bluuebunny/crossref_metadata_2025 huggingface dataset:
A One-Armed Phase I Dose Escalation Trial Design: Personalized Vaccination with IKKβ-Matured, RNA-Loaded Dendritic Cells for Metastatic Uveal Melanoma
Authors: Koch Elias A. T. , Schaft Niels , Kummer Mirko , Berking Carola , Schuler Gerold , Hasumi Kenichiro , Dörrie Jan , Schuler-Thurner Beatrice
Published: February 2022

Uveal melanoma (UM) is an orphan disease with a mortality of 80% within one year upon the development of metastatic disease. UM does hardly respond to chemotherapy and kinase inhibitors and is largely resistant to checkpoint inhibition. Hence, further therapy approaches are urgently needed. To improve clinical outcome, we designed a trial employing the 3rd generation personalized IKKβ-matured RNA-transfected dendritic cell (DC) vaccine which primes T cells and in addition activates NK cells. This ongoing phase I trial [NCT04335890 (www.clinicaltrials.gov), Eudract: 2018-004390-28 (www.clinicaltrialsregister.eu)] investigates patients with treatment-naive metastatic UM. Monocytes are isolated by leukapheresis, differentiated to immature DCs, matured with a cytokine cocktail, and activated via the NF-κB pathway by electroporation with RNA encoding a constitutively active mutant of IKKβ. Three types of antigen-RNA are co-electroporated: i) amplified mRNA of the tumor representing the whole transcriptome, ii) RNA encoding driver mutations identified by exome sequencing, and iii) overexpressed non-mutated tumor antigens detected by transcriptome sequencing. This highly personalized DC vaccine is applied by 9 intravenous infusions in a staggered schedule over one year. Parallel to the vaccination, standard therapy, usually an immune checkpoint blockade (ICB) as mono (anti-PD-1) or combined (anti-CTLA4 and anti-PD-1) regimen is initiated. The coordinated vaccine-induced immune response encompassing tumor-specific T cells and innate NK cells should synergize with ICB, perhaps resulting in measurable clinical responses in this resistant tumor entity. Primary outcome measures of this trial are safety, tolerability and toxicity; secondary outcome measures comprise overall survival and induction of antigen-specific T cells.
A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo
Authors: Peng Jingyi , Wu Jiaguo , Shi Ning , Xu Hua , Luo Longlong , Wang Jing , Li Xinying , Xiao He , Feng Jiannan , Li Xia , Chai Lihui , Qiao Chunxia
Published: February 2022

Abrin, a type-II ribosome inactivating protein from the seed of Abrus precatorius, is classified as a Category B bioterrorism warfare agent. Due to its high toxicity, ingestion by animals or humans will lead to death from multiple organ failure. Currently, no effective agents have been reported to treat abrin poisoning. In this study, a novel anti-abrin neutralizing antibody (S008) was humanized using computer-aided design, which possessed lower immunogenicity. Similar to the parent antibody, a mouse anti-abrin monoclonal antibody, S008 possessed high affinity and showed a protective effect against abrin both in vitro and in vivo, and protected mice that S008 was administered 6 hours after abrin. S008 was found that it did not inhibit entry of abrin into cells, suggesting an intracellular blockade capacity against the toxin. In conclusion, this work demonstrates that S008 is a high affinity anti-abrin antibody with both a neutralizing and protective effect and may be an excellent candidate for clinical treatment of abrin poisoning.
Ecosafety Screening of Photo-Fenton Process for the Degradation of Microplastics in Water
Authors: Piazza Veronica , Uheida Abdusalam , Gambardella Chiara , Garaventa Francesca , Faimali Marco , Dutta Joydeep
Published: February 2022

Microplastic pollution is receiving increased attention due to the realization of its hazards to aquatic and human life. Researchers across the globe are attempting to remove microplastics before its entry into the ecosystem. Therefore, the present work focused on the removal of microplastic from water and studied the potential risks for marine organisms and the ecosystem. The removal of model microplastics, polypropylene (PP) and polyvinyl chloride (PVC), has been studied by using photo-Fenton process. ZnO nanorods coated with SnOx(x < 2) layer and decorated with zero valent iron (Fe0) nanoparticles was used as heterogeneous catalyst for the removal of the microplastics in continuous water flow device. The obtained results demonstrated that high degradation efficiency of PP and PVC microplastics was achieved in a relatively short time and more than 95% of the average particle volume was reduced after 1 week of irradiation. The environmental impact of the photo-Fenton process of the microplastics degradation was investigated by using an ecotoxicological approach. An ecosafety screening has been performed through a series of experiments (bioassays) under controlled conditions, testing water samples after the photo-Fenton degradation of microparticles using a lab scale device. The ecotoxicological impact has been investigated by applying a battery of certified bioassays (UNI EN ISO/EPA standardized techniques) on aquatic organisms at different trophic levels (bacteria, algae, invertebrates). The results obtained on the three model organisms (A. fischeri, P. subcapitata, and D. magna) revealed no toxic effect for samples collected both before and after the photo-Fenton process, thus showing the absence of toxic by-products development during the degradation process.
A Pilot Observational Study Assessing Long-Term Changes in Clinical Parameters, Functional Capacity and Fall Risk of Patients With Chronic Renal Disease Scheduled for Hemodialysis
Authors: Zemp Damiano D. , Giannini Olivier , Quadri Pierluigi , Tettamanti Mauro , Berwert Lorenzo , Lavorato Soraya , Pianca Silvio , Solcà Curzio , de Bruin Eling D.
Published: February 2022

Background

Patients with end-stage renal disease are known to be particularly frail, and the cause is still widely seen as being directly related to specific factors in renal replacement therapy. However, a closer examination of the transitional phase from predialysis to long-term hemodialysis leads to controversial explanations, considering that the frailty process is already well-described in the early stages of renal insufficiency. This study aims to describe longitudinally and multifactorially changes in the period extending from the decision to start the replacement therapy through to the end of 2 years of hemodialysis. We hypothesized that frailty is pre-existent in the predialysis phase and does not worsen with the beginning of the replacement therapy. Between 2015 and 2018 we recruited 25 patients (72.3 ± 5.7 years old) in a predialysis program, with the expectation that replacement therapy would begin within the coming few months.

Methods

The patients underwent a baseline visit before starting hemodialysis, with 4 follow-up visits in the first 2 years of treatment. Health status, physical performance, cognitive functioning, hematology parameters, and adverse events were monitored during the study period.

Results

At baseline, our sample had a high variability with patients ranging from extremely frail to very fit. In the 14 participants that did not drop out of the study, out of 32 clinical and functional measures, a statistically significant worsening was only observed in the Short Physical Performance Battery (SPPB) score (p < 0.01, F = 8.50) and the number of comorbidities (p = 0.01, F = 3.94). A careful analysis, however, reveals a quite stable situation in the first year of replacement therapy, for both frail and fit participants and a deterioration in the second year that in frail participants could lead to death.

Conclusion

Our results should stimulate a reassessment about the role of a predialysis program in reducing complications during the transitional phase, but also about frailty prevention programs once hemodialysis has begun, for both frail and fit patients, to maintain satisfactory health status.
Three-Year Follow-Up of Posterior Corneal Elevation in Thin Corneas After Small Incision Lenticule Extraction
Authors: Zhao Yu , Fu Dan , Chen Zhuoyi , Zhou Xingtao
Published: February 2022

Purpose

To evaluate the changes in posterior corneal elevation in thin corneas after small incision lenticule extraction (SMILE).

Methods

In this prospective study, 97 eyes of 97 patients undergoing SMILE were recruited. Eyes were categorized into the following groups based on the preoperative minimum central corneal thickness (CCT): group A (37 eyes, 480–499 μm), group B (30 eyes, 500–529 μm), and group C (30 eyes, 530–560 μm). The posterior corneal surface was measured with a Pentacam over a 3-year follow-up period. Changes in the posterior corneal elevation at the central point (PCE), thinnest point (PTE), and predetermined area were measured.

Results

No iatrogenic keratectasia was observed during the follow-up period. The mean changes in PCE, PTE, and the inferior area in group A were 1.14 ± 3.40 μm, −0.11 ± 3.20 μm, and −0.26 ± 1.23 μm, respectively (P ≥ 0.125). Although statistically significant change in the central-4 mm area was noted, the value was quite small (0.98 ± 1.67 μm) and was not higher than that in the other two groups (P = 0.003). For all three groups, the elevation remained stable or showed a backward change in the central annulus, while there was a small forward displacement in the 6-mm optical zone. In group A, changes in elevation values yielded negative statistical correlations with residual bed thickness and CCT (P ≤ 0.006) (except for the inferior area, the 4-mm and 6-mm optical zone).

Conclusions

With a strict preoperative assessment, SMILE achieved good safety and efficacy in correcting myopia in thin corneas and enabled a stable posterior corneal surface over a 3-year follow-up period.

Synopsis

Careful preoperative assessment and suitable surgical design should be taken to ensure posterior corneal stability after SMILE in thin corneas.
Comparative Genome Analysis of Three Komagataeibacter Strains Used for Practical Production of Nata-de-Coco
Authors: Ishiya Koji , Kosaka Hideki , Inaoka Takashi , Kimura Keitarou , Nakashima Nobutaka
Published: February 2022

We determined the whole genome sequences of three bacterial strains, designated as FNDCR1, FNDCF1, and FNDCR2, isolated from a practical nata-de-coco producing bacterial culture. Only FNDCR1 and FNDCR2 strains had the ability to produce cellulose. The 16S rDNA sequence and phylogenetic analysis revealed that all strains belonged to the Komagataeibacter genus but belonged to a different clade within the genus. Comparative genomic analysis revealed cross-strain distribution of duplicated sequences in Komagataeibacter genomes. It is particularly interesting that FNDCR1 has many duplicated sequences within the genome independently of the phylogenetic clade, suggesting that these duplications might have been obtained specifically for this strain. Analysis of the cellulose biosynthesis operon of the three determined strain genomes indicated that several cellulose synthesis-related genes, which are present in FNDCR1 and FNDCR2, were lost in the FNDCF1 strain. These findings reveal important genetic insights into practical nata de coco-producing bacteria that can be used in food development. Furthermore, our results also shed light on the variation in their cellulose-producing abilities and illustrate why genetic traits are unstable for Komagataeibacter and Komagataeibacter-related acetic acid bacteria.
Phytochemicals of Euphorbia hirta L. and Their Inhibitory Potential Against SARS-CoV-2 Main Protease
Authors: Cayona Ruel , Creencia Evelyn
Published: February 2022

Euphorbia hirta L.is a medicinal plant widely used in the Philippines and across tropical Asia against various diseases, including respiratory disorders. In this study, the phytochemical components ofE. hirtawere investigatedin silicofor their potential to inhibit the severe acute respiratory syndrome-coronavirus-2 main protease (SARS-CoV-2 Mpro), a coronavirus disease 2019 (COVID-19) drug target that plays a critical role in the infection process of SARS-CoV-2. Phytochemical mining in tandem with virtual screening (PM-VS) was the strategy implemented in this study, which allows efficient preliminaryin silicoassessment of the COVID-19 therapeutic potential of the reported phytochemicals from the plant. The main rationale for consideringE. hirtain the investigation was its reported efficacy against respiratory disorders. It is very promising to investigate the phytochemicals ofE. hirtafor their potential efficacy against diseases, such as COVID-19, that also target the respiratory system. A total of 298E. hirtaphytochemicals were comprehensively collected from the scientific literature. One hundred seventy of these phytochemicals were computed through molecular docking and were shown to have comparable or better binding properties (promising inhibitors) toward SARS-CoV-2 Mpro than knownin vitroinhibitors. In connection to our previous work considering different medicinal plants, antiviral compounds were also rediscovered from the phytochemical composition ofE. hirta. This finding provides additional basis for the potential of the plant (or its phytochemicals) as a COVID-19 therapeutic directly targeting drug targets such as SARS-CoV-2 Mpro and/or addressing respiratory-system-related symptoms. The study also highlights the utility of PM-VS, which can be efficiently implemented in the preliminary steps of drug discovery and development.
Impact of Superparamagnetic Iron Oxide Nanoparticles on THP-1 Monocytes and Monocyte-Derived Macrophages
Authors: Polasky Christina , Studt Tim , Steuer Ann-Kathrin , Loyal Kristin , Lüdtke-Buzug Kerstin , Bruchhage Karl-Ludwig , Pries Ralph
Published: February 2022

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently under examination for magnetic particle imaging, which represents a radiation free technology for three-dimensional imaging with high sensitivity, resolution and imaging speed. SPIONs are rapidly taken up by monocytes and other phagocytes which carry them to the site of inflammation. Therefore, the SPION biocompatibility is an essential parameter for a widespread MPI usage. Many improvements are expected from SPION development and its applications for cell visualization, but the impact of MPI optimized dextran coated SPIONs on the cellular characteristics of monocytic cells has been poorly studied up to now. THP-1 monocytes, monocyte-derived macrophages (MDM) as well as peripheral blood monocytes were incubated with MPI-optimized dextran-coated SPIONs of a size between 83.5 and 86 nm. SPION uptake was measured by FITC fluorescence of labeled SPIONs and Prussian blue staining. The activation of monocytes and MDMs was evaluated by CD14, CD11b and CD86 in flow cytometry. The secretion of IL-1β, and IL-10 was analyzed in supernatants. SPIONs were rapidly taken up by monocytes and monocyte-derived macrophages while no decrease in cell viability was observed. Expression patterns of CD11b, CD14, and CD86 were not affected in THP-1 monocytes and MDMs. Monocyte differentiation in macrophages was hindered during SPION uptake. THP-1 monocytes as well as monocyte-derived macrophages showed significantly increased IL-1β and decreased IL-10 secretion by tendency after SPION treatment. Dextran-coated SPIONs showed a low cytotoxicity on monocytes but exert undesirable inflammatory side effects that have to be considered for imaging applications.
An Efficient Method for the Isolation and Cultivation of Hypothalamic Neural Stem/Progenitor Cells From Mouse Embryos
Authors: Ou Yichao , Che Mengjie , Peng Junjie , Zhou Mingfeng , Wu Guangsen , Gong Haodong , Li Kai , Wang Xingqin , Niu Peirong , Qi Songtao , Feng Zhanpeng
Published: February 2022

The hypothalamus is the key region that regulates the neuroendocrine system as well as instinct behaviors, and hypothalamic dysfunction causes refractory clinical problems. Recent studies have indicated that neural stem/progenitor cell (NSPC) in the hypothalamus play a crucial role in hypothalamic function. However, specific hypothalamic NSPC culture methods have not been established, especially not detailed or efficient surgical procedures. The present study presented a convenient, detailed and efficient method for the isolation and cultivation of hypothalamic NSPCs from embryonic day 12.5 mice. The procedure includes embryo acquisition, brain microdissection to quickly obtain hypothalamic tissue and hypothalamic NSPC culture. Hypothalamic NSPCs can be quickly harvested and grow well in both neurosphere and adherent cultures through this method. Additionally, we confirmed the cell origin and evaluated the proliferation and differentiation properties of cultured cells. In conclusion, we present a convenient and practical method for the isolation and cultivation of hypothalamic NSPCs that can be used in extensive hypothalamic studies.
Performance Evaluation of EEG Based Mental Stress Assessment Approaches for Wearable Devices
Authors: Al-Saggaf Ubaid M. , Naqvi Syed Faraz , Moinuddin Muhammad , Alfakeh Sulhi Ali , Ali Syed Saad Azhar
Published: February 2022

Mental stress has been identified as the root cause of various physical and psychological disorders. Therefore, it is crucial to conduct timely diagnosis and assessment considering the severe effects of mental stress. In contrast to other health-related wearable devices, wearable or portable devices for stress assessment have not been developed yet. A major requirement for the development of such a device is a time-efficient algorithm. This study investigates the performance of computer-aided approaches for mental stress assessment. Machine learning (ML) approaches are compared in terms of the time required for feature extraction and classification. After conducting tests on data for real-time experiments, it was observed that conventional ML approaches are time-consuming due to the computations required for feature extraction, whereas a deep learning (DL) approach results in a time-efficient classification due to automated unsupervised feature extraction. This study emphasizes that DL approaches can be used in wearable devices for real-time mental stress assessment.
Synaptic Role in Facilitating Synchronous Theta Oscillations in a Hybrid Hippocampal Neuronal Network
Authors: Liu Zilu , Wang Qingyun , Han Fang
Published: February 2022

Theta rhythms (4–12 Hz) in the hippocampus are thought to be associated with cognitive functions such as memory processing and spatial navigation. Rhythmic oscillations in the neural system can be induced by synchronization of neural populations, while physiological mechanisms for the emergence, modulation, and regulation of such rhythms are not fully understood. Conceptual reduced models are promising in promoting current understandings toward neural synchronization because of high computational efficiency, while they appear less straightforward in biological relevance. In this study, we use a hybrid E-I network as a conceptual model of the hippocampus to investigate the dynamics of synchronous theta oscillations. Specifically, experimentally constrained Izhikevich neurons and preferential connections among neural groups specific to hippocampal CA1 are incorporated to enhance the biological relevance of the model network. Based on such a model, synaptic factors related to the balance of network excitation and inhibition are the main focus of present study. By careful parameter exploration, the distinct role of synaptic connections in theta rhythm generation, facilitation of synchronization, and induction of burst activities are clarified. It is revealed that theta rhythms can be present with AMPA mediated weak E-I couplings, or with strong NMDA current. Moreover, counter-inhibition, namely inhibition of inhibition, is found effective in modulating the degree of network synchronization, while has little effect on regulating network frequency in both regimes. Under pathological considerations where the effect of pyramidal sprouting is simulated, synchronized burst patterns are observed to be induced by elevated recurrent excitation among pyramidal cells. In the final part, we additionally perform a test on the robustness of our results under heterogeneous parameters. Our simulation results may provide insights into understanding how brain rhythms are generated and modulated, and the proposed model may serve as a useful template in probing mechanisms of hippocampal-related dynamics.
Synchronization Through Uncorrelated Noise in Excitatory-Inhibitory Networks
Authors: Rebscher Lucas , Obermayer Klaus , Metzner Christoph
Published: February 2022

Gamma rhythms play a major role in many different processes in the brain, such as attention, working memory, and sensory processing. While typically considered detrimental, counterintuitively noise can sometimes have beneficial effects on communication and information transfer. Recently, Meng and Riecke showed that synchronization of interacting networks of inhibitory neurons in the gamma band (i.e., gamma generated through an ING mechanism) increases while synchronization within these networks decreases when neurons are subject to uncorrelated noise. However, experimental and modeling studies point towardz an important role of the pyramidal-interneuronal network gamma (PING) mechanism in the cortex. Therefore, we investigated the effect of uncorrelated noise on the communication between excitatory-inhibitory networks producing gamma oscillations via a PING mechanism. Our results suggest that, at least in a certain range of noise strengths and natural frequency differences between the regions, synaptic noise can have a supporting role in facilitating inter-regional communication, similar to the ING case for a slightly larger parameter range. Furthermore, the noise-induced synchronization between networks is generated via a different mechanism than when synchronization is mediated by strong synaptic coupling. Noise-induced synchronization is achieved by lowering synchronization within networks which allows the respective other network to impose its own gamma rhythm resulting in synchronization between networks.
Changes of Vestibular Symptoms in Menière's Disease After Triple Semicircular Canal Occlusion: A Long-Term Follow-Up Study
Authors: Jiang Yumeng , Xu Maoxiang , Yao Qingxiu , Li Zhuangzhuang , Wu Yaqin , Chen Zhengnong , Yu Dongzhen , Shi Haibo , Yin Shankai
Published: February 2022

Background

The clinical efficacy of triple semicircular canal occlusion (TSCO) and vestibular nerve resection (VNS) for patients with Ménière's disease has been unclear.

Objective

To explore changes in vestibular symptoms after TSCO and its advantages compared to the classical operation of VNS in patients with Menière's disease.

Methods

In total, 36 patients with Menière's disease performed TSCO or VNS at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China from May 2005 to July 2021, and all of them were enrolled in our study. Twelve of them underwent TSCO, 23 underwent VNS, and 1 had both treatments. We compared the demographic parameters, clinical symptoms, and selected test results between the two surgical methods. Ten patients each who underwent TSCO and VNS completed the follow-up. We collected and compared data pertaining to changes in vestibular symptoms.

Results

No significant difference in demographic parameters, clinical symptoms, or auditory or vestibular test results was detected between the two groups preoperatively. The TSCO group with vertigo as the main complaint experienced less residual paroxysmal dizziness after surgery than the VNS group (P = 0.020). Also, 57% of the patients in the VNS group had unsteadiness after surgery, while no such problems were reported in the TSCO group (P = 0.025).

Conclusions

Our study shows that TSCO controls vertigo in most Menière's disease patients, and also has the advantage of lower rates of postoperative paroxysmal dizziness and unsteadiness than VNS. Thus, TSCO may be an effective surgery for refractory Menière's disease.
SIRT4 Is Highly Expressed in Retinal Müller Glial Cells
Authors: Wei Wei , Hu Piaopiao , Qin Mengqi , Chen Guiping , Wang Feifei , Yao Shengrui , Jin Ming , Xie Zhi , Zhang Xu
Published: February 2022

Sirtuin 4 (SIRT4) is one of seven mammalian sirtuins that possesses ADP-ribosyltransferase, lipoamidase and deacylase activities and plays indispensable role in metabolic regulation. However, the role of SIRT4 in the retina is not clearly understood. The purpose of this study was to explore the location and function of SIRT4 in the retina. Therefore, immunofluorescence was used to analyze the localization of SIRT4 in rat, mouse and human retinas. Western blotting was used to assess SIRT4 and glutamine synthetase (GS) protein expression at different developmental stages in C57BL/6 mice retinas. We further analyzed the retinal structure, electrophysiological function and the expression of GS protein in SIRT4-deficient mice. Excitotoxicity was caused by intravitreal injection of glutamate (50 nmol) in mice with long-term intraperitoneal injection of resveratrol (20 mg/Kg), and then retinas were subjected to Western blotting and paraffin section staining to analyze the effect of SIRT4 on excitotoxicity. We show that SIRT4 co-locates with Müller glial cell markers (GS and vimentin). The protein expression pattern of SIRT4 was similar to that of GS, and both increased with development. There were no significant retinal structure or electrophysiological function changes in 2-month SIRT4-deficient mice, while the expression of GS protein was decreased. Moreover, long-term administration of resveratrol can upregulate the expression of SIRT4 and GS while reducing the retinal injury caused by excessive glutamate. These results suggest that SIRT4 is highly expressed in retinal Müller glial cells and is relevant to the expression of GS. SIRT4 does not appear to be essential in retinal development, but resveratrol, as an activator of SIRT4, can upregulate GS protein expression and protect the retina from excitotoxicity.
Biocompatible Nanomaterials in Food Science, Technology, and Nutrient Drug Delivery: Recent Developments and Applications
Authors: Ranjha Muhammad Modassar Ali Nawaz , Shafique Bakhtawar , Rehman Abdur , Mehmood Arshad , Ali Ahmad , Zahra Syeda Mahvish , Roobab Ume , Singh Ajay , Ibrahim Salam A. , Siddiqui Shahida Anusha
Published: February 2022

Graphical Abstract

Graphical abstract of functions of biocompatible nanomaterials in food industry.
Biomarker Landscape in Neuroendocrine Tumors With High-Grade Features: Current Knowledge and Future Perspective
Authors: Prisciandaro Michele , Antista Maria , Raimondi Alessandra , Corti Francesca , Morano Federica , Centonze Giovanni , Sabella Giovanna , Mangogna Alessandro , Randon Giovanni , Pagani Filippo , Prinzi Natalie , Niger Monica , Corallo Salvatore , Castiglioni di Caronno Erica , Massafra Marco , Bartolomeo Maria Di , Braud Filippo de , Milione Massimo , Pusceddu Sara
Published: February 2022

Neuroendocrine tumors (NETs) are classified based on morphology and are graded based on their proliferation rate as either well-differentiated low-grade (G1) to intermediate (G2–G3) or poorly differentiated high-grade neuroendocrine carcinomas (NEC G3). Recently, in gastroenteropancreatic (GEP) NETs, a new subgroup of well-differentiated high-grade tumors (NET G3) has been divided from NEC by WHO due to its different clinical–pathologic features. Although several mutational analyses have been performed, a molecular classification of NET is an unmet need in particular for G3, which tends to be more aggressive and have less benefit to the available therapies. Specifically, new possible prognostic and, above all, predictive factors are highly awaited, giving the basis for new treatments. Alteration of KRAS, TP53, and RB1 is mainly reported, but also druggable alterations, including BRAF and high microsatellite instability (MSI-H), have been documented in subsets of patients. In addition, PD-L1 demonstrated to be highly expressed in G3 NETs, probably becoming a new biomarker for G3 neuroendocrine neoplasm (NEN) discrimination and a predictive one for immunotherapy response. In this review, we describe the current knowledge available on a high-grade NET molecular landscape with a specific focus on those harboring potentially therapeutic targets in the advanced setting.
The Diagnostic Performance of Machine Learning-Based Radiomics of DCE-MRI in Predicting Axillary Lymph Node Metastasis in Breast Cancer: A Meta-Analysis
Authors: Zhang Jing , Li Longchao , Zhe Xia , Tang Min , Zhang Xiaoling , Lei Xiaoyan , Zhang Li
Published: February 2022

Objective

The aim of this study was to perform a meta‐analysis to evaluate the diagnostic performance of machine learning(ML)-based radiomics of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) DCE-MRI in predicting axillary lymph node metastasis (ALNM) and sentinel lymph node metastasis(SLNM) in breast cancer.

Methods

English and Chinese databases were searched for original studies. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS) were used to assess the methodological quality of the included studies. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were used to summarize the diagnostic accuracy. Spearman’s correlation coefficient and subgroup analysis were performed to investigate the cause of the heterogeneity.

Results

Thirteen studies (1618 participants) were included in this meta-analysis. The pooled sensitivity, specificity, DOR, and AUC with 95% confidence intervals were 0.82 (0.75, 0.87), 0.83 (0.74, 0.89), 21.56 (10.60, 43.85), and 0.89 (0.86, 0.91), respectively. The meta-analysis showed significant heterogeneity among the included studies. There was no threshold effect in the test. The result of subgroup analysis showed that ML, 3.0 T, area of interest comprising the ALN, being manually drawn, and including ALNs and combined sentinel lymph node (SLN)s and ALNs groups could slightly improve diagnostic performance compared to deep learning, 1.5 T, area of interest comprising the breast tumor, semiautomatic scanning, and the SLN, respectively.

Conclusions

ML-based radiomics of DCE-MRI has the potential to predict ALNM and SLNM accurately. The heterogeneity of the ALNM and SLNM diagnoses included between the studies is a major limitation.
A Risk Model Composed of Complete Blood Count, BRAF V600E and MAP2K1 Predicts Inferior Prognosis of Langerhans Cell Histiocytosis in Children
Authors: Wang Leyuan , Yuan Lin , Du Xizi , Zhou Kai , Yang Yu , Qin Qingwu , Yang Liangchun , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Liu Chi
Published: February 2022

Background

In children, Langerhans cell histiocytosis (LCH), which is the most prevalent histiocytic disorder, exhibits a wide variety of manifestations and outcomes. There is no standard prognosis evaluation system for LCH. We investigated the combined predictive significance of complete blood counts (CBCs), BRAF V600E and MAP2K1 in childhood LCH.

Methods

A cohort of 71 childhood LCH patients was retrospectively studied. The prognosis predictive significance of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), BRAF V600E, and MAP2K1 were analyzed.

Results

Histiocyte Society (HS) classification of LCH patients was correlated with NLR, SIRI, and progression free survival (PFS), bone involvement was correlated with SIRI, liver involvement was correlated with NLR, SII, SIRI, and PFS, spleen involvement was correlated with SIRI, lung involvement was correlated with NLR and PFS, CNS involvement was correlated with PFS, while BRAF V600E was correlated with PLR, NLR, SIRI, SII, PFS, and OS (p <0.05). MAP2K1 was correlated with NLR, SIRI, PFS, and OS (p <0.05). Elevated NLR, PLR SIRI, and SII predicted inferior PFS and OS (p <0.05). PLR, NLE, SIRI, SII, BRAF V600E, and MAP2K1 were used to establish a risk model for stratifying the LCH patients into 3 different risk groups. Respective median PFS for low-, mediate-, and high-risk groups were not reached, 26, and 14 months (p <0.001), and all median OS were not reached (p <0.001).

Conclusion

The risk model combined with CBCs, BRAF V600E, and MAP2K1 might be a promising prognostic system for LCH in children.
Locoregional Control and Survival in Children, Adolescents, and Young Adults With Localized Head and Neck Alveolar Rhabdomyosarcoma—The French Experience
Authors: Machavoine Roxane , Helfre Sylvie , Bernier Valérie , Bolle Stéphanie , Leseur Julie , Corradini Nadège , Rome Angélique , Defachelles Anne-Sophie , Deneuve Sophie , Bernard Sophie , Fayoux Pierre , Nicollas Richard , Mondain Michel , Luscan Romain , Denoyelle Françoise , Simon François , Kadlub Natacha , Kolb Fréderic , Honart Jean-François , Orbach Daniel , Minard-Colin Véronique , Moya-Plana Antoine , Couloigner Vincent
Published: February 2022

Introduction

The head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to lymph nodes (LNs). The aim was to report locoregional control, event-free survival (EFS), and overall survival (OS), according to clinical and pathological features, LN staging, and treatment modalities.

Methods

The study included all patients prospectively enrolled in EpSSG RMS 2005 study under 21 years of age with localized HN ARMS and diagnosed between 2005 and 2016 in France. Medical data including imaging, surgical report, and radiation therapy planes were analyzed.

Results

Forty-eight patients (median age 6 years; range 4 months−21 years), corresponding to 30 parameningeal and 18 non-parameningeal ARMS, were included. There were 33 boys (69%). Tumor locations included the following: orbit (n = 7) among which four cases had bone erosion, paranasal sinuses and nasal cavity (n = 16), deep facial spaces (n = 10), nasolabial fold (n = 8), and other non-parameningeal HN sites (n = 7). A fusion transcript of PAX3-FOXO1 or PAX7-FOXO1 was expressed in 33 of the 45 cases (73%) with molecular analysis. At diagnosis, 10 patients had primary resection of the primary tumor (PRPT) (none with microscopic complete resection) and 9 had LN staging. After induction chemotherapy, 26 patients (54%) had secondary resection of the primary tumor (SRPT) and 13 patients (27%) had cervical LN dissection. A total of 43 patients (90%) were treated with radiation therapy.

With a median follow-up of 7 years (range 2–13 years), 5-year OS and EFS were 78% (95% CI, 63–88%) and 66% (95% CI, 51–78%), respectively. We observed 16 events (10 deaths): 4 local, 4 regional, 1 local and regional, and 7 metastatic. In univariate analysis, OS was only superior for patients under 10 years of age (p = 0.002), while FOXO1-negative ARMS, SRPT for parameningeal ARMS, and LN surgery were associated with significantly better EFS.

Conclusion

Our study confirms a better outcome for fusion-negative ARMS and ARMS in children under 10 years. Moreover, LN surgery and SRPT of parameningeal tumor may improve EFS of ARMS. Larger studies are needed to confirm our findings.
Effect of Helicobacter pylori-Associated Chronic Gastritis on Autonomous Activity and Sleep Quality in Mice
Authors: Liu Haihua , Zheng Wenlong , Zhang Ling , Lin Tangtang , Tang Yang , Hu Ling
Published: February 2022

Many reports have shown that patients with Hp-associated chronic gastritis exhibit anxiety and poor sleep quality. However, less is known about the effects and specific manifestations of Hp-associated chronic gastritis on autonomous activity and sleep quality in animals. Here, we investigated the effect of Helicobacter pylori (Hp)-associated chronic gastritis on autonomous activity and sleep quality in mice. To do this, a Hp-associated chronic gastritis mouse model was first established, then analyzed for autonomous activity, relative to controls, for 15 min using an autonomous activity tester. Next, sleep quality of mice was detected by sodium pentobarbital-induced sleep experiment and results compared between groups. The results showed that male mice in the model group exhibited higher activity counts but lower forelimb lift counts, relative to those in the control group, although there were no significant differences (all p > .05). Conversely, female mice in the model group recorded lower activity counts, albeit at no significant difference (p > .05), and significantly lower counts of forelimb lift (p < .05), relative to those in the control group. Notably, male mice in the model group had longer sleep latency and shorter sleep duration than those in the control group, albeit at no significant differences (all p > .05). On the other hand, female mice in the model group recorded significantly longer sleep latency as well as shorter sleep duration compared to those in the control group (all p < .01). We conclude that Hp-associated chronic gastritis exerts certain effects on autonomous activity and sleep quality of mice in a gender-dependent manner. Notably, female mice with Hp-associated chronic gastritis had lower activity and forelimb lift counts, as well as prolonged sleep latency, and shortened sleep duration. These effects were all statistically significant except for activity counts.
Measurements of Atmospheric Water Vapor by a 1.316 μm Optical Fiber Laser Heterodyne Radiometer
Authors: Huang Jun , Huang Yinbo , Lu Xingji , Liu Dandan , Yuan Zihao , Qi Gang , Cao Zhensong
Published: February 2022

A passive optical fiber laser heterodyne radiometer prototype with a semiconductor laser near 1.316 μm as the local oscillator was built, parameters of the prototype have been optimized. Using the prototype, the water vapor concentration in the atmospheric column was measured with a spectral resolution of 0.009 cm−1 in late October and early November of 2020, the collection time was approximately 3 min, and the signal-to-noise ratio was better than 120. The water vapor column concentration and profiles were inversed based on the optimal estimation method. Compared with the measurement of the Fourier transform spectrometer (EM27/SUN) which was performed simultaneously, the inversion results deviated by less than 14%, and the variation trend of the water vapor concentration showed good consistency. It is demonstrated that the 1.316 μm optical fiber laser heterodyne radiometer possesses good stability and accuracy in the field measurement of atmospheric water vapor concentration.
Integrated Metabolomic and Lipidomic Analysis in the Placenta of Preeclampsia
Authors: Zhang Lizi , Bi Shilei , Liang Yingyu , Huang Lijun , Li Yulian , Huang Minshan , Huang Baoying , Deng Weinan , Liang Jingying , Gu Shifeng , Chen Jingsi , Du Lili , Chen Dunjin , Wang Zhijian
Published: February 2022

Preeclampsia is one of the most common severe pregnancy complications in obstetrics, which is considered a placental source disease. However, the mechanisms underlying preeclampsia remain largely unknown. In this study, UPLC-MS/MS-based metabolomic and lipidomic analysis was used to explore the characteristic placental metabolites in preeclampsia. The results revealed that there were significant changes in metabolites between preeclampsia and normotensive placentas. Weighted correlation network analysis (WGCNA) identified the correlation network module of metabolites highly related to preeclampsia and the clinical traits reflecting disease severity. The metabolic perturbations were primarily associated with glycerophospholipid and glutathione metabolism, which might influent membrane structures of organisms and mitochondria function. Using linear models, three metabolites had an area under receiver operating characteristic curves (AUROC) ≥ 0.80 and three lipids had an AUROC ≥ 0.90. Therefore, metabolomics and lipidomics may offer a novel insight for a better understanding of preeclampsia and provide a useful molecular mechanism underlying preeclampsia.
Research on the Resilience Evaluation and Spatial Correlation of China’s Sports Regional Development Under the New Concept
Authors: Zhang Jing , Gan Jing-Ru , Wu Ying , Liu Jia-Bao , Zhang Su , Shao Bin
Published: February 2022

In order to fully implement the new development concept, bring into full play the potential of sports development, and maintain the resilience of China’s sports development. This paper studies the resilience evaluation and spatial correlation of Chinese sports development under the new development concept. First, we constructed Resilience Evaluation Indexes System for Sports Development in China based on the analysis of the resilience features of sports development and the DPSIR model, which is from the five aspects of “driving force – pressure – state – influence – response.” Second, used Coefficient of Variation and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) Method to measure the resilience level of sports development in 31 provinces in China from 2013 to 2017. Then, we introduced the obstacle degree model to identify the obstacle factors that hinder the resilience of Chinese sports development in different periods. Finally, we used the global and local Moran indexes to analyze the spatial correlation of China sports regional development. The results showed that: (1) overall, the development level of sports resilience in 31 provinces in China showed an upward trend from 2013 to 2017, while some provinces showed obvious fluctuations. (2) The obstacles to the development of sports resilience in China mainly include sports scientific research equipment, the number of national fitness monitoring stations, the number of national fitness centers, the full-time equivalent of (R&D) personnel, and the number of sports scientific research projects. The response subsystem is the main obstacle factor that affects the improvement of the resilience level of sports development in China. (3) There is a positive spatial autocorrelation between the resilience level of sports development and regional spatial distribution, and the correlation shows a weakening trend, and the internal difference is significant. Finally, we concluded that we must take the new development philosophy as the guiding principle. First, we should stick to innovation-driven development to fully upgrade the resilience of China’s sports development. Second, we should adhere to the principle of coordinated development to promote the overall and balanced development of sports. Lastly, we should promote shared development so as to deliver benefits for all in an equal way.
Servant Leadership and Creativity: A Study of the Sequential Mediating Roles of Psychological Safety and Employee Well-Being
Authors: Wang Wenxian , Kang Seung-Wan , Choi Suk Bong
Published: February 2022

With today’s increasingly dynamic and competitive business environment, creativity is critical for enterprises to enhance their competitiveness. Companies today invest and seek new ways to enhance creativity of employees within the organization. Our study describes the effects of servant leadership, psychological safety, and employee well-being on creativity under the conservation of resources theory. We used a sample of 252 full-time employees in the United Kingdom who had been recruited online and collected their data for analysis. We conducted confirmatory factor analyses to test the validity of the measurement model and regression to evaluate the direct effects. Subsequently, we used bootstrapping to confirm mediation and serial mediation effects. The results showed that servant leadership was positively related to creativity and that psychological safety and employee well-being were serial mediators between them.
When Visual Cues Do Not Help the Beat: Evidence for a Detrimental Effect of Moving Point-Light Figures on Rhythmic Priming
Authors: Fiveash Anna , Burger Birgitta , Canette Laure-Hélène , Bedoin Nathalie , Tillmann Barbara
Published: February 2022

Rhythm perception involves strong auditory-motor connections that can be enhanced with movement. However, it is unclear whether just seeing someone moving to a rhythm can enhance auditory-motor coupling, resulting in stronger entrainment. Rhythmic priming studies show that presenting regular rhythms before naturally spoken sentences can enhance grammaticality judgments compared to irregular rhythms or other baseline conditions. The current study investigated whether introducing a point-light figure moving in time with regular rhythms could enhance the rhythmic priming effect. Three experiments revealed that the addition of a visual cue did not benefit rhythmic priming in comparison to auditory conditions with a static image. In Experiment 1 (27 7–8-year-old children), grammaticality judgments were poorer after audio-visual regular rhythms (with a bouncing point-light figure) compared to auditory-only regular rhythms. In Experiments 2 (31 adults) and 3 (31 different adults), there was no difference in grammaticality judgments after audio-visual regular rhythms compared to auditory-only irregular rhythms for either a bouncing point-light figure (Experiment 2) or a swaying point-light figure (Experiment 3). Comparison of the observed performance with previous data suggested that the audio-visual component removed the regular prime benefit. These findings suggest that the visual cues used in this study do not enhance rhythmic priming and could hinder the effect by potentially creating a dual-task situation. In addition, individual differences in sensory-motor and social scales of music reward influenced the effect of the visual cue. Implications for future audio-visual experiments aiming to enhance beat processing, and the importance of individual differences will be discussed.
Examining Crisis Communication Using Semantic Network and Sentiment Analysis: A Case Study on NetEase Games
Authors: Che ShaoPeng , Nan Dongyan , Kamphuis Pim , Zhang Shunan , Kim Jang Hyun
Published: February 2022

The mobile game “Immortal Conquest,” created by NetEase Games, caused a dramatic user dissatisfaction event after an introduction of a sudden and uninvited “pay-to-win” update. As a result, many players filed grievances against NetEase in a court. The official game website issued three apologies, with mix results, to mitigate the crisis. The goal of the present study is to understand user feedback content from the perspective of Situational Crisis Communication Theory through semantic network analysis and sentiment analysis to explore how an enterprise’s crisis communication strategy affects users’ attitudes. First, our results demonstrate that the diminishing crisis communication strategies (excuse and justification) do not change players’ negative attitudes. It was not a failure because it successfully alleviated the players’ legal complaints and refocused their attention on the game itself. Second, the rebuild (apology & compensation) strategy was effective because it significantly increased the percentage of positive emotions and regenerated expectations for the game. The litigation crisis was identified within gamer communications with respect to Chinese gaming companies for the first time. Nevertheless, this does not indicate an increase in overall legal awareness among the larger Chinese population. It may only reflect greater legal awareness among Chinese online gamers. Fourth, gamers emphasized that they and enterprises should be equally involved when communicating with each other. Finally, in-game paid items should be reasonably priced, otherwise, they will drive users to competitors.