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Andrei-Nicolae Vasilescu,1,* Nina Schweinfurth,2,* Stefan Borgwardt,2,* Peter Gass,1 Undine E Lang,2,* Dragos Inta,1,2,* Sarah Eckart2,* 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 2Department of Psychiatry (Universitäre Psychiatrische Kliniken), University of Basel, Basel, Switzerland *These authors contributed equally to this work Abstract: Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment of MDD from the US Food and Drug Administration, representing one of the most promising alternative antidepressants under current investigation. Keywords: depression, glutamate, NMDARs, rapastinel, ketamine

Research background: The economic impact of investing in new transport capacity or improving existing ones is complex and often indirect. Loans for infrastructure are often needed, but they cannot create sufficient conditions for economic growth. Investments in transport infrastructure require public funding. An assessment of their cost-effectiveness is needed to ensure a reasonable and acceptable allocation. Relevant economic, environmental and social effects must be taken into account. There is a growing concern in the transport sector about decisions on the development of the transport system and the effects of scale and externalities they produce. Planners and decision-makers need to know more about the wider economic impact of individual infrastructure projects and transport policies in general. Purpose of the article: This paper aims to present the most important theoretical and practical aspects of the importance of transport investment worldwide, at European level and Romania. Investments in transport infrastructure will not improve the economic vitality of a region unless it has sufficient economic capacity and employment, land use and economic development policies. Methods: This article starts from the hypothesis of the influence of globalization on the development of transport systems in general and applies as a case study on Romania. The paper was based on the analysis of transport legislation, as well as data sets for the period 2011-2019, to observe the gradual development of all types of transport. Findings & Value added: Following these researches, the link between globalization and investments in transport systems was found by emphasizing accessibility to new infrastructures, new horizons and development plans for the main types of transport, which is a key element in economic activity. The main results were disseminated throughout the article and it adds value through the analysis created at global and regional level (at European level) and the interpretation of statistical data related to transport investments.

Labour costs are a fundamental component of production expenses, significantly impacting both the quantity and quality of output. This study explores the determinants of labour costs within EU member states that have implemented minimum wage policies over the past two decades. The research technique includes a comprehensive panel analysis of EU member states to identify significant variables influencing labour costs, as well as cluster analysis to discover underlying patterns across the nations under examination. Our findings reveal that higher minimum wage levels, higher employment rates, increased labour productivity, and greater trade openness are positively correlated with higher labour costs. Specifically, increases in these variables lead to higher wages and a broader tax base, while greater trade openness results in elevated labour costs due to expanded market opportunities. Conversely, gross fixed capital formation negatively affects labour costs, as investments in production assets tend to reduce labour requirements or hours worked. The cluster analysis led to the identification of three distinct groups. The first cluster consists of well-developed economies with modest labour cost increases and average minimum wages. The second cluster includes countries with substantial labour cost increases, low minimum wages, and significant productivity gains. The third cluster features nations with high minimum wages and high employment rates. This paper contributes to the field by highlighting the complex interplay between labour costs and economic factors, offering insights for decision-makers to tailor macroeconomic and company-level strategies to specific local conditions. The findings emphasise the importance of balancing wage policies with sustainable economic development to enhance competitiveness while ensuring fair labour conditions.

Some of the most challenging directions in recent theoretical and practical research concern both the web science and the web applications development. Any alive science and any alive programming language should increase its connection with the web domain. Apart from general advantages provided by the functional language programming Haskell, its specific support for the web applications design and implementation is highlighted in this paper. It is also our target to reveal here some mathematical grounds of the web as a modern and very young science.

Poverty is a challenge for all countries and its eradication is a common goal in the European Union. Our paper analyses the statistical and theoretical relationship between social inequalities and the at-risk-of-poverty rate. For a holistic understanding of the poverty phenomenon in the EU, other variables such as economic growth, social protection expenditure, and the old-age dependency ratio were also included in the analysis. The methodology is based on panel data models. A regression model was built with data for the period 2011-2022, for the 27 EU countries. The econometric model of the at-risk-of-poverty rate highlighted a series of factors, among which the Gini coefficient is one of the most influential. Other important factors were research and development expenditure, social protection expenditure, GDP per capita, the unemployment rate, and the old-age dependency ratio. The cluster analysis grouped the EU countries into three clusters. Understanding the phenomenon of poverty is a prerequisite for alleviating it, generating social solidarity, and rebuilding a fairer society. Our research contributes to the evaluation of the interaction between inequalities and poverty in Romania and the EU.

It is documented that maternal diseases or treatments influence a newborn’s clinical status at birth. If a prenatal medical history is not available, or if signs or symptoms of a mother’s disease are revealed for the first time during pregnancy or postpartum, their effects on the newborn may be misattributed. Objective: The objective of this study is to emphasize the paramount importance of prenatal care, for both mothers and newborns, as a lack of maternal signs and symptoms during pregnancy does not exclude a potential severe neonatal condition. Materials and methods: We present a series of three cases of pregnant women who gave birth to very sick preterm newborns that required admission to the Neonatal Intensive Care Unit (NICU). The mothers were asymptomatic during pregnancy and unaware of their subclinical disease. The newborns’ complications, considered initially as consequences of prematurity or infection, subsequently revealed transient autoimmune disease in two of the cases (myasthenia gravis and hyperthyroidism) and a severe form of thrombophilia in the third case. Results: The newborns’ diagnosis preceded maternal diagnosis and contributed to the identification of the maternal pathology; adequate treatment was prescribed, with favorable short- and long-term outcomes. Conclusions: Prenatal exams and investigations throughout pregnancy are a good opportunity to detect subclinical diseases or predispositions. As newborns usually develop non-specific signs, one should have experience and pay attention to differentiating among etiologies. Our paper takes a reversed approach to the usual medical diagnosis pathway: from infant to mother instead of from mother to infant, proving that inter-specialty collaboration can work bi-directionally.

IntroductionIt is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of recipient gut lymphocyte populations in immunosuppressed conditions.MethodsUsing polychromatic flow cytometry that includes HLA allele group-specific antibodies distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients.ResultsWe confirm the early presence of naïve donor B cells in the circulation (donor age range: 1-14 years, median: 3 years) and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa (recipient age range at the time of transplant: 1-44 years, median: 3 years). Recipient B cell repopulation of the allograft was most rapid in infant (

Abstract Familial cardiomyopathy in pediatric stages is a poorly understood presentation of heart disease in children that is attributed to pathogenic mutations. Through exome sequencing, we report a homozygous variant in tropomodulin 1 (TMOD1; c.565C>T, p.R189W) in three individuals from two unrelated families with childhood-onset dilated and restrictive cardiomyopathy. To decipher the mechanism of pathogenicity of the R189W mutation in TMOD1, we utilized a wide array of methods, including protein analyses, biochemistry and cultured cardiomyocytes. Structural modeling revealed potential defects in the local folding of TMOD1R189W and its affinity for actin. Cardiomyocytes expressing GFP-TMOD1R189W demonstrated longer thin filaments than GFP-TMOD1wt-expressing cells, resulting in compromised filament length regulation. Furthermore, TMOD1R189W showed weakened activity in capping actin filament pointed ends, providing direct evidence for the variant’s effect on actin filament length regulation. Our data indicate that the p.R189W variant in TMOD1 has altered biochemical properties and reveals a unique mechanism for childhood-onset cardiomyopathy.

Our article aims to present an in-depth analysis of the correlation between health status and poverty in European countries. Our research is grounded on two types of data: a survey of the perceptions of the European citizens related to their own physical and mental health conducted in 2017 in European Union countries and the United Kingdom on a sample of 28,000 respondents and macroeconomic data retrieved from Eurostat Database, showing the incidence of poverty and working poor in Europe during the 2017-2019 time span. Multiple logistic regression has revealed that self-rated health status is influenced by the sociodemographic characteristics of the respondents, whereas TwoStep Cluster analysis and Mann-Whitney U test proved that health is an important driver of the differences between countries in terms of poverty and working poor. The originality of our research stems from both the integrated approach, the analysis being made at individual, group, and country levels, and by the results that bring new evidence about population health status as a determinant of quality of life and national competitiveness.

The present article aims to bring to the attention of the public the compensations granted to people injured as a result of traffic accidents. In the lives of each of us, tragic events remind everyone of the importance of abiding by the traffic rules and paying more attention to the road both as drivers and as pedestrians. Car drivers are urged to be cautious, adapt speed to road conditions and avoid reckless behaviour in traffic. Also, pedestrians must know and respect the traffic rules. Practically, these are simple measures that make the difference between life and death, between a happy life and one in which traumas affect the state of well-being, of normality, in similar emergency situations.

An approach to the elementary spectral theory for quaternionic linear operators was presented by the author in a recent paper, quoted and discussed in the Introduction, where, unlike in works by other authors, the construction of the analytic functional calculus used a Riesz-Dunford-Gelfand type kernel, and the spectra were defined in the complex plane. In fact, the present author regards the quaternionic linear operators as a special class of real linear operators, a point of view leading to a simpler and a more natural approach to them. The author's main results in this framework are summarized in the following, and other pertinent comments and remarks are also included in this text. In addition, a quaternionic joint spectrum for pairs of operators is discussed, and an analytic functional calculus which uses a Martinelli type kernel in two variables is recalled.

Metal-ceramics dental prosthetic restorations are clinically recommended for their advantages related to good esthetic features along with strength and long-term clinical use. Given the importance of the quality of the metalceramic (M-C) bond, the metal substructure analysis has a major importance to the quality of the manufactured dental prosthesis. In the present study was analyzed the behavior of experimentally developed novel titanium alloys (TiZr, TiZrNbTa) comparatively with other frequently used titanium alloys (e.g., Ti Cp, Ti6Al4V) designated for the technology of mixed prosthetic restorations. All samples were been plated, simultaneously in the same conditions, with the same titanium specific compatible ceramic plating material (Ti22 Noritake). The examination of the surface of both components was performed by scanning electron microscopy SEM) analysis and EDS analysis, which showed differences in the characteristics of the oxide layer formed, depending on the composition of the metal substructure. The evaluation of the alloy-ceramic adhesion was performed by mechanical tests, which attest to the fact that the adhesion and the quality of the bond between metal and ceramic depend on the thickness of the oxide films formed. The results showed the superiority of titanium novel titanium alloys (TiZr, TiZrNbTa), having highest hardness values, highest values of shear strength, a continuous thin oxide films, and consequently, a better metal-ceramic adhesion. Comparatively, less ductile titanium alloys (TiZrNbTa/Ti3) are generating lower adhesion forces with values above 30MPa in some samples justifying less predictable clinical results.

Duchenne muscular dystrophy (DMD) affects cardiac and skeletal muscles but represents a condition that causes numerous secondary pathologies. Although there is no curative treatment available, multidisciplinary approaches, centered on the needs of the patient, improve the quality and duration of life. Therapies such as physiotherapy, occupational therapy, physical activities, and respiratory physiotherapy, but also the management of cardiac, osteo-muscular, and neuro-psychiatric manifestations, are continuously developing, (as new data becomes available) and are the key to DMD management today. These multidisciplinary approaches can lead to good long-term outcomes by helping patients with muscular dystrophy reduce muscle damage, early detect and treat heart failure, and manage cognitive impairment as best they can.

The corrosion behavior of the TiTaNbZrAg alloys with different amounts of tantalum (0%, 10% and 20%) and with distinct surface topography (smooth and rough) was investigated in phosphate buffer solution (PBS) for long-time immersion (1000 h). By this approach, we expect to bring about new insights into the influence of both the amount of Ta in the alloy composition and the surface topography on the corrosion behavior of the Ti-based alloys. The corrosion resistance was studied by Open Circuit Potential (OCP), Potentiodynamic Polarization (PP), and Electrochemical Impedance Spectroscopy (EIS). From the potentiodynamic investigations, it was observed that all types of samples showed good corrosion resistance (i.e., Rcorr < 10 µm y−1) and may be used successfully for medical applications. However, the samples with smooth surfaces and with a certain amount of Ta (10% and 20%) exhibit the best corrosion performance (Rcorr < 1 µm y−1). As regards the samples with rough surfaces, the results evidenced that they showed lower corrosion resistance (1 < Rcorr < 3 µm y−1), suggesting that the Ta presence does not necessarily hinder the corrosion processes. Actually, the synergetic effect of both the presence of Ta and surface roughness plays an important role in corrosion resistance.

Biosolids from stabilized sludge present a high fertilization potential, due to their rich content of nutrients and organic matter. The intrinsic and subtle properties of such fertilizers may greatly influence the fertilization efficiency. In this sense, the utility, advantages and limitations of advanced characterization methods, for the investigation of structural and dynamic properties at the microscopic scale of slightly different formulations of fertilizers were assessed. For that, three formulas of organo-mineral fertilizers based on biosolids (V1, V2 and V3), having at least 2% N, 2% P2O5, and 2% K2O, were characterized by advanced methods, such as 1H NMR relaxometry, 1H MAS and 13C CP-MAS NMR spectroscopy, 1H double-quantum NMR and FT-IR spectroscopy. Advanced structural characterization was performed using SEM, EDX and X-ray diffraction. Four dynamical components were identified in the NMR T2 distribution showing that the rigid component has a percentage larger than 90%, which explains the broad band of NMR spectra confirmed by the distributions of many components in residual dipolar coupling as were revealed by 1H DQ-NMR measurements. SEM and EDX measurements helped the identification of components from crystalline-like X-ray diffraction patterns. To evaluate the release properties of organo-mineral fertilizers, dynamic measurements of classical electric conductivity and pH were performed by placing 0.25 g of the formulas (V1, V2 and V3) in 200 mL of distilled water. The content of N and P were quantified using specific reactants, combined with VIS-nearIR spectroscopy. Two release mechanisms were observed and characterized. It was found that V3 presents the smallest release velocity but releases the largest number of fertilizers.

Histoplasma capsulatum (H. capsulatum) is considered to be one of the most extensively spread dysmorphic fungi worldwide. Histoplasmosis primarily impacts patients with weakened immune systems and can result in a diverse range of clinical manifestations. In immunocompetent patients, the disease may manifest as a self-limiting or asymptomatic infection; however, in immunocompromised individuals, it can occur as a debilitating, disseminated disease. Diagnosing histoplasmosis may be challenging. A medical professional that specializes in treating endemic fungal illnesses is better able to assist with an accurate and timely diagnosis since they have a deeper grasp of these illnesses. Consequently, the process of diagnosing histoplasmosis might be difficult for less experienced physicians. The case presented is an example of the myriad faces that histoplasmosis can take on, mimicking other common infectious or malignant conditions, leading to extensive work-up and invasive procedures in establishing the diagnosis of this otherwise benign condition. We hereby report the case of disseminated histoplasmosis in a young immunocompetent female patient.

Background: medical teams continue to face challenges with infections following hip replacement surgery, whether they occur shortly after the procedure or months or years later. Certain medical conditions like diabetes, rheumatoid arthritis, and obesity are risk factors that make patients more susceptible to infections. Traditional intervention methods such as DAIR, one-step, or two-step procedures are being enhanced and refined to ensure quicker and more effective treatment. Some cases present particularly difficult challenges, featuring persistent fistulas and unpredictable responses to treatment. Methods: in our article, we share two unique cases, detailing their histories, progressions, and treatment decisions. We explore the use of antibiotic-impregnated calcium biocomposite as a local adjuvant therapy and the application of negative pressure therapy to expedite healing. The system of NWPT has seen widespread uptake and is now implemented routinely for open wounds, such as open fractures, fasciotomies, ulcers, and infected wounds. Results: our findings demonstrate that surgical debridement and calcium sulfate bead insertion successfully treat bone and joint infections without causing any side effects or complications. As a particularity, in the first case, we encountered the exteriorization of Stimulan pearls after surgery, without other complications related to the biocomposite. Conclusions: we have found that NPWT is a beneficial tool in managing complex wounds in both acute and chronic stages, after the infection is cured, reducing the need for frequent dressing changes, shortening hospital stays, and enhancing patient comfort.

As the EU strives to achieve its climate goals, it is becoming increasingly crucial to understand the complex relationships between economic activity, energy consumption, and carbon emissions. In this context, our paper aims to investigate the correlation between carbon emissions, energy consumption, and economic development. To fulfill our aim, we have used Eurostat and OECD data for the EU-27 member states for a period of 13 years (2010–2022), using a linear regression as the main analysis method. Our results have shown that there is a strong correlation between demand-based and production-based CO2 emissions as well as between production-based CO2 emissions and final energy consumption, while at the same time, our findings have shown that there is no direct correlation between energy consumption and economic development, aligning our study with the neutrality hypothesis of the energy growth nexus. This paper expands the ongoing discussion on sustainable development and climate change mitigation by conducting a thorough analysis of the EU-27 countries over a span of thirteen years. The results emphasize the need for integrated strategies that address both production and consumption emissions, emphasize the vital role of energy efficiency, and raise questions about the effectiveness of increasing energy consumption to enhance economic productivity or CO2 efficiency.