bluuebunny/crossref_metadata_2025 huggingface dataset:
Deletion of the Alzheimer’s disease risk gene Abi3 locus results in obesity and systemic metabolic disruption in mice
Authors: Smith Daniel C. , Karahan Hande , Wijeratne H. R. Sagara , Al-Amin Mamun , McCord Brianne , Moon Younghye , Kim Jungsu
Published: December 2022

Alzheimer’s disease (AD) genetics studies have identified a coding variant within ABI3 gene that increases the risk of developing AD. Recently, we demonstrated that deletion of the Abi3 gene locus dramatically exacerbates AD neuropathology in a transgenic mouse model of amyloidosis. In the course of this AD project, we unexpectedly found that deletion of the Abi3 gene locus resulted in a dramatic obese phenotype in non-transgenic mice. Here, we report our investigation into this serendipitous metabolic finding. Specifically, we demonstrate that mice with deletion of the Abi3 gene locus (Abi3–/–) have dramatically increased body weight and body fat. Further, we determined that Abi3–/– mice have impaired energy expenditure. Additionally, we found that deletion of the Abi3 gene locus altered gene expression within the hypothalamus, particularly within immune-related pathways. Subsequent immunohistological analysis of the central nervous system (CNS) revealed that microglia number and area were decreased specifically within the mediobasal hypothalamus of Abi3–/– mice. Altogether, this investigation establishes the functional importance of the Abi3 gene locus in the regulation of systemic metabolism and maintenance of healthy body weight. While our previous findings indicated the importance of Abi3 in neurodegeneration, this study indicates that Abi3 related functions are also essential for metabolic regulation.
Development of stroke predictive model in community-dwelling population: A longitudinal cohort study in Southeast China
Authors: Wang Qi , Zhang Lulu , Li Yidan , Tang Xiang , Yao Ye , Fang Qi
Published: December 2022

Background

Stroke has been the leading cause of death and disability in the world. Early recognition and treatment of stroke could effectively limit brain damage and vastly improve outcomes. This study aims to develop a highly accurate prediction model of stroke with a list of lifestyle behaviors and clinical characteristics to distinguish high-risk groups in the community-dwelling population.

Methods

Participants in this longitudinal cohort study came from the community-dwelling population in Suzhou between November 2018 and June 2019. A total of 4,503 residents participated in the study, while stroke happened to 22 participants in the 2-year follow-up period. Baseline information of each participant was acquired and enrolled in this study. T-test, Chi-square test, and Fisher’s exact test were used to examine the relationship of these indexes with stroke, and a prediction scale was constructed by multivariate logistic regression afterward. Receiver operating characteristic analysis was applied to testify to the prediction accuracy.

Results

A highly accurate prediction model of stroke was constructed by age, gender, exercise, meat and vegetarian diet, BMI, waist circumference, systolic blood pressure, Chinese visceral adiposity index, and waist-height ratio. Two additional prediction models for overweight and non-overweight individuals were formulated based on crucial risk factors, respectively. The stroke risk prediction models for community-dwelling and overweight populations had accuracies of 0.79 and 0.82, severally. Gender and exercise were significant predictors (χ2 > 4.57, p < 0.05) in the community-dwelling population model, while homocysteine (χ2 = 4.95, p < 0.05) was significant in the overweight population model.

Conclusion

The predictive models could predict 2-year stroke with high accuracy. The models provided an effective tool for identifying high-risk groups and supplied guidance for improving prevention and treatment strategies in community-dwelling population.
Neutrophil dynamics and inflammaging in acute ischemic stroke: A transcriptomic review
Authors: Bui Truong An , Jickling Glen C. , Winship Ian R.
Published: December 2022

Stroke is among the leading causes of death and disability worldwide. Restoring blood flow through recanalization is currently the only acute treatment for cerebral ischemia. Unfortunately, many patients that achieve a complete recanalization fail to regain functional independence. Recent studies indicate that activation of peripheral immune cells, particularly neutrophils, may contribute to microcirculatory failure and futile recanalization. Stroke primarily affects the elderly population, and mortality after endovascular therapies is associated with advanced age. Previous analyses of differential gene expression across injury status and age identify ischemic stroke as a complex age-related disease. It also suggests robust interactions between stroke injury, aging, and inflammation on a cellular and molecular level. Understanding such interactions is crucial in developing effective protective treatments. The global stroke burden will continue to increase with a rapidly aging human population. Unfortunately, the mechanisms of age-dependent vulnerability are poorly defined. In this review, we will discuss how neutrophil-specific gene expression patterns may contribute to poor treatment responses in stroke patients. We will also discuss age-related transcriptional changes that may contribute to poor clinical outcomes and greater susceptibility to cerebrovascular diseases.
Current perspective on retinal remodeling: Implications for therapeutics
Authors: Pfeiffer Rebecca L. , Jones Bryan W.
Published: December 2022

The retinal degenerative diseases retinitis pigmentosa and age-related macular degeneration are a leading cause of irreversible vision loss. Both present with progressive photoreceptor degeneration that is further complicated by processes of retinal remodeling. In this perspective, we discuss the current state of the field of retinal remodeling and its implications for vision-restoring therapeutics currently in development. Here, we discuss the challenges and pitfalls retinal remodeling poses for each therapeutic strategy under the premise that understanding the features of retinal remodeling in totality will provide a basic framework with which therapeutics can interface. Additionally, we discuss the potential for approaching therapeutics using a combined strategy of using diffusible molecules in tandem with other vision-restoring therapeutics. We end by discussing the potential of the retina and retinal remodeling as a model system for more broadly understanding the progression of neurodegeneration across the central nervous system.
UAV path planning method for data collection of fixed-point equipment in complex forest environment
Authors: Cui Xiaohui , Wang Yu , Yang Shijie , Liu Hanzhang , Mou Chao
Published: December 2022

In a complicated forest environment, it is usual to install many ground-fixed devices, and patrol personnel periodically collects data from the device to detect forest pests and valuable wild animals. Unlike human patrols, UAV (Unmanned Aerial Vehicles) may collect data from ground-based devices. The existing UAV path planning method for fixed-point devices is usually acceptable for simple UAV flight scenes. However, it is unsuitable for forest patrol. Meanwhile, when collecting data, the UAV should consider the timeliness of the collected data. The paper proposes two-point path planning and multi-point path planning methods to maximize the amount of fresh information collected from ground-fixed devices in a complicated forest environment. Firstly, we adopt chaotic initialization and co-evolutionary algorithmto solve the two-point path planning issue considering all significant UAV performance and environmental factors. Then, a UAV path planning method based on simulated annealing is proposed for the multi-point path planning issue. In the experiment, the paper uses benchmark functions to choose an appropriate parameter configuration for the proposed approach. On simulated simple and complicated maps, we evaluate the effectiveness of the proposed method compared to the existing pathplanning strategies. The results reveal that the proposed ways can effectively produce a UAV patrol path with higher information freshness in fewer iterations and at a lower computing cost, suggesting the practical value of the proposed approach.
Orexin-A exerts neuroprotective effect in experimental intracerebral hemorrhage by suppressing autophagy via OXR1-mediated ERK/mTOR signaling pathway
Authors: Zhang Dexin , Cui Ying , Zhao Manman , Zheng Xuecheng , Li Chunyan , Wei Jingbo , Wang Kaijie , Cui Jianzhong
Published: December 2022

Background

Orexin-A (OXA) is a polypeptide produced in the hypothalamus, which binds to specific receptors and exerts multiple physiological effects. Autophagy plays a vital role in early brain injury (EBI) after intracerebral hemorrhage (ICH). However, the relationship between OXA and autophagy after ICH has not been confirmed.

Methods

In this study, the protective role of OXA was investigated in a model of hemin-induced injury in PC12 cells and blood-injection ICH model in rats, and its potential molecular mechanism was clarified. Neurobehavioral tests, brain water content, and pathologic morphology were assessed after ICH. Cell survival rate was determined using Cell Counting Kit-8 (CCK-8), while apoptosis was detected using flow cytometry. The autophagy protein LC3 that was originally identified as microtubule-associated protein 1 light 3 was evaluated by immunohistochemistry. The ultrastructural changes of cells following ICH were observed by transmission electron microscopy. Western blotting was performed to determine the expression levels of LC3, p62/SQSTM1 (p62), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), total extracellular signal-regulated kinase 1/2 (t-ERK1/2), mammalian target of rapamycin (mTOR), and phosphorylated mammalian target of rapamycin (p-mTOR).

Results

OXA treatment significantly improved neurofunctional outcomes, reduced brain edema, and alleviated neuronal apoptosis. OXA administration upregulated p-mTOR and p62, while it downregulated p-ERK1/2 and LC3; this effect was reversed by the orexin receptor 1 (OXR1) antagonist SB-334867.

Conclusions

This study demonstrates that OXA suppresses autophagy via the OXR1-mediated ERK/mTOR signaling pathway to exert neuroprotective effects, and it might provide a novel therapeutic approach in patients suffering from ICH.
Reciprocal relationships between sleep and smell
Authors: Gaeta Giuliano , Wilson Donald A.
Published: December 2022

Despite major anatomical differences with other mammalian sensory systems, olfaction shares with those systems a modulation by sleep/wake states. Sleep modulates odor sensitivity and serves as an important regulator of both perceptual and associative odor memory. In addition, however, olfaction also has an important modulatory impact on sleep. Odors can affect the latency to sleep onset, as well as the quality and duration of sleep. Olfactory modulation of sleep may be mediated by direct synaptic interaction between the olfactory system and sleep control nuclei, and/or indirectly through odor modulation of arousal and respiration. This reciprocal interaction between sleep and olfaction presents novel opportunities for sleep related modulation of memory and perception, as well as development of non-pharmacological olfactory treatments of simple sleep disorders.
Intracerebral hemorrhage associated with brucellosis: A case report
Authors: Luo Yusong , Tian Guopeng , Lin Maoqiang , Fang Xiang , Bai Shengwei , Pan Yawen
Published: December 2022

Background

Intracerebral hemorrhage is a common disease, but cases of intracerebral hemorrhage with brucellosis are very rare. Here, we are presenting a case of a 60-year-old male patient diagnosed with brucellosis who has a right basal ganglia hemorrhage ruptured into bilateral lateral ventricles.

Case presentation

A 60-year-old male patient with symptoms of intracerebral hemorrhage who had no common risk factors for intracerebral hemorrhage, but having been diagnosed with brucellosis 2 months earlier and telling a shepherd history for 3 years. Cranial computed tomography (CT) and cranial magnetic resonance angiography (MRA) revealed that an intracerebral hemorrhage in the right basal ganglia had broken into bilateral lateral ventricles, and a Brucella serology test was positive. The patient's condition improved significantly after receiving bilateral lateral ventricle cone drainage, hematoma cavity cone drainage and anti-brucellosis treatment.

Conclusions

Herein, we discuss the possible mechanisms and clinical implications between brucellosis and intracerebral hemorrhage. This case suggests whether we can use brucellosis as a routine examination for disease diagnosis and prevention in patients with intracerebral hemorrhage from pastoral areas.
Structural and functional brain damage in women with multiple sclerosis: A mini-review of neuroimaging sex-based studies
Authors: Ceccarelli Antonia
Published: December 2022

Neuroimaging literature in healthy humans has shown that there are sex-related differences in healthy brain's anatomical structure, associated function and susceptibility to neurological diseases. This mini-review summarizes findings derived from the current neuroimaging studies focused on sex-related brain structural and functional damage in women with multiple sclerosis (MS). MS is a chronic, multifactorial, immune-mediated disorder of the central nervous system that affects mostly women. Even if recent neuroimaging studies have shed light on distinctive features of sex-related MS differences in brain structural and functional damage, more research is needed to better elucidate sex-related MS pathological changes and susceptibility and to implement sex-tailored treatment strategies in MS.
A unified framework for focal intensity change detection and deformable image registration. Application to the monitoring of multiple sclerosis lesions in longitudinal 3D brain MRI
Authors: Dufresne Eléonore , Fortun Denis , Kremer Stéphane , Noblet Vincent
Published: December 2022

Registration is a crucial step in the design of automatic change detection methods dedicated to longitudinal brain MRI. Even small registration inaccuracies can significantly deteriorate the detection performance by introducing numerous spurious detections. Rigid or affine registration are usually considered to align baseline and follow-up scans, as a pre-processing step before applying a change detection method. In the context of multiple sclerosis, using deformable registration can be required to capture the complex deformations due to brain atrophy. However, non-rigid registration can alter the shape of appearing and evolving lesions while minimizing the dissimilarity between the two images. To overcome this issue, we consider registration and change detection as intertwined problems that should be solved jointly. To this end, we formulate these two separate tasks as a single optimization problem involving a unique energy that models their coupling. We focus on intensity-based change detection and registration, but the approach is versatile and could be extended to other modeling choices. We show experimentally on synthetic and real data that the proposed joint approach overcomes the limitations of the sequential scheme.
Age effects on cognitive functions and speech-in-noise processing: An event-related potential study with cochlear-implant users and normal-hearing listeners
Authors: Burkhardt Pauline , Müller Verena , Meister Hartmut , Weglage Anna , Lang-Roth Ruth , Walger Martin , Sandmann Pascale
Published: December 2022

A cochlear implant (CI) can partially restore hearing in individuals with profound sensorineural hearing loss. However, electrical hearing with a CI is limited and highly variable. The current study aimed to better understand the different factors contributing to this variability by examining how age affects cognitive functions and cortical speech processing in CI users. Electroencephalography (EEG) was applied while two groups of CI users (young and elderly; N = 13 each) and normal-hearing (NH) listeners (young and elderly; N = 13 each) performed an auditory sentence categorization task, including semantically correct and incorrect sentences presented either with or without background noise. Event-related potentials (ERPs) representing earlier, sensory-driven processes (N1-P2 complex to sentence onset) and later, cognitive-linguistic integration processes (N400 to semantically correct/incorrect sentence-final words) were compared between the different groups and speech conditions. The results revealed reduced amplitudes and prolonged latencies of auditory ERPs in CI users compared to NH listeners, both at earlier (N1, P2) and later processing stages (N400 effect). In addition to this hearing-group effect, CI users and NH listeners showed a comparable background-noise effect, as indicated by reduced hit rates and reduced (P2) and delayed (N1/P2) ERPs in conditions with background noise. Moreover, we observed an age effect in CI users and NH listeners, with young individuals showing improved specific cognitive functions (working memory capacity, cognitive flexibility and verbal learning/retrieval), reduced latencies (N1/P2), decreased N1 amplitudes and an increased N400 effect when compared to the elderly. In sum, our findings extend previous research by showing that the CI users’ speech processing is impaired not only at earlier (sensory) but also at later (semantic integration) processing stages, both in conditions with and without background noise. Using objective ERP measures, our study provides further evidence of strong age effects on cortical speech processing, which can be observed in both the NH listeners and the CI users. We conclude that elderly individuals require more effortful processing at sensory stages of speech processing, which however seems to be at the cost of the limited resources available for the later semantic integration processes.
Applying machine learning technologies to explore students’ learning features and performance prediction
Authors: Su Yu-Sheng , Lin Yu-Da , Liu Tai-Quan
Published: December 2022

To understand students’ learning behaviors, this study uses machine learning technologies to analyze the data of interactive learning environments, and then predicts students’ learning outcomes. This study adopted a variety of machine learning classification methods, quizzes, and programming system logs, found that students’ learning characteristics were correlated with their learning performance when they encountered similar programming practice. In this study, we used random forest (RF), support vector machine (SVM), logistic regression (LR), and neural network (NN) algorithms to predict whether students would submit on time for the course. Among them, the NN algorithm showed the best prediction results. Education-related data can be predicted by machine learning techniques, and different machine learning models with different hyperparameters can be used to obtain better results.
Theta burst stimulation over left cerebellum does not modulate auditory feedback control of vocal production
Authors: Liu Dongxu , Chen Mingyun , Lin Qing , Li Tingni , Chen Xi , Dai Guangyan , Wu Xiuqin , Li Jingting , Liu Hanjun , Liu Peng
Published: December 2022

Background

Accumulating evidence has shown significant contributions of the right cerebellum to auditory-motor integration for vocal production. Whether the left cerebellum is likewise involved in vocal motor control, however, remains unclear.

Methods

By applying neuronavigated continuous and intermittent theta burst stimulation (cTBS/iTBS) over the left cerebellar lobule VII (Crus I), the present event-related potential (ERP) study investigated whether the left cerebellum exerts causal effects in modulating auditory feedback control of vocal pitch production. After receiving cTBS, iTBS, or sham stimulation over the left cerebellum, a group of fifteen young adults produced sustained vowels while hearing their voice unexpectedly shifted in pitch upwards or downwards by 200 cents. The effects of cerebellar stimulation were assessed by measuring the vocal and ERP (N1/P2) responses to pitch perturbations across the conditions.

Results

When compared to sham stimulation, cTBS or iTBS over the left cerebellar lobule VII (Crus I) led to no systematic changes in vocal compensations for pitch perturbations in auditory feedback. Also, the cortical N1/P2 responses did not vary significantly across the three stimulation sessions.

Conclusion

These findings present the first neurobehavioral evidence suggesting that the left cerebellum is not causally associated with auditory feedback control of vocal production. Together with previously reported causal effects of the right cerebellum in modulating vocal pitch regulation, the present study lends support to the hypothesis that there is a functional lateralization of the cerebellum in vocal motor control though auditory feedback.
A review of the circuit-level and cellular mechanisms contributing to locomotor acceleration in the marine mollusk Clione limacina
Authors: Pirtle Thomas J.
Published: December 2022

The pteropod mollusk, Clione limacina, is a useful model system for understanding the neural basis of behavior. Of particular interest are the unique swimming behavior and neural circuitry that underlies this swimming behavior. The swimming system of Clione has been studied by two primary groups—one in Russia and one in the United States of America—for more than four decades. The neural circuitry, the cellular properties, and ion channels that create and change the swimming locomotor rhythm of Clione—particularly mechanisms that contribute to swimming acceleration—are presented in this review.
Research advances in cGAS–stimulator of interferon genes pathway and central nervous system diseases: Focus on new therapeutic approaches
Authors: Ding Jiao , Dai Yijie , Zhu Jiahui , Fan Xuemei , Zhang Hao , Tang Bo
Published: December 2022

Cyclic GMP–AMP synthase (cGAS), a crucial innate immune sensor, recognizes cytosolic DNA and induces stimulator of interferon genes (STING) to produce type I interferon and other proinflammatory cytokines, thereby mediating innate immune signaling. The cGAS–STING pathway is involved in the regulation of infectious diseases, anti-tumor immunity, and autoimmune diseases; in addition, it plays a key role in the development of central nervous system (CNS) diseases. Therapeutics targeting the modulation of cGAS–STING have promising clinical applications. Here, we summarize the cGAS–STING signaling mechanism and the recent research on its role in CNS diseases.
Dietary vitamin D and calcium and periodontitis: A population-based study
Authors: Nascimento Gustavo G. , Leite Fábio R. M. , Gonzalez-Chica David A. , Peres Karen G. , Peres Marco A.
Published: December 2022

Aim

This study aimed to explore the relationship between dietary vitamin D and calcium intake and periodontitis among adults and whether it differs from males to females.

Methods

Cross-sectional analysis of a population-based cohort study with adults aged 20 to 60 from Southern Brazil. Intake of vitamin D and calcium were gathered in 2012 using two 24h-dietary recalls. Clinical examination assessed the clinical attachment level and bleeding on probing. Confounders included sex, age, family income, smoking, and obesity. The controlled direct effect of vitamin D and calcium on periodontitis was examined using marginal structural modeling. Analyses were also stratified by sex.

Results

Of the 1,066 investigated adults (mean age 35 ± 11.7 years; 49% females), 12.3% (95%CI 10.2;14.7) had periodontitis. Calcium intake had a direct protective effect on periodontitis (risk ratio (RR) 0.61; 95%CI 0.45;0.83), whereas no association between vitamin D and periodontitis was observed (RR 1.13; 95%CI 0.82;1.56). Stratified analyses revealed a null association between both vitamin D and calcium intake and periodontitis among men, but a protective association between calcium and intake and periodontitis among women (RR 0.56; 95%CI 0.38;0.79), while vitamin D remained without any association (RR 1.07; 95%CI 0.72;1.61).

Conclusion

Our findings suggest a protective association between dietary calcium intake and periodontitis among women.
Adlay, an ancient functional plant with nutritional quality, improves human health
Authors: Weng Wen F. , Peng Yan , Pan Xin , Yan Jun , Li Xiang D. , Liao Zhi Y. , Cheng Jian P. , Gao An J. , Yao Xin , Ruan Jing J. , Zhou Mei L.
Published: December 2022

Adlay (Coix lacryma-jobi L.), a crop closed related to maize (Zea mays L.) and sorghum (Sorghum bicolor L.), originated in tropical/subtropical regions of Asia and Africa; southwest China primary center of this plant’s origin, evolution and migration. Adlay is a traditional high-value minor crop used for both medicinal and dietary purposes. Adlay has anti-tumor, anti-bacterial, anti-inflammatory, analgesic, blood sugar-lowering, and blood lipid-lowering effects. To clarify the main bioactive components and phytochemical compounds and to fully explore their utility, this review summarizes the research done on the main functional ingredients of adlay, including amino acids and proteins, oils, vitamins and minerals, polysaccharides, and polyphenols. This study also highlighted the application of genome sequencing to tailor nutrient-rich adlay cultivars and nutraceutical product development. Additionally, the acquisition of high-density genomic data combined with next-generation phenotypic analysis will undoubtedly improve our understanding of the potential genetic regulation of adlay nutraceutical traits. This review provides new insights and ideas for the research of adlay in comparison and evolutionary genomics, and a useful reference for molecular breeding and genetic improvement of this important minor crop.
Consumption of sugar-sweetened beverages and fast foods deteriorates adolescents' mental health
Authors: Ra Jin Suk
Published: December 2022

Introduction

Sugar-sweetened beverage (SSB) and fast-food consumption is significantly associated with adolescents' poor mental health. Furthermore, sugar-sweetened beverage and fast-food consumption might form clustered diet patterns with significant positive associations in adolescent high school students. Thus, the combined consumption of SSBs and fast foods may have more negative effects on mental health with synergetic effects than the sum of their independent consumption.

Methods

This study aimed to identify the effects of combining the consumption of sugar-sweetened beverages and fast foods on mental health, including stress, depressive symptoms, and suicidal ideation among Korean high school students. Secondary data from 24,006 high school students were analyzed from the 17th Korea Youth Risk Behavior Web-based Survey, 2021. For statistical analysis, complex sampling analysis using the SPSS Statistics 26.0 software was applied for descriptive statistics and logistic regression analysis.

Results

In Korean adolescents, combining more than medium consumption of sugar-sweetened beverages and fast foods was associated with more stress, depressive symptoms, and suicidal ideation than their independent consumption. In addition, combining high consumption of sugar-sweetened beverages and low to high consumption of fast foods might have dose-dependent negative effects on stress, depressive symptoms, and suicidal ideation in Korean adolescents.

Discussion

Based on the results of this study, healthcare providers in schools and communities might develop various interventions including school/community-based feeding programs and policies targeting the restriction of SSB and fast-food consumption to improve adolescents' mental health.
Immune checkpoint blockade for locally advanced or recurrent/metastatic cervical cancer: An update on clinical data
Authors: Song Zhuo , Zou Kun , Zou Lijuan
Published: December 2022

Immunotherapy has shown great promise in the field of oncology, and recent clinical trials have illustrated that immune checkpoint blockade (ICB) is safe and effective at treating a range of tumor types. Cervical cancer (CC) is the fourth most common malignancy in women. However, first-line treatments for locally advanced cervical cancer (LACC) and recurrent/metastatic (R/M) CC have limited efficacy. Thus, it is necessary to explore new treatment approaches. The National Comprehensive Cancer Network (NCCN) currently recommends pembrolizumab, a programmed cell death protein 1 (PD-1) monoclonal antibody, as a first line therapy for individuals with R/M CC. This study reviews the progress of ICB therapy for LACC and R/M CC and describes the current status of the combination of ICB therapy and other therapeutic modalities, including radiotherapy, chemotherapy, targeted therapy, and other immunotherapies. The focus is placed on studies published since 2018 with the aim of highlighting novel CC-specific immunotherapeutic approaches and treatment targets.
Constructing and validating of m6a-related genes prognostic signature for stomach adenocarcinoma and immune infiltration: Potential biomarkers for predicting the overall survival
Authors: Yang Jing , Wu Zixuan , Wu Xiaoxi , Chen Siya , Xia Xinhua , Zeng Jianguo
Published: December 2022

Background

Stomach adenocarcinoma (STAD) arises from the mutations of stomach cells and has poor overall survival. Chemotherapy is commonly indicated for patients with stomach cancer following surgical resection. The most prevalent alteration that affects cancer growth is N6-methyladenosine methylation (m6A), although the possible function of m6A in STAD prognosis is not recognized.

Method

The research measured predictive FRGs in BLCA samples from the TCGA and GEO datasets. Data on the stemness indices (mRNAsi), gene mutations, copy number variations (CNV), tumor mutation burden (TMB), and corresponding clinical characteristics were obtained from TCGA and GEO. STAD from TCGA and GEO at 24 m6A was investigated. Lasso regression was used to construct the prediction model to assess the m6A prognostic signals in STAD. In addition, the correlation between m6a and immune infiltration in STAD patients was discussed using GSVA and ssGSEA analysis. Based on these genes, GO and KEGG analyses were performed to identify key biological functions and key pathways.

Result

A significant relationship was discovered between numerous m6A clusters and the tumor immune microenvironment, as well as three m6A alteration patterns with different clinical outcomes. Furthermore, GSVA and ssGSEA showed that m6A clusters were significantly associated with immune infiltration in the STAD. The low-m6Ascore group had a lower immunotherapeutic response than the high-m6Ascore group. ICIs therapy was more effective in the group with a higher m6Ascore. Three writers (VIRMA, ZC3H13, and METTL3) showed significantly lower expression, whereas five authors (METTL14, METTL16, WTAP, RBM15, and RBM15B) showed considerably higher expression. Three readers (YTHDC2, YTHDF2, and LRPPRC) had higher levels of expression, whereas eleven readers (YTHDC1, YTHDF1, YTHDF3, HNRNPC, FMR1, HNRNPA2B1, IGFBP1, IGFBP2, IGFBP3, and RBMX) had lower levels. As can be observed, the various types of m6 encoders have varied ramifications for STAD control.

Conclusion

STAD occurrence and progression are linked to m6A-genes. Corresponding prognostic models help forecast the prognosis of STAD patients. m6A-genes and associated immune cell infiltration in the tumor microenvironment (TME) may serve as potential therapeutic targets in STAD, which requires further trials. In addition, the m6a-related gene signature offers a viable alternative to predict bladder cancer, and these m6A-genes show a prospective research area for STAD targeted treatment in the future.
Case Report: Toxic epidermal necrolysis associated with sintilimab in a patient with relapsed thymic carcinoma
Authors: Yang Huayu , Ma Qing , Sun Ying , Zhang Kan , Xing Yunli , Li Hongwei
Published: December 2022

Immune checkpoint inhibitors (ICIs) such as anti-programmed death 1 (PD-1) receptor monoclonal antibody has been shown to be effective in patients with relapsed thymic carcinoma. However, immune-related adverse events (irAE) are increasingly recognized. There is a paucity of clinical data, especially in elderly patients. A patient in his late 80s with a history of thymic carcinoma was treated with sintilimab, an anti-PD1 antibody. After one week of administration, the patient developed diffuse rash. After two cycles of sintilimab, there was rapid progression of the rash with gradual development of blisters and skin detachment. Sintilimab was immediately discontinued, and skin biopsy was performed. The histopathological findings were consistent with the diagnosis of toxic epidermal necrolysis (TEN), which was considered as an irAE. Intravenous methylprednisolone was initially administered, followed by oral prednisone. The patient showed dramatic improvement within 72 hours of initiation of treatment. Unfortunately, the patient died of severe pneumonia three months later. We report a case of TEN, a rare toxicity induced by anti-PD-1 sintilimab in an elderly patient with thymic carcinoma. Since TEN is a life-threatening condition, early recognition and management of this complication is a key imperative.
Automated screening devices for vision screening in preschool children: A comparison of the PlusoptiX S12C photoscreener and retinomax K+3 autorefractor
Authors: Hunter Stephen C. , Suh Donny W. , Molina Iliana , Espinoza Jennifer
Published: December 2022

Introduction

Automated vision screening devices such as photoscreeners and autorefractors have been used to accurately identify amblyopia, refractive amblyopia risk factors (ARFs), and refractive error in young children; however, there is conflicting data about the effectiveness of different screening devices. We compared the performance of two commercially available screening devices in preschool children.

Methods

Children aged 3 to 5 years attending 5 preschools in Anaheim Elementary School District were screened with the PlusoptiX S12C photoscreener using ROC 3 referral criteria and Retinomax K+3 autorefractor in March 2022. Screened children were offered free cycloplegic eye examinations performed by optometrists on the UCI EyeMobile for Children mobile clinic. Children were evaluated for the presence of refractive ARFs using 2021 American Association for Pediatric Ophthalmology and Strabismus age-based referral criteria guidelines for instrument-based screening.

Results

A total of 158 children were screened and 79 children received cycloplegic examinations. At least one refractive ARF was found in 20% of examined children, corresponding to a sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 94%/89%/68%/98% for the PlusoptiX and 100%/65%/42%/100% for the Retinomax.

Discussion

In detecting refractive ARFs, the PlusoptiX was found to have a higher specificity and PPV while the Retinomax had a higher sensitivity and NPV. While both devices demonstrated a high sensitivity and NPV, we found that the PlusoptiX performed better overall as a screening device for our program as the Retinomax referred too many children.
Prevalence of pneumonia and its determinant factors among under-five children in Gamo Zone, southern Ethiopia, 2021
Authors: Solomon Yerukneh , Kofole Zelalem , Fantaye Tewodros , Ejigu Solomon
Published: December 2022

Background

Pneumonia, which is a form of acute lower respiratory tract infection, affects the lung parenchyma and destructs alveolar air space. Pneumonia is the leading cause of morbidity and mortality in under-five children. It was estimated that pneumonia kills 900,000 under-five children each year worldwide. Approximately 172 deaths per 1,000 live births occur in sub-Saharan African countries, with pneumonia being the major cause. This study aimed to assess the prevalence and determinant factors of pneumonia inunder-five children in southern Ethiopia.

Methodology

An institutional cross-sectional study was employed. A total of 239 child–caregiver pairs were included. Data were collected by trained nurses using a semi-structured questionnaire. The collected data were checked for completeness, coded and entered into EPI data version 4.6, and exported to SPSS version 25 for analysis. Results were reported as the mean, frequency, and percentile. Logistic regression was employed to assess statistically significant predictors of pneumonia. Variables with a p-value <0.05 were considered statistically significant factors of pneumonia.

Result

The prevalence of pneumonia in the study area was 30%. Among the factors assessed, place of food cooking—inside the living room [adjusted odd ratio (AOR) = 5.79, 95% confidence interval (CI): 2.47–13.58], nonexclusive breastfeeding (AOR = 3.26, 95% CI: 1.42–7.52), vitamin A supplementation status (AOR = 5.62, 95% CI: 2.65–11.94), and vaccination status (AOR = 3.59, 95% CI: 1.49–8.66) were significantly associated with the occurrence of pneumonia in under-five children.

Conclusion

This study showed that the prevalence of pneumonia was relatively higher in Arba Minch town than other parts of the country. Place of food cooking, nonexclusive breastfeeding, vitamin A supplementation status, and vaccination status of children were significant factors of pneumonia among under-five children. Enhancing caregivers’/mothers’ awareness of predicted factors was needed to reduce the incidence of childhood pneumonia and to enhance children's quality of health.
Apigenin directly interacts with and inhibits topoisomerase 1 to upregulate CD26/DPP4 on colorectal carcinoma cells
Authors: Fux Julia E. , Lefort Émilie C. , Rao Praveen P. N. , Blay Jonathan
Published: December 2022

Introduction:CD26/dipeptidyl peptidase IV (DPP4) is a cell-surface glycoprotein present on most epithelial cells that modulates the local response to external signals. We have previously shown that the dietary flavone apigenin (4′,5,7-trihydroxyflavone) upregulates cell-surface CD26/DPP4 on human colorectal carcinoma (CRC) cells and regulates its activities. We observed a unique synergistic interaction with the CRC chemotherapeutic agent irinotecan, which through its metabolite SN38 elevates CD26 at doses that are sub-cytotoxic. As SN38 interacts with topoisomerase 1 (Topo1) we evaluated whether apigenin influences Topo1 activity.

Methods:We used a radioimmunoassay to selectively measure CD26 at the cell surface of HT-29 cells following various treatments. Topoisomerase 1 mRNA expression was measured by q-RT-PCR and protein abundance by western blot analysis. Direct inhibition of topoisomerase activity was measured using an assay of DNA supercoil relaxation with recombinant human Topo1. The role of Topo1 in the effect of apigenin was shown both pharmacologically and by siRNA silencing of Topo1. Molecular docking analysis was done with SBD computational software using the CDOCKER algorithm.

Results:The interplay between apigenin and irinotecan was not observed when apigenin was combined with other chemotherapeutic drugs including the topoisomerase 2 inhibitors doxorubicin or etoposide. There was no enhancement of irinotecan action if apigenin was replaced with its hydroxylated metabolite luteolin (3′,4′,5,7-tetrahydroxyflavone) or emodin (6-methyl-1,3,8-trihydroxyanthraquinone), which is an inhibitor of the principal kinase target of apigenin, casein kinase 2 (CK2). Apigenin did not alter Topo1 mRNA expression, but siRNA knockdown of functional Topo1 eliminated the effect of apigenin and itself increased CD26 levels. Apigenin inhibited Topo1 activity in intact HT-29 cells and showed comparable inhibition of purified recombinant human Topo1 enzyme activity to that of SN-38, the active metabolite of irinotecan. Apigenin fits into the complex of Topo1 with DNA to directly inhibit Topo1 enzyme activity.

Discussion:We conclude that apigenin has a unique fit into the Topo1-DNA functional complex that leads to direct inhibition of Topo1 activity, and suggest that this is the basis for the exceptional interaction with the CRC drug irinotecan. A combined action of these two agents may therefore exert a role to limit local signals that facilitate tumour progression.
Trilateral association of autophagy, mTOR and Alzheimer’s disease: Potential pathway in the development for Alzheimer’s disease therapy
Authors: Subramanian Arunkumar , Tamilanban T. , Alsayari Abdulrhman , Ramachawolran Gobinath , Wong Ling Shing , Sekar Mahendran , Gan Siew Hua , Subramaniyan Vetriselvan , Chinni Suresh V. , Izzati Mat Rani Nur Najihah , Suryadevara Nagaraja , Wahab Shadma
Published: December 2022

The primary and considerable weakening event affecting elderly individuals is age-dependent cognitive decline and dementia. Alzheimer’s disease (AD) is the chief cause of progressive dementia, and it is characterized by irreparable loss of cognitive abilities, forming senile plaques having Amyloid Beta (Aβ) aggregates and neurofibrillary tangles with considerable amounts of tau in affected hippocampus and cortex regions of human brains. AD affects millions of people worldwide, and the count is showing an increasing trend. Therefore, it is crucial to understand the underlying mechanisms at molecular levels to generate novel insights into the pathogenesis of AD and other cognitive deficits. A growing body of evidence elicits the regulatory relationship between the mammalian target of rapamycin (mTOR) signaling pathway and AD. In addition, the role of autophagy, a systematic degradation, and recycling of cellular components like accumulated proteins and damaged organelles in AD, is also pivotal. The present review describes different mechanisms and signaling regulations highlighting the trilateral association of autophagy, the mTOR pathway, and AD with a description of inhibiting drugs/molecules of mTOR, a strategic target in AD. Downregulation of mTOR signaling triggers autophagy activation, degrading the misfolded proteins and preventing the further accumulation of misfolded proteins that inhibit the progression of AD. Other target mechanisms such as autophagosome maturation, and autophagy-lysosomal pathway, may initiate a faulty autophagy process resulting in senile plaques due to defective lysosomal acidification and alteration in lysosomal pH. Hence, the strong link between mTOR and autophagy can be explored further as a potential mechanism for AD therapy.
Discovery of potent and noncovalent KRASG12D inhibitors: Structure-based virtual screening and biological evaluation
Authors: Wang Yuting , Zhang Hai , Li Jindong , Niu Miao-Miao , Zhou Yang , Qu Yuanqian
Published: December 2022

KRASG12D, the most common oncogenic KRAS mutation, is a promising target for the treatment of pancreatic cancer. Herein, we identified four potent and noncovalent KRASG12D inhibitors (hits 1–4) by using structure-based virtual screening and biological evaluation. The in vitro assays indicated that the four compounds had sub-nanomolar affinities for KRASG12D and showed a dose-dependent inhibitory effect on human pancreatic cancer cells. In particular, the hit compound 3 was the most promising candidate and significantly inhibited the tumor growth of pancreatic cancer in tumor-bearing mice. The hit compound 3 represented a promising starting point for structural optimization in hit-to-lead development. This study shows that hit compound 3 provides a basis for the development of the treatment of cancer driven by KRASG12D.
The role of antifreeze glycoprotein (AFGP) and polyvinyl alcohol/polyglycerol (X/Z-1000) as ice modulators during partial freezing of rat livers
Authors: Tessier Shannon N. , Haque Omar , Pendexter Casie A. , Cronin Stephanie E. J. , Hafiz Ehab O. A. , Weng Lindong , Yeh Heidi , Markmann James F. , Taylor Michael J. , Fahy Gregory M. , Toner Mehmet , Uygun Korkut
Published: December 2022

Introduction: The current liver organ shortage has pushed the field of transplantation to develop new methods to prolong the preservation time of livers from the current clinical standard of static cold storage. Our approach, termed partial freezing, aims to induce a thermodynamically stable frozen state at high subzero storage temperatures (−10°C to −15°C), while simultaneously maintaining a sufficient unfrozen fraction to limit ice-mediated injury.

Methods and results: Using glycerol as the main permeating cryoprotectant agent, this research first demonstrated that partially frozen rat livers showed similar outcomes after thawing from either −10°C or −15°C with respect to subnormothermic machine perfusion metrics. Next, we assessed the effect of adding ice modulators, including antifreeze glycoprotein (AFGP) or a polyvinyl alcohol/polyglycerol combination (X/Z-1000), on the viability and structural integrity of partially frozen rat livers compared to glycerol-only control livers. Results showed that AFGP livers had high levels of ATP and the least edema but suffered from significant endothelial cell damage. X/Z-1000 livers had the highest levels of ATP and energy charge (EC) but also demonstrated endothelial damage and post-thaw edema. Glycerol-only control livers exhibited the least DNA damage on Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining but also had the lowest levels of ATP and EC.

Discussion: Further research is necessary to optimize the ideal ice modulator cocktail for our partial-freezing protocol. Modifications to cryoprotective agent (CPA) combinations, including testing additional ice modulators, can help improve the viability of these partially frozen organs.
Theoretical analysis of guided waves propagation in periodic piezoelectric plates with shunting circuits
Authors: Zhang Youqi , Xia Rongyu , Huang Kefu , Li Zheng
Published: December 2022

The tunable manipulation of guided waves in plates brings out great potential applications in engineering practices, and the electromechanical coupling effects of piezoelectric material with shunting circuits have exhibited powerful tunability and flexibility for guided wave propagation. In this paper, a theoretical model is established to analyze the guided wave propagation in one-dimensional periodic piezoelectric plate constructed from a periodic array of anisotropic piezoelectric materials under periodic electrical boundary conditions. The extended Stroh formalism incorporating with the plane wave expansion method is developed to transform the wave motion equations of the periodic piezoelectric plate into a linear eigenvalue system, and a more concise and elegant solution of generalized displacement and generalized stress can be derived. There are various dispersion relations in terms of the altering electrical boundary conditions to be acquired, if the thin electrodes with shunting circuits are attached periodically to both surfaces of the piezoelectric plate. Analytical results show that the coupling of the local electric resonant mode and propagating elastic wave modes can induce hybridization bandgaps, and the bandgaps of Lamb waves and SH waves in the piezoelectric plate can be tuned by designing appropriate material polarization orientations and shunting circuits. In addition, the Bragg bandgaps can also be influenced by the external circuits. Results indicate that the proposed theoretical model can effectively analyze the performances of guided waves in periodic piezoelectric plate and provide useful theoretical guidance for designing smart wave control devices.