bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 promotes microglial synapse elimination in human brain organoids
Authors: Samudyata  , Oliveira Ana O. , Malwade Susmita , Rufino de Sousa Nuno , Goparaju Sravan K. , Gracias Jessica , Orhan Funda , Steponaviciute Laura , Schalling Martin , Sheridan Steven D. , Perlis Roy H. , Rothfuchs Antonio G. , Sellgren Carl M. 
Published: October 2022

AbstractNeuropsychiatric manifestations are common in both the acute and post-acute phase of SARS-CoV-2 infection, but the mechanisms of these effects are unknown. In a newly established brain organoid model with innately developing microglia, we demonstrate that SARS-CoV-2 infection initiate neuronal cell death and cause a loss of post-synaptic termini. Despite limited neurotropism and a decelerating viral replication, we observe a threefold increase in microglial engulfment of postsynaptic termini after SARS-CoV-2 exposure. We define the microglial responses to SARS-CoV-2 infection by single cell transcriptomic profiling and observe an upregulation of interferon-responsive genes as well as genes promoting migration and synapse engulfment. To a large extent, SARS-CoV-2 exposed microglia adopt a transcriptomic profile overlapping with neurodegenerative disorders that display an early synapse loss as well as an increased incident risk after a SARS-CoV-2 infection. Our results reveal that brain organoids infected with SARS-CoV-2 display disruption in circuit integrity via microglia-mediated synapse elimination and identifies a potential novel mechanism contributing to cognitive impairments in patients recovering from COVID-19.
Signaling pathways and targeted therapies in lung squamous cell carcinoma: mechanisms and clinical trials
Authors: Niu Zhenyi , Jin Runsen , Zhang Yan , Li Hecheng 
Published: October 2022

AbstractLung cancer is the leading cause of cancer-related death across the world. Unlike lung adenocarcinoma, patients with lung squamous cell carcinoma (LSCC) have not benefitted from targeted therapies. Although immunotherapy has significantly improved cancer patients’ outcomes, the relatively low response rate and severe adverse events hinder the clinical application of this promising treatment in LSCC. Therefore, it is of vital importance to have a better understanding of the mechanisms underlying the pathogenesis of LSCC as well as the inner connection among different signaling pathways, which will surely provide opportunities for more effective therapeutic interventions for LSCC. In this review, new insights were given about classical signaling pathways which have been proved in other cancer types but not in LSCC, including PI3K signaling pathway, VEGF/VEGFR signaling, and CDK4/6 pathway. Other signaling pathways which may have therapeutic potentials in LSCC were also discussed, including the FGFR1 pathway, EGFR pathway, and KEAP1/NRF2 pathway. Next, chromosome 3q, which harbors two key squamous differentiation markersSOX2andTP63is discussed as well as its related potential therapeutic targets. We also provided some progress of LSCC in epigenetic therapies and immune checkpoints blockade (ICB) therapies. Subsequently, we outlined some combination strategies of ICB therapies and other targeted therapies. Finally, prospects and challenges were given related to the exploration and application of novel therapeutic strategies for LSCC.
Neandertal introgression partitions the genetic landscape of neuropsychiatric disorders and associated behavioral phenotypes
Authors: Dannemann Michael , Milaneschi Yuri , Yermakovich Danat , Stiglbauer Victoria , Kariis Hanna Maria , Krebs Kristi , Friese Manuel A. , Otte Christian ,   Estonian Biobank Research Team, Esko Tõnu , Metspalu Andres , Milani Lili , Mägi Reedik , Nelis Mari , Lehto Kelli , Penninx Brenda W. J. H. , Kelso Janet , Gold Stefan M. 
Published: October 2022

AbstractDespite advances in identifying the genetic basis of psychiatric and neurological disorders, fundamental questions about their evolutionary origins remain elusive. Here, introgressed variants from archaic humans such as Neandertals can serve as an intriguing research paradigm. We compared the number of associations for Neandertal variants to the number of associations of frequency-matched non-archaic variants with regard to human CNS disorders (neurological and psychiatric), nervous system drug prescriptions (as a proxy for disease), and related, non-disease phenotypes in the UK biobank (UKBB). While no enrichment for Neandertal genetic variants were observed in the UKBB for psychiatric or neurological disease categories, we found significant associations with certain behavioral phenotypes including pain, chronotype/sleep, smoking and alcohol consumption. In some instances, the enrichment signal was driven by Neandertal variants that represented the strongest association genome-wide. SNPs within a Neandertal haplotype that was associated with smoking in the UKBB could be replicated in four independent genomics datasets.Our data suggest that evolutionary processes in recent human evolution like admixture with Neandertals significantly contribute to behavioral phenotypes but not psychiatric and neurological diseases. These findings help to link genetic variants in a population to putative past beneficial effects, which likely only indirectly contribute to pathology in modern day humans
Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants
Authors: Del Vecchio Claudia , Cracknell Daniels Bethan , Brancaccio Giuseppina , Brazzale Alessandra Rosalba , Lavezzo Enrico , Ciavarella Constanze , Onelia Francesco , Franchin Elisa , Manuto Laura , Bianca Federico , Cianci Vito , Cattelan Anna Maria , Dorigatti Ilaria , Toppo Stefano , Crisanti Andrea 
Published: October 2022

AbstractPopulation testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Notably, we find that genomic surveillance systems which rely on antigen population testing to identify samples for sequencing will bias detection of escape antigen test variants. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, including in contexts where the use of antigen tests is widespread.
Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method
Authors: Cai Ye , Cao Huifen , Wang Fang , Zhang Yufei , Kapranov Philipp 
Published: October 2022

AbstractDNA damage plays a critical role in biology and diseases; however, how different types of DNA lesions affect cellular functions is far from clear mostly due to the paucity of high-resolution methods that can map their locations in complex genomes, such as those of mammals. Here, we present the development and validation of SSiNGLe-AP method, which can map a common type of DNA damage, abasic (AP) sites, in a genome-wide and high-resolution manner. We apply this method to six different tissues of mice with different ages and human cancer cell lines. We find a nonrandom distribution of AP sites in the mammalian genome that exhibits dynamic enrichment at specific genomic locations, including single-nucleotide hotspots, and is significantly influenced by gene expression, age and tissue type in particular. Overall, these results suggest that we are only starting to understand the true complexities in the genomic patterns of DNA damage.
Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes
Authors: Wei Wei , Schon Katherine R. , Elgar Greg , Orioli Andrea , Tanguy Melanie , Giess Adam , Tischkowitz Marc , Caulfield Mark J. , Chinnery Patrick F. 
Published: October 2022

AbstractDNA transfer from cytoplasmic organelles to the cell nucleus is a legacy of the endosymbiotic event—the majority of nuclear-mitochondrial segments (NUMTs) are thought to be ancient, preceding human speciation1–3. Here we analyse whole-genome sequences from 66,083 people—including 12,509 people with cancer—and demonstrate the ongoing transfer of mitochondrial DNA into the nucleus, contributing to a complex NUMT landscape. More than 99% of individuals had at least one of 1,637 different NUMTs, with 1 in 8 individuals having an ultra-rare NUMT that is present in less than 0.1% of the population. More than 90% of the extant NUMTs that we evaluated inserted into the nuclear genome after humans diverged from apes. Once embedded, the sequences were no longer under the evolutionary constraint seen within the mitochondrion, and NUMT-specific mutations had a different mutational signature to mitochondrial DNA. De novo NUMTs were observed in the germline once in every 104 births and once in every 103 cancers. NUMTs preferentially involved non-coding mitochondrial DNA, linking transcription and replication to their origin, with nuclear insertion involving multiple mechanisms including double-strand break repair associated with PR domain zinc-finger protein 9 (PRDM9) binding. The frequency of tumour-specific NUMTs differed between cancers, including a probably causal insertion in a myxoid liposarcoma. We found evidence of selection against NUMTs on the basis of size and genomic location, shaping a highly heterogenous and dynamic human NUMT landscape.
Tracing the oomycete pathogen Saprolegnia parasitica in aquaculture and the environment
Authors: Pavić Dora , Grbin Dorotea , Hudina Sandra , Prosenc Zmrzljak Uršula , Miljanović Anđela , Košir Rok , Varga Filip , Ćurko Josip , Marčić Zoran , Bielen Ana 
Published: October 2022

AbstractSaprolegnia parasitica causes saprolegniosis, a disease responsible for significant economic losses in aquaculture and declines of fish populations in the wild, but the knowledge of its distribution and prevalence in the environment is limited. We developed a fast, sensitive and specific S. parasitica droplet digital PCR (ddPCR) assay and demonstrated its applicability for the detection and quantification of the pathogen in environmental samples: swab DNA collected from the host (trout skin, surface of eggs) and environmental DNA extracted from water. The developed assay was used to assess how abiotic (i.e. physico-chemical parameters of the water) and biotic (health status of the host) factors influence the S. parasitica load in the environment. The pathogen load in water samples was positively correlated with some site-specific abiotic parameters such as electrical conductivity (EC) and calcium, while fluorides were negatively correlated, suggesting that physico-chemical parameters are important for determining S. parasitica load in natural waters. Furthermore, skin swabs of injured trout had significantly higher pathogen load than swabs collected from healthy fish, confirming that S. parasitica is a widespread opportunistic pathogen. Our results provide new insights into various environmental factors that influence the distribution and abundance of S. parasitica.
Role of non-invasive methods in detecting liver impairment in familial Mediterranean fever adult patients with persistent hepatic cytolysis
Authors: Deshayes Samuel , Fraisse Thibault , Fellahi Soraya , Steichen Olivier , Savey Léa , Turlin Bruno , Munteanu Mona , Aouba Achille , Bourguiba Rim , Hentgen Véronique , Faintuch Jean-Manuel , Giurgea Irina , Grateau Gilles , Bastard Jean-Philippe , Georgin-Lavialle Sophie 
Published: October 2022

AbstractFamilial Mediterranean fever (FMF) patients may have hepatic cytolysis, although its origin is not formally elucidated. We aimed to evaluate liver involvement in familial Mediterranean fever (FMF) using non-invasive methods. All adult FMF patients harboring two non-ambiguous mutations of the MEFV gene with hepatic cytolysis were identified in a French tertiary adult center for FMF. Liver impairment was explored with FibroMax (a non-invasive method to estimate hepatic steatosis, necrosis, inflammation and fibrosis) and liver ultrasound. Among 520 FMF adult patients, 43 had persistent hepatic cytolysis and 20 patients were included (11 women, median age at inclusion: 49.5 years). According to the FibroMax results, patients were classified as having steatosis, fibrosis, and possible or definite nonalcoholic steato-hepatitis in 10 (50%), 9 (45%) and 7 (35%) of cases, respectively. The score of steatosis did not seem associated with the usual metabolic risk factors. No significant association was found between the cumulated dose of colchicine and any of the scores included in FibroMax. In adult FMF patients with persistent hepatic cytolysis, steatosis is the first cause to consider even in the absence of usual metabolic risk factors, suggesting other mechanisms. Colchicine did not seem to be involved in this toxicity.
Age at first birth and risk of urinary incontinence after delivery: a dose–response meta-analysis
Authors: Ren Yongcheng , Hu Qing , Zou Haiyin , Xue Meifang , Tian Xinjie , Cao Fuqun , Yang Lei 
Published: October 2022

AbstractStudies investigating the impact of age at first birth on urinary incontinence after delivery have reached inconsistent conclusions. We performed this systematic review and meta-analysis of studies assessing the risk of urinary incontinence after delivery, regardless of the type, with age at first birth. MEDLINE via PubMed and Web of science databases were searched up to March 13, 2021. Restricted cubic splines were used to model the dose–response association. Twelve publications were included in this meta-analysis. The summary odds ratio (OR) and 95% confidence interval (CI) per 1-year increase in age at first birth were 1.01 (95% CI (0.99, 1.02)) for urinary incontinence (America: 1.00 (0.99, 1.00); Europe: 1.03 (1.00, 1.06); Asian: 0.99 (0.89, 1.10)). A non-linear dose–response (Pnonlinearity < 0.01) indicated that age at first birth older than 32 (P < 0.05) increases the risk of urinary incontinence. First birth before age 32 make decrease the risk of urinary incontinence after delivery.
Res﻿earch on dust dispersion law of fully mechanized mining faces under different inclinations and tracking closed dust control method
Authors: Zhou Gang , Kong Yang , Meng Qunzhi , Jiang Bingyou , Liu Yongwei , Li Gang , Sun Biao , Wang Jinli , Yan Dong , Li Zhenhua 
Published: October 2022

AbstractBased on the gas–solid two-phase flow theory, numerical simulation of the dust dispersion law of fully mechanized mining work under different inclination angles and comparative analysis of field-measured data show that with the increase of working face inclination, the inclination of airflow into the unmined zone increases from 25° to 50° and the maximum wind speed increases from 2.16 to 2.25 m/s after the mixing of cutting turbulent wind and system ventilation. Meanwhile, the range of high-concentration dust clusters, suspension time, lateral migration intensity, and deposition zone increase to varying degrees; dust clusters increases from 62.02 to 202.46 m3. When X < 53.96 m, the dust concentration in the sidewalk-breathing zone shows a sine function with the length of the working face, and when X ≥ 53.96 m, it satisfies the exponential decay function. Based on this, the tracking closed dust control technology is proposed. Combining the offset angle of the airflow and t the gathering position of dust mass, the wind curtain angle and air velocity are automatically controlled to ensure that the dust is restricted to one side of the cable trough.
Protein interaction, cytotoxic, transcriptomic and proteomic responses to structurally distinct EPAC1 activators in HUVECs
Authors: Wiejak Jolanta , Luchowska-Stańska Urszula , Wang Pingyuan , Zhou Jia , Maffia Pasquale , Morgan David , Barker Graeme , Yarwood Stephen J. 
Published: October 2022

AbstractThe N-acylsulfonamide derivative, I942, represents the first non-cyclic nucleotide partial agonist of EPAC1. This was soon followed by the identification of the I942 analogues, PW0381, PW0521 and PWO577 and a series of benzofuran oxoacetic acid EPAC1 activators, SY006, SY007 and SY009. Protein interaction, cytotoxicity and EPAC1 activation assays applied here identify PWO577 and SY007 as being effective EPAC1 binders that are well tolerated in HUVECs at concentrations greater than 100 μM and up to 48 h incubation and are effective activators of transfected EPAC1 in U2OS cells. Using RNAseq in HUVECs we show that PWO577 and SY007 regulate approximately 11,000 shared genes, with only few differential gene changes being “off-target”. The genes significantly regulated by both PWO577 and SY007 included a subset of genes normally associated with endothelial activation, including ICAM1, MMP1 and CCL2. Of these, only the expression of MMP1 was markedly increased at the protein level, as determined by LC–MS-based proteomics. Both PWO577 and SY007 suppressed IL-6-induced STAT3 activation and associated downstream gene expression, including inhibition of SOCS3, STAT3, IL6ST and JAK3 genes. Together these results demonstrate the utility of structurally distinct, specific and non-toxic EPAC1 activators. Future modifications will be aimed at eliminating the few noted off-target effects.
Structural measurement of electron-phonon coupling and electronic thermal transport across a metal-semiconductor interface
Authors: Jo Wonhyuk , Kee Jungyun , Kim Kooktea , Landahl Eric C. , Longbons Grace , Walko Donald A. , Wen Haidan , Lee Dong Ryeol , Lee Sooheyong 
Published: October 2022

AbstractScattering of energetic charge carriers and their coupling to lattice vibrations (phonons) in dielectric materials and semiconductors are crucial processes that determine the functional limits of optoelectronics, photovoltaics, and photocatalysts. The strength of these energy exchanges is often described by the electron-phonon coupling coefficient, which is difficult to measure due to the microscopic time- and length-scales involved. In the present study, we propose an alternate means to quantify the coupling parameter along with thermal boundary resistance and electron conductivity by performing a high angular-resolution time-resolved X-ray diffraction measurement of propagating lattice deformation following laser excitation of a nanoscale, polycrystalline metal film on a semiconductor substrate. Our data present direct experimental evidence for identifying the ballistic and diffusive transport components occurring at the interface, where only the latter participates in thermal diffusion. This approach provides a robust measurement that can be applied to investigate microscopic energy transport in various solid-state materials.
Spectral characteristics of gold nanoparticle doped optical fibre under axial strain
Authors: Wang Xiang , Benedictus Rinze , Groves Roger M. 
Published: October 2022

AbstractNanoparticle (NP) doping of optical fibres can be used to increase the intensity of the backscattered light used for distributed strain sensing and has shown the advantages of high precision strain detection and multiplex sensing experimentally. However, the backscatter spectral characteristics of NP-doped optical fibres have not been described even though they are quite different from the spectra from fibre Bragg gratings (FBGs) or commercial single mode fibres. In this paper, gold NPs, used as the contrast agent in the optical fibre to increase the intensity of the backscattered light, were investigated from the aspect of their spectra. A single scattering model with Mie theory and an effective refractive index (RI) model were used to evaluate the backscattered light spectra and the Monte Carlo Method was used for seeding NPs. The results showed that the strain responsivity of gold-NP doped fibres with low volume ratio doping (single scattering restriction) are close to FBGs and commercial fibres. High volume ratios of gold NP doping increase the imaginary part of the RI of the optical fibre, which has a significant influence on the spectra in the wavenumber domain. These theoretical insights may promote the future engineering design of NP-doped fibre sensors.
Preparation and characterization of acrylic resins with bioactive glasses
Authors: Raszewski Zbigniew , Chojnacka Katarzyna , Mikulewicz Marcin 
Published: October 2022

AbstractThis study aimed to prepare a bioactive acrylic material by adding different types of glasses. Commercially available polymerized acrylic resin was mixed with 10% of four different types of glasses in the powder form and cured. Flexural strength, sorption, and solubility of the samples were tested according to ISO 20795-1:2013. The total number of samples used in the tests were 60. The materials were placed in artificial saliva of pH 4 and 7, and elution was performed for 0, 1, 28, and 42 days. The collected samples were analyzed using inductively coupled plasma atomic emission spectrometry to detect Ca, P, and Si ions and using ion chromatography to detect F ions. The materials obtained after modification with glasses showed lower compressive strength compared with pure polymethyl methacrylate but met the standard requirements. Two glass types showed higher solubility values compared with the value defined by the ISO standard. Biomin C and S53P4 released Ca, P, and Si ions, respectively, after 42 days in artificial saliva. Acrylic resins modified with 10% Biomin C and S53P4 glasses can be a valuable source of Ca and P ions under acid conditions for 28 and 42 days.
The evolution of parental care in salamanders
Authors: Vági Balázs , Marsh Daniel , Katona Gergely , Végvári Zsolt , Freckleton Robert P. , Liker András , Székely Tamás 
Published: October 2022

AbstractComplex parenting has been proposed to contribute to the evolutionary success of vertebrates. However, the evolutionary routes to complex parenting and the role of parenting in vertebrate diversity are still contentious. Although basal vertebrates provide clues to complex reproduction, these are often understudied. Using 181 species that represent all major lineages of an early vertebrate group, the salamanders and newts (Caudata, salamanders henceforth) here we show that fertilisation mode is tied to parental care: male-only care occurs in external fertilisers, whereas female-only care exclusively occurs in internal fertilisers. Importantly, internal fertilisation opens the way to terrestrial reproduction, because fertilised females are able to deposit their eggs on land, and with maternal care provision, the eggs could potentially develop outside the aquatic environment. Taken together, our results of a semi-aquatic early vertebrate group propose that the diversity and follow-up radiation of terrestrial vertebrates are inherently associated with a complex social behaviour, parenting.