bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occupational quantitative exposure to crystalline silica, solvents and pesticides and risk of clinical forms of systemic sclerosis
Authors: Galli Gaël , De Pous-Gerardin Camille , Hanguehard Remi , Berthy Florine , Le Moal Cyril , Lourde Come , Barnetche Thomas , Skopinski Sophie , Contin-Bordes Cecile , Delva Fleur , Carles Camille , Truchetet Marie-Elise 
Published: November 2023

Abstract

Objectives
To estimate the association between SSc clinical phenotypes and quantitative occupational exposure to crystalline silica, chlorinated solvents, trichloroethylene and pesticides using job-exposure matrices.

Methods
In the VISS-EXPOSITION transversal study, data on declarative occupational exposure to crystalline silica, solvents and pesticides were retrieved. In parallel, the lifetime occupational history was evaluated using a questionnaire and cursus laboris for SSc patients followed at Bordeaux University Hospital (France). Using job-exposure matrices, we assessed patients’ occupational exposure in relation to relevant clinical phenotypic forms of the disease.

Results
Toxic exposure to crystalline silica and pesticides is underestimated by patients. Non-biased job-exposure matrices retrieved more exposed patients than the declarative assessment (10.1% of patients by job-exposure matrices vs 6.3% by declaration for crystalline silica and 25.9% vs 12.2% for pesticides). Patients overestimate their solvent exposure (7.9% for chlorinated solvents and 4.8% for trichlorethylene assessed by job-exposure matrices and 24.4% declarative exposure to solvents at large). Clinical form evaluation revealed a non-significant trend toward an increased risk of crystalline silica occupational exposure in the pulmonary fibrotic group of SSc patients [odds ratio (OR) 3.12 (95% CI 0.80, 12.15)]. We also observed a non-significant trend toward an elevated OR ([2.89 (95% CI 0.93, 8.95)] for chlorinated solvent occupational exposure and the vascular phenotype of SSc. Of note, pesticide occupational exposure evaluation represents one of the largest to date in SSc patients.

Conclusion
This study emphasizes that many exposed SSc patients are unaware of their occupational exposure. Job-exposure matrices allow better exposure screening for SSc secondary prevention and occupational exposure compensation.

Clinical trial registration
clinicaltrials.gov (https://www.clinicaltrials.gov), NCT03543956
Low-intensity shockwave therapy improves baseline erectile function: a randomized sham-controlled crossover trial
Authors: Kennady Emmett H , Bryk Darren J , Ali Marwan M , Ratcliffe Sarah J , Mallawaarachchi Indika V , Ostad Bahrom J , Beano Hamza M , Ballantyne Christopher C , Krzastek Sarah C , Clements Matthew B , Gray Mikel L , Rapp David E , Ortiz Nicolas M , Smith Ryan P 
Published: November 2023

Abstract

Background
Low-intensity shockwave therapy for erectile dysfunction is emerging as a promising treatment option.

Aim
This randomized sham-controlled crossover trial assessed the efficacy of low-intensity shockwave therapy in the treatment of erectile dysfunction.

Methods
Thirty-three participants with organic erectile dysfunction were enrolled and randomized to shockwave therapy (n = 17) or sham (n = 16). The sham group was allowed to cross over to receive shockwave therapy after 1 month.

Outcomes
Primary outcomes were the changes in Sexual Health Inventory for Men (SHIM) score and Erection Hardness Score at 1 month following shockwave therapy vs sham, and secondary outcomes were erectile function measurements at 1, 3, and 6 months following shockwave therapy.

Results
At 1 month, mean SHIM scores were significantly increased in the shockwave therapy arm as compared with the sham arm (+3.0 vs −0.7, P = .024). Participants at 6 months posttreatment (n = 33) showed a mean increase of 5.5 points vs baseline (P &lt; .001), with 20 (54.6%) having an increase ≥5. Of the 25 men with an initial Erection Hardness Score &lt;3, 68% improved to a score ≥3 at 6 months. When compared with baseline, the entire cohort demonstrated significant increases in erectile function outcomes at 1, 3, and 6 months after treatment.

Clinical Implications
In this randomized sham-controlled crossover trial, we showed that 54.6% of participants with organic erectile dysfunction met the minimal clinically important difference in SHIM scores after treatment with low-intensity shockwave therapy.

Strengths and Limitations
Strengths of this study include a sham-controlled group that crossed over to treatment. Limitations include a modest sample size at a single institution.

Conclusions
Low-intensity shockwave therapy improves erectile function in men with erectile dysfunction as compared with sham treatment, which persists even 6 months after treatment.

Clinical Trial Registration
ClinicalTrials.gov NCT04434352.
The unified patent court
Authors: Ullrich Hanns 
Published: November 2023

Abstract
On 1 June 2023, the Unified Patent Court (UPC) for the settlement of disputes relating to European patents and European patents with unitary effect opened its doors as a common court of those European Union (EU) Member States that, in 2012, had joined in an enhanced cooperation in the area of unitary patent protection, and then, in 2013, entered into an ‘Agreement on a Unified Patent Court’ (UPCA) that complements their cooperation and expands it to non-unitary European patents. Although the Court’s jurisdiction is strictly limited to the two main forms of actions that may be brought in the special field of patent protection—infringement and revocation—its establishment deserves an analytical evaluation from the perspective of general European Union law because it is the first time that Member States create a common court aside of the EU’s judicial system not only for the settlement of disputes arising under their own—national or internationally uniform—legal regimes, but also for a legal regime of Union law, the unitary protection of patents. In this regard, it is not so much the sheer size of the new court that attracts attention or the economic importance of the subject matter that comes under its exclusive jurisdiction, but the many fundamental issues and controversies that accompanied its creation and that are still extensively discussed in literature. Leaving aside doctrinal problems of a proper qualification of the UPC as a common court of Member States, the main concerns relate to (i) the need for and the risks of the (over-)specialization of the UPC as a technical expert court; (ii) the legitimacy and democratic deficits of the UPC as a jurisdiction the rules and operation of which are essentially determined through self-regulation by the patent law community; (iii) the difficulties of properly qualifying the nature of the rules of substantive law of both the EU’s Regulation on unitary patent protection and of the UPCA, the ambivalence of which seemingly allowing much room for interpretation and for curtailing the reach and primacy of Union law; (iv) the related problems of adequately defining the relationship between the UPC and the Court of Justice of the EU as regards safeguarding the autonomous and uniform interpretation of Union law; and (v), more generally, the structural imbalances within the EU’s judicial system that may result from the establishment of common courts of Member States the jurisdiction of which covers the very substance of a legal regime of the Union.
Integrating evolutionary theory and social–ecological systems research to address the sustainability challenges of the Anthropocene
Authors: Currie Thomas E. , Borgerhoff Mulder Monique , Fogarty Laurel , Schlüter Maja , Folke Carl , Haider L. Jamila , Caniglia Guido , Tavoni Alessandro , Jansen Raf E. V. , Jørgensen Peter Søgaard , Waring Timothy M. 
Published: November 2023

The rapid, human-induced changes in the Earth system during the Anthropocene present humanity with critical sustainability challenges. Social–ecological systems (SES) research provides multiple approaches for understanding the complex interactions between humans, social systems, and environments and how we might direct them towards healthier and more resilient futures. However, general theories of SES change have yet to be fully developed. Formal evolutionary theory has been applied as a dynamic theory of change of complex phenomena in biology and the social sciences, but rarely in SES research. In this paper, we explore the connections between both fields, hoping to foster collaboration. After sketching out the distinct intellectual traditions of SES research and evolutionary theory, we map some of their terminological and theoretical connections. We then provide examples of how evolutionary theory might be incorporated into SES research through the use of systems mapping to identify evolutionary processes in SES, the application of concepts from evolutionary developmental biology to understand the connections between systems changes and evolutionary changes, and how evolutionary thinking may help design interventions for beneficial change. Integrating evolutionary theory and SES research can lead to a better understanding of SES changes and positive interventions for a more sustainable Anthropocene.
This article is part of the theme issue ‘Evolution and sustainability: gathering the strands for an Anthropocene synthesis’.
Continuities and discontinuities in the cultural evolution of global consciousness
Authors: Zhang Robert Jiqi , Liu James H. , Lee Michelle , Lin Mei-hua , Xie Tian , Chen Sylvia Xiaohua , Leung Angela K.-y. , Lee I-Ching , Hodgetts Darrin , Valdes Evan A. , Choi Sarah Y. 
Published: November 2023

Global consciousness (GC), encompassing cosmopolitan orientation, global orientations (i.e. openness to multicultural experiences) and identification with all humanity, is a relatively stable individual difference that is strongly associated with pro-environmental attitudes and behaviours, less ingroup favouritism and prejudice, and greater pandemic prevention safety behaviours. Little is known about how it is socialized in everyday life. Using stratified samples from six societies, socializing institution factors correlating positively with GC were education, white collar work (and its higher income) and religiosity. However, GC also decreased with increasing age, contradicting a ‘wisdom of elders’ transmission of social learning, and not replicating typical findings that general prosociality increases with age. Longitudinal findings were that empathy-building, network-enhancing elements like getting married or welcoming a new infant, increased GC the most across a three-month interval. Instrumental gains like receiving a promotion (or getting a better job) also showed positive effects. Less intuitively, death of a close-other enhanced rather than reduced GC. Perhaps this was achieved through the ritualized management of meaning where a sense of the smallness of self is associated with growth of empathy for the human condition, as a more discontinuous or opportunistic form of culture-based learning.
This article is part of the theme issue ‘Evolution and sustainability: gathering the strands for an Anthropocene synthesis’.
Applying machine learning to identify ionizable lipids for nanoparticle-mediated delivery of mRNA
Authors: Lewis Mae M. , Beck Travis J. , Ghosh Debadyuti 
Published: November 2023

AbstractmRNA lipid nanoparticles (LNPs) have a tremendous potential to treat, cure, or prevent many diseases. To identify promising candidates for each application, most studies screen dozens to hundreds of formulations with ionizable lipids synthesized using a single type of chemistry. However, this technique leaves the ionizable lipids synthesized through multi-step chemistries underexplored. This gap in the repertoire of structures is of particular significance because it affects the screening of analogs that are structurally similar to SM-102 and ALC-0315, the ionizable lipids used to formulate the clinically approved mRNA LNP COVID-19 vaccines. Herein, we address this by employing LightGBM, a machine learning algorithm, to reduce the burden of screening these types of ionizable lipids by learning from the breadth and diversity of lipids that have already been tested. We first evaluate the ability of LightGBM to predict LNP potency across heterogeneous chemistries from different studies to achieve an R2of 0.94. After establishing the predictive capacity of the model, we then identify the number of outside carbons in the ionizable lipid as the most important factor contributing to transfection efficiency. From this finding, we subsequently apply the algorithm to predict the effect of formulating nanoluciferase mRNA LNPs using analogs of SM-102 and ALC-0315 with small changes in the number of outside carbons on luciferase activity in HEK293T cells and achieve an R2of 0.83. Importantly, this correlation encompasses novel lipids not included within the database used to train the algorithm. Overall, this study demonstrates the potential of machine learning to accelerate the development of new ionizable lipids by simplifying the screening process.
Three-dimensional electro-neural interfaces electroplated on subretinal prostheses
Authors: Butt Emma , Wang Bing-Yi , Shin Andrew , Chen Zhijie Charles , Bhuckory Mohajeet , Shah Sarthak , Galambos Ludwig , Kamins Theodore , Palanker Daniel , Mathieson Keith 
Published: November 2023

AbstractObjectiveHigh-resolution retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables an increase in prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue. We investigate 3-dimensional structures on top of the photovoltaic arrays for enhanced penetration of electric field to permit higher-resolution implants.ApproachWe developed 3D COMSOL models of subretinal photovoltaic arrays that accurately quantify the device electrodynamics during stimulation and verified it experimentally through comparison with the standard (flat) photovoltaic arrays. The models were then applied to optimise the design of 3D electrode structures (pillars and honeycombs) to efficiently stimulate the inner retinal neurons. The return electrodes elevated on top of the honeycomb walls surrounding each pixel orient the electric field inside the cavities vertically, aligning it with bipolar cells for optimal stimulation. Alternatively, pillars elevate the active electrode into the inner nuclear layer, improving proximity to the target neurons. Modelling results informed a microfabrication process of electroplating the 3D electrode structures on top of the existing flat subretinal prosthesis.Main resultsSimulations demonstrate that despite the conductive sidewalls of the 3D electrodes being exposed to electrolyte, most of the charge flows via the high-capacitance sputtered Iridium Oxide film that caps the top of the 3D structures. The 24 µm height of the electroplated honeycomb structures was optimised for integration with the inner nuclear layer cells in rat retina, while 35 µm height of the pillars was optimized for penetrating the debris layer in human patients. Release from the wafer and implantation of the 3D arrays demonstrated that they are mechanically robust to withstand the associated forces. Histology demonstrated successful integration of the 3D structures with the rat retina in-vivo.SignificanceElectroplated 3D honeycomb structures produce a vertically oriented electric field that offers low stimulation threshold, high spatial resolution and high contrast for the retinal implants with pixel sizes down to 20µm in width. Pillar electrodes offer an alternative configuration for extending the stimulation past the debris layers. Electroplating of the 3D structures is compatible with the fabrication process of the flat photovoltaic arrays, thereby enabling much more efficient stimulation than in their original flat configuration.
The influence of internal pressure and neuromuscular agents onC. elegansbiomechanics: an empirical and multi-compartmentalin silicomodelling study
Authors: Essmann Clara L. , Elmi Muna , Rekatsinas Christoforos , Chrysochoidis Nikolaos , Shaw Michael , Pawar Vijay , Srinivasan Mandayam A. , Vavourakis Vasileios 
Published: November 2023

ABSTRACTThe function of a specific tissue and its biomechanics are interdepended, with pathologies or ageing often being intertwined with structural decline. The biomechanics of Caenorhabditis elegans (C. elegans), a model organism widely used in pharmacological and ageing research, has been established as biomarker for healthy ageing, though the mechanics of individual tissues have remained elusive. In this study we investigated the biomechanics of healthyC. eleganscuticle, muscle tissue, and pseudocoelom using a combination of indentation experiments andin silicomodelling. Nematode stiffness measurements were performed using an atomic force microscope. The worm’s cylindrical body was approximated using a novel three-compartmental nonlinear finite element model, enabling analysis of how changes in the elasticity of individual compartments affect the bulk stiffness ofC. elegans. The parameters of the model were then fine-tuned to match the simulation force-indentation output to the experimental data. To test the finite element model, distinct compartments were modified experimentally. Ourin silicoresults, in agreement with previous studies, suggest that hyperosmotic shock reduced stiffness by decreasing theC. elegans’ internal pressure. Unexpectedly, treatment with the neuromuscular agent aldicarb, traditionally associated with muscle contraction, reduced stiffness by decreasing the internal pressure. It challenges previous assumptions about the effects of aldicarb. Furthermore, our finite element model can offer insights into how drugs, mutations or processes like ageing target individual tissues.
Olanzapine, Risperidone and Clozapine prescribing is associated with increased risk for Alzheimer’s Disease reflecting antipsychotic-specific effects on microglial phagocytosis
Authors: Mondal Mrityunjoy , Solomon Shiden , Sun Jiangwei , Sampathkumar Nirmal Kumar , Carre Ivo , Cotel Marie-Caroline , Mehta Puja R. , Rajendran Lawrence , Vernon Anthony C. , Fang Fang , Mitchell Jacqueline 
Published: November 2023

AbstractEpidemiological data provides evidence for a positive correlation between schizophrenia diagnosis and an increased risk to develop dementia. Whether and how use of antipsychotic medication may contribute to this association is however unknown. We therefore conducted a pharmaco-epidemiological study based on Swedish Patient and Prescribed Drug Registers to investigate the effect of three antipsychotics, Olanzapine, Risperidone, and Clozapine, on dementia risk. Our data suggest that prescription of all three antipsychotics is significantly associated with increased risk of Alzheimer’s disease (AD) and other dementias including vascular dementia. To provide a nexus of causality to this association, we explored the impact of these drugs on microglia and neurons using cells derived from human induced pluripotent stem cells (hiPSCs). Acute exposure to Olanzapine and Risperidone did not significantly alter amyloid-β (Aβ) production in hiPSC-derived cortical neurons, but suppressed hiPSC-derived microglial-mediated Aβ clearance, leading to Aβ accumulation. Neither Olanzapine nor Risperidone had any significant effect on hiPSC-derived microglial synaptosome phagocytosis. Conversely, Clozapine significantly reduced Aβ production in neurons, and increased microglial uptake of Aβ but also synaptosomes, consistent with higher lysosomal levels in Clozapine-exposed hiPSC-derived microglia. These data provide the first evidence that antipsychotics prescribed to individuals with schizophrenia are associated with increased risk for dementia and suggest potential cellular bases for this effect via the modulation of microglia uptake of Aβ and synapses in a drug specific manner.
Misclassification of yellow fever vaccination status revealed through hierarchical Bayesian modeling
Authors: Tran Quan Minh , Perkins T. Alex 
Published: November 2023

AbstractVaccination coverage estimates are crucial inputs to decisions about investments in vaccination, yet they can be prone to inaccuracies. At the individual level, inaccuracies can be described in terms of the sensitivity and specificity of vaccination status. We estimated these quantities using a hierarchical Bayesian analysis of data from a test-negative study design with reported yellow fever vaccination status as the exposure. Our analysis accounted for the possibility of misclassification of both the exposure and the test at the country level. Across all countries, our median estimates of the sensitivity and specificity of vaccination status were 0.69 (95% credible interval [CrI]: 0.21-0.98) and 0.70 (95% CrI: 0.21-0.98), respectively. Median estimates at the country level ranged from 0.06 (95% CrI: 0.04-0.09) to 0.96 (95% CrI: 0.94-0.98) for sensitivity, and from 0.15 (95% CrI: 0.09-0.23) to 0.98 (95% CrI: 0.90-1.00) for specificity. This suggests that there is substantial misclassification of yellow fever vaccination status in general and extensive variation in misclassification across countries. Taking into account misclassification in vaccination status, we made adjustments to reported vaccination coverage and showed that reported coverage may be significantly underestimated in 10 out of 20 countries and significantly overestimated in 5 out of 20.
Endonucleosis mediates internalization of cytoplasm into the nucleus in senescent cells
Authors: Galanopoulou Ourania , Tachmatzidi Evangelia C. , Deligianni Elena , Botskaris Dimitris , Nikolaou Kostas C. , Gargani Sofia , Dalezios Yannis , Chalepakis Georges , Talianidis Iannis 
Published: November 2023

AbstractCellular senescence is driven by diverse effector programs, leading to irreversible growth arrest, DNA damage and complex secretomes. Here we show that, in liver-specific Setd8-KO mice, after mitogen treatment, a significant number of hepatocytes become senescent and display unusual features such as enlarged nuclei, chromosomal hyperploidy and nuclear engulfments progressing to the formation of intranuclear vesicles. These vesicles contain glycogen, cytoplasmic proteins and even entire organelles. We term this process “endonucleosis”. Experiments with Setd8/Atg5 double knockout mice, demonstrated that endonucleosis requires the function of the autophagy machinery. Endonucleosis and hyperploidization are temporary, early features of senescence. Larger vesicles brake down into microvesicles over time and are eventually eliminated. The results reveal a senescence phenotype, which function as part of survival mechanisms to prevent necrotic death.