bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative analysis of WDR12 as a potential prognostic and immunological biomarker in multiple human tumors
Authors: Eid Refaat A. , Eldeen Muhammad Alaa , Soltan Mohamed A. , Al-Shraim Mubarak , Aldehri Majed , Alqahtani Leena S. , Alsharif Ghadi , Albogami Sarah , Jafri Ibrahim , Fayad Eman , Park Moon Nyeo , Bibi Shabana , Behairy Mohammed Y. , Kim Bonglee , Zaki Mohamed Samir A.
Published: January 2023

Background: Mammalian WD-repeat protein 12 (WDR12), a family member of proteins containing repeats of tryptophan-aspartic acid (WD), is a potential homolog of yeast Ytm1p and consists of seven repeats of WD.

Aim of the study: This study aims to investigate the potential oncogenic effects of WDR12 in various human malignancies throughout a pan-cancer analysis that has been carried out to examine the various patterns in which this gene is expressed and behaves in tumor tissues.

Methods: Herein, we used The Cancer Genome Atlas (TCGA) and various computational tools to explore expression profiles, prognostic relevance, genetic mutations, immune cell infiltration, as well as the functional characteristics of WDR12 in multiple human cancers.

Results: We found that WDR12 was inconsistently expressed in various cancers and that variations in WDR12 expression predicted survival consequences for cancer patients. Furthermore, we observed a significant correlation between WDR12 gene mutation levels and the prognosis of some tumors. Furthermore, significant correlations were found between WDR12 expression patterns and cancer-associated fibroblast (CAF) infiltration, myeloid-derived suppressor cells (MDSCs), tumor mutation burden, microsatellite instability and immunoregulators. Ultimately, pathway enrichment analysis revealed that WDR12-related pathways are involved in carcinogenesis.

Conclusions: The findings of our study are stisfactory, demonstrating that WDR12 could serve as a promising reliable prognostic biomarker, as well as a therapeutic target for novel cancer therapeutic approaches.
Candidate targets of copy number deletion events across 17 cancer types
Authors: Huang Qingyao , Baudis Michael
Published: January 2023

Genome variation is the direct cause of cancer and driver of its clonal evolution. While the impact of many point mutations can be evaluated through their modification of individual genomic elements, even a single copy number aberration (CNA) may encompass hundreds of genes and therefore pose challenges to untangle potentially complex functional effects. However, consistent, recurring and disease-specific patterns in the genome-wide CNA landscape imply that particular CNA may promote cancer-type-specific characteristics. Discerning essential cancer-promoting alterations from the inherent co-dependency in CNA would improve the understanding of mechanisms of CNA and provide new insights into cancer biology and potential therapeutic targets. Here we implement a model using segmental breakpoints to discover non-random gene coverage by copy number deletion (CND). With a diverse set of cancer types from multiple resources, this model identified common and cancer-type-specific oncogenes and tumor suppressor genes as well as cancer-promoting functional pathways. Confirmed by differential expression analysis of data from corresponding cancer types, the results show that for most cancer types, despite dissimilarity of their CND landscapes, similar canonical pathways are affected. In 25 analyses of 17 cancer types, we have identified 19 to 169 significant genes by copy deletion, including RB1, PTEN and CDKN2A as the most significantly deleted genes among all cancer types. We have also shown a shared dependence on core pathways for cancer progression in different cancers as well as cancer type separation by genome-wide significance scores. While this work provides a reference for gene specific significance in many cancers, it chiefly contributes a general framework to derive genome-wide significance and molecular insights in CND profiles with a potential for the analysis of rare cancer types as well as non-coding regions.
LncRNAs could play a vital role in osteosarcoma treatment: Inhibiting osteosarcoma progression and improving chemotherapy resistance
Authors: Xiaotong Shi , Xiao Li , Shiyu Liao , Zhiguo Bi , Chunyang Feng , Jianguo Liu
Published: January 2023

Osteosarcoma (OS) is one of the most common primary solid malignant tumors in orthopedics, and its main clinical treatments are surgery and chemotherapy. However, a wide surgical resection range, functional reconstruction of postoperative limbs, and chemotherapy resistance remain as challenges for patients and orthopedists. To address these problems, the discovery of new effective conservative treatments is important. Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides in length that do not encode proteins. Researchers have recently found that long non-coding RNAs are closely associated with the development of OS, indicating their potentially vital role in new treatment methods for OS. This review presents new findings regarding the association of lncRNAs with OS and summarizes potential clinical applications of OS with lncRNAs, including the downregulation of oncogenic lncRNAs, upregulation of tumor suppressive lncRNAs, and lncRNAs-based treatment to improve chemotherapy resistance. We hope these potential methods will be translated into clinical applications and greatly reduce patient suffering.
Addressing disparities in pharmacogenomics through rural and underserved workforce education
Authors: Brown Jacob T. , McGonagle Erin , Seifert Randall , Speedie Marilyn , Jacobson Pamala A.
Published: January 2023

Introduction: While pharmacogenomic (PGx) testing is routine in urban healthcare institutions or academic health centers with access to existing expertise, uptake in medically-underserved areas is lagging. The primary objective of this workforce education program is to extend access to didactic, case-based and clinical PGx training for pharmacists serving rural Minnesota and populations experiencing health disparities in Minnesota.

Methods: A PGx workforce training program funded through the Minnesota Department of Health was offered through the University of Minnesota College of Pharmacy (COP) to pharmacists working in rural and/or underserved areas in the state of Minnesota. Learning activities included a 16-week, asynchronous PGx didactic course covering PGx topics, a 15-min recorded presentation, an in-person PGx case-based workshop, and a live international PGx Conference hosted by the University of Minnesota COP and attendance at our PGx Extension of Community Health Outcomes (ECHO).

Results: Twenty-nine pharmacists applied for the initial year of the program, with 12 (41%) being accepted. Four (33%) practiced in a hospital setting, four (33%) in retail pharmacy, two (17%) in managed care, and two (17%) in other areas. The majority had not implemented a PGx program as part of their practice, although nearly all responded definitely or probably yes when asked if they expected their organization to increase its use of PGx testing services over the next three years. All participants either strongly or somewhat agreed that this program helped them identify how and where to access clinical PGx guidelines and literature and improved their ability to read and interpret PGx test results. Eight participants (67%) strongly or somewhat agreed that they expected to increase the number of PGx consultations in their practice, while ten (83%) strongly or somewhat agreed they would be able to apply what they learned in this program to their practice in the next six months to a year.

Discussion: This novel PGx training program focused exclusively on pharmacists in rural and/or underserved areas with a delivery method that could be accomplished conveniently and remotely. Although most participants’ organizations had yet to implement PGx testing routinely, most anticipated this to change in the next few years.
Rice lipid transfer protein, OsLTPL23, controls seed germination by regulating starch-sugar conversion and ABA homeostasis
Authors: Li Quanlin , Zhai Wenxue , Wei Jiaping , Jia Yanfeng
Published: January 2023

Seed germination is vital for ensuring the continuity of life in spermatophyte. High-quality seed germination usually represents good seedling establishment and plant production. Here, we identified OsLTPL23, a putative rice non-specific lipid transport protein, as an important regulator responsible for seed germination. Subcellular localization analysis confirmed that OsLTPL23 is present in the plasma membrane and nucleus. The knockout mutants of OsLTPL23 were generated by CRISPR/Cas9-mediated genome editing, and osltpl23 lines significantly germinated slower and lower than the Nipponbare (NIP). Starch and soluble sugar contents measurement showed that OsLTPL23 may have alpha-amylase inhibitor activity, and high soluble sugar content may be a causal agent for the delayed seed germination of osltpl23 mutants. Transcript profiles in the germinating seeds exhibited that the abscisic acid (ABA)-responsive genes, OsABI3 and OsABI5, and biosynthesis genes, OsNCED1, OsNCED2, OsNCED3 and OsNCED4, are obviously upregulated in the osltpl23 mutants compared to NIP plants, conversely, ABA metabolism genes OsABA8ox1, OsABA8ox2 and OsABA8ox3 are stepwise decreased. Further investigations found that osltpl23 mutants displays weakened early seedling growth, with elevated gene expresssion of ABA catabolism genes and repressive transcription response of defence-related genes OsWRKY45, OsEiN3, OsPR1a, OsPR1b and OsNPR1. Integrated analysis indicated that OsLTPL23 may exert an favorable effect on rice seed germination and early seedling growth via modulating endogenous ABA homeostasis. Collectively, our study provides important insights into the roles of OsLTPL23-mediated carbohydrate conversion and endogenous ABA pathway on seed germination and early seedling growth, which contributes to high-vigor seed production in rice breeding.
Metabolism-associated molecular classification of uterine corpus endometrial carcinoma
Authors: Zhao Munan , Li Wei
Published: January 2023

Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecologic malignancies. Currently, for UCEC cancer, molecular classification based on metabolic gene characteristics is rarely established. Here, we describe the molecular subtype features of UCEC by classifying metabolism-related gene profiles. Therefore, integrative analysis was performed on UCEC patients from the TCGA public database. Consensus clustering of RNA expression data on 2,752 previously reported metabolic genes identified two metabolic subtypes, namely, C1 and C2 subtypes. Two metabolic subtypes for prognostic characteristics, immune infiltration, genetic alteration, and responses to immunotherapy existed with distinct differences. Then, differentially expressed genes (DEGs) among the two metabolic subtypes were also clustered into two subclusters, and the aforementioned features were similar to the metabolic subtypes, supporting that the metabolism-relevant molecular classification is reliable. The results showed that the C1 subtype has high metabolic activity, high immunogenicity, high gene mutation, and a good prognosis. The C2 subtype has some features with low metabolic activity, low immunogenicity, high copy number variation (CNV) alteration, and poor prognosis. Finally, a model was identified, with three gene metabolism-related signatures, which can predict the prognosis. These findings of this study demonstrate a new classification in UCEC based on the metabolic pattern, thereby providing valuable information for understanding UCEC’s molecular characteristics.
Mas-related G protein-coupled receptor MRGPRX2 in human basophils: Expression and functional studies
Authors: Toscano Alessandro , Elst Jessy , Van Gasse Athina L. , Beyens Michiel , van der Poorten Marie-Line , Bridts Chris H. , Mertens Christel , Van Houdt Michel , Hagendorens Margo M. , Van Remoortel Samuel , Timmermans Jean-Pierre , Ebo Didier G. , Sabato Vito
Published: January 2023

Background

Occupancy of MRGPRX2 heralds a new era in our understandings of immediate drug hypersensitivity reactions (IDHRs), but a constitutive expression of this receptor by basophils is debated.

Objective

To explore the expression and functionality of MRGPRX2 in and on basophils.

Methods

Basophils from patients with birch pollen allergy, IDHRs to moxifloxacin, and healthy controls were studied in different conditions, that is, in rest, after stimulation with anti-IgE, recombinant major birch pollen allergen (rBet v 1), moxifloxacin, fMLP, substance P (SP), or other potential basophil secretagogues. In a separate set of experiments, basophils were studied after purification and resuspension in different media.

Results

Resting whole blood basophils barely express MRGPRX2 on their surface and are unresponsive to SP or moxifloxacin. However, surface MRGPRX2 is quickly upregulated upon incubation with anti-IgE or fMLP. Pre-stimulation with anti-IgE can induce a synergic effect on basophil degranulation in IgE-responsive subjects after incubation with SP or moxifloxacin, provided that basophils have been obtained from patients who experienced an IDHR to moxifloxacin. Cell purification can trigger a “spontaneous” and functional upregulation of MRGPRX2 on basophils, not seen in whole blood cells, and its surface density can be influenced by distinct culture media.

Conclusion

Basophils barely express MRGPRX2 in resting conditions. However, the receptor can be quickly upregulated after stimulation with anti-IgE, fMLP, or after purification, making cells responsive to MRGPRX2 occupation. We anticipate that such “conditioned” basophils constitute a model to explore MRGPRX2 agonism or antagonism, including IDHRs originating from the occupation of this receptor.
Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis
Authors: Nagata Naomi , Kanazawa Naomi , Mitsuhata Tomomi , Iizuka Masaki , Nagashima Makoto , Nakamura Masaaki , Kaneko Juntaro , Kitamura Eiji , Nishiyama Kazutoshi , Iizuka Takahiro
Published: January 2023

A variety of neuronal surface (NS) antibodies (NS-Ab) have been identified in autoimmune encephalitis (AE). Tissue-based assay (TBA) using a rodent brain immunohistochemistry (IHC) is used to screen NS-Ab, while cell-based assay (CBA) to determine NS antigens. Commercial rat brain IHC is currently available but its clinical relevance remains unclear. Immunostaining patterns of NS antigens have not been extensively studied yet. To address these issues, we assessed a predictive value of “neuropil pattern” and “GFAP pattern” on commercial IHC in 261 patients, and characterized an immunostaining pattern of 7 NS antigens (NMDAR, LGI1, GABAaR, GABAbR, AMPAR, Caspr2, GluK2). Sensitivity and specificity of “neuropil pattern” for predicting NS-Ab were 66.0% (95% CI 55.7-75.3), and 98.2% (95% CI 94.8-99.6), respectively. False-positive rate was 1.8% (3/164) while false-negative rate was 34.0% (33/97). In all 3 false-positive patients, neuropil-like staining was attributed to high titers of GAD65-Ab. In 33 false-negative patients, NMDAR was most frequently identified (n=18 [54.5%], 16/18 [88.9%] had low titers [< 1:32]), followed by GABAaR (n=5). Of 261 patients, 25 (9.6%) had either GFAP (n=21) or GFAP-mimicking pattern (n=4). GFAP-Ab were identified in 21 of 31 patients examined with CBA (20 with GFAP pattern, 1 with GFAP-mimicking pattern). Immunostaining pattern of each NS antigen was as follows: 1) NMDAR revealed homogenous reactivity in the dentate gyrus molecular layer (DG-ML) with less intense dot-like reactivity in the cerebellar granular layer (CB-GL); 2) both GABAaR and GluK2 revealed intense dot-like reactivity in the CB-GL, but GABAaR revealed homogenous reactivity in the DG-ML while GluK2 revealed intense reactivity along the inner layer of the DG-ML; and 3) LGI1, Caspr2, GABAbR, and AMPAR revealed intense reactivity in the cerebellar ML (CB-ML) but LGI1 revealed intense reactivity along the middle layer of the DG-ML. Whereas, Caspr2, GABAbR, and AMPAR revealed similar reactivity in the DG-ML but some difference in other regions. TBA is useful not only for screening NS- or GFAP-Ab but also for estimating NS antigens; however, negative results should be interpreted cautiously because “neuropil pattern” may be missed on commercial IHC when antibody titers are low. Antigen-specific immunoreactivity is a useful biomarker of AE.
Increased expression of long-isoform thymic stromal lymphopoietin is associated with rheumatoid arthritis and fosters inflammatory responses
Authors: Li Wanlin , Liao Chenghui , Du Jing , Hu Jing , Wang Lu , Song Xun , He Zhendan , Xiao Xiaohua , Ye Liang
Published: January 2023

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that is involved in the pathogenesis of inflammatory diseases and asthma, but the expression and biological implications of the existence of two isoforms, long TSLP (lTSLP) and short TSLP (sTSLP), in RA have yet to be elucidated. Here we report that lTSLP is the predominant TSLP isoform in RA and active RA, whereas sTSLP is the major TSLP isoform in inactive RA and healthy controls. lTSLP expression is associated with disease activity, including 28-joint Disease Activity Score (DAS28) and erythrocyte sedimentation rate (ESR), as well as proinflammatory cytokine expression, irrespective of other laboratory parameters. Importantly, lTSLP alone or combined with LPS promotes the expression of proinflammatory cytokines IL-1β, IL-6, and IL-8 in PBMCs of RA, but restrains anti-inflammatory cytokine IL-10 expression in PBMCs of RA. Furthermore, we found that STAT5 signaling is involved in lTSLP-induced inflammatory accumulation in PBMCs of RA. Therefore, these results highlight the clinical significance of lTSLP in RA pathology and inflammatory response in acute-phase disease, which may provide a therapeutic target for RA.
Innate immunity in pancreatic cancer: Lineage tracing and function
Authors: Ye Longyun , Shi Saimeng , Chen Wei
Published: January 2023

Increasingly, patients with gastrointestinal tumors can benefit from immunotherapy, but not patients with pancreatic cancer. While this lack of benefit has been attributed to lower T-cell infiltration in pancreatic cancer, other studies have demonstrated the presence of numerous T cells in pancreatic cancer, suggesting another mechanism for the poor efficacy of immunotherapy. Single-cell RNA sequencing studies on the pancreatic cancer immune microenvironment have demonstrated the predominance of innate immune cells (e.g., macrophages, dendritic cells, mast cells, and innate immune lymphoid cells). Therefore, in-depth research on the source and function of innate immune lymphocytes in pancreatic cancer could guide pancreatic cancer immunotherapy.
Lack of seroresponse to SARS-CoV-2 booster vaccines given early post-transplant in patients primed pre-transplantation
Authors: Gleeson Sarah , Martin Paul , Thomson Tina , Spensley Katrina J. , Goodall Dawn , Bedi Rachna , Thind Amarpreet Kaur , Seneschall Charlotte , Gan Jaslyn , McAdoo Stephen , Lightstone Liz , Kelleher Peter , Prendecki Maria , Willicombe Michelle
Published: January 2023

SARS-CoV-2 vaccines are recommended pre-transplantation, however, waning immunity and evolving variants mandate booster doses. Currently there no data to inform the optimal timing of booster doses post-transplant, in patients primed pre-transplant. We investigated serial serological samples in 204 transplant recipients who received 2 or 3 SARS-CoV-2 vaccines pre-transplant. Spike protein antibody concentrations, [anti-S], were measured on the day of transplantation and following booster doses post-transplant. In infection-naïve patients, post-booster [anti-S] did not change when V3 (1st booster) was given at 116(78-150) days post-transplant, falling from 122(32-574) to 111(34-682) BAU/ml, p=0.78. Similarly, in infection-experienced patients, [anti-S] on Day-0 and post-V3 were 1090(133-3667) and 2207(650-5618) BAU/ml respectively, p=0.26. In patients remaining infection-naïve, [anti-S] increased post-V4 (as 2nd booster) when given at 226(208-295) days post-transplant, rising from 97(34-1074) to 5134(229-5680) BAU/ml, p=0.0016. Whilst in patients who had 3 vaccines pre-transplant, who received V4 (as 1st booster) at 82(49-101) days post-transplant, [anti-S] did not change, falling from 981(396-2666) to 871(242-2092) BAU/ml, p=0.62. Overall, infection pre-transplant and [anti-S] at the time of transplantation predicted post-transplant infection risk. As [Anti-S] fail to respond to SARS-CoV-2 booster vaccines given early post-transplant, passive immunity may be beneficial to protect patients during this period.
The crosstalk between the gut microbiota and tumor immunity: Implications for cancer progression and treatment outcomes
Authors: Wang Man , Zhang Lei , Chang Wenguang , Zhang Yuan
Published: January 2023

The gastrointestinal tract is inhabited by trillions of commensal microorganisms that constitute the gut microbiota. As a main metabolic organ, the gut microbiota has co-evolved in a symbiotic relationship with its host, contributing to physiological homeostasis. Recent advances have provided mechanistic insights into the dual role of the gut microbiota in cancer pathogenesis. Particularly, compelling evidence indicates that the gut microbiota exerts regulatory effects on the host immune system to fight against cancer development. Some microbiota-derived metabolites have been suggested as potential activators of antitumor immunity. On the contrary, the disequilibrium of intestinal microbial communities, a condition termed dysbiosis, can induce cancer development. The altered gut microbiota reprograms the hostile tumor microenvironment (TME), thus allowing cancer cells to avoid immunosurvelliance. Furthermore, the gut microbiota has been associated with the effects and complications of cancer therapy given its prominent immunoregulatory properties. Therapeutic measures that aim to manipulate the interplay between the gut microbiota and tumor immunity may bring new breakthroughs in cancer treatment. Herein, we provide a comprehensive update on the evidence for the implication of the gut microbiota in immune-oncology and discuss the fundamental mechanisms underlying the influence of intestinal microbial communities on systemic cancer therapy, in order to provide important clues toward improving treatment outcomes in cancer patients.
Successful treatment of a pure red-cell aplasia patient with γδT cells and clonal TCR gene rearrangement: A case report
Authors: Li Xian , Zhu Xinyi , Zhang Xiaohong , Wang Weiqin
Published: January 2023

Pure red-cell aplasia (PRCA) is a syndrome associated with reduced erythroid precursors. This report presents the case of an elderly PRCA patient with significantly proliferated γδT cells and clonal T-cell receptor (TCR) gene rearrangement. The cause of this patient’s PRCA was confirmed to be an autoimmune disorder rather than malignancy on the basis of flow cytometry, TCR gene rearrangement, and positron emission tomography/computed tomography (PET/CT) findings. Moreover, the γδT cell group identified in this case was captured for the first time under the microscope; this CD4+/CD8− (extremely high CD4/CD8 ratio) population is rare in PRCA patients. Our patient with a monoclonal and polyclonal hybrid of TCR gene rearrangement was sensitive to cyclosporin A (CsA), despite previous reports suggesting that patients with TCR clonal rearrangement may respond poorly to this drug. Overall, this case presents valuable clinical findings for the future diagnosis and management of PRCA caused by autoimmune conditions and further research on γδT cells’ autoimmune pathophysiology and gene rearrangement.
The role of Th17 cells in endocrine organs: Involvement of the gut, adipose tissue, liver and bone
Authors: Zi Changyan , Wang Die , Gao Yongxiang , He Lisha
Published: January 2023

T Helper 17 (Th17) cells are adaptive immune cells that play myriad roles in the body. Immune–endocrine interactions are vital in endocrine organs during pathological states. Th17 cells are known to take part in multiple autoimmune diseases over the years. Current evidence has moved from minimal to substantial that Th17 cells are closely related to endocrine organs. Diverse tissue Th17 cells have been discovered within endocrine organs, including gut, adipose tissue, liver and bone, and these cells are modulated by various secretions from endocrine organs. Th17 cells in these endocrine organs are key players in the process of an array of metabolic disorders and inflammatory conditions, including obesity, insulin resistance, nonalcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), osteoporosis and inflammatory bowel disease (IBD). We reviewed the pathogenetic or protective functions played by Th17 cells in various endocrine tissues and identified potential regulators for plasticity of it. Furthermore, we discussed the roles of Th17 cells in crosstalk of gut-organs axis.
Dysregulated B cell function and disease pathogenesis in systemic sclerosis
Authors: Beesley Claire F. , Goldman Nina R. , Taher Taher E. , Denton Christopher P. , Abraham David J. , Mageed Rizgar A. , Ong Voon H.
Published: January 2023

Systemic sclerosis (SSc) is a complex, immune-mediated rheumatic disease characterised by excessive extracellular matrix deposition in the skin and internal organs. B cell infiltration into lesional sites such as the alveolar interstitium and small blood vessels, alongside the production of defined clinically relevant autoantibodies indicates that B cells play a fundamental role in the pathogenesis and development of SSc. This is supported by B cell and fibroblast coculture experiments revealing that B cells directly enhance collagen and extracellular matrix synthesis in fibroblasts. In addition, B cells from SSc patients produce large amounts of profibrotic cytokines such as IL-6 and TGF-β, which interact with other immune and endothelial cells, promoting the profibrotic loop. Furthermore, total B cell counts are increased in SSc patients compared with healthy donors and specific differences can be found in the content of naïve, memory, transitional and regulatory B cell compartments. B cells from SSc patients also show differential expression of activation markers such as CD19 which may shape interactions with other immune mediators such as T follicular helper cells and dendritic cells. The key role of B cells in SSc is further supported by the therapeutic benefit of B cell depletion with rituximab in some patients. It is notable also that B cell signaling is impaired in SSc patients, and this could underpin the failure to induce tolerance in B cells as has been shown in murine models of scleroderma.
Global-scale analysis of socioeconomic impacts of coastal flooding over the 21st century
Authors: Kirezci Ebru , Young Ian R. , Ranasinghe Roshanka , Lincke Daniel , Hinkel Jochen
Published: January 2023

Building on a global database of projected extreme coastal flooding over the coming century, an extensive analysis that accounts for both existing levels of coastal defences (structural measures) and two scenarios for future changes in defence levels is undertaken to determine future expected annual people affected (EAPA) and expected annual damage (EAD). A range of plausible future climate change scenarios is considered along with narratives for socioeconomic change. We find that with no further adaptation, global EAPA could increase from 34M people/year in 2015 to 246M people/year by 2100. Global EAD could increase from 0.3% of global GDP today to 2.9% by 2100. If, however, coastal defences are increased at a rate which matches the projected increase in extreme sea level, by 2100, the total EAPA is reduced to 119M people/year and the EAD will be reduced by a factor of almost three to 1.1% of GDP. The impacts of such flooding will disproportionately affect the developing world. By 2100, Asia, West Africa and Egypt will be the regions most impacted. If no adaptation actions are taken, many developing nations will experience EAD greater than 5% of GDP, whilst almost all developed nations will experience EAD less than 3% of GDP.
A first estimate of the effect of offshore wind farms on sedimentary organic carbon stocks in the Southern North Sea
Authors: Heinatz Knut , Scheffold Maike Iris Esther
Published: January 2023

Offshore wind farms (OWFs) can increase the transfer and stock of organic carbon (OC) in the surrounding sediments during their operational phase, while their construction and decommissioning release carbon. To answer the question whether sediments of OWFs trap more OC than they release, we estimate the net carbon effect over the entire life cycle (construction, operational and decommissioning phases) of OWFs in the Southern North Sea. Based on existing studies we compare the increased OC flux due to the colonization of organisms at the foundations of wind turbines and the OC loss due to sediment-disturbing activities during construction and decommissioning. Our results show that the areal intensity of carbon release in the disturbed areas is about 43.5 times higher than that of carbon trapping in the entire area of the OWFs. However, since the disturbed areas only account for about 0.50 ± 0.06% of the total area of the OWFs, in absolute terms about 4.6 ± 1.4 times more carbon is trapped in the sediment of the OWFs than is released. Due to limited data availability and the resulting need for extensive assumptions, our estimates only represent orders of magnitude. We therefore provide sensitivity estimates that define the limits of our calculations in terms of disturbance depth, remineralisation ratio, scour protection measures and heterogenous OC contents. In addition, we identify shortcomings of our extrapolation. Further research, especially more advanced impact assessments of construction and decommissioning processes must follow to improve the understanding of impacts of OWFs on sedimentary OC.
Spatiotemporal variations of tidal flat landscape patterns and driving forces in the Yangtze River Delta, China
Authors: Cheng Shuo , Zeng Xu , Wang Zihan , Zeng Cong , Cao Ling
Published: January 2023

As a crucial coastal wetland habitat in the transition zone between land and sea, global tidal flats have severely declined by 16% over the last two decades under the dual threats of intense human activities and climate change. The Yangtze River Delta of China, the largest estuary in the western Pacific Ocean, has abundant mudflat resources and a dense human population. It also has some of the most prominent conflicts between economic development and ecological conservation. The current lack of understanding of landscape patterns and influencing factors of the Yangtze River Delta mudflats has severely hampered the region’s ecological conservation and restoration efforts. Based on Landsat time-series images, this study generated a 30-m spatial resolution map of mudflats in the Yangtze River Delta, which shrank by 47% during 1990–2020, with a higher density of mudflat loss in Yancheng and Nantong cities of the Jiangsu province and Hangzhou, Shaoxing, and Ningbo cities of the Zhejiang province. Landscape indices, such as the patch density of tidal flats, have gradually changed since 2000, with most of them showing significant changes in 2010. Mudflats in Lianyungang, northwestern Yancheng, Nanhui, Jiaxing, and Hangzhou showed sharp negative changes in landscape characteristics. Natural and anthropogenic factors had synergistic effects on the above changes in mudflat landscape patterns in the Yangtze River Delta. Mudflat landscape features were mainly influenced by population growth, economic development, reclamation, sediment discharge, and air temperature. Based on the evolving characteristics of mudflat landscape patterns, we recommend improving mudflat landscape management and planning by strengthening mudflat policies, laws, and regulations, developing countermeasures against threats from major stressors, and enhancing the effectiveness of nature reserves for mudflat protection.
A virulence activator of a surface attachment protein in Burkholderia pseudomallei acts as a global regulator of other membrane-associated virulence factors
Authors: Sun Zhenxin , Heacock-Kang Yun , McMillan Ian A. , Cabanas Darlene , Zarzycki-Siek Jan , Hoang Tung T.
Published: January 2023

Burkholderia pseudomallei (Bp), causing a highly fatal disease called melioidosis, is a facultative intracellular pathogen that attaches and invades a variety of cell types. We previously identified BP1026B_I0091 as a surface attachment protein (Sap1) and an essential virulence factor, contributing to Bp pathogenesis in vitro and in vivo. The expression of sap1 is regulated at different stages of Bp intracellular lifecycle by unidentified regulator(s). Here, we identified SapR (BP1026B_II1046) as a transcriptional regulator that activates sap1, using a high-throughput transposon mutagenesis screen in combination with Tn-Seq. Consistent with phenotypes of the Δsap1 mutant, the ΔsapR activator mutant exhibited a significant reduction in Bp attachment to the host cell, leading to subsequent decreased intracellular replication. RNA-Seq analysis further revealed that SapR regulates sap1. The regulation of sap1 by SapR was confirmed quantitatively by qRT-PCR, which also validated the RNA-Seq data. SapR globally regulates genes associated with the bacterial membrane in response to diverse environments, and some of the genes regulated by SapR are virulence factors that are required for Bp intracellular infection (e.g., type III and type VI secretion systems). This study has identified the complex SapR regulatory network and its importance as an activator of an essential Sap1 attachment factor.
Inactivation of antibiotic-resistant bacteria and antibiotic-resistance genes in wastewater streams: Current challenges and future perspectives
Authors: Mosaka Thabang B. M. , Unuofin John O. , Daramola Michael O. , Tizaoui Chedly , Iwarere Samuel A.
Published: January 2023

The discovery of antibiotics, which was once regarded as a timely medical intervention now leaves a bitter aftertaste: antimicrobial resistance (AMR), due to the unregulated use of these compounds and the poor management receiving wastewaters before discharge into pristine environments or the recycling of such treated waters. Wastewater treatment plants (WWTPs) have been regarded a central sink for the mostly unmetabolized or partially metabolised antibiotics and is also pivotal to the incidence of antibiotic resistance bacteria (ARBs) and their resistance genes (ARGs), which consistently contribute to the global disease burden and deteriorating prophylaxis. In this regard, we highlighted WWTP-antibiotics consumption-ARBs-ARGs nexus, which might be critical to understanding the epidemiology of AMR and also guide the precise prevention and remediation of such occurrences. We also discovered the unsophistication of conventional WWTPs and treatment techniques for adequate treatment of antibiotics, ARBs and ARGs, due to their lack of compliance with environmental sustainability, then ultimately assessed the prospects of cold atmospheric plasma (CAP). Herein, we observed that CAP technologies not only has the capability to disinfect wastewater polluted with copious amounts of chemicals and biologicals, but also have a potential to augment bioelectricity generation, when integrated into bio electrochemical modules, which future WWTPs should be retrofitted to accommodate. Therefore, further research should be conducted to unveil more of the unknowns, which only a snippet has been highlighted in this study.
Antioxidant effect of yeast on lipid oxidation in salami sausage
Authors: Liu Yingli , Cao Yating , Yohannes Woldemariam Kalekristos , Zhong Shengjie , Yu Qinglin , Wang Jing
Published: January 2023

Salami is a kind of fermented meat product with rich nutrition and unique flavor. Because it is rich in fat, it is easy to oxidize to produce bad flavor. Compared with the way of adding artificial or natural antioxidants to reduce the degree of sausage oxidation, the antioxidant characteristics of developing the starter itself deserve more attention. In this study, firstly the antioxidant activities of 5 strains of yeast were measured in vitro, and then the mixture of yeast and Lactobacillus rhamnosus YL-1 was applied to fermented sausage model. The effect of the starter in the sausage model was investigated through physicochemical parameters, degree of fat oxidation, free fatty acid content, and though volatile flavor compound analysis, sensory evaluation and various indexes after storage were observed. Metagenomics was used to explore metabolic pathways, functional genes and key enzymes related to lipid oxidizing substances in sausage in yeast. The results showed that Wickerhamomyces anomalus Y12-3 and Y12-4 had strong tolerance to H2O2, and had higher SOD and CAT enzyme activities. The addition of yeast effectively reduced the material value of peroxidation value and active thiobarbiturate in salami. In flavor analysis, the content of flavor compounds associated with lipid oxidation, such as hexanal, heptanal, nonanal and (E)-2-decenal were significantly lower with the use of Debaryomyces hansenii Y4-1 and Y12-3. Meanwhile, the possible pathways of yeast metabolism of flavor substances related to lipid oxidation (mainly aldehydes) were discussed with the help of metagenomic techniques. According to the results of metagenomics, fatty acid degradation (ko00071) metabolic pathway was related to the degradation of aldehydes through aldehyde dehydrogenase, which was the potential key enzyme.
Nucleation control of quantum dot synthesis in a microfluidic continuous flow reactor
Authors: Kim Eun Byoel , Tomczak Kyle M. , Chandrasiri Hashini B. , Pálmai Marcell , Ghaznavi Amirreza , Gritsenko Dmitry , Xu Jie , Snee Preston T.
Published: January 2023

The use of microfluidics in chemical synthesis is topical due to the potential to improve reproducibility and the ability promptly interrogate a wide range of reaction parameters, the latter of which is necessary for the training of artificial intelligence (AI) algorithms. Applying microfluidic techniques to semiconductor nanocrystals, or quantum dots (QDs), is challenging due to the need for a high-temperature nucleation event followed by particle growth at lower temperatures. Such a high-temperature gradient can be realized using complex, segmented microfluidic reactor designs, which represents an engineering approach. Here, an alternative chemical approach is demonstrated using the cluster seed method of nanoparticle synthesis in a simple microfluidic reactor system. This enables quantum dot nucleation at lower temperatures due to the presence of molecular organometallic compounds (NMe4)4[Cd10Se4(SPh)16] and (NMe4)4[Zn10Se4(SPh)16]. This integration of cluster seeding with microfluidics affords a new mechanism to tailor the reaction conditions for optimizing yields and tuning product properties.
Case report: Brachial plexopathy caused by malignant peripheral nerve sheath tumor and review of the literature
Authors: Chen Mengjie , Li Xiuli , Feng Xinhong
Published: January 2023

Brachial plexopathy (BP) is easily misdiagnosed due to its complexity and varying clinical presentation. Malignant peripheral nerve sheath tumors (MPNST) can accumulate in the brachial plexus and share symptoms with BP, which may hinder the differential diagnosis between BP induced by radiation or metastases, and MPNST-derived BP, in patients with a history of breast cancer and radiation exposure. A 34-year-old Chinese female presented with MPNST. The tumor involved the brachial plexus. She had a history of breast cancer and radiotherapy. The first consideration was radiation- or breast cancer metastasis-derived BP. Clinical examination was performed. Finally, a diagnosis of MPNST of the brachial plexus was made, which guided an accurate treatment plan. This report highlights the importance of correctly diagnosing BP etiology for guiding precise treatment. BP caused by MPNST needs to be considered in clinical practice, and biopsy plays a central role in the differential diagnosis. Complete local surgical resection can prolong survival of patients with MPNST and improve treatment prognosis.
Recent advances in the application of ionomics in metabolic diseases
Authors: Zhang Yan , Huang Biyan , Jin Jiao , Xiao Yao , Ying Huimin
Published: January 2023

Trace elements and minerals play a significant role in human health and diseases. In recent years, ionomics has been rapidly and widely applied to explore the distribution, regulation, and crosstalk of different elements in various physiological and pathological processes. On the basis of multi-elemental analytical techniques and bioinformatics methods, it is possible to elucidate the relationship between the metabolism and homeostasis of diverse elements and common diseases. The current review aims to provide an overview of recent advances in the application of ionomics in metabolic disease research. We mainly focuses on the studies about ionomic or multi-elemental profiling of different biological samples for several major types of metabolic diseases, such as diabetes mellitus, obesity, and metabolic syndrome, which reveal distinct and dynamic patterns of ion contents and their potential benefits in the detection and prognosis of these illnesses. Accumulation of copper, selenium, and environmental toxic metals as well as deficiency of zinc and magnesium appear to be the most significant risk factors for the majority of metabolic diseases, suggesting that imbalance of these elements may be involved in the pathogenesis of these diseases. Moreover, each type of metabolic diseases has shown a relatively unique distribution of ions in biofluids and hair/nails from patients, which might serve as potential indicators for the respective disease. Overall, ionomics not only improves our understanding of the association between elemental dyshomeostasis and the development of metabolic disease but also assists in the identification of new potential diagnostic and prognostic markers in translational medicine.
EDEM2 is a diagnostic and prognostic biomarker and associated with immune infiltration in glioma: A comprehensive analysis
Authors: Wu Yuxi , Wang Haofei , Xiang Wei , Yi Dongye
Published: January 2023

Glioma is a highly common pathological brain tumor. Misfolded protein response, which is strongly associated with the growth of cancerous tumors, is mediated by the gene, endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2. However, this gene has not been linked to glioma. To assess the same, we used The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Genotype-Tissue Expression datasets. The gene was overexpressed in gliomas. This overexpression was linked to unfavorable clinical characteristics, such as the World Health Organization grade, isocitrate dehydrogenase mutation, and the combined loss of the short arm chromosome 1 and the long arm of chromosome 19. Quantitative polymerase chain reaction experiments and immunohistochemistry on clinical samples from our institution verified the gene’s expression and clinical importance. The Human Protein Atlas website verified the messenger ribonucleic acid expression of the gene in glioma cell lines, and immunohistochemistry verified the presence of its protein. A previous survival study indicated that its high expression is substantially related to a bad prognosis. It was identified as an independent predictor of primary glioma prognosis using multivariate Cox regression analysis. To forecast individual survival, we created a nomogram based on this (concordance-index = 0.847). Additionally, functional annotation demonstrated its major role in the control of the extracellular matrix and immune system. The scratch assay and transwell migration assay confirmed the decreased invasive ability of U251 glioma cells with the gene knockdown. Its increased expression was found to be related to the extent of macrophage infiltration using the CIBERSORT, ESTIMATE, Single-sample Gene Set Enrichment Analysis, and Tumor Immune Single-Cell Hub (TISCH) algorithms. The Tumor Immune Dysfunction and Exclusion algorithm revealed that the gene can accurately predict the response of immunotherapy (area under the receiver operating characteristic curve = 0.857). Further, isocitrate dehydrogenase 1 mutation is typically more frequent when the gene expression is high. Finally, five medicines targeting this gene were discovered utilizing the molecular docking program and drug sensitivity analysis of the RNAactDrug website. Low expression of the gene inhibited glioma cell invasion. Therefore, the gene is helpful for the diagnosis, prognosis, and case-specific immunotherapy of glioma.
Diagnosis and segmentation effect of the ME-NBI-based deep learning model on gastric neoplasms in patients with suspected superficial lesions - a multicenter study
Authors: Liu Leheng , Dong Zhixia , Cheng Jinnian , Bu Xiongzhu , Qiu Kaili , Yang Chuan , Wang Jing , Niu Wenlu , Wu Xiaowan , Xu Jingxian , Mao Tiancheng , Lu Lungen , Wan Xinjian , Zhou Hui
Published: January 2023

Background

Endoscopically visible gastric neoplastic lesions (GNLs), including early gastric cancer and intraepithelial neoplasia, should be accurately diagnosed and promptly treated. However, a high rate of missed diagnosis of GNLs contributes to the potential risk of the progression of gastric cancer. The aim of this study was to develop a deep learning-based computer-aided diagnosis (CAD) system for the diagnosis and segmentation of GNLs under magnifying endoscopy with narrow-band imaging (ME-NBI) in patients with suspected superficial lesions.

Methods

ME-NBI images of patients with GNLs in two centers were retrospectively analysed. Two convolutional neural network (CNN) modules were developed and trained on these images. CNN1 was trained to diagnose GNLs, and CNN2 was trained for segmentation. An additional internal test set and an external test set from another center were used to evaluate the diagnosis and segmentation performance.

Results

CNN1 showed a diagnostic performance with an accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 90.8%, 92.5%, 89.0%, 89.4% and 92.2%, respectively, and an area under the curve (AUC) of 0.928 in the internal test set. With CNN1 assistance, all endoscopists had a higher accuracy than for an independent diagnosis. The average intersection over union (IOU) between CNN2 and the ground truth was 0.5837, with a precision, recall and the Dice coefficient of 0.776, 0.983 and 0.867, respectively.

Conclusions

This CAD system can be used as an auxiliary tool to diagnose and segment GNLs, assisting endoscopists in more accurately diagnosing GNLs and delineating their extent to improve the positive rate of lesion biopsy and ensure the integrity of endoscopic resection.
Exosomes and cancer immunotherapy: A review of recent cancer research
Authors: Cao Yue , Xu Peng , Shen Yangling , Wu Wei , Chen Min , Wang Fei , Zhu Yuandong , Yan Feng , Gu Weiying , Lin Yan
Published: January 2023

As phospholipid extracellular vesicles (EVs) secreted by various cells, exosomes contain non-coding RNA (ncRNA), mRNA, DNA fragments, lipids, and proteins, which are essential for intercellular communication. Several types of cells can secrete exosomes that contribute to cancer initiation and progression. Cancer cells and the immune microenvironment interact and restrict each other. Tumor-derived exosomes (TDEs) have become essential players in this balance because they carry information from the original cancer cells and express complexes of MHC class I/II epitopes and costimulatory molecules. In the present study, we aimed to identify potential targets for exosome therapy by examining the specific expression and mechanism of exosomes derived from cancer cells. We introduced TDEs and explored their role in different tumor immune microenvironment (TIME), with a particular emphasis on gastrointestinal cancers, before briefly describing the therapeutic strategies of exosomes in cancer immune-related therapy.