bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Impacts of Future Extreme Precipitation Changes on Flood Engineering Design Across the Contiguous United States
Authors: Coelho Gustavo de A. , Ferreira Celso M. , Johnston Jeremy , Kinter James L. , Dollan Ishrat J. , Maggioni Viviana 
Published: March 2022

AbstractThe intensification of extreme precipitation in a warming climate is expected to increase flood risk. In order to support flood resilience efforts, it is important to anticipate and quantify potential changes in design standards under future climate conditions. This study assessed how extreme precipitation is expected to change over the 21st century in relation to current National Oceanic and Atmospheric Administration (NOAA) Atlas 14 design standards over the contiguous United States (CONUS). We used the Community Earth System Model Version 2 large ensemble (CESM2‐LE) simulations from the Coupled Model Intercomparison Project Phase 6 and incorporated future changes into flood engineering design standard with a spatially distributed quantile delta mapping method. Relative changes in extreme daily precipitation were computed for multiple average recurrence intervals (ARIs) up to 100‐year and different planning horizons (2020, 2040, 2060, 2080, and 2100). The results indicated an intensification of extreme precipitation by approximately 10%–40% in northern regions and 20%–80% in southern regions by 2100. The current 100‐year ARI with 24‐hr duration from NOAA Atlas 14 is projected to become the 50‐year ARI in the Northern Great Plains, less than the 25‐year ARI in Southwest areas, and approximately the 25‐year ARI in the other regions by 2100. While a nationwide consensus is still needed, this work presents a possible methodology for incorporating climate uncertainty in engineering design. A comparison across major metropolitan areas also illustrates regional variability in projected changes relative to NOAA Atlas 14, suggesting a need for varied local‐scale responses.
Microbial communities of Auka hydrothermal sediments shed light on vent biogeography and the evolutionary history of thermophily
Authors: Speth Daan R , Yu Feiqiao B , Connon Stephanie A , Lim Sujung , Magyar John S , Peña-Salinas Manet E , Quake Stephen R , Orphan Victoria J 
Published: March 2022

Abstract
Hydrothermal vents have been key to our understanding of the limits of life, and the metabolic and phylogenetic diversity of thermophilic organisms. Here we used environmental metagenomics combined with analysis of physicochemical data and 16S rRNA gene amplicons to characterize the sediment-hosted microorganisms at the recently discovered Auka vents in the Gulf of California. We recovered 325 metagenome assembled genomes (MAGs) representing 54 phyla, over 30% of those currently known, showing the microbial community in Auka hydrothermal sediments is highly diverse. 16S rRNA gene amplicon screening of 224 sediment samples across the vent field indicates that the MAGs retrieved from a single site are representative of the microbial community in the vent field sediments. Metabolic reconstruction of a vent-specific, deeply branching clade within the Desulfobacterota suggests these organisms metabolize sulfur using novel octaheme cytochrome-c proteins related to hydroxylamine oxidoreductase. Community-wide comparison between Auka MAGs and MAGs from Guaymas Basin revealed a remarkable 20% species-level overlap, suggestive of long-distance species transfer over 400 km and subsequent sediment colonization. Optimal growth temperature prediction on the Auka MAGs, and thousands of reference genomes, shows that thermophily is a trait that has evolved frequently. Taken together, our Auka vent field results offer new perspectives on our understanding of hydrothermal vent microbiology.
Human forebrain organoids reveal connections between valproic acid exposure and autism risk
Authors: Meng Qingtuan , Zhang Wendiao , Wang Xuan , Jiao Chuan , Xu Sheng , Liu Chunyu , Tang Beisha , Chen Chao 
Published: March 2022

AbstractValproic acid (VPA) exposure as an environmental factor that confers risk of autism spectrum disorder (ASD), its functional mechanisms in the human brain remain unclear since relevant studies are currently restricted to two-dimensional cell cultures and animal models. To identify mechanisms by which VPA contribute to ASD risk in human, here we used human forebrain organoids (hFOs), in vitro derived three-dimensional cell cultures that recapitulate key human brain developmental features. We identified that VPA exposure in hFOs affected the expression of genes enriched in neural development, synaptic transmission, oxytocin signaling, calcium, and potassium signaling pathways, which have been implicated in ASD. Genes (e.g., CAMK4, CLCN4, DPP10, GABRB3, KCNB1, PRKCB, SCN1A, and SLC24A2) that affected by VPA were significantly overlapped with those dysregulated in brains or organoids derived from ASD patients, and known ASD risk genes, as well as genes in ASD risk-associated gene coexpression modules. Single-cell RNA sequencing analysis showed that VPA exposure affected the expression of genes in choroid plexus, excitatory neuron, immature neuron, and medial ganglionic eminence cells annotated in hFOs. Microelectrode array further identified that VPA exposure in hFOs disrupted synaptic transmission. Taken together, this study connects VPA exposure to ASD pathogenesis using hFOs, which is valuable for illuminating the etiology of ASD and screening for potential therapeutic targets.
Mesenchymal stem cells protect against ferroptosis via exosome-mediated stabilization of SLC7A11 in acute liver injury
Authors: Lin Feiyan , Chen Wenyi , Zhou Jiahang , Zhu Jiaqi , Yao Qigu , Feng Bing , Feng Xudong , Shi Xiaowei , Pan Qiaoling , Yu Jiong , Li Lanjuan , Cao Hongcui 
Published: March 2022

AbstractMesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate liver injury. Here, the protective effect of MSCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI) was investigated. In this study, we illustrated a novel mechanism that ferroptosis, a newly recognized form of regulated cell death, contributed to CCl4-induced ALI. Subsequently, based on the in vitro and in vivo evidence that MSCs and MSC-derived exosomes (MSC-Exo) treatment achieved pathological remission and inhibited the production of lipid peroxidation, we proposed an MSC-based therapy for CCl4-induced ALI. More intriguingly, treatment with MSCs and MSC-Exo downregulated the mRNA level of prostaglandin-endoperoxide synthase 2 (Ptgs2) and lipoxygenases (LOXs) while it restored the protein level of SLC7A11 in primary hepatocytes and mouse liver, indicating that the inhibition of ferroptosis partly accounted for the protective effect of MSCs and MSC-Exo on ALI. We further revealed that MSC-Exo-induced expression of SLC7A11 protein was accompanied by increasing of CD44 and OTUB1. The aberrant expression of ubiquitinated SLC7A11 triggered by CCl4 could be rescued with OTUB1-mediated deubiquitination, thus strengthening SLC7A11 stability and thereby leading to the activation of system XC− to prevent CCl4-induced hepatocyte ferroptosis. In conclusion, we showed that MSC-Exo had a protective role against ferroptosis by maintaining SLC7A11 function, thus proposing a novel therapeutic strategy for ferroptosis-induced ALI.
LPS/Bcl3/YAP1 signaling promotes Sox9+HNF4α+ hepatocyte-mediated liver regeneration after hepatectomy
Authors: Shao Changchun , Jing Yingying , Zhao Shanmin , Yang Xue , Hu Yiming , Meng Yan , Huang Yihua , Ye Fei , Gao Lu , Liu Wenting , Sheng Dandan , Li Rong , Zhang Xiaoren , Wei Lixin 
Published: March 2022

AbstractRecent reports have demonstrated that Sox9+HNF4α+ hepatocytes are involved in liver regeneration after chronic liver injury; however, little is known about the origin of Sox9+HNF4α+ hepatocytes and the regulatory mechanism. Employing a combination of chimeric lineage tracing, immunofluorescence, and immunohistochemistry, we demonstrate that Sox9+HNF4α+ hepatocytes, generated by transition from mature hepatocytes, play an important role in the initial phase after partial hepatectomy (PHx). Additionally, knocking down the expression of Sox9 suppresses hepatocyte proliferation and blocks the recovery of lost hepatic tissue. In vitro and in vivo assays demonstrated that Bcl3, activated by LPS, promotes hepatocyte conversion and liver regeneration. Mechanistically, Bcl3 forms a complex with and deubiquitinates YAP1 and further induces YAP1 to translocate into the nucleus, resulting in Sox9 upregulation and mature hepatocyte conversion. We demonstrate that Bcl3 promotes Sox9+HNF4α+ hepatocytes to participate in liver regeneration, and might therefore be a potential target for enhancing regeneration after liver injury.
Empirical prediction of variant-activated cryptic splice donors using population-based RNA-Seq data
Authors: Dawes Ruebena , Joshi Himanshu , Cooper Sandra T. 
Published: March 2022

AbstractPredicting which cryptic-donors may be activated by a splicing variant in patient DNA is notoriously difficult. Through analysis of 5145 cryptic-donors (versus 86,963 decoy-donors not used; any GT or GC), we define an empirical method predicting cryptic-donor activation with 87% sensitivity and 95% specificity. Strength (according to four algorithms) and proximity to the annotated-donor appear important determinants of cryptic-donor activation. However, other factors such as splicing regulatory elements, which are difficult to identify, play an important role and are likely responsible for current prediction inaccuracies. We find that the most frequently recurring natural mis-splicing events at each exon-intron junction, summarised over 40,233 RNA-sequencing samples (40K-RNA), predict with accuracy which cryptic-donor will be activated in rare disease. 40K-RNA provides an accurate, evidence-based method to predict variant-activated cryptic-donors in genetic disorders, assisting pathology consideration of possible consequences of a variant for the encoded protein and RNA diagnostic testing strategies.
Giant second harmonic transport under time-reversal symmetry in a trigonal superconductor
Authors: Itahashi Yuki M. , Ideue Toshiya , Hoshino Shintaro , Goto Chihiro , Namiki Hiromasa , Sasagawa Takao , Iwasa Yoshihiro 
Published: March 2022

AbstractNonreciprocal or even-order nonlinear responses in symmetry-broken systems are powerful probes of emergent properties in quantum materials, including superconductors, magnets, and topological materials. Recently, vortex matter has been recognized as a key ingredient of giant nonlinear responses in superconductors with broken inversion symmetry. However, nonlinear effects have been probed as excess voltage only under broken time-reversal symmetry. In this study, we report second harmonic transport under time-reversal symmetry in the noncentrosymmetric trigonal superconductor PbTaSe2. The magnitude of anomalous nonlinear transport is two orders of magnitude larger than those in the normal state, and the directional dependence of nonlinear signals are fully consistent with crystal symmetry. The enhanced nonlinearity is semiquantitatively explained by the asymmetric Hall effect of vortex-antivortex string pairs in noncentrosymmetric systems. This study enriches the literature on nonlinear phenomena by elucidating quantum transport in noncentrosymmetric superconductors.
Rho-dependent transcription termination proceeds via three routes
Authors: Song Eunho , Uhm Heesoo , Munasingha Palinda Ruvan , Hwang Seungha , Seo Yeon-Soo , Kang Jin Young , Kang Changwon , Hohng Sungchul 
Published: March 2022

AbstractRho is a general transcription termination factor in bacteria, but many aspects of its mechanism of action are unclear. Diverse models have been proposed for the initial interaction between the RNA polymerase (RNAP) and Rho (catch-up and stand-by pre-terminational models); for the terminational release of the RNA transcript (RNA shearing, RNAP hyper-translocation or displacing, and allosteric models); and for the post-terminational outcome (whether the RNAP dissociates or remains bound to the DNA). Here, we use single-molecule fluorescence assays to study those three steps in transcription termination mediated by E. coli Rho. We find that different mechanisms previously proposed for each step co-exist, but apparently occur on various timescales and tend to lead to specific outcomes. Our results indicate that three kinetically distinct routes take place: (1) the catch-up mode leads first to RNA shearing for RNAP recycling on DNA, and (2) later to RNAP displacement for decomposition of the transcriptional complex; (3) the last termination usually follows the stand-by mode with displacing for decomposing. This three-route model would help reconcile current controversies on the mechanisms.
Neural relational inference to learn long-range allosteric interactions in proteins from molecular dynamics simulations
Authors: Zhu Jingxuan , Wang Juexin , Han Weiwei , Xu Dong 
Published: March 2022

AbstractProtein allostery is a biological process facilitated by spatially long-range intra-protein communication, whereby ligand binding or amino acid change at a distant site affects the active site remotely. Molecular dynamics (MD) simulation provides a powerful computational approach to probe the allosteric effect. However, current MD simulations cannot reach the time scales of whole allosteric processes. The advent of deep learning made it possible to evaluate both spatially short and long-range communications for understanding allostery. For this purpose, we applied a neural relational inference model based on a graph neural network, which adopts an encoder-decoder architecture to simultaneously infer latent interactions for probing protein allosteric processes as dynamic networks of interacting residues. From the MD trajectories, this model successfully learned the long-range interactions and pathways that can mediate the allosteric communications between distant sites in the Pin1, SOD1, and MEK1 systems. Furthermore, the model can discover allostery-related interactions earlier in the MD simulation trajectories and predict relative free energy changes upon mutations more accurately than other methods.
Cube attacks on round-reduced TinyJAMBU
Authors: Teng Wil Liam , Salam Iftekhar , Yau Wei-Chuen , Pieprzyk Josef , Phan Raphaël C.-W. 
Published: March 2022

AbstractLightweight cryptography has recently gained importance as the number of Internet of things (IoT) devices connected to Internet grows. Its main goal is to provide cryptographic algorithms that can be run efficiently in resource-limited environments such as IoT. To meet the challenge, the National Institute of Standards and Technology (NIST) announced the Lightweight Cryptography (LWC) project. One of the finalists of the project is the TinyJAMBU cipher. This work evaluates the security of the cipher. The tool used for the evaluation is the cube attack. We present five distinguishing attacks DA1–DA5 and two key recovery attacks KRA1–KRA2. The first two distinguishing attacks (DA1 and DA2) are launched against the initialisation phase of the cipher. The best result achieved for the attacks is a distinguisher for an 18-bit cube, where the cipher variant consists of the full initialisation phase together with 438 rounds of the encryption phase. The key recovery attacks (KRA1 and KRA2) are also launched against the initialisation phase of the cipher. The best key recovery attack can be applied for a cipher variant that consists of the full initialisation phase together with 428 rounds of the encryption phase. The attacks DA3–DA5 present a collection of distinguishers up to 437 encryption rounds, whose 32-bit cubes are chosen from the plaintext, nonce, or associated data bits. The results are confirmed experimentally. A conclusion from the work is that TinyJAMBU has a better security margin against cube attacks than claimed by the designers.
Detection of subclinical keratoconus using a novel combined tomographic and biomechanical model based on an automated decision tree
Authors: Song Peng , Ren Shengwei , Liu Yu , Li Pei , Zeng Qingyan 
Published: March 2022

AbstractEarly detection of keratoconus is a crucial factor in monitoring its progression and making the decision to perform refractive surgery. The aim of this study was to use the decision tree technique in the classification and prediction of subclinical keratoconus (SKC). A total of 194 eyes (including 105 normal eyes and 89 with SKC) were included in the double-center retrospective study. Data were separately used for training and validation databases. The baseline variables were derived from tomography and biomechanical imaging. The decision tree models were generated using Chi-square automatic interaction detection (CHAID) and classification and regression tree (CART) algorithms based on the training database. The discriminating rules of the CART model selected metrics of the Belin/Ambrósio deviation (BAD-D), stiffness parameter at first applanation (SPA1), back eccentricity (Becc), and maximum pachymetric progression index in that order; On the other hand, the CHAID model selected BAD-D, deformation amplitude ratio, SPA1, and Becc. Further, the CART model allowed for discrimination between normal and SKC eyes with 92.2% accuracy, which was higher than that of the CHAID model (88.3%), BAD-D (82.0%), Corvis biomechanical index (CBI, 77.3%), and tomographic and biomechanical index (TBI, 78.1%). The discriminating performance of the CART model was validated with 92.4% accuracy, while the CHAID model was validated with 86.4% accuracy in the validation database. Thus, the CART model using tomography and biomechanical imaging was an excellent model for SKC screening and provided easy-to-understand discriminating rules.
Acute pancreatitis or severe increase in pancreatic enzyme levels following remdesivir administration in COVID-19 patients: an observational study
Authors: Miyazaki Kazuhito , Yoshimura Yukihiro , Miyata Nobuyuki , Sasaki Hiroaki , Shiba Aya , Aga Masaharu , Hamakawa Yusuke , Taniguchi Yuri , Misumi Yuki , Agemi Yoko , Shimokawa Tsuneo , Okamoto Hiroaki , Tachikawa Natsuo 
Published: March 2022

AbstractRemdesivir has been shown to reduce recovery time and mortality among patients with coronavirus disease 2019 (COVID-19). However, data regarding the efficacy and safety of remdesivir use are limited in Japan. We conducted a single-center retrospective cohort study at Yokohama Municipal Citizen’s Hospital, Kanagawa, Japan. Patients with COVID-19 pneumonia treated with remdesivir were included. The onset of acute pancreatitis and increased pancreatic enzyme levels and clinical, laboratory, treatment, and outcome data were collected and analyzed. A total of 201 patients were included. Among the 201 patients treated with remdesivir, 177 recovered from COVID-19. Increased pancreatic enzyme levels of grade 3 or higher or acute pancreatitis developed in 23 of the 201 patients. The potential etiopathogenetic effects of remdesivir on increased pancreatic enzyme levels of grade 3 or higher or acute pancreatitis were ascertained by reviewing the characteristics of patients hospitalized for COVID-19 who did not receive remdesivir treatment. Only 3 of 159 patients had increased pancreatic enzyme levels of grade 3 or higher during the treatment course. Multivariate analysis indicated remdesivir administration and severe COVID-19 infection by National Institute of Health standards as independent risk factors. Acute pancreatitis and severe increases in pancreatic enzyme levels were observed among patients with COVID-19 treated with remdesivir.
Optical biosensors using plasmonic and photonic crystal band-gap structures for the detection of basal cell cancer
Authors: Khani Shiva , Hayati Mohsen 
Published: March 2022

AbstractOne of the most interesting topics in bio-optics is measuring the refractive index of tissues. Accordingly, two novel optical biosensor configurations for cancer cell detections have been proposed in this paper. These structures are composed of one-dimensional photonic crystal (PC) lattices coupled to two metal–insulator–metal (MIM) plasmonic waveguides. Also, the tapering method is used to improve the matching between the MIM plasmonic waveguides and PC structure in the second proposed topology. The PC lattices at the central part of the structures generate photonic bandgaps (PBGs) with sharp edges in the transmission spectra of the biosensors. These sharp edges are suitable candidates for sensing applications. On the other hand, the long distance between two PBG edges causes that when the low PBG edge is used for sensing mechanism, it does not have an overlapping with the high PBG edge by changing the refractive index of the analyte. Therefore, the proposed biosensors can be used for a wide wavelength range. The maximum obtained sensitivities and FOM values of the designed biosensors are equal to 718.6, 714.3 nm/RIU, and 156.217, 60.1 RIU−1, respectively. The metal and insulator materials which are used in the designed structures are silver, air, and GaAs, respectively. The finite-difference time-domain (FDTD) method is used for the numerical investigation of the proposed structures. Furthermore, the initial structure of the proposed biosensors is analyzed using the transmission line method to verify the FDTD simulations. The attractive and simple topologies of the proposed biosensors and their high sensitivities make them suitable candidates for biosensing applications.
The association between diabetes and hypertension with the number and extent of weight cycles determined from 6 million participants
Authors: Kim Su Hwan , Kwak Jin-Seul , Kim Seong Pyo , Choi Sung Hyouk , Yoon Hyung-Jin 
Published: March 2022

AbstractThe purpose of this study was to elucidate the association between weight cycling and clinical outcomes such as type 2 diabetes and hypertension with differential effects of baseline age and obesity. Nationwide data from 6,132,569 healthy adults who underwent five or more health screenings between 2002 and 2011 were analyzed and followed until December 2019 for type 2 diabetes and hypertension. Weight cycling was defined as a change in body weight followed by another change in the opposite direction. Through the Cox proportional hazards model, the number and degree of weight cycles were positively associated with increased risk of type 2 diabetes and hypertension. The hazard ratios (HRs) of weight cycling for type 2 diabetes and hypertension were as high as 1.263 (1.213–1.315) and 1.175 (1.144–1.207) at two or more weight cycles of 10% of body weight (BW), respectively. The association was stronger for females, individuals with normal body weight/BMI, and older individuals. Weight cycling was significantly associated with an increased risk of adverse health outcomes and was stronger in individuals with normal BMI and females, indicating that these people should be informed about the potential risk of weight cycling.