bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the relationship between post-contrast acute kidney injury and different baseline creatinine standards: A retrospective cohort study
Authors: Ying Jixiang , Wang Junren , Ying Zhiye , Ran Xingwu , Zeng Xiaoxi , Chen Dawei , Gao Yun , Zhong Li
Published: January 2023

Objective

According to previous studies, the incidence of post-contrast acute kidney injury(PC-AKI) in diabetic is far higher than that in the general population. Therefore, we explored the relationship between the incidence of PC-AKI and different baseline serum creatinine (SCr) levels, and determined the relationship between PC-AKI and different types of contrast media (CMs), different doses of CM, and different examination methods in this specific population.

Materials and methods

Patients with diabetes in whom CM was used between 2010 and 2020 at our institution were included. Participants were identified according to the following three schemes: Scheme 1 (n=5911), SCr was detected before and within 72 h after using CM; Scheme 2 (n=2385), SCr was detected within 24 h before and within 24–72 h after using CM; and Scheme 3 (n=81), SCr was detected within 24 h before and within 0–24, 24–48, and 48–72 h after using CM. The incidence of PC-AKI with different types of CM, incidence of PC-AKI on digital subtraction angiography (DSA) and enhanced computed tomography (CT), proportion of PC-AKI with different doses of CM, and baseline SCr at different stages of PC-AKI were compared. Multivariate logistic regression analysis was used to explore risk factors for PC-AKI.

Results

A total of 29,081 patients were included in this study. The incidence of PC-AKI in Scheme 3 (22.22%) was higher than those in Schemes 1 (6.19%) and 2 (7.71%). The incidence of PC-AKI on DSA was higher than that on enhanced CT (8.30% vs. 5.80%; P<0.05). The incidence of PC-AKI in the increased-dose CM group was higher than that in the non-increased-dose CM group (7.9% vs. 5.7%; P<0.01). Moreover, there were differences in baseline SCr values at different stages of PC-AKI (P<0.01). Multivariate logistic regression analysis showed that hypertension, chronic kidney disease, heart failure, peripheral vascular disease, metformin, diuretics, and CM dose were risk factors for PC-AKI.

Conclusion

The incidence of PC-AKI increased significantly with increasing time requirement and frequency of SCr detection. Moreover, before using CM, we should control the blood pressure and heart failure, stop using metformin and diuretics, and use CMs at the minimum dose to avoid PC-AKI.
Characteristics and possible mechanisms of metabolic disorder in overweight women with polycystic ovary syndrome
Authors: Yu Jin , Zhou Yulai , Ding Jie , Zhang Danying , Yu Chaoqin , Huang Hefeng
Published: January 2023

Background

Polycystic ovary syndrome (PCOS) is a kind of endocrine and metabolic disorder, disturbing the females of reproductive age. Here, we aimed to investigate the metabolic characteristics of overweight women with PCOS and analyze the possible mechanisms.

Methods

We conducted a cross-sectional study on 947 patients with PCOS, who were classified according to body mass index (BMI) as overweight (BMI ≥ 24 kg/m2) or non-overweight (BMI ≤ 23.9 kg/m2). The clinical symptoms, endocrine features, metabolic status, and inflammatory levels of the patients were comprehensively assessed and compared between the patients of the two groups. Additionally, a predictive study on the correlation between inflammation and metabolism was performed using STRING and Cytoscape software, and the possible mechanisms of metabolic disorders involved in the overweight PCOS were preliminarily explored.

Results

Overweight PCOS was associated with increased average age, waist-to-hip ratio, and the incidence of acanthosis nigricans. These patients were susceptible to familial hypertension and diabetes, and exhibited evident characteristics of low levels of luteinizing hormone (LH) and the ratio of LH to follicle-stimulating hormone, and were more inclined to insulin resistance (IR). Furthermore, overweight PCOS presented with a chronic low-grade inflammation state with increased levels of inflammatory cytokines complement components C5/C5α, CXCL12/SDF-1, MIF, and Serpin E1/PAI-1 evidently compared with those in non-overweight PCOS. Pearson analysis showed that these inflammatory cytokines were directly or indirectly correlated with IR. The STRING and Cytoscape network analysis predicted that inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1 and MIF might be crucial for inducing IR in overweight PCOS women through various biological functions and signal transductions including the JAK-STAT cascade, ATP biosynthesis, and HIF-1 signaling.

Conclusions

Overweight patients with PCOS are prone to low gonadal levels, IR, and chronic low-grade inflammation. Inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1and MIF might lead to IR through multiple biological functions and signal transductions in overweight PCOS.
Will the embedded service in supply chains play a role in lowering manufacturer’s carbon emission and maintaining economic growth?
Authors: Shi Chengdong , Chen Lulu , Yu Weitong , Zhang Zhiyao
Published: January 2023

Introduction: The carbon cap and trade mechanism (CCTM) is forcing companies to reduce carbon emissions. Due to financial and technical constraints, manufacturers responsible for recycling and remanufacturing begin to seek embedded services from energy service companies (ESCOs), marking the emergence of embedded low-carbon service supply chains. The purpose of this paper is to explore the role of embedded low-carbon service in supply chains in lowering manufacturer’s carbon emissions and maintaining economic growth.

Methods: In this paper, a decision model for risk-averse closed-loop supply chain for embedded low-carbon service in uncertain markets is built by using the Stackelberg theory and mean-variance (MV) approach. Equilibrium decisions, the manufacturer’s expected utility growth, and total carbon emission reduction are obtained. Sensitivity analysis is performed for the main parameters.

Results: The results indicate that only when the manufacturer’s risk aversion level and consumers’ low-carbon preference are within the range of 0.35–0.9, can the manufacturer bring in embedded low-carbon service by cooperating with an ESCO through revenue-sharing contracts. When there is a higher carbon price, embedded low-carbon service can further increase the manufacturer’s expected utility, maintain economic growth and reduce carbon emissions.

Discussion: Embedded low-carbon service in supply chains can play a role in lowering manufacturers’ carbon emissions and maintaining economic growth when the manufacturer’s risk aversion level, carbon price, and consumers’ low-carbon preference are high. Theoretically, this study combines closed-loop supply chains (CLSCs) and embedded low-carbon services, enriching supply chain theories. In addition, the findings provide managerial insights for manufacturers, ESCOs, and governments.
Impact of air quality on enterprise productivity: Evidence from Chinese listed companies
Authors: Liu Su , Yang Yuetao , Cai Ling
Published: January 2023

We provide insights and innovative ideas for China to achieve green development and promote high-quality economic development by studying the impact of air quality on enterprise productivity. This paper uses data from 2008 to 2016 for A-share companies listed on the Shanghai and Shenzhen stock markets, as well as the levels of particulate matter under 2.5 μm in diameter for 214 major Chinese cities. At the same time, this paper innovatively applies regression discontinuity and the Spatial Durbin Model for empirical testing. Considering the endogeneity, we choose the air flow index as an instrumental variable and the generalized space two-stage least squares method for the endogenous test. Additionally, we use dynamic regression and different spatial weight matrix to conduct robustness tests and reselect data from 2008 to 2012 and 2013 to 2016 as samples. Moreover, we test corporate heterogeneity from three perspectives: pollutant type, firm equity, and an industry’s technological level. The results show that the deterioration of local air quality significantly inhibits firm productivity, while the spatial spillover effects of pollution from surrounding cities also have a significant dampening effect on firm productivity. This negative effect is transmitted through research and development innovation capacity, human capital, and government subsidies. This empirical evidence from listed companies can be used for evaluating air quality management to enhance enterprise productivity, as well as to provide policy recommendations for boosting firm productivity through improved air quality.
Genetic variation of endangered Jankowski’s Bunting (Emberiza jankowskii): High connectivity and a moderate history of demographic decline
Authors: Huang Long , Feng Guochen , Li Dan , Shang Weiping , Zhang Lishi , Yan Rongfei , Jiang Yunlei , Li Shi
Published: January 2023

Introduction

Continued discovery of “mismatch” patterns between population size and genetic diversity, involving wild species such as insects, amphibians, birds, mammals, and others, has raised issues about how population history, especially recent dynamics under human disturbance, affects currently standing genetic variation. Previous studies have revealed high genetic diversity in endangered Jankowski’s Bunting. However, it is unclear how the demographic history and recent habitat changes shape the genetic variation of Jankowski’s Bunting.

Methods

To explore the formation and maintenance of high genetic diversity in endangered Jankowski’s Bunting, we used a mitochondrial control region (partial mtDNA CR) and 15 nuclear microsatellite markers to explore the recent demographic history of Jankowski’s Bunting, and we compared the historical and contemporary gene flows between populations to reveal the impact of habitat change on population connectivity. Specifically, we aimed to test the following hypotheses: (1) Jankowski’s Bunting has a large historical Ne and a moderate demographic history; and (2) recent habitat change might have no significant impact on the species’ population connectivity.

Results

The results suggested that large historical effective population size, as well as severe but slow population decline, may partially explain the high observable genetic diversity. Comparison of historical (over the past 4Ne generations) and contemporary (1–3 generations) gene flow indicated that the connectivity between five local populations was only marginally affected by landscape changes.

Discussion

Our results suggest that high population connectivity and a moderate history of demographic decline are powerful explanations for the rich genetic variation in Jankowski’s Bunting. Although there is no evidence that the genetic health of Jankowski’s Bunting is threatened, the time-lag effects on the genetic response to recent environmental changes is a reminder to be cautious about the current genetic characteristics of this species. Where possible, factors influencing genetic variation should be integrated into a systematic framework for conducting robust population health assessments. Given the small contemporary population size, inbreeding, and ecological specialization, we recommend that habitat protection be maintained to maximize the genetic diversity and population connectivity of Jankowski’s Bunting.
Whole genome sequencing of CCR5 CRISPR-Cas9-edited Mauritian cynomolgus macaque blastomeres reveals large-scale deletions and off-target edits
Authors: Schmidt Jenna Kropp , Kim Yun Hee , Strelchenko Nick , Gierczic Sarah R. , Pavelec Derek , Golos Thaddeus G. , Slukvin Igor I.
Published: January 2023

Introduction: Genome editing by CRISPR-Cas9 approaches offers promise for introducing or correcting disease-associated mutations for research and clinical applications. Nonhuman primates are physiologically closer to humans than other laboratory animal models, providing ideal candidates for introducing human disease-associated mutations to develop models of human disease. The incidence of large chromosomal anomalies in CRISPR-Cas9-edited human embryos and cells warrants comprehensive genotypic investigation of editing outcomes in primate embryos. Our objective was to evaluate on- and off-target editing outcomes in CCR5 CRISPR-Cas9-targeted Mauritian cynomolgus macaque embryos.

Methods: DNA isolated from individual blastomeres of two embryos, along with paternal and maternal DNA, was subjected to whole genome sequencing (WGS) analysis.

Results: Large deletions were identified in macaque blastomeres at the on-target site that were not previously detected using PCR-based methods. De novo mutations were also identified at predicted CRISPR-Cas9 off-target sites.

Discussion: This is the first report of WGS analysis of CRISPR-Cas9-targeted nonhuman primate embryonic cells, in which a high editing efficiency was coupled with the incidence of editing errors in cells from two embryos. These data demonstrate that comprehensive sequencing-based methods are warranted for evaluating editing outcomes in primate embryos, as well as any resultant offspring to ensure that the observed phenotype is due to the targeted edit and not due to unidentified off-target mutations.
Development and validation of a genomic instability-related lncRNA prognostic model for hepatocellular carcinoma
Authors: Xun Ziyu , Wang Yanyu , Long Junyu , Li Yiran , Yang Xu , Sun Huishan , Zhao Haitao
Published: January 2023

Genomic instability is a characteristic of tumors, and recent studies have shown that it is related to a poor prognosis of multiple cancers. Long non-coding RNAs (lncRNAs) have become a research hotspot in recent years, and many unknown biological functions are being explored. For example, some lncRNAs play a critical role in the initiation and progression of multiple cancer types by modulating genomic instability. However, the role of genomic instability-related lncRNAs in liver cancer remains unclear. Therefore, we screened genomic instability-related lncRNAs by combining somatic mutation data and RNA-Seq data in The Cancer Genome Atlas (TCGA) database. We established a genomic instability-related lncRNA model (GLncM) involving ZFPM2-AS1 and MIR210HG to predict the hepatocellular carcinoma (HCC) prognosis and further explore the clinical significance of these lncRNAs, and the robustness of the model was validated in the verification set. Thereafter, we calculated the immune score for each patient and explored the relationship between genome instability and the immune microenvironment. The analysis indicated that this model was better than the immune microenvironment in predicting the prognosis of HCC patients, suggesting that the GLncM may be an effective indicator of HCC prognosis and providing a new direction and strategy for estimating the prognosis of HCC patients.
Development of multi-level standards of care recommendations for sickle cell disease: Experience from SickleInAfrica
Authors: Paintsil Vivian , Ally Mwashungi , Isa Hezekiah , Anie Kofi A. , Mgaya Josephine , Nkanyemka Malula , Nembaware Victoria , Oppong-Mensah Yaa Gyamfua , Ndobho Flora , Chirande Lulu , Makubi Abel , Nnodu Obiageli , Wonkam Ambroise , Makani Julie , Ohene-Frempong Kwaku
Published: January 2023

Introduction:Sickle Cell Disease (SCD) causes significant morbidity and mortality particularly in sub-Saharan Africa (SSA) where it contributes to early childhood deaths. There is need to standardize treatment guidelines to help improve overall SCD patient health outcomes. We set out to review existing guidelines on SCD and to set minimum standards for management of SCD for the different referral levels of healthcare.

Methods:A standards of care working group (SoC-WG) was established to develop the SoC recommendations. About 15 available SCD management guidelines and protocols were reviewed and themes extracted from them. The first draft was on chosen themes with 64 major headings and subtopics. Using a summarised WHO levels of referral document, we were able to get six different referral levels of healthcare. The highest referral level was the tertiary facilities whilst the lowest level was the home setting. Recommendations for SCD management for the regional, district, sub-districts, health posts and CHPs compounds were also drafted.

Results:The results from this review yielded a guidelines document which had recommendations for management of SCD on 64 topics and subtopic for all the six (6) different referral levels.

Discussions:Every child with SCD need to receive comprehensive care that is coordinated at each level. This recommendation is unique in terms of the availability of recommendations for different levels of care as compared to the traditional guidelines which is more focused at the tertiary levels. Patients can access care at any of the other lower referral hospitals and be managed with recommendations that are in keeping with institutional resources at that level. When such patients need care that requires expertise that is not available at that level, the recommendations will be to refer to the appropriate referral level where those expertise are available. This encourages patients to have good clinical care nearer their homes but also having access to specialist screening modalities and expertise at the tertiary hospitals if need be. With this, patient are not limited to a specific referral level when interventions cannot be instituted for them.

Conclusion:This SoC recommendations document is a useful material that can be used for consistent standards of treatment in SSA.
Triple negative breast cancer: Immunogenicity, tumor microenvironment, and immunotherapy
Authors: Loizides Sotiris , Constantinidou Anastasia
Published: January 2023

Triple negative breast cancer (TNBC) is a biologically diverse subtype of breast cancer characterized by genomic and transcriptional heterogeneity and exhibiting aggressive clinical behaviour and poor prognosis. In recent years, emphasis has been placed on the identification of mechanisms underlying the complex genomic and biological profile of TNBC, aiming to tailor treatment strategies. High immunogenicity, specific immune activation signatures, higher expression of immunosuppressive genes and higher levels of stromal Tumor Infiltrating Lymphocytes, constitute some of the key elements of the immune driven landscape associated with TNBC. The unprecedented response of TNBC to immunotherapy has undoubtedly changed the standard of care in this disease both in the early and the metastatic setting. However, the extent of interplay between immune infiltration and mutational signatures in TNBC is yet to be fully unravelled. In the present review, we present clinical evidence on the immunogenicity and tumour microenvironment influence on TNBC progression and the current treatment paradigms in TNBC based on immunotherapy.
Functional gene polymorphisms and expression alteration of selected microRNAs and the risk of various gastric lesions in Helicobacter pylori-related gastric diseases
Authors: Liu Qi , Li Danyan , Dai Yunkai , Zhang Yunzhan , Lan Shaoyang , Luo Qi , Ye Jintong , Chen Xu , Li Peiwu , Chen Weijing , Li Ruliu , Hu Ling
Published: January 2023

Background:Helicobacter pylori (Hp) persistent infection is an important pathogenic factor for a series of chronic gastric diseases from chronic gastritis to gastric cancer. Genetic and epigenetic abnormalities of microRNAs may play a vital role in the pathological evolution of gastric mucosa in Helicobacter pylori-related gastric diseases (HPGD). This study aimed to investigate the relationship between miR-146a, miR-196a2, miR-149, miR-499 and miR-27a gene single nucleotide polymorphisms (SNPs) and their expressions with pathological changes in gastric mucosa, and to further analyze the interactions between SNPs and Hp.

Methods: Subjects in this study included patients diagnosed with HPGD and healthy controls. MiR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs2292832, miR-499 rs3746444 and miR-27a rs895819 were genotyped by direct sequencing. Fluorescence quantitative PCR was used to detect microRNA expressions. Gene-gene and gene-environment interactions were evaluated by multifactor dimensionality reduction (MDR) method.

Results: we found that frequency distribution of miR-196a2 rs11614913 CT genotype in gastric precancerous lesion (GPL) group and gastric cancer (GC) group was significantly higher than normal control (NOR) group [adjusted OR = 6.16, 95%CI (1.46–26.03); adjusted OR = 11.83, 95%CI (1.65–84.72), respectively]. CT genotype and C allele of miR-27a rs895819 were associated with increased risk of GC [adjusted OR = 10.14, 95%CI (2.25–45.77); adjusted OR = 3.71, 95%CI(1.46–9.44), respectively]. The MDR analysis results showed that the interaction between miR-196a2 rs11614913 and Hp was associated with the risk of GPL (p = 0.004). Meanwhile, the expression level of miR-196a2 in GC group was significantly higher than NOR, chronic inflammation (CI) and early precancerous lesion (EPL) groups among Hp-positive subjects. And expressions of miR-499 and miR-27a in GC group were both higher than EPL group. Also, miR-27a expression in GC group was higher than CI and gastric atrophy (GA) groups.

Conclusion: miR-196a2 rs11614913 and miR-27a rs895819 may affect the genetic susceptibility to GPL or GC. MiR-196a2 rs11614913 and Hp have a synergistic effect in the occurrence and development of GPL. The up-regulation of miR-499, miR-196a2 and miR-27a expression caused by Hp infection may be an important mechanism of gastric carcinogenesis.
Mapping quantitative trait loci and predicting candidate genes for Striga resistance in maize using resistance donor line derived from Zea diploperennis
Authors: Badu-Apraku B. , Adewale S. , Paterne A. , Offornedo Q. , Gedil M.
Published: January 2023

The parasitic weed, Striga is a major biological constraint to cereal production in sub-Saharan Africa (SSA) and threatens food and nutrition security. Two hundred and twenty-three (223) F2:3 mapping population involving individuals derived from TZdEI 352 x TZEI 916 were phenotyped for four Striga-adaptive traits and genotyped using the Diversity Arrays Technology (DArT) to determine the genomic regions responsible for Striga resistance in maize. After removing distorted SNP markers, a genetic linkage map was constructed using 1,918 DArTseq markers which covered 2092.1 cM. Using the inclusive composite interval mapping method in IciMapping, twenty-three QTLs influencing Striga resistance traits were identified across four Striga-infested environments with five stable QTLs (qGY4, qSC2.1, qSC2.2, qSC5, and qSC6) detected in more than one environment. The variations explained by the QTLs ranged from 4.1% (qSD2.3) to 14.4% (qSC7.1). Six QTLs each with significant additive × environment interactions were also identified for grain yield and Striga damage. Gene annotation revealed candidate genes underlying the QTLs, including the gene models GRMZM2G077002 and GRMZM2G404973 which encode the GATA transcription factors, GRMZM2G178998 and GRMZM2G134073 encoding the NAC transcription factors, GRMZM2G053868 and GRMZM2G157068 which encode the nitrate transporter protein and GRMZM2G371033 encoding the SBP-transcription factor. These candidate genes play crucial roles in plant growth and developmental processes and defense functions. This study provides further insights into the genetic mechanisms of resistance to Striga parasitism in maize. The QTL detected in more than one environment would be useful for further fine-mapping and marker-assisted selection for the development of Striga resistant and high-yielding maize cultivars.
Deep mutational scanning: A versatile tool in systematically mapping genotypes to phenotypes
Authors: Wei Huijin , Li Xianghua
Published: January 2023

Unveiling how genetic variations lead to phenotypic variations is one of the key questions in evolutionary biology, genetics, and biomedical research. Deep mutational scanning (DMS) technology has allowed the mapping of tens of thousands of genetic variations to phenotypic variations efficiently and economically. Since its first systematic introduction about a decade ago, we have witnessed the use of deep mutational scanning in many research areas leading to scientific breakthroughs. Also, the methods in each step of deep mutational scanning have become much more versatile thanks to the oligo-synthesizing technology, high-throughput phenotyping methods and deep sequencing technology. However, each specific possible step of deep mutational scanning has its pros and cons, and some limitations still await further technological development. Here, we discuss recent scientific accomplishments achieved through the deep mutational scanning and describe widely used methods in each step of deep mutational scanning. We also compare these different methods and analyze their advantages and disadvantages, providing insight into how to design a deep mutational scanning study that best suits the aims of the readers’ projects.
mRNA vaccines against SARS-CoV-2 induce comparably low long-term IgG Fc galactosylation and sialylation levels but increasing long-term IgG4 responses compared to an adenovirus-based vaccine
Authors: Buhre Jana Sophia , Pongracz Tamas , Künsting Inga , Lixenfeld Anne S. , Wang Wenjun , Nouta Jan , Lehrian Selina , Schmelter Franziska , Lunding Hanna B. , Dühring Lara , Kern Carsten , Petry Janina , Martin Emily L. , Föh Bandik , Steinhaus Moritz , von Kopylow Vera , Sina Christian , Graf Tobias , Rahmöller Johann , Wuhrer Manfred , Ehlers Marc
Published: January 2023

Background

The new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination.

Objective

However, the impact of these new vaccine formats with unclear effects on the long-term Ab response – including isotype, subclass, and their type of Fc glycosylation – is less explored.

Methods

Here, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270.

Results

We show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses – the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations.

Conclusion

In summary, the study suggests a comparable “adjuvant” potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.
Case report: Autoimmune encephalitis with multiple auto-antibodies with reversible splenial lesion syndrome and bilateral ovarian teratoma
Authors: Li Yaqiang , Zhang Mei , Liu Deshun , Wei Ming , Sheng Jun , Wang Zhixin , Xue Song , Yu Tingting , Xue Weimin , Zhu Beibei , He Jiale
Published: January 2023

Background

Reversible splenial lesion syndrome (RESLES) is a spectrum of disease radiologically characterized by reversible lesions caused by multiple factors, primarily involving the splenium of the corpus callosum (SCC). The most common causes of RESLES include infection, antiepileptic drug use and withdrawal, and severe metabolic disorders. Nevertheless, cases of autoimmune encephalitis (AE) are uncommon.

Case presentation

A 26-year-old female computer programming engineer with no previous medical or psychiatric history reported to the psychiatric hospital due to a 3-day episode of irritability, babbling, limb stiffness, sleepwalking, hallucinations, and paroxysmal mania. Brain MRI revealed abnormal signals of the SCC. Lumbar puncture was performed and further testing for auto-antibodies was conducted in both the CSF and serum. CSF of the patient was positive for anti-NMDAR (titer of 1:3.2) antibodies, and serum was also positive for anti-NMDAR (titer of 1:32) as well as mGluR5 (titer of 1:10) antibodies. Enhanced CT of the pelvis showed an enlarged pelvic mass; bilateral ovarian teratomas (mature teratoma and immature teratoma) were evaluated, which were pathologically confirmed after transabdominal left adnexal resection, right ovarian biopsy, and ovarian cystectomy. The patient considerably improved after intravenous administration of steroids, immunoglobulin, oral prednisone, surgical treatment, and chemotherapy. A follow-up MRI revealed completely resolved lesions. During a 3-month follow-up, the patient experienced complete resolution of symptoms without any sign of recurrence and tumors. The titer of the anti-NMDAR antibody decreased to 1:10 in serum.

Conclusion

Herein, we report a rare case of AE with overlapping auto-antibodies, along with RESLES and bilateral ovarian teratomas. The current case provides the possibility of the concurrence of mGluR5 antibodies in anti-NMDAR encephalitis. However, the underlying mechanism remains elusive. Furthermore, we provide additional evidence that overlapping antibodies-related pathology may be one of the many causes of RESLES. Nonetheless, caution should be observed in interpreting the observation, considering that this is a single-case study.
Recombinant GMA56 and ROP17 of Eimeria magna conferred protection against infection by homologous species
Authors: Xiao Jie , Chen Hao , Zheng Ruoyu , Pu Jiayan , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou
Published: January 2023

One of the most common rabbits coccidia species, Eimeria magna is mainly parasitic in the ileal and jejunal epithelial cells. E. magna infection can affect the growth performance of rabbits or cause other secondary diseases. Traditional methods of anticoccidial treatment typically result in drug resistance and drug residue. Therefore, vaccination is a promising alternative. Gametocyte antigen 56 (GAM56) and rhoptry kinase family proteins (ROPs) are involved in oocyst wall formation and parasite invasion, respectively. A virulence factor, ROP17 contains a serine/threonine kinase catalytic domain. In this study, recombinant E. magna GAM56 (rEmGAM56) and ROP17 (rEmROP17) proteins were obtained from a prokaryotic expression system and their reactogenicity was investigated with immunoblotting. To assess the potential of rEmGAM56 and rEmROP17 as coccidiosis vaccines, New Zealand White rabbits were subcutaneously immunized with 100 μg rEmGAM56 (rGC group) or rEmROP17 (rRC group) twice at 2-week intervals followed by homologous oocyst challenge. The rabbit serum was collected weekly to detect the specific antibody levels. The cytokine levels of pre-challenge serum were measured by enzyme-linked immunosorbent assay and the rabbits were observed and recorded post-challenge for the onset of clinical symptoms. The weight gain, oocyst output, and feed conversion ratio were calculated at the end of the experiment. The results showed that both rEmGAM56 and rEmROP17 had good reactogenicity. The rEmGAM56- or rEmROP17-immunized rabbits had milder clinical symptoms and feed conversion ratios of 3.27:1 and 3.37:1, respectively. The rEmGAM56-immunized rabbits had 81.35% body weight gain and 63.85% oocyst output reduction; the rEmROP17-immunized rabbits had 79.03% body weight gain and 80.10% oocyst output reduction. The ACI of rGC and rRC groups were 162.35 and 171.03, respectively. The specific antibody levels increased rapidly after immunization. Significantly increased interleukin (IL)-2, interferon (IFN)-γ, and IL-17 levels were evident in the rGC and rRC groups (p < 0.05). The rEmGAM56 and rEmROP17 elicited humoral and cellular responses, which protected against E. magna infection in rabbits. Thus, rEmGAM56 and rEmROP17 are potential vaccine candidates against E. magna, and rEmROP17 performed better than rEmGAM56.
Manipulating NK cellular therapy from cancer to invasive fungal infection: promises and challenges
Authors: Oh Bernice Ling Zhi , Chan Louis Wei Yong , Chai Louis Yi Ann
Published: January 2023

The ideal strategy to fight an infection involves both (i) weakening the invading pathogen through conventional antimicrobial therapy, and (ii) strengthening defense through the augmentation of host immunity. This is even more pertinent in the context of invasive fungal infections whereby the majority of patients have altered immunity and are unable to mount an appropriate host response against the pathogen. Natural killer (NK) cells fit the requirement of an efficient, innate executioner of both tumour cells and pathogens – their unique, targeted cell killing mechanism, combined with other arms of the immune system, make them potent effectors. These characteristics, together with their ready availability (given the various sources of extrinsic NK cells available for harvesting), make NK cells an attractive choice as adoptive cellular therapy against fungi in invasive infections. Improved techniques in ex vivo NK cell activation with expansion, and more importantly, recent advances in genetic engineering including state-of-the-art chimeric antigen receptor platform development, have presented an opportune moment to harness this novel therapeutic as a key component of a multipronged strategy against invasive fungal infections.
Spleen tyrosine kinase mediates the γδTCR signaling required for γδT cell commitment and γδT17 differentiation
Authors: Muro Ryunosuke , Narita Tomoya , Nitta Takeshi , Takayanagi Hiroshi
Published: January 2023

The γδT cells that produce IL-17 (γδT17 cells) play a key role in various pathophysiologic processes in host defense and homeostasis. The development of γδT cells in the thymus requires γδT cell receptor (γδTCR) signaling mediated by the spleen tyrosine kinase (Syk) family proteins, Syk and Zap70. Here, we show a critical role of Syk in the early phase of γδT cell development using mice deficient for Syk specifically in lymphoid lineage cells (Syk-conditional knockout (cKO) mice). The development of γδT cells in the Syk-cKO mice was arrested at the precursor stage where the expression of Rag genes and αβT-lineage-associated genes were retained, indicating that Syk is required for γδT-cell lineage commitment. Loss of Syk in γδT cells weakened TCR signal-induced phosphorylation of Erk and Akt, which is mandatory for the thymic development of γδT17 cells. Syk-cKO mice exhibited a loss of γδT17 cells in the thymus as well as throughout the body, and thereby are protected from γδT17-dependent psoriasis-like skin inflammation. Collectively, our results indicate that Syk is a key player in the lineage commitment of γδT cells and the priming of γδT17 cell differentiation.
Immunological consequences of microbiome-based therapeutics
Authors: Alam Md Zahidul , Maslanka Jeffrey R. , Abt Michael C.
Published: January 2023

The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient’s microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.
Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice
Authors: Jiang Lai , Yuan Chunchun , Ye Wenxin , Huang Qixin , Chen Zhuo , Wu Wenzi , Qian Lichun
Published: January 2023

Introduction

Campylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host’s innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored.

Methods

We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques.

Results

We first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni.

Discussion

This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.
Longitudinal white matter alterations in SIVmac239-infected rhesus monkeys with and without regular cART treatment
Authors: Liu Jiaojiao , Nguchu Benedictor Alexander , Liu Dan , Qi Yu , Aili Xire , Han Shuai , Gao Yuxun , Wang Xiaoxiao , Qiao Hongwei , Cai Chao , Huang Xiaojie , Li Hongjun
Published: January 2023

Objective

To use SIV-mac239-infected Chinese rhesus monkeys to study white matter changes with and without regular combined antiretroviral therapy (cART) and the relationships between the changes and clinical results.

Methods

Diffusion tensor imaging (DTI) data were collected at baseline and 10 days, 4 weeks, 12 weeks, 24 weeks, and 36 weeks after viral inoculation. Plasma CD4 T cell counts, CD4/CD8 ratio, plasma viral load, and cerebrospinal fluid (CSF) viral load were collected at baseline and 1 week, 5 weeks, 12 weeks, 24 weeks, and 36 weeks after viral inoculation. Microstructural characteristics were examined within 76 white matter areas defined by the DTI-white matter (WM) atlas for rhesus macaques. Corrections for multiple comparisons were performed using a false discovery rate (p < 0.05, FDR). Correlation analyzes between imaging markers and clinical markers (plasma CD4 T cell counts, CD4/CD8 ratio, plasma viral load, and cerebral spinal fluid viral load) were performed using Pearson correlations.

Results

White matter changes in SIV-infected macaques were detected in different brain regions as early as 4 weeks after inoculation. As time progressed, cART reversed, ameliorated, or even enhanced the effects. The CD4 T cell count was mainly associated with DTI metrics before cART, while the CD4/CD8 ratio was associated with white matter changes with and without cART. Viral load was positively associated with mean diffusivity in HIV patients without cART, and the opposite results were seen in HIV patients with cART.

Conclusion

SIV-mac239 infection may be an ideal tool for studying HIV-induced changes in the brain. The first white matter changes appeared in a structure adjacent to the periventricular area as early as 4 weeks after inoculation. As time progressed, cART had different effects on different regions, reversing, attenuating, or even progressing the pathology. Moreover, these changes were closely related to the CD4/CD8 ratio and viral load, even after cART.
Current experimental methods to investigate the impact of specialized pro-resolving lipid mediators on Sjögren’s syndrome
Authors: dos Santos Harim T. , Nam Kihoon , Gil Diana , Yellepeddi Venkata , Baker Olga J.
Published: January 2023

Sjögren’s syndrome is a chronic inflammatory autoimmune disease characterized by diminished secretory function of the exocrine glands. Although extensive investigation has been done to understand Sjögren’s syndrome, the causes of the disease are as yet unknown and treatments remain largely ineffective, with established therapeutic interventions being limited to use of saliva substitutes with modest effectiveness. A primary feature of Sjögren’s syndrome is uncontrolled inflammation of exocrine tissues and previous studies have demonstrated that lipid-based specialized pro-resolving mediators reduce inflammation and restores tissue integrity in salivary glands. However, these studies are limited to a single specialized pro-resolving lipid mediator’s family member resolvin D1 or RvD1 and its aspirin-triggered epimer, AT-RvD1. Consequently, additional studies are needed to explore the potential benefits of other members of the specialized pro-resolving lipid mediator’s family and related molecules (e.g., additional resolvin subtypes as well as lipoxins, maresins and protectins). In support of this goal, the current review aims to briefly describe the range of current experimental methods to investigate the impact of specialized pro-resolving lipid mediators on Sjögren’s syndrome, including both strengths and weaknesses of each approach where this information is known. With this article, the possibilities presented by specialized pro-resolving lipid mediators will be introduced to a wider audience in immunology and practical advice is given to researchers who may wish to take up this work.
Placental macrophages present distinct polarization pattern and effector functions depending on clinical onset of preeclampsia
Authors: Mercnik Monika Horvat , Schliefsteiner Carolin , Fluhr Herbert , Wadsack Christian
Published: January 2023

Hofbauer cells (HBCs) are resident macrophages of the human placenta, regulating immune tolerance and tissue homeostasis. HBCs of a normal placenta (CTR) exhibit mainly an anti-inflammatory M2 phenotype. Under exaggerated chronic inflammation during pregnancy, as in preeclampsia (PE), a phenotypic switch towards M1 polarization has been proposed. PE, defined as maternally derived syndrome can be distinguished into two different entities: early-onset (EO) preeclampsia and late-onset (LO) preeclampsia. Although the clinical presenting characteristics overlap, both can be identified by biochemical markers, heritability, and different maternal and fetal outcomes. To date, no study has specifically investigated polarization and phenotype of EO- and LO-PE HBCs and looked at possible changes in HBC functionality. Primary HBCs were isolated from CTR and PE placentae. First, in vitro morphological differences were observed between CTR and PE HBCs, with both PE groups exhibiting features of M1 macrophages alongside M2 forms. Interestingly, a different polarization pattern was observed between EO- and LO-PE HBCs. EO-PE HBCs develop a tissue remodeling M2 phenotype that is strongly shifted toward M1 polarization and showed a significant upregulation of CD86, TLR4, and HLA-DR. Furthermore, this pro-inflammatory signature is corroborated by higher expression of IRF5 and of NOS2 (p ≤ 0.05). However, their M2 characteristics is reflected by significant TGF-β secretion and ARG1 expression. In contrast, LO-PE HBCs developed a phagocytic CD209-low M2 phenotype in which the M1 pattern was not as pronounced as they downregulated the NOS2 gene, but expressed increased levels of pro-inflammatory CD80 and TLR1 (p ≤ 0.05). The enhanced phagocytosis and MMP-9 secretion alongside the increased secretion of anti-inflammatory IL -4, IL -13 and TGF-β in both EO- and LO-PE HBCs suggests their adaptive role and plasticity in resolving inflammation and tissue homeostasis.
Application of individualized multimodal radiotherapy combined with immunotherapy in metastatic tumors
Authors: Ji Xiaoqin , Jiang Wanrong , Wang Jiasheng , Zhou Bin , Ding Wei , Liu Shuling , Huang Hua , Chen Guanhua , Sun Xiangdong
Published: January 2023

Radiotherapy is one of the mainstays of cancer treatment. More than half of cancer patients receive radiation therapy. In addition to the well-known direct tumoricidal effect, radiotherapy has immunomodulatory properties. When combined with immunotherapy, radiotherapy, especially high-dose radiotherapy (HDRT), exert superior systemic effects on distal and unirradiated tumors, which is called abscopal effect. However, these effects are not always effective for cancer patients. Therefore, many studies have focused on exploring the optimized radiotherapy regimens to further enhance the antitumor immunity of HDRT and reduce its immunosuppressive effect. Several studies have shown that low-dose radiotherapy (LDRT) can effectively reprogram the tumor microenvironment, thereby potentially overcoming the immunosuppressive stroma induced by HDRT. However, bridging the gap between preclinical commitment and effective clinical delivery is challenging. In this review, we summarized the existing studies supporting the combined use of HDRT and LDRT to synergistically enhance antitumor immunity, and provided ideas for the individualized clinical application of multimodal radiotherapy (HDRT+LDRT) combined with immunotherapy.