bluuebunny/crossref_metadata_2025 huggingface dataset:
AGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling
Authors: Da Xingwen , Li Ziyan , Huang Xiaofan , He Zuhan , Yu Yubing , Tian Tongtong , Xu Chengqi , Yao Yufeng , Wang Qing K.
Published: April 2023

Thoracic aortic aneurysm (TAA) is a localized or diffuse dilatation of the thoracic aortas, and causes many sudden deaths each year worldwide. However, there is no effective pharmacologic therapy. Here, we show that AGGF1 effectively blocks TAA-associated arterial inflammation and remodeling in three different mouse models (mice with transverse aortic constriction, Fbn1C1041G/+ mice, and β-aminopropionitrile-treated mice). AGGF1 expression is reduced in the ascending aortas from the three models and human TAA patients. Aggf1+/- mice and vascular smooth muscle cell (VSMC)-specific Aggf1smcKO knockout mice show aggravated TAA phenotypes. Mechanistically, AGGF1 enhances the interaction between its receptor integrin α7 and latency-associated peptide (LAP)-TGF-β1, blocks the cleavage of LAP-TGF-β1 to form mature TGF-β1, and inhibits Smad2/3 and ERK1/2 phosphorylation in VSMCs. Pirfenidone, a treatment agent for idiopathic pulmonary fibrosis, inhibits TAA-associated vascular inflammation and remodeling in wild type mice, but not in Aggf1+/- mice. In conclusion, we identify an innovative AGGF1 protein therapeutic strategy to block TAA-associated vascular inflammation and remodeling, and show that efficacy of TGF-β inhibition therapies require AGGF1.
RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function
Authors: Shiraishi Chisa , Matsumoto Akinobu , Ichihara Kazuya , Yamamoto Taishi , Yokoyama Takeshi , Mizoo Taisuke , Hatano Atsushi , Matsumoto Masaki , Tanaka Yoshikazu , Matsuura-Suzuki Eriko , Iwasaki Shintaro , Matsushima Shouji , Tsutsui Hiroyuki , Nakayama Keiichi I.
Published: April 2023

Although several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation.
Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients
Authors: Wu Yiming , Gettler Kyle , Kars Meltem Ece , Giri Mamta , Li Dalin , Bayrak Cigdem Sevim , Zhang Peng , Jain Aayushee , Maffucci Patrick , Sabic Ksenija , Van Vleck Tielman , Nadkarni Girish , Denson Lee A. , Ostrer Harry , Levine Adam P. , Schiff Elena R. , Segal Anthony W. , Kugathasan Subra , Stenson Peter D. , Cooper David N. , Philip Schumm L. , Snapper Scott , Daly Mark J. , Haritunians Talin , Duerr Richard H. , Silverberg Mark S. , Rioux John D. , Brant Steven R. , McGovern Dermot P. B. , Cho Judy H. , Itan Yuval
Published: April 2023

Inflammatory bowel disease (IBD) is a group of chronic digestive tract inflammatory conditions whose genetic etiology is still poorly understood. The incidence of IBD is particularly high among Ashkenazi Jews. Here, we identify 8 novel and plausible IBD-causing genes from the exomes of 4453 genetically identified Ashkenazi Jewish IBD cases (1734) and controls (2719). Various biological pathway analyses are performed, along with bulk and single-cell RNA sequencing, to demonstrate the likely physiological relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of Ashkenazi Jewish adult IBD displays significant overlap with very early onset-IBD genetics. Moreover, by performing biobank phenome-wide analyses, we find that IBD genes have pleiotropic effects that involve other immune responses. Finally, we show that polygenic risk score analyses based on genome-wide high impact variants have high power to predict IBD susceptibility.
LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism
Authors: He Xin-yu , Fan Xiao , Qu Lei , Wang Xiang , Jiang Li , Sang Ling-jie , Shi Cheng-yu , Lin Siyi , Yang Jie-cheng , Yang Zuo-zhen , Lei Kai , Li Jun-hong , Ju Huai-qiang , Yan Qingfeng , Liu Jian , Wang Fudi , Shao Jianzhong , Xiong Yan , Wang Wenqi , Lin Aifu
Published: April 2023

Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP,LncRIM(LncRNA Related to Iron Metabolism, also namedZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically,LncRIMdirectly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally,LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression ofLncRIMcorrelates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in whichLncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.
Atomic-scale observation of premelting at 2D lattice defects inside oxide crystals
Authors: Kim Hye-Sung , An Ji-Sang , Bae Hyung Bin , Chung Sung-Yoon
Published: April 2023

Since two major criteria for melting were proposed by Lindemann and Born in the early 1900s, many simulations and observations have been carried out to elucidate the premelting phenomena largely at the crystal surfaces and grain boundaries below the bulk melting point. Although dislocations and clusters of vacancies and interstitials were predicted as possible origins to trigger the melting, experimental direct observations demonstrating the correlation of premelting with lattice defects inside a crystal remain elusive. Using atomic-column-resolved imaging with scanning transmission electron microscopy in polycrystalline BaCeO3, here we clarify the initiation of melting at two-dimensional faults inside the crystals below the melting temperature. In particular, melting in a layer-by-layer manner rather than random nucleation at the early stage was identified as a notable finding. Emphasizing the value of direct atomistic observation, our study suggests that lattice defects inside crystals should not be overlooked as preferential nucleation sites for phase transformation including melting.
Accelerated biological aging and risk of depression and anxiety: evidence from 424,299 UK Biobank participants
Authors: Gao Xu , Geng Tong , Jiang Meijie , Huang Ninghao , Zheng Yinan , Belsky Daniel W. , Huang Tao
Published: April 2023

Theory predicts that biological processes of aging may contribute to poor mental health in late life. To test this hypothesis, we evaluated prospective associations between biological age and incident depression and anxiety in 424,299 UK Biobank participants. We measured biological age from clinical traits using the KDM-BA and PhenoAge algorithms. At baseline, participants who were biologically older more often experienced depression/anxiety. During a median of 8.7 years of follow-up, participants with older biological age were at increased risk of incident depression/anxiety (5.9% increase per standard deviation [SD] of KDM-BA acceleration, 95% confidence intervals [CI]: 3.3%–8.5%; 11.3% increase per SD of PhenoAge acceleration, 95% CI: 9.%–13.0%). Biological-aging-associated risk of depression/anxiety was independent of and additive to genetic risk measured by genome-wide-association-study-based polygenic scores. Advanced biological aging may represent a potential risk factor for incident depression/anxiety in midlife and older adults and a potential target for risk assessment and intervention.
Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase
Authors: Silhan Jan , Klima Martin , Otava Tomas , Skvara Petr , Chalupska Dominika , Chalupsky Karel , Kozic Jan , Nencka Radim , Boura Evzen
Published: April 2023

Monkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2′-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2′-O-RNA MTase with enzymes from unrelated single-stranded RNA viruses (SARS-CoV-2 and Zika) reveals a conserved sinefungin binding mode, implicating that a single inhibitor could be used against unrelated viral families. Indeed, several of our inhibitors such as TO507 also inhibit the coronaviral nsp14 MTase.
DeepFLR facilitates false localization rate control in phosphoproteomics
Authors: Zong Yu , Wang Yuxin , Yang Yi , Zhao Dan , Wang Xiaoqing , Shen Chengpin , Qiao Liang
Published: April 2023

Protein phosphorylation is a post-translational modification crucial for many cellular processes and protein functions. Accurate identification and quantification of protein phosphosites at the proteome-wide level are challenging, not least because efficient tools for protein phosphosite false localization rate (FLR) control are lacking. Here, we propose DeepFLR, a deep learning-based framework for controlling the FLR in phosphoproteomics. DeepFLR includes a phosphopeptide tandem mass spectrum (MS/MS) prediction module based on deep learning and an FLR assessment module based on a target-decoy approach. DeepFLR improves the accuracy of phosphopeptide MS/MS prediction compared to existing tools. Furthermore, DeepFLR estimates FLR accurately for both synthetic and biological datasets, and localizes more phosphosites than probability-based methods. DeepFLR is compatible with data from different organisms, instruments types, and both data-dependent and data-independent acquisition approaches, thus enabling FLR estimation for a broad range of phosphoproteomics experiments.
Structural insights into RNase J that plays an essential role in Mycobacterium tuberculosis RNA metabolism
Authors: Bao Luyao , Hu Juan , Zhan Bowen , Chi Mingzhe , Li Zhengyang , Wang Sen , Shan Chan , Zhao Zhaozhao , Guo Yanchao , Ding Xiaoming , Ji Chaoneng , Tao Shengce , Ni Ting , Zhang Xuelian , Zhao Guoping , Li Jixi
Published: April 2023

Ribonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the β-CASP and the β-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.
Uniform segmented platelet micelles with compositionally distinct and selectively degradable cores
Authors: Tong Zaizai , Xie Yujie , Arno Maria C. , Zhang Yifan , Manners Ian , O’Reilly Rachel K. , Dove Andrew P.
Published: April 2023

The creation of nanoparticles with controlled and uniform dimensions and spatially defined functionality is a key challenge. The recently developed living crystallization-driven self-assembly (CDSA) method has emerged as a promising route to one-dimensional (1D) and 2D core–shell micellar assemblies by seeded growth of polymeric and molecular amphiphiles. However, the general limitation of the epitaxial growth process to a single core-forming chemistry is an important obstacle to the creation of complex nanoparticles with segmented cores of spatially varied composition that can be subsequently exploited in selective transformations or responses to external stimuli. Here we report the successful use of a seeded growth approach that operates for a variety of different crystallizable polylactone homopolymer/block copolymer blend combinations to access 2D platelet micelles with compositionally distinct segmented cores. To illustrate the utility of controlling internal core chemistry, we demonstrate spatially selective hydrolytic degradation of the 2D platelets—a result that may be of interest for the design of complex stimuli-responsive particles for programmed-release and cargo-delivery applications.
Accurate structure models and absolute configuration determination using dynamical effects in continuous-rotation 3D electron diffraction data
Authors: Klar Paul B. , Krysiak Yaşar , Xu Hongyi , Steciuk Gwladys , Cho Jung , Zou Xiaodong , Palatinus Lukas
Published: April 2023

Continuous-rotation 3D electron diffraction methods are increasingly popular for the structure analysis of very small organic molecular crystals and crystalline inorganic materials. Dynamical diffraction effects cause non-linear deviations from kinematical intensities that present issues in structure analysis. Here, a method for structure analysis of continuous-rotation 3D electron diffraction data is presented that takes multiple scattering effects into account. Dynamical and kinematical refinements of 12 compounds—ranging from small organic compounds to metal–organic frameworks to inorganic materials—are compared, for which the new approach yields significantly improved models in terms of accuracy and reliability with up to fourfold reduction of the noise level in difference Fourier maps. The intrinsic sensitivity of dynamical diffraction to the absolute structure is also used to assign the handedness of 58 crystals of 9 different chiral compounds, showing that 3D electron diffraction is a reliable tool for the routine determination of absolute structures.
Inference of phylogenetic trees directly from raw sequencing reads using Read2Tree
Authors: Dylus David , Altenhoff Adrian , Majidian Sina , Sedlazeck Fritz J. , Dessimoz Christophe
Published: April 2023

Current methods for inference of phylogenetic trees require running complex pipelines at substantial computational and labor costs, with additional constraints in sequencing coverage, assembly and annotation quality, especially for large datasets. To overcome these challenges, we present Read2Tree, which directly processes raw sequencing reads into groups of corresponding genes and bypasses traditional steps in phylogeny inference, such as genome assembly, annotation and all-versus-all sequence comparisons, while retaining accuracy. In a benchmark encompassing a broad variety of datasets, Read2Tree is 10–100 times faster than assembly-based approaches and in most cases more accurate—the exception being when sequencing coverage is high and reference species very distant. Here, to illustrate the broad applicability of the tool, we reconstruct a yeast tree of life of 435 species spanning 590 million years of evolution. We also apply Read2Tree to >10,000Coronaviridaesamples, accurately classifying highly diverse animal samples and near-identical severe acute respiratory syndrome coronavirus 2 sequences on a single tree. The speed, accuracy and versatility of Read2Tree enable comparative genomics at scale.
Fibrillin microfibril structure identifies long-range effects of inherited pathogenic mutations affecting a key regulatory latent TGFβ-binding site
Authors: Godwin Alan R. F. , Dajani Rana , Zhang Xinyang , Thomson Jennifer , Holmes David F. , Adamo Christin S. , Sengle Gerhard , Sherratt Michael J. , Roseman Alan M. , Baldock Clair
Published: April 2023

Genetic mutations in fibrillin microfibrils cause serious inherited diseases, such as Marfan syndrome and Weill–Marchesani syndrome (WMS). These diseases typically show major dysregulation of tissue development and growth, particularly in skeletal long bones, but links between the mutations and the diseases are unknown. Here we describe a detailed structural analysis of native fibrillin microfibrils from mammalian tissue by cryogenic electron microscopy. The major bead region showed pseudo eightfold symmetry where the amino and carboxy termini reside. On the basis of this structure, we show that a WMS deletion mutation leads to the induction of a structural rearrangement that blocks interaction with latent TGFβ-binding protein-1 at a remote site. Separate deletion of this binding site resulted in the assembly of shorter fibrillin microfibrils with structural alterations. The integrin αvβ3-binding site was also mapped onto the microfibril structure. These results establish that in complex extracellular assemblies, such as fibrillin microfibrils, mutations may have long-range structural consequences leading to the disruption of growth factor signaling and the development of disease.
HIT-UAV: A high-altitude infrared thermal dataset for Unmanned Aerial Vehicle-based object detection
Authors: Suo Jiashun , Wang Tianyi , Zhang Xingzhou , Chen Haiyang , Zhou Wei , Shi Weisong
Published: April 2023

We present the HIT-UAV dataset, a high-altitude infrared thermal dataset for object detection applications on Unmanned Aerial Vehicles (UAVs). The dataset comprises 2,898 infrared thermal images extracted from 43,470 frames in hundreds of videos captured by UAVs in various scenarios, such as schools, parking lots, roads, and playgrounds. Moreover, the HIT-UAV provides essential flight data for each image, including flight altitude, camera perspective, date, and daylight intensity. For each image, we have manually annotated object instances with bounding boxes of two types (oriented and standard) to tackle the challenge of significant overlap of object instances in aerial images. To the best of our knowledge, the HIT-UAV is the first publicly available high-altitude UAV-based infrared thermal dataset for detecting persons and vehicles. We have trained and evaluated well-established object detection algorithms on the HIT-UAV. Our results demonstrate that the detection algorithms perform exceptionally well on the HIT-UAV compared to visual light datasets, since infrared thermal images do not contain significant irrelevant information about objects. We believe that the HIT-UAV will contribute to various UAV-based applications and researches. The dataset is freely available athttps://pegasus.ac.cn.
Two decades of fumigation data from the Soybean Free Air Concentration Enrichment facility
Authors: Aspray Elise Kole , Mies Timothy A. , McGrath Jesse A. , Montes Christopher M. , Dalsing Bradley , Puthuval Kannan K. , Whetten Andrew , Herriott Jelena , Li Shuai , Bernacchi Carl J. , DeLucia Evan H. , Leakey Andrew D. B. , Long Stephen P. , McGrath Justin M. , Miglietta Franco , Ort Donald R. , Ainsworth Elizabeth A.
Published: April 2023

The Soybean Free Air Concentration Enrichment (SoyFACE) facility is the longest running open-air carbon dioxide and ozone enrichment facility in the world. For over two decades, soybean, maize, and other crops have been exposed to the elevated carbon dioxide and ozone concentrations anticipated for late this century. The facility, located in East Central Illinois, USA, exposes crops to different atmospheric concentrations in replicated octagonal ~280 m2 Free Air Concentration Enrichment (FACE) treatment plots. Each FACE plot is paired with an untreated control (ambient) plot. The experiment provides important ground truth data for predicting future crop productivity. Fumigation data from SoyFACE were collected every four seconds throughout each growing season for over two decades. Here, we organize, quality control, and collate 20 years of data to facilitate trend analysis and crop modeling efforts. This paper provides the rationale for and a description of the SoyFACE experiments, along with a summary of the fumigation data and collation process, weather and ambient data collection procedures, and explanations of air pollution metrics and calculations.
Global 3-hourly wind-wave and swell data for wave climate and wave energy resource research from 1950 to 2100
Authors: Jiang Xingjie , Xie Botao , Bao Ying , Song Zhenya
Published: April 2023

Ocean wave climate, including wind waves and swells, is essential to human marine activities and global or regional climate systems, and is highly related to harnessing wave energy resources. In this study, a global 3-hourly instantaneous wave dataset was established with the third-generation wave model MASNUM-WAM and wind forcings derived from the products of the First Institute of Oceanography-Earth System Model version 2.0, the climate model coupled with wave model, under the unified framework of the Coupled Model Intercomparison Project phase 6. This dataset contains 17 wave parameters, including the information associated with wave energy and spectral shape geometries, from one historical (1950–2014) simulation and three future (2015–2100) scenario experiments (ssp125, ssp245, and ssp585). Moreover, all the parameters can be accessed separately in the form of wind waves and swells. The historical results show that the simulated wave characteristics agree well with satellite observations and the ERA5 reanalysis products. This dataset can provide the community with a unique and informative data source for wave climate and wave energy resource research.
Degradation of paper products due to volatile organic compounds
Authors: Alam Izhar , Sharma Chhaya
Published: April 2023

Paper and packaging materials a lignocellulose-based natural biodegradable polymer that spontaneously releases acetic acid, aldehydes, alcohol, and ester-based volatile organic compounds (VOCs) upon ageing and these VOCs start degrading the paper products and decline their mechanical strength properties. The reactivity of the paper of unbleached wheat straw pulp towards acetic acid and hexanal, which has been proven to have more degrading effects on paper than other VOCs, was considered in this work. The papers were exposed to these volatile compounds for 90 days in an air-tight vessel under ambient environmental conditions. The results showed that hexanal was more destructive than acetic acid with regards to cellulose degradation and depletion in the mechanical strength properties. The paper properties like, tensile, tear and burst index, viscosity, pH and carbonyl group content was measured. The growth of the carbonyl group, evidence of the ageing effects in the paper, detected more in the paper exposed to acetic acid. However, the strength of paper properties declined more with hexanal. FE-SEM analysis of the sample showed the development of pores and damage of cellulose fibre upon ageing. Similarly, the damaging effects of VOCs on cellulose, hemicelluloses and lignin were confirmed by significantly reduced peak detection through FT-IR \analysis. The high crystallinity index of the paper products due to exposure to VOCs was detected by XRD analysis, which confirmed the degradation of the low molecular weight cellulose molecule. Thus, the results are strongly recommended that VOCs that generates due to natural or artificial ageing could be the leading cause of paper degradation.
Efficient shallow learning as an alternative to deep learning
Authors: Meir Yuval , Tevet Ofek , Tzach Yarden , Hodassman Shiri , Gross Ronit D. , Kanter Ido
Published: April 2023

The realization of complex classification tasks requires training of deep learning (DL) architectures consisting of tens or even hundreds of convolutional and fully connected hidden layers, which is far from the reality of the human brain. According to the DL rationale, the first convolutional layer reveals localized patterns in the input and large-scale patterns in the following layers, until it reliably characterizes a class of inputs. Here, we demonstrate that with a fixed ratio between the depths of the first and second convolutional layers, the error rates of the generalized shallow LeNet architecture, consisting of only five layers, decay as a power law with the number of filters in the first convolutional layer. The extrapolation of this power law indicates that the generalized LeNet can achieve small error rates that were previously obtained for the CIFAR-10 database using DL architectures. A power law with a similar exponent also characterizes the generalized VGG-16 architecture. However, this results in a significantly increased number of operations required to achieve a given error rate with respect to LeNet. This power law phenomenon governs various generalized LeNet and VGG-16 architectures, hinting at its universal behavior and suggesting a quantitative hierarchical time–space complexity among machine learning architectures. Additionally, the conservation law along the convolutional layers, which is the square-root of their size times their depth, is found to asymptotically minimize error rates. The efficient shallow learning that is demonstrated in this study calls for further quantitative examination using various databases and architectures and its accelerated implementation using future dedicated hardware developments.
The efficacy of bimatoprost ophthalmic solution combined with NB-UVB phototherapy in non-segmental and segmental vitiligo: a single-blind randomized controlled study
Authors: Silpa-archa Narumol , Likittanasombat Surachanee , Apinuntham Chalermkwan , Pruksaeakanan Chutipon , Charoenpipatsin Norramon , Chaiyabutr Chayada , Wongpraparut Chanisada
Published: April 2023

Bimatoprost ophthalmic solution 0.03% (PGF2α analogues) combined with narrowband ultraviolet B (NB-UVB) was reported to be an effective treatment for vitiligo. To investigate the efficacy and safety of treatment for non-segmental/segmental vitiligo compared among bimatoprost ophthalmic solution 0.01% combined with NB-UVB phototherapy, bimatoprost monotherapy, and placebo. This single-blind randomized controlled study enrolled stable Thai vitiligo patients with at least three similarly sized lesions in the same anatomical area. The treatment duration was 6 months with 1- and 2-month post-treatment follow-ups. The 3 selected lesions on each patient were randomized to receive combination therapy, monotherapy, or placebo. The Vitiligo Area Scoring Index (VASI) was used to evaluate lesion response. Of the 25 initially enrolled subjects, 19 patients were analyzed. There were 13 and 6 non-segmental and segmental vitiligo cases, respectively. Eight and 11 cases had face/neck and non-face/neck lesions, respectively. Non-segmental vitiligo and non-face/neck vitiligo patients in the combination group had significant improvement in VASI score at 3 months, 6 months, and at the 2-month follow-up. No side effects were observed/reported. Bimatoprost combination therapy was shown to be safe and effective for treating Thai patients with non-segmental vitiligo in non-face/neck areas of the body.
Engineering benefits of replacing natural sand with manufactured sand in landfill construction
Authors: Pillai Anjali G. , Gali Madhavi Latha
Published: April 2023

Translational sliding failures in landfills are often triggered by inadequate shear strength of interfaces in liners and covers. Geosynthetic Clay Liners (GCL) are used in different components of landfills to contain the leachate. GCLs are usually placed above a compacted sand subgrade to develop higher shear resistance. In the context of depleting natural sand resources, the present study explores the feasibility of replacing natural sand with manufactured sand (Msand) in landfill construction. Interface shear tests were performed on GCL in contact with river sand and Msand of similar gradation to evaluate the shear strength at different normal stresses and hydration conditions. It is found that Msand provides higher interface shear strength with GCL compared to river sand. Digital image analysis of tested specimens of GCL showed that variation in particle morphology of the two sands has direct influence on the microlevel interaction mechanisms governing the shear strength. Quantification of morphological parameters showed that Msand particles are angular and rough compared to natural sand particles, leading to higher particle interlocking. Hydration of the GCL reduced the interface shear strength, the effect being less in case of Msand. The study highlights that replacement of natural sand with Msand has added benefits.
Watching the human retina breath in real time and the slowing of mitochondrial respiration with age
Authors: Kaynezhad Pardis , Tachtsidis Ilias , Sivaprasad Sobha , Jeffery Glen
Published: April 2023

The retina has the greatest metabolic demand in the body particularly in dark adaptation when its sensitivity is enhanced. This requires elevated level of perfusion to sustain mitochondrial activity. However, mitochondrial performance declines with age leading to reduced adaptive ability. We assessed human retina metabolism in vivo using broad band near-infrared spectroscopy (bNIRS), which records colour changes in mitochondria and blood as retinal metabolism shifts in response to changes in environmental luminance. We demonstrate a significant sustained rise in mitochondrial oxidative metabolism in the first 3 min of darkness in subjects under 50 years old. This was not seen in those over 50 years. Choroidal oxygenation declines in < 50 s as mitochondrial metabolism increases, but gradually rises in the > 50 s. Significant group differences in blood oxygenation are apparent in the first 6 min, consistent with mitochondrial demand leading hemodynamic changes. A greater coupling between mitochondrial oxidative metabolism with hemodynamics is revealed in subjects older than 50, possibly due to reduced capacity in the older retina. Rapid in vivo assessment of retinal metabolism with bNIRS provides a route to understanding fundamental physiology and early identification of retinal disease before pathology is established.
Deciphering the spectrum of cutaneous lymphomas expressing TFH markers
Authors: Donzel Marie , Trecourt Alexis , Balme Brigitte , Harou Olivier , Mauduit Claire , Bachy Emmanuel , Guesquières Hervé , Fontaine Juliette , Ortonne Nicolas , Perier-Muzet Marie , Dalle Stéphane , Traverse-Glehen Alexandra
Published: April 2023

T-follicular helper (TFH) markers are expressed in the microenvironnement of marginal zone B-cell lymphoma (MZL), and in lymphomas arising from TFH-cells, sometimes making the differential diagnosis difficult. In the skin, the “TFH-spectrum” is poorly defined, going from primary cutaneous lymphoproliferative disorder with small/medium CD4+ T-cells (SMLPD) to cutaneous localizations of systemic angioimmunoblastic T-cell lymphoma (cAITL), and may pass through intermediate forms (primary cutaneous T-follicular helper derived lymphoma, not otherwise specified (PCTFHL,NOS)). We retrospectively analyzed 20 MZL, 13 SMLPD, 5 PCTFHL, and 11 cAITL clinically, histologically, and molecularly, to define tools to differentiate them. Characteristics that might favor the diagnosis of MZL over SMLPD are: multiple skin nodules (p < 0.001), nodular architecture (p < 0.01), residual germinal centers with follicular dendritic cell network (p < 0.001), monotypic plasma cells (p < 0.001), and few staining with PD1 (p = 0.016) or CXCL13 (p = 0.03). PCTFHL and cAITL presented as multiple (p < 0.01) lesions, in older patients (p < 0.01), with systemic symptoms and/or biological alterations (p < 0.01). Immunophenotypic loss of T-cell markers (p < 0.001), BCL6 (p = 0.023) and/or CD10 staining (p = 0.08), and a higher proliferative index (≥ 30%, p = 0.039) favoured these diagnoses over SMLPD. Pathogenic variants were observed by genomic sequencing in 47% of MZL (TNFAIP3 (32%), EP300 (21%), NOTCH2 (16%), KMT2D (16%), CARD11 (10.5%)), 8% of SMLPD (TET2), 40% of PCTFHL (SOCS1 (20%), ARID1A (20%)) and 64% of cAITL (TET2 (63.6%), RHOA (36.4%), NOTCH1 (9%)). This study characterizes the various clinical and histological features between cutaneous lymphomas expressing TFH markers and highlights the value of the interest of screening for genomic mutations in difficult cases.
Identification of immune and Toll-like receptor signaling pathway related feature lncRNAs to construct diagnostic nomograms for acute ischemic stroke
Authors: Su Zhuo-Yi , Yu Zi-Qiao , Yao Bo , Zhao De-Xi
Published: April 2023

We aimed to identify the immune and Toll-like receptor (TLR) signaling pathway related feature lncRNAs to construct the diagnostic nomograms for acute ischemic stroke (AIS). Two AIS-associated expression profiles GSE16561 and GSE22255 were downloaded from NCBI Gene Expression Omnibus, the former was the training set and the latter was the validation set. The differential expression genes (DEGs) and lncRNAs (DElncRNAs) related to TLR signaling pathway were identified between AIS and control groups. The single sample gene set enrichment analysis (ssGSEA) was applied to evaluate the immune infiltration. The immune and TLR signaling pathway related DElncRNAs were determined. Three optimization algorithms were utilized to select the immune and TLR signaling pathway related feature lncRNAs to construct the diagnostic nomograms of AIS. Based on the lncRNA signature, a ceRNA network was constructed. 37 DEGs and 28 DElncRNAs related to TLR signaling pathway were identified in GSE16561. 16 immune cell types exhibited significant differences in distribution between AIS and control groups. 28 immune and TLR signaling pathway related DElncRNAs were determined. 8 immune and TLR signaling pathway related feature lncRNAs were selected. The diagnostic nomograms of AIS performed well in both datasets. A ceRNA network was constructed consisting of 7 immune and TLR signaling pathway related feature lncRNAs as well as 19 AIS related miRNAs and 21 TLR signaling pathway related genes. LINC00173, LINC01089, LINC02210, MIR600HG, SNHG14, TP73-AS1, LINC00680 and CASC2 may be the potential biomarkers of AIS diagnosis, and TLR signaling pathway may be a promising immune related therapeutic target for AIS.
Solution of road network problem with the help of m-polar fuzzy graph using isometric and antipodal concept
Authors: Mondal Uttam , Mahapatra Tanmoy , Xin Qin , Pal Madhumangal
Published: April 2023

The isometry in crisp graph theory is a well-known fact. But, isometry under a fuzzy environment was developed recently and studied many facts. In a m-polar fuzzy graph, we have to think m components for each node and edge. Since, in our consideration, we consider m components for each nodes as well as edges, therefore we can not handle this type of situation using fuzzy model as their is a single components for this concept. Again, we can not apply bipolar or intuitionistic fuzzy graph model as each edges or nodes have just two components. Thus, these mPFG models give more efficient fuzziness results than other fuzzy model. Also, it is very interesting to develop and analyze such types of mPFGs with examples and related theorems. Considering all those things together, we have presented isometry under a m-polar fuzzy environment. In this paper, we have discussed the isometric m-polar fuzzy graph along with many exciting facts about it. Metric space properties have also been implemented on m-polar fuzzy isometric graph. We also have initiated a generalized fuzzy graph, namely antipodal m-polar fuzzy graphs, along with several issues. The degree of it is also presented along with edge regularity properties. We also give a relation between m-polar fuzzy antipodal graphs and their underlying crisp graphs. Its properties have also been discussed on m-polar fuzzy odd as well as even cycles, complete graphs, etc. Finally, a real-life application on a road network system in a m-polar fuzzy environment using the $$\mu$$
μ
-distance concept is also presented.
Repeated unilateral handgrip contractions alter functional connectivity and improve contralateral limb response times
Authors: Andrushko Justin W. , Levenstein Jacob M. , Zich Catharina , Edmond Evan C. , Campbell Jon , Clarke William T. , Emir Uzay , Farthing Jonathan P. , Stagg Charlotte J.
Published: April 2023

In humans, motor learning is underpinned by changes in sensorimotor network functional connectivity (FC). Unilateral contractions increase FC in the ipsilateral primary motor cortex (M1) and supplementary motor area (SMA); areas involved in motor planning and execution of the contralateral hand. Therefore, unilateral contractions are a promising approach to augment motor performance in the contralateral hand. In a within-participant, randomized, cross-over design, 15 right-handed adults had two magnetic resonance imaging (MRI) sessions, where functional-MRI and MR-Spectroscopic Imaging were acquired before and after repeated right-hand contractions at either 5% or 50% maximum voluntary contraction (MVC). Before and after scanning, response times (RTs) were determined in both hands. Nine minutes of 50% MVC contractions resulted in decreased handgrip force in the contracting hand, and decreased RTs and increased handgrip force in the contralateral hand. This improved motor performance in the contralateral hand was supported by significant neural changes: increased FC between SMA-SMA and increased FC between right M1 and right Orbitofrontal Cortex. At a neurochemical level, the degree of GABA decline in left M1, left and right SMA correlated with subsequent behavioural improvements in the left-hand. These results support the use of repeated handgrip contractions as a potential modality for improving motor performance in the contralateral hand.
Effect of a novel telehealth device for dietary cognitive behavioral intervention in overweight or obesity care
Authors: Fang Yi-Ya , Lee Jia-In , Wu Nai-Yuan , Chang Chiao-I , Huang Meng-Chuan , Lee Chun-Ying , Huang Jui-Yen , Lee Gwo Giun Chris , Chen Cheng-Sheng
Published: April 2023

Obesity has become a major public health issue which relate to numerous physical problems and highly comorbid with depression and anxiety. Recently, some studies of technology-based interventions for weight reduction emerged to overcome the barriers from time, cost and distance. Mood component and eating behavior related to obesity are less discussed so far with technology-based intervention though. This pilot study was aimed to investigate the effect of telehealth assisted intervention on weight reduction, mood status, and eating behavior change under a smartphone application (app) with novel 3D food picture recognition and incorporated with cognitive behavioral training programs. Adult aged 30–60 years old with overweight were recruited and randomly assigned to control-first group and intervention-first group. In period 1, control-first group had regular life and intervention-first group underwent app intervention; in period 2, two groups went crossover. Body composition and psychological/behavioral questionnaires were collected at baseline, end of period 1, and end of period 2. Nonparametric statistics was performed for data analyzing. A total of 20 participants were enrolled. In control-first group, there were statistically significant reduction in body weight (− 0.55 kg,p = 0.02) and change of body weight percentage (− 0.6%,p = 0.02) after App use. In intervention-first group, the fat percentage decreased by 0.4% after App use in period 1, and increased by 0.05% in period 2. The integrated crossover data revealed that subjects of App group had significant improvements in mindful eating behavior. This pilot study showed the effectiveness in using CogniNU app for weight control and eating behavior. The difference of short-term and long-term effectiveness of technology-based weight control intervention deserves more investigation in the future.

Clinical Trial Registration: ISRCTN16082909.
Control of white mold (Sclerotinia sclerotiorum) through plant-mediated RNA interference
Authors: Walker Philip L. , Ziegler Dylan J. , Giesbrecht Shayna , McLoughlin Austein , Wan Joey , Khan Deirdre , Hoi Vanessa , Whyard Steve , Belmonte Mark F.
Published: April 2023

The causative agent of white mold, Sclerotinia sclerotiorum, is capable of infecting over 600 plant species and is responsible for significant crop losses across the globe. Control is currently dependent on broad-spectrum chemical agents that can negatively impact the agroecological environment, presenting a need to develop alternative control measures. In this study, we developed transgenic Arabidopsis thaliana (AT1703) expressing hairpin (hp)RNA to silence S. sclerotiorum ABHYDROLASE-3 and slow infection through host induced gene silencing (HIGS). Leaf infection assays show reduced S. sclerotiorum lesion size, fungal load, and ABHYDROLASE-3 transcript abundance in AT1703 compared to wild-type Col-0. To better understand how HIGS influences host–pathogen interactions, we performed global RNA sequencing on AT1703 and wild-type Col-0 directly at the site of S. sclerotiorum infection. RNA sequencing data reveals enrichment of the salicylic acid (SA)-mediated systemic acquired resistance (SAR) pathway, as well as transcription factors predicted to regulate plant immunity. Using RT-qPCR, we identified predicted interacting partners of ABHYDROLASE-3 in the polyamine synthesis pathway of S. sclerotiorum that demonstrate co-reduction with ABHYDROLASE-3 transcript levels during infection. Together, these results demonstrate the utility of HIGS technology in slowing S. sclerotiorum infection and provide insight into the role of ABHYDROLASE-3 in the A. thaliana–S. sclerotiorum pathosystem.
STEP-COVID: a pilot study of a prenatal intervention for pregnant women during the COVID-19 pandemic
Authors: Berthelot Nicolas , Garon-Bissonnette Julia , Drouin-Maziade Christine , Bergeron Vanessa , Sériès Thibaut
Published: April 2023

The COVID-19 pandemic has been associated with a global increase in psychological distress in pregnant women. This study evaluated the effects of STEP-COVID, a six-session mentalization-based prenatal group program offered online during the COVID-19 pandemic. The 100 participants were allocated to STEP-COVID or to the natural trajectory of prenatal care. Pre- and post-intervention assessments included measures of psychological distress, post-traumatic symptoms and positive affectivity. Perception of change during pregnancy on resilience-promoting factors was also assessed at post-intervention. A significant decrease in psychological distress and post-traumatic symptoms and an increase in positive affectivity were observed in participants in the intervention condition, whereas only post-traumatic symptoms improved in the control condition. Women who participated in STEP-COVID also reported greater changes during pregnancy on resilience-promoting factors than women in the control condition. Results hold promise for buffering the effect of the pandemic on the mental health of pregnant women using brief online interventions. Clinical trial registration: NCT05419167 (15/06/2022)
High levels of burnout among health professionals treating COVID-19 patients in two Nile basin countries with limited resources
Authors: EL Dabbah Noha Ahmed , Elhadi Yasir Ahmed Mohammed
Published: April 2023

Burnout syndrome is a real cause for concern in African health facilities. Healthcare professionals (HCPs) burnout is considered a great public health problem and especially during pandemics as several physical and emotional stressors on this population can lead to increased burnout. This study aimed to investigate the frequency and associated factors of occupational burnout among HCPs working at COVID-19 isolation facilities in Egypt and Sudan. This is important to summarize lessons learned and inform relevant interventions for future pandemic responses. A cross-sectional survey was conducted among frontline HCPs from May 2021 to July 2021. An online, anonymous, self-administered questionnaire was used for data collection. Occupational burnout was estimated using  the Oldenburg Burnout Inventory. A total of 362 HCPs participated in the study and were equally recruited from Egypt (181) and Sudan (181) with a mean age of (31.84 ± 8.32) years. More than half of HCPs were females (60%) and physicians (58.3%). Most HCPs included in the study had high levels of work disengagement (75.4%) and emotional exhaustion (98.6%). Burnout syndrome was present in 75% of the HCPs with 77% among Egyptian HCPs and 71% among Sudanese HCPs. Multivariate logistic regression was used to determine predictors of burnout, working hours per week were the parameters associated with burnout syndrome among Egyptian HCPs; while for Sudanese HCPs, these were age and number of days off. The study revealed a high level of burnout syndrome among HCPs working at COVID-19 isolation facilities in both Egypt and Sudan. Appropriate actions should be taken to preserve the mental health status of HCPs through the establishment of effective and efficient coping strategies.
Utilizing EEG and fNIRS for the detection of sleep-deprivation-induced fatigue and its inhibition using colored light stimulation
Authors: Shoaib Zeshan , Akbar Arbab , Kim Eung Soo , Kamran Muhammad Ahmad , Kim Jun Hyun , Jeong Myung Yung
Published: April 2023

Drowsy driving is a common, but underestimated phenomenon in terms of associated risks as it often results in crashes causing fatalities and serious injuries. It is a challenging task to alert or reduce the driver’s drowsy state using non-invasive techniques. In this study, a drowsiness reduction strategy has been developed and analyzed using exposure to different light colors and recording the corresponding electrical and biological brain activities. 31 subjects were examined by dividing them into 2 classes, a control group, and a healthy group. Fourteen EEG and 42 fNIRS channels were used to gather neurological data from two brain regions (prefrontal and visual cortices). Experiments shining 3 different colored lights have been carried out on them at certain times when there is a high probability to get drowsy. The results of this study show that there is a significant increase in HbO of a sleep-deprived participant when he is exposed to blue light. Similarly, the beta band of EEG also showed an increased response. However, the study found that there is no considerable increase in HbO and beta band power in the case of red and green light exposures. In addition to that, values of other physiological signals acquired such as heart rate, eye blinking, and self-reported Karolinska Sleepiness Scale scores validated the findings predicted by the electrical and biological signals. The statistical significance of the signals achieved has been tested using repeated measures ANOVA and t-tests. Correlation scores were also calculated to find the association between the changes in the data signals with the corresponding changes in the alertness level.