bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Biological‐Parameter‐Optimized Modeling Study of Physical Drivers Controlling Seasonal Chlorophyll Blooms off the Southern Coast of Java Island
Authors: Gao Guandong , Yang Dezhou , Xu Lingjing , Zhang Kun , Feng Xingru , Yin Baoshu 
Published: October 2022

AbstractA physical‐biogeochemical model consists of many key parameters; theoretically, 10,000 or more numerical experiments are required to obtain a set of optimal biological parameters. The corresponding computing resources are too expensive when running a three‐dimensional and high‐resolution physical‐biogeochemical model. In this study, we improve the performance of a three‐dimensional physical‐biogeochemical model via the conditional nonlinear optimal perturbation method for southern Java Island, where chlorophyll blooms occur seasonally. Based on the improved model results, we calculated the mixed‐layer nutrient budget, thereby characterizing how each physical process transports nutrients into the surface oligotrophic layer and then stimulates the chlorophyll blooms during the southeast monsoon season. Nutrients that upwell along the submarine slope are found in narrow regions along the coast and spread into most of the study area by local wind‐induced offshore transport. The contribution of nonlinearity (advection) is essential to modulating the upslope movement of nutrients off the coast. If local winds are neglected in the model, onshore transport induced by the pressure gradient force in the zonal direction (alongshore) and subsequent downwelling would be dominant, and chlorophyll blooms would diminish in most regions. The role of the South Java Coastal Current varies under the joint influence of remote and local wind forcings. The Indonesian Throughflow from the Lombok Strait also contributes to surface phytoplankton growth along its path off the south of Java Island.
Effects of prophylactic indomethacin on morbidity and mortality in infants <25 weeks’ gestation: a protocol driven intention to treat analysis
Authors: Clyman Ronald I. , Hills Nancy K. 
Published: October 2022

Abstract
Objective
To determine if prophylactic indomethacin (PINDO) decreases death or bronchopulmonary dysplasia-grades 2 and 3 (death/BPD) in newborns <25 weeks.

Study design
Intention-to-treat, cohort-controlled study of 106 infants admitted during three alternating epochs of PINDO or Expectant patent ductus arteriosus (PDA) management.

Results
At 7–8 days 85% of Expectant Management epoch infants had a moderate/large PDA (median exposure was 23 days). Among PINDO epoch infants only 24% still had a PDA at 7–8 days. There were no significant differences in the incidence of death/BPD or of secondary outcomes (BPD, death, necrotizing enterocolitis/spontaneous perforations, or intraventricular hemorrhage (grades 3 or 4)) in either unadjusted or adjusted comparisons between infants born in a PINDO epoch and those born in the Expectant Management epoch.

Conclusion
Despite being at high risk for PDA-related morbidities, PINDO did not appear to alter the rates of our primary and secondary outcomes in infants <25 weeks.
Inhibition of CD40-TRAF6-dependent inflammatory activity halts the onset of diabetic retinopathy in streptozotocin-diabetic mice
Authors: Howell Scott J. , Lee Chieh A. , Zapadka Thomas E. , Lindstrom Sarah I. , Taylor Brooklyn E. , Taylor Zakary R. R. , Barber Katherine G. , Taylor Patricia R. 
Published: October 2022

AbstractDiabetes initiates inflammation that can impair the retinal vasculature, and lead to diabetic retinopathy; one of the leading causes of blindness. Inflammatory pathways have been examined as potential therapeutic targets for diabetic retinopathy, but there is still a need for early-stage treatments. We hypothesized that the CD40-TNF Receptor Associated Factor 6 (TRAF6) axis plays a pivotal role in the onset of diabetic retinopathy, and that the CD40-TRAF6 axis would be a prime therapeutic target for early-stage non-proliferative diabetic retinopathy. The CD40-TRAF6 complex can initiate NFκB activation, inflammation, and tissue damage. Further, CD40 and TRAF6 are constitutively expressed on Muller glia, and upregulated in the diabetic retina. Yet the role of the CD40-TRAF6 complex in the onset of diabetic retinopathy is still unclear. In the current study, we examined the CD40-TRAF6 axis in diabetic retinopathy using a small molecule inhibitor (SMI-6877002) on streptozotocin-induced diabetic mice. When CD40-TRAF6-dependent inflammation was inhibited, retinal vascular leakage and capillary degeneration was ameliorated in diabetic mice. Collectively, these data suggest that the CD40-TRAF6 axis plays a pivotal role in the onset of diabetic retinopathy, and could be a novel therapeutic target for early diabetic retinopathy.
Glioblastoma cell motility depends on enhanced oxidative stress coupled with mobilization of a sulfurtransferase
Authors: Saurty-Seerunghen Mirca S. , Daubon Thomas , Bellenger Léa , Delaunay Virgile , Castro Gloria , Guyon Joris , Rezk Ahmed , Fabrega Sylvie , Idbaih Ahmed , Almairac Fabien , Burel-Vandenbos Fanny , Turchi Laurent , Duplus Eric , Virolle Thierry , Peyrin Jean-Michel , Antoniewski Christophe , Chneiweiss Hervé , El-Habr Elias A. , Junier Marie-Pierre 
Published: October 2022

AbstractCell motility is critical for tumor malignancy. Metabolism being an obligatory step in shaping cell behavior, we looked for metabolic weaknesses shared by motile cells across the diverse genetic contexts of patients’ glioblastoma. Computational analyses of single-cell transcriptomes from thirty patients’ tumors isolated cells with high motile potential and highlighted their metabolic specificities. These cells were characterized by enhanced mitochondrial load and oxidative stress coupled with mobilization of the cysteine metabolism enzyme 3-Mercaptopyruvate sulfurtransferase (MPST). Functional assays with patients’ tumor-derived cells and -tissue organoids, and genetic and pharmacological manipulations confirmed that the cells depend on enhanced ROS production and MPST activity for their motility. MPST action involved protection of protein cysteine residues from damaging hyperoxidation. Its knockdown translated in reduced tumor burden, and a robust increase in mice survival. Starting from cell-by-cell analyses of the patients’ tumors, our work unravels metabolic dependencies of cell malignancy maintained across heterogeneous genomic landscapes.
Inducing forgetting of unwanted memories through subliminal reactivation
Authors: Zhu Zijian , Anderson Michael C. , Wang Yingying 
Published: October 2022

AbstractProcesses that might facilitate the forgetting of unwanted experiences typically require the actual or imagined re-exposure to reminders of the event, which is aversive and carries risks to people. But it is unclear whether awareness of aversive content is necessary for effective voluntary forgetting. Disrupting hippocampal function through retrieval suppression induces an amnesic shadow that impairs the encoding and stabilization of unrelated memories that are activated near in time to people’s effort to suppress retrieval. Building on this mechanism, here we successfully disrupt retention of unpleasant memories by subliminally reactivating them within this amnesic shadow. Critically, whereas unconscious forgetting occurs on these affective memories, the amnesic shadow itself is induced by conscious suppression of unrelated and benign neutral memories, avoiding conscious re-exposure of unwelcome content. Combining the amnesic shadow with subliminal reactivation may offer a new approach to voluntary forgetting that bypasses the unpleasantness in conscious exposure to unwanted memories.
Mendelian randomization accounting for complex correlated horizontal pleiotropy while elucidating shared genetic etiology
Authors: Cheng Qing , Zhang Xiao , Chen Lin S. , Liu Jin 
Published: October 2022

AbstractMendelian randomization (MR) harnesses genetic variants as instrumental variables (IVs) to study the causal effect of exposure on outcome using summary statistics from genome-wide association studies. Classic MR assumptions are violated when IVs are associated with unmeasured confounders, i.e., when correlated horizontal pleiotropy (CHP) arises. Such confounders could be a shared gene or inter-connected pathways underlying exposure and outcome. We propose MR-CUE (MR with Correlated horizontal pleiotropy Unraveling shared Etiology and confounding), for estimating causal effect while identifying IVs with CHP and accounting for estimation uncertainty. For those IVs, we map their cis-associated genes and enriched pathways to inform shared genetic etiology underlying exposure and outcome. We apply MR-CUE to study the effects of interleukin 6 on multiple traits/diseases and identify severalS100genes involved in shared genetic etiology. We assess the effects of multiple exposures on type 2 diabetes across European and East Asian populations.
Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context
Authors: Setten Elisa , Castagna Alessandra , Nava-Sedeño Josué Manik , Weber Jonathan , Carriero Roberta , Reppas Andreas , Volk Valery , Schmitz Jessica , Gwinner Wilfried , Hatzikirou Haralampos , Feuerhake Friedrich , Locati Massimo 
Published: October 2022

AbstractFibrosis is a progressive biological condition, leading to organ dysfunction in various clinical settings. Although fibroblasts and macrophages are known as key cellular players for fibrosis development, a comprehensive functional model that considers their interaction in the metabolic/immunologic context of fibrotic tissue has not been set up. Here we show, by transcriptome-based mathematical modeling in an in vitro system that represents macrophage-fibroblast interplay and reflects the functional effects of inflammation, hypoxia and the adaptive immune context, that irreversible fibrosis development is associated with specific combinations of metabolic and inflammatory cues. The in vitro signatures are in good alignment with transcriptomic profiles generated on laser captured glomeruli and cortical tubule-interstitial area, isolated from human transplanted kidneys with advanced stages of glomerulosclerosis and interstitial fibrosis/tubular atrophy, two clinically relevant conditions associated with organ failure in renal allografts. The model we describe here is validated on tissue based quantitative immune-phenotyping of biopsies from transplanted kidneys, demonstrating its feasibility. We conclude that the combination of in vitro and in silico modeling represents a powerful systems medicine approach to dissect fibrosis pathogenesis, applicable to specific pathological conditions, and develop coordinated targeted approaches.
Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis
Authors: Muto Yoshiharu , Dixon Eryn E. , Yoshimura Yasuhiro , Wu Haojia , Omachi Kohei , Ledru Nicolas , Wilson Parker C. , King Andrew J. , Eric Olson N. , Gunawan Marvin G. , Kuo Jay J. , Cox Jennifer H. , Miner Jeffrey H. , Seliger Stephen L. , Woodward Owen M. , Welling Paul A. , Watnick Terry J. , Humphreys Benjamin D. 
Published: October 2022

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal disease characterized by progressive expansion of kidney cysts. To better understand the cell types and states driving ADPKD progression, we analyze eight ADPKD and five healthy human kidney samples, generating single cell multiomic atlas consisting of ~100,000 single nucleus transcriptomes and ~50,000 single nucleus epigenomes. Activation of proinflammatory, profibrotic signaling pathways are driven by proximal tubular cells with a failed repair transcriptomic signature, proinflammatory fibroblasts and collecting duct cells. We identify GPRC5A as a marker for cyst-lining collecting duct cells that exhibits increased transcription factor binding motif availability for NF-κB, TEAD, CREB and retinoic acid receptors. We identify and validate a distal enhancer regulating GPRC5A expression containing these motifs. This single cell multiomic analysis of human ADPKD reveals previously unrecognized cellular heterogeneity and provides a foundation to develop better diagnostic and therapeutic approaches.
Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data
Authors: Chen Junyi , Wang Xiaoying , Ma Anjun , Wang Qi-En , Liu Bingqiang , Li Lang , Xu Dong , Ma Qin 
Published: October 2022

AbstractDrug screening data from massive bulk gene expression databases can be analyzed to determine the optimal clinical application of cancer drugs. The growing amount of single-cell RNA sequencing (scRNA-seq) data also provides insights into improving therapeutic effectiveness by helping to study the heterogeneity of drug responses for cancer cell subpopulations. Developing computational approaches to predict and interpret cancer drug response in single-cell data collected from clinical samples can be very useful. We propose scDEAL, a deep transfer learning framework for cancer drug response prediction at the single-cell level by integrating large-scale bulk cell-line data. The highlight in scDEAL involves harmonizing drug-related bulk RNA-seq data with scRNA-seq data and transferring the model trained on bulk RNA-seq data to predict drug responses in scRNA-seq. Another feature of scDEAL is the integrated gradient feature interpretation to infer the signature genes of drug resistance mechanisms. We benchmark scDEAL on six scRNA-seq datasets and demonstrate its model interpretability via three case studies focusing on drug response label prediction, gene signature identification, and pseudotime analysis. We believe that scDEAL could help study cell reprogramming, drug selection, and repurposing for improving therapeutic efficacy.
Accelerated water activation and stabilized metal-organic framework via constructing triangular active-regions for ampere-level current density hydrogen production
Authors: Cheng Fanpeng , Peng Xianyun , Hu Lingzi , Yang Bin , Li Zhongjian , Dong Chung-Li , Chen Jeng-Lung , Hsu Liang-Ching , Lei Lecheng , Zheng Qiang , Qiu Ming , Dai Liming , Hou Yang 
Published: October 2022

AbstractTwo-dimensional metal-organic frameworks (MOFs) have been explored as effective electrocatalysts for hydrogen evolution reaction (HER). However, the sluggish water activation kinetics and structural instability under ultrahigh-current density hinder their large-scale industrial applications. Herein, we develop a universal ligand regulation strategy to build well-aligned Ni-benzenedicarboxylic acid (BDC)-based MOF nanosheet arrays with S introducing (S-NiBDC). Benefiting from the closerp-band center to the Fermi level with strong electron transferability, S-NiBDC array exhibits a low overpotential of 310 mV to attain 1.0 A cm−2with high stability in alkaline electrolyte. We speculate the newly-constructed triangular “Ni2-S1” motif as the improved HER active region based on detailed mechanism analysis and structural characterization, and the enhanced covalency of Ni-O bonds by S introducing stabilizes S-NiBDC structure. Experimental observations and theoretical calculations elucidate that such Ni sites in “Ni2-S1” center distinctly accelerate the water activation kinetics, while the S site readily captures the H atom as the optimal HER active site, boosting the whole HER activity.
A warm-white light-emitting diode based on single-component emitter aromatic carbon nitride
Authors: Wang Yunhu , Wang Kunpeng , Dai Fangxu , Zhang Kai , Tang Haifeng , Wang Lei , Xing Jun 
Published: October 2022

AbstractArtificial lighting consumes almost one-fifth of global electricity. As an efficient solid-state lighting technology, white light-emitting diodes (WLEDs) have received increasing attention. However, the white luminescence of the traditional WLEDs comes from multi-component emitters, which leads to complex device structure and unstable emitting color. Therefore, developing single-component materials with white-light electroluminescence is of significance for artificial lighting applications. Here, we fabricate single-component white-light electroluminescence devices based on an aromatic carbon nitride material and improve the performance of WLEDs by adjusting the carrier transport. The carbon nitride LEDs emit warm-white light, of which color coordinates and color temperature are (0.44, 0.52) and 3700 K. The optimized LEDs display a very low turn-on voltage of 3.2 V and achieve a milestone in the maximum luminance and external quantum efficiency of 1885 cd m−2 and 1.20%. Our findings demonstrate the low-cost carbon nitride materials have promising potential for single-component WLEDs application.
Functional selectivity of insulin receptor revealed by aptamer-trapped receptor structures
Authors: Kim Junhong , Yunn Na-Oh , Park Mangeun , Kim Jihan , Park Seongeun , Kim Yoojoong , Noh Jeongeun , Ryu Sung Ho , Cho Yunje 
Published: October 2022

AbstractActivation of insulin receptor (IR) initiates a cascade of conformational changes and autophosphorylation events. Herein, we determined three structures of IR trapped by aptamers using cryo-electron microscopy. The A62 agonist aptamer selectively activates metabolic signaling. In the absence of insulin, the two A62 aptamer agonists of IR adopt an insulin-accessible arrowhead conformation by mimicking site-1/site-2’ insulin coordination. Insulin binding at one site triggers conformational changes in one protomer, but this movement is blocked in the other protomer by A62 at the opposite site. A62 binding captures two unique conformations of IR with a similar stalk arrangement, which underlie Tyr1150 mono-phosphorylation (m-pY1150) and selective activation for metabolic signaling. The A43 aptamer, a positive allosteric modulator, binds at the opposite side of the insulin-binding module, and stabilizes the single insulin-bound IR structure that brings two FnIII-3 regions into closer proximity for full activation. Our results suggest that spatial proximity of the two FnIII-3 ends is important for m-pY1150, but multi-phosphorylation of IR requires additional conformational rearrangement of intracellular domains mediated by coordination between extracellular and transmembrane domains.
A missense variant in the nuclear localization signal of DKC1 causes Hoyeraal-Hreidarsson syndrome
Authors: Chu Chia-Mei , Yu Hsin-Hui , Kao Tsai-Ling , Chen Yi-Hsuan , Lu Hsuan-Hsuan , Wu En-Ting , Yang Yun-Li , Lin Chin-Hsien , Lin Shin-Yu , Tsai Meng-Ju Melody , Chien Yin-Hsiu , Hwu Wuh-Liang , Chen Wen-Pin , Lee Ni-Chung , Tseng Chi-Kang 
Published: October 2022

AbstractHoyeraal-Hreidarsson syndrome (HHS) is the most severe form of dyskeratosis congenita (DC) and is caused by mutations in genes involved in telomere maintenance. Here, we identified male siblings from a family with HHS carrying a hemizygous mutation (c.1345C > G, p.R449G), located in the C-terminal nuclear localization signal (NLS) of the DKC1 gene. These patients exhibit progressive cerebellar hypoplasia, recurrent infections, pancytopenia due to bone marrow failure, and short leukocyte telomere lengths. Single-cell RNA sequencing analysis suggested defects in the NLRP3 inflammasome in monocytes and the activation and maturation of NK cells and B cells. In experiments using induced pluripotent stem cells (iPSCs) from patients, DKC1_R449G iPSCs had short telomere lengths due to reduced levels of human telomerase RNA (hTR) and increased cytosolic proportions of DKC1. Treatment with dihydroquinolizinone RG7834 and 3′deoxyanosine cordycepin rescued telomere length in patient-derived iPSCs. Together, our findings not only provide new insights into immunodeficiency in DC patients but also provide treatment options for telomerase insufficiency disorders.
Lightweight and flexible Cu(In,Ga)Se2 solar minimodules: toward 20% photovoltaic efficiency and beyond
Authors: Ishizuka Shogo , Kamikawa Yukiko , Nishinaga Jiro 
Published: October 2022

AbstractLightweight and flexible photovoltaic solar cells and modules are promising technologies that may result in the wide usage of light-to-electricity energy conversion devices. This communication presents the prospects of Cu(In,Ga)Se2(CIGS)-based lightweight and flexible photovoltaic devices. The current status of flexible CIGS minimodules with photovoltaic efficiency values greater than 18% and future directions to enhance their efficiency values toward >20% are discussed. The effects of cell separation edges, which are formed through a mechanical, laser, or photolithography scribing process used to fabricate solar cells and modules, on the device performance are also discussed. We found that mechanically scribed CIGS device edges, which are present in conventional solar cells and modules, cause deterioration of device performance. In other words, further improvement is expected with appropriate passivation/termination treatment of the edges or replacing mechanical scribing with a damage-free separation process.
Nonreciprocal charge transport in topological superconductor candidate Bi2Te3/PdTe2 heterostructure
Authors: Masuko Makoto , Kawamura Minoru , Yoshimi Ryutaro , Hirayama Motoaki , Ikeda Yuya , Watanabe Ryota , He James Jun , Maryenko Denis , Tsukazaki Atsushi , Takahashi Kei S. , Kawasaki Masashi , Nagaosa Naoto , Tokura Yoshinori 
Published: October 2022

AbstractIn a hybrid system of topological insulator (TI)/superconductor (SC), the proximity-induced topological superconductivity is expected to appear at the interface. Here we propose and demonstrate that a TI/SC hybrid Bi2Te3/PdTe2 heterostructure serves as a platform for exploring topological superconductivity with various features: all made of tellurium compounds, epitaxial growth, and a small charge transfer interface. In the Bi2Te3/PdTe2 heterostructure films, we observe large nonreciprocal charge transport near the superconducting transition temperature under a transverse in-plane magnetic field. The observation indicates the interplay between the topological surface state and superconductivity, suggesting that the Bi2Te3/PdTe2 heterostructure is a candidate for a topological superconductor. Also observed is an unexpected sign reversal of the nonreciprocal coefficient when the in-plane magnetic field is slightly tilted toward the out-of-plane direction. The analysis reveals that the sign reversal occurs with the change of dominant vortex type, that is, the change from spontaneous vortices to external-field induced ones.
Increases in multiple resources promote competitive ability of naturalized non-native plants
Authors: Zhang Zhijie , Liu Yanjie , Hardrath Angelina , Jin Huifei , van Kleunen Mark 
Published: October 2022

AbstractInvasion by non-native plants is frequently attributed to increased resource availability. Still, our understanding is mainly based on effects of single resources and on plants grown without competition despite the fact that plants rely on multiple resources and usually grow in competition. How multiple resources affects competition between native and non-native plants remains largely unexplored. Here, with two similar common garden experiments, one in China and one in Germany, we tested whether nutrient and light availabilities affected the competitive outcomes, in terms of biomass production, between native and naturalized non-native plants. We found that under low resource availability or with addition of only one type of resource non-natives were not more competitive than natives. However, with a joint increase of nutrients and light intensity, non-natives were more competitive than natives. Our finding indicates that addition of multiple resources could greatly reduce the niche dimensionality (i.e. number of limiting factors), favoring dominance of non-native species. It also indicates that habitats experiencing multiple global changes might be more vulnerable to plant invasion.