bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies
Authors: Gallo Selene , El-Gazzar Ahmed , Zhutovsky Paul , Thomas Rajat M. , Javaheripour Nooshin , Li Meng , Bartova Lucie , Bathula Deepti , Dannlowski Udo , Davey Christopher , Frodl Thomas , Gotlib Ian , Grimm Simone , Grotegerd Dominik , Hahn Tim , Hamilton Paul J. , Harrison Ben J. , Jansen Andreas , Kircher Tilo , Meyer Bernhard , Nenadić Igor , Olbrich Sebastian , Paul Elisabeth , Pezawas Lukas , Sacchet Matthew D. , Sämann Philipp , Wagner Gerd , Walter Henrik , Walter Martin ,   PsyMRI, van Wingen Guido
Published: February 2023

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized using GCN-Explainer, an ablation study and univariate t-testing. The results showed a mean classification accuracy of 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Sex classification accuracy was substantially better across datasets (73–81%). Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes. These results suggest that whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity as further supported by the higher accuracy for sex classification using the same methods. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.
GWAS-identified bipolar disorder risk allele in the FADS1/2 gene region links mood episodes and unsaturated fatty acid metabolism in mutant mice
Authors: Yamamoto Hirona , Lee-Okada Hyeon-Cheol , Ikeda Masashi , Nakamura Takumi , Saito Takeo , Takata Atsushi , Yokomizo Takehiko , Iwata Nakao , Kato Tadafumi , Kasahara Takaoki
Published: February 2023

Large-scale genome-wide association studies (GWASs) on bipolar disorder (BD) have implicated the involvement of the fatty acid desaturase (FADS) locus. These enzymes (FADS1 and FADS2) are involved in the metabolism of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are thought to potentially benefit patients with mood disorders. To model reductions in the activity of FADS1/2 affected by the susceptibility alleles, we generated mutant mice heterozygously lacking both Fads1/2 genes. We measured wheel-running activity over six months and observed bipolar swings in activity, including hyperactivity and hypoactivity. The hyperactivity episodes, in which activity was far above the norm, usually lasted half a day; mice manifested significantly shorter immobility times on the behavioral despair test performed during these episodes. The hypoactivity episodes, which lasted for several weeks, were accompanied by abnormal circadian rhythms and a marked decrease in wheel running, a spontaneous behavior associated with motivation and reward systems. We comprehensively examined lipid composition in the brain and found that levels of certain lipids were significantly altered between wild-type and the heterozygous mutant mice, but no changes were consistent with both sexes and either DHA or EPA was not altered. However, supplementation with DHA or a mixture of DHA and EPA prevented these episodic behavioral changes. Here we propose that heterozygous Fads1/2 knockout mice are a model of BD with robust constitutive, face, and predictive validity, as administration of the mood stabilizer lithium was also effective. This GWAS-based model helps to clarify how lipids and their metabolisms are involved in the pathogenesis and treatment of BD.
NSUN2 promotes osteosarcoma progression by enhancing the stability of FABP5 mRNA via m5C methylation
Authors: Yang Min , Wei Renxiong , Zhang Sheng , Hu Sang , Liang Xiaoxiao , Yang Zhiqiang , Zhang Chong , Zhang Yufeng , Cai Lin , Xie Yuanlong
Published: February 2023

5-methylcytosine (m5C) modification, which is mainly induced by the RNA methyltransferase NSUN2 (NOP2/Sun domain family, member 2), is an important chemical posttranscriptional modification in mRNA and has been proven to play important roles in the progression of many cancers. However, the functions and underlying molecular mechanisms of NSUN2-mediated m5C in osteosarcoma (OS) remain unclear. In this study, we found NSUN2 was highly expressed in OS tissues and cells. We also discovered that higher expression of NSUN2 predicted poorer prognosis of OS patients. Our study showed that NSUN2 could promote the progression of OS cells. Moreover, we employed RNA sequencing, RNA immunoprecipitation (RIP), and methylated RIP to screen and validate the candidate targets of NSUN2 and identified FABP5 as the target. We observed that NSUN2 stabilized FABP5 mRNA by inducing m5C modification and further promoted fatty acid metabolism in OS cells. Moreover, both knocking down the expression of FABP5 and adding fatty acid oxidation inhibitor could counterbalance the promoting effect of NSUN2 on the progression of OS. Our study confirms that NSUN2 can up-regulate the expression of FABP5 by improving the stability of FABP5 mRNA via m5C, so as to promote fatty acid metabolism in OS cells, and finally plays the role in promoting the progression of OS. Our findings suggest that NSUN2 is a promising prognostic marker for OS patients and may serve as a potential therapeutic target for OS treatment.
Glioblastoma upregulates SUMOylation of hnRNP A2/B1 to eliminate the tumor suppressor miR-204-3p, accelerating angiogenesis under hypoxia
Authors: Guo Qindong , Fan Yang , Wang Qingtong , Li Boyan , Qiu Wei , Qi Yanhua , Pan Ziwen , Zhang Shouji , Zhao Shulin , Yang Kehui , Xu Hao , Li Ming , Gao Zijie , Xu Jianye , Wang Huizhi , Wang Shaobo , Tang Qilin , Qiu Jiawei , Guo Xing , Deng Lin , Zhang Ping , Zhao Rongrong , Xue Hao , Wang Chengwei , Li Gang
Published: February 2023

Glioma is the most common malignant tumor of the central nervous system in adults. The tumor microenvironment (TME) is related to poor prognosis in glioma patients. Glioma cells could sort miRNA into exosomes to modify TME. And hypoxia played an important role in this sorting process, but the mechanism is not clear yet. Our study was to find miRNAs sorted into glioma exosomes and reveal the sorting process. Sequencing analysis of glioma patients cerebrospinal fluid (CSF) and tissue showed that miR-204-3p tends to be sorted into exosomes. miR-204-3p suppressed glioma proliferation through the CACNA1C/MAPK pathway. hnRNP A2/B1 can accelerate exosome sorting of miR-204-3p by binding a specific sequence. Hypoxia plays an important role in exosome sorting of miR-204-3p. Hypoxia can upregulate miR-204-3p by upregulating the translation factor SOX9. Hypoxia promotes the transfer of hnRNP A2/B1 to the cytoplasm by upregulating SUMOylation of hnRNP A2/B1 to eliminate miR-204-3p. Exosomal miR-204-3p promoted tube formation of vascular endothelial cells through the ATXN1/STAT3 pathway. The SUMOylation inhibitor TAK-981 can inhibit the exosome-sorting process of miR-204-3p to inhibit tumor growth and angiogenesis. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma. This study revealed that glioma cells can eliminate the suppressor miR-204-3p to accelerate angiogenesis under hypoxia by upregulating SUMOylation. The SUMOylation inhibitor TAK-981 could be a potential drug for glioma.
MTSS1 curtails lung adenocarcinoma immune evasion by promoting AIP4-mediated PD-L1 monoubiquitination and lysosomal degradation
Authors: Wang Yuan , Jia Zhenchang , Liang Chenxi , He Yunfei , Cong Min , Wu Qiuyao , Tian Pu , He Dasa , Miao Xiang , Sun Beibei , Yin Yue , Peng Chao , Yao Feng , Fu Da , Liang Yajun , Zhang Peiyuan , Xiong Hua , Hu Guohong
Published: February 2023

Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has shown durable clinical benefits in lung cancer. However, many patients respond poorly to ICB treatment, underscoring an incomplete understanding of PD-L1 regulation and therapy resistance. Here, we find that MTSS1 is downregulated in lung adenocarcinoma, leading to PD-L1 upregulation, impairment of CD8+ lymphocyte function, and enhanced tumor progression. MTSS1 downregulation correlates with improved ICB efficacy in patients. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 for PD-L1 monoubiquitination at Lysine 263, leading to PD-L1 endocytic sorting and lysosomal degradation. In addition, EGFR-KRAS signaling in lung adenocarcinoma suppresses MTSS1 and upregulates PD-L1. More importantly, combining AIP4-targeting via the clinical antidepressant drug clomipramine and ICB treatment improves therapy response and effectively suppresses the growth of ICB-resistant tumors in immunocompetent mice and humanized mice. Overall, our study discovers an MTSS1-AIP4 axis for PD-L1 monoubiquitination and reveals a potential combinatory therapy with antidepressants and ICB.
Slc11a1 gene polymorphism influences dextran sulfate sodium (DSS)-induced colitis in a murine model of acute inflammation
Authors: de Andrade Stephane Tereza Queiroz , Guidugli Tamíris Isabela , Borrego Andrea , Rodrigues Bridilla Luiza Colhado , Fernandes Natália Coelho Couto de Azevedo , Guerra Juliana Mariotti , de Sousa Jean Gabriel , Starobinas Nancy , Jensen José Ricardo , Cabrera Wafa Hanna Koury , De Franco Marcelo , Ibañez Olga Martinez , Massa Solange , Ribeiro Orlando Garcia
Published: February 2023

Ulcerative Colitis (UC) is an inflammatory disease characterized by colonic mucosal lesions associated with an increased risk of carcinogenesis. UC pathogenesis involves environmental and genetic factors. Genetic studies have indicated the association of gene variants coding for the divalent metal ion transporter SLC11A1 protein (formerly NRAMP1) with UC susceptibility in several animal species. Two mouse lines were genetically selected for high (AIRmax) or low (AIRmin) acute inflammatory responses (AIR). AIRmax is susceptible, and AIRmin is resistant to DSS-induced colitis and colon carcinogenesis. Furthermore, AIRmin mice present polymorphism of the Slc11a1 gene. Here we investigated the possible modulating effect of the Slc11a1 R and S variants in DSS-induced colitis by using AIRmin mice homozygous for Slc11a1R (AIRminRR) or S (AIRminSS) alleles. We evaluated UC by the disease activity index (DAI), considering weight loss, diarrhea, blood in the anus or feces, cytokines, histopathology, and cell populations in the distal colon epithelium. AIRminSS mice have become susceptible to DSS effects, with higher DAI, IL6, G-CSF, and MCP-1 production and morphological and colon histopathological alterations than AIRminRR mice. The results point to a role of the Slc11a1 S allele in DSS colitis induction in the genetic background of AIRmin mice.
Uphill energy transfer mechanism for photosynthesis in an Antarctic alga
Authors: Kosugi Makiko , Kawasaki Masato , Shibata Yutaka , Hara Kojiro , Takaichi Shinichi , Moriya Toshio , Adachi Naruhiko , Kamei Yasuhiro , Kashino Yasuhiro , Kudoh Sakae , Koike Hiroyuki , Senda Toshiya
Published: February 2023

Prasiola crispa, an aerial green alga, forms layered colonies under the severe terrestrial conditions of Antarctica. Since only far-red light is available at a deep layer of the colony, P. crispa has evolved a molecular system for photosystem II (PSII) excitation using far-red light with uphill energy transfer. However, the molecular basis underlying this system remains elusive. Here, we purified a light-harvesting chlorophyll (Chl)-binding protein complex from P. crispa (Pc-frLHC) that excites PSII with far-red light and revealed its ring-shaped structure with undecameric 11-fold symmetry at 3.13 Å resolution. The primary structure suggests that Pc-frLHC evolved from LHCI rather than LHCII. The circular arrangement of the Pc-frLHC subunits is unique among eukaryote LHCs and forms unprecedented Chl pentamers at every subunit‒subunit interface near the excitation energy exit sites. The Chl pentamers probably contribute to far-red light absorption. Pc-frLHC’s unique Chl arrangement likely promotes PSII excitation with entropy-driven uphill excitation energy transfer.
Molecular mechanisms of coronary artery disease risk at the PDGFD locus
Authors: Kim Hyun-Jung , Cheng Paul , Travisano Stanislao , Weldy Chad , Monteiro João P. , Kundu Ramendra , Nguyen Trieu , Sharma Disha , Shi Huitong , Lin Yi , Liu Boxiang , Haldar Saptarsi , Jackson Simon , Quertermous Thomas
Published: February 2023

Genome wide association studies for coronary artery disease (CAD) have identified a risk locus at 11q22.3. Here, we verify with mechanistic studies that rs2019090 andPDGFDrepresent the functional variant and gene at this locus. Further, FOXC1/C2 transcription factor binding at rs2019090 is shown to promotePDGFDtranscription through the CAD promoting allele. With single cell transcriptomic and histology studies withPdgfdknockdown in an SMC lineage tracing male atherosclerosis mouse model we find that Pdgfd promotes expansion, migration, and transition of SMC lineage cells to the chondromyocyte phenotype. Pdgfd also increases adventitial fibroblast and pericyte expression of chemokines and leukocyte adhesion molecules, which is linked to plaque macrophage recruitment. Despite these changes there is no effect ofPdgfddeletion on overall plaque burden. These findings suggest thatPDGFDmediates CAD risk by promoting deleterious phenotypic changes in SMC, along with an inflammatory response that is primarily focused in the adventitia.
Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation
Authors: Bernkopf Marie , Abdullah Ummi B. , Bush Stephen J. , Wood Katherine A. , Ghaffari Sahar , Giannoulatou Eleni , Koelling Nils , Maher Geoffrey J. , Thibaut Loïc M. , Williams Jonathan , Blair Edward M. , Kelly Fiona Blanco , Bloss Angela , Burkitt-Wright Emma , Canham Natalie , Deng Alexander T. , Dixit Abhijit , Eason Jacqueline , Elmslie Frances , Gardham Alice , Hay Eleanor , Holder Muriel , Homfray Tessa , Hurst Jane A. , Johnson Diana , Jones Wendy D. , Kini Usha , Kivuva Emma , Kumar Ajith , Lees Melissa M. , Leitch Harry G. , Morton Jenny E. V. , Németh Andrea H. , Ramachandrappa Shwetha , Saunders Katherine , Shears Deborah J. , Side Lucy , Splitt Miranda , Stewart Alison , Stewart Helen , Suri Mohnish , Clouston Penny , Davies Robert W. , Wilkie Andrew O. M. , Goriely Anne
Published: February 2023

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1–2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)—that could be quantified in semen for paternal cases (recurrence risks of 5.6–12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling.
A general thermodynamics-triggered competitive growth model to guide the synthesis of two-dimensional nonlayered materials
Authors: Zhao Zijing , Fang Zhi , Han Xiaocang , Yang Shiqi , Zhou Cong , Zeng Yi , Zhang Biao , Li Wei , Wang Zhan , Zhang Ying , Zhou Jian , Zhou Jiadong , Ye Yu , Hou Xinmei , Zhao Xiaoxu , Gao Song , Hou Yanglong
Published: February 2023

Two-dimensional (2D) nonlayered materials have recently provoked a surge of interest due to their abundant species and attractive properties with promising applications in catalysis, nanoelectronics, and spintronics. However, their 2D anisotropic growth still faces considerable challenges and lacks systematic theoretical guidance. Here, we propose a general thermodynamics-triggered competitive growth (TTCG) model providing a multivariate quantitative criterion to predict and guide 2D nonlayered materials growth. Based on this model, we design a universal hydrate-assisted chemical vapor deposition strategy for the controllable synthesis of various 2D nonlayered transition metal oxides. Four unique phases of iron oxides with distinct topological structures have also been selectively grown. More importantly, ultra-thin oxides display high-temperature magnetic ordering and large coercivity. MnxFeyCo3-x-yO4 alloy is also demonstrated to be a promising room-temperature magnetic semiconductor. Our work sheds light on the synthesis of 2D nonlayered materials and promotes their application for room-temperature spintronic devices.
Wireless communications sensing and security above 100 GHz
Authors: Jornet Josep M. , Knightly Edward W. , Mittleman Daniel M.
Published: February 2023

The field of sub-terahertz wireless communications is advancing rapidly, with major research efforts ramping up around the globe. To address some of the significant hurdles associated with exploiting these high frequencies for broadband and secure networking, systems will require extensive new capabilities for sensing their environment and manipulating their broadcasts. Based on these requirements, a vision for future wireless systems is beginning to emerge. In this Perspective article, we discuss some of the prominent challenges and possible solutions which are at the forefront of current research, and which will contribute to the architecture of wireless platforms beyond 5G.
Endogenous retroviruses and TDP-43 proteinopathy form a sustaining feedback driving intercellular spread of Drosophila neurodegeneration
Authors: Chang Yung-Heng , Dubnau Josh
Published: February 2023

Inter-cellular movement of “prion-like” proteins is thought to explain propagation of neurodegeneration between cells. For example, propagation of abnormally phosphorylated cytoplasmic inclusions of TAR-DNA-Binding protein (TDP-43) is proposed to underlie progression of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). But unlike transmissible prion diseases, ALS and FTD are not infectious and injection of aggregated TDP-43 is not sufficient to cause disease. This suggests a missing component of a positive feedback necessary to sustain disease progression. We demonstrate that endogenous retrovirus (ERV) expression and TDP-43 proteinopathy are mutually reinforcing. Expression of either Drosophila mdg4-ERV (gypsy) or the human ERV, HERV-K (HML-2) are each sufficient to stimulate cytoplasmic aggregation of human TDP-43. Viral ERV transmission also triggers TDP-43 pathology in recipient cells that express physiological levels of TDP-43, whether they are in contact or at a distance. This mechanism potentially underlies the TDP-43 proteinopathy-caused neurodegenerative propagation through neuronal tissue.
Real-space imaging of a phenyl group migration reaction on metal surfaces
Authors: Ruan Zilin , Li Baijin , Lu Jianchen , Gao Lei , Sun Shijie , Zhang Yong , Cai Jinming
Published: February 2023

The explorations to extend present chemical synthetic methods are of great importance to simplify synthetic routes of chemical species. Additionally, understanding the chemical reaction mechanisms is critical to achieve controllable synthesis for applications. Here, we report the on-surface visualization and identification of a phenyl group migration reaction of 1,4-dimethyl-2,3,5,6-tetraphenyl benzene (DMTPB) precursor on Au(111), Cu(111) and Ag(110) substrates. With the combination of bond-resolved scanning tunneling microscopy (BR-STM), noncontact atomic force microscopy (nc-AFM) and density functional theory (DFT) calculations, the phenyl group migration reaction of DMTPB precursor is observed, forming various polycyclic aromatic hydrocarbons on the substrates. DFT calculations reveal that the multiple-step migrations are facilitated by the hydrogen radical attack, inducing cleavage of phenyl groups and subsequent rearomatization of the intermediates. This study provides insights into complex surface reaction mechanisms at the single molecule level, which may guide the design of chemical species.
Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology
Authors: Ng Xin Yi , Wu Yumei , Lin Youneng , Yaqoob Sidra Mohamed , Greene Lois E. , De Camilli Pietro , Cao Mian
Published: February 2023

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by defective dopaminergic (DAergic) input to the striatum. Mutations in two genes encoding synaptically enriched clathrin-uncoating factors, synaptojanin 1 (SJ1) and auxilin, have been implicated in atypical Parkinsonism. SJ1 knock-in (SJ1-KIRQ) mice carrying a disease-linked mutation display neurological manifestations reminiscent of Parkinsonism. Here we report that auxilin knockout (Aux-KO) mice display dystrophic changes of a subset of nigrostriatal DAergic terminals similar to those of SJ1-KIRQ mice. Furthermore, Aux-KO/SJ1-KIRQ double mutant mice have shorter lifespan and more severe synaptic defects than single mutant mice. These include increase in dystrophic striatal nerve terminals positive for DAergic markers and for the PD risk protein SV2C, as well as adaptive changes in striatal interneurons. The synergistic effect of the two mutations demonstrates a special lability of DAergic neurons to defects in clathrin uncoating, with implications for PD pathogenesis in at least some forms of this condition.
WS22 database, Wigner Sampling and geometry interpolation for configurationally diverse molecular datasets﻿
Authors: Pinheiro Jr Max , Zhang Shuang , Dral Pavlo O. , Barbatti Mario
Published: February 2023

Multidimensional surfaces of quantum chemical properties, such as potential energies and dipole moments, are common targets for machine learning, requiring the development of robust and diverse databases extensively exploring molecular configurational spaces. Here we composed the WS22 database covering several quantum mechanical (QM) properties (including potential energies, forces, dipole moments, polarizabilities, HOMO, and LUMO energies) for ten flexible organic molecules of increasing complexity and with up to 22 atoms. This database consists of 1.18 million equilibrium and non-equilibrium geometries carefully sampled from Wigner distributions centered at different equilibrium conformations (either at the ground or excited electronic states) and further augmented with interpolated structures. The diversity of our datasets is demonstrated by visualizing the geometries distribution with dimensionality reduction as well as via comparison of statistical features of the QM properties with those available in existing datasets. Our sampling targets broader quantum mechanical distribution of the configurational space than provided by commonly used sampling through classical molecular dynamics, upping the challenge for machine learning models.
Novel data dependent divider circuit block implementation for complex division and area critical applications
Authors: Patankar Udayan S. , Flores Miguel E. , Koel Ants
Published: February 2023

This article elaborates on the state-of-the-art novel Udayan S. Patankar (USP)-Awadhoot algorithm for distinctive implementation area improvement for area-critical electronic applications. The proposed USP-Awadhoot divider is a digit recurrence class, but it can be flexibly implemented as a restoring or nonrestoring algorithm. The implementation example indicates the use of the Baudhayan-Pythagoras triplet method in association with the proposed USP-Awadhoot divider. The triplet method provides an easy way to generate Mat_Term1, Mat_Term2, and T_Term, which are further utilized with the proposed USP-Awadhoot divider. The USP-Awadhoot divider is implemented in three parts. First is preprocessing circuit stage for executing a dynamic separate scaling operation on input operands, ensuring the inputs are in the correct form. Second is the processing circuit stage for implementing the conversion logic expressed by the Awadhoot matrix, and third is the postprocessing circuit stage for recombining the individual results into the final result. The proposed divider works upto 285 MHz frequency with a power estimation of 3.366 W, also significantly improves the chip area requirements over those of the commercially and noncommercially implemented solutions.
Satellite observation of atmospheric CO2 and water storage change over Iran
Authors: Safaeian Samaneh , Falahatkar Samereh , Tourian Mohammad J.
Published: February 2023

Like many other Middle East countries, Iran has been suffering from severe water shortages over the last two decades, as evidenced by significant decline in surface water and groundwater levels. The observed changes in water storage can be attributed to the mutually reinforcing effects of human activities, climatic variability, and of course the climate change. The objective of this study is to analyze the dependency of atmospheric CO2 increase on the water shortage of Iran, for which we investigate the spatial relationship between water storage change and CO2 concentration using large scale satellite data. We conduct our analysis using water storage change data from GRACE satellite and atmospheric CO2 concentration from GOSAT and SCIAMACHY satellites during 2002–2015. To analyze the long-term behavior of time series we benefit from Mann-Kendal test and for the investigation of the relationship between atmospheric CO2 concentration and total water storage we use Canonical Correlation Analysis (CCA) and Regression model. Our Results show that the water storage change anomaly and CO2 concentration are negatively correlated especially in northern, western, southwest (Khuzestan province), and also southeast (Kerman, Hormozgan, Sistan, and Baluchestan provinces) of Iran. CCA results reveal that in the most of northern regions, the decrease in water storage is significantly influenced by the increase of CO2 concentration. The results further show that precipitation in the highland and peaks does not seem to be influenced by the long and short-term variation in CO2 concentration. Besides, our results show that the CO2 concentration is slightly correlated with a weak positive trend in evapotranspiration over agricultural areas. Thus, the indirect effect of CO2 on increasing evapotranspiration is observed spatially in the whole of Iran. The results of the regression model between total water storage change and carbon dioxide (R2 = 0.91)/water discharge/water consumption show that carbon dioxide has the highest effect on total water storage change at large scale. The results of this study will contribute to both water resource management and mitigation plans to achieve the goal of CO2 emission reduction.
Nature-inspired stochastic hybrid technique for joint and individual inversion of DC and MT data
Authors: Sarkar Kuldeep , Mukesh  , Singh Upendra K.
Published: February 2023

Here, a new naturally-inspired stochastic nonlinear joint and individual inversion technique for integrating direct current (DC) and magnetotelluric (MT) data interpretation-based simulation of a swarm intelligence combo with specific capabilities for exploitation of the variable weight particle swarm optimizer (vPSO) and exploration of the grey wolf optimizer (GWO), vPSOGWO, is used. They are particularly notable for their capacity for information exchange while hunting for food. Through synthetic MT and DC data contaminated with various sets of random noise, the applicability of the anticipated vPSOGWO algorithm based joint and individual inversion algorithm was assessed. The field examples, collected from diversified different geological terrains, including Digha (West Bengal), India; Sundar Pahari (Jharkhand), India; Puga Valley (Ladakh), India; New Brunswick, Canada; and South Central Australia, have shown the practical application of the proposed algorithm. Further, a Bayesian probability density function (bpdf) for estimating a mean global model and uncertainty assessment in posterior; and a histogram for model resolution assessment have also been created using 1000 inverted models. We examined the inverted outcomes and compared them with results from other cutting-edge methodologies, including the GWO, PSO, genetic algorithm (GA), Levenberg–Marquardt (LM), and ridge-regression (RR). Our findings showed that the current methodology is more effective than the GWO, PSO, GA, LM, and RR techniques at consistently improving the convergence of the global minimum. In contrast to earlier approaches, the current cutting-edge strategy vPSOGWO offers an improved resolution of an additional significant crustal thickness of about 65.68 ± 1.96 km over the Puga Valley, in which the inverted crustal thickness determined by vPSOGWO agrees well with the published crustal thickness over the Puga Valley. The new technology brings simulations closer to genuine models by significantly reducing uncertainty and enhancing model resolution.
Effect of in vitro cultivation on human gut microbiota composition using 16S rDNA amplicon sequencing and metabolomics approach
Authors: Średnicka Paulina , Roszko Marek Łukasz , Popowski Dominik , Kowalczyk Monika , Wójcicki Michał , Emanowicz Paulina , Szczepańska Magdalena , Kotyrba Danuta , Juszczuk-Kubiak Edyta
Published: February 2023

Gut microbiota (GM) plays many key functions and helps maintain the host’s health. Consequently, the development of GM cultivation under in vitro stimulating physiological conditions has gained extreme interest in different fields. In this study, we evaluated the impact of four culture media: Gut Microbiota Medium (GMM), Schaedler Broth (SM), Fermentation Medium (FM), and Carbohydrate Free Basal Medium (CFBM) on preserving the biodiversity and metabolic activity of human GM in batch in vitro cultures using PMA treatment coupled with 16S rDNA sequencing (PMA-seq) and LC-HR-MS/MS untargeted metabolomics supplemented with GC–MS SCFA profiling. Before the experiments, we determined the possibility of using the pooled faecal samples (MIX) from healthy donors (n = 15) as inoculum to reduce the number of variables and ensure the reproducibility of in vitro cultivation tests. Results showed the suitability of pooling faecal samples for in vitro cultivation study. Non-cultured MIX inoculum was characterized by higher α-diversity (Shannon effective count, and Effective microbial richness) compared to inocula from individual donors. After 24 h of cultivation, a significant effect of culture media composition on GM taxonomic and metabolomic profiles was observed. The SM and GMM had the highest α-diversity (Shannon effective count). The highest number of core ASVs (125) shared with non-cultured MIX inoculum and total SCFAs production was observed in the SM. These results might contribute to the development of standardized protocols for human GM in vitro cultivation by preventing methodological bias in the data.
Uric acid and risk of pre-eclampsia: results from a large case–control study and meta-analysis of prospective studies
Authors: Colmenares-Mejia Claudia C. , Quintero-Lesmes Doris C. , Bautista-Niño Paula K. , Guío Elizabeth , Paez Maria C. , Beltrán Mónica , Williams David , Gray Kathryn J. , Casas Juan P. , Serrano Norma C.
Published: February 2023

To quantify the association between maternal uric acid levels and pre-eclampsia risk in a large collection of primigravid women. A case–control study (1365 cases of pre-eclampsia and 1886 normotensive controls) was conducted. Pre-eclampsia was defined as blood pressure ≥ 140/90 mmHg and proteinuria ≥ 300 mg/24 h. Sub-outcome analysis included early, intermediate, and late pre-eclampsia. Multivariable analysis for pre-eclampsia and its sub-outcomes was conducted using binary and multinomial logistic regression, respectively. Additionally, a systematic review and meta-analysis of cohort studies measuring uric acid levels < 20 weeks of gestation was performed to rule out reverse causation. There was a positive linear association between increasing uric acid levels and presence of pre-eclampsia. Adjusted odds ratio of pre-eclampsia was 1.21 (95%CI 1.11–1.33) for every one standard deviation increase in uric acid levels. No differences in the magnitude of association were observed between early and late pre-eclampsia. Three studies with uric acid measured < 20 weeks’ gestation were identified, with a pooled OR for pre-eclampsia of 1.46 (95%CI 1.22–1.75) for a top vs. bottom quartile comparison. Maternal uric acid levels are associated with risk of pre-eclampsia. Mendelian randomisation studies would be helpful to further explore the causal role of uric acid in pre-eclampsia.
Validation of an MD simulation approach for electrical field responsive micelles and their application in drug delivery
Authors: Razavi Leila , Raissi Heidar , Farzad Farzaneh
Published: February 2023

In the current work, a new type of micelle is designed that has active connectivity in respond to exterior stimulus and the desired water solubility. Two end-ornamented homopolymers, polystyrene-beta-cyclodextrin (PS-β-CD) and polyethylene oxide-ferrocene (PE-FE), can aggregate as a supramolecular micelle (PS-β-CD/PE-FE) by the guest–host interactions. Our results showed that the Lennard–Jones and hydrophobic interactions are the main powerful forces for the micelle formation process. It was found that the electrical field plays a role as a driving force in the reversible assembly-disassembly of the micellar system. Moreover, for the first time, we examined the PS-β-CD/PE-FE micelle interaction as a drug delivery system with anastrozole (ANS) and mitomycin C (MIC) anti-cancer drugs. The investigation of the total energy between PS-β-CD/PE-FE micelle and drugs predicts the drug adsorption process as favorable (Etotal = − 638.67 and − 259.80 kJ/mol for the Micelle@ANS and Micelle@MIC complexes, respectively). Our results offer a deep understanding of the micelle formation process, the electrical field-respond, and drug adsorption behaviors of the micelle. This simulation study has been accomplished by employing classical molecular dynamics calculation.
Restoring speech intelligibility for hearing aid users with deep learning
Authors: Diehl Peter Udo , Singer Yosef , Zilly Hannes , Schönfeld Uwe , Meyer-Rachner Paul , Berry Mark , Sprekeler Henning , Sprengel Elias , Pudszuhn Annett , Hofmann Veit M.
Published: February 2023

Almost half a billion people world-wide suffer from disabling hearing loss. While hearing aids can partially compensate for this, a large proportion of users struggle to understand speech in situations with background noise. Here, we present a deep learning-based algorithm that selectively suppresses noise while maintaining speech signals. The algorithm restores speech intelligibility for hearing aid users to the level of control subjects with normal hearing. It consists of a deep network that is trained on a large custom database of noisy speech signals and is further optimized by a neural architecture search, using a novel deep learning-based metric for speech intelligibility. The network achieves state-of-the-art denoising on a range of human-graded assessments, generalizes across different noise categories and—in contrast to classic beamforming approaches—operates on a single microphone. The system runs in real time on a laptop, suggesting that large-scale deployment on hearing aid chips could be achieved within a few years. Deep learning-based denoising therefore holds the potential to improve the quality of life of millions of hearing impaired people soon.
Determination of optimum dose based of biological responses of lethal dose (LD25, 50, 75) and growth reduction (GR25, 50, 75) in ‘Yaghouti’ grape due to gamma radiation
Authors: Ghasemi-Soloklui Ali Akbar , Kordrostami Mojtaba , Karimi Rouhollah
Published: February 2023

Ionizing radiations are a helpful technique and have improved financial potential in developing new and unique commercially important fruit tree varieties. The ‘Yaghouti’ grape cuttings were treated with 0 (control), 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 Gy gamma ray (γ) doses. The objectives of this study were to (1) investigate the effects of γ radiation on the survival rate, leaves, shoots, and root morphometric traits after γ irradiation; (2) Measurement of the 25, 50, and 75% lethal dose and 25, 50, and 75% growth reduction dose based on leaves, shoots, and root morphometric characteristics to estimate grape radiosensitivity; (3) Ultimately, determining the optimum dose of γ irradiation based biological responses (LD25, 50, 75 and GR25, 50, 75) in Yaghouti grape. The findings demonstrate that the lethal dose of the ‘Yaghouti’ was 18 Gy for LD25, 30 Gy for LD50, and 48 Gy for LD75, respectively. Furthermore, our findings showed that increasing the γ dose had a harmed ngative effect on vine growth, as evidenced by a decrease in plant height, root number, root volume, leaf area, aerial biomass, root biomass, and internode number of the ‘Yaghouti’ grape plants. Our results showed that between the aerial parts of vines, the leaf area and aerial biomass had higher radiosensitivity than plant height and other aerial parts of the plants based on data from GR25, GR50, and GR75. Moreover, GR studies of root characteristics revealed that root number and biomass root had higher radiation sensitivity than root volume. According to biological responses (LD25, 50, 75 and GR25, 50, 75) in the ‘Yaghouti’ grape, 30 Gy of γ radiation is the optimum dose for preliminary mutagenesis investigations.
Classification of emotional stress and physical stress using a multispectral based deep feature extraction model
Authors: Hong Kan
Published: February 2023

A classification model (Stress Classification-Net) of emotional stress and physical stress is proposed, which can extract classification features based on multispectral and tissue blood oxygen saturation (StO2) characteristics. Related features are extracted on this basis, and the learning model with frequency domain and signal amplification is proposed for the first time. Given that multispectral imaging signals are time series data, time series StO2is extracted from spectral signals. The proper region of interest (ROI) is obtained by a composite criterion, and the ROI source is determined by the universality and robustness of the signal. The frequency-domain signals of ROI are further obtained by wavelet transform. To fully utilize the frequency-domain characteristics, the multi-neighbor vector of locally aggregated descriptors (MN-VLAD) model is proposed to extract useful features. The acquired time series features are finally put into the long short-term memory (LSTM) model to learn the classification characteristics. Through SC-NET model, the classification signals of emotional stress and physical stress are successfully obtained. Experiments show that the classification result is encouraging, and the accuracy of the proposed algorithm is over 90%.
Three-dimensional simulations of embolic stroke and an equation for sizing emboli from imaging
Authors: Hague James P. , Keelan Jonathan , Beishon Lucy , Swienton David , Robinson Thompson G. , Chung Emma M. L.
Published: February 2023

Stroke simulations are needed to run in-silico trials, develop hypotheses for clinical studies and to interpret ultrasound monitoring and radiological imaging. We describe proof-of-concept three-dimensional stroke simulations, carrying out in silico trials to relate lesion volume to embolus diameter and calculate probabilistic lesion overlap maps, building on our previous Monte Carlo method. Simulated emboli were released into an in silico vasculature to simulate 1000 s of strokes. Infarct volume distributions and probabilistic lesion overlap maps were determined. Computer-generated lesions were assessed by clinicians and compared with radiological images. The key result of this study is development of a three-dimensional simulation for embolic stroke and its application to an in silico clinical trial. Probabilistic lesion overlap maps showed that the lesions from small emboli are homogeneously distributed throughout the cerebral vasculature. Mid-sized emboli were preferentially found in posterior cerebral artery (PCA) and posterior region of the middle cerebral artery (MCA) territories. For large emboli, MCA, PCA and anterior cerebral artery (ACA) lesions were comparable to clinical observations, with MCA, PCA then ACA territories identified as the most to least probable regions for lesions to occur. A power law relationship between lesion volume and embolus diameter was found. In conclusion, this article showed proof-of-concept for large in silico trials of embolic stroke including 3D information, identifying that embolus diameter could be determined from infarct volume and that embolus size is critically important to the resting place of emboli. We anticipate this work will form the basis of clinical applications including intraoperative monitoring, determining stroke origins, and in silico trials for complex situations such as multiple embolisation.
The importance of batch sensitization in missing value imputation
Authors: Hui Harvard Wai Hann , Kong Weijia , Peng Hui , Goh Wilson Wen Bin
Published: February 2023

Data analysis is complex due to a myriad of technical problems. Amongst these, missing values and batch effects are endemic. Although many methods have been developed for missing value imputation (MVI) and batch correction respectively, no study has directly considered the confounding impact of MVI on downstream batch correction. This is surprising as missing values are imputed during early pre-processing while batch effects are mitigated during late pre-processing, prior to functional analysis. Unless actively managed, MVI approaches generally ignore the batch covariate, with unknown consequences. We examine this problem by modelling three simple imputation strategies: global (M1), self-batch (M2) and cross-batch (M3) first via simulations, and then corroborated on real proteomics and genomics data. We report that explicit consideration of batch covariates (M2) is important for good outcomes, resulting in enhanced batch correction and lower statistical errors. However, M1 and M3 are error-generating: global and cross-batch averaging may result in batch-effect dilution, with concomitant and irreversible increase in intra-sample noise. This noise is unremovable via batch correction algorithms and produces false positives and negatives. Hence, careless imputation in the presence of non-negligible covariates such as batch effects should be avoided.
Bandgap engineering approach for designing CuO/Mn3O4/CeO2 heterojunction as a novel photocatalyst for AOP-assisted degradation of Malachite green dye
Authors: Gupta Shaswat Vikram , Kulkarni Vihangraj Vijaykumar , Ahmaruzzaman Md.
Published: February 2023

A ternary nanohybrid CuO/Mn3O4/CeO2 was developed in the present work using a co-precipitation-assisted hydrothermal method. The designed photocatalyst's structural, morphology, elemental composition, electronic states of elements, and optical properties were studied using corresponding analytical techniques. Results from PXRD, TEM/HRTEM, XPS, EDAX, and PL showed that the desired nanostructure had formed. Using Tauc's energy band gap plot, it was determined that the nanostructures band gap was ~ 2.44 eV, which showed the band margins of the various moieties, CeO2, Mn3O4, and CuO, had modified. Thus, improved redox conditions led to a substantial decrease in the recombination rate of electron–hole pairs, which was further explained by a PL study in that charge separation plays a key role. Under exposure to visible light irradiation for 60 min, it was revealed that the photocatalyst achieved 98.98% of photodegradation efficiency for malachite green (MG) dye. The process of photodegradation proceeded according to a pseudo-first-order reaction kinetic model with an excellent rate of reaction of 0.07295 min−1 with R2 = 0.99144. The impacts of different reaction variables, inorganic salts, and water matrices were investigated. This research seeks to create a ternary nanohybrid photocatalyst with high photostability, visible spectrum activity, and reusability up to four cycles.
High thermoelectric performance of flexible nanocomposite films based on Bi2Te3 nanoplates and carbon nanotubes selected using ultracentrifugation
Authors: Chiba Tomoyuki , Yabuki Hayato , Takashiri Masayuki
Published: February 2023

Thermoelectric generators with flexibility and high performance near 300 K have the potential to be employed in self-supporting power supplies for Internet of Things (IoT) devices. Bismuth telluride (Bi2Te3) exhibits high thermoelectric performance, and single-walled carbon nanotubes (SWCNTs) show excellent flexibility. Therefore, composites of Bi2Te3 and SWCNTs should exhibit an optimal structure and high performance. In this study, flexible nanocomposite films based on Bi2Te3 nanoplates and SWCNTs were prepared by drop casting on a flexible sheet, followed by thermal annealing. Bi2Te3 nanoplates were synthesized using the solvothermal method, and SWCNTs were synthesized using the super-growth method. To improve the thermoelectric properties of the SWCNTs, ultracentrifugation with a surfactant was performed to selectively obtain suitable SWCNTs. This process selects thin and long SWCNTs but does not consider the crystallinity, chirality distribution, and diameters. A film consisting of Bi2Te3 nanoplates and the thin and long SWCNTs exhibited high electrical conductivity, which was six times higher than that of a film with SWCNTs obtained without ultracentrifugation; this is because the SWCNTs uniformly connected the surrounding nanoplates. The power factor was 6.3 μW/(cm K2), revealing that this is one of the best-performing flexible nanocomposite films. The findings of this study can support the application of flexible nanocomposite films in thermoelectric generators to provide self-supporting power supplies for IoT devices.