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Amar Causevic, N. Haque, Matthew LoCastro, S. Selvakkumaran, Sasja Beslik, S. Causevic

Abstract:In order to address the research gaps on climate finance dynamics in developing countries, especially those with low governance scores, this study assesses the 2016–2020 bilateral climate finance to these countries. The total disbursed bilateral climate finance was US$1.3 billion (92 percent for mitigation, 7 percent for adaptation, and 1 percent for mitigation and adaptation simultaneously). Development-focused loans were the prevailing financial instrument cumulatively, and grants were the prevailing instrument on a per-country level. Japan was the biggest provider of bilateral climate finance (US$1 billion) to fund Uzbekistan's natural gas-fired electric power plants. All major bilateral climate finance providers ranked high on governance scores compared to the ten examined countries. Countries examined in this study will need to receive higher amounts of bilateral climate change finance in order to improve their readiness to address this issue and reduce their vulnerability to climate change impacts.

Nea Korvenlaita, Mireia Gómez-Budia, Flavia Scoyni, C. Pistono, L. Giudice, S. Eamen, Sanna Loppi, Ana Hernández de Sande et al.

Abstract Hypoxia induces changes in the secretion of extracellular vesicles (EVs) in several non‐neuronal cells and pathological conditions. EVs are packed with biomolecules, such as microRNA(miR)‐21‐5p, which respond to hypoxia. However, the true EV association of miR‐21‐5p, and its functional or biomarker relevance, are inadequately characterised. Neurons are extremely sensitive cells, and it is not known whether the secretion of neuronal EVs and miR‐21‐5p are altered upon hypoxia. Here, we characterised the temporal EV secretion profile and cell viability of neurons under hypoxia. Hypoxia induced a rapid increase of miR‐21a‐5p secretion in the EVs, which preceded the elevation of hypoxia‐induced tissue or cellular miR‐21a‐5p. Prolonged hypoxia induced cell death and the release of morphologically distinct EVs. The EVs protected miR‐21a‐5p from enzymatic degradation but a remarkable fraction of miR‐21a‐5p remained fragile and non‐EV associated. The increase in miR‐21a‐5p secretion may have biomarker potential, as high blood levels of miR‐21‐5p in stroke patients were associated with significant disability at hospital discharge. Our data provides an understanding of the dynamic regulation of EV secretion from neurons under hypoxia and provides a candidate for the prediction of recovery from ischemic stroke.

G. Calderini, F. Crescioli, G. Dalla Betta, G. Gariano, C. Gemme, F. Guescini, S. Hadzic, T. Heim et al.

ITk detector, the new ATLAS tracking system at High Luminosity LHC, will be equipped with 3D pixel sensor modules in the innermost layer (L0). The pixel cell dimensions will be either 25 × 100 μm2 (barrel) or 50 × 50 μm2 (endcap), with one read-out electrode at the centre of a pixel and four bias electrodes at the corners. Sensors from pre-production wafers (50 × 50 μm2) produced by FBK have been bump bonded to ITkPixV1.1 chips at IZM. Bare modules have been assembled in Genoa on Single Chip Cards and characterized in laboratory and on beam.

Linda M Seymour, Janille M. Maragh, Paolo Sabatini, Michel Di Tommaso, J. Weaver, A. Masic

Ancient Roman concretes have survived millennia, but mechanistic insights into their durability remain an enigma. Here, we use a multiscale correlative elemental and chemical mapping approach to investigating relict lime clasts, a ubiquitous and conspicuous mineral component associated with ancient Roman mortars. Together, these analyses provide new insights into mortar preparation methodologies and provide evidence that the Romans employed hot mixing, using quicklime in conjunction with, or instead of, slaked lime, to create an environment where high surface area aggregate-scale lime clasts are retained within the mortar matrix. Inspired by these findings, we propose that these macroscopic inclusions might serve as critical sources of reactive calcium for long-term pore and crack-filling or post-pozzolanic reactivity within the cementitious constructs. The subsequent development and testing of modern lime clast–containing cementitious mixtures demonstrate their self-healing potential, thus paving the way for the development of more durable, resilient, and sustainable concrete formulations.

Martina Andellini, Salman Haleem, Massimiliano Angelini, M. Ritrovato, Riccardo Schiaffini, E. Iadanza, L. Pecchia

Purpose Paediatric Type 1 Diabetes (T1D) patients are at greater risk for developing severe hypo and hyperglycaemic events due to poor glycaemic control. To reduce the risk of adverse events, patients need to achieve the best possible glycaemic management through frequent blood glucose monitoring with finger prick or Continuous Glucose Monitoring (CGM) systems. However, several non-invasive techniques have been proposed aiming at exploiting changes in physiological parameters based on glucose levels. The overall objective of this study is to validate an artificial intelligence (AI) based algorithm to detect glycaemic events using ECG signals collected through non-invasive device. Methods This study will enrol T1D paediatric participants who already use CGM. Participants will wear an additional non-invasive wearable device for recording physiological data and respiratory rate. Glycaemic measurements driven through ECG variables are the main outcomes. Data collected will be used to design, develop and validate the personalised and generalized classifiers based on a deep learning (DL) AI algorithm, able to automatically detect hypoglycaemic events by using few ECG heartbeats recorded with wearable devices. Results Data collection is expected to be completed approximately by June 2023. It is expected that sufficient data will be collected to develop and validate the AI algorithm. Conclusion This is a validation study that will perform additional tests on a larger diabetes sample population to validate the previous pilot results that were based on four healthy adults, providing evidence on the reliability of the AI algorithm in detecting glycaemic events in paediatric diabetic patients in free-living conditions. Trial registration ClinicalTrials.gov identifier: NCT03936634. Registered on 11 March 2022, retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT05278143?titles=AI+for+Glycemic+Events+Detection+Via+ECG+in+a+Pediatric+Population&draw=2&rank=1 .

Martin Kondža, Marta Mandić, Ivona Ivančić, S. Vladimir-Knežević, I. Brizić

Artemisia annua L. has long been known for its medicinal properties and isolation of ingredients whose derivatives are used for therapeutic purposes. The CYP2B6 and CYP3A4 enzymes belong to a large family of cytochrome P450 enzymes. These enzymes are involved in the metabolism of drugs and other xeonobiotics. It is known that various compounds can induce or inhibit the activity of these enzymes. The aim of this study was to investigate the nature of the inhibitory effect of Artemisia annua extract on CYP2B6 and CYP3A4 enzymes, as well as the type of inhibition, the presence of reversible or pseudo-irreversible inhibition, and the possible heme destruction. The methanolic extract of Artemisia annua showed an inhibitory effect on CYP2B6 (by almost 90%) and CYP3A4 enzymes (by almost 70%). A significant decrease in heme concentration by 46.8% and 38.2% was observed in different assays. These results clearly indicate that the studied plant extracts significantly inhibited the activity of CYP2B6 and CYP3A4 enzymes. Moreover, they showed irreversible inhibition, which is even more important for possible interactions with drugs and dietary supplements.

S. Štrbac, M. Kašanin-Grubin, L. Pezo, N. Stojić, B. Lončar, Ljiljana Ćurčić, M. Pucarević

With the goal of enhancing the quality of the environment, urban green infrastructure (UGI) is an essential element in sustainable cities, and nature-based solutions (NBS) are being carried out as new infrastructure solutions that increase the resilience of cities. In this research, the method of theoretical analysis and the content analysis as the basic fact-gathering technique was applied to answer to following questions: What are the hindrances and bottlenecks in implementing NBS? Are the current decision-making mechanisms helping NBS get in route to shape cities? Is there any binding policy in practice that promotes NBS? In Belgrade is planned Type 3 of the degree of intervention/level and engineering type—Creation and new ecosystem management in the classifications of intensive urban green space management; urban planning strategies; urban water management; ecological restoration of degraded terrestrial ecosystems; and restoration and creation of semi-natural water bodies and hydrographic networks. In the future, it is essential to implement policies and incentives on national, regional, and local scales that help encourage the usage of NBS in the development of urban infrastructure.

A. Prkić, N. Vermeulen, B. Kooistra, B. The, M. P. J. Bekerom, D. Eygendaal

Purpose: Total elbow arthroplasty (TEA) is rarely performed compared to other arthroplasties. For many surgical procedures, literature shows better outcomes when they are performed by experienced surgeons and in so-called ‘high-volume’ hospitals. We systematically reviewed the literature on the relationship between surgical volume and outcomes following TEA. Methods: A literature search was performed using the MEDLINE, EMBASE and CINAHL databases. The literature was systematically reviewed for original studies comparing TEA outcomes among hospitals or surgeons with different annual or career volumes. For each study, data were collected on study design, indications for TEA, number of included patients, implant types, cut-off values for volume, number and types of complications, revision rate and functional outcome measures. The methodological quality of the included studies was assessed using the Newcastle–Ottawa Scale. Results: Two studies, which included a combined 2301 TEAs, found that higher surgeon volumes were associated with lower revision rates. The examined complication rates did not differ between high- and low-volume surgeons. In one study, low-hospital volume is associated with an increased risk of revision compared to high-volume hospitals, but for other complication types, no difference was found. Conclusions: Based on the results, the evidence suggests that high-volume centers have a lower revision rate in the long term. No minimum amount of procedures per year can be advised, as the included studies have different cut-off values between groups. As higher surgeon- and center-volume, (therefore presumably experience) appear to yield better outcomes, centralization of total elbow arthroplasty should be encouraged.

Tade Popović, V. Tomić, Nikolina Penava, Milena Brkić, Andrej Galić

Background Spontaneous sternal fracture is an extremely rare cause of chest pain during or after childbirth. To date, only three cases of sternal fracture during childbirth have been reported. This case report represents the first documented case of spontaneous sternal fracture among multiparous women. Case Description A 33-year-old multiparous woman with an uncomplicated medical history is described, who delivered a healthy fourth infant vaginally at 41 weeks of pregnancy. After the previous three deliveries, each child had been breastfed for more than a year, and the third delivery was eight months before conception, and she breastfed until 3 months of pregnancy. During the final stage of labor, while performing the Valsalva maneuver in the lithotomy position, she felt a sharp, severe chest pain. Postpartum work-up included cardioselective enzymes that were within reference values, and radiological work-up confirmed a non-displaced sternal fracture, which was treated conservatively with symptomatic therapy, with complete recovery after 6 weeks. Conclusions This case report suggests the need to consider sternal fracture as a differential diagnostic consideration in women who experience chest pain during or immediately after delivery. Changes in metabolism, especially calcium metabolism during pregnancy and lactation, can result in transient osteopenia and, with increased mechanical stress, cause bone fracture. Special attention should be paid to patients who breastfed immediately before conception or who breastfeed during pregnancy, to vitamin and mineral replacement therapy, adequate nutrition, and physical activity. Timely diagnosis of sternal fracture can significantly reduce the need for expensive and invasive diagnostic tests. Further research is needed on osteopenia in pregnant women, especially multiparous women who are breastfeeding immediately before conception or during pregnancy.

Andi Alijagic, N. Scherbak, O. Kotlyar, P. Karlsson, Xuying Wang, I. Odnevall, O. Benada, Ali Amiryousefi et al.

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

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