bluuebunny/crossref_metadata_2025 huggingface dataset:
Indicator diagram analysis based on deep learning
Authors: Cai Wenbin , Sun Zirui , Wang Zhaohuan , Wang Xuecheng , Wang Yi , Yang Guoqiang , Pan Shaowei
Published: August 2022

At present, more than 90% of China’s oil production equipment comprises rod pump production systems. Indicator diagram analysis of the pumping unit is not only an effective method for monitoring the current working condition of a rod pump production system but also the main way to prevent, detect, and rectify various faults in the oil production process. However, the identification of the pumping unit indicator diagram mainly involves manual effort, and the identification accuracy depends on the experience of the monitoring personnel. Automatic and accurate identification and classification of the pumping unit indicator diagram using new computer technology has long been the research focus of studies for monitoring the pumping unit working condition. In this paper, the indicator diagram is briefly introduced, and the AlexNet model is presented to distinguish the indicator diagram of abnormal wells. The influence of the step size, convolution kernel size, and batch normalization (BN) layer on the accuracy of the model is analyzed. Finally, the AlexNet model is improved. The improved model reduces the calculation cost and parameters, accelerates the convergence, and improves the accuracy and speed of the calculation. In the experimental analysis of abnormal well diagnosis, the data are preprocessed via data deduplication, binary filling, random line distortion, random scaling and stretching, and random vertical horizontal displacement. In addition, the image is expanded by transforming several well indicator diagrams. Finally, data sets of 10 types of indicator diagrams are created for better adaptability and application in the analysis and classification of indicator diagrams, and the ideal application effect is achieved in actual working conditions. In summary, this technology not only improves the recognition accuracy but also saves manpower. Thus, it has good application prospects in the field of oil production.
Developing a pedagogical evaluation framework for computational thinking supporting technologies and tools
Authors: Oyelere Solomon Sunday , Agbo Friday Joseph , Sanusi Ismaila Temitayo
Published: August 2022

Frameworks for the evaluation of technological instructional tools provide educators with criteria to assess the pedagogical suitability and effectiveness of those tools to address learners’ needs, support teachers’ understanding of learning progress, and recognize the levels of achievement and the learning outcomes of the students. This study applied secondary document analysis and case study to identify five pedagogical indicators for teaching and learning computational thinking, including technology, pedagogical approaches, assessment techniques, data aspect, and teacher professional development. Based on the pedagogical indicators, this study proposed a computational thinking pedagogical assessment framework (CT-PAF) aimed at supporting educators with a strategy to assess the different technological learning tools in terms of pedagogical impact and outcome. Furthermore, three case-study instructional tools for teaching CT in K-12 were analyzed for the initial assessment of CT-PAF. Scratch, Google Teachable Machine, and the iThinkSmart minigames were marched to the underpinning characteristics and attributes of CT-PAF to evaluate the framework across the instructional tools. The initial assessment of CT-PAF indicates that the framework is suitable for the intended purpose of evaluating technological instructional tools for pedagogical impact and outcome. A need for expanded assessment is, therefore, necessary to further ascertain the relevance of the framework in other cases.
The burden of endometriosis in China from 1990 to 2019
Authors: Wang Yan , Wang Xiaoyan , Liao Kaijun , Luo Baoqin , Luo Jiashou
Published: August 2022

Background

The trends in deaths from and disability-adjusted life years (DALY) of endometriosis in China remain largely unknown. This study revealed these trends and the effects of age, period, and cohort on the death from and DALY of endometriosis in China from 1990 to 2019.

Methods

Data on endometriosis death and DALY in China between 1990 and 2019 were obtained from the Global Burden of Disease Study 2019 (GBD 2019). The annual percentage change and average annual percent change (AAPC) were analyzed by joinpoint regression. The effects of age, period, and birth cohort on death and DALYs were estimated using an age–period–cohort analysis.

Results

The age-standardized death rate (ASDR) and age-standardized DALY rate for endometriosis significantly decreased in China, with AAPC values of −4.7 (95% confidence interval [CI]: −5.10, −4.30) and −1.2 (95% CI: −1.20, −1.10), respectively. The joinpoint regression analysis showed that the ASDR and age-standardized DALY rate decreased across all age groups. Moreover, the effect of age on endometriosis death and DALY decreased with advancing age. Both the period and cohort effects on endometriosis death and DALY showed decreasing trends, with the effects on death decreasing faster than the effects on DALY.

Conclusions

The endometriosis ASDR and age-standardized DALY rate decreased from 1990 to 2019. The effects of the period and birth cohort on endometriosis death and DALY showed a declining trend across all age groups. The effect of age on endometriosis deaths and DALYs decreased with advancing age.
Discrete-time resilient-distributed secondary control strategy against unbounded attacks in polymorphic microgrid
Authors: Wang Fuzhi , Shan Qihe , Zhu Jun , Xiao Geyang
Published: August 2022

This study proposes a polymorphic cooperative control system for microgrid consisting of a service layer, a control layer, a data layer, and a power layer to apply a resilient-distributed secondary control strategy to distributed generators (DGs) from different manufacturers more conveniently. Due to the improvement of network openness, external cyberattacks are more likely to tamper with the neighbor information transmitted in the cooperative control system. In this study, a discrete-time resilient-distributed secondary control strategy is designed to resist potential unbounded false data injection (FDI) attacks, which introduces a virtual network layer interconnecting the control network layer to form a layered network. The strategy can maintain the stability of voltage and frequency under unbounded attacks and then greatly suppress the state estimation difference of voltage and frequency. Meanwhile, the unbounded attack depending on voltage and frequency estimation difference is suppressed to a nearly bounded attack. Finally, a microgrid consisting of six inverter-based DGs is taken as an example to validate the effectiveness of the strategy against unbounded attacks.
Research on multi-phase flow test and flow simulation test in energy enterprise automation
Authors: Liang Ying , Wang Jinxi
Published: August 2022

Abstract:In the process of oil extraction and transportation, due to the interaction between oil, gas and water, hydrates are easily generated and pipelines are blocked. Based on this, from the perspective of energy enterprise automation technology, testing and research on oil and gas multiphase flow models and flow models are carried out. The hydrate formation area is analyzed by using the hydrate formation phase equilibrium theory, and the formation rate, deposition characteristics and blockage formation mechanism are analyzed. The influence of phase flow and heat transfer; after the boundary interface coefficient between oil, gas and water is clarified, a multiphase flow model of oil, gas and water is established. In the experimental test, the differential pressure signal is used to carry out the research on the oil and gas multiphase flow model and flow model, and it is concluded that the minimum critical superficial liquid velocity among the three flow patterns of oil, water and gas is 0.113 m/s, It can clearly characterize the characteristics of the flow pattern transition, which has certain practical significance for the sustainable development of energy enterprises.
Intelligent detection method for substation insulator defects based on CenterMask
Authors: Ye Bo , Li Feng , Li Mingxuan , Yan Peipei , Yang Huiting , Wang Lihua
Published: August 2022

With the development of intelligent operation and maintenance of substations, the daily inspection of substations needs to process massive video and image data. This puts forward higher requirements on the processing speed and accuracy of defect detection. Based on the end-to-end learning paradigm, this article proposes an intelligent detection method for substation insulator defects based on CenterMask. First, the backbone network VoVNet is improved according to the residual connection and eSE module, which effectively solves the problems of deep network saturation and gradient information loss. On this basis, an insulator mask generation method based on a spatial attention-directed mechanism is proposed. Insulators with complex image backgrounds are accurately segmented. Then, three strategies of pixel-wise regression prediction, multi-scale features, and centerness are introduced. The anchor-free single-stage target detector accurately locates the defect points of insulators. Finally, an example analysis is carried out with the substation inspection image of a power supply company in a certain area to verify the effectiveness and robustness of the proposed method.
Computational Analysis of Deleterious SNPs in NRAS to Assess Their Potential Correlation With Carcinogenesis
Authors: Behairy Mohammed Y. , Soltan Mohamed A. , Adam Mohamed S. , Refaat Ahmed M. , Ezz Ehab M. , Albogami Sarah , Fayad Eman , Althobaiti Fayez , Gouda Ahmed M. , Sileem Ashraf E. , Elfaky Mahmoud A. , Darwish Khaled M. , Alaa Eldeen Muhammad
Published: August 2022

The NRAS gene is a well-known oncogene that acts as a major player in carcinogenesis. Mutations in the NRAS gene have been linked to multiple types of human tumors. Therefore, the identification of the most deleterious single nucleotide polymorphisms (SNPs) in the NRAS gene is necessary to understand the key factors of tumor pathogenesis and therapy. We aimed to retrieve NRAS missense SNPs and analyze them comprehensively using sequence and structure approaches to determine the most deleterious SNPs that could increase the risk of carcinogenesis. We also adopted structural biology methods and docking tools to investigate the behavior of the filtered SNPs. After retrieving missense SNPs and analyzing them using six in silico tools, 17 mutations were found to be the most deleterious mutations in NRAS. All SNPs except S145L were found to decrease NRAS stability, and all SNPs were found on highly conserved residues and important functional domains, except R164C. In addition, all mutations except G60E and S145L showed a higher binding affinity to GTP, implicating an increase in malignancy tendency. As a consequence, all other 14 mutations were expected to increase the risk of carcinogenesis, with 5 mutations (G13R, G13C, G13V, P34R, and V152F) expected to have the highest risk. Thermodynamic stability was ensured for these SNP models through molecular dynamics simulation based on trajectory analysis. Free binding affinity toward the natural substrate, GTP, was higher for these models as compared to the native NRAS protein. The Gly13 SNP proteins depict a differential conformational state that could favor nucleotide exchange and catalytic potentiality. A further application of experimental methods with all these 14 mutations could reveal new insights into the pathogenesis and management of different types of tumors.
Case report: Disease phenotype associated with simultaneous biallelic mutations in ABCA4 and USH2A due to uniparental disomy of chromosome 1
Authors: Villafuerte-De la Cruz R. , Chacon-Camacho O. F. , Rodriguez-Martinez A. C. , Xilotl-De Jesus N. , Arce-Gonzalez R. , Rodriguez-De la Torre C. , Valdez-Garcia J. E. , Rojas-Martinez A. , Zenteno J. C.
Published: August 2022

Inherited retinal diseases (IRDs) represent a spectrum of clinically and genetically heterogeneous disorders. Our study describes an IRD patient carryingABCA4andUSH2Apathogenic biallelic mutations as a result of paternal uniparental disomy (UPD) in chromosome 1. The proband is a 9-year-old girl born from non-consanguineous parents. Both parents were asymptomatic and denied family history of ocular disease. Clinical history and ophthalmologic examination of the proband were consistent with Stargardt disease. Whispered voice testing disclosed moderate hearing loss. Next-generation sequencing and Sanger sequencing identified pathogenic variants inABCA4(c.4926C>G and c.5044_5058del) andUSH2A(c.2276G>T). All variants were present homozygously in DNA from the proband and heterozygously in DNA from the father. No variants were found in maternal DNA. Further analysis of single nucleotide polymorphisms confirmed paternal UPD of chromosome 1. This is the first known patient with confirmed UPD for two recessively mutated IRD genes. Our study expands on the genetic heterogeneity of IRDs and highlights the importance of UPD as a mechanism of autosomal recessive disease in non-consanguineous parents. Moreover, a long-term follow-up is essential for the identification of retinal features that may develop as a result ofUSH2A-related conditions.
KGDCMI: A New Approach for Predicting circRNA–miRNA Interactions From Multi-Source Information Extraction and Deep Learning
Authors: Wang Xin-Fei , Yu Chang-Qing , Li Li-Ping , You Zhu-Hong , Huang Wen-Zhun , Li Yue-Chao , Ren Zhong-Hao , Guan Yong-Jian
Published: August 2022

Emerging evidence has revealed that circular RNA (circRNA) is widely distributed in mammalian cells and functions as microRNA (miRNA) sponges involved in transcriptional and posttranscriptional regulation of gene expression. Recognizing the circRNA–miRNA interaction provides a new perspective for the detection and treatment of human complex diseases. Compared with the traditional biological experimental methods used to predict the association of molecules, which are limited to the small-scale and are time-consuming and laborious, computing models can provide a basis for biological experiments at low cost. Considering that the proposed calculation model is limited, it is necessary to develop an effective computational method to predict the circRNA–miRNA interaction. This study thus proposed a novel computing method, named KGDCMI, to predict the interactions between circRNA and miRNA based on multi-source information extraction and fusion. The KGDCMI obtains RNA attribute information from sequence and similarity, capturing the behavior information in RNA association through a graph-embedding algorithm. Then, the obtained feature vector is extracted further by principal component analysis and sent to the deep neural network for information fusion and prediction. At last, KGDCMI obtains the prediction accuracy (area under the curve [AUC] = 89.30% and area under the precision–recall curve [AUPR] = 87.67%). Meanwhile, with the same dataset, KGDCMI is 2.37% and 3.08%, respectively, higher than the only existing model, and we conducted three groups of comparative experiments, obtaining the best classification strategy, feature extraction parameters, and dimensions. In addition, in the performed case study, 7 of the top 10 interaction pairs were confirmed in PubMed. These results suggest that KGDCMI is a feasible and useful method to predict the circRNA–miRNA interaction and can act as a reliable candidate for related RNA biological experiments.
Multi-omics analysis of naïve B cells of patients harboring the C104R mutation in TACI
Authors: Ramirez Neftali , Posadas-Cantera Sara , Langer Niko , de Oteyza Andres Caballero Garcia , Proietti Michele , Keller Baerbel , Zhao Fangwen , Gernedl Victoria , Pecoraro Matteo , Eibel Hermann , Warnatz Klaus , Ballestar Esteban , Geiger Roger , Bossen Claudia , Grimbacher Bodo
Published: August 2022

Common variable immunodeficiency (CVID) is the most prevalent form of symptomatic primary immunodeficiency in humans. The genetic cause of CVID is still unknown in about 70% of cases. Ten percent of CVID patients carry heterozygous mutations in the tumor necrosis factor receptor superfamily member 13B gene (TNFRSF13B), encoding TACI. Mutations in TNFRSF13B alone may not be sufficient for the development of CVID, as 1% of the healthy population carry these mutations. The common hypothesis is that TACI mutations are not fully penetrant and additional factors contribute to the development of CVID. To determine these additional factors, we investigated the perturbations of transcription factor (TF) binding and the transcriptome profiles in unstimulated and CD40L/IL21-stimulated naïve B cells from CVID patients harboring the C104R mutation in TNFRSF13B and compared them to their healthy relatives with the same mutation. In addition, the proteome of stimulated naïve B cells was investigated. For functional validation, intracellular protein concentrations were measured by flow cytometry. Our analysis revealed 8% less accessible chromatin in unstimulated naïve B cells and 25% less accessible chromatin in class-switched memory B cells from affected and unaffected TACI mutation carriers compared to healthy donors. The most enriched TF binding motifs in TACI mutation carriers involved members from the ETS, IRF, and NF-κB TF families. Validation experiments supported dysregulation of the NF-κB and MAPK pathways. In steady state, naïve B cells had increased cell death pathways and reduced cell metabolism pathways, while after stimulation, enhanced immune responses and decreased cell survival were detected. Using a multi-omics approach, our findings provide valuable insights into the impaired biology of naïve B cells from TACI mutation carriers.
Host species and habitats shape the bacterial community of gut microbiota of three non-human primates: Siamangs, white-handed gibbons, and Bornean orangutans
Authors: Ying Chingwen , Siao You-Shun , Chen Wun-Jing , Chen Yi-Ting , Chen Szu-Lung , Chen Yi-Lung , Hsu Jih-Tay
Published: August 2022

The gut microbiome is essential for a host to digest food, maintain health, and adapt to environments. Bacterial communities of gut microbiota are influenced by diverse factors including host physiology and the environment. Many non-human primates (NHPs), which are physiologically close to humans, are in danger of extinction. In this study, the community structure of the gut microbiota in three NHPs: siamangs (Symphalangus syndactylus, Ss), Bornean orangutans (Pongo pygmaeus, Pp), and white-handed gibbons (Hylobates lar, Hl)—housed at the largest Zoo in Taiwan were analyzed. Pp and Ss were housed in the Asian tropical rainforest area, while Hl was housed in two separate areas, the Asian tropical rainforest area and the conservation area. Bacterial community diversity of Ss, indicated by the Shannon index, was significantly higher compared with that of Hl and Pp, while the richness (Chao 1) and observed operational taxonomic units (OTUs) were similar across the three species of NHPs. Host species was the dominant factor shaping the gut microbial community structure. Beta-diversity analysis including non-metric multidimensional scaling (NMDS) and unweighted pair group method with arithmetic mean (UPGMA) suggested gut bacterial communities of Hl housed in the conservation area were closely related to each other, while the bacterial communities of Hl in the rainforest area were dispersedly positioned. Further analysis revealed significantly higher abundances of Lactobacillus fermentum, L. murinus, and an unclassified species of Lactobacillus, and a lower abundance of Escherichia-Shigella in Hl from the conservation area relative to the rainforest area. The ratio of Lactobacillus to Escherichia-Shigella was 489.35 and 0.013 in Hl inhabiting the conservation and rainforest areas, respectively. High abundances of Lactobacillus and Bifidobacterium and a high ratio of Lactobacillus to Escherichia-Shigella were also observed in one siamang with notable longevity of 53 years. Data from the study reveal that host species acted as the fundamental driving factor in modulating the community structure of gut microbiota, but that habitats also acted as key determinants within species. The presence and high abundance of probiotics, such as Bifidobacterium and Lactobacillus, provide potential indicators for future diet and habitat optimization for NHPs, especially in zoological settings.
DNA- and RNA-Binding Proteins Linked Transcriptional Control and Alternative Splicing Together in a Two-Layer Regulatory Network System of Chronic Myeloid Leukemia
Authors: Wang Chuhui , Zong Xueqing , Wu Fanjie , Leung Ricky Wai Tak , Hu Yaohua , Qin Jing
Published: August 2022

DNA- and RNA-binding proteins (DRBPs) typically possess multiple functions to bind both DNA and RNA and regulate gene expression from more than one level. They are controllers for post-transcriptional processes, such as splicing, polyadenylation, transportation, translation, and degradation of RNA transcripts in eukaryotic organisms, as well as regulators on the transcriptional level. Although DRBPs are reported to play critical roles in various developmental processes and diseases, it is still unclear how they work with DNAs and RNAs simultaneously and regulate genes at the transcriptional and post-transcriptional levels. To investigate the functional mechanism of DRBPs, we collected data from a variety of databases and literature and identified 118 DRBPs, which function as both transcription factors (TFs) and splicing factors (SFs), thus called DRBP-SF. Extensive investigations were conducted on four DRBP-SFs that were highly expressed in chronic myeloid leukemia (CML), heterogeneous nuclear ribonucleoprotein K (HNRNPK), heterogeneous nuclear ribonucleoprotein L (HNRNPL), non-POU domain–containing octamer–binding protein (NONO), and TAR DNA-binding protein 43 (TARDBP). By integrating and analyzing ChIP-seq, CLIP-seq, RNA-seq, and shRNA-seq data in K562 using binding and expression target analysis and Statistical Utility for RBP Functions, we discovered a two-layer regulatory network system centered on these four DRBP-SFs and proposed three possible regulatory models where DRBP-SFs can connect transcriptional and alternative splicing regulatory networks cooperatively in CML. The exploration of the identified DRBP-SFs provides new ideas for studying DRBP and regulatory networks, holding promise for further mechanistic discoveries of the two-layer gene regulatory system that may play critical roles in the occurrence and development of CML.
A Kunitz-type inhibitor from tick salivary glands: A promising novel antitumor drug candidate
Authors: Lobba Aline R. M. , Alvarez-Flores Miryam Paola , Fessel Melissa Regina , Buri Marcus Vinicius , Oliveira Douglas S. , Gomes Renata N. , Cunegundes Priscila S. , DeOcesano-Pereira Carlos , Cinel Victor D. , Chudzinski-Tavassi Ana M.
Published: August 2022

Salivary glands are vital structures responsible for successful tick feeding. The saliva of ticks contains numerous active molecules that participate in several physiological processes. A Kunitz-type factor Xa (FXa) inhibitor, similar to the tissue factor pathway inhibitor (TFPI) precursor, was identified in the salivary gland transcriptome of Amblyomma sculptum ticks. The recombinant mature form of this Kunitz-type inhibitor, named Amblyomin-X, displayed anticoagulant, antiangiogenic, and antitumor properties. Amblyomin-X is a protein that inhibits FXa in the blood coagulation cascade and acts via non-hemostatic mechanisms, such as proteasome inhibition. Amblyomin-X selectively induces apoptosis in cancer cells and promotes tumor regression through these mechanisms. Notably, the cytotoxicity of Amblyomin-X seems to be restricted to tumor cells and does not affect non-tumorigenic cells, tissues, and organs, making this recombinant protein an attractive molecule for anticancer therapy. The cytotoxic activity of Amblyomin-X on tumor cells has led to vast exploration into this protein. Here, we summarize the function, action mechanisms, structural features, pharmacokinetics, and biodistribution of this tick Kunitz-type inhibitor recombinant protein as a promising novel antitumor drug candidate.
Gut metabolite trimethylamine N-oxide induces aging-associated phenotype of midbrain organoids for the induced pluripotent stem cell-based modeling of late-onset disease
Authors: Lee Youngsun , Kang Ji Su , Ham On-Ju , Son Mi-Young , Lee Mi-Ok
Published: August 2022

Brain organoids are valuable research models for human development and disease since they mimic the various cell compositions and structures of the human brain; however, they have challenges in presenting aging phenotypes for degenerative diseases. This study analyzed the association between aging and the gut metabolite trimethylamine N-oxide (TMAO), which is highly found in the midbrain of elderly and Parkinson’s disease (PD) patients. TMAO treatment in midbrain organoid induced aging-associated molecular changes, including increased senescence marker expression (P21, P16), p53 accumulation, and epigenetic alterations. In addition, TMAO-treated midbrain organoids have shown parts of neurodegeneration phenotypes, including impaired brain-derived neurotrophic factor (BDNF) signaling, loss of dopaminergic neurons, astrocyte activation, and neuromelanin accumulation. Moreover, we found TMAO treatment-induced pathophysiological phosphorylation of α-synuclein protein at Ser-129 residues and Tau protein at Ser202/Thr205. These results suggest a role of TMAO in the aging and pathogenesis of the midbrain and provide insight into how intestinal dysfunction increases the risk of PD. Furthermore, this system can be utilized as a novel aging model for induced pluripotent stem cell (iPSC)-based modeling of late-onset diseases.
General Pavlovian-to-instrumental transfer in humans: Evidence from Bayesian inference
Authors: Degni Luigi A. E. , Dalbagno Daniela , Starita Francesca , Benassi Mariagrazia , di Pellegrino Giuseppe , Garofalo Sara
Published: August 2022

When repeatedly paired with rewarding outcomes (i.e., Pavlovian conditioning), environmental cues may acquire predictive and motivational significance and later enhance instrumental responding for the same (i.e., outcome-specific transfer) or motivationally similar (i.e., general transfer) outcomes. Although outcome-specific and general Pavlovian-to-Instrumental Transfer (PIT) are characterized by different neural substrates and behavioral mechanisms, general transfer has never been studied in isolation from outcome-specific transfer in humans. The first aim of the present study was to test whether the general transfer effect could emerge in isolation and independently of outcome-specific transfer. Our results showed that general transfer can be elicited without the concurrent presence of outcome-specific transfer, supporting the idea that outcome-specific and general transfer can be studied independently of each other. The second aim of the present study was to clarify whether the affordance-like properties of the outcomes can affect the general transfer. In fact, a critical difference in current studies on general transfer concerns the use of cues associated with outcomes for which an action was previously learned (or not) during the instrumental training. This apparently minor difference affects the affordance-like properties of the outcome and may also be transferred to the cue, in turn impacting general transfer. Results revealed a general transfer of the same magnitude regardless of whether cues were associated with reward earned or not during instrumental conditioning. These findings increase the current knowledge on the incentive motivational mechanism behind general transfer, indicating that it is independent of the motor features of the outcome.
New-onset refractory status epilepticus due to autoimmune encephalitis after vaccination against SARS-CoV-2: First case report
Authors: Werner Jana , Brandi Giovanna , Jelcic Ilijas , Galovic Marian
Published: August 2022

Background:

Vaccination against SARS-CoV-2 has been conducted frequently to limit the pandemic but may rarely be associated with postvaccinal autoimmune reactions or disorders.

Case presentation

We present a 35-year-old woman who developed fever, skin rash, and headache 2 days after the second SARS-CoV-2 vaccination with BNT162b2 (Pfizer/Biontech). Eight days later, she developed behavioral changes and severe recurrent seizures that led to sedation and intubation. Cerebral magnetic resonance imaging showed swelling in the (para-) hippocampal region predominantly on the left hemisphere and bilateral subcortical subinsular FLAIR hyperintensities. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis of 7 cells/μl and normal protein and immunoglobulin parameters. Common causes of encephalitis or encephalopathy such as viral infections, autoimmune encephalitis with well-characterized autoantibodies, paraneoplastic diseases, and intoxications were ruled out. We made a diagnosis of new-onset refractory status epilepticus (NORSE) due to seronegative autoimmune encephalitis. The neurological deficits improved after combined antiepileptic therapy and immunomodulatory treatment including high-dose methylprednisolone and plasma exchange.

Conclusions

Although a causal relationship cannot be established, the onset of symptoms shortly after receiving the SARS-CoV-2 vaccine suggests a potential association between the vaccination and NORSE due to antibody-negative autoimmune encephalitis. After ruling out other etiologies, early immunomodulatory treatment may be considered in such cases.
An asynchronous artifact-enhanced electroencephalogram based control paradigm assisted by slight facial expression
Authors: Lu Zhufeng , Zhang Xiaodong , Li Hanzhe , Zhang Teng , Gu Linxia , Tao Qing
Published: August 2022

In this study, an asynchronous artifact-enhanced electroencephalogram (EEG)-based control paradigm assisted by slight-facial expressions (sFE-paradigm) was developed. The brain connectivity analysis was conducted to reveal the dynamic directional interactions among brain regions under sFE-paradigm. The component analysis was applied to estimate the dominant components of sFE-EEG and guide the signal processing. Enhanced by the artifact within the detected electroencephalogram (EEG), the sFE-paradigm focused on the mainstream defect as the insufficiency of real-time capability, asynchronous logic, and robustness. The core algorithm contained four steps, including “obvious non-sFE-EEGs exclusion,” “interface ‘ON’ detection,” “sFE-EEGs real-time decoding,” and “validity judgment.” It provided the asynchronous function, decoded eight instructions from the latest 100 ms signal, and greatly reduced the frequent misoperation. In the offline assessment, the sFE-paradigm achieved 96.46% ± 1.07 accuracy for interface “ON” detection and 92.68% ± 1.21 for sFE-EEGs real-time decoding, with the theoretical output timespan less than 200 ms. This sFE-paradigm was applied to two online manipulations for evaluating stability and agility. In “object-moving with a robotic arm,” the averaged intersection-over-union was 60.03 ± 11.53%. In “water-pouring with a prosthetic hand,” the average water volume was 202.5 ± 7.0 ml. During online, the sFE-paradigm performed no significant difference (P = 0.6521 and P = 0.7931) with commercial control methods (i.e., FlexPendant and Joystick), indicating a similar level of controllability and agility. This study demonstrated the capability of sFE-paradigm, enabling a novel solution to the non-invasive EEG-based control in real-world challenges.
Clinical significance of albumin to globulin ratio among patients with stroke-associated pneumonia
Authors: Chen Lingli , Xu Minjie , Huang Qiqi , Liu Yuntao , Ren Wenwei
Published: August 2022

Background

It has been proven that the ratio of albumin to globulin (A/G) is a typical biomarker for monitoring inflammation and nutritional status. But the potential role of A/G in stroke-associated pneumonia (SAP) after acute ischemic stroke (AIS) remained unknown.

Patients and methods

Following inclusion criteria, 5,173 AIS patients were included and segmented into SAP (n = 897) and non-SAP (n = 4,276) groups. The differences in variables between groups were compared. The logistic regression model was used to determine the association between A/G and SAP, and a forest plot was drawn.

Results

Compared with the non-SAP group, the SAP group had a lower A/G level (P < 0.001). Then, A/G was divided into quartiles. In comparison to Q3 (A/G = 1.25–1.39), logistic regression revealed that patients with a lower A/G (A/G ≤ 1.09) had a higher risk of SAP (OR = 1.96, 95% CI, 1.56–2.46, P < 0.001). On the contrary, those with a higher A/G (A/G ≥ 1.4) had a lower SAP risk (OR = 0.73, 95% CI, 0.54–0.97, P = 0.029).

Conclusion

The study revealed that a low A/G level was associated with an increased SAP risk. Appropriate preventative measures for SAP should be taken in AIS patients with a low A/G level.
Safety and efficacy of indocyanine green near-infrared fluorescent imaging-guided lymph nodes dissection during radical gastrectomy for gastric cancer: A systematic review and meta-analysis
Authors: Deng Chun , Zhang Zhenyu , Qi Hengduo , Guo Zhi , Liu Yang , Xiao Haimin , Li Xiaojun
Published: August 2022

Background

Indocyanine green (ICG) fluorescence imaging has been a new surgical navigation technique for gastric cancer. However, its clinical value should still be evaluated further. In this meta-analysis, we investigated the safety and efficacy of ICG near-infrared fluorescent imaging-guided lymph nodes (LNs) dissection during radical gastrectomy.

Methods

Studies comparing ICG fluorescence imaging with standard care in patients with gastric cancer were systematically searched from PubMed, Embase, Web of Science, and Cochrane Library through August 2021. The current meta-analysis was performed according to the preferred reporting items for systematic review and meta-analysis guidelines. A pooled analysis was performed for the available data regarding the number of LNs dissection, the number of metastatic LNs dissection, other operative outcomes, and postoperative complications. R software version 4.2.0 and Stata 16.0 software were used for the present meta-analysis.

Results

This analysis included 12 studies with a total of 1365 gastric cancer patients (569 in the ICG group and 796 in the non-ICG group). The number of retrieved LNs in the ICG group was significantly higher (weighted mean difference [WMD]=7.67, 95% confidence intervals [CI]: 4.73 to 10.62, P<0.05) compared to the non-ICG group with moderate heterogeneity (P<0.001, I2 = 70%). The number of metastatic LNs, operative time, and postoperative complications were all comparable and without significant heterogeneity. Additionally, ICG near-infrared fluorescent imaging was associated with reduced intraoperative blood loss (WMD=-10.28, 95% CI: -15.22 to -5.35, P<0.05) with low heterogeneity (P=0.07, I2 = 43%).

Conclusions

ICG near-infrared fluorescent imaging-guided lymphadenectomy was considered to be safe and effective in gastrectomy. ICG was used to increase the number of LNs harvested while reducing intraoperative blood loss without increasing operative time or postoperative complications.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021291863.
Prognostication in palliative radiotherapy—ProPaRT: Accuracy of prognostic scores
Authors: Maltoni Marco , Scarpi Emanuela , Dall’Agata Monia , Micheletti Simona , Pallotti Maria Caterina , Pieri Martina , Ricci Marianna , Romeo Antonino , Tenti Maria Valentina , Tontini Luca , Rossi Romina
Published: August 2022

Background

Prognostication can be used within a tailored decision-making process to achieve a more personalized approach to the care of patients with cancer. This prospective observational study evaluated the accuracy of the Palliative Prognostic score (PaP score) to predict survival in patients identified by oncologists as candidates for palliative radiotherapy (PRT). We also studied interrater variability for the clinical prediction of survival and PaP scores and assessed the accuracy of the Survival Prediction Score (SPS) and TEACHH score.

Materials and methods

Consecutive patients were enrolled at first access to our Radiotherapy and Palliative Care Outpatient Clinic. The discriminating ability of the prognostic models was assessed using Harrell’s C index, and the corresponding 95% confidence intervals (95% CI) were obtained by bootstrapping.

Results

In total, 255 patients with metastatic cancer were evaluated, and 123 (48.2%) were selected for PRT, all of whom completed treatment without interruption. Then, 10.6% of the irradiated patients who died underwent treatment within the last 30 days of life. The PaP score showed an accuracy of 74.8 (95% CI, 69.5–80.1) for radiation oncologist (RO) and 80.7 (95% CI, 75.9–85.5) for palliative care physician (PCP) in predicting 30-day survival. The accuracy of TEACHH was 76.1 (95% CI, 70.9–81.3) and 64.7 (95% CI, 58.8–70.6) for RO and PCP, respectively, and the accuracy of SPS was 70 (95% CI, 64.4–75.6) and 72.8 (95% CI, 67.3–78.3).

Conclusion

Accurate prognostication can identify candidates for low-fraction PRT during the last days of life who are more likely to complete the planned treatment without interruption.

All the scores showed good discriminating capacity; the PaP had the higher accuracy, especially when used in a multidisciplinary way.
Neoadjuvant Savolitinib targeted therapy stage IIIA-N2 primary lung adenocarcinoma harboring MET Exon 14 skipping mutation: A case report
Authors: Fu Meng , Feng Chun-Mei , Xia Da-Qing , Ji Zi-Mei , Xia Huai-Ling , Hu Na-Na , Leng Zai-Jun , Xie Wang , Fang Yuan , Cao Le-Jie , Zhang Jun-Qiang
Published: August 2022

MET exon 14 skipping mutation (METex14m) is rare and occurs in approximately 1-4% of all non-small cell lung cancer (NSCLC) patients and approximately 2.8% of resected stage I-III NSCLC patients. Savolitinib is an oral, potent and highly selective type Ib MET inhibitor, which has been shown to be promising activity and acceptable safety profile in patients with advanced NSCLC harboring METex14m. Most recently, many studies have been probing into the feasibility and efficacy of target therapy for perioperative application in NSCLC. Interestingly, there are very few recorded cases of such treatments. Here, we presented that systemic treatment with the MET inhibitor savolitinib before surgery could provide the potential to prolong overall survival (OS) of patients with locally advanced potentially resectable NSCLC. A 49-year-old woman was diagnosed with stage IIIA (T2bN2M0) primary lung adenocarcinoma exhibiting a METex14m by real-time quantitative polymerase chain reaction (RT-qPCR). Given that the tumor load and the size of lymph nodes experienced a significant downstaging after the neoadjuvant treatment of savolitinib with 600mg once a day for 5 weeks, left lower lobectomy and systemic lymphadenectomy were successfully performed. The pathological response was 50% and the final postoperative pathological staging was pT1cN0M0, IA3 (AJCC, 8th edition). The case provides empirical basis for the neoadjuvant treatment with savolitinib in METex14m-positive locally advanced primary lung adenocarcinoma, which will offer some innovative insights and clinical evidence for more effective clinical treatment of neoadjuvant targeted therapy for METex14m-positive NSCLC.
Development and validation of a novel prognostic model for patients with surgically resected esophageal squamous cell carcinoma
Authors: Hu Haiyang , Zhang Jun , Yan Hang , Qin Chao , Guo Haiyang , Liu Tao , Tang Shengjie , Zhou Haining
Published: August 2022

Background and objectives

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal malignancy in most regions of the world. The study aimed to identify risk factors and develop a predictive model for ESCC following surgical resection.

Patients and methods

A total of 533 ESCC patients who underwent surgical resection from Suining Central Hospital were enrolled in the study. Cox proportional hazards regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression were performed to identify significant prognostic factors. A prognostic model was constructed, and the receiver operating characteristic (ROC) curve, concordance index (C-index), and decision cure analysis (DCA) were used to evaluate the discrimination and calibration of the prognostic model. Subsequently, we built a nomogram for overall survival (OS) incorporating the prognostic factors, and a calibration plot was employed to assess the consistency between the predicted survival and the observed survival. Based on the model risk score, we split the patients into two subgroups, low-risk and high-risk, and we analyzed the survival time of these two groups using Kaplan–Meier (K-M) survival plots.

Results

Five independent prognosis factors were identified as independent risk factors for OS in ESCC patients who underwent surgical resection. The C-index, ROC curve, and DCA showed that the prognostic model had good predictive accuracy and discriminatory power in the training cohort and validation cohort than other clinical features. A nomogram consisting of prognosis factors showed some superior net benefit. K-M survival plots showed significant differences in OS between the low-risk and high-risk groups. Similar results were observed in the subgroup analysis based on age, grade, and stage. Univariate and multivariate Cox regression analyses revealed that both risk score and risk group are independent prognostic factors in the patient cohort.

Conclusions

This study put forward a novel prognostic model based on clinical features; biopsy data and blood biomarkers may represent a promising tool for estimating OS in ESCC patients.
Contribution of MMP14-expressing cancer-associated fibroblasts in the tumor immune microenvironment to progression of colorectal cancer
Authors: Makutani Yusuke , Kawakami Hisato , Tsujikawa Takahiro , Yoshimura Kanako , Chiba Yasutaka , Ito Akihiko , Kawamura Junichiro , Haratani Koji , Nakagawa Kazuhiko
Published: August 2022

Matrix metalloproteinase 14 (MMP14) expression is implicated in progression of colorectal cancer, but its role in the tumor microenvironment (TME) has been unclear. The relevance of MMP14 to colorectal cancer progression was explored by analysis of transcriptomic data for colorectal adenocarcinoma patients (n = 592) in The Cancer Genome Atlas. The role of MMP14 in the TME was investigated in a retrospective analysis of tumor samples from 86 individuals with stage III colorectal cancer by single cell–based spatial profiling of MMP14 expression as performed by 12-color multiplex immunohistochemistry (mIHC). Analysis of gene expression data revealed that high MMP14 expression was associated with tumor progression and implicated both cancer-associated fibroblasts (CAFs) and tumor-associated macrophages in such progression. Spatial profiling by mIHC revealed that a higher percentage of MMP14+ cells among intratumoral CAFs (MMP14+ CAF/CAF ratio) was associated with poorer relapse-free survival. Multivariable analysis including key clinical factors identified the MMP14+ CAF/CAF ratio as an independent poor prognostic factor. Moreover, the patient subset with both a high MMP14+ CAF/CAF ratio and a low tumor-infiltrating lymphocyte density showed the worst prognosis. Our results suggest that MMP14+ CAFs play an important role in progression of stage III colorectal cancer and may therefore be a promising therapeutic target.
Autophagy-related prognostic signature characterizes tumor microenvironment and predicts response to ferroptosis in gastric cancer
Authors: Li Haoran , Xu Bing , Du Jing , Wu Yunyi , Shao Fangchun , Gao Yan , Zhang Ping , Zhou Junyu , Tong Xiangmin , Wang Ying , Li Yanchun
Published: August 2022

Background

Gastric cancer (GC) is an important disease and the fifth most common malignancy worldwide. Autophagy is an important process for the turnover of intracellular substances. Autophagy-related genes (ARGs) are crucial in cancer. Accumulating evidence indicates the clinicopathological significance of the tumor microenvironment (TME) in predicting prognosis and treatment efficacy.

Methods

Clinical and gene expression data of GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A total of 22 genes with differences in expression and prognosis were screened from 232 ARGs. Three autophagy patterns were identified using an unsupervised clustering algorithm and scored using principal component analysis to predict the value of autophagy in the prognosis of GC patients. Finally, the relationship between autophagy and ferroptosis was validated in gastric cancer cells.

Results

The expression of ARGs showed obvious heterogeneity in GC patients. Three autophagy patterns were identified and used to predict the overall survival of GC patients. These three patterns were well-matched with the immunophenotype. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses showed that the biological functions of the three autophagy patterns were different. A scoring system was then set up to quantify the autophagy model and further evaluate the response of the patients to the immunotherapy. Patients with high autophagy scores had a more severe tumor mutation burden and better prognosis. High autophagy scores were accompanied by high microsatellite instability. Patients with high autophagy scores had significantly higher PD-L1 expression and increased survival. The experimental results confirmed that the expression of ferroptosis genes was positively correlated with the expression of autophagy genes in different autophagy clusters, and inhibition of autophagy dramatically reversed the decrease in ferroptotic cell death and lipid accumulation.

Conclusions

Autophagy patterns are involved in TME diversity and complexity. Autophagy score can be used as an independent prognostic biomarker in GC patients and to predict the effect of immunotherapy and ferroptosis-based therapy. This might benefit individualized treatment for GC.