bluuebunny/crossref_metadata_2025 huggingface dataset:
Affinity scores: An individual-centric fingerprinting framework for neuropsychiatric disorders
Authors: Wannan Cassandra M. J. , Pantelis Christos , Merritt Antonia H. , Tonge Bruce , Syeda Warda T.
Published: August 2022

Population-centric frameworks of biomarker identification for psychiatric disorders focus primarily on comparing averages between groups and assume that diagnostic groups are (1) mutually-exclusive, and (2) homogeneous. There is a paucity of individual-centric approaches capable of identifying individual-specific ‘fingerprints’ across multiple domains. To address this, we propose a novel framework, combining a range of biopsychosocial markers, including brain structure, cognition, and clinical markers, into higher-level ‘fingerprints’, capable of capturing intra-illness heterogeneity and inter-illness overlap. A multivariate framework was implemented to identify individualised patterns of brain structure, cognition and clinical markers based on affinity to other participants in the database. First, individual-level affinity scores defined each participant’s “neighbourhood” across each measure based on variable-specific hop sizes. Next, diagnostic verification and classification algorithms were implemented based on multivariate affinity score profiles. To perform affinity-based classification, data were divided into training and test samples, and 5-fold nested cross-validation was performed on the training data. Affinity-based classification was compared to weighted K-nearest neighbours (KNN) classification. The framework was applied to the Australian Schizophrenia Research Bank (ASRB) dataset, which included data from individuals with chronic and treatment resistant schizophrenia and healthy controls. Individualised affinity scores provided a ‘fingerprint’ of brain structure, cognition, and clinical markers, which described the affinity of an individual to the representative groups in the dataset. Diagnostic verification capability was moderate to high depending on the choice of multivariate affinity metric. Affinity score-based classification achieved a high degree of accuracy in the training, nested cross-validation and prediction steps, and outperformed KNN classification in the training and test datasets. Affinity scores demonstrate utility in two keys ways: (1) Early and accurate diagnosis of neuropsychiatric disorders, whereby an individual can be grouped within a diagnostic category/ies that best matches their fingerprint, and (2) identification of biopsychosocial factors that most strongly characterise individuals/disorders, and which may be most amenable to intervention.
Associations between levels of oxidative nucleoside damage and cardiovascular risk in patients newly diagnosed with bipolar disorder and their unaffected relatives
Authors: Bøgh Helena Lykke , Stanislaus Sharleny , Kjærstad Hanne Lie , Sletved Kimie Stefanie Ormstrup , Forman Julie Lyng , Poulsen Henrik Enghusen , Vinberg Maj , Kessing Lars Vedel , Coello Klara
Published: August 2022

Enhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4–35.9%, p = 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8–26.4%, p = 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7–43%, p = 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.
Acute and long-term effects of psilocybin on energy balance and feeding behavior in mice
Authors: Fadahunsi Nicole , Lund Jens , Breum Alberte Wollesen , Mathiesen Cecilie Vad , Larsen Isabella Beck , Knudsen Gitte Moos , Klein Anders Bue , Clemmensen Christoffer
Published: August 2022

Psilocybin and other serotonergic psychedelics have re-emerged as therapeutics for neuropsychiatric disorders, including addiction. Psilocybin induces long-lasting effects on behavior, likely due to its profound ability to alter consciousness and augment neural connectivity and plasticity. Impaired synaptic plasticity in obesity contributes to ‘addictive-like’ behaviors, including heightened motivation for palatable food, and excessive food seeking and consumption. Here, we evaluate the effects of psilocybin on feeding behavior, energy metabolism, and as a weight-lowering agent in mice. We demonstrate that a single dose of psilocybin substantially alters the prefrontal cortex transcriptome but has no acute or long-lasting effects on food intake or body weight in diet-induced obese mice or in genetic mouse models of obesity. Similarly, sub-chronic microdosing of psilocybin has no metabolic effects in obese mice and psilocybin does not augment glucagon-like peptide-1 (GLP-1) induced weight loss or enhance diet-induced weight loss. A single high dose of psilocybin reduces sucrose preference but fails to counter binge-like eating behavior. Although these preclinical data discourage clinical investigation, there may be nuances in the mode of action of psychedelic drugs that are difficult to capture in rodent models, and thus require human evaluation to uncover.
Transcription-coupled and epigenome-encoded mechanisms direct H3K4 methylation
Authors: Oya Satoyo , Takahashi Mayumi , Takashima Kazuya , Kakutani Tetsuji , Inagaki Soichi
Published: August 2022

Mono-, di-, and trimethylation of histone H3 lysine 4 (H3K4me1/2/3) are associated with transcription, yet it remains controversial whether H3K4me1/2/3 promote or result from transcription. Our previous characterizations of Arabidopsis H3K4 demethylases suggest roles for H3K4me1 in transcription. However, the control of H3K4me1 remains unexplored in Arabidopsis, in which no methyltransferase for H3K4me1 has been identified. Here, we identify three Arabidopsis methyltransferases that direct H3K4me1. Analyses of their genome-wide localization using ChIP-seq and machine learning reveal that one of the enzymes cooperates with the transcription machinery, while the other two are associated with specific histone modifications and DNA sequences. Importantly, these two types of localization patterns are also found for the other H3K4 methyltransferases in Arabidopsis and mice. These results suggest that H3K4me1/2/3 are established and maintained via interplay with transcription as well as inputs from other chromatin features, presumably enabling elaborate gene control.
Ultra-deep sequencing validates safety of CRISPR/Cas9 genome editing in human hematopoietic stem and progenitor cells
Authors: Cromer M. Kyle , Barsan Valentin V. , Jaeger Erich , Wang Mengchi , Hampton Jessica P. , Chen Feng , Kennedy Drew , Xiao Jenny , Khrebtukova Irina , Granat Ana , Truong Tiffany , Porteus Matthew H.
Published: August 2022

As CRISPR-based therapies enter the clinic, evaluation of safety remains a critical and active area of study. Here, we employ a clinical next generation sequencing (NGS) workflow to achieve high sequencing depth and detect ultra-low frequency variants across exons of genes associated with cancer, all exons, and genome wide. In three separate primary human hematopoietic stem and progenitor cell (HSPC) donors assessed in technical triplicates, we electroporated high-fidelity Cas9 protein targeted to three loci (AAVS1, HBB, and ZFPM2) and harvested genomic DNA at days 4 and 10. Our results demonstrate that clinically relevant delivery of high-fidelity Cas9 to primary HSPCs and ex vivo culture up to 10 days does not introduce or enrich for tumorigenic variants and that even a single SNP in a gRNA spacer sequence is sufficient to eliminate Cas9 off-target activity in primary, repair-competent human HSPCs.
Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens
Authors: Klemis Verena , Schmidt Tina , Schub David , Mihm Janine , Marx Stefanie , Abu-Omar Amina , Ziegler Laura , Hielscher Franziska , Guckelmus Candida , Urschel Rebecca , Wagenpfeil Stefan , Schneitler Sophie , Becker Sören L. , Gärtner Barbara C. , Sester Urban , Sester Martina
Published: August 2022

Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.
Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription
Authors: Liu Nian , He Jiacheng , Fan Dongdong , Gu Yang , Wang Jianyi , Li Huimu , Zhu Xiaoxiao , Du Ying , Tian Yong , Liu Benyu , Fan Zusen
Published: August 2022

Innate lymphoid cells (ILCs) exert important roles in host defense, tissue repair and inflammatory diseases. However, how ILC lineage specification is regulated remains largely elusive. Here we identify that circular RNA circTmem241 is highly expressed in group III innate lymphoid cells (ILC3s) and their progenitor cells. CircTmem241 deficiency impairs ILC3 commitment and attenuates anti-bacterial immunity. Mechanistically, circTmem241 interacts with Nono protein to recruit histone methyltransferase Ash1l onto Elk3 promoter in ILC progenitor cells (ILCPs). Ash1l-mediated histone modifications on Elk3 promoter enhance chromatin accessibility to initiate Elk3 transcription. Of note, circTmem241−/−, Nono−/− and Ash1l−/− ILCPs display impaired ILC3 differentiation, while Elk3 overexpression rescues ILC3 commitment ability. Finally, circTmem241−/−Elk3−/− mice show lower numbers of ILC3s and are more susceptible to bacterial infection. We reveal that the circTmem241-Nono-Ash1l-Elk3 axis is required for the ILCP differentiation into ILC3P and ILC3 maturation, which is important to manipulate this axis for ILC development on treatment of infectious diseases.
Rational highly dispersed ruthenium for reductive catalytic fractionation of lignocellulose
Authors: Liu Zhenzhen , Li Helong , Gao Xueying , Guo Xuan , Wang Shuizhong , Fang Yunming , Song Guoyong
Published: August 2022

Producing monomeric phenols from lignin biopolymer depolymerization in a detachable and efficient manner comes under the spotlight on the fullest utilization of sustainable lignocellulosic biomass. Here, we report a low-loaded and highly dispersed Ru anchored on a chitosan-derived N-doped carbon catalyst (RuN/ZnO/C), which exhibits outstanding performance in the reductive catalytic fractionation of lignocellulose. Nearly theoretical maximum yields of phenolic monomers from lignin are achieved, corresponding to TON as 431 molphenols molRu−1, 20 times higher than that from commercial Ru/C catalyst; high selectivity toward propyl end-chained guaiacol and syringol allow them to be readily purified. The RCF leave high retention of (hemi)cellulose amenable to enzymatic hydrolysis due to the successful breakdown of biomass recalcitrance. The RuN/ZnO/C catalyst shows good stability in recycling experiments as well as after a harsh hydrothermal treatment, benefiting from the coordination of Ru species with N atoms. Characterizations of the RuN/ZnO/C imply a transformation from Ru single atoms to nanoclusters under current reaction conditions. Time-course experiment, as well as reactivity screening of a series of lignin model compounds, offer insight into the mechanism of current RCF over RuN/ZnO/C. This work opens a new opportunity for achieving the valuable aromatic products from lignin and promoting the industrial economic feasibility of lignocellulosic biomass.
Adenosine triphosphate-activated prodrug system for on-demand bacterial inactivation and wound disinfection
Authors: Weng Yuhao , Chen Huihong , Chen Xiaoqian , Yang Huilin , Chen Chia-Hung , Tan Hongliang
Published: August 2022

The prodrug approach has emerged as a promising solution to combat bacterial resistance and enhance treatment efficacy against bacterial infections. Here, we report an adenosine triphosphate (ATP)-activated prodrug system for on-demand treatment of bacterial infection. The prodrug system benefits from the synergistic action of zeolitic imidazolate framework-8 and polyacrylamide hydrogel microsphere, which simultaneously transports indole-3-acetic acid and horseradish peroxidase in a single carrier while preventing the premature activation of indole-3-acetic acid. The ATP-responsive characteristic of zeolitic imidazolate framework-8 allows the prodrug system to be activated by the ATP secreted by bacteria to generate reactive oxygen species (ROS), displaying exceptional broad-spectrum antimicrobial ability. Upon disruption of the bacterial membrane by ROS, the leaked intracellular ATP from dead bacteria can accelerate the activation of the prodrug system to further enhance antibacterial efficiency. In vivo experiments in a mouse model demonstrates the applicability of the prodrug system for wound disinfection with minimal side effects.
Restructured membrane contacts rewire organelles for human cytomegalovirus infection
Authors: Cook Katelyn C. , Tsopurashvili Elene , Needham Jason M. , Thompson Sunnie R. , Cristea Ileana M.
Published: August 2022

Membrane contact sites (MCSs) link organelles to coordinate cellular functions across space and time. Although viruses remodel organelles for their replication cycles, MCSs remain largely unexplored during infections. Here, we design a targeted proteomics platform for measuring MCS proteins at all organelles simultaneously and define functional virus-driven MCS alterations by the ancient beta-herpesvirus human cytomegalovirus (HCMV). Integration with super-resolution microscopy and comparisons to herpes simplex virus (HSV-1), Influenza A, and beta-coronavirus HCoV-OC43 infections reveals time-sensitive contact regulation that allows switching anti- to pro-viral organelle functions. We uncover a stabilized mitochondria-ER encapsulation structure (MENC). As HCMV infection progresses, MENCs become the predominant mitochondria-ER contact phenotype and sequentially recruit the tethering partners VAP-B and PTPIP51, supporting virus production. However, premature ER-mitochondria tethering activates STING and interferon response, priming cells against infection. At peroxisomes, ACBD5-mediated ER contacts balance peroxisome proliferation versus membrane expansion, with ACBD5 impacting the titers of each virus tested.
A resonant electro-physical transmutation method for water purification
Authors: Lee McKane B. , Ward Nicholas D. , Leach Michael , Kent Randy
Published: August 2022

We present an electro-transmutation (ET) method of water purification using the Quantum Kinetic Fusor™. Electrolysis experiments were performed with residential well water and seawater coupled with two different electrode materials—stainless steel and aluminum—to test the effectiveness of ET in removing contaminants and altering the physiochemistry (e.g., pH, alkalinity) and isotopic composition of water. ET effectively removed contaminants at power inputs as low 0.142 mA cm−2, i.e., 1.9–4.2 watts, which is substantially lower than other electrochemical techniques. The ET process also reduces, and in some cases eliminates, electrode surface area degradation. This outcome is outside the field of traditional Faraday electrolysis, further distinguishing the ET process as potentially more cost-effective than other water purification methods. Importantly, the experiments reveal ET is an exceptionally low input energy generator. This finding is based on the presence of exotic x-rays (Bremsstrahlung) emissions during operation (1–20 KeV).
Context-specific emergence and growth of the SARS-CoV-2 Delta variant
Authors: McCrone John T. , Hill Verity , Bajaj Sumali , Pena Rosario Evans , Lambert Ben C. , Inward Rhys , Bhatt Samir , Volz Erik , Ruis Christopher , Dellicour Simon , Baele Guy , Zarebski Alexander E. , Sadilek Adam , Wu Neo , Schneider Aaron , Ji Xiang , Raghwani Jayna , Jackson Ben , Colquhoun Rachel , O’Toole Áine , Peacock Thomas P. , Twohig Kate , Thelwall Simon , Dabrera Gavin , Myers Richard ,   The COVID-19 Genomics UK (COG-UK) Consortium, Faria Nuno R. , Huber Carmen , Bogoch Isaac I. , Khan Kamran , du Plessis Louis , Barrett Jeffrey C. , Aanensen David M. , Barclay Wendy S. , Chand Meera , Connor Thomas , Loman Nicholas J. , Suchard Marc A. , Pybus Oliver G. , Rambaut Andrew , Kraemer Moritz U. G.
Published: August 2022

The SARS-CoV-2 Delta (Pango lineage B.1.617.2) variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. The emergence of the Delta variant in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 SARS-CoV-2 genomes from England together with 93,649 genomes from the rest of the world to reconstruct the emergence of Delta and quantify its introduction to and regional dissemination across England in the context of changing travel and social restrictions. Using analysis of human movement, contact tracing and virus genomic data, we find that the geographic focus of the expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced more than 1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers reduced onward transmission from importations; however, the transmission chains that later dominated the Delta wave in England were seeded before travel restrictions were introduced. Increasing inter-regional travel within England drove the nationwide dissemination of Delta, with some cities receiving more than 2,000 observable lineage introductions from elsewhere. Subsequently, increased levels of local population mixing—and not the number of importations—were associated with the faster relative spread of Delta. The invasion dynamics of Delta depended on spatial heterogeneity in contact patterns, and our findings will inform optimal spatial interventions to reduce the transmission of current and future variants of concern, such as Omicron (Pango lineage B.1.1.529).
Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells
Authors: Rouhani Foad J. , Zou Xueqing , Danecek Petr , Badja Cherif , Amarante Tauanne Dias , Koh Gene , Wu Qianxin , Memari Yasin , Durbin Richard , Martincorena Inigo , Bassett Andrew R. , Gaffney Daniel , Nik-Zainal Serena
Published: August 2022

We explored human induced pluripotent stem cells (hiPSCs) derived from different tissues to gain insights into genomic integrity at single-nucleotide resolution. We used genome sequencing data from two large hiPSC repositories involving 696 hiPSCs and daughter subclones. We find ultraviolet light (UV)-related damage in ~72% of skin fibroblast-derived hiPSCs (F-hiPSCs), occasionally resulting in substantial mutagenesis (up to 15 mutations per megabase). We demonstrate remarkable genomic heterogeneity between independent F-hiPSC clones derived during the same round of reprogramming due to oligoclonal fibroblast populations. In contrast, blood-derived hiPSCs (B-hiPSCs) had fewer mutations and no UV damage but a high prevalence of acquired BCOR mutations (26.9% of lines). We reveal strong selection pressure for BCOR mutations in F-hiPSCs and B-hiPSCs and provide evidence that they arise in vitro. Directed differentiation of hiPSCs and RNA sequencing showed that BCOR mutations have functional consequences. Our work strongly suggests that detailed nucleotide-resolution characterization is essential before using hiPSCs.
Statistically enriched geospatial datasets of Brazilian municipalities for data-driven modeling
Authors: Abdalla Livia , Augusto Douglas A. , Chame Marcia , Dufek Amanda S. , Oliveira Leonardo , Krempser Eduardo
Published: August 2022

The lack of georeferencing in geospatial datasets hinders the accomplishment of scientific studies that rely on accurate data. This is particularly concerning in the field of health sciences, where georeferenced data could lead to scientific results of great relevance to society. The Brazilian health systems, especially those for Notifiable Diseases, in practice do not register georeferenced data; instead, the records indicate merely the municipality in which the event occurred. Typically in data-driven modeling, accurate disease prediction models based on occurrence requires socioenvironmental characteristics of the exact location of each event, which is often unavailable. To enrich the expressiveness of data-driven models when the municipality of the event is the best available information, we produced datasets with statistical characterization of all 5,570 Brazilian municipalities in 642 layers of thematic data that represent the natural and artificial characteristics of the municipalities’ landscapes over time. This resulted in a collection of datasets comprising a total of 11,556 descriptive statistics attributes for each municipality.
A new Cretaceous thyreophoran from Patagonia supports a South American lineage of armoured dinosaurs
Authors: Riguetti Facundo J. , Apesteguía Sebastián , Pereda-Suberbiola Xabier
Published: August 2022

The early evolution of thyreophoran dinosaurs is thought to have occurred primarily in northern continents since most evidence comes from the Lower and Middle Jurassic of Europe and North America. The diversification into stegosaurs and ankylosaurs is obscured by a patchy fossil record comprising only a handful of fragmentary fossils, most with uncertain phylogenetic affinities. Here we report the discovery of a new armoured dinosaur from the early Late Cretaceous of Argentina, recovered phylogenetically using various datasets either as a basal thyreophoran or a stem ankylosaur, closely related to Scelidosaurus. It bears unusual anatomical features showing that several traits traditionally associated with the heavy Cretaceous thyreophorans did not occur universally. Jakapil kaniukura gen. et sp. nov. is the first definitive thyreophoran species from the Argentinian Patagonia. Unlike most thyreophorans, it seems to show a bipedal stance, as in Scutellosaurus. Jakapil also shows that early thyreophorans had a much broader geographic distribution than previously thought. It is a member of an ancient basal thyreophoran lineage that survived until the Late Cretaceous in South America.
Convolutional neural networks for approximating electrical and thermal conductivities of Cu-CNT composites
Authors: Ejaz Faizan , Hwang Leslie K. , Son Jangyup , Kim Jin-Sang , Lee Dong Su , Kwon Beomjin
Published: August 2022

This article explores the deep learning approach towards approximating the effective electrical and thermal conductivities of copper (Cu)-carbon nanotube (CNT) composites with CNTs aligned to the field direction. Convolutional neural networks (CNN) are trained to map the two-dimensional images of stochastic Cu-CNT networks to corresponding conductivities. The CNN model learns to estimate the Cu-CNT composite conductivities for various CNT volume fractions, interfacial electrical resistances, Rc = 20 Ω–20 kΩ, and interfacial thermal resistances, R″t,c = 10−10–10−7 m2K/W. For training the CNNs, the hyperparameters such as learning rate, minibatch size, and hidden layer neurons are optimized. Without iteratively solving the physical governing equations, the trained CNN model approximates the electrical and thermal conductivities within a second with the coefficient of determination (R2) greater than 98%, which may take longer than 100 min for a convectional numerical simulation. This work demonstrates the potential of the deep learning surrogate model for the complex transport processes in composite materials.
Novel magnetic iron–nickel/poly(ethersulfone) mixed matrix membranes for oxygen separation potential without applying an external magnetic field
Authors: Nady Norhan , Salem Noha , Kandil Sherif H.
Published: August 2022

This work presents novel magnetic mixed matrix poly(ethersulfone) (PES) membranes that combine the advantages of low-cost common PES polymer and low-cost iron–nickel magnetic alloys. Moreover, the presented magnetic mixed matrix PES membranes were fabricated and used without applying an external magnetic field during either the membrane casting or the separating process. The fabricated magnetic membranes were prepared using the phase inversion technique and N-methylpyrrolidone and N,N‐Dimethylformamide solvents mixture with volumetric ratio 1:9 and Lithium chloride as an additive. The used iron–nickel magnetic alloys were prepared by a simple chemical reduction method with unique morphologies (Fe10Ni90; starfish-like and Fe20Ni80; necklace-like). The fabricated membranes were characterized using Scanning Electron Microscope (SEM) and Scanning-Transmission Electron Microscope (STEM) imaging, energy dispersive X-ray (EDX), Thermogravimetric (TGA), and X-ray diffraction (XRD). Also, static water contact angle, membrane thickness, surface roughness, membrane porosity, membrane tensile strength as well as Vibrating Sample Magnetometer (VSM) analysis and oxygen transition rate (OTR) were determined. Moreover, the effect of alloy concentration and using Lithium chloride as an additive on the properties of the fabricated blank PES and magnetic mixed matrix PES membranes were studied. The presented novel magnetic mixed matrix PES membranes have high coercivity up to 106 (emu/g) with 3.61 × 10–5 cm3/cm2·s OTR compared to non-oxygen permeable blank PES membranes. The presented novel magnetic mixed matrix PES membranes have good potential in (oxygen) gas separation.
A disturbed balance between blood complement protective factors (FH, ApoE) and common pathway effectors (C5a, TCC) in acute COVID-19 and during convalesce
Authors: Laudanski Krzysztof , Okeke Tony , Siddiq Kumal , Hajj Jihane , Restrepo Mariana , Gullipalli Damodar , Song Wen-chao
Published: August 2022

A complement effect on homeostasis during infection is determined by both cytotoxic (activate complement component 5 (C5a) terminal cytotoxic complex (TCC)), and cytoprotective elements (complement factor H (FH), as well as apolipoprotein E (ApoE)). Here, we investigated the gap in knowledge in their blood milieu during SARS-CoV-2 infection with respect to the viral burden, level of tissue necrosis, and immunological response. 101 patients hospitalized with a PCR-confirmed diagnosis of COVID-19 had blood collected at H1 (48 h), H2 (3–4 Days), H3 (5–7 days), H4 (more than 7 days up to 93 days). Pre-existing conditions, treatment, the incidence of cerebrovascular events (CVA), a history of deep venous thrombosis (DVT) and pulmonary embolism (PE), and mortality was collected using electronic medical records. Plasma C5a, TCC, FH, and ApoE were considered as a complement milieu. Tissue necrosis (HMGB1, RAGE), non-specific inflammatory responses (IL-6, C-reactive protein), overall viral burden (SARS-CoV-2 spike protein), and specific immune responses (IgG, IgA, IgM directed αS- & N-proteins) were assessed simultaneously. C5a remained elevated across all time points, with the peak at 5–7 days. Studied elements of complement coalesced around three clusters: #0 (↑↑↑C5a, ↑↑TCC, ↓↓ApoE), #1 ↑C5a, ↑TCC, ↑↑↑FH); #2 (↑C5a, ↑TCC, ↑FH, ↑↑↑ApoE). The decline in FH and ApoE was a predictor of death, while TCC and C5a correlated with patient length of stay, APACHE, and CRP. Increased levels of C5a (Δ = 122.64; p = 0.0294; data not shown) and diminished levels of FH (Δ = 836,969; p = 0.0285; data not shown) co-existed with CVA incidence. C5a correlated storngly with blood RAGE and HMGB1, but not with viral load and immunological responsiveness. Remdesivir positively affected FH preservation, while convalescent plasma treatment elevated C5a levels. Three clusters of complement activation demonstrated a various milieu of ApoE & FH vs C5a & TCC in COVID-19 patients. Complement activation is linked to increased necrosis markers but not to viral burden or immune system response.
Discovery of anti-Formin-like 1 protein (FMNL1) antibodies in membranous nephropathy and other glomerular diseases
Authors: Bruschi Maurizio , Cavalli Andrea , Moll Solange , Candiano Giovanni , Scapozza Leonardo , Patel Jigar J. , Tan John C. , Lo Ken C. , Angeletti Andrea , Ghiggeri Gian Marco , Prunotto Marco
Published: August 2022

Evidence has shown that podocyte-directed autoantibodies can cause membranous nephropathy (MN). In the present work we investigated sera of MN patients using a high-density peptide array covering the whole coding sequences of the human genome encompassing 7,499,126 tiled peptides. A panel of 21 proteins reactive to MN sera were identified. We focused our attention on Formin-like 1 (FMNL1), a protein expressed by macrophages in MN patients tissues. High levels of anti-FMNL1 IgG4 were demonstrated in sera of MN patients with an orthogonal methodology (ELISA) contemporary demonstrating FMNL1 positive cells in kidney co-staining with CD68 in glomeruli. High levels of circulating anti-FMNL1 IgG4 were associated with lack of remission of proteinuria, potentially indicating that autoantibodies directed against cells other than podocytes, involved in tissue repair, might play a role in MN disease progression. High serum levels of anti-FMNL1 IgGs were also observed in other non-autoimmune glomerolonephrites, i.e. idiopathic and genetic FSGS, IgAGN. These findings are suggestive of a broader role of those autoantibodies in other glomerular disease conditions.
A 13-gene signature to predict the prognosis and immunotherapy responses of lung squamous cell carcinoma
Authors: Yang Qin , Gong Han , Liu Jing , Ye Mao , Zou Wen , Li Hui
Published: August 2022

Lung squamous cell carcinoma (LUSC) comprises 20–30% of all lung cancers. Immunotherapy has significantly improved the prognosis of LUSC patients; however, only a small subset of patients responds to the treatment. Therefore, we aimed to develop a novel multi-gene signature associated with the immune phenotype of the tumor microenvironment for LUSC prognosis prediction. We stratified the LUSC patients from The Cancer Genome Atlas dataset into hot and cold tumor according to a combination of infiltration status of immune cells and PD-L1 expression level. Kaplan–Meier analysis showed that hot tumors were associated with shorter overall survival (OS). Enrichment analyses of differentially expressed genes (DEGs) between the hot and cold tumors suggested that hot tumors potentially have a higher immune response ratio to immunotherapy than cold tumors. Subsequently, hub genes based on the DEGs were identified and protein–protein interactions were constructed. Finally, we established an immune-related 13-gene signature based on the hub genes using the least absolute shrinkage and selection operator feature selection and multivariate cox regression analysis. This gene signature divided LUSC patients into high-risk and low-risk groups and the former inclined worse OS than the latter. Multivariate cox proportional hazard regression analysis showed that the risk model constructed by the 13 prognostic genes was an independent risk factor for prognosis. Receiver operating characteristic curve analysis showed a moderate predictive accuracy for 1-, 3- and 5-year OS. The 13-gene signature also performed well in four external cohorts (three LUSC and one melanoma cohorts) from Gene Expression Omnibus. Overall, in this study, we established a reliable immune-related 13-gene signature that can stratify and predict the prognosis of LUSC patients, which might serve clinical use of immunotherapy.
Intense isolated attosecond pulses from two-color few-cycle laser driven relativistic surface plasma
Authors: Mondal Sudipta , Shirozhan Mojtaba , Choudhary Shivani , Nelissen Kwinten , Tzallas Paraskevas , Charalambidis Dimitris , Varjú Katalin , Kahaly Subhendu
Published: August 2022

Ultrafast plasma dynamics play a pivotal role in the relativistic high harmonic generation, a phenomenon that can give rise to intense light fields of attosecond duration. Controlling such plasma dynamics holds key to optimize the relevant sub-cycle processes in the high-intensity regime. Here, we demonstrate that the optimal coherent combination of two intense ultrashort pulses centered at two-colors (fundamental frequency, $$\omega$$
ω
and second harmonic, $$2\omega$$

2
ω

) can lead to an optimal shape in relativistic intensity driver field that yields such an extraordinarily sensitive control. Conducting a series of two-dimensional (2D) relativistic particle-in-cell (PIC) simulations carried out for currently achievable laser parameters and realistic experimental conditions, we demonstrate that an appropriate combination of $$\omega -2\omega$$

ω
-
2
ω

along with a precise delay control can lead to more than three times enhancement in the resulting high harmonic flux. Finally, the two-color multi-cycle field synthesized with appropriate delay and polarization can all-optically suppress several attosecond bursts while favourably allowing one burst to occur, leading to the generation of intense isolated attosecond pulses without the need of any sophisticated gating techniques.
Pseudoprogression and peritumoral edema due to intratumoral necrosis after Gamma knife radiosurgery for meningioma
Authors: Jung In-Ho , Chang Kyung Won , Park So Hee , Jung Hyun Ho , Chang Jong Hee , Chang Jin Woo , Chang Won Seok
Published: August 2022

Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant. After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p = 0.009) greater. When a 70% dose volume ≥ 1 cc was used, the possibility of ITN was 5.892-fold (p < 0.001) higher. On average, meningiomas with ITN increased in volume by 128.5% at 6 months after GKRS and then decreased to 94.6% at 12 months. When performing GKRS in meningioma, a 70% dose volume ≥ 1 cc is a risk factor for ITN. At 6 months after GKRS, meningiomas with ITN may experience a transient volume expansion and PTE, which are characteristics of pseudoprogression. These characteristics typically improve at 12 months following GKRS.
The mitochondrial genome and phylogenetic analysis of Rhacophorus rhodopus
Authors: Chen Wei , Qin Haifen , Zhao Zhenkun , Liao Jiahong , Chen Hongzhou , Jiang Lichun , Dayananda Buddhi
Published: August 2022

Classification of the genusRhacophorushas been problematic. In particular there has been considerable controversy surrounding the phylogenetic relationships amongRhacophorus rhodopus,R. bipunctatus,andR. reinwardtii. To examine the relationship among theseRhacophorusspecies, we assembled the complete mitochondrial genome sequence ofR. rhodopus. TheR. rhodopusgenome is 15,789 bp in length with 12 protein-coding genes (PCGs) (losing ND5), two ribosomal genes, 22 transfer RNA genes, and a control region (D-loop). Base composition of the overall sequence was 60.86% for A + T content and 39.14% for C + G content. Most of the PCGs used ATG as a start codon, except for the COX I gene, which used the ATA start codon. COX I and ND6 used AGG and ATP8 stop codons respectively, while ND3 and ND4L used the TAA stop codon. For the remaining seven genes, the stop codons was incomplete. In addition, both 5' and 3' of the control areas had distinct repeating regions. Based on three datasets and two methods (Bayesian inference (BI) and maximum likelihood (ML)), we reconstructed three phylogenetic trees to explore the taxonomic status of the species and the phylogenetic relationship amongR. rhodopus,R. bipunctatusandR. reinwardtii. Our results indicated that these three species are non-monophyletic; thus, the phylogenetic relationship among them is complex and difficult to determine. Further,R. rhodopusis divided into three lineages from different parts of China. The twoRhacophorussamples showed very close phylogenetic relationship withR. rhodopus. Our results add to the mitochondrial genome database of amphibians and will help to disentangle the phylogenetic relationships within the Rhacophoridae.
Catheter-related bloodstream infections in infants hospitalized in neonatal intensive care units: a single center study
Authors: Kochanowicz Julian F. , Nowicka Agnieszka , Al-Saad Salwan R. , Karbowski Lukasz M. , Gadzinowski Janusz , Szpecht Dawid
Published: August 2022

Sepsis in neonates carries a high morbidity and mortality rate and is among the most feared complications in the neonatal intensive care unit (NICU). Catheter-related bloodstream infections (CRBSI) are a common etiology of late-onset sepsis. The aim of this study was to compare risk factors and characteristics between patients according to the type of catheter that was utilized and according to birth weight classification. The study included 51 newborns with confirmed CRBSI, which were hospitalized in our level 3 NICU between January 2017 and December 2018. The study population was stratified according to the type of venous catheter utilized (peripherally inserted central catheter, central venous catheter (CVC), and peripheral venous catheter). Infants with low birth weight and those who required prolonged parenteral nutrition were most likely to develop CRBSI in our study group. The type of venous catheter was not associated with blood culture results. Also, infants with a birth weight of < 1500 g and > 1500 g did not differ in sepsis etiology. Further research is required to assess venous catheters relative risk of causing sepsis and if the outcome can be traced back specifically to catheter type or patient characteristics.
Red blood cell distribution width is associated with increased interactions of blood cells with vascular wall
Authors: Ananthaseshan Sharan , Bojakowski Krzysztof , Sacharczuk Mariusz , Poznanski Piotr , Skiba Dominik S. , Prahl Wittberg Lisa , McKenzie Jordan , Szkulmowska Anna , Berg Niclas , Andziak Piotr , Menkens Hanna , Wojtkowski Maciej , Religa Dorota , Lundell Fredrik , Guzik Tomasz , Gaciong Zbigniew , Religa Piotr
Published: August 2022

The mechanism underlying the association between elevated red cell distribution width (RDW) and poor prognosis in variety of diseases is unknown although many researchers consider RDW a marker of inflammation. We hypothesized that RDW directly affects intravascular hemodynamics, interactions between circulating cells and vessel wall, inducing local changes predisposing to atherothrombosis. We applied different human and animal models to verify our hypothesis. Carotid plaques harvested from patients with high RDW had increased expression of genes and proteins associated with accelerated atherosclerosis as compared to subjects with low RDW. In microfluidic channels samples of blood from high RDW subjects showed flow pattern facilitating direct interaction with vessel wall. Flow pattern was also dependent on RDW value in mouse carotid arteries analyzed with Magnetic Resonance Imaging. In different mouse models of elevated RDW accelerated development of atherosclerotic lesions in aortas was observed. Therefore, comprehensive biological, fluid physics and optics studies showed that variation of red blood cells size measured by RDW results in increased interactions between vascular wall and circulating morphotic elements which contribute to vascular pathology.
Water quality assessment of Lugu Lake based on Nemerow pollution index method
Authors: Su Kai , Wang Qin , Li Linxiao , Cao Rong , Xi Yingwei
Published: August 2022

In this paper, three monitoring sections were set up in Lugu Lake, and water samples were collected in 2019, 2020, and 2021 for the determination of physical and chemical properties such as permanganate index, chemical oxygen demand, biochemical oxygen demand (BOD5) and so on. By using the single factor pollution index method and the Nemerow pollution index method, the water quality of three monitoring sections and the whole Lugu Lake was assessed, and the temporal and spatial changes of water quality were analyzed. The findings demonstrate that Lugu Lake's overall water quality is excellent, and that it has not altered significantly in three years.The results of evaluating the water quality by the single factor pollution index method show that, in the past three years, the water quality of the three monitoring sections and the whole of Lugu Lake is Category I, which belongs to no pollution, and the measured indicators all meet the water quality standard of Category I. It can be seen from the evaluation results of the Nemerow index method that the water quality pollution index of Lugu Lake is between 0.22 and 0.34 in the past three years and the water quality evaluation of Changdao Bay, Lake center, Zhaojia Bay and the whole are Category I standards in 2019, 2020 and 2021. In terms of time changes, the water quality of Lugu Lake has remained stable between 2019 and 2021, and the water quality has been good. From the perspective of spatial changes, in 2019 and 2020, the water quality in Lake center is better than the monitoring sections of Changdao Bay and Zhaojia Bay.
Biological evaluation, molecular modeling and dynamics simulation of phenanthrenes isolated from Bletilla striata as butyrylcholinesterase inhibitors
Authors: Liu Yi , Tu Yanbei , Kang Yunyao , Zhu Chao , Wu Chuanhai , Chen Gang , Liu Zerong , Li Yanfang
Published: August 2022

As part of our continuous studies on natural cholinesterase inhibitors from plant kingdom, the 95% ethanol extract from tubers of Bletillastriata showed promising butyrylcholinesterase (BChE) inhibition (IC50 = 8.6 μg/mL). The extracts with different polarities (petroleum ether, ethyl acetate, n-butanol, and water) were prepared and evaluated for their inhibition of cholinesterases. The most active ethyl acetate extract was subjected to a bioassay-guided isolation and afforded twenty-two bibenzyls and phenanthrenes (1–22). All isolates were further evaluated for their BChE inhibition activity, and five phenanthrenes presented promising capacity (IC50 < 10 μM). Further kinetic studies indicated their modes of inhibition. Compounds 6, 8, and 14 were found to be mixed-type inhibitors, while compounds 10 and 12 could be classified as non-competitive inhibitors. The potential interaction mechanism of them with BChE was demonstrated by molecular docking and molecular dynamics simulation, showing that they could interact with catalytic active site and peripheral anionic site of BChE. These natural phenanthrenes provide new scaffold for the further design and optimization, with the aim to discover new selective BChE inhibitors for the treatment of AD.
Efflux dynamics of the antiseizure drug, levetiracetam, through the P-glycoprotein channel revealed by advanced comparative molecular simulations
Authors: Behmard Esmaeil , Barzegari Ebrahim , Najafipour Sohrab , Kouhpayeh Amin , Ghasemi Younes , Asadi-Pooya Ali A.
Published: August 2022

Understanding the precise mechanistic details of the possible binding and transport of antiseizure medications (ASMs) through the P-glycoprotein (P-gp) efflux pump is essential to find strategies for the treatment of patients with epilepsy resistant to ASMs. In the present work, conventional molecular dynamics, binding free energy calculations, steered molecular dynamics and umbrella sampling were applied to study the interactions of levetiracetam and brivaracetam with P-gp and their possible egress path from the binding site. Comparative results for the control drugs, zosuquidar and verapamil, confirmed their established P-gp inhibitory activity. Brivaracetam, a non-substrate of P-gp, demonstrated stronger static and dynamic interactions with the exporter protein, than levetiracetam. The potential of mean force calculations indicated that the energy barriers through the ligand export were the lowest for levetiracetam, suggesting the drug as a P-gp substrate with facile passage through the transporter channel. Our findings also stressed the contribution of nonpolar interactions with P-gp channel lining as well as with membrane lipid molecules to hamper the ASM efflux by the transmembrane exporter. Appropriate structural engineering of the ASMs is thus recommended to address drug-resistant epilepsy.