bluuebunny/crossref_metadata_2025 huggingface dataset:
Method of forming digital models of geoid heights for reference coordinate systems
Authors:   Siberian State University of Geosystems and Technologies, Shendrik N. K.
Published: October 2023

A technique was developed for generating digital models of geoid heights for reference coordinate systems using the Trimble Bussines Center software (TBC software). The source models can be the publicly available high-precision global geoid elevation models EGM2008, EIGEN6C4 and other models whose files with the *.ggf extension are compatible with the TBC software. The technique is based on the possibility of exporting orthometric heights from the TBC software in ASCII format to a user-specified area on the surface of the global WGS-84 ellipsoid for a uniform grid of nodes in lati-tude and longitude. The resulting data table is the starting point for calculating geoid heights for reference coordinate systems, which are determined by the parameters of the corresponding reference ellipsoids and Helmert parameters - spatial position, orientation and linear scale relative to the global coordinate system, according to Standard. The initial data are sufficient to calculate the digital model of the geoid heights for an arbitrary reference coordinate system. The expediency of the developed technique lies in the possibility of its use for a much more accurate calculation of the Helmert parameters for regional and other territories compared to the accepted standard values and, accordingly, a more accurate transformation of the three-dimensional positions of points between the general earth and reference coordinate systems (these issues will be discussed in a subsequent publication by the author). Approbation of the technique was carried out for several regional territories: Novosibirsk and Moscow regions, the territory of Western Siberia, the Republic of Belarus in the SK42 and SK95 coordinate systems, and the results are presented graphically in the form of geoid height maps.
Monitoring of water bodies by remote methods
Authors:   St. Petersburg Mining University, Mustafin M. G. , Valkov V. A. ,   St. Petersburg Mining University, Pavlov N. S. ,   St. Petersburg Mining University, Vinogradov K. P. ,   St. Petersburg Mining University, Bogolyubova A. A. ,   St. Petersburg Mining University
Published: October 2023

A technique has been developed that allows determining the volume of water resources of hydro-graphic objects using materials from remote sensing of the Earth and a digital terrain model (DEM) of the terrain. The task is relevant, especially in conditions of inaccessibility or difficult approaches to the object. The technique includes the use or construction of a DEM of the bottom of a water body according to bathymetric survey data, the transformation of satellite images into a projection most corresponding to the Earth's surface at these latitudes, the definition of the contour of the shoreline of the reservoir and the calculation of the volume of water. For the purpose of testing, a shallow-water object was selected on the territory of Russia, for which seasonal fluctuations in the water level lead to significant changes in resources. The results revealed a good convergence of the proposed approaches with the accumulated materials of traditional bathymetric survey.
Using the satellite leveling technique for creating a height network in Lebanon
Authors:   St. Petersburg Mining University, Mustafin M. G. , Moussa H. I. ,   St. Petersburg Mining University, Abboud M. R. ,   Lebanese International University, Jalloul A. H. ,   Lebanese International University
Published: October 2023

The article deals with the issue of using satellite leveling technology to create referenced height networks. The topic is relevant with the possibility of determining normal heights according to satellite determinations. At the same time, ensuring that the appropriate accuracy is associated with the solution of technological and computational problems. The first one is connected with the formulation of experimental studies to clarify the degree of variability of the reference surfaces, on which the transfer of the mark depends on the geometric leveling method. The second one is aimed to clarify the quasi-geoid marks for certain territories according to satellite determinations, quasi-geoid model, and geometric leveling. The use of satellite leveling technology is especially appropriate for countries with either no existing state geodetic network, or an undeveloped one, which in turns prevents finding a full-fledged solution of the practical problems. The presented method of satellite leveling includes the analysis of the deviations accuracy from the plumb line. An example of testing the methodology in Lebanon is given.
The examination of a possibility for usage of an Iphone 12 Pro lidar to indoor measurements for state cadastral registration
Authors:   Saint Petersburg Mining University, Suranov N. A , Romanchikov A. Yu. ,   Saint Petersburg Mining University, Valkov V. A. ,   Saint Petersburg Mining University
Published: October 2023

The paper is devoted to an examintaion of a possibilty for usage of LiDAR integrated into modern smartphones (on the example of iPhone 12 Pro) to indoor measurements. Most often this type of measurements is carried out for inventory or state cadastral registration. For this the mentioned device was used to collect data of two complex shaped rooms. Afterwards the data were compared with two point clouds created by ground-based LiDAR providing the accuracy of the claimed works and accepted as standard measurement data. The comparison was provided both for point clouds (using CloudCompare) and for room plans made using these clouds. For the first room the average square error of measurement deviation was 5–6 cm, for the second is 2–3 cm. The deviation less than 5 cm between point clouds created by smartphone and those of LiDAR refers to 78% in the first room and 32% in the second room. The results illustrate that the current technology is not appropriate for an indoor measurement accuracy which is defined as 1 cm in Russia.
Improvement of the scheme of technological verification of the digital level after its repair
Authors:   Siberian State University of Geosystems and Technologies, Ustavich G. A. , Yambayev K. K. ,   Moscow State University of Geodesy and Cartography, Birukov D. V. ,   Siberian State University of Geosystems and Technologies, Minaeva M. A. ,   Siberian State University of Geosystems and Technologies, Sitnikova E. V. ,   Siberian State University of Geosystems and Technologies, Kalenitsky A. I. ,   Siberian State University of Geosystems and Technologies
Published: October 2023

To ensure the normal operation of the "digital level-barcode rail" system, it is necessary to annually perform its periodic verification to determine the image scale (average meter length), which is performed on a stationary interference comparator. In addition to the annual periodic verification, there is often a need for its exceptional conduct after accidental mechanical impact on the body of the digital level, which can lead to its repair. The main task in this case is to determine the working efficiency of the electronic channel of the digital level. Currently, these verifications are performed on a stationary interference comparator. The organizational disadvantage of this verification technique is a significant difficulty in its imple-mentation, since the number of interference comparators is extremely small, and they are located at a considerable distance from the sites of leveling work. This, in turn, leads to significant financial costs for its implementation. With this in mind, in order to ensure the procedure for conducting an exceptional verification, this article proposes a technique that allows it to be performed with the required accuracy at the site of leveling operations without using an interference comparator. This eliminates significant organizational and financial components in its implementation.
Creation of a spatial model based on the results of geodetic measurements to analyze the environmental impact in small open pits
Authors:   Siberian State University of Geosystems and Technologies, Basargin А. А.
Published: October 2023

Mining, especially open pit mining, has a significant impact on the terrain. The article discusses the use of geodetic methods to monitor the process of mining and its possible impact on the environ-ment. The created relief model can be used to design the process of quarry restoration after their closure. The mineral wealth of a country is considered an important factor and is linked to the country's economy. Mineral resources are non-renewable, and their extraction and subsequent processing must take into account the rarity of their occurrence, the level of mining technologies to track spatial changes in mining operations. The main idea of this scientific study is to apply geodetic measurement methods to determine the current scale of mining in a quarry using a 3D terrain model. The paper presents an overview of the technologies used in performing geodetic measurements, as well as processing the measured data to assess the state of the spatial distribution of a quarry in order to determine the impact of mining on the landscape. The purpose of this article is to create a spatial terrain model based on the results of geodetic measurements to analyze the impact on the environment in small open pits. Methods of geodetic observations were used to create a spatial model of the terrain. Digital maps were also created by photogrammetric processing of aerial stereo images and subsequent semi-automatic removal of vegetation and other objects.
Models of Hfq interactions with small non-coding RNA in Gram-negative and Gram-positive bacteria
Authors: Watkins Derrick , Arya Dev
Published: October 2023

Hfq is required by many Gram-negative bacteria to chaperone the interaction between small non-coding RNA (sRNA) and mRNA to facilitate annealing. Conversely and despite the presence of Hfq in many Gram-positive bacteria, sRNAs in Gram-positive bacteria bind the mRNA target independent of Hfq. Details provided by the Hfq structures from both Gram-negative and Gram-positive bacteria have demonstrated that despite a conserved global structure of the protein, variations of residues on the binding surfaces of Hfq results in the recognition of different RNA sequences as well as the ability of Hfq to facilitate the annealing of the sRNA to the mRNA target. Additionally, a subset of Gram-negative bacteria has an extended C-terminal Domain (CTD) that has been shown to affect the stability of the Hfq hexamer and increase the rate of release of the annealed sRNA-mRNA product. Here we review the structures of Hfq and biochemical data that have defined the interactions of the Gram-negative and Gram-positive homologues to highlight the similarities and differences in the interactions with RNA. These interactions provided a deeper understanding of the how Hfq functions to facilitate the annealing of sRNA-mRNA, the selectivity of the interactions with RNA, and the role of the CTD of Hfq in the interactions with sRNA.
Analysis of Accessible Digital Musical Instruments through the lens of disability models: a case study with instruments targeting d/Deaf people
Authors: Duarte Erivan Gonçalves , Cossette Isabelle , Wanderley Marcelo M.
Published: October 2023

Music educators and researchers have grown increasingly aware of the need for traditional musical practices to promote inclusive music for disabled people. Inclusive music participation has been addressed by Accessible Digital Musical Instruments (ADMIs), which welcome different ways of playing and perceiving music, with considerable impact on music-making for disabled people. ADMIs offer exciting possibilities for instrument design to consider and incorporate individual constraints (e.g., missing arm, low vision, hearing loss, etc.) more than traditional acoustic instruments, whose generally fixed design allows little room for disabled musicians inclusivity. Relatively few works discuss ADMIs in the context of disability studies, and no work has investigated the impact of different disability models in the process of designing inclusive music technology. This paper proposes criteria to classify ADMIs according to the medical, social, and cultural models of disability, then applies these criteria to evaluate eleven ADMIs targeting d/Deaf people. This analysis allows us to reflect on the design of ADMIs from different perspectives of disability, giving insights for future projects and deepening our understanding of medical, social, and cultural aspects of accessible music technology.
Mannose-functionalization of reconstituted high-density lipoprotein nanoparticles improves payload delivery and enhances M2-to-M1 phenotype reprogramming of RAW 264.7 macrophages polarized by B16-F10 melanoma cells
Authors: Dossou Akpedje S. , Mantsch Morgan E. , Sabnis Nirupama , Berg Rance E. , Fudala Rafal , Lacko Andras G.
Published: October 2023

The targeting and conversion of the immunosuppressive (M2) tumor-associated macrophages (TAMs) to an immunostimulatory (M1) phenotype can induce tumor regression in advanced melanoma. We have previously characterized and reported the ability of reconstituted high-density lipoprotein nanoparticles (rHDL NPs) functionalized with DSPE-PEG-mannose (DPM) to deliver payload to macrophages. Herein, we investigate the modulation of macrophage phenotype and payload delivery mechanisms of the rHDL-DPM NPs in RAW 264.7 murine macrophages exposed to the conditioned medium (CM) from murine B16-F10 melanoma cells. The rHDL-DPM NPs loaded with the Stimulator of Interferon genes agonist, DMXAA, reduced protein levels of M2 markers. Through the mannose moiety, the rHDL-DPM-DMXAA NPs enhanced the production of interferon β and CXCL10 compared to the free DMXAA in the B16-F10 CM-educated RAW 264.7 macrophages. Compared to their non-mannosylated counterpart, the rHDL-DPM NPs delivered their payload more efficiently to the B16-F10 CM-educated RAW 264.7 macrophages. Mechanistically, both the scavenger receptor type B class 1 (SR-B1) and the mannose receptor (CD206) facilitated payload delivery to the macrophages via endocytic and non-endocytic mechanisms. Finally, the CM from rHDL-DPM-DMXAA NPs -treated macrophages enhanced paclitaxel (paclitaxel)-mediated cytotoxicity in B16-F10 cells. Together, these in vitro findings demonstrate the potential of the mannose-functionalized rHDL NPs in improving the targeting of M2-like TAMs and treatment outcomes when combined with immunotherapy or PTX in B16-F10 melanoma in vivo models.
Low switched memory B cells are associated with no humoral response after SARS-CoV-2 vaccine boosters in kidney transplant recipients
Authors: Seija Mariana , García-Luna Joaquin , Rammauro Florencia , Brugnini Andreína , Trías Natalia , Astesiano Rossana , Santiago José , Orihuela Natalia , Zulberti Catherine , Machado Danilo , Recalde Cecilia , Yandián Federico , Guerisoli Ana , Noboa Javier , Orihuela Sergio , Curi Lilian , Bugstaller Emma , Noboa Oscar , Nin Marcelo , Bianchi Sergio , Tiscornia Adriana , Lens Daniela
Published: October 2023

Introduction

The humoral response after SARS-CoV-2 vaccination and boosters in kidney transplant recipients (KTRs) is heterogeneous and depends on immunosuppression status. There is no validated immune measurement associated with serological response in clinical practice. Multicolor flow cytometric immunophenotyping could be useful for measuring immune response. This study aimed to study B- and T-cell compartments through Standardized EuroFlow PID Orientation after SARS-CoV-2 vaccination and their association with IgG SARS-CoV-2 seropositivity status after two doses or boosters.

Methods

We conducted a multicenter prospective study to evaluate humoral response after SARS-CoV-2 vaccination in KTRs. Heterologous regimen: two doses of inactivated SARS-CoV-2 and two boosters of BNT162b2 mRNA (n=75). Homologous vaccination: two doses of BNT162b2 mRNA and one BNT162b2 mRNA booster (n=13). Booster doses were administrated to KTRs without taking into account their IgG SARS-CoV-2 seropositivity status. Peripheral blood samples were collected 30 days after the second dose and after the last heterologous or homologous booster. A standardized EuroFlow PID Orientation Tube (PIDOT) and a supervised automated analysis were used for immune monitoring cellular subsets after boosters.

Results

A total of 88 KTRs were included and divided into three groups according to the time of the first detected IgG SARS-CoV-2 seropositivity: non-responders (NRs, n=23), booster responders (BRs, n=41), and two-dose responders (2DRs, n=24). The NR group was more frequent on mycophenolate than the responder groups (NRs, 96%; BRs, 80%; 2DRs, 42%; p=0.000). Switched memory B cells in the 2DR group were higher than those in the BR and NR groups (medians of 30, 17, and 10 cells/ul, respectively; p=0.017). Additionally, the absolute count of central memory/terminal memory CD8 T cells was higher in the 2DR group than in the BR and NR groups. (166, 98, and 93 cells/ul, respectively; p=0.041). The rest of the T-cell populations studied did not show a statistical difference.

Conclusion

switched memory B cells and memory CD8 T-cell populations in peripheral blood were associated with the magnitude of the humoral response after SARS-CoV-2 vaccination. Boosters increased IgG anti-SARS-CoV-2 levels, CM/TM CD8 T cells, and switched MBCs in patients with seropositivity after two doses. Interestingly, no seropositivity after boosters was associated with the use of mycophenolate and a lower number of switched MBCs and CM/TM CD8 T cells in peripheral blood.
The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial
Authors: Qiao Qian , Han Chun , Ye Sisi , Li Juan , Shao Guoliang , Bai Yuxian , Xu Aibing , Sun Meili , Wang Wei , Wu Jian , Huang Ming , Song Lijie , Huang Luke , Liu Ting , Liu Wei , Wang Zhongmin Maxwell , Li Baiyong , Xia Michelle , Bai Li
Published: October 2023

Purpose

This multicenter, open-label, phase Ib/II study aimed to assess the efficacy and safety of cadonilimab, a humanized, tetravalent, bispecific antibody plus lenvatinib in first-line treatment of advanced hepatocellular carcinoma (aHCC).

Methods

Patients with histologically confirmed aHCC were included to receive either 6 mg/kg cadonilimab every 2 weeks plus lenvatinib (cohort A) or 15 mg/kg cadonilimab every 3 weeks plus lenvatinib (cohort B). The primary endpoint was objective response rate (ORR) by RECIST v1.1, while the secondary endpoints were safety, progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and time to response (TTR).

Results

A total of 59 patients were enrolled (31 in cohort A and 28 in cohort B). The median follow-up time was 27.4 months as of the data cutoff date (July 28, 2023). The ORR in cohort A was 35.5% (95% CI: 19.2, 54.6) and that in cohort B was 35.7% (95% CI: 18.6, 55.9), and the median DoR was 13.6 months (95% CI: 4.14, NE) and 13.67 months (95% CI: 3.52, NE), respectively. The median PFS was 8.6 months (95% CI: 5.2, 15.2) and 9.8 months (95% CI: 6.9, 15.2), respectively. The median OS was 27.1 months (95% C: 15.7, NE) for cohort A, while it was not reached for cohort B. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 66.1% of patients, with serious TRAEs occurring in 39.0% of cases. Decreased platelet count (47.5%), proteinuria (45.8%), hypertension (44.1%), and white blood cell count (44.1%) were the most common TRAEs.

Conclusion

This novel combination therapy showed promising efficacy and manageable toxicity that could provide an option in first-line setting of aHCC.

Clinical Trial Registration

[www.ClinicalTrials.gov], NCT04444167.
Preferential differential gene expression within the WC1.1+ γδ T cell compartment in cattle naturally infected with Mycobacterium bovis
Authors: Bhat Sajad A. , Elnaggar Mahmoud , Hall Thomas J. , McHugo Gillian P. , Reid Cian , MacHugh David E. , Meade Kieran G.
Published: October 2023

Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterise differential gene expression in γδ T cells – a subgroup of T cells that bridge innate and adaptive immunity and have known anti-mycobacterial response mechanisms. γδ T cell subsets are classified based on expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB disease may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n = 10–12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and γδ-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 189 genes were significantly differentially expressed in the M. bovis-infected compared to the control groups for the WC1.1+ γδ T cell compartment (absolute log2 FC ≥ 1.5 and FDR Padj. ≤ 0.1). The majority of these DEGs (168) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factors (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM, and GZMH) and multiple killer cell immunoglobulin-like receptor (KIR) proteins indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis, and cytotoxicity of lymphocytes. In conclusion, γδ T cells have important inflammatory and regulatory functions in cattle, and we provide evidence for preferential differential activation of the WC1.1+ specific subset in cattle naturally infected with M. bovis.
The safety and anti-tumor effect of multiple peptides-pulsed dendritic cells combined with induced specific cytotoxic T lymphocytes for patients with solid tumors
Authors: Zhao Xuan , Zhang Zhen , Wen Chunli , Huang Jianmin , Yang Shuangning , Liu Jinyan , Geng Huizhen , Peng Bing , Li Zibo , Zhang Yi
Published: October 2023

Objective

The aim of this study was to explore the safety and efficacy of multiple peptide-pulsed autologous dendritic cells (DCs) combined with cytotoxic T lymphocytes (CTLs) in patients with cancer.

Methods

Five patients diagnosed with cancer between November 2020 and June 2021 were enrolled and received DC-CTLs therapy. Peripheral blood was collected and antigenic peptides were analyzed. The phenotype and function of DC-CTLs and the immune status of patients were detected using flow cytometry or IFN-γ ELISPOT analysis.

Results

DCs acquired a mature phenotype and expressed high levels of CD80, CD86, CD83, and HLA-DR after co-culture with peptides, and the DC-CTLs also exhibited high levels of IFN-γ. Peripheral blood mononuclear cells from post-treatment patients showed a stronger immune response to peptides than those prior to treatment. Importantly, four of five patients maintained a favorable immune status, of which one patient’s disease-free survival lasted up to 28.2 months. No severe treatment-related adverse events were observed.

Conclusion

Our results show that multiple peptide-pulsed DCs combined with CTLs therapy has manageable safety and promising efficacy for cancer patients, which might provide a precise immunotherapeutic strategy for cancer.
From aging to long COVID: exploring the convergence of immunosenescence, inflammaging, and autoimmunity
Authors: Müller Ludmila , Di Benedetto Svetlana
Published: October 2023

The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. This mini-review navigates through the complex landscape of age-associated immune changes, chronic inflammation, age-related autoimmune tendencies, and their potential links with immunopathology of Long COVID. Immunosenescence serves as an introductory departure point, elucidating alterations in immune cell profiles and their functional dynamics, changes in T-cell receptor signaling, cytokine network dysregulation, and compromised regulatory T-cell function. Subsequent scrutiny of chronic inflammation, or “inflammaging,” highlights its roles in age-related autoimmune susceptibilities and its potential as a mediator of the immune perturbations observed in Long COVID patients. The introduction of epigenetic facets further amplifies the potential interconnections. In this compact review, we consider the dynamic interactions between immunosenescence, inflammation, and autoimmunity. We aim to explore the multifaceted relationships that link these processes and shed light on the underlying mechanisms that drive their interconnectedness. With a focus on understanding the immunological changes in the context of aging, we seek to provide insights into how immunosenescence and inflammation contribute to the emergence and progression of autoimmune disorders in the elderly and may serve as potential mediator for Long COVID disturbances.
Microalgae as functional feed for Atlantic salmon: effects on growth, health, immunity, muscle fatty acid and pigment deposition
Authors: Mueller Jonas , Pauly Matteo , Molkentin Joachim , Ostermeyer Ute , van Muilekom Doret R. , Rebl Alexander , Goldammer Tom , Lindemeyer Jacqueline , Schultheiß Thekla , Seibel Henrike , Schulz Carsten
Published: October 2023

Microalgae are increasingly being investigated as functional feed additives in a variety of fish species, but our knowledge on how microalgae supplementation affects Atlantic salmon remains limited. We hypothesized that microalgae inclusion of 8% in the feed would improve performance, fatty acid and pigment deposition as well as health and immunity of Atlantic salmon reared in recirculating aquaculture systems (RAS). We fed Atlantic salmon smolts with five different microalgae enriched diets containing Tetraselmis chuii (TC), Arthrospira platensis (AP), Schizochytrium limacinum (SL) or Chlorella vulgaris, either intact (CVI) or as broken cell wall derivative (CVB) or a control diet (CD). After eight weeks of feeding in brackish water (13 psu), all groups were transferred to seawater (32 psu) for additional two weeks. Our results indicate that CVB improved feed conversion and protein retention, but reduced condition factor (p < 0.05) compared to fish fed with a control diet. Voluntary feed intake decreased in seawater, but was similar among diet groups. The amount of docosahexaenoic acid was particularly high in SL-fed fish and alpha-linolenic acid was enriched in fish fed CVI, CVB and TC (p < 0.05). Following seawater transfer, fat content and monounsaturated fatty acids decreased in the muscle, while polyunsaturated fatty acids increased. Lutein was present in all muscle samples, but highest concentrations were found in CVB-, CVI- and TC-fed fish. In the anterior intestine, microalgae supplementation induced differentially regulated trout protein 1 (drtp1) expression in CVI- and CVB-fed fish, but reduced the expression of interleukin 1 and 10 receptor (il1r2 & il10rb) in CVI-fed fish. In the liver, feeding CVI and SL induced complement C1q like 2 (c1ql2) expression, while reducing serum amyloid A5 (saa5) expression. Superoxide-dismutase protein concentration was induced in the liver of fish fed SL, while myeloperoxidase was reduced in most microalgae-fed groups. In conclusion, we show that commercially relevant microalgae can be used as functional feed additives for Atlantic salmon promoting different health aspects without negatively affecting their growth performance when cultivated in RAS.
Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration
Authors: Chen Jingjing , Jiang Xiaolong , Gao Xin , Wu Wen , Gu Zhengsheng , Yin Ge , Sun Rui , Li Jiasi , Wang Ruoru , Zhang Hailing , Du Bingying , Bi Xiaoying
Published: October 2023

Background

Major depression disorder (MDD) is a devastating neuropsychiatric disease, and one of the leading causes of suicide. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in numerous diseases. The study aimed to construct and validate a gene signature for diagnosing MDD based on ferroptosis-related genes (FRGs) and further explore the biological functions of these genes in MDD.

Methods

The datasets were downloaded from the Gene Expression Omnibus (GEO) database and FRGs were obtained from the FerrDb database and other literatures. Least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were performed to develop a gene signature. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic power of the signature. Gene ontology (GO) enrichment analysis was used to explore the biological roles of these diagnostic genes, and single sample gene set enrichment analysis (ssGSEA) algorithm was used to evaluate immune infiltration in MDD. Animal model of depression was constructed to validate the expression of the key genes.

Results

Eleven differentially expressed FRGs were identified in MDD patients compared with healthy controls. A signature of three FRGs (ALOX15B, RPLP0, and HP) was constructed for diagnosis of MDD. Afterwards, ROC analysis confirmed the signature’s discriminative capacity (AUC = 0.783, 95% CI = 0.719–0.848). GO enrichment analysis revealed that the differentially expressed genes (DEGs) related to these three FRGs were mainly involved in immune response. Furthermore, spearman correlation analysis demonstrated that these three FRGs were associated with infiltrating immune cells. ALOX15B and HP were significantly upregulated and RPLP0 was significantly downregulated in peripheral blood of the lipopolysaccharide (LPS)-induced depressive model.

Conclusion

Our results suggest that the novel FRG signature had a good diagnostic performance for MDD, and these three FRGs correlated with immune infiltration in MDD.
Synthetic oligonucleotides as quantitative PCR standards for quantifying microbial genes
Authors: Han Xingguo , Beck Karin , Bürgmann Helmut , Frey Beat , Stierli Beat , Frossard Aline
Published: October 2023

Real-time quantitative PCR (qPCR) has been widely used to quantify gene copy numbers in microbial ecology. Despite its simplicity and straightforwardness, establishing qPCR assays is often impeded by the tedious process of producing qPCR standards by cloning the target DNA into plasmids. Here, we designed double-stranded synthetic DNA fragments from consensus sequences as qPCR standards by aligning microbial gene sequences (10–20 sequences per gene). Efficiency of standards from synthetic DNA was compared with plasmid standards by qPCR assays for different phylogenetic marker and functional genes involved in carbon (C) and nitrogen (N) cycling, tested with DNA extracted from a broad range of soils. Results showed that qPCR standard curves using synthetic DNA performed equally well to those from plasmids for all the genes tested. Furthermore, gene copy numbers from DNA extracted from soils obtained by using synthetic standards or plasmid standards were comparable. Our approach therefore demonstrates that a synthetic DNA fragment as qPCR standard provides comparable sensitivity and reliability to a traditional plasmid standard, while being more time- and cost-efficient.
Primary cilia-mediated regulation of microglial secretion in Alzheimer’s disease
Authors: Yeo Seungeun , Jang Jaemyung , Jung Hyun Jin , Lee Hyeyoung , Choe Youngshik
Published: October 2023

Graphical Abstract

Microglial phagocytosis and exocytosis of Aβ are mediated by primary cilia, which influence extracellular proteostasis, Aβ plaque formation, and neurite dystrophy. When microglia in wild-type mice develop into the disease-associated state, they require genes involved in primary ciliogenesis and extracellular vesicle secretion. Inhibition of Ift88, a key cilia gene, in microglia stimulates phagocytosis and the secretion of extracellular vesicles with an altered proteomic composition, leading to the failure of extracellular proteostasis and neurite degeneration.
Regulation of axon pathfinding by astroglia across genetic model organisms
Authors: Rapti Georgia
Published: October 2023

Glia and neurons are intimately associated throughout bilaterian nervous systems, and were early proposed to interact for patterning circuit assembly. The investigations of circuit formation progressed from early hypotheses of intermediate guideposts and a “glia blueprint”, to recent genetic and cell manipulations, and visualizations in vivo. An array of molecular factors are implicated in axon pathfinding but their number appears small relatively to circuit complexity. Comprehending this circuit complexity requires to identify unknown factors and dissect molecular topographies. Glia contribute to both aspects and certain studies provide molecular and functional insights into these contributions. Here, I survey glial roles in guiding axon navigation in vivo, emphasizing analogies, differences and open questions across major genetic models. I highlight studies pioneering the topic, and dissect recent findings that further advance our current molecular understanding. Circuits of the vertebrate forebrain, visual system and neural tube in zebrafish, mouse and chick, the Drosophila ventral cord and the C. elegans brain-like neuropil emerge as major contexts to study glial cell functions in axon navigation. I present astroglial cell types in these models, and their molecular and cellular interactions that drive axon guidance. I underline shared principles across models, conceptual or technical complications, and open questions that await investigation. Glia of the radial-astrocyte lineage, emerge as regulators of axon pathfinding, often employing common molecular factors across models. Yet this survey also highlights different involvements of glia in embryonic navigation or pioneer axon pathfinding, and unknowns in the molecular underpinnings of glial cell functions. Future cellular and molecular investigations should complete the comprehensive view of glial roles in circuit assembly.
Synaptic remodeling follows upper motor neuron hyperexcitability in a rodent model of TDP-43
Authors: Dyer Marcus S. , Odierna G. Lorenzo , Clark Rosemary M. , Woodhouse Adele , Blizzard Catherine A.
Published: October 2023

Amyotrophic Lateral Sclerosis (ALS) is an incurable disease characterized by relentlessly progressive degeneration of the corticomotor system. Cortical hyperexcitability has been identified as an early pre-symptomatic biomarker of ALS. This suggests that hyperexcitability occurs upstream in the ALS pathological cascade and may even be part of the mechanism that drives development of symptoms or loss of motor neurons in the spinal cord. However, many studies also indicate a loss to the synaptic machinery that mediates synaptic input which raises the question of which is the driver of disease, and which is a homeostatic response. Herein, we used an inducible mouse model of TDP-43 mediated ALS that permits for the construction of detailed phenotypic timelines. Our work comprehensively describes the relationship between intrinsic hyperexcitability and altered synaptic input onto motor cortical layer 5 pyramidal neurons over time. As a result, we have constructed the most complete timeline of electrophysiological changes following induction of TDP-43 dysfunction in the motor cortex. We report that intrinsic hyperexcitability of layer 5 pyramidal neurons precedes changes to excitatory synaptic connections, which manifest as an overall loss of inputs onto layer 5 pyramidal neurons. This finding highlights the importance of hyperexcitability as a primary mechanism of ALS and re-contextualizes synaptic changes as possibly representing secondary adaptive responses. Recognition of the relationship between intrinsic hyperexcitability and reduced excitatory synaptic input has important implications for the development of useful therapies against ALS. Novel strategies will need to be developed that target neuronal output by managing excitability against synapses separately.
Spatial frequency channels depend on stimulus bandwidth in normal and amblyopic vision: an exploratory factor analysis
Authors: Reynaud Alexandre , Min Seung Hyun
Published: October 2023

The Contrast Sensitivity Function (CSF) is the measure of an observer’s contrast sensitivity as a function of spatial frequency. It is a sensitive measure to assess visual function in fundamental and clinical settings. Human contrast sensitivity is subserved by different spatial frequency channels. Also, it is known that amblyopes have deficits in contrast sensitivity, particularly at high spatial frequencies. Therefore, the aim of this study was to assess whether the contrast sensitivity function is subtended by the same spatial frequency channels in control and amblyopic populations. To determine these spatial frequency channels, we performed an exploratory factor analysis on five datasets of contrasts sensitivity functions of amblyopic and control participants measured using either gratings or noise patches, taken from our previous studies. In the range of 0.25–10 c/d, we identified two spatial frequency channels. When the CSF was measured with noise patches, the spatial frequency channels presented very similar tuning in the amblyopic eye and the fellow eye and were also similar to what was observed in controls. The only major difference was that the weight attributed to the high frequency channel was reduced by approximately 50% in the amblyopic eye. However, when the CSF was measured using gratings, the spatial frequency channels of the amblyopic eye were tuned toward lower spatial frequencies. These findings suggest that there is no mechanistic deficit for contrast sensitivity in amblyopia and that amblyopic vision may just be subjected to excessive internal noise and attenuation at higher spatial frequencies, thereby supporting the use of therapeutic strategies that involve rebalancing contrast.
Functional changes of default mode network and structural alterations of gray matter in patients with irritable bowel syndrome: a meta-analysis of whole-brain studies
Authors: Zhao Mengqi , Hao Zeqi , Li Mengting , Xi Hongyu , Hu Su , Wen Jianjie , Gao Yanyan , Antwi Collins Opoku , Jia Xize , Yu Yang , Ren Jun
Published: October 2023

Background

Irritable bowel syndrome (IBS) is a brain-gut disorder with high global prevalence, resulting from abnormalities in brain connectivity of the default mode network and aberrant changes in gray matter (GM). However, the findings of previous studies about IBS were divergent. Therefore, we conducted a meta-analysis to identify common functional and structural alterations in IBS patients.

Methods

Altogether, we identified 12 studies involving 194 IBS patients and 230 healthy controls (HCs) from six databases using whole-brain resting state functional connectivity (rs-FC) and voxel-based morphometry. Anisotropic effect-size signed differential mapping (AES-SDM) was used to identify abnormal functional and structural changes as well as the overlap brain regions between dysconnectivity and GM alterations.

Results

Findings indicated that, compared with HCs, IBS patients showed abnormal rs-FC in left inferior parietal gyrus, left lingual gyrus, right angular gyrus, right precuneus, right amygdala, right median cingulate cortex, and left hippocampus. Altered GM was detected in the fusiform gyrus, left triangular inferior frontal gyrus (IFG), right superior marginal gyrus, left anterior cingulate gyrus, left rectus, left orbital IFG, right triangular IFG, right putamen, left superior parietal gyrus and right precuneus. Besides, multimodal meta-analysis identified left middle frontal gyrus, left orbital IFG, and right putamen as the overlapped regions.

Conclusion

Our results confirm that IBS patients have abnormal alterations in rs-FC and GM, and reveal brain regions with both functional and structural alterations. These results may contribute to understanding the underlying pathophysiology of IBS.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42022351342.
Research hotspots and trends in post-stroke dysphagia: a bibliometric analysis
Authors: Xu Fangyuan , Bai Lin , Dai Ziliang , Cheng Hongliang
Published: October 2023

Background

Dysphagia represents one of the common complications following a stroke, and post-stroke dysphagia (PSD) can lead to aspiration, pneumonia, and malnutrition, thus prolonging hospital stay, escalating medical expenditures, and imposing a substantial economic strain on both patients and society. The utilization of bibliometric analysis offers a quantitative approach for investigating the existing literature and recognizes the current status of the research. However, bibliometric analysis on the subject of PSD remains absent. Consequently, we carried out this study to provide researchers with insights, facilitating their further exploration of PSD.

Methods

Conducting a bibliometric analysis of articles pertaining to PSD retrieved over the past two decades enables us to acquire the research hotspots and trends in this area. The publications concerning PSD were searched from the Core Collection of Web of Science, spanning the period ranging from 2003 to 2023. Articles or reviews published in English were included in this study. Subsequently, we employed CiteSpace and VOSviewer software to visualize the retrieved articles, thereby identifying the cooperative relationships of authors, institutions, and countries, as well as relevant information about journals and references.

Results

This study comprised 866 papers in total, and the number of articles published each year shows an overall growth trend. As for the analysis of the authors, Dziewas R. was the most prolific author with 21 articles. The most frequently published institutions, countries, and journals were the University of Manchester, China, and Dysphagia, with 28, 254, and 75 publications, respectively. And the co-cited authors and journals with the highest counts were Martino R and Stroke. According to the analysis of keywords and references, dysphagia screening and assessment, prevention of pneumonia, rehabilitation approaches, and nutritional management of PSD are considered research hotpots. Additionally, future research may focus on the topics of systematic review and meta-analysis, noninvasive brain stimulation, and lesion location.

Conclusion

Through the bibliometrics analysis of PSD, we can capture the research hotspots and frontiers of PSD, thereby providing inspiration and reference for subsequent studies in this field.
Hippocampal atrophy is associated with hearing loss in cognitively normal adults
Authors: Shim Ye Ji , Jung Wi Hoon , Billig Alexander J. , Sedley William , Song Jae-Jin
Published: October 2023

Objectives

A growing body of evidence suggests that age-related hearing loss (HL) is associated with morphological changes of the cerebral cortex, but the results have been drawn from a small amount of data in most studies. The aim of this study is to investigate the correlation between HL and gray matter volume (GMV) in a large number of subjects, strictly controlling for an extensive set of possible biases.

Methods

Medical records of 576 subjects who underwent pure tone audiometry, brain magnetic resonance imaging (MRI), and the Korean Mini-Mental State Exam (K-MMSE) were reviewed. Among them, subjects with normal cognitive function and free of central nervous system disorders or coronary artery disease were included. Outliers were excluded after a sample homogeneity check. In the end, 405 subjects were enrolled. Pure tone hearing thresholds were determined at 0.5, 1, 2, and 4 kHz in the better ear. Enrolled subjects were divided into 3 groups according to pure tone average: normal hearing (NH), mild HL (MHL), and moderate-to-severe HL (MSHL) groups. Using voxel-based morphometry, we evaluated GMV changes that may be associated with HL. Sex, age, total intracranial volume, type of MRI scanner, education level, K-MMSE score, smoking status, and presence of hypertension, diabetes mellitus and dyslipidemia were used as covariates.

Results

A statistically significant negative correlation between the hearing thresholds and GMV of the hippocampus was elucidated. Additionally, in group comparisons, the left hippocampal GMV of the MSHL group was significantly smaller than that of the NH and MHL groups.

Conclusion

Based on the negative correlation between hearing thresholds and hippocampal GMV in cognitively normal old adults, the current study indicates that peripheral deafferentation could be a potential contributing factor to hippocampal atrophy.
Reproductive-dependent effects of B vitamin deficiency on lifespan and physiology
Authors: Yu Guixiang , Liu Shaowei , Yang Kun , Wu Qi
Published: October 2023

B vitamins constitute essential micronutrients in animal organisms, executing crucial roles in numerous biological processes. B vitamin deficiency can result in severe health consequences, including the impairment of reproductive functions and increased susceptibility to age-related diseases. However, the understanding of how reproduction alters the requirements of each individual B vitamins for healthy aging and lifespan remains limited. Here, utilizing Drosophila as a model organism, we revealed the substantial impacts of deficiencies in specific B vitamins on lifespan and diverse physiological functions, with the effects being significantly shaped by reproductive status. Notably, the dietary absence of VB1, VB3, VB5, VB6, or VB7 significantly decreased the lifespan of wild-type females, yet demonstrated relatively little effect on ovoD1 infertile mutant females’ lifespan. B vitamin deficiencies also resulted in distinct impacts on the reproduction, starvation tolerance and fat metabolism of wild-type females, though no apparent effects were observed in the infertile mutant females. Moreover, a deficiency in VB1 reshaped the impacts of macronutrient intervention on the physiology and lifespan of fertile females in a reproductive-dependent manner. Overall, our study unravels that the reproductive status of females serves as a critical modulator of the lifespan and physiological alterations elicited by B-vitamin deficiencies.
The role of daratumumab in relapsed/refractory CD38 positive acute leukemias—case report on three cases with a literature review
Authors: Prejzner Witold , Piekoś Oliwia , Bełdzińska Karolina , Sadowska-Klasa Alicja , Zarzycka Ewa , Bieniaszewska Maria , Lewandowski Krzysztof , Zaucha Jan Maciej
Published: October 2023

Primary refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) and mixed phenotype myeloid/T-cell acute leukemia have dismal prognoses. New treatment approaches, preferably targeting specific leukemic aberrations to overcome resistance, are urgently needed. The bright expression of the CD38 antigen found in several cases of T-ALL led to an investigation into the role of anti-CD38 antibodies in the treatment of T-ALL. Here, we present three cases of resistant and relapsed T-ALL and myeloid/T-cell treated with daratumumab-based therapy, including venetoclax and bortezomib (Dara-Ven-Bor). All patients achieved complete remission, with minimal residual disease negativity within four weeks of treatment, allowing them to proceed to allogeneic hematopoietic cell transplantation. The toxicity of the triple schema was acceptable. Our patients and other cases reviewed here suggest that daratumumab combined with venetoclax and bortezomib may be a very effective and relatively safe salvage treatment, even in primary resistant T-ALL.