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Introduction: This observational study conducted across seven emergency care units compares the efficacy of four D‐dimer detection methods, namely HemosIL D‐dimer HS (HS), HemosIL D‐dimer HS‐500 (HS‐500), VIDAS D‐dimer (VIDAS), and HemosIL AcuStar D‐dimer (ACUSTAR). The primary focus is on patients with a clinical suspicion of deep venous thrombosis (DVT) or pulmonary embolism (PE). Methods: A total of 149 samples were collected from patients with suspected DVT or PE. The confirmation of DVT/PE was based on calf ultrasound or computed tomography‐Angiography. Direct comparisons were made between the different detection methods, considering both their analytical performance and clinical utility. Additionally, the impact of an age‐adjusted cut‐off on the diagnostic accuracy of each method was assessed. Results: The results revealed comparable negative predictive value, sensitivity, and specificity across the methods, with a notable exception of increased specificity for HS compared with HS‐500 (50.8% vs. 41.5%, p = 0.03). Further analysis incorporating an age‐adjusted cut‐off demonstrated a significant improvement in specificity for HS. When using the age‐adjusted cut‐off, HS exhibited a substantial increase in specificity compared with HS‐500 (63.1% vs. 49.2%, p = 0.004) and demonstrated significantly higher specificity compared with VIDAS (63.1% vs. 53.8%, p = 0.04). Conclusion: The study emphasizes the nonuniversal effect of an age‐adjusted cut‐off and discusses the potential necessity for different cut‐off values, particularly in the case of HS‐500. These findings contribute to the understanding of D‐dimer detection methods in the context of DVT and PE, providing insights into their relative performances and the potential optimization through age‐adjusted cut‐offs. [ABSTRACT FROM AUTHOR]

As urbanization and population growth continue, cities concentrate an increasing amount of people, energy, and economy. Multi-story buildings enable densification, requiring vertical transport for access to upper floors. This is crucial for people with disabilities, who may face barriers in the built environment. Elevators are essential for accessibility, allowing everyone, including people with disabilities, to comfortably access multi-story buildings. However, barriers to inclusivity remain, often subtle and hard to define. This paper highlights one such example, focusing on elevator use by individuals with varying degrees of hearing loss. Currently, they cannot establish one-to-one communication with the outside world if trapped in an elevator. Under EN standards, this issue stems from alarm system requirements that lack effective alternatives to voice communication. Based on this evidence, the research was carried out in two steps, with the aim of understanding the needs of deaf individuals when using elevators by directly involving them in the study. First, a questionnaire conducted in Italy collected information regarding the safety and usability of elevators. Second, a test campaign involving both deaf and normal-hearing participants was carried out to quantify the severity of the issue and evaluate potential solutions to address the identified challenges. The conclusions indicate that current alarm systems in elevators are inadequate for individuals with hearing impairments, and effective alternatives must be implemented. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is the most common respiratory disease in preterm and is still associated with increased mortality and morbidity. The great interest lies in identifying early biomarkers that can predict the development of BPD. This pilot study explores the potential of e-nose for the early identification of BPD risk in premature infants by analyzing volatile organic compounds (VOCs) in the exhaled breath condensate (EBC). Fourteen mechanically ventilated very preterm infants were included in this study. The clinical parameters and EBC were collected within the first 24 h of life. The discriminative ability of breath prints between preterms who did and did not develop BPD was investigated using pattern recognition, a machine learning algorithm, and standard statistical methods. We found that e-nose probes can significantly predict the outcome of "no-BPD" vs. "BPD". Specifically, a subset of probes (S18, S24, S14, and S6) were found to be significantly predictive, with an AUC of 0.87, 0.89, 0.82, 0.8, and p = 0.019, 0.009, 0.043, 0.047, respectively. The e-nose is an easy-to-use, handheld, non-invasive electronic device that quickly samples breath. Our preliminary study has shown that it has the potential for early prediction of BPD in preterms. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are professional antigen‐presenting cells involved in promoting and controlling immune responses. Different subsets of DC, named tolerogenic (tol)DC, play a critical role in the maintenance of tissue homeostasis and in fostering tolerance. These unique skills make tolDC especially attractive for strategies aimed at re‐establishing/inducing tolerance in immune‐mediated conditions. The generation of potent tolDC in vitro from peripheral blood monocytes has seen remarkable advancements. TolDC modulate T cell dynamics by favoring regulatory T cells (Tregs) and curbing effector/pathogenic T cells. Among the several methods developed for in vitro tolDC generation, IL‐10 conditioning has been proven to be the most efficient, as IL‐10‐modulated tolDC were demonstrated to promote Tregs with the strongest suppressive activities. Investigating the molecular, metabolic, and functional profiles of tolDC uncovers essential pathways that facilitate their immunoregulatory functions. This Review provides an overview of current knowledge on the role of tolDC in health and disease, focusing on IL‐10 production, functional characterization of in vitro generated tolDC, molecular and metabolic changes occurring in tolDC induced by tolerogenic agents, clinical applications of tolDC‐based therapy, and finally new perspectives in the generation of effective tolDC. [ABSTRACT FROM AUTHOR]

Opioids have been utilized for both medical and recreational purposes since their discovery. Primarily recognized for their analgesic properties, they are also associated with the development of tolerance and dependence, contributing to a significant public health concern worldwide. Sex differences in opioid use disorder reveal that while men historically exhibit higher rates of abuse, women may develop dependence more quickly and are more susceptible to the addictive nature of opioids. This narrative review explores sex differences in opioid response in both clinical and experimental models, focusing on opioid receptor mechanisms, pain modulation, and hormonal influences. Additionally, it discusses the complexities of opioid addiction and withdrawal, highlighting sex-specific responses and the role of opioid replacement therapies. Diverse experimental outcomes, together with observational data, underscore the need for further research into sex-specific opioid biological mechanisms in a wider context, including demographic, cultural, and health-related factors. A comprehensive understanding of these complexities holds the potential to enhance personalized opioid therapies. [ABSTRACT FROM AUTHOR]

Adopting an advanced microscopic model of the Au–graphite interaction, a systematic study of Au nanoclusters (up to sizes of 11 238 atoms) on graphene and on graphite is carried out to explore their structure and energy landscape. Using parallel tempering molecular dynamics, structural distribution as a function of temperature is calculated in the entire temperature range. Low‐energy structures are identified through a combination of structural optimization and Wulff–Kaischew construction which are then used to explore the energy landscape. The potential energy surface (PES), which is energy as a function of translation and rotation, is calculated for a few Au nanoclusters along specific directions on carbon lattice. Minimum‐energy pathways are identified on the PES indicating a reduced barrier for pathways involving simultaneous rotation and translation. Diffusion simulations of Au233 on graphite show that diffusion mechanism is directly related to the PES, and the information of the cluster pinning events is already present in the PES. Finally, a comparison of various interaction models highlights the importance of reasonably correct Au–C interactions which is crucial for studying the energy landscape and cluster sliding. [ABSTRACT FROM AUTHOR]

The interactions of microorganisms among themselves and with their multicellular host take place at the microscale, forming complex networks and spatial patterns. Existing technology does not allow the simultaneous investigation of spatial interactions between a host and the multitude of its colonizing microorganisms, which limits our understanding of host–microorganism interactions within a plant or animal tissue. Here we present spatial metatranscriptomics (SmT), a sequencing-based approach that leverages 16S/18S/ITS/poly-d(T) multimodal arrays for simultaneous host transcriptome- and microbiome-wide characterization of tissues at 55-µm resolution. We showcase SmT in outdoor-grown Arabidopsis thaliana leaves as a model system, and find tissue-scale bacterial and fungal hotspots. By network analysis, we study inter- and intrakingdom spatial interactions among microorganisms, as well as the host response to microbial hotspots. SmT provides an approach for answering fundamental questions on host–microbiome interplay. Interactions among plant hosts, bacteria and fungi are measured at high spatial resolution. [ABSTRACT FROM AUTHOR]

Many recent studies have emphasized the important role of structural variation (SV) in determining human genetic and phenotypic variation. In plants, studies aimed at elucidating the extent of SV are still in their infancy. Evidence has indicated a high presence and an active role of SV in driving plant genome evolution in different plant species.With the aim of characterizing the size and the composition of the poplar pan-genome, we performed a genome-wide analysis of structural variation in three intercrossable poplar species: Populus nigra, Populus deltoides, and Populus trichocarpa We detected a total of 7,889 deletions and 10,586 insertions relative to the P. trichocarpa reference genome, covering respectively 33.2 Mb and 62.9 Mb of genomic sequence, and 3,230 genes affected by copy number variation (CNV). The majority of the detected variants are inter-specific in agreement with a recent origin following separation of species.Insertions and deletions (INDELs) were preferentially located in low-gene density regions of the poplar genome and were, for the majority, associated with the activity of transposable elements. Genes affected by SV showed lower-than-average expression levels and higher levels of dN/dS, suggesting that they are subject to relaxed selective pressure or correspond to pseudogenes.Functional annotation of genes affected by INDELs showed over-representation of categories associated with transposable elements activity, while genes affected by genic CNVs showed enrichment in categories related to resistance to stress and pathogens. This study provides a genome-wide catalogue of SV and the first insight on functional and structural properties of the poplar pan-genome.

Introdução: A Gestão do Conhecimento é um desafio para as empresas na Sociedade da Informação. Metodologias como a de Nonaka e Takeuchi vêm ao encontro desse desafio para sistematizar e organizar a criação de conhecimento em todos os níveis das empresas. O conhecimento é considerado um ativo intangível e que pode ser protegido para garantir a manutenção da cadeia de valor das Organizações. Neste contexto, a Segurança da Informação visa proteger informações acessíveis no âmbito organizacional. Uma estrutura de Gerenciamento de Conhecimento Seguro é necessária para obter controles relevantes de segurança na Gestão de Conhecimento. Método: Apresenta caráter qualitativo, com o uso da metodologia Delphi para a construção de uma estrutura de Gerenciamento do Conhecimento Seguro. Resultados: Os pontos de congruência entre Gerenciamento de Conhecimento e Segurança da Informação ficaram evidentes na pesquisa. Na fase de socialização, evidenciam-se dois controles com mais de 80% de congruência. Na fase de externalização, os dois pontos ficaram acima de 70%. Não há uma fase de combinação combinada, resultado de 60% de congruência em quatro controles e fase de internalização, registro de unanimidade na escola de controle, tendo um ponto com 100% de congruência. Conclusões: Os profissionais que adotaram a técnica Delphi conseguiram encontrar pontos de congruência entre os assuntos de pesquisa temática, subsidiando uma retórica da compatibilidade entre gerenciamento de conhecimento e Segurança da Informação. Dessa forma, destaca-se a necessidade de cocriação de conhecimento sob uma ótica de um framework que considere Segurança de Informação.

Abstract Background Interest in studying the spatial distribution of gene expression in tissues is rapidly increasing. Spatial Transcriptomics is a novel sequencing-based technology that generates high-throughput information on the distribution, heterogeneity and co-expression of cells in tissues. Unfortunately, manual preparation of high-quality sequencing libraries is time-consuming and subject to technical variability due to human error during manual pipetting, which results in sample swapping and the accidental introduction of batch effects. All these factors complicate the production and interpretation of biological datasets. Results We have integrated an Agilent Bravo Automated Liquid Handling Platform into the Spatial Transcriptomics workflow. Compared to the previously reported Magnatrix 8000+ automated protocol, this approach increases the number of samples processed per run, reduces sample preparation time by 35%, and minimizes batch effects between samples. The new approach is also shown to be highly accurate and almost completely free from technical variability between prepared samples. Conclusions The new automated Spatial Transcriptomics protocol using the Agilent Bravo Automated Liquid Handling Platform rapidly generates high-quality Spatial Transcriptomics libraries. Given the wide use of the Agilent Bravo Automated Liquid Handling Platform in research laboratories and facilities, this will allow many researchers to quickly create robust Spatial Transcriptomics libraries.

A economia global sofreu um grande impacto decorrente da pandemia causada pelo vírus SARS-CoV-2. Tanto economias desenvolvidas, em desenvolvimento e as não desenvolvidas, sentiram o impacto econômico nos mais variados setores e, no estado do Rio Grande do Sul (RS) não foi diferente. Como parte indissociável da economia, o emprego também foi afetado. Ao todo, o RS perdeu cerca de 86 mil empregos formais desde o início da pandemia, ou seja, o estado ocupou no período entre março e setembro de 2020, o quarto lugar em número de vagas perdidas no país. Dessa forma, o objetivo do presente estudo é realizar uma análise do impacto da pandemia sobre os empregos formais no estado do Rio Grande do Sul. Para tanto, foi feita uma análise relacional e de impacto causal em indicadores econômicos e de emprego do estado do Rio Grande do Sul durante os meses de março a setembro de 2020, em meio a pandemia da COVID-19. Os resultados demonstram que não há uma relação dos casos de covid-19 número de infectados, com admissões e demissões, entretanto relação com desempenho econômico. Observou-se que regiões economicamente mais ativas tiveram impactos maiores com relação aos casos de covid-19. Entretanto, a pesquisa demonstrou que os efeitos da COVID-19 nas demissões e admissões não são significativos, apesar da significância estar relacionada tanto a desigualdade social quanto ao PIB de cada um dos COREDEs estudados.

A indústria têxtil, a partir da década de 1980, passou por uma profunda expansão graças à consolidação do fast fashion, fazendo com que o tempo de vida das roupas reduzissem em 35%. Como resultado, hoje o setor têxtil é o segundo que mais polui o meio ambiente, ficando atrás da indústria do petróleo. No Brasil, estima-se que sejam gerados 160 mil toneladas ao ano, tendo 60% como destino os aterros sanitários. Em frente a tal problema, a Economia Circular (EC) se apresenta como melhor alternativa ao atual modelo econômico linear. Para que a EC seja implementada, todo o sistema produtivo deve ser abrangido, ou seja, a nível macro, meso e micro. Contudo, carecem de estudos ligados a nível micro, local onde se encontram as confecções. Desta forma, o estudo debruçou-se sob a análise sistemática da literatura, relacionando os conceitos e princípios da EC com a indústria de confecção. Como resultado, foi desenvolvido um framework conceitual, a partir da junção das 32 práticas sugeridas nas 13 publicações pesquisadas, divididas em seis estágios, onde cada estágio fornece subsídios para o próximo. O framework contempla todas as etapas produtivas, possibilitando a transição do sistema linear para o circular.

BackgroundAcute ischemic stroke (AIS) is a possible complication of coronavirus disease 2019 (COVID-19) infection. Although peculiar clinical features and underlying specific mechanisms of thrombogenesis have been suggested so far, there is no consensus on the appropriate vascular preventive drug regimen in patients with COVID-19.Aim and MethodsFrom a larger clinical series of consecutive acute ischemic strokes related to COVID-19 admitted to three cerebrovascular units in Northern Italy, herein, we describe the clinical features of a subgroup of patients in whom stroke occurred despite therapeutic anticoagulation.ResultsA total of seventeen/80 AIS related to COVID-19 (21.2%) occurred in anticoagulated patients. Although no blood level was available for Direct Oral AntiCoagulant, the drug dosage was appropriate according to guidelines. Their National Institute of Health Stroke Scale (NIHSS) at admission was 12.0 (SD = 7.4) and 58.8% of them had evidence of large vessel occlusion. The case fatality rate was as high as 64.7%.Discussion and ConclusionsThe occurrence of an anticoagulation failure seems to be increased in the setting of COVID-19 infection, with worse clinical outcomes if compared to non-COVID-19 related ischemic strokes. We discuss the diagnostic and therapeutic implications of such evidence, suggesting that some arterial thrombotic complications might be either resistant to or independent of the anticoagulation effect.

The human genome counts hundreds of GPCRs specialized to sense thousands of different extracellular cues, including light, odorants and nutrients in addition to hormones. Primordial GPCRs were likely glucose transporters that became sensors to monitor the abundance of nutrients and direct the cell to switch from aerobic metabolism to fermentation. Human β cells express multiple GPCRs that contribute to regulate glucose homeostasis, cooperating with many others expressed by a variety of cell types and tissues. These GPCRs are intensely studied as pharmacological targets to treat type 2 diabetes in adults. The dramatic rise of type 2 diabetes incidence in pediatric age is likely correlated to the rapidly evolving lifestyle of children and adolescents of the new century. Current pharmacological treatments are based on therapies designed for adults, while youth and puberty are characterized by a different hormonal balance related to glucose metabolism. This review focuses on GPCRs functional traits that are relevant for β cells function, with an emphasis on aspects that could help to differentiate new treatments specifically addressed to young type 2 diabetes patients.

Recent proteomic, metabolomic, and transcriptomic studies have highlighted a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms. Secondary assays to assess the function of these organelles appear fundamental to validate these -omics findings. Although mitochondrial membrane potential is widely recognized as an indicator of mitochondrial activity, high-content imaging-based approaches coupled to multiparametric to measure it have not been established yet. In this paper, we describe a methodology for the unbiased high-throughput quantification of mitochondrial membrane potential in vitro, which is suitable for 2D to 3D models. We successfully used our method to analyze mitochondrial membrane potential in monolayers of human fibroblasts, neural stem cells, spheroids, and isolated muscle fibers. Moreover, by combining automated image analysis and machine learning, we were able to discriminate melanoma cells from macrophages in co-culture and to analyze the subpopulations separately. Our data demonstrated that our method is a widely applicable strategy for large-scale profiling of mitochondrial activity.

Human skeletal muscle atrophy and a disproportionate force loss occur within a few days of unloading in space and on Earth, but the underlying mechanisms are not fully understood. Disruption of neuromuscular junction homeostasis has been proposed as one of the possible causes. Here, we investigated the potential mechanisms involved in this neuromuscular disruption induced by a 10-day unilateral lower limb suspension (ULLS) in humans. Specifically, we investigated hemichannels’ upregulation, neuromuscular junction and axonal damage, neurotrophins’ receptor downregulation and inflammatory transcriptional signatures. Biomarkers were evaluated at local and systemic levels. At the sarcolemmal level, changes were found to be associated with an increased expression of connexin 43 and pannexin-1. Upregulation of the inflammatory transcripts revealed by deep transcriptomics was found after 10 days of ULLS. The destabilisation of the neuromuscular junction was not accompanied by changes in the secretion of the brain-derived neurotrophic factor and neurotrophin-4, while their receptor, BDNF/NT growth factors receptor (TrkB), decreased. Furthermore, at 5 days of ULLS, there was already a significant upregulation of the serum neurofilament light chain concentration, an established clinical biomarker of axonal injury. At 10 days of ULLS, other biomarkers of early denervation processes appeared. Hence, short periods of muscle unloading induce sarcolemmal hemichannels upregulation, inflammatory transcripts upregulation, neuromuscular junction instability and axonal damage.

This study examined the practices of innovation management used by Brazilian industries. A survey was carried out with specialists that assessed 27 practices (PR) proposed by ISO 56002, considering two types of firms: small and medium-sized industries (SMI) and large industries (LI). The methodological approach included Hierarchical Cluster Analysis to identify the similarities between the specialists and define levels of specialists, as well as Fuzzy TOPSIS and frequency and sensitivity analyses to examine their responses. PR1 (analysis of internal and external issues that impact innovation management) was deemed the best practice for LIs, whereas PR10 (adequate assessment of potential partnerships) was best evaluated for SMIs. The PR27 (periodic audits to identify opportunities for improvement) received the lowest rating from both LIs and SMIs. In general, SMIs in the Brazilian context have more severe deficiencies in terms of applying innovation management practices than LIs. A broad overview of the innovation practices adopted in the Brazilian industrial scenario is provided. The study’s findings may assist managers and policymakers to develop initiatives and actions to improve the capacity of Brazilian industries to innovate. This research can also support future studies aimed at better understanding specific practices related to the topic.

In this work, an extended classical nucleation theory (CNT), including line tension, is used to disentangle classical and non-classical effects in the nucleation of vapor from a liquid confined between two hydrophobic plates at a nanometer distance. The proposed approach allowed us to gauge, from the available simulation work, the importance of elusive nanoscale effects, such as line tension and non-classical modifications of the nucleation mechanism. Surprisingly, the purely macroscopic theory is found to be in quantitative accord with the microscopic data, even for plate distances as small as 2 nm, whereas in extreme confinement (< 1.5 nm), the CNT approximations proved to be unsatisfactory. These results suggest how classical nucleation theory still offers a computationally inexpensive and predictive tool useful in all domains where nanoconfined evaporation occurs—including nanotechnology, surface science, and biology. [ABSTRACT FROM AUTHOR]

The KCNA2 gene encodes the Kv1.2 channel, a mammalian Shaker-like voltage-gated K+ channel, whose defections are linked to neuronal deficiency and childhood epilepsy. Despite the important role in the kinetic behavior of the channel, the inactivation remained hereby elusive. Here, we studied the Kv1.2 inactivation via a combined simulation/network theoretical approach that revealed two distinct pathways coupling the Voltage Sensor Domain and the Pore Domain to the Selectivity Filter. Additionally, we mutated some residues implicated in these paths and we explained microscopically their function in the inactivation mechanism by computing a contact map. Interestingly, some pathological residues shown to impair the inactivation lay on the paths. In summary, the presented results suggest two pathways as the possible molecular basis of the inactivation mechanism in the Kv1.2 channel. These pathways are consistent with earlier mutational studies and known mutations involved in neuronal channelopathies.

CRAC channel is ubiquitous and its importance in the regulation of the immune system is testified by the severe immunodeficiencies caused by its mutations. In this work we took advantage of the availability of open and closed structures of this channel to run for the first time simulations of the whole gating process reaching the relevant time-scale with an enhanced sampling technique, Targeted Molecular Dynamics. Our simulations highlighted a complex allosteric propagation of the conformational change from peripheral helices, where the activator STIM1 binds, to the central pore helices. In agreement with mutagenesis data, our simulations revealed the key role of residue H206 whose displacement creates an empty space behind the hydrophobic region of the pore, thus releasing a steric brake and allowing the opening of the channel. Conversely, the process of pore closing culminates with the formation of a bubble that occludes the pore even in the absence of steric block. This mechanism, known as “hydrophobic gating”, has been observed in an increasing number of biological ion channels and also in artificial nanopores. Our study therefore shows promise not only to better understand the molecular origin of diseases caused by disrupted calcium signaling, but also to clarify the mode of action of hydrophobically gated ion channels, possibly even suggesting strategies for the biomimetic design of synthetic nanopores.

Neuroblastoma (NB) is the most common extracranial tumor of early childhood and accounts for 15% of all pediatric cancer mortalities. However, the precise pathways and genes underlying its progression are unknown. Therefore, we performed a differential gene expression analysis of neuroblastoma stage 1 and stage 4 + 4S to discover biological processes associated with NB progression. From this preliminary analysis, we found that NB samples (stage 4 + 4S) are characterized by altered expression of some proteins involved in mitochondria function and mitochondria–ER contact sites (MERCS). Although further analyses remain necessary, this review may provide new hints to better understand NB molecular etiopathogenesis, by suggesting that MERCS alterations could be involved in the progression of NB.

Rutting (i.e., depressions along the wheel path) is a distress exhibited by flexible asphalt pavements at high in-service temperatures negatively affecting ride comfort and safety. In this regard, the fine asphalt mortar (i.e., bitumen filler and fine sand) plays a key role in the rutting potential of the asphalt mixtures. Given this background, this manuscript presents a small-scale laboratory experimentation aimed at assessing the rutting-related performance of a plain bitumen combined with natural (limestone) or manufactured (steel slag) fine aggregates (size up to 0.18 mm) through advanced experimental and theoretical approaches. Specific rheological tests through dynamic shear were carried out to achieve this goal. The investigated asphalt blends came from a wider research project focused on the implementation of a pavement solar collector (a road system to harvest the solar energy irradiating the pavement). In particular, the present paper aimed at verifying the mechanical suitability of the produced asphalt mixes with respect to permanent deformation resistance. Such a small-scale investigation mainly showed that the previously selected constituent materials did not imply criticisms in terms of rutting response.

Large contact angle hysteresis surfaces were the topic of a contribution in Ref. [19]. They address the relation between vapor of a liquid, a finite contact angle, and a possible wetting transition at saturation vapor pressure. In Ref. [15], the authors apply surfaces with low contact angle hysteresis to the evaporation of drops of salt solutions. Low contact angle hysteresis implies that contact lines or sessile drops move without much resistance. [Extracted from the article]