bluuebunny/crossref_metadata_2025 huggingface dataset:
Soil Microbial Resource Limitations and Community Assembly Along a Camellia oleifera Plantation Chronosequence
Authors: Qiao Hang , Chen Longsheng , Hu Yajun , Deng Chenghua , Sun Qi , Deng Shaohong , Chen Xiangbi , Mei Li , Wu Jinshui , Su Yirong
Published: December 2021

Understanding soil microbial element limitation and its relation with the microbial community can help in elucidating the soil fertility status and improving nutrient management of planted forest ecosystems. The stand age of a planted forest determines the aboveground forest biomass and structure and underground microbial function and diversity. In this study, we investigated 30 plantations of Camellia oleifera distributed across the subtropical region of China that we classified into four stand ages (planted <9 years, 9–20 years, 21–60 years, and >60 years age). Enzymatic stoichiometry analysis showed that microbial metabolism in the forests was mainly limited by C and P. P limitation significantly decreased and C limitation slightly increased along the stand age gradient. The alpha diversity of the soil microbiota remained steady along stand age, while microbial communities gradually converged from scattered to clustered, which was accompanied by a decrease in network complexity. The soil bacterial community assembly shifted from stochastic to deterministic processes, which probably contributed to a decrease in soil pH along stand age. Our findings emphasize that the stand age regulated the soil microbial metabolism limitation and community assembly, which provides new insight into the improvement of C and P management in subtropical planted forest.
Alone Yet Not Alone: Frankia Lives Under the Same Roof With Other Bacteria in Actinorhizal Nodules
Authors: Ghodhbane-Gtari Faten , D’Angelo Timothy , Gueddou Abdellatif , Ghazouani Sabrine , Gtari Maher , Tisa Louis S.
Published: December 2021

Actinorhizal plants host mutualistic symbionts of the nitrogen-fixing actinobacterial genus Frankia within nodule structures formed on their roots. Several plant-growth-promoting bacteria have also been isolated from actinorhizal root nodules, but little is known about them. We were interested investigating the in planta microbial community composition of actinorhizal root nodules using culture-independent techniques. To address this knowledge gap, 16S rRNA gene amplicon and shotgun metagenomic sequencing was performed on DNA from the nodules of Casuarina glauca. DNA was extracted from C. glauca nodules collected in three different sampling sites in Tunisia, along a gradient of aridity ranging from humid to arid. Sequencing libraries were prepared using Illumina NextEra technology and the Illumina HiSeq 2500 platform. Genome bins extracted from the metagenome were taxonomically and functionally profiled. Community structure based off preliminary 16S rRNA gene amplicon data was analyzed via the QIIME pipeline. Reconstructed genomes were comprised of members of Frankia, Micromonospora, Bacillus, Paenibacillus, Phyllobacterium, and Afipia. Frankia dominated the nodule community at the humid sampling site, while the absolute and relative prevalence of Frankia decreased at the semi-arid and arid sampling locations. Actinorhizal plants harbor similar non-Frankia plant-growth-promoting-bacteria as legumes and other plants. The data suggests that the prevalence of Frankia in the nodule community is influenced by environmental factors, with being less abundant under more arid environments.
Emergence of Colistin Resistance in Carbapenem-Resistant Hypervirulent Klebsiella pneumoniae Under the Pressure of Tigecycline
Authors: Zhang Yawei , Wang Xiaojuan , Wang Shifu , Sun Shijun , Li Henan , Chen Hongbin , Wang Qi , Wang Hui
Published: December 2021

Colistin and tigecycline are the last options against carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP). Intersecting resistance determinants have been detected between these antibiotics; however, there is only limited evidence of such association. Here, we describe a colistin-resistant CR-hvKP isolated from a patient with severe neonatal bacteremia treated with tigecycline as opposed to colistin before isolation of this strain, providing a clinical clue to colistin resistance under tigecycline pressure. Furthermore, an ST11-K64 KPC-2–producing, colistin-susceptible CR-hvKP strain was subjected to experimental evolution toward colistin resistance under tigecycline and colistin pressure to verify this phenomenon in vitro. The biological impact of acquiring colistin resistance on fitness and virulence was also studied. As expected, the parental strain rapidly developed colistin resistance under both tigecycline and colistin selection. However, different from the colistin resistance mechanism in the clinical strain that was due to an ISKpn26 insertion in the mgrB gene, the mutants in this study developed colistin resistance through a ∼4.4 or ∼4.6 kb deletion including the mgrB locus as well as the kdgR, yobH, yebO, yobF, cspC, ftsI, and rlmA genes. Although the virulence of the colistin-resistant mutants, as determined in the Galleria mellonella model, decreased compared with that of the parent strain, it was still higher than that of NTUH-K2044. This suggests a slight virulence cost when CR-hvKP develops colistin resistance under tigecycline or colistin pressure. Together, our results provide clinical and experimental evidence for the association between colistin resistance and tigecycline pressure in CR-hvKP, highlighting a critical issue in the clinical setting.
Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
Authors: Rodel Hylton E. , Ferreira Isabella A. T. M. , Ziegler Carly G. K. , Ganga Yashica , Bernstein Mallory , Hwa Shi-Hsia , Nargan Kievershen , Lustig Gila , Kaplan Gilla , Noursadeghi Mahdad , Shalek Alex K. , Steyn Adrie J. C. , Sigal Alex
Published: December 2021

Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission.
Dual RNA-Seq Analysis of the Interaction Between Edible Fungus Morchella sextelata and Its Pathogenic Fungus Paecilomyces penicillatus Uncovers the Candidate Defense and Pathogenic Factors
Authors: Yu Yang , Tan Hao , Liu Tianhai , Liu Lixu , Tang Jie , Peng Weihong
Published: December 2021

Morels (Morchella spp.) are economically important mushrooms cultivated in many countries. However, their production and quality are hindered by white mold disease because of Paecilomyces penicillatus infection. In this study, we aimed to understand the genetic mechanisms of interactions between P. penicillatus and Morchella. M. sextelata, the most prevalent species of Morchella in China, was inoculated with P. penicillatus; then, the expression profiles of both fungi were determined simultaneously at 3 and 6 days post-inoculation (dpi) using a dual RNA-Seq approach. A total of 460 and 313 differentially expressed genes (DEGs) were identified in P. penicillatus and M. sextelata, respectively. The CAZymes of β-glucanases and mannanases, as well as subtilase family, were upregulated in P. penicillatus, which might be involved in the degradation of M. sextelata cell walls. Chitin recognition protein, caffeine-induced death protein, and putative apoptosis-inducing protein were upregulated, while cyclin was downregulated in infected M. sextelata. This indicates that P. penicillatus could trigger programmed cell death in M. sextelata after infection. Laccase-2, tyrosinases, and cytochrome P450s were also upregulated in M. sextelata. The increased expression levels of these genes suggest that M. sextelata could detoxify the P. penicillatus toxins and also form a melanin barrier against P. penicillatus invasion. The potential pathogenic mechanisms of P. penicillatus on M. sextelata and the defense mechanisms of M. sextelata against P. penicillatus were well described.
Global Characterization of Fungal Mitogenomes: New Insights on Genomic Diversity and Dynamism of Coding Genes and Accessory Elements
Authors: Fonseca Paula L. C. , De-Paula Ruth B. , Araújo Daniel S. , Tomé Luiz Marcelo Ribeiro , Mendes-Pereira Thairine , Rodrigues Wenderson Felipe Costa , Del-Bem Luiz-Eduardo , Aguiar Eric R. G. R. , Góes-Neto Aristóteles
Published: December 2021

Fungi comprise a great diversity of species with distinct ecological functions and lifestyles. Similar to other eukaryotes, fungi rely on interactions with prokaryotes and one of the most important symbiotic events was the acquisition of mitochondria. Mitochondria are organelles found in eukaryotic cells whose main function is to generate energy through aerobic respiration. Mitogenomes (mtDNAs) are double-stranded circular or linear DNA from mitochondria that may contain core genes and accessory elements that can be replicated, transcribed, and independently translated from the nuclear genome. Despite their importance, investigative studies on the diversity of fungal mitogenomes are scarce. Herein, we have evaluated 788 curated fungal mitogenomes available at NCBI database to assess discrepancies and similarities among them and to better understand the mechanisms involved in fungal mtDNAs variability. From a total of 12 fungal phyla, four do not have any representative with available mitogenomes, which highlights the underrepresentation of some groups in the current available data. We selected representative and non-redundant mitogenomes based on the threshold of 90% similarity, eliminating 81 mtDNAs. Comparative analyses revealed considerable size variability of mtDNAs with a difference of up to 260 kb in length. Furthermore, variation in mitogenome length and genomic composition are generally related to the number and length of accessory elements (introns, HEGs, and uORFs). We identified an overall average of 8.0 (0–39) introns, 8.0 (0–100) HEGs, and 8.2 (0–102) uORFs per genome, with high variation among phyla. Even though the length of the core protein-coding genes is considerably conserved, approximately 36.3% of the mitogenomes evaluated have at least one of the 14 core coding genes absent. Also, our results revealed that there is not even a single gene shared among all mitogenomes. Other unusual genes in mitogenomes were also detected in many mitogenomes, such as dpo and rpo, and displayed diverse evolutionary histories. Altogether, the results presented in this study suggest that fungal mitogenomes are diverse, contain accessory elements and are absent of a conserved gene that can be used for the taxonomic classification of the Kingdom Fungi.
Distribution, Function, and Evolution of a Gene Essential for Trichothecene Toxin Biosynthesis in Trichoderma
Authors: Gutiérrez Santiago , McCormick Susan P. , Cardoza Rosa E. , Kim Hye-Seon , Yugueros Laura Lindo , Vaughan Martha Marie , Carro-Huerga Guzmán , Busman Mark , Sáenz de Miera Luis E. , Jaklitsch Walter M. , Zhuang Wen-Ying , Wang Chao , Casquero Pedro A. , Proctor Robert Henry
Published: December 2021

Trichothecenes are terpenoid toxins produced by species in 10 fungal genera, including species ofTrichoderma. The trichothecene biosynthetic gene (tri) cluster typically includes thetri5gene, which encodes a terpene synthase that catalyzes formation of trichodiene, the parent compound of all trichothecenes. The twoTrichodermaspecies,Trichoderma arundinaceumandT. brevicompactum, that have been examined are unique in thattri5is located outside thetricluster in a genomic region that does not include other knowntrigenes. In the current study, analysis of 35 species representing a wide range of the phylogenetic diversity ofTrichodermarevealed that 22 species hadtri5, but only 13 species had bothtri5and thetricluster.tri5was not located in the cluster in any species. Using complementation analysis of aT. arundinaceum tri5deletion mutant, we demonstrated that sometri5homologs from species that lack atricluster are functional, but others are not. Phylogenetic analyses suggest thatTrichoderma tri5was under positive selection following its divergence from homologs in other fungi but beforeTrichodermaspecies began diverging from one another. We propose two models to explain these diverse observations. One model proposes that the location oftri5outside thetricluster resulted from loss oftri5from the cluster in an ancestral species followed by reacquisitionviahorizontal transfer. The other model proposes that in species that have a functionaltri5but lack thetricluster, trichodiene production provides a competitive advantage.
Nutrient L-Alanine-Induced Germination of Bacillus Improves Proliferation of Spores and Exerts Probiotic Effects in vitro and in vivo
Authors: Lu Shuang , Liao Xianyin , Zhang Li , Fang Ying , Xiang Meixian , Guo Xiaohua
Published: December 2021

As alternatives to antibiotics in feed, probiotic Bacillus carries multiple advantages in animal production. Spores undergo strain-related germination in the gastrointestinal tract, but it is still unknown whether the probiotic function of the Bacillus depends on the germination of spores in vivo. In this study, based on 14 potential probiotic Bacillus strains from fermented food and feed, we detected the germination response of these Bacillus spores in relation to different germinating agents. The results showed the germination response was strain-specific and germinant-related, and nutrient germinant L-alanine significantly promoted the growth of strains with germination potential. Two strains of Bacillus subtilis, S-2 and 312, with or without a high spore germination response to L-alanine, were selected to study their morphological and genic differences induced by L-alanine through transmission electron microscopy and comparative transcriptomics analysis. Consequently, after L-alanine treatment, the gray phase was largely increased under microscopy, and the expression of the germination response genes was significantly up-regulated in the B. subtilis S-2 spores compared to the B. subtilis 312 spores (p < 0.05). The protective effect of L-alanine-induced spore germination of the two strains was comparatively investigated both in the IPEC-J2 cell model and a Sprague–Dawley (SD) rat model challenged by enterotoxigenic Escherichia coli K99. The result indicated that L-alanine helped B. subtilis S-2 spores, but not 312 spores, to decrease inflammatory factors (IL-6, IL-8, IL-1 β, TNF-α; p < 0.05) and promote the expression of occludin in IPEC-J2 cells. Besides, supplement with L-alanine-treated B. subtilis S-2 spores significantly improved the growth of the SD rats, alleviated histopathological GIT lesions, and improved the ratio of jejunal villus length to crypt depth in comparison to the B. subtilis S-2 spores alone (p < 0.05). Improved species diversity and abundance of fecal microbiota were only observed in the group with L-alanine-treated S-2 spores (p < 0.05). The study demonstrates L-alanine works well as a probiotic Bacillus adjuvant in improving intestinal health, and it also provides a solution for the practical and accurate regulation of their use as antibiotic alternatives in animal production.
5-Methylcytosine RNA Methyltransferases-Related Long Non-coding RNA to Develop and Validate Biochemical Recurrence Signature in Prostate Cancer
Authors: Wang Ke , Zhong Weibo , Long Zining , Guo Yufei , Zhong Chuanfan , Yang Taowei , Wang Shuo , Lai Houhua , Lu Jianming , Zheng Pengxiang , Mao Xiangming
Published: December 2021

The effects of 5-methylcytosine in RNA (m5C) in various human cancers have been increasingly studied recently; however, the m5C regulator signature in prostate cancer (PCa) has not been well established yet. In this study, we identified and characterized a series of m5C-related long non-coding RNAs (lncRNAs) in PCa. Univariate Cox regression analysis and least absolute shrinkage and selector operation (LASSO) regression analysis were implemented to construct a m5C-related lncRNA prognostic signature. Consequently, a prognostic m5C-lnc model was established, including 17 lncRNAs: MAFG-AS1, AC012510.1, AC012065.3, AL117332.1, AC132192.2, AP001160.2, AC129510.1, AC084018.2, UBXN10-AS1, AC138956.2, ZNF32-AS2, AC017100.1, AC004943.2, SP2-AS1, Z93930.2, AP001486.2, and LINC01135. The high m5C-lnc score calculated by the model significantly relates to poor biochemical recurrence (BCR)-free survival (p < 0.0001). Receiver operating characteristic (ROC) curves and a decision curve analysis (DCA) further validated the accuracy of the prognostic model. Subsequently, a predictive nomogram combining the prognostic model with clinical features was created, and it exhibited promising predictive efficacy for BCR risk stratification. Next, the competing endogenous RNA (ceRNA) network and lncRNA–protein interaction network were established to explore the potential functions of these 17 lncRNAs mechanically. In addition, functional enrichment analysis revealed that these lncRNAs are involved in many cellular metabolic pathways. Lastly, MAFG-AS1 was selected for experimental validation; it was upregulated in PCa and probably promoted PCa proliferation and invasion in vitro. These results offer some insights into the m5C's effects on PCa and reveal a predictive model with the potential clinical value to improve the prognosis of patients with PCa.
Impact of the Extent of Surgical Resection on Patients With Intradural Extramedullary Bronchogenic Cysts: A Retrospective Institutional Experience and Review of the Literature
Authors: Liu Jinghui , Wang Yuan , Li Chen , Ji Peigang , Guo Shaochun , Zhai Yulong , Wang Na , Lou Miao , Xu Meng , Chao Min , Feng Fuqiang , Yan Ming , Wang Liang
Published: December 2021

Intradural extramedullary bronchogenic cysts (IEBC) are rare congenital cystic lesions. The clinical manifestations, radiological characteristics, especially the optimal treatment regimen are not well-understood. We retrospectively analyzed a series of patients with confirmed IEBC in Tangdu hospital and reviewed the published works to gain a comprehensive understanding of IEBC. In our institution, nine consecutive patients had pathologically confirmed IEBC between 2005 and 2018. We also identified 27 patients from previous studies. The most common presentations on magnetic resonance imaging (MRI) were hypointensity on T1-weighted images (T1WI), hyperintensity on T2-weighted images(T2WI), and no improvement on T1WI contrast-enhanced with gadolinium (94.4%). All patients in our center and the patients we reviewed received surgical resection; gross total resection (GTR) and partial resection (PR) were achieved in 20 (55.6%) and 16 (44.4%) patients, respectively. The symptom remission rate of patients who underwent GTR was 100%, which was similar to those who underwent PR (93.8%) (P = 0.457). The recurrence rate was 12.5% in the group who underwent PR and nil after GTR (P = 0.202). According to our current investigation, the surgical resection degree is irrelevant to the symptom remission rate. Therefore, we suggest that total resection should not be recommended for cases with tight adhesion. For patients with PR, longer follow-up will be necessary to determine the long-term outcome.
Efficacy and Safety of Immunotherapies in Refractory Myasthenia Gravis: A Systematic Review and Meta-Analysis
Authors: Feng Xuelin , Song Zubiao , Wu Mengli , Liu Yanmei , Luo Sushan , Zhao Chongbo , Zhang Weixi
Published: December 2021

Introduction: Approximately 10–20% of patients WITH myasthenia gravis (MG) are refractory to conventional immunotherapies. The purpose of this study was to conduct a systematic review and meta-analysis to explore the optimal therapies for refractory MG.

Method: Correlative studies were performed through a search in PubMed, Cochrane Library, and Embase databases. The primary outcome was defined by changes in the quantitative myasthenia gravis score (QMG). Secondary outcomes were defined by the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL), Myasthenia Gravis Foundation of America (MGFA) post intervention status, adverse events, and disease exacerbation after treatment.

Result: A total of 16 studies were included with 403 patients with refractory MG on therapies with rituximab, eculizumab, tacrolimus, and cladribine. Therapeutic efficacy of rituximab and eculizumab was identified with an estimated reduction in QMG score (4.158 vs. 6.928) and MG-ADL (4.400 vs. 4.344), respectively. No significant changes were revealed in efficacy or exacerbation density between the two independent therapeutic cohorts. The estimated adverse event density of eculizumab was more significant than that in the rituximab group (1.195 vs. 0.134 per patient-year), while the estimated serious event density was similar.

Conclusion: The efficacy and safety of rituximab and eculizumab have been approved in patients with refractory MG. Rituximab had a superior safety profile than eculizumab with a lower incidence of adverse events.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236818, identifier CRD42021236818.
Effects of Neuromuscular Electrical Stimulation on Plantarflexors Spasticity, Gait Performance, and Self-Reported Health Outcomes in People With Chronic Stroke: A Study Protocol for a Double-Blinded Randomized Clinical Trial
Authors: Almutairi Sattam M. , Khalil Mohamed E. , Almutairi Nadiah , Alenazi Aqeel M.
Published: December 2021

Introduction: Rehabilitation approaches have been used for people with stroke to decrease spasticity and improve functions, but little is known about the effect of neuromuscular electrical stimulation (NMES) in this population. Therefore, the primary purpose of this study was to establish a protocol for a double-blinded randomized clinical trial to examine using NMES on plantarflexors spasticity, dorsiflexor muscle strength, physical functions, and self-reported health outcomes in people with chronic stroke in Saudi Arabia.

Material and Methods: This randomized clinical trial with two arms and double-blinded registered in ClinicalTrials (NCT04673045) will enroll 44 participants with chronic stroke and randomized them into either the experimental group (EG), including electrical stimulation (ES) with conventional therapy or the control sham group (NMESsham) including placebo electrical stimulation with conventional therapy. The frequency will be set at 80 Hz for 30 min. The intervention will be three times a week for 4 weeks for both groups. Data collection for pre- and post-intervention outcomes will include measurements for the primary outcomes including paretic limb (plantarflexor spasticity, ankle range of motion, and dorsiflexor muscles strength), and gait speed using 10-m walk test (10-MWT). The secondary outcomes including mobility function using Timed Up and Go (TUG), walking endurance using 6 Minutes Walk Test (6-MWT), activity of daily living using the Arabic version of Barthel Index (BI), and self-reported health measures such as quality of life using the Medical Outcomes Survey (Short Form 36, SF-36), physical activity using Rapid Assessment of Physical Activity (RAPA), depression symptoms using Patient Health Questionnaire-9 (PHQ-9), fatigue level using Fatigue Severity Scale (FSS), and risk of fall using Fall Efficacy Scale International (FES-I). An independent t-test will be utilized to examine the effect of the intervention on the outcome measures.

Results: The recruitment has started and is ongoing.

Conclusions: Using 4 weeks of NMES will provide information about its effect in improving plantarflexor spasticity, dorsiflexor muscles strength, gait speed, mobility functions, and other self-reported health outcomes in people with chronic stroke when compared to NMESsham.
Predicting Autonomous Shuttle Acceptance in Older Drivers Based on Technology Readiness/Use/Barriers, Life Space, Driving Habits, and Cognition
Authors: Classen Sherrilene , Mason Justin R. , Hwangbo Seung Woo , Sisiopiku Virginia
Published: December 2021

Shared autonomous vehicle services (i. e., automated shuttles, AS) are being deployed globally and may improve older adults (>65 years old) mobility, independence, and participation in the community. However, AS must be user friendly and provide safety benefits if older drivers are to accept and adopt this technology. Current potential barriers to their acceptance of AS include a lack of trust in the systems and hesitation to adopt emerging technology. Technology readiness, perceived ease of use, perceived barriers, and intention to use the technology, are particularly important constructs to consider in older adults' acceptance and adoption practices of AS. Likewise, person factors, i.e., age, life space mobility, driving habits, and cognition predict driving safety among older drivers. However, we are not sure if and how these factors may also predict older adults' intention to use the AS. In the current study, we examined responses from 104 older drivers (Mage = 74.3, SDage = 5.9) who completed the Automated Vehicle User Perception Survey (AVUPS) before and after riding in an on-road automated shuttle (EasyMile EZ10). The study participants also provided information through the Technology Readiness Index, Technology Acceptance Measure, Life Space Questionnaire, Driving Habits Questionnaire, Trail-making Test Part A and Part B (TMT A and TMT B). Older drivers' age, cognitive scores (i.e., TMT B), driving habits (i.e., crashes and/or citations, exposure, and difficulty of driving) and life space (i.e., how far older adults venture from their primary dwelling) were entered into four models to predict their acceptance of AVs—operationalized according to the subscales (i.e., intention to use, perceived barriers, and well-being) and the total acceptance score of the AVUPS. Next, a partial least squares structural equation model (PLS-SEM) elucidated the relationships between, technology readiness, perceived ease of use, barriers to AV acceptance, life space, crashes and/or citations, driving exposure, driving difficulty, cognition, and intention to use AS. The regression models indicated that neither age nor cognition (TMT B) significantly predicted older drivers' perceptions of AVs; but their self-reported driving difficulty (p = 0.019) predicted their intention to use AVs: R2 = 6.18%, F (2,101) = 4.554, p = 0.040. Therefore, intention to use was the dependent variable in the subsequent PLS-SEM. Findings from the PLS-SEM (R2 = 0.467) indicated the only statistically significant predictors of intention to use were technology readiness (β = 0.247, CI = 0.087-0.411) and barriers to AV acceptance (β = −0.504, CI = 0.285-0.692). These novel findings provide evidence suggesting that technology readiness and barriers must be better understood if older drivers are to accept and adopt AS.
Exploring Fatigue Effects on Performance Variation of Intensive Brain–Computer Interface Practice
Authors: Li Songwei , Duan Junyi , Sun Yu , Sheng Xinjun , Zhu Xiangyang , Meng Jianjun
Published: December 2021

Motor imagery (MI) is an endogenous mental process and is commonly used as an electroencephalogram (EEG)-based brain–computer interface (BCI) strategy. Previous studies of P300 and MI-based (without online feedback) BCI have shown that mental states like fatigue can negatively affect participants’ EEG signatures. However, exogenous stimuli cause visual fatigue, which might have a different mechanism than endogenous tasks do. Furthermore, subjects could adjust themselves if online feedback is provided. In this sense, it is still unclear how fatigue affects online MI-based BCI performance. With this question, 12 healthy subjects are recruited to investigate this issue, and an MI-based online BCI experiment is performed for four sessions on different days. The first session is for training, and the other three sessions differ in rest condition and duration—no rest, 16-min eyes-open rest, and 16-min eyes-closed rest—arranged in a pseudo-random order. Multidimensional fatigue inventory (MFI) and short stress state questionnaire (SSSQ) reveal that general fatigue, mental fatigue, and distress have increased, while engagement has decreased significantly within certain sessions. However, the BCI performances, including percent valid correct (PVC) and information transfer rate (ITR), show no significant change across 400 trials. The results suggest that although the repetitive MI task has affected subjects’ mental states, their BCI performances and feature separability within a session are not affected by the task significantly. Further electrophysiological analysis reveals that the alpha-band power in the sensorimotor area has an increasing tendency, while event-related desynchronization (ERD) modulation level has a decreasing trend. During the rest time, no physiological difference has been found in the eyes-open rest condition; on the contrary, the alpha-band power increase and subsequent decrease appear in the eyes-closed rest condition. In summary, this experiment shows evidence that mental states can change dramatically in the intensive MI-BCI practice, but BCI performances could be maintained.
Do Certain Flavonoid IMPS Have a Vital Function?
Authors: Seigler David S. , Friesen J. Brent , Bisson Jonathan , Graham James G. , Bedran-Russo Ana , McAlpine James B. , Pauli Guido F.
Published: December 2021

Flavonoids are a vast group of metabolites that are essential for vascular plant physiology and, thus, occur ubiquitously in plant-based/-derived foods. The solitary designation of thousands of known flavonoids hides the fact that their metabolomes are structurally highly diverse, consist of disparate subgroups, yet undergo a certain degree of metabolic interconversion. Unsurprisingly, flavonoids have been an important theme in nutrition research. Already in the 1930s, it was discovered that the ability of synthetic Vitamin C to treat scurvy was inferior to that of plant extracts containing Vitamin C. Subsequent experimental evidence led to the proposal of Vitamin P (permeability) as an essential phytochemical nutrient. However, attempts to isolate and characterize Vitamin P gave confusing and sometimes irreproducible results, which today can be interpreted as rooted in the unrecognized (residual) complexity of the intervention materials. Over the years, primarily flavonoids (and some coumarins) were known as having Vitamin P-like activity. More recently, in a NAPRALERT meta-analysis, essentially all of these Vitamin P candidates were identified as IMPs (Invalid/Improbable/Interfering Metabolic Panaceas). While the historic inability to define a single compound and specific mode of action led to general skepticism about the Vitamin P proposition for “bioflavonoids,” the more logical conclusion is that several abundant and metabolically labile plant constituents fill this essential role in human nutrition at the interface of vitamins, cofactors, and micronutrients. Reviewing 100+ years of the multilingual Vitamin P and C literature provides the rationales for this conclusion and new perspectives for future research.
Novel Nanocrystal Injection of Insoluble Drug Anlotinib and Its Antitumor Effects on Hepatocellular Carcinoma
Authors: Luo Mei , Sun Huiwei , Jiang Qiyu , Chai Yantao , Li Congshu , Yang Bin , Hong Zhixian
Published: December 2021

The molecularly targeted agent anlotinib offers a novel therapeutic strategy against advanced hepatocellular carcinoma (HCC). With this study, we aimed to solve the technical problem of anlotinib being insoluble in injectable solutions; we also aimed to assess the antitumor activity of anlotinib on hepatocellular carcinoma cells. We prepared an anlotinib nanocrystal injection by wet grinding, and we optimized the prescription process using a transmission electron microscope (TEM) and a laser particle size analyzer (LPSA). The release of anlotinib from the injected nanocrystals was evaluated using LC-MS/MS in vitro, and the drug’s anti-tumor effects were assessed in a nude mice tumor model. The anlotinib nanocrystals had a uniform particle size distribution (the average nanoparticle size was ~200 nm). The preparation of anlotinib into nanocrystals did not change the original crystal structure. The intravenous injection of anlotinib nanocrystals achieved anti-tumor activity at very low doses compared to those required for oral administration of an anlotinib suspension: anlotinib nanocrystals at a dose of 50 μg/kg inhibited the subcutaneous growth of the HCC cell line MHCC97-H; whereas the dose of anlotinib suspension required for an equivalent effect was 1 mg/kg. Therefore, our novel anlotinib nanocrystal injection preparation provides an option for achieving a safe and effective molecularly targeted therapy against advanced HCC.
Long Non-Coding RNA Neighbor of BRCA1 Gene 2: A Crucial Regulator in Cancer Biology
Authors: Wang Ting , Li Zhaosheng , Yan Liujia , Yan Feng , Shen Han , Tian Xinyu
Published: December 2021

Long non-coding RNAs (lncRNAs) are involved in fundamental biochemical and cellular processes. The neighbor of BRCA1 gene 2 (NBR2) is a long intergenic non-coding RNA (lincRNA) whose gene locus is adjacent to the tumor suppressor gene breast cancer susceptibility gene 1 (BRCA1). In human cancers, NBR2 expression is dysregulated and correlates with clinical outcomes. Moreover, NBR2 is crucial for glucose metabolism and affects the proliferation, survival, metastasis, and therapeutic resistance in different types of cancer. Here, we review the precise molecular mechanisms underlying NBR2-induced changes in cancer. In addition, the potential application of NBR2 in the diagnosis and treatment of cancer is also discussed, as well as the challenges of exploiting NBR2 for cancer intervention.
Selinexor Enhances NK Cell Activation Against Malignant B Cells via Downregulation of HLA-E
Authors: Fisher Jack G. , Walker Christopher J. , Doyle Amber DP. , Johnson Peter WM. , Forconi Francesco , Cragg Mark S. , Landesman Yosef , Khakoo Salim. I. , Blunt Matthew D.
Published: December 2021

Selinexor is an FDA approved selective inhibitor of the nuclear export protein exportin-1 (XPO1) and causes specific cancer cell death via nuclear accumulation of tumor suppressor proteins. Design of rational studies for the use of selinexor in combination with other therapeutic agents, such as immunotherapies, requires a fundamental understanding of the effects of selinexor on the immune system. One important emerging area of immunotherapy are natural killer (NK) cell based therapeutics. NK cell function is tightly regulated by a balance of signals derived from multiple activating and inhibitory receptors. Thus in cancer, up-regulation of stress ligands recognised by activating receptors or down-regulation of HLA class I recognised by inhibitory receptors can result in an anti-cancer NK cell response. Changes in XPO1 function therefore have the potential to affect NK cell function through shifting this balance. We therefore sought to investigate how selinexor may affect NK cell function. Selinexor pre-treatment of lymphoma cells significantly increased NK cell mediated cytotoxicity against SU-DHL-4, JeKo-1 and Ramos cells, concurrent with increased CD107a and IFNγ expression on NK cells. In addition, selinexor enhanced ADCC against lymphoma cells coated with the anti-CD20 antibodies rituximab and obinutuzumab. In probing the likely mechanism, we identified that XPO1 inhibition significantly reduced the surface expression of HLA-E on lymphoma cell lines and on primary chronic lymphocytic leukemia cells. HLA-E binds the inhibitory receptor NKG2A and in accordance with this, selinexor selectively increased activation of NKG2A+ NK cells. Our data reveals that selinexor, in addition to its direct cytotoxic activity, also activates an anti-cancer immune response via disruption of the inhibitory NKG2A:HLA-E axis.
Gastrin Vaccine Alone and in Combination With an Immune Checkpoint Antibody Inhibits Growth and Metastases of Gastric Cancer
Authors: Smith Jill P. , Cao Hong , Chen Wenqiang , Mahmood Kanwal , Phillips Teresa , Sutton Lynda , Cato Allen
Published: December 2021

Gastric cancer is a leading cause of cancer-related deaths worldwide. Recently, clinical studies have demonstrated that many of those with advanced gastric cancer are responsive to immune checkpoint antibody therapy, although the median survival even with these new agents is less than 12 months for advanced disease. The gastrointestinal peptide gastrin has been shown to stimulate growth of gastric cancer in a paracrine and autocrine fashion through the cholecystokinin-B receptor (CCK-BR), a receptor that is expressed in at least 56.6% of human gastric cancers. In the current investigation, we studied the role of the gastrin-CCK-BR pathway in vitro and in vivo as well as the expression of the CCK-BR in a human gastric cancer tissue array. CCK-BR and PD-L1 receptor expression and gastrin peptide was found in two murine gastric cancer cells (NCC-S1 and YTN-16) by qRT-PCR and immunocytochemistry. Treatment of NCC-S1 cells with gastrin resulted in increased growth. In vivo, the effects of a cancer vaccine that targets gastrin peptide (polyclonal antibody stimulator—PAS) alone or in combination with a Programed Death-1 antibody (PD-1 Ab) was evaluated in immune competent mice (N = 40) bearing YTN-16 gastric tumors. Mice were treated with PBS, PD-1 Ab (50 µg), PAS (250 µg), or the combination of PD-1 Ab with PAS. Tumor growth was significantly slower than controls in PAS-treated mice, and tumor growth was decreased even more in combination-treated mice. There were no metastases in any of the mice treated with PAS either alone or in combination with PD-1 Ab. Tumor proliferation by the Ki67 staining was significantly decreased in mice treated with PAS monotherapy or the combination therapy. PAS monotherapy or combined with PD-1 Ab increased tumor CD8+ T-lymphocytes and decreased the number of immunosuppressive M2-polarized tumor-associated macrophages. CCK-BR expression was identified in samples from a human tissue array by immunohistochemistry confirming the clinical relevance of this study. These results confirm the significance of the gastrin-CCK-BR signaling pathway in gastric cancer and suggest that the addition of a gastrin vaccine, PAS, to therapy with an immune checkpoint antibody may decrease growth and metastases of gastric cancer by altering the tumor microenvironment.
The Prognostic Value of NANO Scale Assessment in IDH-Wild-Type Glioblastoma Patients
Authors: Kasper Johannes , Wende Tim , Fehrenbach Michael Karl , Wilhelmy Florian , Jähne Katja , Frydrychowicz Clara , Prasse Gordian , Meixensberger Jürgen , Arlt Felix
Published: December 2021

Background

IDH-wild-type glioblastoma (GBM) is the most frequent brain-derived malignancy. Despite intense research efforts, it is still associated with a very poor prognosis. Several parameters were identified as prognostic, including general physical performance. In neuro-oncology (NO), special emphasis is put on focal deficits and cognitive (dys-)function. The Neurologic Assessment in Neuro-Oncology (NANO) scale was proposed in order to standardize the assessment of neurological performance in NO. This study evaluated whether NANO scale assessment provides prognostic information in a standardized collective of GBM patients.

Methods

The records of all GBM patients treated between 2014 and 2019 at our facility were retrospectively screened. Inclusion criteria were age over 18 years, at least 3 months postoperative follow-up, and preoperative and postoperative cranial magnetic resonance imaging. The NANO scale was assessed pre- and postoperatively as well as at 3 months follow-up. Univariate and multivariate survival analyses were carried to investigate the prognostic value.

Results

One hundred and thirty-one patients were included. In univariate analysis, poor postoperative neurological performance (HR 1.13, p = 0.004), poor neurological performance at 3 months postsurgery (HR 1.37, p < 0.001), and neurological deterioration during follow-up (HR 1.38, p < 0.001), all assessed via the NANO scale, were associated with shorter survival. In multivariate analysis including other prognostic factors such as the extent of resection, adjuvant treatment regimen, or age, NANO scale assessment at 3 months postoperative follow-up was independently associated with survival prediction (HR 1.36, p < 0.001). The optimal NANO scale cutoff for patient stratification was 3.5 points.

Conclusion

Neurological performance assessment employing the NANO scale might provide prognostic information in patients suffering from GBM.
Ferroptosis in Lung Cancer: From Molecular Mechanisms to Prognostic and Therapeutic Opportunities
Authors: Tabnak Peyman , HajiEsmailPoor Zanyar , Soraneh Soroush
Published: December 2021

Lung cancer is the second commonly diagnosed malignancy worldwide and has the highest mortality rate among all cancers. Tremendous efforts have been made to develop novel strategies against lung cancer; however, the overall survival of patients still is low. Uncovering underlying molecular mechanisms of this disease can open up new horizons for its treatment. Ferroptosis is a newly discovered type of programmed cell death that, in an iron-dependent manner, peroxidizes unsaturated phospholipids and results in the accumulation of radical oxygen species. Subsequent oxidative damage caused by ferroptosis contributes to cell death in tumor cells. Therefore, understanding its molecular mechanisms in lung cancer appears as a promising strategy to induce ferroptosis selectively. According to evidence published up to now, significant numbers of research have been done to identify ferroptosis regulators in lung cancer. Therefore, this review aims to provide a comprehensive standpoint of molecular mechanisms of ferroptosis in lung cancer and address these molecules’ prognostic and therapeutic values, hoping that the road for future studies in this field will be paved more efficiently.
Evaluating the Quality of Life of 231 Children With Primary Nephrotic Syndrome and Assessing Parental Awareness of the Disease
Authors: Li Na , Hao Jia , Fu Tong , Du Yue
Published: December 2021

Objective: This study aims to investigate the quality of life of children with primary nephrotic syndrome (PNS), assess their parents' disease awareness, and provide a basis for the comprehensive management of children with PNS.

Methods: A total of 231 children with PNS who were hospitalized in the Department of Pediatric Renal Rheumatology and Immunology in the ShengJing Hospital of the China Medical University from March 2019 to October 2020 were selected as the study subjects. The subjects and their parents were surveyed via a disease education and communication WeChat group and online questionnaire to investigate the children's quality of life, the needs of the parents, and their knowledge related to the disease.

Results: In 93.51% of cases, the child's quality of life was affected, with mild to moderate effects being the most frequent (90.47%). The lowest overall quality of life scores were recorded for children who had been diagnosed 1–3 year prior to inclusion in the study, and the scores plateaued thereafter. On the physical functioning scale, the longer the illness, the greater the physical impact, with children typically experiencing pain and fatigue. The children generally scored low on the emotional functioning scale, exhibiting sleep disturbances for up to 5 years and worrying about accidents. The children's average score on the social functioning scale was high, with males achieving significantly higher scores (69.61 ± 25.42) than females (62.30 ± 27.51), and more than one-third of the children experiencing problems getting along with other teenagers and making friends. The primary problems expressed by parents were anxiety (59%), sadness (44%), fear (43%), and depression (40%), and several parents indicated that they struggled with issues of self-blame.

Conclusion: PNS impacts the physical and psychological wellbeing of children suffering from the condition, significantly reduces their quality of life, and negatively impacts the psychological wellbeing of their parents. Therefore, children with PNS and their families need integrated management by doctors, nurses, dieticians, psychotherapists, educational institutions, and social stakeholders to improve their quality of life.
Case Report: Clinical Features of Congenital Portosystemic Shunts in the Neonatal Period
Authors: Xu Suhua , Zhang Peng , Hu Liyuan , Zhou Wenhao , Cheng Guoqiang
Published: December 2021

Objective: The aim of this single-center retrospective study was to analyze the clinical characteristics, treatment options, and course of neonatal-onset congenital portosystemic shunts (CPSS).

Methods: We included all patients with CPSS who presented with clinical symptoms within the neonatal period in our institution between 2015 and 2020.

Results: Sixteen patients were identified, including 13 patients with intrahepatic portosystemic shunts (IPSS) and three patients with extrahepatic portosystemic shunts (EPSS). The median age of diagnosis was 16 days (range prenatal 24 weeks−12 months). Hyperammonemia (60%), neonatal cholestasis (44%), elevated liver enzyme (40%), hypoglycemia (40%), thrombocytopenia (38%), and coagulation abnormalities (23%) appeared in neonatal CPSS. Twelve patients (75%) presented with congenital anomalies, of which congenital heart disease (CHD) (44%) was the most common. Thirteen patients with IPSS initially underwent conservative treatment, but two of them were recommended for the catheter interventional therapy and liver transplantation, respectively, due to progressive deterioration of liver function. Spontaneous closure occurred in nine patients with IPSS. The shunt was closed using transcatheter embolization in one patient with EPSS type II. Another patient with EPSS type II underwent surgical treatment of CHD firstly. The remaining patient with EPSS type Ib received medical therapy and refused liver transplantation.

Conclusion: Hyperammonemia, neonatal cholestasis, elevated liver enzyme, hypoglycemia, and thrombocytopenia are the main complications of neonatal CPSS. Moreover, CPSS is associated with multiple congenital abnormalities, especially CHD. Intrahepatic portosystemic shunts may close spontaneously, and conservative treatment can be taken first. Extrahepatic portosystemic shunts should be closed to prevent complications.