bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Talk Between m6A- and m5C-Related lncRNAs to Construct a Novel Signature and Predict the Immune Landscape of Colorectal Cancer Patients
Authors: Song Wei , Ren Jun , Xiang Rensheng , Yuan Wenzheng , Fu Tao
Published: March 2022

Background

N6-methyladenosine (m6A) and 5-methylcytosine (m5C) can modify long non-coding RNAs (lncRNAs), thereby affecting tumorigenesis and tumor progression. However, there is a lack of knowledge regarding the potential roles and cross-talk of m6A- and m5C-related lncRNAs in the tumor microenvironment (TME) and their effect on prognosis.

Methods

We systematically evaluated the expression patterns of m6A- and m5C-related lncRNAs in 1358 colorectal cancer (CRC) samples from four datasets. Consensus clustering was conducted to identify molecular subtypes of CRC, and the clinical significance, TME, tumor-infiltrating immune cells (TIICs), and immune checkpoints in the different molecular subtypes were analyzed. Finally, we established a m6A- and m5C-related lncRNA signature and a prognostic nomogram.

Results

We identified 141 m6A- and m5C-related lncRNAs by co-expression analysis, among which 23 lncRNAs were significantly associated with the overall survival (OS) of CRC patients. Two distinct molecular subtypes (cluster A and cluster B) were identified, and these two distinct molecular subtypes could predict clinicopathological features, prognosis, TME stromal activity, TIICs, immune checkpoints. Next, a m6A- and m5C-related lncRNA signature for predicting OS was constructed, and its predictive capability in CRC patients was validated. We then constructed a highly accurate nomogram for improving the clinical applicability of the signature. Analyses of clinicopathological features, prognosis, TIICs, cancer stem cell (CSC), and drug response revealed significant differences between two risk groups. In addition, we found that patients with a low-risk score exhibited enhanced response to anti-PD-1/L1 immunotherapy. Functional enrichment analysis showed that these lncRNAs related to the high-risk group were involved in the development and progression of CRC.

Conclusions

We conducted a comprehensive analysis of m6A- and m5C-related lncRNAs in CRC and revealed their potential functions in predicting tumor-immune-stromal microenvironment, clinicopathological features, and prognosis, and determined their role in immunotherapy. These findings may improve our understanding of the cross-talk between m6A- and m5C-related lncRNAs in CRC and pave a new road for prognosis assessment and more effective immunotherapy strategies.
Kinetics of Severity Biomarkers and Immunological Features of Methylprednisolone Therapy for Severe COVID-19 Patients
Authors: Fan Qinghong , Deng Kai , Huang Huang , He Ruiying , Deng Xizi , Lan Yun , Tan Yizhou , Chen Weilie , Wang Yaping , Deng Xilong , Hu Fengyu , Li Feng
Published: March 2022

In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the “core signature” cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The “core signature” cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed “core signature” cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.
Neutralization of SARS-CoV-2 Variants by mRNA and Adenoviral Vector Vaccine-Elicited Antibodies
Authors: Tada Takuya , Zhou Hao , Samanovic Marie I. , Dcosta Belinda M. , Cornelius Amber , Herati Ramin S. , Mulligan Mark J. , Landau Nathaniel R.
Published: March 2022

The increasing prevalence of SARS-CoV-2 variants has raised concerns regarding possible decreases in vaccine effectiveness. Here, neutralizing antibody titers elicited by mRNA-based and adenoviral vector-based vaccines against variant pseudotyped viruses were measured. BNT162b2 and mRNA-1273-elicited antibodies showed modest neutralization resistance against Beta, Delta, Delta plus and Lambda variants whereas Ad26.COV2.S-elicited antibodies from a significant fraction of vaccinated individuals had less neutralizing titer (IC50 <50). The data underscore the importance of surveillance for breakthrough infections that result in severe COVID-19 and suggest a potential benefit by second immunization following Ad26.COV2.S to increase protection from current and future variants.
Genome-Wide ChIP-seq and RNA-seq Analyses of STAT3 Target Genes in TLRs Activated Human Peripheral Blood B Cells
Authors: Wu Jing , Jin Ying-Ying , Gong Ruo-Lan , Yang Fan , Su Xiao-Ya , Chen Tong-Xin
Published: March 2022

Toll like receptors (TLRs) induced response plays a vital role in B-cell development and activation, in which TLR7-mediated and TLR9-mediated response interact together and play antagonistic or cooperative roles at different situations. Previous studies showed that the transcription factor signal transducer and activator of transcription (STAT) 3 was one of the key transcriptional factors (TFs) needed for both TLR7 and TLR9 signaling in B cell, and patients with autosomal dominant hyper IgE syndromes (AD-HIES) due to STAT3 mutations having defective TLRs response in B cells. However, how STAT3 affects its target genes and the downstream signaling pathways in B cell upon TLRs stimulation remains unclarified on a genome-wide level. ChIP-seq and RNA-seq was used in this study to identify the STAT3 targets in response to TLRs stimulation in human B cell. STAT3 ChIP-seq results showed a total of 611 and 2,289 differential STAT3-binding sites in human B cell after TLR7 and TLR9 agonists stimulation, respectively. RNA-seq results showed 1,186 and 1,775 differentially expressed genes after TLR7 and TLR9 activation, respectively. We identified 47 primary STAT3 target genes after TLR7 activation and 189 target genes after TLR9 activation in B cell by integration of STAT3 ChIP-seq and RNA-seq data. Among these STAT3 primary targets, we identified 7 TFs and 18 TFs for TLR7 and TLR9 response, respectively. Besides, we showed that STAT3 might regulate TLR9, but not TLR7 response in B cells through directly regulating integrin signaling pathway, which might further affect the antagonism between TLR7 and TLR9 signaling in B cell. Our study provides insights into the molecular mechanism of human TLRs response in B cell and how it can be regulated, which helps to better understand and modulate TLR-mediated pathogenic immune responses in B cell.
Evolution of Cryoglobulinemia in Direct-Acting Antiviral-Treated Asian Hepatitis C Patients With Sustained Virological Responses: A 4-Year Prospective Cohort Study
Authors: Chang Ming-Ling , Cheng Jur-Shan , Chuang Ya-Hui , Pao Li-Heng , Wu Ting-Shu , Chen Shiang-Chi , Chang Ming-Yu , Chien Rong-Nan
Published: March 2022

Background

How cryoglobulinemia evolves after sustained virological response (SVR) following direct-acting antiviral (DAA) treatment in Asian hepatitis C virus (HCV)-infected patients remains elusive.

Methods

A prospective cohort study was conducted in 422 Taiwanese patients (358 completed DAA therapy and 353 experienced SVRs). Serum cryoglobulins were surveyed at baseline and every 3-6 months posttherapy.

Results

Of 422, 227 (53.8%) had cryoglobulinemia, 8 (1.89%) had cryoglobulinemic vasculitis. Of 227, 54 (23.8%), 57 (25.1%) and 116 (51.1%) had 1, 2 and 3 cryoglobulins, respectively; those with 3 cryoglobulins had the highest alanine aminotransferase, immunoglobulin G (IgG) and fibrosis-4 index. During a 4-year follow-up, among SVR patients, cryoglobulinemia rates decreased from 56.4% to 15.4%, single cryoglobulin rates increased (21.6% to 63.9%) and 3 cryoglobulin rates decreased (55.7% to 11.1%). Compared with baseline values, among SVR patients with baseline cryoglobulinemia, complement component 4 levels increased, and IgG and IgM levels decreased until 48 weeks posttherapy for those without posttherapy cryoglobulinemia. All 8 cryoglobulinemic vasculitis patients exhibited SVRs; 5 (62.5%) achieved complete clinical response 12 weeks posttherapy, of whom, 2 (40%) experienced clinical relapse 24~48 weeks posttherapy. Baseline IgM levels were associated with posttherapy cryoglobulinemia in SVR patients (cut-off values at 12, 24, 48 weeks and 4 years posttherapy: 130, 105, 118 and 168 mg/dL, respectively).

Conclusions

Among DAA-treated SVR patients, in 4 years, cryoglobulinemia rates decreased from 56.4% to 15.4%, multiple cryoglobulin rates decreased, cryoglobulinemia signals reversed, 62.5% of cryoglobulinemic vasculitis patients achieved complete clinical response (40% had relapse), and baseline IgM levels indicated posttherapy cryoglobulinemia.
Metabolic Landscape of Bronchoalveolar Lavage Fluid in Coronavirus Disease 2019 at Single Cell Resolution
Authors: Shao Ming-Ming , Shi Meier , Du Juan , Pei Xue-Bin , Gu Bei-Bei , Yi Feng-Shuang
Published: March 2022

Abnormal function of immune cells is one of the key mechanisms leading to severe clinical symptoms in coronavirus disease 2019 patients, and metabolic pathways can destroy the function of the immune system by affecting innate and adaptive immune responses. However, the metabolic characteristics of the immune cells of the SARS-CoV-2 infected organs in situ remaining elusive. We reanalyzed the metabolic-related gene profiles in single-cell RNA sequencing data, drew the metabolic landscape in bronchoalveolar lavage fluid immune cells, and elucidated the metabolic remodeling mechanism that might lead to the progression of COVID-19 and the cytokine storm. Enhanced glycolysis is the most important common metabolic feature of all immune cells in COVID-19 patients. CCL2+ T cells, Group 2 macrophages with high SPP1 expression and myeloid dendritic cells are among the main contributors to the cytokine storm produced by infected lung tissue. Two metabolic analysis methods, including Compass, showed that glycolysis, fatty acid metabolism, bile acid synthesis and purine and pyrimidine metabolism levels of CCL2+ T cells, Group 2 macrophages and myeloid dendritic cells were upregulated and correlated with cytokine storms of COVID-19 patients. This might be the key metabolic regulatory factor for immune cells to produce large quantities of cytokines.
Pathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis
Authors: Nuñez-Borque Emilio , Fernandez-Bravo Sergio , Yuste-Montalvo Alma , Esteban Vanesa
Published: March 2022

Anaphylaxis is a systemic hypersensitivity reaction that can be life threatening. Mechanistically, it results from the immune activation and release of a variety of mediators that give rise to the signs and symptoms of this pathological event. For years, most of the research in anaphylaxis has focused on the contribution of the immune component. However, approaches that shed light on the participation of other cellular and molecular agents are necessary. Among them, the vascular niche receives the various signals (e.g., histamine) that elicit the range of anaphylactic events. Cardiovascular manifestations such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and cardiac alterations are crucial in the pathophysiology of anaphylaxis and are highly involved to the development of the most severe cases. Specifically, the endothelium, vascular smooth muscle cells, and their molecular signaling outcomes play an essential role downstream of the immune reaction. Therefore, in this review, we synthesized the vascular changes observed during anaphylaxis as well as its cellular and molecular components. As the risk of anaphylaxis exists both in clinical procedures and in routine life, increasing our knowledge of the vascular physiology and their molecular mechanism will enable us to improve the clinical management and how to treat or prevent anaphylaxis.

Key Message

Anaphylaxis, the most severe allergic reaction, involves a variety of immune and non-immune molecular signals that give rise to its pathophysiological manifestations. Importantly, the vascular system is engaged in processes relevant to anaphylactic events such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and decreased cardiac output. The novelty of this review focuses on the fact that new studies will greatly improve the understanding of anaphylaxis when viewed from a vascular molecular angle and specifically from the endothelium. This knowledge will improve therapeutic options to treat or prevent anaphylaxis.
Targeted Gene Expression Profiling of Human Myeloid Cells From Blood and Lung Compartments of Patients With Tuberculosis and Other Lung Diseases
Authors: Kotze Leigh Ann , van der Spuy Gian , Leonard Bryan , Penn-Nicholson Adam , Musvosvi Munyaradzi , McAnda Shirley , Malherbe Stephanus T. , Erasmus Mzwandile , Scriba Thomas , Koegelenberg Coenraad F. N. , Allwood Brian W. , Walzl Gerhard , du Plessis Nelita
Published: March 2022

Myeloid-derived suppressor cells (MDSC) have been identified in the peripheral blood and granulomas of patients with active TB disease, but their phenotype-, function-, and immunosuppressive mechanism- spectrum remains unclear. Importantly, the frequency and signaling pathways of MDSC at the site of disease is unknown with no indication how this compares to MDSC identified in peripheral blood or to those of related myeloid counterparts such as alveolar macrophages and monocytes. Most phenotypic and functional markers have been described in oncological studies but have not yet been validated in TB. Using a panel of 43 genes selected from pathways previously shown to contribute to tumor-derived MDSC, we set out to evaluate if the expression of these additional functional markers and properties may also be relevant to TB-derived MDSC. Differential expression was investigated between MDSC, alveolar macrophages and monocytes enriched from bronchoalveolar lavage fluid and peripheral blood of patients with active TB, patients with other lung diseases (OLD). Results demonstrated that anatomical compartments may drive compartment-specific immunological responses and subsequent MDSC immunosuppressive functions, demonstrated by the observation that MDSC and/or monocytes from PB alone can discriminate, via hierarchical clustering, between patients with active TB disease and OLD. Our data show that the gene expression patterns of MDSC in peripheral blood and bronchoalveolar lavage fluid do not cluster according to disease states (TB vs OLD). This suggests that MDSC from TB patients may display similar gene expression profiles to those found for MDSC in cancer, but this needs to be validated in a larger cohort. These are important observations for TB research and may provide direction for future studies aimed at repurposing and validating cancer immunotherapies for use in TB.
How the Innate Immune System of the Blood Contributes to Systemic Pathology in COVID-19-Induced ARDS and Provides Potential Targets for Treatment
Authors: Nilsson Bo , Persson Barbro , Eriksson Oskar , Fromell Karin , Hultström Michael , Frithiof Robert , Lipcsey Miklos , Huber-Lang Markus , Ekdahl Kristina N.
Published: March 2022

Most SARS-CoV-2 infected patients experience influenza-like symptoms of low or moderate severity. But, already in 2020 early during the pandemic it became obvious that many patients had a high incidence of thrombotic complications, which prompted treatment with high doses of low-molecular-weight heparin (LMWH; typically 150-300IU/kg) to prevent thrombosis. In some patients, the disease aggravated after approximately 10 days and turned into a full-blown acute respiratory distress syndrome (ARDS)-like pulmonary inflammation with endothelialitis, thrombosis and vascular angiogenesis, which often lead to intensive care treatment with ventilator support. This stage of the disease is characterized by dysregulation of cytokines and chemokines, in particular with high IL-6 levels, and also by reduced oxygen saturation, high risk of thrombosis, and signs of severe pulmonary damage with ground glass opacities. The direct link between SARS-CoV-2 and the COVID-19-associated lung injury is not clear. Indirect evidence speaks in favor of a thromboinflammatory reaction, which may be initiated by the virus itself and by infected damaged and/or apoptotic cells. We and others have demonstrated that life-threatening COVID-19 ARDS is associated with a strong activation of the intravascular innate immune system (IIIS). In support of this notion is that activation of the complement and kallikrein/kinin (KK) systems predict survival, the necessity for usage of mechanical ventilation, acute kidney injury and, in the case of MBL, also coagulation system activation with thromboembolism. The general properties of the IIIS can easily be translated into mechanisms of COVID-19 pathophysiology. The prognostic value of complement and KKsystem biomarkers demonstrate that pharmaceuticals, which are licensed or have passed the phase I trial stage are promising candidate drugs for treatment of COVID-19. Examples of such compounds include complement inhibitors AMY-101 and eculizumab (targeting C3 and C5, respectively) as well as kallikrein inhibitors ecallantide and lanadelumab and the bradykinin receptor (BKR) 2 antagonist icatibant. In this conceptual review we discuss the activation, crosstalk and the therapeutic options that are available for regulation of the IIIS.
Sublethal Injuries and Physical Abnormalities in Maldives Manta Rays, Mobula alfredi and Mobula birostris
Authors: Strike Elspeth M. , Harris Joanna L. , Ballard Kirsty L. , Hawkins Julie P. , Crockett Jennifer , Stevens Guy M. W.
Published: March 2022

Manta ray populations worldwide are vulnerable to sublethal injuries resulting from human activities, e.g., entanglement in fishing line and boat strikes, which have the potential to impact an individual’s health, fitness, and behaviour. Sublethal injuries and physical abnormalities also occur naturally from predation events, deformity, parasites, and disease. To determine the type and frequency of anthropogenic and natural originated injury events affecting Mobula alfredi and M. birostris in the Maldives, we examined data from the Manta Trust’s Maldivian Manta Ray Project (MMRP) database, which contains 73,638 photo-identification (photo-ID) sightings of the two manta ray species from 1987 to 2019. The likely origin of each injury or physical abnormality was determined based on visual assessment of the photo-ID images. Multiple injuries to an individual originating from the same event were grouped for analysis. Generalised linear mixed models (GLMM) were used to investigate the relationship between the occurrence of injury events and the explanatory variables sex and maturity status for both species, with the additional variable site function (cleaning, feeding, cruising) investigated for M. alfredi. Spatial and temporal variations in M. alfredi injury events, and their origin and type, were investigated by calculating the percentage of injury events per sighted individual at each Maldivian atoll, and per re-sighted individual in each year from 2005 to 2019. For both species, injury events were predominantly of natural origin, with predatory bites being the most frequent type. The most common anthropogenic injury type was entanglement in fishing line. Injuries to M. alfredi were significantly more likely to be observed on juveniles than adults, males than females, and at cleaning stations as opposed to feeding or cruising sites. Neither sex nor maturity status were significant explanatory variables for the occurrence of injuries to M. birostris. Highest percentages of anthropogenic injuries per sighted M. alfredi were recorded in North Malé, South Malé, Baa, Addu, and Laamu Atolls, where boat traffic, fishing, and tourism activities are concentrated. Overall, this work greatly improves understanding of the sublethal threats faced by manta rays in the Maldives; identifying focus areas where conservation management actions are required to ensure more effective protection of this threatened species group.
A Review of National Monitoring Requirements to Support Offshore Carbon Capture and Storage
Authors: Turrell William R. , Berx Barbara , Bresnan Eileen , León Pablo , Rouse Sally , Webster Lynda , Walsham Pamela , Wilson Jared , Wright Peter
Published: March 2022

There is an urgent need to reduce global greenhouse gas emissions. One method of achieving this is through Carbon Capture and Storage (CCS). Geological structures that lie offshore under continental shelf seas offer huge CCS storage potential. An emerging marine industry is developing to exploit this potential and national marine monitoring agencies will soon need to consider the potential impacts of this emerging industry. This review of published literature is aimed at generalists responsible for the delivery of national marine monitoring, as well as those involved in the management of the marine environment. It briefly summarizes why the emerging offshore CCS industry is needed, how large it may be and what marine infrastructure may be involved. For the purposes of this paper, a hypothetical 20 Mtpa industry has been used to gauge the potential impact of a developing offshore CCS industry. The probability of CO2 leaks from such an industry is low. If they do occur, the spatial scale of impact will be small, and the potential environmental impacts will be low. Irrespective of how CO2 is transported or stored within shelf seas, leaked CO2 will enter the sea as a gas or as a solution dissolved in sediment pore water. CO2 as a gas will dissolve into seawater and/or directly vent to the atmosphere, depending on the initial conditions of the leak. The most probable source of leaks in a developed CCS industry is from pipelines (currently a 2-year event per 1000 km pipeline). The most probable source of leakage from geological storage is through abandoned wells (a 20- to 80-year event for a 20 Mtpa industry). The source of leaks from a CCS scheme with the potential to release the greatest mass of CO2 is through geological faults, as these may go undetected (if they occur) for long periods. The probability of leaks from geological storage, through faults or abandoned wells, is site dependent and minimized by the site selection process. The review concludes with recommended priorities for future marine science development.
High Performance Copper Based Metal Organic Framework for Removal of Heavy Metals From Wastewater
Authors: Haso Hussien Waritu , Dubale Amare Aregahegn , Chimdesa Mitiku Abdisa , Atlabachew Minaleshewa
Published: March 2022

The biggest challenge of this century is the generation of wastewater which is released to the environment due to industrial expansion. Industrial development has caused the release of various pollutants including heavy metals such as Cd, Pb, and Cr into the environment. In this study, copper diphenylamine metal-organic framework (Cu-DPA MOF) has been synthesized via hydrothermal method and its adsorption capacity toward the removal of heavy metals from wastewater was examined. The removal efficiency of heavy metals by Cu-DPA MOF was tested at optimized adsorption parameters such as optimal adsorbent dosage, pH, initial metals concentration, and adsorption time. The heavy metals concentration in the wastewater before treated with the as-synthesized MOF was determined to be 0.3027, 0.0098, and 0.1021 mg/L for Cr, Cd, and Pb, respectively. The corresponding concentrations of heavy metals in wastewater were reduced to 0.0015, 0.00024, and 0.00016 mg/L when treated with the as-synthesized MOF. As a result, a maximum removal efficiency of 97.6%, 99.5%, and 99.5% was achieved for Cd, Cr, and Pb metals, respectively. This is possibly due to the high porous nature and huge surface area of the as-synthesized MOF. The adsorption data were best fitted with Freundlich isotherm throughout this study. The study sheds light on the design of adsorbents with high removal efficiency of pollutants found in the environment.
A Unified Model for Fibers With Divergent Pullout Behaviors in Strain Hardening Cementitious Composites (SHCC)
Authors: She Peiyun , Wang Jiajie , Pang Zhiming , Lu Cong
Published: March 2022

Strain Hardening Cementitious Composites (SHCC) are materials exhibiting high tensile ductility with the formation of multiple cracks. Since the mechanical properties of SHCC members are governed by the interfacial characteristics between fibers and matrix, understanding the mechanism of single fiber pullout behavior is crucial for SHCC material design. Existing model was set up based on Polyvinyl Alcohol (PVA) fibers, making it inapplicable to other kinds of synthetic fibers those exhibit divergent pullout behaviors. As a result, the simulated curves cannot agree well with the tested results of SHCC made with other fibers or hybrid fibers. In this study, a unified single fiber pullout model was proposed to take divergent kinds of fiber pullout behavior into account. Five parameters were defined to describe the single fiber pullout behavior, where the frictional strength during the pullout stage and the blocking length of fiber under pulley force were for the first time introduced. For verification purpose, fiber-pullout samples with Polyethylene terephthalate (PET) and PVA fibers were tested and the results agree well with the simulated curves from proposed model. The stochasticity of each parameters were then analyzed and described by normal distribution, through which fibers with various random pullout behaviors can be incorporated into a larger scale modelling. Therefore, the fiber-bridging constitutive law for a single crack was calculated and compared with the single crack test results, which confirmed again the validity of the proposed model.
Survival Outcome of Surgical Resection vs. Radiotherapy in Brain Metastasis From Colorectal Cancer: A Meta-Analysis
Authors: Chang Yu , Wong Chia-En , Lee Po-Hsuan , Huang Chi-Chen , Lee Jung-Shun
Published: March 2022

Background

The incidence of brain metastasis from colorectal cancer (CRC) increases along with the greater survival rate for CRC because of the advances in therapeutic modalities. Local treatment strategies for brain metastasis include surgical resection and radiotherapy. Nevertheless, given the incongruent literature, the optimal therapeutic approach remains to be investigated. This study aims to systematically compare the real-world survival outcome of surgical resection and radiotherapy in patients with brain metastasis from CRC.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines (PROSPERO, ID: CRD42021240200), the Cochrane Library, Embase, and Medline were searched from the inception of the database to August 2021. Meta-analyses were conducted with results pooled using hazard ratios with corresponding 95% CIs to evaluate the overall survival (OS) following local treatment for brain metastasis from CRC. Summary effects were evaluated using a series of random-effect models.

Results

In this review, 17 retrospective studies comprising 1,438 participants were included. In comparison with radiotherapy, the OS of patients who received brain metastasectomy was generally longer (HR, 0.53; 95% CI, 0.47–0.60). Extracerebral metastases (HR, 1.58; 95% CI, 1.34–1.86) and multiple brain metastases (HR, 1.38; 95% CI, 1.10–1.72) were associated with worse survival outcomes.

Conclusions

For patients with brain metastasis from CRC, the current real-world evidence demonstrated the survival benefit of aggressive neurosurgical management in suitable patients. Additionally, patients with extracerebral metastases and multiple brain metastases had worse survival outcomes.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=240200.
Construction and Interpretation of Prediction Model of Teicoplanin Trough Concentration via Machine Learning
Authors: Ma Pan , Liu Ruixiang , Gu Wenrui , Dai Qing , Gan Yu , Cen Jing , Shang Shenglan , Liu Fang , Chen Yongchuan
Published: March 2022

Objective

To establish an optimal model to predict the teicoplanin trough concentrations by machine learning, and explain the feature importance in the prediction model using the SHapley Additive exPlanation (SHAP) method.

Methods

A retrospective study was performed on 279 therapeutic drug monitoring (TDM) measurements obtained from 192 patients who were treated with teicoplanin intravenously at the First Affiliated Hospital of Army Medical University from November 2017 to July 2021. This study included 27 variables, and the teicoplanin trough concentrations were considered as the target variable. The whole dataset was divided into a training group and testing group at the ratio of 8:2, and predictive performance was compared among six different algorithms. Algorithms with higher model performance (top 3) were selected to establish the ensemble prediction model and SHAP was employed to interpret the model.

Results

Three algorithms (SVR, GBRT, and RF) with high R2 scores (0.676, 0.670, and 0.656, respectively) were selected to construct the ensemble model at the ratio of 6:3:1. The model with R2 = 0.720, MAE = 3.628, MSE = 22.571, absolute accuracy of 83.93%, and relative accuracy of 60.71% was obtained, which performed better in model fitting and had better prediction accuracy than any single algorithm. The feature importance and direction of each variable were visually demonstrated by SHAP values, in which teicoplanin administration and renal function were the most important factors.

Conclusion

We firstly adopted a machine learning approach to predict the teicoplanin trough concentration, and interpreted the prediction model by the SHAP method, which is of great significance and value for the clinical medication guidance.
Microbiome Transmission During Sexual Intercourse Appears Stochastic and Supports the Red Queen Hypothesis
Authors: Ma Zhanshan (Sam)
Published: March 2022

Microbes inhabit virtually everywhere on and/or in our bodies, including the seminal and vaginal fluids. They have significant importance in maintaining reproductive health and protecting hosts from diseases. The exchange of microbes during sexual intercourse is one of the most direct and significant microbial transmissions between men and women. Nevertheless, the mechanism of this microbial transmission was little known. Is the transmission mode stochastic, passive diffusion similar to the random walk of particles, or driven by some deterministic forces? What is the microbial transmission probability? What are the possible evolutionary implications, particularly from the perspective of sexual reproduction (selection)? We tackle these intriguing questions by leveraging the power of Hubbell’s unified neutral theory of biodiversity, specifically implemented as the HDP-MSN (hierarchical Dirichlet process approximated multi-site neutral model), which allows for constructing truly multi-site metacommunity models, simultaneously including vaginal and semen microbiomes. By reanalyzing the microbiome datasets of seminal and vaginal fluids from 23 couples both before and after sexual intercourses originally reported by Mändar and colleagues, we found that the microbial transmission between seminal and vaginal fluids is a stochastic, passive diffusion similar to the random walk of particles in physics, rather than driven by deterministic forces. The transmission probability through sexual intercourse seems to be approximately 0.05. Inspired by the results from the HDP-MSN model, we further conjecture that the stochastic drifts of microbiome transmissions during sexual intercourses can be responsible for the homogeneity between semen and vaginal microbiomes first identified in a previous study, which should be helpful for sexual reproduction by facilitating the sperm movement/survival and/or egg fertilization. This inference seems to be consistent with the classic Red Queen hypothesis, which, when extended to the co-evolutionary interactions between humans and their symbiotic microbiomes, would predict that the reproductive system microbiomes should support sexual reproduction.
Formulation of a Culture Medium to Optimize the Production of Lipopeptide Biosurfactant by a New Isolate of Bacillus sp.: A Soil Heavy Metal Mitigation Approach
Authors: Kalvandi Sahar , Garousin Hamidreza , Pourbabaee Ahmad Ali , Alikhani Hossein Ali
Published: March 2022

This research aimed to optimize a lipopeptide biosurfactant produced from Bacillus sp. SHA302 due to its high efficiency of heavy metal release in soil. The results demonstrated that the metal release capacity of the lipopeptide biosurfactant alone increased with increasing the biosurfactant concentration. Among treatments with different biosurfactant concentrations plus acid, the highest metal release rates of 53.8% ± 1.4 and 39.3% ± 1.7 for Zn and Pb, respectively, were observed in the critical micelle concentration (CMC) + HCl treatment. The results of a factorial experiment designed for optimizing biosurfactant production showed that among five inexpensive carbon sources and six mineral nitrogen sources, sugar beet molasses (1%) and ammonium chloride (0.1%) were the most efficient sources in lowering the surface tension (ST) of the culture media to 32.2 ± 0.76 mN/m. The second step of the experiment was a Plackett–Burman design with 11 factors and showed that the four factors of pH, ammonium chloride, magnesium sulfate, and molasses significantly affected (P < 0.05) the changes in ST and biosurfactant production. The third step of the experiment was done using the response surface methodology (RSM) with a central composite design. The results showed that a pH of 7.3, 1.5 g/l of ammonium chloride, 0.3 g/l of magnesium sulfate, and 10% of sugar beet molasses yielded values of 29.2 ± 0.71 mN/m and 5.74 ± 0.52 g/l for the two variables of ST and biosurfactant production, respectively, which reached their most optimal levels.
Comparison of Cecal Microbiota and Performance Indices Between Lean-Type and Fatty-Type Pekin Ducks
Authors: Yang Tingshuo , Jiang Yong , Tang Jing , Chang Guobin , Zhao Wenming , Hou Shuisheng , Chen Guohong
Published: March 2022

Fatty-type (FT) Pekin ducks exhibit higher lipid deposition than lean-type (LT) ducks. The gut microbiota plays an important role in modulating fat metabolism. We compared the growth performance, slaughter performance, and cecal microbiota of FT and LT Pekin ducks and analyzed the role of cecal microbiota in lipid deposition in Pekin ducks. A total of 140 1-day-old FT and LT Pekin ducks with similar body weights were randomly assigned to 10 cages, with 14 ducks in each replicate. All ducks were fed commercial diets from 28 to 42 days of age. Results showed that the average body weight and feed intake of FT ducks were higher than those of LT ducks. The breast muscle and eviscerated percentages of LT ducks were higher than those of FT ducks; the abdominal fat and sebum percentages of LT ducks were lower than those of FT ducks at 6 weeks of age (P < 0.01). 16S DNA sequencing of the cecal microbiota revealed that the bacterial abundance differed between FT and LT ducks at 4 and 6 weeks of age. The abundance of Firmicutes was higher, while that of Fusobacteria and Fusobacterium was lower in LT ducks than in FT ducks at 4 weeks of age. The abundance of Spirochaetes was higher, while that of Firmicutes and Bacteroides was lower in LT ducks than in FT ducks at 6 weeks of age. The abundance of Spirochaetes and Brachyspira in LT ducks was higher at 6 weeks than at 4 weeks of age. Interestingly, the abundance of Firmicutes and Bacteroides in FT ducks was higher at 6 weeks of age than at 4 weeks of age, while that of Fusobacteria and Fusobacterium was lower at 6 weeks than at 4 weeks of age. Linear discriminant analysis effect size analysis showed that Spirochaetes, Brachyspira, Alistipes, Campylobacter, Megamonas, Butyricicoccus, and Fusobacteria may be involved in the fat metabolism pathway as specific markers. We reveal the differences in microbial abundance in the cecal microbiota between FT and LT Pekin ducks and provide an insight into the role of cecal microbiota in lipid deposition in Pekin ducks.
Antibacterial Mode of Eucommia ulmoides Male Flower Extract Against Staphylococcus aureus and Its Application as a Natural Preservative in Cooked Beef
Authors: Xing Min , Liu Shun , Yu Yaping , Guo Ling , Wang Yao , Feng Yage , Fei Peng , Kang Huaibing , Ali Md. Aslam
Published: March 2022

The research was conducted to elucidate the antibacterial performance and mode of action of Eucommia ulmoides male flower extract (EUMFE) against Staphylococcus aureus and its application as a natural preservative in cooked beef. The antibacterial activity was evaluated by determining the diameter of inhibition zone (DIZ), minimum inhibitory concentration (MIC), and minimum bactericide concentration (MBC). The changes in membrane potential, contents of bacterial DNA and protein, integrity and permeability of the cell membrane, and cell morphology were analyzed to reveal the possible mode of action. The effect of EUMFE on the counts of S. aureus, pH, color, total volatile basic nitrogen (TVB-N), and thiobarbituric acid reactive substances (TBARS) of the cooked beef stored at 4°C for 9 days were studied. The results showed that the DIZ, MIC, and MBC of EUMFE against S. aureus were 12.58 ± 0.23 mm, 40 mg/mL, and 80 mg/mL, respectively. The mode of action of EUMFE against S. aureus included hyperpolarization of cell membrane, decrease in bacterial DNA and protein contents, destruction of cell membrane integrity, increase in cell membrane permeability, and damage of cell morphology. After treatments with EUMFE, the growth of S. aureus and lipid oxidation in cooked beef were significantly inhibited (P < 0.05). The pH and TVB-N values of cooked beef treated with EUMFE were significantly reduced as compared to control group (P < 0.05). The color of cooked beef samples containing EUMFE showed decreased L* and b* values, and increased a* and ΔE* values. Therefore, our findings showed that EUMFE had a good antibacterial effect on S. aureus, and provided a theoretical basis for the application of EUMFE as a natural preservative in the preservation of cooked beef.
Long Non-Coding RNAs in Cardiac Hypertrophy
Authors: Mangraviti Nicolò , De Windt Leon J.
Published: March 2022

Heart disease represents one of the main challenges in modern medicine with insufficient treatment options. Whole genome sequencing allowed for the discovery of several classes of non-coding RNA (ncRNA) and widened our understanding of disease regulatory circuits. The intrinsic ability of long ncRNAs (lncRNAs) and circular RNAs (circRNAs) to regulate gene expression by a plethora of mechanisms make them candidates for conceptually new treatment options. However, important questions remain to be addressed before we can fully exploit the therapeutic potential of these molecules. Increasing our knowledge of their mechanisms of action and refining the approaches for modulating lncRNAs expression are just a few of the challenges we face. The accurate identification of novel lncRNAs is hampered by their relatively poor cross-species sequence conservation and their low and context-dependent expression pattern. Nevertheless, progress has been made in their annotation in recent years, while a few experimental studies have confirmed the value of lncRNAs as new mechanisms in the development of cardiac hypertrophy and other cardiovascular diseases. Here, we explore cardiac lncRNA biology and the evidence that this class of molecules has therapeutic benefit to treat cardiac hypertrophy.
Elevated Serum Uric Acid Increases the Risk of Ischemic Stroke Recurrence and Its Inflammatory Mechanism in Older Adults
Authors: Zhu Han-Yu , Zhao Shu-Zhen , Zhang Meng-Li , Wang Yan , Pan Zhi-Ming , Cheng Hao-Ran , Zhao Ke , Wang Zhen
Published: March 2022

Background

Serum uric acid (UA) has been reported to be associated with ischemic stroke and inflammation. However, whether or not UA is related to the recurrence of ischemic stroke, and whether inflammation plays a role in the relationship between them remain inconclusive.

Objective

We sought to explore the relationship between UA and the recurrence of ischemic stroke and to define the role of neutrophil-to-lymphocyte ratio (NLR) in the aforementioned relationship.

Methods

A total of 8,995 patients were included in this study. Basic information and blood samples were collected, and whether or not each participant experienced ischemic stroke recurrence within 3 years was documented. Patients were stratified into three groups according to their UA level, as follows: ≤ 266, 267–339, and ≥ 340 μmol/L. COX regression and restricted cubic spline regression models were used to evaluate the clinical correlation between UA and ischemic stroke recurrence, mediation analysis and interaction and joint analysis were used to evaluate the role of NLR in the association of UA and ischemic stroke recurrence, and sensitivity and subgroup analyses were performed to test the robustness of the data.

Results

Ischemic stroke recurrence was related to male sex, older age, higher UA level, higher NLR, hypertension, diabetes, and cardiovascular disease. Following adjustment for potential confounders, a high level of UA (≥ 340 μmol/L) increased the risk of recurrence by 92.6% in patients with previous ischemic stroke. We also found that NLR affects the association between UA and the recurrence of ischemic stroke in older adults, suggesting that patients with high NLR and high UA levels are at greater risk for ischemic stroke recurrence.

Conclusion

UA level is non-linearly associated with recurrence, and NLR has an additive interaction between UA and ischemic stroke recurrence.
Effects of Individualized Gait Rehabilitation Robotics for Gait Training on Hemiplegic Patients: Before-After Study in the Same Person
Authors: Guo Zhao , Ye Jing , Zhang Shisheng , Xu Lanshuai , Chen Gong , Guan Xiao , Li Yongqiang , Zhang Zhimian
Published: March 2022

Background

Lower-limb exoskeleton robots are being widely used in gait rehabilitation training for patients with stroke. However, most of the current rehabilitation robots are guided by predestined gait trajectories, which are often different from the actual gait trajectories of specific patients. One solution is to train patients using individualized gait trajectories generated from the physical parameters of patients. Hence, we aimed to explore the effect of individual gaits on energy consumption situations during gait rehabilitation training for hemiplegic patients with lower-limb exoskeleton robots.

Methods

A total of 9 unilateral-hemiplegic patients were recruited for a 2-day experiment. On the first day of the experiment, the 9 patients were guided by a lower-limb exoskeleton robot, walking on flat ground for 15 min in general gait trajectory, which was gained by clinical gait analysis (CGA) method. On the other day, the same 9 patients wore the identical robot and walked on the same flat ground for 15 min in an individualized gait trajectory. The main physiological parameters including heart rate (HR) and peripheral capillary oxygen saturation (SpO2) were acquired via cardio tachometer and oximeter before and after the walking training. The energy consumption situation was indicated by the variation of the value of HR and SpO2 after walking training compared to before.

Results

Between-group comparison showed that the individualized gait trajectory training resulted in an increase in HR levels and a decrease in SpO2 levels compared to the general gait trajectory training. The resulting difference had a statistical significance of p < 0.05.

Conclusion

Using individualized gait guidance in rehabilitation walking training can significantly improve energy efficiency for hemiplegic patients with stroke.
Multi-Exposure Image Fusion Algorithm Based on Improved Weight Function
Authors: Xu Ke , Wang Qin , Xiao Huangqing , Liu Kelin
Published: March 2022

High-dynamic-range (HDR) image has a wide range of applications, but its access is limited. Multi-exposure image fusion techniques have been widely concerned because they can obtain images similar to HDR images. In order to solve the detail loss of multi-exposure image fusion (MEF) in image reconstruction process, exposure moderate evaluation and relative brightness are used as joint weight functions. On the basis of the existing Laplacian pyramid fusion algorithm, the improved weight function can capture the more accurate image details, thereby making the fused image more detailed. In 20 sets of multi-exposure image sequences, six multi-exposure image fusion methods are compared in both subjective and objective aspects. Both qualitative and quantitative performance analysis of experimental results confirm that the proposed multi-scale decomposition image fusion method can produce high-quality HDR images.
Linear and Nonlinear Directed Connectivity Analysis of the Cardio-Respiratory System in Type 1 Diabetes
Authors: Sorelli Michele , Hutson T. Noah , Iasemidis Leonidas , Bocchi Leonardo
Published: March 2022

In this study, we explored the possibility of developing non-invasive biomarkers for patients with type 1 diabetes (T1D) by quantifying the directional couplings between the cardiac, vascular, and respiratory systems, treating them as interconnected nodes in a network configuration. Towards this goal, we employed a linear directional connectivity measure, the directed transfer function (DTF), estimated by a linear multivariate autoregressive modelling of ECG, respiratory and skin perfusion signals, and a nonlinear method, the dynamical Bayesian inference (DBI) analysis of bivariate phase interactions. The physiological data were recorded concurrently for a relatively short time period (5 min) from 10 healthy control subjects and 10 T1D patients. We found that, in both control and T1D subjects, breathing had greater influence on the heart and perfusion with respect to the opposite coupling direction and that, by both employed methods of analysis, the causal influence of breathing on the heart was significantly decreased (p < 0.05) in T1D patients compared to the control group. These preliminary results, although obtained from a limited number of subjects, provide a strong indication for the usefulness of a network-based multi-modal analysis for the development of biomarkers of T1D-related complications from short-duration data, as well as their potential in the exploration of the pathophysiological mechanisms that underlie this devastating and very widespread disease.