bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of the teachers’ augmented reality competences (TARC) scale
Authors: Nikou Stavros A. , Perifanou Maria , Economides Anastasios A.
Published: July 2023

While augmented reality (AR) can offer many advantages in education, one reason for the difficulty of integrating it in instructional practices is the lack of teachers’ AR competences. Therefore, there is an increasing need to address the required competences needed by teachers to effectively integrate augmented reality (AR) in their teaching. This study develops and validates a comprehensive augmented reality competences scale for teachers. The suggested instrument encompasses skills related to the creation, use and management of augment reality resources for teaching. The scale was validated on a sample of 150 educators from 45 countries teaching in primary, secondary or tertiary levels. Confirmatory factor analysis demonstrated valid results in terms of model fit criteria, factor loadings, validity, and reliability. The final scale is composed of 11 items and 4 competence components. Teaching subject, general digital skills and previous AR class experience revealed significant differences across the scale components, while gender and age did not reveal any significant associations. Educators in higher education institutions self-reported higher competence level for designing, developing, and modifying AR resources compared to secondary and primary levels. The scale can be used by educators to self-assess their AR competences, teacher professional development institutions and policy makers to develop training programs in AR and software companies to develop AR experiences that can empower educators.
A Two-Eyed Seeing Teaching and Learning Framework for Science Education
Authors: Cirkony Connie , Kenny John , Zandvliet David
Published: July 2023

Worldwide, education jurisdictions are looking for authentic ways to address First Nations perspectives in the K-12 curriculum, including science education. At the same time, there have been ongoing efforts to integrate authentic and engaging approaches to teaching science, including those that are student-centred, inquiry-based, multimodal, and linked to meaningful contexts. Both goals may be realised through the principle of Two-Eyed Seeing (TES), which seeks to integrate the strengths of Indigenous ways of knowing with one eye, and Western ways of knowing with the other eye, for the benefit of all students. This theoretical paper presents a Two-Eyed Seeing for Science Education (TESSE) Framework, which brings together two pedagogical models. One is from a contemporary science perspective, the 5Es representation-rich inquiry approach, which scaffolds authentic student-centred conceptually focused learning experiences. The other is from an Indigenous perspective, the 8 Aboriginal Ways of Learning, which illustrates different ways of knowing—many of which are familiar with First Peoples across the world (e.g., place-based, visual, holistic). The TESSE Framework aims to act as a strengths-based interface between the two knowledge systems to support a culturally responsive approach to teaching and learning science. It is designed to support meaningful connections through curriculum and pedagogy in ways that are contextually relevant to place. Through empirical investigation and in collaboration with local communities, the Framework has the potential to inform current approaches to science education in schools and universities and provide a pathway towards decolonisation and reconciliation.
Phytoremediation as a Tool to Remove Drivers of Antimicrobial Resistance in the Aquatic Environment
Authors: Chowdhury Kaniz F. , Hall Rebecca J. , McNally Alan , Carter Laura J.
Published: July 2023

Antimicrobials, heavy metals, and biocides are ubiquitous contaminants frequently detected in water bodies across the globe. These chemicals are known as drivers of antimicrobial resistance (AMR), as these chemicals can select for resistance. Tools and processes, are therefore, needed to remove these chemicals from the environment to tackle the environmental component of AMR. Aquatic phytoremediation is a nature-inspired green solution to remove contaminants from the environment. Phytoremediation utilises macrophytes’ ability to sequester and degrade chemical pollutants in aquatic environments. In this review, we define the problem statement by highlighting the presence of AMR drivers in the aquatic environment. We also provide an in-depth review of phytoremediation to tackle chemical pollution by evaluating mechanisms for the removal and degradation of chemicals. This review identifies potential hyper-accumulators and understands how plant species and chemical composition can influence the potential for accumulation. Different pollutants accumulate to different extents in a range of aquatic macrophytes. Therefore, the combined use of floating, submerged and emergent plants would facilitate the optimum removal of AMR drivers considered in this review. A suggested configuration includes Helianthus annus around the edge of a contaminated site, followed by a belt of submerged plants (Myriophyllum aquaticum) and a bed of floating plants (e.g., Lemna species) together with the hyperaccumulator, Phragmites australis. Whilst phytoremediation offers a promising option to treat contaminated water, several critical knowledge gaps still exist. The effect of co-exposure to contaminants on the accumulation potential of plants and the fate of antibiotic-resistant genes and bacteria during the phytoremediation process are highlighted in this review. Based on this understanding, targeted areas for future research are proposed.
Reduced CO2 footprint of buildings in agro-industrial communities in Qatar with improved insulation standards and solar cooling
Authors: Heithorst B. , Khan M. , Hassabou A. , Spinnler M. , Sattelmayer T.
Published: July 2023

Food production in arid countries like Qatar is strongly linked to water and energy resources to grow plants or rear cattle in a protected and controlled environment. The high energy demand for air conditioning in agro-industrial communities leads to significant CO2 emissions. In a case-study on buildings that are typical in the agro-industrial sector, the reduction potential for these emissions is investigated. Therefore, greenhouses and community buildings with an insulation according to the Passivhaus standard and solar cooling with photovoltaic driven compression chillers are compared to conventional buildings.

An innovative solar cooling system is developed: Power is generated in hybrid photovoltaic / thermal collectors to enhance the electric efficiency of the photovoltaic cells and to deliver heat for food processing or other purposes at a high temperature level. A compression chiller model is designed, that is based on the experimentally determined performance of the refrigeration cycle for the harsh operating conditions in Qatar. Different refrigerants are compared regarding their cycle performance and Global Warming Potential.

A result of the study at hand is that greenhouses are very well suited for solar cooling since their cooling load is nearly congruent to photovoltaic power generation due to their low thermal inertia and radiative cooling during the night.

The case study reveals that an insulation according to the Passivhaus standard combined with the proposed solar cooling system reduces the CO2 emissions caused by the air conditioning of greenhouses by 98% and of residential buildings by 94.7% compared to conventional buildings and air conditioning systems.
Halogenated volatile anaesthetics for prolonged sedation in pediatric intensive care unit: first experience in two French pediatric intensive care units
Authors: Berger Léo , Soreze Yohan , Rambaud Jérome , Starck Julie , Levy Yael , Tissières Pierre , Miatello Jordi , Morin Luc , Léger Pierre-Louis
Published: July 2023

Objective

Sedation is necessary for patients to achieve comfort and safety, but prolonged sedation can lead to the need for increased doses, resulting in withdrawal syndrome and delayed extubation. Inhaled anaesthetics (IAs) may cause less withdrawal syndrome while providing similar sedative effects to intravenous agents. This study aims to describe the efficacy of halogenated IAs during prolonged sedation and identify any adverse effects on the PICU.

Design

This is a retrospective, bicentric cohort study.

Setting

The study was conducted at two PICUs in university hospitals in Paris between January 2018 and December 2020.

Patients

The study included 50 children (aged 2.2 years, [0.8–7.2]) who received prolonged sedation (> 72 h) and were sedated with volatile anaesthetics for at least 24 h.

Interventions

No interventions were performed.

Measurements and main results

The study found a statistically significant reduction in benzodiazepine dosages (μg/kg/h) (118 [62.5; 200] vs 80.0 [32.5; 120], p < 0.01). Similar results were observed for other hypnotics (ketamine 2.00 [1.00; 2.00] vs 1.50 [1.00; 2.00], p = 0.036, mg/kg/h; clonidine: 0.55 [0.35; 1.27] vs 0.20 [0.12; 0.43], p = 0.036, μg/kg/h). For opioids (μg/kg/h), no significant reduction in doses was observed 24 h after IA introduction (4 [1.00; 8.00] vs 4.00 [1.00; 6.70], p = 0.7). No major adverse effects were reported, although 26% of patients developed withdrawal syndrome.

Conclusions

Halogenated IAs appear to be a promising therapy to reduce the dosages of hypnotics and opioids used during prolonged sedations.
Criminal Politics and Botched Development in Contemporary Latin America
Authors: Feldmann Andreas E. , Luna Juan Pablo
Published: July 2023

This Element investigates the relationship between the narcotics industry and politics and assesses how it influences domestic political dynamics, including economic development prospects in Latin America. It argues that links between criminal organizations, politicians, and state agents give rise to criminal politics (i.e., the interrelated activity of politicians, organized crime actors, and state agents in pursuing their respective agendas and goals). Criminal politics is upending how countries function politically and, consequently, impacting the prospects and nature of their social and economic development. The Element claims that diverse manifestations of criminal politics arise depending on how different phases of drug-trafficking activity (e.g., production, trafficking, and money laundering) interact with countries' distinct politico-institutional endowments. The argument is probed through the systematic examination of four cases that have received scant attention in the specialized literature: Chile,Paraguay, Peru, and Uruguay.
The Publications of the Bedfordshire Historical Record Society Volume I
Authors: Austin William , Fowler G. Herbert , Page-Turner F. A.
Published: July 2023

Includes 'The Beauchamps, Barons of Bedford', by C. Gore Chambers and G. Herbert Fowler.
'Clerical Subsidies in the Archdeaconry of Bedford, 1390-2, 1400-1', by J. E. Brown.
'Domesday Notes', by G. Herbert Fowler.
 'A Lease of Caddington Manor in 1299', by C. Gore Chambers.
'Sir William Harper, Knt.', by F. A. Page-Turner.
'Early Charters of the Priory of Chicksand', by G. Herbert Fowler.
'Notes on Two Trades: (i) Strawplaiting, (ii) Brickmaking', by William Austin.
'The Bedford Eyre, 1202', by G. Herbert Fowler.
'Records of Northill College, No. I', by C. Gore Chambers.
Property in Land in South Bedfordshire, 1750-1832
Authors: Payne Ernest Oscar
Published: July 2023

In the first part of the book, based on his University of London PhD thesis, the author draws on the correspondence and other writings of Richard How of Aspley Guise (1727-1801?) to present a picture of life in the Bedfordshire village of Aspley Guise in the eighteenth century - the effect of land tax, poor rates, parish disputes and enclosure. The second part is a study of land transfers based on land tax assessments in Tilsworth, Sundon, Milton Byran, Billington, Aspley Guise, Whipsnade, Studham, Chalgrave, Harlington and Toddington. A chart shows the changes in land ownership in Tilsworth between 1797 and 1826.
Colonel John Okey 1606-1662
Authors: Tibbutt H. G.
Published: July 2023

John Okey was an Anabaptist, London merchant, Parliamentary soldier, active in Parliamentarian politics, a regicide and an MP for Bedfordshire in 1658. This book recounts his life against the backdrop of the Civil War and its aftermath. It draws on Okey’s letters to give a vivid first hand account of military campaigns. After he and other colonels published the Humble Petition of Several Colonels of the Army in 1654, for which he was disciplined and lost his commission, he retired to his estates in Bedfordshire. He lived in the Round House at Brogborough during the 1650s and his estates included the honour of Ampthill, the manor of Millbrook, Brogborough Park and Lodge and lands in Leighton Buzzard. During this period he was active in Bedfordshire affairs and as a Justice of the Peace. He may have been involved in the establishment of John Bunyan’s first Baptist church in Bedford.

After the Restoration he fled abroad, but was betrayed, arrested and returned to England where he was tried and executed as a regicide. Three contemporary accounts of Okey’s speech at his trial are printed side by side, providing an interesting commentary on different methods of reporting - official, friendly and a newspaper account.
Risk management with local least squares Monte Carlo
Authors: Hainaut Donatien , Akbaraly Adnane
Published: July 2023

The least squares Monte Carlo method has become a standard approach in the insurance and financial industries for evaluating a company’s exposure to market risk. However, the non-linear regression of simulated responses on risk factors poses a challenge in this procedure. This article presents a novel approach to address this issue by employing an a-priori segmentation of responses. Using a K-means algorithm, we identify clusters of responses that are then locally regressed on their corresponding risk factors. The global regression function is obtained by combining the local models with logistic regression. We demonstrate the effectiveness of the proposed local least squares Monte Carlo method through two case studies. The first case study investigates butterfly and bull trap options within a Heston stochastic volatility model, while the second case study examines the exposure to risks in a participating life insurance scenario.
Petty bribery, pluralistic ignorance, and the collective action problem
Authors: Hoffmann Leena K. , Patel Raj N.
Published: July 2023

Bribery for access to public goods and services remains a widespread and seemingly innocuous practice which disproportionately targets the poor and helps keep them poor. Furthermore, its aggregate effects erode the legitimacy of government institutions and their capacity to fairly administer public goods and services as well as protection under the law. Drawing on original evidence using social norms methodology, this research tests underlying beliefs and expectations which sustain persistent forms of bribery and draws attention to the presence of pluralistic ignorance and consequent collective action problems. With examples focused on bribery in traffic law enforcement, healthcare, and education—three critical areas where bribery is often identified as an entrenched practice—this article contributes new evidence of: (a) the presence of pluralistic ignorance, a common social comparison error, surrounding bribery behavior; (b) differing social evaluations of bribe-solicitation; and finally, (c) how this context might exacerbate collective action problems. This empirical case study of Nigeria shows that even though more people are likely to be directly affected by bribery during routine interactions with public officials and institutions and many believe this practice is wrong, most people incorrectly believe that others in their community tolerate or even accept bribery behavior.
Dreams in Plutarch’sLivesof Alcibiades and Demosthenes
Authors: Catenaccio Claire
Published: July 2023

This article argues that theante mortemdreams of Alcibiades and Demosthenes articulate key themes of moral doubt in Plutarch’s biography of each man. Alcibiades’ dream of being dressed as a courtesan alludes to his uneasy stance between masculine and feminine postures; Demosthenes’ dream of himself as a failed tragic actor draws upon his lifelong concern with performance and insincerity. In these twoLives,Plutarch deploys the ambiguity and uncertainty of dreams to pose an interpretive problem for the reader which can never fully be resolved, particularly appropriate to these unpredictable and untrustworthy men.
Adaptive and iterative learning control to simultaneously control end-effector force and direction by normal vectors learning
Authors: Han Liang , Gao Yu , Huang Yunzhi , Xu Wenfu , He Lei
Published: July 2023

It is very challenging for robots to perform grinding and polishing tasks on surfaces with unknown geometry. Most existing methods solve this problem by modeling the relationship between the force sensing information and surface normal vectors by analyzing the forces on special end tools such as spherical tools and cylindrical tools and simplified friction model. In this paper, we propose a normal vectors learning method to simultaneously control end-effector force and direction on unknown surfaces. First, the relation that mapping the force sensing information to the surface normal vectors is learned from the demonstrated data on the known plane using locally weighted regression. Next, the learned relation is used to estimate surface normal vectors on the unknown surface. To improve the force control precision on the unknown geometry surface, the adaptive force control is developed. To improve the direction control precision due to friction, the iterative learning control is developed. The proposed method is verified by comparative simulations and experiments using the Franka robot. Results show that the end-effector can be controlled perpendicular to the surface with a certain force.
Stability in the integrated bilingual grammar: Tense exponency in North American Norwegian
Authors: Natvig David , Putnam Michael T. , Lykke Alexander K.
Published: July 2023

Decades of research on bilingual grammars corroborate the integrated nature of these systems, leading to the conjecture that these representations are ‘shared’ (Marian & Spivey 2003, Kroll & Gollan 2014, Putnam et al. 2018). A specific population of bilinguals, namelyheritage language speakers, shows a tendency for highly variable allomorphy (Polinsky 2018, Putnam et al. 2021); however, with this aspect of grammar that is often in a state of flux, there are instances of stability. Here we thoroughly investigate the stability of tense allomorphy of in North American Norwegian (NAmNo), a moribund heritage language spoken in the Upper Midwestern United States. Formally, we build upon initial observations provided by Lykke (2020), showing how a late-insertion approach to the syntax–phonological interface in combination withevents, features, and precedence(EFP) phonology (Raimy 2000, Papillon 2020, Idsardi 2022) provides a straightforward account of the structural complexities that determine exponency in bilingual grammars.
Impact of Heavy Snowfall on Emergency Transport and Prognosis of Out-of-Hospital Cardiac Arrest Patients: A Nation-Wide Cohort Study
Authors: Omatsu Kentaro , Uchiyama Mieko , Shimizu Utako , Ling Yiwei , Okuda Shujiro , Koyama Yu
Published: July 2023

Background:

Out-of-hospital cardiac arrest (OHCA) is a significant global cause of mortality, and Emergency Medical Services (EMS) response interval is critical for survival and a neurologically-favorable outcome. Currently, it is unclear whether EMS response interval, neurologically-intact survival, and overall survival differ between snowy and non-snowy periods at heavy snowfall areas.

Methods:

A nation-wide population-based cohort of OHCA patients, registered from 2017 through 2019 in the All-Japan Utstein Registry, was divided into four groups according to areas (heavy snowfall area or other area) and seasons (winter or non-winter): heavy snowfall-winter, heavy snowfall-non-winter, other area-winter, and other area-non-winter. The first coprimary outcome was EMS response interval, and the secondary coprimary outcome was one-month survival and a neurologically-favorable outcome at one month.

Results:

A total of 337,781 OHCA patients were divided into four groups: heavy snowfall-winter (N = 15,627), heavy snowfall-non-winter (N = 97,441), other area-winter (N = 32,955), and other area-non-winter (N = 191,758). Longer EMS response intervals (>13 minutes) were most likely in the heavy snowfall-winter group (OR = 1.86; 95% CI, 1.76 to 1.97), and also more likely in heavy snowfall areas in non-winter (OR = 1.44; 95% CI, 1.38 to 1.50). One-month survival in winter was worse not only in the heavy snowfall area (OR = 0.86; 95% CI, 0.78 to 0.94) but also in other areas (OR = 0.91; 95% CI, 0.87 to 0.94). One-month neurologically-favorable outcomes were also comparable between heavy snowfall-winter and other area-non-winter groups.

Conclusions:

This study showed OHCA in heavy snowfall areas in winter resulted in longer EMS response intervals. However, heavy snowfall had little effect on one-month survival or neurologically-favorable outcome at one month.
Incorporating Psychological Science Into Policy	Making
Authors: Kozyreva Anastasia , Smillie Laura , Lewandowsky Stephan
Published: July 2023

Abstract: The spread of false and misleading information in online social networks is a global problem in need of urgent solutions. It is also a policy problem because misinformation can harm both the public and democracies. To address the spread of misinformation, policymakers require a successful interface between science and policy, as well as a range of evidence-based solutions that respect fundamental rights while efficiently mitigating the harms of misinformation online. In this article, we discuss how regulatory and nonregulatory instruments can be informed by scientific research and used to reach EU policy objectives. First, we consider what it means to approach misinformation as a policy problem. We then outline four building blocks for cooperation between scientists and policymakers who wish to address the problem of misinformation: understanding the misinformation problem, understanding the psychological drivers and public perceptions of misinformation, finding evidence-based solutions, and co-developing appropriate policy measures. Finally, through the lens of psychological science, we examine policy instruments that have been proposed in the EU, focusing on the strengthened Code of Practice on Disinformation 2022.
The Psychological Impacts and Message Features of Health	Misinformation
Authors: Schmid Philipp , Altay Sacha , Scherer Laura D.
Published: July 2023

Abstract: What does health misinformation look like, and what is its impact? We conducted a systematic review of 45 articles containing 64 randomized controlled trials (RCTs; N = 37,552) on the impact of health misinformation on behaviors and their psychological antecedents. We applied a planetary health perspective by framing environmental issues as human health issues and focusing on misinformation about diseases, vaccination, medication, nutrition, tobacco consumption, and climate change. We found that in 49% of the cases exposure to health misinformation damaged the psychological antecedents of behaviors such as knowledge, attitudes, or behavioral intentions. No RCTs evaluated the impact of exposure to misinformation on direct measures of health or pro-environmental behaviors (e.g., vaccination), and few studies explored the impact of misinformation on feelings, social norms, and trust. Most misinformation was based on logical fallacies, conspiracy theories, or fake experts. RCTs evaluating the impact of impossible expectations and cherry-picking are scarce. Most research focused on healthy adult US populations and used online samples. Future RCTs can build on our analysis and address the knowledge gaps we identified.
Navigating Gender at Sea
Authors: McMonigal Kay , Evans Natalya , Jones Dani , Brett Jay , James Reece C. , Arroyo Mar C. , Gong A‐bel Y. , Miller Lee C. , Kelly Colette , Middleton Jule , Spear Chris , Holmes Wil , Lane Dakota
Published: July 2023

Fieldwork, including work done at sea, is a key component of many geoscientists' careers. Recent studies have highlighted the pervasive harassment faced by women and LGBTQ+ people during fieldwork. However, transgender and gender diverse (TGD) scientists face obstacles which have not yet been thoroughly examined. We fill this gap by sharing our experiences as TGD people. We have experienced sexual harassment, misconduct, privacy issues, and legal and medical struggles as we conduct seagoing work. In this work, we provide recommendations for individuals, cruise leaders, and institutions for making seagoing work safer for our communities.
Post‐Sunset Field‐Line Resonances at Equatorial Latitudes Observed by Swarm
Authors: Ghadjari Hossein , Knudsen David , Skone Susan
Published: July 2023

In this study employing data from the Swarm satellites at an altitude of ≈500 km, we present evidence of field‐line resonances (FLRs) in the Pc2‐3 (0.02–0.2 Hz) frequency band in the undisturbed post‐sunset region of the equatorial ionosphere. We identify 26 events extending to magnetic latitudes as low as 2°, which was previously thought to be too low for FLRs to exist due to ionospheric damping. Identification of FLRs is supported by a narrow‐band fundamental and first harmonics, an oscillating field‐aligned Poynting vector, a relative phase shift between E and δB of ≈90°, and in one case observation of one wave in conjugate hemispheres by two satellites separated by 4 min. We show that, contrary to the non‐uniform trend of ground‐based observations, the fundamental frequencies of these occurrences decline monotonically with increasing field‐line length. Their frequencies differ from those of ground‐based magnetometer observations reported in the literature.
Efferocytosis by bone marrow mesenchymal stromal cells disrupts osteoblastic differentiation via mitochondrial remodeling
Authors: Quarato Emily R. , Salama Noah A. , Li Allison J. , Smith Charles O. , Zhang Jane , Kawano Yuko , McArthur Matthew , Liesveld Jane L. , Becker Michael W. , Elliott Michael R. , Eliseev Roman A. , Calvi Laura M.
Published: July 2023

The efficient clearance of dead and dying cells, efferocytosis, is critical to maintain tissue homeostasis. In the bone marrow microenvironment (BMME), this role is primarily fulfilled by professional bone marrow macrophages, but recent work has shown that mesenchymal stromal cells (MSCs) act as a non-professional phagocyte within the BMME. However, little is known about the mechanism and impact of efferocytosis on MSCs and on their function. To investigate, we performed flow cytometric analysis of neutrophil uptake by ST2 cells, a murine bone marrow-derived stromal cell line, and in murine primary bone marrow-derived stromal cells. Transcriptional analysis showed that MSCs possess the necessary receptors and internal processing machinery to conduct efferocytosis, with Axl and Tyro3 serving as the main receptors, while MerTK was not expressed. Moreover, the expression of these receptors was modulated by efferocytic behavior, regardless of apoptotic target. MSCs derived from human bone marrow also demonstrated efferocytic behavior, showing that MSC efferocytosis is conserved. In all MSCs, efferocytosis impaired osteoblastic differentiation. Transcriptional analysis and functional assays identified downregulation in MSC mitochondrial function upon efferocytosis. Experimentally, efferocytosis induced mitochondrial fission in MSCs. Pharmacologic inhibition of mitochondrial fission in MSCs not only decreased efferocytic activity but also rescued osteoblastic differentiation, demonstrating that efferocytosis-mediated mitochondrial remodeling plays a critical role in regulating MSC differentiation. This work describes a novel function of MSCs as non-professional phagocytes within the BMME and demonstrates that efferocytosis by MSCs plays a key role in directing mitochondrial remodeling and MSC differentiation. Efferocytosis by MSCs may therefore be a novel mechanism of dysfunction and senescence. Since our data in human MSCs show that MSC efferocytosis is conserved, the consequences of MSC efferocytosis may impact the behavior of these cells in the human skeleton, including bone marrow remodeling and bone loss in the setting of aging, cancer and other diseases.
High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis
Authors: Cao Fang , Jiang Yunpeng , Chang Lin , Du Hongzhen , Chang De , Pan Chunxiao , Huang Xiaozheng , Yu Donglin , Zhang Mi , Fan Yongna , Bian Xiaocui , Li Kailong
Published: July 2023

Pancreatic cancer is a leading cause of cancer death due to its early metastasis and limited response to the current therapies. Metastasis is a complicated multistep process, which is determined by complex genetic alterations. Despite the identification of many metastasis-related genes, distinguishing the drivers from numerous passengers and establishing the causality in cancer pathophysiology remains challenging. Here, we established a high-throughput and piggyBac transposon-based genetic screening platform, which enables either reduced or increased expression of chromosomal genes near the incorporation site of the gene search vector cassette that contains a doxycycline-regulated promoter. Using this strategy, we identified YWHAZ as a key regulator of pancreatic cancer metastasis. We demonstrated that functional activation of Ywhaz by the gene search vector led to enhanced metastatic capability in mouse pancreatic cancer cells. The metastasis-promoting role of YWHAZ was further validated in human pancreatic cancer cells. Overexpression of YWHAZ resulted in more aggressive metastatic phenotypes in vitro and a shorter survival rate in vivo by modulating epithelial-to-mesenchymal transition. Hence, our study established a high-throughput screening method to investigate the functional relevance of novel genes and validated YWHAZ as a key regulator of pancreatic cancer metastasis.
The complete and fully-phased diploid genome of a male Han Chinese
Authors: Yang Chentao , Zhou Yang , Song Yanni , Wu Dongya , Zeng Yan , Nie Lei , Liu Panhong , Zhang Shilong , Chen Guangji , Xu Jinjin , Zhou Hongling , Zhou Long , Qian Xiaobo , Liu Chenlu , Tan Shangjin , Zhou Chengran , Dai Wei , Xu Mengyang , Qi Yanwei , Wang Xiaobo , Guo Lidong , Fan Guangyi , Wang Aijun , Deng Yuan , Zhang Yong , Jin Jiazheng , He Yunqiu , Guo Chunxue , Guo Guoji , Zhou Qing , Xu Xun , Yang Huanming , Wang Jian , Xu Shuhua , Mao Yafei , Jin Xin , Ruan Jue , Zhang Guojie
Published: July 2023

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere. Outside the centromere, we discovered 11,413 structural variations, including numerous novel ones. We also detected thousands of CN1 alleles that have accumulated high substitution rates and a few that have been under positive selection in the East Asian population. Further, we found that CN1 outperforms CHM13 as a reference genome in mapping and variant calling for the East Asian population owing to the distinct structural variants of the two references. Comparison of SNP calling for a large cohort of 8869 Chinese genomes using CN1 and CHM13 as reference respectively showed that the reference bias profoundly impacts rare SNP calling, with nearly 2 million rare SNPs miss-called with different reference genomes. Finally, applying the CN1 as a reference, we discovered 5.80 Mb and 4.21 Mb putative introgression sequences from Neanderthal and Denisovan, respectively, including many East Asian specific ones undetected using CHM13 as the reference. Our analyses reveal the advances of using CN1 as a reference for population genomic studies and paleo-genomic studies. This complete genome will serve as an alternative reference for future genomic studies on the East Asian population.
X-linked intellectual disability related to a novel variant of KLHL15
Authors: Kido Jun , Egami Kimiyasu , Misumi Yohei , Sugawara Keishin , Tsuchida Naomi , Matsumoto Naomichi , Ueda Mitsuharu , Nakamura Kimitoshi
Published: July 2023

Kelch-like (KLHL) 15, localized on chromosome Xp22.11, was recently identified as an X-linked intellectual disability gene. Herein, we report a case of a male patient with a novel nonsense variant, c.736 C > T p.(Arg246*), in KLHL15, who presented with impaired intelligence, short stature, frequent hypoglycemia, and periodic fever. Patients with nonsense variants in KLHL15 may develop intellectual disabilities, minor skeletal anomalies, and facial dysmorphisms.
Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization
Authors: Berquez Marine , Chen Zhiyong , Festa Beatrice Paola , Krohn Patrick , Keller Svenja Aline , Parolo Silvia , Korzinkin Mikhail , Gaponova Anna , Laczko Endre , Domenici Enrico , Devuyst Olivier , Luciani Alessandro
Published: July 2023

Differentiation is critical for cell fate decisions, but the signals involved remain unclear. The kidney proximal tubule (PT) cells reabsorb disulphide-rich proteins through endocytosis, generating cystine via lysosomal proteolysis. Here we report that defective cystine mobilization from lysosomes through cystinosin (CTNS), which is mutated in cystinosis, diverts PT cells towards growth and proliferation, disrupting their functions. Mechanistically, cystine storage stimulates Ragulator-Rag GTPase-dependent recruitment of mechanistic target of rapamycin complex 1 (mTORC1) and its constitutive activation. Re-introduction of CTNS restores nutrient-dependent regulation of mTORC1 in knockout cells, whereas cell-permeant analogues of L-cystine, accumulating within lysosomes, render wild-type cells resistant to nutrient withdrawal. Therapeutic mTORC1 inhibition corrects lysosome and differentiation downstream of cystine storage, and phenotypes in preclinical models of cystinosis. Thus, cystine serves as a lysosomal signal that tailors mTORC1 and metabolism to direct epithelial cell fate decisions. These results identify mechanisms and therapeutic targets for dysregulated homeostasis in cystinosis.
The RNA-binding protein LRPPRC promotes resistance to CDK4/6 inhibition in lung cancer
Authors: Zhou Wei , Wang Wenxi , Liang Yuxin , Jiang Ruibin , Qiu Fensheng , Shao Xiying , Liu Yang , Fang Le , Ni Maowei , Yu Chenhuan , Zhao Yue , Huang Weijia , Li Jiong , Donovan Michael J. , Wang Lina , Ni Juan , Wang Dachi , Fu Ting , Feng Jianguo , Wang Xiaojia , Tan Weihong , Fang Xiaohong
Published: July 2023

Kinase inhibitors against Cyclin Dependent Kinase 4 and 6 (CDK4/6i) are promising cancer therapeutic drugs. However, their effects are limited by primary or acquired resistance in virtually all tumor types. Here, we demonstrate that Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) controls CDK4/6i response in lung cancer by forming a feedback loop with CDK6. LRPPRC binds to CDK6-mRNA, increasing the stability and expression of CDK6. CDK6 and its downstream E2F Transcription Factor 1 (E2F1), bind to the LRPPRC promoter and elevate LRPPRC transcription. The activation of the LRPPRC-CDK6 loop facilitates cell cycle G1/S transition, oxidative phosphorylation, and cancer stem cell generation. Gossypol acetate (GAA), a gynecological medicine that has been repurposed as a degrader of LRPPRC, enhances the CDK4/6i sensitivity in vitro and in vivo. Our study reveals a mechanism responsible for CDK4/6i resistance and provides an enlightening approach to investigating the combinations of CDK4/6 and LRPPRC inhibitors in cancer therapy.
Instabilities of heavy magnons in an anisotropic magnet
Authors: Bai Xiaojian , Zhang Shang-Shun , Zhang Hao , Dun Zhiling , Phelan W. Adam , Garlea V. Ovidiu , Mourigal Martin , Batista Cristian D.
Published: July 2023

The search for new elementary particles is one of the most basic pursuits in physics, spanning from subatomic physics to quantum materials. Magnons are the ubiquitous elementary quasiparticle to describe the excitations of fully-ordered magnetic systems. But other possibilities exist, including fractional and multipolar excitations. Here, we demonstrate that strong quantum interactions exist between three flavors of elementary quasiparticles in the uniaxial spin-one magnet FeI2. Using neutron scattering in an applied magnetic field, we observe spontaneous decay between conventional and heavy magnons and the recombination of these quasiparticles into a super-heavy bound-state. Akin to other contemporary problems in quantum materials, the microscopic origin for unusual physics in FeI2is the quasi-flat nature of excitation bands and the presence of Kitaev anisotropic magnetic exchange interactions.
Association between cell-free DNA fetal fraction and pregnant character: a retrospective cohort study of 27,793 maternal plasmas
Authors: Hou Yaping , Yang Jiexia , Deng Fuli , Wang Fanghua , Peng Haishan , Guo Fangfang , Wang Dongmei , Yin Aihua
Published: July 2023

To determine the association between cell-free DNA fetal fraction (cffDNA) and various prenatal characters to better guide the clinical application of noninvasive prenatal screening (NIPS), a retrospective cohort study of 27,793 women with singleton pregnancies was conducted. Results indicated that no significant difference on cffDNA between trisomy/sex chromosome aneuploidy (SCA) and non-trisomy groups was found. However, the fetal fraction (FF) in the T18 and T13 subgroups were significantly lower than that in the non-trisomy group, while the FF in the T21 group was significantly higher than the non-trisomy group. Pearson’s correlation analysis revealed a positive correlation between √FF and gestational week in the T21, SCA, and non-trisomy groups. A negative correlation between maternal age and √FF in T21 and non-trisomy cases was found, but a positive correlation in SCA group. Compared to the decreasing trend in FF in the T21 group, no significant difference was observed in the SCA group. The √FF level was negatively correlated to maternal BMI in T21 and non-trisomy group, while a positive correlation in SCA group. FF was close related to the result of NIPS and related maternal factors. Though NIPS has increased accuracy, the complexity still should be recognized especially in clinical practice.
Gut dysbiosis in Thai intrahepatic cholangiocarcinoma and hepatocellular carcinoma
Authors: Pomyen Yotsawat , Chaisaingmongkol Jittiporn , Rabibhadana Siritida , Pupacdi Benjarath , Sripan Donlaporn , Chornkrathok Chidchanok , Budhu Anuradha , Budhisawasdi Vajarabhongsa , Lertprasertsuke Nirush , Chotirosniramit Anon , Pairojkul Chawalit , Auewarakul Chirayu U. , Ungtrakul Teerapat , Sricharunrat Thaniya , Phornphutkul Kannikar , Sangrajang Suleeporn , Loffredo Christopher A. , Harris Curtis C. , Mahidol Chulabhorn , Wang Xin Wei , Ruchirawat Mathuros ,   TIGER-LC Consortium
Published: July 2023

Primary liver cancer (PLC), which includes intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC), has the highest incidence of all cancer types in Thailand. Known etiological factors, such as viral hepatitis and chronic liver disease do not fully account for the country’s unusually high incidence. However, the gut-liver axis, which contributes to carcinogenesis and disease progression, is influenced by the gut microbiome. To investigate this relationship, fecal matter from 44 Thai PLC patients and 76 healthy controls were subjected to whole-genome metagenomic shotgun sequencing and then analyzed by marker gene-based and assembly based methods. Results revealed greater gut microbiome heterogeneity in iCCA compared to HCC and healthy controls. Two Veillonella species were found to be more abundant in iCCA samples and could distinguish iCCA from HCC and healthy controls. Conversely, Ruminococcus gnavus was depleted in iCCA patients and could distinguish HCC from iCCA samples. High Veillonella genus counts in the iCCA group were associated with enriched amino acid biosynthesis and glycolysis pathways, while enriched phospholipid and thiamine metabolism pathways characterized the HCC group with high Blautia genus counts. These findings reveal distinct landscapes of gut dysbiosis among Thai iCCA and HCC patients and warrant further investigation as potential biomarkers.
Spin-charge separation and quantum spin Hall effect of $$\beta$$-bismuthene
Authors: Tyner Alexander C. , Goswami Pallab
Published: July 2023

Multiple works suggest the possibility of classification of quantum spin Hall effect with magnetic flux tubes, which cause separation of spin and charge degrees of freedom and pumping of spin or Kramers-pair. However, the proof of principle demonstration of spin-charge separation is yet to be accomplished for realistic, ab initio band structures of spin-orbit-coupled materials, lacking spin-conservation law. In this work, we perform thought experiments with magnetic flux tubes on $$\beta$$
β
-bismuthene, and demonstrate spin-charge separation, and quantized pumping of spin for three insulating states, that can be accessed by tuning filling fractions. With a combined analysis of momentum-space topology and real-space response, we identify important role of bands supporting even integer invariants, which cannot be addressed with symmetry-based indicators. Our work sets a new standard for the computational diagnosis of two-dimensional, quantum spin-Hall materials by going beyond the $$\mathbb {Z}_{2}$$

Z
2

paradigm and providing an avenue for precise determination of the bulk invariant through computation of quantized, real-space response.
A study on the influencing factors and related paths of farmer’s participation in food safety governance—based on DEMATEL-ISM-MICMAC model
Authors: Xie Jie-Hui , Tian Fu-Jun , Li Xue-Yuan , Chen Yu-Qing , Li Shi-Yi
Published: July 2023

Farmers' participation in food safety governance is an important part of food safety social co-governance, and the accurate identification of its influencing factors and their related paths is of guiding significance to the scientific decision-making of food safety governance. The system of influencing factors of farmers' participation in food safety governance was constructed from four dimensions, and the influence network of each dimension was revealed by decision laboratory analysis (DEMATEL). The hierarchical structure and correlation path of influencing factors were determined by interpretive structural model (ISM), and the attributes of influencing factors were further classified by cross influence matrix multiplication (MICMAC). The results show that the influencing factors of farmers' participation in food safety governance can be divided into seven levels, among which the level of education and the status of village cadres are the fundamental characteristic factors. The degree of rural informatization, the intensity of government supervision, the promotion of village committees, the response of the government and the degree of disclosure of government information are the deep core factors, and risk cognition, political trust and family eating habits are special factors. Taking the importance and attribute status of farmers' participation in food safety governance into decision-making considerations is of great significance to improve the efficiency of food safety governance.
Molecular detection of human Plasmodium species using a multiplex real time PCR
Authors: Lazrek Yassamine , Florimond Célia , Volney Béatrice , Discours Manon , Mosnier Emilie , Houzé Sandrine , Pelleau Stéphane , Musset Lise
Published: July 2023

Molecular detection methods have revealed higher sensitivity and specificity than conventional microscopy or rapid diagnostic tests for malaria diagnosis. In this study, we implemented, evaluated and validated according to the ISO 15,189 requirements, a multiplex real-time PCR assay to detect and identify the five human malaria parasites. DNA samples were extracted from whole blood or dried blood spots drawn from patients. Based on the External Quality Assessment (whole blood), this method shows 100% sensitivity and specificity. This PCR detected P. vivax up to 0.25 p/µl, P. falciparum and P. knowlesi up to 0.5 p/µl, P. ovale up to 1 p/µl and P. malariae up to 5 p/µl of blood. From blood spots (extraction from four punches), it detected P. vivax at 5 p/µl, P. falciparum, P. ovale and P. knowlesi at 20 p/µl and P. malariae at 125 p/µl. In conclusion, this quantitative PCR shows excellent performance, is easy to use and DNA saver. It is especially useful to actively screen large population groups and identify the five human malaria parasites in a context of low malaria transmission.
A 1500-year record of mercury isotopes in seal feces documents sea ice changes in the Antarctic
Authors: Liu Hongwei , Zheng Wang , Bergquist Bridget A. , Gao Yuesong , Yue Fange , Yang Lianjiao , Sun Liguang , Xie Zhouqing
Published: July 2023

Temporal and spatial variations in sea ice coverage at high Northern Hemisphere latitudes have been shown to affect the photodegradation of methylmercury in seawater and the mercury isotope signatures in biological samples, suggesting the potential of mercury isotopes to reconstruct sea ice variability. Here we study the mercury isotopic composition of a 1500-year sediment profile strongly affected by seal activities on the Fildes Peninsula, King George Island, Antarctic Peninsula. The mass independent isotope fractionation of mercury (represented by Δ199Hg) in sediments dominated by seal feces input reflects the Δ199Hg of marine methylmercury before entering the food web, documenting the changes in the degree of photodemethylation. We found much higher Δ199Hg in sediments deposited during a warm period (~700-1000 years ago), suggesting that reduced sea ice promoted greater photodemethylation. Thus, this study demonstrates the modulation of methylmercury photodegradation by sea ice in the Antarctic, and that mercury isotopes can record historical sea ice changes.
Engineering cuboctahedral N-doped C-coated p-CuO/n-TiO2 heterojunctions toward high-performance photocatalytic cross-dehydrogenative coupling
Authors: Zhou Shuo , Shen Qiuyan , Yang Feng-Lei , Zhan Wenwen , Wang Xiaojun , Han Xiguang
Published: July 2023

A cuboctahedral N-doped C-coated CuO/TiO2 p–n heterojunction has been synthesized by directly calcining a benzimidazole-modulated HKUST-1 containing titanium ions. The nanocomposite shows outstanding photocatalytic activity toward CDC reactions.
Nanoparticles with transformable physicochemical properties for overcoming biological barriers
Authors: Lu Qianqian , Yu Hongyue , Zhao Tiancong , Zhu Guanjia , Li Xiaomin
Published: July 2023

The properties of nanoparticles, such as size, shape, surface properties,etc., can strongly affect their delivery efficacy. Here, the design and synthesis of nanoparticles with well-designed transformable physicochemical properties are reviewed.
Observation of positive trions in α-MoO3/MoS2 van der Waals heterostructures
Authors: Kumar Ravindra , Mishra Vikash , Dixit Tejendra , Barman Prahalad Kanti , Nayak Pramoda K. , Rao M. S. Ramachandra
Published: July 2023

vdW heterostructure of α-MoO3/MoS2 leads to formation of a quasiparticle (+ve trion) due to charge transfer from MoS2 to α-MoO3.
Combining photocatalytic collection and degradation of microplastics using self-asymmetric Pac-Man TiO2
Authors: Chattopadhyay Purnesh , Ariza-Tarazona Maria Camila , Cedillo-González Erika Iveth , Siligardi Cristina , Simmchen Juliane
Published: July 2023

Pac-Man TiO2 particles exhibit excellent photocatalytic properties. Degradation of highly reactive H2O2 leads to microscale propulsion, and the reactive oxygen species enable dye and polymer decomposition, even though at much slower time scales.