bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor Sp9 is a negative regulator of D1-type MSN development
Authors: Li Zhenmeiyu , Shang Zicong , Sun Mengge , Jiang Xin , Tian Yu , Yang Lin , Wang Ziwu , Su Zihao , Liu Guoping , li Xiaosu , You Yan , Yang Zhengang , Xu Zhejun , Zhang Zhuangzhi 
Published: June 2022

AbstractThe striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson’s Disease. In the present study, we demonstrated that Sp9-positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSN identity and repressing D1-MSN identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2-like MSNs survived normally in adulthood. Taken together, our findings supported that Sp9 was sufficient to promote D2-MSN identity and repress D1-MSN identity, and Sp9 was a negative regulator of D1-MSN fate.
A trifunctional peptide broadly inhibits SARS-CoV-2 Delta and Omicron variants in hamsters
Authors: Zhao Hanjun , To Kelvin Kai-Wang , Lam Hoiyan , Zhang Chuyuan , Peng Zheng , Meng Xinjie , Wang Xiankun , Zhang Anna Jinxia , Yan Bingpeng , Cai Jianpiao , Yeung Man Lung , Chan Jasper Fuk-Woo , Yuen Kwok-Yung 
Published: June 2022

AbstractThe emergence of highly transmissible SARS-CoV-2 variants has led to the waves of the resurgence of COVID-19 cases. Effective antivirals against variants are required. Here we demonstrate that a human-derived peptide 4H30 has broad antiviral activity against the ancestral virus and four Variants of Concern (VOCs) in vitro. Mechanistically, 4H30 can inhibit three distinct steps of the SARS-CoV-2 life cycle. Specifically, 4H30 blocks viral entry by clustering SARS-CoV-2 virions; prevents membrane fusion by inhibiting endosomal acidification; and inhibits the release of virions by cross-linking SARS-CoV-2 with cellular glycosaminoglycans. In vivo studies show that 4H30 significantly reduces the lung viral titers in hamsters, with a more potent reduction for the Omicron variant than the Delta variant. This is likely because the entry of the Omicron variant mainly relies on the endocytic pathway which is targeted by 4H30. Moreover, 4H30 reduces syncytia formation in infected hamster lungs. These findings provide a proof of concept that a single antiviral can inhibit viral entry, fusion, and release.
A deep Tasman outflow of Pacific waters during the last glacial period
Authors: Struve Torben , Wilson David J. , Hines Sophia K. V. , Adkins Jess F. , van de Flierdt Tina 
Published: June 2022

AbstractThe interoceanic exchange of water masses is modulated by flow through key oceanic choke points in the Drake Passage, the Indonesian Seas, south of Africa, and south of Tasmania. Here, we use the neodymium isotope signature (εNd) of cold-water coral skeletons from intermediate depths (1460‒1689 m) to trace circulation changes south of Tasmania during the last glacial period. The key feature of our dataset is a long-term trend towards radiogenic εNd values of ~−4.6 during the Last Glacial Maximum and Heinrich Stadial 1, which are clearly distinct from contemporaneous Southern Ocean εNd of ~−7. When combined with previously published radiocarbon data from the same corals, our results indicate that a unique radiogenic and young water mass was present during this time. This scenario can be explained by a more vigorous Pacific overturning circulation that supported a deeper outflow of Pacific waters, including North Pacific Intermediate Water, through the Tasman Sea.
Associations between long-term drought and diarrhea among children under five in low- and middle-income countries
Authors: Wang Pin , Asare Ernest , Pitzer Virginia E. , Dubrow Robert , Chen Kai 
Published: June 2022

AbstractClimate change is projected to intensify drought conditions, which may increase the risk of diarrheal diseases in children. We constructed log-binomial generalized linear mixed models to examine the association between diarrhea risk, ascertained from global-scale nationally representative Demographic and Health Surveys, and drought, represented by the standardized precipitation evapotranspiration index, among children under five in 51 low- and middle-income countries (LMICs). Exposure to 6-month mild or severe drought was associated with an increased diarrhea risk of 5% (95% confidence interval 3–7%) or 8% (5–11%), respectively. The association was stronger among children living in a household that needed longer time to collect water or had no access to water or soap/detergent for handwashing. The association for 24-month drought was strong in dry zones but weak or null in tropical or temperate zones, whereas that for 6-month drought was only observed in tropical or temperate zones. In this work we quantify the associations between exposure to long-term drought and elevated diarrhea risk among children under five in LMICs and suggest that the risk could be reduced through improved water, sanitation, and hygiene practices, made more urgent by the likely increase in drought due to climate change.
Optimised weight programming for analogue memory-based deep neural networks
Authors: Mackin Charles , Rasch Malte J. , Chen An , Timcheck Jonathan , Bruce Robert L. , Li Ning , Narayanan Pritish , Ambrogio Stefano , Le Gallo Manuel , Nandakumar S. R. , Fasoli Andrea , Luquin Jose , Friz Alexander , Sebastian Abu , Tsai Hsinyu , Burr Geoffrey W. 
Published: June 2022

AbstractAnalogue memory-based deep neural networks provide energy-efficiency and per-area throughput gains relative to state-of-the-art digital counterparts such as graphics processing units. Recent advances focus largely on hardware-aware algorithmic training and improvements to circuits, architectures, and memory devices. Optimal translation of software-trained weights into analogue hardware weights—given the plethora of complex memory non-idealities—represents an equally important task. We report a generalised computational framework that automates the crafting of complex weight programming strategies to minimise accuracy degradations during inference, particularly over time. The framework is agnostic to network structure and generalises well across recurrent, convolutional, and transformer neural networks. As a highly flexible numerical heuristic, the approach accommodates arbitrary device-level complexity, making it potentially relevant for a variety of analogue memories. By quantifying the limit of achievable inference accuracy, it also enables analogue memory-based deep neural network accelerators to reach their full inference potential.
Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0
Authors: Domenzain Iván , Sánchez Benjamín , Anton Mihail , Kerkhoven Eduard J. , Millán-Oropeza Aarón , Henry Céline , Siewers Verena , Morrissey John P. , Sonnenschein Nikolaus , Nielsen Jens 
Published: June 2022

AbstractGenome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into such models was first enabled by the GECKO toolbox, allowing the study of phenotypes constrained by protein limitations. Here, we upgrade the toolbox in order to enhance models with enzyme and proteomics constraints for any organism with a compatible GEM reconstruction. With this, enzyme-constrained models for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus are generated to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions reveal that upregulation and high saturation of enzymes in amino acid metabolism are common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO is expanded with an automated framework for continuous and version-controlled update of enzyme-constrained GEMs, also producing such models for Escherichia coli and Homo sapiens. In this work, we facilitate the utilization of enzyme-constrained GEMs in basic science, metabolic engineering and synthetic biology purposes.
Voltage-driven gigahertz frequency tuning of spin Hall nano-oscillators
Authors: Choi Jong-Guk , Park Jaehyeon , Kang Min-Gu , Kim Doyoon , Rieh Jae-Sung , Lee Kyung-Jin , Kim Kab-Jin , Park Byong-Guk 
Published: June 2022

AbstractSpin Hall nano-oscillators (SHNOs) exploiting current-driven magnetization auto-oscillation have recently received much attention because of their potential for neuromorphic computing. Widespread applications of neuromorphic devices with SHNOs require an energy-efficient method of tuning oscillation frequency over broad ranges and storing trained frequencies in SHNOs without the need for additional memory circuitry. While the voltage-driven frequency tuning of SHNOs has been demonstrated, it was volatile and limited to megahertz ranges. Here, we show that the frequency of SHNOs is controlled up to 2.1 GHz by an electric field of 1.25 MV/cm. The large frequency tuning is attributed to the voltage-controlled magnetic anisotropy (VCMA) in a perpendicularly magnetized Ta/Pt/[Co/Ni]n/Co/AlOx structure. Moreover, the non-volatile VCMA effect enables cumulative control of the frequency using repetitive voltage pulses which mimic the potentiation and depression functions of biological synapses. Our results suggest that the voltage-driven frequency tuning of SHNOs facilitates the development of energy-efficient neuromorphic devices.
Ion-cluster-mediated ultrafast self-healable ionoconductors for reconfigurable electronics
Authors: Kim Yong Min , Kwon Jin Han , Kim Seonho , Choi U Hyeok , Moon Hong Chul 
Published: June 2022

AbstractImplementing self-healing capabilities in a deformable platform is one of the critical challenges for achieving future wearable electronics with high durability and reliability. Conventional systems are mostly based on polymeric materials, so their self-healing usually proceeds at elevated temperatures to promote chain flexibility and reduce healing time. Here, we propose an ion-cluster-driven self-healable ionoconductor composed of rationally designed copolymers and ionic liquids. After complete cleavage, the ionoconductor can be repaired with high efficiency (∼90.3%) within 1 min even at 25 °C, which is mainly attributed to the dynamic formation of ion clusters between the charged moieties in copolymers and ionic liquids. By taking advantages of the superior self-healing performance, stretchability (∼1130%), non-volatility (over 6 months), and ability to be easily shaped as desired through cutting and re-assembly protocol, reconfigurable, deformable light-emitting electroluminescent displays are successfully demonstrated as promising electronic platforms for future applications.
Tight junction channel regulation by interclaudin interference
Authors: Shashikanth Nitesh , France Marion M. , Xiao Ruyue , Haest Xenia , Rizzo Heather E. , Yeste Jose , Reiner Johannes , Turner Jerrold R. 
Published: June 2022

AbstractTight junctions form selectively permeable seals across the paracellular space. Both barrier function and selective permeability have been attributed to members of the claudin protein family, which can be categorized as pore-forming or barrier-forming. Here, we show that claudin-4, a prototypic barrier-forming claudin, reduces paracellular permeability by a previously unrecognized mechanism. Claudin-4 knockout or overexpression has minimal effects on tight junction permeability in the absence of pore-forming claudins. However, claudin-4 selectively inhibits flux across cation channels formed by claudins 2 or 15. Claudin-4-induced loss of claudin channel function is accompanied by reduced anchoring and subsequent endocytosis of pore-forming claudins. Analyses in nonepithelial cells show that claudin-4, which is incapable of independent polymerization, disrupts polymeric strands and higher order meshworks formed by claudins 2, 7, 15, and 19. This process of interclaudin interference, in which one claudin disrupts higher order structures and channels formed by a different claudin, represents a previously unrecognized mechanism of barrier regulation.
Ultrahigh-transparency and pressure-sensitive iontronic device for tactile intelligence
Authors: Tang Jie , Zhao Chao , Luo Qian , Chang Yu , Yang Zhenguo , Pan Tingrui 
Published: June 2022

AbstractEmerging tactile sensing devices mimic biological functions of human mechanoreception. By introducing the feature of optical transparency, it can lead to a combined capacities of tactile and visual intelligence into single system. Yet, it is difficult to realize ultrahigh level of optical transparency and device sensitivity in single structure, for the widely used methods for sensitivity improvement, such as elevating the interfacial roughness, may further reduce the transparency. By utilizing a transparent ionic material with tunable surface topologies, as well as introducing a strategy of refractive index matching, we have proposed a transparent iontronic sensing (TIS) device based on the iontronic sensing mechanism, simultaneously offering combined high device sensitivity (83.9 kPa−1), with ultrahigh optical transparency (96.9%), the highest reported value in literature. Benefiting from its comprehensive performance in sensing and optical characteristics, the TIS devices hold enormous potential for the human-machine interfaces for industrial and medical applications.
The specialist in regeneration—the Axolotl—a suitable model to study bone healing?
Authors: Polikarpova A. , Ellinghaus A. , Schmidt-Bleek O. , Grosser L. , Bucher C. H. , Duda G. N. , Tanaka E. M. , Schmidt-Bleek K. 
Published: June 2022

AbstractWhile the axolotl’s ability to completely regenerate amputated limbs is well known and studied, the mechanism of axolotl bone fracture healing remains poorly understood. One reason might be the lack of a standardized fracture fixation in axolotl. We present a surgical technique to stabilize the osteotomized axolotl femur with a fixator plate and compare it to a non-stabilized osteotomy and to limb amputation. The healing outcome was evaluated 3 weeks, 3, 6 and 9 months post-surgery by microcomputer tomography, histology and immunohistochemistry. Plate-fixated femurs regained bone integrity more efficiently in comparison to the non-fixated osteotomized bone, where larger callus formed, possibly to compensate for the bone fragment misalignment. The healing of a non-critical osteotomy in axolotl was incomplete after 9 months, while amputated limbs efficiently restored bone length and structure. In axolotl amputated limbs, plate-fixated and non-fixated fractures, we observed accumulation of PCNA+ proliferating cells at 3 weeks post-injury similar to mouse. Additionally, as in mouse, SOX9-expressing cells appeared in the early phase of fracture healing and amputated limb regeneration in axolotl, preceding cartilage formation. This implicates endochondral ossification to be the probable mechanism of bone healing in axolotls. Altogether, the surgery with a standardized fixation technique demonstrated here allows for controlled axolotl bone healing experiments, facilitating their comparison to mammals (mice).
Immunogenicity and protective efficacy of RSV G central conserved domain vaccine with a prefusion nanoparticle
Authors: Rainho-Tomko Jennifer N. , Pavot Vincent , Kishko Michael , Swanson Kurt , Edwards Darin , Yoon Heesik , Lanza Lilibeth , Alamares-Sapuay Judith , Osei-Bonsu Robert , Mundle Sophia T. , Murison Dave A. , Gallichan Scott , Delagrave Simon , Wei Chih-Jen , Zhang Linong , Nabel Gary J. 
Published: June 2022

AbstractRespiratory syncytial virus (RSV) G glycoprotein has recently reemerged as a vaccine antigen due to its ability to elicit potent neutralizing antibodies and ameliorate disease in animal models. Here we designed three constructs to display the G central conserved domain (Gcc) focused on inducing broad and potent neutralizing antibodies. One construct displaying Gcc from both RSV subgroups trimerized via a C-terminal foldon (Gcc-Foldon) was highly immunogenic in mice and in MIMIC, a pre-immune human in vitro model. To explore an optimal RSV vaccine, we combined the Gcc-Foldon antigen with a stabilized pre-fusion-F nanoparticle (pre-F-NP) as a bivalent vaccine and detected no antigenic interference between the two antigens in the MIMIC model. In RSV-primed macaques, the bivalent vaccine elicited potent humoral responses. Furthermore, both Gcc-Foldon and the bivalent vaccine conferred effective protection against RSV challenge in mice. This two-component vaccine could potentially provide effective protection against RSV infection in humans and warrants further clinical evaluation.
Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer
Authors: Joanito Ignasius , Wirapati Pratyaksha , Zhao Nancy , Nawaz Zahid , Yeo Grace , Lee Fiona , Eng Christine L. P. , Macalinao Dominique Camat , Kahraman Merve , Srinivasan Harini , Lakshmanan Vairavan , Verbandt Sara , Tsantoulis Petros , Gunn Nicole , Venkatesh Prasanna Nori , Poh Zhong Wee , Nahar Rahul , Oh Hsueh Ling Janice , Loo Jia Min , Chia Shumei , Cheow Lih Feng , Cheruba Elsie , Wong Michael Thomas , Kua Lindsay , Chua Clarinda , Nguyen Andy , Golovan Justin , Gan Anna , Lim Wan-Jun , Guo Yu Amanda , Yap Choon Kong , Tay Brenda , Hong Yourae , Chong Dawn Qingqing , Chok Aik-Yong , Park Woong-Yang , Han Shuting , Chang Mei Huan , Seow-En Isaac , Fu Cherylin , Mathew Ronnie , Toh Ee-Lin , Hong Lewis Z. , Skanderup Anders Jacobsen , DasGupta Ramanuj , Ong Chin-Ann Johnny , Lim Kiat Hon , Tan Emile K. W. , Koo Si-Lin , Leow Wei Qiang , Tejpar Sabine , Prabhakar Shyam , Tan Iain Beehuat 
Published: June 2022

AbstractThe consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined ‘IMF’ classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F).
Groundwater level prediction based on a combined intelligence method for the Sifangbei landslide in the Three Gorges Reservoir Area
Authors: Zeng Taorui , Yin Kunlong , Jiang Hongwei , Liu Xiepan , Guo Zizheng , Peduto Dario 
Published: June 2022

AbstractThe monitoring and prediction of the groundwater level (GWL) significantly influence the landslide kinematics. Based on the long-term fluctuation characteristics of the GWL and the time lag of triggering factors, a dynamic prediction model of the GWL based on the Maximum information coefficient (MIC) algorithm and the long-term short-term memory (LSTM) model was proposed. The Sifangbei landslide in the Three Gorges Reservoir area (TGRA) in China, wherein eight GWL monitoring sensors were installed in different locations, was taken as a case study. The monitoring data represented that the fluctuation of the GWL has a specific time lag concerning the accumulated rainfall (AR) and the reservoir water level (RWL). In addition, there were spatial differences in the fluctuation of the GWL, which was controlled by the elevation and the micro landform. From January 19, 2015, to March 6, 2017, the measured data were used to set up the predicted models. The MIC algorithm was adopted to calculate the lag time of the GWL, the RWL, and the AR. The LSTM model is a time series prediction algorithm that can transmit historical information. The Gray wolf optimization (GWO) algorithm was used to seek the most suitable hyperparameter of the LSTM model under the specific prediction conditions. The single-factor GWO-LSTM model without considering triggering factors and the support vector machine regression (SVR) model were considered to compare the prediction results. The results indicate that the MIC-GWO-LSTM model reached the highest accuracy and improved the prediction accuracy by considering the factor selection process with the learner training process. The proposed MIC-GWO-LSTM model combines the advantages of each algorithm and effectively constructs the response relationship between the GWL fluctuation and triggering factors; it also provides a new exploration for the GWL prediction, monitoring, and early warning system in the TGRA.
Preoperative physical performance predicts pulmonary complications after coronary artery bypass grafting: a prospective study
Authors: Li Lin , Yang Qin , Guo Qi , Liu Dandan , Gao Hui , Liu Yaping 
Published: June 2022

AbstractThe purpose of this study is to evaluate the relationship between preoperative physical performance (grip strength, gait speed, timed up and go) and postoperative pulmonary complications (PPCs) in patients who have undergone coronary artery bypass grafting (CABG). From September 2019 to August 2021, a total of 497 CABG patients who met the inclusion criteria of this study were examined for grip strength, 4-m gait speed, and timed up and go (TUG) before CABG surgery. Among them, 438 were included in the final analysis. PPCs were classified according to the operational definition of Kroenke et al. and patients with clinically significant PPCs were included in the data analysis. Logistic regression was utilised to analyse the relationship between physical performance and clinically significant PPCs. Besides, the receiver operating characteristic (ROC) curve was applied to analyse the predictive effect of grip strength, gait speed, and TUG on clinically significant PPCs after the CABG procedure. In total, 103 (23.5%) patients developed clinically significant PPCs after CABG. After making adjustments for the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and confounding factors, we established that low grip/weight (OR 0.510; 95% CI 0.363–0.715), slow gait speed (OR 0.619; 95% CI 0.517–0.741), and prolonged TUG (OR 1.617; 95% CI 1.379–1.895) were all independently correlated with clinically significant PPCs after CABG. The ROC curve analysis indicated that the area under the ROC curve of the integrated model of the three indicators (AUC 0.792 vs. 0.682, 0.754, 0.765) was larger than that of the model with a single indicator. Besides the predictive effect of the integrated model was superior to the models using grip/weight, gait speed, or TUG alone. Physical performance, including grip/weight, gait speed, and TUG, is a predictive factor for PPCs in CABG patients, and can be used in preoperative evaluations to and help improve the management of high-risk patients.