bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding etiology of community-acquired central nervous system infections using metagenomic next-generation sequencing
Authors: Zhang Shanshan , Wu Gang , Shi Yuru , Liu Ting , Xu Liangfei , Dai Yuanyuan , Chang Wenjiao , Ma Xiaoling
Published: September 2022

Background

Community-acquired central nervous system infections (CA-CNS infections) have the characteristics of acute onset and rapid progression, and are associated with high levels of morbidity and mortality worldwide. However, there have been only limited studies on the etiology of this infections. Here, metagenomic next-generation sequencing (mNGS), a comprehensive diagnosis method, facilitated us to better understand the etiology of CA-CNS infections.

Methods

We conducted a single-center retrospective study between September 2018 and July 2021 in which 606 cerebrospinal fluid (CSF) samples were collected from suspected CNS infectious patients for mNGS testing, and all positive samples were included in this analysis

Results

After the exclusion criteria, a total of 131 mNGS-positive samples were finally enrolled. Bacterial, viral, fungal, parasitic, specific pathogen and mixed infections were accounted for 32.82% (43/131), 13.74% (18/131), 0.76% (1/131), 2.29% (3/131) and 6.87% (9/131), respectively. A total of 41 different pathogens were identified, including 16 bacteria, 12 viruses, 10 fungi, and 1 parasite and 3 specific pathogens. The most frequent infecting pathogens are Epstein-Barr virus (n = 14), Herpes simplex virus 1 (n = 14), Mycobacterium tuberculosis (n = 13), Streptococcus pneumoniae (n = 13), and Cryptococcus neoformans (n = 8). Some difficult-to-diagnose pathogen infections were also detected by mNGS, such as Streptococcus suis, Pseudorabies virus, Bunyavirus, Orientia tsutsugamushi and Toxoplasma gondii.

Conclusion

In this study, mNGS identified a wide variety of pathogens of CA-CNS infections and many of which could not be detected by conventional methods. Our data provide a better understanding of the etiology of CA-CNS infections and show that mNGS represents a comparative screening of CSF in an unbiased manner for a broad range of human pathogens.
The IL-20RB receptor and the IL-20 signaling pathway in regulating host defense in oral mucosal candidiasis
Authors: Beute John E. , Kim Alex Y. , Park Jamie J. , Yang Allen , Torres-Shafer Keshia , Mullins David W. , Sundstrom Paula
Published: September 2022

Pseudomembranous candidiasis (thrush), erythematous candidiasis, and fungal esophagitis are infections of the barrier mucosa of the upper gastrointestinal tract. The majority of these infections are caused by Candida albicans, an opportunistic fungal pathogen that frequently exists as a harmless commensal on mucosal surfaces lining the gastrointestinal tract. Oral infections are initiated in the superficial stratified squamous epithelium, in which keratinocytes are the most abundant host cells and are the initial points of contact with C. albicans present in saliva. Intrinsic features of oral keratinocytes are likely to play important roles in host defense and tissue homeostasis in oral candidiasis. One understudied pathway that may be important for modulating oral candidiasis is the IL-20 cytokine signaling pathway that employs keratinocyte IL-20RB receptors as ligands for IL-19, IL-20, and IL-24. We report that production of human oral keratinocyte il24 mRNA and protein are stimulated during co-culture with C. albicans. To test the role of the IL-20 family signaling pathway in oral candidiasis, Il20rb-/- mice (lacking the IL-20RB receptor) were compared to wild-type mice in a murine model of oropharyngeal candidiasis. Fungal burdens and percent loss in body weight were determined. Despite comparable fungal burdens, the Il20rb-/- mice exhibited less weight loss over the course of their infection compared to the B6 mice, suggestive of reduced overall disease consequences in the mutant mice. Interference with IL-20 family cytokine signaling may be useful for augmenting the ability of the host to defend itself against pathogens.
Live cell screening identifies glycosides as enhancers of cardiomyocyte cell cycle activity
Authors: Magadum Ajit , Renikunta Harsha V. , Singh Neha , Estaras Conchi , Kishore Raj , Engel Felix B.
Published: September 2022

Promoting cardiomyocyte proliferation is a promising strategy to regenerate the heart. Yet, so far, it is poorly understood how cardiomyocyte proliferation is regulated, and no factor identified to promote mammalian cardiomyocyte proliferation has been translated into medical practice. Therefore, finding a novel factor will be vital. Here, we established a live cell screening based on mouse embryonic stem cell-derived cardiomyocytes expressing a non-functional human geminin deletion mutant fused to Azami Green (CM7/1-hgem-derived cardiomyocytes). We screened for a subset of compounds of the small molecule library Spectrum Collection and identified 19 potential inducers of stem cell-derived cardiomyocyte proliferation. Furthermore, the pro-proliferative potential of identified candidate compounds was validated in neonatal and adult rat cardiomyocytes as well as human induced pluripotent stem cell-derived cardiomyocytes. 18 of these compounds promoted mitosis and cytokinesis in neonatal rat cardiomyocytes. Among the top four candidates were two cardiac glycosides, peruvoside and convallatoxin, the flavonoid osajin, and the selective α-adrenoceptor antagonist and imidazoline I1 receptor ligand efaroxan hydrochloride. Inhibition of PTEN and GSK-3β enhanced cell cycle re-entry and progression upon stimulation with cardiac glycosides and osajin, while inhibition of IP3 receptors inhibited the cell cycle-promoting effect of cardiac glycosides. Collectively, we established a screening system and identified potential compounds to promote cardiomyocyte proliferation. Our data suggest that modulation of calcium handling and metabolism promotes cardiomyocyte proliferation, and cardiac glycosides might, besides increasing myocardial contraction force, contribute to cardiac repair by inducing cardiomyocyte proliferation.
Multi-objective cluster based bidding algorithm for E-commerce search engine marketing system
Authors: Jie Cheng , Wang Zigeng , Xu Da , Shen Wei
Published: September 2022

Search engine marketing (SEM) is an important channel for the success of e-commerce. With the increasing scale of catalog items, designing an efficient modern industrial-level bidding system usually requires overcoming the following hurdles: 1. the relevant bidding features are of high sparsity, preventing an accurate prediction of the performances of many ads. 2. the large volume of bidding requests induces a significant computation burden to offline and online serving. In this article, we introduce an end-to-end structure of a multi-objective bidding system for search engine marketing for Walmart e-commerce, which successfully handles tens of millions of bids each day. The system deals with multiple business demands by constructing an optimization model targeting a mixture of metrics. Moreover, the system extracts the vector representations of ads via the Transformer model. It leverages their geometric relation to building collaborative bidding predictions via clustering to address performance features' sparsity issues. We provide theoretical and numerical analyzes to discuss how we find the proposed system as a production-efficient solution.
A qualitative exploration of university students’ perspectives on distance education in Jordan: An application of Moore’s theory of transactional distance
Authors: Al-Tammemi Ala’a B. , Nheili Rana , Jibuaku Chiamaka H. , Al Tamimi Dua’a , Aljaberi Musheer A. , Khatatbeh Moawiah , Barakat Muna , Al-Maqableh Hindya O. , Fakhouri Hussam N.
Published: September 2022

The current study aimed at exploring university students’ perspectives on the emergency distance education strategy that was implemented during the COVID-19 crisis in Jordan, one of the countries in the Eastern Mediterranean Region. Utilizing a qualitative design supported by Moore’s theory of transactional distance, a total of 17 semi-structured interviews were conducted with university students of various study levels and disciplines. Data were inductively analyzed using thematic analysis as suggested by Braun and Clarke. Seven themes have emerged, including, (i) students’ psychological response to the sudden transition in educational process, (ii) students’ digital preparedness, equality, and digital communication, (iii) students’ and teachers’ technical competencies and technostress, (iv) student–student and student–teacher interpersonal communication, (v) quality and quantity of learning materials, (vi) students’ assignments, examinations, and non-reliable evaluation methods, and (vii) opportunities with positive impact of distance learning. The study findings provide evidence that the sudden transition from traditional on-campus to online distance education was significantly challenging in many aspects and was not a pleasant experience for many participants. Various factors under the jurisdiction of academic institutions and decision-makers are considered main contributing factors to the students’ educational experiences amid the pandemic crisis. Therefore, better planning and more sustainable utilization of educational resources have paramount importance in providing a high-quality education. Additionally, more dedicated efforts in terms of equitable, reliable, and credible evaluation systems should be considered in Jordan’s distance education strategy.
A multidimensional and analytical perspective on Open Educational Practices in the 21st century
Authors: Brandenburger Bonny
Published: September 2022

Participatory approaches to teaching and learning are experiencing a new lease on life in the 21st century as a result of the rapid technology development. Knowledge, practices, and tools can be shared across spatial and temporal boundaries in higher education by means of Open Educational Resources, Massive Open Online Courses, and open-source technologies. In this context, the Open Education Movement calls for new didactic approaches that encourage greater learner participation in formal higher education. Based on a representative literature review and focus group research, in this study an analytical framework was developed that enables researchers and practitioners to assess the form of participation in formal, collaborative teaching and learning practices. The analytical framework is focused on the micro-level of higher education, in particular on the interaction between students and lecturers when organizing the curriculum. For this purpose, the research reflects anew on the concept of participation, taking into account existing stage models for participation in the educational context. These are then brought together with the dimensions of teaching and learning processes, such as methods, objectives and content, etc. This paper aims to make a valuable contribution to the opening up of learning and teaching, and expands the discourse around possibilities for interpreting Open Educational Practices.
Treatment with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and diabetic liver pathology
Authors: Maksymchuk Oksana , Shysh Angela , Stroy Dmytro
Published: September 2022

An increase in CYP2E1 expression is a key factor in the development of diabetic oxidative liver damage. Long-term treatment with omega-3 PUFAs, which are CYP2E1 substrates, may affect CYP2E1 expression in the liver. In this work, we performed Western blot analysis, biochemical methods, and microscopic ultrastructural studies of the liver in a streptozotocin-induced rat model of type 1 diabetes to investigate whether long-term treatment with omega-3 PUFAs could induce CYP2E1-dependent oxidative stress and diabetic liver pathology. Significant hyperglycemia and lack of natural weight gain were observed in the diabetic rats compared to non-diabetic controls. A 2.5-fold increase in CYP2E1 expression (protein content and activity) was also observed in the diabetic rats. In addition, signs of oxidative stress were found in the liver of the diabetic rats. A significant increase in transaminases and GGT level in blood serum was also observed, which could indicate marked destruction of liver tissue. Diabetic dyslipidemia (increased triacylglycerol levels and decreased HDL-C levels) was found. Treatment of the diabetic animals with an omega-3-enriched pharmaceutical composition of PUFAs had no effect on CYP2E1 levels but contributed to a two-fold decrease in enzyme activity. The intensity of lipid peroxidation also remained close to the diabetic group. However, at the same time, antioxidant protection was provided by induction of antioxidant enzyme activity. Examination of the liver ultrastructure revealed no characteristic signs of diabetic pathology. However, omega-3 PUFAs did not normalize blood glucose levels and serum lipid profile. Thus, long-term treatment of diabetic rats with omega-3 PUFAs does not increase the risk of CYP2E1-dependent oxidative stress and development of liver pathology but prevents some diabetic ultrastructural damage to hepatocytes.
Role of irisin in physiology and pathology
Authors: Liu Shiqiang , Cui Fengqi , Ning Kaiting , Wang Zhen , Fu Pengyu , Wang Dongen , Xu Huiyun
Published: September 2022

Irisin, out-membrane part of fibronectin type III domain–containing 5 protein (FNDC5), was activated by Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) during physical exercise in skeletal muscle tissues. Most studies have reported that the concentration of irisin is highly associated with health status. For instance, the level of irisin is significantly lower in patients with obesity, osteoporosis/fractures, muscle atrophy, Alzheimer’s disease, and cardiovascular diseases (CVDs) but higher in patients with cancer. Irisin can bind to its receptor integrin αV/β5 to induce browning of white fat, maintain glucose stability, keep bone homeostasis, and alleviate cardiac injury. However, it is unclear whether it works by directly binding to its receptors to regulate muscle regeneration, promote neurogenesis, keep liver glucose homeostasis, and inhibit cancer development. Supplementation of recombinant irisin or exercise-activated irisin might be a successful strategy to fight obesity, osteoporosis, muscle atrophy, liver injury, and CVDs in one go. Here, we summarize the publications of FNDC5/irisin from PubMed/Medline, Scopus, and Web of Science until March 2022, and we review the role of FNDC5/irisin in physiology and pathology.
Impact of oil prices on the Islamic and conventional stock indexes’ performance in Malaysia during the COVID-19 pandemic: Fresh evidence from the wavelet-based approach
Authors: Khan Ali Burhan , Sharif Arshian , Islam Muhammad Saif Ul , Ali Anis , Fareed Muhammad , Zulfaqar Maria
Published: September 2022

The motivation behind conducting this research is to study the association between oil prices and Islamic and conventional stock indexes’ performance in the Malaysian market during COVID-19 using the wavelet analysis technique. The daily data on selected variables were collected from 1 January 2020, to 10 June 2021. Empirical investigation was made with wavelet analysis along with the Toda-Yamamoto test. The results revealed the significant response of both indexes to the oil price. Such response was negative for the short- and medium terms; however, it became positive in the long run. Our research has several important implications and recommendations for asset managers and policymakers. Policymakers and regulators should promote awareness and adopt effective action plans to minimize the risk of change in oil prices during the COVID-19 period. This research will enable investors, scholars, and policymakers to improve their current structure and prepare them for any potential future crisis.
A control strategy for improving power system resilience in N-k contingency
Authors: Shi Zhongpei , Wen Xichang , Liu Hongjun , Wang Huaizhi , Wu Ting
Published: September 2022

With the global climate change, the frequency of extreme weather is getting higher and higher, and the threat to the safe operation of the power system is gradually increasing, which is likely to cause large-scale power outages and then result in N-k contingencies. Meanwhile, the Modular Multi-level Converter (MMC) based Multi-Terminal High Voltage Direct Current (MTDC) power system has been confirmed that can provide the possibility for the network interconnection between regional power systems and various renewable energy resources to boost supply reliability and economy. To enhance the resilience of the power grid, a generation rescheduling scheme by optimal emergency control that considers the risk-based dynamic security constraint and reactive power constraints is proposed. Based on the transient stability criterion of the rotor angle speed of the center of inertia (COI), the active power is adjusted to improve the transient stability of the system. The usefulness of the proposed control strategy is highlighted on a 10-machine-39-bus hybrid power system built on MATMTDC, a MATLAB-based open-source software. The obtained results demonstrate that the state optimization control strategy is capable of enhancing the resilience of hybrid power systems and improving the transient stability when suffering N-k contingencies.
Identification and validation of P4HB as a novel autophagy-related biomarker in diabetic nephropathy
Authors: Bai Fang , Yu Kuipeng , Yang Yanjiang , Zhang Yimeng , Ding Lin , An Xin , Feng Feng , Sun Nan , Fan Jiahui , Liu Lei , Yang Huimin , Yang Xiangdong
Published: September 2022

Diabetic nephropathy (DN), a frequent microvascular complication of diabetes, has been recognized as a primary cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Previous studies found that autophagy of renal tubular epithelial cells plays an important role in DN pathogenesis. Our research aimed to investigate the differentially expressed autophagy-related genes (DEARGs) between DN and healthy renal tubule samples and identify a novel autophagy-related biomarker associated with tubulointerstitial injury in DN. In this study, gene expression profiles of renal tubules from 10 DN patients and 24 healthy controls in the GSE30122 dataset were analyzed, and 43 DEARGs were identified by bioinformatics analysis. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and correlation analysis were performed on DEARGs, and the hub gene prolyl 4-hydroxylase subunit beta (P4HB) was screened by protein–protein interaction and verified by utilizing other datasets and stimulating HK-2 cells under high glucose concentration. We found that the expression of P4HB in renal tubules was correlated with renal function. In summary, our research provided novel insights for comprehension of DN molecular mechanisms and identified P4HB as a novel autophagy-related biomarker of DN.
De novo mutations, genetic mosaicism and human disease
Authors: Mohiuddin Mohiuddin , Kooy R. Frank , Pearson Christopher E.
Published: September 2022

Mosaicism—the existence of genetically distinct populations of cells in a particular organism—is an important cause of genetic disease. Mosaicism can appear as de novo DNA mutations, epigenetic alterations of DNA, and chromosomal abnormalities. Neurodevelopmental or neuropsychiatric diseases, including autism—often arise by de novo mutations that usually not present in either of the parents. De novo mutations might occur as early as in the parental germline, during embryonic, fetal development, and/or post-natally, through ageing and life. Mutation timing could lead to mutation burden of less than heterozygosity to approaching homozygosity. Developmental timing of somatic mutation attainment will affect the mutation load and distribution throughout the body. In this review, we discuss the timing of de novo mutations, spanning from mutations in the germ lineage (all ages), to post-zygotic, embryonic, fetal, and post-natal events, through aging to death. These factors can determine the tissue specific distribution and load of de novo mutations, which can affect disease. The disease threshold burden of somatic de novo mutations of a particular gene in any tissue will be important to define.
The application of short and highly polymorphic microhaplotype loci in paternity testing and sibling testing of temperature-dependent degraded samples
Authors: Wen Dan , Xing Hao , Liu Ying , Li Jienan , Qu Weifeng , He Wei , Wang Chudong , Xu Ruyi , Liu Yi , Jia Hongtao , Zha Lagabaiyila
Published: September 2022

Paternity testing and sibling testing become more complex and difficult when samples degrade. But the commonly used genetic markers (STR and SNP) cannot completely solve this problem due to some disadvantages. The novel genetic marker microhaplotype proposed by Kidd’s research group combines the advantages of STR and SNP and is expected to become a promising genetic marker for kinship testing in degraded samples. Therefore, in this study, we intended to select an appropriate number of highly polymorphic SNP-based microhaplotype loci, detect them by the next-generation sequencing technology, analyze their ability to detect degraded samples, calculate their forensic parameters based on the collected 96 unrelated individuals, and evaluate their effectiveness in paternity testing and sibling testing by simulating kinship relationship pairs, which were also compared to 15 STR loci. Finally, a short and highly polymorphic microhaplotype panel was developed, containing 36 highly polymorphic SNP-based microhaplotype loci with lengths smaller than 100 bp and Ae greater than 3.00, of which 29 microhaplotype loci could not reject the Hardy-Weinberg equilibrium and linkage equilibrium after the Bonferroni correction. The CPD and CPE of these 29 microhaplotype loci were 1-2.96E-26 and 1-5.45E-09, respectively. No allele dropout was observed in degraded samples incubated with 100°C hot water for 40min and 60min. According to the simulated kinship analysis, the effectiveness at the threshold of 4/−4 reached 98.39% for relationship parent-child vs. unrelated individuals, and the effectiveness at the threshold of 2/−2 for relationship full-sibling vs. unrelated individuals was 93.01%, which was greater than that of 15 STR loci (86.75% for relationship parent-child vs. unrelated individuals and 81.73% for relationship full-sibling vs. unrelated individuals). After combining our 29 microhaplotype loci with other 50 short and highly polymorphic microhaplotype loci, the effectiveness values at the threshold of 2/−2 were 82.42% and 90.89% for relationship half-sibling vs. unrelated individuals and full-sibling vs. half-sibling. The short and highly polymorphic microhaplotype panel we developed may be very useful for paternity testing and full sibling testing in degraded samples, and in combination with short and highly polymorphic microhaplotype loci reported by other researchers, may be helpful to analyze more distant kinship relationships.
Effect of Sun exposure-induced ferroptosis mechanisms on pathology and potential biological processes of primary melanoma by microarray data analysis
Authors: Gao Yakun , Hou Qiang , Guo Rong , Ying Jianghui , Xiong Jiachao , Jiang Hua
Published: September 2022

Objectives: Sunlight exposure is an important environmental factor in the pathogenesis of skin cutaneous melanoma (SKCM). Ultraviolet (UV) from sunlight can cause excessive intracellular production of reactive oxygen species (ROS), resulting in damage from oxidative stress to cells. As a major iron-rich and ROS-producing organelle, mitochondria are considered as an important place for cell ferroptosis. Thus, the pathology and potential biological process of UV exposure-induced ferroptosis in the development of SKCM has aroused our strong interest.

Methods: Gene expression profile datasets of melanoma cell line datasets (GSE31909) and UV-irradiated mitochondria dataset (GSE3632) were downloaded from the Gene Expression Omnibus (GEO) database, and ferroptosis-related genes were obtained from the FerrDb v2 database. After identifying the common differentially expressed genes (DEGs), comprehensive analyzes were performed, including functional annotation, protein-protein interaction (PPI) network construction, hub gene identification, and gene and tissue protein expression levels, survival analysis, and immune cell infiltration analysis.

Results: A total of 14 common DEGs was identified for subsequent analyses. Seven DEGs, including PSMB4, CRELD2, CDKN2A, TIMP1, NDRG1, ATF3 and JUND, have consistent performance in mRNA and protein expression in normal skin and SKCM tissues can be regarded as a good biomarker with SKCM diagnostic effectiveness. Functional enrichment analysis results indicate that HIF-1 signaling pathway and angiogenesis involved in the pathogenesis and development of SKCM. Induction of ferroptosis in tumor cells by enhancing the function of CD8+ T cells is expected to be an effective intervention to promote tumor therapy.

Conclusion: Our study reveals the pathogenesis and potential biological processes of UV exposure-induced ferroptosis in the development of SKCM, which may provide potential immunotherapy targets for SKCM treatment via tumor cell ferroptosis mechanisms.
POP1 inhibits MSU-induced inflammasome activation and ameliorates gout
Authors: de Almeida Lucia , Devi Savita , Indramohan Mohanalaxmi , Huang Qi-Quan , Ratsimandresy Rojo A. , Pope Richard M. , Dorfleutner Andrea , Stehlik Christian
Published: September 2022

Canonical inflammasomes are innate immune protein scaffolds that enable the activation of inflammatory caspase-1, and subsequently the processing and release of interleukin (IL)-1β, IL-18, and danger signals, as well as the induction of pyroptotic cell death. Inflammasome assembly and activation occurs in response to sensing of infectious, sterile and self-derived molecular patterns by cytosolic pattern recognition receptors, including the Nod-like receptor NLRP3. While these responses are essential for host defense, excessive and uncontrolled NLRP3 inflammasome responses cause and contribute to a wide spectrum of inflammatory diseases, including gout. A key step in NLRP3 inflammasome assembly is the sequentially nucleated polymerization of Pyrin domain (PYD)- and caspase recruitment domain (CARD)-containing inflammasome components. NLRP3 triggers polymerization of the adaptor protein ASC through PYD-PYD interactions, but ASC polymerization then proceeds in a self-perpetuating manner and represents a point of no return, which culminates in the activation of caspase-1 by induced proximity. In humans, small PYD-only proteins (POPs) lacking an effector domain regulate this key process through competitive binding, but limited information exists on their physiological role during health and disease. Here we demonstrate that POP1 expression in macrophages is sufficient to dampen MSU crystal-mediated inflammatory responses in animal models of gout. Whether MSU crystals are administered into a subcutaneous airpouch or into the ankle joint, the presence of POP1 significantly reduces neutrophil infiltration. Also, airpouch exudates have much reduced IL-1β and ASC, which are typical pro-inflammatory indicators that can also be detected in synovial fluids of gout patients. Exogenous expression of POP1 in mouse and human macrophages also blocks MSU crystal-induced NLRP3 inflammasome assembly, resulting in reduced IL-1β and IL-18 secretion. Conversely, reduced POP1 expression in human macrophages enhances IL-1β secretion. We further determined that the mechanism for the POP1-mediated inhibition of NLRP3 inflammasome activation is through its interference with the crucial NLRP3 and ASC interaction within the inflammasome complex. Strikingly, administration of an engineered cell permeable version of POP1 was able to ameliorate MSU crystal-mediated inflammation in vivo, as measured by neutrophil infiltration. Overall, we demonstrate that POP1 may play a crucial role in regulating inflammatory responses in gout.
Construction of a nomogram to predict the survival of metastatic gastric cancer patients that received immunotherapy
Authors: Gou Miaomiao , Qian Niansong , Zhang Yong , Wei Lihui , Fan Qihuang , Wang Zhikuan , Dai Guanghai
Published: September 2022

Background

Immunotherapy has shown promising results for metastatic gastric cancer (MGC) patients. Nevertheless, not all patients can benefit from anti-PD-1 treatment. Thus, this study aimed to develop and validate a prognostic nomogram for MGC patients that received immunotherapy.

Methods

Herein, MGC patients treated with anti-PD-1 between 1 October 2016 and 1 June 2022 at two separate Chinese PLA General Hospital centers were enrolled and randomly divided into training and validation sets (186 and 80 patients, respectively). The nomogram was constructed based on a multivariable Cox model using baseline variables from the training cohort. Its predictive accuracy was validated by the validation set. The consistency index (C-index) and calibration plots were used to evaluate the discriminative ability and accuracy of the nomogram. The net benefit of the nomogram was evaluated using decision curve analysis (DCA). Finally, we stratified patients by median total nomogram scores and performed Kaplan–Meier survival analyses.

Results

We developed the nomogram based on the multivariate analysis of the training cohort, including four parameters: surgery history, treatment line, lung immune prognostic index (LIPI), and platelet-to-lymphocyte ratio (PLR). The C-index of the nomogram was 0.745 in the training set. The calibration curve for 1- and 2-year survival showed good agreement between nomogram predictions and actual observations. In the validation group, the calibration curves demonstrated good performance of the nomogram, with a C-index for overall survival (OS) prediction of 0.713. The OS of patients with a score greater than the median nomogram score was significantly longer than patients with a score lower or equal to the median (p < 0.001).

Conclusion

We constructed a nomogram to predict the outcomes of MGC patients that received immunotherapy. This nomogram might facilitate individualized survival predictions and be helpful during clinical decision-making for MGC patients under anti-PD-1 therapy.
Case Report: Immune reconstitution inflammatory syndrome after hematopoietic stem cell transplantation for severe combined immunodeficiency
Authors: Liu Shuangjun , Huo Feng , Dai Guorui , Wu Jie , Qin Maoquan , Mao Huawei , Wang Quan
Published: September 2022

We report a case of immune reconstitution inflammatory syndrome (IRIS) after hematopoietic stem cell transplantation (HSCT). The patient had sever bacillus Calmette–Guerin (BCG) vaccine–caused disseminated infection and had received allogeneic HSCT for X-linked severe combined immunodeficiency disease. After HSCT, complicated by treatment-responding veno-occlusive disease and acute graft-versus-host disease, at the time when immunosuppressants were withdrawn, the patient experienced recurrent fever accompanied by elevated inflammatory indicators. After receiving glucocorticoids and ibuprofen, the patient’s condition improved, and a diagnosis with BCG-related IRIS was made.
Analysis of two cooperating antibodies unveils immune pressure imposed on HIV Env to elicit a V3-glycan supersite broadly neutralizing antibody lineage
Authors: Finkelstein Maxwell T. , Parker Miller Emma , Erdman Molly C. , Fera Daniela
Published: September 2022

Elicitation of broadly neutralizing antibodies (bnAbs) is a goal of vaccine design as a strategy for targeting highly divergent strains of HIV-1. Current HIV-1 vaccine design efforts seek to elicit bnAbs by first eliciting their precursors through prime-boost regimens. This requires an understanding of the co-evolution between viruses and antibodies. Towards this goal, we have analyzed two cooperating antibodies, DH475 and DH272, which exerted pressure on the HIV population in an infected donor, called CH848, to evolve in such a way that it became sensitive to the V3-glycan supersite DH270 bnAb lineage. We obtained a 2.90Å crystal structure of DH475 in complex with the Man9 glycan and a negative stain EM model of DH272 in complex with the HIV-1 spike trimer, Env. Coupled with additional modeling studies and biochemical data, our studies reveal that DH475 contacts a V3- and V4-glycan dependent epitope accessible on an open or shed Env and that DH272 makes critical contacts with the V1V2 and V3 loops on HIV-1 Env. Using these data, we suggest a prime-boost regimen that may facilitate the initiation of DH270-like bnAb precursors.
Procedures and potential pitfalls for constructing a bee-infecting RNA virus clone
Authors: Huang Wei-Fone , Li Runlin , Jin Lang , Huang Shaokang
Published: September 2022

Viruses are factors that can fluctuate insect populations, including honey bees. Most honey bee infecting viruses are single positive-stranded RNA viruses that may not specifically infect honey bees and can be hazardous to other pollinator insects. In addition, these viruses could synergize with other stressors to worsen the honey bee population decline. To identify the underlying detailed mechanisms, reversed genetic studies with infectious cDNA clones of the viruses are necessary. Moreover, an infectious cDNA clone can be applied to studies as an ideal virus isolate that consists of a single virus species with a uniform genotype. However, only a few infectious cDNA clones have been reported in honey bee studies since the first infectious cDNA clone was published four decades ago. This article discusses steps, rationales, and potential issues in bee-infecting RNA virus cloning. In addition, failed experiences of cloning a Deformed wing virus isolate that was phylogenetically identical to Kakugo virus were addressed. We hope the information provided in this article can facilitate further developments of reverse-genetic studies of bee-infecting viruses to clarify the roles of virus diseases in the current pollinator declines.
Two new species of the genus Amiantofusus (Gastropoda: Fasciolariidae) from seamounts in the tropical western Pacific, with remarks on the taxonomy of A. candoris and A. sebalis
Authors: Zhang Shuqian , Fraussen Koen , Zhang Suping
Published: September 2022

During two scientific expeditions to the seamounts near the Mariana Trench in the tropical western Pacific, two undescribed gastropod species belonging to the genus Amiantofusus Fraussen et al., 2007 were collected from the upper bathyal zone. In the present study, we describe and illustrate them as new species. Amiantofusus granulus sp. nov. was collected from Magellan and Caroline Seamounts at depths of 1357–1473 m, and Amiantofusus tchangsii sp. nov. was discovered from Caroline Seamounts at depths of 1893–2291 m. The new species are distinguished from each other and congeners by shell morphology. Phylogenetic analyses based on the cytochrome oxidase c subunit I (COI) gene using Bayesian inference indicate that Amiantofusus granulus sp. nov. is a sister group to other congeners, and Amiantofusus tchangsii sp. nov. shows a close relationship with Amiantofusus sp. JQ950210 from the Philippines. The results provide additional support for the assignment of the new species to the genus Amiantofusus and their separation from congeners. In addition, our molecular analysis reveals that Amiantofusus candoris Fraussen et al., 2007 and Amiantofusus sebalis Fraussen et al., 2007 have almost identical COI sequences. Their taxonomic relationship is briefly discussed, and it is concluded that A. candoris should be regarded as a junior synonym of A. sebalis.
Enhanced Carboxymethylcellulose Sponge for Hemostasis and Wound Repair
Authors: Bi Zhanjian , Teng Haifeng , Li Qiujing , Zhang Shukun
Published: September 2022

Skin is the interface between human beings and the outside world. After skin injury, bleeding control and wound protection is urgently needed. In the study, the carboxymethyl cellulose/carboxymethyl chitosan-polydopamine (CMC/CMCS-PDA) sponge is prepared for skin hemostasis and repair. The self-polymerization of dopamine (DA) and cross-linking between DA and CMCS are simultaneously completed by Michael addition reaction to form CMCS-PDA under alkaline conditions. CMCS-PDA is introduced into the CMC sponge by EDC/NHS to improve the hemostasis ability and wound repair. By increasing the dosage of CMCS to get CMC/CMCS-PDA1, CMC/CMCS-PDA2, and CMC/CMCS-PDA3 sponges, and the stability of CMC/CMCS-PDA sponge is improved with the increasing addition of CMCS. Compared with a simple CMC/PDA sponge, CMC/CMCS-PDA sponge has a high hemostatic effect for its dispersion stability and CMC/CMCS-PDA2 exhibits the best hemostatic ability with proper crosslinking. At the same time, the prepared CMC/CMCS-PDA sponge has good antibacterial and antioxidant properties. Rat skin wound model showed that CMC/CMCS-PDA sponge can better promote wound repair. Therefore, CMC/CMCS-PDA sponge could be a potential wound dressing for skin hemostasis and repair.
Graft survival differences in kidney transplants related to recipient sex and age
Authors: Sancho Asuncion , Gavela Eva , Kanter Julia , Beltrán Sandra , Castro Cristina , Escudero Verónica , Pantoja Jonay , Molina Pablo , Vizcaíno Belen , González Mercedes , Calatayud Emma , Avila Ana
Published: September 2022

Background

In recent years, there has been increasing interest in studying differences in recipient sex in renal disease treatment, access to renal replacement therapy, and subsequent outcomes. Our aim was to find out whether there are differences in outcomes after renal transplantation between female and male kidney transplant recipients in our series, particularly in adults under 60 years of age during long-term follow-up.

Methods

This was a retrospective study of our kidney transplant series (n = 1,101) to compare graft survival depending on the sex of the recipient in the entire series and patients < 60 years of age (n = 687) during long-term follow-up.

Results

We observed no association between recipient sex and graft survival throughout the series, regardless of recipient sex. However, adult female recipients under 60 years of age had lower graft survival than male recipients (p = 0.040). Pre-transplant sensitization (HR 2.438, p = 0.002) and donor age (HR: 1.021, p = 0.017) were the independent variables associated with graft failure.

Conclusion

Female recipients younger than 60 years of age had lower graft survival than male recipients, although there were no gender differences in graft or patient survival in the overall study population. Recipient sex per se was not related to graft failure, but the greater immunological risk in women and more frequent use of expanded criteria donors in female recipients under 60 years of age were the main factors related to their poorer graft survival. Further studies and new strategies are needed to identify these differences and develop the best approach to address them.
The right microbe-associated molecular patterns for effective recognition by plants
Authors: Lü Pengpeng , Liu Yi , Yu Xixi , Shi Chun-Lin , Liu Xiaokun
Published: September 2022

Plants are constantly exposed to diverse microbes and thus develop a sophisticated perceive system to distinguish non-self from self and identify non-self as friends or foes. Plants can detect microbes in apoplast via recognition of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) on the cell surface to activate appropriate signaling in response to microbes. MAMPs are highly conserved but essential molecules of microbes and often buried in microbes’ complex structure. Mature MAMPs are released from microbes by invasion-induced hydrolytic enzymes in apoplast and accumulate in proximity of plasma membrane-localized PRRs to be perceived as ligands to activate downstream signaling. In response, microbes developed strategies to counteract these processing. Here, we review how the form, the concentration, and the size of mature MAMPs affect the PRR-mediated immune signaling. In particular, we describe some potential applications and explore potential open questions in the fields.
Reducing culture medium nitrogen supply coupled with replenishing carbon nutrient simultaneously enhances the biomass and lipid production of Chlamydomonas reinhardtii
Authors: Zheng Shiyan , Zou Shangyun , Wang Hongyan , Feng Tian , Sun Shourui , Chen Hui , Wang Qiang
Published: September 2022

Chlamydomonas reinhardtii is a model strain to explore algal lipid metabolism mechanism, and exhibits great potentials in large-scale production of lipids. Completely lacking nitrogen is an efficient strategy to trigger the lipid synthesis in microalgal cells, while it always leads to the obvious reduction in the biomass. To illustrate the optimal culture substrate carbon (C) and nitrogen (N) levels to simultaneously stimulate the growth and lipid production of C. reinhardtii, cells were cultivated under altered C and N concentrations. Results showed that replenishing 6 g/L sodium acetate (NaAc) could increase 1.50 and 1.53 times biomass and lipid productivity compared with 0 g/L NaAc treatment (the control), but total lipid content slightly decreased. Reducing 75% of basic medium (TAP) N level (0 g/L NaAc + 0.09 g/L NH4Cl treatment) could promote 21.57% total lipid content in comparison with the control (containing 0.38 g/L NH4Cl), but decrease 44.45% biomass and 34.15% lipid productivity. The result of the central composite design (CCD) experiment suggested the optimum total lipid content together with higher biomass and lipid productivity could be obtained under the condition of 4.12 g/L NaAc and 0.20 g/L NH4Cl. They reached 32.14%, 1.68 g/L and 108.21 mg/L/d, and increased by 36.77%, 93.10% and 1.75 times compared with the control, respectively. It suggests moderately increasing C supply and decreasing N levels could synchronously improve the biomass and lipid content of C. reinhardtii.
No time to die: Comparative study on preservation protocols for anaerobic fungi
Authors: Vinzelj Julia , Joshi Akshay , Young Diana , Begovic Ljubica , Peer Nico , Mosberger Lona , Luedi Katharina Cécile Schmid , Insam Heribert , Flad Veronika , Nagler Magdalena , Podmirseg Sabine Marie
Published: September 2022

Anaerobic fungi (AF, phylum Neocallimastigomycota) are best known for their ability to anaerobically degrade recalcitrant lignocellulosic biomass through mechanic and enzymatic means. While their biotechnological potential is well-recognized, applied research on AF is still hampered by the time-consuming and cost-intensive laboratory routines required to isolate, maintain, and preserve AF cultures. Reliable long-term preservation of specific AF strains would aid basic as well as applied research, but commonly used laboratory protocols for AF preservation can show erratic survival rates and usually exhibit only moderate resuscitation success for up to one or two years after preservation. To address both, the variability, and the preservation issues, we have set up a cross-laboratory, year-long study. We tested five different protocols for the preservation of AF. The experiments were performed at three different laboratories (Austria, Germany, Switzerland) with the same three morphologically distinct AF isolates (Anaeromyces mucronatus, Caeocmyces sp., and Neocallimastix cameroonii) living in stable co-culture with their naturally occurring, syntrophic methanogens. We could show that handling greatly contributes to the variability of results, especially in Anaeromyces mucronatus. Cryopreservation of (mature) biomass in liquid nitrogen had the highest overall survival rates (85–100%, depending on the strain and laboratory). Additionally, preservation on agar at 39°C had surprisingly high survival rates for up to 9 months, if pieces of agar containing mature AF thalli were resuscitated. This low-cost, low-effort method could replace consecutive batch cultivation for periods of up to 6 months, while long-term preservation is best done by cryopreservation in liquid nitrogen. Regardless of the method, however, preserving several replicates (>three) of the same strain is highly advisable.
Elucidating the microbiome of the sustainable peat replacers composts and nature management residues
Authors: Pot Steffi , Tender Caroline De , Ommeslag Sarah , Delcour Ilse , Ceusters Johan , Vandecasteele Bart , Debode Jane , Vancampenhout Karen
Published: September 2022

Sustainable peat alternatives, such as composts and management residues, are considered to have beneficial microbiological characteristics compared to peat-based substrates. Studies comparing microbiological characteristics of these three types of biomass are, however, lacking. This study examined if and how microbiological characteristics of subtypes of composts and management residues differ from peat-based substrates, and how feedstock and (bio)chemical characteristics drive these characteristics. In addition, microbiome characteristics were evaluated that may contribute to plant growth and health. These characteristics include: genera associated with known beneficial or harmful microorganisms, microbial diversity, functional diversity/activity, microbial biomass, fungal to bacterial ratio and inoculation efficiency with the biocontrol fungus Trichoderma harzianum. Bacterial and fungal communities were studied using 16S rRNA and ITS2 gene metabarcoding, community-level physiological profiling (Biolog EcoPlates) and PLFA analysis. Inoculation with T. harzianum was assessed using qPCR. Samples of feedstock-based subtypes of composts and peat-based substrates showed similar microbial community compositions, while subtypes based on management residues were more variable in their microbial community composition. For management residues, a classification based on pH and hemicellulose content may be relevant for bacterial and fungal communities, respectively. Green composts, vegetable, fruit and garden composts and woody composts show the most potential to enhance plant growth or to suppress pathogens for non-acidophilic plants, while grass clippings, chopped heath and woody fractions of compost show the most potential for blends for calcifuge plants. Fungal biomass was a suitable predictor for inoculation efficiency of composts and management residues.
Engineering of lysin by fusion of antimicrobial peptide (cecropin A) enhances its antibacterial properties against multidrug-resistant Acinetobacter baumannii
Authors: Islam Md Maidul , Kim Dooyoung , Kim Kyeongmin , Park Su-Jin , Akter Samia , Kim Jeongah , Bang Seunghyeok , Kim Shukho , Kim Jungmin , Lee Je Chul , Hong Chang-Won , Shin Minsang
Published: September 2022

Most clinical isolates of Acinetobacter baumannii, a nosocomial pathogen, are multidrug-resistant (MDR), fueling the search for alternative therapies. Bacteriophage-derived endolysins have potent antibacterial activities and are considered as alternatives to antibiotics against A. baumannii infection. Gram-negative bacteria possess outer lipid membrane that prevents direct contact between the endolysins and the cell wall. We hypothesized that the fusion of antimicrobial peptide (AMP) with endolysin could help to reduce bacterial endolysin resistance and increase antimicrobial activity by membrane permeability action. Accordingly, we fused cecropin A, a commonly used AMP, with the N-terminus of AbEndolysin, which enhances the bactericidal activity of the chimeric endolysin. The bactericidal activity of cecropin A-fused AbEndolysin increased by at least 2–8 fold for various MDR A. baumannii clinical isolates. The in vitro bactericidal activity results also showed higher bacterial lysis by the chimeric endolysin than that by the parental lysin. The engineered AbEndolysin (eAbEndolysin) showed synergistic effects with the beta-lactam antibiotics cefotaxime, ceftazidime, and aztreonam, and an additive effect with meropenem and imipenem. eAbEndolysin had no cytotoxic effect on A549 cell line and rescued mice (40% survival rate) from systemic A. baumannii infection. Together, these findings suggest the potential of lysin therapy and may prompt its use as an alternative to antibiotics.