bluuebunny/crossref_metadata_2025 huggingface dataset:
Laboratory investigation on short design wave extreme responses for floating hinged-raft wave energy converters
Authors: Jin S. , Brown S. A. , Tosdevin T. , Hann M. R. , Greaves D. M.
Published: November 2022

In offshore renewable energy design procedures, accurate predictions of extreme responses are required in order to design for survivability whilst minimising associated costs. At present, the established method for predicting extreme responses is to conduct a large number of long-duration simulations, which is practical only in cases where the structural behaviour is captured by a computationally efficient linear approach. Many applications, however, will require a nonlinear approach, which significantly increases the computational cost, and hence the time required to analyse a problem. Should high-fidelity numerical approaches be the appropriate analysis tool, the long-duration simulations are likely to be impractical and in many cases infeasible. Laboratory testing can be utilised to address this to some extent, but this still time-consuming and expensive from a financial perspective. Consequently, there has been considerable interest in the use of short design waves as an alternative method for speeding up the design process. Currently, standards advise that short design waves can be utilised in the design of fixed offshore structures, but application to floating offshore structures needs verification before it becomes an established procedure. This study considers application of single and constrained short design waves to a floating hinged-raft wave energy converter using a 1:50 scale physical modelling approach, and compares with equivalent irregular sea states. The single wave approaches considered here are “NewWave” and the “Most Likely Extreme Response” wave, which are derived from the frequency content of the wave spectrum and response spectrum, respectively. The constrained approach considered in this study is the “Conditional Random Response Wave,” where the Most Likely Extreme Response wave is embedded within a random short irregular background. Results show that the single wave approaches under-estimate the extreme loading for the hinge-angle and mooring system compared with the irregular and constrained approaches. The discrepancy between single and constrained waves implies that memory effects are non-negligible, and hence it is critical that they are accounted for when utilising short design waves for floating applications.
Strategy of micro-environmental adaptation to cold seep among different brittle stars’ colonization
Authors: Chen Zelin , Ma Shaobo , Qin Geng , Qu Meng , Zhang Bo , Lin Qiang
Published: November 2022

Diffusing fluid from methane seepage in cold seep field creates zones with physicochemical gradients and divergent ecosystems like the mussel beds and clam beds. Three species of brittle stars (Ophiuroidea) were discovered in the Haima cold seep fields, of which Ophiophthalmus serratus and Histampica haimaensis were found on top of or within mussel beds and clam beds, whereas Amphiura sp. was only collected from muds in the clam bed assemblage. Here, we evaluated the genetic signatures of micro-environmental adaptation of brittle stars to cold seep through the comparison of mitogenomes. This study provided two complete mitogenome sequences of O. serratus and Amphiura sp. and compared with those of H. haimaensis and other non-seep species. We found that the split events of the seep and non-seep species were as ancient as the Cretaceous period (∼148–98 Mya). O. serratus and H. haimaensis display rapid residue mutation and mitogenome rearrangements compared to their shallow or deep-sea relatives, in contrast, Amphiura sp. only show medium, regardless of nucleotide mutation rate or mitogenome rearrangement, which may correlate with their adaptation to one or two micro-ecosystems. Furthermore, we identified 10 positively selected residues in ND4 in the Amphiura sp. lineage, suggesting important roles of the dehydrogenase complex in Amphiura sp. adaptive to the cold seep environment. Our results shed light on the different evolutionary strategies during colonization in different micro-environments.
Characterization of immune microenvironment infiltration and m6A regulator-mediated RNA methylation modification patterns in osteoarthritis
Authors: Ouyang Yulong , Tu Yuanqing , Chen Shuilin , Min Huan , Wen Zhexu , Zheng Guihao , Wan Ting , Fan Hao , Yang Wenzhao , Sun Guicai
Published: November 2022

Background

Few studies have been reported the potential role of N6-methyladenosine (m6A) modification in osteoarthritis (OA). We investigated the patterns of m6A modification in the immune microenvironment of OA.

Methods

We evaluated the m6A modification patterns based on 22 m6A regulators in 139 OA samples and systematically associated these modification patterns with immune cell infiltration characteristics. The function of m6A phenotype-related differentially expressed genes (DEGs) was investigated using gene enrichment analysis. An m6A score model was constructed using principal component analysis (PCA), and an OA prediction model was established based on the key m6A regulators. We used real-time PCR analysis to detect the changes of gene expression in the cell model of OA.

Results

Healthy and OA samples showed significant differences in the expression of m6A regulators. Nine key m6A regulators, two m6A modification patterns, m6A-related genes and two gene clusters were identified. Some m6A regulators had a strong correlation with each other. Gene clusters and m6A clusters have high similarity, and cluster A corresponds to a high m6A score. Immunocytes infiltration differed significantly between the two clusters, with the m6A cluster B and gene cluster B having more types of infiltrating immunocytes than cluster A. The predictive model can also predict the progression of OA through m6A regulators expression. The results of real-time PCR analysis showed that the gene expression in the cell model of OA is similar to that of the m6A cluster B.

Conclusions

Our study reveals for the first time the potential regulatory mechanism of m6A modification in the immune microenvironment of OA. This study also sheds new light on the pathogenesis of OA.
An EGFR L858R mutation identified in 1862 Chinese NSCLC patients can be a promising neoantigen vaccine therapeutic strategy
Authors: Lin Jing , Liu Jun , Hao Shi-guang , Lan Bin , Zheng Xiao-bin , Xiong Jia-ni , Zhang Ying-qian , Gao Xuan , Chen Chuan-ben , Chen Ling , Huang Yu-fang , Luo Hong , Yi Yu-ting , Yi Xin , Lu Jian-ping , Zheng Xiong-wei , Chen Gang , Wang Xue-feng , Chen Yu
Published: November 2022

Background

This study aimed to develop a vaccine that targets mutation-derived neoantigen in Chinese non-small-cell lung cancer (NSCLC).

Methods

A cohort of 1862 Chinese NSCLC patients who underwent targeted sequencing with a 1021-gene panel was investigated. HLA typing was done using OptiType v1.0 and neoantigens were predicted by netMHCpan v4.0. HLA LOH was inferred using the lohhla algorithm and TMB were quantified by counting the total number of non-synonymous ones based on our panel data. CIBERSORT was utilized to estimate the TME in different EGFR mutant subtype by using TCGA data.

Results

HLA-A*11:01(42.59%) was the top one allele and HLA-A*33:03(12.94%) ranked 12th. EGFR L858R (22.61%) was the most prevalent gene variant. The binding affinity (IC50 MT = 22.9 nM) and shared frequency (2.93%) of EGFR L858R in combination with HLA-A*33:03 were optimal. In a subsequent further analysis on immunological features of EGFR mutant subtypes, 63.1% HLA loss of heterozygosity LOH (HLA LOH) and 0.37% (7 of 1862) B2M aberrations were found in our population, both had no significant association with EGFR mutant subtypes suggesting that the process of antigen presentation involved HLA LOH and B2M mechanisms in EGFR L858R is working. Tumor mutation burden (TMB) was investigated by utilizing our panel and showed that EGFR L858R had the lowest TMB compared with other EGFR mutant subtypes. In addition, analysis of 22 immune cell types from The Cancer Genome Atlas (TCGA) data showed EGFR L858R was correlated with low level of CD8 T cells, activated CD4 memory T cells and elevated level of macrophage M2 suggesting an inhibited tumor microenvironment (TME).

Conclusion

Our study identified that EGFR L858R neoantigen had the potential to generate cancer vaccines in NSCLC patients with HLA A*33:03. The neoantigen-based vaccines may become an effective salvage regimen for EGFR L858R subgroup after targeted therapy or immune checkpoint inhibitors (ICIs) failure.
Case report: Camrelizumab associated with central retinal vein occlusion
Authors: Zhan Yixiang , Zhao Weipeng , Ni Kemin , Liu Zhaoce , Su Yanjun , Li Xichuan , Zhang Heng , Zhang Chunze
Published: November 2022

Immunotherapy has revolutionized cancer treatment and become one of the five pillars of cancer therapy. The clinical applications of immunotherapy have been adapted to range from the management of melanoma to most tumor types. As the clinical applications of cancer immunotherapies expand, understanding the treatment-related adverse events of these drugs becomes critical in clinical practice. We report a rare case of ocular immune-related side effects associated with camrelizumab that resulted in vision loss. A 56-year-old male patient was diagnosed with small cell lung cancer. The tumor involved the porta pulmonis and mediastinum upon initial diagnosis; therefore, surgery was not possible. Upon receiving the 10th immunotherapy session with camrelizumab 200 mg, the patient’s visual acuity began to decrease in his right eye and a central retinal vein occlusion. Optical coherence tomography revealed significant cystoid exudation in the macular area and vitreous hemorrhage. The patient underwent vitrectomy, phacoemulsification and intraocular lens implantation after symptom onset. Following surgery, the patient’s vision was limitedly restored. This is the first clinical report in China of central retinal vein occlusion and vitreous hemorrhage associated with anti-PD-1 therapy, ultimately leading to blindness. Although rare, clinical practitioners should be concerned about ocular adverse events associated with anti-PD-1 immunotherapy and develop a high index of suspicion for this possibility since ophthalmic manifestations that are rapidly detected, closely monitored, and appropriately managed are treatable.
Inflammation and immune cell abnormalities in intracranial aneurysm subarachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies
Authors: Jin Jing , Duan Jian , Du Leiya , Xing Wenli , Peng Xingchen , Zhao Qijie
Published: November 2022

Intracranial aneurysm subarachnoid hemorrhage (SAH) is a cerebrovascular disorder associated with high overall mortality. Currently, the underlying mechanisms of pathological reaction after aneurysm rupture are still unclear, especially in the immune microenvironment, inflammation, and relevant signaling pathways. SAH-induced immune cell population alteration, immune inflammatory signaling pathway activation, and active substance generation are associated with pro-inflammatory cytokines, immunosuppression, and brain injury. Crosstalk between immune disorders and hyperactivation of inflammatory signals aggravated the devastating consequences of brain injury and cerebral vasospasm and increased the risk of infection. In this review, we discussed the role of inflammation and immune cell responses in the occurrence and development of aneurysm SAH, as well as the most relevant immune inflammatory signaling pathways [PI3K/Akt, extracellular signal-regulated kinase (ERK), hypoxia-inducible factor-1α (HIF-1α), STAT, SIRT, mammalian target of rapamycin (mTOR), NLRP3, TLR4/nuclear factor-κB (NF-κB), and Keap1/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/ARE cascades] and biomarkers in aneurysm SAH. In addition, we also summarized potential therapeutic drugs targeting the aneurysm SAH immune inflammatory responses, such as nimodipine, dexmedetomidine (DEX), fingolimod, and genomic variation-related aneurysm prophylactic agent sunitinib. The intervention of immune inflammatory responses and immune microenvironment significantly reduces the secondary brain injury, thereby improving the prognosis of patients admitted to SAH. Future studies should focus on exploring potential immune inflammatory mechanisms and developing additional therapeutic strategies for precise aneurysm SAH immune inflammatory regulation and genomic variants associated with aneurysm formation.
Integrated bioinformatic analysis identified a novel prognostic pan-programmed cell death signature for bladder cancer
Authors: Zhang Lusi , Peng Mou
Published: November 2022

Programmed cell death (PCD) refers to a molecularly regulated form of cell death that functions as an essential anticancer defense mechanism and serves as a target of anticancer therapies. Multiple types of PCD comprehensively regulate tumorigenesis and tumor progression and metastasis. However, a systemic exploration of the multiple types of PCD in cancers, especially bladder cancer, is lacking. In this study, we evaluated the expression pattern of genes associated with multiple types of PCD in bladder cancer using the “ssGSEA” method and conceptualized the multiple types of PCD as being collectively involved in “Pan-PCD”. Based on the differentially expressed genes related to Pan-PCD, we developed a Pan-PCD-related prognostic signature (PPRPS) to predict patient prognosis via univariate and multivariate Cox regression analysis. The PPRPS is an independent prognostic factor, and the AUC (Area Under Curve) for 3-year overall survival was 0.748. Combined with age and stage, PPRPS displayed excellent predictive ability. Based on the PPRPS, higher levels of immune cell infiltration, tumor microenvironment, and immune checkpoint molecules were observed in the high-PPRPS group. Furthermore, PPRPS enabled accurate risk prediction for metastatic urothelial carcinoma after anti-PD-L1 monoclonal antibody treatment. Patients in the high-PPRPS group had poor prognoses. Docetaxel, staurosporine, and luminespib were identified as potentially effective drugs for high-PPRPS bladder cancer patients. In summary, we developed the Pan-PCD signature to improve the accuracy of bladder cancer prognostic predictions and to provide a novel classification method to guide treatment selection.
Hemocytes and fat body cells, the only professional immune cell types in Drosophila, show strikingly different responses to systemic infections
Authors: Vaibhvi Vaibhvi , Künzel Sven , Roeder Thomas
Published: November 2022

The fruit fly Drosophila is an excellent model to study the response of different immunocompetent organs during systemic infection. In the present study, we intended to test the hypothesis that the only professional immune organs of the fly, the fat body and hemocytes, show substantial similarities in their responses to systemic infection. However, comprehensive transcriptome analysis of isolated organs revealed highly divergent transcript signatures, with the few commonly regulated genes encoding mainly classical immune effectors from the antimicrobial peptide family. The fat body and the hemocytes each have specific reactions that are not present in the other organ. Fat body-specific responses comprised those enabling an improved peptide synthesis and export. This reaction is accompanied by transcriptomic shifts enabling the use of the energy resources of the fat body more efficiently. Hemocytes, on the other hand, showed enhanced signatures related to phagocytosis. Comparing immune-induced signatures of both cell types with those of whole-body responses showed only a minimal correspondence, mostly restricted again to antimicrobial peptide genes. In summary, the two major immunocompetent cell types of Drosophila show highly specific responses to infection, which are closely linked to the primary function of the respective organ in the landscape of the systemic immune response.
Tolerogenic dendritic cells pulsed with islet antigen induce long-term reduction in T-cell autoreactivity in type 1 diabetes patients
Authors: Nikolic Tatjana , Suwandi Jessica S. , Wesselius Joris , Laban Sandra , Joosten Antoinette M. , Sonneveld Petra , Mul Dick , Aanstoot Henk-Jan , Kaddis John S. , Zwaginga Jaap Jan , Roep Bart O.
Published: November 2022

Introduction

Restoration of immune tolerance may halt progression of autoimmune diseases. Tolerogenic dendritic cells (tolDC) inhibit antigen-specific proinflammatory T-cells, generate antigen-specific regulatory T-cells and promote IL-10 production in-vitro, providing an appealing immunotherapy to intervene in autoimmune disease progression.

Methods

A placebo-controlled, dose escalation phase 1 clinical trial in nine adult patients with long-standing type 1 diabetes (T1D) demonstrated the safety and feasibility of two (prime-boost) vaccinations with tolDC pulsed with a proinsulin peptide. Immunoregulatory effects were monitored by antigen-specific T-cell assays and flow and mass cytometry.

Results

The tolDC vaccine induced a profound and durable decline in pre-existing autoimmune responses to the vaccine peptide up to 3 years after therapy and temporary decline in CD4 and CD8+ T-cell responses to other islet autoantigens. While major leukocyte subsets remained stable, ICOS+CCR4+TIGIT+ Tregs and CD103+ tissue-resident and CCR6+ effector memory CD4+ T-cells increased in response to the first tolDC injection, the latter declining thereafter below baseline levels.

Discussion

Our data identify immune correlates of mechanistic efficacy of intradermally injected tolDC reducing proinsulin autoimmunity in T1D.
Multi-component prime-boost Chlamydia trachomatis vaccination regimes induce antibody and T cell responses and accelerate clearance of infection in a non-human primate model
Authors: Lorenzen Emma , Contreras Vanessa , Olsen Anja W. , Andersen Peter , Desjardins Delphine , Rosenkrands Ida , Juel Helene Bæk , Delache Benoit , Langlois Sebastien , Delaugerre Constance , Joubert Christophe , Dereuddre-Bosquet Nathalie , Bébéar Cécile , De Barbeyrac Bertille , Touati Arabella , McKay Paul F. , Shattock Robin J. , Le Grand Roger , Follmann Frank , Dietrich Jes
Published: November 2022

It is of international priority to develop a vaccine against sexually transmittedChlamydia trachomatisinfections to combat the continued global spread of the infection. The optimal immunization strategy still remains to be fully elucidated. The aim of this study was to evaluate immunization strategies in a nonhuman primate (NHP) model. Cynomolgus macaques (Macaqua fascicularis) were immunized following different multi-component prime-boost immunization-schedules and subsequently challenged withC. trachomatisSvD in the lower genital tract. The immunization antigens included the recombinant protein antigen CTH522 adjuvanted with CAF01 or aluminium hydroxide, MOMP DNA antigen and MOMP vector antigens (HuAd5 MOMP and MVA MOMP). All antigen constructs were highly immunogenic raising significant systemicC. trachomatis-specific IgG responses. In particularly the CTH522 protein vaccinated groups raised a fast and strong pecificsIgG in serum. The mapping of specific B cell epitopes within the MOMP showed that all vaccinated groups, recognized epitopes near or within the variable domains (VD) of MOMP, with a consistent VD4 response in all animals. Furthermore, serum from all vaccinated groups were able toin vitroneutralize both SvD, SvE and SvF. Antibody responses were reflected on the vaginal and ocular mucosa, which showed detectable levels of IgG. Vaccines also inducedC. trachomatis-specific cell mediated responses, as shown byin vitrostimulation and intracellular cytokine staining of peripheral blood mononuclear cells (PBMCs). In general, the protein (CTH522) vaccinated groups established a multifunctional CD4 T cell response, whereas the DNA and Vector vaccinated groups also established a CD8 T cells response. Following vaginal challenge withC. trachomatisSvD, several of the vaccinated groups showed accelerated clearance of the infection, but especially the DNA group, boosted with CAF01 adjuvanted CTH522 to achieve a balanced CD4/CD8 T cell response combined with an IgG response, showed accelerated clearance of the infection.
Standardization of neutrophil CD64 and monocyte HLA-DR measurement and its application in immune monitoring in kidney transplantation
Authors: Peng Bo , Yang Min , Zhuang Quan , Li Junhui , Zhang Pengpeng , Liu Hong , Cheng Ke , Ming Yingzi
Published: November 2022

Background

Infections cause high mortality in kidney transplant recipients (KTRs). The expressions of neutrophil CD64 (nCD64) and monocyte HLA-DR (mHLA-DR) provide direct evidence of immune status and can be used to evaluate the severity of infection. However, the intensities of nCD64 and mHLA-DR detected by flow cytometry (FCM) are commonly measured by mean fluorescence intensities (MFIs), which are relative values, thus limiting their application. We aimed to standardize nCD64 and mHLA-DR expression using molecules of equivalent soluble fluorochrome (MESF) and to explore their role in immune monitoring for KTRs with infection.

Methods

The study included 50 KTRs diagnosed with infection, 65 immunologically stable KTRs and 26 healthy controls. The blood samples were collected and measured simultaneously by four FCM protocols at different flow cytometers. The MFIs of nCD64 and mHLA-DR were converted into MESF by Phycoerythrin (PE) Fluorescence Quantitation Kit. The intraclass correlation coefficients (ICCs) and the Bland-Altman plots were used to evaluate the reliability between the four FCM protocols. MESFs of nCD64 and mHLA-DR, nCD64 index and sepsis index (SI) with the TBNK panel were used to evaluate the immune status. Comparisons among multiple groups were performed with ANOVA one-way analysis. Receiver operating characteristics (ROC) curve analysis was performed to diagnose infection or sepsis. Univariate and multivariate logistic analysis examined associations of the immune status with infection.

Results

MESFs of nCD64 and mHLA-DR measured by four protocols had excellent reliability (ICCs 0.993 and 0.957, respectively). The nCD64, CD64 index and SI in infection group were significantly higher than those of stable KTRs group. Patients with sepsis had lower mHLA-DR but higher SI than non-sepsis patients. ROC analysis indicated that nCD64 had the highest area under the curve (AUC) for infection, and that mHLA-DR had the highest AUC for sepsis. Logistic analysis indicated that nCD64 > 3089 and B cells counts were independent risk factors for infection.

Conclusion

The standardization of nCD64 and mHLA-DR made it available for widespread application. MESFs of nCD64 and mHLA-DR had good diagnostic performance on infection and sepsis, respectively, which could be promising indicators for immune status of KTRs and contributed to individualized treatment.
Case report: Optimized ruxolitinib-based therapy in an infant with familial hemophagocytic lymphohistiocytosis type 3
Authors: Niizato Daiki , Isoda Takeshi , Mitsuiki Noriko , Kaneko Shuya , Tomomasa Dan , Kamiya Takahiro , Takagi Masatoshi , Imai Kohsuke , Kajiwara Michiko , Shimizu Masaki , Morio Tomohiro , Kanegane Hirokazu
Published: November 2022

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare and fatal autosomal recessive immune disorder characterized by uncontrolled activation of T and NK cells, macrophages, and overproduction of inflammatory cytokines. Early hematopoietic cell transplantation (HCT) is required for long-term survival. Current therapy is based on the HLH-94/2004 protocol, but is insufficient to fully control disease activity. This case report describes an infant with FHL type 3 who, despite initial therapy with dexamethasone and etoposide, showed aberrant cytokine levels, including interleukin-18 (IL-18), chemokine ligand 9 (CXCL9), soluble interleukin-2 receptor (sIL-2R), and soluble tumor necrosis factor receptor type II (sTNF-RII). The Janus kinase inhibitor ruxolitinib was therefore coadministered. The patient was treated with dose-adjusted ruxolitinib guided by cytokine profiles, and was successfully prepared for HCT. The results demonstrate the effectiveness and safety of dose-adjusted ruxolitinib as a bridging therapy for FHL, and the value of monitoring cytokine levels, especially IL-18, CXCL9, sIL-2R, and sTNF-RII, as disease-activity markers for FHL.
Chitosan particle stabilized Pickering emulsion/interleukin-12 adjuvant system for Pgp3 subunit vaccine elicits immune protection against genital chlamydial infection in mice
Authors: Shu Mingyi , Zhao Lanhua , Shi Keliang , Lei Wenbo , Yang Yewei , Li Zhongyu
Published: November 2022

Considering the shortcomings in current chlamydia infection control strategies, a major challenge in curtailing infection is the implementation of an effective vaccine. The immune response induced byC. trachomatisplasmid encoded Pgp3 was insufficient againstC. trachomatisinfection, which requires adjuvant applications to achieve the robust immune response induced by Pgp3. There is increasing promising in developing adjuvant systems relying on the delivery potential of Pickering emulsions and the immunomodulatory effects of interleukin (IL)-12. Here, owing to the polycationic nature, chitosan particles tended to absorb on the oil/water interphase to prepare the optimized chitosan particle-stabilized Pickering emulsion (CSPE), which was designed as a delivery system for Pgp3 protein and IL-12. Our results showed that the average droplets size of CSPE was 789.47 ± 44.26 nm after a series of optimizations and about 90% antigens may be absorbed by CSPE owing to the positively charged surface (33.2 ± 3mV), and CSPE promoted FITC-BSA proteins uptake by macrophages. Furthermore, as demonstrated by Pgp3-specific antibody production and cytokine secretion, CSPE/IL-12 system enhanced significantly higher levels of Pgp3-specific IgG, IgG1, IgG2a, sIgA and significant cytokines secretion of IFN-γ, IL-2, TNF-α, IL-4. Similarly, vaginal chlamydial shedding and hydrosalpinx pathologies were markedly reduced in mice immunized with Pgp3/CSPE/IL-12. Collectively, vaccination with Pgp3/CSPE/IL-12 regimen elicited robust cellular and humoral immune response in mice resulting in an obvious reduction of live chlamydia load in the vaginal and inflammatory pathologies in the oviduct, which further propells the development of vaccines againstC. trachomatisinfection.
Agouti overexpression in a transgenic model regulates integrity, permeability and electrogenic amino acid transport in zebrafish intestine
Authors: Leal Esther , Angotzi Anna Rita , Godino-Gimeno Alejandra , Gregório Silvia F. , Rotllant Josep , Saera-Vila Alfonso , Fuentes Juan , Cerdá-Reverter José Miguel
Published: November 2022

Overexpression of asip1 in transgenic zebrafish disrupts dorsoventral pigment pattern in addition to increasing food intake levels and linear growth. A higher feed intake is unnecessary in transgenic fish to enable larger and heavier growth. A plausible explanation may rely on the enhanced feeding efficiency mediated by improved nutrient absorption in transgenic animals. To test this hypothesis, wide scope transcriptomic techniques were used to elucidate the potential pathways involved in the enhanced nutrient absorption and intestinal epithelium permeability/integrity. In addition, the electrogenic capacity for amino acid transport was analysed. Transcriptomic analysis reveal that amino acid, monocarboxylates, ionic and vitamin transmembrane transporters were substantially modified. Enrichment analysis also revealed an inhibition of intestinal lipid metabolism and down-regulation of KEGG pathways related to membrane integrity suggesting augmented intestinal laxity that may enhance paracellular transport. Electrophysiological experiments carried out in Ussing chambers show that asip1 overexpression decrease membraned tissue resistance (Rt), indicating a modification of the intestinal barrier function in ASIP1 transgenic animals. Similarly, paracellular permeability was higher in transgenic zebrafish. Both the decrease in Rt and the increase in permeability point to an ASIP1-dependent decrease in the tissue barrier function. Electrogenic amino acid transport was also enhanced in transgenic animals providing strong indication that ASIP1 fish can extract more amino acids from their diet at similar feeding levels. Both transcriptomic and electrophysiological results suggest that asip1-overexpressing zebrafish display improved nutrient absorption and by extension a higher feed efficiency which explains enhanced growth in the absence of augmented food intake. The enhanced growth of ASIP1 zebrafish potentially mediated by improved nutrient uptake and feed efficiency suggests that the melanocortin system, specifically asip1 overexpression, is a potential target for the development of genetically engineered fish displaying improved performance and no differential lipid accumulation.
Determining the drift characteristics of open lifeboats based on large-scale drift experiments
Authors: Tu Haiwen , Mu Lin , Xia Kai , Wang Xiaodi , Zhu Kui
Published: November 2022

Lifeboat is one of the most important life-saving equipment for escaping at sea when a ship is abandoned in an extreme emergency. An accurate drift model can help rescuers find the drift position of lifeboat in the shortest time, thus improving the efficiency of marine search and rescue (SAR) at sea and ensuring the safety of wrecked people. The purpose of this paper is to investigate the drift characteristics and to develop an accurate drift prediction model for the open lifeboat. First, large-scale drift experiments were conducted to analyze the drift characteristics with three 6.5-meter-long real-size open lifeboats in the South China Sea. Next, three drift prediction models of the lifeboats were developed using the least squares method based on the drift experimental data. Finally, the drift prediction models of the lifeboats were compared and evaluated using the Lagrangian method and Monte Carlo technique, respectively. Results indicate that the probability of positive crosswind leeway (CWL) of the open lifeboat is 47.5%. The jibing frequency is 6% per hour, and the maximum leeway divergence angle is 45°. These drift characteristics are very important for the prediction of the open lifeboat drift trajectory. The comparison results of three drift models show that the improved drift model is more accurate than the other two drift models for predicting drift trajectories of the open lifeboat, which can be directly applied to maritime search and rescue operations in the South China Sea.
Fish surveys on the move: Adapting automated fish detection and classification frameworks for videos on a remotely operated vehicle in shallow marine waters
Authors: Connolly Rod M. , Jinks Kristin I. , Herrera Cesar , Lopez-Marcano Sebastian
Published: November 2022

Mobile underwater cameras, diver-operated or on underwater vehicles, have become popular for monitoring fisheries. Replacing divers with cameras has clear advantages, such as creating permanent records and accessing waters unavailable to divers. The use of cameras, however, typically produces large quantities of video that are time-consuming to process manually. Automated analysis of underwater videos from stationary cameras using deep learning techniques has advanced considerably in recent years, but the use of mobile cameras potentially raises new challenges for existing methods. We tested how well three automation procedures for stationary underwater cameras, taking an object-centric rather than background-centric approach, performed on surveys of fish using a mobile camera. We analyzed underwear drone videos from reef and seagrass habitat to detect and count two marine fisheries species, luderick (Girella tricuspidata) and yellowfin bream (Acanthopagrus australis). Three convolutional neural network (CNN) frameworks were compared: Detectron Faster R-CNN, Detectron2 Faster R-CNN (using a Regional Proposal Network, RPN), and YOLOv5 (a single-stage detector, SSD). Models performed well overall. Per frame, overall F1 scores ranged 81.4 - 87.3%, precision 88.2 – 96.0%, and recall 73.2 - 88.2%. For quantifying MaxN per video, overall F1 ranged 85.9 – 91.4%, precision 81.9 – 95.3%, and recall 87.1 – 91.1%. For luderick, F1 was > 80% for all frameworks per frame and 89% or higher for MaxN. For yellowfin bream, F1 scores were lower (35.0 - 73.8% for frames, 43.4 - 73.0% for MaxN). Detectron2 performed poorly, and YOLOv5 and Detectron performed similarly with advantages depending on metrics and species. For these two frameworks, performance was as good as in videos from stationary cameras. Our findings show that object detection technology is very useful for extracting fish data from mobile underwater cameras for the system tested here. There is a need now to test performance over a wider range of environments to produce generalizable models. The key steps required area to test and enhance performance: 1. for suites of species in the same habitats with different water clarity, 2. in other coastal environments, 3. trialing cameras moving at different speeds, and 4. using different frame-rates.
Seagrasses benefit from mild anthropogenic nutrient additions
Authors: Vieira Vasco M. N. C. S. , Lobo-Arteaga Jorge , Santos Rafael , Leitão-Silva David , Veronez Arthur , Neves Joana M. , Nogueira Marta , Creed Joel C. , Bertelli Chiara M. , Samper-Villarreal Jimena , Pettersen Mats R. S.
Published: November 2022

Seagrasses are declining globally, in large part due to increased anthropogenic coastal nutrient loads that enhance smothering by macroalgae, attenuate light, and are toxic when in excessive concentrations of inorganic nitrogen and phosphorus. However, as sanitation is improved many seagrass meadows have been observed to recover, with a few studies suggesting that they may even benefit from mild anthropogenic nutrient additions. Monitoring seagrass demography and health has faced difficulties in establishing the adequate variables and metrics. Such uncertainty in the methods has caused uncertainty of the significance of results presented and compromised extrapolations to other seasons, areas, or species. One solution has come from within the plant self-thinning theories. During the 1980s, an interspecific boundary line (IBL) was determined as the upper limit of the combination of plant density and above-ground biomass for any stand on Earth, setting their maximum possible efficiency in space occupation. Recently, two meta-analyses to determine specific IBLs for algae and for seagrasses have been performed. The recently updated seagrass dataset comprises 5,052 observations from 78 studies on 18 species. These IBLs opened new perspectives for monitoring: the observed distance of a stand to the respective IBL (i.e., each stand’s relative efficiency of space occupation) was demonstrated to be a valuable indicator of a population’s health. Thus, this metric can be used to determine the impact of nutrients and pollutants on algae and seagrass populations. Furthermore, because the IBLs are common to all species, they may be used to compare all species from any location worldwide. This novel approach showed that Halodule wrightii, Halodule beaudettei, Halophila baillonii, Zostera marina, and Zostera noltei meadows benefit from anthropogenic additions of nitrogen and phosphorus, as long as these additions are moderate. In fact, the healthier Z. noltei meadows in Portugal (and among the healthiest meadows worldwide) were the ones exposed to effluents from wastewater treatment plants (WWTP) and a food factory. We conclude that those effluents are providing water with enough quality and that their optimal management should coordinate the technological solutions of the WWTP with the natural potential of seagrass meadows as water purifiers and biomass producers.
Biophysical controls on spatial and summer/winter distributions of total and chromophoric dissolved organic matter in the Taiwan Strait
Authors: Hung Jia-Jang , Lu Wan-Tzu , Yang Hsin-Mei , Lin Yen-Hui , Guo Laodong
Published: November 2022

This study examined the physical and biogeochemical processes that determine the spatial and summer/winter distributions of dissolved organic matter (DOM) and chromophoric dissolved organic matter (CDOM) in the Taiwan Strait (TS). The hydrological conditions in the TS varied between early summer and winter because of differences in terrestrial input as well as input from the poleward South China Sea Water (SCSW) during the warm summer and the strong, nutrient-rich, equatorward China Coastal Water (CCW) in winter. Concentrations of dissolved organic carbon (DOC) ranged from 60 to 100 μM-C in early summer and from 70 to 144 μM-C in winter. The average stoichiometric ratio of DOC : DON:DOP was high (353:49:1) in the land-source impacted zones and low (168:21:1) in the SCSW-laden areas, both of which are higher than the Redfield ratio. The concentrations of DOC and nutrients were higher in the western TS (on the coast of China) than in the eastern TS (on the coast of Taiwan), and the highest concentrations were mostly found in the Minjiang River plume, reflecting the profound effects of freshwater input in early summer and CCW inflow in winter. The absorption and emission characteristics of the CDOM varied to a large extent with locations because of the mixing of the shelf water with different source waters. Although the absorption coefficient (aCDOM(325)) and fluorescence intensity of the terrestrial humic-like CDOM (Ft: Ex/Em= 260/400-460) were both strongly inversely correlated with salinity, as an optical tracer, Ft may be more effective than aCDOM(325) in examining the mixing among source waters, given that aCDOM(325) may be subject to various photobleaching effects in the TS. Ft was also significantly correlated with the concentrations of terrestrially derived nitrate and nitrite (N+N) and silicate. The results of factor analysis elucidated the complexity of the hydrological and biological processes that affect the distributions of DOM and CDOM in the TS.
The effect of basalt fiber addition on cement concrete: A review focused on basalt fiber shotcrete
Authors: Liu Qianqian , Song Pengfei , Li Lianwei , Wang Yuzhong , Wang Xuhao , Fang Jian
Published: November 2022

Basalt fiber, as a natural silicate fiber, has excellent engineering performance in high and low temperature resistance, high fracture strength, toughness, shear and elastic modulus in nature. Shotcrete was widely used in tunnel lining, slope support, coal mine roadway and other projects. With the continuous development of shotcrete technology, scholars found that adding fiber to shotcrete would greatly improve the performance of shotcrete. Compared with traditional plain shotcrete and steel fiber shotcrete, shotcrete incorporated with basalt fiber can dramatically improve the bending resistance, toughness and durability, therefore effectively improving the engineering performance of concrete structure, such as lining support. This paper summarized and discussed the mechanical properties, early age performance, durability and practical applications of basalt fiber reinforced concrete with a focus on basalt fiber shotcrete (BFSC). Meanwhile, it focused on the engineering performance improvement and enhancement mechanisms of basalt fiber as a mineral admixture into shotcrete, and assessed the deficiencies existing in the current research. Eventually, the suggestions and prospects for future BFSC related research were proposed.
Health self-perception is associated with life-styles and comorbidities and its effect on mortality is confounded by age. A population based study
Authors: Rañó-Santamaría Oscar , Fernandez-Merino Carmen , Castaño-Carou Ana Isabel , Lado-Baleato Óscar , Fernández-Domínguez María José , Sanchez-Castro Juan Jose , Gude Francisco
Published: November 2022

Background

Health self-perception (HSP) is the individual and subjective concept that a person has of their state of health. Despite its simplicity, HSP is considered a valid and relevant indicator employed in epidemiological research and in professional practice as an overall measure of health.

Objectives

(1) To describe and analyze the associations between HSP and demographic variables, lifestyle and diseases prevalent in a population and (2) to investigate the relationship between HSP and mortality.

Materials and methods

In a primary care setting, we conducted a longitudinal study of a random populational sample of a Galician municipality, stratified by decade of life. A total of 1,516 adults older than 18 years, recruited by the 2013–2015 AEGIS study, were followed-up for more than 5 years. During the clinical interview, data were collected on lifestyle and prevalent diseases. The HSP was grouped into 2 categories (good/poor). The statistical analysis consisted of a logistic regression, Kaplan–Meier curves and Cox regression.

Results

A total of 540 (35.6%) participants reported poor HSP. At the end of the follow-up, 78 participants had died (5.1%). The participants with increased age and body mass index and chronic diseases (anxiety, depression, ischemic heart disease, diabetes, and cancer) presented a poorer subjective health. A high level of physical activity and moderate alcohol consumption were associated with better HSP. A poorer HSP was associated with increased mortality, an association that disappeared after adjusting for the rest of the covariates (HR, 0.82; 95% CI 0.50–1.33).

Conclusion

(1) Health self-perception is associated with age, lifestyle, and certain prevalent diseases. (2) A poorer HSP is associated with increased mortality, but this predictive capacity disappeared after adjusting for potential confounders such as age, lifestyle, and prevalent diseases.
Trends in Helicobacter pylori-related gastric ulcer research from 2012 to 2022: A bibliometric and visual analysis
Authors: Yu Chang , Qiu Jingyue , Xiong Meng , Ou Chen , Zeng Meiyan , Song Houpan
Published: November 2022

Background

Helicobacter pylori-related gastric ulcer (H. pylori-related GU) is one of the most common digestive system diseases that have received widespread attention from researchers. The purpose of this article was to analyze the research status and hotspots of H. pylori-related GU and to predict its future research directions.

Methods

The article and review papers associated with H. pylori-related GU published from 2012 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The analysis of knowledge maps and bibliometrics was done with CiteSpace 6.1.R2 Basic and VOSviewer 1.6.18.

Results

A total of 2,971 articles were included in the study. Between 2012 and 2022, the number of papers published showed an increasing trend. China was the most prolific country, and the United States was the most influential country. Baylor College of Medicine had the largest number of publications and citations among publishing agencies. World Journal of Gastroenterology published the most articles on the H. pylori-related GU field, and GUT was the journal with the most cited articles. Yamaoka Y from Japan was the most productive author, and Graham DY from the USA was the most influential author. A keyword and reference analysis showed that the hot topics of research were the mechanism of H. pylori and the treatment of H. pylori-related GU. The keywords that emerged in the recent 5 years were oxidative stress, probiotics, competitive acid blocker, vonoprazan, gut microbiota, and neutrophil-activating protein.

Conclusion

Over the recent 10 years, research on H. pylori-related GU has generally shown an increasing trend. The treatment and pathogenesis of H. pylori-related GU remain a hot topic of research. The treatment of H. pylori by oxidative stress and competitive acid inhibitor mechanisms, the influence of gastrointestinal flora on H. pylori, probiotic adjuvant therapy of H. pylori-related GU, and the immunoprotective effect of neutrophil activator protein could be popular research directions and trends in the future.
Predicting COVID-19 progression in hospitalized patients in Belgium from a multi-state model
Authors: Mertens Elly , Serrien Ben , Vandromme Mathil , Peñalvo José L.
Published: November 2022

Objectives

To adopt a multi-state risk prediction model for critical disease/mortality outcomes among hospitalised COVID-19 patients using nationwide COVID-19 hospital surveillance data in Belgium.

Materials and methods

Information on 44,659 COVID-19 patients hospitalised between March 2020 and June 2021 with complete data on disease outcomes and candidate predictors was used to adopt a multi-state, multivariate Cox model to predict patients’ probability of recovery, critical [transfer to intensive care units (ICU)] or fatal outcomes during hospital stay.

Results

Median length of hospital stay was 9 days (interquartile range: 5–14). After admission, approximately 82% of the COVID-19 patients were discharged alive, 15% of patients were admitted to ICU, and 15% died in the hospital. The main predictors of an increased probability for recovery were younger age, and to a lesser extent, a lower number of prevalent comorbidities. A patient’s transition to ICU or in-hospital death had in common the following predictors: high levels of c-reactive protein (CRP) and lactate dehydrogenase (LDH), reporting lower respiratory complaints and male sex. Additionally predictors for a transfer to ICU included middle-age, obesity and reporting loss of appetite and staying at a university hospital, while advanced age and a higher number of prevalent comorbidities for in-hospital death. After ICU, younger age and low levels of CRP and LDH were the main predictors for recovery, while in-hospital death was predicted by advanced age and concurrent comorbidities.

Conclusion

As one of the very few, a multi-state model was adopted to identify key factors predicting COVID-19 progression to critical disease, and recovery or death.
Targeted alpha therapy with the 224Ra/212Pb-TCMC-TP-3 dual alpha solution in a multicellular tumor spheroid model of osteosarcoma
Authors: Tornes Anna Julie Kjøl , Stenberg Vilde Yuli , Larsen Roy Hartvig , Bruland Øyvind Sverre , Revheim Mona-Elisabeth , Juzeniene Asta
Published: November 2022

Osteosarcoma patients with overt metastases at primary diagnosis have a 5-year survival rate of less than 20%. TP-3 is a murine IgG2b monoclonal antibody with high affinity for an epitope residing on the p80 osteosarcoma cell surface membrane antigen. The tumor-associated antigen p80 is overexpressed in osteosarcomas, and has very low normal tissue expression. We propose a novel dual alpha targeting solution containing two radionuclides from the same decay chain, including the bone-seeking 224Ra, and cancer cell-surface seeking 212Pb-TCMC-TP-3 for the treatment of osteoblastic bone cancers, circulating cancer cells and micrometastases. In this in vitro study, the cytotoxic effects of 212Pb-TCMC-TP-3 (single alpha solution) and 224Ra/212Pb-TCMC-TP-3 (dual alpha solution) were investigated in a multicellular spheroid model mimicking micrometastatic disease in osteosarcoma. OHS spheroids with diameters of 253 ± 98 μm treated with 4.5, 2.7, and 3.3 kBq/ml of 212Pb-TCMC-TP-3 for 1, 4, and 24 h, respectively, were disintegrated within 3 weeks. The 212Pb-TCMC-TP-3 induced a 7-fold delay in spheroid doubling time compared to a 28-times higher dose with the non-specific 212Pb-TCMC-rituximab. The 224Ra/212Pb-TCMC-TP-3 completely disintegrated spheroids with diameters of 218–476 μm within 3 and 2 weeks after 4 and 24 h incubation with 5 kBq/ml, respectively. Treatment with 1 kBq/ml of 224Ra/212Pb-TCMC-TP-3 for 24 h caused an 11.4-fold reduction in spheroid viability compared with unconjugated 224Ra/212Pb. The single and dual alpha solutions with TP-3 showed cytotoxicity in spheroids of clinically relevant size, which warrant further testing of the dual alpha solution using in vivo osteosarcoma models.