bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Pediatric Coeliac Disease Patients Suggests Potential Pre-Seroconversion Markers
Authors: Ramírez-Sánchez Aarón D. , Chu Xiaojing , Modderman Rutger , Kooy-Winkelaar Yvonne , Koletzko Sibylle , Korponay-Szabó Ilma R. , Troncone Riccardo , Wijmenga Cisca , Mearin Luisa , Withoff Sebo , Jonkers Iris H. , Li Yang
Published: March 2022

Celiac Disease (CeD) is a complex immune disorder involving villous atrophy in the small intestine that is triggered by gluten intake. Current CeD diagnosis is based on late-stage pathophysiological parameters such as detection of specific antibodies in blood and histochemical detection of villus atrophy and lymphocyte infiltration in intestinal biopsies. To date, no early onset biomarkers are available that would help prevent widespread villous atrophy and severe symptoms and co-morbidities. To search for novel CeD biomarkers, we used single-cell RNA sequencing (scRNAseq) to investigate PBMC samples from 11 children before and after seroconversion for CeD and 10 control individuals matched for age, sex and HLA-genotype. We generated scRNAseq profiles of 9559 cells and identified the expected major cellular lineages. Cell proportions remained stable across the different timepoints and health conditions, but we observed differences in gene expression profiles in specific cell types when comparing patient samples before and after disease development and comparing patients with controls. Based on the time when transcripts were differentially expressed, we could classify the deregulated genes as biomarkers for active CeD or as potential pre-diagnostic markers. Pathway analysis showed that active CeD biomarkers display a transcriptional profile associated with antigen activation in CD4+ T cells, whereas NK cells express a subset of biomarker genes even before CeD diagnosis. Intersection of biomarker genes with CeD-associated genetic risk loci pinpointed genetic factors that might play a role in CeD onset. Investigation of potential cellular interaction pathways of PBMC cell subpopulations highlighted the importance of TNF pathways in CeD. Altogether, our results pinpoint genes and pathways that are altered prior to and during CeD onset, thereby identifying novel potential biomarkers for CeD diagnosis in blood.
Intestinal Mucosal Immunity-Mediated Modulation of the Gut Microbiome by Oral Delivery of Enterococcus faecium Against Salmonella Enteritidis Pathogenesis in a Laying Hen Model
Authors: Huang Shimeng , Rong Xiaoping , Liu Meiling , Liang Zhongjun , Geng Yanqiang , Wang Xinyue , Zhang Jianyun , Ji Cheng , Zhao Lihong , Ma Qiugang
Published: March 2022

Enterococcus faecium (E. faecium) is a protective role that has crucial beneficial functions on intestinal homeostasis. This study aimed to investigate the effects of E. faecium on the laying performance, egg quality, host metabolism, intestinal mucosal immunity, and gut microbiota of laying hens under the Salmonella Enteritidis (S. Enteritidis) challenge. A total of 400 45-week-old laying hens were randomly divided into four treatments (CON, EF, SCON, and SEF groups) with five replicates for each group and 20 hens per replicate and fed with a basal diet or a basal diet supplemented with E. faecium (2.5 × 108 cfu/g feed). The experiment comprised two phases, consisting of the pre-salmonella challenged phase (from day 14 to day 21) and the post-salmonella challenged phase (from day 21 to day 42). At day 21 and day 22, the hens in SCON and SEF groups were orally challenged with 1.0 ml suspension of 109 cfu/ml S. Enteritidis (CVCC3377) daily, whereas the hens in CON and EF groups received the same volume of sterile PBS. Herein, our results showed that E. faecium administration significantly improved egg production and shell thickness during salmonella infection. Also, E. faecium affected host lipid metabolism parameters via downregulating the concentration of serum triglycerides, inhibited oxidative stress, and enhanced immune functions by downregulating the level of serum malondialdehyde and upregulating the level of serum immunoglobulin G. Of note, E. faecium supplementation dramatically alleviated intestinal villi structure injury and crypt atrophy, and improved intestinal mucosal barrier injuries caused by S. Enteritidis challenge. Moreover, our data revealed that E. faecium supplementation ameliorated S. Enteritidis infection-induced gut microbial dysbiosis by altering the gut microbial composition (reducing Bacteroides, Desulfovibrio, Synergistes, and Sutterella, and increasing Barnesiella, Butyricimonas, Bilophila, and Candidatus_Soleaferrea), and modulating the gut microbial function, such as cysteine and methionine metabolism, pyruvate metabolism, fatty acid metabolism, tryptophan metabolism, salmonella infection, and the PI3K-Akt signaling pathway. Taken together, E. faecium has a strong capacity to inhibit the S. Enteritidis colonization of hens. The results highlight the potential of E. faecium supplementation as a dietary supplement to combat S. Enteritidis infection in animal production and to promote food safety.
Automated Virtual Design of Organic Semiconductors Based on Metal-Organic Frameworks
Authors: Mostaghimi Mersad , Rêgo Celso R. C. , Haldar Ritesh , Wöll Christof , Wenzel Wolfgang , Kozlowska Mariana
Published: March 2022

The arrangement of organic semiconductor molecules in a material can be modulated using different supramolecular approaches, including the metal–organic framework (MOF) approach. These arrangements result in different frameworks topologies and structures. Fabrication of materials comprising optimized assemblies and functional molecules enables efficient tailoring of material properties, including electronic responses. Since semiconducting properties are sensitive to subtle changes in the nanostructure of the material, the exploitation of MOFs has promising potential in the development of new materials with designed structure and function. Based on decade-long method development, virtual design strategies have become ever more important, and such design methods profit from the availability of automated tools. Such tools enable screening of huge libraries of organic molecules in in silico models of the structure of three-dimensional nanoscale assemblies as the prerequisite to predict their functionality. In this report, we present and demonstrate the application of an automated workflow tool developed for MOFs of the primitive cubic (PCU) topology. We use pentacene-based ditopic linkers of a varied chemical composition and pillar linkers of different molecular sizes to automatically generate PCU MOFs, sample their structural dynamics at finite temperature, and predict electronic coupling matrix elements in vibrationally averaged assemblies. We demonstrate the change of the intermolecular ordering in the resulting MOFs and its impact on the semiconducting properties. This development lays the basis of an extendable framework to automatically model a wide variety of MOFs and characterize their function with respect to properties, such as conduction properties, absorption, and interaction with light. The developed workflow protocol and tools are available at https://github.com/KIT-Workflows/PCU-MOF.
Broadband Polarization Manipulation Based on W-Shaped Metasurface
Authors: Xu Guangyuan , Gao Lei , Chen Yongqiang , Ding Yaqiong , Wang Jun , Fang Yu , Wu Xingzhi , Sun Yong
Published: March 2022

We present a metasurface consisting of W-shaped resonators to realize broadband reflective linear and circular polarization conversions. We find that the cross polarization conversion ratio for normal incidence is over 0.95 from 9.2 to 18.7 GHz, covering 68.1% of the central frequency. We also show that, the conversion performance is almost insensitive to the angle of incident waves. Furthermore, by simply adjusting the geometrical parameters of the W-shaped metasurface, the broadband circular polarization conversion is also achieved. We emphasize that the bandwidth of axis ratio less than 3.0 dB covers from 10.1 to 17.7 GHz, equivalent to 54.7% relative bandwidth. Due to these broadband and high-efficiency polarization conversion features, our proposal may have a wide application prospect.
Gray-White Matter Ratio at the Level of the Basal Ganglia as a Predictor of Neurologic Outcomes in Cardiac Arrest Survivors: A Literature Review
Authors: Zhou Fating , Wang Hongxia , Jian Mengyao , Wang Zhiyuan , He Yarong , Duan Haizhen , Gan Lu , Cao Yu
Published: March 2022

Loss of gray-white matter discrimination is the primary early imaging finding within of cranial computed tomography in cardiac arrest survivors, and this has been also regarded as a novel predictor for evaluating neurologic outcome. As displayed clearly on computed tomography and based on sensitivity to hypoxia, the gray-white matter ratio at basal ganglia (GWR-BG) region was frequently detected to assess the neurologic outcome by several studies. The specificity of GWR-BG is 72.4 to 100%, while the sensitivity is significantly different. Herein we review the mechanisms mediating cerebral edema following cardiac arrest, demonstrate the determination procedures with respect to GWR-BG, summarize the related researches regarding GWR-BG in predicting neurologic outcomes within cardiac arrest survivors, and discuss factors associated with predicting the accuracy of this methodology. Finally, we describe the effective measurements to increase the sensitivity of GWR-BG in predicting neurologic outcome.
Case Report: A Neuro-Ophthalmological Assessment of Vision Loss in a Pediatric Case of McCune-Albright Syndrome
Authors: Lemme Jordan D. , Tucker-Bartley Anthony , Drubach Laura A. , Shah Nehal , Romo Laura , Cay Mariesa , Voss Stephan , Kwatra Neha , Kaban Leonard B. , Hassan Adam S. , Boyce Alison M. , Upadhyay Jaymin
Published: March 2022

Patients diagnosed with McCune-Albright Syndrome (MAS) frequently manifest craniofacial fibrous dysplasia (FD). Craniofacial FD can impinge nerve fibers causing visual loss as well as craniofacial pain. Surgical decompression of affected nerves is performed, with variable efficacy, in an attempt to restore function or alleviate symptoms. Here, we present a case of a 12-year-old MAS patient with visual deficits, particularly in the left eye (confirmed by enlarged blind spots on Goldmann visual field testing), and craniofacial pain. Decompression surgery of the left optic nerve mildly improved vision, while persistent visual deficits were noted at a 3-month follow-up assessment. An in-depth, imaging-based evaluation of the visual system, including the retinal nerve fiber layer, optic nerves, and central nervous system (CNS) visual pathways, revealed multiple abnormalities throughout the visual processing stream. In the current FD/MAS patient, a loss of white matter fiber density within the left optic radiation and functional changes involving the left primary visual cortex were observed. Aberrant structural and functional abnormalities embedded within central visual pathways may play a role in facilitating deficits in vision in FD/MAS and contribute to the variable outcome following peripheral nerve decompression surgery.
A Novel Toll-Like Receptor 2 Agonist Protects Mice in a Prophylactic Treatment Model Against Challenge With Bacillus anthracis
Authors: Chiang Chih-Yuan , Lane Douglas J. , Zou Yefen , Hoffman Tim , Pan Jianfeng , Hampton Janice , Maginnis Jillian , Nayak Bishnu P. , D’Oro Ugo , Valiante Nicholas , Miller Andrew T. , Cooke Michael , Wu Tom , Bavari Sina , Panchal Rekha G.
Published: March 2022

Current therapies for anthrax include the use of antibiotics (i.e., doxycycline, and ciprofloxacin), an anthrax vaccine (BioThrax) and Bacillus anthracis-specific, monoclonal antibody (mAb) (i.e., Raxibacumab and obiltoxaximab). In this study, we investigated the activity of immunomodulators, which potentiate inflammatory responses through innate immune receptors. The rationale for the use of innate immune receptor agonists as adjunctive immunomodulators for infectious diseases is based on the concept that augmentation of host defense should promote the antimicrobial mechanism of the host. Our aim was to explore the anti-B. anthracis effector function of Toll-like receptor (TLR) agonists using a mouse model. Amongst the six TLR ligands tested, Pam3CSK4 (TLR1/2 ligand) was the best at protecting mice from lethal challenge of B. anthracis. We then evaluated the activity of a novel TLR2 ligand, DA-98-WW07. DA-98-WW07 demonstrated enhanced protection in B. anthracis infected mice. The surviving mice that received DA-98-WW07 when re-challenged with B. anthracis 20 days post the first infection showed increased survival rate. Moreover, ciprofloxacin, when treated in adjunct with a suboptimal concentration of DA-98-WW07 demonstrated augmented activity in protecting mice from B. anthracis infection. Taken together, we report the prophylactic treatment potential of DA-98-WW07 for anthrax and the utility of immunomodulators in combination with an antibiotic to treat infections caused by the B. anthracis bacterium.
Development and Validation of Multiplex Quantitative Real-Time PCR Assays for Simultaneous Detection and Differentiation of HTLV-1 and HTLV-2, Using Different PCR Platforms and Reagent Brands
Authors: Gonçalves Maria Gisele , Fukasawa Lucila Okuyama , Campos Karoline Rodrigues , Higa Fábio Takenori , Caterino-de-Araujo Adele
Published: March 2022

Brazil currently has the highest number of individuals infected with human T-lymphotropic virus 1- and 2- (HTLV-1 and HTLV-2) globally. At present, neither molecular protocols nor commercial assays are available for HTLV-1/-2 diagnosis or validated by the Brazilian Ministry of Health regulatory agency (ANVISA). We developed and validated two in-house multiplex quantitative real-time PCR for HTLV-1/-2 (mqPCR_HTLV) assays, targeting the pol and tax genes, for the simultaneous identification of HTLV-1, HTLV-2, and the albumin reference gene. The robustness of the assays was evaluated on two platforms using seven commercial master mix formulations. The reactions employed double plasmids (pHTLV1-Alb and pHTLV2-Alb) for the standard curve’s construction and for expressing the detection limit of the assays. They were able to detect 10 and 10 copies of HTLV-1 and 10 and 70 copies of HTLV-2 for the tax and pol targets, respectively. High efficiency was obtained using both the platforms and all the reagents evaluated and were successfully reproduced by other analysts. DNA samples from HTLV-1/-2-infected and non-infected patients and from HIV/HTLV-coinfected patients were evaluated to determine the feasibility of their use in routine diagnosis. The mqPCR_HTLV (pol and tax) assays demonstrated an overall specificity of 100% and a sensitivity of 97.4% when testing samples from patients without HIV infection, and sensitivities of 77.1% (pol) and 74.6% (tax) in samples from HIV/HTLV-coinfected patients. In addition, they resolved the issue of HTLV western blotting (WB) indeterminate and WB-untyped results in 45.5 and 66.7% of cases, respectively. The developed mqPCR_HTLV (pol and tax) assays indicated their feasibility for efficient and reliable HTLV diagnosis in various core facility laboratories under different conditions and supplies.
An Adenosine Triphosphate- Dependent 5′-3′ DNA Helicase From sk1-Like Lactococcus lactis F13 Phage
Authors: Chmielewska-Jeznach Magdalena , Steczkiewicz Kamil , Kobyłecki Kamil , Bardowski Jacek K. , Szczepankowska Agnieszka K.
Published: March 2022

Here, we describe functional characterization of an early gene (gp46) product of a virulent Lactococcus lactis sk1-like phage, vB_Llc_bIBBF13 (abbr. F13). The GP46F13 protein carries a catalytically active RecA-like domain belonging to the P-loop NTPase superfamily. It also retains features characteristic for ATPases forming oligomers. In order to elucidate its detailed molecular function, we cloned and overexpressed the gp46 gene in Escherichia coli. Purified GP46F13 protein binds to DNA and exhibits DNA unwinding activity on branched substrates in the presence of adenosine triphosphate (ATP). Size exclusion chromatography with multi-angle light scattering (SEC-MALS) experiments demonstrate that GP46F13 forms oligomers, and further pull-down assays show that GP46F13 interacts with host proteins involved in replication (i.e., DnaK, DnaJ, topoisomerase I, and single-strand binding protein). Taking together the localization of the gene and the obtained results, GP46F13 is the first protein encoded in the early-expressed gene region with helicase activity that has been identified among lytic L. lactis phages up to date.
Systematic Analysis and Accurate Identification of DNA N4-Methylcytosine Sites by Deep Learning
Authors: Yu Lezheng , Zhang Yonglin , Xue Li , Liu Fengjuan , Chen Qi , Luo Jiesi , Jing Runyu
Published: March 2022

DNA N4-methylcytosine (4mC) is a pivotal epigenetic modification that plays an essential role in DNA replication, repair, expression and differentiation. To gain insight into the biological functions of 4mC, it is critical to identify their modification sites in the genomics. Recently, deep learning has become increasingly popular in recent years and frequently employed for the 4mC site identification. However, a systematic analysis of how to build predictive models using deep learning techniques is still lacking. In this work, we first summarized all existing deep learning-based predictors and systematically analyzed their models, features and datasets, etc. Then, using a typical standard dataset with three species (A. thaliana, C. elegans, and D. melanogaster), we assessed the contribution of different model architectures, encoding methods and the attention mechanism in establishing a deep learning-based model for the 4mC site prediction. After a series of optimizations, convolutional-recurrent neural network architecture using the one-hot encoding and attention mechanism achieved the best overall prediction performance. Extensive comparison experiments were conducted based on the same dataset. This work will be helpful for researchers who would like to build the 4mC prediction models using deep learning in the future.
Neuronal Ensembles Organize Activity to Generate Contextual Memory
Authors: Marks William D. , Yokose Jun , Kitamura Takashi , Ogawa Sachie K.
Published: March 2022

Contextual learning is a critical component of episodic memory and important for living in any environment. Context can be described as the attributes of a location that are not the location itself. This includes a variety of non-spatial information that can be derived from sensory systems (sounds, smells, lighting, etc.) and internal state. In this review, we first address the behavioral underpinnings of contextual memory and the development of context memory theory, with a particular focus on the contextual fear conditioning paradigm as a means of assessing contextual learning and the underlying processes contributing to it. We then present the various neural centers that play roles in contextual learning. We continue with a discussion of the current knowledge of the neural circuitry and physiological processes that underlie contextual representations in the Entorhinal cortex-Hippocampal (EC-HPC) circuit, as the most well studied contributor to contextual memory, focusing on the role of ensemble activity as a representation of context with a description of remapping, and pattern separation and completion in the processing of contextual information. We then discuss other critical regions involved in contextual memory formation and retrieval. We finally consider the engram assembly as an indicator of stored contextual memories and discuss its potential contribution to contextual memory.
Control of a Robotic Arm With an Optimized Common Template-Based CCA Method for SSVEP-Based BCI
Authors: Peng Fang , Li Ming , Zhao Su-na , Xu Qinyi , Xu Jiajun , Wu Haozhen
Published: March 2022

Recently, the robotic arm control system based on a brain-computer interface (BCI) has been employed to help the disabilities to improve their interaction abilities without body movement. However, it's the main challenge to implement the desired task by a robotic arm in a three-dimensional (3D) space because of the instability of electroencephalogram (EEG) signals and the interference by the spontaneous EEG activities. Moreover, the free motion control of a manipulator in 3D space is a complicated operation that requires more output commands and higher accuracy for brain activity recognition. Based on the above, a steady-state visual evoked potential (SSVEP)-based synchronous BCI system with six stimulus targets was designed to realize the motion control function of the seven degrees of freedom (7-DOF) robotic arm. Meanwhile, a novel template-based method, which builds the optimized common templates (OCTs) from various subjects and learns spatial filters from the common templates and the multichannel EEG signal, was applied to enhance the SSVEP recognition accuracy, called OCT-based canonical correlation analysis (OCT-CCA). The comparison results of offline experimental based on a public benchmark dataset indicated that the proposed OCT-CCA method achieved significant improvement of detection accuracy in contrast to CCA and individual template-based CCA (IT-CCA), especially using a short data length. In the end, online experiments with five healthy subjects were implemented for achieving the manipulator real-time control system. The results showed that all five subjects can accomplish the tasks of controlling the manipulator to reach the designated position in the 3D space independently.
A Decentralized ComBat Algorithm and Applications to Functional Network Connectivity
Authors: Bostami Biozid , Hillary Frank G. , van der Horn Harm Jan , van der Naalt Joukje , Calhoun Vince D. , Vergara Victor M.
Published: March 2022

Recent studies showed that working with neuroimage data collected from different research facilities or locations may incur additional source dependency, affecting the overall statistical power. This problem can be mitigated with data harmonization approaches. Recently, the ComBat method has become commonly adopted for various neuroimage modalities. While open neuroimaging datasets are becoming more common, a substantial amount of data is still unable to be shared for various reasons. In addition, current approaches require moving all the data to a central location, which requires additional resources and creates redundant copies of the same datasets. To address these issues, we propose a decentralized harmonization approach that does not create redundant copies of the original datasets and performs remote operations on the datasets separately without sharing any individual subject data, ensuring a certain level of privacy and reducing regulatory hurdles. We proposed a novel approach called “Decentralized ComBat” which can harmonize datasets separately without combining the datasets. We tested our model by harmonizing functional network connectivity datasets from two traumatic brain injury studies in a decentralized way. Also, we used simulations to analyze the performance and scalability of our model when the number of data collection sites increases. We compare the output with centralized ComBat and show that the proposed approach produces similar results, increasing the sensitivity of the functional network connectivity analysis and validating our approach. Simulations show that our model can be easily scaled to many more datasets based on the requirement. In sum, we believe this provides a powerful tool, further complementing open data and allowing for integrating public and private datasets.
A Hybrid Deep Learning Method for Early and Late Mild Cognitive Impairment Diagnosis With Incomplete Multimodal Data
Authors: Jin Leiming , Zhao Kun , Zhao Yan , Che Tongtong , Li Shuyu
Published: March 2022

Multimodality neuroimages have been widely applied to diagnose mild cognitive impairment (MCI). However, the missing data problem is unavoidable. Most previously developed methods first train a generative adversarial network (GAN) to synthesize missing data and then train a classification network with the completed data. These methods independently train two networks with no information communication. Thus, the resulting GAN cannot focus on the crucial regions that are helpful for classification. To overcome this issue, we propose a hybrid deep learning method. First, a classification network is pretrained with paired MRI and PET images. Afterward, we use the pretrained classification network to guide a GAN by focusing on the features that are helpful for classification. Finally, we synthesize the missing PET images and use them with real MR images to fine-tune the classification model to make it better adapt to the synthesized images. We evaluate our proposed method on the ADNI dataset, and the results show that our method improves the accuracies obtained on the validation and testing sets by 3.84 and 5.82%, respectively. Moreover, our method increases the accuracies for the validation and testing sets by 7.7 and 9.09%, respectively, when we synthesize the missing PET images via our method. An ablation experiment shows that the last two stages are essential for our method. We also compare our method with other state-of-the-art methods, and our method achieves better classification performance.
Internalization of Muscle-Specific Kinase Is Increased by Agrin and Independent of Kinase-Activity, Lrp4 and Dynamin
Authors: Gemza Anna , Barresi Cinzia , Proemer Jakob , Hatami Jasmin , Lazaridis Margarita , Herbst Ruth
Published: March 2022

Muscle-specific kinase (MuSK) is a receptor tyrosine kinase absolutely required for neuromuscular junction formation. MuSK is activated by binding of motor neuron-derived Agrin to low-density lipoprotein receptor related protein 4 (Lrp4), which forms a complex with MuSK. MuSK activation and downstream signaling are critical events during the development of the neuromuscular junction. Receptor tyrosine kinases are commonly internalized upon ligand binding and crosstalk between endocytosis and signaling has been implicated. To extend our knowledge about endocytosis of synaptic proteins and its role during postsynaptic differentiation at the neuromuscular junction, we studied the stability and internalization of Lrp4, MuSK and acetylcholine receptors (AChRs) in response to Agrin. We provide evidence that MuSK but not Lrp4 internalization is increased by Agrin stimulation. MuSK kinase-activity is not sufficient to induce MuSK internalization and the absence of Lrp4 has no effect on MuSK endocytosis. Moreover, MuSK internalization and signaling are unaffected by the inhibition of Dynamin suggesting that MuSK endocytosis uses a non-conventional pathway and is not required for MuSK-dependent downstream signaling.
The Cross-Talks Among Bone Morphogenetic Protein (BMP) Signaling and Other Prominent Pathways Involved in Neural Differentiation
Authors: Manzari-Tavakoli Asma , Babajani Amirhesam , Farjoo Mohammad Hadi , Hajinasrollah Mostafa , Bahrami Soheyl , Niknejad Hassan
Published: March 2022

The bone morphogenetic proteins (BMPs) are a group of potent morphogens which are critical for the patterning, development, and function of the central nervous system. The appropriate function of the BMP pathway depends on its interaction with other signaling pathways involved in neural differentiation, leading to synergistic or antagonistic effects and ultimately favorable biological outcomes. These opposite or cooperative effects are observed when BMP interacts with fibroblast growth factor (FGF), cytokines, Notch, Sonic Hedgehog (Shh), and Wnt pathways to regulate the impact of BMP-induced signaling in neural differentiation. Herein, we review the cross-talk between BMP signaling and the prominent signaling pathways involved in neural differentiation, emphasizing the underlying basic molecular mechanisms regarding the process of neural differentiation. Knowing these cross-talks can help us to develop new approaches in regenerative medicine and stem cell based therapy. Recently, cell therapy has received significant attention as a promising treatment for traumatic or neurodegenerative diseases. Therefore, it is important to know the signaling pathways involved in stem cell differentiation toward neural cells. Our better insight into the cross-talk of signaling pathways during neural development would improve neural differentiation within in vitro tissue engineering approaches and pre-clinical practices and develop futuristic therapeutic strategies for patients with neurological disease.
The Minimal Subcortical Electronic Threshold Predicts the Motor Deficit and Survivals in Non-Awake Surgery for Gliomas Involving the Motor Pathway
Authors: Ren Xiaohui , Yang Xiaocui , Huang Wei , Yang Kaiyuan , Liu Li , Cui Yong , Guo Lanjun , Qiao Hui , Lin Song
Published: March 2022

Purpose

Direct subcortical motor mapping is the golden criterion to detect and monitor the motor pathway during glioma surgery. Minimal subcortical monopolar threshold (MSCMT) means the minimal distance away from the motor pathway and is critical to decide to continue or interrupt glioma resection. However, the optimal cutoff value of MSCMT for glioma resection in non-awake patients has not been reported discreetly. In this study, we try to establish the safe cutoff value of MSCMT for glioma resection and analyzed its relationship with postoperative motor deficit and long-term survivals.

Methods

We designed this prospective study with high-frequency electronic stimulus method. The cutoff MSCMT of postoperative motor deficits was statistically calculated by receiver operating characteristic (ROC) curve, and its relationship with motor deficit and survivals was analyzed by logistic and Cox regression, respectively.

Results

The cutoff MSCMT to predict motor deficit after surgery was 3.9 mA on day 1, 3.7 mA on day 7, 5.2 mA at 3 months, and 5.2 mA at 6 months. MSCMT ≤3.9 mA and MSCMT ≤5.2 mA independently predicted postoperative motor deficits at four times after surgery (P < 0.05) but had no effect on the removal degree of tumor (P > 0.05). In high-grade gliomas, MSCMT ≤3.9 mA independently predicted shorter progression-free survival [odds ratio (OR) = 3.381 (1.416–8.076), P = 0.006] and overall survival [OR = 3.651 (1.336–9.977), P = 0.012]. Power model has the best fitness for paired monopolar and bipolar high-frequency thresholds.

Conclusions

This study showed strong cause–effect relation between MSCMT and postoperative motor deficit and prognoses. The cutoff MSCMT was dug out to avoid postoperative motor deficit. Further studies are needed to establish the results above.
Lipid Droplet-Related PLIN2 in CD68+ Tumor-Associated Macrophage of Oral Squamous Cell Carcinoma: Implications for Cancer Prognosis and Immunotherapy
Authors: He Yijia , Dong Yuexin , Zhang Xinwen , Ding Zhuang , Song Yuxian , Huang Xiaofeng , Chen Sheng , Wang Zhiyong , Ni Yanhong , Ding Liang
Published: March 2022

Background

PLIN2 (adipose differentiation-related protein) belongs to the perilipin family and is a marker of lipid droplets (LDs). Numerous types of tumor exhibit a high PLIN2 level, but its tumorigenic or tumor-suppressive role has been in debate. Recently, LDs serve as innate immune hubs and show antimicrobial capacity. We here aimed to investigate the heterogeneous functions of PLIN2 in the tumor microenvironment and immune regulation.

Methods

This retrospective study included 96 oral squamous cell carcinoma (OSCC) samples and analyzed the spatial distribution of PLIN2 by immunohistochemistry (IHC) and LD level by oil red O staining. A total of 21 serial sections were obtained to analyze the relationship between PLIN2 and immune cells by IHC and immunofluorescence (IF). Single-cell sequencing was used to analyze the cell locations of PLIN2. The values of diagnosis and prognosis of PLIN2 were also evaluated. Tumor Immune Estimation Resource (TIMER), cBioPortal databases, and IHC analysis were used to investigate the relationship between PLIN2 and OSCC immune microenvironment.

Results

PLIN2 was mainly expressed in tumor-infiltrating immunocytes (TIIs) of OSCC. Patients with high PLIN2 harbored more cytoplastic LDs. CD68+ tumor-associated macrophages (TAMs), instead of T cells and B cells, were found to be the main resource of PLIN2 in OSCC stroma and lung, pancreas, prostate, and testis. However, CD56+ NK cells also showed less extent of PLIN2 staining in OSCC. Moreover, patients with a high PLIN2 level in immune cells had a higher TNM stage and were susceptible to postoperative metastasis, but the escalated PLIN2 level in invasive tumor front independently predicted shorter metastasis-free survival. Furthermore, a high PLIN2 presentation in the microenvironment induced immune suppression which was featured as less infiltration of CD8+ T cells and more CD68+ TAMs and Foxp3+ Tregs, accompanied by more immune checkpoint molecules such as CSF1R, LGALS9, IL-10, CTLA-4, and TIGIT.

Conclusion

CD68+ TAM-derived PLIN2 might participate in regulating immune balance of OSCC patients, which provides new insight into immune checkpoint therapy.
Sporadic Vestibular Schwannoma Size and Location Do not Correlate With the Severity of Hearing Loss at Initial Presentation
Authors: Brown Alyssa , Early Samuel , Vasilijic Sasa , Stankovic Konstantina M.
Published: March 2022

Vestibular schwannoma (VS) is a non-malignant intracranial neoplasm arising from the vestibular branch of the 8th cranial nerve; sensorineural hearing loss (SNHL) is the most common associated symptom. Understanding whether VS imaging characteristics at the time of VS diagnosis can be associated with severity of VS-induced SNHL can impact patient counseling and define promising areas for future research. Patients diagnosed with VS at Massachusetts Eye and Ear (MEE) from 1994 through 2018 were analyzed if magnetic resonance imaging at VS presentation and sequential audiometry were available. Results were compared with original studies available in PubMed, written in English, on VS imaging characteristics and their impact on hearing in patients. A total of 477 patients with unilateral VS from the MEE database demonstrated no significant correlation between any features of tumor imaging at the time of VS diagnosis, such as VS size, impaction or location, and any hearing loss metric. Twenty-three published studies on the impact of VS imaging characteristics on patient hearing met inclusion criteria, with six solely involving NF2 patients and three including both sporadic and NF2-related VS patients. Fifteen studies reported a significant relationship between SNHL and at least one VS imaging characteristic; however, these trends were universally limited to NF2 patients or involved small patient populations, and were not reproduced in larger studies. Taken together, SNHL in sporadic VS patients is not readily associated solely with any tumor imaging characteristics. This finding motivates future studies to define how VS microenvironment and secreted molecules influence VS-induced SNHL.
Comparison of Supraclavicular Oblique Incision With Traditional Low Collar Incision Approach for Thyroidectomy in Differentiated Thyroid Cancer
Authors: Jiang Bo , Qu Cheng , Jiang Chaoyu , Zhang Chen , Shen Song , Luo Yuqian , Su Lei
Published: March 2022

Background

Various incisions and approaches for thyroidectomy have been developed to treat differentiated thyroid cancer (DTC). Supraclavicular oblique incision (SOI) thyroidectomy (SOIT) has been applied in DTC patients over the past ten years. However, the safety and efficacy of this approach were yet to be confirmed.

Aim

This study aimed to compare the surgical and patient-related outcomes between SOIT and traditional low collar incision thyroidectomy (TLCIT) in patients with DTC.

Methods

We retrospectively screened all patients with DTC who received thyroid lobectomy from October 2020 to October 2021. The surgical results and patient-related outcomes assessed at 1 and 6 months after surgery by questionnaire were compared between the SOIT and TLCIT groups.

Results

A total of 128 patients were included in this study, of whom 38 patients (30.5%) were operated on with SOIT and 89 patients (69.5%) with TLCIT. There was no significant difference in demographic characteristics and thyroid features between the two groups. Despite comparable operative time (61.9 ± 12.1 vs. 59.9 ± 15.0 min, p = 0.425), the SOIT group had a smaller neck incision (4.4 ± 0.7 vs. 5.0 ± 1.0 cm, p = 0.002), a shorter duration of postoperative drainage (2.4 ± 0.5 vs. 2.7 ± 0.9 days, p = 0.019), less volume of postoperative drainage (48.4 ± 24.6 vs. 60.3 ± 22.8 ml, p = 0.040), and shorter postoperative hospitalization (3.2 ± 0.5 vs. 3.6 ± 0.9 days p = 0.006), as compared with the TLCIT group. At 1-month follow-up after surgery, SOIT showed better performance in preventing hypoparathyroidism (p = 0.026) and abnormal neck sensation (p = 0.010) and in improving cosmetic satisfaction (p = 0.036) than TLCIT. At 6-month follow-up, SOIT was feedback with better cosmetic satisfaction (p < 0.001) and a lower percent of abnormal neck sensation (p = 0.031) or movement (p = 0.005).

Conclusion

Our study suggests that minimally invasive surgery using the SOI provides superior surgical and patient-related outcomes compared with surgery using a traditional low collar incision (TLCI) in patients with DTC.
Geometric and Dosimetric Evaluation of the Automatic Delineation of Organs at Risk (OARs) in Non-Small-Cell Lung Cancer Radiotherapy Based on a Modified DenseNet Deep Learning Network
Authors: Zhang Fuli , Wang Qiusheng , Yang Anning , Lu Na , Jiang Huayong , Chen Diandian , Yu Yanjun , Wang Yadi
Published: March 2022

Purpose

To introduce an end-to-end automatic segmentation model for organs at risk (OARs) in thoracic CT images based on modified DenseNet, and reduce the workload of radiation oncologists.

Materials and Methods

The computed tomography (CT) images of 36 lung cancer patients were included in this study, of which 27 patients’ images were randomly selected as the training set, 9 patients’ as the testing set. The validation set was generated by cross validation and 6 patients’ images were randomly selected from the training set during each epoch as the validation set. The autosegmentation task of the left and right lungs, spinal cord, heart, trachea and esophagus was implemented, and the whole training time was approximately 5 hours. Geometric evaluation metrics including the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95) and average surface distance (ASD), were used to assess the autosegmentation performance of OARs based on the proposed model and were compared with those based on U-Net as benchmarks. Then, two sets of treatment plans were optimized based on the manually contoured targets and OARs (Plan1), as well as the manually contours targets and the automatically contoured OARs (Plan2). Dosimetric parameters, including Dmax, Dmean and Vx, of OARs were obtained and compared.

Results

The DSC, HD95 and ASD of the proposed model were better than those of U-Net. The differences in the DSC of the spinal cord and esophagus, differences in the HD95 of the spinal cord, heart, trachea and esophagus, as well as differences in the ASD of the spinal cord were statistically significant between the two models (P<0.05). The differences in the dose-volume parameters of the two sets of plans were not statistically significant (P>0.05). Moreover, compared with manual segmentation, autosegmentation significantly reduced the contouring time by nearly 40.7% (P<0.05).

Conclusions

The bilateral lungs, spinal cord, heart and trachea could be accurately delineated using the proposed model in this study; however, the automatic segmentation effect of the esophagus must still be further improved. The concept of feature map reuse provides a new idea for automatic medical image segmentation.
Comparison of Single-Incision Scrotal Orchiopexy and Traditional Two-Incision Inguinal Orchiopexy for Primary Palpable Undescended Testis in Children: A Systematic Review and Meta-Analysis
Authors: Yu Chengjun , Hu Yang , Wang Ling , Kang Lian , Zhao Jie , Lu Jiandong , Lin Tao , He Dawei , Wu Shengde , Wei Guanghui
Published: March 2022

Purpose

To compare the safety, efficacy, and cosmetic results of single-incision scrotal orchiopexy (SISO) and traditional two-incision inguinal orchiopexy (TTIO) for primary palpable undescended testes (PUDTs) in children.

Materials and Methods

A systematic literature search of all relevant studies published on PubMed, Embase, Medline, Cochrane Library, Web of Science database, and Wanfang data until July 2021 was conducted. The operative time, hospitalization duration, conversion rate, wound infection or dehiscence, scrotal hematoma or swelling, testicular atrophy, reascent, hernia or hydrocele, analgesics needs, and cosmetic results were compared between SISO and TTIO using the Mantel–Haenszel or inverse-variance method.

Results

A total of 17 studies involving 2,627 children (1,362 SISOs and 1,265 TTIOs) were included in the final analysis. The conversion rate of SISO was 3.6%. The SISO approach had a statistically significant shorter operative time than the TTIO approach for PUDT (weighted mean difference−11.96, 95% confidence interval −14.33 to −9.59, I2 = 79%, P < 0.00001) and a shorter hospital stay (weighted mean difference−1.05, 95% confidence interval −2.07 to −0.03, P = 0.04). SISO needed fewer analgesics and had better cosmetic results than TTIO. SISO had a similar total, short-term, or long-term complication rate with TTIO.

Conclusion

Compared with TTIO, SISO has the advantages of shorter operative time, shorter hospitalization duration, less postoperative pain, and better cosmetic appealing results. SISO is a safe, effective, promising, and potential minimal invasive surgical approach for PUDT. SISO is an alternative to TTIO in selected cryptorchid patients, especially for lower positioned ones.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021268562.
Investigation of Allergic Sensitizations in Children With Allergic Rhinitis and/or Asthma
Authors: Dai Lingman , Liu Jinling , Zhao Qi , Li Mengyao , Zhou Yunlian , Chen Zhimin , Zhang Yuanyuan
Published: March 2022

Objective

Allergic rhinitis (AR) and asthma are becoming one of the most prevalent diseases in children. Identifying sensitization to aeroallergens is seemed to be valuable for diagnosing allergic disease and guiding its treatment. This study aimed to analyze the profiles of sensitization to aeroallergen in children with AR and/or asthma by skin prick test (SPT) and explore the differences of sensitization between different kinds of allergic diseases, different sexes, and different ages.

Methods

A total of 230 children with AR and/or asthma who were hospitalized in our hospital from June 2017 to September 2019 were eligible in this retrospective study. All patients completed standardized questionnaires and SPT. Based on the sex, age, or classification of allergic disease, the sensitizations to 13 aeroallergens were compared.

Results

Of the 230 patients, 67.4% of enrolled were positive for SPT; the top 5 allergens were Dermatophagoides pteronyssinus (Der.p) (59.3%), Dermatophagoides farina (Der.f ) (58.7%), Blomia tropicalis (Blot.) (40.3%), dog hair (36.1%), and Blattella germanica (20.4%). More than 90% of patients were sensitized to two or more allergens. As to the effect of age on aeroallergens, we found that the sensitizations of Blot., dog fur, and multiple sensitizations (≥5 allergens) were more common in adolescence (P < 0.01, P < 0.05). Regarding sex, we found that the positive rate of SPT and the percentages of double-allergen sensitizations in boys were much higher than girls (P < 0.01, P < 0.01), and the positive rate to Der.p, Der.f , and ragweed were also significantly higher in boys (P < 0.01, P < 0.05, and P < 0.05, respectively). Furthermore, we found that asthma–rhinitis multimorbidity increased the incidences of sensitizations; patients with AR and asthma had significantly higher positive rates to Der.p and Der.f when compared with the AR or asthma group (P < 0.05, P < 0.05).

Conclusion

Allergic sensitizations were common in children with AR and/or asthma; sex, age, and asthma–rhinitis multimorbidity might affect the prevalence of sensitizations to aeroallergens.
Integrating Evidence of the Traditional Chinese Medicine Collateral Disease Theory in Prevention and Treatment of Cardiovascular Continuum
Authors: Cheang Iokfai , Liao Shengen , Zhu Qingqing , Ni Gehui , Wei Cong , Jia Zhenhua , Wu Yiling , Li Xinli
Published: March 2022

Cardiovascular disease has become a major public health problem. The concept of “cardiovascular continuum” refers to the continuous process from the risk factors that lead to arteriosclerosis, vulnerable plaque rupture, myocardial infarction, arrhythmia, heart failure, and death. These characteristics of etiology and progressive development coincide with the idea of “preventing disease” in traditional Chinese medicine (TCM), which corresponds to the process of systemic intervention. With the update of the understandingviatranslational medicine, this article reviews the current evidence of the TCM collateral disease theory set prescriptions in both mechanical and clinical aspects, which could lead to the development of new therapeutic strategies for prevention and treatment.
Perceptual and Ventilatory Responses to Hypercapnia in Athletes and Sedentary Individuals
Authors: Harrison Olivia K. , Russell Bruce R. , Pattinson Kyle T. S.
Published: March 2022

Purpose

Hypercapnic chemosensitivity traditionally captures the ventilatory response to elevated pressures of carbon dioxide in the blood. However, hypercapnia also contributes to subjective breathing perceptions, and previously we demonstrated a closer matching of perception to changes in ventilation in athletes compared to controls. Here we investigated any potential underlying hypercapnic chemosensitivity differences between groups, and explored whether these measures relate to ventilatory and perceptual responses during exercise as well as trait levels of affect.

Methods

A hypercapnic challenge, incremental maximal exercise test and affective questionnaires were completed by 20 endurance athletes and 20 age-/sex-matched sedentary controls. The hypercapnic challenge involved elevating end-tidal PCO2 by 0.8% (6.1 mmHg) and 1.5% (11.2 mmHg) for 3 min each (randomised), with constant end-tidal oxygen. Ventilatory and perceptual responses to hypercapnia were compared between groups, and within each group the relationships between hypercapnic chemosensitivity (slope analyses) and exercising ventilation and perceptions were calculated using Spearman’s non-parametric correlations.

Results

While absolute ventilation differences during hypercapnia and exercise were observed, no group differences were found across hypercapnic chemosensitivity (slope) measures. Correlation analyses revealed the anxiety hypercapnic response was related to maximal exercise anxiety, but only in sedentary individuals.

Conclusion

Ventilatory and perceptual hypercapnic chemosensitivity do not differ between athletes and sedentary individuals. However, ventilatory and anxiety hypercapnic chemosensitivities were related to ventilatory and anxiety responses during exercise in untrained individuals only. Athletes may employ additional strategies during exercise to reduce the influence of chemosensitivity on ventilatory and perceptual responses.