bluuebunny/crossref_metadata_2025 huggingface dataset:
Maintenance of pluripotency-like signature in the entire ectoderm leads to neural crest stem cell potential
Authors: Pajanoja Ceren , Hsin Jenny , Olinger Bradley , Schiffmacher Andrew , Yazejian Rita , Abrams Shaun , Dapkunas Arvydas , Zainul Zarin , Doyle Andrew D. , Martin Daniel , Kerosuo Laura
Published: September 2023

The ability of the pluripotent epiblast to contribute progeny to all three germ layers is thought to be lost after gastrulation. The later-forming neural crest (NC) rises from ectoderm and it remains poorly understood how its exceptionally high stem-cell potential to generate mesodermal- and endodermal-like derivatives is obtained. Here, we monitor transcriptional changes from gastrulation to neurulation using single-cell-Multiplex-Spatial-Transcriptomics (scMST) complemented with RNA-sequencing. We show maintenance of pluripotency-like signature (Nanog, Oct4/PouV, Klf4-positive) in undecided pan-ectodermal stem-cells spanning the entire ectoderm late during neurulation with ectodermal patterning completed only at the end of neurulation when the pluripotency-like signature becomes restricted to NC, challenging our understanding of gastrulation. Furthermore, broad ectodermal pluripotency-like signature is found at multiple axial levels unrelated to the NC lineage the cells later commit to, suggesting a general role in stemness enhancement and proposing a mechanism by which the NC acquires its ability to form derivatives beyond “ectodermal-capacity” in chick and mouse embryos.
A subset of type-II collagen-binding antibodies prevents experimental arthritis by inhibiting FCGR3 signaling in neutrophils
Authors: Xu Zhongwei , Xu Bingze , Lundström Susanna L. , Moreno-Giró Àlex , Zhao Danxia , Martin Myriam , Lönnblom Erik , Li Qixing , Krämer Alexander , Ge Changrong , Cheng Lei , Liang Bibo , Tong Dongmei , Stawikowska Roma , Blom Anna M. , Fields Gregg B. , Zubarev Roman A. , Holmdahl Rikard
Published: September 2023

Rheumatoid arthritis (RA) involves several classes of pathogenic autoantibodies, some of which react with type-II collagen (COL2) in articular cartilage. We previously described a subset of COL2 antibodies targeting the F4 epitope (ERGLKGHRGFT) that could be regulatory. Here, using phage display, we developed recombinant antibodies against this epitope and examined the underlying mechanism of action. One of these antibodies, R69-4, protected against cartilage antibody- and collagen-induced arthritis in mice, but not autoimmune disease models independent of arthritogenic autoantibodies. R69-4 was further shown to cross-react with a large range of proteins within the inflamed synovial fluid, such as the complement protein C1q. Complexed R69-4 inhibited neutrophil FCGR3 signaling, thereby impairing downstream IL-1β secretion and neutrophil self-orchestrated recruitment. Likewise, human isotypes of R69-4 protected against arthritis with comparable efficiency. We conclude that R69-4 abrogates autoantibody-mediated arthritis mainly by hindering FCGR3 signaling, highlighting its potential clinical utility in acute RA.
Large-scale capture of hidden fluorescent labels for training generalizable markerless motion capture models
Authors: Butler Daniel J. , Keim Alexander P. , Ray Shantanu , Azim Eiman
Published: September 2023

Deep learning-based markerless tracking has revolutionized studies of animal behavior. Yet the generalizability of trained models tends to be limited, as new training data typically needs to be generated manually for each setup or visual environment. With each model trained from scratch, researchers track distinct landmarks and analyze the resulting kinematic data in idiosyncratic ways. Moreover, due to inherent limitations in manual annotation, only a sparse set of landmarks are typically labeled. To address these issues, we developed an approach, which we term GlowTrack, for generating orders of magnitude more training data, enabling models that generalize across experimental contexts. We describe: a) a high-throughput approach for producing hidden labels using fluorescent markers; b) a multi-camera, multi-light setup for simulating diverse visual conditions; and c) a technique for labeling many landmarks in parallel, enabling dense tracking. These advances lay a foundation for standardized behavioral pipelines and more complete scrutiny of movement.
Structural basis for calcium-stimulating pore formation of Vibrio α-hemolysin
Authors: Chiu Yu-Chuan , Yeh Min-Chi , Wang Chun-Hsiung , Chen Yu-An , Chang Hsiang , Lin Han-You , Ho Meng-Chiao , Lin Shih-Ming
Published: September 2023

Vibrio α-hemolysins (αHLs) are β-pore-forming toxins secreted by Vibrio pathogens, crucial for the facilitation of bacterial infections through host cell lysis. These toxins are produced as inactive precursors, requiring proteolytic maturation and membrane association for activation within host tissues. Here, we investigate Vibrio campbellii αHL (VcαHL), and establish that its hemolytic activity is significantly stimulated by calcium ions, with an EC50 that aligns with physiological calcium concentrations. Furthermore, we illustrate the vital contribution of calcium ions to the oligomerization of VcαHL on membranes. Using X-ray crystallography and cryo-electron microscopy, we decipher both the immature and assembled structures of VcαHL and elucidate the conformational changes corresponding to toxin assembly. We also identify a calcium-binding module that is integral for VcαHL’s calcium-dependent activation. These findings provide insights into the regulatory mechanisms of VcαHL and have the potential to inform the development of targeted therapeutic strategies against Vibrio infections.
Size-dependent deformation behavior in nanosized amorphous metals suggesting transition from collective to individual atomic transport
Authors: Liu Naijia , Sohn Sungwoo , Na Min Young , Park Gi Hoon , Raj Arindam , Liu Guannan , Kube Sebastian A. , Yuan Fusen , Liu Yanhui , Chang Hye Jung , Schroers Jan
Published: September 2023

The underlying atomistic mechanism of deformation is a central problem in mechanics and materials science. Whereas deformation of crystalline metals is fundamentally understood, the understanding of deformation of amorphous metals lacks behind, particularly identifying the involved temporal and spatial scales. Here, we reveal that at small scales the size-dependent deformation behavior of amorphous metals significantly deviates from homogeneous flow, exhibiting increasing deformation rate with reducing size and gradually shifted composition. This transition suggests the deformation mechanism changes from collective atomic transport by viscous flow to individual atomic transport through interface diffusion. The critical length scale of the transition is temperature dependent, exhibiting a maximum at the glass transition. While viscous flow does not discriminate among alloy constituents, diffusion does and the constituent element with higher diffusivity deforms faster. Our findings yield insights into nano-mechanics and glass physics and may suggest alternative processing methods to epitaxially grow metallic glasses.
Bifidobacteria shape antimicrobial T-helper cell responses during infancy and adulthood
Authors: Vogel Katrin , Arra Aditya , Lingel Holger , Bretschneider Dirk , Prätsch Florian , Schanze Denny , Zenker Martin , Balk Silke , Bruder Dunja , Geffers Robert , Hachenberg Thomas , Arens Christoph , Brunner-Weinzierl Monika C.
Published: September 2023

Microbial infections early in life are challenging for the unexperienced immune system. The SARS-CoV-2 pandemic again has highlighted that neonatal, infant, child, and adult T-helper(Th)-cells respond differently to infections, and requires further understanding. This study investigates anti-bacterial T-cell responses against Staphylococcus aureus aureus, Staphylococcus epidermidis and Bifidobacterium longum infantis in early stages of life and adults and shows age and pathogen-dependent mechanisms. Beside activation-induced clustering, T-cells stimulated with Staphylococci become Th1-type cells; however, this differentiation is mitigated in Bifidobacterium-stimulated T-cells. Strikingly, prestimulation of T-cells with Bifidobacterium suppresses the activation of Staphylococcus-specific T-helper cells in a cell-cell dependent manner by inducing FoxP3+CD4+ T-cells, increasing IL-10 and galectin-1 secretion and showing a CTLA-4-dependent inhibitory capacity. Furthermore Bifidobacterium dampens Th responses of severely ill COVID-19 patients likely contributing to resolution of harmful overreactions of the immune system. Targeted, age-specific interventions may enhance infection defence, and specific immune features may have potential cross-age utilization.
Structure of the peroxisomal Pex1/Pex6 ATPase complex bound to a substrate
Authors: Rüttermann Maximilian , Koci Michelle , Lill Pascal , Geladas Ermis Dionysios , Kaschani Farnusch , Klink Björn Udo , Erdmann Ralf , Gatsogiannis Christos
Published: September 2023

The double-ring AAA+ ATPase Pex1/Pex6 is required for peroxisomal receptor recycling and is essential for peroxisome formation. Pex1/Pex6 mutations cause severe peroxisome associated developmental disorders. Despite its pathophysiological importance, mechanistic details of the heterohexamer are not yet available. Here, we report cryoEM structures of Pex1/Pex6 from Saccharomyces cerevisiae, with an endogenous protein substrate trapped in the central pore of the catalytically active second ring (D2). Pairs of Pex1/Pex6(D2) subdomains engage the substrate via a staircase of pore-1 loops with distinct properties. The first ring (D1) is catalytically inactive but undergoes significant conformational changes resulting in alternate widening and narrowing of its pore. These events are fueled by ATP hydrolysis in the D2 ring and disengagement of a “twin-seam” Pex1/Pex6(D2) heterodimer from the staircase. Mechanical forces are propagated in a unique manner along Pex1/Pex6 interfaces that are not available in homo-oligomeric AAA-ATPases. Our structural analysis reveals the mechanisms of how Pex1 and Pex6 coordinate to achieve substrate translocation.
TAGET: a toolkit for analyzing full-length transcripts from long-read sequencing
Authors: Xia Yuchao , Jin Zijie , Zhang Chengsheng , Ouyang Linkun , Dong Yuhao , Li Juan , Guo Lvze , Jing Biyang , Shi Yang , Miao Susheng , Xi Ruibin
Published: September 2023

Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for full-length transcriptome analysis. We present an integrated computational toolkit named TAGET for Iso-seq full-length transcript data analyses, including transcript alignment, annotation, gene fusion detection, and quantification analyses such as differential expression gene analysis and differential isoform usage analysis. We evaluate the performance of TAGET using a public Iso-seq dataset and newly sequenced Iso-seq datasets from tumor patients. TAGET gives significantly more precise novel splice site prediction and enables more accurate novel isoform and gene fusion discoveries, as validated by experimental validations and comparisons with RNA-seq data. We identify and experimentally validate a differential isoform usage gene ECM1, and further show that its isoform ECM1b may be a tumor-suppressor in laryngocarcinoma. Our results demonstrate that TAGET provides a valuable computational toolkit and can be applied to many full-length transcriptome studies.
Non-uniform temporal scaling of developmental processes in the mammalian cortex
Authors: Paolino Annalisa , Haines Elizabeth H. , Bailey Evan J. , Black Dylan A. , Moey Ching , García-Moreno Fernando , Richards Linda J. , Suárez Rodrigo , Fenlon Laura R.
Published: September 2023

The time that it takes the brain to develop is highly variable across animals. Although staging systems equate major developmental milestones between mammalian species, it remains unclear how distinct processes of cortical development scale within these timeframes. Here, we compare the timing of cortical development in two mammals of similar size but different developmental pace: eutherian mice and marsupial fat-tailed dunnarts. Our results reveal that the temporal relationship between cell birth and laminar specification aligns to equivalent stages between these species, but that migration and axon extension do not scale uniformly according to the developmental stages, and are relatively more advanced in dunnarts. We identify a lack of basal intermediate progenitor cells in dunnarts that likely contributes in part to this timing difference. These findings demonstrate temporal limitations and differential plasticity of cortical developmental processes between similarly sized Therians and provide insight into subtle temporal changes that may have contributed to the early diversification of the mammalian brain.
Ultra-durable superhydrophobic cellular coatings
Authors: Gu Wancheng , Li Wanbo , Zhang Yu , Xia Yage , Wang Qiaoling , Wang Wei , Liu Ping , Yu Xinquan , He Hui , Liang Caihua , Ban Youxue , Mi Changwen , Yang Sha , Liu Wei , Cui Miaomiao , Deng Xu , Wang Zuankai , Zhang Youfa
Published: September 2023

Developing versatile, scalable, and durable coatings that resist the accretion of matters (liquid, vapor, and solid phases) in various operating environments is important to industrial applications, yet has proven challenging. Here, we report a cellular coating that imparts liquid-repellence, vapor-imperviousness, and solid-shedding capabilities without the need for complicated structures and fabrication processes. The key lies in designing basic cells consisting of rigid microshells and releasable nanoseeds, which together serve as a rigid shield and a bridge that chemically bonds with matrix and substrate. The durability and strong resistance to accretion of different matters of our cellular coating are evidenced by strong anti-abrasion, enhanced anti-corrosion against saltwater over 1000 h, and maintaining dry in complicated phase change conditions. The cells can be impregnated into diverse matrixes for facile mass production through scalable spraying. Our strategy provides a generic design blueprint for engineering ultra-durable coatings for a wide range of applications.
Mechanical metamaterials and beyond
Authors: Jiao Pengcheng , Mueller Jochen , Raney Jordan R. , Zheng Xiaoyu , Alavi Amir H.
Published: September 2023

Mechanical metamaterials enable the creation of structural materials with unprecedented mechanical properties. However, thus far, research on mechanical metamaterials has focused on passive mechanical metamaterials and the tunability of their mechanical properties. Deep integration of multifunctionality, sensing, electrical actuation, information processing, and advancing data-driven designs are grand challenges in the mechanical metamaterials community that could lead to truly intelligent mechanical metamaterials. In this perspective, we provide an overview of mechanical metamaterials within and beyond their classical mechanical functionalities. We discuss various aspects of data-driven approaches for inverse design and optimization of multifunctional mechanical metamaterials. Our aim is to provide new roadmaps for design and discovery of next-generation active and responsive mechanical metamaterials that can interact with the surrounding environment and adapt to various conditions while inheriting all outstanding mechanical features of classical mechanical metamaterials. Next, we deliberate the emerging mechanical metamaterials with specific functionalities to design informative and scientific intelligent devices. We highlight open challenges ahead of mechanical metamaterial systems at the component and integration levels and their transition into the domain of application beyond their mechanical capabilities.
Tensorial stress-plastic strain fields in α - ω Zr mixture, transformation kinetics, and friction in diamond-anvil cell
Authors: Levitas Valery I. , Dhar Achyut , Pandey K. K.
Published: September 2023

Various phenomena (phase transformations (PTs), chemical reactions, microstructure evolution, strength, and friction) under high pressures in diamond-anvil cell are strongly affected by fields of stress and plastic strain tensors. However, they could not be measured. Here, we suggest coupled experimental-analytical-computational approaches utilizing synchrotron X-ray diffraction, to solve an inverse problem and find fields of all components of stress and plastic strain tensors and friction rules before, during, and after α-ω PT in strongly plastically predeformed Zr. Results are in good correspondence with each other and experiments. Due to advanced characterization, the minimum pressure for the strain-induced α-ω PT is changed from 1.36 to 2.7 GPa. It is independent of the plastic strain before PT and compression-shear path. The theoretically predicted plastic strain-controlled kinetic equation is verified and quantified. Obtained results open opportunities for developing quantitative high-pressure/stress science, including mechanochemistry, synthesis of new nanostructured materials, geophysics, astrogeology, and tribology.
Grinding-induced supramolecular charge-transfer assemblies with switchable vapochromism toward haloalkane isomers
Authors: Wu Jia-Rui , Wu Gengxin , Li Dongxia , Li Meng-Hao , Wang Yan , Yang Ying-Wei
Published: September 2023

Synthetic macrocycles have proved to be of great application value in functional charge-transfer systems in the solid state in recent years. Here we show a switchable on-off type vapochromic system toward 1-/2-bromoalkane isomers by constructing solid-state charge-transfer complexes between electron-rich perethylated pillar[5]arene and electron-deficient aromatic acceptors including 4-nitrobenzonitrile and 1,4-dinitrobenzene. These charge-transfer complexes with different colors show opposite color changes upon exposure to the vapors of 1-bromoalkanes (fading) and 2-bromoalkanes (deepening). Single-crystal structures incorporating X-ray powder diffraction and spectral analyses demonstrate that this on-off type vapochromic behavior is mainly attributed to the destruction (off) and reconstruction (on) of the charge-transfer interactions between perethylated pillar[5]arene and the acceptors, for which the competitive host-guest binding of 1-bromoalkanes and the solid-state structural transformation triggered by 2-bromoalkanes are respectively responsible. This work provides a simple colorimetric method for distinguishing positional isomers with similar physical and chemical properties.
Single-chain dimers from de novo immunoglobulins as robust scaffolds for multiple binding loops
Authors: Roel-Touris Jorge , Nadal Marta , Marcos Enrique
Published: September 2023

Antibody derivatives have sought to recapitulate the antigen binding properties of antibodies, but with improved biophysical attributes convenient for therapeutic, diagnostic and research applications. However, their success has been limited by the naturally occurring structure of the immunoglobulin dimer displaying hypervariable binding loops, which is hard to modify by traditional engineering approaches. Here, we devise geometrical principles for de novo designing single-chain immunoglobulin dimers, as a tunable two-domain architecture that optimizes biophysical properties through more favorable dimer interfaces. Guided by these principles, we computationally designed protein scaffolds that were hyperstable, structurally accurate and robust for accommodating multiple functional loops, both individually and in combination, as confirmed through biochemical assays and X-ray crystallography. We showcase the modularity of this architecture by deep-learning-based diversification, opening up the possibility for tailoring the number, positioning, and relative orientation of ligand-binding loops targeting one or two distal epitopes. Our results provide a route to custom-design robust protein scaffolds for harboring multiple functional loops.
The leaderless communication peptide (LCP) class of quorum-sensing peptides is broadly distributed among Firmicutes
Authors: Aggarwal Shifu , Huang Elaine , Do Hackwon , Makthal Nishanth , Li Yanyan , Bapteste Eric , Lopez Philippe , Bernard Charles , Kumaraswami Muthiah
Published: September 2023

The human pathogen Streptococcus pyogenes secretes a short peptide (leaderless communication peptide, LCP) that mediates intercellular communication and controls bacterial virulence through interaction with its receptor, RopB. Here, we show that LCP and RopB homologues are present in other Firmicutes. We experimentally validate that LCPs with distinct peptide communication codes act as bacterial intercellular signals and regulate gene expression in Streptococcus salivarius, Streptococcus porcinus, Enterococcus malodoratus and Limosilactobacillus reuteri. Our results indicate that LCPs are more widespread than previously thought, and their characterization may uncover new signaling mechanisms and roles in coordinating diverse bacterial traits.
Monolithic 3D integration of 2D transistors and vertical RRAMs in 1T–4R structure for high-density memory
Authors: Xie Maosong , Jia Yueyang , Nie Chen , Liu Zuheng , Tang Alvin , Fan Shiquan , Liang Xiaoyao , Jiang Li , He Zhezhi , Yang Rui
Published: September 2023

Emerging data-intensive computation has driven the advanced packaging and vertical stacking of integrated circuits, for minimized latency and energy consumption. Yet a monolithic three-dimensional (3D) integrated structure with interleaved logic and high-density memory layers has been difficult to achieve due to challenges in managing the thermal budget. Here we experimentally demonstrate a monolithic 3D integration of atomically-thin molybdenum disulfide (MoS2) transistors and 3D vertical resistive random-access memories (VRRAMs), with the MoS2transistors stacked between the bottom-plane and top-plane VRRAMs. The whole fabrication process is integration-friendly (below 300 °C), and the measurement results confirm that the top-plane fabrication does not affect the bottom-plane devices. The MoS2transistor can drive each layer of VRRAM into four resistance states. Circuit-level modeling of the monolithic 3D structure demonstrates smaller area, faster data transfer, and lower energy consumption than a planar memory. Such platform holds a high potential for energy-efficient 3D on-chip memory systems.
Towards interoperability in infection control: a standard data model for microbiology
Authors: Rinaldi Eugenia , Drenkhahn Cora , Gebel Benjamin , Saleh Kutaiba , Tönnies Hauke , von Loewenich Friederike D. , Thoma Norbert , Baier Claas , Boeker Martin , Hinske Ludwig Christian , Diaz Luis Alberto Peña , Behnke Michael , Ingenerf Josef , Thun Sylvia
Published: September 2023

The COVID-19 pandemic has made it clear: sharing and exchanging data among research institutions is crucial in order to efficiently respond to global health threats. This can be facilitated by defining health data models based on interoperability standards. In Germany, a national effort is in progress to create common data models using international healthcare IT standards. In this context, collaborative work on a data set module for microbiology is of particular importance as the WHO has declared antimicrobial resistance one of the top global public health threats that humanity is facing. In this article, we describe how we developed a common model for microbiology data in an interdisciplinary collaborative effort and how we make use of the standard HL7 FHIR and terminologies such as SNOMED CT or LOINC to ensure syntactic and semantic interoperability. The use of international healthcare standards qualifies our data model to be adopted beyond the environment where it was first developed and used at an international level.
Improved accuracy in colorectal cancer tissue decomposition through refinement of established deep learning solutions
Authors: Prezja Fabi , Äyrämö Sami , Pölönen Ilkka , Ojala Timo , Lahtinen Suvi , Ruusuvuori Pekka , Kuopio Teijo
Published: September 2023

Hematoxylin and eosin-stained biopsy slides are regularly available for colorectal cancer patients. These slides are often not used to define objective biomarkers for patient stratification and treatment selection. Standard biomarkers often pertain to costly and slow genetic tests. However, recent work has shown that relevant biomarkers can be extracted from these images using convolutional neural networks (CNNs). The CNN-based biomarkers predicted colorectal cancer patient outcomes comparably to gold standards. Extracting CNN-biomarkers is fast, automatic, and of minimal cost. CNN-based biomarkers rely on the ability of CNNs to recognize distinct tissue types from microscope whole slide images. The quality of these biomarkers (coined ‘Deep Stroma’) depends on the accuracy of CNNs in decomposing all relevant tissue classes. Improving tissue decomposition accuracy is essential for improving the prognostic potential of CNN-biomarkers. In this study, we implemented a novel training strategy to refine an established CNN model, which then surpassed all previous solutions . We obtained a 95.6% average accuracy in the external test set and 99.5% in the internal test set. Our approach reduced errors in biomarker-relevant classes, such as Lymphocytes, and was the first to include interpretability methods. These methods were used to better apprehend our model’s limitations and capabilities.
Urban intelligent assistant on the example of the escalator passenger safety management at the subway stations
Authors: Tianxing Man , Vodyaho Alexander , Zhukova Nataly , Subbotin Alexey , Shichkina Yulia
Published: September 2023

Intelligent assistants often struggle with the complexity of spatiotemporal models used for understanding objects and environments. The construction and usage of such models demand significant computational resources. This article introduces a novel multilevel spatiotemporal model and a computationally efficient construction method. To facilitate model construction on different levels, we employ a meta-mining technique. Furthermore, the proposed model is specifically designed to excel in foggy environments. As a practical application, we develop an intelligent assistant focused on enhancing subway passenger safety. We present case examples involving jammed objects, such as shoes, in escalator combs. Our results demonstrate the effectiveness of the proposed model and method. Specifically, the accuracy of breakdown detection has improved by 10% compared to existing information systems used in subways. Moreover, the time required to build a spatiotemporal model is reduced by 2.3 times, further highlighting the efficiency of our approach. Our research offers a promising solution for intelligent assistants dealing with complex spatiotemporal modeling, with practical applications in ensuring subway passenger safety.
Early weaning and biological sex shape long-term immune and metabolic responses in pigs
Authors: Fardisi Mahsa , Thelen Kyan , Groenendal Allegra , Rajput Mrigendra , Sebastian Kimberly , Contreras G. Andres , Moeser Adam J.
Published: September 2023

During the early pre and postnatal life, host and environmental factors can impart a major influence on immune development, thus shaping lifelong disease resistance. Two major factors known to influence immune function and mortality in animals and people are early life stress and biological sex. How these two factors interact to shape long-term immune development and later life disease risk is poorly understood. Here we investigated how early weaning, a common early life stressor in pigs, and biological sex impacts long-term systemic inflammatory responses and hypothalamic–pituitary–adrenal axis (HPA axis) activation later in life. Ten-week-old female (F), intact-male (IM) and castrated-male (CM) pigs that were randomly assigned to early weaning (EW) and later weaning (LW) (at 15 or 28 days of age, respectively) were intramuscularly injected with either saline vehicle or lipopolysaccharide (LPS) to induce a systemic inflammatory response. Complete blood counts (CBC), proinflammatory cytokines, cortisol, testosterone, estradiol, and rectal temp were measured at 0 h, 2 h, and 4 h post-LPS challenge. At 4 h post-LPS, peritoneal fluid (PF) and white blood cells (WBC) were collected for differential analysis. LPS challenge significantly increased rectal temp and plasma cortisol level in all treatment groups. Together, the CBC results and immune cell counts in peritoneal cavity indicated that EW-F exhibited greater systemic immune response characterized by increased neutrophils to lymphocytes ratio (NLR) and enhanced neutrophil trafficking to the peritoneal cavity. Early weaning had an opposite effect on IM and CM pigs, which exhibited a suppressed LPS-induced neutrophil migration. Early weaning induced significantly greater cortisol responses only in IM pigs indicating a heightened HPA axis responses in EW-IM. how early weaning and biological sex affect immune and stress responses in pigs. Together, these results demonstrate that early weaning and biological sex and castration shape later life immune responses in pigs and provides insight into potential mechanisms driving sex differences in later life inflammatory disease risk and mortality.
Deep learning for tumor margin identification in electromagnetic imaging
Authors: Mirbeik Amir , Ebadi Negar
Published: September 2023

In this work, a novel method for tumor margin identification in electromagnetic imaging is proposed to optimize the tumor removal surgery. This capability will enable the visualization of the border of the cancerous tissue for the surgeon prior or during the excision surgery. To this end, the border between the normal and tumor parts needs to be identified. Therefore, the images need to be segmented into tumor and normal areas. We propose a deep learning technique which divides the electromagnetic images into two regions: tumor and normal, with high accuracy. We formulate deep learning from a perspective relevant to electromagnetic image reconstruction. A recurrent auto-encoder network architecture (termed here DeepTMI) is presented. The effectiveness of the algorithm is demonstrated by segmenting the reconstructed images of an experimental tissue-mimicking phantom. The structure similarity measure (SSIM) and mean-square-error (MSE) average of normalized reconstructed results by the DeepTMI method are about 0.94 and 0.04 respectively, while that average obtained from the conventional backpropagation (BP) method can hardly overcome 0.35 and 0.41 respectively.
Numerical analysis of pile group, piled raft, and footing using finite element software PLAXIS 2D and GEO5
Authors: Chimdesa Firanboni Fituma , Chimdesa Firaol Fituma , Jilo Nagessa Zerihun , Hulagabali Anand , Babalola Olusola Emmanuel , Tiyasha Tiyasha , Ramaswamy Krishnaraj , Kumar Adarsh , Bhagat Suraj Kumar
Published: September 2023

Foundation plays a vital role in weight transfer from the superstructure to substructure. However, foundation characteristics such as pile group, piled raft, and footing remain unfolded due to their highly non-linear behaviour in different soil types. Bibliography analysis using VOSvierwer algorithm supported the significance of the research. Hence, this study investigates the load-bearing capacity of different types of foundations, including footings, pile groups, and piled rafts, by analyzing experimental data using finite element tools such as PLAXIS 2D and GEO5. The analysis involves examining the impact of various factors such as the influence of surcharge and the effect of different soil types on the load-bearing capabilities of the different types of foundation. For footing, parametric investigations using PLAXIS 2D are conducted to explore deformational changes. Pile groups are analyzed using GEO5 to assess their factor of safety (FOS.) and settling under various criteria, such as pile length and soil type. The study also provides insight into selecting the right type of foundation for civil engineering practice. Findings showed that different soil types have varying deformational behaviours under high loads with sandy soil having less horizontal deformation than clayey soil. Also, it was observed that increasing the pile thickness by 50% resulted in a reduction of 13.88% in settlement and an improvement of 16.66% in the FOS. In conclusion, this study highlights the importance of professionalism, exceptional talent, and outstanding decision-making when assessing the load-bearing capabilities of various foundation types for building structures.
Nano-CT characterization of dentinal tubule occlusion in SDF-treated dentin
Authors: Menzel Matthias , Kiesow Andreas , de Souza e Silva Juliana Martins
Published: September 2023

Dentin hypersensitivity is an oral health concern affecting a large percentage of the world's adult population. Occlusion of the exposed dentinal tubules is among the treatment options available, and silver diammine fluoride (SDF) is an occluding agent used for interrupting or dampening the stimulus of the dental pulp nerves that produce pain. In addition to dentin permeability testing, the evaluation of desensitizing agents occluding dentinal tubules strongly relies on microscopic techniques, such as scanning electron microscopy (SEM). Limitations of SEM are that it provides only surface images that lack detailed information on the depth of penetration and amount of material present within the treated specimen, and it is prone to sample preparation artifacts. Here, we present high-resolution X-ray computed tomography (nano-CT) as a potential method for investigating dentin specimens with occluded tubules. We studied human dentin treated with SDF as an exemplary dentinal occlusion treatment option. We evaluated the silver deposits formed on the dentin surface region near the dentinal tubules and in the tubular regions using cross-section SEM, Energy Dispersive X-ray (EDX) analysis, and nano-CT. The resulting images obtained by SEM and nano-CT had comparable resolutions, and both techniques produced images of the tubules' occlusion. Nano-CT provided three-dimensional images adequate to quantitate tubule size and orientation in space. Moreover, it enabled clear visualization of dentinal tubules in any virtual plane and estimation of the amount and depth of occluding material. Thus, nano-CT has the potential to be a valuable technique for evaluating the occluding effects of virtually any material applied to dentinal tubules, supporting deciding between the best occluding treatment options.
Serum Erythropoietin level in anemia of elderly with unclear etiology
Authors: Seong Ju Yong , Shin Dong-Yeop , Byun Ja Min , Koh Youngil , Hong Junshik , Kim Inho , Yoon Sung-Soo
Published: September 2023

Anemia is a common condition, but its causes are often unclear, especially in elderly adults. Erythropoietin (EPO) levels are known to be elevated in myelodysplastic syndrome and hematologic malignancies, but decreased in chronic benign anemia. This study aimed to investigate whether EPO levels could be used to identify underlying bone marrow diseases including malignancies, among elderly anemic patients with unclear etiology. This single centered retrospective study included patients presented with isolated anemia and had their EPO levels measured at their first visit. Patients were divided into two groups: bone marrow disease and benign etiologic anemia, based on observation and bone marrow test results. Out of 1180 patients reviewed, 81 patients with anemia of unclear etiology were identified, including 67 with benign anemia and 14 with bone marrow disease. Statistically significant difference in EPO levels between these two groups (P < 0.001) were observed. The receiver operating characteristic curve analysis showed that an EPO cut-off value of 36.4 mU/mL had a sensitivity and specificity of 92.8% and 94.0% for detecting underlying bone marrow disease, respectively. We suggest measuring serum EPO levels can aid in the early detection of benign anemia from bone marrow disease, including malignancies, with high sensitivity and specificity.
Improving CNNs classification with pathologist-based expertise: the renal cell carcinoma case study
Authors: Ponzio Francesco , Descombes Xavier , Ambrosetti Damien
Published: September 2023

The prognosis of renal cell carcinoma (RCC) malignant neoplasms deeply relies on an accurate determination of the histological subtype, which currently involves the light microscopy visual analysis of histological slides, considering notably tumor architecture and cytology. RCC subtyping is therefore a time-consuming and tedious process, sometimes requiring expert review, with great impact on diagnosis, prognosis and treatment of RCC neoplasms. In this study, we investigate the automatic RCC subtyping classification of 91 patients, diagnosed with clear cell RCC, papillary RCC, chromophobe RCC, or renal oncocytoma, through deep learning based methodologies. We show how the classification performance of several state-of-the-art Convolutional Neural Networks (CNNs) are perfectible among the different RCC subtypes. Thus, we introduce a new classification model leveraging a combination of supervised deep learning models (specifically CNNs) and pathologist’s expertise, giving birth to a hybrid approach that we termed ExpertDeepTree (ExpertDT). Our findings prove ExpertDT’s superior capability in the RCC subtyping task, with respect to traditional CNNs, and suggest that introducing some expert-based knowledge into deep learning models may be a valuable solution for complex classification cases.
SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis
Authors: Mavrakanas Thomas A. , Tsoukas Michael A. , Brophy James M. , Sharma Abhinav , Gariani Karim
Published: September 2023

The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79–0.95) and of heart failure (RR 0.67; 95% CI 0.61–0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75–1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68–0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72–0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.
Analysis of the utility of transbronchial lung biopsy culture under endobronchial ultrasonography with a guide-sheath
Authors: Shimoda Masafumi , Morimoto Kozo , Tanaka Yoshiaki , Ito Masashi , Moue Iori , Yoshimori Kozo , Ohta Ken
Published: September 2023

Transbronchial lung biopsy (TBLB) culture is not common in clinical practice, and TBLB culture for patients with mycobacterial disease provide limited value because the diagnostic accuracy of TBLB culture is very low. Recently, bronchoscopic devices have been further developed, such as endobronchial ultrasonography with a guide-sheath (EBUS-GS). Therefore, this study investigated the utility of TBLB culture obtained by using EBUS-GS compared to washing cultures. A total of 31 patients who underwent TBLB culture by using EBUS-GS (GS-TBLB) were collected retrospectively at Fukujuji Hospital from January 2018 to December 2022. The diagnostic accuracies of GS-TBLB culture and bronchial and device washing cultures (namely, washing culture) were compared. The patients comprised 13 individuals with nontuberculous mycobacteriosis, 7 with pulmonary aspergillosis, 6 with lung abscess, and 5 with pulmonary tuberculosis. The diagnostic accuracy of GS-TBLB culture was lower to that of TBLB culture than those of washing culture (n = 11 [35.5%] vs. n = 20 [64.5%], p = 0.016), and there was only one patient with positive GS-TBLB culture results and negative washing culture results. Comparing between patients with mycobacteria and non-mycobacteria, GS-TBLB culture positivity were no significant difference between patients with mycobacteria and non-mycobacteria (n = 6 [33.3%] vs. n = 5 [38.5%], p = 1.000), however, patients with mycobacteria diagnosed by washing culture more than those with non-mycobacteria (n = 15 [83.3%] vs. n = 5 [38.5%], p = 0.021). Our results demonstrate that the utility of TBLB culture for the diagnosis of pulmonary infections might provide limited value even if EBUS-GS is performed and lung tissue is successfully obtained.
Promising application of probiotic microorganisms as Pickering emulsions stabilizers
Authors: Nejadmansouri Maryam , Eskandari Mohammad Hadi , Yousefi Gholam Hossein , Riazi Masoud , Hosseini Seyed Mohammad Hashem
Published: September 2023

The purpose of this work was to study the ability of nineteen food-grade microorganisms as Pickering emulsion (PE) stabilizers. Medium-chain triacylglycerol (MCT) oil-in-water (50:50) PEs were fabricated by 10 wt% or 15 wt% of thermally-inactivated yeast, cocci, Bacillus spp. and lactobacilli cells. The characteristics of microorganisms related to “Pickering stabilization” including morphology, surface charge, interfacial tension, and “contact angle” were firstly studied. After that, the cells-stabilized PEs were characterized from both kinetic and thermodynamic viewpoints, microstructure and rheological properties. The interfacial tension and “contact angle” values of various microorganisms ranged from 16.33 to 38.31 mN/m, and from 15° to 106°, respectively. The mean droplet size of PEs ranged from 11.51 to 57.69 µm. Generally, the physical stability of cell-stabilized PEs followed this order: lactobacilli > Bacillus spp. > cocci > yeast. These variations were attributed to the morphology and cell wall composition. Increasing the microorganism concentration significantly increased the physical stability of PEs from a maximum of 12 days at 10 wt% to 35 days at 15 wt% as a result of better interface coverage. Shear-thinning and dominant elastic behaviors were observed in PEs. Physical stability was affected by the free energy of detachment. Therefore, food-grade microorganisms are suggested for stabilizing PEs.
Development of a novel virtual reality-enabled remote monitoring device for maintenance of cathodic protection systems on oil and gas pipelines
Authors: Mgbemena Chika Edith , Onuoha David Obike , Godwin Harold Chukwuemeka
Published: September 2023

Periodic inspections are required for oil and gas pipelines equipped with cathodic protection systems (CPS) to prevent corrosion. This inspection takes time and requires money, mobilisation of specialised staff, and accessibility of pipeline right of way which is often hindered by security issues, and bad terrain. A novel virtual reality-enabled remote monitoring device, developed using the NACE SP0169 standard, which measures the pipe-to-soil potential (PSP) reading, transmits the measured data to an IoT server, and a virtual environment for analysis and feedback while providing an immersive experience to the user, all in real-time, is presented. The hardware and software components are developed using Sensors, Arduino Mega 2560 board, AWS Sumerian 1.2.0 software, ThingSpeak IoT server, Blender modelling software and AutoCAD. When implemented on real test posts of oil and gas facilities and compared with the traditional methodology, the system showed consistency of data measurement and analysis, with real-time feedback to users, and a Spearman rank’s correlation coefficient of 0.998944. The study is significant as it provides the oil industry with an expert, easy-to-understand tool which helps to reduce the rate of oil spillage and losses through corrosion.
Identification of MIR600HG/hsa-miR-342-3p/ANLN network as a potential prognosis biomarker associated with lmmune infiltrates in pancreatic cancer
Authors: Qian Baolin , Liu Qi , Wang Chaoqun , Lu Shounan , Ke Shanjia , Yin Bing , Li Xinglong , Yu Hongjun , Wu Yaohua , Ma Yong
Published: September 2023

Pancreatic cancer is one of the tumors with the worst prognosis, causing serious harm to human health. The RNA network and immune response play an important role in tumor progression. While a systematic RNA network linked to the tumor immune response remains to be further explored in pancreatic cancer. Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, the MIR600HG/hsa-miR-342-3p/ANLN network was determined. WB and IHC were used to confirm the high expression of ANLN in pancreatic cancer. The prognostic model based on the RNA network could effectively predict the survival prognosis of patients. The analysis of immune infiltration showed that the MIR600HG/hsa-miR-342-3p/ANLN network altered the level of infiltration of T helper 2 (Th2) and effector memory T (Tem) cells. Furthermore, we found that the chemokines chemokine ligand (CCL) 5 and CCL14 may play a key role in immune cell infiltration mediated by the RNA network. In conclusion, this study constructed a prognostic model based on the MIR600HG/hsa-miR-342-3p/ANLN network and found that it may function in tumor immunity.
Global insight into understanding wheat yield and production through Agro-Ecological Zoning
Authors: Dadrasi Amir , Chaichi Mehrdad , Nehbandani Alireza , Soltani Elias , Nemati Ahmad , Salmani Fatemeh , Heydari Moslem , Yousefi Ali Reza
Published: September 2023

Global food security requires food production to be increased in the future decades. Agro-Ecological Zones (AEZ) methodology is a successful approach used in land evaluation studies to support sustainable agricultural development. This approach can facilitate finding suitable areas for wheat production on a global scale. This study was conducted based on a climate zone map, soil data, wheat cultivation area, yield, and production under irrigated and rainfed conditions, worldwide. The results for irrigated wheat indicated that there is an area of 59.5 Mha with an average yield of 4.02 t/ha which leads to the production of about 239.6 Mt of grain yield. Furthermore, climate zones (CZs) of 8002, 5203, 5302, 5403, and 8102 have the highest wheat production with an average of 20.7, 14.2, 13.3, 11.8, 11.5 Mt, respectively. The highest amount of irrigated wheat production has been achieved in soil type code 17 (Loam LF120), which has a cultivation area of around 23.6 Mha and a production of about 106.8 Mt. Rainfed wheat production is 410 Mt, and the cultivation area is 160.2 Mha. The highest rainfed wheat production with an average of 17 Mt was related to the 3702 CZ, followed by the other CZs (3802, 1303, 1203, 3602, 4602, etc.). The soil codes 11 (Loam HF120), 10 (Loam HF180), and 14 (Loam MF120) showed the highest rainfed wheat production. The findings of this study can be useful for agricultural scientists, authorities, and decision-makers around the world to find suitable lands to expand wheat cultivation and also to find new locations for increasing global wheat production to feed the increasing population in the world.