bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique mobile elements and scalable gene flow at the prokaryote–eukaryote boundary revealed by circularized Asgard archaea genomes
Authors: Wu Fabai , Speth Daan R. , Philosof Alon , Crémière Antoine , Narayanan Aditi , Barco Roman A. , Connon Stephanie A. , Amend Jan P. , Antoshechkin Igor A. , Orphan Victoria J. 
Published: January 2022

AbstractEukaryotic genomes are known to have garnered innovations from both archaeal and bacterial domains but the sequence of events that led to the complex gene repertoire of eukaryotes is largely unresolved. Here, through the enrichment of hydrothermal vent microorganisms, we recovered two circularized genomes of Heimdallarchaeum species that belong to an Asgard archaea clade phylogenetically closest to eukaryotes. These genomes reveal diverse mobile elements, including an integrative viral genome that bidirectionally replicates in a circular form and aloposons, transposons that encode the 5,000 amino acid-sized proteins Otus and Ephialtes. Heimdallaechaeal mobile elements have garnered various genes from bacteria and bacteriophages, likely playing a role in shuffling functions across domains. The number of archaea- and bacteria-related genes follow strikingly different scaling laws in Asgard archaea, exhibiting a genome size-dependent ratio and a functional division resembling the bacteria- and archaea-derived gene repertoire across eukaryotes. Bacterial gene import has thus likely been a continuous process unaltered by eukaryogenesis and scaled up through genome expansion. Our data further highlight the importance of viewing eukaryogenesis in a pan-Asgard context, which led to the proposal of a conceptual framework, that is, the Heimdall nucleation–decentralized innovation–hierarchical import model that accounts for the emergence of eukaryotic complexity.
Intracranial electrophysiological recordings from the human brain during memory tasks with pupillometry
Authors: Cimbalnik Jan , Dolezal Jaromir , Topçu Çağdaş , Lech Michal , Marks Victoria S. , Joseph Boney , Dobias Martin , Van Gompel Jamie , Worrell Gregory , Kucewicz Michal 
Published: January 2022

AbstractData comprise intracranial EEG (iEEG) brain activity represented by stereo EEG (sEEG) signals, recorded from over 100 electrode channels implanted in any one patient across various brain regions. The iEEG signals were recorded in epilepsy patients (N = 10) undergoing invasive monitoring and localization of seizures when they were performing a battery of four memory tasks lasting approx. 1 hour in total. Gaze tracking on the task computer screen with estimating the pupil size was also recorded together with behavioral performance. Each dataset comes from one patient with anatomical localization of each electrode contact. Metadata contains labels for the recording channels with behavioral events marked from all tasks, including timing of correct and incorrect vocalization of the remembered stimuli. The iEEG and the pupillometric signals are saved in BIDS data structure to facilitate efficient data sharing and analysis.
Production of hydrogen peroxide in an intra-meander hyporheic zone at East River, Colorado
Authors: Yuan Xiu , Liu Tongxu , Fox Patricia , Bhattacharyya Amrita , Dwivedi Dipankar , Williams Kenneth H. , Davis James A. , Waite T. David , Nico Peter S. 
Published: January 2022

AbstractThe traditionally held assumption that photo-dependent processes are the predominant source of H2O2 in natural waters has been recently questioned by an increrasing body of evidence showing the ubiquitiousness of H2O2 in dark water bodies and in groundwater. In this study, we conducted field measurement of H2O2 in an intra-meander hyporheic zone and in surface water at East River, CO. On-site detection using a sensitive chemiluminescence method suggests H2O2 concentrations in groundwater ranging from 6 nM (at the most reduced region) to ~ 80 nM (in a locally oxygen-rich area) along the intra-meander transect with a maxima of 186 nM detected in the surface water in an early afternoon, lagging the maximum solar irradiance by ∼ 1.5 h. Our results suggest that the dark profile of H2O2 in the hyporheic zone is closely correlated to local redox gradients, indicating that interactions between various redox sensitive elements could play an essential role. Due to its transient nature, the widespread presence of H2O2 in the hyporheic zone indicates the existence of a sustained balance between H2O2 production and consumption, which potentially involves a relatively rapid succession of various biogeochemically important processes (such as organic matter turnover, metal cycling and contaminant mobilization). More importantly, this study confirmed the occurrence of reactive oxygen species at a subsurface redox transition zone and further support our understanding of redox boundaries on reactive oxygen species generation and as key locations of biogeochemical activity.
Tracking hidden crisis in India’s capital from space: implications of unsustainable groundwater use
Authors: Garg Shagun , Motagh Mahdi , Indu J. , Karanam Vamshi 
Published: January 2022

AbstractNational Capital Region (NCR, Delhi) in India is one of the fastest-growing metropolitan cities which is facing a severe water crisis due to increasing water demand. The over-extraction of groundwater, particularly from its unconsolidated alluvial deposits makes the region prone to subsidence. In this study, we investigated the effects of plummeting groundwater levels on land surface elevations in Delhi NCR using Sentinel-1 datasets acquired during the years 2014–2020. Our analysis reveals two distinct subsidence features in the study area with rates exceeding 11 cm/year in Kapashera—an urban village near IGI airport Delhi, and 3 cm/year in Faridabad throughout the study period. The subsidence in these two areas are accelerating and follows the depleting groundwater trend. The third region, Dwarka shows a shift from subsidence to uplift during the years which can be attributed to the strict government policies to regulate groundwater use and incentivizing rainwater harvesting. Further analysis using a classified risk map based on hazard risk and vulnerability approach highlights an approximate area of 100 square kilometers to be subjected to the highest risk level of ground movement, demanding urgent attention. The findings of this study are highly relevant for government agencies to formulate new policies against the over-exploitation of groundwater and to facilitate a sustainable and resilient groundwater management system in Delhi NCR.
Revealing lost secrets about Yingpan Man and the Silk Road
Authors: Wang Tingting , Fuller Benjamin T. , Jiang Hongen , Li Wenying , Wei Dong , Hu Yaowu 
Published: January 2022

AbstractYingpan Man, is one of the most exquisitely preserved mummies found in the Xinjiang Uyghur Autonomous Region of China. Here links between Yingpan Man and the Silk Road are explored through a detailed isotopic and bioarchaeological investigation of his life history. Analytical techniques of carbon, nitrogen, and sulfur stable isotope ratio analysis on hair, teeth, muscle and bones as well as associated animal and plant remains, radiocarbon dating and starch grain analysis of dental calculus are presented to visualize never before seen aspects of Yingpan Man’s life, including: environment, breastfeeding and weaning practices, adolescent and adult diet, disease and nutritional status as well as season of death. Furthermore, in combination with a detailed review of his associated grave goods, this research examines the social status and identity of Yingpan Man, and demonstrates the profound impact and cultural fusion that the Silk Road had upon the peoples of Xinjiang and Eurasia.
Impact of freezing temperature (Tfr) of Al2O3 and molecular diameter (H2O)d on thermal enhancement in magnetized and radiative nanofluid with mixed convection
Authors: Adnan  , Ashraf Waqas , Khan Umar , Al-Johani Amnah S. , Ahmed Naveed , Mohyud-Din Syed Tauseef , Khan Ilyas , Andualem Mulugeta 
Published: January 2022

AbstractThe dynamics of nanofluid by considering the role of imposed Lorentz forces, thermal radiations and velocity slip effects over a vertically convectively heated surface is a topic of huge interest. Therefore, the said study is conducted for Al2O3-H2O nanofluid. Mathematical modelling of the problem is done via nanofluid effective correlations comprising the influences of freezing temperature, molecular diameter and similarity transformations. The results for multiple parameters are plotted and provide comprehensive discussion. From the analysis, it is examined that Al2O3-H2O nanofluid motion drops by strengthening Lorentz forces. The temperature in the nanofluid (Al2O3-H2O) is improved by inducing viscous dissipation effects (Ec number), surface convection (Biot number) and thermal radiations (Rd). Moreover, the shear stresses at the surface decreased due to higher magnetic field effects and rises due to velocity slip. A significant rise in Local Nusselt number is observed due to thermal radiations and Biot effects. Finally, enhanced heat transport mechanism in Al2O3-H2O is examined than a conventional liquid. Therefore, nanofluids are better for industrial applications and the uses of conventional liquids are limited due to low thermal conductivity.
Multimodal transistors as ReLU activation functions in physical neural network classifiers
Authors: Surekcigil Pesch Isin , Bestelink Eva , de Sagazan Olivier , Mehonic Adnan , Sporea Radu A. 
Published: January 2022

AbstractArtificial neural networks (ANNs) providing sophisticated, power-efficient classification are finding their way into thin-film electronics. Thin-film technologies require robust, layout-efficient devices with facile manufacturability. Here, we show how the multimodal transistor’s (MMT’s) transfer characteristic, with linear dependence in saturation, replicates the rectified linear unit (ReLU) activation function of convolutional ANNs (CNNs). Using MATLAB, we evaluate CNN performance using systematically distorted ReLU functions, then substitute measured and simulated MMT transfer characteristics as proxies for ReLU. High classification accuracy is maintained, despite large variations in geometrical and electrical parameters, as CNNs use the same activation functions for training and classification.
Upregulation of IFNɣ-mediated chemokines dominate the immune transcriptome of muscle-invasive urothelial carcinoma
Authors: Olkhov-Mitsel Ekaterina , Hodgson Anjelica , Liu Stan K. , Vesprini Danny , Bayani Jane , Bartlett John M. S. , Xu Bin , Downes Michelle R. 
Published: January 2022

AbstractTumor inflammation is prognostically significant in high-grade muscle-invasive bladder cancer (MIBC). However, the underlying mechanisms remain elusive. To identify inflammation-associated immune gene expression patterns, we performed transcriptomic profiling of 40 MIBC archival tumors using the NanoString nCounter Human v.1.1 PanCancer Panel. Findings were validated using the TCGA MIBC dataset. Unsupervised and supervised clustering identified a distinctive immune-related gene expression profile for inflammation, characterized by significant upregulation of 149 genes, particularly chemokines, a subset of which also had potential prognostic utility. Some of the most enriched biological processes were lymphocyte activation and proliferation, leukocyte adhesion and migration, antigen processing and presentation and cellular response to IFN-γ. Upregulation of numerous IFN-γ-inducible chemokines, class II MHC molecules and immune checkpoint genes was detected as part of the complex immune response to MIBC. Further, B-cell markers linked to tertiary lymphoid structures were upregulated, which in turn is predictive of tumor response to immunotherapy and favorable outcome. Our findings of both an overall activated immune profıle and immunosuppressive microenvironment provide novel insights into the complex immune milieu of MIBC with inflammation and supports its clinical significance for predicting prognosis and immunotherapeutic responsiveness, which warrants further investigation. This may open novel opportunities to identify mechanisms for developing new immunotherapeutic strategies.
Genomic features and tumor immune microenvironment alteration in NSCLC treated with neoadjuvant PD-1 blockade
Authors: Wang Shuhang , Yuan Pei , Mao Beibei , Li Ning , Ying Jianming , Tao Xiuli , Tang Wei , Zhang Lei , Geng Xiao , Zhang Fan , Xue Qi , Wu Lijia , Zhang Henghui , Gao Shugeng , He Jie 
Published: January 2022

AbstractSeveral clinical trials have shown the safety and effectiveness of PD-1/PD-L1 inhibitors in neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC). However, 18–83% patients can benefit from it. In this study, we aimed to assess the association of PD-L1 expression, tumor mutation burden, copy number alteration (CNA, including copy number gain and loss) burden with the pathologic response to neoadjuvant PD-1 blockade and investigate the changes in the tumor immune microenvironment (TIME) during neoadjuvant immunotherapy in NSCLC. Pre-immunotherapy treatment tumor samples from twenty-nine NSCLC patients who received neoadjuvant immunotherapy with sintilimab, an anti-PD-1 drug, were subjected to targeted DNA sequencing and PD-L1 immunochemistry staining. The pathological response was positively correlated with tumor proportion score (TPS) of PD-L1 and negatively correlated with copy number gain (CNgain) burden. Of note, the combination of CNgain burden and TPS can better stratify major pathological response (MPR) patients than did CNgain or TPS alone. Whereas, TMB showed a limited correlation with pathological regression. Additionally, PD-1 blockade led to an increase in CD8+PD-1−T cells which was clinically relevant to MPR as evaluated by multiplex immunofluorescence. A significant reduction in CD19+ cells was observed in the Non-MPR group but not in the MPR group, indicating the involvement of B cells in improving neoadjuvant immunotherapy response in NSCLC. Together, our study provides new data for the correlation of PD-L1 expression and genomic factors with drug response in neoadjuvant immunotherapy settings in NSCLC. The changes of TIME may provide novel insight into the immune responses to neoadjuvant anti-PD-1 therapy.
Non-contact physiological monitoring of post-operative patients in the intensive care unit
Authors: Jorge João , Villarroel Mauricio , Tomlinson Hamish , Gibson Oliver , Darbyshire Julie L. , Ede Jody , Harford Mirae , Young John Duncan , Tarassenko Lionel , Watkinson Peter 
Published: January 2022

AbstractProlonged non-contact camera-based monitoring in critically ill patients presents unique challenges, but may facilitate safe recovery. A study was designed to evaluate the feasibility of introducing a non-contact video camera monitoring system into an acute clinical setting. We assessed the accuracy and robustness of the video camera-derived estimates of the vital signs against the electronically-recorded reference values in both day and night environments. We demonstrated non-contact monitoring of heart rate and respiratory rate for extended periods of time in 15 post-operative patients. Across day and night, heart rate was estimated for up to 53.2% (103.0 h) of the total valid camera data with a mean absolute error (MAE) of 2.5 beats/min in comparison to two reference sensors. We obtained respiratory rate estimates for 63.1% (119.8 h) of the total valid camera data with a MAE of 2.4 breaths/min against the reference value computed from the chest impedance pneumogram. Non-contact estimates detected relevant changes in the vital-sign values between routine clinical observations. Pivotal respiratory events in a post-operative patient could be identified from the analysis of video-derived respiratory information. Continuous vital-sign monitoring supported by non-contact video camera estimates could be used to track early signs of physiological deterioration during post-operative care.
Single-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson’s disease
Authors: Novak Gabriela , Kyriakis Dimitrios , Grzyb Kamil , Bernini Michela , Rodius Sophie , Dittmar Gunnar , Finkbeiner Steven , Skupin Alexander 
Published: January 2022

AbstractParkinson’s disease (PD) is the second-most prevalent neurodegenerative disorder, characterized by the loss of dopaminergic neurons (mDA) in the midbrain. The underlying mechanisms are only partly understood and there is no treatment to reverse PD progression. Here, we investigated the disease mechanism using mDA neurons differentiated from human induced pluripotent stem cells (hiPSCs) carrying the ILE368ASN mutation within the PINK1 gene, which is strongly associated with PD. Single-cell RNA sequencing (RNAseq) and gene expression analysis of a PINK1-ILE368ASN and a control cell line identified genes differentially expressed during mDA neuron differentiation. Network analysis revealed that these genes form a core network, members of which interact with all known 19 protein-coding Parkinson’s disease-associated genes. This core network encompasses key PD-associated pathways, including ubiquitination, mitochondrial function, protein processing, RNA metabolism, and vesicular transport. Proteomics analysis showed a consistent alteration in proteins of dopamine metabolism, indicating a defect of dopaminergic metabolism in PINK1-ILE368ASN neurons. Our findings suggest the existence of a network onto which pathways associated with PD pathology converge, and offers an inclusive interpretation of the phenotypic heterogeneity of PD.
Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs
Authors: Cipriano Madalena , Schlünder Katharina , Probst Christopher , Linke Kirstin , Weiss Martin , Fischer Mona Julia , Mesch Lena , Achberger Kevin , Liebau Stefan , Mesquida Marina , Nicolini Valeria , Schneider Anneliese , Giusti Anna Maria , Kustermann Stefan , Loskill Peter 
Published: January 2022

AbstractDisorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies.
Demonstration of targeted crossovers in hybrid maize using CRISPR technology
Authors: Kouranov Andrei , Armstrong Charles , Shrawat Ashok , Sidorov Vladimir , Huesgen Scott , Lemke Bryce , Boyle Timothy , Gasper Michelle , Lawrence Richard , Yang Samuel 
Published: January 2022

AbstractNaturally occurring chromosomal crossovers (CO) during meiosis are a key driver of genetic diversity. The ability to target CO at specific allelic loci in hybrid plants would provide an advantage to the plant breeding process by facilitating trait introgression, and potentially increasing the rate of genetic gain. We present the first demonstration of targeted CO in hybrid maize utilizing the CRISPR Cas12a system. Our experiments showed that stable and heritable targeted CO can be produced in F1 somatic cells using Cas12a at a significantly higher rate than the natural CO in the same interval. Molecular characterization of the recombinant plants demonstrated that the targeted CO were driven by the non-homologous end joining (NHEJ) or HDR repair pathways, presumably during the mitotic cell cycle. These results are a step towards the use of RNA-guided nuclease technology to simplify the creation of targeted genome combinations in progeny and accelerate breeding.
Maternal diabetes-mediated RORA suppression in mice contributes to autism-like offspring through inhibition of aromatase
Authors: Yu Hong , Niu Yanbin , Jia Guohua , Liang Yujie , Chen Baolin , Sun Ruoyu , Wang Min , Huang Saijun , Zeng Jiaying , Lu Jianpin , Li Ling , Guo Xiaoling , Yao Paul 
Published: January 2022

AbstractRetinoic acid-related orphan receptor alpha (RORA) suppression is associated with autism spectrum disorder (ASD) development, although the mechanism remains unclear. In this study, we aim to investigate the potential effect and mechanisms of RORA suppression on autism-like behavior (ALB) through maternal diabetes-mediated mouse model. Our in vitro study in human neural progenitor cells shows that transient hyperglycemia induces persistent RORA suppression through oxidative stress-mediated epigenetic modifications and subsequent dissociation of octamer-binding transcription factor 3/4 from the RORA promoter, subsequently suppressing the expression of aromatase and superoxide dismutase 2. The in vivo mouse study shows that prenatal RORA deficiency in neuron-specific RORA null mice mimics maternal diabetes-mediated ALB; postnatal RORA expression in the amygdala ameliorates, while postnatal RORA knockdown mimics, maternal diabetes-mediated ALB in offspring. In addition, RORA mRNA levels in peripheral blood mononuclear cells decrease to 34.2% in ASD patients (n = 121) compared to the typically developing group (n = 118), and the related Receiver Operating Characteristic curve shows good sensitivity and specificity with a calculated 84.1% of Area Under the Curve for ASD diagnosis. We conclude that maternal diabetes contributes to ALB in offspring through suppression of RORA and aromatase, RORA expression in PBMC could be a potential marker for ASD screening.
Observation of a transition to a localized ultrasonic phase in soft matter
Authors: Matis Bernard R. , Liskey Steven W. , Gangemi Nicholas T. , Edmunds Aaron D. , Wilson William B. , Wheeler Virginia D. , Houston Brian H. , Baldwin Jeffrey W. , Photiadis Douglas M. 
Published: January 2022

AbstractAnderson localization arises from the interference of multiple scattering paths in a disordered medium, and applies to both quantum and classical waves. Soft matter provides a unique potential platform to observe localization of non-interacting classical waves because of the order of magnitude difference in speed between fast and slow waves in conjunction with the possibility to achieve strong scattering over broad frequency bands while minimizing dissipation. Here, we provide long sought evidence of a localized phase spanning up to 246 kHz for fast (sound) waves in a soft elastic medium doped with resonant encapsulated microbubbles. We find the transition into the localized phase is accompanied by an anomalous decrease of the mean free path, which provides an experimental signature of the phase transition. At the transition, the decrease in the mean free path with changing frequency (i.e., disorder strength) follows a power law with a critical exponent near unity. Within the localized phase the mean free path is in the range 0.4–1.0 times the wavelength, the transmitted intensity at late times is well-described by the self-consistent localization theory, and the localization length decreases with increasing microbubble volume fraction. Our work sets the foundation for broadband control of localization and the associated phase transition in soft matter, and affords a comparison of theory to experiment.