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.

Simple Summary The treatment outcomes in patients with head and neck cancer vary greatly, and serious side effects are often observed. Being able to predict therapy effects is therefore crucial for choosing the best treatment option for each patient. In this study, we developed an assay to evaluate how head and neck tumor cells respond to radiation and chemotherapy. Treatment of thin patient-derived cancer tissue slices in the laboratory (in vitro) resulted in large differences in individual tumor’s reactions to treatment. In the sensitive tumors, cancer cells repaired the DNA damage inflicted by therapy only partially, stopped multiplying, and showed increased levels of cell death. On the other hand, resistant tumors were able to recover from the damage caused by the treatment. The next crucial step is to investigate whether the differences we observed in vitro can indeed predict the treatment outcomes; this is currently being tested in an ongoing clinical trial. Abstract Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient. Methods: Resection material of 17 primary HNSCC patients was cultured ex vivo, irradiated or cisplatin-treated, after which the effect on tumor cell vitality was analyzed several days after treatment. Results: Ionizing radiation (IR) affected tumor cell growth and viability with a clear dose-response relationship, and marked heterogeneity between tumors was observed. After a single dose of 5Gy, proliferation in IR-sensitive tumors dropped below 30% of the untreated level, while IR-resistant tumors maintained at least 60% of proliferation. IR-sensitive tumors showed on average a twofold increase in apoptosis, as well as an increased number and size of DNA damage foci after treatment. No differences in the homologous recombination (HR) proficiency between IR-sensitive and –resistant tumors were detected. Cisplatin caused a decrease in proliferation, as well as induction of apoptosis, again with marked variation between the samples. Conclusions: Our functional ex vivo assay discriminated between IR-sensitive and IR-resistant HNSCC tumors, and may also be suitable for predicting response to cisplatin. Its predictive value is currently under investigation in a prospective clinical study.

Edge computing is one of the key features of the 5G technology-scape that is realizing new and enhanced automotive use cases for improving road safety and emergency response management. Back Situation Awareness (BSA) is such a use case that provides an advance notification to the vehicles of an arriving emergency vehicle (EmV). This paper presents an algorithm for enhancing the accuracy of the advanced Estimated Time of Arrival (ETA) notification of an approaching EmV towards the other vehicles on the highway. The notification is expected to ensure timely reaction by the vehicles to create a clear corridor for the EmV to pass through unhindered, thereby saving critical time to reach the emergency event in a safe manner. The main features of the presented solution are i) the self-correcting algorithm, ii) adaptive and dynamic dissemination areas size allocation, as a response to traffic changes, and iii) the evaluation of the ETA estimation accuracy. We have used the real travel time data measurements collected on the E313 highway (Antwerp, Belgium), to evaluate the performance of the algorithm. The performance is evaluated and compared in terms of accuracy and run-time complexity, using different methods such as Kalman filter, Filter-less method, Moving Average, and Exponential Moving Average filters. It is observed that the Kalman filter provides better accuracy on the ETA estimation, thereby reducing the estimation error by around 14% on average.

Computed tomography (CT) is a diagnostic imaging process that uses ionising radiation to obtain information about the interior anatomic structure of the human body. Considering that the medical use of ionising radiation implies exposing patients to radiation that may lead to unwanted stochastic effects and that those effects are less probable at lower doses, optimising imaging protocols is of great importance. In this paper, we used an assembled 3D-printed infant head phantom and matched its image quality parameters with those obtained for a commercially available adult head phantom using the imaging protocol dedicated for adult patients. In accordance with the results, an optimised scanning protocol was designed which resulted in dose reductions for paediatric patients while keeping image quality at an adequate level.

In this paper, we analyze the impact of the marketing authorization of EMA-approved vaccines on the returns of equity funds in the EU. Using the event study methodology, we report that the introduction of all vaccines had a positive impact on the funds' returns. Higher abnormal returns were associated with the earlier vaccines, indicating the first-mover advantage and the abnormal returns were persistent across several event windows. The findings imply that equity markets welcomed the vaccine administration as an important pharmaceutical intervention to support the quasi-revival of business activities. Consequently, there was a significant uplift in the economic bottom line.

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.

The emergence of SARS-CoV-2 variants of concern (VOC) is driven by mutations that mediate escape from neutralizing antibodies. There is also evidence that mutations can cause loss of T cell epitopes. However, studies on viral escape from T cell immunity have been hampered by uncertain estimates of epitope prevalence. Here, we map and quantify CD8 T cell responses to SARS-CoV-2-specific minimal epitopes in blood drawn from April to June 2020 from 83 COVID-19 convalescents. Among 37 HLA ligands eluted from five prevalent alleles and an additional 86 predicted binders, we identify 29 epitopes with an immunoprevalence ranging from 3% to 100% among individuals expressing the relevant HLA allele. Mutations in VOC are reported in 10.3% of the epitopes, while 20.6% of the non-immunogenic peptides are mutated in VOC. The nine most prevalent epitopes are conserved in VOC. Thus, comprehensive mapping of epitope prevalence does not provide evidence that mutations in VOC are driven by escape of T cell immunity.

Background Clinical guidelines recommend the identification of asthma comorbidities, especially treatable problems such as parental behaviours and child and parent anxiety. Purpose We aimed to (1) explore associations of asthma severity with child and parent state anxiety, trait anxiety, and asthma-related anxiety as well as with caregiver behaviours around physical activity and (2) explore if caregiver behaviours around physical activity were associated with use of inhaled β-Agonists when symptomatic, and with child and parent anxiety. Patients and methods Patients ages 3–17 years with asthma (n = 72) and their parents were recruited from the Pulmonology-Allergology Pediatric clinic University Hospital Centre Split in Split, Croatia during 2021. During a clinical visit, the pharmacological regimen was assessed and spirometry was performed. Children completed the State-Trait Anxiety Inventory for Children (STAI-C) and the Youth Asthma-Related Anxiety Scale (YASS). Parents completed the State-Trait Anxiety Inventory (STAI), the Parent Asthma-Related Anxiety Scale (PASS), and the Physical Activity Parenting Practices – Short Form (PAPP). Results Most patients had mild asthma (69.4%). Children with moderate to severe asthma had increased asthma-related anxiety (mean = 11.94 ± 6.1) compared with children with mild asthma (mean = 5.97 ± 6.39, p = 0.003). Parents of children with mild asthma reported behaviours allowing unsupervised physical activity outside more often when compared to parents of children with moderate or severe asthma. Physical activity facilitation parenting behaviour reduced the odds of a child's need for quick-reliever medication when symptomatic (OR = 0.376,95% CI = −1.885 to −0.072; p = 0.034); more coercive parenting increased the odds of a child's additional use of such medications (OR = 2.602; 95% CI = 0.005 to 1.908; p = 0.049). Parents of children in the highest quartile of trait anxiety showed less non-directive support (1.97 ± 1.01 vs. 2.89 ± 1.19, p = 0.031) and less autonomy support (3.14 ± 1.32 vs. 4.11 ± 1.23, p = 0.037) of physical activity in their children than those with less trait anxiety. Conclusion Asthma-related anxiety was an important construct in this sample of children, associated with their disease severity as well as their parent's behaviours around the child's physical activities. Current research, conducted during the COVID-19 pandemic, recognised the tangible ways that parents support or avoid the asthmatic children's physical activity participation. Child anxiety and recognised parental physical activity behaviours are potentially important factors to assess and target for intervention.

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.

Abstract Orevactaene yellow pigment was produced by solid-state fermentation of broken rice using Epicoccum nigrum. The pigment was extracted using water as a solvent and subjected to stability studies at different temperatures (30, 40, 60, and 80°C), pH (4, 6, and 8), sterilization, and sunlight exposure treatment. The observed data were fitted in the first-order kinetic model. Yellow pigment stability was found to vary at different temperatures studied. At 30°C, only a 4% decrease in color intensity was observed after 2 h; at 40°C, an 8% decrease was observed, and at 80°C and pH 6.0, 17% of color intensity was lost. These results showed that the orevactaene pigment produced by E. nigrum is heat-sensitive and changes in color intensity should be expected in heat-processed products. After 180 min at 80°C, yellow pigments maintained 82 and 76% of the initial color at pH 6 and 8, while a 65% decrease in color intensity was observed at 80°C, pH 4. Autoclaving resulted in 69% decay and exposure of pigment to sunlight for 2 h showed 1% decay. The half-life period of the pigment at different temperatures varied from 82.5 to 5.25 h. The decimal reduction time decreased from 275 to 17.5 h with an increase in the temperature. Thermodynamic parameters for pigment decay at pH 6.0 were represented in terms of enthalpy ∆H, activation energy E a, free energy ∆G, and entropy ∆S. The values observed were 44.52–44.93, 48.48, 96.60–105.18 kJ/mol, and −170.50 to −171.85 J/mol/K, respectively. All these parameters help in predicting the quality changes in terms of appearance during thermal processing and optimizing the process.

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.

In this study, the authors summarize the current knowledge on epidemiology, demographics, risk factors, and prognostic factors that influence outcomes in patients with adult Chiari malformation type I (CM-I) who underwent posterior fossa decompression surgery with duraplasty. Furthermore, they describe the contribution of their research group to the field of adult CM-I treatment, including association of increased body mass index with severity of CM-I and syringomyelia, relevant surgical anatomy, and surgical technique of 270° microsurgical decompression of foramen magnum. The authors also report on common complications in the literature and describe techniques for prevention of complications.