Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with a distinct set of facial features, growth limitations, and limb anomalies. Its clinical spectrum is broad and presents significant challenges in pediatric diagnosis and management. The variable presentation of the disorder, due to cohesin complex mutations, requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients, alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, with an emphasis on innovations in genetic testing, including the detection of mosaicism and novel genetic variations. The aim is to synthesise case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment, and aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life.

In this study we propose a semi-parametric, parsimonious Value at Risk forecasting model, based on quantile regression and machine learning methods, combined with readily available market prices of option contracts from the over-the-counter foreign exchange rate interbank market. We aim at improving existing methods for VaR prediction of currency investments using machine learning. We employ two different methods - ensemble methods and neural networks. Explanatory variables are implied volatilities with plausible economic interpretation. The forward-looking nature of the model, achieved by the application of implied volatilities as risk factors, ensures that new information is rapidly reflected in Value at Risk estimates. To the best of our knowledge, this paper is the first to utilize information in the volatility surface, combined with machine learning and quantile regression, for VaR prediction of currency investments. The proposed ensemble models achieve good estimates across all quantiles. The light gra-dient-boosting machine model and the categorical boosting model both yield estimates which are better than, or equal to, those of the benchmark model. The neural network models are in general quite unstable.

Negative work behavior (NWB) threatens employee well-being. There are numerous constructs that reflect NWBs, such as bullying, aggression, and discrimination and they are often examined in isolation of each other, limiting scientific integration of these studies. We aim to contribute to this research field by developing a diagnostic tool with content validity on the full spectrum of NWBs. First, we provide a full description of how we tapped and organized content from 44 existing NWB measurement instruments and 48 studies. Second, we discussed our results with experts (N = 3) in this research field to check for missing studies and to discuss our integration results. This two-stage process yielded a questionnaire measuring physical, material, psychological, sociocultural, and digital NWB. Furthermore, the questions include a range of potential actors of NWB, namely internal (employees, managers) and external actors (clients, customers, public, family members) at work and their roles (i.e., target, perpetrator, perpetrator's assistant, target's defender, outsider, and witness of NWBs). Finally, the questionnaire measures what type of harm is experienced (i.e., bodily, material, mental, and social harm).

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

The present paper aims to elucidate the impact of climate change on the availability and security of water and energy in the Middle East and North Africa Region (MENA Region). The region is particularly challenged by a number of factors including a large variability of bio-geographical characteristics, extreme population growth over the last few decades and substantial societal and economical transitions as well as armed conflicts in some of the countries of the region. Anticipated changes in climate conditions will exacerbate the challenges with regard to providing sufficient amounts of water and energy to the communities in the region. Impacts of climate change will materialize as an increasing number of heat waves, primarily in urban structures and the decline in water availability as a result of enhanced droughts and a growing numbers of dry spells. The interrelationships between energy and water and their mutual dependencies are addressed by the Water-Energy-Nexus concept. With regard to the challenges addressed here, Cyprus and the Eastern Mediterranean are a particular point in case. Mitigation and adaptation strategies include enhanced efficiency of energy and water use, integrated technology assessments regarding electricity generation and the production of potable water and electricity through concentrated solar power.

Abstract: Obstructive sleep apnea (OSA) is well known to often improve with non-supine positioning as opposed to su¬pine positioning. Emerging research supports a role for sleep position management in patients with central sleep apnea (CSA) as well. We report a case of de novo Complex Sleep apnea Syndrome (CompSAS) in a 78-year-old female, who presented after a car accident due to unclear syncope. Diagnostic polysomnography (PSG) showed a moderate OSA. A CompSAS developed under Automatic positive airway pressure (APAP), while download data of 4 years showed a good adherence. No significant benefit was reported under Adaptive Servo Ventilation (ASV) and BiPAP-ST, while a reduction of CSA in non-supine position was noticed. Oxygen and sleep positional therapy (SPT) were considered resulting in a significant improvement of CSA and sleep quality. Further research on the prevalence of positional CSA is needed.

“De-[Constructing] Growth” is offered as a deeper and more useful conceptualization that avoids the negative connotations of, and resistance to, “degrowth” by decoupling profit from unsustainable consumption, production, and inequality.

Foam concrete is a highly cellularized cementitious material that undergoes extensive plastic deformation when loaded to failure. Under compression, the foam structure gets progressively crushed at a steady stress stage such that a substantial amount of energy is dissipated. Understanding foam concrete crushing behavior is of special importance for its engineering applications such as energy absorber, but the current studies are insufficient to define material properties for design of field applications. This study characterizes the crushing strength and foam modulus of samples with penetration test and resonant frequency test, respectively. A four-phase crushing behavior is observed. The yield strength and plateau strength are identified to characterize the foam crushing. Using the experimental inputs, the modulus-strength constitutive equations are then established. These findings are useful for expanding the knowledge of normal concrete to studies on foam concrete, as well as design of applications.Foam concrete is a highly cellularized cementitious material that undergoes extensive plastic deformation when loaded to failure. Under compression, the foam structure gets progressively crushed at a steady stress stage such that a substantial amount of energy is dissipated. Understanding foam concrete crushing behavior is of special importance for its engineering applications such as energy absorber, but the current studies are insufficient to define material properties for design of field applications. This study characterizes the crushing strength and foam modulus of samples with penetration test and resonant frequency test, respectively. A four-phase crushing behavior is observed. The yield strength and plateau strength are identified to characterize the foam crushing. Using the experimental inputs, the modulus-strength constitutive equations are then established. These findings are useful for expanding the knowledge of normal concrete to studies on foam concrete, as well as design of applications.

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.

Since life on earth developed, parasitic microbes have thrived. Increases in host numbers, or the conquest of a new species, provides an opportunity for such a pathogen to enjoy, before host defense systems kick in, a similar upsurge in reproduction. Outbreaks ‒ caused by ‘endemic’ pathogens ‒ and epidemics ‒ caused by ‘novel’ pathogens ‒ have thus been creating chaos and destruction since prehistorical times. To study such (pre)historic epidemics, recent advances in the ancient DNA field, applied to both archeological and historical remains, have helped tremendously to elucidate the evolutionary trajectory of pathogens. These studies offered new and unexpected insights in the evolution of, for instance, smallpox virus, hepatitis B virus and the plague-causing bacterium Yersinia pestis. Furthermore, burial patterns and historical publications can help in tracking down ancient pathogens. Another source of information is our genome, where selective sweeps in immune-related genes relate to past pathogen attacks, while multiple viruses have left their genomes behind for us to study.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

Aim: To analyze a single center's experience with Short Bowel Syndrome/ Chronic Intestinal Failure (SBS/CIF) in adult patients treated with Home Parenteral Nutrition (HPN). Materials and methods: In the last thirty years, 13 patients with SBS/CIF were included in an HPN program. Results: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of the starting HPN was 44 years old. Most are submitted to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients have died while on HPN for a median of 42 months. The causes of death HPN-related were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide, with good tolerance, and need reduction of HPN support. All these eight patients have a satisfactory quality of life (parenteral support needs range between five to two nutrition bags per week). Conclusion: HPN remains the gold standard of SBS/CIF treatment, although Teduglutide may reduce HPN needs and HPN complications and provide a better quality of life. An HPN multidisciplinary healthcare group support is essential to ensure these patients' survival and quality of life. Keywords Short bowel Syndrome, Chronic Intestinal failure, Home Parenteral Nutrition, Teduglutide, Complications of Parenteral Support.

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

Background. Inferior quality of biological material compromises data, slows discovery, and wastes research funds. The gut microbiome plays a critical role in human health and disease, yet little attention has been given to optimizing collection and processing methods of human stool. Methods. We collected the entire bowel movement from 2 healthy volunteers: one to examine stool sample heterogeneity and one to test stool sample handling parameters. Sequencing and bi-oinformatic analyses were used to examine the microbiome composition. Results. The microbiome profile varied depending on where the subsample was obtained from the stool. The exterior cortex of the stool was rich in specific phyla and deficient in others while the interior core of the stool revealed opposite microbiome profiles. Sample processing also re-sulted in varying microbiome profiles. Homogenization and stabilization at 4°C gave superior microbial diversity profiles compared to the fresh or frozen subsamples of the same stool sample. Bacterial proliferation continued in the fresh subsample when processed at ambient temperature. Bacteroidetes proliferated and Firmicutes diminished during the 30-minute processing of fresh sample. The frozen sample had good overall diversity but Proteobacteria diminished likely be-cause of the freeze/thaw. Conclusions. The microbiome profile is specific to the section of the stool being sampled. Stool sample collection, homogenization, and stabilization at 4°C for 24 hours provides a “neat”, high-quality sample of sufficient quantity that can be banked into aliquots with nearly identical microbial diversity profiles. This collection pipeline is essential to accelerate our understanding of the gut microbiome in health and disease.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Foam concrete is a construction material with controllable low strength and untraditional physical properties. Its highly crushable nature leaves it a niche as an engineered energy-absorbing material in many value-added applications; however, fundamental understanding of the material properties is crucial. As foam concrete is highly cellularized and ductile, conventional concrete testing methods such as compression test are insufficient to characterize the key material attributes of foam concrete, especially when the foam density is low. The resonant frequency test (ASTM C215) is specified for evaluating dynamic Young’s modulus of normal concrete. Inspired by the non-destructive feature of this test, we investigate the possibility of using the resonant frequency test to continuously monitor the modulus build-up of foam concrete with age. For the representativeness of the samples, three variables are considered in material design—bulk density ranging from 0.4 to 1.2 g/cm3, water to cementitious materials ratio of 0.42 and 0.47, and fly ash replacement of 10 and 30% by weight of cement. After examining the different vibration modes, the fundamental transverse frequency is determined most suitable for interpreting the foam modulus. The experimental results demonstrate good accuracy of using this approach for the measurement of different samples. It is also confirmed that, for a given foam concrete, the foam modulus can be predicted by knowing the foam density and solid modulus of its base cement paste, which provides an important insight for the further studies and real applications of foam concrete.

Abstract: Panfacial fractures are complex injuries involving multiple regions of the facial skele-ton simultaneously, which may necessitate multiple surgeries over a relatively short period. They are often associated with polytrauma and other injuries including brain trauma, which re-quire either immediate airway management, prolonged intubation, or repeated intubations for staged surgeries. Given the frequent need for intermaxillary fixation and the potential involve-ment of the central nasal complex or skull base, conventional oro-tracheal or nasotracheal intu-bation often presents challenges. Submental intubation is the most reported method of airway management with the aim to avoid tracheostomy and its related complications. A review of the different techniques of airway management in the elective treatment of panfacial fractures was performed focusing on the advantages and disadvantages of each method. Most of the literature consisted of retrospective studies, with only one prospective study comparing submental intu-bation to tracheostomy in panfacial fractures. There is abundant literature that favours the sub-mental intubation for its rapid establishment and low complication rate. Other techniques less reported were retromolar intubation, nasotracheal to orotracheal switch, tracheostomy or crico-thyroidotomy. An algorithm for the management of the airway in panfacial fractures is pre-sented.

Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads with differing fermentation times but similar nutritional profiles on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. The double-blind clinical trial randomized participants to consume over two-months Elias Boulanger® long fermentation (48h) sourdough bread (EBLong) or Elias Boulanger® short fermentation (2h) sourdough bread (EBShort). We assessed clinical parameters, inflammatory- and satiety-related biomarkers; and richness and abundance of gut microbiota at baseline and follow-up. 31 individuals (mean age: 67, 55.7% female) participated. EBShort was associated with reduced soluble intercellular adhesion molecule (sICAM) levels, and irrespective of the adjudicated intervention, all participants had a decrease in sICAM and diastolic pressure relative to baseline (p<0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. High-quality sourdough bread may offer mild benefits in blood pressure and inflammation for those with metabolic syndrome, however, only EBLong was associated to reduced Enterobacteriaceae abundance. Further research is needed to understand potential benefits and mechanisms of sourdough bread in managing metabolic syndrome and improving cardiovascular health.

The Gilles de la Tourette syndrome (GTS) and Non-Coeliac Gluten Sensitivity (NCGS) may be associated. We analyse the efficacy of a gluten-free diet (GFD) in 29 patients with GTS (23 children; 6 adults) in a prospective pilot study. All of them followed a GFD for one year. The YGTSS, Y-BOCS/CY-BOCS and GTS-QOL questionnaires were compared before and after the GFD. 74% of children and 50% of adults were males, not significant (NS). At the beginning of the study, 69% of children and 100% of adults had associated OCD (NS). At baseline, the YGTSS scores were 55.0 ± 17.5 (children) and 55.8 ± 19.8 (adults) (NS), the Y-BOCS/CY-BOCS scores were 15.3 (SD = 12.3) (children) and 26.8 (9.2) (adults) (p = 0.043), and the GTS-QOL scores were 42.8 ± 18.5 (children) and 64 ± 7.9 (adults) (p = 0.000). NCGS was frequent in both groups, with headaches reported by 47.0% of children and 83.6% of adults (p = 0.001). After one year on a GFD there was a marked reduction in measures of tics (YGTSS) (p = 0.001), and the intensity and frequency of OCD (Y-BOCS/CY-BOCS) (p = 0.001), along with improved QOL (p = 0.001) in children and adults. In conclusion, a GFD maintained for one year in GTS patients led to a marked reduction in tics and OCD both in children and adults.

Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investigated differences in the biomechanical responses among human cartilage of ICRS grades I, II and III using polymer dynamics theory. We collected 24 explants of human articular cartilage (eight each of ICRS grade I, II and III) and acquired stress-relaxation data applying a continuous load on the articular surface of each cartilage explant for 1180 s. We observed a significant decrease in Young’s modulus, stress-relaxation time, and stretching exponent in advanced stages of OA (ICRS grade III). The stretch exponential model indicated that significant loss in hyaluronic acid polymer might be the reason for the loss of proteoglycan in advanced OA. This work encourages further biomechanical modelling of osteoarthritic cartilage utilizing these data as input parameters to enhance the fidelity of computational models aimed at revealing how mechanical behaviors play a role in pathogenesis of OA.

Background: The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study is to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Methods: changes in PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the trombogram graphic (thrombin variation over time); lagTime; Endogenous Thormbin Potential(ETP); peak; time to reach peak(ttpeak), startTail e velocity Index. Platelet aggregation was assessed by testing different agonists using turbidimetry method. Results: Four FCS patients and 4 matched healthy controls were included in the present study. Changes in PLC at Tw12 was 30% and 34% at T36w. Thrombin generation results show values in normal range (for patients and controls respectively lagTime:10,42±4,40 and 9,25±0,99; ttPeak:14,33± 4,01 and 13,10±0,67; startTail:32,13±3,54 and 29,46±1,69; velocityIndex:20,21±3,63 and 33,05±13,21; ETP 599,80±73,47 and 900,2±210,99; peak value 76,84±1,07 and 123,30±39,45) and no significant difference between cases and controls. Platelet aggregation test showed values in range with no significant difference with healthy controls Conclusions: Our study showed for the first time that no significant changes in the general haemostasis assessed by TG and in platelet function have been observed in FCS patients receiving volanesorsen.

Prereactive complexes in noncovalent organocatalysis are sensitive to the relative chirality of the binding partners and to hydrogen bond isomerism. Both effects are present when a transiently chiral alcohol docks on a chiral α-hydroxy ester, turning such 1:1 complexes into elementary, non-reactive model systems for chirality induction in the gas phase. With the help of linear infrared and Raman spectroscopy in supersonic jet expansions, conformational preferences are investigated for benzyl alcohol in combination with methyl lactate, also exploring p-chlorination of the alcohol and the achiral homolog methyl glycolate to identify potential London dispersion and chirality effects on the energy sequence. Three of the four combinations prefer barrierless complexation via the hydroxy group of the ester (association). In contrast, the lightest complex shows predominantly insertion into the intramolecular hydrogen bond, like the analogous lactate and glycolate complexes of methanol. The experimental findings are rationalized with computations and a uniform helicality induction in the alcohol by the lactate is predicted, independent on insertion into or association with the internal lactate hydrogen bond. p-Chlorination of benzyl alcohol has a stabilizing effect on association, because the insertion motif prevents a close contact between the chlorine and the hydroxy ester. After simple anharmonicity and substitution corrections, the B3LYP-D3 approach offers a fairly systematic description of the known spectroscopic data on alcohol complexes with α-hydroxy esters.

Popular geo-computer vision works make use of aerial imager with sizes ranging from 64 × 64 to 1024 × 1024 pixels without any overlap, although the learning process of deep learning models can be affected by the reduced semantic context or the lack of information near image boundaries. In this work, the impact of three image sizes (256 × 256, 512 × 512, and 1024 × 1024 pixels) and two image overlap levels (no overlap and 12.5% overlap) on the performance of road classification models was statistically evaluated. For this, two convolutional neural networks used in various tasks of geospatial object extraction were trained (using the same hyperparameters) on a large dataset (containing aerial image data covering 8650 km² of the Spanish territory that was labelled with binary road information) under twelve different scenarios, each scenario featuring a different combination of tile size and overlap. To assess their generalisation capacity, the performance of all resulting models was evaluated on a data from novel areas covering approximately 825 km². The performance metrics obtained were analysed using appropriate descriptive and inferential statistical techniques to evaluate the impact of the performance at distinct levels of the fixed factors (tile size, tile overlap, neural network architecture). Statistical tests were applied to study the main and interaction effects of the fixed factors on the performance. A significance level of 0.05 was applied to all the null hypothesis tests. The results were highly significant for the main effects (p-values lower than 0.001), while the two-way and three-way interaction effects among them had different levels of significance. The results indicate that the training of road classification models on images with a higher tile size (more semantic context) and tile overlap (additional border context and continuity) significantly impacts their performance. The best model was trained on a dataset featuring tiles with a size of 1024 × 1024 pixels and a 12.5% overlap and achieved a loss value of 0.0984, an F1 score of 0.8728, and an ROC-AUC score of 0.9766, together with an error rate of 3.5% on the test set.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

Background: Since 2000, vaccine coverage in Sub-Saharan Africa (SSA) has surpassed multiple milestones. Its contribution to global health, especially in low-middle-income countries is one of the achievements in global governance of modern medicine, averting 2-3 million child deaths every year. However, in Nigeria, vaccine-preventable-diseases still account for one in eight child deaths before their fifth-year birthday and remains one of the ten countries where 4.3 million children under five are without complete immunization. The reasons for declining childhood vaccine demand are unclear. Therefore, the goal of this contribution is to shed light on the reasons to set a foundation for future interventions. Methods: Four focus group discussions were conducted. The primary targets were mothers of children 0 – 12 months old in Nigeria. A simplified quota sampling approach was used to select mothers in four geographical clusters of Nigeria’s Federal Capital Territory. At least six mothers from each cluster were randomly included, giving a total of 24 participants. An interview guide developed from the 5C psychological antecedence model was used (assessing confidence, complacency, calculation, constraints, collective responsibility); two additional variables were included that had proved meaningful in previous work (religion and masculinity). The data were analyzed using meta-aggregation approach such as framework synthesis, which summarized data in a stepwise fashion. Results: The sample was generally relatively positive towards vaccination. Still, mothers reported low trust in vaccine safety and the healthcare system (confidence). Yet, they had great interest in seeking additional information during antenatal visits (calculation), difficulties in prioritizing vaccination over other equally competing priorities (constraints) and were aware that vaccination translates into overall community health and wellbeing (collective responsibility). They had a bias towards God as ultimate giver of good health (religion) and reported that their husbands played a dominant role in vaccination decision-making (masculinity). Mothers perceived their children vulnerable to disease outbreaks, which motivated them to get them vaccinated (complacency). Conclusion: The 5C model and the added determinants provided a useful qualitative tool for understanding mothers’ vaccination decision-making in low resources settings.

Background: Besides anemia, iron deficiency may cause more subtle symptoms including those of the restless legs syndrome (RLS), the chronic fatigue syndrome (CFS) or sleeping disorders. Objective: The aim of this pre-planned secondary analysis was to compare the frequency and severity of symptoms associated with iron deficiency before and after (intravenous or oral) iron supplementation in iron deficient blood donors. Methods/Design: Prospective, randomized, controlled, single centre trial. (ClinicalTrials.gov: NCT01787526). Setting: Tertiary care center in Graz, Austria Participants: 138 female and 38 male whole blood and platelet apheresis donors aged ≥18 and ≤65 years with iron deficiency (ferritin ≤30ng/ml at the time of blood donation). Interventions: Intravenous iron (1 g ferric carboxymaltose, n=86) or oral iron supplementation (10 g iron fumarate, 100 capsules, n=90). Measurements: Clinical symptoms were evaluated by a survey before iron therapy (visit 0, V0) and after 8-12 weeks (visit 1, V1) including questions about symptoms of RLS, CFS, sleeping disorders, quality of life and symptoms like headaches, dyspnoea, dizziness, palpitations, pica and trophic changes of fingernails or hair. Results: We found a significant improvement in the severity of symptoms for RLS, fatigue and sleep quality (p<0.001). Furthermore, a significant decrease of headaches, dyspnoea, dizziness and palpitations was reported (p<0.05). There was no difference between the type of iron supplementation (intravenous versus oral) and clinical outcome data. Conclusion: Iron supplementation in iron deficient blood donors may be an effective strategy to improve symptoms related to iron deficiency and the wellbeing of blood donors.

Phenol is added to acetophenone (methyl phenyl ketone) and to six of its halogenated derivatives in a supersonic jet expansion to determine the hydrogen bonding preference of the cold and isolated 1:1 complexes by linear infrared spectroscopy. Halogenation is found to have a pronounced effect on the docking site in this intermolecular ketone balance experiment. The spectra unambiguously decide between competing variants of phenyl group stacking due to their differences in hydrogen bond strength. Structures where the phenyl group interaction strongly distorts the hydrogen bond are more difficult to quantify in the experiment. For unsubstituted acetophenone, phenol clearly prefers the methyl side despite a predicted sub-kJ/mol advantage which is nearly independent of zero point vibrational energy, turning this complex into a challenging benchmark system for electronic structure methods which include long range dispersion interactions in some way.

We analyze the humoral and B-cell mediated immunogenic response induced by GP5 lineal epitopes from porcine reproductive and respiratory syndrome virus (PRRSV) to explore the role of this protein in the protective response. For inoculation, pigs aged twenty-one days were allocated into six groups (seven pigs per group): control (PBS), vehicle (carrier), vaccinated (Ingelvac-PRRSV, MLV®), non-vaccinated and naturally infected, GP5-B and GP5-B3. Subsequently blood samples were collected and analyzed. Cytokine were measured by ProcartaPlex kit. Peptide-specific IgGs and cross-reactivity against peptides were analyzed by ELISA and B-cell subpopulations were analyzed by flow cytometry. At 2 days post-immunization (dpi), the GP5-B3 peptide increased the serum concentrations of cytokines associated to activate adaptive cellular immunity (IL-1β and IL-12). The concentration of IgGs anti-GP5-B increased in both cases at 21 and 42 dpi, while IgGs anti-GP5-B3 increased at 21 dpi and remained at the same level until 42 dpi. Also, antibody-forming/Plasma B cells (CD2+/CD21-) and primed B cells (CD2-/CD21+) from immunized pigs showed an increase at 42 dpi. Conversely the naïve B cells from immunized pigs decreased compared with the controls. Importantly, Both GP5-B and GP5-B3 peptides exhibited immunoreactivity against serum antibodies from vaccinated group, as well as non-vaccinated and naturally infected group. In conclusion, GP5-B and GP5-B3 peptides elicited immunogenicity mediated by antigen specific IgG´s and B-cell activation.

In mammals, Tripartite motif-containing (TRIM) proteins modulate the immune response by coordinating pro-inflammatory related processes such as antiviral restriction, cellular autophagy and inflammasome activation. In fish, TRIM proteins have been reported mainly in cyprinids (e.g., carp, zebrafish) and salmonids (rainbow trout). However, their molecular mechanisms and functions are still being described these animals. Our study focused on characterizing novel TRIM proteins involved in the innate immune response of gill cells from rainbow trout stimulated with LPS or poly(I:C). Also, a fish trial was performed to detect TRIM proteins of rainbow trout after a challenge with Flavobacterium psychrophilum, a salmonid bacterial pathogen. At in vitro level, the results showed that, among several TRIM proteins, OmTRIM25 triggered an LPS-induced expression of pro-inflammatory cytokines (TNF-α2 and IL-1β), suggesting a potential local modulatory function. Moreover, in the fish trial, while OmTRIM25 and finTRIM2 were up-regulated in the gills two days post infection (dpi), IL-1β and TNF-α2 reached their peaks of expression at four- and six-dpi. Finally, after delving into the function of OmTRIM25 by RNA interference (RNAi) gene-silencing, we propose that TRIM proteins such as OmTRIM25 are needed to induce the pro-inflammatory response in the gills of rainbow trout, which confirms their immunomodulatory function.

Alpha-methyl-p-tyrosine (AMPT; also referred as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in few other illnesses. Chronic fatigue syndrome (CFS) is an heterogenous disorder with genetically associated vulnerability of catecholamine metabolism (e.g. catechol O-methyltransferase polymorphisms) holding an important impact of environmental factors. The current case report compiles genetic and longitudinal biochemical data for over a year follow-up of one patient sequentially diagnosed with sustained overstress, neurasthenia, CFS, and POTS (postural orthostatic tachycardia syndrome) over a 10-year period, and reports patient’s symptom improvement in response to low-medium doses of AMPT.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p&lt;0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p&lt;0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p&lt;0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p&lt;0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol &lt;40 mg/dL in men or &lt;50 mg/dL in women (OR = 1.70); (p&lt;0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

Introduction: Birth Asphyxia is a severe condition that includes many potential pathways of occurrence both in utero and during childbirth. We aimed to identify and describe specific macroscopic and microscopic placental injuries in birth asphyxia to serve as a quick tool to stratify a newborn’s potential further evolution, as hypoxic-ischemic encephalopathy can be responsible for neonatal death or severe neurologic sequelae further compromising the affected persons’ quality of life. Materials and methods: We conducted an observational prospective study over 3 years. 62 patients diagnosed with birth asphyxia which had placental histopathological examination performed were enrolled. The control group consisted of 69 term newborns that required neonatal intensive care for at least three days, in the same period, for any other reason and that also had available placental exams. In our study, placental histopathological lesions identified in birth asphyxia have been classified according to Amsterdam Criteria. Results: We analysed data gathered from both groups by applying specific statistical tests for each type of variable and hypothesis. Thus, umbilical cord abnormalities were associated with hypoxic-ischemic encephalopathy in a statistically significant manner when comparing the birth asphyxia group of newborns with the control group. Also, we identified a high statistical level of significance for maternal and fetal vascular malperfusion and the occurrence of hypoxic-ischemic syndrome when comparing the two groups (p = .00). Conclusion: The macroscopic and microscopic placental examination can provide important information on the evolution of the disease in selected newborns according to the identified lesions.

An explanation of the origin of dark matter is suggested in this work. The argument is based on symmetry considerations about the concept of mass. In the Wigner's view, the rest mass and the spin of a free elementary particle in flat space-time are the two invariants that characterize the associated unitary irreducible representation of the Poincar\'e group. The Poincar\'e group has two and only two deformations with maximal symmetry. They describe respectively the de Sitter (dS) and Anti de Sitter (AdS) kinematic symmetries. Analogously to their shared flat space-time limit, two invariants, spin and energy scale for de Sitter and rest energy for Anti de Sitter, characterize the unitary irreducible representation associated with dS and AdS elementary systems. While the dS energy scale is a simple deformation of the Poincaré rest energy and so has a purely mass nature, AdS rest energy is the sum of a purely mass component and a kind of zero-point energy derived from the curvature. An analysis based on recent estimates on the chemical freeze-out temperature marking in Early Universe the phase transition quark-gluon plasma epoch to the hadron epoch supports the guess that dark matter energy might originate from an effective AdS curvature energy.

Hardened air void analysis provides essential information of concrete freeze-thaw durability based on the size and spacing of air voids in the material. As the physical freeze-thaw experiment is time-consuming and costly, the characteristics of concrete air voids are often deemed as a proxy of the freeze-thaw performance. This analysis is typically done by measuring the 2D air void intersections on polished samples, but the current interpretation of the 2D void characters does not accurately represent the actual void structure in 3D. To solve this problem, a 2D-to-3D unfolding technique has been proposed in the field of stereology. However, the unfolding analysis is known to be sensitive to several factors, such as void population and size along with a binning scheme, where improper unfolding can considerably bias the prediction of the actual concrete void system. This study investigates the optimal strategy of conducting the unfolding analysis for concrete. The investigation is carried out on both idealized void systems to interrogate the influence of the critical factors individually, and real concrete samples with varying levels of air entrainment to assess the concrete-specific impacts. The concrete void system is studied based on a stereological model emulating the intersected 3D air voids on the surface of polished concrete. The results highlight that, for unfolding concrete voids, logarithmic binning scheme is far more accurate to linear binning. The low unfolding error of the concrete samples indicates that the proposed methodology enables an accurate restoration of 3D void size distribution.

The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There is a limited number of antifungal medications available for treating IFIs and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, have become increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity: manogepix, rezafungin, ibrexafungerp, and olorofim against 100 isolates of Aspergillus section Terrei, containing amphotericin B (AmB) wildtypes/non-wildtypes and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against tested isolates, exhibiting a geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentrations (MIC) range respectively as follows: manogepix (0.048 mg/L, 0.032-0.5 mg/L), rezafungin (0.020 mg/L, 0.016-0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032-2 mg/L), and olorofim (0.008 mg/L, 0.008-0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus and cryptic species that were azole-resistant and AmB non-wildtype.

Metabolic syndrome (MetS) refers to the group of several interconnected risk factors that collectively double the risk of cardiovascular disease. Epilepsy is linked to MetS across all age groups, though its prevalence differs across various studies. This can be understood from the perspective of seizure-related metabolic abnormalities, long-term antiepileptic drugs (AEDs) use, and a more sedentary lifestyle due to epilepsy. The factors that are considered in developing MetS for patients with epilepsy (PWE) are age, residence, level of physical activity, food intake status, epilepsy subtype, epilepsy duration, current (AEDs) use, drug responsiveness status, body-mass index (BMI), total cholesterol and LDL-cholesterol levels. A deeper understanding of the epilepsy-AED-MetS connection and the exploration of lifestyle interventions hold the promise of significantly improving the overall health and well-being of PWE. Clinicians managing PWE should closely monitor various risk factors for developing MetS and consider them when selecting AED treatment.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) are constantly threatening global public health. With no end date, the pandemic still persists with the emergence of novel variants that threaten the effectiveness of diagnostic tests and vaccines. Mutations in the Spike surface protein of the virus are regularly observed in the new variants, potentializing the emergence of novel viruses with different tropism from the current ones, which may change the severity and symptoms of the disease. Growing evidence has shown that mutations are being selected in favor of variants that are more capable of evading the action of neutralizing antibodies. In this context, the most important factor guiding the evolution of SARS-CoV-2 is its interaction with the host’s immune system. Thus, as current vaccines cannot block the transmission of the virus, measures complementary to vaccination, such as the use of masks, hand hygiene, and keeping environments ventilated remain essential to delay the emergence of new variants. Importantly, in addition to the involvement of the immune system in the evolution of the virus, we highlight several chemical parameters that influence the molecular interactions between viruses and host cells during invasion and are also critical tools making novel variants more transmissible. In this review, we dissect the impacts of the Spike mutations on biological parameters such as (1) increase of Spike binding affinity to hACE2; (2) bound time for the receptor to be cleaved by the proteases; (3) how mutations associate with increase of RBD up-conformation state in the Spike ectodomain; (4) expansion of uncleaved Spike protein in the virion particles; (5) increment of Spike concentration per virion particles; and (6) evasion of the immune system. These factors play key roles in the fast spreading of SARS-CoV-2 variants of concern, including the Omicron.

Solidago virgaurea L. (European goldenrod, Woundwort), Asteraceae, is a familiar medicinal plant in Europe and other parts of the world, widely used and among the most researched species from its genus. The aerial parts of European goldenrod have long been used for urinary tract conditions and as an anti-inflammatory agent in the traditional medicine of different peoples. Its main chemical constituents are flavonoids (mainly derived from quercetin and kaempferol), C6-C1 and C6-C3 compounds, terpenes (mostly from the essential oil), and a large number of saponin molecules (mainly virgaureasaponins and solidagosaponins). Published research on its potential activities is critically reviewed here: antioxidant, antiinflammatory, analgesic, spasmolitic, antihypertensive, diuretic, antibacterial, antifungal, antiparasite, cytotoxic and antitumor, antimutagenic, antiadipogenic, antidiabetic, cardioprotective, and antisenescence. The evidence concerning its potential benefits is mainly derived from non-clinical studies, some effects are rather modest, whereas others are more promising, but need more confirmation in both non-clinical models and clinical trials.

Introduction Cone Beam Computed Tomography (CBCT) scans should be digitally oriented using a reference plane before being evaluated for patient growth and treatment outcome. Current orientation planes are usually dependent on the Porion points. Using more reliable landmarks than the Porion, we introduce the Acta plane and investigate its reliability as an alternative reference plane for cases in which the Porion point is inaccessible. Methods To test its reliability, a dental student and an orthodontist located sixteen skeletal and dental landmarks in sixteen CBCT scans, before and after reorientation. Also, four measurements were calculated based on these landmarks’ coordinates. The reorientation of these CBCT scans with the Acta plane was done by another dental student. Intraclass Correlation Coefficient (ICC) was calculated before and after orientation, intra- and inter-examiner. The data were tested for significance through the Shapiro Wilk test with a threshold set at 0.05. Through the ICC variation of the points’ coordinates, this article also evaluated the reliability of this plane with the t-paired and exact-sign tests. Results: The identification of landmarks was more reliable in the reoriented CBCT images than in the original images, with a significant increase of 0.012 in the median of the ICC. Linear and angular measures showed no significant differences between groups. Conclusion This plane is a reliable alternative for the orientation of CBCT images. The design of the Acta plane might allow the use of a smaller field of view and, consequently, a reduction in the radiation dose.

Lambert-Eaton myasthenic syndrome is a primary autoimmune or paraneoplastic neuromuscular disorder, which causes muscle weakness, areflexia and autonomic disorders through the production of antibodies to voltage-gated calcium channels. Diagnosis may be challenging, yet at the same time extremely important, allowing the detection of a possible underlying malignancy, in cases of paraneoplastic presentation. Some antibodies have good sensitivity and specificity for malignancy and are also discussed. Although most of times being correlated to small cell lung cancer, other types of tumors may be also found in the paraneoplastic syndrome. Misdiagnosis with Myasthenia Gravis may occur and differences between these two disorders are discussed. Therapy choice may vary from each patient depending on drug response and the situation in which the patient is encounter. Overall, the present paper brings a review of Lambert-Eaton, involving the diagnosis, as well as, the pathophysiology, differential diagnosis, tumor investigation and treatment. Also, a brief overview through guidance on therapy during the Corona Virus Disease 2019 pandemic is analyzed.

Two novel dsRNA mycoviruses were found in different isolates of Diplodia fraxini, NW FVA 1581 and NW FVA 1706, which were isolated from a root, associated with stem collar necrosis of Fraxinus excelsior L. Both mycelia are infected by a novel fusagravirus, which was named Diplodia fraxini fusagravirus 1 (DfFV1), and isolate NW FVA 1706 is additionally infected by a novel partitivirus, which was denominated as Diplodia fraxini partitivirus 1 (DfPV1). The one-segmented, bicistronic genome of DfFV1 is composed of about 8,500 bp. Their ORFs are connected by a 1 slippery heptamer sequence and the 3’ terminal ORF is coding for the viral RdRp. The genome of DfPV1 is composed of three, monocistronic dsRNA segments ranging from 1,755 bp (dsRNA 1) over 1,588 bp (dsRNA 2) to 1,233 bp (dsRNA 3). Based on genome organization and phylogenetic positions, DfFV1 was assigned to the proposed family of “Fusagraviridae” and DfPV1 to the genus Gammapartitivirus within the family of Partitiviridae. Ultra-structural analysis showed that polysomal structures were stabilized in the single infection and none of these structures could be isolated in the double infection. It is assumed that DfFV1 has an opportunistic lifestyle, being either protected by ribosomes or by transcapsidation from particles of DfPV1.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

As a form of protection, a nature park is often created to protect and valorise natural and cultural heritage in peripheral rural areas. However, in terms of multi-functionality, new nature parks are incorporated into traditional productive activities, such as recreational and tourist activities, which sometimes compromise sustainability. The research objective is to study the relationship between tourism and sustainability in the Nature Parks of “Sierra de Aracena y Picos de Aroche”, “Sierra Norte de Sevilla” and “Sierra de Hornachuelos” that makes up the Dehesas de Sierra Morena Biosphere Reserve in Andalusia, Spain. Therefore, selective interviews have been carried out with the stakeholders to establish their perception of sustainable tourism and the presence of dominant discourses. The main conclusions indicate (1) the presence of different dominant discourses on sustainability, namely the conservationist and mercantilist ones, with the prevalence of the economic dimension; (2) poor awareness and adaptation to the context of global change; and (3) the presence of competitive relationships that generate difficulties for the governance of sustainable tourism.

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age representing the primary cause of anovulatory infertility. The nonapeptide oxytocin (OT) plays an important role in cognitive, emotional, and reproductive functions in human beings. Oxytocin receptors are expressed in several body parts including the ovaries. Despite this, the possible role played by oxytocin in symptoms of PCOS is not clear. The present systematic review aimed at understanding, the presence of possible oxytocin level alterations in PCOS, the connection between alterations of OT levels and the symptoms of PCOS, and the effect of oxytocin administration in PCOS. After a systematic search in the principal databases, seven studies, five human and two animal, were included. Most of the studies highlighted the role played by oxytocin in fertility issues related to PCOS. Studies that analyzed oxytocin basal levels in PCOS women agreed that PCOS is associated with a reduction in the serum level of oxytocin. Two studies found that in PCOS the serum levels of oxytocin were lower than healthy controls. One human and one animal study agreed about lower levels of PCOS, confirming a possible implication of a dysfunction of OT, in the pathogenesis of PCOS.

Mastocytosis is characterized by pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

Superior mesenteric artery (SMA) syndrome or Wilkie’s syndrome is a vascular compression disorder that causes abnormal compression of the third portion of the duodenum by the SMA. It has a low incidence rate, higher in young women, and is rarely associated with the Nutcracker phenomenon: a condition of compression of the left renal vein between the SMA and the aorta, which manifests as pain in the left flank and pelvis. Here we report the case of a 54-year-old woman with a history of repeated episodes of abdominal pain caused by the Nutcracker syndrome and Wilkie's syndrome.

Male obesity secondary hypogonadism (MOSH) impairs fertility, sexual function, bone mineralization, fat metabolism, cognitive function, deteriorates muscle mass and alters body composition. The aim of this pilot study was to evaluate the effect of dietary intervention and physical activity on the MOSH patient’s hormonal profile after a 10% weight loss compared to baseline. Fourteen male patients were enrolled. Hormonal, lipid, glycemic profiles and body composition were determined at baseline and after a 10% weight loss. Aging Male Symptoms Scale (AMS) and Yale Food Addiction Scale (YFAS) were administered to patients in order to investigate hypogonadal symptoms and food addiction. Compared to baseline, a significant increase of Total Testosterone (TT) (300.2 ± 79.5 ng/dl vs 408.3 ± 125.9, p = 0.002, 95% CI 26.8; 167.7) and a reduction of 17-Beta Estradiol level (48.3 ± 14.9 pg/mL vs 39.2 ± 15.2, p = 0.049, 95% CI 3.1; 0.0) were observed. Total Fat Mass (FM) percentage, android and gynoid fat mass percentage (39.2 ± 6.4% vs 36.2 ± 5.8%, p = 0.0001, 95% CI 22.5; 62.3; 51.5 ± 6.8% vs 47.6 ± 6.8%, p = 0.001, 95% CI 0.6; 1.8, vs 39.2 ± 6.2% vs 36.5 ± 6.3% p= 0.0001, 95% CI 0.9; 2.0 respectively) were significantly decreased after nutritional intervention. In addition, total Fat Free Mass (FFM) in kg was significantly reduced after 10% weight loss (62.3± 2.8 kg vs 60.3± 7.7 kg, p = 0.002, 95% CI 45.0; 93.0). Lifestyle changes, specifically dietotherapy and physical activity, induce positive effects on hypogonadism due to obesity.

We discuss the consequences of the unique symmetry of the de Sitter spacetime. This symmetry leads to the specific thermodynamic properties of the de Sitter vacuum, which produces the thermal bath for matter. The de Sitter spacetime is invariant under the modified translations, ${\bf r}\rightarrow {\bf r} -e^{Ht}{\bf a}$, where $H$ is the Hubble parameter. For $H\rightarrow 0$, this symmetry corresponds to the conventional invariance of Minkowski spacetime under translations ${\bf r}\rightarrow {\bf r} -{\bf a}$. Due to this symmetry, all the comoving observers at any point of the de Sitter space perceive the de Sitter environment as the thermal bath with temperature $T=H/\pi$, which is twice larger than the Gibbons-Hawking temperature of the cosmological horizon. This temperature does not violate the de Sitter symmetry, and thus does not require the preferred reference frame, as distinct from thermal state of matter, which violates the de Sitter symmetry. This leads to the heat exchange between gravity and matter, and to instability of de Sitter state towards the creation of matter, its further heating, and finally to the decay of the de Sitter state. The temperature $T=H/\pi$ determines different processes in the de Sitter environment, which are not possible in the Minkowski vacuum, such as the process of ionization of an atom in the de Sitter environment. This temperature also determines the local entropy of the de Sitter vacuum state, and this allows us to calculate the total entropy inside the cosmological horizon. The result reproduces the Gibbons-Hawking area law, which is related to the cosmological horizon, $S_{\rm hor}=4\pi KA$, where $K=1/16\pi G$. This supports the holographic properties of the cosmological event horizon. We extend the consideration of the local thermodynamics of the de Sitter state using the $f({\cal R})$ gravity. In this thermodynamics, the Ricci scalar curvature ${\cal R}$ and the effective gravitational coupling, $K$, are thermodynamically conjugate variables. The holographic connection between the bulk entropy of the Hubble volume, and the surface entropy of the cosmological horizon remains the same, but with the gravitational coupling $K=df/d{\cal R}$. Such connection takes place only in the $3+1$ spacetime, where there is the special symmetry due to which the variables $K$ and ${\cal R}$ have the same dimensionality. We also consider the lessons from the de Sitter symmetry for the thermodynamics of black and white holes.

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&lt;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&gt;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&lt;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&lt;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.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

The macro-litter (plastic) sea bottom pollution of 14 city harbors and marinas in North Africa and in the western Baltic Sea was investigated using a new simple mobile underwater camera system. The study was complemented by a harbor manager survey and 3D-hydrodynamic transport simulations. The average pollution in German marinas was 0.1 particles/m² sea floor (0.04–1.75). The pollution in North African marinas on average was 7 times higher (0.7 particles/m²) and exceeded 3 particles/m² in city center harbors. The resulting &gt;100,000 litter particles per harbor indicate the existence of a problem. With 73%-74%, plastic particles are dominating. Existing legal and management frameworks explain the lack of plastic bottles and bags on sea floors in Germany and are one reason for the lower pollution levels. Items that indicate the role of untreated sewage water were not found. Harbor festivals seem not to be quantitatively relevant for open sea bottom pollution. Our method tends to underestimate the pollution level. Model simulations indicate that storms can cause litter reallocations and sediment cleanings. However, marina sea floor monitoring is recommendable, because it addresses pollution hot-spots, is cost-effective and takes place close to emission sources. Further, the effectiveness of land-based pollution reduction measures can easily be assessed.

As more cases of COVID-19 are studied and treated world-wide, it had become apparent that lethal and most severe cases of pneumonia are due to an out-of-control inflammatory response to the SARS-CoV2 virus. I explored the putative causes of this specific feature through a detailed genomic comparison with the closest SARS-CoV-2 relatives isolated from bats, as well as previous coronavirus strains responsible for the previous epidemics (SARS-CoV, and MERS-CoV). The high variability region of the nsp3 protein was confirmed to exhibit the most variations between closest strains. It was then studied in the context of physiological and molecular data available in the literature. A number of convergent findings point out de-mono-ADP-ribosylation (de-MARylation) of STAT1 by the SARS-CoV-2 nsp3 as a likely cause of the cytokine storm observed in the most severe cases of COVID-19. This may suggest new therapeutic approaches and an assay to predict the virulence of naturally circulating SARS-like animal coronaviruses.

Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with themselves, their environment, and hosts via metabolites and signaling molecules. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding between microbiologists and modelers/bioinformaticians, stemming from a lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored for microbiologists, researchers new to microbiome modeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metagenomics methods, and modeling formalisms. Furthermore, the review explains model building, examples of microbiome model applications for prediction, optimization, and control. It concludes with guidelines, software, and repositories for modeling. Each section provides entry-level information, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A&gt;G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.

Over the last two decades, a considerable amount of equipment has been acquired (spreaders, seeders, sprayers, among others) to respond to the challenges of Precision Agriculture (PA) concept. Most of this equipment has been purchased at a high cost. However, many of them, despite still being functional and equipped with sensors, actuators, and electronic processing units capable of adjusting to variations in speed, have become obsolete in terms of communication, and incompatible with new monitoring and control systems based on the “Isobus” protocol. This work aims to present a solution for updating the control system (“Ferticontrol”) of a “Vicon RS-EDW” spreader with variable rate application (VRA), making it compatible with the “InCommand” system from “Ag Leader”. The solution includes low-cost “Arduino” and “Raspberry Pi” microcontrollers and open-source software. The development shows that it is possible to implement a solution that is accessible to farmers in general. It also provides a niche business opportunity for young researchers to set up small technology-based enterprises associated with universities and research centers. These partnerships guarantee permanent innovation and represent a decisive step towards modern, technological, competitive, and sustainable agriculture.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

Background: The newly introduced COVID-19 vaccines have reduced disease severity and hospitalizations. However, they do not significantly prevent infection or transmission. In the same context, measuring IgM and IgG antibody levels is important, but it doesn't provide information about the status of the mucosal immune response. This article describes a comprehensive mapping of IgA epitopes of the S protein, its cross-reactivity, and the development of an ELISA-peptide assay. Methods: IgA epitope mapping was conducted using Spot-synthesis and sera from RT-qPCR COVID-19-positive patients. Specific and cross-reacting epitopes were identified, and an evolutionary analysis from the early Wuhan strain to the Omicron variant was performed using bioinformatics tools and a microarray of peptides. The selected epitopes were chemically synthesized and evaluated using ELISA-IgA. Results: 40 IgA epitopes were identified, with 23 in S1 and 17 in the S2 subunit. Among these, at least 23 epitopes showed cross-reactivity with DENV and other organisms and 24 with other associated coronaviruses. Three MAP4 polypeptides were validated by ELISA, demonstrating a sensitivity of 90-99.96% and a specificity of 100%. Among the six IgA-RBD epitopes, only the SC/18 epitope of the Omicron variants (BA.2 and BA.2.12.1) presented a single IgA epitope. Conclusions: This research unveiled the IgA epitome of the S protein and identified many epitopes that exhibit cross-reactivity with DENV and other coronaviruses. The S protein of variants from Wuhan to Omicron retains many conserved IgA epitopes, except for one epitope (#SCov/18). The cross-reactivity with DENV suggests limitations in using the whole S protein or the S1/S2/RBD segment for IgA serological diagnostic tests for COVID-19. The expression of these identified specific epitopes as diagnostic biomarkers could facilitate monitoring mucosal immunity to COVID-19, potentially leading to more accurate diagnoses and alternative mucosal vaccines.

The extensive metabolic diversity of microalgae, coupled with their rapid growth rates and cost-effective production, position these organisms as highly promising resources for a wide range of biotechnological applications. These characteristics allow microalgae to address crucial needs in both the agricultural, medical, and industrial sectors. Microalgae are proving to be val-uable in various fields, including the remediation of diverse wastewater types, the production of biofuels and biofertilizers, and the extraction of various products from their biomass. For decades, the microalga Chlamydomonas has been widely used as a fundamental research model organism in various areas such as photosynthesis, respiration, sulfur and phosphorus metabolism, nitrogen metabolism, and flagella synthesis, among others. However, in recent years, the potential of Chlamydomonas as a biotechnological tool for bioremediation, biofertilization, biomass, and bio-products production has been increasingly recognized. Bioremediation of wastewater using Chlamydomonas presents significant potential for sustainable reduction of contaminants and fa-cilitates resource recovery and valorization of microalgal biomass, offering important economic benefits. Chlamydomonas has also established itself as a platform for the production of a wide va-riety of biotechnologically interesting products, such as different types of biofuels, and high-value-added products. The aim of this review is to achieve a comprehensive understanding of the potential of Chlamydomonas in these aspects, and to explore their interrelationship, which would offer significant environmental and biotechnological advantages.

The double burden of malnutrition (DBM) is escalating in low- and middle-income countries (LMICs), including in Rwanda, most notably in urbanizing areas. The 2019-2020 Rwanda Demographic Health Survey (DHS) revealed 33% of children under 5 are stunted while 42% of women in urban areas are overweight or obese. This coexistence has contributed to a surge in non-communicable diseases (NCDs), particularly in secondary cities. Using the World Health Organization’s (WHOs) “double-duty action” (DDA) concept, this study aims to identify and evaluate interventions with double-duty potential in Rwanda, focusing on the districts of Rusizi and Rubavu. Guided by Hawkes et al.’s conceptual framework for identifying DDA entry points, a desk review of national policies pinpointed 4 programs with DDA potential: early childhood development (ECD) centers, the school feeding program, farmer field schools (FFS), and the provision of nutrition-sensitive direct support. In-person interviews with key stakeholders assessed their implementation and a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis informed context-specific recommendations for their improvement. Recommendations include targeting beliefs surrounding nutrition, improving trainings for community educators, enhancing parent – particularly father – involvement, and close follow-up. These findings offer actionable strategies for governments and nutrition stakeholders and may benefit similar interventions in other rapidly urbanizing LMICs.

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state of the art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states which interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological sates, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented adding an exponential cutoff to the interaction term of PPP model. In this way, an adjusted cutoff distance λ = 2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond Hubbard model but not completely unscreened as is the case for the PPP model.

Background: Lynch syndrome, the most frequent form of hereditary colorectal cancer and involves mutations in mismatch repair genes. The aim of this study was to identify mutations in MSH6 from 97 subjects negative for mutations in MLH1 and MSH2. Methods: By direct sequencing, we identified 27 MSH6 variants, of which, nine were novel. To verify the pathogenicity of these novel variants we performed in silico and segregation analyses. Results: Three novel variants were predicted by in silico analysis as damaging mutations and segregated with the disease phenotype. While, a novel frameshift deletion variant that was predicted to yield a premature stop codon, did not segregate with the LS phenotype in 3 of 4 cases in the family. Interestingly, another frame-shift variant identified in this study, already described in the literature, also did not segregate with the LS phenotype in 1 of 2 affected subjects in the family. In all affected subjects of both families, no mutation was detected in other MMR genes. Therefore, it is expected that within these families other genetic factors contribute to the disease either alone or in combination with MSH6 variants. Conclusion: We conclude that caution should be exercised in counseling for MSH6-associated LS family members.

The detection of early biomarkers and molecular mechanisms in Parkinson’s disease (PD) remains a challenge. Recent research has pointed to potential roles for peptidylarginine deiminases (PADs), a family of calcium activated enzymes, and associated post-translational protein citrul-lination/deimination in early stages of the disease, with a focus on hippocampal and cortex re-gions of the brain. Further analysis of brain region specific changes in PAD isozymes and identi-fication of brain-region specific citrullinomes, therefore remain to be studied. This study assessed brain-region specific PAD isozyme expression (PADs 1-4; PAD6) and associated citrullinated protein targets in the 6-hydroxydopamine (6-OHDA) induced rat model of pre-motor PD. Cortex, hippocampus, striatum, midbrain, cerebellum and olfactory bulb were compared between con-trols/shams and the PD model. In cortex, a significant increase of PAD2 and PAD3 was observed in the PD model. In hippocampus, PAD3, PAD4 and PAD6 showed strongest levels, but with no significant changes observed between PD and controls. In striatum, a significant reduction in all PAD isozymes was observed in the PD model. In the olfactory bulb, PAD3 was significantly el-evated in PD. In midbrain, PAD2, PAD4 and PAD6 showed strongest signal but with no signifi-cant changes between PD and controls. In cerebellum, a significant increase was seen in PAD3, PAD4 and PAD6 in the PD model. Citrullinated protein hits were most abundant in cortex and hippocampus, while for the PD model an increase in citrullinated hits was particularly observed in cortex and cerebellum, compared to controls. For all brain regions there was a considerable difference in citrullinated protein IDs between the PD model and the controls. Citrullinome as-sociated KEGG pathways differed in the six brain regions; some were overlapping for controls and PD, some were identified for the PD model only, and some were identified in control brains only. KEGG pathways identified in PD brains onlywere: “Axon guidance”; “Spinocerebellar ataxia”; “Hippo signalling pathway”; “NOD-like receptor signalling pathway”; “Phosphatidyl-inositol signalling system”; “Rap1 signalling pathway”; “Platelet activation”; “Yersinia infection”; “Fc gamma R-mediated phagocytosis”; “Human cytomegalovirus infection”; “Inositol phosphate metabolism”; “Thyroid hormone signalling pathway”; “Progesterone-mediated oocyte matura-tion”; “Oocyte meiosis”; and “Choline metabolism in cancer”. Our findings highlight differences in PAD isozymes, citrullinated proteins and associated KEGG pathways between brain regions, in pre-motor PD.

During the last years there has been a high interest in the development of new purely-organic single-component conductors. Very recently, we have reported a new neutral radical conductor based on the perchlorotriphenylmethyl (PTM) radical moiety linked to a monopyrrolo-tetrathiafulvalene (MPTTF) unit by a -conjugated bridge (1). Interestingly, this system behaves as a semiconductor with high conductivity and small energy gap under high pressure. With the aim of developing a new material with improved conducting properties, we have designed and synthesized the radical dyad 2 which was functionalized with an ethylenedithio (EDT) group in order to improve the intermolecular interactions of the TTF subunits. The physical properties of the new radical dyad 2 were studied in detail in solution to further analyze its electronic structure as well as its potential use as radical conductor in the solid state.

The chestnut tree (Castanea sativa Mill.) is gaining importance in the mountainous regions of southern Europe due to the high value of its fruits. It is essential to establish effective cultivation protocols, considering that this species is still relatively understudied. In this study, we present the outcomes of the initial establishment of a chestnut orchard conducted through a nutrient omission trial for four years. The treatments included a fertilization plan with nitrogen, phosphorus, potassium, and boron (NPKB), the control, and four other treatments corresponding to the omission of each nutrient (-NPKB, N-PKB, NP-KB, NPK-B). The -NPKB and NP-KB treatments showed significantly lower trunk circumferences and canopy volumes compared to the other treatments. The NPK-B treatment resulted in the lowest fruit production, with a total accumulated yield (2020-2022) of 0.56 kg tree–1, a value significantly lower than that of NPKB (1.12 kg tree–1) and N-PKB (1.19 kg tree–1). The assessment of nutrient concentrations in the leaves revealed plants with deficient levels of B and K in treatments that did not receive these nutrients. Conversely, N levels in the leaves in the -NPKB treatment fell within the sufficiency range (20 to 28 g kg–1). This suggests that the sufficiency range should be adjusted to higher values, given the treatment's effect on tree growth. It was also observed that the -NPKB treatment led to lower soil organic matter compared to the other treatments, likely due to reduced herbaceous vegetation development under the canopy, leading to decreased organic substrate deposition in the soil. The main findings of this study are that N and K were crucial elements for the optimal growth of chestnut trees, while B played a significant role in fruit production.

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

Fragile X syndrome (FXS) is caused by the full mutation in the FMR1 gene on the Xq27.3 chromosome region. It is the most common monogenic cause of Autism Spectrum Disorder (ASD) and inherited intellectual disability (ID). Besides ASD, ID and other issues, individuals with FXS may exhibit sleep problems and impairment of circadian rhythm (CR). The Drosophila melanogaster models of FXS, such as dFMR1B55, present excellent model for research in the FXS field. During this study, sleep pattern and CR in dFMR1B55 mutants were analyzed, using a new platform based on continuous high-resolution videography in integration with a highly-customized version of software. This methodology provides more sensitive results, which could be crucial for all further research in this model of fruit flies. The study revealed that dFMR1 B55 male mutants can be considered weak rhythmic flies rather than totally arrhythmic, and present a good alternative animal model of genetic disorder, which includes impairment of CR and sleep behavior. The combination of videography and software used in the current study should be recommended as a gold-standard methodology for such further research.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

This study aims to establish whether the use of biomaterials, particularly polydimethylsiloxane (PDMS), for surgical reconstruction of the esophagus with templates, Montgomery salivary tube, after radical oncology surgery for malignant neoplasia is an optimal choice for patients’ safety and for optimal function preservation and organ rehabilitation. Methods: Structural analysis by Raman spectrometry and biomechanical properties with dynamic mechanical analysis are performed for fatigue strength and toughness, essential factors in durability of a prosthesis in the reconstruction practice of the esophagus. Nanocomposites with silicone elastomers and nanoparticles used in implantable devices and in the reconstruction surgery are facing risks of infection and fatigue strength when required to perform a mechanical effort for long periods of time. Results: This report takes into account the effect of silver (Ag) nanoparticles on the fatigue strength using polydimethylsiloxane (PDMS) matrix, representative for silicon elastomers used in implantable devices. PDMS with 5% (wt) Ag nanoparticles of 100-150 nm during mechanical fatigue testing at shear strength loses elasticity properties after 400 loading-unloading cycles and up to 15% shear strain. The fatigue strength, toughness, maximum shear strength are the key issues in designing Montgomery salivary tube with appropriate biomechanical behavior for each patient. Conclusions: Prosthesis design needs to indulge both clinical outcome as well as design methods and research in the field of biomaterials.

The self-assembly is an intriguing process of great importance in general soft matter and thus re-ceives an ever-growing scientific interest. Its most trivial example is the entropy-driven crystalli-zation of hard spheres. Past works have established the similarities and differences in the phase behavior of monomers and chains made of hard spheres. In the present work, inspired by the dif-ference in the melting points of the pure components, we study, through Monte Carlo simulations, the phase behavior of athermal mixtures composed of fully flexible polymers and individual monomers of uniform size. We analyze how the relative number fraction and the packing density affect crystallization and the established ordered morphologies. A synergetic effect is observed in the crystallization leading to synchronous crystallization of the two species. Structural analysis of the resulting ordered morphologies shows perfect mixing and thus no phase separation, which could split the system into polymer-rich and monomer-rich domains. Due to the constraints imposed by chain connectivity, the local environment of the individual spheres is systematically more spherical and more symmetric compared to the one of spheres belonging to chains. In general, increasing polymer content leads to reduction of the degree of crystallinity. According to the present findings, relative concentration is another determining factor to control the phase behavior of hard colloidal systems based on polymers.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

Proximal Junctional Kyphosis (PJK) as one of the most discussed problems after corrective surgery in adolescent idiopathic scoliosis (AIS), is still not fully clarified and seems to be multifactorial. Biome-chanical and few clinical studies have shown the influence of destruction of posterior ligaments by re-section of spinous processes and some parameters concerning rod contouring as risk factors for PJK. To verify these results 192 patients with AIS and corrective surgery via posterior approach between 2009 and 2017 were included. Radiographic parameters were analyzed preoperatively (preOP), postoperatively (postOP), and with a mean follow up (FU) of 27 months. The participants were divided into two groups (PJK group and non-PJK group). The incidence of PJK was 15.6%. Contrary to the results of biomechanical studies, we could not find any significant influence of the spinous process resection. However, the PJK group had significantly larger preOP T4-T12 kyphosis (31.1°±13.93° vs. 23.3°±14.93°, p=.016). Furthermore, the PJK group showed a significantly larger rod contour angle (RCA) (8.0°±4.44° vs. 5.9°±3.28°, p=.003) and mismatch of postOP proximal junctional angle (PJA) and RCA (3.5°±5.72° vs. 0.9°±4.86°, p=.010) compared to the non-PJK group. An increase of the mismatch of postOP PJA and RCA (OR=1.14, p=.008) and a high RCA are risk factors for PJK and need to be focused on by surgeons.

The demand for explainable and transparent models increases with the continued success of reinforcement learning. In this article, we explore the potential of generating shallow decision trees (DT) as simple and transparent surrogate models for opaque deep reinforcement learning (DRL) agents. We investigate three algorithms for generating training data for axis-parallel and oblique DTs with the help of DRL agents ("oracles") and evaluate these methods on classic control problems from OpenAI Gym. The results show that one of our newly developed algorithms, the iterative training, outperforms traditional sampling algorithms, resulting in well-performing DTs that often even surpass the oracle from which they were trained. Even higher dimensional problems can be solved with surprisingly shallow DTs. We discuss the advantages and disadvantages of different sampling methods and insights into the decision-making process made possible by the transparent nature of DTs. Our work contributes to the development of not only powerful but also explainable RL agents and highlights the potential of DTs as a simple and effective alternative to complex DRL models.

In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be latently activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8 and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of latently activated granulocytes upon IL8 stimulation, and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.

Global public health systems have continuously faced challenges from the advent of novel infectious illnesses, necessitating quick and efficient actions to stop their spread.First discovered in Saudi Arabia in 2012, Middle East respiratory syndrome (MERS) is a viral respiratory disorder caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). Since then, the nation has reported most cases and fatalities related to this sickness, with occasional outbreaks happening in other nations and regions. Severe sickness and high mortality are caused by MERS-CoV, especially in older persons and those with underlying chronic conditions. Through intimate contact, the virus can spread from people to dromedary camels and vice versa. It has sparked multiple epidemics both domestically and abroad in the Middle East, raising the possibility of fatalities and widespread transmission, especially in susceptible groups. The Riyadh region was the main target of the most current MERS-CoV outbreak in Saudi Arabia, which began in 2023 and ended on September 1, 2023, with 312 confirmed cases and ninety-seven fatalities. With the use of published studies and their contributions to the field, we hope to present a thorough overview of the MERS-CoV outbreak in Saudi Arabia in this review of the literature, including its epidemiological investigation, public health response, impact, and lessons learned. In addition to highlighting the importance and continued relevance of this problem, our work suggests ways to lower the risk of MERS-CoV transmission and avert further outbreaks.

Ménière's disease (MD) has an unclear cause. The microvascular dysregulation of the inner ear has been increasingly pointed as a potential contributor. This study investigates the prevalence of cardiovascular risk factors (CVRFs) in MD patients compared to those with posterior circulation cerebral infarction (POCI). CVRFs like hypertension, diabetes, dyslipidemia, obesity, coronary heart disease, and smoking were assessed in both MD and POCI patients. Brain MRI identified POCI etiology as "small vessel occlusion" (SVO) or "other etiology" (OE). The study included 64 MD and 84 POCI patients. Compared to MD, POCI OE showed a higher prevalence of CVRFs across various age groups, including hypertension, diabetes, dyslipidemia, and smoking. Notably, the odds of having POCI OE were significantly higher for individuals with hypertension and smoking. On the other hand, POCI SVO showed similar prevalence of CVRFs compared to MD. This study reveals no significant difference in CVRF prevalence between MD and smaller vessel POCI. However, a clear distinction emerges when comparing MD to POCI with involvement of larger blood vessels. Further research is needed to confirm these findings and explore potential shared risk factors between POCI (SVO) and MD.

When profit-driven renewal is difficult to implement, many historic districts are “frozen protected” in China. In the social context of “building cities for the people” in recent years, the public value-oriented renewal of urban historic areas plays an important role in the transformation of cities. This study investigates the strategies of historic district regeneration in China by integrating spatial form, urban governance, and public value. We propose a novel framework to analyze the regeneration of historic districts, using Taiyuan Bell Tower Street as a case study. The framework distinguishes between two dimensions: spatial and economic-social. In the spatial dimension, we focus on the transformation of spatial form to regenerate public value, emphasizing the attribute of "publicness" as central to urban regeneration efforts. This involves a tiered approach of excavating and upgrading historic districts at macro, meso, and micro levels. In the economic-social dimension, we explore urban governance to strengthen public value, involving government, market, and societal actors in a collaborative renewal process. The analysis highlights that a public value-oriented approach to heritage regeneration offers greater sustainability and could serve as a model for other cities seeking similar outcomes.

Fragile X syndrome (FXS), the most common monogenic cause of inherited intellectual disability and autism spectrum disorder, is caused by a full mutation (&gt;200 CGG repeats) in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene. Individuals with FXS experience a wide range of challenges related to social interaction (SI). Animal models, such as Drosophila melanogaster model for FXS where the only ortholog of human FMR1 (dFMR1) is mutated, have played a crucial role in understanding of FXS. The aim of this study was to investigate SI in the dFMR1B55 mutants using the novel Drosophila Shallow Chamber and a Python data processing pipeline based on social network analysis (SNA). In comparison with wild-type flies (w1118), SNA analysis in dFMR1B55 mutants revealed hypoactivity, fewer connections in their networks, a lower ability to efficiently transmit information, fewer alternative pathways for information transmission, a higher variability in the number of interactions they achieved, and tended to stay near the boundaries of the testing chamber. These observed alterations indicate the presence of characteristic strain-dependent social networks in dFMR1B55 flies, commonly referred to as the group phenotype. Finally, a combination of novel research tools is a valuable method for SI research in fruit flies.

Objective: To analyse the association between maternal risk factors such as age, body mass index (BMI) and cigarette smoking, with perinatal outcomes. Materials and Methods: This a retrospective analysis from prospectively collected data performed at Hospital Universitario de Torrejón (Madrid, Spain), between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate. Association between preeclampsia, preterm birth, gestational diabetes mellitus (GDM), small for gestational age (SGA) or fetal growth restricted (FGR) neonates and type of delivery according to maternal age, BMI, and cigarrete smoking was studied. Logistic mixed models were used to analyze the data. Results: 1921 patients were included in the analysis. Women of 40 years old had a significantly higher risk of having GDM (Odds Ratio (OR) 1.61, 95% Confidence Interval (CI) 1.08 to 2.36), and SGA neonates (OR 1.54, 95% CI 1.00 to 2.37). Women with a BMI &lt;18 had an increased rate of birth SGA and FGR neonates (OR 3.28, 95% CI 1.51 to 7.05, and OR 3.73, 95% CI 1.54 to 8.37, respectively), whereas women with a BMI ≥35 had a higher risk of GDM (OR 3.10, 95% CI 1.95 to 4.89). Smoking increased the risk of having SGA and FGR neonates (OR 1.83, 95% CI 1.36 to 2.46, and OR 1.91, 95% CI 1.29 to 2.78). Conclusions: Advanced maternal age, low or high BMI, and smoking status are significant risk factors for pregnancy complications. Both clinicians and society should concentrate their efforts on addressing these factors to enhance reproductive health.

Background: Metabolic syndrome (MS) is associated with a greater risk of morbimortality. Ob-jective: To estimate the prevalence of Metabolic Syndrome (MS) and associated factors in patients of a Psychosocial Care Center (CAPS) in the city of Salvador, state of Bahia, Brazil. Method: Cross-sectional study set at CAPS in the city of Salvador-Bahia, between August 2019 and February 2020. MS was evaluated according to the National Cholesterol Education Program's Adult Treatment Panel III. In addition to descriptive statistics, gross and adjusted prevalence ratios were described. Results: MS was found in 100 (35.2%) individuals, 116 (40.9%) were obese and 165 (58.1%) had increased waist circumference. Polypharmacy was identified in 63 (22.3%) patients and 243 (85.9%) used antipsychotics. In the gross evaluation, the female (PR = 1.88; 95% CI: 1.35-2.63) and the use of antidepressants (PR = 1.41; 95%CI: 1.05-1.88) were associated with MS. After logistic re-gression, depression (PR = 1.86; 95%CI: 1.38-2.51), acanthosis (PR = 1.50; 95%CI: 1.18 - 1.90), use of antipsychotics (PR = 1.88; 95%CI: 1.13 - 2.75) and the hypertriglyceremic waist (PR = 3.33; 95%CI: 2.48- 4.46) were associated with MS. Conclusion: The prevalence of MS alerts to multimorbidity among individuals with mental disorders and the need for clinical screening.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden as well, if the absolute risk of infection during child-bearing age increases. Dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with low current burden and high transmission intensity. Low or declining rubella virus transmission intensity is concurrently associated with both greater disease burden and greater vaccine effectiveness. The risk of increasing burden through vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase and a large, immediate burden decrease strongly favors RCV introduction.

Kisspeptin, a key neuropeptide derived from the KISS1 gene, is renowned for its critical role in regulating the hypothalamic-pituitary-gonadal axis and reproductive hormone secretion. Beyond its primary function in reproductive biology, emerging research has illuminated its influence in various cancers, mediating significant effects through its interaction with the G-protein coupled receptor, Kisspeptin receptor. This interaction has been implicated in modulating cellular pro-cesses such as proliferation and metastasis, making it a potential target for therapeutic interven-tion. Our study initially screened ten kisspeptin-10 analogs through cytotoxic effects of kisspep-tin-10 (KP10) and its analogs in several cancer types, including cervical, prostate, breast, and gastric cancers, with a particular focus on cervical cancer where the most profound effects were observed. Further exploration using kinase array assays revealed that these analogs specifically alter key kinases involved in cancer progression. Migration assays demonstrated a substantial decrease in cell motility, and Bioluminiscence Resonance Energy Transfer assays confirmed these analogs strong interactions with the kisspeptin receptor. Overall, our results indicate that these KP10 analogs not only hinder cervical cancer cell proliferation but also curtail migration through targeted modulation of kinase signaling, suggesting their potential as therapeutic ayfgents in managing cervical cancer progression. This comprehensive approach underscores the therapeutic promise of exploiting kisspeptin signaling in cancer treatment strategies.

The Interdisciplinary Canadian Collaborative ME Research Network (ICanCME), established in 2019, aims to foster research in Canada and contribute to finding the causes and possible treatments for myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS), thereby reducing the impact of ME/CFS on the health of Canadians. The main objectives of this paper are to suggest standards for ME/CFS research for the collection of data from participants (Recommended Data Elements) and to consider other factors, such as design, language, cultural issues, equity, and diversity. Consensus of the relevant contents of this research guideline was reached during the ICanCME working group meetings and were based on existing guidelines. Members of the working group contributed to guideline development based on their respective expertise. The proposed research guidelines could improve research quality and advance knowledge in the field of ME/CFS, and ultimately benefit ME/CFS patients.

Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both exponential and stationary phases. Moreover, we could differentiate between triggered (induced by antibiotics, such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

The purpose of the evaluation of the Peruvian energy generation system is to project the electricity generation and demand until the year 2050. To achieve this, three alternative scenarios have been defined and analyzed using the LEAP (Long-range Energy Alternatives Planning) software. The scenarios are as follows: the first one, Business-as-Usual scenario, based on normal trends according to historical data and referencing projections made by Peruvian state entities; the second one is focused on Energy Efficiency, the highlighted characteristic is taking into consideration the efficient conditions in transmission and distribution of electric energy; and the third one, centered on Geothermal Energy, focused on the development of this type of energy source and prioritizing it. The primary purpose of this analysis is to identity advantages and disadvantages inherent in each scenario in order to get the best of each one. In this way, the intention is to propose solutions based on Peru’s national reality or possible uses of the country’s energy potential to supply its energy demand. Currently, Peru’s energy demand relies on fossil fuels, hydraulic, and thermal energy. However, there is the possibility of transforming this system into a sustainable one, by strengthening existing and growing energy sources such as solar and wind energy, and new technologies for hydraulic and thermal energy, in addition to considering geothermal energy as the main energy source in the third scenario. The new system mentioned satisfactorily indicate that the CO2 equivalent emissions decrease significantly in the third scenario, with a 15.8% reduction compared to the first scenario and a 9.7% reduction in comparison to the second. On the other hand, the second scenario shows a 5.6% decrease in CO2 emissions compared to the first, resulting from improvements in technology and energy efficiency without requiring significant modifications or considerable investments, as in the third scenario.

In voice analysis, the electroglottographic (EGG) signal has long been recognized as a useful complement to the acoustic signal, if only when the vocal folds are actually contacting, such that this signal has an appreciable amplitude. However, phonation can occur also without vocal fold contacting, as in breathy voice, in which case the EGG amplitude is low, but not zero. It is of great interest to identify the transition from non-contacting to contacting, because this will substantially change the nature of the vocal fold oscillations; yet that transition is not in itself audible. The magnitude of the normalized peak derivative of the EGG signal is a convenient indicator of contacting, but no current EGG hardware has a sufficient signal-to-noise ratio of the derivative. The textbook techniques of spectral thresholding and static notch filtering are straightforward to implement, can run in real time, and can mitigate several noise problems in EGG hardware.

Recently quantum cosmology in tomographic representation was considered. as an important tool to analyze the quantum states of the early universe in relation with the subsequent classical evolution. Given a wave function the correspondent tomogram is defined proportional to the square modulus of its fractional Fourier transform. The classical limit obtained by taking the limit ℏ→0 can be compared with the classical tomogram obtained from the classical hamiltonian formalism. In this paper we show that a set of tomograms can be derived as exact solutions of a third order equation when a de Sitter quantum universe is considered. We finally discuss the limits of this approach to quantum cosmology because the extension to equations with arbitrary potentials can become extremely complicated for potentials given by algebraic polynomials of degree greater than two and therefore also for potentials expressible by arbitrary functions.

Despite advances in algorithms and computational platforms, de-novo genome assembly remains a challenging process. Due to the constant innovation in sequencing technologies (Sanger, SOLiD, Illumina, 454, PacBio and Oxford Nanopore), genome assembly has evolved to respond to the changes in input data type. This paper includes a broad and comparative review of the most recent short-read, long-read and hybrid assembly techniques. In this review, we provide (1) an algorithmic description of the important processes in the workflow that introduces fundamental concepts and improvements; (2) a review of existing software that explains possible options for genome assembly; and (3) a comparison of the accuracy and the performance of existing methods executed on the same computer using the same processing capabilities and using the same set of real and synthetic datasets. Such evaluation allows a fair and precise comparison of accuracy in all aspects. As a result, this paper identifies both the strengths and weaknesses of each method. This comparative review is unique in providing a detailed comparison of a broad spectrum of cutting-edge algorithms and methods.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Obesity is a risk factor for the development of gestational diabetes mellitus (GDM). However, the most optimal type of nutritional intervention to prevent GDM in high-risk women is not clearly defined. This study investigates if nutritional treatment based on the Mediterranean diet (MedDiet) before 12th gestational week (GW) in women at high risk due to a body mass index (BMI)≥25kg/m2, reduces the rate of GDM and metabolic syndrome (MetS) at 3 years postpartum. We performed a post-hoc analysis of the San Carlos Gestational Prevention Study. A total of 735 women with BMI≥25kg/m2 were evaluated between 2015-2018, 246 in standard diet control group (CG) and 489 in MedDiet intervention group (IG). The rate of GDM was significantly lower in IG compared to CG (25.1%vs31.7%;p=0.037). Postnatal follow-up was completed by 141 women in CG (57%) and 312 women in IG (64%). At 3 years postpartum, we observed a reduction (relative risk 95% confidence interval) in the rates of impaired fasting glucose (IFG) (0.51 (0.28-0.92);p=0.019), obesity (0.51 (0.28-0.92),p=0.041), waist circumference (WC)≥89.5cm (0.54 (0.31-0.94);p=0.022) and MetS (0.56 (0.33-0.94);p=0.003). MedDiet reduces the rate of GDM and postpartum MetS in women with BMI)≥25kg/m2, suggesting that its implementation should be routinely recommended from the first GWs.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Nitrates can cause severe ecological imbalances in aquatic ecosystems, with considerable consequences for human health. Therefore, monitoring this inorganic form of nitrogen becomes essential for any water quality management structure. This research aimed at developing a novel Nitrate Portable Measurement System (NPMS) for monitoring nitrate concentrations in water samples. NPMS is a reagent-free ultraviolet system developed using low-cost electronic components. Its operation principle is based on Beer-Lambert law for measuring Nitrate concentrations in water samples through light absorption in the spectral range 295-315 nm. The system is equipped with ready to use ultraviolet sensor, Light Emission Diode (LED), op-amp, microcontroller, liquid crystal display, quartz cuvette, temperature sensor, and battery. All the components are assembled in a 3D-printed enclosure box which allows a very compact self-contained equipment, with high portability, enabling field and near real time measurements. The proposed methodology and the developed instrument were used to analyse multiple nitrate standard solutions. The performance was evaluated in comparison with the Nicolet Evolution 300, a classical UV-Vis spectrophotometer. The results demonstrate a strong correlation between the retrieved measurements by both instruments within the investigated spectral band and for concentrations above 5 mg NO3- /l.

Soil management in orchards can have several economic and environmental implications. In this study, three different soil management systems were compared in a dry-farmed olive grove: conventional tillage (Tillage), glyphosate-based herbicide (Herbicide) and Sheep Walking. The experiment lasted eleven years (2011-2022) and was carried out after a previous trial conducted on the same plot with the same treatments and duration (2001-2011). However, in the earlier trial, the Herbicide and Sheep Walking treatments switched positions in the plot, while the tillage treatment remained in its original place. The average total accumulated olive yields between 2011 and 2022 were 225.1, 230.9, and 245.0 kg tree–1 for the Sheep Walking, Tillage, and Herbicide treatments, respectively. However, no significant differences were observed between the treatments. The levels of total organic carbon in the soil, measured in samples collected in the last year of the study, were 41.3, 33.7, and 37.3 g kg–1, respectively for the same treatments. These findings indicated that the Tillage treatment exhibited lower soil organic matter content and reduced bioavailability of some nutrients, which raises concerns about its sustainability. On the contrary, employing Sheep Walking with an appropriate stocking rate, effectively controlling vegetation in the spring, ensured favourable soil properties and olive yields comparable to the other treatments. Moreover, the Sheep Walking approach provides supplementary advantages to the farmer, including revenue from the sale of animal products and the opportunity to transition to organic farming systems, which better align with the preferences of contemporary societies.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there are few data available on the description of parasites circulating in this area, especially on protozoan belonging to the phy-lum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on Oxford Nanopore Technologies sequencing platform using the 18S gene of fourteen Apicomplexa-positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify as Apicom-plexa-positive 10 samples out of 14 and reveal the presence of co-carriages. The same samples were also sequenced with Illumina platform, for validation purposes. On samples identified as Apicomplexa-positive by both platforms, a strong positive correlation at up to genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detec-tion, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.