bluuebunny/crossref_metadata_2025 huggingface dataset:
An overview of mindfulness theories applied to tourism: systematic review update and bibliometric analysis
Authors: Iacob Vivien , de Jesus Saúl Neves , Carmo Cláudia
Published: September 2023

This paper presents a systematic review update regarding mindfulness theories applied to tourism, complemented with a bibliometric analysis. Scientific studies listed in the WOS, SCOPUS, PubMed and PsycInfo databases were analysed using PRISMA guidelines. Twenty-five studies were selected for review from 670 records identified. In recent years, mindfulness has proved to be a promising area of research in tourism, and the number of published studies is increasing. The findings reveal a positive association between mindfulness and tourism experiences, suggesting that tourists who adopt states of mindfulness during their travels benefit from increased pro-environmental behaviours, satisfaction levels, and memorable experiences, leading to destination loyalty. This study provides an in-depth overview of the literature, and helps redress the lack of bibliometric studies in this field. It also identifies common areas of current research interest, offers insights into commonly studied themes, and seeks to raise awareness about the relevance of the concept of mindfulness in tourist experiences and well-being by suggesting implications for research and tourism management.
An overview of consensus models for group decision-making and group recommender systems
Authors: Tran Thi Ngoc Trang , Felfernig Alexander , Le Viet Man
Published: September 2023

Group decision-making processes can be supported by group recommender systems that help groups of users obtain satisfying decision outcomes. These systems integrate a consensus-achieving process, allowing group members to discuss with each other on the potential items, adapt their opinions accordingly, and achieve an agreement on a selected item. Such a process, therefore, helps to generate group recommendations with a high satisfaction level of group members. Our article provides a rigorous review of the existing consensus approaches to group decision-making. These approaches are classified depending on the applied consensus models such asreference domainwhere a set of group members or items is selected for calculating consensus measures,coincidence methodthat calculates the consensus degree between group members depending on the coincidence concept,operatorsthat aggregate user preferences,guidance measureswhere the consensus-achieving process is guided by different consensus measures, andrecommendation generationandindividual centralitythat enhance the role of a moderator or a leader in the consensus-achieving process. Further consensus techniques for group decision-making in heterogeneous and large-scale groups are also discussed in this article. Besides, to provide an overall landscape of consensus approaches, we also discuss new consensus models in group recommender systems. These models attempt to improve basic aggregation strategies, further consider social relationship interactions, and provide group members with intuitive descriptions regarding the current consensus state of the group. Finally, we point out challenges and discuss open topics for future work.
Estimation of Mean Velocity Upstream and Downstream of a Bridge Model Using Metaheuristic Regression Methods
Authors: Kisi Ozgur , Ardiçlioğlu Mehmet , Hadi Arzu M. W. , Kuriqi Alban , Kulls Christoph
Published: September 2023

This study compares four data-driven methods, Gaussian process regression (GPR), multivariate adaptive regression spline (MARS), M5 model tree (M5Tree), and multilinear regression (MLR), in estimating mean velocity upstream and downstream of bridges. Data were obtained through multiple experiments in a rectangular laboratory flume with glass walls 9.5 m long, 0.6 m wide, and 0.6 m deep. Four different bridge models were placed at the 6th meter of the channel to determine the average velocities upstream and downstream. Different data-driven models were implemented with different combinations of effective parameters as input. They were evaluated and compared using root mean square error (RMSE), mean absolute relative error (MARE), and Nash–Sutcliffe efficiency (NSE). The results showed that the MARS had the best efficiency in estimating the mean velocity upstream of the bridge model. At the same time, the M5Tree provided the highest performance in estimating the mean velocity downstream. The MARS method improved the estimation accuracy of GPR, M5Tree, and MLR in the test phase by 23.8%, 45.1%, and 47.4% concerning the RMSE at the upstream. The M5Tree provided better RMSE accuracy of 31.8%, 70.4%, and 75.5% at the downstream compared to MARS, GPR, and MLR, respectively. The study recommends the MARS and M5Tree for estimating mean velocities upstream and downstream of the bridge.
Electrochemical biostimulation of aerobic metabolic TCE degradation in a bioaugmentation approach
Authors: Hertle Steffen , de Boni Nick , Schell Heico , Tiehm Andreas
Published: September 2023

Chloroethenes are globally prevalent groundwater contaminants. Since 2014, TCE has been shown to be degradable in an aerobic metabolic process where it is used as sole energy source and growth substrate by a mixed bacteria culture (SF culture). In 2019, the SF culture was shown to be successfully used in bioaugmentation approaches under field-relevant conditions. In this study, a combined bio-/electro-approach to stimulate the TCE degradation by the SF culture was investigated in laboratory experiments. Column experiments were set up to compare a bioaugmentation approach with an electrochemical biostimulated bioaugmentation approach. Low strength direct current increased the amount of degraded TCE to about 150 % of the control. Through lowering the inflow concentration of oxygen, the effect of the electro-biostimulation in a low oxygen setting confirmed the potential of the bio-electro process for treatment of oxygen-deprived, TCE-contaminated sites.
Automated Gaze-Based Identification of Students’ Strategies in Histogram Tasks through an Interpretable Mathematical Model and a Machine Learning Algorithm
Authors: Boels Lonneke , Moreno-Esteva Enrique Garcia , Bakker Arthur , Drijvers Paul
Published: September 2023

As a first step toward automatic feedback based on students’ strategies for solving histogram tasks we investigated how strategy recognition can be automated based on students’ gazes. A previous study showed how students’ task-specific strategies can be inferred from their gazes. The research question addressed in the present article is how data science tools (interpretable mathematical models and machine learning analyses) can be used to automatically identify students’ task-specific strategies from students’ gazes on single histograms. We report on a study of cognitive behavior that uses data science methods to analyze its data. The study consisted of three phases: (1) using a supervised machine learning algorithm (MLA) that provided a baseline for the next step, (2) designing an interpretable mathematical model (IMM), and (3) comparing the results. For the first phase, we used random forest as a classification method implemented in a software package (Wolfram Research Mathematica, ‘Classify Function’) that automates many aspects of the data handling, including creating features and initially choosing the MLA for this classification. The results of the random forests (1) provided a baseline to which we compared the results of our IMM (2). The previous study revealed that students’ horizontal or vertical gaze patterns on the graph area were indicative of most students’ strategies on single histograms. The IMM captures these in a model. The MLA (1) performed well but is a black box. The IMM (2) is transparent, performed well, and is theoretically meaningful. The comparison (3) showed that the MLA and IMM identified the same task-solving strategies. The results allow for the future design of teacher dashboards that report which students use what strategy, or for immediate, personalized feedback during online learning, homework, or massive open online courses (MOOCs) through measuring eye movements, for example, with a webcam.
Contributions of Intraspecific Variation to Drought Tolerance in Trees
Authors: Gazol Antonio , Fajardo Alex , Camarero J. Julio
Published: September 2023

Purpose of Review

The capacity of woody plants to cope with climate change depends on their adjustments to changing environmental conditions by phenotypic plasticity or by genotypic changes (i.e., local adaptation). To determine whether intraspecific trait variation (ITV) translates into resistance or tolerance to drought and eventually how it relates to performance when facing drought, we reviewed the recent literature on the intraspecific variation in woody plant functional traits along aridity gradients.

Recent Findings

At the intraspecific level, functional traits vary along aridity gradients, but this variation depends on the considered trait and species. While ITV is ubiquitous and of relevant magnitude, its relationship with tree performance in the case of growth or survival is unclear and very idiosyncratic.

ITV varies along aridity gradients and, for several traits, is of comparable magnitude as interspecific trait variation. However, the relationship between ITV and tree performance is not consistent among species. This makes the use of ITV challenging when quantifying its contribution to drought tolerance.
Micro–Nano Water Film Enabled High-Performance Interfacial Solar Evaporation
Authors: Yu Zhen , Su Yuqing , Gu Ruonan , Wu Wei , Li Yangxi , Cheng Shaoan
Published: September 2023

Interfacial solar evaporation holds great promise to address the freshwater shortage. However, most interfacial solar evaporators are always filled with water throughout the evaporation process, thus bringing unavoidable heat loss. Herein, we propose a novel interfacial evaporation structure based on the micro–nano water film, which demonstrates significantly improved evaporation performance, as experimentally verified by polypyrrole- and polydopamine-coated polydimethylsiloxane sponge. The 2D evaporator based on the as-prepared sponge realizes an enhanced evaporation rate of 2.18 kg m−2 h−1 under 1 sun by fine-tuning the interfacial micro–nano water film. Then, a homemade device with an enhanced condensation function is engineered for outdoor clean water production. Throughout a continuous test for 40 days, this device demonstrates a high water production rate (WPR) of 15.9–19.4 kg kW−1 h−1 m−2. Based on the outdoor outcomes, we further establish a multi-objective model to assess the global WPR. It is predicted that a 1 m2 device can produce at most 7.8 kg of clean water per day, which could meet the daily drinking water needs of 3 people. Finally, this technology could greatly alleviate the current water and energy crisis through further large-scale applications.
Artificial Intelligence-Enabled Mode-Locked Fiber Laser: A Review
Authors: Ma Qiuying , Yu Haoyang
Published: September 2023

Owing to their compactness, robustness, low cost, high stability, and diffraction-limited beam quality, mode-locked fiber lasers play an indispensable role in micro/nanomanufacturing, precision metrology, laser spectroscopy, LiDAR, biomedical imaging, optical communication, and soliton physics. Mode-locked fiber lasers are a highly complex nonlinear optical system, and understanding the underlying physical mechanisms or the flexible manipulation of ultrafast laser output is challenging. The traditional research paradigm often relies on known physical models, sophisticated numerical calculations, and exploratory experimental attempts. However, when dealing with several complex issues, these traditional approaches often face limitations and struggles in finding effective solutions. As an emerging data-driven analysis and processing technology, artificial intelligence (AI) has brought new insights into the development of mode-locked fiber lasers. This review highlights the areas where AI exhibits potential in accelerating the development of mode-locked fiber lasers, including nonlinear dynamics prediction, ultrashort pulse characterization, inverse design, and automatic control of mode-locked fiber lasers. Furthermore, the challenges and potential future development are discussed.
Genetische Analyse beim Prostatakarzinom – wer darf was machen?
Authors: Hassler Melanie R.
Published: September 2023

Genetische Analysen an Patienten mit fortgeschrittenem Prostatakrebs entwickelten sich in den letzten Jahren zu einem wichtigen Bestandteil der Diagnostik. Aufgrund der sensiblen Daten und potenziellen Auswirkungen auf Familienmitglieder bei Feststellung einer Disposition zu einer hereditären Krebserkrankung erließen sowohl Deutschland als auch Österreich gesetzliche Regelungen, um sicherzustellen, dass solche Analysen auf sichere, ethische und verantwortungsvolle Weise durchgeführt werden. Die Vorschriften in beiden Ländern sehen vor, dass sich die Betroffenen vor der Durchführung eines Gentests einer genetischen Beratung unterziehen und dass die Tests von zugelassenen Labors durchgeführt werden, welche die in den jeweiligen Gentestgesetzen festgelegten Qualitäts- und Sicherheitsstandards erfüllen. Obwohl es einige Unterschiede zwischen den rechtlichen Rahmenbedingungen in den beiden Ländern gibt, weisen sie viele Gemeinsamkeiten auf und sollen die Gesundheit und das Wohlbefinden von Personen schützen, die sich einer genetischen Analyse bei Prostatakrebs unterziehen.
Validation of a Fast LC-PDA Method for the Quantification of Cannabinoids in Commercial Tea Samples
Authors: Mouton Michaela , Gerber Minja , Van der Kooy Frank
Published: September 2023

Cannabis and cannabinoids are currently being used to treat a wide variety of medical conditions including, but not limited to, cancer, epilepsy, and pain management. Since the legalization of cannabis-containing (mainly cannabidiol) products, in many countries, and the subsequent upsurge in the number of available commercial products, an increased need exists for a fast and reliable quality control method. Here, we describe the development and validation of a fast (7.5 min) and reliable method for the quantification of cannabidiol and tetrahydrocannabinol, and their respective acid precursors, cannabidiolic acid and tetrahydrocannabinolic acid, in ten commercial tea products using LC-PDA. Due to the lipophilic nature of cannabinoids, all tea samples were also prepared according to the manufacturer’s recommendations and analyzed with the validated method. By extracting the tea samples with acetonitrile, it was found that the actual cannabidiol content in all products tested deviated significantly from their label claims by having as much as 80% less than claimed. By preparing the samples as described on the packaging, no cannabidiol could be detected, indicating that boiling or hot water fails to extract any significant amount of cannabidiol present in these products. It can therefore be concluded that based on the lipophilic nature of cannabidiol, very little to no cannabidiol will be consumed when these products are used as prescribed and therefore may nullify the various health claims made for these popular products.

Graphical Abstract
A causal roadmap for generating high-quality real-world evidence
Authors: Dang Lauren E. , Gruber Susan , Lee Hana , Dahabreh Issa J. , Stuart Elizabeth A. , Williamson Brian D. , Wyss Richard , Díaz Iván , Ghosh Debashis , Kıcıman Emre , Alemayehu Demissie , Hoffman Katherine L. , Vossen Carla Y. , Huml Raymond A. , Ravn Henrik , Kvist Kajsa , Pratley Richard , Shih Mei-Chiung , Pennello Gene , Martin David , Waddy Salina P. , Barr Charles E. , Akacha Mouna , Buse John B. , van der Laan Mark , Petersen Maya
Published: September 2023

Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized trials with outcomes assessed using RWD to fully observational studies. Yet, many proposals for generating RWE lack sufficient detail, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. TheCausal Roadmapis an explicit, itemized, iterative process that guides investigators to prespecify study design and analysis plans; it addresses a wide range of guidance within a single framework. By supporting the transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on prespecified criteria, theRoadmapcan help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend theCausal Roadmapframework for use by clinical and translational researchers; three companion papers demonstrate applications of theCausal Roadmapfor specific use cases.
A systematic investigation into the effect of roughness on self-propelled swimming plates
Authors: Massey J.M.O. , Ganapathisubramani B. , Weymouth G.D.
Published: September 2023

This study examines the effects of surface topography on the flow and performance of a self-propelled swimming (SPS) body. We consider a thin flat plate with an egg-carton roughness texture undergoing prescribed undulatory swimming kinematics at Strouhal number

$0.3$

and tail amplitude to length ratio

$0.1$

; we use plate Reynolds numbers

$Re=6$

, 12 and

$24\times 10^3$

, and focus on

$12\,000$

. As the roughness wavelength is decreased, we find that the undulation wave speed must be increased to overcome the additional drag from the roughness and maintain SPS. Correspondingly, the extra wave speed raises the power required to maintain SPS, making the swimmer less efficient. To decouple the roughness and the kinematics, we compare the rough plates to equivalent smooth cases by matching the kinematic conditions. We find that all but the longest roughness wavelengths reduce the required swimming power and the unsteady amplitude of the forces when compared to a smooth plate undergoing identical kinematics. Additionally, roughness can enhance flow enstrophy by up to 116 % compared to the smooth cases without a corresponding spike in forces; this suggests that the increased mixing is not due to increased vorticity production at the wall. Instead, the enstrophy is found to peak strongly when the roughness wavelength is approximately twice the boundary layer thickness over the

$Re$

range, indicating the roughness induces large-scale secondary flow structures that extend to the edge of the boundary layer. This study reveals the nonlinear interaction between roughness and kinematics beyond a simple increase or decrease in drag, illustrating that roughness studies on static shapes do not transfer directly to unsteady swimmers.
Perceptions of regional origin and social attributes of phonetic variants used in Iberian Spanish
Authors: Henriksen Nicholas , García-Amaya Lorenzo , Fischer Micha , Czapla Jessica , Dakki Natalie , Galvano Amber , Khansa Sarah , Maly Ellie G. , Phillips Zoe , Premkumar Vidhya , Topouzian Stepan , Wiaduck Thomas
Published: September 2023

Sociodemographic information, such as a speaker’s regional origin, is intimately related to the judgments and social evaluations that listeners assign to that speaker. This association between linguistic form and social information can also lead to linguistic profiling, a harmful form of discrimination. The present study examines the geographic classifications and social attitudes attributed to ten phonetic variants used within regional varieties of Iberian (i.e., European) Spanish. We are specifically interested in understanding listeners’ geographical classifications and language attitudes held toward Andalusian Spanish, which is a less privileged regional variety spoken in Spain’s southern region, as compared to north-central Peninsular Spanish (NCPS). The results of an online survey show that 165 listeners were fairly consistent when geographically classifying Andalusian-sounding stimuli as originating from the south of Spain. Importantly, the respondents also attributed less favorable social meaning to the Andalusian-sounding stimuli in comparison to the NCPS-sounding stimuli. We link the findings to broader themes in sociolinguistics, such as language-based discrimination, linguistic insecurity, and the social motivations of language change.
Using morphological, chemical, and molecular data to study the diversity of Xanthoparmelia species from South Africa (Ascomycota, Parmeliaceae)
Authors: Barcenas-Peña Alejandrina , Sipman Harrie J. M. , Wirth Volkmar , Grewe Felix , Lumbsch H. Thorsten
Published: September 2023

There is still a high diversity of lichen-forming fungi that remains undescribed, especially cryptic lineages at the species level. Integrating morphological, chemical, and DNA sequence data has proved useful in corroborating species descriptions and delimitations. Here we reviewed morphological features, secondary metabolites and the DNA sequences of ITS, mtSSU and nuLSU markers to study the diversity of Xanthoparmelia in southern Africa. A total of 37 species were recorded. Three of these appear undescribed, and we therefore describe them here as new: Xanthoparmelia nimisii, with a sorediate thallus and broad lobes, is well supported as a clade separate from X. annexa; X. pseudochalybaeizans with a white medulla is phylogenetically distinct from the otherwise similar X. chalybaeizans; and X. sipmaniana, well supported as a separate clade from the similar X. hypoprocetrarica. In addition, the separation of Xanthoparmelia capensis and X. tinctina requires further studies.
Nimisora (Lecanoraceae, Ascomycota), a new genus for a common lecideoid epiphytic species from the central Iberian Peninsula
Authors: Pérez-Ortega Sergio , Turégano Yolanda , Svensson Måns , Zamora Juan Carlos
Published: September 2023

The new genus Nimisora Pérez-Ort., M. Svenss. & J. C. Zamora is introduced to accommodate a puzzling lecideoid epiphyte common in the central Iberian Peninsula. Nimisora is characterized by the following combination of characters: lecideoid apothecia, excipulum composed of sparingly branched radiating hyphae with narrow lumina, thick walls and swollen terminal cells, the presence of a brown K+ olivaceous green pigment in the epihymenium, an ascus tip similar to the Bacidia-type, and the presence of simple ellipsoid ascospores. Molecular analyses based on nrITS, nrLSU and mtSSU sequences unequivocally place the new genus within the Lecanoraceae; however, its phylogenetic affinities with other genera of the family remain largely unresolved. Comparisons with the morphologically closest genera are provided. The single species of the genus, Nimisora iberica Pérez-Ort., Turégano, M. Svenss. & J. C. Zamora sp. nov., is also described as new to science.
From pets to plates: network analysis of trafficking in tortoises and freshwater turtles representing different types of demand
Authors: Sengottuvel Ramya Roopa , Mendis Aristo , Sultan Nazneen , Shukla Shivira , Chaudhuri Anirban , Mendiratta Uttara
Published: September 2023

Despite being protected under the law, illegal trade in tortoises and freshwater turtles is common in India, with different species being trafficked for different markets. Indian species of tortoises and hard-shell turtles are predominantly trafficked for the pet trade and soft-shell turtles for the meat trade. Given their distinct markets, the operation of trade may vary between these different groups of tortoises and freshwater turtles, thereby necessitating different types of interventions. However, a systematic examination of illegal trade in tortoises and freshwater turtles that takes into account the differences between these markets is currently lacking. Here we compare the supply networks of tortoises/hard-shell turtles (in demand for pet trade) vs soft-shell turtles (meat trade), using information from 78 and 64 seizures, respectively, that were reported in the media during 2013–2019. We used social network analysis to compare the two networks and the role of individual nodes (defined as locations at the district or city scale) within these networks. We found that the tortoise/hard-shell turtle network had a larger geographical scale, with more international trafficking links, than the soft-shell turtle network. We recorded convoluted smuggling routes in tortoise/hard-shell turtle trafficking, whereas soft-shell turtle trafficking was uni-directional from source to destination. Within both networks, we found that a few nodes played disproportionately important roles as key exporting, importing or transit nodes. Our study provides insights into the similarities and differences in the illegal supply networks of different groups of tortoises and freshwater turtles, in demand for different markets. We highlight the need for intervention strategies tailored to address the illegal trade in each of these groups.
Comparison of Empirical and Theoretical Models of the Thermospheric Density Enhancement During the 3–4 February 2022 Geomagnetic Storm
Authors: He Jianhui , Astafyeva Elvira , Yue Xinan , Pedatella Nicholas M. , Lin Dong , Fuller‐Rowell Timothy J. , Fedrizzi Mariangel , Codrescu Mihail , Doornbos Eelco , Siemes Christian , Bruinsma Sean , Pitout Frederic , Kubaryk Adam
Published: September 2023

On 3 February 2022, at 18:13 UTC, SpaceX launched and a short time later deployed 49 Starlink satellites at an orbit altitude between 210 and 320 km. The satellites were meant to be further raised to 550 km. However, the deployment took place during the main phase of a moderate geomagnetic storm, and another moderate storm occurred on the next day. The resulting increase in atmospheric drag led to 38 out of the 49 satellites reentering the atmosphere in the following days. In this work, we use both observations and simulations to perform a detailed investigation of the thermospheric conditions during this storm. Observations at higher altitudes, by Swarm‐A (∼438 km, 09/21 Local Time [LT]) and the Gravity Recovery and Climate Experiment Follow‐On (∼505 km, 06/18 LT) missions show that during the main phase of the storms the neutral mass density increased by 110% and 120%, respectively. The storm‐time enhancement extended to middle and low latitudes and was stronger in the northern hemisphere. To further investigate the thermospheric variations, we used six empirical and first‐principle numerical models. We found the models captured the upper and lower thermosphere changes, however, their simulated density enhancements differ by up to 70%. Further, the models showed that at the low orbital altitudes of the Starlink satellites (i.e., 200–300 km) the global averaged storm‐time density enhancement reached up to ∼35%–60%. Although such storm effects are far from the largest, they seem to be responsible for the reentry of the 38 satellites.
A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir
Authors: Zhang Yumin , Sun Yuan , Xie Yuanchao , Shang Weijuan , Wang Zhen , Jiang Hualiang , Shen Jingshan , Xiao Gengfu , Zhang Leike
Published: September 2023

During the ongoing pandemic, providing treatment consisting of effective, low-cost oral antiviral drugs at an early stage of SARS-CoV-2 infection has been a priority for controlling COVID-19. Although Paxlovid and molnupiravir have received emergency approval from the FDA, some side effect concerns have emerged, and the possible oral agents are still limited, resulting in optimized drug development becoming an urgent requirement. An oral remdesivir derivative, VV116, has been reported to have promising antiviral effects against SARS-CoV-2 and positive therapeutic outcomes in clinical trials. However, whether VV116 has broad-spectrum anti-coronavirus activity and potential synergy with other drugs is not clear. Here, we uncovered the broad-spectrum antiviral potency of VV116 against SARS-CoV-2 variants of concern (VOCs), HCoV-OC43, and HCoV-229E in various cell lines. In vitro drug combination screening targeted RdRp and proteinase, highlighting the synergistic effect of VV116 and nirmatrelvir on HCoV-OC43 and SARS-CoV-2. When co-administrated with ritonavir, the combination of VV116 and nirmatrelvir showed significantly enhanced antiviral potency with noninteracting pharmacokinetic properties in mice. Our findings will facilitate clinical treatment with VV116 or VV116+nirmatrelvir combination to fight coronavirus infection.
Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Authors: Gao Chao , Jiang Jingwen , Tan Yuyan , Chen Shengdi
Published: September 2023

Microglia activation is observed in various neurodegenerative diseases. Recent advances in single-cell technologies have revealed that these reactive microglia were with high spatial and temporal heterogeneity. Some identified microglia in specific states correlate with pathological hallmarks and are associated with specific functions. Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates and play detrimental roles due to excessive uptake of protein aggregates, which would lead to microglial phagocytic ability impairment, neuroinflammation, and eventually neurodegeneration. In addition, peripheral immune cells infiltration shapes microglia into a pro-inflammatory phenotype and accelerates disease progression. Microglia also act as a mobile vehicle to propagate protein aggregates. Extracellular vesicles released from microglia and autophagy impairment in microglia all contribute to pathological progression and neurodegeneration. Thus, enhancing microglial phagocytosis, reducing microglial-mediated neuroinflammation, inhibiting microglial exosome synthesis and secretion, and promoting microglial conversion into a protective phenotype are considered to be promising strategies for the therapy of neurodegenerative diseases. Here we comprehensively review the biology of microglia and the roles of microglia in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies and Huntington’s disease. We also summarize the possible microglia-targeted interventions and treatments against neurodegenerative diseases with preclinical and clinical evidence in cell experiments, animal studies, and clinical trials.
Tauopathy promotes spinal cord-dependent production of toxic amyloid-beta in transgenic monkeys
Authors: Tu Zhuchi , Yan Sen , Han Bofeng , Li Caijuan , Liang Weien , Lin Yingqi , Ding Yongyan , Wei Huiyi , Wang Lu , Xu Hao , Ye Jianmeng , Li Bang , Li Shihua , Li Xiao-Jiang
Published: September 2023

Tauopathy, characterized by the hyperphosphorylation and accumulation of the microtubule-associated protein tau, and the accumulation of Aβ oligomers, constitute the major pathological hallmarks of Alzheimer’s disease. However, the relationship and causal roles of these two pathological changes in neurodegeneration remain to be defined, even though they occur together or independently in several neurodegenerative diseases associated with cognitive and movement impairment. While it is widely accepted that Aβ accumulation leads to tauopathy in the late stages of the disease, it is still unknown whether tauopathy influences the formation of toxic Aβ oligomers. To address this, we generated transgenic cynomolgus monkey models expressing Tau (P301L) through lentiviral infection of monkey embryos. These monkeys developed age-dependent neurodegeneration and motor dysfunction. Additionally, we performed a stereotaxic injection of adult monkey and mouse brains to express Tau (P301L) via AAV9 infection. Importantly, we found that tauopathy resulting from embryonic transgenic Tau expression or stereotaxic brain injection of AAV-Tau selectively promoted the generation of Aβ oligomers in the monkey spinal cord. These Aβ oligomers were recognized by several antibodies to Aβ1–42 and contributed to neurodegeneration. However, the generation of Aβ oligomers was not observed in other brain regions of Tau transgenic monkeys or in the brains of mice injected with AAV9-Tau (P301L), suggesting that the generation of Aβ oligomers is species- and brain region-dependent. Our findings demonstrate for the first time that tauopathy can trigger Aβ pathology in the primate spinal cord and provide new insight into the pathogenesis and treatment of tauopathy.
Loss of PDE4D7 expression promotes androgen independence, neuroendocrine differentiation and alterations in DNA repair: implications for therapeutic strategies
Authors: Gulliver Chloe , Huss Sebastian , Semjonow Axel , Baillie George S. , Hoffmann Ralf
Published: September 2023

Background

Androgen signalling remains the seminal therapeutic approach for the management of advanced prostate cancer. However, most tumours eventually shift towards an aggressive phenotype, characterised by androgen independence and treatment resistance. The cyclic adenosine monophosphate (cAMP) pathway plays a crucial role in regulating various cellular processes, with the phosphodiesterase PDE4D7 being a vital modulator of cAMP signalling in prostate cancer cells.

Methods

Using shRNA-mediated PDE4D7 knockdown in LNCaP cells and downstream analysis via RNA sequencing and phenotypic assays, we replicate clinical observations that diminished PDE4D7 expression promotes an aggressive prostate cancer phenotype.

Results

Our study provides evidence that loss of PDE4D7 expression represents a pivotal switch driving the transition from an androgen-sensitive state to hormone unresponsiveness and neuroendocrine differentiation. In addition, we demonstrate that PDE4D7 loss affects DNA repair pathways, conferring resistance to poly ADP ribose polymerase (PARP) inhibitors.

Conclusion

Reinstating PDE4D7 expression sensitises prostate cancer cells to anti-androgens, DNA damage response inhibitors, and cytotoxic therapies. These findings provide significant insight into the regulatory role of PDE4D7 in the development of lethal prostate cancer and the potential of its modulation as a novel therapeutic strategy.
Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level
Authors: Atallah N. M. , Alsaleem M. , Toss M. S. , Mongan N. P. , Rakha E.
Published: September 2023

Background

Increasing data indicate that HER2-positive (HER2 + ) breast cancer (BC) subtypes exhibit differential responses to targeted anti-HER2 therapy. This study aims to investigate these differences and the potential underlying molecular mechanisms.

Methods

A large cohort of BC patients (n = 7390) was utilised. The clinicopathological characteristics and differential gene expression (DGE) of HER2+ immunohistochemical (IHC) subtypes, specifically HER2 IHC 3+ and IHC 2 + /Amplified, were assessed and correlated with pathological complete response (pCR) and survival in the neoadjuvant and adjuvant settings, respectively. The role of oestrogen receptor (ER) status was also investigated.

Results

Compared to HER2 IHC 3+ tumours, BC patients with IHC 2 + /Amplified showed a significantly lower pCR rate (22% versus 57%, P < 0.001), shorter survival regardless of HER2 gene copy number, were less classified as HER2 enriched, and enriched for trastuzumab resistance and ER signalling pathway genes. ER positivity significantly decreased response to anti-HER2 therapy in IHC 2 + /Amplified, but not in IHC 3 + BC patients.

Conclusion

In HER2 + BC, overexpression of HER2 protein is the driver of the oncogenic pathway, and it is the main predictor of response to anti-HER2 therapy. ER signalling pathways are more dominant in BC with equivocal HER2 expression. personalised anti-HER2 therapy based on IHC classes should be considered.
Seasonal pigment fluctuation in diploid and polyploid Arabidopsis revealed by machine learning-based phenotyping method PlantServation
Authors: Akiyama Reiko , Goto Takao , Tameshige Toshiaki , Sugisaka Jiro , Kuroki Ken , Sun Jianqiang , Akita Junichi , Hatakeyama Masaomi , Kudoh Hiroshi , Kenta Tanaka , Tonouchi Aya , Shimahara Yuki , Sese Jun , Kutsuna Natsumaro , Shimizu-Inatsugi Rie , Shimizu Kentaro K.
Published: September 2023

Long-term field monitoring of leaf pigment content is informative for understanding plant responses to environments distinct from regulated chambers but is impractical by conventional destructive measurements. We developed PlantServation, a method incorporating robust image-acquisition hardware and deep learning-based software that extracts leaf color by detecting plant individuals automatically. As a case study, we applied PlantServation to examine environmental and genotypic effects on the pigment anthocyanin content estimated from leaf color. We processed >4 million images of small individuals of fourArabidopsisspecies in the field, where the plant shape, color, and background vary over months. Past radiation, coldness, and precipitation significantly affected the anthocyanin content. The synthetic allopolyploidA. kamchaticarecapitulated the fluctuations of natural polyploids by integrating diploid responses. The data support a long-standing hypothesis stating that allopolyploids can inherit and combine the traits of progenitors. PlantServation facilitates the study of plant responses to complex environments termed “in natura”.
Manipulation of nonlinear optical responses in layered ferroelectric niobium oxide dihalides
Authors: Ye Liangting , Zhou Wenju , Huang Dajian , Jiang Xiao , Guo Qiangbing , Cao Xinyu , Yan Shaohua , Wang Xinyu , Jia Donghan , Jiang Dequan , Wang Yonggang , Wu Xiaoqiang , Zhang Xiao , Li Yang , Lei Hechang , Gou Huiyang , Huang Bing
Published: September 2023

Realization of highly tunable second-order nonlinear optical responses, e.g., second-harmonic generation and bulk photovoltaic effect, is critical for developing modern optical and optoelectronic devices. Recently, the van der Waals niobium oxide dihalides are discovered to exhibit unusually large second-harmonic generation. However, the physical origin and possible tunability of nonlinear optical responses in these materials remain to be unclear. In this article, we reveal that the large second-harmonic generation in NbOX2 (X = Cl, Br, and I) may be partially contributed by the large band nesting effect in different Brillouin zone. Interestingly, the NbOCl2 can exhibit dramatically different strain-dependent bulk photovoltaic effect under different polarized light, originating from the light-polarization-dependent orbital transitions. Importantly, we achieve a reversible ferroelectric-to-antiferroelectric phase transition in NbOCl2 and a reversible ferroelectric-to-paraelectric phase transition in NbOI2 under a certain region of external pressure, accompanied by the greatly tunable nonlinear optical responses but with different microscopic mechanisms. Our study establishes the interesting external-field tunability of NbOX2 for nonlinear optical device applications.
A conserved membrane protein negatively regulates Mce1 complexes in mycobacteria
Authors: Chen Yushu , Wang Yuchun , Chng Shu-Sin
Published: September 2023

Tuberculosis continues to pose a serious threat to global health. Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen that relies on various mechanisms to survive and persist within the host. Among their many virulence factors, mycobacteria encode Mce systems. Some of these systems are implicated in lipid uptake, but the molecular basis for Mce function(s) is poorly understood. To gain insights into the composition and architecture of Mce systems, we characterized the putative Mce1 complex involved in fatty acid transport. We show that the Mce1 system in Mycobacterium smegmatis comprises a canonical ATP-binding cassette transporter associated with distinct heterohexameric assemblies of substrate-binding proteins. Furthermore, we establish that the conserved membrane protein Mce1N negatively regulates Mce1 function via a unique mechanism involving blocking transporter assembly. Our work offers a molecular understanding of Mce complexes, sheds light on mycobacterial lipid metabolism and its regulation, and informs future anti-mycobacterial strategies.
Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection
Authors: Reid Madigan M. , Belayev Ludmila , Khoutorova Larissa , Mukherjee Pranab K. , Obenaus Andre , Shelvin Kierany , Knowles Stacey , Hong Sung-Ha , Bazan Nicolas G.
Published: September 2023

Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in the subcortex. Additionally, the FFAs elicit a comprehensive downregulation of inflammatory microglia/monocyte-derived macrophages and astrocyte-associated genes in the subcortical region. Functional analysis reveals inhibition of immune-related pathways and production of upstream molecules related to detrimental signaling events in post-stroke acute and subacute phases.
In vivo spectroscopy and machine learning for the early detection and classification of different stresses in apple trees
Authors: Prechsl Ulrich E. , Mejia-Aguilar Abraham , Cullinan Cameron B.
Published: September 2023

The use of in vivo spectroscopy to detect plant stress in its early stages has the potential to enhance food safety and reduce the need for plant protection products. However, differentiating between various stress types before symptoms appear remains poorly studied. In this study, we investigated the potential of Vis–NIR spectroscopy to differentiate between stress types in apple trees (Malus x domestica Borkh.) exposed to apple scab, waterlogging, and herbicides in a greenhouse. Using a spectroradiometer, we collected spectral signatures of leaves still attached to the tree and utilized machine learning techniques to develop predictive models for detecting stress presence and classifying stress type as early as 1–5 days after exposure. Our findings suggest that changes in spectral reflectance at multiple regions accurately differentiate various types of plant stress on apple trees. Our models were highly accurate (accuracies between 0.94 and 1) when detecting the general presence of stress at an early stage. The wavelengths important for classification relate to photosynthesis via pigment functioning (684 nm) and leaf water (~ 1800–1900 nm), which may be associated with altered gas exchange as a short-term stress response. Overall, our study demonstrates the potential of spectral technology and machine learning for early diagnosis of plant stress, which could lead to reduced environmental burden through optimizing resource utilization in agriculture.
Varied effects of tobacco smoke and e-cigarette vapor suggest that nicotine does not affect endothelium-dependent relaxation and nitric oxide signaling
Authors: Wölkart Gerald , Kollau Alexander , Russwurm Michael , Koesling Doris , Schrammel Astrid , Mayer Bernd
Published: September 2023

Chronic smoking causes dysfunction of vascular endothelial cells, evident as a reduction of flow-mediated dilation in smokers, but the role of nicotine is still controversial. Given the increasing use of e-cigarettes and other nicotine products, it appears essential to clarify this issue. We studied extracts from cigarette smoke (CSE) and vapor from e-cigarettes (EVE) and heated tobacco (HTE) for their effects on vascular relaxation, endothelial nitric oxide signaling, and the activity of soluble guanylyl cyclase. The average nicotine concentrations of CSE, EVE, and HTE were 164, 800, and 85 µM, respectively. At a dilution of 1:3, CSE almost entirely inhibited the relaxation of rat aortas and porcine coronary arteries to acetylcholine and bradykinin, respectively, while undiluted EVE, with a 15-fold higher nicotine concentration, had no significant effect. With about 50% inhibition at 1:2 dilution, the effect of HTE was between CSE and EVE. Neither extract affected endothelium-independent relaxation to an NO donor. At the dilutions tested, CSE was not toxic to cultured endothelial cells but, in contrast to EVE, impaired NO signaling and inhibited NO stimulation of soluble guanylyl cyclase. Our results demonstrate that nicotine does not mediate the impaired endothelium-dependent vascular relaxation caused by smoking.
Electric field stimulation unmasks a subtle role for T-type calcium channels in regulating lymphatic contraction
Authors: Davis Michael J. , Castorena-Gonzalez Jorge A. , Zawieja Scott D.
Published: September 2023

We previously identified two isoforms of T-type, voltage-gated calcium (Cav3) channels (Cav3.1, Cav3.2) that are functionally expressed in murine lymphatic muscle cells; however, contractile tests of lymphatic vessels from single and double Cav3 knock-out (DKO) mice, exhibited nearly identical parameters of spontaneous twitch contractions as wild-type (WT) vessels, suggesting that Cav3 channels play no significant role. Here, we considered the possibility that the contribution of Cav3 channels might be too subtle to detect in standard contraction analyses. We compared the sensitivity of lymphatic vessels from WT and Cav3 DKO mice to the L-type calcium channel (Cav1.2) inhibitor nifedipine and found that the latter vessels were significantly more sensitive to inhibition, suggesting that the contribution of Cav3 channels might normally be masked by Cav1.2 channel activity. We hypothesized that shifting the resting membrane potential (Vm) of lymphatic muscle to a more negative voltage might enhance the contribution of Cav3 channels. Because even slight hyperpolarization is known to completely silence spontaneous contractions, we devised a method to evoke nerve-independent, twitch contractions from mouse lymphatic vessels using single, short pulses of electric field stimulation (EFS). TTX was present throughout to block the potential contributions of voltage-gated Na+ channels in perivascular nerves and lymphatic muscle. In WT vessels, EFS evoked single contractions that were comparable in amplitude and degree of entrainment to those occurring spontaneously. When Cav1.2 channels were blocked or deleted, only small residual EFS-evoked contractions (~ 5% of normal amplitude) were present. These residual, EFS-evoked contractions were enhanced (to 10–15%) by the KATP channel activator pinacidil (PIN) but were absent in Cav3 DKO vessels. Our results point to a subtle contribution of Cav3 channels to lymphatic contractions that can be unmasked in the absence of Cav1.2 channel activity and when the resting Vm is more hyperpolarized than normal.