bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenome Sequencing Reveals the Microbiome of Aedes albopictus and Its Possible Relationship With Dengue Virus Susceptibility
Authors: Zhao Teng , Li Bo-qi , Gao He-ting , Xing Dan , Li Man-jin , Dang Yun-qi , Zhang Heng-duan , Zhao Yue-e , Liu Zhu , Li Chun-xiao
Published: May 2022

Dengue fever virus (DENV) is a mosquito-borne flavivirus that poses a serious risk to human health. Aedes albopictus is a widely distributed vector of dengue fever in China. Based on the impact of physiological activity, the microbiome in A. albopictus will provide a novel environment-friendly approach to control DENV transmission. We performed metagenomic sequencing on A. albopictus before and after exposure to DENV blood meal to detect microbiome variation of A. albopictus with different susceptibilities to DENV. The dominant phyla in A. albopictus microbiome were Proteobacteria and Ascomycota, and the dominant genera were Aspergillus and Metarhizium. Gammaproteobacteria bacterium, Lactobacillus harbinensis, and Neurospora crassa differed significantly after DENV infection. There were 15 different microorganisms found to be involved in mosquito immunity and metabolism, such as Alphaproteobacteria bacterium, Methyloglobulus morosus, and Shigella sonnei, which might have an impact on the DENV susceptibility of A. albopictus. It was hypothesized that the lack of specific bacteria may lead to increased susceptibility of A. albopictus to DENV. Interventions in the microbiome composition or specific bacteria of A. albopictus may affect the susceptibility to DENV and control the mosquito-borne diseases efficiently.
Resilience Analysis of Additive Manufacturing-enabled Supply Chains: An Exploratory Study
Authors: Patel Pinkesh , Defersha Fantahun , Yang Sheng
Published: May 2022

Unparalleled level of globalization and fierce competition have made supply chains (SCs) exceedingly complex and fragile as ever before. Increased incidences of natural disasters and unprecedented COVID-19 have highlighted the significance of improving supply chain resilience (SCR) by divulging its susceptibility to the external events. Additive manufacturing (AM) is envisioned as the disruptive technology that allows layer-wised fabrication and has been claimed to be an important contributor to the improved SCR as it could bring new opportunities through expanded design freedom, improved material efficiency, shortened supply chains, and decentralized manufacturing. Nonetheless, rare research has quantitatively measured the impacts of AM on SCR. To fill this research gap, the indices for assessing SCR of AM-enabled supply chains (AM-SCs) are first proposed, and then, the technique for order of preference by similarity to ideal solution (TOPSIS) is employed to derive a quantifiable SCR score that can be used to measure the performance of different SCs. A case study of a gas pedal assembly is presented with three different SC configurations: the original assembly with conventional manufacturing, original assembly with AM, and redesigned assembly with AM. The exploratory study shows that the redesigned assembly with AM considerations could improve the SCR by 200%. Sensitivity analysis also revealed that part count and reaction time of suppliers are influential factors of improving SCR. Last, challenges and limitations of the proposed framework are also deliberated upon alongside future research scope.
Chronic Ethanol Causes Persistent Increases in Alzheimer’s Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment
Authors: Tucker Autumn E. , Alicea Pauneto Coral del Mar , Barnett Alexandra M. , Coleman Leon G.
Published: May 2022

Epidemiological studies have found that heavy alcohol use is associated with increased risk for Alzheimer’s disease (AD), with frequent drinking earlier in adulthood increasing risk. The increases in neuroinflammation featured in both heavy alcohol use and AD may be partially responsible for this link. However, it is unknown if abstinence mitigates this risk. We hypothesized that binge ethanol during mid adult life would persistently increase AD pathology even after prolonged abstinence. Male and female 3xTg-AD mice (APPSwe, tauP301, Psen1tm1Mpm) which feature progressive amyloid (Aβ) and tau pathology, received chronic binge ethanol (5g/kg/day, 5-days-on/2-days-off, i.g.) or water during adulthood (from 5.5 to 9 months of age), followed by abstinence and assessment at 14 months of age. The effects of ethanol on protective AD genes (e.g., APOE and TREM2) as well as proinflammatory genes were measured by PCR. Levels of pathologic tau and Aβ were measured by immunohistochemistry and western blot. Ethanol caused persistent reductions in protective AD genes: APOE (25% reduction, *p < 0.05), TREM2 (28%, *p < 0.05), LPL (40%, **p < 0.01), and CTSD (24%, *p < 0.05) and promoted a proinflammatory gene signature in female, but not male cortex. Concurrently, ethanol increased total and hyperphosphorylated tau (AT8) in piriform cortex and hippocampus of females, but not males. Levels of AT8 were negatively correlated with APOE (R = –0.67, *p < 0.05) and TREM2 (R = –0.78, **p < 0.005) suggesting protective roles in pathogenesis. No differences were found in levels of main regulators of tau phosphorylation state (GSK3β, PKA, PP2A), suggesting ethanol disrupted clearance of tau. Therefore, we measured the effect of ethanol on lysosomes, which degrade tau, and lysosomal localization of tau using co-immunofluorescence. In females, ethanol caused a persistent reduction in mature LAMP1 lysosomes in CA1 of hippocampus (35%, *p < 0.05), along with a 60% increase in total tau (*p < 0.05). Thus, chronic binge ethanol during mid adult life causes a persistent enhancement of tau pathology in cortical and hippocampal brain regions of females. Persistent AD pathology was associated with an increased proinflammatory signature and a reduction of mature lysosomes. This implicates binge ethanol exposure with increased risk of AD pathologic progression in females.
Altered Brain Connectivity Patterns of Individual Differences in Insightful Problem Solving
Authors: Lin Jiabao , Chen Yajue , Xie Jiushu , Mo Lei
Published: May 2022

Insightful problem solving (IPS) attracts widespread attention in creative thinking domains. However, the neural underpinnings of individual differences in IPS are still unclear. The purpose of this research was to investigate inherent full-brain connectivity patterns at voxel-level in IPS. Sixty-two healthy participants were enrolled in the study. We used a voxelwise full-brain network measurement, degree centrality (DC), to depict the characteristics of cerebral network involved in individual differences in IPS. For each participant, we employed a chunk decomposition paradigm, using Mandarin characters as stimuli, to estimate the individual differences in IPS. Results showed that DC in the inferior frontal gyrus, and the middle frontal gyrus/precentral gyrus positively correlated with IPS, while the anterior cingulate cortex, and the brainstern/cerebellum/thalamus exhibited negative correlations with IPS. Using each cluster above as a seed, we performed seed-based functional connectivity analysis further. Results showed that IPS was mainly involved in the default mode network, containing the key regions of precuneus and medial prefrontal cortex. All in all, this research may shed new lights on understanding the neural underpinnings of individual differences in IPS.
Development of Modular and Adaptive Laboratory Set-Up for Neuroergonomic and Human-Robot Interaction Research
Authors: Savković Marija , Caiazzo Carlo , Djapan Marko , Vukićević Arso M. , Pušica Miloš , Mačužić Ivan
Published: May 2022

The industry increasingly insists on academic cooperation to solve the identified problems such as workers' performance, wellbeing, job satisfaction, and injuries. It causes an unsafe and unpleasant working environment that directly impacts the quality of the product, workers' productivity, and effectiveness. This study aimed to give a specialized solution for tests and explore possible solutions to the given problem in neuroergonomics and human–robot interaction. The designed modular and adaptive laboratory model of the industrial assembly workstation represents the laboratory infrastructure for conducting advanced research in the field of ergonomics, neuroergonomics, and human–robot interaction. It meets the operator's anatomical, anthropometric, physiological, and biomechanical characteristics. Comparing standard, ergonomic, guided, and collaborative work will be possible based on workstation construction and integrated elements. These possibilities allow the industry to try, analyze, and get answers for an identified problem, the condition, habits, and behavior of operators in the workplace. The set-up includes a workstation with an industry work chair, a Poka–Yoke system, adequate lighting, an audio 5.0 system, containers with parts and tools, EEG devices (a cap and smartfones), an EMG device, touchscreen PC screen, and collaborative robot. The first phase of the neuroergonomic study was performed according to the most common industry tasks defined as manual, monotonous, and repetitive activities. Participants have a task to assemble the developed prototype model of an industrial product using prepared parts and elements, and instructed by the installed touchscreen PC. In the beginning, the participant gets all the necessary information about the experiment and gets 15 min of practice. After the introductory part, the EEG device is mounted and prepared for recording. The experiment starts with relaxing music for 5 min. The whole experiment lasts two sessions per 60 min each, with a 15 min break between the sessions. Based on the first experiments, it is possible to develop, construct, and conduct complex experiments for industrial purposes to improve the physical, cognitive, and organizational aspects and increase workers' productivity, efficiency, and effectiveness. It has highlighted the possibility of applying modular and adaptive ergonomic research laboratory experimental set-up to transform standard workplaces into the workplaces of the future.
Sortilin Modulates Schwann Cell Signaling and Remak Bundle Regeneration Following Nerve Injury
Authors: Ulrichsen Maj , Gonçalves Nádia P. , Mohseni Simin , Hjæresen Simone , Lisle Thomas L. , Molgaard Simon , Madsen Niels K. , Andersen Olav M. , Svenningsen Åsa F. , Glerup Simon , Nykjær Anders , Vægter Christian B.
Published: May 2022

Peripheral nerve regeneration relies on the ability of Schwann cells to support the regrowth of damaged axons. Schwann cells re-differentiate when reestablishing contact with the sprouting axons, with large fibers becoming remyelinated and small nociceptive fibers ensheathed and collected into Remak bundles. We have previously described how the receptor sortilin facilitates neurotrophin signaling in peripheral neurons via regulated trafficking of Trk receptors. This study aims to characterize the effects of sortilin deletion on nerve regeneration following sciatic crush injury. We found that Sort1–/– mice displayed functional motor recovery like that of WT mice, with no detectable differences in relation to nerve conduction velocities and morphological aspects of myelinated fibers. In contrast, we found abnormal ensheathment of regenerated C-fibers in injured Sort1–/– mice, demonstrating a role of sortilin for Remak bundle formation following injury. Further studies on Schwann cell signaling pathways showed a significant reduction of MAPK/ERK, RSK, and CREB phosphorylation in Sort1–/– Schwann cells after stimulation with neurotrophin-3 (NT-3), while Schwann cell migration and myelination remained unaffected. In conclusion, our results demonstrate that loss of sortilin blunts NT-3 signaling in Schwann cells which might contribute to the impaired Remak bundle regeneration after sciatic nerve injury.
Transgene and Chemical Transdifferentiation of Somatic Cells for Rapid and Efficient Neurological Disease Cell Models
Authors: Ng Neville , Newbery Michelle , Maksour Simon , Dottori Mirella , Sluyter Ronald , Ooi Lezanne
Published: May 2022

For neurological diseases, molecular and cellular research relies on the use of model systems to investigate disease processes and test potential therapeutics. The last decade has witnessed an increase in the number of studies using induced pluripotent stem cells to generate disease relevant cell types from patients. The reprogramming process permits the generation of a large number of cells but is potentially disadvantaged by introducing variability in clonal lines and the removal of phenotypes of aging, which are critical to understand neurodegenerative diseases. An under-utilized approach to disease modeling involves the transdifferentiation of aged cells from patients, such as fibroblasts or blood cells, into various neural cell types. In this review we discuss techniques used for rapid and efficient direct conversion to neural cell types. We examine the limitations and future perspectives of this rapidly advancing field that could improve neurological disease modeling and drug discovery.
Proteins Involved in Synaptic Plasticity Are Downregulated in the Cerebrospinal Fluid of Infants With Clinical Sepsis Complicated by Neuroinflammation
Authors: Jiang Ping-Ping , Peng Shan-Shan , Pankratova Stanislava , Luo Ping , Zhou Ping , Chen You
Published: May 2022

Newborn infants are prone to sepsis and related inflammation of different organs. Neuroinflammation has been associated with long-term adverse neuronal (neuropsychiatric/neurodegenerative) outcomes, including attention deficit hyperactivity disorder (ADHD) or even Alzheimer's disease. Despite a vast number of findings on sepsis-induced inflammatory responses in the central nervous system (CNS), how neuroinflammation affects brain development remains largely elusive. In this study, neonates with clinical sepsis and screened for meningitis were included and classified by the neuroinflammation status based on cerebrospinal fluid (CSF) parameters (INF vs. NOINF). CSF samples collected from clinical screening were subjected to proteomics analysis. Proteins with differential abundance were subjected to enrichment analysis to reveal affected biological pathways. INF and NOINF infants had similar demographic data and hematological and biochemical parameters in blood and CSF. The CSF proteomes were essentially different between the two groups. All 65 proteins with differential abundance showed lower abundance in the INF group and functionally covered pivotal developmental processes, including axonal and synaptic function and extracellular homeostasis. CSF proteins, PTPRZ1 and IGFBP4, were correlated with C-reactive protein (CRP) and ratios of immature/total neutrophils in blood. In general, a substantial change in the CSF protein profile was found under neuroinflammation, and these changes are related to systemic conditions. The results suggest that changes in CSF proteins may be involved in sepsis-affected neurodevelopment, such as disturbances in circuit formation, which has the potential to predispose neonates to long-term adverse outcomes.
Data-Driven Model of Postsynaptic Currents Mediated by NMDA or AMPA Receptors in Striatal Neurons
Authors: Carannante Ilaria , Johansson Yvonne , Silberberg Gilad , Hellgren Kotaleski Jeanette
Published: May 2022

The majority of excitatory synapses in the brain uses glutamate as neurotransmitter, and the synaptic transmission is primarily mediated by AMPA and NMDA receptors in postsynaptic neurons. Here, we present data-driven models of the postsynaptic currents of these receptors in excitatory synapses in mouse striatum. It is common to fit two decay time constants to the decay phases of the current profiles but then compute a single weighted mean time constant to describe them. We have shown that this approach does not lead to an improvement in the fitting, and, hence, we present a new model based on the use of both the fast and slow time constants and a numerical calculation of the peak time using Newton's method. Our framework allows for a more accurate description of the current profiles without needing extra data and without overburdening the comptuational costs. The user-friendliness of the method, here implemented in Python, makes it easily applicable to other data sets.
IE-Vnet: Deep Learning-Based Segmentation of the Inner Ear's Total Fluid Space
Authors: Ahmadi Seyed-Ahmad , Frei Johann , Vivar Gerome , Dieterich Marianne , Kirsch Valerie
Published: May 2022

Background

In-vivo MR-based high-resolution volumetric quantification methods of the endolymphatic hydrops (ELH) are highly dependent on a reliable segmentation of the inner ear's total fluid space (TFS). This study aimed to develop a novel open-source inner ear TFS segmentation approach using a dedicated deep learning (DL) model.

Methods

The model was based on a V-Net architecture (IE-Vnet) and a multivariate (MR scans: T1, T2, FLAIR, SPACE) training dataset (D1, 179 consecutive patients with peripheral vestibulocochlear syndromes). Ground-truth TFS masks were generated in a semi-manual, atlas-assisted approach. IE-Vnet model segmentation performance, generalizability, and robustness to domain shift were evaluated on four heterogenous test datasets (D2-D5, n = 4 × 20 ears).

Results

The IE-Vnet model predicted TFS masks with consistently high congruence to the ground-truth in all test datasets (Dice overlap coefficient: 0.9 ± 0.02, Hausdorff maximum surface distance: 0.93 ± 0.71 mm, mean surface distance: 0.022 ± 0.005 mm) without significant difference concerning side (two-sided Wilcoxon signed-rank test, p>0.05), or dataset (Kruskal-Wallis test, p>0.05; post-hoc Mann-Whitney U, FDR-corrected, all p>0.2). Prediction took 0.2 s, and was 2,000 times faster than a state-of-the-art atlas-based segmentation method.

Conclusion

IE-Vnet TFS segmentation demonstrated high accuracy, robustness toward domain shift, and rapid prediction times. Its output works seamlessly with a previously published open-source pipeline for automatic ELS segmentation. IE-Vnet could serve as a core tool for high-volume trans-institutional studies of the inner ear. Code and pre-trained models are available free and open-source under https://github.com/pydsgz/IEVNet.
Polyvagal Theory: A Science of Safety
Authors: Porges Stephen W.
Published: May 2022

Contemporary strategies for health and wellbeing fail our biological needs by not acknowledging that feelings of safety emerge from internal physiological states regulated by the autonomic nervous system. The study of feelings of safety has been an elusive construct that has historically been dependent upon subjectivity. Acknowledging that feelings of safety have a measurable underlying neurophysiological substrate would shift investigations of feelings of safety from a subjective to an objective science. Polyvagal Theory provides an innovative scientific perspective to study feelings of safety that incorporates an understanding of neuroanatomy and neurophysiology. This perspective identifies neural circuits that downregulate neural regulation of threat reactions and functionally neutralize defensive strategies via neural circuits communicating cues of safety that enable feelings of safety to support interpersonal accessibility and homeostatic functions. Basically, when humans feel safe, their nervous systems support the homeostatic functions of health, growth, and restoration, while they simultaneously become accessible to others without feeling or expressing threat and vulnerability. Feelings of safety reflect a core fundamental process that has enabled humans to survive through the opportunistic features of trusting social engagements that have co-regulatory capacities to mitigate metabolically costly defense reactions. Through the study of neural development and phylogeny, we can extract foundational principles and their underlying mechanisms through which the autonomic nervous system leads to feelings of safety and opportunities to co-regulate. Several principles highlight the validity of a science of safety that when implemented in societal institutions, ranging from healthcare to education, would enhance health, sociality, and lead to greater productivity, creativity, and a sense of wellbeing. By respecting our need to feel safe as a biological imperative linked to survival, we respect our phylogenetic heritage and elevate sociality as a neuromodulator that functionally provides the scientific validation for a societal focus on promoting opportunities to experience feelings of safety and co-regulation.
Different Synaptic Plasticity After Physiological and Psychological Stress in the Anterior Insular Cortex in an Observational Fear Mouse Model
Authors: Shi Wenlong , Fu Yuan , Shi Tianyao , Zhou Wenxia
Published: May 2022

Post-traumatic stress disorder (PTSD) can be triggered not only in people who have personally experienced traumatic events but also in those who witness them. Physiological and psychological stress can have different effects on neural activity, but little is known about the underlying mechanisms. There is ample evidence that the insular cortex, especially the anterior insular cortex (aIC), is critical to both the sensory and emotional experience of pain. It is therefore worthwhile to explore the effects of direct and indirect stress on the synaptic plasticity of the aIC. Here, we used a mouse model of observational fear to mimic direct suffering (Demonstrator, DM) and witnessing (Observer, OB) of traumatic events. After observational fear training, using a 64-channel recording system, we showed that both DM and OB mice exhibited a decreased ratio of paired-pulse with intervals of 50 ms in the superficial layers of the aIC but not in the deep layers. We found that theta-burst stimulation (TBS)–induced long-term potentiation (LTP) in OB mice was significantly higher than in DM mice, and the recruitment of synaptic responses occurred only in OB mice. Compared with naive mice, OB mice showed stronger recruitment and higher amplitude in the superficial layers of the aIC. We also used low-frequency stimulation (LFS) to induce long-term depression (LTD). OB mice showed greater LTD in both the superficial and deep layers of the aIC than naive mice, but no significant difference was found between OB and DM mice. These results provide insights into the changes in synaptic plasticity in the aIC after physiological and psychological stress, and suggest that different types of stress may have different mechanisms. Furthermore, identification of the possible causes of the differences in stress could help treat stress-related disorders.
Impact of the Malnutrition on Mortality in Patients With Osteoporosis: A Cohort Study From NHANES 2005-2010
Authors: Shangguan Xiaohui , Xiong Jialing , Shi Shanshan , Liao Ying , Chen Liling , Deng Jiayi , Wu Wanxia , Wang Junjie , Tu Jiabin , Xiu Jiaming , Wu Weihao , Chen Longtian , Chen Kaihong
Published: May 2022

Background

Osteoporosis is the most common metabolic bone disease. Recent studies have shown that malnutrition can promote the development of osteoporosis. However, the incidence of malnutrition in patients with osteoporosis and the relationship between malnutrition and all-cause mortality has not been adequately studied. Therefore, our study investigated the relationship between malnutrition and all-cause mortality in patients with osteoporosis.

Methods

We analyzed data on 7,700 adults ≥20 years of age during National Health and Nutrition Examination Survey (NHANES) 2005-2010. Each patient was assigned to one of three groups: normal nutritional status, mild malnutrition, and moderate to severe malnutrition. Survival curves and univariate and multivariable cox regressions based on the NHANES recommended weights were used to assess the association between malnutrition status and mortality. Moreover, cox proportional hazards regression analyses were performed on the matched pairs.

Results

Overall, 7,700 eligible individuals with osteoporosis were included in the final analysis, and the mean age was 52.0 ± 0.4 years. From the Kaplan–Meier curves for long-term all-cause mortality of malnutrition, worsening malnutrition status was associated with higher incidence of all-cause mortality. In the fully adjusted models, the adjusted hazard ratio (aHR) was 1.54 [95% confidence interval (CI), 1.02–2.31, p = 0.039] at mild malnutrition status and 2.70 (95%CI, 1.95–3.74, p < 0.001) at moderate to severe malnutrition status. The cox model after matching indicated that malnutrition was still a high mortality risk than no malnutrition (aHR = 2.23, 95% CI, 1.66–3.01, p < 0.001).

Conclusions

Poor malnutrition status, common in osteoporotic patients, is strongly associated with a risk for all-cause mortality comparable to that seen with normal nutritional status. These findings highlight the importance of risk stratification for nutritional status in osteoporotic patients and the implementation of strategies that is now available to help prevent malnutrition in these patients.
Deep Learning Analysis of the Adipose Tissue and the Prediction of Prognosis in Colorectal Cancer
Authors: Lin Anqi , Qi Chang , Li Mujiao , Guan Rui , Imyanitov Evgeny N. , Mitiushkina Natalia V. , Cheng Quan , Liu Zaoqu , Wang Xiaojun , Lyu Qingwen , Zhang Jian , Luo Peng
Published: May 2022

Research has shown that the lipid microenvironment surrounding colorectal cancer (CRC) is closely associated with the occurrence, development, and metastasis of CRC. According to pathological images from the National Center for Tumor diseases (NCT), the University Medical Center Mannheim (UMM) database and the ImageNet data set, a model called VGG19 was pre-trained. A deep convolutional neural network (CNN), VGG19CRC, was trained by the migration learning method. According to the VGG19CRC model, adipose tissue scores were calculated for TCGA-CRC hematoxylin and eosin (H&E) images and images from patients at Zhujiang Hospital of Southern Medical University and First People's Hospital of Chenzhou. Kaplan-Meier (KM) analysis was used to compare the overall survival (OS) of patients. The XCell and MCP-Counter algorithms were used to evaluate the immune cell scores of the patients. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to analyze upregulated and downregulated pathways. In TCGA-CRC, patients with high-adipocytes (high-ADI) CRC had significantly shorter OS times than those with low-ADI CRC. In a validation queue from Zhujiang Hospital of Southern Medical University (Local-CRC1), patients with high-ADI had worse OS than CRC patients with low-ADI. In another validation queue from First People's Hospital of Chenzhou (Local-CRC2), patients with low-ADI CRC had significantly longer OS than patients with high-ADI CRC. We developed a deep convolution network to segment various tissues from pathological H&E images of CRC and automatically quantify ADI. This allowed us to further analyze and predict the survival of CRC patients according to information from their segmented pathological tissue images, such as tissue components and the tumor microenvironment.
Vitamin D Intake and Factors Associated With Self-Reported Vitamin D Deficiency Among US Adults: A 2021 Cross-Sectional Study
Authors: Andrade Jeanette M. , Grandoff Philip G. , Schneider Sydney T.
Published: May 2022

Vitamin D deficiency is a global issue that may be attributed to various factors such as dietary habits, sun exposure, age, race and chronic conditions. The purpose of this study was to determine the relationship between vitamin D intake from food/supplements and factors that may be associated with self-reported vitamin D deficiency among US adults. A cross-sectional online study was conducted among 1,637 adults using a 38-item questionnaire. Frequency counts and percentages were tabulated and a multiple linear regression was performed. Statistical significance was determined at p < 0.05. Participants (n = 554, 33.8%) were considered vitamin D deficient and consumed an average of 347.05 ± 307.8 IUs of vitamin D through foods/beverages. The multivariate linear regression showed no statistically significant difference with vitamin D intake from foods/beverages on vitamin D deficiency status. Significant positive correlations were seen with vitamin D deficiency status and certain chronic conditions such as chronic kidney disease (p = 0.04), depression (p < 0.001), diabetes (p = 0.02), and vitamin D supplement use (p < 0.001). Significant negative correlations were observed with vitamin D deficiency status and age (p = 0.01) and sun exposure (p < 0.001). Future focus should be on educating individuals about factors associated with vitamin D to reduce the prevalence of vitamin D deficiency.
Predictive Value of Endoscopic Observations and Biopsy After Neoadjuvant Chemoradiotherapy in Assessing the Pathologic Complete Response of Patients With Esophageal Squamous Cell Carcinoma
Authors: Taghizadeh Kermani Ali , Ghanbarzadeh Raha , Joudi Mashhad Mona , Javadinia Seyed Alireza , Emadi Torghabeh Ali
Published: May 2022

Introduction

No standard method has been defined to evaluate the therapeutic response of esophageal cancer to neoadjuvant chemoradiotherapy (CRT). This study aimed to determine the predictive value of endoscopic evaluation and biopsy after CRT in predicting the complete pathological response to neoadjuvant CRT in patients with esophageal squamous cell carcinoma (SCC).

Materials and Method

This prospective, descriptive study was conducted on patients with stage II and III esophageal SCC who could undergo esophagectomy. Patients underwent neoadjuvant CRT. Four to six weeks after the end of treatment, re-endoscopy was performed and a biopsy was taken in the presence of a tumor lesion. In the absence of a tumor lesion, the marked site of the esophagus was removed as a blind biopsy. Gastrologist observations during endoscopy and the result of the pathological examination of an endoscopic biopsy were recorded. The patient underwent esophagectomy. The pathology obtained from endoscopic biopsy was compared with the pathology response obtained from esophagectomy.

Results

Sixty-nine patients were included in the study, of which 32 underwent esophagectomy. In an endoscopic examination after CRT, 28 patients had macroscopic tumor remnants and 4 patients did not. Pathological examination of the samples obtained from endoscopy showed no tumor remnants in 10 patients (31.3%), and in 22 patients (68.7%), living tumor remnants were seen in the biopsy specimen. Pathologic evaluation of the samples obtained by surgical resection showed that in 13 patients, there were no viable carcinomas in the esophagus or lymph nodes removed, and the rate of pathologic complete response was 40.6. Sensitivity, specificity, positive predictive, and negative predictive values of endoscopic observations were 94.7, 23, 64.2, and 75%, respectively. Preoperative biopsy sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 68.4, 30.7, 59, and 40%, respectively.

Conclusion

Considering the negative and positive predictive values of endoscopic observations and biopsy after neoadjuvant CRT, it seems that these two methods alone are not suitable for assessing the pathologic complete response after neoadjuvant treatment.
FAT1 Upregulates in Oral Squamous Cell Carcinoma and Promotes Cell Proliferation via Cell Cycle and DNA Repair
Authors: Lan Ting , Ge Qi , Zheng Ke , Huang Li , Yan Yuxiang , Zheng Lixin , Lu Youguang , Zheng Dali
Published: May 2022

Objective

Previous studies have revealed that FAT atypical cadherin 1 (FAT1) plays a tumor-suppressive or oncogenic role in a context-dependent manner in various cancers. However, the functions of FAT1 are ambiguous in tumorigenesis owing to inconsistent research in oral squamous cell carcinoma (OSCC). The present study aimed at gaining an insight into the role of FAT1 in the tumor genesis and development.

Methods

The expression, mutant, and survival data analyses were done using data from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database, verified with clinical samples via real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunohistochemical (IHC) staining. OSCC cells transfected with siRNA were employed for in vitro assessment in cell proliferation, apoptosis, and migration ability in appropriate ways. The underlying mechanism was explored by RNA sequencing after FAT1 silencing.

Results

Overall, FAT1 significantly increased in OSCC with a poor prognosis outcome. The in vitro experiment showed the promoting effect of FAT1 in the proliferation and migration of OSCC cells. FAT1 can also inhibit both the early and late apoptosis of OSCC cells. RNA-sequencing analysis of FAT1 silencing revealed that the cell cycle, DNA replication, and some core genes (MCM2, MCM5, CCNE1 SPC24, MYBL2, KIF2C) may be the potential mechanism in OSCC.

Conclusions

FAT1 may act as an oncogene in OSCC with potential mechanism influencing the cell cycle and DNA repair.
First-Line Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: A Systematic Analysis and Treatment Recommendation
Authors: Liu Hailing , Shi Xiao , Fang Huizi , Cao Lei , Miao Yi , Zhao Xiaoli , Wu Wei , Xu Wei , Li Jianyong , Fan Lei
Published: May 2022

Background

In the era of immunotherapy, autologous stem cell transplantation (ASCT) in first-line therapy in patients with mantle cell lymphoma (MCL) has been a controversial topic. This report aimed to explore the association between ASCT and MCL survival through a systematic review with meta-analysis.

Methods

We performed a systematic search of original articles published from inception to September 2021 using PubMed, MEDLINE, Embase, and Cochrane Library databases.

Results

We included studies that compared ASCT with non-ASCT consolidation in newly diagnosed transplant-eligible MCL. The endpoints were progression-free survival (PFS) and overall survival (OS). There were seven eligible studies (one randomized clinical trial, one prospective cohort study, and five observational studies) published between 2012 and 2021, in which the total number of participants was 3,271. In the non-intensive induction subgroup, patients with ASCT experienced a significant PFS but no OS benefit compared with those without ASCT. In the intensive induction subgroup, the PFS benefit from ASCT still existed but largely attenuated; no OS benefit was observed though only one study was suitable for evaluation. When compared to the rituximab maintenance arm, ASCT had a worse PFS and OS.

Conclusions

In the rituximab plus HiDAC era, the benefit of ASCT as a component of first-line treatment has been weakened. First-line maintenance strategy instead of ASCT seems worth exploring.
RNA Sequencing Reveals Alterations and Similarities in Cell Metabolism, Hypoxia and Immune Evasion in Primary Cell Cultures of Clear Cell Renal Cell Carcinoma
Authors: Simon Adrian Georg , Esser Laura Kristin , Ellinger Jörg , Ritter Manuel , Kristiansen Glen , Muders Michael H. , Mayr Thomas , Toma Marieta Ioana
Published: May 2022

The treatment of advanced renal cell carcinoma remains a challenge. To develop novel therapeutic approaches, primary cell cultures as an in vitro model are considered more representative than commercial cell lines. In this study, we analyzed the gene expression of previously established primary cell cultures of clear cell renal cell carcinoma by bulk (3’m)RNA sequencing and compared it to the tissue of origin. The objectives were the identification of dysregulated pathways under cell culture conditions. Furthermore, we assessed the suitability of primary cell cultures for studying crucial biological pathways, including hypoxia, growth receptor signaling and immune evasion. RNA sequencing of primary cell cultures of renal cell carcinoma and a following Enrichr database analysis revealed multiple dysregulated pathways under cell culture conditions. 444 genes were significantly upregulated and 888 genes downregulated compared to the tissue of origin. The upregulated genes are crucial in DNA repair, cell cycle, hypoxia and metabolic shift towards aerobic glycolysis. A downregulation was observed for genes involved in pathways of immune cell differentiation and cell adhesion. We furthermore observed that 7275 genes have a similar mRNA expression in cell cultures and in tumor tissue, including genes involved in the immune checkpoint signaling or in pathways responsible for tyrosine kinase receptor resistance. Our findings confirm that primary cell cultures are a representative tool for specified experimental approaches. The results presented in this study give further valuable insights into the complex adaptation of patient-derived cells to a new microenvironment, hypoxia and other cell culture conditions, which are often neglected in daily research, and allow new translational and therapeutic approaches.
Over-Expression of Long Non-Coding RNA-AC099850.3 Correlates With Tumor Progression and Poor Prognosis in Lung Adenocarcinoma
Authors: Chen Xi , Guo Jishu , Zhou Fan , Ren Wenjun , Pu Jun , Mutti Luciano , Niu Xiaoqun , Jiang Xiulin
Published: May 2022

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) have been implicated in the initiation and progression of various cancers. LncRNA-AC099850.3 is a novel lncRNA that is abnormally expressed in diverse cancer types including LUAD. However, the clinical significance, prognostic value, diagnostic value, immune role, and potential biological function of AC099850.3 LUAD remain elusive. In this study, we found that AC099850.3 was highly expressed in LUAD and associated with an advanced tumor stage, poor prognosis, and immune infiltration. Receiver operating curve analysis revealed the significant diagnostic ability of AC099850.3 (AUC=0.888). Functionally, the knockdown of AC099850.3 restrained LUAD cell proliferation and migration in vitro. Finally, we constructed a competitive endogenous RNAs (ceRNA) network that included hsa-miR-101-3p and 4 mRNAs (ESPL1, AURKB, BUB3, and FAM83D) specific to AC099850.3 in LUAD. Kaplan–Meier survival analysis showed that a lower expression of miR-101-3p and a higher expression of ESPL1, AURKB, BUB3, and FAM83D, were associated with adverse clinical outcomes in patients with LUAD. This finding provided a comprehensive view of the AC099850.3-mediated ceRNA network in LUAD, thereby highlighting its potential role in the diagnosis and prognosis of LUAD.
The Value of Lung Ultrasound Score in Neonatology
Authors: Zong Haifeng , Huang Zhifeng , Zhao Jie , Lin Bingchun , Fu Yongping , Lin Yanqing , Huang Peng , Sun Hongyan , Yang Chuanzhong
Published: May 2022

Point-of-care lung ultrasound (LUS) is increasingly applied in the neonatal intensive care unit (NICU). Diagnostic applications for LUS in the NICU contain the diagnosis of many common neonatal pulmonary diseases (such as Respiratory distress syndrome, Transient tachypnea of the newborn, Meconium aspiration syndrome, Pneumonia, Pneumothorax, and Pleural effusion) which have been validated. In addition to being employed as a diagnostic tool in the classical sense of the term, recent studies have shown that the number and type of artifacts are associated with lung aeration. Based on this theory, over the last few years, LUS has also been used as a semi-quantitative method or as a “functional” tool. Scores have been proposed to monitor the progress of neonatal lung diseases and to decide whether or not to perform a specific treatment. The semi-quantitative LUS scores (LUSs) have been developed to predict the demand for surfactant therapy, the need of respiratory support and the progress of bronchopulmonary dysplasia. Given their ease of use, accuracy and lack of invasiveness, the use of LUSs is increasing in clinical practice. Therefore, this manuscript will review the application of LUSs in neonatal lung diseases.
Neonatal Pain, Opioid, and Anesthetic Exposure; What Remains in the Human Brain After the Wheels of Time?
Authors: van den Bosch Gerbrich E. , Tibboel Dick , de Graaff Jurgen C. , El Marroun Hanan , van der Lugt Aad , White Tonya , van Dijk Monique
Published: May 2022

Objective

To evaluate possible negative long-term effects of neonatal exposure to pain, opioids and anesthetics in children and adolescents.

Study Design

We studied five unique groups of children recruited from well-documented neonatal cohorts with a history of neonatal exposure to pain, opioids or anesthetics at different points along the continuum from no pain to intense pain and from no opioid exposure to very high opioid exposure in the presence or absence of anesthetics. We evaluated children who underwent major surgery (group 1 and 2), extracorporeal membrane oxygenation (group 3), preterm birth (group 4) and prenatal opioid exposure (group 5) in comparison to healthy controls. Neuropsychological functioning, thermal detection and pain thresholds and high-resolution structural and task-based functional magnetic resonance imaging during pain were assessed. In total 94 cases were included and compared to their own control groups.

Results

Children and adolescents in groups 3 and 5 showed worse neuropsychological functioning after high opioid exposure. A thicker cortex was found in group 1 (pain, opioid and anesthetic exposure) in only the left rostral-middle-frontal-cortex compared to controls. We found no differences in other brain volumes, pain thresholds or brain activity during pain in pain related brain regions between the other groups and their controls.

Conclusions

No major effects of neonatal pain, opioid or anesthetic exposure were observed in humans 8–19 years after exposure in early life, apart from neuropsychological effects in the groups with the highest opioid exposure that warrants further investigation. Studies with larger sample sizes are needed to confirm our findings and test for less pronounced differences between exposed and unexposed children.
A New Generation of Cell Therapies Employing Regulatory T Cells (Treg) to Induce Immune Tolerance in Pediatric Transplantation
Authors: Bernaldo-de-Quirós Esther , Pion Marjorie , Martínez-Bonet Marta , Correa-Rocha Rafael
Published: May 2022

Kidney transplantation is the most common solid organ transplant and the preferred treatment for pediatric patients with end-stage renal disease, but it is still not a definitive solution due to immune graft rejection. Regulatory T cells (Treg) and their control over effector T cells is a crucial and intrinsic tolerance mechanism in limiting excessive immune responses. In the case of transplants, Treg are important for the survival of the transplanted organ, and their dysregulation could increase the risk of rejection in transplanted children. Chronic immunosuppression to prevent rejection, for which Treg are especially sensitive, have a detrimental effect on Treg counts, decreasing the Treg/T-effector balance. Cell therapy with Treg cells is a promising approach to restore this imbalance, promoting tolerance and thus increasing graft survival. However, the strategies used to date that employ peripheral blood as a Treg source have shown limited efficacy. Moreover, it is not possible to use this approach in pediatric patients due to the limited volume of blood that can be extracted from children. Here, we outline our innovative strategy that employs the thymus removed during pediatric cardiac surgeries as a source of therapeutic Treg that could make this therapy accessible to transplanted children. The advantageous properties and the massive amount of Treg cells obtained from pediatric thymic tissue (thyTreg) opens a new possibility for Treg therapies to prevent rejection in pediatric kidney transplants. We are recruiting patients in a clinical trial to prevent rejection in heart-transplanted children through the infusion of autologous thyTreg cells (NCT04924491). If its efficacy is confirmed, thyTreg therapy may establish a new paradigm in preventing organ rejection in pediatric transplants, and their allogeneic use would extend its application to other solid organ transplantation.
The Efficacy of Targeted Exercise on Gross Motor and Neuromuscular Performance in Survivors of Childhood Leukemia: A Pilot Study
Authors: Marchese Victoria , Rock Kelly , York Teresa , Ruble Kathryn , Gray Vicki L.
Published: May 2022

Objectives:

This quasi-experimental study examined the efficacy of targeted exercise training on gross motor performance and neuromuscular impairments in survivors of childhood acute lymphoblastic leukemia (ALL CCS).

Materials and Methods

Ten ALL CCS (median age: 10 years; range: 6–14 years) performed a 6-week training program three times per week (five in-person sessions), including a warm-up, total body stretching, progressive jump rope training, and a cool down. Gross motor performance (test of gross motor proficiency) and lower extremity rate of muscle activation (electromyography), joint torques (motion capture and force plate), and jump height (motion capture) were measured during a countermovement jump at baseline and post-training.

Results

Post-training, ALL CCS demonstrated improvements in body coordination, strength and agilty, bilateral coordination, running speed and agility, and strength gross motor performance (mean change: 1.6–8.1; p < 0.05), the rate of muscle activation of the tibialis anterior and vastus lateralis muscles (mean change: 0.58–0.75; p < 0.05), hip and ankle joint torques (mean change: 0.07; p < 0.05), and jump height (mean change: 0.05; p < 0.05).

Conclusion

This study demonstrated that targeted exercise training can improve gross motor performance and neuromuscular impairments in ALL CCS post-medical treatment.
Post COVID-19 Condition in Children and Adolescents: An Emerging Problem
Authors: Izquierdo-Pujol Jon , Moron-Lopez Sara , Dalmau Judith , Gonzalez-Aumatell Alba , Carreras-Abad Clara , Mendez Maria , Rodrigo Carlos , Martinez-Picado Javier
Published: May 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became a pandemic in 2020 and by March 2022 had caused more than 479 million infections and 6 million deaths worldwide. Several acute and long-term symptoms have been reported in infected adults, but it remains unclear whether children/adolescents also experience persistent sequelae. Hence, we conducted a review of symptoms and pathophysiology associated with post-coronavirus disease 2019 (post-COVID-19) condition in children and adolescents. We reviewed the scientific literature for reports on persistent COVID-19 symptoms after SARS-CoV-2 infection in both children/adolescents and adults from 1 January 2020 to 31 March 2022 (based on their originality and relevance to the broad scope of this review, 26 reports were included, 8 focused on adults and 18 on children/adolescents). Persistent sequelae of COVID-19 are less common in children/adolescents than in adults, possibly owing to a lower frequency of SARS-CoV-2 infection and to the lower impact of the infection itself in this age group. However, cumulative evidence has shown prolonged COVID-19 to be a clinical entity, with few pathophysiological associations at present. The most common post-COVID-19 symptoms in children/adolescents are fatigue, lack of concentration, and muscle pain. In addition, we found evidence of pathophysiology associated with fatigue and/or headache, persistent loss of smell and cough, and neurological and/or cardiovascular symptoms. This review highlights the importance of unraveling why SARS-CoV-2 infection may cause post-COVID-19 condition and how persistent symptoms might affect the physical, social, and psychological well-being of young people in the future.