bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal workflows optimally predict response to repetitive transcranial magnetic stimulation in patients with schizophrenia: a multisite machine learning analysis
Authors: Dong Mark Sen , Rokicki Jaroslav , Dwyer Dominic , Papiol Sergi , Streit Fabian , Rietschel Marcella , Wobrock Thomas , Müller-Myhsok Bertram , Falkai Peter , Westlye Lars Tjelta , Andreassen Ole A. , Palaniyappan Lena , Schneider-Axmann Thomas , Hasan Alkomiet , Schwarz Emanuel , Koutsouleris Nikolaos 
Published: April 2024

AbstractThe response variability to repetitive transcranial magnetic stimulation (rTMS) challenges the effective use of this treatment option in patients with schizophrenia. This variability may be deciphered by leveraging predictive information in structural MRI, clinical, sociodemographic, and genetic data using artificial intelligence. We developed and cross-validated rTMS response prediction models in patients with schizophrenia drawn from the multisite RESIS trial. The models incorporated pre-treatment sMRI, clinical, sociodemographic, and polygenic risk score (PRS) data. Patients were randomly assigned to receive active (N = 45) or sham (N = 47) rTMS treatment. The prediction target was individual response, defined as ≥20% reduction in pre-treatment negative symptom sum scores of the Positive and Negative Syndrome Scale. Our multimodal sequential prediction workflow achieved a balanced accuracy (BAC) of 94% (non-responders: 92%, responders: 95%) in the active-treated group and 50% in the sham-treated group. The clinical, clinical + PRS, and sMRI-based classifiers yielded BACs of 65%, 76%, and 80%, respectively. Apparent sadness, inability to feel, educational attainment PRS, and unemployment were most predictive of non-response in the clinical + PRS model, while grey matter density reductions in the default mode, limbic networks, and the cerebellum were most predictive in the sMRI model. Our sequential modelling approach provided superior predictive performance while minimising the diagnostic burden in the clinical setting. Predictive patterns suggest that rTMS responders may have higher levels of brain grey matter in the default mode and salience networks which increases their likelihood of profiting from plasticity-inducing brain stimulation methods, such as rTMS. The future clinical implementation of our models requires findings to be replicated at the international scale using stratified clinical trial designs.
A potential strategy for bladder cancer treatment: inhibiting autophagy to enhance antitumor effects of Nectin-4-MMAE
Authors: Wang Yichen , Nan Yanyang , Ma Chunguang , Lu Xiaolin , Wang Qian , Huang Xiting , Xue Wenjing , Fan Jiajun , Ju Dianwen , Ye Dingwei , Zhang Xuyao 
Published: April 2024

AbstractResearch and development on Nectin-4 antibody-drug conjugates (ADC) have been greatly accelerated since the approval of enfortumab vedotin to treat uroepithelial cancer. During the course of this study, we identified that autophagy serves as a cytoprotective mechanism during Nectin-4-MMAE treatment and proposed a strategy to enhance the antitumor effects of Nectin-4-MMAE in bladder cancer. Nectin-4-MMAE rapidly internalized into bladder cancer cells in 30 minutes and released MMAE, inducing the onset of caspase-mediated apoptosis and leading to the inhibition of tumor cell growth. Transcriptomics showed significant alterations in autophagy-associated genes in bladder cancer cells treated with Nectin-4-MMAE, which suggested autophagy was activated by Nectin-4-MMAE. Furthermore, autophagy activation was characterized by ultrastructural analysis of autophagosome accumulation, immunofluorescence of autophagic flux, and immunoblotting autophagy marker proteins SQSTM1 and LC3 I/II. Importantly, inhibiting autophagy by LY294002 and chloroquine significantly enhances the cytotoxicity effects of Nectin-4-MMAE in bladder cancer cells. Additionally, we detected the participation of the AKT/mTOR signaling cascade in the induction of autophagy by Nectin-4-MMAE. The combination of Nectin-4-MMAE and an autophagy inhibitor demonstrated enhanced antitumor effects in the HT1376 xenograft tumor model. After receiving a single dose of Nectin-4-MMAE, the group that received the combination treatment showed a significant decrease in tumor size compared to the group that received only one type of treatment. Notably, one mouse in the combination treatment group achieved complete remission of the tumor. The combination group exhibited a notable rise in apoptosis and necrosis, as indicated by H&E staining and immunohistochemistry (cleaved caspase-3, ki67). These findings demonstrated the cytoprotective role of autophagy during Nectin-4-MMAE treatment and highlighted the potential of combining Nectin-4-MMAE with autophagy inhibitors for bladder cancer treatment.
Artificial light at night affects the daily profile of pulse pressure and protein expression in the thoracic aorta of rats
Authors: Mauer Sutovska Hana , Obermajer Viktor , Zeman Michal , Molcan Lubos 
Published: April 2024

AbstractArtificial light at night (ALAN) disrupts 24-h variability of blood pressure, but the molecular mechanisms underlying these effects are unknown. Therefore, we analysed the daily variability of pulse pressure, the maximum value of acceleration rate of aortic pressure (dP/dt(max)) measured by telemetry and protein expression in the thoracic aorta of normotensive male rats exposed to ALAN (1–2 lx) for 3 weeks. Daily, 24-h variability of pulse pressure and dP/dt(max) was observed during a regular light/dark regimen with higher values during the dark compared to the light phase of the day. ALAN suppressed 24-h variability and enhanced ultradian (<12-h) periods of pulse pressure and dP/dt(max) in duration-dependent manners. From beat-to-beat blood pressure variability, ALAN decreased low-frequency bands (a sympathetic marker) and had minimal effects on high-frequency bands. At the molecular level, ALAN decreased angiotensin II receptor type 1 expression and reduced 24-h variability. ALAN caused the appearance of 12-h oscillations in transforming growth factor β1 and fibulin 4. Expression of sarco/endoplasmic reticulum Ca2+-ATPase type 2 was increased in the middle of the light and dark phase of the day, and ALAN did not affect its daily and 12-h variability. In conclusion, ALAN suppressed 24-h variability of pulse pressure and dP/dt(max), decreased the power of low-frequency bands and differentially affected the expression of specific proteins in the rat thoracic aorta. Suppressed 24-h oscillations by ALAN underline the pulsatility of individual endocrine axes with different periods, disrupting the cardiovascular control of central blood pressure.
Numb positively regulates Hedgehog signaling at the ciliary pocket
Authors: Liu Xiaoliang , Yam Patricia T. , Schlienger Sabrina , Cai Eva , Zhang Jingyi , Chen Wei-Ju , Torres Gutierrez Oscar , Jimenez Amilburu Vanesa , Ramamurthy Vasanth , Ting Alice Y. , Branon Tess C. , Cayouette Michel , Gen Risako , Marks Tessa , Kong Jennifer H. , Charron Frédéric , Ge Xuecai 
Published: April 2024

AbstractHedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.
Bat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets
Authors: Halwe Nico Joel , Hamberger Lea , Sehl-Ewert Julia , Mache Christin , Schön Jacob , Ulrich Lorenz , Calvelage Sten , Tönnies Mario , Fuchs Jonas , Bandawane Pooja , Loganathan Madhumathi , Abbad Anass , Carreño Juan Manuel , Bermúdez-González Maria C. , Simon Viviana , Kandeil Ahmed , El-Shesheny Rabeh , Ali Mohamed A. , Kayali Ghazi , Budt Matthias , Hippenstiel Stefan , Hocke Andreas C. , Krammer Florian , Wolff Thorsten , Schwemmle Martin , Ciminski Kevin , Hoffmann Donata , Beer Martin 
Published: April 2024

AbstractInfluenza A viruses (IAVs) of subtype H9N2 have reached an endemic stage in poultry farms in the Middle East and Asia. As a result, human infections with avian H9N2 viruses have been increasingly reported. In 2017, an H9N2 virus was isolated for the first time from Egyptian fruit bats (Rousettus aegyptiacus). Phylogenetic analyses revealed that bat H9N2 is descended from a common ancestor dating back centuries ago. However, the H9 and N2 sequences appear to be genetically similar to current avian IAVs, suggesting recent reassortment events. These observations raise the question of the zoonotic potential of the mammal-adapted bat H9N2. Here, we investigate the infection and transmission potential of bat H9N2 in vitro and in vivo, the ability to overcome the antiviral activity of the human MxA protein, and the presence of N2-specific cross-reactive antibodies in human sera. We show that bat H9N2 has high replication and transmission potential in ferrets, efficiently infects human lung explant cultures, and is able to evade antiviral inhibition by MxA in transgenic B6 mice. Together with its low antigenic similarity to the N2 of seasonal human strains, bat H9N2 fulfils key criteria for pre-pandemic IAVs.
Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion
Authors: Gao Junjun , Zhang Song , Deng Pan , Wu Zhigang , Lemaitre Bruno , Zhai Zongzhao , Guo Zheng 
Published: April 2024

AbstractAmino acid availability is monitored by animals to adapt to their nutritional environment. Beyond gustatory receptors and systemic amino acid sensors, enteroendocrine cells (EECs) are believed to directly percept dietary amino acids and secrete regulatory peptides. However, the cellular machinery underlying amino acid-sensing by EECs and how EEC-derived hormones modulate feeding behavior remain elusive. Here, by developing tools to specifically manipulate EECs, we find thatDrosophilaneuropeptide F (NPF) from mated female EECs inhibits feeding, similar to human PYY. Mechanistically, dietary L-Glutamate acts through the metabotropic glutamate receptor mGluR to decelerate calcium oscillations in EECs, thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive EEC-derived NPF and relay an anorexigenic signal to the brain. Thus, our findings provide mechanistic insights into how EECs assess food quality and identify a conserved mode of action that explains how gut NPF/PYY modulates food intake.
Emerging trends in chiral inorganic nanomaterials for enantioselective catalysis
Authors: Li Si , Xu Xinxin , Xu Liguang , Lin Hengwei , Kuang Hua , Xu Chuanlai 
Published: April 2024

AbstractAsymmetric transformations and synthesis have garnered considerable interest in recent decades due to the extensive need for chiral organic compounds in biomedical, agrochemical, chemical, and food industries. The field of chiral inorganic catalysts, garnering considerable interest for its contributions to asymmetric organic transformations, has witnessed remarkable advancements and emerged as a highly innovative research area. Here, we review the latest developments in this dynamic and emerging field to comprehensively understand the advances in chiral inorganic nanocatalysts and stimulate further progress in asymmetric catalysis.
NMR characterization of RNA binding property of the DEAD-box RNA helicase DDX3X and its implications for helicase activity
Authors: Toyama Yuki , Shimada Ichio 
Published: April 2024

AbstractThe DEAD-box RNA helicase (DDX) plays a central role in many aspects of RNA metabolism by remodeling the defined structure of RNA molecules. While a number of structural studies have revealed the atomistic details of the interaction between DDX and RNA ligands, the molecular mechanism of how this molecule unwinds a structured RNA into an unstructured single-stranded RNA (ssRNA) has largely remained elusive. This is due to challenges in structurally characterizing the unwinding intermediate state and the lack of thermodynamic details underlying this process. In this study, we use solution nuclear magnetic resonance (NMR) spectroscopy to characterize the interaction of human DDX3X, a member of the DDX family, with various RNA ligands. Our results show that the inherent binding affinity of DDX3X for ssRNA is significantly higher than that for structured RNA elements. This preferential binding, accompanied by the formation of a domain-closed conformation in complex with ssRNA, effectively stabilizes the denatured ssRNA state and thus underlies the unwinding activity of DDX3X. Our results provide a thermodynamic and structural basis for the DDX function, whereby DDX can recognize and remodel a distinct set of structured RNAs to participate in a wide range of physiological processes.
Confining single Er3+ ions in sub-3 nm NaYF4 nanoparticles to induce slow relaxation of the magnetisation
Authors: Gálico Diogo A. , Rodrigues Emille M. , Halimi Ilias , Toivola Juho , Zhao He , Xu Jiahui , Moilanen Jani O. , Liu Xiaogang , Hemmer Eva , Murugesu Muralee 
Published: April 2024

AbstractMolecular systems known as single-molecule magnets (SMMs) exhibit magnet-like behaviour of slow relaxation of the magnetisation and magnetic hysteresis and have potential application in high-density memory storage or quantum computing. Often, their intrinsic magnetic properties are plagued by low-energy molecular vibrations that lead to phonon-induced relaxation processes, however, there is no straightforward synthetic approach for molecular systems that would lead to a small amount of low-energy vibrations and low phonon density of states at the spin-resonance energies. In this work, we apply knowledge accumulated over the last decade in molecular magnetism to nanoparticles, incorporating Er3+ ions in an ultrasmall sub-3 nm diamagnetic NaYF4 nanoparticle (NP) and probing the slow relaxation dynamics intrinsic to the Er3+ ion. Furthermore, by increasing the doping concentration, we also investigate the role of intraparticle interactions within the NP. The knowledge gained from this study is anticipated to enable better design of magnetically high-performance molecular and bulk magnets for a wide variety of applications, such as molecular electronics.
Nanosecond anomaly detection with decision trees and real-time application to exotic Higgs decays
Authors: Roche S. T. , Bayer Q. , Carlson B. T. , Ouligian W. C. , Serhiayenka P. , Stelzer J. , Hong T. M. 
Published: April 2024

AbstractWe present an interpretable implementation of the autoencoding algorithm, used as an anomaly detector, built with a forest of deep decision trees on FPGA, field programmable gate arrays. Scenarios at the Large Hadron Collider at CERN are considered, for which the autoencoder is trained using known physical processes of the Standard Model. The design is then deployed in real-time trigger systems for anomaly detection of unknown physical processes, such as the detection of rare exotic decays of the Higgs boson. The inference is made with a latency value of 30 ns at percent-level resource usage using the Xilinx Virtex UltraScale+ VU9P FPGA. Our method offers anomaly detection at low latency values for edge AI users with resource constraints.
Warming drives dissolved organic carbon export from pristine alpine soils
Authors: Pearson Andrew R. , Fox Bethany R. S. , Hellstrom John C. , Vandergoes Marcus J. , Breitenbach Sebastian F. M. , Drysdale Russell N , Höpker Sebastian N. , Wood Christopher T. , Schiller Martin , Hartland Adam 
Published: April 2024

AbstractDespite decades of research, the influence of climate on the export of dissolved organic carbon (DOC) from soil remains poorly constrained, adding uncertainty to global carbon models. The limited temporal range of contemporary monitoring data, ongoing climate reorganisation and confounding anthropogenic activities muddy the waters further. Here, we reconstruct DOC leaching over the last ~14,000 years using alpine environmental archives (two speleothems and one lake sediment core) across 4° of latitude from Te Waipounamu/South Island of Aotearoa New Zealand. We selected broadly comparable palaeoenvironmental archives in mountainous catchments, free of anthropogenically-induced landscape changes prior to ~1200 C.E. We show that warmer temperatures resulted in increased allochthonous DOC export through the Holocene, most notably during the Holocene Climatic Optimum (HCO), which was some 1.5–2.5 °C warmer than the late pre-industrial period—then decreased during the cooler mid-Holocene. We propose that temperature exerted the key control on the observed doubling to tripling of soil DOC export during the HCO, presumably via temperature-mediated changes in vegetative soil C inputs and microbial degradation rates. Future warming may accelerate DOC export from mountainous catchments, with implications for the global carbon cycle and water quality.
Efficient ammonia synthesis from the air using tandem non-thermal plasma and electrocatalysis at ambient conditions
Authors: Liu Wei , Xia Mengyang , Zhao Chao , Chong Ben , Chen Jiahe , Li He , Ou Honghui , Yang Guidong 
Published: April 2024

AbstractWhile electrochemical N2 reduction presents a sustainable approach to NH3 synthesis, addressing the emission- and energy-intensive limitations of the Haber-Bosch process, it grapples with challenges in N2 activation and competing with pronounced hydrogen evolution reaction. Here we present a tandem air-NOx-NOx−-NH3 system that combines non-thermal plasma-enabled N2 oxidation with Ni(OH)x/Cu-catalyzed electrochemical NOx− reduction. It delivers a high NH3 yield rate of 3 mmol h−1 cm−2 and a corresponding Faradaic efficiency of 92% at −0.25 V versus reversible hydrogen electrode in batch experiments, outperforming previously reported ones. Furthermore, in a flow mode concurrently operating the non-thermal plasma and the NOx− electrolyzer, a stable NH3 yield rate of approximately 1.25 mmol h−1 cm−2 is sustained over 100 h using pure air as the intake. Mechanistic studies indicate that amorphous Ni(OH)x on Cu interacts with hydrated K+ in the double layer through noncovalent interactions and accelerates the activation of water, enriching adsorbed hydrogen species that can readily react with N-containing intermediates. In situ spectroscopies and density functional theory (DFT) results reveal that NOx− adsorption and their hydrogenation process are optimized over the Ni(OH)x/Cu surface. This work provides new insights into electricity-driven distributed NH3 production using natural air at ambient conditions.
Purines enrich root-associated Pseudomonas and improve wild soybean growth under salt stress
Authors: Zheng Yanfen , Cao Xuwen , Zhou Yanan , Ma Siqi , Wang Youqiang , Li Zhe , Zhao Donglin , Yang Yanzhe , Zhang Han , Meng Chen , Xie Zhihong , Sui Xiaona , Xu Kangwen , Li Yiqiang , Zhang Cheng-Sheng 
Published: April 2024

AbstractThe root-associated microbiota plays an important role in the response to environmental stress. However, the underlying mechanisms controlling the interaction between salt-stressed plants and microbiota are poorly understood. Here, by focusing on a salt-tolerant plant wild soybean (Glycine soja), we demonstrate that highly conserved microbes dominated by Pseudomonas are enriched in the root and rhizosphere microbiota of salt-stressed plant. Two corresponding Pseudomonas isolates are confirmed to enhance the salt tolerance of wild soybean. Shotgun metagenomic and metatranscriptomic sequencing reveal that motility-associated genes, mainly chemotaxis and flagellar assembly, are significantly enriched and expressed in salt-treated samples. We further find that roots of salt stressed plants secreted purines, especially xanthine, which induce motility of the Pseudomonas isolates. Moreover, exogenous application for xanthine to non-stressed plants results in Pseudomonas enrichment, reproducing the microbiota shift in salt-stressed root. Finally, Pseudomonas mutant analysis shows that the motility related gene cheW is required for chemotaxis toward xanthine and for enhancing plant salt tolerance. Our study proposes that wild soybean recruits beneficial Pseudomonas species by exudating key metabolites (i.e., purine) against salt stress.
Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean
Authors: Taylor-Salmon Emma , Hill Verity , Paul Lauren M. , Koch Robert T. , Breban Mallery I. , Chaguza Chrispin , Sodeinde Afeez , Warren Joshua L. , Bunch Sylvia , Cano Natalia , Cone Marshall , Eysoldt Sarah , Garcia Alezaundra , Gilles Nicadia , Hagy Andrew , Heberlein Lea , Jaber Rayah , Kassens Elizabeth , Colarusso Pamela , Davis Amanda , Baudin Samantha , Rico Edhelene , Mejía-Echeverri Álvaro , Scott Blake , Stanek Danielle , Zimler Rebecca , Muñoz-Jordán Jorge L. , Santiago Gilberto A. , Adams Laura E. , Paz-Bailey Gabriela , Spillane Melanie , Katebi Volha , Paulino-Ramírez Robert , Mueses Sayira , Peguero Armando , Sánchez Nelissa , Norman Francesca F. , Galán Juan-Carlos , Huits Ralph , Hamer Davidson H. , Vogels Chantal B. F. , Morrison Andrea , Michael Scott F. , Grubaugh Nathan D. 
Published: April 2024

AbstractDengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.