bluuebunny/crossref_metadata_2025 huggingface dataset:
The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome
Authors: Nielsen-Dandoroff Emily , Ruegg Mischa S. G. , Bicknell Louise S.
Published: April 2023

High-throughput sequencing has become a standard first-tier approach for both diagnostics and research-based genetic testing. Consequently, this hypothesis-free testing manner has revealed the true breadth of clinical features for many established genetic disorders, including Meier-Gorlin syndrome (MGORS). Previously known as ear-patella short stature syndrome, MGORS is characterized by growth delay, microtia, and patella hypo/aplasia, as well as genital abnormalities, and breast agenesis in females. Following the initial identification of genetic causes in 2011, a total of 13 genes have been identified to date associated with MGORS. In this review, we summarise the genetic and clinical findings of each gene associated with MGORS and highlight molecular insights that have been made through studying patient variants. We note interesting observations arising across this group of genes as the number of patients has increased, such as the unusually high number of synonymous variants affecting splicing in CDC45 and a subgroup of genes that also cause craniosynostosis. We focus on the complicated molecular genetics for DONSON, where we examine potential genotype-phenotype patterns using the first 3D structural model of DONSON. The canonical role of all proteins associated with MGORS are involved in different stages of DNA replication and in addition to summarising how patient variants impact on this process, we discuss the potential contribution of non-canonical roles of these proteins to the pathophysiology of MGORS.
Oncogenic drivers dictate immune control of acute myeloid leukemia
Authors: Austin Rebecca J. , Straube Jasmin , Halder Rohit , Janardhanan Yashaswini , Bruedigam Claudia , Witkowski Matthew , Cooper Leanne , Porter Amy , Braun Matthias , Souza-Fonseca-Guimaraes Fernando , Minnie Simone A. , Cooper Emily , Jacquelin Sebastien , Song Axia , Bald Tobias , Nakamura Kyohei , Hill Geoffrey R. , Aifantis Iannis , Lane Steven W. , Bywater Megan J.
Published: April 2023

Acute myeloid leukemia (AML) is a genetically heterogeneous, aggressive hematological malignancy induced by distinct oncogenic driver mutations. The effect of specific AML oncogenes on immune activation or suppression is unclear. Here, we examine immune responses in genetically distinct models of AML and demonstrate that specific AML oncogenes dictate immunogenicity, the quality of immune response and immune escape through immunoediting. Specifically, expression of NrasG12D alone is sufficient to drive a potent anti-leukemia response through increased MHC Class II expression that can be overcome with increased expression of Myc. These data have important implications for the design and implementation of personalized immunotherapies for patients with AML.
Repurposing host-guest chemistry to sequester virulence and eradicate biofilms in multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii
Authors: Jonkergouw Christopher , Beyeh Ngong Kodiah , Osmekhina Ekaterina , Leskinen Katarzyna , Taimoory S. Maryamdokht , Fedorov Dmitrii , Anaya-Plaza Eduardo , Kostiainen Mauri A. , Trant John F. , Ras Robin H. A. , Saavalainen Päivi , Linder Markus B.
Published: April 2023

The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify a water-soluble synthetic macrocycle, Pillar[5]arene, that is non-bactericidal/bacteriostatic and has a mechanism of action that involves binding to both homoserine lactones and lipopolysaccharides, key virulence factors in Gram-negative pathogens. Pillar[5]arene is active against Top Priority carbapenem- and third/fourth-generation cephalosporin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, suppressing toxins and biofilms and increasing the penetration and efficacy of standard-of-care antibiotics in combined administrations. The binding of homoserine lactones and lipopolysaccharides also sequesters their direct effects as toxins on eukaryotic membranes, neutralizing key tools that promote bacterial colonization and impede immune defenses, both in vitro and in vivo. Pillar[5]arene evades both existing antibiotic resistance mechanisms, as well as the build-up of rapid tolerance/resistance. The versatility of macrocyclic host-guest chemistry provides ample strategies for tailored targeting of virulence in a wide range of Gram-negative infectious diseases.
In mitosis integrins reduce adhesion to extracellular matrix and strengthen adhesion to adjacent cells
Authors: Huber Maximilian , Casares-Arias Javier , Fässler Reinhard , Müller Daniel J. , Strohmeyer Nico
Published: April 2023

To enter mitosis, most adherent animal cells reduce adhesion, which is followed by cell rounding. How mitotic cells regulate adhesion to neighboring cells and extracellular matrix (ECM) proteins is poorly understood. Here we report that, similar to interphase, mitotic cells can employ integrins to initiate adhesion to the ECM in a kindlin- and talin-dependent manner. However, unlike interphase cells, we find that mitotic cells cannot engage newly bound integrins to actomyosin via talin or vinculin to reinforce adhesion. We show that the missing actin connection of newly bound integrins leads to transient ECM-binding and prevents cell spreading during mitosis. Furthermore, β1 integrins strengthen the adhesion of mitotic cells to adjacent cells, which is supported by vinculin, kindlin, and talin1. We conclude that this dual role of integrins in mitosis weakens the cell-ECM adhesion and strengthens the cell-cell adhesion to prevent delamination of the rounding and dividing cell.
Photoacoustic 2D actuator via femtosecond pulsed laser action on van der Waals interfaces
Authors: Chen Xin , Kislyakov Ivan M. , Wang Tiejun , Xie Yafeng , Wang Yan , Zhang Long , Wang Jun
Published: April 2023

Achieving optically controlled nanomachine engineering can satisfy the touch-free and non-invasive demands of optoelectronics, nanotechnology, and biology. Traditional optical manipulations are mainly based on optical and photophoresis forces, and they usually drive particles in gas or liquid environments. However, the development of an optical drive in a non-fluidic environment, such as on a strong van der Waals interface, remains difficult. Herein, we describe an efficient 2D nanosheet actuator directed by an orthogonal femtosecond laser, where 2D VSe2 and TiSe2 nanosheets deposited on sapphire substrates can overcome the interface van der Waals forces (tens and hundreds of megapascals of surface density) and move on the horizontal surfaces. We attribute the observed optical actuation to the momentum generated by the laser-induced asymmetric thermal stress and surface acoustic waves inside the nanosheets. 2D semimetals with high absorption coefficient can enrich the family of materials suitable to implement optically controlled nanomachines on flat surfaces.
OBERON3 and SUPPRESSOR OF MAX2 1-LIKE proteins form a regulatory module driving phloem development
Authors: Wallner Eva-Sophie , Tonn Nina , Shi Dongbo , Luzzietti Laura , Wanke Friederike , Hunziker Pascal , Xu Yingqiang , Jung Ilona , Lopéz-Salmerón Vadir , Gebert Michael , Wenzl Christian , Lohmann Jan U. , Harter Klaus , Greb Thomas
Published: April 2023

Spatial specificity of cell fate decisions is central for organismal development. The phloem tissue mediates long-distance transport of energy metabolites along plant bodies and is characterized by an exceptional degree of cellular specialization. How a phloem-specific developmental program is implemented is, however, unknown. Here we reveal that the ubiquitously expressed PHD-finger protein OBE3 forms a central module with the phloem-specific SMXL5 protein for establishing the phloem developmental program in Arabidopsis thaliana. By protein interaction studies and phloem-specific ATAC-seq analyses, we show that OBE3 and SMXL5 proteins form a complex in nuclei of phloem stem cells where they promote a phloem-specific chromatin profile. This profile allows expression of OPS, BRX, BAM3, and CVP2 genes acting as mediators of phloem differentiation. Our findings demonstrate that OBE3/SMXL5 protein complexes establish nuclear features essential for determining phloem cell fate and highlight how a combination of ubiquitous and local regulators generate specificity of developmental decisions in plants.
Priming a vascular-selective cytokine response permits CD8+ T-cell entry into tumors
Authors: Kim Dae Joong , Anandh Swetha , Null Jamie L. , Przanowski Piotr , Bhatnagar Sanchita , Kumar Pankaj , Shelton Sarah E. , Grundy Erin E. , Chiappinelli Katherine B. , Kamm Roger D. , Barbie David A. , Dudley Andrew C.
Published: April 2023

Targeting DNA methyltransferase 1 (DNMT1) has immunomodulatory and anti-neoplastic activity, especially when paired with cancer immunotherapies. Here we explore the immunoregulatory functions of DNMT1 in the tumor vasculature of female mice. Dnmt1 deletion in endothelial cells (ECs) impairs tumor growth while priming expression of cytokine-driven cell adhesion molecules and chemokines important for CD8+ T-cell trafficking across the vasculature; consequently, the efficacy of immune checkpoint blockade (ICB) is enhanced. We find that the proangiogenic factor FGF2 promotes ERK-mediated DNMT1 phosphorylation and nuclear translocation to repress transcription of the chemokines Cxcl9/Cxcl10 in ECs. Targeting Dnmt1 in ECs reduces proliferation but augments Th1 chemokine production and extravasation of CD8+ T-cells, suggesting DNMT1 programs immunologically anergic tumor vasculature. Our study is in good accord with preclinical observations that pharmacologically disrupting DNMT1 enhances the activity of ICB but suggests an epigenetic pathway presumed to be targeted in cancer cells is also operative in the tumor vasculature.
Constrained catecholamines gain β2AR selectivity through allosteric effects on pocket dynamics
Authors: Xu Xinyu , Shonberg Jeremy , Kaindl Jonas , Clark Mary J. , Stößel Anne , Maul Luis , Mayer Daniel , Hübner Harald , Hirata Kunio , Venkatakrishnan A. J. , Dror Ron O. , Kobilka Brian K. , Sunahara Roger K. , Liu Xiangyu , Gmeiner Peter
Published: April 2023

G protein-coupled receptors (GPCRs) within the same subfamily often share high homology in their orthosteric pocket and therefore pose challenges to drug development. The amino acids that form the orthosteric binding pocket for epinephrine and norepinephrine in the β1and β2adrenergic receptors (β1AR and β2AR) are identical. Here, to examine the effect of conformational restriction on ligand binding kinetics, we synthesized a constrained form of epinephrine. Surprisingly, the constrained epinephrine exhibits over 100-fold selectivity for the β2AR over the β1AR. We provide evidence that the selectivity may be due to reduced ligand flexibility that enhances the association rate for the β2AR, as well as a less stable binding pocket for constrained epinephrine in the β1AR. The differences in the amino acid sequence of the extracellular vestibule of the β1AR allosterically alter the shape and stability of the binding pocket, resulting in a marked difference in affinity compared to the β2AR. These studies suggest that for receptors containing identical binding pocket residues, the binding selectivity may be influenced in an allosteric manner by surrounding residues, like those of the extracellular loops (ECLs) that form the vestibule. Exploiting these allosteric influences may facilitate the development of more subtype-selective ligands for GPCRs.
Certification of non-classicality in all links of a photonic star network without assuming quantum mechanics
Authors: Wang Ning-Ning , Pozas-Kerstjens Alejandro , Zhang Chao , Liu Bi-Heng , Huang Yun-Feng , Li Chuan-Feng , Guo Guang-Can , Gisin Nicolas , Tavakoli Armin
Published: April 2023

Networks composed of independent sources of entangled particles that connect distant users are a rapidly developing quantum technology and an increasingly promising test-bed for fundamental physics. Here we address the certification of their post-classical properties through demonstrations of full network nonlocality. Full network nonlocality goes beyond standard nonlocality in networks by falsifying any model in which at least one source is classical, even if all the other sources are limited only by the no-signaling principle. We report on the observation of full network nonlocality in a star-shaped network featuring three independent sources of photonic qubits and joint three-qubit entanglement-swapping measurements. Our results demonstrate that experimental observation of full network nonlocality beyond the bilocal scenario is possible with current technology.
Integration of clinical features and deep learning on pathology for the prediction of breast cancer recurrence assays and risk of recurrence
Authors: Howard Frederick M. , Dolezal James , Kochanny Sara , Khramtsova Galina , Vickery Jasmine , Srisuwananukorn Andrew , Woodard Anna , Chen Nan , Nanda Rita , Perou Charles M. , Olopade Olufunmilayo I. , Huo Dezheng , Pearson Alexander T.
Published: April 2023

Gene expression-based recurrence assays are strongly recommended to guide the use of chemotherapy in hormone receptor-positive, HER2-negative breast cancer, but such testing is expensive, can contribute to delays in care, and may not be available in low-resource settings. Here, we describe the training and independent validation of a deep learning model that predicts recurrence assay result and risk of recurrence using both digital histology and clinical risk factors. We demonstrate that this approach outperforms an established clinical nomogram (area under the receiver operating characteristic curve of 0.83 versus 0.76 in an external validation cohort,p = 0.0005) and can identify a subset of patients with excellent prognoses who may not need further genomic testing.
Aberrant neurophysiological signaling associated with speech impairments in Parkinson’s disease
Authors: Wiesman Alex I. , Donhauser Peter W. , Degroot Clotilde , Diab Sabrina , Kousaie Shanna , Fon Edward A. , Klein Denise , Baillet Sylvain ,   PREVENT-AD Research Group, Villeneuve Sylvia ,   Quebec Parkinson Network
Published: April 2023

Difficulty producing intelligible speech is a debilitating symptom of Parkinson’s disease (PD). Yet, both the robust evaluation of speech impairments and the identification of the affected brain systems are challenging. Using task-free magnetoencephalography, we examine the spectral and spatial definitions of the functional neuropathology underlying reduced speech quality in patients with PD using a new approach to characterize speech impairments and a novel brain-imaging marker. We found that the interactive scoring of speech impairments in PD (N = 59) is reliable across non-expert raters, and better related to the hallmark motor and cognitive impairments of PD than automatically-extracted acoustical features. By relating these speech impairment ratings to neurophysiological deviations from healthy adults (N = 65), we show that articulation impairments in patients with PD are associated with aberrant activity in the left inferior frontal cortex, and that functional connectivity of this region with somatomotor cortices mediates the influence of cognitive decline on speech deficits.
A comprehensive dataset of annotated brain metastasis MR images with clinical and radiomic data
Authors: Ocaña-Tienda Beatriz , Pérez-Beteta Julián , Villanueva-García José D. , Romero-Rosales José A. , Molina-García David , Suter Yannick , Asenjo Beatriz , Albillo David , Ortiz de Mendivil Ana , Pérez-Romasanta Luis A. , González-Del Portillo Elisabet , Llorente Manuel , Carballo Natalia , Nagib-Raya Fátima , Vidal-Denis Maria , Luque Belén , Reyes Mauricio , Arana Estanislao , Pérez-García Víctor M.
Published: April 2023

Brain metastasis (BM) is one of the main complications of many cancers, and the most frequent malignancy of the central nervous system. Imaging studies of BMs are routinely used for diagnosis of disease, treatment planning and follow-up. Artificial Intelligence (AI) has great potential to provide automated tools to assist in the management of disease. However, AI methods require large datasets for training and validation, and to date there have been just one publicly available imaging dataset of 156 BMs. This paper publishes 637 high-resolution imaging studies of 75 patients harboring 260 BM lesions, and their respective clinical data. It also includes semi-automatic segmentations of 593 BMs, including pre- and post-treatment T1-weighted cases, and a set of morphological and radiomic features for the cases segmented. This data-sharing initiative is expected to enable research into and performance evaluation of automatic BM detection, lesion segmentation, disease status evaluation and treatment planning methods for BMs, as well as the development and validation of predictive and prognostic tools with clinical applicability.
Over-production of exopolysaccharide by Lacticaseibacillus rhamnosus CNCM I-3690 strain cutbacks its beneficial effect on the host
Authors: Martín R. , Benítez-Cabello A. , Kulakauskas S. , Viana M. V. C. , Chamignon C. , Courtin P. , Carbonne C. , Chain F. , Pham H. P. , Derrien Muriel , Bermúdez-Humarán L. G. , Chapot-Chartier M. P. , Smokvina T. , Langella P.
Published: April 2023

Most lactobacilli produce extracellular polysaccharides that are considered to contribute to the probiotic effect of many strains. Lacticaseibacillus rhamnosus CNCM I-3690 is an anti-inflammatory strain able to counterbalance gut barrier dysfunction. In this study ten spontaneous variants of CNCM I-3690 with different EPS-production were generated and characterized by their ropy phenotype, the quantification of the secreted EPS and genetic analysis. Amongst them, two were further analysed in vitro and in vivo: an EPS over-producer (7292) and a low-producer derivative of 7292 (7358, with similar EPS levels than the wild type (WT) strain). Our results showed that 7292 does not have anti-inflammatory profile in vitro, and lost the capacity to adhere to the colonic epithelial cells as well as the protective effect on the permeability. Finally, 7292 lost the protective effects of the WT strain in a murine model of gut dysfunction. Notably, strain 7292 was unable to stimulate goblet cell mucus production and colonic IL-10 production, all key features for the beneficial effect of the WT strain. Furthermore, transcriptome analysis of colonic samples from 7292-treated mice showed a down-regulation of anti-inflammatory genes. Altogether, our results point out that the increase of EPS production in CNCM I-3690 impairs its protective effects and highlight the importance of the correct EPS synthesis for the beneficial effects of this strain.
The stability of transient relationships
Authors: Hidd Valentín Vergara , López Eduardo , Centellegher Simone , Roberts Sam G. B. , Lepri Bruno , Dunbar Robin I. M.
Published: April 2023

In contrast to long-term relationships, far less is known about the temporal evolution of transient relationships, although these constitute a substantial fraction of people’s communication networks. Previous literature suggests that ratings of relationship emotional intensity decay gradually until the relationship ends. Using mobile phone data from three countries (US, UK, and Italy), we demonstrate that the volume of communication between ego and its transient alters does not display such a systematic decay, instead showing a lack of any dominant trends. This means that the communication volume of egos to groups of similar transient alters is stable. We show that alters with longer lifetimes in ego’s network receive more calls, with the lifetime of the relationship being predictable from call volume within the first few weeks of first contact. This is observed across all three countries, which include samples of egos at different life stages. The relation between early call volume and lifetime is consistent with the suggestion that individuals initially engage with a new alter so as to evaluate their potential as a tie in terms of homophily.
Photoexcitation of perovskite precursor solution to induce high-valent iodoplumbate species for wide bandgap perovskite solar cells with enhanced photocurrent
Authors: Naikaew Atittaya , Krajangsang Taweewat , Srathongsian Ladda , Seriwattanachai Chaowaphat , Sakata Patawee , Burimart Supavudh , Sanglee Kanyanee , Khotmungkhun Kittikhun , Ruankham Pipat , Romphosri Suwat , Limmanee Amornrat , Kanjanaboos Pongsakorn
Published: April 2023

Solution-processed organic–inorganic hybrid perovskite solar cells are among the candidates to replace the traditional silicon solar cells due to their excellent power conversion efficiency (PCE). Despite this considerable progress, understanding the properties of the perovskite precursor solution is critical for perovskite solar cells (PSCs) to achieve high performance and reproducibility. However, the exploration of perovskite precursor chemistry and its effects on photovoltaic performances has been limited thus far. Herein, we modified the equilibrium of chemical species inside the precursor solution using different photoenergy and heat pathways to identify the corresponding perovskite film formation. The illuminated perovskite precursors exhibited a higher density of high-valent iodoplumbate species, resulting in the fabricated perovskite films with reduced defect density and uniform distribution. Conclusively, the perovskite solar cells prepared by the photoaged precursor solution had not only improved PCE but also enhanced current density, confirmed by device performance, conductive atomic force microscopy (C-AFM), and external quantum efficiency (EQE). This innovative precursor photoexcitation is a simple and effective physical process for boosting perovskite morphology and current density.
A new extremophile ostracod crustacean from the Movile Cave sulfidic chemoautotrophic ecosystem in Romania
Authors: Iepure Sanda , Wysocka Anna , Sarbu Serban M. , Kijowska Michalina , Namiotko Tadeusz
Published: April 2023

Sulfidic cave ecosystems are remarkable evolutionary hotspots that have witnessed adaptive radiation of their fauna represented by extremophile species having particular traits. Ostracods, a very old group of crustaceans, exhibit specific morphological and ecophysiological features that enable them to thrive in groundwater sulfidic environments. Herein, we report a peculiar new ostracod species Pseudocandonamovilaensis sp. nov. thriving in the chemoautotrophic sulfidic groundwater ecosystem of Movile Cave (Romania). The new species displays a set of homoplastic features specific for unrelated stygobitic species, e.g., triangular carapace in lateral view with reduced postero-dorsal part and simplification of limb chaetotaxy (i.e., loss of some claws and reduction of secondary male sex characteristics), driven by a convergent or parallel evolution during or after colonization of the groundwater realm. P.movilaensis sp. nov. thrives exclusively in sulfidic meso-thermal waters (21 °C) with high concentrations of sulphides, methane, and ammonium. Based on the geometric morphometrics-based study of the carapace shape and molecular phylogenetic analyses based on the COI marker (mtDNA), we discuss the phylogenetic relationship and evolutionary implication for the new species to thrive in groundwater sulfidic groundwater environments.
Structural basis for sequence-specific recognition of guide and target strands by the Archaeoglobus fulgidus Argonaute protein
Authors: Manakova Elena , Golovinas Edvardas , Pocevičiūtė Reda , Sasnauskas Giedrius , Grybauskas Algirdas , Gražulis Saulius , Zaremba Mindaugas
Published: April 2023

Argonaute (Ago) proteins are found in all three domains of life. The best-characterized group is eukaryotic Argonautes (eAgos). Being the structural core of RNA interference machinery, they use guide RNA molecules for RNA targeting. Prokaryotic Argonautes (pAgos) are more diverse, both in terms of structure (there are eAgo-like ‘long’ and truncated ‘short’ pAgos) and mechanism, as many pAgos are specific for DNA, not RNA guide and/or target strands. Some long pAgos act as antiviral defence systems. Their defensive role was recently demonstrated for short pAgo-encoding systems SPARTA and GsSir2/Ago, but the function and action mechanisms of all other short pAgos remain unknown. In this work, we focus on the guide and target strand preferences of AfAgo, a truncated long-B Argonaute protein encoded by an archaeon Archaeoglobus fulgidus. We demonstrate that AfAgo associates with small RNA molecules carrying 5′-terminal AUU nucleotides in vivo, and characterize its affinity to various RNA and DNA guide/target strands in vitro. We also present X-ray structures of AfAgo bound to oligoduplex DNAs that provide atomic details for base-specific AfAgo interactions with both guide and target strands. Our findings broaden the range of currently known Argonaute-nucleic acid recognition mechanisms.
Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers
Authors: Rybicka Magda , Verrier Eloi R. , Baumert Thomas F. , Bielawski Krzysztof Piotr
Published: April 2023

The study enrolled 284 patients with chronic hepatitis B virus infection. Participants included people with mild fibrotic lesions (32.5%), moderate to severe fibrotic lesions (27.5%), cirrhotic lesions (22%), hepatocellular carcinoma (HCC) in 5%, and people with no fibrotic lesions in 13%. Eleven SNPs within DIO2, PPARG, ATF3, AKT, GADD45A, and TBX21 were genotyped by mass spectrometry. The rs225014 TT (DIO2) and rs10865710 CC (PPARG) genotypes were independently associated with susceptibility to advanced liver fibrosis. However, cirrhosis was more prevalent in individuals with the GADD45A rs532446 TT and ATF3 rs11119982 TT genotypes. In addition, the rs225014 CC variant of DIO2 was more frequently found in patients with a diagnosis of HCC. These findings suggest that the above SNPs may play a role in HBV-induced liver damage in a Caucasian population.
Impact of the COVID-19 pandemic on young people with and without pre-existing mental health problems
Authors: Kleine Ronja , Galimov Artur , Hanewinkel Reiner , Unger Jennifer , Sussman Steve , Hansen Julia
Published: April 2023

The objective was to examine pandemic-related changes in depression and anxiety symptoms in adolescents and young adults in Germany considering pre-existing depression and anxiety problems. In this cross-sectional study, 11,523 adolescents and young adults aged 14–21 years who perceived an impact of the Coronavirus disease (COVID-19) pandemic on their mental health reported the frequencies of depression and anxiety symptoms retrospectively for different pre-pandemic and pandemic phases. Data were collected using web-based questionnaires between January 5th and February 20th, 2022. Depression and anxiety were assessed with a modified version of the Patient Health Questionnaire (PHQ-4). Scale-fit cut-offs were used to identify pre-existing elevated depression and anxiety scores. Multilevel mixed linear models were conducted to assess changes in depression and anxiety symptoms from 2019 to 2021 and compare for age, gender and pre-pandemic mental health problems. Among young people who were experiencing mental health changes as a result of the pandemic, the frequency of depression and anxiety symptoms increased during the COVID-19 pandemic. This association was moderated by age, gender, and pre-existing elevated depression/anxiety scores. For young people without elevated pre-pandemic depression/anxiety, the scores increased strongly over time, with 61% reporting elevated depression symptoms and 44% reporting elevated anxiety symptoms in 2021. In contrast, self-perceived change was minimal for adolescents and young adults with elevated pre-pandemic depression and anxiety. Among young people whose mental health has been affected by the COVID-19 pandemic, the group without pre-pandemic mental health conditions reported greater deterioration than those with elevated pre-pandemic depression and anxiety scores. Thus, adolescents and young adults without pre-existing depression and anxiety problems who perceived a change in general mental health due to the pandemic reported an alarming increase in symptoms of depression and anxiety during the COVID-19 pandemic period.
A new stochastic diffusion model for influence maximization in social networks
Authors: Rezvanian Alireza , Vahidipour S. Mehdi , Meybodi Mohammad Reza
Published: April 2023

Most current studies on information diffusion in online social networks focus on the deterministic aspects of social networks. However, the behavioral parameters of online social networks are uncertain, unpredictable, and time-varying. Thus, deterministic graphs for modeling information diffusion in online social networks are too restrictive to solve most real network problems, such as influence maximization. Recently, stochastic graphs have been proposed as a graph model for social network applications where the weights associated with links in the stochastic graph are random variables. In this paper, we first propose a diffusion model based on a stochastic graph, in which influence probabilities associated with its links are unknown random variables. Then we develop an approach using the set of learning automata residing in the proposed diffusion model to estimate the influence probabilities by sampling from the links of the stochastic graph. Numerical simulations conducted on real and artificial stochastic networks demonstrate the effectiveness of the proposed stochastic diffusion model for influence maximization.
Improved diagnosis of histological capsule in hepatocallular carcinoma by using nonenhancing capsule appearance in addition to enhancing capsule appearance in gadoxetic acid-enhanced MRI
Authors: Nishioka Eiko , Sofue Keitaro , Maruyama Koji , Ueshima Eisuke , Ueno Yoshiko , Tsurusaki Masakatsu , Komatsu Shohei , Fukumoto Takumi , Murakami Takamichi
Published: April 2023

To assess the value of nonenhancing capsule by adding to enhancing capsule in gadoxetic acid-enhanced MRI (EOB-MRI) in comparison with contrast-enhanced CT (CE-CT) for diagnosing histological capsule in hepatocellular carcinoma (HCC). One-hundred fifty-one patients with HCC who underwent both CE-CT and EOB-MRI were retrospectively reviewed. Liver Imaging-Reporting and Data System (LI-RADS) v2018 imaging features, including enhancing and nonenhancing capsule were evaluated by two readers in CE-CT and EOB-MRI. Frequencies of each imaging feature were compared between CE-CT and EOB-MRI. The area under the receiver operating characteristic (AUC) curve for the diagnosis of histological capsule was compared across the following three imaging criteria: (1) enhancing capsule in CE-CT, (2) enhancing capsule in EOB-MRI, and (3) enhancing/nonenhancing capsule in EOB-MRI. Enhancing capsule in EOB-MRI was significantly less frequently depicted than that in CE-CT (p < 0.001 and = 0.016 for reader 1 and 2). Enhancing/nonenhancing capsule in EOB-MRI achieved a similar frequency of enhancing in CE-CT (p = 0.590 and 0.465 for reader 1 and 2). Adding nonenhancing capsule to enhancing capsule in EOB-MRI significantly increased AUCs (p < 0.001 for both readers) and achieved similar AUCs compared with enhancing capsule in CE-CT (p = 0.470 and 0.666 for reader 1 and 2). Adding nonenhancing capsule to the definition of capsule appearance can improve the diagnosis of capsule in EOB-MRI for the diagnosis of histological capsule in HCC and decrease discordance of capsule appearance between EOB-MRI and CE-CT.
The association of UBAP2L and G3BP1 mediated by small nucleolar RNA is essential for stress granule formation
Authors: Asano-Inami Eri , Yokoi Akira , Sugiyama Mai , Hyodo Toshinori , Hamaguchi Tomonari , Kajiyama Hiroaki
Published: April 2023

Stress granules (SGs) are dynamic, non-membranous structures composed of non-translating mRNAs and various proteins and play critical roles in cell survival under stressed conditions. Extensive proteomics analyses have been performed to identify proteins in SGs; however, the molecular functions of these components in SG formation remain unclear. In this report, we show that ubiquitin-associated protein 2-like (UBAP2L) is a crucial component of SGs. UBAP2L localized to SGs in response to various stresses, and its depletion significantly suppressed SG organization. Proteomics and RNA sequencing analyses found that UBAP2L formed a protein-RNA complex with Ras-GTP-activating protein SH3 domain binding protein 1 (G3BP1) and small nucleolar RNAs (snoRNAs). In vitro binding analysis demonstrated that snoRNAs were required for UBAP2L association with G3BP1. In addition, decreased expression of snoRNAs reduced the interaction between UBAP2L and G3BP1 and suppressed SG formation. Our results reveal a critical role of SG component, the UBAP2L/snoRNA/G3BP1 protein-RNA complex, and provide new insights into the regulation of SG assembly.
Moderate white light exposure enhanced spatial memory retrieval by activating a central amygdala-involved circuit in mice
Authors: Shang MengJuan , Shen MeiLun , Xu RuoTong , Du JingYu , Zhang JiMeng , OuYang Ding , Du JunZe , Hu JunFeng , Sun ZhiChuan , Wang BingXia , Han Qian , Hu Yang , Liu YiHong , Guan Yun , Li Jing , Guo GuoZhen , Xing JunLing
Published: April 2023

Light exposure can profoundly affect neurological functions and behaviors. Here, we show that short-term exposure to moderate (400 lux) white light during Y-maze test promoted spatial memory retrieval and induced only mild anxiety in mice. This beneficial effect involves the activation of a circuit including neurons in the central amygdala (CeA), locus coeruleus (LC), and dentate gyrus (DG). Specifically, moderate light activated corticotropin-releasing hormone (CRH) positive (+) CeA neurons and induced the release of corticotropin-releasing factor (CRF) from their axon terminals ending in the LC. CRF then activated tyrosine hydroxylase-expressing LC neurons, which send projections to DG and release norepinephrine (NE). NE activated β-adrenergic receptors on CaMKIIα-expressing DG neurons, ultimately promoting spatial memory retrieval. Our study thus demonstrated a specific light scheme that can promote spatial memory without excessive stress, and unraveled the underlying CeA-LC-DG circuit and associated neurochemical mechanisms.
Pan-Atlantic decadal climate oscillation linked to ocean circulation
Authors: Nnamchi Hyacinth C. , Farneti Riccardo , Keenlyside Noel S. , Kucharski Fred , Latif Mojib , Reintges Annika , Martin Thomas
Published: April 2023

Atlantic climate displays an oscillatory mode at a period of 10–15 years described as pan-Atlantic decadal oscillation. Prevailing theories on the mode are based on thermodynamic air-sea interactions and the role of ocean circulation remains uncertain. Here we uncover ocean circulation variability associated with the pan-Atlantic decadal oscillation using observational datasets from 1900–2009. Specifically, a sea level-derived index of ocean circulation also exhibits 10-15 year periodicity and leads the surface climate oscillation. The underlying ocean circulation links the extratropical and tropical Atlantic, where the maximum variance in surface-ocean temperature feeds back on the North Atlantic Oscillation (the leading mode of atmospheric variability over the North Atlantic region). Our findings imply that, rather than a passive role postulated by the thermodynamic paradigm, ocean circulation across the Atlantic plays an active role for the pan-Atlantic decadal climate oscillation.
Welcome to Fluorescent Chemosensors
Authors: Wu Luling , Sedgwick Adam C. , He Xiao-Peng , James Tony D.
Published: April 2023

We would like to welcome you to the wonderful world of fluorescent chemosensors. This book consists of 16 chapters that take you on a journey from receptor-based to reaction-based sensing systems. The quest includes both molecular-based and nanoparticle-based systems that can be used for medical diagnostics, theranostics and environmental sensing applications. The techniques included embrace two-photon fluorescence, ratiometric and aggregation-induced emission.
Activity-based Sensing: Principles and Probes for Selective Bioimaging
Authors: Jia Shang , Chang Christopher J.
Published: April 2023

Chemical sensors for detection of biological analytes in their native settings with spatial and temporal resolution can enable the study of their physiological and pathological contributions by molecular imaging. An emerging area of sensor research is activity-based sensing (ABS), which leverages the unique chemical reactivity of a given analyte of interest, rather than traditional binding-based approaches that rely on lock-and-key molecular recognition, to achieve selectivity in the complex biological environments. This chapter summarizes foundational design principles of ABS and provides a survey of three representative examples of activity-based imaging probes using oxidative, reductive, or redox-neutral reactivity for selective analyte detection, highlighting the broad applicability of this synthetic reaction chemistry approach to identify and characterize new biology.
Two-photon Fluorescent Probes
Authors: Juvekar Vinayak , Kim Hwan Myung
Published: April 2023

Two-photon microscopy (TPM) is an indispensable bioimaging tool. TPM, which uses photons of a near-infrared wavelength as an excitation source for fluorophores, can result in deeper tissue images, which can potentially be measured beyond a depth of 1000 µm with relative stability in biological systems. With continuous development in deep-tissue optical microscopy and improvements in imaging algorithms, TPM is gaining immense support in biomedical applications. Furthermore, it has propelled the continuous development of appropriate two-photon (TP) probes with improved sensitivities for measuring target analytes in biological specimens. In this chapter, the photo-physiological process, basic TP probe design strategies, and representative TP sensors of TPM that researchers have reported are presented to provide significant information regarding specific targets in biological systems.
Ratiometric Fluorescent Chemosensors: Photophysical/Chemical Mechanism Principles and Design Strategies
Authors: Shin Jinwoo , An Jusung , Kim Jungryun , Noh Yuvin , Jangili Paramesh , Kim Jong Seung
Published: April 2023

Fluorescent techniques have attracted significant attention in bioimaging, analyte sensing, and disease diagnosis in recent years. Conventional fluorescent chemosensors provide significant advantages in monitoring/detecting different analytes; however, physiological or experimental factors may influence the single-targeted fluorophore absolute intensity-dependent signal acquisition, which can be cause misleading and strong non-specific background signals in molecular sensing and imaging applications. The simple alternative to minimize these non-specific effects is a ratiometric measurement strategy. This is a self-calibration method for recording two or more analyte-induced signals, in which one signal is a reference factor to normalize other signals. Due to its self-calibrating internal standard system obtained from the ratio between two or more emission bands, ratiometric approaches have become the most effective fluorescence method for quantitative analysis measurements, compensating for a number of analyte-independent parameters and eliminating most ambiguities that may affect the fluorescence signal. In particular, by taking advantage of various photophysical/chemical sensing theories, ratiometric fluorophores successfully endow structural design for detection of biologically/environmentally important analytes. This chapter will highlight the basic principles and design strategies of ratiometric fluorescent chemosensors, including photophysical/chemical sensing mechanisms based on different molecular types (i.e., small molecules and nanoparticles) with appropriate examples.
Fluorescent Chemosensors for Phosphates
Authors: Butler S. M. , Jolliffe K. A.
Published: April 2023

This chapter outlines the development of small-molecule fluorescent chemosensors for phosphate species. Phosphate species are ubiquitous in nature, play diverse roles in biological systems, and display extensive variation in the functionality attached to the phosphate group. These molecules have a diffuse negative charge, are highly solvated, and are all linked by a common phosphate group. Together, these features present a significant challenge for the development of species-selective chemosensors that function in aqueous media with appropriate binding affinities. This challenge has been tackled via a variety of approaches, including chemosensors that bind the phosphate group via charge–charge, hydrogen-bonding, and metal–cation interactions. Key examples of each of these interaction types, varied approaches to chemosensor design, and fluorescence response mechanisms are highlighted.
The Activity-based Sensing of Biological Transition Metals
Authors: Hirayama T.
Published: April 2023

Metal ions are involved in various biological processes, and their essential roles and pathological involvement have facilitated the development of new synthetic chemical tools for the detection and monitoring of metal ions in cells and living organisms. For example, fluorescent and other optical probes have been used to study metal homeostasis and alterations with spatial and temporal resolution. They are categorized into chelation-based and activity-based probes based on their detection mechanism. Chelation-based probes have been used since the 1980s and operate through the complexation of a metal ion with a chelator tethered to a fluorophore, which is detected as a change in fluorescence intensity and/or wavelength. On the other hand, activity-based sensing has only been developed in the last decade for the selective detection of metal ions that are difficult to detect using chelation-based probes. These activity-based probes provide new possibilities in the detection of biological metals because they can avoid the disadvantages of chelation-based probes, including the fluorescence-quenching effect of d-unsaturated metal ions and metal-ion depletions. In this chapter, specific examples of activity-based probes for metal-ion detection are introduced, and their sensing mechanisms and features are discussed.
Time-delayed Lanthanide Luminescent Sensors and Probes
Authors: Bradberry Samuel J. , D’Agostino Bruno , Caffrey David F. , dos Santos Cidália M. G. , Kotova Oxana , Gunnlaugsson Thorfinnur
Published: April 2023

The development of lanthanide-based signalling systems that can monitor the concentration, nature and presence of certain analytes has grown rapidly over the last 25 years or so. Given their unique photophysical properties, which includes line-like emission bands/transitions, long-wavelength emission range (spanning from the visible to the near-infrared) and long-lived excited states, it comes as no surprise that today luminescent lanthanide sensors, probes and materials (e.g. films, polymers, particles, etc.) have been developed for the recognition, sensing and imaging of ions, small molecules as well as large biomolecules (nucleic acids, peptides and proteins, etc.), systems and processes (such as enzymes, etc.). This chapter gives some insight into this rapidly developing field of research. A selected number of samples will be featured and their properties and function discussed. The object herein is to demonstrate the structural versatility and the various applications that such lanthanide luminescence systems have to offer, along with expanding on how the lanthanide ions act as sensing platforms, which is seldomly seen for their organic counterparts.
Simultaneous measurement of 19 steroid hormones in dried blood spots using ultra-performance liquid chromatography-tandem mass spectrometry
Authors: Wu Jie , Li Zenghe , Chen Baorong
Published: April 2023

In this article, a method for the measurement of 19 steroid hormones in dried blood spots was developed using UPLC-MS/MS. Meanwhile, we initially established the distribution range of 19 steroid hormones in dried blood spots of healthy individuals.
A method for reliable quantification of mercury in occupational and environmental medical urine samples by inductively coupled plasma mass spectrometry
Authors: Winter Martin , Lessmann Frederik , Harth Volker
Published: April 2023

Using a specific mixture of HNO3, HCl and thiourea for sample preparation overcomes common challenges of mercury determination in urine samples by inductively coupled plasma mass spectrometry.
Osteomatrix as a personalized 3D tissue-specific invasion test-bed for oral carcinoma
Authors: V. S. Sukanya , Giri Pravin Shankar , Nellore Vijaykumar , Rath Subha Narayan
Published: April 2023

The schematic illustration of the workflow to develop a 3D in vitro patient-specific bone invasion model for oral carcinoma.
Liposome-embedded SOD attenuated DSS-induced ulcerative colitis in mice by ameliorating oxidative stress and intestinal barrier dysfunction
Authors: Zhang Chi , Hu Yujia , Yuan Yi , Guo Jingke , Li Henian , Li Qiaoling , Liu Shutao
Published: April 2023

Liposome encapsulation improves the efficacy of SOD for UC treatment, with a bell-shaped distribution of therapeutic effects relative to the administered dose, by ameliorating oxidative stress and subsequent inflammation and intestinal barrier dysfunction.
Image recovery from unknown network mechanisms for DNA sequencing-based microscopy
Authors: Fernandez Bonet David , Hoffecker Ian T.
Published: April 2023

Optimal image reconstruction is an open problem in the field of imaging-by-sequencing. We implement an algorithm that is scalable and robust to different network types by using structural discovery.
Thermally reversible pattern formation in arrays of molecular rotors
Authors: DeLuca Marcello , Pfeifer Wolfgang G. , Randoing Benjamin , Huang Chao-Min , Poirier Michael G. , Castro Carlos E. , Arya Gaurav
Published: April 2023

In this work, we describe the development of a computational model for arrays of rotary DNA origami elements which can self-organize on a large scale and explore the interesting morphologies and order–disorder transition behavior of these systems.
The aromatic Claisen rearrangement of a 1,2-azaborine
Authors: Robichaud Hannah M. , Ishibashi Jacob S. A. , Ozaki Tomoya , Lamine Walid , Miqueu Karinne , Liu Shih-Yuan
Published: April 2023

The first aromatic Claisen rearrangement of a 1,2-azaborine is described along with a quantitative kinetic comparison of the reaction of the azaborine with its direct all-carbon analogue.
Influence of high altitude on the strength of aerated concrete
Authors: Liu Biwen , Zhang Qian , Zhao Yuxiang , Huan Dongdong , Liu Xinzhong
Published: April 2023

The specimens prepared with different temperature have different content and crystallinity of tobermorite, resulting in different strength.
A novel test device and quantitative colorimetric method for the detection of human chorionic gonadotropin (hCG) based on Au@Zn–salen MOF for POCT applications
Authors: Mohamed Reda M. , El-Sheikh Said M. , Kadi Mohammad W. , Labib Ammar A. , Sheta Sheta M.
Published: April 2023

The human chorionic gonadotropin (hCG) hormone is a biomarker that can predict tumors and early pregnancy; however, it is challenging to develop sensitive qualitative-quantitative procedures that are also effective, inventive, and unique.
Dynamic behaviours of epoxy resin thin films during the curing process
Authors: Hoshino Taiki , Okamoto Yasushi , Yamamoto Atsushi , Masunaga Hiroyasu
Published: April 2023

Capillary waves during the curing process of epoxy resin thin films were investigated using grazing incidence X-ray photon correlation spectroscopy, and we succeeded in observing the freezing behaviour.