bluuebunny/crossref_metadata_2025 huggingface dataset:
Vignette of Vigna domestication: From archives to genomics
Authors: Verma Sachin Kumar , Singh Chandan Kumar , Taunk Jyoti , Gayacharan  , Chandra Joshi Dinesh , Kalia Sanjay , Dey Nrisingha , Singh Amit Kumar
Published: October 2022

The genus Vigna comprises fast-growing, diploid legumes, cultivated in tropical and subtropical parts of the world. It comprises more than 200 species among which Vigna angularis, Vigna radiata, Vigna mungo, Vigna aconitifolia, Vigna umbellata, Vigna unguiculata, and Vigna vexillata are of enormous agronomic importance. Human selection along with natural variability within these species encompasses a vital source for developing new varieties. The present review convokes the early domestication history of Vigna species based on archeological pieces of evidence and domestication-related traits (DRTs) together with genetics of domestication. Traces of early domestication of Vigna have been evidenced to spread across several temperate and tropical regions of Africa, Eastern Asia, and few parts of Europe. Several DRTs of Vigna species, such as pod shattering, pod and seed size, dormancy, seed coat, seed color, maturity, and pod dehiscence, can clearly differentiate wild species from their domesticates. With the advancement in next-generation high-throughput sequencing techniques, exploration of genetic variability using recently released reference genomes along with de novo sequencing of Vigna species have provided a framework to perform genome-wide association and functional studies to figure out different genes related to DRTs. In this review, genes and quantitative trait loci (QTLs) related to DRTs of different Vigna species have also been summarized. Information provided in this review will enhance the in-depth understanding of the selective pressures that causes crop domestication along with nature of evolutionary selection made in unexplored Vigna species. Furthermore, correlated archeological and domestication-related genetic evidence will facilitate Vigna species to be considered as suitable model plants.
Comprehensive analysis of m5C-Related lncRNAs in the prognosis and immune landscape of hepatocellular carcinoma
Authors: Lu Qian , Liu Lianyu , Wang Shuai , Zhang Qi , Li Li
Published: October 2022

5-Methyladenosine (m5C) is a type of epigenetic modification involved in the progression of various cancers. To investigate the role of m5C-related long non-coding RNAs (lncRNAs) in the prognosis and immune cell infiltration in hepatocellular carcinoma (HCC), we obtained patients’ clinical information and transcriptome data of HCC from the Cancer Genome Atlas (TCGA) database. We applied Pearson correlation analysis to construct an m5C-related lncRNA–messenger RNA (mRNA) co-expression network. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis were employed to establish an m5C-related lncRNA prognostic risk model. We then verified the model using Kaplan–Meier analysis, principal component analysis, as well as univariate and multivariate Cox analyses. The expression of m5C-related lncRNAs was validated in HCC tissues and different cell lines. Combining the risk score and clinicopathological features, a nomogram was established for predicting the overall survival (OS) of HCC patients. Furthermore, gene set enrichment analysis (GSEA) revealed that some tumor-associated pathways were significantly enriched in the high-risk group. Immune cell infiltration analysis demonstrated that the levels of Treg cells, neutrophils, and M2 macrophages were higher in the high-risk group. In addition, patients with high tumor mutation burden (TMB) had worse OS than those with low TMB. We also assessed the immune checkpoint level and chemotherapeutic agent sensibility. Then in vitro experiments were performed to examine the biological function of MKLN1-AS in HCC cells and found that knockdown of MKLN1-AS suppressed the proliferation, migration, and invasion. In conclusion, m5C-related lncRNAs played a critical role in predicting the prognosis of patients with HCC and may serve as new therapeutic targets for HCC patients.
A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival
Authors: Barrón-Gallardo Carlos A. , Garcia-Chagollán Mariel , Morán-Mendoza Andres J. , Delgadillo-Cristerna Raul , Martínez-Silva María G. , Villaseñor-García María M. , Aguilar-Lemarroy Adriana , Jave-Suárez Luis F.
Published: October 2022

Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. Objective. To identify prognostic markers for treatment and survival in HER2+ patients. Methods. Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). Results. A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). Conclusion: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.
Integrated metabolomics and lipidomics study of patients with atopic dermatitis in response to dupilumab
Authors: Zhang Lishan , Wen Xueyi , Hou Yibo , Yang Yongshi , Song Wei , Zeng Yueping , Sun Jinlyu
Published: October 2022

Background

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Dupilumab, a monoclonal antibody that targets the interleukin (IL)-4 and IL-13 receptors, has been widely used in AD because of its efficacy. However, metabolic changes occurring in patients with AD in response to dupilumab remains unknown. In this study, we integrated metabolomics and lipidomics analyses with clinical data to explore potential metabolic alterations associated with dupilumab therapeutic efficacy. In addition, we investigated whether the development of treatment side effects was linked to the dysregulation of metabolic pathways.

Methods

A total of 33 patients with AD were included in the current study, with serum samples collected before and after treatment with dupilumab. Comprehensive metabolomic and lipidomic analyses have previously been developed to identify serum metabolites (including lipids) that vary among treatment groups. An orthogonal partial least squares discriminant analysis model was established to screen for differential metabolites and metabolites with variable importance in projection > 1 and p < 0.05 were considered potential metabolic biomarkers. MetaboAnalyst 5.0 was used to identify related metabolic pathways. Patients were further classified into two groups, well responders (n = 19) and poor responders (n = 14), to identify differential metabolites between the two groups.

Results

The results revealed significant changes in serum metabolites before and after 16 weeks of dupilumab treatment. Variations in the metabolic profile were more significant in the well-responder group than in the poor-responder group. Pathway enrichment analysis revealed that differential metabolites derived from the well-responder group were mainly involved in glycerophospholipid metabolism, valine, leucine and isoleucine biosynthesis, the citrate cycle, arachidonic acid metabolism, pyrimidine metabolism, and sphingolipid metabolism.

Conclusion

Serum metabolic profiles of patients with AD varied significantly after treatment with dupilumab. Differential metabolites and their related metabolic pathways may provide clues for understanding the effects of dupilumab on patient metabolism.
On TCR binding predictors failing to generalize to unseen peptides
Authors: Grazioli Filippo , Mösch Anja , Machart Pierre , Li Kai , Alqassem Israa , O’Donnell Timothy J. , Min Martin Renqiang
Published: October 2022

Several recent studies investigate TCR-peptide/-pMHC binding prediction using machine learning or deep learning approaches. Many of these methods achieve impressive results on test sets, which include peptide sequences that are also included in the training set. In this work, we investigate how state-of-the-art deep learning models for TCR-peptide/-pMHC binding prediction generalize to unseen peptides. We create a dataset including positive samples from IEDB, VDJdb, McPAS-TCR, and the MIRA set, as well as negative samples from both randomization and 10X Genomics assays. We name this collection of samples TChard. We propose the hard split, a simple heuristic for training/test split, which ensures that test samples exclusively present peptides that do not belong to the training set. We investigate the effect of different training/test splitting techniques on the models’ test performance, as well as the effect of training and testing the models using mismatched negative samples generated randomly, in addition to the negative samples derived from assays. Our results show that modern deep learning methods fail to generalize to unseen peptides. We provide an explanation why this happens and verify our hypothesis on the TChard dataset. We then conclude that robust prediction of TCR recognition is still far for being solved.
Rheumatoid factor IgM autoantibodies control IgG homeostasis
Authors: Nicolò Antonella , Amendt Timm , El Ayoubi Omar , Young Marc , Finzel Stephanie , Senel Makbule , Voll Reinhard E. , Jumaa Hassan
Published: October 2022

Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation due to autoantibodies targeting multiple self-proteins. Most patients with poor prognosis show elevated titers of IgM antibodies specifically binding to IgG. Such autoreactive antibodies are referred to as rheumatoid factor (RF). However, their biological function and contribution to disease progression remains elusive. We have recently shown that autoreactive antibodies are present in healthy individuals and play an important role in regulating physiological processes. This regulatory mechanism is determined by the class and affinity of the autoreactive antibody, as low-affinity autoreactive IgM neutralizes the recognized autoantigen while high-affinity IgM protects its autoantigen from degradation. Here, we show that RFs possessing a high affinity and mono-specificity to IgG have a stabilizing effect on IgG, whereas low-affinity polyreactive RFs neutralize IgGin vivo. These results suggest that autoreactive IgM antibodies recognizing IgG play a crucial role in regulating IgG homeostasis and that a disbalance between IgM-mediated IgG degradation and stabilization might affect the onset and progression of autoimmune diseases. Consequently, restoring this balance using low-affinity anti-IgG IgM might be a promising therapeutic approach for autoimmune diseases involving autoreactive IgG.
Ras inhibitors gate chemoattractant concentration range for chemotaxis through controlling GPCR-mediated adaptation and cell sensitivity
Authors: Xu Xuehua , Jin Tian
Published: October 2022

Chemotaxis plays an essential role in recruitment of leukocytes to sites of inflammation. Eukaryotic cells sense chemoattractant with G protein-coupled receptors (GPCRs) and chemotax toward gradients with an enormous concentration range through adaptation. Cells in adaptation no longer respond to the present stimulus but remain sensitive to stronger stimuli. Thus, adaptation provides a fundamental strategy for eukaryotic cells to chemotax through a gradient. Ras activation is the first step in the chemosensing GPCR signaling pathways that displays a transient activation behavior in both model organism Dictyostelium discoideum and mammalian neutrophils. Recently, it has been revealed that C2GAP1 and CAPRI control the GPCR-mediated adaptation in D. discoideum and human neutrophils, respectively. More importantly, both Ras inhibitors regulate the sensitivity of the cells. These findings suggest an evolutionarily conserved molecular mechanism by which eukaryotic cells gate concentration range of chemoattractants for chemotaxis.
Archetypal type II and III Toxoplasma gondii oocysts induce different immune responses and clinical outcomes in experimentally infected piglets
Authors: Largo-de la Torre Andrea , Diezma-Díaz Carlos , Calero-Bernal Rafael , Atencia-Cibreiro Gabriela , Sánchez-Sánchez Roberto , Ferre Ignacio , Regidor-Cerrillo Javier , Ortega-Mora Luis Miguel
Published: October 2022

Livestock animals, such as swine, are an important source of Toxoplasma gondii in the human population. Currently, there is limited knowledge regarding the potential influence that the T. gondii genotype might exert on establishing infection in swine. Herein, we investigated the role of 2 T. gondii isolates, type II and III, representative of the genotypes circulating in Europe, in the immune responses and infection dynamics in piglets. Recently obtained oocysts (103) from the T. gondii field isolates TgShSp1 (type II, ToxoDB genotype #3) and TgShSp24 (type III, #2) were used for oral infection. Thirteen 50-day-old female piglets of the Landrace-Large White crossbreed were randomly allocated into three different groups: Group 1 (G1, n=5), inoculated with TgShSp1; Group 2 (G2, n=5), inoculated with TgShSp24; and Group 3 (G3, n=3), a non-infected control group. Clinical signs were monitored daily until 42 days post-infection (dpi) when piglets were euthanized. Blood samples were collected weekly to test the cellular immune response in parasite-stimulated peripheral blood and specific IgG, IgG1 and IgG2, responses in sera. Parasite distribution and burden were evaluated in target tissues using a mouse bioassay and quantitative RT−PCR (qPCR). Apathy and a moderate decrease in feed consumption were observed in G1 and G2 piglets between 5 and 8 dpi, coinciding with fever (>40°C). G2 piglets had higher temperatures for a longer duration. Using mouse bioassay and qPCR, the detection frequency was higher in G2 vs. G1, and the highest parasite burdens in target tissues were also found in G2. Seroconversion was detected at 14 dpi in both infected groups, but higher antibody levels were observed in G2 piglets. Cytokine analyses revealed the production of IL-8, IL-1β and IFN-ɤ from 7 dpi in both infected groups. Moreover, IL-12 was produced from 7 dpi in G1 and from 14 dpi in G2. Levels of IL-8 were higher in G2, but IL-1β, IL-12 and IFN-ɤ were higher in G1 at 14 dpi. This cytokine profile reveals a predominant proinflammatory response that could be involved in limiting T. gondii infection in piglets, although it is more efficient against TgShSp1 type II-driven infection.
Polysaccharide from Atractylodes macrocephala Koidz. ameliorates DSS-induced colitis in mice by regulating the Th17/Treg cell balance
Authors: Yang Mengjiao , Zhang Qianwen , Taha Reham , Abdelmotalab Mohammed Ismail , Wen Qing , Yuan Yuzhu , Zhao Yongrui , Li Qingyu , Liao Chunyu , Huang Xin , Jiang Zhenzhou , Chu Chenghan , Jiao Chunhua , Sun Lixin
Published: October 2022

Atractylodes macrocephala Koidz. is one of the most frequently used traditional Chinese medicines for the treatment of ulcerative colitis (UC). The beneficial effect of polysaccharide from Atractylodes macrocephala Koidz. (PAMK) on UC has been reported, while the underlying mechanism and target remain unclear. In this study, we systematically investigated the therapeutic effect and the underlying mechanism of PAMK in UC based on a mouse model of dextran sodium sulfate (DSS)-induced colitis. PAMK treatment (100 mg/kg, 200 mg/kg and 400 mg/kg) significantly ameliorated DSS-induced colitis, manifested as a reduction in weight loss, disease activity index (DAI), colon shortening, spleen index and histological score. Moreover, PAMK treatment inhibited inflammation and improved the integrity of the intestinal barrier in colitis mice. Mechanistically, microarray analysis determined the critical role of the immunoregulatory effect of PAMK in alleviating UC. Flow cytometry analysis further demonstrated that PAMK treatment regulated the balance between T helper (Th) 17 and regulatory T (Treg) cells in the mesenteric lymph nodes (MLN) and spleen in mice with colitis. In addition, PAMK treatment downregulated the expression of IL-6 and suppressed the phosphorylation of STAT3. Together, these data revealed that PAMK treatment alleviated DSS-induced colitis by regulating the Th17/Treg cell balance, which may be dependent on the inhibition of the IL-6/STAT3 signaling pathway. Our study is the first to elucidate that the underlying mechanism by which PAMK treatment alleviates DSS-induced colitis is associated with an improved the Th17/Treg cell balance. Collectively, the study provides evidence for the potential of PAMK to treat UC.
Bibliometric and visual analysis of neutrophil extracellular traps from 2004 to 2022
Authors: Wan Yantong , Shen Junyi , Ouyang Jiafu , Dong Peng , Hong Yinghao , Liang Lixin , Liu Jinghua
Published: October 2022

Background

Neutrophil extracellular traps (NETs) are specialized structures formed by neutrophils that were initially found to be important in killing pathogenic bacteria during infection. With the development of related research, the relationship between NETs and diseases such as sepsis, cancer, and systemic lupus erythematosus has received close attention. However, there is a lack of reports that comprehensively and objectively present the current status of NETs-related studies. Therefore, this study aims to visually analyze the current status and trends of NETs-related research by means of bibliometrics and knowledge mapping.

Methods

NETs-related articles and reviews were retrieved using the Web of Science core collection subject search, and bibliometric analysis was performed in Excel 365, CiteSpace, VOSviewer, and Bibliometrix (R-Tool of R-Studio).

Results

A total of 4866 publications from 2004 to 2022 were included in the bibliometric analysis. The number of publications shows an increasing trend from year to year. Collaborative network analysis shows that the United States and Germany are the most influential countries in this field, with the highest number of publications and citations. The journal with the most publications is Frontiers in Immunology. Brinkmann Volker is an authoritative author in this field, and his publication “Neutrophil extracellular traps kill bacteria” is the most frequently cited. The literature and keyword analysis shows that the relationship between NETs and diseases (hematological diseases, sepsis, cancer, etc.) and cell death (apoptosis, necroptosis, pyroptosis, etc.) is a popular research topic. Currently, NETs and SARS-CoV-2-related studies are at the forefront of the field.

Conclusion

This study is the first to visualize the research in NETs-related fields using bibliometric methods, revealing the trends and frontiers of NETs research. This study will provide valuable references for scholars to find research focus questions and partners.
PET/CT molecular imaging in the era of immune-checkpoint inhibitors therapy
Authors: Gao Yuan , Wu Caixia , Chen Xueqi , Ma Linlin , Zhang Xi , Chen Jinzhi , Liao Xuhe , Liu Meng
Published: October 2022

Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage cancers. Accumulating evidence suggests that as a molecular imaging modality, positron emission tomography/computed tomography (PET/CT) can play a vital role in the management of ICIs therapy by using different molecular probes and metabolic parameters. In this review, we will provide a comprehensive overview of the clinical data to support the importance of 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging in the treatment of ICIs, including the evaluation of the tumor microenvironment, discovery of immune-related adverse events, evaluation of therapeutic efficacy, and prediction of therapeutic prognosis. We also discuss perspectives on the development direction of 18F-FDG PET/CT imaging, with a particular emphasis on possible challenges in the future. In addition, we summarize the researches on novel PET molecular probes that are expected to potentially promote the precise application of ICIs.
Inhibiting EGFR/HER-2 ameliorates neuroinflammatory responses and the early stage of tau pathology through DYRK1A
Authors: Kim Jieun , Kim Su-Jin , Jeong Ha-Ram , Park Jin-Hee , Moon Minho , Hoe Hyang-Sook
Published: October 2022

The FDA-approved EGFR/HER2 inhibitor varlitinib inhibits tumor growth and is used in cancer treatment. However, the neuroinflammatory response associated with EGFR/HER2 and its underlying mechanism have not been elucidated. This study evaluates the impact of varlitinib on LPS- and tau-mediated neuroinflammatory responses for the first time. In BV2 microglial cells, varlitinib reduced LPS-stimulated il-1β and/or inos mRNA levels and downstream AKT/FAK/NF-kB signaling. Importantly, varlitinib significantly diminished LPS-mediated microglial nlrp3 inflammasome activation in BV2 microglial cells. In primary astrocytes, varlitinib downregulated LPS-evoked astroglial il-1β mRNA levels, AKT signaling, and nlrp3 inflammasome activation. In LPS-treated wild-type mice, varlitinib significantly reduced LPS-stimulated glial activation and IL-1β/NLRP3 inflammasome formation. Moreover, varlitinib significantly reduced micro- and astroglial activation and tau hyperphosphorylation in 3-month-old tau-overexpressing PS19 mice by downregulating tau kinase DYRK1A levels. However, in 6-month-old tau-overexpressing PS19 mice, varlitinib only significantly diminished astroglial activation and tau phosphorylation at Thr212/Ser214. Taken together, our findings suggest that varlitinib has therapeutic potential for LPS- and tau-induced neuroinflammatory responses and the early stages of tau pathology.
Stereo electronic principles for selecting fully-protective, chemically-synthesised malaria vaccines
Authors: Patarroyo Manuel E. , Bermudez Adriana , Alba Martha P. , Patarroyo Manuel A. , Suarez Carlos , Aza-Conde Jorge , Moreno-Vranich Armando , Vanegas Magnolia
Published: October 2022

Major histocompatibility class II molecule-peptide-T-cell receptor (MHCII-p-TCR) complex-mediated antigen presentation for a minimal subunit-based, multi-epitope, multistage, chemically-synthesised antimalarial vaccine is essential for inducing an appropriate immune response. Deep understanding of this MHCII-p-TCR complex’s stereo-electronic characteristics is fundamental for vaccine development. This review encapsulates the main principles for achieving such epitopes’ perfect fit into MHC-II human (HLADRβ̞1*) orAotus(Aona DR) molecules. The enormous relevance of several amino acids’ physico-chemical characteristics is analysed in-depth, as is data regarding a 26.5 ± 2.5Å distance between the farthest atoms fitting into HLA-DRβ1* structures’ Pockets 1 to 9, the role of polyproline II-like (PPIIL) structures having their O and N backbone atoms orientated for establishing H-bonds with specific HLA-DRβ1*-peptide binding region (PBR) residues. The importance of residues having specific charge and orientation towards the TCR for inducing appropriate immune activation, amino acids’ role and that of structures interfering with PPIILformation and other principles are demonstrated which have to be taken into account when designing immune, protection-inducing peptide structures (IMPIPS) against diseases scourging humankind, malaria being one of them.
Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic-encephalomyelitis/chronic fatigue syndrome
Authors: Apostolou Eirini , Rizwan Muhammad , Moustardas Petros , Sjögren Per , Bertilson Bo Christer , Bragée Björn , Polo Olli , Rosén Anders
Published: October 2022

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic disease considered to be triggered by viral infections in a majority of cases. Symptoms overlap largely with those of post-acute sequelae of COVID-19/long-COVID implying common pathogenetic mechanisms. SARS-CoV-2 infection is risk factor for sustained latent virus reactivation that may account for the symptoms of post-viral fatigue syndromes. The aim of this study was first to investigate whether patients with ME/CFS and healthy donors (HDs) differed in their antibody response to mild/asymptomatic SARS-CoV-2 infection. Secondly, to analyze whether COVID-19 imposes latent virus reactivation in the cohorts.

Methods

Anti-SARS-CoV-2 antibodies were analyzed in plasma and saliva from non-vaccinated ME/CFS (n=95) and HDs (n=110) using soluble multiplex immunoassay. Reactivation of human herpesviruses 1-6 (HSV1, HSV2, VZV, EBV, CMV, HHV6), and human endogenous retrovirus K (HERV-K) was detected by anti-viral antibody fingerprints in saliva.

Results

At 3-6 months after mild/asymptomatic SARS-CoV-2 infection, virus-specific antibodies in saliva were substantially induced signifying a strong reactivation of latent viruses (EBV, HHV6 and HERV-K) in both cohorts. In patients with ME/CFS, antibody responses were significantly stronger, in particular EBV-encoded nuclear antigen-1 (EBNA1) IgG were elevated in patients with ME/CFS, but not in HDs. EBV-VCA IgG was also elevated at baseline prior to SARS-infection in patients compared to HDs.

Conclusion

Our results denote an altered and chronically aroused anti-viral profile against latent viruses in ME/CFS. SARS-CoV-2 infection even in its mild/asymptomatic form is a potent trigger for reactivation of latent herpesviruses (EBV, HHV6) and endogenous retroviruses (HERV-K), as detected by antibody fingerprints locally in the oral mucosa (saliva samples). This has not been shown before because the antibody elevation is not detected systemically in the circulation/plasma.
Antibody production in mice requires neither vitamin D, nor the vitamin D receptor
Authors: Plum Lori A. , Blaser William , Peter Logan , Prahl Jean , Seeman Jeremy , DeLuca Hector F.
Published: October 2022

The vitamin D receptor as well as its ligand have been localized to various immune tissues and cells. These observations have led researchers to hypothesize a role for vitamin D in the immune system. However, a specific role for vitamin D in immunity has yet to be clearly delineated. The work in this report was undertaken to determine if mounting an antibody response is altered in the face of vitamin D-deficiency or when the signaling pathway is eliminated by removal of the nuclear receptor. This investigation provides direct evidence vitamin D is not necessary for producing antibodies, a process paramount for optimal attack against many foreign organisms. The idea that vitamin D plays a significant role in immunity has been proposed repeatedly for many years. To address this important idea we have carried out studies in mice to determine if vitamin D plays a significant role in antibody production. Two animal models were utilized: mice depleted of vitamin D and mice devoid of the vitamin D receptor. Further, a possible role of hypocalcemia resulting from vitamin D deficiency in antibody production was determined. Neither the absence of vitamin D or the vitamin D receptor nor hypocalcemia affected the ability of mice to mount an antibody response to an antigen challenge. Thus, we found no evidence that vitamin D or normal serum calcium is required for this major form of immunity.
Incidence and factors associated with cutaneous immune-related adverse events to immune check point inhibitors: An ambispective cohort study
Authors: Luangnara Athitaya , Kiratikanon Salin , Ketpueak Thanika , Suksombooncharoen Thatthan , Charoentum Chaiyut , Chewaskulyong Busyamas , Tovanabutra Napatra , Chiewchanvit Siri , Nochaiwong Surapon , Chuamanochan Mati
Published: October 2022

Background

Although immune checkpoint inhibitors (ICIs) have become the frontline treatment option for patients with various advanced cancers due to improved survival, they can be associated with a spectrum of cutaneous immune-related adverse events (cirAEs). However, little is known regarding the occurrence and patterns of cirAE-related ICI therapy in patients of different races other than white populations. Therefore, we investigated the incidence and associated factors of cirAEs among cancer patients in northern Thailand.

Methods

A referral-center-based ambispective cohort study was conducted from January 1, 2017, to March 31, 2021. Based on a linked database and merged patient-level data, adult patients with pathologically confirmed cancer who were diagnosed and received ICI therapy regardless of cancer type and followed up through August 31, 2021, were included. All cirAE-related ICI therapy was based on clinical evaluation and ascertainment by a board-certified dermatologist. The incidence of cirAE-related ICI therapy with confidence intervals (CIs) across cancer- and ICI therapy-specific groups was estimated. Factors associated with cirAEs were evaluated using multivariable modified Poisson regression to estimate risk ratios (RRs) and 95% CIs.

Results

The study included 112 patients (67 men [59.8%]; mean age, 65.0 [range, 31.0-88.0] years), who were mainly diagnosed with lung cancer (56.3%), followed by liver cancer (19.6%). The overall incidence of cirAE-related ICI therapy was 32.1% (95% CI, 24.1-41.4); however, there was no substantial difference in sex, cancer type, or individual ICI therapy. The two identified prognostic risk factors of cirAE-related ICI therapy were age >75 years (adjusted RR, 2.13; 95% CI, 1.09-4.15; P=0.027) and pre-existing chronic kidney disease stages 3-4 (adjusted RR, 3.52; 95% CI, 2.33-5.31; P<0.001).

Conclusions

The incidence of cirAE-related ICI therapy among Thai cancer patients was comparable to that in white populations. Early identification, particularly in elderly patients and those with CKD, should be implemented in clinical practice to help optimize therapeutic decision-making and patient health outcomes.
The rectal mucosal immune environment and HIV susceptibility among young men who have sex with men
Authors: Ackerley Cassie G. , Smith S. Abigail , Murray Phillip M. , Amancha Praveen K. , Arthur Robert A. , Zhu Zhengyi , Chahroudi Ann , Amara Rama R. , Hu Yi-Juan , Kelley Colleen F.
Published: October 2022

Young men who have sex with men (YMSM) represent a particularly high-risk group for HIV acquisition in the US, despite similarly reported rates of sexual activity as older, adult MSM (AMSM). Increased rates of HIV infection among YMSM compared to AMSM could be partially attributable to differences within the rectal mucosal (RM) immune environment associated with earlier sexual debut and less lifetime exposure to receptive anal intercourse. Using an ex vivo explant HIV challenge model, we found that rectal tissues from YMSM supported higher levels of p24 at peak viral replication timepoints compared to AMSM. Among YMSM, the RM was characterized by increased CD4+ T cell proliferation, as well as lower frequencies of tissue resident CD8+ T cells and pro-inflammatory cytokine producing CD4+ and CD8+ T cells. In addition, the microbiome composition of YMSM was enriched for anaerobic taxa that have previously been associated with HIV acquisition risk, including Prevotella, Peptostreptococcus, and Peptoniphilus. These distinct immunologic and microbiome characteristics were found to be associated with higher HIV replication following ex vivo challenge of rectal explants, suggesting the RM microenvironment of YMSM may be uniquely conducive to HIV infection.
Identification of serum glycobiomarkers for Hepatocellular Carcinoma using lectin microarrays
Authors: Zhang Yue , Zhang Sihua , Liu Jianhua , Zhang Yunli , Liu Yanjie , Shen Shuang , Tian Fangfang , Yan Gaobo , Gao Yongqing , Qin Xiaosong
Published: October 2022

Objective

Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer and ranks third in mortality among all malignant tumors; as a result, HCC represents a major human health issue. Although aberrant glycosylation is clearly implicated in HCC, changes in serum immunoglobulin (Ig)G and IgM glycosylation have not been comprehensively characterized. In this study, we used lectin microarrays to evaluate differences in serum IgG and IgM glycosylation among patients with HCC, hepatitis B cirrhosis (HBC), or chronic hepatitis B (CHB), and healthy normal controls (NC) and aimed to establish a model to improve the diagnostic accuracy of HCC.

Methods

In total, 207 serum samples collected in 2019–2020 were used for lectin microarray analyses, including 97 cases of HCC, 50 cases of HBC, 30 cases of CHB, and 30 cases of NC. Samples were randomly divided into training and validation groups at a 2:1 ratio. Training group data were used to investigate the diagnostic value of the relative signal intensity for the lectin probe combined with alpha-fetoprotein (AFP). The efficacy of models for HCC diagnosis were analyzed by receiver operating characteristic (ROC) curves.

Results

In terms of IgG, a model combining three lectins and AFP had good diagnostic accuracy for HCC. The area under the ROC curve was 0.96 (P < 0.05), the sensitivity was 82.54%, and the specificity was 100%. In terms of IgM, a model including one lectin combined with AFP had an area under the curve of 0.90 (P < 0.05), sensitivity of 75.41%, and specificity of 100%.

Conclusion

Estimation of serum IgG and IgM glycosylation could act as complementary techniques to improve diagnosis and shed light on the occurrence and development of the HCC
IL7RA single nucleotide polymorphisms are associated with the size and function of the MAIT cell population in treated HIV-1 infection
Authors: Han Fei , Gulam Muhammad Yaaseen , Zheng Yichao , Zulhaimi Nurul Syuhada , Sia Wan Rong , He Dan , Ho Amanda , Hadadi Leila , Liu Zhenyu , Qin Peiwu , Lobie Peter E. , Kamarulzaman Adeeba , Wang Lin-Fa , Sandberg Johan K. , Lewin Sharon R. , Rajasuriar Reena , Leeansyah Edwin
Published: October 2022

MAIT cells are persistently depleted and functionally exhausted in HIV-1-infected patients despite long-term combination antiretroviral therapy (cART). IL-7 treatment supports MAIT cell reconstitution in vivo HIV-1-infected individuals and rescues their functionality in vitro. Single-nucleotide polymorphisms (SNPs) of the IL-7RA gene modulate the levels of soluble(s)IL-7Rα (sCD127) levels and influence bioavailability of circulating IL-7. Here we evaluate the potential influence of IL-7RA polymorphisms on MAIT cell numbers and function in healthy control (HC) subjects and HIV-1-infected individuals on long-term cART. Our findings indicate that IL-7RA haplotype 2 (H2*T), defined as T-allele carriers at the tagging SNP rs6897932, affects the size of the peripheral blood MAIT cell pool, as well as their production of cytokines and cytolytic effector proteins in response to bacterial stimulation. H2*T carriers had lower sIL-7Rα levels and higher MAIT cell frequency with enhanced functionality linked to higher expression of MAIT cell-associated transcription factors. Despite an average of 7 years on suppressive cART, MAIT cell levels and function in HIV-1-infected individuals were still significantly lower than those of HC. Notably, we observed a significant correlation between MAIT cell levels and cART duration only in HIV-1-infected individuals carrying IL-7RA haplotype 2. Interestingly, treatment with sIL-7Rα in vitro suppressed IL-7-dependent MAIT cell proliferation and function following cognate stimulations. These observations suggest that sIL-7Rα levels may influence MAIT cell numbers and function in vivo by limiting IL-7 bioavailability to MAIT cells. Collectively, these observations suggest that IL-7RA polymorphisms may play a significant role in MAIT cell biology and influence MAIT cells recovery in HIV-1 infection. The potential links between IL7RA polymorphisms, MAIT cell immunobiology, and HIV-1 infection warrant further studies going forward.
Spatial distribution and morphometry of the Namibian coral mounds controlled by the hydrodynamic regime and outer-shelf topography
Authors: Tamborrino Leonardo , Titschack Jürgen , Wienberg Claudia , Purkis Sam , Eberli Gregor P. , Hebbeln Dierk
Published: October 2022

Cold-water corals mounds develop over millennial timescales as a result of sustained coral growth and concurrent with sediment deposition within their coral frameworks. So far, coral mounds have been primarily investigated as deep-sea biodiversity hotspots and geo-biological paleo-archives, whereas their morphological appearance and spatial arrangement have received much less attention. Here, we analysed the spatial distribution and the morphometry of coral mounds that developed on the Namibian shelf during a single short period dating back to the Early. The spatial distribution of these “early-stage” mounds and their morphological characteristics revealed a hierarchy of three different patterns. These comprise an alongslope mound distribution at a regional scale (first-order pattern), a topography-steered downslope alignment of mounds at a local scale (second-order pattern), and a hydrodynamic-controlled downslope orientation of the individual mounds at a mound scale (third-order pattern). In addition, because the Namibian mounds rarely exceed 20 m in height, key steps in the development of early-stage coral mounds (e.g. elongation, merging, limited gain in height compared to lateral extension) have been identified. With increasing size, coral mounds are more elongated, parallel to the prevailing tidal system, which is interpreted to reflect the transition from an “inherited” to a “developed” mound morphology. Besides supporting this earlier hypothesis on mound development, we could show that this transition takes place when the Namibian coral mounds reach ~150 m in length and ~8 m in height. This study reveals that the spatial-morphological appearance of coral mounds, often treated as a descriptive information, can provide valid information to understand their formation.
Durability and life prediction analysis of recycled aggregate concrete with ceramic waste powder under freeze-thaw conditions based on impact-echo method and Grey-Markov model
Authors: Yu Jianqiao , Liu Dawei , Zhang Zhigang
Published: October 2022

Utilizing recycled aggregate concrete (RAC) for cyclic usage in building materials is one of the most feasible methods for reducing the demand for natural aggregates in the construction sector and disposing of construction and demolition trash in landfills. Previous research has demonstrated that the weak freeze-thaw (F-T) resistance of RAC poses a significant threat to the safety of RAC structures in severe cold regions. Therefore, this paper explores the influence of ceramic waste powder (CWP) at various replacement rates on the freeze-thaw resilience of RAC. In this experiment, six groups of CWP doping ratios of 0%, 10%, 20%, 30%, 40, and 50% were designed. Before the F-T cycling test, each group of specimens’ basic mechanical and physical performance data was measured throughout the regular curing age. At the conclusion of each F-T cycle, the durability performance of RAC was tested using the impact-echo method and compressive strength test. To predict the lifetime of RAC mixtures, a Grey-Markov model was created. It was found that the impact-echo method is more appropriate for assessing the durability of RAC in a freeze-thaw condition. The RAC’s F-T resistance is greatest when the CWP content is 20%. The Grey-Markov model has a high degree of predictive accuracy, effectively reflecting the relationship between RAC durability and F-T cycles, and has wide practical applications.
Solvothermal growth of moiré superlattices in antimony telluride spiral-type nanoplates
Authors: Link Robert , Marcus Gabriel , Carroll David
Published: October 2022

The study of moiré superlattices (MSLs) has surged in recent years, as they have been found to host several emergent quantum phenomena associated with high electron correlations. In this study, we put forward a viable chemical route to the formation of moiré patterns in antimony telluride (Sb2Te3) nanoplates by leveraging screw dislocation-driven growth. These Sb2Te3 MSLs are synthesized using a scalable, one-pot, colloidal solution-liquid-solid (SLS) procedure. We report twist angles up to 0.52° (estimated using a combination of transmission electron microscope (TEM) image analysis and computer simulation). We investigate the early growth stages of Sb2Te3 spiral-type nanoplates under TEM, and we detail the growth of Sb2Te3 spiral-type nanoplates that feature a central nanopore, caused by tandem growth with nanorods. We hope that these methods will facilitate future investigation into the electronic properties of Sb2Te3 MSLs.
A face-based immersed boundary method for compressible flows using a uniform interpolation stencil
Authors: Kasturi Rangan M. L. N. V. , Ghosh Santanu
Published: October 2022

In this study, an immersed boundary method developed for compressible viscous flows (Ramakrishnan, R., Girdhar, A., & Ghosh, S. (2016). Immersed Boundary Methods for Compressible Laminar Flows) is modified to improve their stability and robustness. The embedded object is represented as a set of line segments in two dimensions with their outward unit normal vectors specified. A forcing method that leverages the finite volume approach is used, wherein the solution at the cell interfaces that lie near the boundaries of the embedded solid is reconstructed to implicitly satisfy boundary conditions at the immersed surface. The proposed immersed boundary method is validated for transonic inviscid flow past a bump in a channel, supersonic flow past a circular cylinder, transonic viscous flow past a NACA0012 airfoil, and supersonic viscous flow past a circular cylinder. The results are compared with simulations from the literature using contours of flow properties, surface pressure, or Mach number plots and show good agreement.
Harnessing artificial intelligence to infer novel spatial biomarkers for the diagnosis of eosinophilic esophagitis
Authors: Larey Ariel , Aknin Eliel , Daniel Nati , Osswald Garrett A. , Caldwell Julie M. , Rochman Mark , Wasserman Tanya , Collins Margaret H. , Arva Nicoleta C. , Yang Guang-Yu , Rothenberg Marc E. , Savir Yonatan
Published: October 2022

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. Second only to gastroesophageal reflux disease, EoE is one of the leading causes of chronic refractory dysphagia in adults and children. EoE is a clinicopathologic disorder and the histological portion of the diagnosis requires enumerating the density of esophageal eosinophils in esophageal biopsies, and evaluating additional features such as basal zone hyperplasia is helpful. However, this task requires time-consuming, somewhat subjective manual analysis, thus reducing the ability to process the complex tissue structure and infer its relationship with the patient's clinical status. Previous artificial intelligence (AI) approaches that aimed to improve histology-based diagnosis focused on recapitulating identification and quantification of the area of maximal eosinophil density, the gold standard manual metric for determining EoE disease activity. However, this metric does not account for the distribution of eosinophils or other histological features, over the whole slide image. Here, we developed an artificial intelligence platform that infers local and spatial biomarkers based on semantic segmentation of intact eosinophils and basal zone distributions. Besides the maximal density of eosinophils [referred to as Peak Eosinophil Count (PEC)] and a maximal basal zone fraction, we identify the value of two additional metrics that reflect the distribution of eosinophils and basal zone fractions. This approach enables a decision support system that predicts EoE activity and potentially classifies the histological severity of EoE patients. We utilized a cohort that includes 1,066 biopsy slides from 400 subjects to validate the system's performance and achieved a histological severity classification accuracy of 86.70%, sensitivity of 84.50%, and specificity of 90.09%. Our approach highlights the importance of systematically analyzing the distribution of biopsy features over the entire slide and paves the way toward a personalized decision support system that will assist not only in counting cells but can also potentially improve diagnosis and provide treatment prediction.
Circulating microRNA203 and its target genes' role in psoriasis pathogenesis
Authors: Mostafa Sally Abdallah , Mohammad Mai H. S. , Negm Walaa A. , Batiha Gaber El Saber , Alotaibi Saqer S. , Albogami Sarah M. , Waard Michel De , Tawfik Noha Z. , Abdallah Hoda Y.
Published: October 2022

Numerous microRNAs (miRNAs) have been found to have an aberrant expression in the peripheral blood or psoriasis patients' lesions. Psoriasis was shown to have the abnormal expression of microRNA-203 (miR-203). It is a skin-specific signal that governs cellular proliferation in a protein kinase C-dependent manner and is mostly generated by keratinocytes. This work evaluated the expression levels of the circulating miR-203 target genes SOCS3, SOCS6, TP63, TNF-, IL8, and IL24 in psoriasis patients. Using a relative quantitation PCR technique, we determined the expression levels of miR-203 and its target genes (SOCS3, SOCS6, TP63, TNF-, IL8, and IL24) in the plasma of 120 psoriatic patients and matched healthy controls. The disease characteristics of the patients were then correlated with the expression results. We also conducted numerous enrichment analyses for the diseases, functions, and pathways connected to the under-researched biomarkers. Compared to healthy controls, psoriatic patients had significantly increased levels of miR-203 expression; 7.1 (4.4–9.9). In contrast, psoriatic patients had significantly lower expression of all the examined genes compared to healthy controls. Regarding all the study biomarkers, the receiver operating characteristic (ROC) curve analysis demonstrated significant sensitivity and specificity for differentiating between psoriatic patients and healthy controls. According to the results of the disease matching score generated by miR-203 and its target genes, psoriasis was ranked first with a score of 4.45. The third-place finisher with a value of 3.98, it also demonstrated that miR-203 and its target genes are connected to various skin disorders. Our results show that miR-203 contributes to psoriasis pathogenesis not only locally in skin lesions but also in circulation, indicating that it may contribute to the systemic symptoms of the illness. MiR-203 overexpression in psoriasis suggests that miR-203 may be involved in an anti-inflammatory response because it targets both SOCS gene family members and pro-inflammatory cytokines.