bluuebunny/crossref_metadata_2025 huggingface dataset:
SAP domain facilitates efficient loading of Ku onto DNA ends
Authors: Fulneček Jaroslav , Klimentová Eva , Cairo Albert , Bukovcakova Sona Valuchova , Alexiou Panagiotis , Prokop Zbynek , Riha Karel
Published: June 2023

Recognition and processing of DNA ends play a central role in maintaining genome integrity. The evolutionarily conserved DNA repair complex Ku serves as the primary sensor of free DNA ends in eukaryotic cells. Its rapid association with DNA ends is crucial for several cellular processes, including non-homologous end joining (NHEJ) DNA repair and telomere protection. In this study, we conducted a transient kinetic analysis to investigate the impact of the SAP domain on individual phases of the Ku-DNA interaction. Specifically, we examined the initial binding, the subsequent docking of Ku onto DNA, and the sliding of Ku along DNA. Our findings revealed that the C-terminal domain of Ku70, known as SAP ((SAF-A/B, Acinus and PIAS), facilitates the initial phases of Ku-DNA interaction, but does not affect the sliding process. This suggests that SAP may either establish the first interactions with DNA, or stabilize these initial interactions during loading. To assess the biological role of SAP, we generated Arabidopsis plants expressing Ku lacking the SAP domain (ΔSAP). Intriguingly, despite the decreased efficiency of the ΔSAP Ku complex in loading onto DNA, the mutant plants exhibited full proficiency in classical NHEJ and telomere maintenance. This indicates that the speed of Ku loading onto telomeres or DNA double-strand breaks (DSBs) is not the decisive factor in stabilizing these DNA structures.
Genetic atlas of hygro- and thermosensory cells in the vinegar flyDrosophilamelanogaster
Authors: Corthals Kristina , Andersson Vilma , Churcher Allison , Reimegård Johan , Enjin Anders
Published: June 2023

The ability of animals to perceive and respond to sensory information is essential for their survival in diverse environments. While much progress has been made in understanding various sensory modalities, the sense of hygrosensation, which involves the detection and response to humidity, remains poorly understood. In this study, we focused on the hygrosensory, and closely related thermosensory, systems in the vinegar flyDrosophila melanogasterto unravel the molecular profile of the cells of these senses. Using a transcriptomic analysis of over 37,000 nuclei, we identified twelve distinct clusters of cells corresponding to temperature-sensing arista neurons, humidity-sensing sacculus neurons, and support cells relating to these neurons. By examining the expression of known and novel marker genes, we validated the identity of these clusters and characterized their gene expression profiles. We found that each cell type could be characterized by a unique expression profile of ion channels, GPCR signaling molecules, synaptic vesicle cycle proteins, and cell adhesion molecules. Our findings provide valuable insights into the molecular basis of hygro- and thermosensation. Understanding the mechanisms underlying hygro- and thermosensation may shed light on the broader understanding of sensory systems and their adaptation to different environmental conditions in animals.
C2CAplus: a one-pot isothermal circle-to-circle DNA amplification system
Authors: Grasemann Laura , Pizarro Paula Thiel , Maerkl Sebastian J.
Published: June 2023

Rolling circle amplification (RCA) is a widely used DNA amplification method that uses circular template DNA as input and produces multimeric, linear single or double stranded DNA. Circle-to-circle amplification (C2CA) has further expanded this method by implementing product re-circularization using restriction and ligation, leading to a higher amplification yield, and enabling the generation of circular products. However, C2CA is a multistep, non-isothermal method, requiring multiple fluid manipulations and thereby compromises several advantages of RCA. Here, we improved C2CA to implement a one-pot, single step, isothermal reaction at temperatures ranging from 25 to 37°C. Our C2CAplus method is simple, robust, and produces large quantities of product DNA that can be seen with the naked eye.
Deep speech-to-text models capture the neural basis of spontaneous speech in everyday conversations
Authors: Goldstein Ariel , Wang Haocheng , Niekerken Leonard , Zada Zaid , Aubrey Bobbi , Sheffer Tom , Nastase Samuel A. , Gazula Harshvardhan , Schain Mariano , Singh Aditi , Rao Aditi , Choe Gina , Kim Catherine , Doyle Werner , Friedman Daniel , Devore Sasha , Dugan Patricia , Hassidim Avinatan , Brenner Michael , Matias Yossi , Devinsky Orrin , Flinker Adeen , Hasson Uri
Published: June 2023

Humans effortlessly use the continuous acoustics of speech to communicate rich linguistic meaning during everyday conversations. In this study, we leverage 100 hours (half a million words) of spontaneous open-ended conversations and concurrent high-quality neural activity recorded using electrocorticography (ECoG) to decipher the neural basis of real-world speech production and comprehension. Employing a deep multimodal speech-to-text model named Whisper, we develop encoding models capable of accurately predicting neural responses to both acoustic and semantic aspects of speech. Our encoding models achieved high accuracy in predicting neural responses in hundreds of thousands of words across many hours of left-out recordings. We uncover a distributed cortical hierarchy for speech and language processing, with sensory and motor regions encoding acoustic features of speech and higher-level language areas encoding syntactic and semantic information. Many electrodes—including those in both perceptual and motor areas—display mixed selectivity for both speech and linguistic features. Notably, our encoding model reveals a temporal progression from language-to-speech encoding before word onset during speech production and from speech-to-language encoding following word articulation during speech comprehension. This study offers a comprehensive account of the unfolding neural responses during fully natural, unbounded daily conversations. By leveraging a multimodal deep speech recognition model, we highlight the power of deep learning for unraveling the neural mechanisms of language processing in real-world contexts.
Protein engineering, production, reconstitution in lipid nanoparticles, and initial characterization of theMycobacterium tuberculosisEfpA drug exporter
Authors: Ishola Olamide , Ogunbowale Adeyemi , Islam Md Majharul , Hadadianpour Elaheh , Majeed Saman , Adetuyi Oluwatosin , Georgieva Elka R.
Published: June 2023

Mycobacterium tuberculosis(Mtb) drug exporters contribute an efficient mechanism for drug resistance. Therefore, understanding the structure–function relationship in these proteins is important. We focused on theMtbEfpA efflux pump, which belongs to the major facilitator superfamily (MSF) and transports anti-tuberculosis drugs outside the bacterial cell. Here, we report on our advancements in producing and characterization of this protein. We engineered a construct of apolipoprotein A-I (apoAI) fused to the N-terminus of EfpA (apoAI-EfpA) and cloned it in anE. coliexpression vector. This fusion construct was found in a membrane-bound form, unlike the deposited in inclusion bodies EfpA without apoAI. We purified the apoAI-EfpA in detergent to a sufficient degree and reconstituted it in DOPC/DOPS lipids. We found that upon reconstitution in lipid, the apoAI-EfpA forms discoidal protein-lipid nanostructures with a diameter of about 20 nm, resembling nanodiscs. We further detected apoAI-EfpA oligomers in β-DDM and lipid. To the best of our knowledge, this is the first complete protocol on the expression, purification, and lipid reconstitution of theMtbEfpA transported. AlphaFold2 also predicted EfpA oligomers and further bioinformatic analysis confirmed the earlier proposed 14-transmembrane helices of theMtbEfpA. We also found very high identity, >80%, among the EfpA-s of diversemycobacterialspecies. Outside ofmycobacteria, EfpA has no close homologues with only low identity with the QacA family of transporters. These findings possibly indicate high specificity of EfpA mechanisms. Our developments provide a foundation for more comprehensive in vitro studies on the EfpA exporter.
Hundreds of myosin 10s are pushed to the tips of filopodia and could cause traffic jams on actin
Authors: Shangguan Julia , Rock Ronald S
Published: June 2023

Myosin 10 (Myo10) is a motor protein known for its role in filopodia formation. Although Myo10-driven filopodial dynamics have been characterized, there is no information about the absolute number of Myo10 molecules during the filopodial lifecycle. To better understand molecular stoichiometries and packing restraints in filopodia, we measured Myo10 abundance in these structures. We combined SDS-PAGE densitometry with epifluorescence microscopy to quantitate HaloTag-labeled Myo10 in U2OS cells. About 6% of total intracellular Myo10 localizes to filopodia, where it enriches at opposite cellular ends. Hundreds of Myo10s are in a typical filopodium, and their distribution across filopodia is log-normal. Some filopodial tips even contain more Myo10 than accessible binding sites on the actin filament bundle. Live-cell movies reveal a dense cluster of over a hundred Myo10 molecules that initiates filopodial elongation. Hundreds of Myo10 molecules continue to accumulate during filopodial growth, but accumulation ceases when retraction begins. Rates of filopodial elongation, second-phase elongation, and retraction are inversely related to Myo10 quantities. Our estimates of Myo10 molecules in filopodia provide insight into the physics of packing Myo10, its cargo, and other filopodia-associated proteins in narrow membrane compartments. Our protocol provides a framework for future work analyzing Myo10 abundance and distribution upon perturbation.
Effects of policy and economic uncertainty on investment activities and corporate financial reporting: a study of developing countries in Asia-Pacific
Authors: Kurniawan Firdaus , Amanati Hilma Tsani , Nugroho Albertus Henri Listyanto , Pusparini Nandya Octanti
Published: June 2023

Purpose

This study investigates the impact of government and economic policy uncertainty (EPU) on companies' business operations, especially risk-taking tendencies and corporate financial reporting quality (FRQ).

Design/methodology/approach

The study employs the generalised least squares regression model. The final sample comprised 27,376 company-year observations from eight countries in the Asia-Pacific region.

Findings

EPU has a negative and significant effect on investment activity and FRQ. Higher EPU leads to a decline in investment and FRQ.

Research limitations/implications

There are several limitations in this study. First, the authors used abnormal investments to measure investments, without considering the degree of irreversibility investment objectives. Second, although control variables are included at the company and country levels, they may only partially control for companies' mitigation effects. Third, the sample is limited to developing countries with unique characteristics in Asia-Pacific; therefore, the findings cannot be generalised.

Practical implications

The findings can help investors, analysts and regulators evaluate EPU's impact on companies' business activities by offering an overview regarding the decline in investment efficiency and FRQ. The results can also be used as input for regulators in formulating policies that encourage companies to regulate investment levels without harming other stakeholders and maintain FRQ during periods of uncertainty.

Originality/value

This research provides intriguing insights into EPU's effects on companies' investment activity and FRQ in developing countries, which are sensitive to changes in macroeconomic conditions.
Exploring innovation deployment of construction contracting firms through the lens of exploratory–exploitative learning: a Hong Kong case study
Authors: Sumanarathna Nipuni , Duodu Bismark , Memon Shoeb Ahmed , Rowlinson Steve
Published: June 2023

Purpose

This study aims to explore the innovation deployment of construction contracting firms through exploratory–exploitative learning and organisational ambidexterity.

Design/methodology/approach

Firstly, a literature-based conceptual framework was developed to explain innovation implementation through exploratory–exploitative learning and organisational ambidexterity. A prominent Hong Kong construction contracting firm was then selected as the case study to explore its innovation deployment at different organisational levels (i.e. firm and project levels). Qualitative data were attained by conducting 12 semi-structured interviews with industry experts and document analysis. The thematic analysis using NVivo 12 software was adopted to analyse data.

Findings

Findings reveal that the case study firm successfully fosters innovation when ambidexterity is achieved through the balance between exploratory (i.e. radical innovation) and exploitative learnings (i.e. incremental innovation).

Research limitations/implications

Establishing uniform ambidexterity (i.e. 50:50) at the firm or project level is not mandatory to deploy innovation successfully. The ratio can vary based on the characteristics and requirements of construction firms.

Practical implications

This paper shall motivate construction practitioners to adopt radical–incremental innovation ambidexterity in firms and ultimately enhance the productivity and efficiency of the construction industry.

Originality/value

Previous construction innovation research has frequently explored firm or project-level innovation separately. This study identified a multi-level focus on innovation. Through the lens of exploratory–exploitative theory, different forms of innovation ambidexterity for different levels are suggested rather than one specific ambidexterity.
Not all innovation is prioritized: economic policy uncertainty, industry environmental, and firms' relative exploitative innovation emphasis
Authors: Zhong Xi , Ren Ge , Wu Xiaojie
Published: June 2023

Purpose

Economic policy uncertainty has increased around the world since the financial crisis of 2007–2008. While scholars have devoted a lot of time and energy to investigating the impact of economic policy uncertainty (EPU) on firm innovation, they have not reached consistent research conclusions. This study aimed to clarify the above research differences by exploring the impact of EPU on firms' relative exploitative innovation emphasis, so as to provide a more comprehensive and granular understanding of the relationship between EPU and firm innovation.

Design/methodology/approach

This study obtained 17,165 firm-year data points from 3,107 listed companies in China. It analyzed the above data with a fixed effects model. In addition, this study used an instrumental variables method to solve potential endogeneity problems.

Findings

Based on real options theory and contingency theory, the authors proposed and found that EPU has a significant positive effect on relative exploitative innovation emphasis. In addition, the authors proposed and found that this effect is more pronounced in industries with high technological uncertainty, low competitive intensity, and low state monopolization.

Originality/value

This study is the first to explore why firms prefer exploitative innovation over exploratory innovation from the perspective of EPU. In doing so, this study expands and enriches the EPU literature and the innovation literature. Furthermore, by introducing the moderating role of industry environment, this study deepens the authors' understanding of how complex interactions between industry and institutional environments work together to shape firm strategic choices, and especially firm innovation. Finally, the conclusions of this study have important practical implications for shareholders to take measures to balance exploitative innovation and exploratory innovation to achieve better development.
Exploring (r)evolutionary college-going literacies with immigrant youth in a youth participatory action research (YPAR) seminar
Authors: Filipiak Danielle , Caraballo Limarys
Published: June 2023

Purpose

This paper aims to examine critical, college-going identities and literacies of first-generation immigrant youth within a dual enrollment, youth participatory action research seminar.

Design/methodology/approach

This study is a qualitative case study drawn from a larger, critical ethnographic study.

Findings

Findings illustrate that youth’s multiple literacies, forged in a deliberately intergenerational and relational space, served as a powerful site of analysis as well as a means to disrupt restrictive definitions of success, supporting youth’s worldmaking amidst the construction and negotiation of new and critical “academic” identities grounded in the familial, cultural and historical knowledges that their inquiries surfaced.

Originality/value

This research attends to the transformative power afforded by humanizing collectives that center youth voices and perspectives, specifically those of first-generation immigrant students.
The status of open access repositories in the field of technology: insights from OpenDOAR
Authors: Wani Javaid Ahmad , Sofi Taseef Ayub , Sofi Ishrat Ayub , Ganaie Shabir Ahmad
Published: June 2023

Purpose

Open-access repositories (OARs) are essential for openly disseminating intellectual knowledge on the internet and providing free access to it. The current study aims to evaluate the growth and development of OARs in the field of technology by investigating several characteristics such as coverage, OA policies, software type, content type, yearly growth, repository type and geographic contribution.

Design/methodology/approach

The directory of OARs acts as the source for data harvesting, which provides a quality-assured list of OARs across the globe.

Findings

The study found that 125 nations contributed a total of 4,045 repositories in the field of research, with the USA leading the list with the most repositories. Maximum repositories were operated by institutions having multidisciplinary approaches. The DSpace and Eprints were the preferred software types for repositories. The preferred upload content by contributors was “research articles” and “electronic thesis and dissertations”.

Research limitations/implications

The study is limited to the subject area technology as listed in OpenDOAR; therefore, the results may differ in other subject areas.

Practical implications

The work can benefit researchers across disciplines and, interested researchers can take this study as a base for evaluating online repositories. Moreover, policymakers and repository managers could also get benefitted from this study.

Originality/value

The study is the first of its kind, to the best of the authors’ knowledge, to investigate the repositories of subject technology in the open-access platform.
Accessible heritage cities
Authors: Doan Tin , Nguyen Hai
Published: June 2023

Purpose

This viewpoint note aims to discuss the challenges and the suggestions of using assistive technologies to improve the accessibility for travellers with disabilities and their companions at heritage cities.

Design/methodology/approach

The viewpoint note used the narrative approach which conceptualised accessible tourism, challenges and solutions of using assistive technologies for improving the heritage cities visit experience of travellers with disabilities.

Findings

The viewpoint note discussed three challenges (physical, informational and attitudinal) and three approaches of accessible platform, navigation system, and accessible and interactive heritage interpretation solutions for accessible heritage cities.

Originality/value

The viewpoint note presents the expert opinion of authors who investigated the accessibility issue in heritage cities. The first author of this note is a person with disabilities who has been living and studying about experience of travellers with disabilities at many heritage cities. The other author is an expert in heritage tourism.
Generation Y’s behavioural usage of small businesses’ retail websites: gender difference
Authors: Lim Allen , Goi Chai Lee , Dell Peter , Goi Mei Teh
Published: June 2023

Purpose

To better understand continuities and changes in consumer behaviour, it is also important to examine the original antecedents of unified theory of acceptance and use of technology 2 (UTAUT2). Studying Generation Y is crucial for developing competitive online marketing strategies, as Generation Y plays a substantial role in online purchases. Therefore, this study aims to examine the actual use of small business websites based on the UTAUT2 among Generation Y.

Design/methodology/approach

A total of 375 valid questionnaires were collected via a systematic sampling among Generation Y in Canada. All participants in the study had at least a high school education, were internet and computer literate, and had purchased a good/service from the retail websites of Canadian small businesses.

Findings

The results show performance expectancy, hedonic motivation, social influence and habit have significant effects on behavioural intentions. The habit and behavioural intentions also have significant effects on actual usage of small businesses’ retail websites. Additionally, this study supported the significant difference between male and female UTAUT2 models.

Practical implications

The study examines how small retail businesses can attract and retain Generation Y customers by improving their website’s performance. Performance expectancy, hedonic motivation and social influence are significant factors in determining behavioral intention. Small businesses can enhance their website usability, design and content to increase customer satisfaction and loyalty. Hedonic motivation is crucial for Generation Y customers, who seek pleasure and excitement when visiting websites. Social influence is crucial for male customers, whereas performance expectancy, hedonic motivation and habit are more important for female customers. The study also suggests that Canadian governments should encourage online purchasing to increase the usage of small retail business websites.

Originality/value

This study provided few valuable insights into small businesses’ retail websites behavioural intentions and actual usage between males and females in Canada.
Determinants of patients' service choice in online health communities: an elaboration likelihood model perspective
Authors: Chen Yuangao , Liu Meng , Chen Mingjing , Wang Lu , Sun Le , Xuan Gang
Published: June 2023

Purpose

The purpose of this research paper is to explore the determinants of patients' service choices between telephone consultation and text consultation in online health communities (OHCs).

Design/methodology/approach

This study utilized an empirical model based on the elaboration likelihood model and examined the effect of information, regarding service quality (the central route) and service price (the peripheral route), using online health consultation data from one of the largest OHCs in China.

Findings

The logistic regression results indicated that both physician- and patient-generated information can influence the patients' service choices; service price signals will lead patients to cheaper options. However, individual motivations, disease risk and consulting experience change a patients' information processing regarding central and peripheral cues.

Originality/value

Previous researchers have investigated the mechanism of patient behavior in OHCs; however, the researchers have not focused on the patients' choices regarding the multiple health services provided in OHCs. The findings of this study have theoretical and practical implications for future researchers, OHC designers and physicians.
Climate change and food security at household level in the central dry zone in Myanmar
Authors: Zaw Aung Kyaw , Charoenratana Sayamol
Published: June 2023

Purpose

The central dry zone of Myanmar is a climatic risk area in which the inhabitants are experiencing food insecurity, demonstrating the link between water scarcity and climate risk in agricultural production. Households in the region face the challenge of developing adaptation strategies to cope with the impact of climate change on food security. This study aims to seek an effective climate change solution and analyse its impact on Myanmar's food security and household adaptation.

Design/methodology/approach

The authors draw on insights from mixed-method research using a qualitative method followed by quantitative methods. In the qualitative phase, the authors used purposive sampling with two focus group discussions and three stakeholder interviews. In the quantitative phase, data were collected from 102 face-to-face interviews with members of households selected from Pauk Township, Pakokku District, Magway Region, Myanmar. The household food insecurity access scale (HFIAS) was used in the analysis.

Findings

The HFIAS indicated that 13% of households have adapted to climate change. The study illustrates that climate change adaptation strategies in production activities are related to food insecurity. The results further demonstrated the effect of climate change on crops, which impacts debt, access to food, selling assets and urban migration. The findings also suggest that climate change adaptation to improve food security has played an important role in providing outside support, which leads to household food insecurity.

Originality/value

To the authors' best knowledge, the study is one of the first to use mixed-method research to investigate climate change, food security and household adaptation in the central dry zone of Myanmar.
Exploring the nexus of social support, work–life balance and life satisfaction in hybrid work scenario in learning organizations
Authors: Mishra Nidhi , Bharti Teena
Published: June 2023

Purpose

The purpose of this paper is to examine the nexus of social support (SS), work–life balance (WLB) and satisfaction with life (SWL) in hybrid work (HW) scenario in learning organizations.

Design/methodology/approach

The data were collected via questionnaire method from 531 employees working in learning organizations (IT/ITES sector) in India. The hypotheses were tested using hierarchical regression.

Findings

The findings of the study showed that HW was positively related to SS dimensions, WLB and SWL. Further, the study established the mediating role of SS between HW and WLB as well as WLB as a mediator between HW-SWL relationships.

Research limitations/implications

This study has certain limitations owing to the cross-sectional nature of the data and the specific sector under study. The findings have significant implications for policy making to determine the conditions under which both employees and organizations can benefit from HW. Further, the study has implications for uncertain and volatile environments as had been created by COVID-19 pandemic, where HW arrangements may not be a choice but become necessity.

Originality/value

This study contributes to the conservation of resources theory. It identifies the importance of true autonomy and flexibility for employees.
Cyanobacteria as a critical reservoir of the environmental antimicrobial resistome
Authors: Timms V. J. , Hassan K. A. , Pearson L. A. , Neilan B. A.
Published: June 2023

Antimicrobial resistance (AMR) is predicted to cause a worldwide annual toll of 10 million deaths by 2050. This looming public health threat has been linked to antibiotic overuse and pollution, which places selective pressures on AMR maintenance and transfer in and between microbial populations. We examined the distribution, diversity and potential mobility of AMR genes in cyanobacteria. While cyanobacteria are not pathogenic, we hypothesised that they could be a major environmental reservoir for AMR genes. Genes encoding AMR to seven antimicrobial drug classes were found in 10% of cyanobacterial genomes. AMR genes were found in 13% of freshwater, 19% of terrestrial, 34% of symbiotic, 2% of thermal spring, and 3% of marine genomes. AMR genes were found in five cyanobacterial orders with 23% of Nostocales and 8% of Oscillatoriales strains containing AMR genes. The most frequently observed alleles were ansamycin resistance genes, which were present in 7% of strains. AMR genes responsible for resistance to broad‐spectrum β‐lactams, chloramphenicols, tetracyclines, macrolides, and aminoglycosides were associated with mobile genetic elements or plasmid replicons or both. These results suggest that cyanobacteria are an extensive reservoir, and potential vector, for AMR genes in diverse terrestrial and aquatic habitats.
Enhancing the efficacy of instructing and adjusting information: An exploration of interactivity and vividness
Authors: Zhou Ziyuan , Zhang Xueying , Ki Eyun‐Jung
Published: June 2023

Instructing and adjusting information is required to protect stakeholders during a crisis. However, it is unwise to assume that people, especially young adults, automatically follow the information once it is provided. Using a 2 (interactivity: low [email] vs. high [mobile app]) × 2 (vividness: low [text‐only] vs. high [infographic]) between‐subject lab experiment, this study found that infographics were effective in improving self‐efficacy, proxy efficacy, and trust in the organization. In addition, an interaction was observed between interactivity and vividness on participants' intention to follow instructing and adjusting information. The findings of this study provide evidence of the advantage of using infographics during a crisis.
Climate elasticity assessment on groundwater recharge to the Edwards Balcones Fault Zone Aquifer, United States
Authors: Yang Changbing , Bertetti F. Paul
Published: June 2023

This study presents a comprehensive analysis of the characteristics of precipitation, temperature, and groundwater recharge in the recharge zone of the nine basins of the San Antonio segment of the Edwards Balcones Fault Zone Aquifer, which is one of the major groundwater systems in the United States and serves as primary water sources for approximately 1.7 million people in south‐central Texas. Datasets of monthly precipitation and average temperature (1895–2019) and groundwater recharge (1934–2019) are used to examine the decadal variability in precipitation, temperature, and groundwater recharge on the annual scale with a normalized 20‐year moving average of variance. Climate elasticity (precipitation and potential evapotranspiration) of groundwater recharge is estimated to evaluate impacts of climate change on groundwater recharge. The results of this study show that precipitation and temperature variability exhibit decadal cyclic patterns. Elasticity analysis of groundwater recharge indicates that a 1% change in annual precipitation may result in 2%, with a likely range of 0.15%–2.8%, change in groundwater recharge, and a 1% change in annual potential evapotranspiration may lead to −3.3% change in groundwater recharge with a likely range of −8.9% to 4% in the study area. This study suggests that climate elasticity of groundwater recharge may provide an alternative means for evaluating climate impacts on groundwater recharge to an aquifer.
Efficacy of lazertinib for symptomatic or asymptomatic brain metastases in treatment‐naive patients with advanced EGFR mutation‐positive non‐small cell lung cancer: Protocol of an open‐label, single‐arm phase II trial
Authors: Lee Bora , Ji Wonjun , Lee Jae Cheol , Song Si Yeol , Shin Young Seob , Cho Young Hyun , Park Ji Eun , Park Hyungjun , Choi Chang‐Min
Published: June 2023

Introduction

Non‐small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild‐type EGFR mutations. Osimertinib, a third‐generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR‐TKI sensitizing and T790M‐resistance mutations and has a higher brain penetration rate relative to first‐ and second‐generation EGFR‐TKIs. Therefore, osimertinib has become a preferred first‐line therapy for advanced EGFR mutation‐positive NSCLC. However, lazertinib, an emerging EGFR‐TKI, has shown higher selectivity toward EGFR mutations and improved penetration of the blood–brain barrier compared to osimertinib in preclinical studies. This trial will evaluate the efficacy of lazertinib as a first‐line therapy in patients with EGFR mutation‐positive NSCLC who have brain metastases, with or without additional local therapy.

Methods

This is a single‐center, open‐label, single‐arm phase II trial. A total of 75 patients with advanced EGFR mutation‐positive NSCLC will be recruited. Eligible patients will receive oral lazertinib 240 mg, once daily until disease progression or intolerable toxicity is detected. Patients with moderate to severe symptoms related to brain metastasis will simultaneously receive local therapy for the brain. The primary endpoints are progression‐free survival and intracranial progression‐free survival.

Discussion

Lazertinib, in combination with local therapy for the brain, if necessary, is expected to improve the clinical benefit in advanced EGFR mutation‐positive NSCLC with brain metastases, as a first‐line treatment.
Pyrroloquinoline quinone alleviates natural aging‐related osteoporosis via a novel MCM3‐Keap1‐Nrf2 axis‐mediated stress response and Fbn1 upregulation
Authors: Li Jie , Zhang Jing , Xue Qi , Liu Boyang , Qin Ran , Li Yiping , Qiu Yue , Wang Rong , Goltzman David , Miao Dengshun , Yang Renlei
Published: June 2023

Age‐related osteoporosis is associated with increased oxidative stress and cellular senescence. Pyrroloquinoline quinone (PQQ) is a water‐soluble vitamin‐like compound that has strong antioxidant capacity; however, the effect and underlying mechanism of PQQ on aging‐related osteoporosis remain unclear. The purpose of this study was to investigate whether dietary PQQ supplementation can prevent osteoporosis caused by natural aging, and the potential mechanism underlying PQQ antioxidant activity. Here, we found that when 6‐month‐old or 12‐month‐old wild‐type mice were supplemented with PQQ for 12 months or 6 months, respectively, PQQ could prevent age‐related osteoporosis in mice by inhibiting osteoclastic bone resorption and stimulating osteoblastic bone formation. Mechanistically, pharmmapper screening and molecular docking studies revealed that PQQ appears to bind to MCM3 and reduces its ubiquitination‐mediated degradation; stabilized MCM3 then competes with Nrf2 for binding to Keap1, thus activating Nrf2‐antioxidant response element (ARE) signaling. PQQ‐induced Nrf2 activation inhibited bone resorption through increasing stress response capacity and transcriptionally upregulating fibrillin‐1 (Fbn1), thus reducing Rankl production in osteoblast‐lineage cells and decreasing osteoclast activation; as well, bone formation was stimulated by inhibiting osteoblastic DNA damage and osteocyte senescence. Furthermore, Nrf2 knockout significantly blunted the inhibitory effects of PQQ on oxidative stress, on increased osteoclast activity and on the development of aging‐related osteoporosis. This study reveals the underlying mechanism of PQQ's strong antioxidant capacity and provides evidence for PQQ as a potential agent for clinical prevention and treatment of natural aging‐induced osteoporosis.
Early response of herbaceous vegetation toRhododendron ponticumsubsp.baeticuminvasion in European Atlantic forests
Authors: Casati Marion , Spicher Fabien , Kichey Thomas , Decocq Guillaume
Published: June 2023

Questions

Rhododendron ponticumsubsp.baeticumis an invasive shrub of growing concern in continental Europe, but little is known about its impact on native plant communities. Here we ask: do environmental conditions differ between forest stands invaded by it and uninvaded stands? Do these differences correlate withR. ponticum's cover? Are these differences associated with differences in taxonomic and functional diversity of vascular plant species of the herb layer? Can these vegetation changes be explained by the sorting of certain life‐history traits byR. ponticum‐induced environmental changes?

Location

Several forests invaded byR. ponticumin the French Atlantic domain.

Methods

We recorded vegetation composition and a number of environmental variables in 400‐m2plots that were established in 64 paired forest stands (32 invaded vs 32 uninvaded). We compiled traits from existing databases. We computed several metrics of taxonomic and functional diversity. We compared environmental variables and diversity metrics between invaded and uninvaded stands. We used correlation and regression analyses to relate them withR. ponticum's cover. We ran RLQ and fourth‐corner analyses to explore the relationships betweenR. ponticuminvasion, environmental variables, species traits, and vegetation composition.

Results

Independent of its abundance,R. ponticuminvasion was associated with lower light arrival at the forest floor and increased litter thickness. Concomitantly, species richness and diversity and trait diversity were reduced. The major driver of species assemblages was soil pH, which strongly interacted with the invasion gradient.R. ponticumdid not sort species according to traits associated with shade tolerance and thick‐litter tolerance. However, tree and shrub saplings were more abundant in invaded than uninvaded stands, at the expense of graminoid and fern species.

Conclusions

AsR. ponticumbecomes the dominant shrub, it exerts new selection forces on life‐history traits of extant species, mostly via reduced light availability, increased litter thickness, and physical competition, thereby reducing taxonomic and functional diversity of the herb layer, without impeding tree and shrub self‐regeneration, at least in the short term.
Transformative medical ethics: A framework for changing practice according to normative–ethical requirements
Authors: Kuehlmeyer Katja , Jansky Bianca , Mertz Marcel , Marckmann Georg
Published: June 2023

We propose a step‐by‐step methodological framework of translational bioethics that aims at changing medical practice according to normative–ethical requirements, which we will thus call “transformative medical ethics.” The framework becomes especially important when there is a gap between widely acknowledged, ethically justified normative claims and their realization in the practice of biomedicine and technology (ought–is gap). Building on prior work on translational bioethics, the framework maps a process with six different phases and 12 distinct translational steps. The steps involve various research activities including conceptual philosophical inquiry and (socio‐)empirical research. On the one hand, the framework can be used as a heuristic tool to identify barriers to the transformation process. On the other hand, it can provide guidance for researchers and practitioners to develop appropriate (conceptual action and practice) models, which are then implemented and evaluated in specific practice contexts. We use the example of realizing the norm of respect for autonomy in the practice of medical decision‐making to illustrate the framework. Further research is required, for example, to theoretically underpin the framework, to apply it to other ought–is gaps, and to evaluate its feasibility and effectiveness in various practice areas. Overall, the framework of transformative medical ethics suggests a strategic process to investigate and promote practice change that is ethically informed in all phases.
Outcomes of haploidentical haematopoietic stem cell transplantation for adolescent and young adults with acute myeloid leukaemia
Authors: Huo Wen‐Xuan , Wen Qi , Zhang Xiao‐Hui , Xu Lan‐Ping , Wang Yu , Yan Chen‐Hua , Chen Huan , Chen Yu‐Hong , Han Wei , Wang Feng‐Rong , Wang Jing‐Zhi , Huang Xiao‐Jun , Mo Xiao‐Dong
Published: June 2023

We aimed to identify the efficacy of haploidentical related donor (HID) haematopoietic stem cell transplantation (HSCT) in adolescent and young adults (AYAs) with acute myeloid leukaemia (AML) in a large cohort. Consecutive AML AYAs (15–39 years old, n = 599) receiving HID HSCT in complete remission (CR) were included. The 3‐year cumulative incidence of measurable residual disease occurrence, relapse and non‐relapse mortality after HID HSCT was 28.6% (95% CI: 25.0–32.2), 11.6% (95% CI: 9.0–14.2) and 6.7% (95% CI: 4.7–8.7) respectively. The 3‐year probability of event‐free survival, leukaemia‐free survival (LFS) and overall survival (OS) after HID HSCT was 60.7% (95% CI: 56.9–64.8), 81.7% (95% CI: 78.7–84.9) and 85.6% (95% CI: 82.8–88.4) respectively. In multivariable analysis, AML risk category at diagnosis and comorbidity burdens before HID HSCT were independently associated with LFS and OS. Compared to the older adults (≥ 40 years, n = 355) with AML receiving HID HSCT in CR during the same time period, AYAs have a lower incidence of non‐relapse mortality and higher probabilities of LFS and OS. Thus, we firstly confirmed the safety and efficacy of HID HSCT in AYAs with AML‐CR.
Czechoslovakia and its Position within the Solidarity Network of Chilean Communism: A Reflection on the Coup and Resistance against Pinochet from a Country with Worn‐out Revolutionary Ideals
Authors: Zourek Michal
Published: June 2023

The article will analyse the development of the Chilean cause in the politics of Eastern Europe countries since 1973, focusing on the Czechoslovak case. On the one hand, it will prove that during the communist government Czechoslovakia played an important role in the international campaign for the resistance against the dictatorship at a worldwide level. On the other hand, it posits that the propaganda aimed at Czechoslovakia, which sought to kindle society's belief in the revolutionary ideals strongly affected after the Soviet invasion in 1968, turned out to be much less effective.
Labels and descriptions of dental behaviour support techniques: A scoping review of clinical practice guidelines
Authors: Mac Giolla Phadraig Caoimhin , Kammer Pedro Vitali , Asimakopoulou Koula , Healy Olive , Fleischmann Isabel , Buchanan Heather , Newton Jonathon Tim , Daly Blánaid , Posse Jacobo Limeres , Hosey Marie Therese , Yarascavitch Carilynne , MacAuley Yvonne , Stirling Chris , Ahmad Fisal Aisyah Binti , Nunn June
Published: June 2023

Introduction

There is no agreed taxonomy of the techniques used to support patients to receive professional oral healthcare. This lack of specification leads to imprecision in describing, understanding, teaching and implementing behaviour support techniques in dentistry (DBS).

Methods

This review aims to identify the labels and associated descriptors used by practitioners to describe DBS techniques, as a first step in developing a shared terminology for DBS techniques. Following registration of a protocol, a scoping review limited to Clinical Practice Guidelines only was undertaken to identify the labels and descriptors used to refer to DBS techniques.

Results

From 5317 screened records, 30 were included, generating a list of 51 distinct DBS techniques. General anaesthesia was the most commonly reported DBS (n = 21). This review also explores what term is given to DBS techniques as a group (Behaviour management was most commonly used (n = 8)) and how these techniques were categorized (mainly distinguishing between pharmacological and non‐pharmacological).

Conclusions

This is the first attempt to generate a list of techniques that can be selected for patients and marks an initial step in future efforts at agreeing and categorizing these techniques into an accepted taxonomy, with all the benefits this brings to research, education, practice and patients.
Mini‐VLAT: A Short and Effective Measure of Visualization Literacy
Authors: Pandey Saugat , Ottley Alvitta
Published: June 2023

The visualization community regards visualization literacy as a necessary skill. Yet, despite the recent increase in research into visualization literacy by the education and visualization communities, we lack practical and time‐effective instruments for the widespread measurements of people's comprehension and interpretation of visual designs. We present Mini‐VLAT, a brief but practical visualization literacy test. The Mini‐VLAT is a 12‐item short form of the 53‐item Visualization Literacy Assessment Test (VLAT). The Mini‐VLAT is reliable (coefficient omega = 0.72) and strongly correlates with the VLAT. Five visualization experts validated the Mini‐VLAT items, yielding an average content validity ratio (CVR) of 0.6. We further validate Mini‐VLAT by demonstrating a strong positive correlation between study participants' Mini‐VLAT scores and their aptitude for learning an unfamiliar visualization using a Parallel Coordinate Plot test. Overall, the Mini‐VLAT items showed a similar pattern of validity and reliability as the 53‐item VLAT. The results show that Mini‐VLAT is a psychometrically sound and practical short measure of visualization literacy.
xOpat: eXplainable Open Pathology Analysis Tool
Authors: Horák J. , Furmanová K. , Kozlíková B. , Brázdil T. , Holub P. , Kačenga M. , Gallo M. , Nenutil R. , Byška J. , Rusňák V.
Published: June 2023

Histopathology research quickly evolves thanks to advances in whole slide imaging (WSI) and artificial intelligence (AI). However, existing WSI viewers are tailored either for clinical or research environments, but none suits both. This hinders the adoption of new methods and communication between the researchers and clinicians. The paper presents xOpat, an open‐source, browser‐based WSI viewer that addresses these problems. xOpat supports various data sources, such as tissue images, pathologists' annotations, or additional data produced by AI models. Furthermore, it provides efficient rendering of multiple data layers, their visual representations, and tools for annotating and presenting findings. Thanks to its modular, protocol‐agnostic, and extensible architecture, xOpat can be easily integrated into different environments and thus helps to bridge the gap between research and clinical practice. To demonstrate the utility of xOpat, we present three case studies, one conducted with a developer of AI algorithms for image segmentation and two with a research pathologist.