bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-channel system for joint unambiguous measurement of DFS and AOA based on serrodyne modulation
Authors: Li Yan , Guo Yuxiao , Yin Bin , Wang Zixiao , He Qinglong , Wang Muguang
Published: August 2023

In this paper, a photonic-assisted system for simultaneous and unambiguous measurement of the Doppler frequency shift (DFS) and angle-of-arrival (AOA) using a dual-parallel dual-drive Mach–Zehnder modulator (DP-DDMZM) is proposed and investigated. The echo signals received by two receiving antennas are applied to the radio frequency ports of one sub-DDMZM of the DP-DDMZM. The bias port of the sub-DDMZM is fed by a binary electrical signal that is used to construct two different mapping curves on the relationship between the phase difference and the power of the output intermediate frequency (IF) signal. Therefore, unambiguous AOA measurement with extended range can be realized. The transmitted signal is input into the other sub-DDMZM to implement single-sideband modulation, which is then frequency shifted based on serrodyne modulation. Both the value and direction of DFS can be derived intuitively from the frequency of the output IF signal. Simulation results show that the measurement error of unambiguous DFS measurement is no more than ±0.008Hz in the range of −100kHz to 100 kHz, and the measurement error of unambiguous AOA is less than ±0.2∘ in the range of −70.8∘ to 70.8°. Moreover, since the scheme does not involve the construction of multi-channels or use of any filter or polarization dependent device, the system has concise structure, high accuracy, large operating bandwidth, and strong robustness, and can be considered as a very promising solution for actual applications.
Retaining terahertz intensity modulation at second harmonic generation of a chirped pulse
Authors: Martyanov Mikhail , Poteomkin Anatoly , Kuzmin Igor , Mironov Sergey
Published: August 2023

Terahertz modulation of chirped laser pulse intensity was achieved with phase-only spectral modulation. Preservation of this modulation during second harmonic generation together with almost 30% conversion efficiency was demonstrated employing noncollinear frequency mixing of 60-µJ oppositely chirped laser pulses.
Tunable random lasers via phase transition for information encryption
Authors: Tong Junhua , Ruan Jun , Iqbal Naeem , Ma He , Ge Kun , Lin Chengyou , Zhai Tianrui
Published: August 2023

Introducing phase transition materials to random systems provides a promising route to create new optoelectronic functionalities of random lasers. Here, a phase transition random laser with switchable lasing modes is reported, which is designed with a thermoresponsive hydrogel as scattering medium. By manipulating the phase transition in hydrogel, random lasing modes can be switched reversibility between incoherent and coherent random lasing. The phenomenon derives from the changing of light scattering properties in different phase states, thus affecting the optical feedback path of random lasing. Besides, based on its controllable and easily detectable time-domain characteristics, the phase transition random laser is applied in information encoding and transmission. It is the first time that the transition from coherent to incoherent random lasing is observed by varying the sample phase states. This work will inspire the design and application of novel random lasers in photoelectric device.
Metamaterial graphene sensors for the detection of two food additives
Authors: Wu Guifang , Wang Wei , Zhang Rui , Yan Fengping , Liang Lanju , Yan Xin , Yao Haiyun , Wang Ziqun , Li Zhenhua , Xu Liang
Published: August 2023

Food safety is an important consideration for the food industry and for daily life, and food additives are essential in the modern food industry. Graphene-based metamaterial sensors are of great value and have potential applications in the detection of food additives, due to their ultra-sensitivity. This paper proposes a metasurface sensor consisting of graphene and dual elliptical ring resonators (Gr-DERRs) sensor for the detection of two common food additives. The limit of detection (LOD) for Sudan I solution is 581.43 fg/ml and, for taurine, 52.86 fg/ml. This ultra-sensitive detection is achieved by exploiting the unique electromagnetic properties of electromagnetically induced transparency (EIT) resonance, together with the Fermi energy level of graphene moving to the Dirac point, resulting in a dramatic change in the dielectric environment. The Gr-DERRs sensor has brings significant improvement in the detection of food additives with detection limits reduced to the femtogram level.
Nonlinear gain models in a quantum cascade laser
Authors: Kolek Andrzej , Sobaszek Mirosław
Published: August 2023

Density matrix analysis of a three-state model of quantum cascade laser (QCL) reveals that in this device, the optical gain is composed of the linear part (proportional to population inversion Δn) and the remaining nonlinear part. The nonlinear component non-negligibly contributes even to the small-signal response of the medium. In many attempts to modeling QCLs, the common practice to account for nonlinear gain components is to complement the equation for the gain, g = g
c
Δn, g
c
is the gain cross-section, by a compression factor f. In this paper, improved (but still simple) models of the optical gain in QCL are proposed, which preserve the two-component gain structure. With these models, there is no need to solve the Hamiltonian with time-dependent potentials, so that extraordinary numerical loads can be avoided, but simultaneously the essential physics of the phenomena is kept. The improved gain models defined by Eqs. (12), (15) and (16) enable accounting for its nonlinear components while preserving the load-saving, scattering-like approach to light-matter interaction. It is also shown that as long as the populations and dc coherences are determined such that they account for the interaction with the optical field, the small-signal formulation of the gain gives its realistic estimate also for a large optical signal. This conjecture validates the use of non-equilibrium Green’s function-based approaches, in which the interaction with the optical field is included through electron-photon selfenergies. The small-signal formulation of the gain can be used in this approach to monitor the saturation process, estimate the clamping flux and the light-current characteristic.
Disturbance-free single-pixel imaging camera via complementary detection
Authors: Gong Wenlin
Published: August 2023

We present a technique called single-pixel imaging camera based on complementary detection and optimized encoded modulation (CSPI camera), which can significantly reduce the influence of the disturbance light to single-pixel imaging (SPI). The experiments demonstrates that when the probability of the value “1” for each binary encoded pattern is P=0.5, CSPI camera is still disturbance-free even if the intensity fluctuation of the disturbance light is much larger than the signal’s intensity. The reconstruction results of both traditional SPI and differential SPI are also compared. This technique of CSPI camera can dramatically promote real application of single-pixel imaging Lidar.
Non-paraxial region adaptive aberration compensation using the phase transfer function
Authors: Tang Xinlan , Kong Lingbao , Song Huixin
Published: August 2023

The optical transfer function is crucial for imaging system design and characterization. However, practical optical systems often deviate from linear spatial invariance due to aberrations and field-of-view considerations, posing challenges for optical transfer function characterization and aberration compensation in non-paraxial region imaging. Partitioning the field-of-view into isoplanatic regions and measuring the optical transfer function for each region is a potential solution, but practical implementation is hindered by the lack of field-of-view information. This Letter introduces a compensation method for the phase modulation function based on spatial frequency domain division, specifically tailored for scenarios where high imaging quality is not essential. The proposed method addresses the challenge by filling the phase transfer function in an annular form corresponding to aberrations in different isoplanatic regions, offers a valuable solution for adaptive aberration compensation in non-paraxial region imaging, and presents a practical illustration of its effectiveness.
Gradient-assisted metasurface absorber with dual-band chiral switching and quasi-linearly tunable circular dichroism
Authors: Chen Jiafei , Zong Shu , Liu Xiaoshan , Liu Guiqiang , Zhan Xuefeng , Liu Zhengqi
Published: August 2023

Chiral metasurfaces with tunable or switchable circular dichroism (CD) responses hold great potential for advanced optical devices. In this work, we theoretically propose and numerically demonstrate a chiral metasurface absorber composed of periodically serrated Ge2Sb2Te5 (GST) resonators. By harnessing strong plasmonic resonance using the gradient geometry, we achieve a strongly enhanced chiral response with a CD value of 0.98 at λ2 = 2359 nm and a CD value of 0.7 at λ1 = 2274 nm. Additionally, by controlling the gradient difference in the serrated GST resonator, we can modify the CD intensity in multiple dimensions and near-perfectly optimize the chiral properties. Furthermore, it is worth noting that the CD value can be strongly varied by adjusting the phase transition characteristics of GST in the range of 0.007 to 0.7 at λ1 and 0.002 to 0.98 at λ2, corresponding to a switch between “on” and “off” states. The findings give new insight into multi-functional chiroptics and hold wide applications.
Wave-scattering processes: path-integrals designed for the numerical handling of complex geometries
Authors: Dauchet Jérémi , Charon Julien , Blanco Stéphane , Brunel Laurent , Cornet Jean-François , Coustet Christophe , El Hafi Mouna , Eymet Vincent , Forest Vincent , Fournier Richard , Gros Fabrice , Piaud Benjamin , Terrée Guillaume , Vourc’h Thomas
Published: August 2023

Relying on Feynman–Kac path-integral methodology, we present a new statistical perspective on wave single-scattering by complex three-dimensional objects. The approach is implemented on three models—Schiff approximation, Born approximation, and rigorous Born series—and familiar interpretative difficulties such as the analysis of moments over scatterer distributions (size, orientation, shape, etc.) are addressed. In terms of the computational contribution, we show that commonly recognized features of the Monte Carlo method with respect to geometric complexity can now be available when solving electromagnetic scattering.
High-NA broadband achromatic metalens in the visible range
Authors: Sun XiaoHong , Yan MengMeng , Huo Shuang , Fan JiaJin , Zhao SaiLi , Guo RuiJun , Zeng Yong
Published: August 2023

We designed a high-NA (High numerical aperture) broadband achromatic metalens consisting of elliptical TiO2-based integrated-resonant unit-cells. The phase profile for the designed metalens is constituted by incorporating the geometric phase with the transmission phase, where the geometric phase contributes to the basic phase profile of the metalens and the transmission phase is used to compensate phase profile at different incident wavelengths. With the method of finite element simulation, the results demonstrate that the metalens has an average focusing efficiency of 36.4% in the visible range from 530 nm to 850 nm. Compared with chromatic metalens, the axial chromatic aberration of achromatic metalens is reduced by 2.66 times. Furthermore, the designed metalens has a high-NA of 0.564. This work can be potentially applied in various fields, such as optical communications, microscopy imaging, and optical instruments.
Compact asymmetric multimode interference coupler-based Electro-optic switches with Bezier S-bend waveguides
Authors: Afsary Noor , Alam Md Koushik , Hoque Karimul , Rasel MD Omar Faruk
Published: August 2023

High-speed and energy-efficient electro-optic (EO) switches are crucial for next-generation data communication systems. This paper introduces a novel EO switch with a multimode inference (MMI) coupler-based approach in a Lithium Niobate (LiNbO3) platform, which is developed with Bezier S-bend waveguides to reduce the bending losses, resulting in a substantial bending loss reduction of 0.18 dB. This Bezier-bend EO switch shows an excess loss of 0.33 dB and crosstalk of -20.44 dB for the bar port switching, while cross port switching exhibits an excess loss of 0.64 dB and crosstalk of -13.66 dB. Applying a 3.27 V voltage achieves a balanced splitting ratio of 29:29:29 between the three outputs. The length of this EO switch is 4.09 mm, which needs 4.1V to create a phase shift, showing a voltage efficiency of 1.68 V/cm. This study presents a promising pathway for a novel EO switch design and introduces improved signal management for next-generation high-speed computing systems.
Maximizing electro-optic switch performance with a compact asymmetric coupler enhanced by Bezier bends
Authors: Afsary Noor , Alam Md Koushik , Hoque Karimul , Rasel MD Omar Faruk
Published: August 2023

The pursuit of high-speed and energy-efficient data transmission has spotlighted electro-optic (EO) switches as crucial components shaping the future of communication networks. This paper introduces a novel EO switch utilizing a coupler-based approach implemented on the Lithium Niobate (LiNbO3) platform. The aim is to optimize the efficiency and functionality of EO switches. Notably, this switch strategically incorporates a Bezier S bend to mitigate bending losses, resulting in a substantial 0.18 dB reduction in bending loss. The proposed switch demonstrates an excess loss of 0.33 dB and crosstalk of -20.44 dB for bar port switching, while cross port switching exhibits an excess loss of 0.64 dB and crosstalk of -13.66 dB. By applying a 3.27 V voltage, a balanced splitting ratio of 29:29:29 is achieved among the cores, highlighting the switch's precise control over signal distribution. The switch is 4.09 mm long and needs 4.1V to create a phase shift, showing a voltage efficiency of 1.68 V/cm. This study presents a promising pathway for advanced EO switch design, promising improved signal management in modern communication systems.
Relativistic-guided stable mode of few-cycle 20 μm level infrared radiation
Authors: Huang Yongsheng , Si Meiyu , Ruan Manqi , Shen Baifei , Xu Zhangli , Yu Tong-Pu , Wang Xiongfei , Chen Yuan
Published: August 2023

The generation of intense infrared radiation with a wavelength greater than 10 μm is limited by the optical materials of traditional methods and the laser-plasma parameters of plasma-bubble methods. In this study, we propose a new scheme to produce an intense field of ~ tens of GV/m, a tunable long wavelength few-cycle infrared radiation from 20 to 30 μm and even longer based on the oscillations of the surface electron film that using a relativistic electron beam propagates in the micro-tube. The radiation source is guided entirely by a relativistic electron beam and formed a stable $\mathrm{TM}$ propagation mode in the micro-tube. The wavelength and intensity are regulated by changing the micro-tube radius and the charge of the driving electron beam, both of which change nearly linearly. This opens up new opportunities for applications of the relativistic intensity infrared radiation to high-field physics, shorter attosecond pulses generation and charged particle acceleration.
Metabolic modeling of sex-specific liver tissue suggests mechanism of differences in toxicological responses
Authors: Moore Connor J. , Holstege Christopher P. , Papin Jason A.
Published: August 2023

Male subjects in animal and human studies are disproportionately used for toxicological testing. This discrepancy is evidenced in clinical medicine where females are more likely than males to experience liver-related adverse events in response to xenobiotics. While previous work has shown gene expression differences between the sexes, there is a lack of systems-level approaches to understand the direct clinical impact of these differences. Here, we integrate gene expression data with metabolic network models to characterize the impact of transcriptional changes of metabolic genes in the context of sex differences and drug treatment. We used Tasks Inferred from Differential Expression (TIDEs), a reaction-centric approach to analyzing differences in gene expression, to discover that several metabolic pathways exhibit sex differences including glycolysis, fatty acid metabolism, nucleotide metabolism, and xenobiotics metabolism. When TIDEs is used to compare expression differences in treated and untreated hepatocytes, we find several subsystems with differential expression overlap with the sex-altered pathways such as fatty acid metabolism, purine and pyrimidine metabolism, and xenobiotics metabolism. Finally, using sex-specific transcriptomic data, we create individual and averaged male and female liver models and find differences in the pentose phosphate pathway and other metabolic pathways. These results suggest potential sex differences in the contribution of the pentose phosphate pathway to oxidative stress, and we recommend further research into how these reactions respond to hepatotoxic pharmaceuticals.
A subcomponent-guided deep learning method for interpretable cancer drug response prediction
Authors: Liu Xuan , Zhang Wen
Published: August 2023

Accurate prediction of cancer drug response (CDR) is a longstanding challenge in modern oncology that underpins personalized treatment. Current computational methods implement CDR prediction by modeling responses between entire drugs and cell lines, without the consideration that response outcomes may primarily attribute to a few finer-level ‘subcomponents’, such as privileged substructures of the drug or gene signatures of the cancer cell, thus producing predictions that are hard to explain. Herein, we present SubCDR, a subcomponent-guided deep learning method for interpretable CDR prediction, to recognize the most relevant subcomponents driving response outcomes. Technically, SubCDR is built upon a line of deep neural networks that enables a set of functional subcomponents to be extracted from each drug and cell line profile, and breaks the CDR prediction down to identifying pairwise interactions between subcomponents. Such a subcomponent interaction form can offer a traceable path to explicitly indicate which subcomponents contribute more to the response outcome. We verify the superiority of SubCDR over state-of-the-art CDR prediction methods through extensive computational experiments on the GDSC dataset. Crucially, we found many predicted cases that demonstrate the strength of SubCDR in finding the key subcomponents driving responses and exploiting these subcomponents to discover new therapeutic drugs. These results suggest that SubCDR will be highly useful for biomedical researchers, particularly in anti-cancer drug design.
STREAK: A supervised cell surface receptor abundance estimation strategy for single cell RNA-sequencing data using feature selection and thresholded gene set scoring
Authors: Javaid Azka , Frost Hildreth Robert
Published: August 2023

The accurate estimation of cell surface receptor abundance for single cell transcriptomics data is important for the tasks of cell type and phenotype categorization and cell-cell interaction quantification. We previously developed an unsupervised receptor abundance estimation technique named SPECK (Surface Protein abundance Estimation using CKmeans-based clustered thresholding) to address the challenges associated with accurate abundance estimation. In that paper, we concluded that SPECK results in improved concordance with Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) data relative to comparative unsupervised abundance estimation techniques using only single-cell RNA-sequencing (scRNA-seq) data. In this paper, we outline a new supervised receptor abundance estimation method called STREAK (gene Set Testing-based Receptor abundance Estimation using Adjusted distances and cKmeans thresholding) that leverages associations learned from joint scRNA-seq/CITE-seq training data and a thresholded gene set scoring mechanism to estimate receptor abundance for scRNA-seq target data. We evaluate STREAK relative to both unsupervised and supervised receptor abundance estimation techniques using two evaluation approaches on six joint scRNA-seq/CITE-seq datasets that represent four human and mouse tissue types. We conclude that STREAK outperforms other abundance estimation strategies and provides a more biologically interpretable and transparent statistical model.
Beyond a PPR-RNA recognition code: Many aspects matter for the multi-targeting properties of RNA editing factor PPR56
Authors: Yang Yingying , Ritzenhofen Kira , Otrzonsek Jessica , Xie Jingchan , Schallenberg-Rüdinger Mareike , Knoop Volker
Published: August 2023

The mitochondrial C-to-U RNA editing factor PPR56 of the moss Physcomitrium patens is an RNA-binding pentatricopeptide repeat protein equipped with a terminal DYW-type cytidine deaminase domain. Transferred into Escherichia coli, PPR56 works faithfully on its two native RNA editing targets, nad3eU230SL and nad4eU272SL, and also converts cytidines into uridines at over 100 off-targets in the bacterial transcriptome. Accordingly, PPR56 is attractive for detailed mechanistic studies in the heterologous bacterial setup, allowing for scoring differential RNA editing activities of many target and protein variants in reasonable time. Here, we report (i) on the effects of numerous individual and combined PPR56 protein and target modifications, (ii) on the spectrum of off-target C-to-U editing in the bacterial background transcriptome for PPR56 and two variants engineered for target re-direction and (iii) on combinations of targets in tandem or separately at the 5’- and 3’-ends of large mRNAs. The latter experimentation finds enhancement of RNA editing at weak targets in many cases, including cox3eU290SF as a new candidate mitogenome target. We conclude that C-to-U RNA editing can be much enhanced by transcript features also outside the region ultimately targeted by PPRs of a plant editing factor, possibly facilitated by its enrichment or scanning along transcripts.
Tau protein aggregation associated with SARS-CoV-2 main protease
Authors: Eberle Raphael Josef , Coronado Mônika Aparecida , Gering Ian , Sommerhage Simon , Korostov Karolina , Stefanski Anja , Stühler Kai , Kraemer-Schulien Victoria , Blömeke Lara , Bannach Oliver , Willbold Dieter
Published: August 2023

The primary function of virus proteases is the proteolytic processing of the viral polyprotein. These enzymes can also cleave host cell proteins, which is important for viral pathogenicity, modulation of cellular processes, viral replication, the defeat of antiviral responses and modulation of the immune response. It is known that COVID-19 can influence multiple tissues or organs and that infection can damage the functionality of the brain in multiple ways. After COVID-19 infections, amyloid-β, neurogranin, tau and phosphorylated tau were detected extracellularly, implicating possible neurodegenerative processes. The present study describes the possible induction of tau aggregation by the SARS-CoV-2 3CL protease (3CLpro) possibly relevant in neuropathology. Further investigations demonstrated that tau was proteolytically cleaved by the viral protease 3CL and, consequently, generated aggregates. However, more evidence is needed to confirm that COVID-19 is able to trigger neurodegenerative diseases.
Allometric relationships for eight species of 4–5 year old nitrogen-fixing and non-fixing trees
Authors: Carreras Pereira K. A. , Wolf Amelia A. , Kou-Giesbrecht Sian , Akana Palani R. , Funk Jennifer L. , Menge Duncan N. L.
Published: August 2023

Allometric equations are often used to estimate plant biomass allocation to different tissue types from easier-to-measure quantities. Biomass allocation, and thus allometric equations, often differs by species and sometimes varies with nutrient availability. We measured biomass components for five nitrogen-fixing tree species (Robinia pseudoacacia,Gliricidia sepium,Casuarina equisetifolia,Acacia koa,Morella faya) and three non-fixing tree species (Betula nigra,Psidium cattleianum,Dodonaea viscosa) grown in field sites in New York and Hawaii for 4–5 years and subjected to four fertilization treatments. We measured total aboveground, foliar, main stem, secondary stem, and twig biomass in all species, and belowground biomass inRobinia pseudoacaciaandBetula nigra, along with basal diameter, height, and canopy dimensions. The individuals spanned a wide size range (<1–16 cm basal diameter; 0.24–8.8 m height). For each biomass component, aboveground biomass, belowground biomass, and total biomass, we determined the following four allometric equations: the most parsimonious (lowest AIC) overall, the most parsimonious without a fertilization effect, the most parsimonious without canopy dimensions, and an equation with basal diameter only. For some species, the most parsimonious overall equation included fertilization effects, but fertilization effects were inconsistent across fertilization treatments. We therefore concluded that fertilization does not clearly affect allometric relationships in these species, size classes, and growth conditions. Our best-fit allometric equations without fertilization effects had the following R2values: 0.91–0.99 for aboveground biomass (the range is across species), 0.95 for belowground biomass, 0.80–0.96 for foliar biomass, 0.94–0.99 for main stem biomass, 0.77–0.98 for secondary stem biomass, and 0.88–0.99 for twig biomass. Our equations can be used to estimate overall biomass and biomass of tissue components for these size classes in these species, and our results indicate that soil fertility does not need to be considered when using allometric relationships for these size classes in these species.
Evaluation of soil quality in Inner Mongolia desert steppe—A case study of Siziwang Banner
Authors: Jiang Hongtao , Li Xiaojia , Guo Chunrong , Zhang Yufeng , Zhou Ruiping , Hai Chunxing , Hu Zheru
Published: August 2023

As a natural ecological fragile region, the vast desert steppe in the Inner Mongolia has a developed animal husbandry, and thus posed great impacts on soil quality. In order to accurately evaluate the current situation of soil quality in the desert steppe, it is therefore imperative to adopt a suitable method to effectively assess the soil quality in the region. In this study, the minimum data set (MDS) was established with the help of principal component analysis, Norm value calculation, and correlation analysis, and four indicators, including organic matter, sand grains, soil erosion degree, and pH, were established to evaluate the soil quality of the desert steppe in the Siziwang Banner, a county in the Inner Mongolia. The results from the minimum data set (MDS) method were validated based on the total data set (TDS) method, and the validation indicated that the MDS method can be representative of the soil quality of the study area. The results indicated: 1) the soil quality index (SQI) of 0–30 cm in more than 90% of the study area falls in the range of 0.4 and 0.6 (medium level), while the better level (SQI ≥0.6) only accounted less than 10% of the study area; 2) For the MDS indexes, soil organic matter content at all depths decreased in the southern mountains, central hills, and northern plateau, which is consistent with the changing trends of SQI; 3) The sand grain was the dominant particle in the study region, which was in accordance with the intense wind erosion; 4) The negative correlation was found between the soil pH value and SQI (the high value in pH corresponded to the low value in SQI), which reflected that soil pH has a more stressful effect on the local vegetation. Overall, the MDS indexes in this study can objectively and practically reflect the soil quality in the study area, which can provide a cost effective method for SQI assessment in the desert steppe, which is important for the further grassland ecological construction and grassland management to improve the soil quality in the desert steppes.
Microbial Gene Ontology informed deep neural network for microbe functionality discovery in human diseases
Authors: Liu Yunjie , Zhang Yao-zhong , Imoto Seiya
Published: August 2023

The human microbiome plays a crucial role in human health and is associated with a number of human diseases. Determining microbiome functional roles in human diseases remains a biological challenge due to the high dimensionality of metagenome gene features. However, existing models were limited in providing biological interpretability, where the functional role of microbes in human diseases is unexplored. Here we propose to utilize a neural network-based model incorporating Gene Ontology (GO) relationship network to discover the microbe functionality in human diseases. We use four benchmark datasets, including diabetes, liver cirrhosis, inflammatory bowel disease, and colorectal cancer, to explore the microbe functionality in the human diseases. Our model discovered and visualized the novel candidates’ important microbiome genes and their functions by calculating the important score of each gene and GO term in the network. Furthermore, we demonstrate that our model achieves a competitive performance in predicting the disease by comparison with other non-Gene Ontology informed models. The discovered candidates’ important microbiome genes and their functions provide novel insights into microbe functional contribution.
Widespread infection, diversification and old host associations of Nosema Microsporidia in European freshwater gammarids (Amphipoda)
Authors: Bacela-Spychalska Karolina , Wattier Remi , Teixeira Maria , Cordaux Richard , Quiles Adrien , Grabowski Michal , Wroblewski Piotr , Ovcharenko Mykola , Grabner Daniel , Weber Dieter , Weigand Alexander M. , Rigaud Thierry
Published: August 2023

The microsporidian genus Nosema is primarily known to infect insects of economic importance stimulating high research interest, while other hosts remain understudied. Nosema granulosis is one of the formally described Nosema species infecting amphipod crustaceans, being known to infect only two host species. Our first aim was to characterize Nosema spp. infections in different amphipod species from various European localities using the small subunit ribosomal DNA (SSU) marker. Second, we aimed to assess the phylogenetic diversity, host specificity and to explore the evolutionary history that may explain the diversity of gammarid-infecting Nosema lineages by performing a phylogenetic reconstruction based on RNA polymerase II subunit B1 (RPB1) gene sequences. For the host species Gammarus balcanicus, we also analyzed whether parasites were in excess in females to test for sex ratio distortion in relation with Nosema infection. We identified Nosema spp. in 316 individuals from nine amphipod species being widespread in Europe. The RPB1-based phylogenetic reconstruction using newly reported sequences and available data from other invertebrates identified 39 haplogroups being associated with amphipods. These haplogroups clustered into five clades (A-E) that did not form a single amphipod-infecting monophyletic group. Closely related sister clades C and D correspond to Nosema granulosis. Clades A, B and E might represent unknown Nosema species infecting amphipods. Host specificity seemed to be variable with some clades being restricted to single hosts, and some that could be found in several host species. We show that Nosema parasite richness in gammarid hosts is much higher than expected, illustrating the advantage of the use of RPB1 marker over SSU. Finally, we found no hint of sex ratio distortion in Nosema clade A infecting G. balcanicus. This study shows that Nosema spp. are abundant, widespread and diverse in European gammarids. Thus, Nosema is as diverse in aquatic as in terrestrial hosts.
The small non-coding RNA B11 regulates multiple facets of Mycobacterium abscessus virulence
Authors: Bar-Oz Michal , Martini Maria Carla , Alonso Maria Natalia , Meir Michal , Lore Nicola Ivan , Miotto Paolo , Riva Camilla , Angala Shiva K , Xiao Junpei , Masiello Catherine S , Misiakou Maria-Anna , Sun Huaming , Moy Justin K , Jackson Mary , Johansen Helle Krogh , Cirillo Daniela Maria , Shell Scarlet S , Barkan Daniel
Published: August 2023

Mycobacterium abscessus causes severe disease in patients with cystic fibrosis. Little is known in M. abscessus about the roles of small regulatory RNAs (sRNA) in gene regulation. We show that the sRNA B11 controls gene expression and virulence-associated phenotypes in this pathogen. B11 deletion from the smooth strain ATCC_19977 produced a rough strain, increased pro-inflammatory signaling and virulence in multiple infection models, and increased resistance to antibiotics. Examination of clinical isolate cohorts identified isolates with B11 mutations or reduced expression. We used RNAseq and proteomics to investigate the effects of B11 on gene expression and test the impact of mutations found in clinical isolates. Over 200 genes were differentially expressed in the deletion mutant. Strains with the clinical B11 mutations showed expression trends similar to the deletion mutant, suggesting partial loss of function. Among genes upregulated in the B11 mutant, there was a strong enrichment for genes with B11-complementary sequences in their predicted ribosome binding sites (RBS), consistent with B11 functioning as a negative regulator that represses translation via base-pairing to RBSs. Comparing the proteomes similarly revealed that upregulated proteins were strongly enriched for B11-complementary sequences. Intriguingly, genes upregulated in the absence of B11 included components of the ESX-4 secretion system, critical for M. abscessus virulence. Many of these genes had B11-complementary sequences at their RBSs, which we show is sufficient to mediate repression by B11 through direct binding. Altogether, our data show that B11 acts as a direct negative regulator and mediates (likely indirect) positive regulation with pleiotropic effects on gene expression and clinically important phenotypes in M. abscessus. The presence of hypomorphic B11 mutations in clinical strains is consistent with the idea that lower B11 activity may be advantageous for M. abscessus in some clinical contexts. This is the first report on an sRNA role in M. abscessus.
The circRNA circVAMP3 restricts influenza A virus replication by interfering with NP and NS1 proteins
Authors: Min Jie , Li Yucen , Li Xinda , Wang Mingge , Li Huizi , Bi Yuhai , Xu Ping , Liu Wenjun , Ye Xin , Li Jing
Published: August 2023

Circular RNAs (circRNAs) are involved in various biological roles, including viral infection and antiviral immune responses. To identify influenza A virus (IAV) infection-related circRNAs, we compared the circRNA profiles of A549 cells upon IAV infection. We found that circVAMP3 is substantially upregulated after IAV infection or interferon (IFN) stimulation. Furthermore, IAV and IFN-β induced the expression of QKI-5, which promoted the biogenesis of circVAMP3. Overexpression of circVAMP3 inhibited IAV replication, while circVAMP3 knockdown promoted viral replication, suggesting that circVAMP3 restricts IAV replication. We verified the effect of circVAMP3 on viral infection in mice and found that circVAMP3 restricted IAV replication and pathogenesis in vivo. We also found that circVAMP3 functions as a decoy to the viral proteins nucleoprotein (NP) and nonstructural protein 1 (NS1). Mechanistically, circVAMP3 interfered with viral ribonucleoprotein complex activity by reducing the interaction of NP with polymerase basic 1, polymerase basic 2, or vRNA and restored the activation of IFN-β by alleviating the inhibitory effect of NS1 to RIG-I or TRIM25. Our study provides new insights into the roles of circRNAs, both in directly inhibiting virus replication and in restoring innate immunity against IAV infection.
Investigation of the Relationship Between Soil Erosion, Land Cover and Hemeroby Level in Cserépfalu by Analysing Soil Profiles
Authors: Dobos Anna , Hegyi Tamás Péter , Zelei Zoltán , Hegyi Balázs
Published: August 2023

We can measure the effects of anthropogenic processes to the nature in case of hilly agricultural areas with the rate of soil (water) erosion. There is actual question what kind of connection could be shown between the rate of soil erosion, land cover categories and hemeroby levels? How can the intensity of antropogenic effects influence the rate of soil erosion? We did some research work in the North Hungarian Region, in Cserépfalu in 2014. In Cserépfalu, the northern areas are under nature conservation and belong to the Southern Bükk Mountains while the southern dissected pediment is the extensive agricultural territory. We described the soil types in the southern areas using the soil description method of FAO. We collected data about the rate of soil erosion, the land cover types, slope angle, slope forms, slope aspect and data for the relief conditions too. We could point out the sheet erosion around the 15 investigated soil profiles and we could found 3 strongly eroded, 8 medium eroded and 4 accumulated soil profiles. The land cover categories were given based on FAO category system and topographic map from 1990. Our results showed that land cover categories were changed in time and it caused the change of hemeroby levels as well. The intensity of land cultivation in investigated areas was changed. We could point out in some cases that the stronger soil erosion rate was caused by former land cover system. In summary, some former agricultural areas were changed and became as an abandoned areas so that the antropogenic effects were decreased in extensive agricultural areas in Cserépfalu. Our results can be compared with another pediments dissected by valleys where extensive agricultural areas are characteristic in Hungary.
The effect of crest shape on discharge coefficient at linear weirs
Authors: Lakusic Stjepan
Published: August 2023

A detailed experimental laboratory analysis of the effect of crest shape on the discharge coefficient of sharp-crested weirs is presented in the paper. The experiments were conducted for four different crest shapes. The experiments and analyses show that discharge capacity, and discharge coefficient in particular, are significantly affected by weir crest height. It is stated in conclusion that rounded crest shape has the highest discharge capacity. In practice, sharp crested weirs are generally preferred to other crest shapes due to construction facility, although the discharge coefficient values of sharp crested weirs are lower compared to rounded crest shape.
Local injection therapy in the complex treatment of musculoskeletal disorders: principles of application, evidence base, safety
Authors: Lila A. M. , Zagorodniy N. V. , Karateev A. E. , Alekseeva L. I. , Chichasova N. V. , Lazishvili G. D. , Akhtyamov I. F. , Bialik E. I. , Makarov M. A. , Taskina E. A. , Schmidt E. I. , Krylov V. V. , Bialik V. E. , Nesterenko V. A.
Published: August 2023

Local injection therapy (LIT)  is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT.  LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.

The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.

The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.
Evaluation of the influence of polymorphisms of the transporter genes (RFC1, MDR1) and GGH on the efficacy of methotrexate in rheumatoid arthritis
Authors: Devald I. V. , Hodus E. A. , Nokhrin D. Yu. , Khromova E. B. , Ignatova G. L. , Stashkevich D. S. , Lila A. M. , Burmistrova A. L.
Published: August 2023

The efficacy of methotrexate (MT) in patients with rheumatoid arthritis (RA) may be determined by genetic factors.

Objective: to evaluate the isolated and combined effects of single nucleotide polymorphisms (SNPs) of membrane transporter proteins (RFC1 80G>A and MDR1 3435C>T) and the GGH -401C>T gamma-glutamyl hydrolase enzyme genes on the efficacy of MT in patients with RA.

Material and methods. The study group consisted of 85 patients with a confirmed diagnosis of RA, who received therapy with MT starting at 10 mg/week and increasing in dose to a maximum of 25 mg/week. Efficacy was assessed after six months of treatment using the dynamics of the DAS28 index, identifying patients who responded and those who did not respond to MT therapy.

Genotyping of RFC1, MDR1 and GGH gene polymorphisms was performed by real-time polymerase chain reaction. Three different approaches were used to analyze the results: 1) analysis for each of the genes; 2) logistic regression; and 3) multifactor dimensionality reduction (MDR).

Results and discussion. Single gene analysis was used to determine the most likely predictors of non-response to therapy: 1) for GGH-401C>T, TT genotype (odds ratio, OR 5.09; 95% confidence interval, C11.11—23.3); 2) forMDR13435C>T, the TT genotype (OR 2.38; 95% CI0.89-6.37); 3) for RFC180G>A, not - AA genotype (OR 1.87; 95% CI 0.93-3.76).

The logistic regression model showed a significant effect of homozygous genotype GGH -401TT on the efficacy of MT with low sensitivity of the method. The multifactorial dimensionality reduction results show a significant synergistic effect of the MT transport genes (MDR1, RFC1) and the GGH enzyme encoding the conversion of MT to the elimination form.

Conclusion. Using various statistical methods, the following results were obtained: Single gene analysis revealed the most likely predictors of nonresponse to MT therapy: GGH -401C>T - TT genotype, MDR1 3435C>T - TT genotype, RFC1 80G>A - not-AA genotype; the method of multiple logistic regression allowed to determine the significant effect of GGH -401ТТ genotype on the effect of the drug with a low sensitivity of the method; the isolated effect of polymorphisms is probably less pronounced than their combined effect on the effectiveness of MT. SNP synergism is a major contributor to the development of treatment resistance. MDR is a promising method that can be used in the future to assess the impact of SNPs.
Efficacy of tumor necrosis factor-α inhibitors in the treatment of various immunoinflammatory diseases: focus on immunogenicity
Authors: Nuriahmetova T. Yu. , Valeeva I. Kh. , Shevnina Y. O. , Petrov A. V. , Cheremina N. A. , Sukhorukova E. V. , Vasiliev A. G. , Abdulganieva D. I.
Published: August 2023

In clinical practice, differences in the efficacy of tumor necrosis factor-α inhibitors (iTNF-α) have been observed in different diseases.

Objective: to evaluate the efficacy of iTNF-α in patients with immune-mediated diseases and its relation to the immunogenicity of these drugs.

Material and methods. The study included 70 patients with rheumatic diseases (RD) and 53 with inflammatory bowel disease (IBD) treated with infliximab (IFN), adalimumab, or certolizumab pegol (CZP). Disease activity and response to therapy were evaluated, as well as measurement of the minimal residual concentration of iTNF-α and the level of anti-drug antibodies.

Results and discussion. Therapy efficacy was maintained in 60 (85.7%) patients with RD and 35 (66.0%) with IBD (odds ratio, OR 1.3; p=0.01). Event-free survival of therapy was observed more frequently in RD and was longer than in IBD (p<0.01). The incidence of treatment failure was 3.13 times higher in IBD than in RD (p<0.01). In contrast to IBD, low TNF-α levels were more common in RD patients who did not respond to treatment than in those who did (80% and 40%, respectively; OR 6.0; p<0.05). Anti-TNF-α antibodies were detected in 75% of patients with ineffective treatment with INF and CZP in the RD group and in 14.3% in the IBD group (OR 0.06; p<0.05).

Conclusion. In patients with RD, the effect of iTNF-α lasted more frequently and longer than in patients with IBD. In ankylosing spondylitis and rheumatoid arthritis, the ineffectiveness of iTNF-α was associated with the formation of anti-drug antibodies or their low concentration in most cases, but in IBD only in half of the cases.
Dystrophic calciphylaxis in panniculitis: features of the clinical picture and diagnosis
Authors: Egorova O. N. , Datsina A. V. , Severinova M. V.
Published: August 2023

The clinical presentation of lobular panniculitis (PN) associated with calciphylaxis (CP, calcification) can vary widely and may be associated with joint and internal organs involvement, making the diagnosis of the disease difficult.

Objective: to evaluate the frequency and significance of CP in patients with PN using long-term prospective follow-up.

Material and methods. From 2018 to 2023, at the V.A. Nasonova Research Institute of Rheumatology 217 patients with referral diagnosis "erythema nodosum" or "panniculitis" were examined. In 19.3% of cases (9 men and 33 women aged 37 to 72 years) CP was confirmed with an average disease duration of 56.3±11.2 months. Clinical examination of patients was performed according to the standards recommended by the Russian Association of Rheumatologists. International criteria were used to confirm the diagnosis of systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM), systemic sclerosis (SS), and lipodermatosclerosis (LDS). In 12 patients with indurations, pathological examination of biopsy specimens of skin and subcutaneous fatty tissue from the area of induration was performed, which allowed confirming the diagnosis of idiopathic lobular PN (ILPN) in 3 cases. 

Four grades of calcification were distinguished according to the size and depth of the calcifications. In addition, considering the type of radiological changes and clinical manifestations, four subtypes of CP were identified: mousse-like, stone-like, mesh-like and lamellar-like.

Results and discussion. In the study group, the ratio of women to men was 3.6:1, and the mean age was 43.8±7.6 years. On clinical examination we determined, in 60% of cases CP predominantly stone-like subtype (71.4%) of first grade (47.6%), which was significantly more frequently located on the upper and/or lower extremities and/or trunk (57.1%; p=0.05). Using clinical, laboratory and instrumental data, we confirmed the development of CP in ILPN (n=3), SLE (n=3), LDS (n=21), IIM (n=5), SS (n=1), and idiopathic CP (n=9) with a mean disease duration of 8.7±2.4 years.

An increase in ESR and CRP levels occurred in different diseases, while urinary syndrome was associated with SLE (66.6%) and an increase in creatinine phosphokinase with IIM. Decreased calcium and 25-hydroxyvitamin D levels and increased phosphorus and parathyroid hormone levels were found in many patients studied.

Conclusion. In the absence of clear diagnostic criteria for CP in patients with PN, early diagnosis is critical for the development of an effective multidisciplinary treatment plan.