Background: Co-treatment of the fetal estrogen estetrol (E4) with androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) may further inhibit endocrine PCa tumor stimulators including testosterone (T), prostate-specific antigen (PSA), follicle-stimulating hormone (FSH), and insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study in advanced PCa patients requiring ADT (the PCombi study) was conducted to assess the effect of E4 co-treatment with LHRH agonist ADT on total T, free T, PSA, FSH, and IGF-1. Patients starting ADT were randomized 2:1 to 40 mg E4 (n=41) or placebo (n=21) for 24 weeks. Analyses were performed on the per-protocol population (PP), using the Wilcoxon-rank sum and the Kruskal-Wallis test. Results: The PP population consisted of 57 patients (37 ADT+E4; 20 ADT+placebo). All individual data of the four endocrine tumor stimulators are presented in figures in the paper and in supplementary tables, showing that E4 co-treatment almost completely suppressed FSH levels in all patients, on average by 98% versus 37% in the placebo group (p

In the succinic acid-producing bacterium Pseudoclostridium thermosuccinogenes the fumarate reductase (FRD) genes reside in an operon together with those encoding an electron bifurcating complex (FlxABCD-HdrABC) that shuttles electrons from NADH to ferredoxin and a disulfide bond. Based on phylogeny and genomic co-occurrence we propose two hypothetical mechanisms via which the FRD is involved in electron bifurcation: (I) A disulfide bond from a hitherto unknown cofactor is reduced by the electron-bifurcating FlxABCD-HdrABC complex, using NADH to generate two thiol groups, while facilitating the unfavourable reduction of ferredoxin by NADH. The disulfide bond is subsequently regenerated via the reduction of fumarate by the FRD using the previously formed thiol groups. (II) The FRD forms an integral part of the FlxABCD-HdrABC complex, and NADH is used to reduce ferredoxin and fumarate directly, without an intermediate disulfide-forming cofactor. Either way enables the conservation of additional energy by a soluble FRD, analogous to fumarate respiration.

This study presents the development and pilot implementation of an assessment and shared deci-sion-making methodology called the Gezamenlijk Inschatten van Zorgbehoeften (GIZ), designed for youth (health) care professionals working with children and families. The three-phase approach included a needs assessment, development of the GIZ methodology, and pilot implementation in a preventive youth health care and youth care setting, involving parents, adolescents, and youth (health) care professionals. The needs assessment produced nine criteria that the GIZ methodology needed to meet. Based on these criteria, the GIZ methodology was developed and described using the Template for Intervention Description and Replication (TIDieR). The pilot implementation demonstrated high client engagement, satisfaction, and feasibility in daily practice. The GIZ ap-proach promotes appropriate support for families by improving the joint assessment and shared decision-making process in youth (health) care. This study supports the implementation of GIZ in youth (health) care practice and highlights the need for further focus on implementation and sus-tainability.

Disruptive technologies can be conceptualized in different ways. Depending on how they are conceptualized, different ethical issues come into play. This article contributes to a general framework to navigate the ethics of disruptive technologies. It proposes three basic distinctions to be included in such a framework. First, emerging technologies may instigate localized “first-order” disruptions, or systemic “second-order” disruptions. The ethical significance of these disruptions differs: first-order disruptions tend to be of modest ethical significance, whereas second-order disruptions are highly significant. Secondly, technologies may be classified as disruptive based on their technological features or based on their societal impact. Depending on which of these classifications one adopts and takes as the starting point of ethical inquiry, different ethical questions are foregrounded. Thirdly, the ethics of disruptive technology raises concerns at four different levels of technology assessment: the technology level, the artifact level, the application level, and the society level. The respective suitability of approaches in technology ethics to address concerns about disruptive technologies co-varies with the respective level of analysis. The article clarifies these distinctions, thereby laying some of the groundwork for an ethical framework tailored for assessing disruptive technologies.

While the foundations of climate science and ethics are well established, fine-grained climate predictions, as well as policy-decisions, are beset with uncertainties. This chapter maps climate uncertainties and classifies them as to their ground, extent and location. A typology of uncertainty is presented, centered along the axes of scientific and moral uncertainty. This typology is illustrated with paradigmatic examples of uncertainty in climate science, climate ethics and climate economics. Subsequently, the chapter discusses the IPCC’s preferred way of representing uncertainties and evaluates its strengths and weaknesses from a risk management perspective. Three general strategies for decision-makers to cope with climate uncertainty are outlined, the usefulness of which largely depends on whether or not decision-makers find themselves in a context of deep uncertainty. The chapter concludes by offering two recommendations to ease the work of policymakers, faced with the various uncertainties engrained in climate discourse.

MRI is the gold standard for treatment response assessment in glioblastoma. However, there is no consensus regarding the optimal interval for MRI follow-up during standard treatment. Moreover, reliable assessment of treatment response is hindered by the occurrence of pseudoprogression. It is unknown if a radiological follow-up strategy with 2-3 months intervals actually benefits patients and how it influences clinical decision making about continuation or discontinuation of treatment. This study assessed the consequences of scheduled follow-up scans (post-chemoradiotherapy [post-CCRT], after 3 cycles of adjuvant chemotherapy [TMZ3/6], after completion of treatment [TMZ6/6]) and unscheduled scans on treatment decisions during standard concomitant and adjuvant treatment in glioblastoma patients. Additionally, we evaluated how often follow-up scans resulted in diagnostic uncertainty (tumor progression versus pseudoprogression), and whether perfusion MRI improved clinical decision making. Scheduled follow-up scans during standard treatment in glioblastoma patients rarely resulted in early termination of treatment (2.3% post-CCRT, 3.2% TMZ3/6, and 7.8% TMZ6/6), but introduced diagnostic uncertainty in 27.7% of cases. Unscheduled scans resulted in more major treatment consequences (30%; p<0.001). Perfusion MRI caused less diagnostic uncertainty (p=0.021) but did not influence treatment consequences (p=0.871). This study does not support the current pragmatic follow-up strategy and suggests a more tailored follow-up approach.

Suicidal behaviour remains difficult to predict and prevent, even for experienced mental health care professionals. The known distal risk factors for suicidal behaviour are not sufficiently specific to fully understand the complex dynamic processes that precede a suicide attempt. Real-time mobile monitoring data can be used to analyse proximal risk mechanisms within the suicidal process. At the same time smartphone-based safety planning and self-monitoring may enhance a patient’s self-management skills thereby increasing their capacity to respond to a suicidal crisis and to become more aware of crisis symptoms. The current paper describes the theoretical and conceptual rationale for the CASPAR study which applies an innovative approach to the study of suicidal processes. It uses basic science approaches to inform the implementation of an innovative suicide prevention intervention. We aim to develop and implement mobile safety plan in conjunction with real-time monitoring in order to both directly implement suicide prevention interventions and to study the ongoing dynamics of individual suicidal behaviour by applying network analysis.

This paper presents preliminary research that investigates the relationship between the flow of a group of jazz musicians, quantified through multi-person pose synchronization, and their collective emotions. Building upon previous studies that measured the physical synchronicity of team members by tracking their body movements and measuring the difference in arm, leg, and head movements, we introduce a novel metric termed "team entanglement". We employ facial expression recognition to evaluate the musicians’ collective emotions. Through correlation and regression analysis, we establish that higher levels of synchronized body and head movements correspond to lower levels of disgust, anger, sadness and higher levels of joy among the musicians. Furthermore, we utilize a Convolutional Neural Network (CNN) based deep learning model to predict the collective emotions of the musicians. This model leverages 17 body synchrony keypoint vectors as features, resulting in a training accuracy of 61.47% and a test accuracy of 66.17%.

This paper introduces the complex Rayleigh-van der Pol-Duffing oscillators (RVDOs), which are hyperchaotic and can be either autonomous or non-autonomous. The fundamental dynamics of the autonomous and nonautonomous complex RVDOs including dissipation, symmetry, fixed points and their stability are studied. These oscillators are found in various important fields of physics and engineering. The paper proposes a scheme to achieve phase synchronization (PS) and antiphase synchronization (APS) for different dimensional models. These kinds of synchronization are considered as generalization of several other types of synchronization. For this scheme we use the active control method based on Lyapunov stability theory. By analytically determining the control functions, the scheme achieved PS and APS. Our scheme is applied to study PS of hyperchaotic behaviours for two distinct hyperchaotic non-autonomous and autonomous complex RVDOs. Additionally, the scheme is employed to achieve APS of chaotic real non-autonomous RVDO and hyperchaotic complex autonomous RVDO, including those with different dimensions. Our work presents numerical results that plot the amplitudes and phases of these hyperchaotic behaviours, demonstrating the successful achievement of PS and APS.

This article argues for five correctives to the current ethical debate about speciesism, and proposes normative, conceptual, methodological and experimental avenues to move this debate forward. Firstly, it clarifies the Principle of Equal Consideration of Interests and points out limitations of its scope. Secondly, it disambiguates between ‘favouritist’ and ‘species-relative’ views about moral treatment. Thirdly, it argues that not all moral intuitions about speciesism should be given equal weight. Fourthly, it emphasizes the importance of empirical research to corroborate statements about ‘folk speciesism’. Fifthly, it disambiguates between the moral significance of species and the moral status of their individual members. For each of these issues, it is shown that they have either been overlooked, or been given inapt treatment, in recent contributions to the debate. Building on the correctives, new directions are proposed for ethical inquiry into the moral relevance of species and species membership.

Background and Objectives: The aim of this study was to determine the job-related and individual features that influence BS and depression levels among dentists working in faculties, oral and dental health centres (ODHC) and private clinics. Materials and Methods: This prospective, cross sectional study was carried out on dentists working in different regions of Turkey. Data were collected using an on-line questionnaire created using Google Forms. The questionnaire consisted of demographic data, Maslach BS Inventory (MBI) and Beck Depression Inventory (BDI) sections. Demographics were age, height, weight, marital status, blood type, gender, monthly income, income satisfaction and having enough free time. The dentists were divided into 3 groups as faculty, private clinic and ODHC according to the institutions in which they worked. Results: Of the total 290 dentists enrolled in the study, there were 172 males and 118 females with a mean age of 36.98±5.6 years. 128 of the dentists worked in faculties, 72 in private clinics and 90 in ODHCs. It was observed that women's EE scores were higher than men's (P<0.05). No statistically significant difference was found between the groups when comparing BS and depression scores according to marital status and blood group (P>0.05). There was no significant relationship between emotional exhaustion (EE), depersonalisation (DP), personal accomplishment (PA) and depression scores according to age, BMI and work experience, age, work experience and BMI (P<0.05). It was found that the EE scores of the dentists working in the faculty and private clinic were lower than those of the dentists working in the ODHC (P<0.05). Monthly income was associated with depression (r = -0.35). Conclusions: This study showed that dentists working in ODHCs had more EE. These findings suggest that there is a need for improvement in the working conditions of dentists, particularly in ODHCs.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

In this short paper we study some properties of the lines associated with van Aubel’s theorem in the special case when squares are replaced with equilateral triangles constructed on the sides of an arbitrary quadrilateral.

The sustainable use of precious water resources requires effective water management. In the European Union, water management is mainly regulated by the Water Framework Directive (2000/60/EC), introducing an integrated river basin management approach. As EU directive, the legislation needs to be implemented in the Member States, entailing not only legal transposition, but also application and enforcement in Member States. One major instrument introduced by the Water Framework Directive is the environmental goal achievement obligation of art. 4 WFD, containing also a deterioration ban with several exemptions. This study compares transposition, application and enforcement of the exemption of permanent deterioration (art. 4 (7) WFD) in the context of the environmental goal achievement obligation regime in Lower Saxony (Germany) and the Netherlands. The study rests on a legal analysis of literature, policy documents and jurisprudence. Although based on the same EU directive wording and case law of the European Court of Justice, the deterioration ban and the exemption of permanent deterioration are implemented rather differently: While the deterioration ban is predominantly understood as planning obligation in the Netherlands, it became an important permit requirement in Lower Saxony since the Weser-ruling of the European Court of Justice.

The aim of this study was to evaluate the effect of two different insertion speeds at 8 different insertion torque values ranging from 25-60 during implantation in a dense polyurethane D1 bone model on the placement status and removal torque of dental implants. In this study, 50 pcf single layer polyurethane plates were used. In the study, a total of 320 implant sockets were divided into 2 groups as Group 1 (30 rpm) and Group 2 (50 rpm) in terms of insertion speed. Group 1 and Group 2 were divided into 8 subgroups as 25, 30, 35, 40, 45, 50, 55 and 60 torques. There were 20 implant sockets in each subgroup. During the implantations, implant placement status and removal torque values were assessed. There was a statistically significant difference between the 30 and 50 RPM groups in terms of overall implant placement status (p<0.01). It was found that the removal torque values at 50 RPM were statistically significantly higher than those at 30 RPM (p<0.01). This study showed that in dense D1 bone, the minimum parameters at which all implants could be placed at bone level were 50 torque at 30 rpm and 40 torque at 50 rpm.

The goal of the study was to assess the farmers’ acceptance of three sustainable production strategies, namely ‘Agro-forestry’, ‘Alternative protein source’ and ‘Prolonged maternal feeding’. Data on the acceptance of these strategies were collected by a survey of dairy farmers in six EU countries (AT, BE, DK, FI, IT, UK). An extended version of the Technology Acceptance Model (TAM) was applied by means of Structural Equation Modelling to testing various hypotheses on attitudes and intentions of dairy farmers towards these novel production strategies, as well as the influence of organic practices and collaborative behaviours along the supply chain. We found that the most preferred strategy - across all countries - was soy substitution by alternative protein sources. We also found that the intention to adopt a sustainable production strategy may derive from the influence of opinions (and behaviours) of relevant others, showing the role of interactions among farmers and other stakeholders in the adoption of innovations. Finally, the perceived usefulness of all investigated strategies is higher for organic farmers, while collaborative patterns reduce the impact of subjective norm on usefulness and overall acceptance. Our findings should encourage policy makers to consider the important role of supply chain management practices, including collaboration, to enhance the sustainability of dairy farming systems.

Repeated single-point measurements of thoracic bioimpedance at single (low)-frequency are strongly related to fluid changes during hemodialysis. Extension to semi-continuous measurements may provide longitudinal details in the time pattern of the bioimpedance signal, and multifrequency measurements may add in-depth information on the distribution between intra- and extracellular fluid. This study aims to investigate the feasibility of semi-continuous multifrequency thoracic bioimpedance measurements by a wearable device in hemodialysis patients. Therefore, thoracic bioimpedance was recorded semi-continuously (i.e. every ten minutes) at nine frequencies (8 – 160 kHz) in 68 patients during two consecutive hemodialysis sessions, complemented by a single-point measurement at home in-between both sessions. On average, the resistance signals increased during both hemodialysis sessions and decreased during the interdialytic interval. The increase during dialysis was larger at 8 kHz (∆ 32.6 Ω during session 1 and ∆ 10 Ω during session 2) compared to 160 kHz (∆ 29.5 Ω during session 1 and ∆ 5.1 Ω during session 2). Whereas the resistance at 8 kHz showed a linear time pattern, the evolution of the resistance at 160 kHz was significantly different [p < 0.0001]. Measuring bioimpedance semi-continuously and with a multifrequency current is a major step forward in the understanding of fluid dynamics in hemodialysis patients. This study paves the road towards remote fluid monitoring.

Van Wyk Grumbach syndrome refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be done; Here we present a case of a 10-year-old girl with Down syndrome, short stature, and vitiligo presented with vaginal bleeding, and a pelvic mass, in whom bilateral gonadectomy was performed. Most cases of Van Wyk Grumbach syndrome present in women, and classic hypothyroidism symptoms always precede the diagnosis; 11% of patients have Down Syndrome, sometimes tumor markers get elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen sign, pituitary hyperplasia, and severe anemia), that respond to levothyroxine treatment; Conclusions: Children with peripheral precocious puberty and gonadal masses, must be studied for hypothyroidism before any radical decision is made. Keywords: Puberty, Precocious; Ovarian Cysts, gonadectomy, Van Wyk Grumbach Syndrome

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p&lt;0.05; p&lt;0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p&lt;0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

In this paper, we classify the function space of all real-valued functions on R denoted as F(R,R) into 28 distinct blocks. Each block contains elements that share common features in terms of the cardinality of their sets of continuity and differentiability. Alongside this classification, we introduce the concept of the Connection, which reveals a special relationship structure between four well-known real-valued functions in real analysis: the Cantor function, Dirichlet function, the Thomae function, and the Weierstrass function. Despite the significance of this field, several perspectives remain unexplored.

This paper explores the ethical imperative of rehoming all healthy animals of sentient species after experiments have finished or when they have become otherwise redundant. We take into account disparate perspectives in animal ethics and see how they point in the same direction. We illustrate our case with our own rehoming experience from the joint Animal Welfare Body of Utrecht University and the University Medical Centre Utrecht, the Netherlands. The primary pilot proved successful, after which the principle of rehoming became standing policy and common practice. We discuss several challenges and our responses to those through continuous evaluation of the adoption program.

In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography- mass spectrometry analysis revealed that main compounds from LCO were Z-Ligustilide (44.58%) and Senkyunolide A (26.92%), and that of LO were geranial (42.16%) and neral (32.58%), respectively. The mixture of LCO and LO showed significant synergy against A. citricola, with a common-toxicity coefficient (CTC) value of 221.46 at the optimal ratio of LCO to LO (4: 1, w/w). Based on the results of solvents and emulsifiers screening, L. Chuanxiong oil · Lemongrass oil 20% emulsifiable concentrate (20% LCO · LO EC) was developed, which was confirmed to meet the requirements of a commercial pesticide by quality test. Field trials indicated that the insecticidal activity of the diluted 20% LCO · LO EC (1000 fold dilution) was comparable to conventional pesticide (20% imidacloprid EC) on A. citricola 7 days after application. Thus, the mixture of LCO and LO has the potential to be further developed as a botanical pesticide.

In this paper, we have established Hermite-Hadamard inequalities for r-preinvex functions via fractional integrals.

The Kwee van Woerden (KvW) method for the determination of eclipse minimum times has been a staple in eclipsing binary research for decades, due its simplicity and independence of external input parameters. However, its estimates of the timing error have been known to be of low reliability. During the analysis of very precise photometry of CM Draconis eclipses from TESS space mission data, KvW’s original equation for the timing error estimate produced numerical errors, which evidenced a fundamental problem in this equation. This contribution introduces an improved way to calculate the timing error with the KvW method. A code that implements this improved method, together with several further updates over the original method is presented as well. An example application on the CM Draconis light curves from TESS is given, where we show that its timing error estimates of about 1 second are in excellent agreement with error estimates obtained by other means.

Leigh Van Valen was an American evolutionary biologist who made major contributions to evolutionary theory and is particularly remembered by his groundbreaking paper "A New Evolutionary Law" (1973) where he provided evidence from fossil record data that this law maintains that the probability of extinction within any group remains es­sentially constant through time. In order to explain such unexpected result, Van Valen formulated a very influential idea that he dubbed the "Red Queen hypothesis". It states that the constant decay must be a consequence of evolutionary interactions among connected species within ecological networks. In Van Valen's picture, species do not merely evolve: they also coevolve with other species. As a consequence, when thinking in adaptation to an external environment, the other species must be considered as part (may be a major part) of such external world. Van Valen's law provided the first complex systems theory of coevolutionary dynamics and inspired a whole range of theoretical and experimental developments and scholars from very diverse fields, from economics to physics. In that respect, Leigh Van Valen's contribution percolated far beyond its original formulation. Red Queen arms races are nowadays considered a widespread feature of complex adaptive systems.

Illicit drug consumption is posing critical concerns in our society causing health issues, crime-related activities, and the disruption of border trade. The smuggling of illicit drugs urges the development of new tools for rapid on-site identification in cargos. Current methods used by law enforcement officers rely on presumptive color tests and portable spectroscopic techniques. However, these methods sometimes exhibit inaccurate results due to commonly used cutting agents, the colorful nature of the sample or because the drugs are smuggled (hidden or mixed) in common goods. Interestingly, electrochemical sensors can deal with these specific problems. Herein, an electrochemical device is presented that uses affordable screen-printed electrodes for the electrochemical profiling of illicit drugs by square-wave voltammetry (SWV). The identification of the illicit compound is based on the oxidation potential of the analyte. Hence, a library of electrochemical profiles is built upon the analysis of illicit drugs and common cutting agents. This library allows the design of a tailor-made script that enables the identification of each drug through a user-friendly interface (laptop or mobile phone). Importantly, the electrochemical test is compared by analyzing 48 confiscated samples with other portable devices based on Raman and FTIR spectroscopy as well as a laboratory standard method (i.e. gas chromatography – mass spectrometry). Overall, the electrochemical results obtained through the analysis of different samples from confiscated cargos at an end-user site, present a promising alternative to current methods, offering low-cost and rapid testing in the field.

Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults, and evaluated the effect of a digital lifestyle program on the nutritional status and nutrition health behaviors of these individuals. A micronutrient panel was measured in 348 participants, alongside a dietary assessment. One-hundred users subsequently underwent a remeasurement. We identified at least one nutritional imbalance in 301 individuals (86.5%). 80% improved and normalized B6, 67% improved folate, 70% improved B12, and 86% improved vitamin D. Iron abnormalities were corrected in 75% of participants. In conclusion, this study found micronutrient deficiencies of easily obtainable vitamins through diet or supplementation such as B vitamins and vitamin D were more prevalent than expected in a Dutch population. This can partly be explained by an insufficient consumption of food groups rich in B vita-mins. Our preliminary results in those remeasured after a digitally-enabled lifestyle intervention show these imbalances can be corrected with adequate behavioral support in a “food as medicine” approach complemented with supplementation where needed.

We show that the van der Waals gas does not exhibit just the celebrated liquid-gas 1 transition but also a quantum-classical one. We study the issue with reference to the LMC statistical 2 complexity and in relation to the order-disorder contrast.

Presenting a case report about a 14-year-old female patient presenting with a history of weakness in all four limbs since the age of 5. The patient has a history of difficulty in walking, wearing footwear, climbing stairs, and performing fine motor tasks. During the neurological examination showed mild spasticity, muscle weakness, areflexia, ill-sustained clonus, and sensory deficits. Radiological examination, including a contrast-enhanced MRI of the brain was done which showed findings that are consistent with Megalencephalic leukoencephalopathy with subcortical cysts, also known as Van der Knaap disease.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

Introduction: VULTO-VAN SILFHOUT-DE VRIES SYNDROME (VSVS;OMIM#615828) is an extremely rare hereditary disease associated with impaired intellectual development and speech, delayed psychomotor development and behavioral anomalies, including autistic behavioral traits and poor eye contact. To date, 27 patients with VSVS have been reported in the world literature. Materials and Methods: We describe a 23y.o. male patient with autism spectrum disorder (ASD) who was admitted to the gastroenterological hospital with signs of pseudomembranous colitis. ASD was first noted in the patient at the age of 2.5y.o. Later he developed epileptic seizers and prominent growth retardation. Prior to the hospitalization he was excluded chromosomal aberrations, Martin-Bell syndrome, aminoacidopathies/aminoacidurias associated with ASD. Whole genome sequencing was prescribed to the patient at 23y.o. Results: The patient appeared to be a heterozygous carrier of “de novo” variant c.662C>T (p.S221L) in ex 4 of the DEAF1 gene. c.662C> T had not been previously described in genomic databases. According to the ACMG criteria this missense variant was considered to be pathogenic. VSVS was diagnosed in the patient. Conclusions: The phenotype of the patient is very similar to the data presented in the world literature. However, growth retardation and cachexia, not previously described in the articles, are of interest.

The path towards decarbonization requires a progressive adaptation of all refrigeration systems, but only stationary ones have been intensely studied to improve their environmental performance. However, refrigerated transport is a vital piece of the cold chain, and it must be considered in the green transition. In this paper, we propose a model for a hybrid refrigerated van that includes photovoltaic panels and electric batteries to decrease total greenhouse gas emissions from the engine. Thermal, electrical, and battery sub-models are considered and integrated into the comprehensive hybrid solar-powered refrigerated van model. Different technologies are compared in economic terms, including Lithium and Lead-acid batteries and three different types of photovoltaic panels. The model was validated regarding van fuel consumption, showing a 4% deviation. Single and multiple delivery scenarios are considered to assess the energetic, economic, and environmental benefits. Monthly CO2,e emissions could be reduced to 20% compared to a standard refrigerated van. Despite the environmental benefits provided by this sustainable solution, the payback period is still too long (above 20 years) because of the necessary investment to adapt the vehicle and considering fuel and electricity prices currently.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Given a fuzzy normed space $ \left( X,N \right) $‎, ‎we will introduce the notion of fuzzy near best approximation within a relative distance $ \rho \geq 0 $‎. ‎Some basic properties are characterized and also many examples for illustration are presented‎.

It has been proven that in standard Einstein gravity, exotic matter (i.e. matter violating the point-wise and averaged weak and null energy conditions) is required to stabilize traversable wormholes. Quantum field theory permits these violations due to the quantum coherent effects found in any quantum field . Even reasonable classical scalar fields violate the energy conditions. In the case of the Casimir effect and squeezed vacuum states, these violations have been experimentally proven. It is advantageous to investigate methods of minimizing the use of exotic matter. One such area of interest is extended theories of Einstein gravity. It has been claimed that in some extended theories, stable traversable wormholes solutions can be found without the use of exotic matter. There are many extended theories of gravity and in this review paper we first explore f(R) theories and then explore some wormhole solutions in f(R) theories including Lovelock gravity.

A significant percentage of children suffer from neurodevelopmental aberrations, which have long-term effects on both individuals and society. Since the developmental timelines of different brain regions vary, the type, severity and timing of harmful exposures are crucial for understanding the specific pathological processes and consequences involved. During development, the cerebellum is one of the first brain structures to begin to differentiate, but one of the last to achieve maturity. This relatively long period underscores its vulnerability to detrimental environmental exposures throughout gestation. Moreover, as the postnatal functionality of the cerebellum is multifaceted, enveloping sensorimotor, cognitive, and emotional domains, prenatal disruptions in cerebellar development can result in a variety of neurological and mental health disorders. Here, we review major intrauterine insults that affect cerebellar development in both humans and rodents, ranging from abuse of toxic chemical agents such as alcohol and nicotine, to stress and sleep, malnutrition as well as infections. Understanding these pathological mechanisms in the context of the different stages of cerebellar development in humans and rodents may help us to identify critical and vulnerable periods and thereby to prevent the risk of associated prenatal and early postnatal damage that can lead to lifelong neurological and cognitive disabilities.

A position sensing glove, called SmartScan, that creates a 3D virtual model of a real object is presented. The data from the glove is processed by a volume minimization algorithm to validate the position sensor data. This allows only data from the object’s surface to be retained. The data validation algorithm allows the user to progressively improve an image by repeatedly moving their hand over the object. In addition, the user can choose their own balance between feature resolution and invalid data rejection. The SmartScan glove is tested on a foot model and is shown to be robust against motion artifacts, and has a mean accuracy of 2.9 mm (compared to a 3D model generated from optical imaging) without calibration.

Persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.

Reelin depletion and stress seem to affect similar pathways including GABAergic and glutamatergic signaling and both are implicated in psychiatric disorders in late adolescence/early adulthood. The interaction between reelin depletion and stress, however, remains unclear. To investigate this, male and female heterozygous reelin mice (HRM) and wildtype (WT) controls were treated with the stress hormone, corticosterone (CORT), during late adolescence to simulate chronic stress. Glucocorticoid receptors (GR), N-methyl-D-aspartate receptor (NMDAr) subunits, glutamic acid decarboxylase (GAD67) and parvalbumin (PV) were measured in the hippocampus and the prefrontal cortex (PFC) in adulthood. While no changes were seen in male mice, female HRM showed a significant reduction in GR expression in the dorsal hippocampus. In addition, CORT reduced GR levels as well as GluN2B and GluN2C subunits of NMDAr in the dorsal hippocampus in female mice only. CORT furthermore reduced GluN1 levels in the PFC of female mice. The combined effect of HRM and CORT treatment appeared to be additive in terms of GR expression in the dorsal hippocampus. Female-specific CORT-induced changes were associated with overall higher circulating CORT levels in female compared to male mice. This study shows differential effects of reelin depletion and CORT treatment on GR and NMDAr protein expression in male and female mice, suggesting that females are more susceptible to reelin haploinsufficiency as well as late-adolescent stress. These findings shed more light on female-specific vulnerability to stress and have implications for stress-associated mental illnesses with a female bias including anxiety and major depression.

Micellar Casein Concentrate (MCC) is manufactured from microfiltration (MF) of skim milk utilizing ceramic or polymeric membrane filtration. While ceramic filtration has higher efficiency, use of polymeric is cost effective and the process is familiar to several US dairy processors. The aim of the present study was to develop an optimized membrane filtration process to produce MCC using spiral wound polymeric membrane filtration (SW MF) system by systematic selection of transmembrane pressure (TMP) and level of diafiltration (DF). Using skim milk as feed material, preliminary lab-scale MF experiments were conducted using 0.5 µm polyvinylidene fluoride (PVDF) membrane. Three TMP (34.5, 62.1, and 103.4 kPa) and three levels of DF (70, 100, and 150%) along with a process without DF as control were used in the study. Effect of TMP and effectiveness of DF on flux rates, SP removal, casein to total protein (CN/TKN) ratio, casein to true protein (CN/TP) ratio, rejection of casein (rej CN) and SP (rej SP) were evaluated. At all TMP values used in the study, the overall flux (O Flux) increased with the level of DF. Highest O Flux of 30.77 liter per meter square per hour (LMH) was obtained with 34.5 kPa pressure and 150% DF. The impact of DF was more pronounced at lower pressures than at the higher pressures used in the study. With controlled DF, instantaneous flux was maintained within 80% of initial flux for the entire process run. For all the experiments, casein has a rejection of 0.97 to 1.0, while serum protein has the lowest rejection of 0.10 at 34.5 kPa pressure and 150% DF level. Use of 34.5 kPa and DF level of 150 % contributed to 81.45% SP removal, and casein to true protein ratio of 0.96. SP removal data from the lab-scale experiments were fitted into a mathematical model using DF and square of TMP as factors. The model predicts SP removal within 90-95% of actual SP removal got from the pilot plant experiments.

The Van der Pol oscillator is a chaotic non-linear system. Small perturbations in initial conditions may result in wildly different trajectories. Because of its chaotic nature, controlling, or forcing, the behavior of a Van der Pol oscillator is difficult to achieve through traditional adaptive control methods. Connecting two Van der Pol oscillators together where the output of one oscillator, the driver, drives the behavior of its partner, the responder, is a proven technique for controlling the Van der Pol oscillator. Deterministic AI (DAI) is an adaptive feedback control method that leverages the known physics of the Van der Pol system to learn optimal system parameters for the forcing function. We assessed the performance of DAI employing three different online parameter estimation algorithms. Our evaluation criteria include mean absolute error (MAE) between the target trajectory and the response oscillator trajectory over time. RLS with exponential forgetting (RLS-EF) had the lowest MAE overall, with a 2.46% reduction in error. However, another method was notable. Least Mean Squares with normalized gradient adaptation (LMS-NG) had worse initial error in the first 10% of the simulation, but after that point had consistently better performance. We found that over the last 90% of the simulation, DAI with LMS-NG had a 48.7% reduction in MAE compared to feedforward alone.

Feline panleukopenia (FPL), a highly contagious and frequently fatal disease of cats, is caused by Feline parvovirus (FPV) and Canine parvovirus (CPV). We characterized the diversity of these Carnivore protoparvovirus 1 variants in 18 faecal samples collected from domestic cats with FPL during an outbreak, using targeted parvoviral DNA metagenomics to a mean depth of >10,000 X coverage per site. All samples comprised FPV alone. Compared to the reference FPV genome, isolated in 1967, 44 mutations were detected. Ten of these were non-synonymous, including 9 in non-structural genes and one in VP1/VP2 (Val232Ile), which was the only one to exhibit inter-host diversity, being present in five sequences. There were five other polymorphic nucleotide positions, all with synonymous mutations. Intra-host diversity at all polymorphic positions was low with sub-consensus variant frequencies (SVF) of >1% except for two positions (2108 and 3208) in two samples with SVF of 1.1 – 1.3%. Intra-host nucleotide diversity was measured across the whole genome (0.7 - 1.5%) and for each gene, and was highest in the NS2 gene of four samples (1.2 – 1.9%). Overall, intra-host viral genetic diversity was limited and most mutations observed were synonymous, indicative of a low background mutation rate and strong selective constraints.

Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.7 for pure fat metabolism and 1.0 for pure carbohydrate metabolism. While the nutritional determinants of metabolic flexibility are known, the role of low energy expenditure and sedentary behavior in the development of metabolic inflexibility is less studied. In this study we present a new description of metabolic flexibility in genome-scale metabolic models which accounts for energy expenditure, and we study the interactions between physical activity and nutrition in a set of patient-derived models of skeletal muscle metabolism in older adults. The simulations show that fuel choice is sensitive to ATP consumption rate in all models tested. The ability to adapt fuel utilization to energy demands is an intrinsic property of the metabolic network

Objective: This study aimed to demonstrate the availability of portable devices for nasal FeNO measurement, which could replace exhaled NO measurement based on the continuous aspiration of multiple flow measurement systems. Methods: A descriptive cross-sectional study. The healthy subjects without rhinosinusis disorders (control group) and those with diagnosed allergic rhinitis (AR group) were enrolled in the study. They underwent nasal and bronchial FeNO measurements by both fixed flow NObreath® connected to nasal mask and multiple flows HypAir FeNO®. Results: A total of 153 people were recruited including 63 healthy subjects and 90 subjects with AR. There were no statistically significant differences in anthropometric characteristics between the two groups (P > 0.05). There were a significant increase in FeNO values in the AR group compared to the control group; concentrations of nasal and bronchial FeNO mearsured by NObreath® were 76.0 ± 50.7 ppb (vs 36.0 ± 28.1 ppb, P < 0.01) and 32.3 ± 15.4 ppb (vs 9.2 ± 5.6 ppb, P < 0.001), and those mearsured by NObreath® Hypair FeNO® were 1796.9 ± 523.3 ppb (vs 400.2 ± 123.1 ppb, P < 0.001) and 37.3 ± 23.0 ppb (vs 17.4 ± 18.3 ppb, P < 0.01). A weak correlation between the values measured by NObreath® and Hypair FeNO® devices was observed (r = 0.023 and r = 0.089, respectively; p < 0.05). Conclusions: The handheld NObreath® device is effective in measuring FeNO concentrations in both normal subjects and AR patients. The advantages in price and size, creating a compact, low-cost device that is convenient for use and research.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg⁹ bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

The effective Supervisory Control and Data Acquisition (SCADA) system can improve the reliability, safety and economic benefits of microgrid operation. In this research, the lower central controller and upper WEB monitoring system are connected by the SCADA system which is as the hub of microgrid intelligent monitoring platform. This system contains a set of specific functions programmed by Java as a middleware which can provide control and communication between the central controller and the upper monitoring system. The system realizes the real-time data acquisition and storage, the control instructions parsing and transmitting, the microgrid security and stability, the load balancing and resource recovery of the microgrid. All that functions have been tested and verified in the actual operation.

The study explored the contribution of ICT-based information sources to market participation among smallholder livestock farmers. Use of ICTs is considered paramount for providing smallholder farmers with required market information, in order to reduce market asymmetries. A Double Hurdle regression was utilized to analyze data collected from 150 smallholder livestock farmers in the study area. The results show that while use of ICT-based market information sources significantly influenced market participation, the effect of using ICT-based information sources on intensity of market participation was not significant. Other variables shown to influence both market participation and the intensity of market participation were age, additional income and membership of farmer cooperatives. This suggests the need to also consider other associated factors in the application of interventions which utilize ICT-based information sources in achieving planned market interventions.

Biodiversity has become an issue of global anxiety over the past decades due to its rapid decline worldwide. Bangladesh as one of the most densely populated countries in the world is no more exception. The country, although, was once very rich in biodiversity, during the last few decades as a consequence of the rapid reduction in forest area, urbanisation, habitat modification, unsustainable natural resources use and collection and overall climate change it has decreased alarmingly. Of late, the government, as a signatory of various regional and international conservation treaties, has taken various initiatives to improve country’s dwindling biodiversity. This paper reviews the present situation of biodiversity in Bangladesh, management trends and major causes of biodiversity loss. A separate statutory body is fundamental to ensure conservation, sustainable use and equitable sharing of benefits arisen from biodiversity in the country.

Proteases are integral enzymes of the plant immune system. Multiple aspects of defence are regulated by proteases, including the hypersensitive response, pathogen recognition, priming and peptide hormone release. These processes are regulated by unrelated proteases residing at different subcellular locations. In this review we discuss ten prominent plant proteases contributing to the plant immune system, highlighting the diversity of roles they perform in plant defence.

Land degradation and climate change are among the main threats to the sustainability of ecosystems worldwide. Therefore, the restoration of degraded landscapes is essential to maintain the functionality of ecosystems, especially those with greater social, economic and environmental vulnerability. Nevertheless, policy-makers are frequently challenged by deciding on where to prioritize restoration actions, which usually includes to deal with multiple and complex needs under an always short budget. If these decisions are not taken based on proper data and processes, restoration implementation can easily fail. To help decision-makers taking informed decisions on where to implement restoration activities, we have developed a semiautomatic geospatial platform to prioritize areas for restoration activities based on ecological, social and economic variables. This platform takes advantage of the potential to integrate R coding, Google Earth Engine cloud computing and GIS visualization services to generate an interactive geospatial decision-maker tool for restoration. Here, we present a prototype version called "RePlant alpha" which was tested with data from the Central Zone of Chile. This exercise proved that integrating R and GEE was feasible, and that the analysis, with at least six indicators and for a specific region was also feasible to implement even from a personal computer. Therefore, the use of a virtual machine in the cloud with a large number of indicators over large areas is both possible and practical.

Previous studies demonstrate the critical importance of non-coding RNAs interfacing with chromatin-modifying machinery resulting in promoter-enhancer-based gene regulation and raise the possibility that many other enhancer-like RNAs may operate via similar mechanisms. Critically, more than 80% of the disease-linked variations identified in genome-wide studies are located in the non-coding regions of genomes, especially non-coding RNA, suggesting non-coding RNAs are relevant to disease. Thus, a critical path forward for understanding non-coding RNAs' role, especially long non-coding RNAs, is to understand the genomic regions' transcriptional regulation, especially non-coding regions. Here, we developed a user-friendly R package called SomaGene for studying and identifying enhancer-like non-coding RNAs with enriched somatic mutations in the cancer genome. SomaGene accepts different genomic variants (whole genome/exome somatic point mutations, structural variations, copy number variations) to identify those RNAs that significantly mutated in diseases (e.g., cancer). It then uses multiple publicly available genomics and epigenetics datasets including ENCODE epigenomics annotations, FANTOM5 tissue-specific expression profiles, disease-associated genome-wide association SNPs, and tissue-specific eQTL pairs to identify those RNAs with potentially enhancer function. SomaGene, as a powerful R package, can provide the opportunity to cancer scientists to study the roles of non-coding RNAs in different cancer genomes.

Molenaar’s manifesto on psychology as idiographic science brought the N = 1 times series perspective firmly to the attention of developmental scientists. The rich intraindividual variation in complex developmental processes requires the study of these processes at the level of the individual. Yet, the idiographic approach is all but easy in practical research. One major limitation is the collection of short interval times series of high quality data on developmental processes. In this paper we present a novel measurement approach to this problem. We developed an online practice and monitoring system which is now used by thousands of Dutch primary school children on a daily or weekly basis, providing a new window on cognitive development. We will introduce the origin of this new instrument, called Math Garden, explain its setup, and present and discuss ways to analyze children’s individual developmental pathways.

In the dynamic interplay between people and their physical environments, the Global South stands as a mosaic undergoing a multitude of transformative influences in architecture and urbanism where examining social sustainability becomes imperative. While prevailing attention remains on environmental and economic sustainability, this study addresses a persistent gap in the urban literature by focusing on the dynamic and manifold nature of social sustainability. Positioning itself within the context of sustainable development, the study links the pursuit of social aspects of sustainability with selected unique urban contexts from the Global South. Five cases that include Alexandria (Egypt), Tripoli (Libya), Basra (Iraq), Lilongwe (Malawi), and Accra (Ghana) are discussed through multi-layered investigations that involve attitude surveys, interviews, focus groups, participatory systematic observations, and behavioral mapping, engaging directly with inhabitants and stakeholders. Uncovering people-place narratives in the identified contexts, the cases are developed into five knowledge typologies that serve as practical tools for planning and design decision-making, policy formulation, and academic discourse. Discussions are conceived to demonstrate the transformative role people-place narratives play in fostering a more sustainable and equitable urban future. Conclusions are drawn to offer practical insights for stakeholders involved in various capacities in shaping the urban landscape of the Global South.

The production and secretion of very-low density lipoproteins (VLDL) by hepatocytes has a direct impact on liver fat content as well as the concentration of cholesterol and triglycerides in the circulation and thus affects liver and cardiovascular health, respectively. Importantly, excess caloric intake and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased levels of atherogenic lipoproteins. Cholesterol as well as triglycerides in remnant particles after VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease (ASCVD) and have garnered increasing attention over the last few decades. To date, however, increased risk of ASCVD is not the only concern when considering today’s cardiometabolic patients, as they often also suffer from hepatic steatosis. This notion highlights the importance of understanding the molecular regulation of VLDL biogenesis. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, that has led to many exciting new molecular insights, the topic of this review. We think that increasing our understanding of the biology of this pathway will help improve the health of the cardiometabolic patient in the long term.

Fertility preservation technologies have existed for decades, and the field is rapidly advancing; limited data exist regarding the use of these technologies by transgender patients. Many options are available for transgender patients who wish to preserve fertility before transitioning. These options include the cryopreservation of gametes, ovarian tissue, or embryos. Currently, ejaculated, or testicular sperm, immature oocytes, and ovarian tissue can be preserved for later use, but no such use option exists for immature testicular tissue. Many financial, sociological, and legal barriers and a lack of awareness among physicians and patients also hindered the utilization of these fertility preservation services. While options are abundant, usage rates are relatively low. The initial data regarding the successful use of preserved tissues appears promising, with birth rates not dissimilar to non-transgender patients. Further investigations into this area are needed. In addition, counseling regarding fertility preservation options should become a significant part of the provider-patient conversation before transitioning therapies.; fertility; transgender; reproductive technology.

We consider the Dirac field in polar formulation, showing that when torsion is taken in effective approximation the theory has the thermodynamic properties of a van der Waals gas, that when the limit of zero chiral angle is taken the theory reduces to that of a Weyssenhoff fluid, and that under the spinless condition it gives the Newtonian particle. This nesting of approximations will allow us to interpret the various objects pertaining to the spinor, with torsion providing a form of negative pressure, and the chiral angle being related to a type of internal dynamics.

The effect of atomic and molecular microfied dynamics on spectral line shapes is under consideration. This problem is treated in the framework of the Frequency Fluctuation Model (FFM). For the first time the FFM is tested for the broadening of a spectral line by neutral particles. The usage of the FFM allows one to derive simple analytical expressions and perform fast calculations of the intensity profile. The obtained results was compared with Chen and Takeo theory (CT), which is in a good agreement with experimental data. It was demonstrated that for moderate values of temperature and density the FFM successfully describes the effect of the microfield dynamics on a spectral line shape.

Beta-glucan-stimulated mammalian macrophages show an increased responsiveness to secondary stimulation in a nonspecific manner. This phenomenon is known as trained innate immunity. Our study aimed to explore training of primary chicken monocytes. We hypothesized that primary chicken monocytes, similar to their mammalian counterparts, can be trained with β-glucan resulting in increased responses of these cells to a secondary stimulus. Primary blood monocytes of white leghorn chickens were primary stimulated with β-glucan microparticulates (M-βG), LPS, recombinant chicken interleukin-4 (IL-4) or combinations of these components for 48 h. On day 6, the primary stimulated cells were secondary stimulated with LPS. Nitric oxide (NO) production levels were measured as an indicator of pro-inflammatory activity. In addition, the cells were analysed by flow cytometry to characterize the population of trained cells and to investigate the expression of surface markers associated with activation. After the secondary LPS stimulation, surface expression of CSF1R and the activation markers CD40 and MHC-II was higher on macrophages that were trained with a combination of M-βG and IL-4 compared to unstimulated cells. This increased expression was paralleled by enhanced NO production. In conclusion, this study showed that trained innate immunity can be induced in primary chicken monocytes with β-glucan, which is in line with previous experiments in mammalian species. Innate immune training may have potential to improve health and vaccination strategies within the poultry sector.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

This study aimed to optimize the bioelectricity production process using a vinasse solution through the application of Plackett-Burman and Box-Behnken designs. An electrochemical cell was constructed using Arduino to measure the potential difference between the anode and cathode immersed in the vinasse solution, a byproduct of wine production containing organic compounds and ions that undergo redox reactions. The Plackett-Burman design identified the most influential variables among eight previously selected, including vinasse concentration, agitation, and yeast, which positively affected millivolt production, while temperature showed a negative correlation. Based on these results, the Box-Behnken design was used for process optimization, varying parameters such as concentration, stirring, and sodium chloride. Response surface graphs demonstrated the relationship between these variables and millivolt production. The findings indicate that higher agitation levels, lower concentrations of vinasse, and the addition of sodium chloride can enhance bioelectricity generation. The study provides insights into the bioelectricity production process from vinasse, contributing to the understanding and potential for sustainable energy generation. The methodology involving Arduino-based measurement and the utilization of experimental designs offers a systematic approach to optimize bioelectricity production from vinasse.

The exceptional increase in molecular DNA sequence data in open repositories is mirrored by an ever-growing interest among evolutionary biologists to harvest and use those data for phylogenetic inference. Many quality issues, however, are known and the sheer amount and complexity of data available can pose considerable barriers to their usefulness. A key issue in this domain is the high frequency of sequence mislabelling encountered when searching for suitable sequences for phylogenetic analysis. These issues include the incorrect identification of sequenced species, non-standardised and ambiguous sequence annotation, and the inadvertent addition of paralogous sequences by users, among others. Taken together, these issues likely add considerable noise, error or bias to phylogenetic inference, a risk that is likely to increase with the size of phylogenies or the molecular datasets used to generate them. Here we present a software package, phylotaR, that bypasses the above issues by using instead an alignment search tool to identify orthologous sequences. Our package builds on the framework of its predecessor, PhyLoTa, by providing a modular pipeline for identifying overlapping sequence clusters using up-to-date GenBank data and providing new features, improvements and tools. We demonstrate our pipeline’s effectiveness by presenting trees generated from phylotaR clusters for two large taxonomic clades: palms and primates. Given the versatility of this package, we hope that it will become a standard tool for any research aiming to use GenBank data for phylogenetic analysis.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells, due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells – hMSCs) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSCs from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in normal cells, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 hours after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA repair system after X ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of normal cells from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.

Since the 1980s, a growing interest in goat milk was noticed due to the nutritional values and health benefits of this milk, which resulted in increasing goat populations and milk production worldwide. This comprehensive review elaborates on goat milk composition compared to other types of milk. It is also an overview of goat milk production, properties, nourishment-value, applications in dairy products, and potential health benefits. Goat milk composition and its characteristics are slightly different from other types of milk and can be utilized to manufacture many dairy products. Fresh goat milk and goat milk products (e.g., yogurt and kefir were found to provide various potential health benefits, such as anti-inflammatory, prevent cardiovascular disease, anti-diabetic and antihypertensive, strengthen bones, boost immunity, and improve metabolism.

In the software development process, the decision-maker (DM) has a range of problems inherent to its function. Wrong choices during software planning can bring great risk to the project. Therefore, the planning of software releases to be delivered to the customer should be well done. This is not an easy task because releases are made up of many requirements that contain complex variables that must be considered, such as precedence, cost, requirement stability, among other features that make the requirements-selection process challenging. To make this process less exhaustive, DM can use tools that facilitate this work. In software engineering, we can find fields of research specialists in this context, such as Search-Based Software Engineering (SBSE). The SBSE makes use of advanced metaheuristics to search for optimal solutions or the closest to it. In this work, we try to use another field of research to solve this same problem type, the Verbal Decision Analysis (VDA). To do this, we elaborate a workflow that will use the same source data, execute two solutions using the two search fields (SBSE and VDA) and compare the results. In the end, we evaluated and commented on the results.

The Fusarium fujikuroi species complex (FFSC) includes socioeconomically important pathogens that cause disease and/or mycotoxin contamination on numerous crops. Here, we used comparative genomics to elucidate processes underlying the ability of pine-associated and grass-associated FFSC species to colonize tissues of their respective plant hosts. We characterized the identity, possible functions, evolutionary origins, and chromosomal positions of the host-range-associated genes encoded by the two groups of fungi. The 72 and 47 genes identified as unique to the respective genome groups were potentially involved in diverse processes, ranging from transcription, regulation, and substrate transport, through to virulence/pathogenicity. Most emerged early during the evolution of Fusarium/FFSC and were subsequently retained only in some lineages, while some had origins outside Fusarium. Although differences in the densities of these genes were especially noticeable on the conditionally dispensable chromosome of F. temperatum (representing the grass-associates) and F. circinatum (representing the pine-associates), the host-range-associated genes tended to be located towards the subtelomeric regions of chromosomes. Taken together, these results demonstrate that multiple mechanisms drive the emergence of genes in grass- and pine-associated FFSC taxa examined and highlighted the diversity of molecular processes potentially underlying niche-specificity in these and other Fusarium species.

Copper, the highly toxicity micronutrient, plays two essential roles: it is a catalytic and structural cofactor for Cu-dependent enzymes, and it acts as a secondary messenger. In the cells, copper is imported by CTR1, a transmembrane high-affinity copper importer, and DMT1 (divalent metal transporter). In cytosol, enzyme-specific chaperones receive copper from CTR1 C-terminus and deliver it to their apoenzymes. DMT1 cannot be a donor of catalytic copper because it does not have cytosol domain which is required for copper transfer to the Cu-chaperons and following to cuproenzymes. Here we assume that DMT1 can mediate copper way required for regulatory copper pool. To verify this thought, we used CRISPR/Cas9 to generate H1299 cell line with CTR1 or DMT1 single knockout (KO) and CTR1/DMT1 double knockout (DKO). To confirm KOs of the genes qRT-PCR were used. Two independent clones for each gene were selected for further studies. In CTR1-KO cells, expression of the DMT1 gene was significantly increased. In subcellular compartments, copper concentration decreased dramatically in DKO cells. CTR1-KO cells, but not DMT1-KO, demonstrated reduced sensitivity to cisplatin and silver ions, agents that enter the cell through CTR1. The expression of genes, whose protein products require copper: HIF1α, XIAP, COMMD1, CCS, Cp, but not SOD1 and NF-kB, changed their level. Perhaps these data will help to understand how the disturbances of copper homeodynamics lead to the development of neurodegenerative and oncological disorders. Possibility of using CTR1 KO and DMT1 KO cells to study homeodynamics of catalytic and signaling copper selectively is discussed.

Regulatory T cells (Tregs) are major drivers behind immunosuppressive mechanisms and present a major hurdle for cancer therapy. Tregs are characterized by high expression of CD25, which is a potentially valuable target for Treg depletion to alleviate immune suppression. The preclinical anti-CD25 (αCD25) antibody, clone PC-61, has met with modest anti-tumor activity, due to its capacity to clear Tregs from circulation and lymph nodes but not those that reside in the tumor. Optimization of the Fc domain of this antibody clone has been shown to enhance intratumoral Treg depletion capacity. Here, we generated a stable cell line that produces optimized recombinant Treg depleting antibodies. A genome engineering strategy in which CRISPR-Cas9 was combined with homology directed repair (CRISPR-HDR) was utilized to optimize the Fc domain of the hybridoma PC-61 for effector functions by switching it from the original rat IgG1 to a mouse IgG2a isotype. In a syngeneic tumor mouse model the resulting αCD25-m2a antibody mediated effective depletion of tumor resident Tregs leading to a high effector T cell (Teff) to Treg ratio. Moreover, combination of the αCD25-m2a with αPD-L1 treatment augmented tumor eradication in mice, demonstrating the potential for αCD25 as a cancer immunotherapy.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

Physical symptoms are defined as symptoms for which adequate examination does not reveal a sufficient underlying root cause, e.g., pain and fatigue. The extant literature of the neurobiological underpinnings of physical symptoms has been largely inconsistent and primarily consists of (clinical) case-control studies with relatively small samples sizes. Therefore, we studied the association of brain morphology with physical symptoms in pre-adolescents from two independent and population-based cohorts. This study included 2,683 individuals from the Generation R Study (51% girls, 10.1 ± 0.6 years old) and 10,567 pre-adolescents from the ABCD Study (48% girls, 9.9 ± 0.6 years old). High- resolution structural magnetic resonance imaging (MRI) was collected using 3-Tesla MRI systems. Physical symptoms were evaluated using the somatic complaints syndrome scale from the parent-reported school-age version of the Child Behavior Checklist. Linear regression models were fitted for global brain metrics (i.e., cortical and subcortical grey matter volume and total white matter volume) as well as surface-based vertex-wise measures (surface area and cortical thickness). Analyses were initially conducted separately in each cohort and later meta-analysed. No associations were observed in either cohort separately. In the combined vertex-wise meta-analysis of both cohorts; the right hemisphere surface area, most notably the rostral middle frontal gyrus, superior frontal gyrus and anterior cingulate cortex, were related to physical symptoms after correcting for multiple comparisons (cluster area = 1,882 mm2). The present study, which is the most representative and well-powered to date, suggests that surface area, but not other measures of brain morphology, are modestly related to physical symptoms in pre- adolescents. While these effects are subtle, future longitudinal research is warranted to elucidate whether such associations indicate a cause or a consequence of the physical symptoms.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

In an age of market liberalization, globalization, and expanding agribusiness, there is a danger that small-scale farmers will find difficulty in fully participating in the market economy. One of the solutions to solve the above situation is to strengthen linkages between farmers and firms through contract farming. The purpose of this study is to assess the factors affecting the level of linkages between businesses and farmers in crop development in Thai Binh province, Vietnam. The two main research methods used were exploratory factor analysis (EFA) and regression analysis with survey data which was conducted from 300 farmers, 10 firms, and 15 factors related to contract-farming. The results indicated that there are 5 factors that significantly affect the level of participation of farmers in the linking process, the order of impacts from strong to weak is as follows: (1) Commitment and sharing of benefits and risks between farmers and firms in the linking process, (2) Issues related to management skills and enterprises capacity of link firms, (3) Price issues that farmers are interested in in the process of implementing links with firms, (4) Policy environment - Institutions related to farmer contracts between firms and farmers, (5) Household awareness about the benefits brought about by farmer contracts with firms. Based on results, a number of specific solutions have been proposed to enhance the efficiency of farming contracts between firms and farmers in cultivation production.

Hydrophilic coatings have recently emerged as a new approach to avoid the adhesion of (bio)organisms on surfaces immersed in water. In these coatings the hydrophilic character is crucial for the anti-fouling (AF) performance. However, this property can be rapidly lost due to the inevitable damages which occur at the surface, reducing the long-term effectiveness of the AF functionality. We report hydrophilic polycarbonate-mPEG polyurethane coatings with tunable hydrophilic properties as well as an excellent and long-term stability in water. The coatings exhibit low protein adhesion values and are able to self-replenish their hydrophilicity after damage, due to the existence of a reservoir of hydrophilic dangling chains incorporated in the bulk. The combination of low T_g and sufficient mobility of the mPEG dangling chains (enabled by chains with higher molecular weight) proved to be crucial to ensure autonomous surface hydrophilicity recovery when the coatings were immersed in water. This coatings and design approach offer new possibilities towards high performance AF coatings with an extended service life-time which can be used in several major applications areas, such as marine and biomedical coatings, with major economic and environmental benefits.

Numerous researchers and institutions have been developing in ovo sexing technologies to improve animal welfare by identifying male embryos in an early embryonic stage and disposing of them before pain perception. This review gives a complete overview of the technological approaches reported in papers and patents by performing a thorough search using Web of Science and Patstat databases for papers and patents, respectively. Based on a total of 45 papers and 100 patent families up until 2021 reported worldwide, 11 technology categories were defined: six non-optical and five optical techniques. Every category was described for its characteristics while assessing its potential for application. Next, the dynamics of the publications of in ovo sexing techniques in both paper and patent fields were described through growth curves, and the interest or actual status was visualized using the number of paper citations and the actual legal status of the patents. When comparing the reported technologies in papers to those in patents, scientific gaps were observed, as some of the patented technologies were not reported in the scientific literature, e.g., ion mobility and mass spectrometry approaches. Generally, more diverse approaches in all categories were found in patents, although they do require more scientific evidence through papers or industrial adoption to prove their robustness. Moreover, although there is a recent trend for non-invasive techniques, invasive methods like analyzing DNA through PCR or hormones through immunosensing are still being reported (and might continue to be) in papers and patents. It was also observed that none of the technologies complies with all the industry requirements. Thus, more research and harmony between consumers, industry, and governments is necessary.

We report on recent experimental results on β decay into self-conjugate (N=Z) nuclei with mass number 58≤A≤70. Super-allowed β decays from the Jπ=0+ ground state of a Z=N+2 parent nucleus are to the isobaric analogue state, through so-called Fermi transitions, and to Jπ=1+ states, by way of Gamow–Teller (GT) transitions. The operator of the latter decay is a generator of Wigner’s SU(4) algebra and as a consequence GT transitions obey selection rules associated with this symmetry. Since SU(4) is progressively broken with increasing A, mainly as a consequence of the spin–orbit interaction, this symmetry is not relevant for the nuclei considered here. We argue, however, that the pseudo-spin–orbit splitting can be small in nuclei with 58≤A≤70, in which case nuclear states exhibit an approximate pseudo-SU(4) symmetry. To test this conjecture, GT decay strength is calculated with use of a schematic Hamiltonian with pseudo-SU(4) symmetry. Some generic features of the GT β decay due to pseudo-SU(4) symmetry are pointed out. The experimentally observed GT strength indicates a restoration of pseudo-SU(4) symmetry for A=70.

The segmentation and de-noising are basic operations, required in every signal processing and classification system. The classical segmentation and de-noising approaches are time-invariant. Consequently, it results in the post processing of an unnecessary information and causes an increase in the system processing activity and power consumption. In this context, an efficient event-driven segmentation and de-noising technique is proposed. It is founded on the principles of level crossing and activity selection. Therefore, it can adapt its sampling frequency, segmentation window length and position along with the filter order by analyzing the input signal local characteristics. As a result, the computational complexity and the power consumption of the proposed system is reduced compared to the counter ones. The suggested system performance is compared with the classical one. It is done for the case of a multi-channel Electroencephalogram (EEG) signals. Results show a noticeable compression gain with an effective adaptation of the de-noising filters order. It aptitudes a significant computational gain, transmission data rate reduction and power consumption reduction of the proposed technique, compared to the counter ones. It shows that the proposed solution is an attractive candidate to embed in the new generation EEG wearables.

For a nonzero normed linear space X‎, ‎we will define some different classes of fuzzy norms on X generated by linear and bounded linear functionals‎. ‎Also separate continuity of the elements of each class are investigated‎. ‎The aim of this research is to introduce a source of examples and counterexamples in the field of fuzzy normed spaces‎.

It has been shown that the Micro-Rain Radar (MRR) can be used to derive rainfall rates every 10 m over a depth of 1.28 km using the mean vertical air velocity corrected Doppler raindrop fall speed spectra. Furthermore, it has been shown that by assuming a reasonable advection velocity for the rain, these data can be analyzed to produce spatial radial power spectra often readily fit using a power function. Previous work has shown, however, that each spectrum applies only to each particular set of data and usually lacks the statistical qualifications necessary to be considered generally applicable. However, this limitation does not preclude the potential existence of other generalizations that can be used to explore the rainfall formation processes. The intent of this study, then, is to perform an initial look for such possible behaviors using time-height profiles of the rainfall rate. It is found that once the rainfall rate, R, exceeds about 20 mm h-1, there is, apparently, an associated flattening of the spectra with increasing R so that the smaller scales play an ever increasingly important role in such rain near the ground perhaps reflecting the increasing importance of such scales in the formation of pockets of more intense convective rain. The true generality of this finding needs additional scrutiny using more data particularly from two spatially separated MRR as is currently under preparation.

Wind energy in Europe is aimed to grow at a steady, high pace, but opposition from residents to local wind farm plans is one of the obstacles to further growth. A large body of evidence shows that local populations want to be involved and respected for their concerns, but in practice this is a complex process that cannot be solved with simple measures such as financial compensation. The visual presence and the acoustic impact of a wind farm is an important concern for residents. Generally environmental noise management aims to reduce the exposure of the population, usually based on acoustics and restricted to a limited number of sources (such as transportation or industry) and sound descriptors (such as Lden). Individual perceptions are taken into account only at an aggregate, statistical level (such as percentage of exposed, annoyed or sleep-disturbed persons in the population). Individual perceptions and reactions to sound vary in intensity and over different dimensions (such as pleasure/fear or distraction). Sound level is in fact a weak predictor of the perceived health effects of sound. The positive or negative perception of and attitude to the source of the sound is a better predictor of its effects. This article aims to show how the two perspectives (based on acoustics and on perception) can lead to a combined approach in the management of a wind farm aimed to reduce annoyance, not primarily of sound level. An important aspect in this approach is what the sound means to people: is it associated with the experience of having no say in plans, does it lead to anxiety or worry, is it appropriate? The available knowledge will be applied to wind farm management: planning as well as operation.

The Food Boost Challenge (FBC) was developed using a participatory action research approach to enhance healthy eating behaviors, here vegetable and fruit products (V&amp;F-products) among adolescents, particularly those with lower education levels. FBC is a quadruple helix innovation process, involving adolescents, (peer)researchers, and food system partners of non-governmental and commercial organizations. In 2021-2022, 34 partners provided both cash and in-kind contributions to join the FBC-community. Phase 1 involved 200 students identifying barriers and drivers for consumption of F&amp;V-products among 1000 pre-vocational adolescents, aged 12-20 years. In phase 2, student teams submitted innovative ideas, resulting in 25 concepts fitting into ≥1 of 4 routes: I) innovative technology for a healthy diet, II) new food products/concepts for adolescents, III) hotspots improving F&amp;V-product experience, and IV) new routes to market. In phase 3 consortia of adolescents, students and partners were formed to develop 10 selected concepts into prototypes, and phase 4 offered teams a national platform. Results show FBC resonates with all stakeholders, generating valuable insights to increase F&amp;V-intake. Prototypes in all 4 routes have been developed, with some already in the implementation stage. Additionally, other regions in the Netherlands have adopted the FBC approach. Overall, FBC is an approach that transforms ideas into actionable measures and shows potential to be adapted to promote various healthy eating behaviors among school students.

: Cytokine storm is usually described as one of the main reasons behind COVID-associated mor-tality. Cytokines are essential protein molecules engaged in immune responses; they play a critical role in protection against infections. However, they also contribute to inflammatory reactions and tissue damage, becoming a double-edged sword in the context of COVID-19. Recent studies have suggested various cytokines and chemokines that play a crucial role in the immune response to SARS-CoV-2 infection. One such cytokine is Interleukin 27 (IL-27), which has been found to be elevated in the blood plasma of patients with COVID-19. Within this study, we will explore the role of IL-27 in immune responses and address our own findings concerning this cytokine in COVID-19. It affects a wide variety of immune cells; regardless of the pathological process it is involved in, IL-27 is critical for upholding the necessary balance between tissue damage and cytotoxicity against in-fectious agents and/or tumors. In COVID-19, it is involved in multiple processes, including antiviral cytotoxicity via CD8+ cells, IgG subclass switching, and even the activation of Tregs.

Aerococcus urinae is an aerobic Gram-positive coccus that grows as tiny alpha-hemolytic colonies. Actinotignum schaalii is a slow-growing facultative anaerobic Gram-positive rod. These bacteria are part of the urogenital microbiota of healthy patients, but can also be involved in urinary tract infections (UTIs), particularly in elderly men and young children [1–3]. Because A. urinae and A. schaalii are fastidious and are difficult to identify with phenotypic methods, they are underestimated causes of UTIs. Their growth is slow and requires a blood-enriched medium and an incubation time of 48 hours under anaerobic or 5% CO2 atmosphere. Furthermore, accurate identification is only possible using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or molecular-based methods. In rare cases, these bacteria can be responsible for invasive infections. We describe here the second case of bacteremic UTI caused by both A. schaalii and A. urinae in an 89-year-old woman who presented dyspnea and asymptomatic bacteriuria. This challenging clinical and microbiological diagnosis was made by our laboratory by Gram staining urine with a leucocyte count &gt;50/μL and/or a bacterial count &gt;14/μL, urinary culture on blood agar plate, and direct bacterial identification on positive blood culture bottles (BCBs) by MALDI-TOF MS. After 10 days of antimicrobial treatment consisting of 2g amoxicillin PO t.i.d the patient was discharged with complete clinical and biological recovery. A. schaalii and A. urinae are probably still underestimated causes of UTIs. Microbiologists should assess the presence of these two bacteria in urine using the appropriate culture and identification methods where direct examination is positive for small Gram-positive cocci or rods, and a urinary dipstick is negative for nitrites and associated with leukocyturia.

We discuss a remote sensing system that is used to simultaneously detect range-resolved differential absorption LIDAR (light detection and ranging; DIAL) signals and integrated path DIAL signals (IP-DIAL) from aerosol targets for ranges up to 22 km. The DIAL/IP-DIAL frequency converter consists of an OPO pumped at 1064 nm to produce light at 1.6 μm and operates at 100 Hz pulse repetition frequency. The probe light is free space coupled to a movable platform that contains one transmitter and two receiver telescopes. Hybrid photon counting/current systems increase the dynamic range for detection by two orders of magnitude. Range resolved and column integrated dry-air CO2 and CH4 mixing ratios are obtained from line shape fits of CO2 and CH4 centered at 1602.2 nm and 1645.5 nm, respectively and measured at 10 different frequencies over ≈ 1.5 cm-1 bandwidth. The signal-to-noise ratios (SNR) of the IP-DIAL returns from cloud aerosols approach 1000:1 and the uncertainties in the mixing ratios weighted according to the integrated counts over the cloud segments range from 0.1 % to 1 %. The range averaged DIAL mixing ratios are in good agreement with the IP-DIAL mixing ratios at the 1 % to 2 % level for both CO2 and CH4. These results can serve as a validation method for future active and passive satellite observational systems.

The Vu Gia - Thu Bon River Basin (VG-TB) is confronting numerous challenges related to water security (WS), particularly in the face of the impacts of climate change. These challenges manifest in salinity intrusion, altered rainfall patterns, and reduced water supply in downstream areas. To assess the current state of water security in the basin, the study employed statistical analysis methods, Process Analysis Method (PAM), SMART, and Analytic Hierarchy Process (AHP) to develop a comprehensive Assessment Framework for Water Security (AFWS) in the VG-TB. The AFWS encompasses five key dimensions, 17 indicators, and 28 variables, aligning with the UN-Water definition of water security and addressing the Sustainable Development Goal 6 (SDG6) criteria for global water sustainability. It also adheres to the Asian Development Bank's (ADB) approach to water security assessment as outlined in the Asian Water Development Outlook (AWDO) reports. This allows for the computation of a comprehensive Water Security Index (WSI) for specific regions, serving as a foundation for decision-making and policy formulation aimed at enhancing water security in the context of climate change and facilitating sustainable basin development in the future.

Two-dimensional mass spectrometry (2D MS) is a method for tandem mass spectrometry that relies on manipulating ion motions to correlate precursor and fragment ion signals. 2D mass spectra are obtained by performing a Fourier transform in both the precursor ion mass-to-charge ratio (m/z) dimension and the fragment ion m/z dimension. The phase of the ion signals evolves linearly in the precursor m/z dimension and quadratically in the fragment m/z dimension. This study demonstrates that phase-corrected absorption mode 2D mass spectrometry improves signal-to-noise ratios by a factor of 2 and resolving power by a factor of 2 in each dimension compared to magnitude mode. Furthermore, phase correction leads to an easier differentiation between ion signals and artefacts, and therefore easier data interpretation.

Studies comparing provider and patient views and experiences of self-management within primary healthcare are particularly scarce in disadvantaged settings. In this qualitative study, patient and provider perceptions of self-management were investigated in five socio-economically disadvantaged communities in Stockholm. Twelve individual interviews and three group interviews were conducted. Semi-structured interview guides included questions on perceptions of diabetes diagnosis, diabetes care services available at primary health care centers, patient and provider interactions, and self-management support. Data was analysed using thematic analysis. Two overarching themes were identified. These were characterized by inherent dilemmas representing confusions and conflicts that patients and providers experienced in their daily life or practice respectively: adopting and maintaining new routines through practical and appropriate lifestyle choices (patients); and balancing expectations and pre-conceptions of self-management (providers). Patients found it difficult to tailor information and lifestyle advice to fit their daily life. Healthcare providers recognized that patients were in need of support to change behavior, but saw themselves as inadequately equipped to deal with the different cultural and social aspects of self-management. This study highlights patient and provider dilemmas that influence the interaction and collaboration between patients and providers with respect to communication and uptake of self-management advice.

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCV-VSD viruses is incompletely understood, and antivirals for FCV have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2’-C-methylcytidine (2CMC) and NITD-008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCV-URTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino acid residues from the hypervariable E region of the capsid in the cultured viruses provided no support for the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose-response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4-0.6 µM, TI 21; 2CMC EC50, 2.7-5.3 µM, TI >18; NITD-008, 0.5 to 0.9 µM, TI >111. Investigation of these antivirals for treatment of FCV-VSD is warranted.

Low-resource languages often face the problem of insufficient data, which leads to poor quality in machine translation. One approach to address this issue is data augmentation. Data augmentation involves creating new data by transforming existing data through methods such as flipping, cropping, rotating, and adding noise. Traditionally, pseudo-parallel corpora are generated by randomly replacing words in low-resource language machine translation. However, this method can introduce ambiguity as the same word may have different meanings in different contexts. This study proposes a new approach for low-resource language machine translation, which involves generating pseudo-parallel corpora by replacing phrases. The performance of this approach is compared with other data augmentation methods, and it is observed that combining it with other data augmentation methods further improves performance. To enhance the robustness of the model, R-Drop regularization is also used. R-Drop is an effective method for improving the quality of machine translation. The proposed method was tested on Chinese-Kazakh (Latin script) translation tasks, resulting in performance improvements of 4.99 and 7.7 for Chinese-to-Kazakh and Kazakh-to-Chinese translations, respectively.

The aim of this study was to evaluate whether alterations in food availability compromise the metabolic homeostasis of honey bees exposed to three fungicides alone or together. Ten honey bee colonies were utilized, with half receiving energy-protein supplementation for 15 weeks while another five colonies had their protein supply reduced with pollen traps. Subsequently, forager bees were collected and exposed by contact to 1 or 7 µg of bixafen, prothioconazole, and trifloxystrobin, either individually or in combination. After 48 hours, abdomens without the intestine was used for the analysis of expression of antioxidant genes (SOD-1, CAT, and GPX-1), detoxification genes (GST-1 and CYP306A1), the storage protein gene vitellogenin, and immune system antimicrobial peptide genes (Defensin-1, Abaecin, Hymenoptaecin, and Apidaecin), through real-time PCR. All pesticide treatments induced changes in gene expression, with bixafen showing the most prominent upregulation. Exposure to 1 µg of each of the three pesticides resulted in upregulation of genes associated with detoxification and nutrition processes, and downregulation of immune system genes. When the three pesticides were combined at a dose of 7 µg each, there was a pronounced downregulation of all genes. Dietary supplementation led to a slight reduction in gene expression alterations provoked by the fungicides.

Uncovering hidden mixture correlation among variables have been investigating in the literature using mixture R-vine copula models. These models are hierarchical in nature. They provides a huge flexibility for modelling multivariate data. As the dimensions increases, the number of the model parameters that need to be estimated is increased dramatically, which becomes along with huge computational times and efforts. This situation becomes even much more harder and complicated in the mixture Regular vine models. Incorporating truncation method with mixture Regular vine models will reduce the computation difficulty for the mixture based models. In this paper, tree-by-tree estimation mixture model is joined with the truncation method, in order to reduce the computational time and the number of the parameters that need to be estimated in the mixture vine copula models. A simulation study and a real data applications illustrated the performance of the method. In addition, the real data applications show the affect of the mixture components on the truncation level.

During the Renaissance, Leonardo Da Vinci was the first person to successfully detail the anatomy of the aortic root and its adjacent structures. Ever since, novel insights into morphology, function and their interplay have accumulated resulting in advanced knowledge on complex functional characteristics of the aortic valve (AV) and root. This shifted the vision from the AV as being a static structure towards that of a dynamic interconnected apparatus within the aortic root as a functional unit, exhibiting a complex interplay with adjacent structures via both humoral and mechanical stimuli. This paradigm shift has stimulated surgical treatment strategies of valvular disease that seek to recapitulate healthy AV function, whereby AV disease can no longer be seen as an isolated morphological pathology which needs to be replaced. As prostheses still cannot reproduce the complexity of human nature, treatment of diseased AVs, whether stenotic or insufficient, has tremendously evolved with a similar shift towards treatments options that are more hemodynamically centered such as the Ross procedure and valve-conserving surgery. Native AV and root components allow for an efficient Venturi effect over the valve to allow for optimal opening during the cardiac cycle, while also alleviating the left ventricle. Next to that, several receptors are present on native AV leaflets, enabling messenger pathways based on their interaction with blood and other shear-stress related stimuli. Many of these physiological and hemodynamical processes are under acknowledged but may hold important clues for innovative treatment strategies, or as potential novel targets for therapeutic agents that halt or reverse the process of valve degeneration. A structured overview of these pathways and their implications for cardiothoracic surgeons and cardiologists is lacking. As such, we provide an overview on embryology, hemodynamics, and messenger pathways of the healthy and diseased AV and its implications for clinical practice, by relating this knowledge to current treatment alternatives and clinical decision-making.

Reservoirs are recognized as one of the most efficient infrastructure components in integrated water resources management and development. At present, with the ongoing advancement of social economy and requirement of water, the water resources shortage problem has worsened, and the operation of reservoirs, in terms of consumption of flood water, has become significantly important. Reservoirs perform both regulation of flood and integrated water resources management, in which the flood limited water level is considered as the most important parameter for trade-off between regulation of flood and conservation. To achieve optimal operating policies for reservoirs, large numbers of simulation and optimization models have been developed in the course of recent decades, which vary notably in their applications and working. Since each model has their own limitations, the determination of fitting model for derivation of reservoir operating policies is challenging and most often there is always a scope for further improvement as the selection of model depends on availability of data. Subsequently, assessment and evaluation associated with the operation of reservoir stays conventional. In the present study, the Soil and Water Assessment Tool (SWAT) models and a Genetic Algorithm model has been developed and applied to two reservoirs in Ganga River basin, India to derive the optimal operational policies. The objective function is set to minimize the annual sum of squared deviation form desired irrigation release and desired storage volume. The decision variables are release for irrigation and other demands (industrial and municipal demands), from the reservoir. As a result, a simulation-based optimization model was recommended for optimal reservoir operation, such as allocation of water, flood regulation, hydropower generation, irrigation demands and navigation and e-flows using a definite combination of decision variables. Since the rule curves are derived through random search it is found that the releases are same as that of demand requirements. Hence based on simulated result, in the present case study it is concluded that GA-derived policies are promising and competitive and can be effectively used operation of the reservoir.

This article aims to identify the current development of cross-border tourism between Vietnam and China. The paper analyzes the perception and strategy of cross-border tourism development in the two countries, especially in the context of China’s implementation of the “Belt and Road Initiative” (BRI). The article emphasizes that Vietnam and China have recently made efforts to promote cross-border tourism development. At the same time, Vietnam and China see cross-border tourism development as a significant part of comprehensive border cooperation between the two countries. However, the development plans for cross-border tourism between the two countries are still mainly on the desk, not yet implemented effectively. Thus, its achievements are relatively modest. Besides, the article emphasizes that the interests of the people living in the border area, especially the Vietnam side, are almost “forgotten” in the development of cross-border travel between the two countries. Besides, the article also analyzes the challenges that the two sides are facing, especially the Vietnam side, in promoting the development of cross-border tourism between the two countries.

Aging is accompanied by frontal lobe and non-dominant hemisphere recruitment that supports executive functioning, such as inhibitory control, which is crucial to all cognitive functions. Yet, the spatio-temporal sequence of processing underlying successful inhibition and how it changes with age is understudied. Thus, we assessed N200 (conflict monitoring) and P300 (response inhibition, performance evaluation) event-related potentials (ERPs) in young and healthy older adults during comparably performed successful stop-signal inhibition. We additionally interrogated the continuous spatio-temporal dynamics of N200- and P300-related activation within each group. Young adults had left hemisphere dominant N200, while older adults had overall larger amplitudes and right hemisphere dominance. N200 activation was biphasic in both groups but differed in scalp topography. P300 also differed, with larger right amplitudes in young, but bilateral amplitudes in old, with old larger than young in the left hemisphere. P300 was characterized by an early parieto-occipital peak in both groups, followed by a parietal slow wave only in older adults. A temporally similar but topographically different final wave followed in both groups that showed anterior recruitment in older adults. These findings illuminate differential age-related spatio-temporal recruitment patterns for conflict monitoring and response inhibition that are critically important for understanding age-related compensatory activation.

Accurate repair of DNA is critical for genome stability and cancer prevention. DNA double-strand breaks are one of the most toxic lesions and can be repaired using homologous recombination (HR). HR is a high-fidelity DNA repair pathway that uses a homologous template for repair. One central HR step is RAD51 nucleoprotein filament formation on the single-stranded DNA ends, a step required for the homology search and strand invasion steps of HR. RAD51 filament formation is tightly controlled by many positive and negative regulators, collectively termed the RAD51 mediators. The RAD51 mediators function to nucleate, elongate, stabilize, and disassemble RAD51 during repair. In model organisms, RAD51 paralogs are RAD51 mediator proteins that structurally resemble RAD51 and promote its HR activity. New functions for the RAD51 paralogs during replication and in RAD51 filament flexibility have recently been uncovered. Mutations in the human RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3, and SWSAP1) are found in a subset of breast and ovarian cancers. Despite their discovery three decades ago, few advances have been made in understanding the function of the human RAD51 paralogs. Here we discuss the current perspective on the RAD51 paralogs in vivo and in vitro function and their relationship with cancer in vertebrate models.