bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Spawning- and Natal-Site Fidelity of Larimichthys polyactis in the Southern Yellow Sea Using Otolith Microchemistry
Authors: Song Dade , Xiong Ying , Jiang Tao , Yang Jian , Zhong Xiaming , Tang Jianhua , Kang Zhongjie
Published: February 2022

Small yellow croaker Larimichthys polyactis is an important commercial fish species; however, industrial-scale fishing has largely contributed to the changes in its biological characteristics, such as individual miniaturization, faster growth, and younger average age. Robust understanding of the pivotal life history of L. polyactis, a typical oceanodromous species, is needed for its conservation and restoration. However, L. polyactis fidelity to natal or spawning sites is not well understood and, at present, there is no effective management strategy to guarantee the sustainable exploitation of L. polyactis. This study used laser ablation inductively coupled plasma-mass spectrometry to analyse the elemental composition of otoliths from 60 adult yellow croakers caught in the southern Yellow Sea, including two spawning groups with 1- and 2-year-old fish (S1 and S2, respectively) sampled close to China and one overwintering group including two-year-old fish (O2) sampled close to South Korea. The ratios of elements (Li, Na, Sr, and Ba) to Ca in the otolith core zones were significantly higher (P < 0.05) than in those of the year one (Y1) and year two (Y2) annual rings, but there were no significant differences in the elemental ratios between the Y1 and Y2 zones. Principal component analysis (PCA) of the elemental otolith signatures of the core, Y1, and Y2 zones in the three groups revealed two distinct clusters (cluster 1: S1-core, S2-core, and O2-core zones; cluster 2: S2–Y1, O2–Y1, S2–Y2, and O2–Y2 zones) and one zone (S1–Y1), suggesting spawning-site fidelity and natal-site fidelity uncertainty, especially considering the dispersal by current in prolonged period (50 h) from fertilized eggs to hatching and internal effect, such as yolk sac and maternal effect. Furthermore, these results indicated that the S2 and O2 groups could represent the same population, suggesting a stable migratory route for L. polyactis in Chinese and South Korean waters, whereas the S1 group could represent another population. This suggests the possibility a mixed L. polyactis population in the southern Yellow Sea. Characterization L. polyactis spawning-site fidelity is a crucial step toward linking spawning-site fidelity of this overexploited species with thorough conservation and management strategies.
Seasonal Variation of Food Web Structure and Stability of a Typical Artificial Reef Ecosystem in Bohai Sea, China
Authors: Li Shengpeng , Wang Ruyue , Jiang Yueming , Li Yanyu , Zhu Lin , Feng Jianfeng
Published: February 2022

The last 30 years have witnessed the degradation and loss of function in the ecosystem of the Bohai Sea, China. Great efforts, such as artificial reefs, have been used to restore the ecosystem of the Bohai Sea in recent years. In this study, we examined the seasonal variation of food webs in artificial reefs of Juehua Island by the Ecopath model. Results showed that the number of species, range of trophic level, energy cycle proportion, energy complexity, nutrition transfer efficiency, and ecosystem maturity have increased from summer to autumn. However, the food web stability of artificial reefs has no obvious change from summer to autumn. Loop analysis revealed that the heaviest feedback loops are the interactions among benthos, zooplankton, and phytoplankton, and the predator-prey negative interaction strength between zooplankton and phytoplankton dominated the stability of the artificial reef, whether in summer or autumn. This study suggests that stability is a more robust indicator for ecosystem assessment and could provide useful information in future restoration plans of the marine ecosystem.
The Clustered Regularly Interspaced Short Palindromic Repeats-Associated System and Its Relationship With Mobile Genetic Elements in Klebsiella
Authors: Zhou Yuqiao , Zhou Wei , Zhou Jinzhi , Yan Jinchang , Xu Dingting , Zheng Xiner , Zong Shuaizhou , Jiang Ping , Tian Shiyi , Han Jianzhong , Qu Daofeng
Published: February 2022

Microorganisms have developed many strategies in the process of long-term defense against external attacks, one of which is the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) bacterial immunological system. In this study, the whole genome of 300 strains of Klebsiella was collected, the CRISPR-Cas system in the strains was statistically analyzed, and the types and structures of CRISPR system in Klebsiella were explored, as well as the correlation between CRISPR and mobile genetic elements (MGEs). Through principal component analysis (PCA), we found that Cas gene, plasmids, integron, IS1, IS609, and enzymes of DNA metabolism were closely related to CRISPR-Cas. Compared the structural characteristics of plasmids, the DinG family helicases, Cas6, Csf2, and IS5 were observed near the CRISPR loci in plasmid, which is also confirmed by the results of PCA that they may be important factors affecting the plasmid with CRISPR.
Evaluation of LipL32 and LigA/LigB Knockdown Mutants in Leptospira interrogans Serovar Copenhageni: Impacts to Proteome and Virulence
Authors: Fernandes Luis G. V. , Putz Ellie J. , Stasko Judith , Lippolis John D. , Nascimento Ana L. T. O. , Nally Jarlath E.
Published: February 2022

Leptospirosis is a worldwide zoonosis caused by pathogenic species of the genus Leptospira. The recent application of CRISPR interference (CRISPRi) to Leptospira facilitates targeted gene silencing and provides a new tool to investigate pathogenic mechanisms of leptospirosis. CRISPRi relies on the expression of a catalytically “dead” Cas9 (dCas9) and a single-guide RNA (sgRNA). Previously, our group generated a LipL32 and a double LigA/LigB (LigAB) mutant, which, in the current study, are characterized by whole-cell proteomics in comparison with control leptospires harboring plasmid expressing dCas9 alone. Comparison of control and LigAB mutant leptospires identified 46 significantly differentially expressed (DE) proteins, including 27 proteins that were less abundant and 19 proteins that were more abundant in the LigAB mutant compared with the control. Comparison of the control and LipL32 mutant leptospires identified 243 DE proteins, of which 84 proteins were more abundant and 159 were less abundant in the LipL32 mutant strain. Significantly increased amounts of known virulence impactors and surface membrane receptors, including LipL45, LipL31, LigB, and LipL41, were identified. The virulence of LipL32 and LigAB mutants were evaluated in the hamster model of leptospirosis; the LigAB mutant was unable to cause acute disease although mutant leptospires could still be recovered from target organs, albeit at a significantly lower bacterial burden (<850 and <16-fold in liver and kidney, respectively, in comparison with control), indicating attenuation of virulence and a shift to chronic bacterial persistence. Notably, the LipL32 mutant displayed augmented virulence as evidenced by early onset of clinical symptoms and increased numbers of circulating foamy macrophages. Validation of LipL32 and LigAB mutants recovered from liver and kidney in the presence or absence of antibiotic selection revealed high plasmid stability and, by extension, gene silencing in vivo. Collectively, this work emphasizes the advantages and feasibility of using CRISPRi technology to evaluate and characterize virulence factors of leptospires and their respective host–pathogen interactions in animal models of leptospirosis. Importantly, it also provides insight into the requirements of LigA and LigB for acute disease and explores the impact of silencing expression of lipL32, which resulted in substantial changes in amounts of outer membrane proteins.
Enterovirus 71 Antagonizes Antiviral Effects of Type III Interferon and Evades the Clearance of Intestinal Intraepithelial Lymphocytes
Authors: Dong Yuanmin , Liu Jing , Lu Nan , Zhang Cai
Published: February 2022

Enterovirus 71 (EV71) is the major pathogen causing severe neurological complications and hand, foot, and mouth disease. The intestinal mucosal immune system has a complete immune response and immune regulation mechanism, consisting of densely arranged monolayer intestinal epithelial cells (IECs) and intestinal intraepithelial lymphocytes (iIELs) distributed among the IECs, which constitute the first line of intestinal mucosa against infection of foreign pathogens. As an enterovirus, EV71 is transmitted by the intestinal tract; however, the mechanisms it uses to evade the immunosurveillance of the intestinal mucosal immune system are still incompletely clarified. The present study investigated how EV71 evades from recognizing and eliminating IECs, iIELs, and iNK cells. We found that EV71 infection induced a higher level of type III interferons (IFN-λ) than type I interferons (IFN-β) in IECs, and the addition of IFN-λ markedly restricted EV71 replication in IECs. These results indicate that IFN-λ plays a more important role in anti-EV71 intestinal infection. However, EV71 infection could markedly attenuate the antiviral responses of IFN-λ. Mechanistically, 2A protease (2Apro) and 3C protease (3Cpro) of EV71 inhibited the IFN-λ production and IFN-λ receptor expression and further decreased the response of IECs to IFN-λ. In addition, we found that EV71-infected IECs were less susceptible to the lysis of intestinal NK (iNK) cells and CD3+iIELs. We revealed that the viral 2Apro and 3Cpro could significantly reduce the expression of the ligands of natural killer group 2D (NKG2D) and promote the expression of PD-L1 on IECs, rendering them to evade the recognition and killing of iNK and CD3+iIELs. These results provide novel evasion mechanisms of EV71 from intestinal mucosal innate immunity and may give new insights into antiviral therapy.
The Evolution of Ecological Diversity in Acidobacteria
Authors: Sikorski Johannes , Baumgartner Vanessa , Birkhofer Klaus , Boeddinghaus Runa S. , Bunk Boyke , Fischer Markus , Fösel Bärbel U. , Friedrich Michael W. , Göker Markus , Hölzel Norbert , Huang Sixing , Huber Katharina J. , Kandeler Ellen , Klaus Valentin H. , Kleinebecker Till , Marhan Sven , von Mering Christian , Oelmann Yvonne , Prati Daniel , Regan Kathleen M. , Richter-Heitmann Tim , Rodrigues João F. Matias , Schmitt Barbara , Schöning Ingo , Schrumpf Marion , Schurig Elisabeth , Solly Emily F. , Wolters Volkmar , Overmann Jörg
Published: February 2022

Acidobacteria occur in a large variety of ecosystems worldwide and are particularly abundant and highly diverse in soils. In spite of their diversity, only few species have been characterized to date which makes Acidobacteria one of the most poorly understood phyla among the domain Bacteria. We used a culture-independent niche modeling approach to elucidate ecological adaptations and their evolution for 4,154 operational taxonomic units (OTUs) of Acidobacteria across 150 different, comprehensively characterized grassland soils in Germany. Using the relative abundances of their 16S rRNA gene transcripts, the responses of active OTUs along gradients of 41 environmental variables were modeled using hierarchical logistic regression (HOF), which allowed to determine values for optimum activity for each variable (niche optima). By linking 16S rRNA transcripts to the phylogeny of full 16S rRNA gene sequences, we could trace the evolution of the different ecological adaptations during the diversification of Acidobacteria. This approach revealed a pronounced ecological diversification even among acidobacterial sister clades. Although the evolution of habitat adaptation was mainly cladogenic, it was disrupted by recurrent events of convergent evolution that resulted in frequent habitat switching within individual clades. Our findings indicate that the high diversity of soil acidobacterial communities is largely sustained by differential habitat adaptation even at the level of closely related species. A comparison of niche optima of individual OTUs with the phenotypic properties of their cultivated representatives showed that our niche modeling approach (1) correctly predicts those physiological properties that have been determined for cultivated species of Acidobacteria but (2) also provides ample information on ecological adaptations that cannot be inferred from standard taxonomic descriptions of bacterial isolates. These novel information on specific adaptations of not-yet-cultivated Acidobacteria can therefore guide future cultivation trials and likely will increase their cultivation success.
Metagenomic Next-Generation Sequencing for the Microbiological Diagnosis of Abdominal Sepsis Patients
Authors: Li Dongkai , Gai Wei , Zhang Jiahui , Cheng Wei , Cui Na , Wang Hao
Published: February 2022

Objectives

For patients with intra-abdominal infection (IAI), the rapid and accurate identification of pathogens remains a challenge. Metagenomic next-generation sequencing (mNGS) is a novel technique for infectious diseases, but its application in IAI is limited. In this study, we compared the microbiological diagnostic ability of plasma mNGS with that of conventional peritoneal drainage (PD) culture in critical care settings.

Methods

From January 2018 to December 2020, a prospective observational study was performed at a tertiary teaching hospital in China and data on 109 abdominal sepsis patients were collected. The pathogen detection performance of plasma mNGS and PD culture method were compared.

Measurements and Results

Ninety-two positive cases detected on PD culture, while plasma mNGS detected 61 positive cases. Forty-five patients (44.0%) had at least one matched pair of plasma mNGS and PD culture results. Compared with PD culture, the plasma mNGS was more rapid (27.1 ± 4.0 vs. 68.9 ± 22.3 h, p < 0.05). The patients received initial antibiotic treatment matched with mNGS detection showed better clinical outcomes.

Conclusion

For abdominal sepsis patients, plasma mNGS can provide early, noninvasive, and rapid microbiological diagnosis. Compared with conventional PD smear, culture, and blood culture methods, plasma mNGS promote the rapid detection of pathogenic bacteria.
Cell-Free Expression to Probe Co-Translational Insertion of an Alpha Helical Membrane Protein
Authors: Blackholly Laura R. , Harris Nicola J. , Findlay Heather E. , Booth Paula J.
Published: February 2022

The majority of alpha helical membrane proteins fold co-translationally during their synthesis on the ribosome. In contrast, most mechanistic folding studies address refolding of full-length proteins from artificially induced denatured states that are far removed from the natural co-translational process. Cell-free translation of membrane proteins is emerging as a useful tool to address folding during translation by a ribosome. We summarise the benefits of this approach and show how it can be successfully extended to a membrane protein with a complex topology. The bacterial leucine transporter, LeuT can be synthesised and inserted into lipid membranes using a variety of in vitro transcription translation systems. Unlike major facilitator superfamily transporters, where changes in lipids can optimise the amount of correctly inserted protein, LeuT insertion yields are much less dependent on the lipid composition. The presence of a bacterial translocon either in native membrane extracts or in reconstituted membranes also has little influence on the yield of LeuT incorporated into the lipid membrane, except at high reconstitution concentrations. LeuT is considered a paradigm for neurotransmitter transporters and possesses a knotted structure that is characteristic of this transporter family. This work provides a method in which to probe the formation of a protein as the polypeptide chain is being synthesised on a ribosome and inserting into lipids. We show that in comparison with the simpler major facilitator transporter structures, LeuT inserts less efficiently into membranes when synthesised cell-free, suggesting that more of the protein aggregates, likely as a result of the challenging formation of the knotted topology in the membrane.
Tract Specific White Matter Lesion Load Affects White Matter Microstructure and Their Relationships With Functional Connectivity and Cognitive Decline
Authors: Kim Tae , Aizenstein Howard J. , Snitz Beth E. , Cheng Yu , Chang Yue-Fang , Roush Rebecca E. , Huppert Theodore J. , Cohen Annie , Doman Jack , Becker James T.
Published: February 2022

White matter hyperintensities (WMHs) are associated with cognitive decline. Assessing the effect of WMH on WM microstructural changes and its relationships with structural and functional connectivity to multiple cognitive domains are helpful to better understand the pathophysiological processes of cognitive impairment. 65 participants (49 normal and 16 MCI subjects, age: 67.4 ± 8.3 years, 44 females) were studied at 3T. The WMHs and fifty fiber tracts were automatically segmented from the T1/T2-weighted images and diffusion-weighted images, respectively. Tract-profiles of WMH were compared with those of apparent fiber density (AFD). The relationship between AFD and tract connectivity (TC) was assessed. Functional connectivity (FC) between tract ends obtained from resting-state functional MRI was examined in relation to TC. Tract-specific relationships of WMH, TC and FC with a multi-domain neuropsychological test battery and Montreal Cognitive Assessment (MoCA) were also separately assessed by lasso linear regression. Indirect pathways of TC and FC between WMH and multiple cognitive measures were tested using the mediation analysis. Higher WMH loads in WM tracts were locally matched with the reduced AFD, which was related to decrease in TC. However, no direct relationship was found between TC and FC. Tract-specific changes on WMH, TC and FC for each cognitive performance may explain that macro- and microstructural and functional changes are associated differently with each cognitive domain in a fiber specific manner. In these identified tracts, the differences between normal and MCI for WMH and TC were increased, and the relationships of WMH, TC and FC with cognitive outcomes were more significant, compared to the results from all tracts. Indirect pathways of two-step (TC-FC) between WMH and all cognitive domains were significant (p < 0.0083 with Bonferroni correction), while the separated indirect pathways through TC and through FC were different depending on cognitive domain. Deterioration in specific cognitive domains may be affected by alterations in a set of different tracts that are differently associated with macrostructural, microstructural, and function changes. Thus, assessments of WMH and its associated changes on specific tracts help for better understanding of the interrelationships of multiple changes in cognitive impairment.
Safety and Feasibility of Tele-Supervised Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder
Authors: Cappon Davide , den Boer Tim , Jordan Caleb , Yu Wanting , Lo Alexander , LaGanke Nicole , Biagi Maria Chiara , Skorupinski Pawel , Ruffini Giulio , Morales Oscar , Metzger Eran , Manor Bradley , Pascual-Leone Alvaro
Published: February 2022

Major depressive disorder (MDD) is a worldwide cause of disability in older age, especially during the covid pandemic. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has shown encouraging efficacy for treatment of depression. Here, we investigate the feasibility of an innovative protocol where tDCS is administered within the homes of older adults with MDD (patient participants) with the help of a study companion (i.e. caregiver). We further analyze the feasibility of a remotely-hosted training program that provides the knowledge and skills to administer tDCS at home, without requiring them to visit the lab. We also employed a newly developed multi-channel tDCS system with real-time monitoring designed to guarantee the safety and efficacy of home-based tDCS. Patient participants underwent a total of 37 home-based tDCS sessions distributed over 12 weeks. The protocol consisted of three phases each lasting four weeks: an acute phase, containing 28 home-based tDCS sessions, a taper phase containing nine home-based tDCS sessions, and a follow up phase, with no stimulation sessions. We found that the home-based, remotely-supervised, study companion administered, multi-channel tDCS protocol for older adults with MDD was feasible and safe. Further, the study introduces a novel training program for remote instruction of study companions in the administration of tDCS. Future research is required to determine the translatability of these findings to a larger sample.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04799405?term=NCT04799405&draw=2&rank=1, identifier NCT04799405.
Case Series: Acute Hemorrhagic Encephalomyelitis After SARS-CoV-2 Vaccination
Authors: Ancau Mihai , Liesche-Starnecker Friederike , Niederschweiberer Johanna , Krieg Sandro M. , Zimmer Claus , Lingg Charlotte , Kumpfmüller Daniela , Ikenberg Benno , Ploner Markus , Hemmer Bernhard , Wunderlich Silke , Mühlau Mark , Knier Benjamin
Published: February 2022

We present three cases fulfilling diagnostic criteria of hemorrhagic variants of acute disseminated encephalomyelitis (acute hemorrhagic encephalomyelitis, AHEM) occurring within 9 days after the first shot of ChAdOx1 nCoV-19. AHEM was diagnosed using magnetic resonance imaging, cerebrospinal fluid analysis and brain biopsy in one case. The close temporal association with the vaccination, the immune-related nature of the disease as well as the lack of other canonical precipitating factors suggested that AHEM was a vaccine-related adverse effect. We believe that AHEM might reflect a novel COVID-19 vaccine-related adverse event for which physicians should be vigilant and sensitized.
Alterations of Regional Homogeneity in Crohn's Disease With Psychological Disorders: A Resting-State fMRI Study
Authors: Huang Mengting , Li Xin , Fan Wenliang , Li Jing , Zhu Liangru , Lei Ping , Wu Linxia , Sun Qing , Zou Yan , Han Ping
Published: February 2022

Abnormal psychological processing in the central nervous system has been found in Crohn's disease (CD) patients. Resting-state functional magnetic resonance images of 57 inactive and 58 active CD patients, and 92 healthy controls (HC) were obtained. The psychological assessment used a psychological questionnaire that was collected within 1 week before functional MRI examination. We investigated the neural basis of CD patients and the correlation among regional homogeneity (ReHo), clinical features and psychological assessment scores. We found that more severe psychological assessment disorder scores were observed in the active CD group than in the inactive CD group and HC group (P<0.001). Compared with HC, the active CD patients exhibited higher ReHo values in the frontal superior medial, frontal middle and lower values in the postcentral, supplementary motor area, and temporal middle. Meanwhile, inactive CD patients exhibited higher ReHo values in the frontal middle and lower ReHo values in the precentral, postcentral and putamen (all voxel P< 0.001, cluster P<0.01, corrected). The values of the frontal superior medial, postcentral and supplementary motor area were correlation with psychological assessment scores (r = 0.38, −0.41, −0.32, P = 0.001, 0.014, 0.003), and the clinical features of simple endoscopic score for Crohn's disease and erythrocyte sedimentation rate were negatively correlated with psychological assessment scores in active CD patients (r = −0.35, −0.34, P = 0.06, 0.08). These results provide evidence for abnormal resting-state brain activity in CD and suggest that the psychological of CD may play a critical role in brain function.
T2/FLAIR Abnormity Could be the Sign of Glioblastoma Dissemination
Authors: Li Mingxiao , Huang Wei , Chen Hongyan , Jiang Haihui , Yang Chuanwei , Shen Shaoping , Cui Yong , Dong Gehong , Ren Xiaohui , Lin Song
Published: February 2022

Purpose

Newly emerged or constantly enlarged contrast-enhancing (CE) lesions were the necessary signs for the diagnosis of glioblastoma (GBM) progression. This study aimed to investigate whether the T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) abnormal transformation could predict and assess progression for GBMs, especially for tumor dissemination.

Methods

A consecutive cohort of 246 GBM patients with regular follow-up and sufficient radiological data was included in this study. The series of T2/FLAIR and T1CE images were retrospectively reviewed. The patients were separated into T2/FLAIR and T1CE discordant and accordant subgroups based on the initial progression images.

Results

A total of 170 qualified patients were finally analyzed. The incidence of discordant T2/FLAIR and T1CE images was 25.9% (44/170). The median time-span of T2/FLAIR indicated tumor progression was 119.5 days (ranging from 57 days-unreached) prior to T1CE. Nearly half of patients (20/44, 45.5%) in the discordant subgroup suffered from tumor dissemination, substantially higher than accordant patients (23/126, 20.6%, p < 0.001). The median time to progression (TTP), post-progression survival (PPS), and overall survival (OS) were not statistically different (all p > 0.05) between discordant and accordant patients.

Conclusions

T2/FLAIR abnormity could be the sign of GBM progression, especially for newly emerged lesions disseminating from the primary cavity. Physicians should cast more attention on the dynamic change of T2/FLAIR images, which might be of great significance for progression assessment and subsequent clinical decision-making.
A Prognostic Model for Acute Myeloid Leukemia Based on IL-2/STAT5 Pathway-Related Genes
Authors: Tang Yigang , Xiao Shujun , Wang Zhengyuan , Liang Ying , Xing Yangfei , Wu Jiale , Lu Min
Published: February 2022

Accurate prognostic stratification of patients can provide guidance for personalized therapy. Many prognostic models for acute myeloid leukemia (AML) have been reported, but most have considerable inaccuracies due to contained variables with insufficient capacity of predicting survival and lack of adequate verification. Here, 235 genes strongly related to survival in AML were systematically identified through univariate Cox regression analysis of eight independent AML datasets. Pathway enrichment analysis of these 235 genes revealed that the IL-2/STAT5 signaling pathway was the most highly enriched. Through Cox proportional-hazards regression model and stepwise algorithm, we constructed a six-gene STAT5-associated signature based on the most robustly survival-related genes related to the IL-2/STAT5 signaling pathway. Good prognostic performance was observed in the training cohort (GSE37642-GPL96), and the signature was validated in seven other validation cohorts. As an independent prognostic factor, the STAT5-associated signature was positively correlated with patient age and ELN2017 risk levels. An integrated score based on these three prognostic factors had higher prognostic accuracy than the ELN2017 risk category. Characterization of immune cell infiltration indicated that impaired B-cell adaptive immunity, immunosuppressive effects, serious infection, and weakened anti-inflammatory function tended to accompany high-risk patients. Analysis of in-house clinical samples revealed that the STAT5-assocaited signature risk scores of AML patients were significantly higher than those of healthy people. Five chemotherapeutic drugs that were effective in these high-risk patients were screened in silico. Among the five drugs, MS.275, a known HDAC inhibitor, selectively suppressed the proliferation of cancer cells with high STAT5 phosphorylation levels in vitro. Taken together, the data indicate that the STAT5-associated signature is a reliable prognostic model that can be used to optimize prognostic stratification and guide personalized AML treatments.
Masseter Muscle Metastasis of Renal Cell Carcinoma: A Case Report and Literature Review
Authors: Qin Fei , Zhang Xiaofei , Zhang Jie , Liu Shuaihong , Wang Zijie , Xie Fei , Zhang Mingxin , Zhang Tianwei , Wang Shuangyi , Jiao Wei
Published: February 2022

Background

Patients with renal cell carcinoma are often troubled by metastases, but masseter muscle metastases are particularly rare.

Case Presentation

We reported a 76-year-old male who did not show any recurrence and metastasis after the nephrectomy until 5 years later. The metastatic mass was found with the protrusion of masseter muscle area. Computed tomography and ultrasonography indicated a hypervascular mass, and pathology confirmed the masseter muscle metastasis of renal cell carcinoma. Complete metastasectomy was performed with the preserval of facial function and appearance. No local recurrence or distant metastasis was found in follow-up.

Conclusion

Our report indicates masseter muscle can be a metastatic site of renal cell carcinoma, regardless of its rarity. Long-term comprehensive surveillance is needed for patients with renal cell carcinoma. Muscle metastases can disguise as benign mass, while multiple imaging and pathology are important in identifying their sources. If possible, complete metastasectomy with function retention is recommended for masseter muscle metastases.
Immune Infiltration Associated MAN2B1 Is a Novel Prognostic Biomarker for Glioma
Authors: Lin Xuelei , Liu Hongwei , Zhao Hongyu , Xia Shunjin , Li Yueshuo , Wang Chaoqian , Huang Qi , Wanggou Siyi , Li Xuejun
Published: February 2022

Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. Alteration in MAN2B1 has been proved to be accountable for several diseases. However, the relationship between MAN2B1 and glioma malignancy remains unclear. In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. We found that MAN2B1 was elevated in glioma and was correlated with malignant clinical and molecular features. Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. Moreover, MAN2B1 expression was strongly correlated with M2 macrophages and weakly correlated with M1 macrophages. Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration.
Bispecific Antibodies and Other Non-CAR Targeted Therapies and HSCT: Decreased Toxicity for Better Transplant Outcome in Paediatric ALL?
Authors: Kállay Krisztián Miklós , Algeri Mattia , Buechner Jochen , Krauss Aviva C.
Published: February 2022

This review will address the place of innovative, non-chemotherapy, non-CAR-T targeted therapies in the treatment of Acute Lymphoblastic Leukaemia (ALL), focusing on their use in the hematopoietic stem cell transplant (HSCT) context. The focus will be on the agent with the most experience to date, namely the bispecific T-cell engater (BiTE) blinatumomab, but references to antibody-drug conjugates (ADCs) such as inotuzumab ozogamicin and monoclonal antibodies such as daratumamab will be made as well. Specific issues to be addressed include: (1) The use of these agents to reduce measurable residual disease (MRD) prior to HSCT and their potential for improved transplant outcomes due to reduced toxicity compared to traditional chemotherapy salvage, as well as potentially increased toxicity with HSCT with particular agents; (2) the appropriate sequencing of innovative therapies, i.e., when to use BiTEs or antibodies versus CARs pre- and/or post-HSCT; this will include also the potential for impact on response of one group of agents on response to the other; (3) the role of these agents particularly in the post-HSCT relapse setting, or as maintenance to prevent relapse in this setting; (4) special populations in which these agents may substitute for traditional chemotherapy during induction or consolidation in patients with predisposing factors for toxicity with traditional therapy (e.g., Trisomy 21, infants), or those who develop infectious complications precluding delivery of full standard-of-care (SOC) chemotherapy during induction/consolidation (e.g., fungal infections); (5) the evidence we have to date regarding the potential for substitution of blinatumomab for some of the standard chemotherapy agents used pre-HSCT in patients without the above risk factors for toxicity, but with high risk disease going into transplant, in an attempt to decrease current rates of transplant-related mortality as well as morbidity; (6) the unique toxicity profile of these agents and concerns regarding particular side effects in the HSCT context. The manuscript will include both the data we have to date regarding the above issues, ongoing studies that are trying to explore them, and suggestions for future studies to further refine our knowledge base.
A Model Perspective Explanation of the Long-Term Sustainability of a Fully Human BCMA-Targeting CAR (CT103A) T-Cell Immunotherapy
Authors: Mu Wei , Long Xiaolu , Cai Haodong , Chen Caixia , Hu Guang , Lou Yaoyao , Xing Shugang , Wang Di , Wang Jue , Xiao Min , Wang Kun , Sun Zhongyi , Li Chunrui , Zhou Jianfeng , Chen Liting
Published: February 2022

Different from canonical drugs, CAR T-cells are “living drugs”, which derived from patient’s own blood. Studies of the pharmacokinetics of CAR T-cells could improve our understanding of their efficacy, safety, optimal dosage, and other characterizes. We previously reported a phase I study of a novel fully human BCMA-targeting CAR (CT103A) in 18 patients with relapsed/refractory multiple myeloma. CT103A exhibited extraordinary persistence with low anti-drug antibody positivity. To figure out the pharmacokinetic characterizes and investigate the potential reason of CT103A’s long-term persistence, we established a population pharmacokinetic (PopPK) model of CT103A based on 18 patients cohort by applying nonlinear mixed-effects modeling and analyzed the CAR T-cell clonal evolution. The results suggested that extramedullary spreading was found to impair Cmax and was therefore added as a covariate to the modified model. The model revealed tocilizumab and corticosteroids showed no impact on the CT103A expansion rate. No dominant clone existed in patients with persistently high peripheral CT103A by CAR integration sites analysis. Finally, patients with lower contraction rate constants and higher Cmax as well as memory CT103A fraction could achieve better clinical responses. Taken together, this study developed a PopPK model of a fully human anti-BCMA CAR T-cell therapy, and summarized its model characteristics. We suggested that the long-term persistence of CT103A was attributed to the memory CAR T-cell fraction but not the clonal evolution. This study will improve people’s understanding of pharmacokinetics and PopPK of CAR T-cell immunotherapy.
Early Abnormal Placentation and Evidence of Vascular Endothelial Growth Factor System Dysregulation at the Feto-Maternal Interface After Periconceptional Alcohol Consumption
Authors: Gualdoni Gisela Soledad , Jacobo Patricia Verónica , Barril Camila , Ventureira Martín Ricardo , Cebral Elisa
Published: February 2022

Adequate placentation, placental tissue remodeling and vascularization is essential for the success of gestation and optimal fetal growth. Recently, it was suggested that abnormal placenta induced by maternal alcohol consumption may participate in fetal growth restriction and relevant clinical manifestations of the Fetal Alcohol Spectrum Disorders (FASD). Particularly, periconceptional alcohol consumption up to early gestation can alter placentation and angiogenesis that persists in pregnancy beyond the exposure period. Experimental evidence suggests that abnormal placenta following maternal alcohol intake is associated with insufficient vascularization and defective trophoblast development, growth and function in early gestation. Accumulated data indicate that impaired vascular endothelial growth factor (VEGF) system, including their downstream effectors, the nitric oxide (NO) and metalloproteinases (MMPs), is a pivotal spatio-temporal altered mechanism underlying the early placental vascular alterations induced by maternal alcohol consumption. In this review we propose that the periconceptional alcohol intake up to early organogenesis (first trimester) alters the VEGF-NO-MMPs system in trophoblastic-decidual tissues, generating imbalances in the trophoblastic proliferation/apoptosis, insufficient trophoblastic development, differentiation and migration, deficient labyrinthine vascularization, and uncompleted remodelation and transformation of decidual spiral arterioles. Consequently, abnormal placenta with insufficiency blood perfusion, vasoconstriction and reduced labyrinthine blood exchange can be generated. Herein, we review emerging knowledge of abnormal placenta linked to pregnancy complications and FASD produced by gestational alcohol ingestion and provide evidence of the early abnormal placental angiogenesis-vascularization and growth associated to decidual-trophoblastic dysregulation of VEGF system after periconceptional alcohol consumption up to mid-gestation, in a mouse model.
Hyperspectral Imaging With Machine Learning to Differentiate Cultivars, Growth Stages, Flowers, and Leaves of Industrial Hemp (Cannabis sativa L.)
Authors: Lu Yuzhen , Young Sierra , Linder Eric , Whipker Brian , Suchoff David
Published: February 2022

As an emerging cash crop, industrial hemp (Cannabis sativa L.) grown for cannabidiol (CBD) has spurred a surge of interest in the United States. Cultivar selection and harvest timing are important to produce CBD hemp profitably and avoid economic loss resulting from the tetrahydrocannabinol (THC) concentration in the crop exceeding regulatory limits. Hence there is a need for differentiating CBD hemp cultivars and growth stages to aid in cultivar and genotype selection and optimization of harvest timing. Current methods that rely on visual assessment of plant phenotypes and chemical procedures are limited because of its subjective and destructive nature. In this study, hyperspectral imaging was proposed as a novel, objective, and non-destructive method for differentiating hemp cultivars, growth stages as well as plant organs (leaves and flowers). Five cultivars of CBD hemp were grown greenhouse conditions and leaves and flowers were sampled at five growth stages 2–10 weeks in 2-week intervals after flower initiation and scanned by a benchtop hyperspectral imaging system in the spectral range of 400–1000 nm. The acquired images were subjected to image processing procedures to extract the spectra of hemp samples. The spectral profiles and scatter plots of principal component analysis of the spectral data revealed a certain degree of separation between hemp cultivars, growth stages, and plant organs. Machine learning based on regularized linear discriminant analysis achieved the accuracy of up to 99.6% in differentiating the five hemp cultivars. Plant organ and growth stage need to be factored into model development for hemp cultivar classification. The classification models achieved 100% accuracy in differentiating the five growth stages and two plant organs. This study demonstrates the effectiveness of hyperspectral imaging for differentiating cultivars, growth stages and plant organs of CBD hemp, which is a potentially useful tool for growers and breeders of CBD hemp.
Increased Yield and High Resilience of Microbiota Representatives With Organic Soil Amendments in Smallholder Farms of Uganda
Authors: Köberl Martina , Kusstatscher Peter , Wicaksono Wisnu Adi , Mpiira Samuel , Kalyango Francis , Staver Charles , Berg Gabriele
Published: February 2022

Organic matter inputs positively affect soil fertility and quality but management effects on the soil and plant microbiome are less understood. Therefore, we studied the response of microbial colonization of the East African highland banana cultivar “Mpologoma” (AAA genome) under different mulch and manure treatments on three representative smallholder farms in Uganda. In general, the gammaproteobacterial community appeared stable with no significant response to organic matter inputs after 24 months of treatment. Significant differences (p< 0.05) in the plant-associated carpo-, phyllo-, and rhizosphere microbial community composition and diversity were found among individual sampled farms, independent of added soil inputs. Across farms, banana fruit harbored a richer and more balanced gammaproteobacterial community than the rhizo- and endospheres. Gammaproteobacterial beta diversity was shaped by the microenvironment (44%) as well as the sampling site (4%). Global effects of treatments in the rhizosphere analyzed using linear discriminant analysis effect size showed significantly enriched genera, such asEnterobacter, under manure and mulch treatments. As shown in previous works, bunch size and total yield were highly increased with manure and mulch, however, our results highlight general short-term microbial stability of Ugandan banana cropping systems with increases in the gammaproteobacterial community.
Revisiting the Causes of the Pull-to-Centre Effect: Evidence From China
Authors: Yang Lushuang , Cai Dahai
Published: February 2022

Prior experimental studies have shown that individuals' actual ordering decisions significantly deviate from the theoretical optimum in newsvendor problems and show the robust pull-to-centre (PTC) effect. Several human behaviours have been confirmed to be the causes of the PTC. However, most newsvendor experiments have been conducted in multicultural countries (e.g., the United States and Germany). As there exist mutual influences between culture and behaviour, in this study, we revisit the ordering biases in a monocultural country to examine the robustness of the PTC and whether the causes can still explain this phenomenon. Our results show that the PTC still prevails and heuristics still work. However, overconfidence cannot perfectly interpret the PTC in China for probable inconsistent confidence levels in individual judgments and decisions. Moreover, the “centre" may no longer be the mean demand but the average value of the realised demand. We explain these changes from the perspective of cultural differences. To be more specific, collectivism, holistic style, and Doctrine of the Mean play vital roles in Chinese newsvendors' decisions.
Key Subordinate Executive Governance, CEO Overconfidence, and Accounting Conservatism: From the Perspective of Sustainable Development
Authors: Wu Fan , Kuang Xuewen
Published: February 2022

Key subordinate executives play the role of connecting superiors and subordinates within the top management team (TMT). Based on the heterogeneity of TMT preference, this article takes the data of Chinese A-share listed companies from 2010 to 2019 as a sample to examine whether key subordinate executive governance can affect the short-sighted behavior of CEOs. The empirical result shows that there is a positive relationship between key subordinate executive governance and accounting conservatism, and CEO overconfidence can positively moderate the relationship. The study also shows that there is a significant positive relationship between key subordinate executive governance and accounting conservatism in private enterprises and enterprises with high market competition, that is, the key subordinate executives of these two types of enterprises can better enhance the conservatism under the stimulation of CEO overconfidence. This study contributes to the literature by examining how key subordinate executives affect accounting conservatism and link the prudential attitude of key subordinate executives with the behavioral tendency of CEO overconfidence, which has managerial implications for improving the power balance mechanism of TMT and strengthening the human resource incentive of key subordinate executives.
An Evaluation of the Implementation of a “No Force First” Informed Organisational Guide to Reduce Physical Restraint in Mental Health and Learning Disability Inpatient Settings in the UK
Authors: Haines-Delmont Alina , Goodall Katie , Duxbury Joy , Tsang Anthony
Published: February 2022

Background

The use of physical restraint on vulnerable people with learning disabilities and mental health problems is one of the most controversial and criticised forms of restrictive practice. This paper reports on the implementation of an organisational approach called “No Force First” within a large mental health organisation in England, UK. The aim was to investigate changes in violence/aggression, harm, and physical restraint following implementation.

Methods

The study used a pretest-posttest quasi-experimental design. Recorded incidents of violence/aggression from 44 inpatient mental health and learning disabilities (including forensic) wards were included (n = 13,599). Two study groups were created for comparison: the “intervention” group comprising all incidents on these wards during the 24 months post-implementation (2018–2019) (n = 6,551) and the “control” group comprising all incidents in the 24 months preceding implementation (2015–2016) (n = 7,048). Incidents recorded during implementation (i.e., 2017) were excluded (n = 3,705). Incidence rate ratios (IRR) were calculated with 95% confidence intervals (95% CI). Multivariate regression models using generalised estimating equations were performed to estimate unadjusted and adjusted prevalence ratios (aPR) of physical restraint and harm, using type of wards, incident, and violence/aggression as key covariates.

Results

A significant 17% reduction in incidence of physical restraint was observed [IRR = 0.83, 95% CI 0.77–0.88, p < 0.0001]. Significant reductions in rates of harm sustained and aggression/violence were also observed, but not concerning the use of medication during restraint. The prevalence of physical restraint was significantly higher in inpatients on forensic learning disability wards than those on forensic mental health wards both pre- (aPR = 4.26, 95% CI 2.91–6.23) and post-intervention (aPR = 9.09, 95% CI 5.09–16.23), when controlling for type of incident and type of violence/aggression. Physical assault was a significantly more prevalent risk factor of restraint use than other forms of violence/aggression, especially that directed to staff (not to other patients).

Conclusions

This is a key study reporting the positive impact that organisational models and guides such as “No Force First” can have on equipping staff to focus more on primary and secondary prevention as opposed to tertiary coercive practices such as restraint in mental health and learning disabilities settings.