bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare t(X;14)(q28;q32) translocation reveals link between MTCP1 and chronic lymphocytic leukemia
Authors: Walker Janek S. , Hing Zachary A. , Sher Steven , Cronin James , Williams Katie , Harrington Bonnie , Skinner Jordan N. , Cempre Casey B. , Gregory Charles T. , Pan Alexander , Yano Max , Beaver Larry P. , Walker Brandi R. , Labanowska Jadwiga M. , Heerema Nyla A. , Mrózek Krzysztof , Woyach Jennifer A. , Ruppert Amy S. , Lehman Amy , Ozer Hatice Gulcin , Coppola Vincenzo , Yan Pearlly , Byrd John C. , Blachly James S. , Lapalombella Rosa
Published: November 2021

Rare, recurrent balanced translocations occur in a variety of cancers but are often not functionally interrogated. Balanced translocations with the immunoglobulin heavy chain locus (IGH; 14q32) in chronic lymphocytic leukemia (CLL) are infrequent but have led to the discovery of pathogenic genes including CCND1, BCL2, and BCL3. Following identification of a t(X;14)(q28;q32) translocation that placed the mature T cell proliferation 1 gene (MTCP1) adjacent to the immunoglobulin locus in a CLL patient, we hypothesized that this gene may have previously unrecognized importance. Indeed, here we report overexpression of human MTCP1 restricted to the B cell compartment in mice produces a clonal CD5+/CD19+ leukemia recapitulating the major characteristics of human CLL and demonstrates favorable response to therapeutic intervention with ibrutinib. We reinforce the importance of genetic interrogation of rare, recurrent balanced translocations to identify cancer driving genes via the story of MTCP1 as a contributor to CLL pathogenesis.
Computational design and optimization of electro-physiological sensors
Authors: Nittala Aditya Shekhar , Karrenbauer Andreas , Khan Arshad , Kraus Tobias , Steimle Jürgen
Published: November 2021

Electro-physiological sensing devices are becoming increasingly common in diverse applications. However, designing such sensors in compact form factors and for high-quality signal acquisition is a challenging task even for experts, is typically done using heuristics, and requires extensive training. Our work proposes a computational approach for designing multi-modal electro-physiological sensors. By employing an optimization-based approach alongside an integrated predictive model for multiple modalities, compact sensors can be created which offer an optimal trade-off between high signal quality and small device size. The task is assisted by a graphical tool that allows to easily specify design preferences and to visually analyze the generated designs in real-time, enabling designer-in-the-loop optimization. Experimental results show high quantitative agreement between the prediction of the optimizer and experimentally collected physiological data. They demonstrate that generated designs can achieve an optimal balance between the size of the sensor and its signal acquisition capability, outperforming expert generated solutions.
Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes
Authors: Jindal Sonali , Pennock Nathan D. , Sun Duanchen , Horton Wesley , Ozaki Michelle K. , Narasimhan Jayasri , Bartlett Alexandra Q. , Weinmann Sheila , Goss Paul E. , Borges Virginia F. , Xia Zheng , Schedin Pepper
Published: November 2021

Young women’s breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.
A habenula-insular circuit encodes the willingness to act
Authors: Khalighinejad Nima , Garrett Neil , Priestley Luke , Lockwood Patricia , Rushworth Matthew F. S.
Published: November 2021

The decision that it is worth doing something rather than nothing is a core yet understudied feature of voluntary behaviour. Here we study “willingness to act”, the probability of making a response given the context. Human volunteers encountered opportunities to make effortful actions in order to receive rewards, while watching a movie inside a 7 T MRI scanner. Reward and other context features determined willingness-to-act. Activity in the habenula tracked trial-by-trial variation in participants’ willingness-to-act. The anterior insula encoded individual environment features that determined this willingness. We identify a multi-layered network in which contextual information is encoded in the anterior insula, converges on the habenula, and is then transmitted to the supplementary motor area, where the decision is made to either act or refrain from acting via the nigrostriatal pathway.
Physics-informed deep learning characterizes morphodynamics of Asian soybean rust disease
Authors: Cavanagh Henry , Mosbach Andreas , Scalliet Gabriel , Lind Rob , Endres Robert G.
Published: November 2021

Medicines and agricultural biocides are often discovered using large phenotypic screens across hundreds of compounds, where visible effects of whole organisms are compared to gauge efficacy and possible modes of action. However, such analysis is often limited to human-defined and static features. Here, we introduce a novel framework that can characterize shape changes (morphodynamics) for cell-drug interactions directly from images, and use it to interpret perturbed development of Phakopsora pachyrhizi, the Asian soybean rust crop pathogen. We describe population development over a 2D space of shapes (morphospace) using two models with condition-dependent parameters: a top-down Fokker-Planck model of diffusive development over Waddington-type landscapes, and a bottom-up model of tip growth. We discover a variety of landscapes, describing phenotype transitions during growth, and identify possible perturbations in the tip growth machinery that cause this variation. This demonstrates a widely-applicable integration of unsupervised learning and biophysical modeling.
Transcription recycling assays identify PAF1 as a driver for RNA Pol II recycling
Authors: Chen Zhong , Hankey William , Zhao Yue , Groth Jeff , Huang Furong , Wang Hongyan , Campos Alexandre Rosa , Huang Jiaoti , Roeder Robert G. , Wang Qianben
Published: November 2021

RNA Polymerase II (Pol II) transcriptional recycling is a mechanism for which the required factors and contributions to overall gene expression levels are poorly understood. We describe an in vitro methodology facilitating unbiased identification of putative RNA Pol II transcriptional recycling factors and quantitative measurement of transcriptional output from recycled transcriptional components. Proof-of-principle experiments identified PAF1 complex components among recycling factors and detected defective transcriptional output from Pol II recycling following PAF1 depletion. Dynamic ChIP-seq confirmed PAF1 silencing triggered defective Pol II recycling in human cells. Prostate tumors exhibited enhanced transcriptional recycling, which was attenuated by antibody-based PAF1 depletion. These findings identify Pol II recycling as a potential target in cancer and demonstrate the applicability of in vitro and cellular transcription assays to characterize Pol II recycling in other disease states.
Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies
Authors: Fenix Aidan M. , Miyaoka Yuichiro , Bertero Alessandro , Blue Steven M. , Spindler Matthew J. , Tan Kenneth K. B. , Perez-Bermejo Juan A. , Chan Amanda H. , Mayerl Steven J. , Nguyen Trieu D. , Russell Caitlin R. , Lizarraga Paweena P. , Truong Annie , So Po-Lin , Kulkarni Aishwarya , Chetal Kashish , Sathe Shashank , Sniadecki Nathan J. , Yeo Gene W. , Murry Charles E. , Conklin Bruce R. , Salomonis Nathan
Published: November 2021

Mutations in the cardiac splicing factor RBM20 lead to malignant dilated cardiomyopathy (DCM). To understand the mechanism of RBM20-associated DCM, we engineered isogenic iPSCs with DCM-associated missense mutations in RBM20 as well as RBM20 knockout (KO) iPSCs. iPSC-derived engineered heart tissues made from these cell lines recapitulate contractile dysfunction of RBM20-associated DCM and reveal greater dysfunction with missense mutations than KO. Analysis of RBM20 RNA binding by eCLIP reveals a gain-of-function preference of mutant RBM20 for 3′ UTR sequences that are shared with amyotrophic lateral sclerosis (ALS) and processing-body associated RNA binding proteins (FUS, DDX6). Deep RNA sequencing reveals that the RBM20 R636S mutant has unique gene, splicing, polyadenylation and circular RNA defects that differ from RBM20 KO. Super-resolution microscopy verifies that mutant RBM20 maintains very limited nuclear localization potential; rather, the mutant protein associates with cytoplasmic processing bodies (DDX6) under basal conditions, and with stress granules (G3BP1) following acute stress. Taken together, our results highlight a pathogenic mechanism in cardiac disease through splicing-dependent and -independent pathways.
Reversion analysis reveals the in vivo immunogenicity of a poorly MHC I-binding cancer neoepitope
Authors: Ebrahimi-Nik Hakimeh , Moussa Marmar , Englander Ryan P. , Singhaviranon Summit , Michaux Justine , Pak HuiSong , Miyadera Hiroko , Corwin William L. , Keller Grant L. J. , Hagymasi Adam T. , Shcheglova Tatiana V. , Coukos George , Baker Brian M. , Mandoiu Ion I. , Bassani-Sternberg Michal , Srivastava Pramod K.
Published: November 2021

High-affinity MHC I-peptide interactions are considered essential for immunogenicity. However, some neo-epitopes with low affinity for MHC I have been reported to elicit CD8 T cell dependent tumor rejection in immunization-challenge studies. Here we show in a mouse model that a neo-epitope that poorly binds to MHC I is able to enhance the immunogenicity of a tumor in the absence of immunization. Fibrosarcoma cells with a naturally occurring mutation are edited to their wild type counterpart; the mutation is then re-introduced in order to obtain a cell line that is genetically identical to the wild type except for the neo-epitope-encoding mutation. Upon transplantation into syngeneic mice, all three cell lines form tumors that are infiltrated with activated T cells. However, lymphocytes from the two tumors that harbor the mutation show significantly stronger transcriptional signatures of cytotoxicity and TCR engagement, and induce greater breadth of TCR reactivity than those of the wild type tumors. Structural modeling of the neo-epitope peptide/MHC I pairs suggests increased hydrophobicity of the neo-epitope surface, consistent with higher TCR reactivity. These results confirm the in vivo immunogenicity of low affinity or ‘non-binding’ epitopes that do not follow the canonical concept of MHC I-peptide recognition.
Global distribution, trends, and drivers of flash drought occurrence
Authors: Christian Jordan I. , Basara Jeffrey B. , Hunt Eric D. , Otkin Jason A. , Furtado Jason C. , Mishra Vimal , Xiao Xiangming , Randall Robb M.
Published: November 2021

Flash drought is characterized by a period of rapid drought intensification with impacts on agriculture, water resources, ecosystems, and the human environment. Addressing these challenges requires a fundamental understanding of flash drought occurrence. This study identifies global hotspots for flash drought from 1980–2015 via anomalies in evaporative stress and the standardized evaporative stress ratio. Flash drought hotspots exist over Brazil, the Sahel, the Great Rift Valley, and India, with notable local hotspots over the central United States, southwestern Russia, and northeastern China. Six of the fifteen study regions experienced a statistically significant increase in flash drought during 1980–2015. In contrast, three study regions witnessed a significant decline in flash drought frequency. Finally, the results illustrate that multiple pathways of research are needed to further our understanding of the regional drivers of flash drought and the complex interactions between flash drought and socioeconomic impacts.
A chemosensor-based chiral coassembly with switchable circularly polarized luminescence
Authors: Cheng Qiuhong , Hao Aiyou , Xing Pengyao
Published: November 2021

Fluorescent chemosensors represent fast response to analytes with pronounced luminescent variations. They are promising as potential candidates in controlling luminescence and chiroptical activities of self-assembled chiral systems, which however have not been accomplished to date. We present a coassembled multiple component system that could respond to SO2 derivatives, giving rise to dynamic aggregation behaviors and switchable luminescence as well as circularly polarized luminescence (CPL). Cholesteryl-naphthalimide and coumarin derivatives coassemble into vesicles and nanohelices under the solvent strategy, behaving as energy transfer donor and accepter respectively. Energy transfer enables CPL transition from green to red depending on the molar fraction. After the addition of SO2 derivatives, hypochromic shifts occur to CPL due to the nucleophilic addition reaction to coumarin domain, hindering energy transfer and allow for the emergence of pristine luminescence. Here, we show a protocol to control over luminescence and chiroptical features of supramolecular chiral self-assemblies using fluorescent chemosensors.
Nanoscale neural network using non-linear spin-wave interference
Authors: Papp Ádám , Porod Wolfgang , Csaba Gyorgy
Published: November 2021

We demonstrate the design of a neural network hardware, where all neuromorphic computing functions, including signal routing and nonlinear activation are performed by spin-wave propagation and interference. Weights and interconnections of the network are realized by a magnetic-field pattern that is applied on the spin-wave propagating substrate and scatters the spin waves. The interference of the scattered waves creates a mapping between the wave sources and detectors. Training the neural network is equivalent to finding the field pattern that realizes the desired input-output mapping. A custom-built micromagnetic solver, based on the Pytorch machine learning framework, is used to inverse-design the scatterer. We show that the behavior of spin waves transitions from linear to nonlinear interference at high intensities and that its computational power greatly increases in the nonlinear regime. We envision small-scale, compact and low-power neural networks that perform their entire function in the spin-wave domain.
Substrate strain tunes operando geometric distortion and oxygen reduction activity of CuN2C2 single-atom sites
Authors: Han Guokang , Zhang Xue , Liu Wei , Zhang Qinghua , Wang Zhiqiang , Cheng Jun , Yao Tao , Gu Lin , Du Chunyu , Gao Yunzhi , Yin Geping
Published: November 2021

Single-atom catalysts are becoming increasingly significant to numerous energy conversion reactions. However, their rational design and construction remain quite challenging due to the poorly understood structure–function relationship. Here we demonstrate the dynamic behavior of CuN2C2 site during operando oxygen reduction reaction, revealing a substrate-strain tuned geometry distortion of active sites and its correlation with the activity. Our best CuN2C2 site, on carbon nanotube with 8 nm diameter, delivers a sixfold activity promotion relative to graphene. Density functional theory and X-ray absorption spectroscopy reveal that reasonable substrate strain allows the optimized distortion, where Cu bonds strongly with the oxygen species while maintaining intimate coordination with C/N atoms. The optimized distortion facilitates the electron transfer from Cu to the adsorbed O, greatly boosting the oxygen reduction activity. This work uncovers the structure–function relationship of single-atom catalysts in terms of carbon substrate, and provides guidance to their future design and activity promotion.
Explainable machine learning model for predicting spontaneous bacterial peritonitis in cirrhotic patients with ascites
Authors: Hu Yingying , Chen Ruijia , Gao Haibing , Lin Haitao , Wang Jinye , Wang Xiaowei , Liu Jingfeng , Zeng Yongyi
Published: November 2021

Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis. We aimed to develop an explainable machine learning model to achieve the early prediction and outcome interpretation of SBP. We used CatBoost algorithm to construct MODEL-1 with 46 variables. After dimensionality reduction, we constructed MODEL-2. We calculated and compared the sensitivity and negative predictive value (NPV) of MODEL-1 and MODEL-2. Finally, we used the SHAP (SHapley Additive exPlanations) method to provide insights into the model’s outcome or prediction. MODEL-2 (AUROC: 0.822; 95% confidence interval [CI] 0.783–0.856), liked MODEL-1 (AUROC: 0.822; 95% CI 0.784–0.856), could well predict the risk of SBP in cirrhotic ascites patients. The 6 most influential predictive variables were total protein, C-reactive protein, prothrombin activity, cholinesterase, lymphocyte ratio and apolipoprotein A1. For binary classifier, the sensitivity and NPV of MODEL-1 were 0.894 and 0.885, respectively, while for MODEL-2 they were 0.927 and 0.904, respectively. We applied CatBoost algorithm to establish a practical and explainable prediction model for risk of SBP in cirrhotic patients with ascites. We also identified 6 important variables closely related to the occurrence of SBP.
Traumatic brain injury augurs ill for prolonged deficits in the brain’s structural and functional integrity following controlled cortical impact injury
Authors: Mohamed Abdalla Z. , Cumming Paul , Nasrallah Fatima A.
Published: November 2021

Previous neuroimaging studies in rodents investigated effects of the controlled cortical impact (CCI) model of traumatic brain injury (TBI) within one-month post-TBI. This study extends this temporal window to monitor the structural–functional alterations from two hours to six months post-injury. Thirty-seven male Sprague–Dawley rats were randomly assigned to TBI and sham groups, which were scanned at two hours, 1, 3, 7, 14, 30, 60 days, and six months following CCI or sham surgery. Structural MRI, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were acquired to assess the dynamic structural, microstructural, and functional connectivity alterations post-TBI. There was a progressive increase in lesion size associated with brain volume loss post-TBI. Furthermore, we observed reduced fractional anisotropy within 24 h and persisted to six months post-TBI, associated with acutely reduced axial diffusivity, and chronic increases in radial diffusivity post-TBI. Moreover, a time-dependent pattern of altered functional connectivity evolved over the six months’ follow-up post-TBI. This study extends the current understanding of the CCI model by confirming the long-term persistence of the altered microstructure and functional connectivity, which may hold a strong translational potential for understanding the long-term sequelae of TBI in humans.
Artificial flexible sperm-like nanorobot based on self-assembly and its bidirectional propulsion in precessing magnetic fields
Authors: Celi Nuoer , Gong De , Cai Jun
Published: November 2021

Sperm cells can move at a high speed in biofluids based on the flexible flagella, which inspire novel flagellar micro-/nanorobots to be designed. Despite progress in fabricating sperm-type robots at micro scale, mass fabrication of vivid sperm-like nanorobots with flagellar flexibility is still challenging. In this work, a facile and efficient strategy is proposed to produce flexible sperm-like nanorobots with self-assembled head-to-tail structure, and its bidirectional propulsion property was studied in detail. The nanorobots were composed of a superparamagnetic head and a flexible Au/PPy flagellum, which were covalently linked via biotin-streptavidin bonding with a high yield. Under precessing magnetic fields, the head drove the flexible tail to rotate and generated undulatory bending waves propagating along the body. Bidirectional locomotion was investigated, and moving velocity as well as direction varied with the actuating conditions (field strength, frequency, direction) and the nanorobot’s structure (tail length). Effective flagellar propulsion was observed near the substrate and high velocities were attained to move back and forth without U-turn. Typical modelling based on elastohydrodynamics and undulatory wave propagation were utilized for propulsion analysis. This research presents novel artificial flexible sperm-like nanorobots with delicate self-assembled head-to-tail structures and remarkable bidirectional locomotion performances, indicating significant potentials for nanorobotic design and future biomedical application.
A systematic approach for developing mechanistic models for realistic simulation of cancer cell motion and deformation
Authors: Keshavarz Motamed Pouyan , Maftoon Nima
Published: November 2021

Understanding and predicting metastatic progression and developing novel diagnostic methods can highly benefit from accurate models of the deformability of cancer cells. Spring-based network models of cells can provide a versatile way of integrating deforming cancer cells with other physical and biochemical phenomena, but these models have parameters that need to be accurately identified. In this study we established a systematic method for identifying parameters of spring-network models of cancer cells. We developed a genetic algorithm and coupled it to the fluid–solid interaction model of the cell, immersed in blood plasma or other fluids, to minimize the difference between numerical and experimental data of cell motion and deformation. We used the method to create a validated model for the human lung cancer cell line (H1975), employing existing experimental data of its deformation in a narrow microchannel constriction considering cell-wall friction. Furthermore, using this validated model with accurately identified parameters, we studied the details of motion and deformation of the cancer cell in the microchannel constriction and the effects of flow rates on them. We found that ignoring the viscosity of the cell membrane and the friction between the cell and wall can introduce remarkable errors.
Toxicity thresholds of nine herbicides to coral symbionts (Symbiodiniaceae)
Authors: Marzonie Magena , Flores Florita , Sadoun Nora , Thomas Marie C. , Valada-Mennuni Anais , Kaserzon Sarit , Mueller Jochen F. , Negri Andrew P.
Published: November 2021

Over 30 herbicides have been detected in catchments and waters of the Great Barrier Reef (GBR) and their toxicity to key tropical species, including the coral endosymbiotic algae Symbiodiniaceae, is not generally considered in current water quality guideline values (WQGVs). Mutualistic symbionts of the family Symbiodiniaceae are essential for the survival of scleractinian corals. We tested the effects of nine GBR-relevant herbicides on photosynthetic efficiency (ΔF/Fm′) and specific growth rate (SGR) over 14 days of cultured coral endosymbiont Cladocopium goreaui (formerly Symbiodinium clade C1). All seven Photosystem II (PSII) herbicides tested inhibited ΔF/Fm′ and SGR, with toxicity thresholds for SGR ranging between 2.75 and 320 µg L−1 (no effect concentration) and 2.54–257 µg L−1 (EC10). There was a strong correlation between EC50s for ΔF/Fm′ and SGR for all PSII herbicides indicating that inhibition of ΔF/Fm′ can be considered a biologically relevant toxicity endpoint for PSII herbicides to this species. The non-PSII herbicides haloxyfop and imazapic did not affect ΔF/Fm′ or SGR at the highest concentrations tested. The inclusion of this toxicity data for Symbiodiniaceae will contribute to improving WQGVs to adequately inform risk assessments and the management of herbicides in tropical marine ecosystems.
Salt inducible kinases 2 and 3 are required for thymic T cell development
Authors: Nefla Meriam , Darling Nicola J. , van Gijsel Bonnello Manuel , Cohen Philip , Arthur J. Simon C.
Published: November 2021

Salt Inducible Kinases (SIKs), of which there are 3 isoforms, are established to play roles in innate immunity, metabolic control and neuronal function, but their role in adaptive immunity is unknown. To address this gap, we used a combination of SIK knockout and kinase-inactive knock-in mice. The combined loss of SIK1 and SIK2 activity did not block T cell development. Conditional knockout of SIK3 in haemopoietic cells, driven by a Vav-iCre transgene, resulted in a moderate reduction in the numbers of peripheral T cells, but normal B cell numbers. Constitutive knockout of SIK2 combined with conditional knockout of SIK3 in the haemopoietic cells resulted in a severe reduction in peripheral T cells without reducing B cell number. A similar effect was seen when SIK3 deletion was driven via CD4-Cre transgene to delete at the DP stage of T cell development. Analysis of the SIK2/3 Vav-iCre mice showed that thymocyte number was greatly reduced, but development was not blocked completely as indicated by the presence of low numbers CD4 and CD8 single positive cells. SIK2 and SIK3 were not required for rearrangement of the TCRβ locus, or for low level cell surface expression of the TCR complex on the surface of CD4/CD8 double positive thymocytes. In the absence of both SIK2 and SIK3, progression to mature single positive cells was greatly reduced, suggesting a defect in negative and/or positive selection in the thymus. In agreement with an effect on negative selection, increased apoptosis was seen in thymic TCRbeta high/CD5 positive cells from SIK2/3 knockout mice. Together, these results show an important role for SIK2 and SIK3 in thymic T cell development.
Experimental demonstration of confidential communication with quantum security monitoring
Authors: Gong Yupeng , Wonfor Adrian , Hunt Jeffrey H. , White Ian H. , Penty Richard V.
Published: November 2021

Security issues and attack management of optical communication have come increasingly important. Quantum techniques are explored to secure or protect classical communication. In this paper, we present a method for in-service optical physical layer security monitoring that has vacuum-noise level sensitivity without classical security loopholes. This quantum-based method of eavesdropping detection, similar to that used in conventional pilot tone systems, is achieved by sending quantum signals, here comprised of continuous variable quantum states, i.e. weak coherent states modulated at the quantum level. An experimental demonstration of attack detection using the technique was presented for an ideal fibre tapping attack that taps 1% of the ongoing light in a 10 dB channel, and also an ideal correlated jamming attack in the same channel that maintains the light power with excess noise increased by 0.5 shot noise unit. The quantum monitoring system monitors suspicious changes in the quantum signal with the help of advanced data processing algorithms. In addition, unlike the CV-QKD system which is very sensitive to channel excess noise and receiver system noise, the quantum monitoring is potentially more compatible with current optical infrastructure, as it lowers the system requirements and potentially allows much higher classical data rate communication with links length up to 100 s km.
Single cell transcriptomics reveals the heterogeneity of the human cornea to identify novel markers of the limbus and stroma
Authors: Català Pere , Groen Nathalie , Dehnen Jasmin A. , Soares Eduardo , van Velthoven Arianne J. H. , Nuijts Rudy M. M. A. , Dickman Mor M. , LaPointe Vanessa L. S.
Published: November 2021

The cornea is the clear window that lets light into the eye. It is composed of five layers: epithelium, Bowman’s layer, stroma, Descemet’s membrane and endothelium. The maintenance of its structure and transparency are determined by the functions of the different cell types populating each layer. Attempts to regenerate corneal tissue and understand disease conditions requires knowledge of how cell profiles vary across this heterogeneous tissue. We performed a single cell transcriptomic profiling of 19,472 cells isolated from eight healthy donor corneas. Our analysis delineates the heterogeneity of the corneal layers by identifying cell populations and revealing cell states that contribute in preserving corneal homeostasis. We identified expression of CAV1, HOMER3 and CPVL in the corneal epithelial limbal stem cell niche, CKS2, STMN1 and UBE2C were exclusively expressed in highly proliferative transit amplifying cells, CXCL14 was expressed exclusively in the suprabasal/superficial limbus, and NNMT was exclusively expressed by stromal keratocytes. Overall, this research provides a basis to improve current primary cell expansion protocols, for future profiling of corneal disease states, to help guide pluripotent stem cells into different corneal lineages, and to understand how engineered substrates affect corneal cells to improve regenerative therapies.
The rumen microbiome inhibits methane formation through dietary choline supplementation
Authors: Li Yang , Kreuzer Michael , Clayssen Quentin , Ebert Marc-Olivier , Ruscheweyh Hans-Joachim , Sunagawa Shinichi , Kunz Carmen , Attwood Graeme , Amelchanka Sergej , Terranova Melissa
Published: November 2021

Enteric fermentation from ruminants is a primary source of anthropogenic methane emission. This study aims to add another approach for methane mitigation by manipulation of the rumen microbiome. Effects of choline supplementation on methane formation were quantified in vitro using the Rumen Simulation Technique. Supplementing 200 mM of choline chloride or choline bicarbonate reduced methane emissions by 97–100% after 15 days. Associated with the reduction of methane formation, metabolomics analysis revealed high post-treatment concentrations of ethanol, which likely served as a major hydrogen sink. Metagenome sequencing showed that the methanogen community was almost entirely lost, and choline-utilizing bacteria that can produce either lactate, ethanol or formate as hydrogen sinks were enriched. The taxa most strongly associated with methane mitigation wereMegasphaera elsdeniiandDenitrobacterium detoxificans, both capable of consuming lactate, which is an intermediate product and hydrogen sink. Accordingly, choline metabolism promoted the capability of bacteria to utilize alternative hydrogen sinks leading to a decline of hydrogen as a substrate for methane formation. However, fermentation of fibre and total organic matter could not be fully maintained with choline supplementation, while amino acid deamination and ethanolamine catabolism produced excessive ammonia, which would reduce feed efficiency and adversely affect live animal performance.
Real-time detection of particleboard surface defects based on improved YOLOV5 target detection
Authors: Zhao Ziyu , Yang Xiaoxia , Zhou Yucheng , Sun Qinqian , Ge Zhedong , Liu Dongfang
Published: November 2021

Particleboard surface defect detection technology is of great significance to the automation of particleboard detection, but the current detection technology has disadvantages such as low accuracy and poor real-time performance. Therefore, this paper proposes an improved lightweight detection method of You Only Live Once v5 (YOLOv5), namely PB-YOLOv5 (Particle Board-YOLOv5). Firstly, the gamma-ray transform method and the image difference method are combined to deal with the uneven illumination of the acquired images, so that the uneven illumination is well corrected. Secondly, Ghost Bottleneck lightweight deep convolution module is added to Backbone module and Neck module of YOLOv5 detection algorithm to reduce model volume. Thirdly, the SELayer module of attention mechanism is added into Backbone module. Finally, replace Conv in Neck module with depthwise convolution (DWConv) to compress network parameters. The experimental results show that the PB-YOLOv5 model proposed in this paper can accurately identify five types of defects on the particleboard surface: Bigshavings, SandLeakage, GlueSpot, Soft and OliPollution, and meet the real-time requirements. Specifically, recall, F1 score, mAP@.5, mAP@.5:.95 values of pB-Yolov5s model were 91.22%, 94.5%, 92.1%, 92.8% and 67.8%, respectively. The results of Soft defects were 92.8%, 97.9%, 95.3%, 99.0% and 81.7%, respectively. The detection of single image time of the model is only 0.031 s, and the weight size of the model is only 5.4 MB. Compared with the original YOLOv5s, YOLOv4, YOLOv3 and Faster RCNN, the PB-Yolov5s model has the fastest Detection of single image time. The Detection of single image time was accelerated by 34.0%, 55.1%, 64.4% and 87.9%, and the weight size of the model is compressed by 62.5%, 97.7%, 97.8% and 98.9%, respectively. The mAP value increased by 2.3%, 4.69%, 7.98% and 13.05%, respectively. The results show that the PB-YOLOV5 model proposed in this paper can realize the rapid and accurate detection of particleboard surface defects, and fully meet the requirements of lightweight embedded model.
Many-body and temperature effects in two-dimensional quantum droplets in Bose–Bose mixtures
Authors: Boudjemâa Abdelâali
Published: November 2021

We study the equilibrium properties of self-bound droplets in two-dimensional Bose mixtures employing the time-dependent Hartree–Fock–Bogoliubov theory. This theory allows one to understand both the many-body and temperature effects beyond the Lee–Huang–Yang description. We calculate higher-order corrections to the excitations, the sound velocity, and the energy of the droplet. Our results for the ground-state energy are compared with the diffusion Monte Carlo data and good agreement is found. The behavior of the depletion and anomalous density of the droplet is also discussed. At finite temperature, we show that the droplet emerges at temperatures well below the Berezinskii–Kosterlitz–Thouless transition temperature. The critical temperature strongly depends on the interspecies interactions. Our study is extended to the finite size droplet by numerically solving the generalized finite-temperature Gross-Pitaevskii equation which is obtained self-consistently from our formalism in the framework of the local density approximation.
Acute objective and subjective intoxication effects of legal-market high potency THC-dominant versus CBD-dominant cannabis concentrates
Authors: Drennan M. L. , Karoly H. C. , Bryan A. D. , Hutchison K. E. , Bidwell L. C.
Published: November 2021

As the market for cannabis concentrate products grows, the lack of research regarding the effects of concentrated THC and CBD becomes more glaring. The present study analyzes cannabinoid blood levels and subjective outcomes of physical sensation and affective state after ad libitum use of legal-market concentrate products. Recreational cannabis users were randomly assigned to THC- or CBD-dominant concentrate products, completing a baseline session, and an experimental mobile laboratory session consisting of timepoints before, immediately after, and one-hour after concentrate use. THC-dominant concentrates induced higher intoxication, and higher ratings of drug effect and drug liking than the CBD-dominant concentrate. Both products induced immediate feelings of elation, diminishing over the subsequent hour. Subjective outcomes in the CBD-dominant group revealed immediate decreases in tension and anxiety relative to pre-use, while the THC-dominant group only saw significant decreases in anxiety after one hour. Paranoia spiked immediately post-use in THC-dominant concentrate users, returning to baseline within an hour. Overall, the CBD-dominant concentrate invoked positive mood effects, lower intoxication and an absence of undesirable effects experienced with the THC-dominant concentrate, potentially mitigating negative effects when combined. Results support the need for further investigation into harm-reduction potential of concentrated CBD when used alone and with THC.
Deep visual domain adaptation and semi-supervised segmentation for understanding wave elevation using wave flume video images
Authors: Kim Jinah , Kim Taekyung , Oh Sang-Ho , Do Kideok , Ryu Joon-Gyu , Kim Jaeil
Published: November 2021

Accurate water surface elevation estimation is essential for understanding nearshore processes, but it is still challenging due to limitations in measuring water level using in-situ acoustic sensors. This paper presents a vision-based water surface elevation estimation approach using multi-view datasets. Specifically, we propose a visual domain adaptation method to build a water level estimator in spite of a situation in which ocean wave height cannot be measured directly. We also implemented a semi-supervised approach to extract wave height information from long-term sequences of wave height observations with minimal supervision. We performed wave flume experiments in a hydraulic laboratory with two cameras with side and top viewpoints to validate the effectiveness of our approach. The performance of the proposed models were evaluated by comparing the estimated time series of water elevation with the ground-truth wave gauge data at three locations along the wave flume. The estimated time series were in good agreement within the averaged correlation coefficient of 0.98 and 0.90 on the measurement and 0.95 and 0.85 on the estimation for regular and irregular waves, respectively.
The Bloch point 3D topological charge induced by the magnetostatic interaction
Authors: Tejo F. , Heredero R. Hernández , Chubykalo-Fesenko O. , Guslienko K. Y.
Published: November 2021

A hedgehog or Bloch point is a point-like 3D magnetization configuration in a ferromagnet. Regardless of widely spread treatment of a Bloch point as a topological defect, its 3D topological charge has never been calculated. Here, applying the concepts of the emergent magnetic field and Dirac string, we calculate the 3D topological charge (Hopf index) of a Bloch point and show that due to the magnetostatic energy contribution it has a finite, non-integer value. Thus, Bloch points form a new class of hopfions—3D topological magnetization configurations. The calculated Bloch point non-zero gyrovector leads to important dynamical consequences such as the appearance of topological Hall effect.
Timing and efficacy of transjugular intrahepatic portosystemic shunt in patients with pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome
Authors: Wu Fan , Yu Jiao , Gan Hongying , Zhang Heng , Tian Deying , Zheng Dan
Published: November 2021

There is no specific treatment for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS). It is not clear when transjugular intrahepatic portosystemic shunt (TIPS) should be implemented in PA-HSOS patients. This study aimed to evaluate the timing of TIPS using total bilirubin (TBIL) as a measure, and to investigate efficacy of TIPS. We retrospectively analyzed the medical records of 10 PA-HSOS patients, among whom 4 patients had received TIPS (TIPS group), and the remaining patients were assigned to the internal medicine group. In the TIPS group, the TBIL level before TIPS was 84.4 ± 45.2 µmol/L (> 3 mg/dL), and TBIL levels were increased to different degrees after TIPS. With the extension of time, serum TBIL levels gradually decreased, and no liver failure occurred. With regards to the short-term outcomes, 3 patients recovered, 1 developed chronic illness and 0 died in the TIPS group. Moreover, 0 patients recovered, 5 developed chronic illness and 1 died in the internal medicine group. The rank sum test of group design revealed significant differences in clinical outcomes (P = 0.02). It was suggested that when the internal medicine effect of PA-HSOS patients is poor, TIPS should be considered, which is no trestricted to the limit of 3 mg/dL TBIL. It was also found TIPS effectively promote the recovery of liver function and reduce the occurrence of chronicity.
The Wzi outer membrane protein mediates assembly of a tight capsular polysaccharide layer on the Acinetobacter baumannii cell surface
Authors: Tickner Jacob , Hawas Sophia , Totsika Makrina , Kenyon Johanna J.
Published: November 2021

Identification of novel therapeutic targets is required for developing alternate strategies to treat infections caused by the extensively drug-resistant bacterial pathogen, Acinetobacter baumannii. As capsular polysaccharide (CPS) is a prime virulence determinant required for evasion of host immune defenses, understanding the pathways for synthesis and assembly of this discrete cell-surface barrier is important. In this study, we assess cell-bound and cell-free CPS material from A. baumannii AB5075 wildtype and transposon library mutants and demonstrate that the Wzi outer membrane protein is required for the proper assembly of the CPS layer on the cell surface. Loss of Wzi resulted in an estimated 4.4-fold reduction in cell-associated CPS with a reciprocal increase in CPS material shed in the extracellular surrounds. Transmission electron microscopy revealed a disrupted CPS layer with sparse patches of CPS on the external face of the outer membrane when Wzi function was lost. However, this genotype did not have a significant effect on biofilm formation. Genetic analysis demonstrated that the wzi gene is ubiquitous in the species, though the nucleotide sequences were surprisingly diverse. Though divergence was not concomitant with variation at the CPS biosynthesis K locus, an association between wzi type and the first sugar of the CPS representing the base of the structure most likely to interact with Wzi was observed.
The spatial distribution characteristics of typical pathogens and nitrogen and phosphorus in the sediments of Shahe Reservoir and their relationships
Authors: Sun Wen , Yang Ke , Li Risheng , Chen Tianqing , Xia Longfei , Wang Zhao , Sun Xubo
Published: November 2021

Using samples collected in Shahe Reservoir in the upper North Canal in China, this research analyzes the structure of a microorganism group in sediment and the absolute abundance of two typical pathogenic bacteria (Escherichia coli and Enterococcus), and their relationship with environmental factors including total nitrogen (TN) and total phosphorus (TP). The study of samples collected from the surface (0–20 cm) and sediment cores shows that the absolute abundance of E. coli in horizontal distribution in the sediment is highest in downstream of the reservoir and point source pollution area. In vertical distribution, the absolute gene expression level of the two pathogenic bacteria in the sediment tends to decrease with increasing depth, although its highest value at 10–30 cm depth. The relative abundance the two pathogenic bacteria is much greater in the sediment of Shahe Reservoir with the structure of horizontal groups including Clortridium sensu stricto, unclassified Anaeroineaceae, and Povalibacter, while Anaeroineaceae is much more abundant in the group structure of the vertical distribution. Pearson correlation analysis suggests positive correlation in horizontal distribution for E. coli and TN and TP (P < 0.05) and for Enterococcus and TP (P < 0.05). The results clearly show that the amount of pathogenic bacteria in the sediment in Shahe Reservoir is most likely due to water eutrophication.
Prevalence and risk factors of type-2 diabetes mellitus in Ethiopia: systematic review and meta-analysis
Authors: Zeru Melkamu A. , Tesfa Endalamaw , Mitiku Aweke A. , Seyoum Awoke , Bokoro Tesfaye Abera
Published: November 2021

Diabetes mellitus (DM) is a public health problem in developing as well as developed nations. DM leads to many complications that are associated with higher morbidity and mortality worldwide. Therefore, the current study was planned to assess the prevalence and risk factors of type-2 DM in Ethiopian population. Six electronic databases such as: PubMed, Scopus, Hinari, Web of science, Google Scholar, and African Journals Online were searched for studies published in English up December 30, 2020. Newcastle–Ottawa Scale was used for quality assessment of the included studies. The data was extracted by Microsoft excel and analyzed through Stata version 16 software. The random effect meta-regression analysis was computed at 95% CI to assess the pooled prevalence and risk factors of type-2 DM. Forty observational studies were included in this systematic review and meta-analysis. The pooled prevalence of DM in Ethiopia was 6.5% (95% CI (5.8, 7.3)). The sub-group analysis revealed that the highest prevalence of DM was found in Dire Dawa city administration (14%), and the lowest prevalence was observed in Tigray region (2%). The pooled prevalence of DM was higher (8%) in studies conducted in health facility. Factors like: Age ≥ 40 years ((Adjusted Odds Ratio (AOR): 1.91 (95% CI: 1.05, 3.49)), Illiterate (AOR: 2.74 (95% CI: 1.18, 6.34)), Cigarette smoking (AOR: 1.97 (95% CI: 1.17, 3.32)), Body mass index (BMI) ≥ 25 kg/m2(AOR: 2.01 (95 CI: 1.46, 2.27)), family history of DM (AOR: 6.14 (95% CI: 2.80, 13.46)), history of hypertension (AOR: 3.00 (95% CI: 1.13, 7.95)) and physical inactivity (AOR: 5.79 (95% CI: 2.12, 15.77)) were significantly associated with type-2 DM in Ethiopian population. In this review, the prevalence of type-2 DM was high. Factors like: Older age, illiteracy, cigarette smoking, MBI ≥ 25, family history of DM, history of hypertension and physical inactivity were an identified risk factors of type-2 DM. Therefore, health education and promotion will be warranted. Further, large scale prospective studies will be recommended to address possible risk factors of type-2 DM in Ethiopian population.