We explored the outcomes of germline BRCA1/2 pathogenic/likely pathogenic variants (PVs/LPVs) in the endocrine-sensitive disease treated with first line standard of care cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Three studies retrospectively showed a reduction in overall survival (OS) and progression free survival (PFS) in gBRCA1/2m patients compared to both germinal BRCA1/2 wild type (gBRCA1/2wt) and to the untested population. Regarding the efficacy of PI3K inhibitors, there are no subgroup or biomarker analyses in which germinal BRCA status was explored. However, the biological interactions between the PIK3CA/AKT/mTOR pathway and BRCA1/2 at a molecular level could help us to understand the activity of these drugs when used to treat BC in BRCA1/2 PVs/LPVs carriers. The efficacy of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC) targeting HER2 for HER2-low and HER2-positive (HER2+) BC, has been increasingly described. Unfortunately, data on T-DXd in HER2+ or HER2-low metastatic BC harboring germinal BRCA1/2 PVs/LPVs is lacking. Including germinal BRCA1/2 status in the subgroup analysis of the registration trials of this ADC would be of great interest, especially in the phase III trial DESTINY-breast04. This trial enrolled patients with HER2-negative (HER2-) and both HR+ and HR- metastatic disease, which can now be categorized as HER2-low. The HER2-low subgroup includes tumors that were previously classified as triple negative, so it is highly likely that some women were germline BRCA1/2 PVs/LPVs carriers and this data was not reported. Germline BRCA1/2 status will be available for a higher number of individuals with BC in the near future and data on the prognostic and predictive role of these PVs/LPVs is needed in order to choose the best treatment options.

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation followed by deleterious effects at the cellular and systemic level is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders including metabolic syndrome, diabetes mellitus and cardiovascular diseases. In this review an interplay between pathways leading to MGO generation and scavenging is addressed, in regard to this system’s impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

It is crucial to forecast the water demand accurately for supplying water efficiently and stably in a water supply system. In particular, accurately forecasting short-term water demand helps in saving energy and reducing operating costs. With the introduction of the Smart Water Grid (SWG) in a water supply system, the amount of water consumption is obtained in real time through an advanced metering infrastructure (AMI) sensor, which can be used for forecasting the short-term water demand. The models widely used for water demand forecasting include the autoregressive integrated moving average, radial basis function-artificial neural network, quantitative multi-model predictor plus, and long short-term memory. However, there is a lack of research on assessing the performance of models and forecasting the short-term water demand by applying the data on the amount of water consumption by purpose and the pipe diameter of an end-use level of the SWG demonstration plant in each demand forecasting model. Therefore, in this study, the short-term water demand was forecasted for each model using the data collected from the AMI, and the performance of each model was assessed. The Smart Water Grid Research Group installed ultrasonic-wave-type AMI sensors in the block 112 located in YeongJong Island, Incheon, and the actual data used for operating the SWG demonstration plant were adopted. The performance of the model was assessed by using the residual, root mean square error (RMSE), normalized root mean square error (NRMSE), Nash–Sutcliffe efficiency (NSE), and Pearson correlation coefficient (PCC) as indices. The water demand forecast was slightly underestimated in models that employed the assessment results based on the RMSE and NRMSE. Furthermore, the forecasting accuracy was low for the NSE due to a large number of negative values; the correlation between the observed and forecasted values of the PCC was not high, and it was difficult to forecast the peak amount of water consumption. Therefore, as the short-term water demand forecasting models using only time and the amount of water consumption have limitations in reflecting the characteristics of consumers, a water supply system can be managed more precisely if other factors (weather, customer behavior, etc.) influencing the water demand are applied.

Casein hydrolysate improves arterial stiffness, as estimated by brachial ankle pulse wave velocity (baPWV), in untreated hypertensive subjects. Facial pigmentation is a useful biomarker for arterial stiffness. This trial evaluated whether casein hydrolysate improves facial pigmentation in association with changes in arterial stiffness. A randomized, double-blind, placebo-controlled trial was conducted in 80 non-hypertensive Japanese participants randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation and baPWV were measured at baseline and at the end of the intervention. Other biochemical atherosclerosis-related parameters were also measured, including advanced glycation end products (AGEs). Changes in facial pigmentation showed a significant difference between the groups. Change in baPWV was significantly better in the active than in the placebo group. In contrast, no significant association was seen between changes in facial pigmentation and those in baPWV. Among other atherosclerosis-related factors, changes in advanced glycation products (AGEs) were significantly decreased in the active compared to the placebo group. Further, changes in facial pigmentation were positively correlated with those in AGEs. Changes in AGEs were independently associated with changes in facial pigmentation. Casein hydrolysate improves facial pigmentation in non-hypertensive participants. Casein hydrolysate may have beneficial effects on glycation stress.

This comprehensive review traces the transformative journey of genomic mapping, ushering in the era of "Genomic Atlas 2.0," characterized by advanced strategies and cutting-edge technologies. Beginning with a historical overview, it highlights the evolution from early linkage analysis to the current landscape shaped by high-throughput sequencing. Key breakthroughs are emphasized, showcasing the pivotal role of platforms such as Illumina and Oxford Nanopore in accelerating the identification of genetic variations. Long-read sequencing technologies, including PacBio and Oxford Nanopore, are explored as transformative elements overcoming limitations associated with short-read sequencing. The review delves into spatial genomics and chromatin conformation capture techniques, revealing the three-dimensional intricacies of the genome, with a particular focus on the revolutionary impact of Hi-C in understanding chromatin interactions. CRISPR technologies emerge as indispensable tools in Genomic Atlas 2.0, enabling targeted genome editing and the generation of precise genetic models. Functional genomics screens, utilizing RNA interference and CRISPR-based techniques, are discussed for their scalable precision in deciphering genome functions. Navigating challenges, the review addresses complexities in data integration and ethical considerations, offering strategies to ensure the robustness and ethical conduct of genetic mapping. Looking optimistically towards the future, it explores opportunities such as improved sequencing accuracy and novel applications of CRISPR technologies. Envisioning the expansion of genomics into personalized medicine, agriculture, and conservation biology, the review serves as a guiding resource for researchers, scientists, and students navigating the intricate terrain of Genomic Atlas 2.0.

The incidence and mortality of cervical cancer are high in Romania compared to other European countries, particularly for locally advanced cervical cancer cases, which are predominant at the time of diagnosis. Widely accepted therapeutic guidelines indicate that the treatment for locally advanced cervical cancer consists of concurrent chemoradiotherapy (total dose 85-90Gy at point A), with surgery not being necessary as it does not lead to improved survival and results in significant additional morbidity. In Romania, the treatment for locally advanced cervical cancer differs, involving lower-dose chemotherapy (total dose 60-65Gy at point A), followed by surgery which, under these circumstances, ensures better local control. In this regard, we attempted to evaluate the role and necessity of surgery in Romania, considering that in our study, residual lesions were found in 55.84% of cases on resected specimens, especially in cases with unfavorable histology (adenocarcinoma and adenosquamous carcinoma). This type of surgery was associated with significant morbidity (28.22%) in our study. The recurrence rate was 24.21% for operated patients compared to 62% for non-operated patients receiving suboptimal concurrent chemotherapy alone. In conclusion, In Romania, surgery will continue to play a predominant role until radiotherapy achieves the desired effectiveness for local control.

Background: Continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS) have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). Despite a similar outcome of all device-aided therapies (DATs), some patients switch or combine DATs. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons and their frequency for switching/combining were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale. Non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in total 30 patients (6%), who either switched DAT (N=24: 7 LCIG-to-STN-DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN-DBS, 8 CSAI-to-LCIG, 1 STN-DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN-DBS, and 1 STN-DBS-to-CSAI-to-LCIG) or combined DATs (N=6: 5 STN-DBS+LCIG and 1 STN-DBS+CSAI-to-STN-DBS+LCIG). In most of these patients, inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT related complications.

Advanced paternal age at fertilization has been suggested to be a risk factor for neurodevelopmental, psychiatric and other disorders in offspring. One emerging hypothesis suggests that altered offspring phenotype is linked with age-related accumulation of epigenetic changes in the sperm of fathers. Given that paternal age is increasing in the developed world, understanding aging-related epigenetic changes in sperm is needed as well as environmental factors that modify such changes. In this study, we characterize age-dependent changes in sperm DNA methylation profiles between young pubertal (postnatal day (PNDs) 65) and mature (PND120) Wistar rats. We also analyze these changes in rats exposed perinatally to 0.2 mg/kg of ubiquitous environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). Reduced representation bisulfite sequencing (RRBS) libraries were prepared from caudal epididymal sperm DNA and differentially methylated regions (DMRs; ≥ 10x coverage depth, ≥ 3 CpGs per cluster, ≥ 5% methylation change, q < 0.05) were identified via MethPipe package. In control animals, 5,319 age-dependent DMRs were identified, with 99.3% DMRs hypermethylated in mature animals compared to young pubertal rats. These age-related DMRs were enriched for functional categories essential for embryonic development, such as pattern specification, forebrain and sensory organ development, Hippo and Wnt pathways. Age-related changes in sncRNA, reported in different study, target similar list of genes and biological categories.In BDE-47 exposed rats, sperm DNA methylation was higher in young pubertal and lower in mature animals when compared to controls, which resulted in a significant attenuation in the number of age-dependent DMRs (N = 189) identified in the exposed group. In conclusion, our results indicate that the natural aging process has profound effects on sperm methylation levels and this effect may be modified by environmental exposures. Moreover, our results further support the role of epigenetic mechanisms as a likely link betwen paternal age and offspring health and development.

Is it true that the nuclear technology applied to electric energy generation offers a clean, safe, reliable and affordable i.e. sustainable alternative? Yes it is, but its impact on the environment strongly depends on the implementation bearing residual risks due to a human factor, technical failures or natural catastrophes. A full response is therefore difficult and can first be given when the wicked multi-disciplinary problems get well formulated and “solved”. These problems have multi-dimensional nature lying at the interface between: necessary R&D effort, the industrial deployment and the technology impact in view of the environmental sustainability including the management of produced hazardous waste. This enormous complexity indicates that just a description of the problem might represent a problem. The paper proposes a holistic approach to assess the nuclear energy systems potential with respect to sustainable performance applying Multi-criteria decision analysis with a suitable objective tree and a multi-level criteria structure and examines the trading-off techniques for ranking of the alternatives. The framework proposes a multi-criteria and multi-stakeholders treatment which can be used as a pre-decisional support towards an implementation of nuclear fuel cycles adapted to national preferences and priorities. Proposed approach addresses some aspects of the environmental footprint of nuclear energy systems. Advanced nuclear fuel cycles, previously investigated by the NEA/OECD expert group WASTEMAN, are analyzed as a case study. Sustainability facets of waste management, resource utilization and economics are in focus.

The paper presents the design and the implementation of different advanced control strategies that are applied to a nonlinear model of a thermal unit. A data–driven grey–box identification approach provided the physically meaningful nonlinear continuous–time model, which represents the benchmark exploited in this work. The control problem of this thermal unit is important since it constitutes the key element of passive air conditioning systems. The advanced control schemes analysed in this paper are used to regulate the outflow air temperature of the thermal unit by exploiting the inflow air speed, whilst the inflow air temperature is considered as an external disturbance. The reliability and robustness issues of the suggested control methodologies are verified with a Monte–Carlo analysis for simulating modelling uncertainty, disturbance and measurement errors. The achieved results serve to demonstrate the effectiveness and the viable application the suggested control solutions to air conditioning systems. The benchmark model represents one of the key issues of this study, which is exploited for benchmarking different model–based and data–driven advanced control methodologies through extensive simulations. Moreover, this work highlights the main features of the proposed control schemes, while providing practitioners and heating, ventilating and air conditioning engineers with tools to design robust control strategies for air conditioning systems.

The inherited ‘EIA’ process at Brexit is based on a ‘Project’ period from Inception tothe start of construction works. The ‘Incompleteness’ of the process covers andidentifies stages that will impact on the environmental cycle: construction period,operational life, de-commissioning and a return to acceptable environmental footprint.A master environment structure-plan framework is required to commence with theupgrading of the complete ‘EIA’ process, embracing separate limbs for the UK’spriority environmental targets for climate change, and other major adverse effectswhich result in serious ‘harm’ to the UK environment. The identification of the processfor ‘incompleteness’ requires effective sustainability, and inclusion of effectivemanagement tools, for the essential ‘monitoring/control/recording’ proceduresthroughout the project life and the natural environmental cycle. This will allow theopportunity for a new approach to a structured ‘Suite of EIAR Directives’, to enable a‘EIAR’ regime that ‘will remain fit and proper for UK purpose’.

Advanced composite materials have drawn significant interest in the last years as an alternative to traditional materials due to their higher performance. However, industry struggle to provide low-cost, higher occupational safety, lower footprint with composites, making them suitable for holistic analyses. Therefore, the material design becomes an essential element that can impact the competitiveness, particularly in terms of productivity, circularity, safety, sustainability, and quality of the value chain. The Material Design-for-eXcellence is a state-of-art methodology for material performance multi-dimensional assessment along its life cycle phases, either useful to support ma-terial selection for new products or also to new material design support optimizing resource effi-ciency. In this methodology, the material behaviour and its multiple characteristics assessment, and the manufacturing processes efficiency are evaluated. The framework considers the analogy of product design holistic approaches, as Lean Design-for-X, to organize and assess the mul-ti-dimensional performance for each “X” Material Property. In this work, it was possible to observe that the bio-based composites solutions could be a good sustainable alternative for several sectors. Every day researchers are creating more new materials, having a diversity of properties at different scales, Material Design-for-eXcellence must also in the near future consider other factors. Hence, additional studies are thus foreseen to explore and develop this new tool.

In a dynamic and rapidly changing world, customers’ often conflicting demands plus fluid economic requirements, often driven by geo-politics, have continued to evolve, out-striping the capability of existing production systems. With its inherent shortcomings, the traditional factory has proven to be incapable of addressing these modern-day manufacturing challenges. Recent advancements in Industry 4.0 have catalyzed the development of new manufacturing paradigms (or smart factory visions) under different monikers (e.g., Smart factory, Intelligent factory, Digital factory, Cloud-based factory etc.) would help fix these challenges. Due to a lack of consensus on a general nomenclature for these manufacturing paradigms, the term Future Factory (or Factory of the Future) is here used as a collective euphemism, without prejudice. The Future Factory constitutes a creative convergence of multiple technologies, techniques and capabilities that represent a significant change in current production capabilities, models, and practices. It is a data-driven manufacturing approach and system that harnesses intelligence from multiple information streams i.e., assets (including people), processes, and subsystems to help create new forms of production efficiency and flexibility. Serving both as a review monograph and reference companion, this paper details the meanings, characteristics, and technological underpinnings of the Future Factory. It also elucidates on the architectural models that guide the structured deployment of these modern factories with particular emphasis on three advanced communication technologies capable of speeding up advancements in the field. It not only highlights the relevance of communication between assets but also lays out mechanisms to achieve these interactions using the Administration shell. Finally, the paper also discusses the key enabling technologies that are typically embedded into bare bone factories to help improve their visibility, resilience, intelligence, and capacity, in addition to how these technologies are being deployed and to what effect. At the onset of the study, we were interested in developing a monograph which would serve as a comprehensive but concise review of general principles, fundamental concepts, major characteristics, key building blocks and implementation guidelines for the Future Factory within the overall context of the manufacturing ecosystem, in the age of Industry 4.0. Our hope is that this paper would enrich the extant literature on advanced manufacturing, help shape policy and research, and provide insights on how some of the identified pathways can be diffused into industry.

Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.

The objective of this study was to identify the key elements used by prehospital emergency physicians (EP) to decide whether or not to attempt advanced life support (ALS) in asystolic out-of-hospital cardiac arrest (OHCA). From 01.01.2009 to 01.01.2017, all adult victims of asystolic OHCA in Geneva, Switzerland, were retrospectively included. Patients with signs of "obvious death" or with a Do-Not-Attempt-Resuscitation order were excluded. Patients were categorized as having received ALS if this was mentioned in the medical record, or, failing that, if at least one dose of adrenaline had been administered during cardio-pulmonary resuscitation (CPR). Prognostic factors known at the time of EP's decision were included in a multivariable logistic regression model. 784 patients were included. Factors favourably influencing the decision to provide ALS were witnessed OHCA (OR=2.14, 95%CI1.43–3.20) and bystander CPR (OR=4.10, 95%CI2.28–7.39). Traumatic aetiology (OR=0.04, 95%CI0.02–0.08), age >80 years (OR=0.14, 95%CI0.09–0.24) and a Charlson comorbidity index greater than 5 (OR=0.12, 95%CI0.06–0.27) were the factors most strongly associated with the decision not to attempt ALS. Factors influencing the EP’s decision to attempt ALS in asystolic OHCA are the relatively young age of the patients, few comorbidities, presumed medical aetiology, witnessed OHCA and bystander CPR.

UV-A (ca. 365 nm wavelength, a.k.a. 'black light') photocatalysis has been investigated to comprehensively mitigate odor and selected air pollutants in the livestock environment. This study was conducted to confirm the performance of UV-A photocatalysis on the swine farm. The objectives of this research were to (1) scale-up of the UV-A photocatalysis treatment, (2) evaluate the mitigation of odorous gases from swine slurry pit, and (3) test different UV sources, (4) evaluate the effect of suspended particulate matter (PM), and (5) conduct preliminary economic analyses. We tested UV-A photocatalysis at a mobile laboratory-scale capable of treating ~0.2 - 0.8 m3·s-1 of barn exhaust air. The targeted gaseous emissions of barn exhaust air were significantly mitigated (p < 0.05) up to 40% reduction of measured odor; 63%, 44%, 32%, 40%, 66%, and 49% reduction of dimethyl disulfide, isobutyric acid, butanoic acid, p-cresol, indole, and skatole, respectively; 40% reduction of H2S; 100% reduction of O3; and 13% reduction of N2O. The PM mitigation effect was not significant. Formaldehyde levels did not change, and a 21% generation of CO2 was observed. The percent reduction of targeted gases decreased as the airborne PM increased. Simultaneous chemical and sensory analysis confirmed that UV-A treatment changed the overall nuisance odor character of swine barn emissions into weaker manure odor with 'toothpaste and 'mint' notes. The smell of benzoic acid generated in UV-A treatment was likely one of the compounds responsible for the less-offensive overall odor character of the UV-treated emissions. Results are needed to inform the design of a farm-scale trial, where the interior barn walls can be treated with the photocatalyst, and foul air will be passively treated as it moves through the barn.

With an estimated 3 to 5 million human cases annually and the potential to infect domestic and wild animal populations, influenza viruses are one of the greatest health and economic burdens to our society [1] and pose an ongoing threat of large-scale pandemics. Despite our knowledge of many important aspects of influenza virus biology, there is still much to learn about how influenza viruses replicate in infected cells, for instance how they use entry receptors or exploit host cell trafficking pathways. These gaps in our knowledge are due, in part, to the difficulty of directly observing viruses in living cells. In recent years, advances in light microscopy, including super-resolution microscopy and single-molecule imaging, have enabled many viral replication steps to be visualised dynamically in living cells. In particular, the ability to track single virions and their components, in real time, now allows specific pathways to be interrogated providing new insights to various aspects of the virus-host cell interaction. In this review, we discuss how state-of-the-art imaging technologies, notably quantitative live-cell and super-resolution microscopy, are shedding new nanoscale and molecular insights into influenza virus replication and revealing new opportunities for developing antiviral strategies.

Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialised multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains, developed in 2018 and validated in 2023, to identify the level of complexity in patients with advanced cancer. Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. Method: An observational, prospective, multicentre study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were: a) instability ratio (IR), defined as the probability of level change or death; b) emergency department visits; c) days of hospitalisation; d) hospital death; e) survival. All variables were analysed monthly according to the level of complexity assigned at the baseline visit. Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p

Background and Objectives: The purpose of this study was to assess the bleeding that occurs during the first weeks of gestation and its implications throughout pregnancy. Secondarily, we studied the associated complications that appeared and tried to identify possible risk factors that could serve to select women at a greater risk of adverse outcomes that could benefit from an early diagnosis and improved monitoring. Materials and Methods: We selected all the women who consulted for first trimester metrorrhagia in the Emergency Department of the Hospital QuirónSalud in Malaga over the year 2015. We refer to first trimester metrorrhagia as that which occurs until week 12+6. Once the pregnant women were identified, we studied certain risk factors already present prior to the gestation and others associated with the gestation and its evolution. Results: After reviewing the visits to the obstetrics and gynecology emergency department, we selected those patients that met the inclusion criteria, resulting in a sample of 696 patients that we followed up. The average age of our patients was 34.1 years, with an average number of visits to the hospital of 1.67, most of them between the 5th and 8th weeks of pregnancy. 45.3% of these pregnancies resulted in a first trimester miscarriage, mainly between weeks 6 and 8. We tried to establish associations in order to identify possible risk factors, finding a relationship between increased maternal age and a higher risk of first trimester pregnancy loss, which rises as maternal age increases (33,37 4,316 years vs 35,01 4,740 years). This increase in risk is proportional to the increase in age. We made subgroups of women over 35 and over 40 and confirmed that increased age led to worse outcomes. We also studied several gestational complications and concluded that they appeared more frequently among older women. These complications include prematurity (33.11 vs 34.48 years), gestational diabetes (33.11 vs 36.06 years) and preeclampsia (33.25 vs 35 years). We reviewed the obstetric history of pregnant women whose gestation resulted in miscarriage and found that 50.5% of them had previously had another loss. Conclusions: Comparing the results with data from the general population, we found that the rate of first trimester miscarriage is up to 3 times higher among women who present bleeding during the first weeks of gestation compared to those who do not develop this complication. Maternal age is a risk factor for first trimester pregnancy loss and for the development of complications associated with pregnancy.

High-resolution (2 km) high-frequency (hourly) SST data from 2015-2020 provided by the Advanced Himawari Imager (AHI) onboard the Japanese Himawari-8 geostationary satellite positioned over 140.7°E were used to study spatial and temporal variability of the China Coastal Front (CCF) in the East China Sea. The hourly SST data were processed with the Belkin and O’Reilly (2009) algorithm to generate long-term mean monthly maps of SST gradient magnitude (GM) and frontal frequency (FM) using a GM threshold of 0.1°C/km. Horizontal structure of SST field in the vicinity of the CCF was investigated from cross-frontal distributions of SST along 8 parallels from 31°N to 24°N. The high resolution (2 km) monthly distributions of SST along these 8 parallels were used to determine inshore and offshore boundaries of the CCF and calculate the CCF strength defined as the total cross-frontal SST step dSST=Offshore SST – Inshore SST. The CCF emerges in November, fully develops in December and peaks in strength in January-February. The front’s fragmentation and shrinking/weakening begins in February and March, respectively. In winter (December-February), the front’s strength dSST exceeds 5°C offshore the Zhejiang-Fujian coast and could be as high as 7.5°C when nearshore waters cool down to 7°C. In winter, the front’s strength decreases downstream from 31°N to 24°N. The CCF changes its physical nature as the seasons progress. In winter, the CCF is a water mass front between cold and fresh water coming from the north and warm and salty water coming from the south. In summer, the CCF becomes a coastal upwelling front maintained largely by southerly winds. In winter, the CCF’s cross-frontal structure in the SST field is ramp-shaped, with SST increasing monotonously in the offshore direction. In summer, the CCF’s cross-frontal structure in the SST field is V-shaped or U-shaped, featuring a minimum SST formed by cold upwelled water at some distance from the shore. Thus, the summer SST structure effectively consists of two fronts, a nearshore and offshore, with a minimum SST in-between. Across the inshore/offshore front, the SST decreases/increases in the offshore direction. The local bathymetry, especially the relatively steep shelf slope between 20-m and 50-m isobath, steers the front, which does not meander in winter offshore the Zhejiang-Fujian coast. As the cold season progresses, the front’s axis gradually shifts into deeper waters, from ~20 m to ~50 m.

On April 17, 2019, a coach with tourists from Germany crashed in Madeira requiring repatriation by the German Air Force. The Advance Trauma Life Support (ATLS) concept was the central component of patient care. Data in Madeira were collected through a structured interview. The analysis of the Aeromedical Evacuation was based on intensive care transport records. In Germany all available were reviewed for data collection. Quality of life (HRQoL) was evaluated by the 12-item Short-Form Health Survey (SF-12). Twenty-eight prehospital patients were transported to the Level III Trauma Center in Funchal (Madeira). Five operative procedures were performed. Fifteen patients were eligible for Aeromedical Evacuation (AE). In the second hospital phase in Germany in total 82 radiological images and nine operations were performed. Hospital stay lasted 11 days (median, IQR 10–18). Median Follow-up (14 of 15 patients) was 16 months (IQR 16–21). 80% (8 out of 10) showed an increased risk for post-traumatic stress disorder (PTSD). Six key findings were identified in this study: divergent injury classification, impact of AE mission on health status, lack of communication, need of PTSD prophylaxis, patient identification, media coverage. Those findings may improve AE missions in the future e.g. required after armed conflicts.

Seeds represent the major source of food protein, impacting on both human nutrition and animal feeding. Therefore, seed quality needs to be appropriately addressed in the context of viability and food safety. Indeed, long-term and inappropriate storage of seeds might result in enhancement of protein glycation, which might affect their quality and longevity. Glycation of seed proteins can be probed by exhaustive acid hydrolysis and quantification of the glycation adduct N^ɛ-(carboxymethyl)lysine (CML) by liquid chromatography-mass spectrometry (LC-MS). This approach, however, does not allow analysis of thermally and chemically labile glycation adducts, like glyoxal-, methylglyoxal- and 3-deoxyglucosone-derived hydroimidazolones. Although enzymatic hydrolysis might be a good solution in this context, it requires aqueous conditions, which cannot ensure reconstitution of seed protein isolates. Because of this, the complete profiles of seed AGEs are not characterized so far. Therefore, here we propose the approach, giving access to quantitative solubilization of seed proteins in presence of sodium dodecyl sulfate (SDS) and their quantitative enzymatic hydrolysis prior to removal of SDS by reversed phase solid phase extraction (RP-SPE). Using MG-H1 as a case example, we demonstrate the applicability of this method for reliable and sensitive LC-MS-based quantification of chemically labile AGEs and its compatibility with bioassays.

Magnesium nanoparticles of various mean diameters (53 – 239 nm) were synthesized herein via Pulsed Laser Ablation in Liquid (PLAL) from millimeter sized magnesium powders within iso-propyl alcohol. It was observed via a 3x3 full factorial DOE that the processing parameters can control the nanoparticle distribution to produce three size-distribution types (bimodal, skewed and normal). Ablation times of 2, 5, and 25 minutes where investigated. An ablation time of 2 minutes produced a bimodal distribution with the other types seen at higher periods of processing. Mg nanoparticle UV-Vis absorbance at 204 nm increased linearly with increasing ablation time, indicating an increase in nanoparticle count. The colloidal density (mg/ml) generally increased with increasing nanoparticle mean diameter as noted via increasing UV-vis absorbance. High la-ser scan speeds (within the studied range of 3000 - 3500 mm/s) tend to increase the nanoparticle count/yield. For the first time, the effect of scan speed on colloidal density, UV-vis absorbance and nanoparticle diameter from metallic powder ablation was investigated and is reported herein. The nanoparticles formed dendritic structures after being drop cast on aluminum foil as observed via FESEM analysis. Dynamic light scattering was used to measure the size of the nanoparticles. Magnesium nanoparticles have promising use in the fabrication of wearables, such as in conductive tracks or battery electrodes, owing to their low heat capacity, high melting point and bio-compatibility.

Ultrafast laser 3D lithography based on non-linear light-matter interactions, widely known as multi-photon lithography (MPL), offers unrivaled precision rapid prototyping and flexible additive manufacturing options. 3D printing equipment based on MPL are already commercially available, yet there is still no comprehensive understanding of factors determining spatial resolution, accuracy, fabrication throughput, repeatability, and standardized metrology methods for the accurate characterization of the produced 3D objects and their functionalities. The photoexcitation mechanisms, spatial-control or photo-modified volumes, and the variety of processable materials are topics actively investigated. The complexity of the research field is underlined by limited understanding and fragmented knowledge of light-excitation and material response. Research to date has only provided case-specific findings on photoexcitation, chemical modification, and material characterization of the experimental data. In this review, we aim to provide a consistent and comprehensive summary of the existing literature on photopolymerization mechanisms under highly confined spatial and temporal conditions, where, besides the excitation and cross-linking, parameters such as diffusion, temperature accumulation, and the finite amount of monomer molecules start to become of critical importance. Key parameters such as, photoexcitation, polymerization kinetics, and the properties of the additively manufactured materials at the nanoscale in 3D are examined, whereas, the perspectives for future research and as well as emerging applications are outlined.

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications, formed by reducing sugars and carbonyl products of their degradation. Resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied in respect of glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in dramatic suppression of primary seed metabolism, although secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.

This study proposes a methodology for identifying time intervals in which time-of-use (ToU) energy tariffs can be set. This is achieved by analyzing the variability in electric power demand and esti-mating the potential for demand flexibility. The proposed methodology is as follows: first, data preprocessing is performed, focusing on the organization and cleaning of individual consumption records. Subsequently, the data are processed and classified by using consumption variability analysis and clustering techniques. Then, representative clusters are selected and time intervals are analyzed to identify periods of high electric power consumption variability. This methodology was tested with real data from smart meters in the Colombian electrical system, in which time intervals with potential for settinh ToU tariffs were ultimately identified. This work promotes the implementation of demand response strategies that enhance sustainability and facilitate the transition to a more resilient energy landscape both nationally and internationally. The findings are expected to contribute to the formulation of tariff schemes that encourage con-scious changes in electric energy consumption patterns.

The increasing social pressure for decarbonization has placed businesses under considerable scrutiny to actively reduce carbon emissions. A critical step towards achieving this objective is to shift conventional production and consumption systems to more sustainable alternatives. Thus, there is the emergent need to understand the patterns and drivers of the transformative business models (BMs) that underpin that shift. This study adopts a mixed-methods approach that integrates different literature streams--including Sustainability Transitions Theory (STT), Strategic Niche Management (SNM), and the Business Models approach--and stakeholders’ interviews to investigate the key elements of business models that lead towards sustainable practices. This research examines the organizational arrangements of European start-ups operating between 2014 and 2020. The transformation towards decarbonized production and consumption is characterized by efficient combination of business strategies that incorporate advanced technologies (ATs), such as artificial intelligence (AI), machine learning (ML) and its algorithms, along with sustainable elements, resulting in transformative business models. By exploring the driving elements behind the transition to low-carbon approaches, this study fills a significant gap in the existing literature on business models. The findings from this research also hold relevance for policymakers to promote decarbonization.

Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles Schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end products (AGEs) accumulation, oxidative stress, and mitochondrial function via inhibition of NF-κB activity, in turn through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2''-O-acetylvitexin (8-C-(2''-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in development or disease improvement in patients of DR.

This comprehensive analysis thoroughly examines the topic of adversarial attacks in artificial intelligence (AI), providing a detailed overview of the various methods used to compromise machine learning models. It explores different attack techniques, ranging from the simple Fast Gradient Sign Method (FGSM) to the intricate Carlini and Wagner Attack (C&W), emphasising the wide range of adversarial approaches and their intended goals. The discussion also distinguishes between targeted and non-targeted attacks, highlighting the adaptability and versatility of these malicious efforts. Additionally, the study delves into the realm of black-box attacks, revealing the capability of adversarial strategies to compromise models even with limited knowledge. Real-life examples illustrate the tangible consequences and potential dangers of adversarial attacks in various fields such as self-driving cars, multimedia, and voice assistants. These cases highlight the difficulties in ensuring the legitimacy and dependability of AI-powered technologies and programs. The article stresses the importance of ongoing research and innovation to address the growing difficulties posed by advanced methods like deepfakes and disguised voice commands in preserving the security of AI systems. This study provides valuable insights on how different adversarial strategies and defence mechanisms interact within AI. The results emphasise the urgent need for stronger and more secure AI models to combat the increasing number of adversarial threats in today's AI landscape. These findings can guide future research and innovations in developing more resilient AI technologies that can better withstand various adversarial vulnerabilities and challenges.

Smart grid software interconnects multiple Engineering disciplines (power systems, communication, software and hardware technology, instrumentation, big data, etc.). The software architecture is an evolving concept in smart grid systems in which systematic architecture development is a challenging process. The architecture has to realize the complex legacy power grid systems and cope up with current Information and Communication Technologies (ICT). The distributed generation in smart grid environment expects the software architecture to be distributed and to enable local control. Smart grid architecture should also be modular, flexible and adaptable to technology upgrades. In this paper, the authors have made a comprehensive review on architecture for smart grids. An in depth analysis of layered and agent based architectures is presented and compared under various domains.

Abstract: This review addresses the complexities of type 1 diabetes (T1D)and its associated complications, with a par-ticular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of the review is devoted to technological advances in diabetes management, particu-larly the use of Hybrid Closed Loop systems (HCLS) and to the potential of open-source HCLS systems, which could be easily adapted to different patiens’needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient outcomes.

Abstract:Shown is the derivation of Lorentz-Einstein k-factor in SRT as an amplitude-term of oscillation-differential equations of second order.This case is shown for classical Lorentz-factor as solution of an equation for undamped oscillation as well as the developed theorem as a second solution for advanced SRT of fourth order with an equation for damped oscillation-states.This advanced term allows a calculation for any velocities by real rest mass