bluuebunny/crossref_metadata_2025 huggingface dataset:
What are the barriers and facilitators of clozapine use in early psychosis? A survey of UK early intervention clinicians
Authors: Oloyede Ebenezer , Blackman Graham , Mantell Bethany , Harris Eleanor , Williams Julie , Taylor David , MacCabe James , McGuire Philip
Published: April 2023

Clozapine is the most effective medication for treatment-resistant psychosis, but evidence points to substantial underuse, especially within early intervention psychosis (EIP) services. We explored clinicians’ views on perceived barriers and facilitators to offering patients clozapine within EIP services. A cross-sectional survey was distributed electronically to clinicians practising in EIP services across England. A mixed methods approach was used to assess barriers to clozapine, and attitudes and opinions concerning clozapine underutilisation. Based on the barriers identified in the literature, clinicians were asked to rate each one (scale:1-7) based on importance, with a higher score indicating higher importance. Clinicians were also asked open-ended questions on barriers to clozapine and how access can be improved in EIP services. Quantitative data were analysed using descriptive and inferential statistics, and qualitative responses were analysed thematically. One hundred and nineteen EIP clinicians from 35 services in England completed the survey. In total, 37% (n = 45) of clinicians perceived that clozapine was under-prescribed in their EIP service. The most important barrier to utilising clozapine were patient concerns with side effects, followed by monitoring requirements and clinician concerns with side effects. Thematic analysis identified 17 perceived barriers, which were grouped into three major themes: administrative (5 subthemes), clinician-related (6 subthemes), and patient-related (6 subthemes). Perceived facilitators to improving clozapine use were greater training, improved resources, and optimised monitoring. The main barriers to clozapine in EIP services, as identified by clinicians, are patient concerns regarding side effects and monitoring requirements. Identified facilitators for improved clozapine use include clinician training, improved resources, guidelines, and point-of-care testing.
Colonoscopy aspiration lavages for mucosal metataxonomic profiling of spondylarthritis-associated gastrointestinal tract alterations
Authors: Marquez-Ortiz Ricaurte A. , Leon Moises , Abril Deisy , Escobar-Perez Javier , Florez-Sarmiento Cristian , Parra-Izquierdo Viviana , Chalem Philippe , Romero-Sanchez Consuelo
Published: April 2023

The study of the GI-tract microbiota of spondylarthritis (SpA) patients has focused on the analysis of feces samples, that picture mostly the luminal microbiota. The aim of this study was to determine the contribution of mucosal and luminal microbiome to the gut dysbiosis in SpA, using colonoscopy aspiration lavages (CAL), a recent alternative for regional studies of the GI-tract. We analyzed 59 CAL (from sigmoid colon and distal ileum), and 41 feces samples, from 32 SpA patients and 7 healthy individuals, using 16S rRNA gene-targeted metataxonomic profiling. It was found high prevalence of GI-tract manifestations among SpA patients (65.3%). Metataxonomic profiling, confirmed CAL samples from the lower GI tract (colon or ileum) presented a distinctive and undifferentiated bacteriome and separate from that found in feces’ samples or in the beginning of the GI tract (oral cavity (OC)). Lower GI-tract samples and feces of SpA patients exhibited similar behavior to the microbiota of IBD group with reduced microbial richness and diversity, comparing to the healthy controls. Interestingly, it was found increase in proinflammatory taxa in SpA patients, such as Enterobacteriaceae family (mostly in the ileum), Succinivibrio spp. and Prevotella stercorea. Conversely, SpA patients presented significant decrease in the SCFA producers Coprococcus catus and Eubacterium biforme. Our data support the value of CAL samples for the regional study of GI-tract and contribute with information of potential “disruptor taxa” involved in the GI-tract associated disorders observed in SpA patients.
Upregulation of extracellular proteins in a mouse model of Alzheimer’s disease
Authors: Kim Sangkyu , Fuselier Jessica , Latoff Anna , Manges Justin , Jazwinski S. Michal , Zsombok Andrea
Published: April 2023

Various risk factors of Alzheimer’s disease (AD) are known, such as advanced age, possession of certain genetic variants, accumulation of toxic amyloid-β (Aβ) peptides, and unhealthy lifestyle. An estimate of heritability of AD ranges from 0.13 to 0.25, indicating that its phenotypic variation is accounted for mostly by non-genetic factors. DNA methylation is regarded as an epigenetic mechanism that interfaces the genome with non-genetic factors. The Tg2576 mouse model has been insightful in AD research. These transgenic mice express a mutant form of human amyloid precursor protein linked to familial AD. At 9–13 months of age, these mice show elevated levels of Aβ peptides and cognitive impairment. The current literature lacks integrative multiomics of the animal model. We applied transcriptomics and DNA methylomics to the same brain samples from ~ 11-month-old transgenic mice. We found that genes involved in extracellular matrix structures and functions are transcriptionally upregulated, and genes involved in extracellular protein secretion and localization are differentially methylated in the transgenic mice. Integrative analysis found enrichment of GO terms related to memory and synaptic functionability. Our results indicate a possibility of transcriptional modulation by DNA methylation underlying AD neuropathology.
Sulfated endospermic nanocellulose crystals prevent the transmission of SARS-CoV-2 and HIV-1
Authors: Carvajal-Barriga Enrique Javier , Fitzgerald Wendy , Dimitriadis Emilios K. , Margolis Leonid , Fields R. Douglas
Published: April 2023

Biomaterials with antimicrobial activity are gaining attention due to their biodegradability and efficacy in interacting with a wide range of microorganisms. A new cellulose nano-biomaterial, endospermic nanocellulose crystals (ENC) obtained from parenchymal tissue of ivory nut endosperm, has a natural capacity as a universal binder. This feature is enhanced when it is chemically functionalized, and can be exploited in the fight against microbes. We tested the ability of sulfated ENC in aqueous suspension to encapsulate viruses through a crosslinking reaction mediated by cations. 0.25% w/v ENC suspensions efficiently encapsulated spike (S) protein, preventing its interaction with ACE2 receptor. ENC was further able to encapsulate SARS-CoV-2 pseudoviruses and prevent infection of 293T-hsACE2 cells. ENC also suppressed infection of MT-4 cells with HIV-1LAI.04. This antiviral activity of sulfated ENC is due to the irreversible interaction of ENC with viral particles mediated by crosslinking, as antiviral activity was less effective in the absence of cations. Additionally, ENC was used as a matrix to immobilize recombinant ACE2 receptors and anti-S IgG, creating molecular lures that efficiently inhibited SARS-CoV-2 infections in vitro. These results show that sulfated ENC from ivory nuts can be used as an efficient antiviral material.
Nickel ions influence the transepithelial sodium transport in the trachea, intestine and skin
Authors: Hołyńska-Iwan Iga , Sobiesiak Marta , Kowalczyk Wojciech , Wróblewski Marcin , Cwynar Anna , Szewczyk-Golec Karolina
Published: April 2023

Measurements of transepithelial potential and resistance in tissue and organ model systems enable the evaluation of the Ni2+ effect on the epithelial sodium channels, aquaporin 3, and the sodium–potassium pump in the epithelial cells. The aim of the presented study was to assess the immediate and prolonged effect of nickel ions on the transport of sodium ions in tissues exposed to direct contact with nickel, including airways, digestive tract and the skin. The influence of 0.1 mM nickel solution was performed on the trachea (n = 34), intestine (n = 44), and skin (n = 51) samples descended from 16 New Zealand albino rabbits. The electrophysiological parameters were measured in a modified Ussing chamber in stationary conditions and during a 15-s mechanical-chemical stimulation. A statistically significant decrease in the electric resistance values and the smallest range of the measured potential were observed for the Ni-treated trachea specimens. The use of nickel solution did not affect the sodium transport in the intestine epithelium. The skin fragments showed altered sodium ion transport, as demonstrated by the lower range and intensity of the measured potential. The gastrointestinal tract seems to be an organ best adapted to contact with nickel ions. In airways, nickel ions most likely enter epithelial cells and the space between them, modifying proteins and the airway surface liquid. The skin turned out to be the most sensitive tissue to the intensification of sodium ion transport through nickel ions.
Piezoelectric energy extraction from a cylinder undergoing vortex-induced vibration using internal resonance
Authors: Joy Annette , Joshi Vaibhav , Narendran Kumar , Ghoshal Ritwik
Published: April 2023

A novel concept of utilizing the kinetic energy from ocean currents/wind by means of internal resonance is proposed to address the increasing global energy demand by generating clean and sustainable power. In this work, a non-linear rotative gravity pendulum is employed to autoparametrically excite the elastically mounted cylinder for a wide range of flow velocities. This concept is adopted to increase the oscillation amplitude of the cylinder due to vortex-induced vibration (VIV) in the de-synchronized region for energy harvesting. In this regard, a VIV-based energy harvesting device is proposed that consists of a cylinder with an attached pendulum, and energy is harvested with bottom-mounted piezoelectric transducers. The cylinder undergoes VIV when it is subjected to fluid flow and this excites the coupled fluid-multibody cylinder-pendulum system autoparametrically. In the de-synchronized region, when the vortex shedding frequency becomes two times the natural frequency of the pendulum, an internal resonance occurs. This helps in achieving a higher oscillation amplitude of the cylinder which does not happen otherwise. This study is focused on the two degree-of-freedom (2-DoF) cylinder-pendulum system where the cylinder is free to exhibit cross-flow vortex-induced vibrations subjected to the fluid. The objective of this work is to numerically investigate the effect of a non-linear rotative gravity pendulum (NRGP) on the VIV characteristics and piezoelectric efficiency of the system. The numerical model is based on the wake-oscillator model coupled with the piezoelectric constitutive equation. The influence of the frequency ratio, mass ratio, torsional damping ratio, and ratio of cylinder diameter to pendulum length of the NRGP device on response characteristics due to VIV is also investigated. A detailed comparative analysis in terms of electric tension and efficiency is performed numerically for flows with a wide range of reduced velocities for the cylinder with and without NRGP. A comprehensive study on the implications of internal resonance between the pendulum and a cylinder undergoing VIV on generated electric tension is also reported.
Thin-slice computed tomography enables to classify pulmonary subsolid nodules into pre-invasive lesion/minimally invasive adenocarcinoma and invasive adenocarcinoma: a retrospective study
Authors: Li Min , Zhu Lei , Lv Yilv , Shen Leilei , Han Yuchen , Ye Bo
Published: April 2023

The aim was to investigate the ability of thin-slice computed tomography (TSCT) to differentiate invasive pulmonary adenocarcinomas (IACs) from pre-invasive/minimally invasive adenocarcinoma (AAH-MIAs), manifesting as subsolid nodules (SSNs) of diameter less than 30 mm. The CT findings of 810 patients with single subsolid nodules diagnosed by pathology of resection specimens were analyzed (atypical adenomatous hyperplasia, n = 13; adenocarcinoma in situ, n = 175; minimally invasive adenocarcinoma, n = 285; and invasive adenocarcinoma, n = 337). According to the classification of lung adenocarcinoma published by WHO classification of thoracic tumors in 2015, TSCT features of 368 pure ground-glass nodules (pGGN) and 442 part-solid nodules (PSNs) were compared AAH-MIAs with IACs. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. In pGGNs, multivariate analysis of factors found to be significant by univariate analysis revealed that higher mean-CT values (p = 0.006, OR 1.006, 95% CI 1.002–1.010), larger tumor size (p < 0.001, OR 1.483, 95% CI 1.304–1.688) with air bronchogram and non-smooth margins were significantly associated with IACs. The optimal cut-off tumor diameter for AAH-MIAs lesions was less than 10.75 mm (sensitivity, 82.8%; specificity, 80.6%) and optimal cut-off mean-CT value − 629HU (sensitivity, 78.1%; specificity, 50.7%). In PSNs, multivariate analysis of factors found to be significant by univariate analysis revealed that smaller tumor diameter (p < 0.001, OR 0.647, 95% CI 0.481–0.871), smaller size of solid component (p = 0.001, OR 83.175, 95% CI 16.748–413.079),and lower mean-CT value of solid component (p < 0.001, OR 1.009, 95% CI 1.004–1.014) were significantly associated with AAH-MIAs (p < 0.05). The optimal cut-off tumor diameter, size of solid component, and mean-CT value of solid component for AAH-MIAs lesions were less than 14.595 mm (sensitivity, 71.1%; specificity, 83.4%), 4.995 mm (sensitivity, 97.8%; specificity, 92.3%) and − 227HU (sensitivity, 65.6%; specificity, 76.3%), respectively. In subsolid nodules, whether pGGN or PSNs, the characteristics of TSCT can help in distinguishing IACs from AAH-MIAs.
Understanding physical climate risks and their implication for community adaptation in the borana zone of southern Ethiopia using mixed-methods research
Authors: Shibru Mulugeta , Opere Alfred , Omondi Philip , Gichaba Maina
Published: April 2023

Pastoralists in the Borana zone of southern Ethiopia are grappling with climatic risks and impacts, and their livelihoods appear to be precarious. The long-term changes in precipitation, temperature and extreme events are under-researched aspects of climate risk in the study area. Climate observations, local people’s experiences, and memories of weather and drought patterns were analysed in this work to better understand the climate risks in the study region and provide actionable knowledge to facilitate adaptations. In southern Ethiopia, the primary drivers of climate risks are rainfall variabilities, rising temperatures, and drought. The annual rainfall variability observed in the study area (20–35%) is greater than the overall estimate for Eastern Africa (15–25%), indicative of a heightened climate risk in this area. Furthermore, seasonal and intra-seasonal rainfall variabilities are being aggravated by rising temperatures, leading to increased frequency and magnitude of extreme events, particularly in the lowland area. These changes, specifically droughts of different intensities occurring every 2–3 years, erode the livelihood of the pastoralists. The lack of consensus among stakeholders as to the causes and aggravating factors of these climate changes impedes adaptation actions. The authors recommend the importance of initiating a participatory platform that will facilitate discussion on climate change to create a common understanding of the problem and relate it to public policy. The use of gridded precipitation and temperature data is recommended in future research to improve the availability of climate information for climate risk management. In addition, the use of mixed methods and local knowledge, as demonstrated in this study, is highly recommended to better understand climate risks, particularly when there is a limited availability and quality of long-time-series climate data.
Predictors and survival of cardiomyopathy determined by echocardiography in Thai patients with early systemic sclerosis: an inception cohort study
Authors: Wangkaew Suparaporn , Prasertwitayakij Narawudt , Intum Jirapath , Euathrongchit Juntima
Published: April 2023

Available data including the incidence, predictors and long-term outcome of early systemic sclerosis patients associated with suspected cardiomyopathy(SSc-CM) is limited. Therefore, we aimed to study the incidence, predictors and survival of SSc-CM. An inception cohort study was conducted for early SSc patients seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, Thailand, from January 2010 to December 2019. All patients were determined for clinical manifestations and underwent echocardiography and HRCT at enrollment and then annually. SSc-CM was determined and classified using echocardiography. 135 early SSc patients (82 female,108 DcSSc) were enrolled. With the mean follow-up period of 6.4 years, 32 patients developed SSc-CM. The incidence of SSc-CM was 5.3 per 100-person years. The multivariate Cox regression analysis showed that baseline anti-topoisomerase I-positive (Hazard ratio[HR] 4.86, p = 0.036), dysphagia (HR 3.35, p = 0.001), CK level ≥ 500 U/L(HR 2.27, p = 0.045) and low oxygen saturation (HR 0.82, p = 0.005) were predictors of SSc-CM. The survival rates after SSc-CM diagnosis at 1, 5 and 10 years were 90.3%, 73.1%, and 56.1%, respectively. In this study cohort, the incidence of SSc-CM was 5.3 per 100-person years, and tended to have low survival. The presence of anti-topoisomerase I antibody, dysphagia, CK level ≥ 500 U/L, and low oxygen saturation were independent baseline predictors for developing SSc-CM.
Novel mitochondrial genome rearrangements including duplications and extensive heteroplasmy could underlie temperature adaptations in Antarctic notothenioid fishes
Authors: Minhas Bushra Fazal , Beck Emily A. , Cheng C.-H. Christina , Catchen Julian
Published: April 2023

Mitochondrial genomes are known for their compact size and conserved gene order, however, recent studies employing long-read sequencing technologies have revealed the presence of atypical mitogenomes in some species. In this study, we assembled and annotated the mitogenomes of five Antarctic notothenioids, including four icefishes (Champsocephalus gunnari,C. esox,Chaenocephalus aceratus, andPseudochaenichthys georgianus) and the cold-specializedTrematomus borchgrevinki. Antarctic notothenioids are known to harbor some rearrangements in their mt genomes, however the extensive duplications in icefishes observed in our study have never been reported before. In the icefishes, we observed duplications of the protein coding geneND6, two transfer RNAs,and the control region with different copy number variants present within the same individuals and with someND6duplications appearing to follow the canonical Duplication-Degeneration-Complementation (DDC) model inC. esoxandC. gunnari. In addition, using long-read sequencing and k-mer analysis, we were able to detect extensive heteroplasmy inC. aceratusandC. esox. We also observed a large inversion in the mitogenome ofT. borchgrevinki, along with the presence of tandem repeats in its control region. This study is the first in using long-read sequencing to assemble and identify structural variants and heteroplasmy in notothenioid mitogenomes and signifies the importance of long-reads in resolving complex mitochondrial architectures. Identification of such wide-ranging structural variants in the mitogenomes of these fishes could provide insight into the genetic basis of the atypical icefish mitochondrial physiology and more generally may provide insights about their potential role in cold adaptation.
MMP9 and TYROBP affect the survival of circulating tumor cells in clear cell renal cell carcinoma by adapting to tumor immune microenvironment
Authors: Guo Lingyu , An Tian , Zhou Haibin , Wan Ziyan , Huang Zhixin , Chong Tie
Published: April 2023

Circulating tumor cells (CTCs) play a key role in tumor metastasis. CTCs have altered gene expression and can survive in the bloodstream. Finding the key genes whose expression are altered in CTCs could help explain the mechanism of tumor metastasis. We searched for genes differentially expressed in CTCs by analyzing four CTCs and primary tumor gene expression datasets in the GEO database. Key genes of clear cell renal cell carcinoma (ccRCC) CTCs were identified. The correlation between key genes and the immune microenvironment of ccRCC was explored. Finally, the CTCs cell model of ccRCC was constructed by in vivo screening method, and the expression of key genes was detected at the cell and tissue levels. A total of 771 DEGs were obtained. Gene enrichment analysis showed that DEGs of CTCs were mainly involved in the regulation of the tumor immune process and tumor cell apoptosis. Finally, we found 2 key genes, MMP9 and TYROBP in ccRCC CTCs. The high expression of these 2 genes predicted a poor prognosis of ccRCC, and the expression levels of these 2 genes were significantly increased in CTCs and ccRCC tissues. Our study suggested that genetic alterations in CTCs contribute to the ability of CTCs to survive in the blood by adapting to the tumor microenvironment. MMP9 and TYROBP are potential therapeutic and prognostic targets for ccRCC.
A multiscale approach reveals elaborate circulatory system and intermittent heartbeat in velvet worms (Onychophora)
Authors: Jahn Henry , Hammel Jörg U. , Göpel Torben , Wirkner Christian S. , Mayer Georg
Published: April 2023

An antagonistic hemolymph-muscular system is essential for soft-bodied invertebrates. Many ecdysozoans (molting animals) possess neither a heart nor a vascular or circulatory system, whereas most arthropods exhibit a well-developed circulatory system. How did this system evolve and how was it subsequently modified in panarthropod lineages? As the closest relatives of arthropods and tardigrades, onychophorans (velvet worms) represent a key group for addressing this question. We therefore analyzed the entire circulatory system of the peripatopsid Euperipatoides rowelli and discovered a surprisingly elaborate organization. Our findings suggest that the last common ancestor of Onychophora and Arthropoda most likely possessed an open vascular system, a posteriorly closed heart with segmental ostia, a pericardial sinus filled with nephrocytes and an impermeable pericardial septum, whereas the evolutionary origin of plical and pericardial channels is unclear. Our study further revealed an intermittent heartbeat—regular breaks of rhythmic, peristaltic contractions of the heart—in velvet worms, which might stimulate similar investigations in arthropods.
MASI enables fast model-free standardization and integration of single-cell transcriptomics data
Authors: Xu Yang , Kramann Rafael , McCord Rachel Patton , Hayat Sikander
Published: April 2023

Single-cell transcriptomics datasets from the same anatomical sites generated by different research labs are becoming increasingly common. However, fast and computationally inexpensive tools for standardization of cell-type annotation and data integration are still needed in order to increase research inclusivity. To standardize cell-type annotation and integrate single-cell transcriptomics datasets, we have built a fast model-free integration method, named MASI (Marker-Assisted Standardization and Integration). We benchmark MASI with other well-established methods and demonstrate that MASI outperforms other methods, in terms of integration, annotation, and speed. To harness knowledge from single-cell atlases, we demonstrate three case studies that cover integration across biological conditions, surveyed participants, and research groups, respectively. Finally, we show MASI can annotate approximately one million cells on a personal laptop, making large-scale single-cell data integration more accessible. We envision that MASI can serve as a cheap computational alternative for the single-cell research community.
DNA double-strand break-free CRISPR interference delays Huntington’s disease progression in mice
Authors: Seo Jung Hwa , Shin Jeong Hong , Lee Junwon , Kim Daesik , Hwang Hye-Yeon , Nam Bae-Geun , Lee Jinu , Kim Hyongbum Henry , Cho Sung-Rae
Published: April 2023

Huntington’s disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. CRISPR-Cas9 nuclease causes double-strand breaks (DSBs) in the targeted DNA that induces toxicity, whereas CRISPR interference (CRISPRi) using dead Cas9 (dCas9) suppresses the target gene expression without DSBs. Delivery of dCas9-sgRNA targeting CAG repeat region does not damage the targeted DNA in HEK293T cells containing CAG repeats. When this study investigates whether CRISPRi can suppress mutant HTT (mHTT), CRISPRi results in reduced expression of mHTT with relative preservation of the wild-type HTT in human HD fibroblasts. Although both dCas9 and Cas9 treatments reduce mHTT by sgRNA targeting the CAG repeat region, CRISPRi delays behavioral deterioration and protects striatal neurons against cell death in HD mice. Collectively, CRISPRi can delay disease progression by suppressing mHtt, suggesting DNA DSB-free CRISPRi is a potential therapy for HD that can compensate for the shortcoming of CRISPR-Cas9 nuclease.
Structural basis for the ligand promiscuity of the neofunctionalized, carotenoid-binding fasciclin domain protein AstaP
Authors: Kornilov Fedor D. , Slonimskiy Yury B. , Lunegova Daria A. , Egorkin Nikita A. , Savitskaya Anna G. , Kleymenov Sergey Yu. , Maksimov Eugene G. , Goncharuk Sergey A. , Mineev Konstantin S. , Sluchanko Nikolai N.
Published: April 2023

Fasciclins (FAS1) are ancient adhesion protein domains with no common small ligand binding reported. A unique microalgal FAS1-containing astaxanthin (AXT)-binding protein (AstaP) binds a broad repertoire of carotenoids by a largely unknown mechanism. Here, we explain the ligand promiscuity of AstaP-orange1 (AstaPo1) by determining its NMR structure in complex with AXT and validating this structure by SAXS, calorimetry, optical spectroscopy and mutagenesis. α1-α2 helices of the AstaPo1 FAS1 domain embrace the carotenoid polyene like a jaw, forming a hydrophobic tunnel, too short to cap the AXT β-ionone rings and dictate specificity. AXT-contacting AstaPo1 residues exhibit different conservation in AstaPs with the tentative carotenoid-binding function and in FAS1 proteins generally, which supports the idea of AstaP neofunctionalization within green algae. Intriguingly, a cyanobacterial homolog with a similar domain structure cannot bind carotenoids under identical conditions. These structure-activity relationships provide the first step towards the sequence-based prediction of the carotenoid-binding FAS1 members.
The Newfoundland and Labrador mosaic founder population descends from an Irish and British diaspora from 300 years ago
Authors: Gilbert Edmund , Zurel Heather , MacMillan Margaret E. , Demiriz Sedat , Mirhendi Sadra , Merrigan Michael , O’Reilly Seamus , Molloy Anne M. , Brody Lawrence C. , Bodmer Walter , Leach Richard A. , Scott Roderick E. M. , Mugford Gerald , Randhawa Ranjit , Stephens J. Claiborne , Symington Alison L. , Cavalleri Gianpiero L. , Phillips Michael S.
Published: April 2023

The founder population of Newfoundland and Labrador (NL) is a unique genetic resource, in part due to its geographic and cultural isolation, where historical records describe a migration of European settlers, primarily from Ireland and England, to NL in the 18th and 19th centuries. Whilst its historical isolation, and increased prevalence of certain monogenic disorders are well appreciated, details of the fine-scale genetic structure and ancestry of the population are lacking. Understanding the genetic origins and background of functional, disease causing, genetic variants would aid genetic mapping efforts in the Province. Here, we leverage dense genome-wide SNP data on 1,807 NL individuals to reveal fine-scale genetic structure in NL that is clustered around coastal communities and correlated with Christian denomination. We show that the majority of NL European ancestry can be traced back to the south-east and south-west of Ireland and England, respectively. We date a substantial population size bottleneck approximately 10-15 generations ago in NL, associated with increased haplotype sharing and autozygosity. Our results reveal insights into the population history of NL and demonstrate evidence of a population conducive to further genetic studies and biomarker discovery.
Bidirectional wave-propelled capillary spinners
Authors: Barotta Jack-William , Thomson Stuart J. , Alventosa Luke F. L. , Lewis Maya , Harris Daniel M.
Published: April 2023

When a solid body floats at the interface of a vibrating liquid bath, the motion of the object generates outwardly propagating surface waves. We here demonstrate that chiral objects on a vibrating fluid interface are set into steady rotation, with the angular speed and direction of rotation controlled by the interplay between object geometry and driving parameters. Scaling laws and a simplified model of the wavefield reveal the underlying physical mechanism of rotation, while collapsing measurements of the angular velocity across parameters. Leveraging the control over the chiral object’s direction of rotation, we demonstrate that a body with an asymmetric mass distribution and chirality can be remotely steered along two-dimensional trajectories via modulation of the driving frequency. This accessible and tunable macroscopic system serves as a potential platform for explorations of chiral active and driven matter, and demonstrates a mechanism by which wave-mediated forces can be manipulated for directed propulsion.
Prefectures vulnerable to water scarcity are not evenly distributed across China
Authors: Zhao Fubo , Wang Xi , Wu Yiping , Singh Shailesh Kumar
Published: April 2023

Water scarcity has become a significant constraint to sustainable development. While the water scarcity has been widely assessed, its social impacts are infrequently evaluated. Here, we developed a framework to integrate the water scarcity and climate sensitivity to examine social vulnerability at the prefecture level across China. Results showed that 41% of the 301 prefectures were highly water stressed and 30% were highly sensitive to changing climate. We identified 44 hotspot prefectures using a combination of high water scarcity and climate sensitivity. We mapped the gradient in social vulnerability to water stress and climate sensitivity in these 44 prefectures and found that prefectures with ‘very high’ social vulnerability were primarily distributed in Central and Southwest China. These ‘very high’ vulnerable prefectures are home to more than 58 million people. The consideration of both water scarcity and climate sensitivity across management units has potential to formulate policies regarding water resources management.
Molecular modelling of the thermophysical properties of fluids: expectations, limitations, gaps and opportunities
Authors: Tillotson Marcus J. , Diamantonis Nikolaos I. , Buda Corneliu , Bolton Leslie W. , Müller Erich A.
Published: April 2023

This manuscript provides an overview of the current state of the art in terms of the molecular modelling of the thermophysical properties of fluids.
Role of graphene quantum dots with discrete band gaps on SnO2 nanodomes for NO2 gas sensors with an ultralow detection limit
Authors: Lee Jinho , Park Minsu , Song Young Geun , Cho Donghwi , Lee Kwangjae , Shim Young-Seok , Jeon Seokwoo
Published: April 2023

The decoration of graphene quantum dots enhances the NO2 gas sensing performance of SnO2 nanodomes by utilizing both electrical and chemical sensitization effects, leading to an impressive reduction in the theoretical detection limit.
Will the circle be unbroken? The climate mitigation and sustainable development given by a circular economy of carbon, nitrogen, phosphorus and water
Authors: McKenna Patrick , Zakaria Fiona , Guest Jeremy , Evans Barbara , Banwart Steven
Published: April 2023

Closing the loop in the flow of C, nutrients and water between agriculture, the human diet and sanitation services offers benefits for humanity across multiple platforms of public health, food security and climate mitigation.
Restoring endothelial function: shedding light on cardiovascular stent development
Authors: Liu Wen , Wang Xiaoyu , Feng Yakai
Published: April 2023

This review generalizes the pathogenic factors interfering with the endothelial functionand the progress based on ameliorating endothelial function, aiming to shed light on the development of next-generation cardiovascular stents.
Self-assembly of a fluorescent hydrogen-bonded capsule based on an amino-acid functionalised tetraphenylethylene
Authors: Brzechwa-Chodzyńska Anna , Markiewicz Grzegorz , Cecot Piotr , Harrowfield Jack , Stefankiewicz Artur R.
Published: April 2023

The self-assembly of an amino-acid substituted tetraphenylethylene (TPE) into a hydrogen-bonded dimeric capsule and an aggregate is reported. Depending on the conditions applied they exhibit bluish photoluminescence with QYs up to 24%.
Factors driving the Ni/Cu cooperative asymmetric propargylation of aldimine esters
Authors: Sciortino Giuseppe , Maseras Feliu
Published: April 2023

The factors driving the Ni0(binap)/CuI(phospherrox) cooperative asymmetric propargylation of aldimine esters are unveiled through DFT calculations.
Bionic electroluminescent perovskite light-emitting device
Authors: Xiang Hengyang , Zhao Saichao , Wang Yifei , Wang Run , Li Xinxin , Wang Hao , Laigao Yuquan , Liu Jun , Wu Fan , Xie Aming , Li Weijin , Zeng Haibo
Published: April 2023

The FC-PeLED system simulates the natural process of bionics of plant colors from green to brown through a low energy input.
Organolithium aggregation as a blueprint to construct polynuclear lithium nickelate clusters
Authors: Borys Andryj M. , Hevia Eva
Published: April 2023

Exploiting the high aggregation of organolithium complexes, a new structurally diverse family of lithium nickelate clusters has been uncovered, which can be accessed by treating Ni(COD)2 with a large excess of aliphatic lithium acetylides.
Growth mechanism of [100]-oriented TaON film through an endotaxial transformation from a (012)-LiTaO3 single crystal substrate
Authors: Qin Xuesen , Li Huiliang , Wang Zeyan , Zheng Zhaoke , Wang Peng , Cheng Hefeng , Liu Yuanyuan , Fan Yuchen , Dai Ying , Huang Baibiao
Published: April 2023

An endotaxial transformation growth mechanism has been proposed, which enables the successful fabrication of [100]-oriented free-standing TaON film from a (012)-LiTaO3 single crystal substrate through a CCl4-assisted nitridation process.
Ferroelectricity in a nematic liquid crystal under a direct current electric field
Authors: Mrukiewicz Mateusz , Perkowski Paweł , Karcz Jakub , Kula Przemysław
Published: April 2023

We investigated the influence of the DC electric field on the electrical and optical properties of a liquid crystal compound 4-(4-nitrophenoxycarbonyl)phenyl 2,4-dimethoxybenzoate, known as RM734, exhibiting a ferroelectric nematic phase.
On the relationship between the Debye process in dielectric response and a dissociation–association phenomenon in phenyl alcohols
Authors: Czaderna-Lekka Anna , Tarnacka Magdalena , Wojnarowska Zaneta , Hachuła Barbara , Paluch Marian , Kamiński Kamil
Published: April 2023

We observed the agreement between energies barrier for dissociation determined by Rubinstein and van’t Hoff approaches, which implies that the dielectric Debye-like process of phenyl alcohols is governed by the association–dissociation phenomenon.
A quest for ideal electric field-driven MX@C70 endohedral fullerene memristors: which MX fits the best?
Authors: Tučková Lucie , Jaroš Adam , Foroutan-Nejad Cina , Straka Michal
Published: April 2023

New candidates for MX@C70 fullerene-based memristors are presented. General guidelines for the design of MX@Cn fullerene molecular memristors are derived.
Exploring the catalytic activity of graphene-based TM-NxC4-xsingle atom catalysts for the oxygen reduction reactionviadensity functional theory calculation
Authors: Du Zhengwei , Deng Kaiming , Kan Erjun , Zhan Cheng
Published: April 2023

Electrocatalysts for the oxygen reduction reaction (ORR) are extremely crucial for advanced energy conversion technologies, such as fuel cell batteries.
Correction: Molecular sonification for molecule to music information transfer
Authors: Mahjour Babak , Bench Jordan , Zhang Rui , Frazier Jared , Cernak Tim
Published: April 2023

Correction for ‘Molecular sonification for molecule to music information transfer’ by Babak Mahjour et al., Digital Discovery, 2023, 2, 520–530, https://doi.org/10.1039/D3DD00008G.
Unraveling the reaction mechanisms for furfural electroreduction on copper
Authors: Liu Sihang , Mukadam Zamaan , Scott Soren B. , Sarma Saurav Ch. , Titirici Maria-Magdalena , Chan Karen , Govindarajan Nitish , Stephens Ifan E. L. , Kastlunger Georg
Published: April 2023

Combining theory and experiment, we unveil the mechanisms for furfural electroreduction on copper and provide a rationale to tune reaction conditions to increase activity towards value-added products.
Metal-free photosensitized aminosulfonylation of alkenes: a practical approach to β-amido sulfones
Authors: Chen Meiling , Sun Wenyan , Yang Jingjing , Yuan LuLu , Chen Jian-Qiang , Wu Jie
Published: April 2023

A general and environmentally friendly organic photo-induced strategy was developed for the synthesis of diverse alkyl-substituted β-amino sulfone derivatives, including primary, secondary, and tertiary alkyl-substituted products.
Investigation of matrix effects in nitrogen microwave inductively coupled atmospheric-pressure plasma mass spectrometry (MICAP-MS) for trace element analysis in steels
Authors: Winckelmann Alexander , Roik Janina , Recknagel Sebastian , Abad Carlos , You Zengchao
Published: April 2023

We investigated the performance of nitrogen microwave inductively coupled atmospheric-pressure plasma mass spectrometry (MICAP-MS) under matrix effects and its applicability to trace element analysis in steels.
Multi-doped ceria-based composite as a promising low-temperature electrolyte with enhanced ionic conductivity for steam electrolysis
Authors: Liu Yuheng , Xu Ming , Zhao Yunlong , Amini Horri Bahman
Published: April 2023

A lithium–bismuth–copper co-doped GDC composite (Ce0.712Gd0.178Li0.05Bi0.05Cu0.01O1.801) capable of sintering at ∼750 °C with an electrical conductivity of 29.6 mS cm−1 was developed for the first time for metal-supported solid oxide electrolysers.
2-Aminofluorene based triazole cocktailed with organosilane as UV-visible and fluorescence sensor for the highly selective detection of Fe(iii) ion and its anti-leishmanial activity
Authors: Singh Gurjaspreet , Gupta Sofia , Pawan  , Mohit  , Diksha  , Saini Isha , Vikas  , Mohan Brij , Soni Sanjeev
Published: April 2023

This paper synthesizes triazole-attached 2-aminofluorene-based organosilane for sensing Fe3+ion using UV-Vis and fluorescence. Probe6a's inhibitory effect on the leishmania protein was studied. DFT explained6a's complexation with Fe3+ion.
Enhancing the photothermal performance of graphene oxide by embedding perylene diimide radical anions/α-phenylethylamine hydrogen bonded complexes in graphene oxide films for solar water evaporation
Authors: Li Yuanyuan , Liu Jinming , Li Wei , Li Yingru , Zhao Wei , Zhang Haiquan
Published: April 2023

Perylene diimine radical anions stabilized by α-phenylethylamine were compounded with graphene oxide having excellent thermal conductivity, which has a high temperature increase of 84.2 °C and could be used for solar water evaporation.
CoFe layered double hydroxides with adjustable composition and structure for enhanced oxygen evolution reaction
Authors: Rong Wan , Dang Rui , Chen Yunfei , Huang Kang , Xia Jiuyang , Zhang Bowei , Liu Jianfei , Li Meixin , Cao Qigao , Wu Junsheng
Published: April 2023

Gram-scale preparation of CoFe-LDH for highly efficient electrochemical water oxidation.
Recent progresses on ion beam irradiation induced structure and performance modulation of two-dimensional materials
Authors: Wu Xin , Luo Xinchun , Cheng Hailong , Yang Ruxue , Chen Xiyue
Published: April 2023

Ion beam irradiation techniques have been demonstrated to have obvious advantages in manipulating the structure and performance of 2D materials. This paper reviews the research progress in the interaction between energetic ions and 2D materials.
Exploring a general mechanistic map on NHC-catalyzed activation/transformation reactions of saturated carboxylic anhydrides
Authors: Liu Shuang-Liang , Qiao Yan , Wang Yang
Published: April 2023

A general mechanistic map involving multiple intermediates and pathways has been proposed and systematically studied for NHC-catalyzed transformation reactions of saturated carboxylic anhydrides.
Deoxyglucose-conjugated persistent luminescent nanoparticles for theragnostic application in fibrosarcoma tumor model
Authors: Sharma K. S. , Melwani Pooja K. , Yadav Hansa D. , Joshi Rashmi , Shetake Neena G. , Dubey Akhil K. , Singh Bheeshma Pratap , Phapale Suhas , Phadnis Prasad P. , Vatsa Rajesh K. , Ningthoujam Raghumani Singh , Pandey Badri N.
Published: April 2023

Deoxyglucose conjugated nanoparticles with persistent luminescence have shown theragnostic potential.
Removal of heavy metals from binary and multicomponent adsorption systems using various adsorbents – a systematic review
Authors: Bayuo Jonas , Rwiza Mwemezi J. , Sillanpää Mika , Mtei Kelvin Mark
Published: April 2023

The review revealed that both natural and engineered adsorbents could remove heavy metals from multicomponent systems. However, the competitive effects among heavy metal ions in the multicomponent system influences their individual uptake capacity.
Impact of thermal treatment on the Li-ion transport, interfacial properties, and composite preparation of LLZO garnets for solid-state electrolytes
Authors: Ghorbanzade Pedram , Pesce Arianna , Gómez Kerman , Accardo Grazia , Devaraj Shanmukaraj , López-Aranguren Pedro , López del Amo Juan Miguel
Published: April 2023

Heat treatment of LLZO garnets can effectively remove lithium hydroxide and carbonate layers from its surface, increase the Li dynamics in the structure and improve the processing of composite polymer electrolytes for solid-state batteries.
Carbon-centered radical based dynamic covalent chemistry for stimuli-responsive chromic materials
Authors: Xu Tingting , Zhu Jun , Han Yi , Chi Chunyan
Published: April 2023

Stimuli-responsive chromic materials have received increasing research attention. This review summarizes the most cutting-edge carbon-centered radicals, with a focus on their structures, properties and applications as stimuli-chromic materials.
Surface-passivated MAPbBr3 microwire with enhanced stability and suppressed ion migration
Authors: Han Zeyao , Liu Yang , Zou Yousheng , Li Junyu , He Yin , Zeng Haibo
Published: April 2023

PEABr and BABr are introduced as surface passivators for MAPbBr3 microwire to not only effectively passivate defects, but also provide resistance towards moisture. Devices exhibit higher optoelectronic performance, suppressed ion migration and improved stability for >21 days.
Visual analysis of pyrophosphatase assisted by red and green two-color distance-reading test strips for the diagnosis of hyperthyroidism
Authors: Shi Tian , Peng Wu , Yan Li , Zhao Maoyuan , Zhan Zixuan , Ying Binwu , Chen Piaopiao
Published: April 2023

Using CdTe QDs and Probe-Cu2+ as signal reporters, a dual-fluorescence, binary-color distance-reading method for PPase analysis was developed; dip-dying and ink-jet printing were used to make test strips for the clinical diagnosis of hyperthyroidism.
The VEGFR/PDGFR tyrosine kinase inhibitor, ABT-869, blocks necroptosis by targeting RIPK1 kinase
Authors: Pierotti Catia L. , Jacobsen Annette V. , Grohmann Christoph , Dempsey Ruby K. , Etemadi Nima , Hildebrand Joanne M. , Fitzgibbon Cheree , Young Samuel N. , Davies Katherine A. , Kersten Wilhelmus J. A. , Silke John , Lowes Kym N. , Jousset Sabroux Hélène , Huang David C. S. , van Delft Mark F. , Murphy James M. , Lessene Guillaume
Published: April 2023

Necroptosis is a mode of programmed, lytic cell death that is executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following activation by the upstream kinases, receptor-interacting serine/threonine protein kinase (RIPK)-1 and RIPK3. Dysregulated necroptosis has been implicated in the pathophysiology of many human diseases, including inflammatory and degenerative conditions, infectious diseases and cancers, provoking interest in pharmacological targeting of the pathway. To identify small molecules impacting on the necroptotic machinery, we performed a phenotypic screen using a mouse cell line expressing an MLKL mutant that kills cells in the absence of upstream death or pathogen detector receptor activation. This screen identified the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) tyrosine kinase inhibitor, ABT-869 (Linifanib), as a small molecule inhibitor of necroptosis. We applied a suite of cellular, biochemical and biophysical analyses to pinpoint the apical necroptotic kinase, RIPK1, as the target of ABT-869 inhibition. Our study adds to the repertoire of established protein kinase inhibitors that additionally target RIPK1 and raises the prospect that serendipitous targeting of necroptosis signalling may contribute to their clinical efficacy in some settings.
Sculpting with stiffness: rigidity as a regulator of morphogenesis
Authors: Shellard Adam , Mayor Roberto
Published: April 2023

From a physical perspective, morphogenesis of tissues results from interplay between their material properties and the mechanical forces exerted on them. The importance of mechanical forces in influencing cell behaviour is widely recognised, whereas the importance of tissue material properties in vivo, like stiffness, has only begun to receive attention in recent years. In this mini-review, we highlight key themes and concepts that have emerged related to how tissue stiffness, a fundamental material property, guides various morphogenetic processes in living organisms.
Determining the preferred directions of magnetisation in cubic crystals using symmetric polynomial inequalities
Authors: Samad Fabian , Hellwig Olav
Published: April 2023

For a magnetic material, the easy and hard magnetic axes describe the directions of favourable respectively unfavourable alignment of the magnetisation. In this article, we describe how to determine these axes for cubic magnetic crystals. Usually it is assumed without further reasoning that they coincide with some principal symmetry directions of the crystal [Bozorth, Phys. Rev.50, 1076–1081 (1936)], which is however invalid in general. In contrast, we present a full and elementary analysis using symmetric polynomial inequalities, which are well suited to the symmetry of the problem.
Interpreting the cosmic ray spectrum and composition measurements across the ankle and up to the highest energies with the data of the Pierre Auger Observatory
Authors: Guido Eleonora
Published: April 2023

In this work we present a combined fit of the energy spectrum and mass composition data above 6×1017 eV as measured by the Pierre Auger Collaboration and we show that our data can be reproduced by the superposition of two (or more) components, either Galactic or extragalactic. We use a simple astrophysical model with two extragalactic components, one dominant at high energy and the other at low energy, whose superposition generates the so-called “ankle” feature. We find that the component dominating the low (high) energy region is required to be emitted from the sources with a very soft (hard) spectrum. In our best fit scenario the sources contributing above the ankle emit a mixed and increasingly heavier mass composition, whereas a mix of protons and intermediate-mass nuclei is observed below the ankle, which reach the Earth almost una↵ected by the propagation in the intergalactic space. The possible presence of a Galactic population providing the intermediate-mass contribution at low energy is also explored.

In order to evaluate our capability to constrain astrophysical models, we finally discuss the impact on the fit results of the main experimental systematic uncertainties and of the assumptions on the quantities a↵ecting propagation, both in the atmosphere and in the intergalactic medium.