bluuebunny/crossref_metadata_2025_split huggingface dataset:
R&D Subsidies in Spain: are they Really Useful?
Authors: Rodríguez-Gutiérrez César , Canal-Domínguez Juan Francisco 
Published: July 2024

AbstractThis article is aimed at estimating the impact of R&D subsidies on the demand for researchers, using information provided by a panel of Spanish firms belonging to the industrial and services sectors followed up during the 2004–2016 period. Estimates include corrections for the endogeneity bias generated by wages and by a set of variables measuring R&D public financing, as well as for the sample selection bias coming from the fact that the only wage data available are those from firms that are internal R&D performers and hire researchers. Estimate results show that public R&D financing has a positive and relevant impact on the demand for researchers. This result allows supporting the implementation of policies to promote public research funding in Spain, regardless of the origin of the funds received.
Paclitaxel-loaded elastic liposomes synthesised by microfluidics technique for enhance transdermal delivery
Authors: Jaradat Eman , Meziane Adam , Lamprou Dimitrios A. 
Published: July 2024

Abstract
The inherent flexibility of elastic liposomes (EL) allows them to penetrate the small skin pores and reach the dermal region, making them an optimum candidate for topical drug delivery. Loading chemotherapy in ELs could improve chemotherapy’s topical delivery and localise its effect on skin carcinogenic tissues. Chemotherapy-loaded EL can overcome the limitations of conventional administration of chemotherapies and control the distribution to specific areas of the skin. In the current studies, Paclitaxel was utilised to develop Paclitaxel-loaded EL. As an alternative to the conventional manufacturing methods of EL, this study is one of the novel investigations utilising microfluidic systems to examine the potential to enhance and optimise the quality of Els by the microfluidics method. The primary aim was to achieve EL with a size of < 200 nm, high homogeneity, high encapsulation efficiency, and good stability. A phospholipid (DOPC) combined with neutral and anionic edge activators (Tween 80 and sodium taurocholate hydrate) at various lipid-to-edge activator ratios, was used for the manufacturing of the ELs. A preliminary study was performed to study the size, polydispersity (PDI), and stability to determine the optimum microfluidic parameters and lipid-to-edge activator for paclitaxel encapsulation. Furthermore, physiochemical characterisation was performed on the optimised Paclitaxel–loaded EL using a variety of methods, including Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy, Atomic force microscopy, elasticity, encapsulation efficiency, and In vitro release. The results reveal the microfluidics’ significant impact in enhancing the EL characteristics of EL, especially small and controllable size, Low PDI, and high encapsulation efficiency. Moreover, the edge activator type and concentration highly affect the EL characteristics. The Tween 80 formulations with optimised concentration provide the most suitable size and higher encapsulation efficiency. The release profile of the formulations showed more immediate release from the EL with higher edge activator concentration and a higher % of the released dug from the Tween 80 formulations.

Graphical Abstract
Innovative approaches for vaccine trials as a key component of pandemic preparedness – a white paper
Authors: Bethe Ullrich , Pana Zoi D. , Drosten Christian , Goossens Herman , König Franz , Marchant Arnaud , Molenberghs Geert , Posch Martin , Van Damme Pierre , Cornely Oliver A. 
Published: July 2024

Abstract
Background
WHO postulates the application of adaptive design features in the global clinical trial ecosystem. However, the adaptive platform trial (APT) methodology has not been widely adopted in clinical research on vaccines.

Methods
The VACCELERATE Consortium organized a two-day workshop to discuss the applicability of APT methodology in vaccine trials under non-pandemic as well as pandemic conditions. Core aspects of the discussions are summarized in this article.

Results
An “ever-warm” APT appears ideally suited to improve efficiency and speed of vaccine research. Continuous learning based on accumulating APT trial data allows for pre-planned adaptations during its course. Given the relative design complexity, alignment of all stakeholders at all stages of an APT is central. Vaccine trial modelling is crucial, both before and in a pandemic emergency. Various inferential paradigms are possible (frequentist, likelihood, or Bayesian). The focus in the interpandemic interval may be on research gaps left by industry trials. For activation in emergency, template Disease X protocols of syndromal design for pathogens yet unknown need to be stockpiled and updated regularly. Governance of a vaccine APT should be fully integrated into supranational pandemic response mechanisms.

Discussion
A broad range of adaptive features can be applied in platform trials on vaccines. Faster knowledge generation comes with increased complexity of trial design. Design complexity should not preclude simple execution at trial sites. Continuously generated evidence represents a return on investment that will garner societal support for sustainable funding. Adaptive design features will naturally find their way into platform trials on vaccines.
Fueling the future: biomass applications for green and sustainable energy
Authors: Ali Farhad , Dawood Asadullah , Hussain Akbar , Alnasir M Hisham , Khan Muhammad Asad , Butt Tehmeena Maryum , Janjua Naveed Kausar , Hamid Anum 
Published: July 2024

AbstractBiomass has become a key contender in the race to find sustainable energy options, as we move toward a more environmentally friendly future. This extensive assessment explores the potential of biomass to transform the global energy landscape. We have examined different conversion technologies, including thermal technologies such as combustion and gasification, as well as biochemical technologies such as anaerobic digestion and biofuel production, and we delved into the renewable nature of biomass, which is derived from organic sources such as agricultural residues, forestry waste, and special energy crops. We highlight the adaptability of biomass for the production of energy, heat, and biofuels. Furthermore, we evaluated the socioeconomic and environmental impacts of biomass use, including greenhouse gas emissions, land use, and community effects. To increase the potential of biomass as a renewable energy source, it is essential to understand how these three factors interact. To maximize energy production while curtailing environmental problems, this review examines obstacles, ongoing research, and recent developments in effective biomass-based energy systems.
Graphical Abstract
The Modeled Seasonal Cycles of Surface N2O Fluxes and Atmospheric N2O
Authors: Sun Qing , Joos Fortunat , Lienert Sebastian , Berthet Sarah , Carroll Dustin , Gong Cheng , Ito Akihiko , Jain Atul K. , Kou‐Giesbrecht Sian , Landolfi Angela , Manizza Manfredi , Pan Naiqing , Prather Michael , Regnier Pierre , Resplandy Laure , Séférian Roland , Shi Hao , Suntharalingam Parvadha , Thompson Rona L. , Tian Hanqin , Vuichard Nicolas , Zaehle Sönke , Zhu Qing 
Published: July 2024

AbstractNitrous oxide (N2O) is a greenhouse gas and stratospheric ozone‐depleting substance with large and growing anthropogenic emissions. Previous studies identified the influx of N2O‐depleted air from the stratosphere to partly cause the seasonality in tropospheric N2O (aN2O), but other contributions remain unclear. Here, we combine surface fluxes from eight land and four ocean models from phase 2 of the Nitrogen/N2O Model Intercomparison Project with tropospheric transport modeling to simulate aN2O at eight remote air sampling sites for modern and pre‐industrial periods. Models show general agreement on the seasonal phasing of zonal‐average N2O fluxes for most sites, but seasonal peak‐to‐peak amplitudes differ several‐fold across models. The modeled seasonal amplitude of surface aN2O ranges from 0.25 to 0.80 ppb (interquartile ranges 21%–52% of median) for land, 0.14–0.25 ppb (17%–68%) for ocean, and 0.28–0.77 ppb (23%–52%) for combined flux contributions. The observed seasonal amplitude ranges from 0.34 to 1.08 ppb for these sites. The stratospheric contributions to aN2O, inferred by the difference between the surface‐troposphere model and observations, show 16%–126% larger amplitudes and minima delayed by ∼1 month compared to Northern Hemisphere site observations. Land fluxes and their seasonal amplitude have increased since the pre‐industrial era and are projected to grow further under anthropogenic activities. Our results demonstrate the increasing importance of land fluxes for aN2O seasonality. Considering the large model spread, in situ aN2O observations and atmospheric transport‐chemistry models will provide opportunities for constraining terrestrial and oceanic biosphere models, critical for projecting carbon‐nitrogen cycles under ongoing global warming.
Understanding Precipitation Moisture Sources and Their Dominant Factors During Droughts in the Vietnamese Mekong Delta
Authors: Zhou Keke , Shi Xiaogang 
Published: July 2024

AbstractThe Vietnamese Mekong Delta (VMD) is the most productive region in Vietnam in terms of agriculture and aquaculture. Unsurprisingly, droughts have been a prevalent concern for stakeholders across the VMD over the past decades. However, the VMD precipitation moisture sources and their dominant factors during drought conditions were not well understood. Using the ERA5 reanalysis data as inputs, the Water Accounting Model‐2layers (WAM‐2layers), a moisture tracking tool, was applied to identify the VMD precipitation moisture sources from 1980 to 2020. The modeling simulation indicates that the moisture sources transported from the upwind regions dominate the VMD precipitation by 60.4%–93.3%, and the moisture source areas vary seasonally with different monsoon types. Results of the causal inference algorithms indicate that the humidity and wind speed in the upwind area are the dominant factors for driving moisture transport and determining the amount of VMD precipitation in dry and wet seasons, respectively. The local atmospheric conditions may also have a causal effect on moisture recycling. During the drought events in 2015–2016 and 2019–2020, the reduced moisture transport in the 2016 dry season was mainly caused by the anomalies in both humidity and wind speed, while the below average moisture sources in the 2020 dry season were dominated by humidity. In the 2019 wet season, an anomaly in wind speed led to a decrease in the tracked moisture. These findings are of great significance for understanding the moisture sources of precipitation and further improving drought prediction in the VMD.
Challenges Facing Scientific Publishing in the Field of Earth & Space Sciences
Authors:   AGU Editorial Network
Published: July 2024

AbstractThe scientific publishing landscape is evolving rapidly. This evolution is driven by a confluence of internal and external forces, including the growth of metrics‐based evaluation of scientists; an increasing volume of manuscripts combined with expectations for rapid review and publication; an increasing number of journals, including for‐profit Open Access publications; and the adoption of preprint servers across a growing range of disciplines. Many of these forces are contributing to personal anxiety and fatigue for authors, reviewers, and editors. Collectively, they are placing substantial stress on scientific publishing, which is a foundational pillar of the scientific enterprise. As editors of American Geophysical Union journals and books, we remain confident in the fundamental foundations of scientific publishing, but we are concerned about the impact of these increasing stressors. By affirming and investing in editorial values, respecting scientific integrity and credibility, and committing to accessibility, transparency, and accountability, we can fortify the foundations of the scientific enterprise during a time of rapid change.
Similarities and Differences Between Natural and Simulated Slow Earthquakes
Authors: Gualandi A. , Dal Zilio L. , Faranda D. , Mengaldo G. 
Published: July 2024

AbstractWe investigate similarities and differences between natural and simulated slow earthquakes using nonlinear dynamical system tools. We use spatio‐temporal slip potency rate data derived from Global Navigation Satellite System (GNSS) position time series in the Cascadia subduction zone and numerical simulations intended to reproduce their pulse‐like behavior and scaling laws. We provide metrics to evaluate the accuracy of simulations in mimicking slow earthquake dynamics. We investigate the influence of spatio‐temporal coarsening as well as observational noise. Despite the use of many degrees of freedom, numerical simulations display a surprisingly low average dimension, akin to natural slow earthquakes. Instantaneous dynamical indices can reach large values (>10) instead, and differences persist between numerical simulations and natural observations. We propose to use the suggested metrics as an additional tool to narrow the divergence between slow earthquake observations and dynamical simulations.
The Role of Advection in Storm Surge for Hurricane Michael (2018)
Authors: Bilskie M. V. , Luettich R. A. 
Published: July 2024

AbstractHurricane Michael (2018) made landfall near Mexico Beach, FL, as a Category 5 hurricane, with gauge‐measured water levels over 4 m. Wind and pressure fields were created by blending a parametric near‐field model with a gridded far‐field model. Winds and modeled water levels were well validated across Michael's large impact a‐ea. A detailed analysis of the coastal surge caused by Michael demonstrates that advection contributed significantly to Michael's highest water levels and the timing of the water level across a large portion of the Michael impact area. A momentum balance in a streamwise‐normal coordinate system demonstrates that the advection contributions due to spatial gradients in the flow are identified with streamwise convergence/expansion of the flow field (Bernoulli acceleration) and curvature in the flow field (centrifugal acceleration). These effects are created by the regional geometry and the storm's wind field and are most likely to affect back barrier water levels and along curved coastlines. These findings provide an improved understanding of the role of advection in determining storm surge and, thus, the importance of including it in storm surge models.
Acute, chronic and conditioned effects of intranasal oxytocin in the mu-opioid receptor knockout mouse model of autism: Social context matters
Authors: Pantouli Fani , Pujol Camille N , Derieux Cécile , Fonteneau Mathieu , Pellissier Lucie P. , Marsol Claire , Karpenko Julie , Bonnet Dominique , Hibert Marcel , Bailey Alexis , Le Merrer Julie , Becker Jerome A. J. 
Published: July 2024

AbstractAutism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behaviours. Multiple studies have highlighted the potential of oxytocin (OT) to ameliorate behavioural abnormalities in animal models and subjects with ASD. Clinical trials, however, yielded disappointing results. Our study aimed at assessing the behavioural effects of different regimens of OT administration in the Oprm1 null mouse model of ASD. We assessed the effects of intranasal OT injected once at different doses (0.15, 0.3, and 0.6 IU) and time points (5, 15, and 30 min) following administration, or chronically, on ASD-related behaviours (social interaction and preference, stereotypies, anxiety, nociception) in Oprm1+/+and Oprm1-/- mice. We then tested whether pairing intranasal OT injection with social experience would influence its outcome on ASD-like symptoms, and measured gene expression in the reward/social circuit. Acute intranasal OT at 0.3 IU improved social behaviour in Oprm1-/- mice 5 min after administration, with limited effects on non-social behaviours. Chronic (8–17 days) OT maintained rescuing effects in Oprm1 null mice but was deleterious in wild-type mice. Finally, improvements in the social behaviour of Oprm1-/- mice were greater and longer lasting when OT was administered in a social context. Under these conditions, the expression of OT and vasopressin receptor genes, as well as marker genes of striatal projection neurons, was suppressed. We detected no sex difference in OT effects. Our results highlight the importance of considering dosage and social context when evaluating the effects of OT treatment in ASD.
Biochemical role of FOXM1-dependent histone linker H1B in human epidermal stem cells
Authors: Polito Maria Pia , Marini Grazia , Fabrizi Alessandra , Sercia Laura , Enzo Elena , De Luca Michele 
Published: July 2024

AbstractEpidermal stem cells orchestrate epidermal renewal and timely wound repair through a tight regulation of self-renewal, proliferation, and differentiation. In culture, human epidermal stem cells generate a clonal type referred to as holoclone, which give rise to transient amplifying progenitors (meroclone and paraclone-forming cells) eventually generating terminally differentiated cells. Leveraging single-cell transcriptomic data, we explored the FOXM1-dependent biochemical signals controlling self-renewal and differentiation in epidermal stem cells aimed at improving regenerative medicine applications. We report that the expression of H1 linker histone subtypes decrease during serial cultivation. At clonal level we observed that H1B is the most expressed isoform, particularly in epidermal stem cells, as compared to transient amplifying progenitors. Indeed, its expression decreases in primary epithelial culture where stem cells are exhausted due to FOXM1 downregulation. Conversely, H1B expression increases when the stem cells compartment is sustained by enforced FOXM1 expression, both in primary epithelial cultures derived from healthy donors and JEB patient. Moreover, we demonstrated that FOXM1 binds the promotorial region of H1B, hence regulates its expression. We also show that H1B is bound to the promotorial region of differentiation-related genes and negatively regulates their expression in epidermal stem cells. We propose a novel mechanism wherein the H1B acts downstream of FOXM1, contributing to the fine interplay between self-renewal and differentiation in human epidermal stem cells. These findings further define the networks that sustain self-renewal along the previously identified YAP-FOXM1 axis.
Analysis of 14,392 whole genomes reveals 3.5% of Qataris carry medically actionable variants
Authors: Elfatih Amal , Saad Chadi ,   The Qatar Genome Program Research Consortium,   Qatar Genome Project Management, Ismail Said , Al-Muftah Wadha , Badji Radja , Darwish Dima , Fadl Tasnim , Yasin Heba , Ennaifar Maryem , Abdel-latif Rania , Alkuwari Fatima , Alvi Muhammad , Sarraj Yasser Al , Althani Asmaa ,   Biobank and Sample Preparation, Fthenou Eleni , Qafoud Fatima , Alkhayat Eiman , Afifi Nahla ,   Sequencing and Genotyping group, Tomei Sara , Liu Wei , Lorenz Stephan ,   Applied Bioinformatics Core, Syed Najeeb , Almabrazi Hakeem , Vempalli Fazulur Rehaman , Temanni Ramzi ,   Data Management and Computing Infrastructure group, Saqri Tariq Abu , Khatib Mohammed husen , Hamza Mehshad , Zaid Tariq Abu , El Khouly Ahmed , Pathare Tushar , Poolat Shafeeq , Al-Ali Rashid ,   Consortium Lead Principal Investigators, Albagha Omar M. E. , Al-Khodor Souhaila , Alshafai Mashael , Badii Ramin , Chouchane Lotfi , Estivill Xavier , Fakhro Khalid , Mbarek Hamdi , Mokrab Younes , Puthen Jithesh V. , Suhre Karsten , Tatari Zohreh , Mifsud Borbala , Mbarek Hamdi 
Published: July 2024

AbstractArabic populations are underrepresented in large genome projects; therefore, the frequency of clinically actionable variants among Arabs is largely unknown. Here, we investigated genetic variation in 14,392 whole genomes from the Qatar Genome Program (QGP) across the list of 78 actionable genes (v3.1) determined by the American College of Medical Genetics and Genomics (ACMG). Variants were categorized into one of the following groups: (1) Pathogenic (P), (2) Likely pathogenic (LP), and (3) Rare variants of uncertain significance with evidence of pathogenicity. For the classification, we used variant databases, effect predictors, and the disease-relevant phenotypes available for the cohort. Data on cardiovascular disease, cancer, and hypercholesterolemia allowed us to assess the disease-relevant phenotype association of rare missense variants. We identified 248 distinct variants in 50 ACMG genes that fulfilled our criteria to be included in one of the three groups affecting 1036 genotype-positive participants of the QGP cohort. The most frequent variants were in TTN, followed by RYR1 and ATP7B. The prevalence of reportable secondary findings was 3.5%. A further 46 heterozygous variants in six genes with an autosomal recessive mode of inheritance were detected in 200 individuals, accounting for an additional 1.4%. Altogether, they affect 5% of the population. Due to the high consanguinity rate in the QGP cohort (28% in spouses and 60% in parents), P and LP variants both in genes with dominant and recessive inheritance are important for developing better treatment options and preventive strategies in Qatar and the Arabic population of the Middle East.
Nanosecond chain dynamics of single-stranded nucleic acids
Authors: Nüesch Mark F. , Pietrek Lisa , Holmstrom Erik D. , Nettels Daniel , von Roten Valentin , Kronenberg-Tenga Rafael , Medalia Ohad , Hummer Gerhard , Schuler Benjamin 
Published: July 2024

AbstractThe conformational dynamics of single-stranded nucleic acids are fundamental for nucleic acid folding and function. However, their elementary chain dynamics have been difficult to resolve experimentally. Here we employ a combination of single-molecule Förster resonance energy transfer, nanosecond fluorescence correlation spectroscopy, and nanophotonic enhancement to determine the conformational ensembles and rapid chain dynamics of short single-stranded nucleic acids in solution. To interpret the experimental results in terms of end-to-end distance dynamics, we utilize the hierarchical chain growth approach, simple polymer models, and refinement with Bayesian inference to generate structural ensembles that closely align with the experimental data. The resulting chain reconfiguration times are exceedingly rapid, in the 10-ns range. Solvent viscosity-dependent measurements indicate that these dynamics of single-stranded nucleic acids exhibit negligible internal friction and are thus dominated by solvent friction. Our results provide a detailed view of the conformational distributions and rapid dynamics of single-stranded nucleic acids.