bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of exposure to solar radiation on human health
Authors: Neale R. E. , Lucas R. M. , Byrne S. N. , Hollestein L. , Rhodes L. E. , Yazar S. , Young A. R. , Berwick M. , Ireland R. A. , Olsen C. M.
Published: March 2023

This assessment by the Environmental Effects Assessment Panel (EEAP) of the Montreal Protocol under the United Nations Environment Programme (UNEP) evaluates the effects of ultraviolet (UV) radiation on human health within the context of the Montreal Protocol and its Amendments. We assess work published since our last comprehensive assessment in 2018. Over the last four years gains have been made in knowledge of the links between sun exposure and health outcomes, mechanisms, and estimates of disease burden, including economic impacts. Of particular note, there is new information about the way in which exposure to UV radiation modulates the immune system, causing both harms and benefits for health. The burden of skin cancer remains high, with many lives lost to melanoma and many more people treated for keratinocyte cancer, but it has been estimated that the Montreal Protocol will prevent 11 million cases of melanoma and 432 million cases of keratinocyte cancer that would otherwise have occurred in the United States in people born between 1890 and 2100. While the incidence of skin cancer continues to rise, rates have stabilised in younger populations in some countries. Mortality has also plateaued, partly due to the use of systemic therapies for advanced disease. However, these therapies are very expensive, contributing to the extremely high economic burden of skin cancer, and emphasising the importance and comparative cost-effectiveness of prevention. Photodermatoses, inflammatory skin conditions induced by exposure to UV radiation, can have a marked detrimental impact on the quality of life of sufferers. More information is emerging about their potential link with commonly used drugs, particularly anti-hypertensives. The eyes are also harmed by over-exposure to UV radiation. The incidence of cataract and pterygium is continuing to rise, and there is now evidence of a link between intraocular melanoma and sun exposure. It has been estimated that the Montreal Protocol will prevent 63 million cases of cataract that would otherwise have occurred in the United States in people born between 1890 and 2100. Despite the clearly established harms, exposure to UV radiation also has benefits for human health. While the best recognised benefit is production of vitamin D, beneficial effects mediated by factors other than vitamin D are emerging. For both sun exposure and vitamin D, there is increasingly convincing evidence of a positive role in diseases related to immune function, including both autoimmune diseases and infection. With its influence on the intensity of UV radiation and global warming, the Montreal Protocol has, and will have, both direct and indirect effects on human health, potentially changing the balance of the risks and benefits of spending time outdoors.

Graphical abstract
The Epidemiological Profile of Multiple Casualty Incidents in Northern Spain: 2014-2020
Authors: Arcos Gonzalez Pedro , Vargas Campos Carlos Adrian , Cernuda Martinez José Antonio , Naves Gomez Cecilia , Villellas Aguilar Ignacio , Lea Castro Begoña , Dorribo Masid Marta , Dominguez Sanchez Emilio , Castro Delgado Rafael
Published: March 2023

Objective:

To describe the epidemiological profile of multiple casualty incidents (MCI) and contribute to the better understanding of their impacts in Northern Spain.

Method:

Retrospective, population-based observational study of MCI between 2014 and 2020 in 5 autonomous communities (Aragón, Castilla y León, Galicia, the Basque Country and Principado de Asturias) that participated in the MCI Database of Northern Spain. Inclusion criteria was any incident with 4 or more patients needing ambulance mobilization. A total of 54 variables were collected. This study presents the most relevant results.

Results:

There were 253 MCI. Of these, 79.8% were road traffic accidents, 12.3% fires or explosions, 2.0% poisonings and 5.9% defined as others. Monthly average was 2.9 (SD = 0.35; EEM = 15.90), average of victims by MCI was 6.8 (CI95% 6.16 - 7.60). There were significantly (P < 0.05) more victims in 3 types of MCI (fires, poisonings, and others). We saw 37.7% of MCI involved 4 victims, 18.8% 5 victims, and 37.9% more than 5. Mean response time was 30.8 minutes (95% CI 28.6 - 33.1), longer in maritime incidents. A total of 67% (95% CI 64.5 - 69.5) of victims were mild.

Conclusions:

Road traffic accidents are the most frequent MCI and minor injuries predominate. More than 50% of the MCI have 5 or fewer patients. Fires had significantly more mild patients and significantly more resources deployed. Maritime incidents had a significantly longer response time.
The Good, the Bad and the Rest: How the European Union Responded to the COVID-19 Pandemic in the Transport Sector
Authors: Settembri Pierpaolo , Kumar Rishi
Published: March 2023

Due to its severity, the COVID-19 pandemic is one of the greatest crises to have tested the European Union’s (EU) ability to take effective action. The restrictive measures adopted by the Member States to curb its spread affected in particular the free movement of people and partly of goods. This prompted the EU to take action inter alia to maintain essential travel, protect supply chains, enhance contact tracing and facilitate the coordinated resumption of travel. Building on the notion of “output legitimacy”, this paper assesses the EU’s success in responding to the COVID-19 pandemic in transport by looking at the four main initiatives between the end of 2020 and June 2022, namely: (1) the EU Digital COVID Certificates; (2) cross-border contact tracing through Passenger Locator Forms; (3) the “Green Lanes” for freight transport; and (4) the coordinated approach to facilitating safe and free movement. These initiatives are measured against the EU’s legal competence, economic interests, political pressure and the added value of EU action. While recognising the small set of cases, the results show that, although legal competence is a decisive factor for success, EU initiatives can achieve equivalent effect even in its absence, provided other conditions are met.
Using machine learning methods to predict dry matter intake from milk mid-infrared spectroscopy data on Swedish dairy cattle
Authors: Salleh Suraya Mohamad , Danielsson Rebecca , Kronqvist Cecilia
Published: March 2023

In this research communication we compare three different approaches for developing dry matter intake (DMI) prediction models based on milk mid-infrared spectra (MIRS), using data collected from a research herd over five years. In dairy production, knowledge of individual DMI could be important and useful, but DMI can be difficult and expensive to measure on most commercial farms as cows are commonly group-fed. Instead, this parameter is often estimated based on the age, body weight, stage of lactation and body condition score of the cow. Recently, milk MIRS have also been used as a tool to estimate DMI. There are different methods available to create prediction models from large datasets. The main data used were total DMI calculated as a 3-d average, coupled with milk MIRS data available fortnightly. Data on milk yield and lactation stage parameters were also available for each animal. We compared the performance of three prediction approaches: partial least-squares regression, support vector machine regression and random forest regression. The full milk MIRS alone gave low to moderate prediction accuracy (R2 = 0.07–0.40), regardless of prediction modelling approach. Adding more variables to the model improved R2 and decreased the prediction error. Overall, partial least-squares regression proved to be the best method for predicting DMI from milk MIRS data, while MIRS data together with milk yield and concentrate DMI at 3–30 d in milk provided good prediction accuracy (R2 = 0.52–0.65) regardless of the prediction tool used.
Flexible syntax–prosody mapping of Intonational Phrases in the context of varying verb height
Authors: Borise Lena , Erschler David
Published: March 2023

This paper provides new evidence in support of the hypothesis that the syntax–prosody mapping of Intonational Phrases is flexible (Hamlaoui and Szendrői 2015). In the traditional ‘rigid’ approaches, Intonational Phrases are taken to map onto particular syntactic projections. In contrast, in the ‘flexible’ approach, the Intonational Phrase corresponds to the highest projection of the verb (HVP). Accordingly, the ‘flexible’ approach predicts that the HVP should also determine the size of Intonational Phrases in a language where the verb height depends on the utterance type. Our evidence comes from a language of this type, Iron Ossetic (East Iranian). First, we demonstrate that verbs in Iron Ossetic occupy different functional heads in different contexts. Then, based on novel prosodic data, we show that the HVP indeed directly determines the size of Intonational Phrases in clauses with narrow foci and negative indefinites. Additionally, in wh-questions, language-specific mapping constraints come into play.
Argumentation models and their use in corpus annotation: Practice, prospects, and challenges
Authors: Lopes Cardoso Henrique , Sousa-Silva Rui , Carvalho Paula , Martins Bruno
Published: March 2023

The study of argumentation is transversal to several research domains, from philosophy to linguistics, from the law to computer science and artificial intelligence. In discourse analysis, several distinct models have been proposed to harness argumentation, each with a different focus or aim. To analyze the use of argumentation in natural language, several corpora annotation efforts have been carried out, with a more or less explicit grounding on one of such theoretical argumentation models. In fact, given the recent growing interest in argument mining applications, argument-annotated corpora are crucial to train machine learning models in a supervised way. However, the proliferation of such corpora has led to a wide disparity in the granularity of the argument annotations employed. In this paper, we review the most relevant theoretical argumentation models, after which we survey argument annotation projects closely following those theoretical models. We also highlight the main simplifications that are often introduced in practice. Furthermore, we glimpse other annotation efforts that are not so theoretically grounded but instead follow a shallower approach. It turns out that most argument annotation projects make their own assumptions and simplifications, both in terms of the textual genre they focus on and in terms of adapting the adopted theoretical argumentation model for their own agenda. Issues of compatibility among argument-annotated corpora are discussed by looking at the problem from a syntactical, semantic, and practical perspective. Finally, we discuss current and prospective applications of models that take advantage of argument-annotated corpora.
Process matters: the variegated effects of municipal amalgamation features on voter turnout revealed in a 10-country comparative investigation
Authors: Bolgherini Silvia , Paparo Aldo
Published: March 2023

Most literature finds a detrimental effect of amalgamation on voter turnout in municipal elections. Some other studies reveal instead null or even positive effects. We argue that this inconsistency derives from the fact that previous research has only analysed the amalgamation/turnout relation in single case studies. The contribution of this article is therefore twofold. First, it proposes a unified framework to investigate the amalgamation/turnout relation in comparative perspective, which clarifies the shortcut between size and amalgamation, disentangles the multifaced nature of municipal amalgamation, and outlines clear testable hypotheses related to its implementation – both at the national and at the local level. Secondly, it provides an original 10-European-country dataset of municipal amalgamations in the last decades (comprising Albania, Austria, Denmark, Finland, Germany, Iceland, Italy, Luxembourg, the Netherlands, and Norway) to empirically verify such hypotheses concerning the effects of the amalgamation features on voter turnout. Our study crucially reveals the relevance of the characteristics of the amalgamation process. When the amalgamation is imposed by the national government, turnout is particularly low, similarly to when the amalgamation occurs independently from a wide reform scheme. On the other hand, municipal turnout after amalgamation is higher when a larger number of municipalities are merged and when the amalgamated municipalities had a similar population before being merged. Moreover, our empirical evidence confirms the importance of traditional second-order predictors of turnout in municipal elections, even with specific reference to the post-amalgamation elections. Conversely, in such elections, the overall size of the (final) municipality is not a significant predictor of voter turnout.
Immunotherapy in Non-Small-Cell Lung Cancer (NSCLC)
Authors: Merle Geoffrey , Addeo Alfredo
Published: March 2023

Abstract. Treatment of non-small-cell lung cancer depends heavily on the cancer stage, and immunotherapy can play a major role at any stage. For locally advanced stages, the addition of an immune checkpoint inhibitor (ICI) to neoadjuvant chemotherapy improves pathological response and event-free survival. In the adjuvant setting, adding ICI, after adjuvant chemotherapy for resectable cancer, increases the disease-free survival. In unresectable stage III treated with concomitant chemotherapy and radiotherapy, adding ICI as a maintenance therapy increases progression-free survival and overall survival. In the metastatic setting, the addition of ICI to chemotherapy improves overall survival, progression-free survival, and response rates irrespective of the PD-L1 expression. ICI on its own may be considered in cases of PD-L1 expression equal or greater than at least 50%.
Cardiovascular, Renal and Pulmonary Toxicity of Immune Checkpoint Inhibitors in Cancer: What the GP Should Know
Authors: Smekens Laure , Genoud Vassilis , Usdin Nita , Ben Aïssa Assma
Published: March 2023

Abstract. Immunotherapy with immune checkpoint inhibitors (ICI) is administered in different cancer types and can lead to a wide range of immune-related adverse events including toxicity in vital organs such as the lungs, the kidneys, and the heart. The main hypothesis suggests an overactivation of the immune cells in the different organs. Whereas immune-related cardiotoxicity is very rare but life threatening, ICI-induced acute kidney injury and pneumonitis are more frequent but in general less severe. Renal toxicity corresponds in more than 90% to an acute tubulo-interstitial nephritis. Checkpoint inhibitors pneumonitis is diagnosed mainly on respiratory symptoms with new radiological features, especially under the form of a cryptogenic organising pneumonia. Cardiotoxicity is predominantly marked by myocarditis but also pericarditis and arrhythmias, among others. Early recognition, temporary or definitive cessation of ICI therapy and rapid initiation of high-dose corticosteroids are the cornerstones of the management, which must to be multidisciplinary in a specialised center.
Subduction Initiation of the Southern Branch of the Paleo‐Asian Ocean in the Middle Ordovician in the Southern Beishan Orogen
Authors: Mao Qigui , Xiao Wenjiao , Ao Songjian , Yang He , Song Dongfang , Zhang Zhiyong , Sang Miao , Wang Hao , Tan Zhou , Li Rui
Published: March 2023

The subduction initiation and the early‐stage tectonics of the southern Paleo‐Asian Ocean have rarely been discussed. To address these problems, we report new geochemical and geochronological data of arc‐related volcanic rocks in the Huaniushan arc of the southern Beishan. Basaltic andesites and high‐Mg rocks yield zircon U‐Pb ages of 449–422 Ma and 460–437 Ma, respectively. The basaltic andesite is a continental arc‐related tholeiite with moderate amounts of TiO2; and is enriched in light rare earth elements (LREE), such as Rb, Ba, Th and Sr; it is also depleted in Nb, Ta and Eu; and has moderate εHf (t) (−0.3 to +5.5) and εNd (t) (−3.48 to +0.03) values; and high (87Sr/86Sr)i (0.7066–0.7079) values. The high‐Mg andesite and dacite are sanukitic‐type high‐Mg rocks, which have high MgO (Mg# = 49–62) contents, A/CNK (0.82–2.36) and (La/Sm)N values, low Sr/Y (3–15) and Ba/Th (11–182) ratios, moderate to low εHf (t) (−16.7 to +7.6) and εNd (t) (−3.74 to +0.05), and high (87Sr/86Sr)i values. All geochemical data indicate that they were sourced from mixing between mantle‐peridotite‐derived melts and silicic melts generated by the subducting oceanic slab and/or sediments in a hot subduction setting. After integrating the Sanukitic high‐Mg andesites (HMAs) with previously reported Nb‐enriched basalt, volumes of arc‐related tholeiitic to calc‐alkaline volcanic rocks, I‐ to S‐type granites, and HT eclogites, we conclude that the subduction initiation was one of the most likely geodynamic process for the metamorphism and magmatism in the Middle Ordovician to early Silurian.
Winter Nighttime Enhancement of the Midlatitude Ionosphere: Contribution From the Diffusive and Wind‐Driven Plasma Transport
Authors: Li Quan‐Han , Hao Yong‐Qiang , Guo Jian‐Guang , Zhang Xiao‐Xin , Zhang Dong‐He , Xiao Zuo , Cui Jun
Published: March 2023

The characteristics of winter nighttime enhancement (WNE) of the midlatitude ionosphere at 300, 550, and 750 km altitude are presented, based on the radio occultation data from the Constellation Observing System for Meteorology, Ionosphere, and Climate. WNE at 750 km altitude has earlier start time and larger increasing rate than that at 550 km, possibly due to the downward plasma diffusion from above that dominates the most upper part of the ionosphere. Theoretical calculation of the plasma transport at 300 km altitude reveals the largest effect of downward diffusion at 45° geomagnetic latitude, consistent with the latitudinal distribution of WNE. Meanwhile, the wind‐driven plasma transport also contributes to WNE, at 30°W–180°W geographic longitude in the Southern Hemisphere. The strength and end time of WNE vary with longitude, and are correlated with the longitudinal variations of the enhancement in the conjugate (summer) hemisphere. This may be attributed to the transport processes in the interhemispheric geomagnetic flux tubes, which redistribute and balance the plasma between the conjugate hemispheres at night. The plasma flux from above is hence an important plasma source for further understanding of both the winter and summer nighttime enhancements.
Local Structure and Density of Liquid Fe‐C‐S Alloys at Moon's Core Conditions
Authors: Zhao Bin , Morard Guillaume , Boulard Eglantine , Boccato Silvia , Siersch Nicki C. , Rivoldini Attilio , Guignot Nicolas , Henry Laura , King Andrew , Zurkowski Claire , Fei Yingwei , Antonangeli Daniele
Published: March 2023

The local structure and density of ternary Fe‐C‐S liquid alloys have been studied using a combination of in situ X‐ray diffraction and absorption experiments between 1 and 5 GPa and 1600–1900 K. The addition of up to 12 at% of carbon (C) to Fe‐S liquid alloys does not significantly modify the structure, which is largely controlled by the perturbation to the Fe‐Fe network induced by S atoms. The liquid density determined from diffraction and/or absorption techniques allows us to build a non‐ideal ternary mixing model as a function of pressure, temperature, and composition in terms of the content of alloying light elements. The composition of the Moon's core is addressed based on this thermodynamic model. Under the assumption of a homogeneous liquid core proposed by two recent Moon models, the sulfur content would be 27–36 wt% or 12–23 wt%, respectively, while the carbon content is mainly limited by the Fe‐C‐S miscibility gap, with an upper bound of 4.3 wt%. On the other hand, if the core is partially molten, the core temperature is necessarily lower than 1850 K estimated in the text, and the composition of both the inner and outer core would be controlled by aspects of the Fe‐C‐S phase diagram not yet sufficiently constrained.
A Regional Ionospheric Storm Forecasting Method Using a Deep Learning Algorithm: LSTM
Authors: Ban Panpan , Guo Lixin , Zhao Zhenwei , Sun Shuji , Xu Tong , Xu Zhengwen , Sun Fengjuan
Published: March 2023

An ionospheric storm forecasting method was proposed using a deep learning algorithm, LSTM (long short‐term memory). We used the perturbation index to denote the level of an ionospheric storm, deduced from foF2 data, and helped to remove most of the local time and seasonal variations in the ionosphere. In constructing the model, a number of correlated factors were used as inputs, including the properties of coronal mass ejections, solar flare bursts, interplanetary conditions, and geomagnetic and ionospheric states, and the output was whether an ionospheric storm occurred locally in the next 24 hr. Data sets from 2007 to 2014 were used to train the model, and those from 2015 to 2016 were used for validation. The results showed that the model behaved well in most events. The mean precision rate, recall rate, accuracy, and F1 score of the model were 71.7%, 59.7%, 92.7%, and 65.0% in northern China and 78.9%, 56.3%, 96.3% and 65.0% in southern China, respectively. The LSTM forecasting model performed better than other models such as persistence, multiple‐layer perceptron and support vector machine models. Case studies also showed good performance during geomagnetic storms of different strengths. We believe that this model can be beneficial for functional ionospheric storm operation.
TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway
Authors: Lee Seul Gi , Chae Jongbeom , Woo Seon Min , Seo Seung Un , Kim Ha-Jeong , Kim Sang-Yeob , Schlaepfer David D. , Kim In-San , Park Hee-Sae , Kwon Taeg Kyu , Nam Ju-Ock
Published: March 2023

Extracellular matrix proteins are associated with metabolically healthy adipose tissue and regulate inflammation, fibrosis, angiogenesis, and subsequent metabolic deterioration. In this study, we demonstrated that transforming growth factor-beta (TGFBI), an extracellular matrix (ECM) component, plays an important role in adipose metabolism and browning during high-fat diet-induced obesity. TGFBI KO mice were resistant to adipose tissue hypertrophy, liver steatosis, and insulin resistance. Furthermore, adipose tissue from TGFBI KO mice contained a large population of CD11b+ and CD206+ M2 macrophages, which possibly control adipokine secretion through paracrine mechanisms. Mechanistically, we showed that inhibiting TGFBI-stimulated release of adipsin by Notch-1-dependent signaling resulted in adipocyte browning. TGFBI was physiologically bound to Notch-1 and stimulated its activation in adipocytes. Our findings revealed a novel protective effect of TGFBI deficiency in obesity that is realized via the activation of the Notch-1 signaling pathway.
Microfabricated polymer-metal biosensors for multifarious data collection from electrogenic cellular models
Authors: Didier Charles M. , Orrico Julia F. , Cepeda Torres Omar S. , Castro Jorge Manrique , Baksh Aliyah , Rajaraman Swaminathan
Published: March 2023

Benchtop tissue cultures have become increasingly complex in recent years, as more on-a-chip biological technologies, such as microphysiological systems (MPS), are developed to incorporate cellular constructs that more accurately represent their respective biological systems. Such MPS have begun facilitating major breakthroughs in biological research and are poised to shape the field in the coming decades. These biological systems require integrated sensing modalities to procure complex, multiplexed datasets with unprecedented combinatorial biological detail. In this work, we expanded upon our polymer-metal biosensor approach by demonstrating a facile technology for compound biosensing that was characterized through custom modeling approaches. As reported herein, we developed a compound chip with 3D microelectrodes, 3D microfluidics, interdigitated electrodes (IDEs) and a microheater. The chip was subsequently tested using the electrical/electrochemical characterization of 3D microelectrodes with 1 kHz impedance and phase recordings and IDE-based high-frequency (~1 MHz frequencies) impedimetric analysis of differential localized temperature recordings, both of which were modeled through equivalent electrical circuits for process parameter extraction. Additionally, a simplified antibody-conjugation strategy was employed for a similar IDE-based analysis of the implications of a key analyte (l-glutamine) binding to the equivalent electrical circuit. Finally, acute microfluidic perfusion modeling was performed to demonstrate the ease of microfluidics integration into such a polymer-metal biosensor platform for potential complimentary localized chemical stimulation. Overall, our work demonstrates the design, development, and characterization of an accessibly designed polymer-metal compound biosensor for electrogenic cellular constructs to facilitate comprehensive MPS data collection.
Extrachromosomal circular DNA in colorectal cancer: biogenesis, function and potential as therapeutic target
Authors: Chen Yinnan , Qiu Quanpeng , She Junjun , Yu Jun
Published: March 2023

Extrachromosomal circular DNA (ecDNA) has gained renewed interest since its discovery more than half a century ago, emerging as critical driver of tumor evolution. ecDNA is highly prevalent in many types of cancers, including colorectal cancer (CRC), which is one of the most deadly cancers worldwide. ecDNAs play an essential role in regulating oncogene expression, intratumor heterogeneity, and resistance to therapy independently of canonical chromosomal alterations in CRC. Furthermore, the existence of ecDNAs is attributed to the patient’s prognosis, since ecDNA-based oncogene amplification adversely affects clinical outcomes. Recent understanding of ecDNA put an extra layer of complexity in the pathogenesis of CRC. In this review, we will discuss the current understanding on mechanisms of biogenesis, and distinctive features of ecDNA in CRC. In addition, we will examine how ecDNAs mediate oncogene overexpression, gene regulation, and topological interactions with active chromatin, which facilitates genetic heterogeneity, accelerates CRC malignancy, and enhances rapid adaptation to therapy resistance. Finally, we will discuss the potential diagnostic and therapeutic implications of ecDNAs in CRC.
Fighting age-related orthopedic diseases: focusing on ferroptosis
Authors: Ru Qin , Li Yusheng , Xie Wenqing , Ding Yilan , Chen Lin , Xu Guodong , Wu Yuxiang , Wang Fudi
Published: March 2023

Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It is closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid metabolism, and the biosynthesis of compounds with antioxidant activities, including glutathione. In the past 10 years, increasing evidence has indicated a potentially strong relationship between ferroptosis and the onset and progression of age-related orthopedic diseases, such as osteoporosis and osteoarthritis. Therefore, in-depth knowledge of the regulatory mechanisms of ferroptosis in age-related orthopedic diseases may help improve disease treatment and prevention. This review provides an overview of recent research on ferroptosis and its influences on bone and cartilage homeostasis. It begins with a brief overview of systemic iron metabolism and ferroptosis, particularly the potential mechanisms of ferroptosis. It presents a discussion on the role of ferroptosis in age-related orthopedic diseases, including promotion of bone loss and cartilage degradation and the inhibition of osteogenesis. Finally, it focuses on the future of targeting ferroptosis to treat age-related orthopedic diseases with the intention of inspiring further clinical research and the development of therapeutic strategies.
Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity
Authors: Kim Chang H.
Published: March 2023

Immune tolerance deletes or suppresses autoreactive lymphocytes and is established at multiple levels during the development, activation and effector phases of T and B cells. These mechanisms are cell-intrinsically programmed and critical in preventing autoimmune diseases. We have witnessed the existence of another type of immune tolerance mechanism that is shaped by lifestyle choices, such as diet, microbiome and microbial metabolites. Short-chain fatty acids (SCFAs) are the most abundant microbial metabolites in the colonic lumen and are mainly produced by the microbial fermentation of prebiotics, such as dietary fiber. This review focuses on the preventive and immunomodulatory effects of SCFAs on autoimmunity. The tissue- and disease-specific effects of dietary fiber, SCFAs and SCFA-producing microbes on major types of autoimmune diseases, including type I diabetes, multiple sclerosis, rheumatoid arthritis and lupus, are discussed. Additionally, their key regulatory mechanisms for lymphocyte development, tissue barrier function, host metabolism, immunity, autoantibody production, and inflammatory effector and regulatory lymphocytes are discussed. The shared and differential effects of SCFAs on different types and stages of autoimmune diseases are discussed.
Emissions and fate of organophosphate esters in outdoor urban environments
Authors: Rodgers Timothy F. M. , Giang Amanda , Diamond Miriam L. , Gillies Emma , Saini Amandeep
Published: March 2023

Cities are drivers of the global economy, containing products and industries that emit many chemicals. Here, we use the Multimedia Urban Model (MUM) to estimate atmospheric emissions and fate of organophosphate esters (OPEs) from 19 global mega or major cities, finding that they collectively emitted ~81,000 kg yr−1 of ∑10OPEs in 2018. Typically, polar “mobile” compounds tend to partition to and be advected by water, while non-polar “bioaccumulative” chemicals do not. Depending on the built environment and climate of the city considered, the same compound behaves like either a mobile or a bioaccumulative chemical. Cities with large impervious surface areas, such as Kolkata, mobilize even bioaccumulative contaminants to aquatic ecosystems. By contrast, cities with large areas of vegetation fix and transform contaminants, reducing loadings to aquatic ecosystems. Our results therefore suggest that urban design choices could support policies aimed at reducing chemical releases to the broader environment without increasing exposure for urban residents.
Crystal structure of a subtilisin-like autotransporter passenger domain reveals insights into its cytotoxic function
Authors: Hor Lilian , Pilapitiya Akila , McKenna James A. , Panjikar Santosh , Anderson Marilyn A. , Desvaux Mickaël , Paxman Jason J. , Heras Begoña
Published: March 2023

Autotransporters (ATs) are a large family of bacterial secreted and outer membrane proteins that encompass a wide range of enzymatic activities frequently associated with pathogenic phenotypes. We present the structural and functional characterisation of a subtilase autotransporter, Ssp, from the opportunistic pathogen Serratia marcescens. Although the structures of subtilases have been well documented, this subtilisin-like protein is associated with a 248 residue β-helix and itself includes three finger-like protrusions around its active site involved in substrate interactions. We further reveal that the activity of the subtilase AT is required for entry into epithelial cells as well as causing cellular toxicity. The Ssp structure not only provides details about the subtilase ATs, but also reveals a common framework and function to more distantly related ATs. As such these findings also represent a significant step forward toward understanding the molecular mechanisms underlying the functional divergence in the large AT superfamily.
Origin of superconductivity in hole doped SrBiO3 bismuth oxide perovskite from parameter-free first-principles simulations
Authors: Varignon Julien
Published: March 2023

The recent discovery of nickel oxide superconductors have highlighted the importance of first-principles simulations for understanding the formation of the bound electrons at the core of superconductivity. Nevertheless, superconductivity in oxides is often ascribed to strong electronic correlation effects that density functional theory (DFT) cannot properly take into account, thereby disqualifying this technique. Being isostructural to nickel oxides, Sr1-xKxBiO3 superconductors form an ideal testbed for unveiling the lowest theory level needed to model complex superconductors and the underlying pairing mechanism yielding superconductivity. Here I show that parameter-free DFT simulations capture all the experimental features and related quantities of Sr1-xKxBiO3 superconductors, encompassing the prediction of an insulating to metal phase transition upon increasing the K doping content and of an electron-phonon coupling constant of 1.22 in sharp agreement with the experimental value of 1.3 ± 0.2. The proximity of a disproportionated phase is further demonstrated to be a prerequisite for superconductivity in bismuthates.
Premorbid performances determine the deleterious effects of nigrostriatal degeneration and pramipexole on behavioural flexibility
Authors: Decourt Mélina , Balado Eric , Francheteau Maureen , Solinas Marcello , Benoît-Marand Marianne , Fernagut Pierre-Olivier
Published: March 2023

Subtle cognitive impairment can occur early in the course of Parkinson’s disease (PD) and may manifest under different forms of executive dysfunction such as impaired cognitive flexibility. The precise contribution of nigrostriatal dopaminergic neurodegeneration to these non-motor features of the disease is poorly known. Whether such cognitive impairment associated with the disease process may also predate and contribute to the development of neuropsychiatric side-effects following dopamine replacement therapy remains largely unknown. To address these issues, we investigated the respective contributions of nigrostriatal degeneration and chronic treatment with the dopamine D3-preferring agonist pramipexole on behavioral flexibility in a rat model of PD. Flexible, intermediate and inflexible rats were identified based on baseline assessment of behavioral flexibility using an operant set-shifting task. Nigrostriatal degeneration was induced by bilateral viral-mediated expression of A53T mutated human α-synuclein in the substantia nigra pars compacta and behavioral flexibility was assessed after induction of nigrostriatal degeneration, and during chronic pramipexole treatment. Nigrostriatal degeneration impaired behavioral flexibility in flexible but not in inflexible rats. Pramipexole induced a decrease of behavioral flexibility that was exacerbated in lesioned rats and in the most flexible individuals. Furthermore, the deficits induced by pramipexole in lesioned rats affected different components of the task between flexible and inflexible individuals. This study demonstrates that nigrostriatal degeneration and pramipexole unequally impair behavioral flexibility, suggesting that the susceptibility to develop non-motor impairments upon treatment initiation could primarily depend on premorbid differences in behavioral flexibility.
Experimental quantum end-to-end learning on a superconducting processor
Authors: Pan Xiaoxuan , Cao Xi , Wang Weiting , Hua Ziyue , Cai Weizhou , Li Xuegang , Wang Haiyan , Hu Jiaqi , Song Yipu , Deng Dong-Ling , Zou Chang-Ling , Wu Re-Bing , Sun Luyan
Published: March 2023

Machine learning can be enhanced by a quantum computer via its inherent quantum parallelism. In the pursuit of quantum advantages for machine learning with noisy intermediate-scale quantum devices, it was proposed that the learning model can be designed in an end-to-end fashion, i.e., the quantum ansatz is parameterized by directly manipulable control pulses without circuit design and compilation. Such gate-free models are hardware friendly and can fully exploit limited quantum resources. Here, we report the experimental realization of quantum end-to-end machine learning on a superconducting processor. The trained model can achieve 98% recognition accuracy for two handwritten digits (via two qubits) and 89% for four digits (via three qubits) in the MNIST (Mixed National Institute of Standards and Technology) database. The experimental results exhibit the great potential of quantum end-to-end learning for resolving complex real-world tasks when more qubits are available.
Tropical deforestation causes large reductions in observed precipitation
Authors: Smith C. , Baker J. C. A. , Spracklen D. V.
Published: March 2023

Tropical forests play a critical role in the hydrological cycle and can influence local and regional precipitation1. Previous work has assessed the impacts of tropical deforestation on precipitation, but these efforts have been largely limited to case studies2. A wider analysis of interactions between deforestation and precipitation—and especially how any such interactions might vary across spatial scales—is lacking. Here we show reduced precipitation over deforested regions across the tropics. Our results arise from a pan-tropical assessment of the impacts of 2003–2017 forest loss on precipitation using satellite, station-based and reanalysis datasets. The effect of deforestation on precipitation increased at larger scales, with satellite datasets showing that forest loss caused robust reductions in precipitation at scales greater than 50 km. The greatest declines in precipitation occurred at 200 km, the largest scale we explored, for which 1 percentage point of forest loss reduced precipitation by 0.25 ± 0.1 mm per month. Reanalysis and station-based products disagree on the direction of precipitation responses to forest loss, which we attribute to sparse in situ tropical measurements. We estimate that future deforestation in the Congo will reduce local precipitation by 8–10% in 2100. Our findings provide a compelling argument for tropical forest conservation to support regional climate resilience.
Genome-wide hydroxymethylation profiles in liver of female Nile tilapia with distinct growth performance
Authors: Konstantinidis Ioannis , Sætrom Pål , Fernandes Jorge M. O.
Published: March 2023

The mechanisms underlying the fast genome evolution that occurs during animal domestication are poorly understood. Here, we present a genome-wide epigenetic dataset that quantifies DNA hydroxymethylation at single nucleotide resolution among full-sib Nile tilapia (Oreochromis niloticus) with distinct growth performance. In total, we obtained 355 million, 75 bp reads from 5 large- and 5 small-sized fish on an Illumina NextSeq500 platform. We identified several growth-related genes to be differentially hydroxymethylated, especially within gene bodies and promoters. Previously, we proposed that DNA hydroxymethylation greatly affects the earliest responses to adaptation and potentially drives genome evolution through its targeted enrichment and elevated nucleotide transversion rates. This dataset can be analysed in various contexts (e.g., epigenetics, evolution and growth) and compared to other epigenomic datasets in the future, namely DNA methylation and histone modifications. With forthcoming advancements in genome research, this hydroxymethylation dataset will also contribute to better understand the epigenetic regulation of key genomic features, such as cis-regulatory and transposable elements.
Effects of molecular weight fraction on antioxidation capacity of rice protein hydrolysates
Authors: Chen Hui-Ju , Dai Fan-Jhen , Chen Cheng-You , Fan Siao-Ling , Zheng Ji-Hong , Chau Chi-Fai , Lin Yung-Sheng , Chen Chin-Shuh
Published: March 2023

Rice protein was used as a starting material to provide rice protein hydrolysates (RPH) through enzyme-assisted extraction. RPH was further fractionated using ultrafiltration membrane (UF) and classified by molecular weight (MW; MW < 1 kDa, MW 1–10 kDa, and MW > 10 kDa). Peptides with MW < 1 kDa possessed superior antioxidant properties (p < 0.05). Therefore, UF demonstrated great efficacy in selectively separating antioxidant peptides. A Pearson correlation analysis revealed that the total phenolic concentration was correlated with oxygen radical absorbance capacity (ORAC; r = 0.999, p < 0.05). Amino acid contents had negative correlations with the scavenging activity (specifically, IC50) of 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (r =  − 0.986 to − 1.000). Reducing power was related to aromatic amino acid contents (r = 0.997, p < 0.05). In this study, enzymatic hydrolysis was discovered to be an effective method of extracting and isolating natural antioxidant proteins from broken rice, thus preserving the nutritional quality of rice and making those proteins more accessible in future applications.
Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions
Authors: Karere Genesio M. , Glenn Jeremy P. , Li Ge , Konar Ayati , VandeBerg John L. , Cox Laura A.
Published: March 2023

Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, -451a, -191-5p, -148a-3p, -17-5p, -378c, and -144-3p) were differentially expressed between paired fatty streak lesion and no-lesion sites of the tissue, and 27 miRNAs (e.g., miR-92a-3p, -5001, -342-3p, miR-28-3p, -21-5p, -221-3p, 146a-5p, and -16-5p) in fibrous plaques. The expression of 14 blood miRNAs significantly correlated with extent of lesions and the number of plaques. We identified coordinately regulated miRNA-gene networks in which miR-17-5p and miR-146a-5p are central hubs and miR-5001 and miR-7975 are potentially novel miRNAs associated with early atherosclerosis. In summary, we have identified miRNAs expressed in lesions and in blood that correlate with lesion burden and are potential therapeutic targets and biomarkers. These findings are a first step in elucidating miRNA regulated molecular mechanisms that underlie early atherosclerosis in a baboon model, enabling translation of our findings to humans.
Multiple solutions for non-linear radiative mixed convective hybrid nanofluid flow over an exponentially shrinking surface
Authors: Sarfraz Mahnoor , Yasir Muhammad , Khan Masood
Published: March 2023

Hybrid nanofluids have gained too much attention due to their enhanced thermophysical properties and practical applications. In comparison to conventional nanofluids, their capacity to enhance heat transport is impressive. The simultaneous numerical calculations of hybrid and mono nanofluids across an exponentially shrinking surface in a porous medium are taken into consideration here. The analysis of the thermal energy distribution is carried out by using the convective boundary conditions. Shrinking, permeability, and magnetohydrodynamic controlled the motion of the flow. The objective of this research is to conduct stability analysis and identify the existence of dual solutions in the presence of heat source/sink and nonlinear Roseland thermal radiation. The technique, bvp4c, a collocation method is used to achieve numerical results. It is noted that the energy transport is enhanced immensely due to the presence of a mixture of nanoparticles (hybrid) in comparison to mono nanofluids. The stability analysis shows that the solutions for the upper branch were stable, while the solutions for the lower branch were unstable. Moreover, shrinking parameter contributes significantly to exhibit the dual nature of the solutions. Due to the increment in the heat generation/absorption and temperature ratio, the kinetic energy is inclined, which causes the temperature distribution to rise for both branches. For stable branches, an increase in wall stress values is evident as a result of permeability and stretching of sheet, whereas unstable branches show the opposite trend.
Training-induced impairment of endothelial function in track and field female athletes
Authors: Grandys Marcin , Majerczak Joanna , Frolow Marzena , Chlopicki Stefan , Zoladz Jerzy A.
Published: March 2023

Professional athletes are often exposed to high training loads that may lead to overfatigue, overreaching and overtraining that might have a detrimental effects on vascular health. We determined the effects of high training stress on endothelial function assessed by the flow-mediated dilation (FMD) and markers of glycocalyx shedding. Vascular examination as well as broad biochemical, hormonal and cardiometabolic evaluation of sprint and middle-distance female runners were performed after 2 months of preparatory training period and compared to age-matched control group of women. Female athletes presented with significantly reduced FMD (p < 0.01) and higher basal serum concentrations of hyaluronan (HA) and syndecan-1 (SDC-1) (p < 0.05 and p < 0.001, respectively), that was accompanied by significantly lower basal serum testosterone (T) and free testosterone (fT) concentrations (p < 0.05) and higher cortisol (C) concentration (p < 0.05). It resulted in significantly lower T/C and fT/C ratios in athletes when compared to controls (p < 0.01). Moreover, fT/C ratio were significantly positively correlated to FMD and negatively to HA concentrations in all studied women. Accordingly, the training load was significantly negatively correlated with T/C, fT/C and FMD and positively with the concentrations of HA and SDC-1. We concluded that young female track and field athletes subjected to physical training developed impairment of endothelial function that was associated with anabolic-catabolic hormone balance disturbances. Given that training-induced impairment of endothelial function may have a detrimental effects on vascular health, endothelial status should be regularly monitored in the time-course of training process to minimalize vascular health-risk in athletes.
DFMA-oriented modular and parametric design and secondary splitting of vertical PC components
Authors: Dong Daode , Zou Yiquan , Pan Han , Zhou Guowei , Feng Yu , Tang Yuchen
Published: March 2023

The design and production of assembled buildings are difficult to standardise, which limits their extensive application. In this paper, the design for manufacture and assembly (DFMA) concept is applied to the design of vertical precast concrete (PC) components for assembled buildings. Taking vertical PC components as an example, the rapid modelling and whole life-cycle application of DFMA-oriented PC components for assembled buildings are investigated. Firstly, the modular design method is introduced. By combining parametric design and building information modelling (BIM), we propose a modular, parametric design method and process of PC components based on DFMA. Secondly, the design of standard modules after secondary splitting is introduced for a better DFMA-oriented parametric design of PC components. We explored the secondary development process of DFMA and BIM and the module creation process of the parametric standard based on family templates and DFMA. Thirdly, based on the parametric standard module, the application of the optimised whole life cycle of design, manufacture and assembly of PC components is introduced. Finally, the feasibility of this method is verified by practical cases. The design process for PC components is fast, accurate and standardised. The integrated application of BIM is accelerated, and digital collaboration in assembly construction is strengthened. The study results are conducive to establishing a standardised design and production system for PC components, reducing design costs, improving design efficiency and the comprehensive benefits of assembled buildings.