neural mechanisms of the excessive hoarding behavior in HD are still unknown. Using viral infections and brain slice electrophysiology recordings, we found that increased glutamatergic neuronal activity and decreased GABAergic neuronal activity in medial prefrontal cortex (mPFC) accelerated the hoarding-like behavior in mice. Respectively, chemogenetic manipulation to reduce glutamatergic neuronal activity or enhance GABAergic neuronal activity could improve the hoarding-like behavioral response. These results reveal a critical role played by alterations in the activity of specific types of neurons in hoarding-like behavior, and that targeted therapies for HD may be possible by precisely modulating these types of neurons.
A map of evidence using transcranial direct current stimulation (tDCS) to improve cognition in adults with traumatic brain injury (TBI)
Authors: Schwertfeger Julie Lynn , Beyer Charlotte , Hung Paul , Ung Nathaniel , Madigan Caroline , Cortes Alvi Renzyl , Swaminathan Bharathi , Madhavan Sangeetha
Published: May 2023

Introduction

Cognition impairments often occur after a traumatic brain injury and occur at higher rates in military members. Cognitive symptoms impair daily function, including balance and life quality, years after the TBI. Current treatments to regain cognitive function after TBI, including medications and cognitive rehabilitation, have shown limited effectiveness. Transcranial direct current stimulation (tDCS) is a low-cost, non-invasive brain stimulation intervention that improves cognitive function in healthy adults and people with neuropsychologic diagnoses beyond current interventions. Despite the available evidence of the effectiveness of tDCS in improving cognition generally, only two small TBI trials have been conducted based on the most recent systematic review of tDCS effectiveness for cognition following neurological impairment. We found no tDCS studies that addressed TBI-related balance impairments.

Methods

A scoping review using a peer-reviewed search of eight databases was completed in July 2022. Two assessors completed a multi-step review and completed data extraction on included studies using a priori items recommended in tDCS and TBI research guidelines.

Results

A total of 399 results were reviewed for inclusion and 12 met the criteria and had data extracted from them by two assessors using Google Forms. Consensus on combined data results included a third assessor when needed. No studies using tDCS for cognition-related balance were found.

Discussion

Guidelines and technology measures increase the identification of brain differences that alter tDCS effects on cognition. People with mild-severe and acute-chronic TBI tolerated and benefited from tDCS. TBI-related cognition is understudied, and systematic research that incorporates recommended data elements is needed to advance tDCS interventions to improve cognition after TBI weeks to years after injury.
Clinical-radiomic models based on digital breast tomosynthesis images: a preliminary investigation of a predictive tool for cancer diagnosis
Authors: Murtas Federica , Landoni Valeria , Ordòñez Pedro , Greco Laura , Ferranti Francesca Romana , Russo Andrea , Perracchio Letizia , Vidiri Antonello
Published: May 2023

Objective

This study aimed to develop a clinical–radiomic model based on radiomic features extracted from digital breast tomosynthesis (DBT) images and clinical factors that may help to discriminate between benign and malignant breast lesions.

Materials and methods

A total of 150 patients were included in this study. DBT images acquired in the setting of a screening protocol were used. Lesions were delineated by two expert radiologists. Malignity was always confirmed by histopathological data. The data were randomly divided into training and validation set with an 80:20 ratio. A total of 58 radiomic features were extracted from each lesion using the LIFEx Software. Three different key methods of feature selection were implemented in Python: (1) K best (KB), (2) sequential (S), and (3) Random Forrest (RF). A model was therefore produced for each subset of seven variables using a machine-learning algorithm, which exploits the RF classification based on the Gini index.

Results

All three clinical–radiomic models show significant differences (p < 0.05) between malignant and benign tumors. The area under the curve (AUC) values of the models obtained with three different feature selection methods were 0.72 [0.64,0.80], 0.72 [0.64,0.80] and 0.74 [0.66,0.82] for KB, SFS, and RF, respectively.

Conclusion

The clinical–radiomic models developed by using radiomic features from DBT images showed a good discriminating power and hence may help radiologists in breast cancer tumor diagnoses already at the first screening.
Identification of novel serum autoantibody biomarkers for early esophageal squamous cell carcinoma and high-grade intraepithelial neoplasia detection
Authors: Chen Zhibin , Xing Jie , Zheng Cuiling , Zhu Qianyu , He Pingping , Zhou Donghu , Li Xiaojin , Li Yanmeng , Qi Saiping , Ouyang Qin , Zhang Bei , Xie Yibin , Ren Jiansong , Cao Bangwei , Zhu Shengtao , Huang Jian
Published: May 2023

Background

Early diagnosis of esophageal squamous cell carcinoma (ESCC) is critical for effective treatment and optimal prognosis; however, less study on serum biomarkers for the early ESCC detection has been reported. The aim of this study was to identify and evaluate several serum autoantibody biomarkers in early ESCC.

Methods

We initially screened candidate tumor-associated autoantibodies (TAAbs) associated with ESCC by serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (nano-LC-Q-TOF-MS/MS), and the TAAbs were further subjected to analysis by Enzyme-linked immunosorbent assay (ELISA) in a clinical cohort (386 participants, including 161 patients with ESCC, 49 patients with high-grade intraepithelial neoplasia [HGIN] and 176 healthy controls [HC]). Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic performance.

Results

The serum levels of CETN2 and POFUT1 autoantibodies which were identified by SERPA were statistically different between ESCC or HGIN patients and HC in ELISA analysis with the area under the curve (AUC) values of 0.709 (95%CI: 0.654-0.764) and 0.741 (95%CI: 0.689-0.793), 0.717 (95%CI: 0.634-0.800) and 0.703 (95%CI: 0.627-0.779) for detection of ESCC and HGIN, respectively. Combining these two markers, the AUCs were 0.781 (95%CI: 0.733-0.829), 0.754 (95%CI: 0.694-0.814) and 0.756 (95%CI: 0.686-0.827) when distinguishing ESCC, early ESCC and HGIN from HC, respectively. Meanwhile, the expression of CETN2 and POFUT1 was found to be correlated with ESCC progression.

Conclusions

Our data suggest that CETN2 and POFUT1 autoantibodies have potential diagnostic value for ESCC and HGIN, which may provide novel insights for early ESCC and precancerous lesions detection.
Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette–Guérin instillation in non-muscle-invasive bladder cancer: a network meta-analysis
Authors: Zeng Na , Xu Meng-Yao , Sun Jian-Xuan , Liu Chen-Qian , Xu Jin-Zhou , An Ye , Zhong Xing-Yu , Ma Si-Yang , He Hao-Dong , Xia Qi-Dong , Wang Shao-Gang
Published: May 2023

Introduction

With the shortage of bacillus Calmette–Guérin (BCG) vaccine, it is important to find an alternative to BCG instillation, which is the most commonly used adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC) patients after transurethral resection of bladder tumor treatment (TURBt) to delay tumor recurrence. Hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C (MMC) is a potential treatment choice. We aim to compare HIVEC with BCG instillation for the preventive efficacy of bladder tumor recurrence and progression.

Methods

A network meta-analysis (NMA) was taken with MMC instillation and TURBt as the attached comparators. Randomized controlled trials (RCTs) with NIMBC patients after TURBt were included. Articles with pure BCG unresponsive patients and combined therapies were excluded. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023390363).

Results

It was found that HIVEC had a non-significant 22% relative reduction in bladder tumor recurrence compared with BCG instillation [HIVEC vs. BCG: HR 0.78, 95% credible interval (CrI) 0.55–1.08] and a nonsignificant higher risk of bladder tumor progression (BCG vs. HIVEC: HR 0.77, 95% CrI 0.22–3.03).

Discussion

HIVEC is a potential alternative to BCG, and it is expected to be the standard therapy for NMIBC patients after TURBt during the global shortage of BCG.

Systematic Review Registration

PROSPERO identifier, CRD42023390363
Case report: Apatinib combined with neoadjuvant therapy for primary squamous cell carcinoma of the breast: a case report
Authors: Gao Fangfang , Li Jingtai , Liao Haoran , Fan Pingming , Wang Minjian , Liu Yu , Ding Linwei , Du Guankui
Published: May 2023

Primary squamous cell carcinoma of the breast is a rare subtype of carcinoma of chemosis for which there is no effective chemotherapy regimen. Breast squamous cell carcinoma is usually “triple negative”, with poor chemotherapy effects and poor prognosis. Here, we report a successful case of primary breast squamous cell carcinoma treated with apatinib. The patient was treated with 2 cycles of apatinib. The efficacy was evaluated as partial remission, and a sublesion of approximately 4 cm fell off.
Effect of sodium bicarbonate on cardiovascular outcome and mortality in patients with advanced chronic kidney disease
Authors: Cheng Ya-Lien , Huang Shu-Chun , Ho Ming-Yun , Li Yan-Rong , Yen Chieh-Li , Chen Kuan-Hsing , Sun Wei-Chiao , Fan Pei-Yi , Chen Jung-Sheng , Lin Chihung , Hsiao Ching-Chung
Published: May 2023

Background: Metabolic acidosis is a common complication in patients with chronic kidney disease (CKD). Oral sodium bicarbonate is often used to treat metabolic acidosis and prevent CKD progression. However, there is limited information about the effect of sodium bicarbonate on major adverse cardiovascular events (MACE) and mortality in patients with pre-dialysis advanced CKD.

Method: 25599 patients with CKD stage V between January 1, 2001 and December 31, 2019 were identified from the Chang Gung Research Database (CGRD), a multi-institutional electronic medical record database in Taiwan. The exposure was defined as receiving sodium bicarbonate or not. Baseline characteristics were balanced using propensity score weighting between two groups. Primary outcomes were dialysis initiation, all-cause mortality, and major adverse cardiovascular events (MACE) (myocardial infarction, heart failure, stroke). The risks of dialysis, MACE, and mortality were compared between two groups using Cox proportional hazards models. In addition, we performed analyzes using Fine and Gray sub-distribution hazard models that considered death as a competing risk.

Result: Among 25599 patients with CKD stage V, 5084 patients (19.9%) were sodium bicarbonate users while 20515 (80.1%) were sodium bicarbonate non-users. The groups had similar risk of dialysis initiation (hazard ratio (HR): 0.98, 95% confidence interval (CI): 0.95-1.02, p < 0.379). However, taking sodium bicarbonate was associated with a significantly lower risks of MACE (HR: 0.95, 95% CI 0.92–0.98, p < 0.001) and hospitalizations for acute pulmonary edema (HR: 0.92, 95% CI 0.88–0.96, p < 0.001) compared with non-users. The mortality risks were significantly lower in sodium bicarbonate users compared with sodium bicarbonate non-users (HR: 0.75, 95% CI 0.74–0.77, p < 0.001).

Conclusion: This cohort study revealed that in real world practice, use of sodium bicarbonate was associated with similar risk of dialysis compared with non-users among patients with advanced CKD stage V. Nonetheless, use of sodium bicarbonate was associated with significantly lower rate of MACE and mortality. Findings reinforce the benefits of sodium bicarbonate therapy in the expanding CKD population. Further prospective studies are needed to confirm these findings.
Research progress of interleukin-15 in cancer immunotherapy
Authors: Cai Menghan , Huang Xuan , Huang Xiting , Ju Dianwen , Zhu Yi Zhun , Ye Li
Published: May 2023

Interleukin-15 (IL-15) is a cytokine that belongs to the interleukin-2 (IL-2) family and is essential for the development, proliferation, and activation of immune cells, including natural killer (NK) cells, T cells and B cells. Recent studies have revealed that interleukin-15 also plays a critical role in cancer immunotherapy. Interleukin-15 agonist molecules have shown that interleukin-15 agonists are effective in inhibiting tumor growth and preventing metastasis, and some are undergoing clinical trials. In this review, we will summarize the recent progress in interleukin-15 research over the past 5 years, highlighting its potential applications in cancer immunotherapy and the progress of interleukin-15 agonist development.
The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy
Authors: Sun Jiaao , Yu Liyan , Qu Xueling , Huang Tao
Published: May 2023

Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for over 3 decades and consist of three isotypes, including PPARα, γ, and β/δ, that were originally considered key metabolic regulators controlling energy homeostasis in the body. Cancer has become a leading cause of human mortality worldwide, and the role of peroxisome proliferator-activated receptors in cancer is increasingly being investigated, especially the deep molecular mechanisms and effective cancer therapies. Peroxisome proliferator-activated receptors are an important class of lipid sensors and are involved in the regulation of multiple metabolic pathways and cell fate. They can regulate cancer progression in different tissues by activating endogenous or synthetic compounds. This review emphasizes the significance and knowledge of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anti-cancer treatment by summarizing recent research on peroxisome proliferator-activated receptors. In general, peroxisome proliferator-activated receptors either promote or suppress cancer in different types of tumor microenvironments. The emergence of this difference depends on various factors, including peroxisome proliferator-activated receptor type, cancer type, and tumor stage. Simultaneously, the effect of anti-cancer therapy based on drug-targeted PPARs differs or even opposes among the three peroxisome proliferator-activated receptor homotypes and different cancer types. Therefore, the current status and challenges of the use of peroxisome proliferator-activated receptors agonists and antagonists in cancer treatment are further explored in this review.
Genome-wide association analysis reveals the optimal genomic regions for pod size in bean
Authors: Li Mao , Wu Xinyi , Wang Baogen , Wu Xiaohua , Wang Ying , Wang Jian , Dong Junyang , Wu Jian , Lu Zhongfu , Sun Yuyan , Dong Wenqi , Yang Jing , Li Guojing
Published: May 2023

The snap bean is the most commonly grown vegetable legume worldwide, and its pod size is both an important yield and appearance quality trait. However, the improvement of pod size in snap beans grown in China has been largely hindered by a lack of information on the specific genes that determine pod size. In this study, we identified 88 snap bean accessions and evaluated their pod size traits. Through a genome-wide association study (GWAS), 57 single nucleotide polymorphisms (SNPs) significantly associated with pod size were detected. Candidate gene analysis showed that cytochrome P450 family genes, WRKY, and MYB transcription factors were the predominant candidate genes for pod development, and eight of these 26 candidate genes showed relatively higher expression patterns in flowers and young pods. A significant pod length (PL) SNP and a single pod weight (SPW) SNP were successfully converted into kompetitive allele-specific polymerase chain reaction (KASP) markers and validated in the panel. These results enhance our understanding of the genetic basis of pod size, and also provide genetic resources for the molecular breeding of pod size in snap beans.
Effect of replacing synthetic nitrogen fertilizer with animal manure on grain yield and nitrogen use efficiency in China: a meta‐analysis
Authors: Ren Keyu , Sun Yue , Zou Hongqin , Li Dejin , Lu Changai , Duan Yinghua , Zhang Wenju
Published: May 2023

To reduce reliance on synthetic nitrogen (N) fertilizer and sustain food production, replacing synthetic N fertilizer with animal manure as an effective method is widely used. However, the effects of replacing synthetic N fertilizer with animal manure on crop yield and nitrogen use efficiency (NUE) remain uncertain under varying fertilization management practices, climate conditions, and soil properties. Here, we performed a meta-analysis of wheat (Triticum aestivum L.), maize (Zea mays L.), and rice (Oryza sativa L.) based on 118 published studies conducted in China. Overall, the results indicated that substituting synthetic N fertilizer with manure increased yield by 3.3%−3.9% for the three grain crops and increased NUE by 6.3%−10.0%. Crop yields and NUE did not significantly increase at a low N application rate (≤120 kg ha−1) or high substitution rate (>60%). Yields and NUE values had higher increases for upland crops (wheat and maize) in temperate monsoon climate/temperate continental climate regions with less average annual rainfall (AAR) and lower mean annual temperature (MAT), while rice had higher increases in subtropical monsoon climate regions with more AAR and higher MAT. The effect of manure substitution was better in soil with low organic matter and available phosphorus. Our study shows that the optimal substitution rate was 44% and the total N fertilizer input cannot be less than 161 kg ha−1 when substituting synthetic N fertilizer with manure. Moreover, site‐specific conditions should also be considered.
Genome-wide association and epistasis studies reveal the genetic basis of saline-alkali tolerance at the germination stage in rice
Authors: Zhang Guogen , Bi Zhiyuan , Jiang Jing , Lu Jingbing , Li Keyang , Bai Di , Wang Xinchen , Zhao Xueyu , Li Min , Zhao Xiuqin , Wang Wensheng , Xu Jianlong , Li Zhikang , Zhang Fan , Shi Yingyao
Published: May 2023

Introduction

Saline-alkali stress is one of the main abiotic factors limiting rice production worldwide. With the widespread use of rice direct seeding technology, it has become increasingly important to improve rice saline-alkali tolerance at the germination stage.

Methods

To understand the genetic basis of saline-alkali tolerance and facilitate breeding efforts for developing saline-alkali tolerant rice varieties, the genetic basis of rice saline-alkali tolerance was dissected by phenotyping seven germination-related traits of 736 diverse rice accessions under the saline-alkali stress and control conditions using genome-wide association and epistasis analysis (GWAES).

Results

Totally, 165 main-effect quantitative trait nucleotides (QTNs) and 124 additional epistatic QTNs were identified as significantly associated with saline-alkali tolerance, which explained a significant portion of the total phenotypic variation of the saline-alkali tolerance traits in the 736 rice accessions. Most of these QTNs were located in genomic regions either harboring saline-alkali tolerance QTNs or known genes for saline-alkali tolerance reported previously. Epistasis as an important genetic basis of rice saline-alkali tolerance was validated by genomic best linear unbiased prediction in which inclusion of both main-effect and epistatic QTNs showed a consistently better prediction accuracy than either main-effect or epistatic QTNs alone. Candidate genes for two pairs of important epistatic QTNs were suggested based on combined evidence from the high-resolution mapping plus their reported molecular functions. The first pair included a glycosyltransferase gene LOC_Os02g51900 (UGT85E1) and an E3 ligase gene LOC_Os04g01490 (OsSIRP4), while the second pair comprised an ethylene-responsive transcriptional factor, AP59 (LOC_Os02g43790), and a Bcl-2-associated athanogene gene, OsBAG1 (LOC_Os09g35630) for salt tolerance. Detailed haplotype analyses at both gene promoter and CDS regions of these candidate genes for important QTNs identified favorable haplotype combinations with large effects on saline-alkali tolerance, which can be used to improve rice saline-alkali tolerance by selective introgression.

Discussion

Our findings provided saline-alkali tolerant germplasm resources and valuable genetic information to be used in future functional genomic and breeding efforts of rice saline-alkali tolerance at the germination stage.
Low canopy temperature and high stomatal conductance contribute to high grain yield of contrasting japonica rice under aerobic conditions
Authors: Gong Wenliu , Proud Christopher , Fukai Shu , Mitchell Jaquie
Published: May 2023

Water limitation is a major concern in rice production. It has been suggested that with adapted genotypes, aerobic rice production offers the maintenance of grain yield while saving water. However, there has been limited exploration of japonica germplasm adapted for high-yield aerobic environments. Therefore, three aerobic field experiments with different levels of relatively high-water availability were conducted across two seasons to explore genetic variation in grain yield and physiological traits that contributed to high yield. In the first season, a japonica rice diversity set was explored under well-watered (WW20) conditions. While in the second season, a well-watered (WW21) experiment and an intermittent water deficit (IWD21) experiment were conducted to examine the performance of a subset of 38 genotypes selected for low (mean of −6.01°C) and high (mean of −8.22°C) canopy temperature depression (CTD). In WW20, CTD explained 19% of the variation in grain yield which was similar to the variation explained by plant height, lodging, and leaf death response to heat. In WW21, a relatively high average grain yield (9.09 t ha−1) was achieved, while a 31% reduction was achieved in IWD21. Compared with the low CTD group, the high CTD group had 21% and 28% higher stomatal conductance, 32% and 66% higher photosynthetic rate, and 17% and 29% higher grain yield in the WW21 and IWD21, respectively. This work demonstrated the advantage of higher stomatal conductance and cooler canopy temperature which resulted in higher photosynthetic rate and higher grain yield. Two promising genotypes with high grain yield, cooler canopy temperature, and high stomatal conductance were identified as donor genotypes for use by the rice breeding program when aerobic rice production is a target. Field screening for cooler canopies within a breeding program with high-throughput phenotyping tools would be of value for genotype selection for aerobic adaption.
Grafting enhances drought tolerance by regulating and mobilizing proteome, transcriptome and molecular physiology in okra genotypes
Authors: Razi Kaukab , Muneer Sowbiya
Published: May 2023

Drought stress poses a serious concern to the growth, development, and quality of the okra crop due to factors including decreased yield, inadequate development of dietary fibre, increased mite infestation, and decreased seed viability. Grafting is one of the strategies that have been developed to increase the drought stress tolerance of crops. We conducted proteomics, transcriptomics and integrated it with molecular physiology to assess the response of sensitive okra genotypes; NS7772 (G1), Green gold (G2) and OH3312 (G3) (scion) grafted to NS7774 (rootstock). In our studies we observed that sensitive okra genotypes grafted to tolerant genotypes mitigated the deleterious effects of drought stress through an increase in physiochemical parameters, and lowered reactive oxygen species. A comparative proteomic analysis showed a stress responsive proteins related to Photosynthesis, energy and metabolism, defence response, protein and nucleic acid biosynthesis. A proteomic investigation demonstrated that scions grafted onto okra rootstocks increased more photosynthesis-related proteins during drought stress, indicating an increase in photosynthetic activity when plants were subjected to drought stress. Furthermore, transcriptome of RD2, PP2C, HAT22, WRKY and DREB increased significantly, specifically for grafted NS7772 genotype. Furthermore, our study also indicated that grafting improved the yield components such as number of pods and seeds per plant, maximum fruit diameter, and maximum plant height in all genotypes which directly contributed towards their high resistance towards drought stress.