bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of stress on avoidance in rodents: An unresolved matter
Authors: López-Moraga Alba , Beckers Tom , Luyten Laura
Published: September 2022

In the face of a possible threat, a range of physiological (e.g., increased heart rate) and behavioral (e.g., avoidance or escape) responses are recruited. Here, we will focus on avoidance, in its persistent form one of the core symptoms of anxiety disorders and obsessive-compulsive disorder. The initial goal of fear and avoidance responses is to increase survival, but if they become persistent or overgeneralize, they can disrupt normal daily functioning, and ultimately even result in anxiety-related disorders. Relatedly, acute stress responses promote adaptation and survival, while chronic stress has been found to aggravate pathophysiology. Thus, stress might trigger the transition from adaptive to maladaptive responses, e.g., from goal-directed to persistent avoidance. Animal models are prime tools to unravel if and how stress influences avoidance. This is typically done by performing stress inductions prior to the assessment of (passive or active) avoidance behavior. Despite its clinical relevance, the current literature on this topic is fragmented, and an overall conclusion is lacking. In this Review, we first recapitulate the state of the art regarding stress and active as well as passive avoidance procedures. We then summarize the behavioral effects of acute and chronic stress on active and passive avoidance, and discuss the main neurobiological findings of the field. Finally, we highlight possible reasons for the largely contradictory findings in the literature and we propose strategies to further unravel the effect of stress on avoidance behavior. A deeper understanding of this currently unresolved matter may provide further insights in the etiology and treatment of anxiety-related disorders.
Predicting futile recanalization, malignant cerebral edema, and cerebral herniation using intelligible ensemble machine learning following mechanical thrombectomy for acute ischemic stroke
Authors: Zeng Weixiong , Li Wei , Huang Kaibin , Lin Zhenzhou , Dai Hui , He Zilong , Liu Renyi , Zeng Zhaodong , Qin Genggeng , Chen Weiguo , Wu Yongming
Published: September 2022

Purpose

To establish an ensemble machine learning (ML) model for predicting the risk of futile recanalization, malignant cerebral edema (MCE), and cerebral herniation (CH) in patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) and recanalization.

Methods

This prospective study included 110 patients with premorbid mRS ≤ 2 who met the inclusion criteria. Futile recanalization was defined as a 90-day modified Rankin Scale score >2. Clinical and imaging data were used to construct five ML models that were fused into a logistic regression algorithm using the stacking method (LR-Stacking). We added the Shapley Additive Explanation method to display crucial factors and explain the decision process of models for each patient. Prediction performances were compared using area under the receiver operating characteristic curve (AUC), F1-score, and decision curve analysis (DCA).

Results

A total of 61 patients (55.5%) experienced futile recanalization, and 34 (30.9%) and 22 (20.0%) patients developed MCE and CH, respectively. In test set, the AUCs for the LR-Stacking model were 0.949, 0.885, and 0.904 for the three outcomes mentioned above. The F1-scores were 0.882, 0.895, and 0.909, respectively. The DCA showed that the LR-Stacking model provided more net benefits for predicting MCE and CH. The most important factors were the hypodensity volume and proportion in the corresponding vascular supply area.

Conclusion

Using the ensemble ML model to analyze the clinical and imaging data of AIS patients with successful recanalization at admission and within 24 h after MT allowed for accurately predicting the risks of futile recanalization, MCE, and CH.
Anatomical distribution of CGRP-containing lumbosacral spinal afferent neurons in the mouse uterine horn
Authors: Dodds Kelsi N. , Kyloh Melinda A. , Travis Lee , Cox Mack , Hibberd Tim J. , Spencer Nick J.
Published: September 2022

Sensory stimuli from the uterus are detected by spinal afferent neurons whose cell bodies arise from thoracolumbar and lumbosacral dorsal root ganglia (DRG). Using an in vivo survival surgical technique developed in our laboratory to remove select DRG from live mice, we recently quantified the topographical distribution of thoracolumbar spinal afferents innervating the mouse uterine horn, revealed by loss of immunoreactivity to calcitonin gene-related peptide (CGRP). Here, we used the same technique to investigate the distribution of lumbosacral uterine spinal afferents, in which L5-S1 DRG were unilaterally removed from adult female C57BL/6J mice (N = 6). Following 10–12 days recovery, CGRP immunoreactivity was quantified along the length of uterine horns using fluorescence immunohistochemistry. Relative to myometrial thickness, overall CGRP density in uterine tissues ipsilateral to L5-S1 DRG removal was reduced compared to the DRG-intact, contralateral side (P = 0.0265). Regionally, however, myometrial CGRP density was unchanged in the cranial, mid, and caudal portions. Similarly, CGRP-expressing nerve fiber counts, network lengths, junctions, and the proportion of area occupied by CGRP immunoreactivity were unaffected by DRG removal (P ≥ 0.2438). Retrograde neuronal tracing from the caudal uterine horn revealed fewer spinal afferents here arise from lumbosacral than thoracolumbar DRG (P = 0.0442) (N = 4). These data indicate that, unlike thoracolumbar DRG, lumbosacral spinal afferent nerves supply relatively modest sensory innervation across the mouse uterine horn, with no regional specificity. We conclude most sensory information between the mouse uterine horn and central nervous system is likely relayed via thoracolumbar spinal afferents.
Altered regional homogeneity of spontaneous brain activity in patients with toothache: A resting-state functional magnetic resonance imaging study
Authors: Yang Jun , Shao Yi , Li Bin , Yu Qiu-Yue , Ge Qian-Min , Li Biao , Pan Yi-Cong , Liang Rong-Bin , Wu Shi-Nan , Li Qiu-Yu , He Yu-Lin
Published: September 2022

Toothache (TA) is a common and severe pain, but its effects on the brain are somewhat unclear. In this study, functional magnetic resonance imaging (fMRI) was used to compare regional homogeneity (ReHo) between TA patients and a normal control group and to explore the brain activity changes during TA, establishing the theoretical basis for the mechanism of neuropathic pain. In total, 20 TA patients and 20 healthy controls (HCs) were recruited and underwent assessment of pain, and then resting-state fMRI (rs-fMRI). The ReHo method was used to analyze the original whole-brain images. Pearson’s correlation analysis was used to assess the relationship between mean ReHo values in each brain region and clinical symptoms, and the receiver operating characteristic (ROC) curve was used to conduct correlation analysis on the brain regions studied. The ReHo values of the right lingual gyrus (RLG), right superior occipital gyrus (RSOG), left middle occipital gyrus (LMOG) and right postcentral gyrus (RPG) in the TA group were significantly higher than in HCs. The mean ReHo values in the RLG were positively correlated with the anxiety score (AS) (r = 0.723, p < 0.001), depression score (DS) (r = 0.850, p < 0.001) and visual analogue score (VAS) (r = 0.837, p < 0.001). The mean ReHo values of RSOG were also positively correlated with AS (r = 0.687, p = 0.001), DS (r = 0.661, p = 0.002) and VAS (r = 0.712, p < 0.001). The areas under the ROC curve of specific brain area ReHo values were as follows: RLG, 0.975; RSOG, 0.959; LMOG, 0.975; RPG, 1.000. Various degrees of brain activity changes reflected by ReHo values in different areas of the brain indicate the impact of TA on brain function. These findings may reveal related neural mechanisms underlying TA.
Melatonin: Manager of psychosomatic and metabolic disorders in polymorbid cardiovascular pathology
Authors: Partsernyak Alexander S. , Polyakova Victoria O. , Trufanov Artem G. , Medvedev Dmitriy S. , Trotsyuk Dina V. , Markin Kirill , Kurasov Evgeniy S. , Kuznetsova Evgeniya V. , Krasichkov Alexander S.
Published: September 2022

Objectives

To investigate the relationship between changes in circadian patterns of melatonin and clinical manifestations of polymorbid cardiovascular pathology (PCVP) in young men and to analyze the effectiveness of their complex treatment.

Materials and methods

We made the immunohistochemical (IHC) analysis of epiphysis tissues from autopsies of 25 men aged 32–44 with PCVP and metabolic syndrome (MS) who had died as a result of ischemic cardiomyopathy (IC) and 25 persons after the car accident as a control group. Then, 93 young men aged 35–44 with PCVP, metabolic syndrome, and depressive spectrum disorders (DSD) were divided into three groups: (1) standard therapy; (2) standard therapy and psychotherapy sessions; (3) standard therapy in combination with psychotherapeutic and psychophysiological visual and auditory correction sessions. The control group included 24 conditionally healthy male volunteers. Before and after the treatment, we studied the anthropometric status, lipid and carbohydrate metabolism indicators, the level of urinary 6-hydroxymelatonin sulfate, the degree of nocturnal decrease in blood pressure (BP), and the relationship of these indicators with circadian variations of melatonin excretion.

Results

Young polymorbid patients who died from IC have a lower expression of melatonin type 1 and 2 receptors. All patients with PCVP showed a decrease in the nocturnal melatonin excretion fraction and a correlation with higher severity of depressive (r = −0.72) and anxiety (r = −0.66) symptoms. Reduced values of the 6-hydroxymelatonin sulfate (6-SM) in the 1st (r = 0.45), 2nd (r = 0.39), and 3rd (r = 0.51) groups before treatment was associated with periods of increased BP. The achievement of melatonin excretion reference values and normalization of biochemical parameters of carbohydrate and lipid metabolism, daily BP profile, and psychophysiological state were noted in all three patients’ groups, with a more pronounced effect in group 3.

Conclusion

Low nocturnal melatonin excretion levels are associated with greater severity of clinical symptoms and a higher risk of death in patients with PCVP. Therefore, comprehensive therapy may be more effective for correcting this disease.
Intention-based predictive information modulates auditory deviance processing
Authors: Widmann Andreas , Schröger Erich
Published: September 2022

The human brain is highly responsive to (deviant) sounds violating an auditory regularity. Respective brain responses are usually investigated in situations when the sounds were produced by the experimenter. Acknowledging that humans also actively produce sounds, the present event-related potential study tested for differences in the brain responses to deviants that were produced by the listeners by pressing one of two buttons. In one condition, deviants were unpredictable with respect to the button-sound association. In another condition, deviants were predictable with high validity yielding correctly predicted deviants and incorrectly predicted (mispredicted) deviants. Temporal principal component analysis revealed deviant-specific N1 enhancement, mismatch negativity (MMN) and P3a. N1 enhancements were highly similar for each deviant type, indicating that the underlying neural mechanism is not affected by intention-based expectation about the self-produced forthcoming sound. The MMN was abolished for predictable deviants, suggesting that the intention-based prediction for a deviant can overwrite the prediction derived from the auditory regularity (predicting a standard). The P3a was present for each deviant type but was largest for mispredicted deviants. It is argued that the processes underlying P3a not only evaluate the deviant with respect to the fact that it violates an auditory regularity but also with respect to the intended sensorial effect of an action. Overall, our results specify current theories of auditory predictive processing, as they reveal that intention-based predictions exert different effects on different deviance-specific brain responses.
Ties between reading faces, bodies, eyes, and autistic traits
Authors: Pavlova Marina A. , Romagnano Valentina , Kubon Julian , Isernia Sara , Fallgatter Andreas J. , Sokolov Alexander N.
Published: September 2022

While reading covered with masks faces during the COVID-19 pandemic, for efficient social interaction, we need to combine information from different sources such as the eyes (without faces hidden by masks) and bodies. This may be challenging for individuals with neuropsychiatric conditions, in particular, autism spectrum disorders. Here we examined whether reading of dynamic faces, bodies, and eyes are tied in a gender-specific way, and how these capabilities are related to autistic traits expression. Females and males accomplished a task with point-light faces along with a task with point-light body locomotion portraying different emotional expressions. They had to infer emotional content of displays. In addition, participants were administered the Reading the Mind in the Eyes Test, modified and Autism Spectrum Quotient questionnaire. The findings show that only in females, inferring emotions from dynamic bodies and faces are firmly linked, whereas in males, reading in the eyes is knotted with face reading. Strikingly, in neurotypical males only, accuracy of face, body, and eyes reading was negatively tied with autistic traits. The outcome points to gender-specific modes in social cognition: females rely upon merely dynamic cues while reading faces and bodies, whereas males most likely trust configural information. The findings are of value for examination of face and body language reading in neuropsychiatric conditions, in particular, autism, most of which are gender/sex-specific. This work suggests that if male individuals with autistic traits experience difficulties in reading covered with masks faces, these deficits may be unlikely compensated by reading (even dynamic) bodies and faces. By contrast, in females, reading covered faces as well as reading language of dynamic bodies and faces are not compulsorily connected to autistic traits preventing them from paying high costs for maladaptive social interaction.
Effects of probiotic and magnesium co-supplementation on mood, cognition, intestinal barrier function and inflammation in individuals with obesity and depressed mood: A randomized, double-blind placebo-controlled clinical trial
Authors: Mahboobi Sepideh , Ghasvarian Marzieh , Ghaem Haleh , Alipour Hamzeh , Alipour Shohreh , Eftekhari Mohammad Hassan
Published: September 2022

Background

The co-occurrence of obesity and mood impairments named as “metabolic mood syndrome” (MMS) is often neglected in the obesity management. This study aimed to evaluate effects of Probio-Tec ®BG-VCap-6.5 and magnesium co-supplementation on mood, cognition, intestinal barrier function and serum C reactive protein (CRP) levels in participants with obesity and depressed mood.

Design

Seventy-four eligible participants were randomly allocated to either Probio-Tec®BG-VCap-6.5 [containing Lactobacillus rhamnosus (LGG®) and Bifidobacterium animalis subsp. Lactis (BB-12®)] + Magnesium chloride or placebo for 9 weeks. Sociodemographic data were collected in the beginning. Anthropometric, dietary and physical activity (PA) assessments were carried out. Beck Depression Inventory-II (BDI-II) and Montreal Cognitive Assessment (MoCA) scores were assessed through validated questionnaires. Fasting plasma zonulin, lipopolysaccharide (LPS) and (CRP) were measured by ELIZA kits.

Results

Of seventy-four participants (mean age 37.51 ± 8.10), 52 completed the study. Changes in serum LPS and zonulin were not different significantly between groups (−3.04 ± 44.75 ng/dl, 0.11 ± 5.13, ng/dl, p > 0.05 for LPS and 1.40 ± 48.78 ng/dl, −0.17 ± 6.60, p > 0.05 for zonulin, respectively). CRP levels reduced significantly in intervention group compared to placebo [−474.75 (−1,300.00, −125.00) mg/l vs. 175.20 (−957.75, 1,683.25) mg/l, p = 0.016]. Changes in BDI-II and MoCA scores were not significantly different between intervention (−7.13 ± 5.67, 1.20 ± 2.16, respectively) and placebo (−5.42 ± 6.71, 1.94 ± 1.86, respectively) groups (p > 0.05).

Conclusion

Nine weeks of probiotic and magnesium co-supplementation resulted in decreased CRP levels as an indicator of inflammatory state with no significant effects on mood, cognition and intestinal integrity in individuals with obesity and depressed mood.
Increased diversity of a cervical microbiome associates with cervical cancer
Authors: Zeber-Lubecka Natalia , Kulecka Maria , Lindner Bogusław , Krynicki Ryszard , Paziewska Agnieszka , Nowakowski Andrzej , Bidzinski Mariusz , Ostrowski Jerzy
Published: September 2022

The cervical microbiome (CM) is a complex ecosystem that can change in response to gynecological cancers. We aimed to evaluate changes in the CM of patients who underwent chemoradiation (CRT) therapy for locally advanced cervical cancer. Before and after CRT, cervical swab samples were collected from 16 patients with squamous cell carcinoma of the cervix, and 30 healthy women. All samples were subjected to 16s rRNA-Seq analysis. In healthy premenopausal women the CM comprised mostly Lactobacillus (>90%); the CM community in samples from both pre- and postmenopausal pre-treatment cancer patients was heterogeneous, with a low proportion of Lactobacillus in younger cases. On the genus level, 27 and 11 taxa differentiated healthy controls from cancer patients in pre- and postmenopausal age groups, while 31 and 2 genera differentiated pre- and post-radiation samples and pre-radiation and the follow-up samples, respectively. Microbiome diversity was significantly higher in pre-treatment patients than in healthy controls. The results reveal significant alterations in the CM of cervical cancer patients relative to that in healthy controls; these changes were more striking after CRT. However, further research is needed to determine whether alteration of the CM offers new therapeutic options.
The role of hepatocyte nuclear factor 4α (HNF4α) in tumorigenesis
Authors: Sang Lei , Wang Xingshun , Bai Weiyu , Shen Junling , Zeng Yong , Sun Jianwei
Published: September 2022

Hepatocyte Nuclear Factor 4 Alpha (HNF4α) is a master transcription factor mainly expressed in the liver, kidney, intestine and endocrine pancreas. It regulates multiple target genes involved in embryonic development and metabolism. HNF4α-related diseases include non-alcoholic fatty liver disease (NAFLD), obesity, hypertension, hyperlipidemia, metabolic syndrome and diabetes mellitus. Recently, HNF4α has been emerging as a key player in a variety of cancers. In this review, we summarized the role and mechanism of HNF4α in different types of cancers, especially in liver and colorectal cancer, aiming to provide additional guidance for intervention of these diseases.
Maintenance tegafur-plus-uracil after adjuvant concurrent chemoradiotherapy may improve outcome for resected oral cavity squamous cell carcinoma with extranodal extension
Authors: Huang Pei-Wei , Lin Chien-Yu , Lee Li-Yu , Hsieh Chia-Hsun , Hsu Cheng-Lung , Liau Chi-Ting , Fan Kang-Hsing , Huang Shiang-Fu , Liao Chun-Ta , Chang Tung-Chieh , Wang Hung-Ming
Published: September 2022

Objectives

To evaluate whether tegafur-uracil maintenance (UFTm) following postoperation adjuvant cisplatin-based concurrent chemoradiotherapy (CCRT) may reduce distant metastasis in patients with resected oral cavity squamous cell carcinoma (OSCC) with pathologic extranodal extension (pENE+).

Methods

A retrospective comparison was conducted between two cohorts of patients with resected pENE+ OSCC who completed adjuvant CCRT between March 2015 and December 2017, including one cohort of a phase II trial using UFTm and a trial-eligible but off-protocol cohort without using UFTm (non-UFTm) after their adjuvant CCRT. The UFTm trial enrolled patients without relapse within 2 months after the end of adjuvant CCRT and administered UFT 400 mg/day for 1 year. Kaplan–Meier methods estimated the actuarial rate of distant metastasis-free (DMF), locoregional control (LRC), event-free survival (EFS), and overall survival (OS).

Results

A total of 103 patients were included in this study, 64 patients in UFTm and 39 patients in non-UFTm. Severe adverse events in UFTm included grade 3 anemia (n = 1, 1.6%) and grade 3 mucositis (n = 1, 1.6%). A total of 40 (62.5%) patients completed the full course of UFTm, while the remaining terminated UFTm earlier due to disease relapse (n = 14, 21.8%), poor compliance (n = 9, 14.1%), and adverse event (n = 1, 1.6%). The median (range) follow-up time of surviving patients was 43 (22–65) months. The outcomes compared between UFTm and non-UFTm were OS (hazard ratio [HR] 0.31 [95% CI: 0.17–0.57], p < 0·001), EFS (0.45 [0.25–0.82], 0.009), LRC (0.45 [0.19–1.05], 0.067), and DMF (0.47 [0.24–0.95], 0.035). Multivariable analysis, adjusted for UFTm, Charlson comorbidity index score 1–3, site of tongue, and number of ENE+ LN ≧4, confirmed better OS (0.29 [0.16–0.54], <0.001) and EFS (0.47 [0.26–0.85], 0.012) in favor of UFTm over non-UFTm. The 2-year DM rate was 25.8% in UFTm and 44.2% in non-UFTm. For relapsed patients in UFTm vs. non-UFTm, the rate of metastasectomy for oligometastasis was 53% vs. 6%, and the OS was 21.0 (95% CI: 17.8–24.1) months vs. 11.0 (9.1–12.8) months (p < 0.001), respectively.

Conclusions

UFTm may improve the dismal outcomes of the resected pENE+ OSCC. Further investigations are needed to confirm our observations.
PCDH20 inhibits esophageal squamous cell carcinoma proliferation and migration by suppression of the mitogen-activated protein kinase 9/AKT/β-catenin pathway
Authors: Ning Yijiao , Deng Chaoqun , Li Chunhong , Peng Weiyan , Yan Chun , Ran Jing , Chen Weihong , Liu Yujia , Xia Jiuyi , Ye Lin , Wei Zhengqiang , Xiang Tingxiu
Published: September 2022

Aberrant protocadherins (PCDHs) expression trigger tumor invasion and metastasis. PCDH20 anti-tumor functions in various tumor have been identified. Tumor suppression is due to Wnt/β-catenin pathway antagonism and may be suppressed caused by PCDH20 downregulation through promotor methylation, whereas PCDH20 effects and regulation mechanism in esophageal squamous cell carcinoma (ESCC) remains elusive. We analyzed PCDH20 effects on ESCC and underlying action mechanisms for PCDH20. We test PCDH20 expression in ESCC tissues and cells by semi-quantitative PCR (RT-PCR) and q-PCR (real-time quantitative polymerase chain reaction). MSP (methylation-specific PCR) was carried out to assess the methylation of PCDH20 in ESCC cells and tissues. Anti-tumor effects of PCDH20 in vitro were assessed by clone formation assay, CCK8 assay, Transwell assay, and flow cytometry. Nude mice tumorigenicity was used to assess PCDH20 anti-tumor effect in vivo. Online database, qPCR, and Western blotting were used to identify the downregulation of MAP3K9 by PCDH20, associated with AKT/β-catenin signaling inactivation. We found that PCDH20 expression was dramatically attenuated in esophageal cancer tissues and cells, maybe due to promotor methylation, and ectopic PCDH20 expression suppressed ESCC malignant biological phenotypes. PCDH20 exerted anti-tumor effects by MAP3K9 downregulation, which suppressed AKT/β-catenin signaling in ESCC cells.

Conclusion

PCDH20 was a tumor suppressor gene, which antagonized AKT/β-catenin signaling pathway in ESCC by decreasing MAP3K9.
The impact of macrophages on endothelial cells is potentiated by cycling hypoxia: Enhanced tumor inflammation and metastasis
Authors: Delprat Victor , Huart Camille , Feron Olivier , Soncin Fabrice , Michiels Carine
Published: September 2022

Cycling hypoxia (cyH), neo-angiogenesis, and tumor-associated macrophages are key features of the tumor microenvironment. In this study, we demonstrate that cyH potentiates the induction by unpolarized and M1-like macrophages of endothelial inflammatory phenotype and adhesiveness for monocytes and cancer cells. This process triggers a positive feedback loop sustaining tumor inflammation. This work opens the door for innovative therapeutic strategies to treat tumor inflammation and metastasis.

In cancers, the interaction between macrophages and endothelial cells (ECs) regulates tumor inflammation and metastasis. These cells are both affected by cycling hypoxia (cyH), also called intermittent hypoxia, a feature of the tumor microenvironment. cyH is also known to favor tumor inflammation and metastasis. Nonetheless, the potential impact of cyH on the dialog between macrophages and ECs is still unknown. In this work, the effects of unpolarized, M1-like, and M2-like macrophages exposed to normoxia, chronic hypoxia (chH), and cyH on endothelial adhesion molecule expression, pro-inflammatory gene expression, and EC adhesiveness for monocytes and cancer cells were investigated. cyH increased the ability of unpolarized and M1-like macrophages to induce EC inflammation and to increase the expression of the EC endothelial adhesion molecule ICAM1, respectively. Unpolarized, M1-like, and M2-like macrophages were all able to promote EC adhesive properties toward cancer cells. Furthermore, the ability of macrophages (mostly M1-like) to shift EC phenotype toward one allowing cancer cell and monocyte adhesion onto ECs was potentiated by cyH. These effects were specific to cyH because they were not observed with chH. Together, these results show that cyH amplifies the effects of macrophages on ECs, which may promote tumor inflammation and metastasis.
Molecular biology of pancreatic neuroendocrine tumors: From mechanism to translation
Authors: Shen Xiaofei , Wang Xingzhou , Lu Xiaofeng , Zhao Yang , Guan Wenxian
Published: September 2022

Pancreatic neuroendocrine tumors (pNETs) are a group of heterogeneous tumors originated from progenitor cells. As these tumors are predominantly non-functional, most of them display asymptomatic characteristics, making it difficult to be realized from early onset. Therefore, patients with pNETs are usually diagnosed with metastatic disease or at a late disease stage. The relatively low incidence also limits our understanding of the biological background of pNETs, which largely impair the development of new effective drugs. The fact that up to 10% of pNETs develop in patients with genetic syndromes have promoted researchers to focus on the gene mutations and driver mutations in MEN1, DAXX/ATRX and mTOR signaling pathway genes have been implicated in disease development and progression. Recent advances in sequencing technologies have further enriched our knowledge of the complex molecular landscape of pNETs, pointing out crucial roles of genes in DNA damage pathways, chromosomal and telomere alterations and epigenetic dysregulation. These novel findings may not only benefit early diagnosis of pNETs, but also help to uncover tumor heterogeneity and shape the future of translational medical treatment. In this review, we focus on the current molecular biology of pNETs and decipher how these findings may translate into future development of targeted therapy.
m6A-binding protein IGF2BP1 promotes the malignant phenotypes of lung adenocarcinoma
Authors: Wu Hansheng , Xu Haijie , Huang Shujie , Tang Yong , Tang Jiming , Zhou Haiyu , Xie Liang , Qiao Guibin
Published: September 2022

Background

Lung adenocarcinoma (LUAD), the most common type of lung cancer, poses a significant threat to the life of patients. N6-methyladenosine modification is the most abundant epigenetic modification and may play an important role in the lung carcinogenesis. IGF2BP1 is a newly discovered m6A-binding protein, but little is known about its role in LUAD.

Methods

Data from TCGA, GEO, Kaplan–Meier Plotter, and GEPIA databases were systematically analyzed to access the expression and prognostic value of IGF2BP1 on LUAD. Real-time polymerase chain reaction, Western blot, and immunohistochemistry were performed to detect the mRNA and protein level of IGF2BP1 in LUAD tissues and para-carcinoma tissues. Functional cell experiments, including Cell Counting Kit-8 assay, Transwell invasion assay, wound healing assay, Annexin V-FITC/PI double-staining assay, and TUNEL assay, were used to investigate the functions of IGF2BP1 on LUAD cell proliferation, invasion, migration, and apoptosis, respectively. The top 50 genes that were positively or negatively related to the expression of IGF2BP1 were identified, and pathway enrichment analysis was performed. m6A modification sites within IGF2BP1-related genes were predicted by SRAMP.

Result

16 m6A regulators were significantly differentially expressed in LUAD tissues. IGF2BP1 was upregulated in LUAD tissues compared with para-carcinoma tissues. High expression of IGF2PB1 was significantly associated with higher clinical stages and poor prognosis of LUAD patients. Furthermore, our functional experiments indicated that IGF2BP1 facilitated cell proliferation, invasion, and migration and suppressed apoptosis in LUAD. Functional enrichment analysis of IGF2BP1-related genes indicated enrichment in several pathways related to oncogenesis. Additionally, m6A modification sites were detected within IGF2BP1-related genes.

Conclusions

Our findings demonstrate that IGF2BP1 plays a contributory role in the development and progression of LUAD. IGF2BP1 has the potential to become a prognostic predictor and therapeutic target for LUAD.
Safety evaluation of early drain removal following pancreaticoduodenectomy: A single-center retrospective cohort study
Authors: Xie Xuehai , Chen Kai , Liu Zonghao , Wang Feng , Ma Yongsu , Zhang Shupeng , Shao Zhijiang , Yang Yinmo , Tian Xiaodong
Published: September 2022

Objectives

The effects of early drain removal (EDR) on postoperative complications after pancreaticoduodenectomy (PD) remains to be investigated. This single-center retrospective cohort study was designed to explore the safety of EDR after PD.

Methods

A total of 112 patients undergoing PD with drain fluid amylase (DFA) on postoperative day (POD) 1 and 3 <= 5000 were divided into EDR and late drain removal (LDR). Propensity Score Matching (PSM) was used. We compared postoperative outcomes between two groups and explore the risk factors of total complications using univariate and multiple logistic regression analyses.

Results

No statistical differences were found in primary outcomes, including Grade B/C postoperative pancreatic fistula (POPF) (Original cohort: 5.71% vs. 3.90%; P = 1.000; PSM cohort: 3.33% vs. 6.67%; P = 1.000), and total complications (Original cohort: 17.14% vs. 32.47%; P = 0.093; PSM cohort: 13.33% vs. 33.33%; P = 0.067). The EDR was associated with shorter in-hospital stay (Original cohort: 11 days vs. 15 days; P < 0.0001; PSM cohort: 11 days vs. 15 days; P < 0.0001).

Conclusions

EDR on POD 3 is safe for patients undergoing PD with low risk of POPF.
Diagnostic challenges in acute monoblastic/monocytic leukemia in children
Authors: Varotto Elena , Munaretto Eleonora , Stefanachi Francesca , Della Torre Fiammetta , Buldini Barbara
Published: September 2022

Acute monoblastic/monocytic leukemia (AMoL), previously defined as M5 according to FAB classification, is one of the most common subtypes of Acute Myeloid Leukemia (AML) in children, representing ~15–24% of all pediatric AMLs. Currently, the characterization of monocytic-lineage neoplasia at diagnosis includes cytomorphology, cytochemistry, immunophenotyping by multiparametric flow cytometry, cytogenetics, and molecular biology. Moreover, measurable residual disease (MRD) detection is critical in recognizing residual blasts refractory to chemotherapy. Nonetheless, diagnosis and MRD detection may still be challenging in pediatric AMoL since the morphological and immunophenotypic features of leukemic cells potentially overlap with those of normal mature monocytic compartment, as well as differential diagnosis can be troublesome, particularly with Juvenile Myelomonocytic Leukemia and reactive monocytosis in infants and young children. A failure or delay in diagnosis and inaccuracy in MRD assessment may worsen the AMoL prognosis. Therefore, improving diagnosis and monitoring techniques is mandatory to stratify and tailor therapies to the risk profile. This Mini Review aims to provide an updated revision of the scientific evidence on pediatric AMoL diagnostic tools.
Visual analysis of allergic rhinitis in children based on web of science and CiteSpace software
Authors: Liu Fang , Chen Na , Wang Rui , Zhang Lei , Li Youwei
Published: September 2022

Background

In recent years, Allergic Rhinitis (AR) in children has caused widespread public concern. However, there are few studies concerning the overall trends in AR research in children based on bibliometric analysis.

Objective

This study aims to explore hotspots and emerging trends in AR in children.

Methods

The relevant publications were searched for in the Web of Science (WOS) Core Collection on December 31, 2021. The searched studies were exported to CiteSpace and Microsoft Excel for further visualized analysis.

Results

In total, 649 articles were included. The number of publications related to AR in children has increased steadily in the last 20 years. Giorgio Ciprandi from Italy has the most articles and the leading countries were China and the USA. Guangzhou Medical University in China and Hallym University in Korea were the institutions with the most articles. The high-frequency keywords included AR, asthma, children, prevalence, and symptoms. Pathogenesis, comorbidity, epidemiology, symptoms, and therapy of AR in children are research hotspots.

Conclusion

Over the past 20 years, research on AR in children has gradually improved. Visualization analysis indicates that pathogenesis, comorbidity, epidemiology, symptoms, and therapy are research hotspots, and immunotherapy and severity are probably the main research directions.
Efficacy and safety of traditional Chinese medicine for intracranial hemorrhage by promoting blood circulation and removing blood stasis: A systematic review and meta-analysis of randomized controlled trials
Authors: Lin Wenjian , Hou Jingjing , Han Tianxiong , Zheng Li , Liang Huazheng , Zhou Xiaoyu
Published: September 2022

Background: Although blood-activating Chinese medicine (BACM) has been reported as adjuvant therapy for intracranial hemorrhage (ICH) in China, high-quality evidence is still lacking. Our study aimed to collect the latest high-quality randomized controlled trials (RCTs) and to evaluate the efficacy and safety of BACM for ICH.

Methods: RCTs published between January 2015 and March 2022 were searched in databases, including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Sino-Med, Wanfang, PubMed, Web of Science, Cochrane Library, and Embase without language restrictions. Eligible RCTs were included and both primary (clinical efficacy evidenced by decreased neurological deficit scores) and secondary outcomes (increased Barthel index, decreased NIHSS, hematoma volume, the volume of cerebral edema, the incidence of side effects, and mortality) were analyzed. The quality of included RCTs was assessed using the Cochrane risk of bias tool. In the meta-analysis, the pooled results were analyzed using Review Manager 5.3 and STATA14.0. Finally, The GRADEpro GDT software (Guideline Development Tool) was used to summarize the results. Sensitivity and subgroup analyses were conducted based on the follow-up time.

Results: Fifteen RCTs, involving 1,579 participants, were included for analysis in our study. The pooled outcomes indicated that BACM combined with western medicine treatment (WMT) was superior to WMT alone for patients with ICH, demonstrated by the improvements in efficacy (RR = 1.22 (95% CI, [1.13 to 1.32], p < 0.001), neurological functions (MDNIHSS = −2.75, 95% CI [−3.74 to −1.76], p < 0.001), and activities of daily living (MDBarthel index = 5.95, 95% CI [3.92 to 7.98], p < 0.001), as well as decreased cerebral hematoma, cerebral edema (MD cerebral hematoma = −2.94, 95% CI [−3.50 to −2.37, p < 0.001 and MDcerebral edema = −2.66, 95% CI [−2.95 to −2.37], p < 0.001), side effects and mortality (RR = 0.84 (95% CI [0.60 to 1.19], p = 0.330 and RR = 0.51 (95% CI, [0.16 to 1.65], p = 0.260). In addition, Conioselinum anthriscoides “Chuanxiong” [Apiaceae], Camellia reticulata Lindl. [Theaceae], and Bupleurum sibiricum var. jeholense (Nakai) C.D.Chu [Apiaceae]) were the most frequently used herbs in the treatment of ICH. Recently, there was a trend toward the extensive use of another two herbs, including Rheum palmatum L. [Polygonaceae], Astragalus mongholicus Bunge [Fabaceae]) for ICH.

Conclusion: BACM combined with WMT seems to be superior to WMT alone for patients with ICH. Further high-quality RCTs are warranted to confirm the efficacy and safety of BACM.
Advances in RIPK1 kinase inhibitors
Authors: Chen Lu , Zhang Xiaoqin , Ou Yaqing , Liu Maoyu , Yu Dongke , Song Zhiheng , Niu Lihong , Zhang Lijuan , Shi Jianyou
Published: September 2022

Programmed necrosis is a new modulated cell death mode with necrotizing morphological characteristics. Receptor interacting protein 1 (RIPK1) is a critical mediator of the programmed necrosis pathway that is involved in stroke, myocardial infarction, fatal systemic inflammatory response syndrome, Alzheimer’s disease, and malignancy. At present, the reported inhibitors are divided into four categories. The first category is the type I ATP-competitive kinase inhibitors that targets the area occupied by the ATP adenylate ring; The second category is type Ⅱ ATP competitive kinase inhibitors targeting the DLG-out conformation of RIPK1; The third category is type Ⅲ kinase inhibitors that compete for binding to allosteric sites near ATP pockets; The last category is others. This paper reviews the structure, biological function, and recent research progress of receptor interaction protein-1 kinase inhibitors.
Differential expression of plasma exosomal microRNA in severe acute pancreatitis
Authors: Xu Yansong , Sun Yuansong , Yin Ran , Dong Tao , Song Kai , Fang Yang , Liu Guodong , Shen Bing , Li He
Published: September 2022

The incidence rate of acute pancreatitis is increasing, and severe acute pancreatitis (SAP) is associated with a high mortality rate, which may be reduced by a deeper understanding of its pathogenesis. In addition, an early determination of the severity of acute pancreatitis remains challenging. The aim of this study was to match potential biomarkers for early identification and monitoring of acute pancreatitis and to shed light on the underlying pathogenic mechanisms of SAP. The expression levels of plasma exosomal microRNA (miRNA) in patients with pancreatitis have been associated with the disease. Thus, this study compared the expression levels of exosomal miRNA in plasma collected from four patients with SAP and from four healthy participants. Analyses of the miRNA expression profiles indicated that three previously unreported miRNAs were differentially expressed in the patient group: Novel1, which was downregulated, and Novel2 and Novel3, which were upregulated. The miRNA target genes for those novel miRNAs were predicted using Metascape. Of these miRNA target genes, those that were also differentially expressed at different time points after disease induction in a mouse model of acute pancreatitis were determined. The gene for complement component 3 (C3), a target gene of Novel3, was the only gene matched in both the patient group and the mouse model. C3 appeared at most of the time points assessed after induction of acute pancreatitis in mice. These findings are foundational evidence that C3 warrants further study as an early biomarker of SAP, for investigating underlying pathogenic mechanisms of SAP, and as a therapeutic target for ameliorating the occurrence or development of SAP.
Theoretical studies of high-power laser beam smoothing via stimulated brillouin scattering in plasma
Authors: Yuan Hang , Hao Jianing , Dan Ziqiang , Zhu Chengyu , Li Yuxin
Published: September 2022

To achieve uniform irradiation, the focal spot from a high-power laser system must be homogeneous; thus, laser beam smoothing is required. In this study, we theoretically demonstrated a novel spatial smoothing method based on stimulated Brillouin scattering (SBS) in a plasma. As SBS is sensitive to pump intensity, the area of higher intensity in the laser beam has a higher reflectivity, leading to a more homogeneous passed beam. From the theoretical simulation, the laser beam modulation significantly decreased in SBS, while the fluence contrast decreased from 15.9% to 9.7%.
Different responses to glucose overload between two strains of largemouth bass (Micropterus salmoides)
Authors: Lei Caixia , Xie Yujing , Song Hongmei , Jiang Peng , Du Jinxing , Li Shengjie
Published: September 2022

In order to improve the glucose utilization capacity of largemouth bass (Micropterus salmoides), responses to glucose overload between two strains (Y: breeding strain; W: wild strain) were compared at 0, 6, 12, and 24 h after glucose injection (1.67 g/kg). The data revealed that plasma glucose in the Y strain (<12 h) recovered faster than in the W strain (12 h), with the Y strain secreted more insulin within 6 h post-injection. Triglyceride (TG) and low-density lipoprotein-cholesterol (VLDL-CH) content in the Y strain increased, peaking at 12 h, then decreased, whereas the W strain’s TG content was not affected and VLDL-CH content decreased. The hepatic and muscular fatty acid synthetase, liver x receptor-1, and sterol regulatory element-binding protein expressions were consistent with the TG content change. Both strains’ liver and muscle glycogen contents exhibited similar trends to that of the glycogen synthase gene—increasing, then declining, and peaking at 6 and 12 h. The expression levels of hepatic and muscular phosphofructokinase and pyruvate kinase in the Y strain increased, peaking at 12 h. In the W strain, they were suppressed and reached the minimum at 24 h. The mRNA levels of hepatic and muscular phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were enhanced and peaked at 24 h in both strains, hepatic isocitrate dehydrogenase-1, and α-ketoglutarate dehydrogenase complex expression increased after declining, peaking at 12 and 24 h. Two genes in the W strain’s muscles showed a similar trend. Both strains’ transcriptome results identified seven common functional genes for resistance to hyperglycemia that were involved in the circadian rhythm pathway, which is a suggested key pathway for coping with hyperglycemia. Furthermore, 48 differential genes were identified between the two strains, and these genes were enriched in the TGF-beta and cell cycle signaling pathways, indicating that these pathways may be key factors affecting the differential responses to glucose overload. We conducted a comprehensive comparison of glucose overload molecular responses between two strains of M. salmoides, and the results can provide a promising strategy to improve the glucose utilization capacity of M. salmoides based on advantageous pre-existing traits.
Impact of cardiorespiratory rehabilitation program on submaximal exercise capacity of Tunisian male patients with post-COVID19: A pilot study
Authors: Toulgui Emna , Benzarti Wafa , Rahmani Chiraz , Aissa Sana , Ghannouchi Ines , Knaz Asma , Sayhi Amani , Sellami Sana , Mahmoudi Khaoula , Jemni Sonia , Gargouri Imene , Hayouni Abdelaziz , Ouanes Walid , Ammar Achraf , Ben saad Helmi
Published: September 2022

Post-COVID19 patients suffer from persistent respiratory, cardiovascular, neurological, and musculoskeletal health complaints such as dyspnea, chest pain/discomfort, and fatigue. In Tunisia, the potential benefits of a cardiorespiratory rehabilitation program (CRRP) after COVID19 remain unclear. The main aim of this study was to evaluate the impact of a CRRP on submaximal exercise capacity, evaluated through the 6-min walk test (6MWT) data in post-COVID19 Tunisian patients. This was a cross-sectional study including 14 moderate to severe COVID19 patients aged from 50 to 70 years. CRRP was performed after the end of patients’ hospitalization in COVID19 units for extensive or severe extents of COVID19. Dyspnea (modified medical research council), spirometry data, handgrip strength values, 6MWT data, and 6-min walk work (i.e., 6-min walk distance x weight) were evaluated 1-week pre-CRRP, and 1-week post-CRRP. CRRP included 12 sessions [3 sessions (70 min each)/week for 4 weeks]. Exercise-training included aerobic cycle endurance, strength training, and educational sessions. Comparing pre- and post- CRRP results showed significant improvements in the means±standard deviations of dyspnea by 1.79 ± 0.80 points (p < 0.001), forced expiratory volume in one second by 110 ± 180 ml (p = 0.04), 6-min walk distance by 35 ± 42 m (p = 0.01), 6-min walk work by 2,448 ± 3,925 mkg (p = 0.048), resting heart-rate by 7 ± 9 bpm (p = 0.02) and resting diastolic blood pressure by 6 ± 10 mmHg (p = 0.045). In Tunisia, CRRP seems to improve the submaximal exercise capacity of post-COVID19 patients, mainly the 6-min walk distance and work.
Detection of seed purity of hybrid wheat using reflectance and transmittance hyperspectral imaging technology
Authors: Zhang Han , Hou Qiling , Luo Bin , Tu Keling , Zhao Changping , Sun Qun
Published: September 2022

Chemical hybridization and genic male sterility systems are two main methods of hybrid wheat production; however, complete sterility of female wheat plants cannot be guaranteed owing to the influence of the growth stage and weather. Consequently, hybrid wheat seeds are inevitably mixed with few parent seeds, especially female seeds. Therefore, seed purity is a key factor in the popularization of hybrid wheat. However, traditional seed purity detection and variety identification methods are time-consuming, laborious, and destructive. Therefore, to establish a non-destructive classification method for hybrid and female parent seeds, three hybrid wheat varieties (Jingmai 9, Jingmai 11, and Jingmai 183) and their parent seeds were sampled. The transmittance and reflectance spectra of all seeds were collected via hyperspectral imaging technology, and a classification model was established using partial least squares-discriminant analysis (PLS-DA) combined with various preprocessing methods. The transmittance spectrum significantly improved the classification of hybrids and female parents compared to that obtained using reflectance spectrum. Specifically, using transmittance spectrum combined with a characteristic wavelength-screening algorithm, the Detrend-CARS-PLS-DA model was established, and the accuracy rates in the testing sets of Jingmai 9, Jingmai 11, and Jingmai 183 were 95.69%, 98.25%, and 97.25%, respectively. In conclusion, transmittance hyperspectral imaging combined with a machine learning algorithm can effectively distinguish female parent seeds from hybrid seeds. These results provide a reference for rapid seed purity detection in the hybrid production process. Owing to the non-destructive and rapid nature of hyperspectral imaging, the detection of hybrid wheat seed purity can be improved by online sorting in the future.