bluuebunny/crossref_metadata_2025 huggingface dataset:
A metabolism-related gene signature for predicting the prognosis in thyroid carcinoma
Authors: Du Qiujing , Zhou Ruhao , Wang Heng , Li Qian , Yan Qi , Dang Wenjiao , Guo Jianjin
Published: January 2023

Metabolic reprogramming is one of the cancer hallmarks, important for the survival of malignant cells. We investigated the prognostic value of genes associated with metabolism in thyroid carcinoma (THCA). A prognostic risk model of metabolism-related genes (MRGs) was built and tested based on datasets in The Cancer Genome Atlas (TCGA), with univariate Cox regression analysis, LASSO, and multivariate Cox regression analysis. We used Kaplan-Meier (KM) curves, time-dependent receiver operating characteristic curves (ROC), a nomogram, concordance index (C-index) and restricted mean survival (RMS) to assess the performance of the risk model, indicating the splendid predictive performance. We established a three-gene risk model related to metabolism, consisting of PAPSS2, ITPKA, and CYP1A1. The correlation analysis in patients with different risk statuses involved immune infiltration, mutation and therapeutic reaction. We also performed pan-cancer analyses of model genes to predict the mutational value in various cancers. Our metabolism-related risk model had a powerful predictive capability in the prognosis of THCA. This research will provide the fundamental data for further development of prognostic markers and individualized therapy in THCA.
An oxidative stress-related signature for predicting the prognosis of liver cancer
Authors: Wang Luling , Liu Xing
Published: January 2023

Introduction: This study aimed to screen for oxidative stress-related genes (OSRGs) and build an oxidative stress-related signature to predict the prognosis of liver cancer.

Methods: OSRGs with a protein domain correlation score ≥ 6 were downloaded from the GeneCards database and intersected with The Cancer Genome Atlas (TCGA) data for subsequent analyses. Differential immune cells (DICs) and immune and stromal scores between the normal and tumor samples were determined, followed by unsupervised hierarchical cluster analysis. Immune-related OSRGs were identified using weighted gene co-expression network analysis. An OSRG-related risk signature was then built, and the GSE14520 dataset was used for validation. A nomogram evaluation model was used to predict prognosis.

Results: Nine DICs were determined between the normal and tumor groups, and three subtypes were obtained: clusters 1, 2, and 3. Cluster 1 had the best prognosis among the clusters. One hundred thirty-eight immune-related OSRGs were identified, and seven prognosis-related OSRGs were used to build the OSRG score prognostic model. Patients in the high OSRG score group had a poorer prognosis than those in the low OSRG score group. Six immune cell infiltration and enrichment scores of the 16 immune gene sets showed significant differences between the high and low OSRG score groups. Moreover, a nomogram was constructed based on the prognostic signature and clinicopathological features and had a robust predictive performance and high accuracy.

Conclusion: The OSRG-related risk signature and the prognostic nomogram accurately predicted patient survival.
Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
Authors: Lu Keqiang , Yuan Xingxing , Zhao Lingling , Wang Bingyu , Zhang Yali
Published: January 2023

Background: The only curative option for patients with locally or locally advanced adrenocortical carcinoma is primary tumor curative sexual resection (ACC). However, overall survival remains low, with most deaths occurring within the first 2 years following surgery. The 5-year survival rate after surgery is less than 30%. As a result, more accurate prognosis-related predictive biomarkers must be investigated urgently to detect patients’ disease status after surgery.

Methods: Data from FerrDb were obtained to identify ferroptosis-related genes, and ACC gene expression profiles were collected from the GEO database to find differentially expressed ACC ferroptosis-related genes using differential expression analysis. The DEFGs were subjected to Gene Ontology gene enrichment analysis and KEGG signaling pathway enrichment analysis. PPI network building and predictive analysis were used to filter core genes. The expression of critical genes in ACC pathological stage and pan-cancer was then investigated. In recent years, immune-related factors, DNA repair genes, and methyltransferase genes have been employed in diagnosing and prognosis of different malignancies. Cancer cells are mutated due to DNA repair genes, and highly expressed DNA repair genes promote cancer. Dysregulation of methyltransferase genes and Immune-related factors, which are shown to be significantly expressed in numerous malignancies, also plays a crucial role in cancer. As a result, we investigated the relationship of AURKA with immunological checkpoints, DNA repair genes, and methyltransferases in pan-cancer.

Result: The DEGs found in the GEO database were crossed with ferroptosis-related genes, yielding 42 differentially expressed ferroptosis-related genes. Six of these 42 genes, particularly AURKA, are linked to the prognosis of ACC. AURKA expression was significantly correlated with poor prognosis in patients with multiple cancers, and there was a significant positive correlation with Th2 cells. Furthermore, AURKA expression was positively associated with tumor immune infiltration in Lung adenocarcinoma (LUAD), Liver hepatocellular carcinoma (LIHC), Sarcoma (SARC), Esophageal carcinoma (ESCA), and Stomach adenocarcinoma (STAD), but negatively correlated with the immune score, matrix score, and calculated score in these tumors. Further investigation into the relationship between AURKA expression and immune examination gene expression revealed that AURKA could control the tumor-resistant pattern in most tumors by regulating the expression level of specific immune examination genes.

Conclusion: AURKA may be an independent prognostic marker for predicting ACC patient prognosis. AURKA may play an essential role in the tumor microenvironment and tumor immunity, according to a pan-cancer analysis, and it has the potential to be a predictive biomarker for multiple cancers.
Immunoinformatics design of B and T-cell epitope-based SARS-CoV-2 peptide vaccination
Authors: Khan Muhammad Shehzad , Khan Ibrar Muhammad , Ahmad Syed Umair , Rahman Ishrat , Khan Muhammad Zahoor , Khan Muhammad Shah Zeb , Abbas Zain , Noreen Shumaila , Liu Yong
Published: January 2023

SARS-COV-2 is a virulent respiratory virus, first identified in China (Wuhan) at the end of 2019. Scientists and researchers are trying to find any possible solution to this deadly viral disease. Different drug source agents have been identified, including western medicine, natural products, and traditional Chinese medicine. They have the potential to counteract COVID-19. This virus immediately affects the liver and causes a decrease in oxygen levels. In this study, multiple vacciome approaches were employed for designing a multi-epitope subunit vaccine for battling against SARS-COV-2. Vaccine designing, immunogenicity, allergenic, and physico-chemical assessment were performed by using the vacciome approach. The vaccine design is likely to be antigenic and produce potent interactions with ACE2 and NSP3 receptors. The developed vaccine has also been given to in-silico cloning models and immune response predictions. A total number of 12 CTL and 12 HTL antigenic epitopes were predicted from three selected covid-19 virulent proteins (spike protein, nucleocapsid protein, and membrane proteins, respectively) based on C-terminal cleavage and MHC binding scores. These predicted epitopes were amalgamated by AYY and GPGPG linkers, and a β-defensins adjuvant was inserted into the N-terminus of this vaccine. This analysis shows that the recommended vaccine can produce immune responses against SARS-COV-2. Designing and developing of the mentioned vaccine will require further experimental validation.
Case report: Pneumocystis jirovecii pneumonia in a severe case of Aicardi–Goutières syndrome with an IFIH1 gain-of-function mutation mimicking combined immunodeficiency
Authors: Železnik Mojca , Soltirovska Šalamon Aneta , Debeljak Maruša , Goropevšek Aleš , Šuštar Nataša , Ključevšek Damjana , Ihan Alojz , Avčin Tadej
Published: January 2023

Aicardi–Goutières syndrome (AGS) is a genetically determined early-onset progressive encephalopathy caused by mutations leading to overexpression of type I interferon (IFN) and resulting in various clinical phenotypes. A gain-of-function (GOF) mutation in the IFIH1 gene is associated with robust production of type I IFN and activation of the Janus kinase (JAK) signal transducer and activator of the transcription (STAT) pathway, which can cause AGS type 7. We detail the clinical case of an infant who initially presented with Pneumocystis jirovecii pneumonia (PCP), had recurrent respiratory infections, and was later treated with a JAK inhibitor, baricitinib, because of a genetically confirmed GOF mutation in the IFIH1 gene. This spectrum of IFIH1 GOF mutations with overlapping features of hyperinflammation and severe opportunistic infection, which mimics combined immunodeficiency (CID), has not been described before. In this case, therapy with baricitinib effectively blocked IFN-α activation and reduced STAT1 signaling but had no effect on the progression of the neurological disease.
Depressive symptoms predict longitudinal changes of chronic inflammation at the transition to adulthood
Authors: Zhai Shuang , Qu Yang , Zhang Dan , Li Tingting , Xie Yang , Wu Xiaoyan , Zou Liwei , Yang Yajuan , Tao Fangbiao , Tao Shuman
Published: January 2023

Background

Inflammation is closely related to poor mental and physical health, including depressive symptoms and its specific symptoms. To reveal the linear and nonlinear relationships between depressive symptoms and chronic inflammation levels, and perform further analysis of the associations between symptom-specificity of depressive symptoms and inflammation among young adults by using a prospective design.

Methods

In this longitudinal study, we examined college students recruited from two universities in China, who were examined at baseline and 2-years follow-up. Depressive symptoms were measured by applying the Patient Health Questionnaire 9 (PHQ-9) at baseline. Plasma levels of four inflammatory biomarkers, including interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and C reactive protein (CRP) were assayed at baseline and 2-year follow-up. In addition to the conventional generalized linear models, as well as restricted cubic splines were innovatively used to analyze the cross-sectional and longitudinal nonlinear relationships between depressive symptoms and inflammatory biomarkers.

Results

Generalized linear model analysis revealed that there were no statistical associations between depressive symptoms and any inflammatory biomarker levels. The results of the restricted cubic spline demonstrated a U-shaped nonlinear association between depressive symptoms and ΔIL-1β or ΔTNF-α (changes in baseline and 2-year follow-up), but these associations disappeared after adjusting the confounders. Symptom-specificity of depressive symptoms such as sleeping problems and suicidal ideation were associated with lower IL-1β at baseline or changes in IL-1β levels. Sleeping problems and psychomotor changes at baseline were associated with higher CRP at 2-year follow-up. Suicidal ideation at baseline was associated with changes in TNF-α levels.

Conclusion

Our findings suggested that symptom-specificity of depressive symptoms was associated with inflammation during a 2-year follow-up at the transition to adulthood. Simultaneously, more research is warranted to seek the directionality of depressive symptoms and chronic inflammation.
The impact of supervised physical exercise on chemokines and cytokines in recovered COVID-19 patients
Authors: Filgueira Tayrine Ordonio , Carvalho Paulo Roberto Cavalcanti , de Sousa Fernandes Matheus Santos , Castoldi Angela , Teixeira Ana Maria , de Albuquerque Renata Bezerra , de Lima-Filho José Luiz , Souto Fabrício Oliveira
Published: January 2023

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which induces a high release of pro-inflammatory chemokines and cytokines, leading to severe systemic disorders. Further, evidence has shown that recovered COVID-19 patients still have some symptoms and disorders from COVID-19. Physical exercise can have many health benefits. It is known to be a potent regulator of the immune system, which includes frequency, intensity, duration, and supervised by a professional. Given the confinement and social isolation or hospitalization of COVID-19 patients, the population became sedentary or opted for physical exercise at home, assuming the guarantee of the beneficial effects of physical exercise and reducing exposure to SARS-CoV-2. This study aimed to investigate the effects of a supervised exercise protocol and a home-based unsupervised exercise protocol on chemokine and cytokine serum levels in recovered COVID-19 patients. This study was a prospective, parallel, two-arm clinical trial. Twenty-four patients who had moderate to severe COVID-19 concluded the intervention protocols of this study. Participants were submitted to either supervised exercise protocol at the Clinical Hospital of the Federal University of Pernambuco or home-based unsupervised exercise for 12 weeks. We analyzed serum levels of chemokines (CXCL8/IL-8, CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ). Before the interventions, no significant differences were observed in the serum levels of chemokines and cytokines between the supervised and home-based unsupervised exercise groups. The CXCL8/IL-8 (p = 0.04), CCL2/MCP-1 (p = 0.03), and IFN-γ (p = 0.004) levels decreased after 12 weeks of supervised exercise. In parallel, an increase in IL-2 (p = 0.02), IL-6 (p = 0.03), IL-4 (p = 0.006), and IL-10 (p = 0.04) was observed after the supervised protocol compared to pre-intervention levels. No significant differences in all the chemokines and cytokines were found after 12 weeks of the home-based unsupervised exercise protocol. Given the results, the present study observed that supervised exercise was able to modulate the immune response in individuals with post-COVID-19, suggesting that supervised exercise can mitigate the inflammatory process associated with COVID-19 and its disorders.

Clinical trial registration

https://ensaiosclinicos.gov.br/rg/RBR-7z3kxjk, identifier U1111-1272-4730.
IgE-dependent human basophil responses are inversely associated with the sarcoplasmic reticulum Ca2+-ATPase (SERCA)
Authors: Selnø Anette T. Hansen , Sumbayev Vadim V. , Gibbs Bernhard F.
Published: January 2023

Basophils crucially contribute to allergies and other Th2-driven diseases by rapidly releasing inflammatory and immunomodulatory mediators following high-affinity IgE-receptor crosslinking. Although these basophil-mediated responses depend on sensitization with antigen-specific IgE, this does not necessarily predict clinical symptom severity. It is thought that the balance of early stimulatory (e.g. SYK) and inhibitory (e.g. SHIP-1) intracellular signals are associated with basophil responsiveness, which is also critically dependent on calcium mobilization. Previous studies suggest that the sarcoplasmic reticulum Ca2+-ATPase (SERCA2), which regulates cytosolic calcium levels, may be inversely associated with airway smooth muscle reactivity in asthma. Since basophils are implicated in asthma severity, our aims were to address whether SERCA2 is implicated in human basophil responses, especially following IgE-mediated activation. Human basophils were obtained from buffy coats, following research ethics approval, and further purified by immunomagnetic cell sorting. Expressions of SERCA2, and other isoforms, were determined by Western blotting in parallel to measuring IgE-dependent histamine releases from the same donors. The effects of a SERCA-activator and inhibitor were also assessed on their abilities to modulate basophil histamine release. We observed an inverse correlation between basophil responsiveness to IgE-dependent stimulation and SERCA2 expression. Thapsigargin, a highly-specific SERCA inhibitor, stimulated basophil histamine release and potentiated IgE-dependent secretion of the amine. Conversely, disulfiram, a SERCA activator, inhibited IgE-dependent basophil activation. The results obtained from this exploratory study indicate that SERCA2 may be an additional regulator of basophil reactivity alongside early excitatory or inhibitory signal transduction pathways.
Prognostic factors of second hematopoietic allogeneic stem cell transplantation among hematological malignancy patients relapsed after first hematopoietic stem cell transplantation: A single center study
Authors: Lu Yue , Zhang Jian-Ping , Zhao Yan-Li , Xiong Min , Sun Rui-Juan , Cao Xing-Yu , Wei Zhi-Jie , Zhou Jia-Rui , Liu De-Yan , Yang Jun-Fang , Zhang Xian , Lu Dao-Pei , Lu Peihua
Published: January 2023

Introduction

We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1).

Methods

We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021.

Results

The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

Conclusions

Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.
CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells
Authors: Brault Julie , Liu Taylor , Liu Siyuan , Lawson Amanda , Choi Uimook , Kozhushko Nikita , Bzhilyanskaya Vera , Pavel-Dinu Mara , Meis Ronald J. , Eckhaus Michael A. , Burkett Sandra S. , Bosticardo Marita , Kleinstiver Benjamin P. , Notarangelo Luigi D. , Lazzarotto Cicera R. , Tsai Shengdar Q. , Wu Xiaolin , Dahl Gary A. , Porteus Matthew H. , Malech Harry L. , De Ravin Suk See
Published: January 2023

Introduction

Ex vivo gene therapy for treatment of Inborn errors of Immunity (IEIs) have demonstrated significant clinical benefit in multiple Phase I/II clinical trials. Current approaches rely on engineered retroviral vectors to randomly integrate copy(s) of gene-of-interest in autologous hematopoietic stem/progenitor cells (HSPCs) genome permanently to provide gene function in transduced HSPCs and their progenies. To circumvent concerns related to potential genotoxicities due to the random vector integrations in HSPCs, targeted correction with CRISPR-Cas9-based genome editing offers improved precision for functional correction of multiple IEIs.

Methods

We compare the two approaches for integration of IL2RG transgene for functional correction of HSPCs from patients with X-linked Severe Combined Immunodeficiency (SCID-X1 or XSCID); delivery via current clinical lentivector (LV)-IL2RG versus targeted insertion (TI) of IL2RG via homology-directed repair (HDR) when using an adeno-associated virus (AAV)-IL2RG donor following double-strand DNA break at the endogenous IL2RG locus.

Results and discussion

In vitro differentiation of LV- or TI-treated XSCID HSPCs similarly overcome differentiation block into Pre-T-I and Pre-T-II lymphocytes but we observed significantly superior development of NK cells when corrected by TI (40.7% versus 4.1%, p = 0.0099). Transplants into immunodeficient mice demonstrated robust engraftment (8.1% and 23.3% in bone marrow) for LV- and TI-IL2RG HSPCs with efficient T cell development following TI-IL2RG in all four patients’ HSPCs. Extensive specificity analysis of CRISPR-Cas9 editing with rhAmpSeq covering 82 predicted off-target sites found no evidence of indels in edited cells before (in vitro) or following transplant, in stark contrast to LV’s non-targeted vector integration sites. Together, the improved efficiency and safety of IL2RG correction via CRISPR-Cas9-based TI approach provides a strong rationale for a clinical trial for treatment of XSCID patients.
Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials
Authors: Wang Zhongwang , Zhou Hui , Xu Jing , Wang Jinjin , Niu Ting
Published: January 2023

Background

Duvelisib is the first FDA-approved oral dual inhibitor of phosphatidylinositol-3-kinase PI3K-delta (PI3K-δ) and PI3K-gamma (PI3K-γ). Although many clinical studies support the efficacy of duvelisib, the safety of duvelisib remains with great attention. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of duvelisib in treating different relapsed or refractory (RR) lymphoid neoplasm types.

Methods

We searched prospective clinical trials from PUBMED, EMBASE, Cochrane Library, and ClinicalTrials.gov. For efficacy analysis, Overall response rate (ORR), complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), rate of progressive disease (PDR), median progression-free survival (mPFS), 12-/24-month PFS, and 12-month overall survival (OS) were assessed. For safety analysis, the incidences of any grade and grade ≥3 adverse events (AEs), serious AEs, and treatment-related discontinuation and death were evaluated. Subgroup analysis based on the disease type was performed.

Results

We included 11 studies and 683 patients, including 305 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 187 B-cell indolent non-Hodgkin lymphoma (iNHL), 39 B-cell aggressive non-Hodgkin lymphoma (aNHL), and 152 T-cell non-Hodgkin lymphoma (T-NHL) patients. The pooled ORR in CLL/SLL, iNHL, aNHL and T-NHL was 70%, 70%, 28% and 47%, respectively. Additionally, the pooled ORR in CLL/SLL patients with or without TP53 mutation/17p-deletion (62% vs. 74%, p=0.45) and in follicular lymphoma (FL) or other iNHL (69% vs. 57%, p=0.38) had no significant differences. Mantle cell lymphoma (MCL) patients had higher pooled ORR than other aNHL (68% vs. 17%, p=0.04). Angioimmunoblastic TCL (AITL) patients had higher pooled ORR than other PTCL patients (67% vs. 42%, p=0.01). The pooled incidence of any grade, grade ≥3, serious AEs, treatment-related discontinuation and death was 99%, 79%, 63%, 33% and 3%, respectively. The most frequent any-grade AEs were diarrhea (47%), ALT/AST increase (39%), and neutropenia (38%). The most frequent grade ≥3 AEs were neutropenia (25%), ALT/AST increased (16%), diarrhea (12%), and anemia (12%).

Conclusion

Generally, duvelisib could offer favorable efficacy in patients with RR CLL/SLL, iNHL, MCL, and AITL. Risk and severity in duvelisib treatment may be mitigated through proper identification and management.
Single-cell computational machine learning approaches to immune-mediated inflammatory disease: New tools uncover novel fibroblast and macrophage interactions driving pathogenesis
Authors: Fritz Douglas , Inamo Jun , Zhang Fan
Published: January 2023

Recent advances in single-cell sequencing technologies call for greater computational scalability and sensitivity to analytically decompose diseased tissues and expose meaningful biological relevance in individual cells with high resolution. And while fibroblasts, one of the most abundant cell types in tissues, were long thought to display relative homogeneity, recent analytical and technical advances in single-cell sequencing have exposed wide variation and sub-phenotypes of fibroblasts of potential and apparent clinical significance to inflammatory diseases. Alongside anticipated improvements in single cell spatial sequencing resolution, new computational biology techniques have formed the technical backbone when exploring fibroblast heterogeneity. More robust models are required, however. This review will summarize the key advancements in computational techniques that are being deployed to categorize fibroblast heterogeneity and their interaction with the myeloid compartments in specific biological and clinical contexts. First, typical machine-learning-aided methods such as dimensionality reduction, clustering, and trajectory inference, have exposed the role of fibroblast subpopulations in inflammatory disease pathologies. Second, these techniques, coupled with single-cell predicted computational methods have raised novel interactomes between fibroblasts and macrophages of potential clinical significance to many immune-mediated inflammatory diseases such as rheumatoid arthritis, ulcerative colitis, lupus, systemic sclerosis, and others. Third, recently developed scalable integrative methods have the potential to map cross-cell-type spatial interactions at the single-cell level while cross-tissue analysis with these models reveals shared biological mechanisms between disease contexts. Finally, these advanced computational omics approaches have the potential to be leveraged toward therapeutic strategies that target fibroblast-macrophage interactions in a wide variety of inflammatory diseases.
Advances in artificial intelligence to predict cancer immunotherapy efficacy
Authors: Xie Jindong , Luo Xiyuan , Deng Xinpei , Tang Yuhui , Tian Wenwen , Cheng Hui , Zhang Junsheng , Zou Yutian , Guo Zhixing , Xie Xiaoming
Published: January 2023

Tumor immunotherapy, particularly the use of immune checkpoint inhibitors, has yielded impressive clinical benefits. Therefore, it is critical to accurately screen individuals for immunotherapy sensitivity and forecast its efficacy. With the application of artificial intelligence (AI) in the medical field in recent years, an increasing number of studies have indicated that the efficacy of immunotherapy can be better anticipated with the help of AI technology to reach precision medicine. This article focuses on the current prediction models based on information from histopathological slides, imaging-omics, genomics, and proteomics, and reviews their research progress and applications. Furthermore, we also discuss the existing challenges encountered by AI in the field of immunotherapy, as well as the future directions that need to be improved, to provide a point of reference for the early implementation of AI-assisted diagnosis and treatment systems in the future.
Effects of exogenous hormones on the regeneration of juveniles from Sargassum fusiforme holdfasts
Authors: Luo Lin , Zuo Xiaojie , Guo Lina , Pang Guanfeng , Ma Zengling , Wu Mingjiang , Chen Binbin
Published: January 2023

During the cultivation of Sargassum fusiforme, sexual reproduction of superior strains can hinder the stable inheritance of their desirable traits and reduce their economic benefits. However, vegetative reproduction of S. fusiforme holdfasts has high potential for subculture. In this study, we investigated the effects of different concentrations of α-naphthaleneacetic acid (NAA), gibberellin (GA3), and 6-benzyladenine (BAP) on the growth and regeneration of S. fusiforme holdfasts. Exogenous application of 1.5, 2 mg·L-1NAA, 1.5 mg·L-1 GA3 or 2, 3 mg·L-1BAP significantly promoted photosynthetic activity and the absorption and utilization of nitrate nitrogen in S. fusiforme holdfasts, thus improving the relative growth rate (RGR) and regeneration rate (RR) and shortening the time for the regeneration of juveniles from S. fusiforme holdfasts to around the 6th day. Among these, the RGR and RR at the end of the culture period with 1.5 mg·L-1 of NAA increased by 118.9% and 67.4%, respectively, compared with those of the control group. However, treatment with 1.5 mg·L-1 GA3 increased the RR of S. fusiforme holdfasts by 58.8% compared with that of the control group. Under BAP treatment at 3 mg·L-1, the RR of S. fusiforme holdfasts increased by 23.4% compared with that of the control group; its promoting effect was thus weaker than that of NAA and GA3. When the concentration of GA3 or BAP was too high (3 mg·L-1; 5 mg·L-1), the RR of the holdfasts decreased by 46.5% and 42.8%, respectively compared with that of the control group. Therefore, exogenous application of NAA at 1.5 mg·L-1, GA3 at 1.5 mg·L-1, and BAP at 3 mg·L-1 can be used to induce regeneration of S. fusiforme holdfasts, shorten the culture time of regenerated seedlings, and obtain more regenerative seedlings, thereby improving economic efficiency.
Seagrass canopy structure mediates putative bacterial pathogen removal potential
Authors: Liu Songlin , Wu Yunchao , Luo Hongxue , Ren Yuzheng , Jiang Zhijian , Zhang Xia , Fang Yang , Liang Jiening , Huang Xiaoping
Published: January 2023

Bacterial pathogen removal function in seagrass meadows is gaining attention worldwide, with enhancing particle sedimentation as the main potential mechanism. Unfortunately, seagrass meadows are declining to patchiness and fragmentation due to anthropogenic activities and global climate change. However, the effects of seagrass decline on bacterial pathogen removal potential are poorly understood, limiting our ability to understand coastal-living humans and marine organisms that suffered pressure from diseases and other health-related effects in response to seagrass decline. Here we investigated abundance of putative bacterial pathogens (including Vibrio spp., Salmonella spp., Staphylococcus spp., and Enterococcus spp.) in trapped particles under different canopy structures of Enhalus acoroides patches in South China Sea. The abundance of Vibrio spp., Salmonella spp., and Staphylococcus spp. trapped particles, respectively, was observed much greater in seagrass patches with high density and height than other patches, and significantly positive correlations with seagrass density and height were observed. This was mainly ascribed to seagrass patches of high density and height being able to trap more particles. Surprisingly, however, the Enterococcus spp. abundance showed negative correlations with density and area. Enterococcus spp. is generally inhibited in well-oxygenated environments, of which the microenvironment of dissolved oxygen might be mediated by seagrass density and area. Overall, this research suggests that the potential of removal of putative bacterial pathogen was inhibited in fragmented seagrass meadow; therefore, coastal-living humans and marine organisms might suffer from an increasing risk of diseases due to the decline of seagrass meadows.
The use of alternative fuels for maritime decarbonization: Special marine environmental risks and solutions from an international law perspective
Authors: Wang Qiuwen , Zhang Hu , Huang Jiabei , Zhang Pengfei
Published: January 2023

The introduction of several alternative marine fuels is considered an important strategy for maritime decarbonization. These alternative marine fuels include liquefied natural gas (LNG), liquefied biogas (LBG), hydrogen, ammonia, methanol, ethanol, hydrotreated vegetable oil (HVO), etc. In some studies, nuclear power and electricity are also included in the scope of alternative fuels for merchant ships. However, the operation of alternative-fuel-powered ships has some special risks, such as fuel spills, vapor dispersion and fuel pool fires. The existing international legal framework does not address these risks sufficiently. This research adopts the method of legal analysis to examine the existing international legal regime for regulating the development of alternative-fuel-powered ships. From a critical perspective, it evaluates and predicts the consequences of these policies together with their shortcomings. Also, this research explores the potential solutions and countermeasures that might be feasible to deal with the special marine environmental risks posed by alternative-fuel-powered ships in the future.
Challenging the new blue deal by embedding interactions with the non-humans in the offshore renewable energy development
Authors: Boemare Catherine
Published: January 2023

This paper is challenging the new blue deal outlining the need for a change in the expectative. Offshore wind farms (OWFs) are not only a climate-friendly way of producing electricity but also a shifting paradigm unique opportunity, acknowledging the increasing presence of anthropogenic infrastructure in the marine environment and seeing them as the place for recreating relations with non-humans and work with them. We give some ideas that could ground a research program pairing both positive and negative aspects of OWF and study the conditions of realization of mutual beneficial relationship coming from the “mosaic of open-ended assemblages of entangled ways of life.”
Spatio-temporal patterns in coral reef composition and function across an altered environmental gradient: A 15-year study in the Caribbean
Authors: Briand Julia K. , Guzmán Hector M. , Sunday Jennifer M.
Published: January 2023

Coral species, which function to build the framework structure of reef ecosystems, vary across sheltered to exposed environmental gradients. For centuries, conditions in sheltered environments that impact lagoonal reefs have been altered by local anthropogenic disturbances, while conditions in exposed environments that impact forereefs have largely buffered the effects of local anthropogenic disturbances. Yet, bleaching events induced by global anthropogenic disturbances challenge how we predict changes in reef composition and function across environmental gradients. Here, we quantify spatio-temporal variation in the composition and function of 11 coral reefs across sheltered to exposed environmental conditions over 15 years and 3 bleaching events in Bocas del Toro, Panama. We find that the composition and function of lagoonal reefs and forereefs were distinct and shaped by an environmental gradient altered by anthropogenic disturbance. Lagoonal reefs lacked major reef-building species and experienced greater losses in coral species and diversity over time. Although only lagoonal reefs changed in coral species composition, both lagoonal reefs and forereefs became functionally similar over time. Our findings indicate that lagoonal reefs may be less resilient to global environmental change than forereefs due to long-term effects of local anthropogenic disturbances. Additionally, increasing global anthropogenic disturbances might lead to the homogenization of reef function, as reefs adapt to novel environmental conditions.
Surface acoustic wave sensor for formaldehyde gas detection using the multi-source spray-deposited graphene/PMMA composite film
Authors: Wang Beibei , Zhou Lingling , Wang Xiaoqian
Published: January 2023

A surface acoustic wave (SAW) formaldehyde sensor based on a graphene/polymethyl methacrylate (PMMA) composite film with high sensitivity, and short response and recovery time was proposed in this study. Using a novel multi-source spray deposition method, graphene sheets were uniformly dispersed in a PMMA film to fabricate sensitive films with a three-dimensional framework structure for use in SAW devices. The formaldehyde-sensing ability was enhanced by optimizing the film thickness and operating temperature. The highest performance was achieved for a graphene/PPMA film thickness of 2.2 μm at a temperature of 120°C.
Research on the underwater cutting mechanism of flux-cored arc cutting for aluminum alloy process
Authors: Yu Rui , Li Wenhang , Wang Jiayou , Wu Mingfang , Wang Jianxin , Wu Jing , Maksimov Sergii Yuri
Published: January 2023

With the fast-growing demand of aluminum alloys in ships and deep-sea pressure structures, an accurate and efficient underwater cutting operation for aluminum alloy is significant. However, its underwater arc cutting mechanism is still not clear enough, which limits its further application. The challenges lie in poor underwater visibility and complex underwater environment. In this study, process experiments, underwater sensor, and numerical simulations were conducted during cutting process to investigate the cutting mechanism of 5,052 aluminum. Firstly, the effect of parameters were investigated on cutting current, voltage, and water depth on the underwater kerf formation. In addition, three typical kerf formations, including “V” type, “II” type and “∧” type, were found; Secondly, visual sensing system was setup to monitor the cutting arc trajectory and the combustion process during the cutting process. Specially, the underwater burning phenomenon was observed. Finally, Finite Element Analysis was performed to further analyze the underwater arc cutting kerf formation of aluminum alloy. A semi-ellipsoidal composite heat source was applied to simulate the underwater arc, and the aluminum thermal reaction-generated heat was introduced. A dynamic method named “birth and death elements” was utilized to simulate the removal of molten metal. The temperature test results show that the simulation process is feasible. All results showed that different cutting parameters led to different cutting mode and affected the kerf forming. 5,052 aluminum alloy in the deep water environment (≥50 m) kerf significantly narrowed. The kerf cross-section produces an inward concavity and the kerf surface is as wide as the cutting wire. The aluminum kerf forming process is greatly impacted by the process parameters and self-propagating high-temperature synthesis reaction during aluminum alloy cutting. The periodicity of the cutting process was computed by the numerical simulation with the arc motion trajectory monitored by the high-speed camera. The numerical results of temperature distribution and kerf shape were consistent with the experimental data, which revealed the cutting mechanism.
The world is burning: What exactly are firebrands and why should anyone care?
Authors: Manzello Samuel L. , Suzuki Sayaka
Published: January 2023

Large outdoor fires have become commonplace all over the world. The International Organization for Standardization (ISO) defines large outdoor fires as an urban fire, tsunami-generated fire, volcano-generated fire, wildland-urban interface (WUI) fire, wildland fire, or informal settlement fire, where the total burnout area is significant. Perhaps of all the large outdoor fires, it is wildland fires that spread into urban areas, simply called WUI fires that attract the most attention. A glance at the recent headlines in the summer of 2022 reveals numerous catastrophic WUI fires all over Europe. Across the Atlantic Ocean in the USA, there is yet another destructive WUI fire raging in the USA state of California. With the increasing risks from a changing climate, these large outdoor fire disasters are only going to become more and more commonplace all over the world. More homes will be lost and more lives will be lost. It is the authors opinion that a targeted, multi-disciplinary approach is needed to address the large outdoor fire problem. In this short, invited paper to Horizons in Mechanical Engineering, it is argued that large outdoor fire problem is a fascinating and challenging research area and that engineers have the necessary skills and training to impact a problem that influences millions upon millions of people all over the world. An important danger, present in all large outdoor fires, are firebrands. Firebrands are introduced for non-specialist readers, and the most recent literature is reviewed. Several challenges are discussed, in particular, areas where engineers may help move the needle forward on this globally important topic.
Numerical calculation of a 20MN heavy duty hydraulic press for analyzing the double frame pre-stressed steel wire winding
Authors: Zhang Yumin , Wang Xigui , Wang Yongmei
Published: January 2023

The expected preloading effect of a hydraulic press frame parts (upper/lower semi-circular beams and columns) with pre-stressed by means of Winding Steel Wires which is directly related to the reliability and normal safe operation of the hydraulic press. The deformation of the Hydraulic Press Column (HPC) is an important indicator of the optimal preloading effect of the hydraulic press. A novelty of this project is to break through a bottleneck technology, the continuous cumulative deformation of a Hydraulic Press Column under seven time-varying steps is critical issues especially in theoretically calculated for a 20 MN double-frame hydraulic press with pre-stressed using WAW. A solid model with a pre-stressed frame is pre-designed by 3D software, and two simulation methods, equivalent pressure loading and equivalent temperature loading, are used to simulate and analyze the continuous cumulative deformation of the HPC under each step in Ansys Workbench software. By comparing the deformation and error analysis in the three cases above, the feasibility of the two simulation methods is verified, which leads to the advantages and disadvantages of each method in order to guide the subsequent design.
Pancreatic enzyme supplementation versus placebo for improvement of gastrointestinal symptoms in non-responsive celiac disease: A cross-over randomized controlled trial
Authors: Yoosuf Shakira , Barrett Caitlin G. , Papamichael Konstantinos , Madoff Sarah E. , Kurada Satya , Hansen Joshua , Silvester Jocelyn A. , Therrien Amelie , Singh Prashant , Dennis Melinda , Leffler Daniel A. , Kelly Ciaran P.
Published: January 2023

Background

Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to treat non-responsive celiac disease (NRCD) in clinical practice, clinical outcomes are variable and there is limited and low quality evidence to support this practice. The aim of this study was to assess the efficacy of pancreatic enzyme supplements (PES) for improvement of gastrointestinal symptoms in NRCD.

Methods

Prospective, randomized, placebo-controlled, double-blind, cross-over trial in adults with NRCD examining Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores on PES (pancrelipase co-administered with omeprazole) versus placebo (omeprazole only) during a 10-day treatment period. The study was registered under the clinical trials registry (https://clinicaltrials.gov/ number, NCT02475369) on 18 Jun 2015.

Results

Twelve participants (nine female) were included in the per-protocol analysis; one participant had low fecal elastase-1. Pancrelipase was not associated with significant change in CeD-GSRS compared to placebo (−0.03 versus −0.26; P = 0.366). There was a significant decrease in mean values of total CeD-GSRS scores (3.58 versus 2.90, P = 0.004), abdominal pain (2.92 versus 2.42, P = 0.009), and diarrhea sub-scores (3.44 versus 2.92, P = 0.037) during the run-in period with omeprazole.

Conclusion

In this prospective, cross-over randomized, placebo-controlled study, PES did not improve symptoms in patients with NRCD. It is unclear whether this is a trial effect or related to administration of omeprazole.
Associations of the distance-saturation product and low-attenuation area percentage in pulmonary computed tomography with acute exacerbation in patients with chronic obstructive pulmonary disease
Authors: Chen Kuan-Yuan , Kuo Hsiao-Yun , Lee Kang-Yun , Feng Po-Hao , Wu Sheng-Ming , Chuang Hsiao-Chi , Chen Tzu-Tao , Sun Wei-Lun , Tseng Chien-Hua , Liu Wen-Te , Cheng Wun-Hao , Majumdar Arnab , Stettler Marc , Tsai Cheng-Yu , Ho Shu-Chuan
Published: January 2023

Background

Chronic obstructive pulmonary disease (COPD) has high global health concerns, and previous research proposed various indicators to predict mortality, such as the distance-saturation product (DSP), derived from the 6-min walk test (6MWT), and the low-attenuation area percentage (LAA%) in pulmonary computed tomographic images. However, the feasibility of using these indicators to evaluate the stability of COPD still remains to be investigated. Associations of the DSP and LAA% with other COPD-related clinical parameters are also unknown. This study, thus, aimed to explore these associations.

Methods

This retrospective study enrolled 111 patients with COPD from northern Taiwan. Individuals’ data we collected included results of a pulmonary function test (PFT), 6MWT, life quality survey [i.e., the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT)], history of acute exacerbation of COPD (AECOPD), and LAA%. Next, the DSP was derived by the distance walked and the lowest oxygen saturation recorded during the 6MWT. In addition, the DSP and clinical phenotype grouping based on clinically significant outcomes by previous study approaches were employed for further investigation (i.e., DSP of 290 m%, LAA% of 20%, and AECOPD frequency of ≥1). Mean comparisons and linear and logistic regression models were utilized to explore associations among the assessed variables.

Results

The low-DSP group (<290 m%) had significantly higher values for the mMRC, CAT, AECOPD frequency, and LAA% at different lung volume scales (total, right, and left), whereas it had lower values of the PFT and 6MWT parameters compared to the high-DSP group. Significant associations (with high odds ratios) were observed of the mMRC, CAT, AECOPD frequency, and PFT with low- and high-DSP groupings. Next, the risk of having AECOPD was associated with the mMRC, CAT, DSP, and LAA% (for the total, right, and left lungs).

Conclusion

A lower value of the DSP was related to a greater worsening of symptoms, more-frequent exacerbations, poorer pulmonary function, and more-severe emphysema (higher LAA%). These readily determined parameters, including the DSP and LAA%, can serve as indicators for assessing the COPD clinical course and may can serve as a guide to corresponding treatments.