bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying and minimising the impact of fake visual media: Current and future directions
Authors: Nightingale Sophie J. , Wade Kimberley A.
Published: October 2022

Over the past two decades, society has seen incredible advances in digital technology, resulting in the wide availability of cheap and easy-to-use software for creating highly sophisticated fake visual content. This democratisation of creating such content, paired with the ease of sharing it via social media, means that ill-intended fake images and videos pose a significant threat to society. To minimise this threat, it is necessary to be able to distinguish between real and fake content; to date, however, human perceptual research indicates that people have an extremely limited ability to do so. Generally, computational techniques fair better in these tasks, yet remain imperfect. What's more, this challenge is best considered as an arms race – as scientists improve detection techniques, fraudsters find novel ways to deceive. We believe that it is crucial to continue to raise awareness of the visual forgeries afforded by new technology and to examine both human and computational ability to sort the real from the fake. In this article, we outline three considerations for how society deals with future technological developments that aim to help secure the benefits of that technology while minimising its possible threats. We hope these considerations will encourage interdisciplinary discussion and collaboration that ultimately goes some way to limit the proliferation of harmful content and help to restore trust online.
Failing to Fight for the “Russian World”: Pre-War Social Origins of the Pro-Russian Secessionist Organizations in Ukraine
Authors: Laryš Martin
Published: October 2022

The existing literature explains the war in Donbas and the rationale for why conflict broke out there while failing to do so in other Ukrainian provinces, such as Odesa or Kharkiv. Local pro-Russian organizations could not attract considerable attention and support in the pre-war period in all parts of Ukraine, except for Crimea. The social marginalization and negligible influence of the pro-Russian organizations among the locals presumably stemmed from their weak social ties among the local population. The question is why they had such weak social embeddedness in the local societies despite relatively popular pro-Russian sympathies in these regions? Surprisingly, nobody has sought to explain the social origins of the pro-Russian movements as a source of their weakness and failure to be sparked by the anti-Ukrainian rebellion in 2014.
Development of a micro air vehicle
Authors: Watkins S.
Published: October 2022

The aerodynamic characteristics of five planar flying wing plan-forms suitable for micro air vehicles (MAVs) are investigated via a series of wind-tunnel tests. The external boundary of the five plan-forms result from slender carbon fibre (CF) struts under various degrees of buckling. The maximum lift/drag ratios were similar for all the (quite different) shapes but the stall characteristics were found to be markedly different. Results are presented of cross-plane traverses detailing the wake vector field and turbulence characteristics for two of the planforms at conditions close to stall. A MAV, based on mylar-covered buckled CF struts, is described. The MAV utilises elevon control based on modified commercially available micro radio control systems.
Residential Integration on Fair Terms for the Disadvantaged
Authors: Kim Hwa Young , Walton Andrew
Published: October 2022

This article contributes to normative debates about residential segregation and its relationship to inequality. It defends a position often disregarded in literature: that there is merit to advancing residential integration through some scenarios where advantaged individuals move to disadvantaged areas. It develops this case in dialogue with three other views. In relation to advocates of addressing the inequalities of residential segregation through redistribution, it defends integration as a means of tackling social and political factors that sustain injustice. It challenges those who defend relocating disadvantaged individuals to advantaged areas by highlighting the burdens and demand for cultural assimilation this imposes on the disadvantaged. It considers the worry that advantaged individuals relocating to disadvantaged areas harbours the problematic features of gentrification. It responds that these concerns, while important in some cases, do not arise in all scenarios of this kind.
DEFICIENT BY DESIGN? THE TRANSNATIONAL ENFORCEMENT OF THE GDPR
Authors: Gentile Giulia , Lynskey Orla
Published: October 2022

Four years following the entry into force of the EU data protection framework (the GDPR) serious questions remain regarding its enforcement, particularly in transnational contexts. While this transnational under-enforcement is often attributed to the role of key national authorities in the GDPR's procedures, this article identifies more systemic flaws. It examines whether the GDPR procedures are deficient-by-design and, if not, how these flaws might be addressed. The conclusions reached inform our understanding of how to secure effective protection of the EU Charter right to data protection. They are also of significance to EU law enforcement more generally given the increasing prevalence of composite decision-making as the mechanism of choice to administer EU law.
THE DEFINITION OF APARTHEID IN CUSTOMARY INTERNATIONAL LAW AND THE INTERNATIONAL CONVENTION ON THE ELIMINATION OF ALL FORMS OF RACIAL DISCRIMINATION
Authors: Jackson Miles
Published: October 2022

Despite recent and increasing attention to the wrong of apartheid in international politics, some basic definitional questions remain uncertain. This article seeks to delineate the definition of apartheid in international law. Its focus is on the prohibition of apartheid binding States in custom and the obligation in Article 3 of the International Convention on the Elimination of All Forms of Racial Discrimination. In both cases, the article shows that the Apartheid Convention of 1973 supplies the wrong's definition. Thereafter, the article addresses three key elements that will be central to determining an allegation of apartheid: its wrongful acts, its distinctive purpose requirement, and the issue of what constitutes a ‘racial group’. Finally, the article also draws attention to the wider importance of the prohibition of apartheid in the international legal system. International law marks with particular normative significance a set of practices entailing systematic and structural harms that need not involve violations of life or bodily integrity.
Quantifying relational nouns in corpora
Authors: GLASS LELIA
Published: October 2022

While relational nouns (cousin) are traditionally delineated in a binary and theory-dependent manner, this article approximates relationality as a continuous, objective corpus metric (Percent Possessive) – allowing for lexicon-wide exploration of which nouns are more or less relational and why. Comparing across nouns and accounting for the ontological class of the noun's referent (focusing on nouns denoting artifacts, natural kinds, occupations, humans and locations), I find that Percent Possessive is positively correlated with a noun's per-million-word frequency. Comparing across different web communities, I find that a noun is more frequent, and shows a greater ratio of definite to indefinite tokens, in the community where its Percent Possessive is significantly higher. I take these findings to be consistent with the claim that a noun is more easily interpreted as relational (as measured by Percent Possessive) when human interaction with its referent is more conventional (as measured by its frequency and definite-to-indefinite ratio). Inspired by the many authors who have suggested a socio-cultural component to relationality and possession, this article explores at scale in English how nouns reflect the conventions of the people who use them.
Design of a flower shaped compact printed antenna for ultra-wideband communication
Authors: Golait Manohar , Gaikwad Mahendra , Patil Balasaheb H. , Varun Yadav Manish , Baudha Sudeep , Kumar Bramhane Lokesh
Published: October 2022

In this communication, a compact flower shaped printed antenna for ultra-wideband communication is proposed. The “flower-shaped” structure is capable of transmitting UWB-band signals. The designed antenna exhibits a return loss ranging from 2.3 to 11 GHz with an 8.7 GHz central frequency and has 130% relative bandwidth. The suggested design includes a patch in the shape of a flower with several slots fed by a microstrip line. Multiple slots have been designed for better resonances at lower modes. The antenna is constructed with an FR4 substrate, and a 50 Ω A-type connector feeds it. The optimum dimensions of the designed antenna are 12 × 16 × 1.6 cubic-millimeters and 0.092λ × .12λ × 0.012λ in lambda. The proposed structure also demonstrates stable radiation patterns across the operating bandwidth. The proposed radiator has a high gain of 2.67 dBi, and an efficiency of 85%. It is compact, lightweight, and easy to make. Therefore, it can be used for UWB applications.
Provenance Analysis of the Andrée Land Basin and Implications for the Paleogeography of Svalbard in the Devonian
Authors: Anfinson Owen A. , Odlum Margo L. , Piepjohn Karsten , Poulaki Eirini M. , Shephard Grace E. , Stockli Daniel F. , Levang Devin , Jensen Maria A. , Pavlovskaia Elena A.
Published: October 2022

During the Devonian, the Svalbard Archipelago lay at low latitudes, occupying a paleogeographic position at the intersection of Caledonian and Ellesmerian orogens. Provenance analysis, including detrital zircon U‐Pb age studies, of Devonian (ca. 420–360 Ma) strata from the Andrée Land Basin, Svalbard, help reconstruct sediment sources to understand the assembly of the three basement provinces that make up Svalbard, which are presently separated by Devonian sedimentary basins and(or) faults with syn‐to post‐Devonian displacement. The studied Andrée Land Group strata, which are part of the North Atlantic's Old Red Sandstone, consist of the Early Devonian Wood Bay Formation and Middle to Late Devonian Mimerdalen subgroup. Paleocurrent indicators from Lower to lower‐Middle Devonian strata record north‐directed sediment transport. Detrital zircon U‐Pb ages indicate a prominent “Caledonian” signal and include sources from Svalbard's Northwestern and(or) Southwestern basement provinces. In Middle and Upper Devonian strata, paleocurrents and detrital zircon ages record a shift to a predominantly eastern‐northeastern provenance, likely from the uplifting Ny‐Friesland block along the Billefjorden Fault Zone. Late Ediacaran‐early Cambrian detrital zircons in the uppermost Planteryggen Formation (Frasnian) indicate extrabasinal sources possibly associated with the Timanian orogen of Northern Baltica. The combined provenance data suggest Svalbard may have already been assembled, similar to the modern block, with the Andrée Land Basin located between modern exposures of the Southwestern/Northwestern and the Northeastern basement provinces. Comparison of detrital zircon ages from Andrée Land Group strata with those from other circum Arctic Devonian strata provides constraints on Svalbard's paleogeographic position in the Devonian.
A predictive ensemble classifier for the gene expression diagnosis of ASD at ages 1 to 4 years
Authors: Bao Bokan , Zahiri Javad , Gazestani Vahid H. , Lopez Linda , Xiao Yaqiong , Kim Raphael , Wen Teresa H. , Chiang Austin W. T. , Nalabolu Srinivasa , Pierce Karen , Robasky Kimberly , Wang Tianyun , Hoekzema Kendra , Eichler Evan E. , Lewis Nathan E. , Courchesne Eric
Published: October 2022

Autism Spectrum Disorder (ASD) diagnosis remains behavior-based and the median age of diagnosis is ~52 months, nearly 5 years after its first-trimester origin. Accurate and clinically-translatable early-age diagnostics do not exist due to ASD genetic and clinical heterogeneity. Here we collected clinical, diagnostic, and leukocyte RNA data from 240 ASD and typically developing (TD) toddlers (175 toddlers for training and 65 for test). To identify gene expression ASD diagnostic classifiers, we developed 42,840 models composed of 3570 gene expression feature selection sets and 12 classification methods. We found that 742 models had AUC-ROC ≥ 0.8 on both Training and Test sets. Weighted Bayesian model averaging of these 742 models yielded an ensemble classifier model with accurate performance in Training and Test gene expression datasets with ASD diagnostic classification AUC-ROC scores of 85–89% and AUC-PR scores of 84–92%. ASD toddlers with ensemble scores above and below the overall ASD ensemble mean of 0.723 (on a scale of 0 to 1) had similar diagnostic and psychometric scores, but those below this ASD ensemble mean had more prenatal risk events than TD toddlers. Ensemble model feature genes were involved in cell cycle, inflammation/immune response, transcriptional gene regulation, cytokine response, and PI3K-AKT, RAS and Wnt signaling pathways. We additionally collected targeted DNA sequencing smMIPs data on a subset of ASD risk genes from 217 of the 240 ASD and TD toddlers. This DNA sequencing found about the same percentage of SFARI Level 1 and 2 ASD risk gene mutations in TD (12 of 105) as in ASD (13 of 112) toddlers, and classification based only on the presence of mutation in these risk genes performed at a chance level of 49%. By contrast, the leukocyte ensemble gene expression classifier correctly diagnostically classified 88% of TD and ASD toddlers with ASD risk gene mutations. Our ensemble ASD gene expression classifier is diagnostically predictive and replicable across different toddler ages, races, and ethnicities; out-performs a risk gene mutation classifier; and has potential for clinical translation.
High-fat diet induced cyclophilin B enhances STAT3/lncRNA-PVT1 feedforward loop and promotes growth and metastasis in colorectal cancer
Authors: Guo Hanqing , Zhuang Kun , Ding Ning , Hua Rui , Tang Hailing , Wu Yue , Yuan Zuyi , Li Ting , He Shuixiang
Published: October 2022

High-fat diet (HFD) has been implicated to promote colorectal cancer (CRC). Recently, oncogene Cyclophilin B (CypB) is reported to be induced by cholesterol. However, the role of CypB in CRC carcinogenesis and metastasis associated with HFD remains unknown. In the present study, we showed that HFD-induced CypB enhances proliferation and metastasis through an inflammation-driven circuit, including Signal Transducer and Activator of Transcription 3 (STAT3)-triggered transcription of lncRNA-PVT1, and its binding with CypB that promotes activation of STAT3. CypB was found to be upregulated in CRC, which was correlated with elevated body mass index and poor prognosis. HFD induced CypB expression and proinflammatory cytokines in colon of mice. Besides, CypB restoration facilitated growth, invasion and metastasis in CRC cells both in vitro and in vivo. Moreover, RIP sequencing data identified lncRNA-PVT1 as a functional binding partner of CypB. Mechanistically, PVT1 increased the phosphorylation and nuclear translocation of STAT3 in response to IL-6, through directly interaction with CypB, which impedes the binding of Suppressors Of Cytokine Signalling 3 (SOCS3) to STAT3. Furthermore, STAT3 in turn activated PVT1 transcription through binding to its promoter, forming a regulatory loop. Finally, this CypB/STAT3/PVT1 axis was verified in TCGA datasets and CRC tissue arrays. Our data revealed that CypB linked HFD and CRC malignancy by enhancing the CypB/STAT3/PVT1 feedforward axis and activation of STAT3.
Results from a phase 1, randomized, double-blind, multiple ascending dose study characterizing the pharmacokinetics and demonstrating the safety and selectivity of the aldosterone synthase inhibitor baxdrostat in healthy volunteers
Authors: Freeman Mason W. , Bond Mary , Murphy Brian , Hui James , Isaacsohn Jonathan
Published: October 2022

Baxdrostat is a selective inhibitor of aldosterone synthase designed for the treatment of disorders associated with elevated aldosterone. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of multiple ascending doses of baxdrostat in healthy volunteers. Subjects were randomized to receive oral baxdrostat (0.5, 1.5, 2.5, or 5.0 mg) or placebo once daily for 10 days and were placed on either a low-salt or normal-salt diet for the duration of the study. Blood samples were collected before and after dosing on days 1 and 10 to characterize pharmacokinetics and pharmacodynamics. Safety was assessed by adverse events, physical examinations, electrocardiograms, orthostatic vital signs, and clinical laboratory evaluations. Fifty-four subjects completed the study. There were no deaths or serious adverse events, and all treatment-emergent adverse events in subjects receiving baxdrostat were mild in severity. Plasma levels of baxdrostat increased proportionally with ascending doses, with peak concentrations observed within 4 h after dosing and a mean half-life of 26 to 31 h. A dose-dependent reduction of plasma aldosterone occurred with baxdrostat doses ≥1.5 mg, regardless of diet. Decreases in plasma aldosterone were sustained, with levels reduced by approximately 51 to 73% on day 10. Baxdrostat had no meaningful impact on plasma cortisol levels and resulted in mild dose-dependent decreases in plasma sodium levels and increases in potassium levels. Baxdrostat was safe and well tolerated with a half-life that supports once-daily dosing. The dose-dependent reduction in plasma aldosterone and lack of effect on cortisol demonstrate the selective blockade of aldosterone synthase.
Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity
Authors: Lashuel Hilal A. , Mahul-Mellier Anne-Laure , Novello Salvatore , Hegde Ramanath Narayana , Jasiqi Yllza , Altay Melek Firat , Donzelli Sonia , DeGuire Sean M. , Burai Ritwik , Magalhães Pedro , Chiki Anass , Ricci Jonathan , Boussouf Manel , Sadek Ahmed , Stoops Erik , Iseli Christian , Guex Nicolas
Published: October 2022

Antibodies against phosphorylated alpha-synuclein (aSyn) at S129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson’s disease and other neurodegenerative diseases. Herein, we demonstrate that the co-occurrence of multiple pathology-associated C-terminal post-translational modifications (PTMs) (e.g., phosphorylation at Tyrosine 125 or truncation at residue 133 or 135) differentially influences the detection of pS129-aSyn species by pS129-aSyn antibodies. These observations prompted us to systematically reassess the specificity of the most commonly used pS129 antibodies against monomeric and aggregated forms of pS129-aSyn in mouse brain slices, primary neurons, mammalian cells and seeding models of aSyn pathology formation. We identified two antibodies that are insensitive to pS129 neighboring PTMs. Although most pS129 antibodies showed good performance in detecting aSyn aggregates in cells, neurons and mouse brain tissue containing abundant aSyn pathology, they also showed cross-reactivity towards other proteins and often detected non-specific low and high molecular weight bands in aSyn knock-out samples that could be easily mistaken for monomeric or high molecular weight aSyn species. Our observations suggest that not all pS129 antibodies capture the biochemical and morphological diversity of aSyn pathology, and all should be used with the appropriate protein standards and controls when investigating aSyn under physiological conditions. Finally, our work underscores the need for more pS129 antibodies that are not sensitive to neighboring PTMs and more thorough characterization and validation of existing and new antibodies.
Quantitative proteomic analysis of the microbial degradation of 3-aminobenzoic acid by Comamonas sp. QT12
Authors: Zhao Shuxue , Pan Chao , Zhao Junxing , Du Haiyan , Li Min , Yu Hao , Chen Xi
Published: October 2022

A mab cluster associated with 3-aminobenzoic acid (3AB) degradation was identified in Comamonas sp. QT12. However, the cellular response of Comamonas sp. QT12 to 3-aminobenzoic acid remains unclear. In this study, label-free quantitative proteome analysis based on LC–MS/MS was used to study the protein expression difference of strain QT12 under the condition of using 3AB (3AB) and citric acid/ammonium chloride as substrates (3ABCon). A total of 2068 proteins were identified, of which 239 were significantly up-regulated in 3AB group, 124 were significantly down-regulated in 3AB group, 624 were expressed only in 3AB group, and 216 were expressed only in 3ABCon group in 3AB group. KEGG pathway analysis found that 83 pathways were up-regulated and 49 pathways were down-regulated, In GO analysis, 315 paths were up-regulated and 156 paths were down-regulated. There were 6 genes in the mab cluster that were only detected in the 3AB group.The mab cluster was found to be related to degradation of 3AB. By knockout, it was found that the growth rate of the mutant △orf7 and △orf9 were slowed down. HPLC results showed that the mutant △orf7 and △orf9 could still degrade 3AB, it was found that orf7, orf9 were not key genes about 3AB degradation and they could be replaced by other genes in strain QT12. These findings improve our understanding of the molecular mechanisms underlying the cellular response of 3AB degradation in Comamonas bacterium.
An automatic hypothesis generation for plausible linkage between xanthium and diabetes
Authors: Syafiandini Arida Ferti , Song Gyuri , Ahn Yuri , Kim Heeyoung , Song Min
Published: October 2022

There has been a significant increase in text mining implementation for biomedical literature in recent years. Previous studies introduced the implementation of text mining and literature-based discovery to generate hypotheses of potential candidates for drug development. By conducting a hypothesis-generation step and using evidence from published journal articles or proceedings, previous studies have managed to reduce experimental time and costs. First, we applied the closed discovery approach from Swanson’s ABC model to collect publications related to 36 Xanthium compounds or diabetes. Second, we extracted biomedical entities and relations using a knowledge extraction engine, the Public Knowledge Discovery Engine for Java or PKDE4J. Third, we built a knowledge graph using the obtained bio entities and relations and then generated paths with Xanthium compounds as source nodes and diabetes as the target node. Lastly, we employed graph embeddings to rank each path and evaluated the results based on domain experts’ opinions and literature. Among 36 Xanthium compounds, 35 had direct paths to five diabetes-related nodes. We ranked 2,740,314 paths in total between 35 Xanthium compounds and three diabetes-related phrases: type 1 diabetes, type 2 diabetes, and diabetes mellitus. Based on the top five percentile paths, we concluded that adenosine, choline, beta-sitosterol, rhamnose, and scopoletin were potential candidates for diabetes drug development using natural products. Our framework for hypothesis generation employs a closed discovery from Swanson’s ABC model that has proven very helpful in discovering biological linkages between bio entities. The PKDE4J tools we used to capture bio entities from our document collection could label entities into five categories: genes, compounds, phenotypes, biological processes, and molecular functions. Using the BioPREP model, we managed to interpret the semantic relatedness between two nodes and provided paths containing valuable hypotheses. Lastly, using a graph-embedding algorithm in our path-ranking analysis, we exploited the semantic relatedness while preserving the graph structure properties.
Identification of a novel ceRNA network related to prognosis and immunity in HNSCC based on integrated bioinformatic investigation
Authors: Liu Hongbo , Hei Guoli , Zhang Lu , Jiang Yanxia , Lu Haijun
Published: October 2022

Head and neck squamous cell carcinoma (HNSCC) is characterized by an immunosuppression environment and necessitates the development of new immunotherapy response predictors. The study aimed to build a prognosis-related competing endogenous RNA (ceRNA) network based on immune-related genes (IRGs) and analyze its immunological signatures. Differentially expressed IRGs were identified by bioinformatics analysis with Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and ImmPort databases. Finally, via upstream prognosis-related microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) prediction and co-expression analysis, we built an immune-related ceRNA network (LINC00052/hsa-miR-148a-3p/PLAU) related to HNSCC patient prognosis. CIBERSORT analysis demonstrated that there were substantial differences in 11 infiltrating immune cells in HNSCC, and PLAU was closely correlated with 10 type cells, including T cells CD8+ (R =  − 0.329), T cells follicular helper (R = − 0.342) and macrophage M0 (R = 0.278). Methylation and Tumor Immune Dysfunction and Exclusion (TIDE) analyses revealed that PLAU upregulation was most likely caused by hypomethylation and that high PLAU expression may be associated with tumor immune evasion in HNSCC, respectively.
Automatic deep learning-based consolidation/collapse classification in lung ultrasound images for COVID-19 induced pneumonia
Authors: Durrani Nabeel , Vukovic Damjan , van der Burgt Jeroen , Antico Maria , van Sloun Ruud J. G. , Canty David , Steffens Marian , Wang Andrew , Royse Alistair , Royse Colin , Haji Kavi , Dowling Jason , Chetty Girija , Fontanarosa Davide
Published: October 2022

Our automated deep learning-based approach identifies consolidation/collapse in LUS images to aid in the identification of late stages of COVID-19 induced pneumonia, where consolidation/collapse is one of the possible associated pathologies. A common challenge in training such models is that annotating each frame of an ultrasound video requires high labelling effort. This effort in practice becomes prohibitive for large ultrasound datasets. To understand the impact of various degrees of labelling precision, we compare labelling strategies to train fully supervised models (frame-based method, higher labelling effort) and inaccurately supervised models (video-based methods, lower labelling effort), both of which yield binary predictions for LUS videos on a frame-by-frame level. We moreover introduce a novel sampled quaternary method which randomly samples only 10% of the LUS video frames and subsequently assigns (ordinal) categorical labels to all frames in the video based on the fraction of positively annotated samples. This method outperformed the inaccurately supervised video-based method and more surprisingly, the supervised frame-based approach with respect to metrics such as precision-recall area under curve (PR-AUC) and F1 score, despite being a form of inaccurate learning. We argue that our video-based method is more robust with respect to label noise and mitigates overfitting in a manner similar to label smoothing. The algorithm was trained using a ten-fold cross validation, which resulted in a PR-AUC score of 73% and an accuracy of 89%. While the efficacy of our classifier using the sampled quaternary method significantly lowers the labelling effort, it must be verified on a larger consolidation/collapse dataset, our proposed classifier using the sampled quaternary video-based method is clinically comparable with trained experts’ performance.
Contribution of CRISPRable DNA to human complex traits
Authors: Zhai Ranran , Zheng Chenqing , Yang Zhijian , Li Ting , Chen Jiantao , Shen Xia
Published: October 2022

CRISPR-Cas is a powerful genome editing tool for various species and human cell lines, widely used in many research areas including studying the mechanisms, targets, and gene therapies of human diseases. Recent developments have even allowed high-throughput genetic screening using the CRISPR system. However, due to the practical and ethical limitations in human gene editing research, little is known about whether CRISPR-editable DNA segments could influence human complex traits or diseases. Here, we investigated the human genomic regions condensed with different CRISPR Cas enzymes’ protospacer-adjacent motifs (PAMs). We found that Cas enzymes with GC-rich PAMs could interfere more with the genomic regions that harbor enriched heritability for human complex traits and diseases. The results linked GC content across the genome to the functional genomic elements in the heritability enrichment of human complex traits. We provide a genetic overview of the effects of high-throughput genome editing on human complex traits.
Bipolar cell targeted optogenetic gene therapy restores parallel retinal signaling and high-level vision in the degenerated retina
Authors: Kralik Jakub , van Wyk Michiel , Stocker Nino , Kleinlogel Sonja
Published: October 2022

Optogenetic gene therapies to restore vision are in clinical trials. Whilst current clinical approaches target the ganglion cells, the output neurons of the retina, new molecular tools enable efficient targeting of the first order retinal interneurons, the bipolar cells, with the potential to restore a higher quality of vision. Here we investigate retinal signaling and behavioral vision in blind mice treated with bipolar cell targeted optogenetic gene therapies. All tested tools, including medium-wave opsin, Opto-mGluR6, and two new melanopsin based chimeras restored visual acuity and contrast sensitivity. The best performing opsin was a melanopsin-mGluR6 chimera, which in some cases restored visual acuities and contrast sensitivities that match wild-type animals. Light responses from the ganglion cells were robust with diverse receptive-field types, inferring elaborate inner retinal signaling. Our results highlight the potential of bipolar cell targeted optogenetics to recover high-level vision in human patients with end-stage retinal degenerations.
Expression of divergent methyl/alkyl coenzyme M reductases from uncultured archaea
Authors: Shao Nana , Fan Yu , Chou Chau-Wen , Yavari Shadi , Williams Robert V. , Amster I. Jonathan , Brown Stuart M. , Drake Ian J. , Duin Evert C. , Whitman William B. , Liu Yuchen
Published: October 2022

Methanogens and anaerobic methane-oxidizing archaea (ANME) are important players in the global carbon cycle. Methyl-coenzyme M reductase (MCR) is a key enzyme in methane metabolism, catalyzing the last step in methanogenesis and the first step in anaerobic methane oxidation. Divergent mcr and mcr-like genes have recently been identified in uncultured archaeal lineages. However, the assembly and biochemistry of MCRs from uncultured archaea remain largely unknown. Here we present an approach to study MCRs from uncultured archaea by heterologous expression in a methanogen, Methanococcus maripaludis. Promoter, operon structure, and temperature were important determinants for MCR production. Both recombinant methanococcal and ANME-2 MCR assembled with the host MCR forming hybrid complexes, whereas tested ANME-1 MCR and ethyl-coenzyme M reductase only formed homogenous complexes. Together with structural modeling, this suggests that ANME-2 and methanogen MCRs are structurally similar and their reaction directions are likely regulated by thermodynamics rather than intrinsic structural differences.
Stronger adaptive response among small-scale fishers experiencing greater climate change hazard exposure
Authors: Ilosvay Xochitl Édua Elías , Molinos Jorge García , Ojea Elena
Published: October 2022

Progressive climate-driven environmental changes are threatening the global livelihoods of small-scale fishers, yet how their adaptation responses vary in relation to hazard exposure is poorly understood. We use a systematic review approach to identify a global data set of 301 reported adaptation responses (remaining, adaptive, and transformative) of small-scale fishers to climate change and analyse their spatial agreement with estimated geographical location of global coastal hotspot areas for specific climate change hazards associated to those responses (long-term trends in sea surface temperature, cumulative intensity of marine heatwaves, frequency of tropical storms, and intensity of associated storm surges). Only 37% of responses were found in climate change hotspots. Despite this, our results evidence that fishers are responding more passively in areas with lower exposure levels to abrupt climatic events. The relative proportion of adaptive and transformative responses increase with climate change hazard exposure.
Detection of lipid efflux from foam cell models using a label-free infrared method
Authors: Xie Bowen , Njoroge Wanjiku , Dowling Lewis M. , Sulé-Suso Josep , Cinque Gianfelice , Yang Ying
Published: October 2022

Synchrotron-based microFTIR spectroscopy was used to study the process of lipid efflux in a foam cell model. The anti-atherosclerotic drug, atorvastatin, removed low-density lipoprotein from the foam cells in a dose, and time dependent manner.
A new synthesis approach of hierarchical MoS2 nanoflakes toward hydrogen evolution in both acidic and alkaline media
Authors: Liu Changhai , Min Shengkang , Yao Yanhua , Shakouri Mohsen , Zhang Lei , Hu Yongfeng , Chen Zhidong
Published: October 2022

Ultrathin MoS2 flakes were prepared using a synergistic liquid phase precipitation method by applying ultrasound and microwaves simultaneously for a highly efficient HER under both alkaline and acidic conditions.
Electro-oxidation induced O–S cross-coupling of quinoxalinones with sodium sulfinates for synthesizing 2-sulfonyloxylated quinoxalines
Authors: Shi Shi-Hui , Wei Jian , Liang Chun-Miao , Bai Huan , Zhu Hai-Tao , Zhang Yantu , Fu Feng
Published: October 2022

The novel C2–O sulfonylation of quinoxalinones via electro-oxidation induced O–S coupling strategy under mild conditions was reported.
Stabilizing large pores in a flexible metal–organic framework via chemical cross-linking
Authors: Rollins Devin S. , Geary Jackson , Wong Andy H. , Xiao Dianne J.
Published: October 2022

Chemical cross-linking stabilizes the open form of a flexible aluminum metal–organic framework with large 17 Å pores.
Highly reversible aqueous zinc-ion battery using the chelating agent triethanolamine as an electrolyte additive
Authors: Lin Yunhui , Hu Youzuo , Zhang Shu , Xu Ziqiang , Feng Tingting , Zhou Haiping , Wu Mengqiang
Published: October 2022

The chelating agent triethanolamine (TEA) is introduced as an additive in the electrolyte to enhance the cycling stability of aqueous zinc-ion batteries.
Constructing an Al2O3/(NH4)2V4O9 heterostructure as a cathode material for high performance aqueous rechargeable zinc ion batteries
Authors: Zhang Lu , Hou Lihua , Sheng Rui , Li Di , Gu Yuanxiang , Wang Lei
Published: October 2022

The presence of an appropriate amount of Al2O3 makes NH4V4O10 change into a mixture of NH4V4O9 and Zn3(OH)2V2O7·2H2O to act as an active cathode for high capacity aqueous zinc ion batteries during the cycling process.
Energy autonomous paper modules and functional circuits
Authors: Han Jing , Xu Nuo , Yu Jinran , Wang Yifei , Xiong Yao , Wei Yichen , Wang Zhong Lin , Sun Qijun
Published: October 2022

A prototype of energy autonomous paper modules is proposed by integrating triboelectric energy harvester, power management circuits, energy storage units, and functional circuits, which presents new paradigm for sustainable, adaptive, and customized integrative electronics.
Rapid prototyping of functional acoustic devices using laser manufacturing
Authors: Zhang Xiang , Son Rosa , Lin Yen-Ju , Gill Alexi , Chen Shilin , Qi Tong , Choi David , Wen Jing , Lu Yunfeng , Lin Neil Y. C. , Chiou Pei-Yu
Published: October 2022

We present a simple method for manufacturing a functional acoustic device for biomanipulation. This method utilizes laser cutting to achieve high efficiency for rapid prototyping.
Directly visualizing mitochondrial shrinkage and lysosomal expansion during mitophagy using super-resolution microscopy
Authors: Anjum Farhan , Rao Chethana , Yadav Aditya , Kaushik Kush , Mishra Pushpendra Mani , Nandi Chayan Kanti
Published: October 2022

Mitochondria–lysosome contact (MLC) is an essential process for degradation of damaged mitochondria and clearance of these malfunctioned mitochondria is crucial to keep the cell healthy.
Evaluation of novel HIV-1 protease inhibitors with DRV-resistance by utilizing 3D-QSAR molecular docking and molecular dynamics simulation
Authors: Zhang Yan-Jun , Chen Lu , Xu Jie , Jiang Hui-Fang , Zhu Yi-Ren , Wang Zhong-Hua , Xiong Fei
Published: October 2022

Molecular dynamics simulations were performed to explore the interaction mode of DRV derivatives binding to target proteins and to identify new potential HIV-1 PR inhibitors with stronger activity.
Impulsively generated two-fluid magnetoacoustic-gravity waves: Solar chromosphere heating and plasma outflows
Authors: Niedziela R. , Murawski K. , Kadowaki L. , Zaqarashvili T. , Poedts S.
Published: October 2022

Context. We use a two-fluid model to study the heating of the solar chromosphere by magnetoacoustic and magnetoacoustic-gravity waves. In the model, we include energy dissipation as a result of ion–neutral collisions.

Aims. The aim of this paper is to study impulsively generated two-fluid magnetoacoustic and magnetoacoustic-gravity waves and to quantify their contribution to chromosphere heating and the generation of plasma outflows.

Methods. We consider a 2D model of the gravitationally stratified and partially ionized solar atmosphere that is permeated by a vertical magnetic field. To describe the dynamics of the atmosphere, we use a set of two-fluid equations which we solve numerically with the use of the JOANNA code.

Results. We show that large-amplitude impulsively generated magnetoacoustic-gravity waves can efficiently heat the chromosphere and generate plasma outflows in the low solar corona. The chromosphere is heated by ion–neutral collisions, which are most effective at the top of this atmospheric layer. Wider and larger amplitude pulses heat the atmosphere more effectively and generate faster plasma outflows.

Conclusions. Large-amplitude, impulsively generated two-fluid magnetoacoustic-gravity waves have the potential to contribute to the solar chromosphere heating and plasma outflows in the low corona.
The Application of 2-Naphthols in Asymmetric Synthesis of Atropisomers
Authors: Xiang Shao-Hua , Cheng Jun Kee , Tan Bin
Published: October 2022

The venerable axially chiral biaryl skeletons used widely in asymmetric catalysis such as BINOLs, NOBINs, QUINOLs, and CPAs possess a 2-naphthol moiety or are derived from the naphthol precursor. The hydroxy functionality offers the interaction point or serves as functional handle for synthetic elaboration. This prevalence and significance drive our studies to incorporate this nucleophile class to fabricate an assortment of atropisomers. By activating the reacting partners via distinctive mechanisms, the arylation of quinones, azo- or nitroso-naphthalenes, VQM intermediates, 1,2,4-triazole-3,5-diones, isoquinolines, and 1-bromo-2-naphthols with 2-naphthols were successfully attained. A concise account of these developments is provided in this article.

1 Introduction

2 Asymmetric Arylation with Quinones

3 Asymmetric Arylation with Electron-Deficient Arenes

4 Asymmetric Synthesis of Atropisomers with other Electrophiles

5 Conclusion
Prevalence of Dyslipidemia among School-Age Children and Adolescents in Addis Ababa, Ethiopia
Authors: Mohammed Ousman , Kassaw Melkitu , G/Egzeabher Letebrhan , Fekadu Endalkachew , Bikila Demiraw , Getahun Tigist , Challa Feyissa , Abdu Ahmedmenewer , Desta Kassu , Wolde Mistire , Tsegaye Aster
Published: October 2022

Objective Lipid abnormalities during childhood might be associated with a higher risk of atherosclerosis development in adulthood. In Ethiopia, there were no data on this area. The present work was aimed at assessing the lipid profile abnormalities among children and adolescents aged between 5 and 17 years, in Addis Ababa, Ethiopia.

Materials and Methods The present school-based cross-sectional study was done from March 2019 to October 2019 in the capital city, Addis Ababa. A total of 504 students were randomly recruited for this study. The total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein-cholesterol levels were determined using the Cobas c501 automated chemistry analyzer. The prevalence of lipid abnormalities was described in percentages. Bivariate and multivariate analyses were performed, and data with p-value less than 0.05 was considered statistically significant.

Results Dyslipidemia in at least one of the lipid profiles was observed in 322 (63.9%) school children, whereas only one of the participants had an abnormality in all four lipid profile tests. The prevalence of total cholesterol 200 mg/dL or higher, low-density lipoprotein 130 mg/dL or higher, high-density lipoprotein less than 40 mg/dL, and triglycerides 130 mg/dL or higher was in 14 (2.8%), 16 (3.2%), 294 (58.4%), and 46 (19.1%) participants, respectively.

Conclusion In the current work, the majority of the study participants had a normal lipid profile except increased prevalence of a reduced concentration of high-density lipoprotein-cholesterol. The overall prevalence of serum lipid abnormalities was 63.9%. Serum lipid levels did not show significant differences with sex, age, fasting habits, or obesity.
Correlation of Thrombosis and Clinicohematological Parameters with JAK2V617F Mutation in Philadelphia-Negative CMPNs: A Study from India
Authors: Singh Kanwaljeet , V. Pradeep , Ahuja Ankur , Somasundarum Venkatesan , Mishra Kundan , Chatterjee Tathagat
Published: October 2022

Objective Philadelphia-negative chronic myeloproliferative neoplasms (CMPNs), which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are characterized by the presence of JAK2V617F (exon 14) mutation, and this occurs in 90 to 95% cases of PV and 50 to 60% cases of ET and PMF. Still, this is a matter of debate regarding the correlation of this mutation with thrombosis and clinicohematological parameters in CMPNs. So, we conducted this study to ascertain the association of JAK2V617F mutation with thrombotic complications and clinicohematological parameters of these patients.

Materials and Methods This prospective and retrospective study was conducted during 2018 to 2019 at the Department of Laboratory Sciences and Molecular Medicine of a tertiary care hospital, and 160 CMPN patients were enrolled. Complete hemogram was done and DNA was extracted, followed by real-time qualitative polymerase chain reaction to check for JAK2V617F mutation. This mutation was then correlated with complications, mainly thrombosis, hematological parameters, and clinical parameters such as age and splenomegaly.

Results Among 160 CMPN patients, 60 were females and 100 were males, with male to female ratio of 1:0.6, and age range of 27 to 85 years. Total 91 (56.9%) patients were JAK2V617F positive and the remaining 69 (43.1%) were negative for this mutation. We observed statistically significant correlation of leukocyte count, splenomegaly, and thrombosis in JAK2V617F-mutated patients as compared to unmutated patients.

Conclusion This study emphasizes the importance of JAK2V617F mutation in CMPNs and stresses on its association with clinical, hematological phenotype, and thrombotic complications, which may open new horizons in prognostication and management protocol.
Pure Red Cell Aplasia Encountered in a Tertiary Care Hematology Laboratory: A Series of Nine Distinctive Cases
Authors: Kala Mansi , Das Kunal , Baveja Avriti , Raturi Manish , Dhebane Meghali , Ahmad Sohaib , Mehrotra Mansi
Published: October 2022

Pure red cell aplasia (PRCA) is characterized by severe anemia with reticulocytopenia and bone marrow erythroblastopenia. The early erythroblasts are markedly decreased; however, in rare instances, they may be normal or raised in number. There are varied etiologies, namely congenital or acquired and primary or secondary. The congenital PRCA is known as “Diamond-Blackfan anemia.” Thymomas, autoimmune disease, lymphomas, infections, and drugs also may be familiar associates. However, the etiologies of PRCA are numerous, and many diseases/infections can be associated with PRCA. The diagnosis rests on clinical suspicion and appropriate laboratory workup. We evaluated nine cases of red cell aplasia, having severe anemia with reticulocytopenia. Nearly half of the cases showed adequate erythroid (> 5% of the differential count) but with a maturation arrest. The adequacy of the erythroid could confuse the hematologist and may even delay the diagnosis. Hence, it is empirical that PRCA could be considered a differential in every case of severe anemia with reticulocytopenia, even in the presence of adequate erythroid precursors in the bone marrow.
Phase Transition Enthalpy Measurements of Organic Compounds. An Update of Sublimation, Vaporization, and Fusion Enthalpies from 2016 to 2021
Authors: Acree William , Chickos James S.
Published: October 2022

The compendium of phase change enthalpies published in two parts in 2016 is updated to include new fusion, vaporization, and sublimation enthalpies published in the interim and includes some earlier data either previously missed or were unavailable. Also included in this article is an update of recent studies on the phase change enthalpies of polyaromatic hydrocarbons. Group values previously evaluated to adjust for temperature of phase changes are updated for aromatic compounds in view of recent experimental data. The new group parameters have been evaluated on the basis of their consistency in providing appropriate temperature adjustments to phase change enthalpies at T = 298 K as evaluated by a thermochemical cycle. This evaluation provides transition temperatures and about 1000 heats of fusion, 700 heats of vaporization, 500 heats of sublimation, and about 50 other heats of transitions for about 30 polyaromatic hydrocarbons and 1100 other molecules consisting of C1-C57 organic compunds, organometallics, inorganic compounds, and ionic liquids taken from about 900 references.
Enhancement of thermal percolation in composites: A two-dimensional case study
Authors: Zhong Jinxin , Xi Qing , Jin Hongjie , Wang Ziqi , Ma Dengke , Liu Jun , Zhou Jun
Published: October 2022

We investigated the thermal conductivity (TC) of a two-dimensional composite consisting of matrices with low TC and nanowire fillers with high TC using the Monte Carlo method and the finite element method. Compared to the electrical percolation that requires direct contact between fillers, an additional thermal transport channel through non-contact fillers is found to be important for the thermal percolation in composites. This additional channel can lead to an effective expansion of thermal percolation network by including extra fillers into the network. Thus, it can be utilized to enhance the TC of the composite that is helpful to improve the performance of thermal interface materials.