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Problem-solving competency is important not only in many careers but also in everyday life. Successful problem solvers regulate their cognitive processes and emotions. Our research aimed to study the impact of gamified problem sheets designed in Seppo on self-regulated learning skills. The intervention was carried out with second-year students in the specialization of Primary and Preschool Pedagogy. The research tool was a self-regulated problem-solving scale that was used as a pre- and posttest. In the experimental group, gamification lasted for 6 weeks. The game had 3 levels and the players could choose exercises from any level they wished. The results show that the gamified task sheet helped students to stay motivated and made problem-solving more enjoyable, but decreased some of their self-regulated processes, such as checking the correctness of the solution or searching for more solutions. This decrease could be explained by some psychological theories, the game elements, and the rules of the Seppo gamified problem sheets used in the intervention. On the basis of the conclusions, the role of some gamification aspects in developing different self-regulated processes can be identified, and the importance of a careful design of gamified problem sheets is highlighted.

Background: The birth weight of an infant is a significant determinant of morbidity. Birth weight measurement is not always feasible in developing countries thus necessitating alternative measurements as surrogates. Objective: This study was undertaken to determine the most appropriate maximum thigh cir cumference (MTC) measurements corresponding to birth weights of

Summary: A retrospective review of major congenital malformations in 353 newborns delivered at the Lagos University Teaching Hospital during a 10-year period (1981-1990), has revealed an overall incidence of 15.8 per 1000 total births, while the contribution of such malformations to perinatal mortality was 11.9 per cent. Gastrointestinal, central nervous and musculo-skeletal system malforma tions were the commonest seen with individual incidences of 3.9, 3.5 and 2.1 per 1000 total births, respectively. Unclassified congenital malformations had the highest case fatality while central nervous system malformations constituted the commonest cause of death among the malformed neonates. The pattern and incidence of congenital malformations at the hospital would appear to have remained substantially unchanged in the last three decades.

Objective: To determine the perinatal mortality rate in Lagos University Teaching Hospital at the close of the 20th century. Materials and Methods: Routinely collected data from the Departments of Obstetrics & Gynaecology and Paediatrics from January 1996 to December 2000, were analysed. The data included total deliveries, stillbirths and early neonatal deaths. Results: A total of 6,759 deliveries, including 163 multiple pregnancies, occurred during the period. There were 573 perinatal deaths comprising 471(69.7/1000) stillbirths and 102(16.2/ 1000) early neonatal deaths. Autopsy was performed on 115 of the 573 deaths resulting in a perinatal autopsy rate of 20.1 percent. The overall perinatal mortality rate was 84.8/1000 while the perinatal mortality rate for singletons was 83/1000. Analysis of the deaths by the Wigglesworth classification showed that 46.6 percent of the deaths were normally formed macerated stillbirths, 38.7 percent were due to asphyxial conditions and 8.9 percent were attributed to conditions associated with immaturity. Lethal congenital malformations accounted for 3.7 percent while other specific conditions were responsible for 2.1 percent of the deaths. Conclusion: These rates are still very high and strategies to decrease perinatal mortality will need to focus on antenatal and intrapartum obstetric care. All those involved in obstetric and neonatal care require regular education on the need for prompt identification of problems, early referral and prompt intervention.

Background: Vaccine preventable diseases still account for a large proportion of childhood morbidity and mortality in children less than five of age. The decline in immunization coverage over the years has worsened this resulting in the re-emergence of hitherto controlled infections such as diphtheria. Objective: To review the presentation, management and outcome of cases of probable diphtheria seen at the children emergency centre at the Lagos University Teaching Hospital. Methods: The hospital records of all cases of suspected diphtheria adrnitted from September 2007 to September 2008 were reviewed retrospectively. The biodata, presenting complaints, duration of complaints, immunization status, management and outcome were analyzed. Results: Five cases of probable diphtheria were admitted during the study period. Two of the children died, two survived and one absconded. Three of the children had three doses each of diphtheria, pertussis and teranus (DPT) toxoid immunization but none had the 18month booster dose. Diphtheria specificantitoxin was not available for use in the management of any of the cases neither was bacteriological confirmation possible. Conclusion: Efforts to increase immunization coverage rates should be intensified and a policy to include an 18-month booster dose as part of the routine immunization in the National Programme on Immunization may be beneficial. It is recommended that diphtheria specific antitoxin be made available in the country in the event of cases with similar presentation.

Background: Infant and childhood mortality has remained high in developing countries like Nigeria with only marginal reductions achieved over the past two decades despite several interventions to reduce morbidity and mortality from the common causes of death in children. It is therefore important to examine the current pattern of mortality in children and compare it with previous reports from this centre so as to determine if newer interventions are needed or if these current interventions need to be strengthened for more effective reduction in childhood mortality. Objective:The aim of this study was to examine the pattern of childhood mortality in the childrenemergency centre of the Lagos University Teaching Hospital (LUTH). Materials and Methods: Admission and discharge records from October 2007 to November 2 0 0 8 were reviewed retrospectively, the age, sex, diagnosis and duration of hospital stay before death were analyzed. Results: Four hundred and forty six children (446) out of the 4031 children admitted during the study Period died, giving a mortality of 11.1%. More than half of the deaths (55.4%) occurred within 24hours of arrival in hospital. Neonates accounted for 54.7% of deaths. The common causes of death in the neonates were perinatal asphyxia (36.1%) , neonatal jaundice (21.3%), prematurity (16.3%) and septicaemia (11.5%), while in the older children anaemia , septicaemia, severe malaria and acute respiratory illnesses were the commonest conditions accounting for 22.6%, 16.3%, 12.1% and 9.9% of deaths respectively. Conclusion: Childhood mortality in LUTH is still high with majority of deaths occurring in infancy especially in the neonatal period. Efforts to prevent perinatal asphyxia, the most common causeof death in the neonatal period, should be intensified and education on the prevention, early identification and anagement of conditions such as neonataljaundice, malaria, anaemia and acute respiratory illnesses should also be strengthened.

Background: Despite a global decline in mortality and morbidity from measles in the last decade, outbreaks continue to occur in some parts of the world including Nigeria. Objective: To determine antibody response to routine measles vaccination in Nigerian children and evaluate vaccine potency. Methods: A prospective study of 234 children selected from 3 health centres in an urban area of Lagos, Nigeria. Blood was obtained before and 8-12 weeks after routine vaccination with Edmonston- Zagreb strain of measles vaccine. Antibodies were detected using the measles antibody neutralization test. Reconstituted vaccines samples were analysed for potency on monolayers of Vero slam cells in 96-well tissue culture plates. Results: Twenty seven(11.5%) had pre-vaccination antibodies. Seroconversion rate among the 195 who returned for post vaccination sampling was 69.2%: It was however 74.2% in children with no pre-vaccination antibodies compared to 17.6% in those with antibodies. (p

Problem-solving competency is important not only in many careers but also in everyday life. Successful problem solvers regulate their cognitive processes and emotions. Our research aimed to study the impact of gamified problem sheets designed in Seppo on self-regulated learning skills. The intervention was carried out with second-year students in the specialization of Primary and Preschool Pedagogy. The research tool was a self-regulated problem-solving scale that was used as a pre- and posttest. In the experimental group, gamification lasted for 6 weeks. The game had 3 levels and the players could choose exercises from any level they wished. The results show that the gamified task sheet helped students to stay motivated and made problem-solving more enjoyable, but decreased some of their self-regulated processes, such as checking the correctness of the solution or searching for more solutions. This decrease could be explained by some psychological theories, the game elements, and the rules of the Seppo gamified problem sheets used in the intervention. On the basis of the conclusions, the role of some gamification aspects in developing different self-regulated processes can be identified, and the importance of a careful design of gamified problem sheets is highlighted.

Neovascularization is implicated in the pathology of retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD), which are the leading causes of blindness worldwide. In our work, we analyzed how heme released during hemorrhage affects hypoxic response and neovascularization. Our retrospective clinical analysis demonstrated, that hemorrhage was associated with more severe retinal neovascularization in ROP patients. Our heme-stimulated human retinal pigment epithelial (ARPE-19) cell studies demonstrated increased expression of positive regulators of angiogenesis, including vascular endothelial growth factor-A (VEGFA), a key player of ROP, DR and AMD, and highlighted the activation of the PI3K/AKT/mTOR/VEGFA pathway involved in angiogenesis in response to heme. Furthermore, heme decreased oxidative phosphorylation in the mitochondria, augmented glycolysis, facilitated HIF-1α nuclear translocation, and increased VEGFA/GLUT1/PDK1 expression suggesting HIF-1α-driven hypoxic response in ARPE-19 cells without effecting the metabolism of reactive oxygen species. Inhibitors of HIF-1α, PI3K and suppression of mTOR pathway by clinically promising drug, rapamycin, mitigated heme-provoked cellular response. Our data proved that oxidatively modified forms of hemoglobin can be sources of heme to induce VEGFA during retinal hemorrhage. We propose that hemorrhage is involved in the pathology of ROP, DR, and AMD.

Summary: A male infant with isolated prenatal hydrocephalus whose clinical features and family history were consistent with the diagnosis of X-linked hydrocephalus (Bickers-Adams syndrome) is described. Clinical, sero logical and radiological evidence for other causes of congenital hydrocephalus were lacking in the infant. Since the identification of an X-linked hydrocephalus has important consequences for genetic counselling, analysis of the family history of any male infant with isolated hydrocephalus is very important.

We report a case of infantile hypertrophic pyloric stenosis in a ten-week old, third-born girl. She presented with sudden onset of non-projectile vomiting of non-bilious material. The vomiting occurred consistently a few minutes after feeds. No peristaltic waves were seen in the abdomen. The typical olive-shaped mass was only felt under general anaesthesia despite repeated examinations. Definitive diagnosis was made with the aid of barium studies and confirmed intra-operatively. This case emphasizes the need for a high index of suspicion for infantile pyloric stenosis in a persistently vomiting infant irrespective of sex, birth order, presence or absence of projectile nature of vomiting, visible peristalsis or palpable abdominal mass.

Summary: A prospective study of neonatal septicaemia at the newborn unit of Lagos University Teaching Hospital over a ten-month period has revealed an overall rate of 35 per 1000 live births. The commonest causative organism was Klebsiella pneumoniae, be ing responsible for 45 percent of the isolates, a finding that was at variance with that of a study carried out in the same institution over 20 years earlier which showed that E coli was the com monest organism. Staphylococcus aureus and coagulase negative staphylococcus were second and third with 12 percent and nine percent, respectively. Klebsiella pneumoniae was resistant to the commonly used and readily available antibiotics such as gentamicin; conversely, all strains of the organism were sensitive to ofloxacin. While further tests are being carried out on the safety of ofloxacin in neonatal practice, we suggest that, as recommended by others, a combina tion of cloxacillin and amikacin or tobramycin should be the initial therapy in neonatal septicaemia, while awaiting results of bacterial cultures.

Non-aerated compost tea (CT) was prepared from compost derived from rockweed (Ascophyllum nodosum) and fish (cod, common ling, haddock, saithe) residues that fermented in water. Electrical conductivity, pH, concentrations of dry matter, ash, C, macronutrients (N, P, K, Ca, and Mg), and micronutrients (Cu, Fe, Mn, Mo, and Zn) of CT prepared under different fermentation conditions were measured. The effects of process factors, i.e., water/compost mass ratio (4.2–9.8 g/g) and fermentation time (4.2–9.8 days = 100–236 h), on the physicochemical properties of CT were quantified using quadratic polynomial models. CT obtained at optimal levels of process factors (4.2 g/g and 5.6 days = 134 h) was tested for lettuce seed germination and seedling growth. Diluted CT (25% CT + 75% ultrapure water) improved seedling growth while achieving a high germination percentage (97%).

From 2015 to 2023, we conducted a comprehensive study in the 11,893-hectare hunting area managed by the Marcal-Bitvaközi Hunting Company, characterised by its substantial wild boar population. The research was carried out across various settings, including a free-range wild boar garden during large-scale hunts and free-living areas during individual hunts. We examined 216 wild boars in total, with 173 individuals from free-living areas and 43 from free-range areas. Throughout the sample collection process, we encountered numerous technical challenges that are infrequently detailed in the professional literature, often mentioned only tangentially. This oversight in existing publications neglects the significance of addressing field sampling difficulties, which are crucial for ensuring the precision and accuracy of research. This paper details the equipment requirements, sampling methodologies, and practical solutions to streamline fieldwork. While our primary focus was on endoparasitic infections of the stomach and small intestine, the described methodologies and findings are broadly applicable to research involving all internal organs.

Mental calculation is an important competence in everyday life, and it is essential especially for a future primary school teacher. In this research the efficacy of different games, as didactic games, board-games, and mobile games for developing mental calculation skills were studied. The results shows that didactic games and board-games were efficient in developing mental calculation skills when the operations are presented visually, and the didactic games and mobile games, when the operations are presented orally. In case of visually presented operations there is no statistically significant difference between the effects of the three type of games. In case of orally presented operation the didactic games had a significantly higher effect on developing mental calculation skills as the other two type of games.

Abstract The Spike glycoprotein of SARS-CoV-2 mediates viral entry into the host cell via the interaction between its receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2). Spike RBD has been reported to adopt two primary conformations, a closed conformation in which the binding site is shielded and unable to interact with ACE2, and an open conformation that is capable of binding ACE2. Many structural studies have probed the conformational space of the homotrimeric Spike from SARS-CoV-2. However, how sample buffer conditions used during structural determination influence the Spike conformation is currently unclear. Here, we systematically explored the impact of commonly used detergents on the conformational space of Spike. We show that in the presence of detergent, the Spike glycoprotein predominantly occupies a closed conformational state during cryo-EM structural determination. However, in the absence of detergent, such conformational compaction was neither observed by cryo-EM, nor by single-molecule FRET designed to visualize the movement of RBD in solution in real-time. Our results highlight the highly sensitive nature of the Spike conformational space to buffer composition during cryo-EM structural determination, and emphasize the importance of orthogonal biophysical approaches to validate the structural models obtained.

Enhancing our comprehension of mRNA vaccines may facilitate the future design of novel vaccines aimed at augmenting immune protection while minimising reactogenic responses. Before this design is carried out, it is important to determine whether adaptive immunity correlates with the reactogenicity profile of vaccines. We studied a large cohort that was vaccinated with mRNA vaccines to answer this question. This was an observational study with real-world data. Reactogenicity data were obtained from the VigilVacCOVID study. Immunogenicity (humoral and cellular) data were retrieved from health records. One main population (n = 215) and two subpopulations were defined (subpopulation 1, n = 3563; subpopulation 2, n = 597). Sensitivity analyses were performed with subpopulations 1 and 2 to explore the consistency of results. We analysed the association of the intensity and types of adverse reactions with the development and quantity of elicited antibody titres. As an exploratory analysis in subpopulation 1, we assessed the association between reactogenicity and cellular immunogenicity. A higher incidence of fever, malaise, and myalgia including severe cases was significantly associated with the development and quantity of positive antibody titres. No significant findings were observed with cellular immunity. We observed a positive association between immunogenicity and reactogenicity. These findings can be relevant for the future development of our understanding of how mRNA vaccines function.

Summary: Triple-negative breast cancer (TNBC) is a heterogeneous disease with limited treatment options. To characterize TNBC heterogeneity, we defined transcriptional, epigenetic, and metabolic subtypes and subtype-driving super-enhancers and transcription factors by combining functional and molecular profiling with computational analyses. Single-cell RNA sequencing revealed relative homogeneity of the major transcriptional subtypes (luminal, basal, and mesenchymal) within samples. We found that mesenchymal TNBCs share features with mesenchymal neuroblastoma and rhabdoid tumors and that the PRRX1 transcription factor is a key driver of these tumors. PRRX1 is sufficient for inducing mesenchymal features in basal but not in luminal TNBC cells via reprogramming super-enhancer landscapes, but it is not required for mesenchymal state maintenance or for cellular viability. Our comprehensive, large-scale, multiplatform, multiomics study of both experimental and clinical TNBC is an important resource for the scientific and clinical research communities and opens venues for future investigation.

Ascaris suum and Macracanthorhynchus hirudinaceus cause a large loss of yield in farm animals as well as in free-living and captive wild boar herds, thereby causing economic damage. This study compared A. suum and M. hirudinaceus infections in free-ranging and captive wild boars (Sus scrofa) in Hungary. The authors measured the A. suum and M. hirudinaceus infections of a 248-hectare wild boar garden and an 11,893-hectare free-living wild boar herd in the sample area. In all cases, samples were collected from shot wild boars. In total, 216 wild boars were examined from June 2015 to June 2023 in Hungary. Of the 173 dissected wild boars from the wild, 57 (32.9%) were infected with A. suum, while 30 (69.8%) of the 43 individuals from the captive area were infected. The prevalence of M. hirudinaceus in the free-living area population was 9.25% (16 wild boars), while that of the captive population was 34.89% (15 wild boars). In the case of the examined helminths, the captive herd was 36.9% more infected than the herd living in the open area.

The main purpose of this study is to assess the farm-level economic consequences of the planned introduction of a ban on farrowing crates for sows in the EU pig sector, being a response by the European Commission to the ‘End the Cage Age’ Initiative. The impact assessment was carried out in three stages: farm-level analyses based on 225 farm surveys carried out in EU member states and expert consultations, assessments for five alternative scenarios, and the aggregation (scaling-up) of the scenario analysis to the EU-27 sectoral impact. Our findings indicate that the ban on farrowing crates is expected to cause a decrease in the sow population by 21–23%, depending on the scenario, and piglet output in the EU owing to increased sow space requirements, a reduction in production efficiency, and a significant demand for investments. The transition to alternative farrowing systems will lead to increased variable costs related to the farrowing period, namely, veterinary expenses, labour costs, and sow feed costs, as well as expenses associated with higher piglet mortality and increased sow replacement rates. The lower density, resulting from the larger space allowance per sow in free-farrowing systems (approximately 5.5 m2 in free farrowing with temporary confinement and 7 m2 in systems without confinement) will also cause fixed costs per unit (per sow or piglet) to rise in proportion to the decline in the sow herd. Expressed as a percentage of the total production costs per piglet, we can expect a 6–10% increase in the total production costs. The implementation of free-farrowing systems on pig farms will necessitate investments in the modernisation of the existing buildings and new pens for sows. Depending on the scenario, the value of investments ranged from 3.8 to 6.7 billion EUR, at 2021 prices. It should be recognised that beyond the actual improvement in the welfare of sows, there are lingering concerns, including increased production costs, higher piglet mortality rates, and heightened risks to employees. It is essential to consider providing financial assistance to support farms in making a smooth transition to the new systems, as well as an extended transition period to ensure a painless shift.

SHP2 is an important human tyrosine phosphatase with key roles in cancer, immune responses and insulin signaling. Here, the authors explore its substrate recognition mechanism in molecular detail and uncover a complex regulatory mechanism for this enzyme that marks specific target sites for dephosphorylation.

The development of the brain, as well as mood and cognitive functions, are affected by thyroid hormone (TH) signaling. Neurons are the critical cellular target for TH action, with T3 regulating the expression of important neuronal gene sets. However, the steps involved in T3 signaling remain poorly known given that neurons express high levels of type 3 deiodinase (D3), which inactivates both T4 and T3. To investigate this mechanism, we used a compartmentalized microfluid device and identified a novel neuronal pathway of T3 transport and action that involves axonal T3 uptake into clathrin-dependent, endosomal/non-degradative lysosomes (NDLs). NDLs-containing T3 are retrogradely transported via microtubules, delivering T3 to the cell nucleus, and doubling the expression of a T3-responsive reporter gene. The NDLs also contain the monocarboxylate transporter 8 (Mct8) and D3, which transport and inactivate T3, respectively. Notwithstanding, T3 gets away from degradation because D3’s active center is in the cytosol. Moreover, we used a unique mouse system to show that T3 implanted in specific brain areas can trigger selective signaling in distant locations, as far as the contralateral hemisphere. These findings provide a pathway for L-T3 to reach neurons and resolve the paradox of T3 signaling in the brain amid high D3 activity.

Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

BackgroundHumoral and cellular immune responses are known to be crucial for patients to recover from COVID-19 and to protect them against SARS-CoV-2 reinfection once infected or vaccinated.ObjectivesThis study aimed to investigate humoral and T cell responses to SARS-CoV-2 vaccination in patients with autoimmune diseases after the second and third vaccine doses while on rituximab and their potential protective role against reinfection.MethodsTen COVID-19-naïve patients were included. Three time points were used for monitoring cellular and humoral responses: pre-vaccine to exclude virus exposure (time point 1) and post-second and post-third vaccine (time points 2 and 3). Specific IgG antibodies were monitored by Luminex and T cells against SARS-CoV-2 spike-protein by ELISpot and CoVITEST. All episodes of symptomatic COVID-19 were recorded.ResultsNine patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and one with an undifferentiated autoimmune disease were included. Nine patients received mRNA vaccines. The last rituximab infusion was administered for a mean (SD) of 15 (10) weeks before the first vaccine and six patients were CD19-B cell-depleted. After a mean (SD) of 19 (10) and 16 (2) days from the second and third vaccine dose, IgG anti-SARS-CoV-2 antibodies were detected in six (60%) and eight (80%) patients, respectively. All patients developed specific T cell responses by ELISpot and CoVITEST in time points 2 and 3. Previous B cell depletion correlated with anti-SARS-CoV-2 IgG levels. Nine (90%) patients developed mild COVID-19 after a median of 7 months of the third dose.ConclusionRituximab in patients with autoimmune diseases reduces humoral responses but does not avoid the development of T cell responses to SARS-CoV-2 vaccination, which remain present after a booster dose. A steady cellular immunity appears to be protective against subsequent reinfections.

This manuscript summarizes the outcomes of the 6th EuroSpeleo Protection Symposium. Special emphasis was laid on presenting and discussing monitoring activities under the umbrella of the Habitats Directive (EU Council Directive 92/43/EEC) for habitat type 8310 "Caves not open to the public" and the Emerald Network. The discussions revealed a high level of variation in the currently conducted underground monitoring activities: there is no uniform definition of what kind of underground environments the "cave" habitat should cover, how often a specific cave has to be monitored, and what parameters should be measured to evaluate the conservation status. The variation in spatial dimensions in national definitions of caves further affects the number of catalogued caves in a country and the number of caves to be monitored. Not always participants are aware of the complete national monitoring process and that data sets should be freely available or easily accessible. The discussions further showed an inherent dilemma between an anticipated uniform monitoring approach with a coherent assessment methodology and, on the contrary, the uniqueness of caves and subterranean biota to be assessed – combined with profound knowledge gaps and a lack of resources. Nevertheless, some good practices for future cave monitoring activities have been identified by the participants: (1) Cave monitoring should focus on bio- and geodiversity elements alike; (2) Local communities should be involved, and formal agreements envisaged; (3) Caves must be understood as windows into the subterranean realm; (4) Touristic caves should not be excluded ad-hoc from regular monitoring; (5) New digital tools and open FAIR data infrastructures should be implemented; (6) Cave biomonitoring should focus on a large(r) biological diversity; and (7) DNA-based tools should be integrated. Finally, the importance of the 'forgotten' Recommendation No. 36 from the Bern Convention as a guiding legal European document was highlighted.

This paper focuses on optimizing resource management strategies in chimeric antigen receptor (CAR) T-cell therapies using reinforcement learning (RL). CAR T-cell therapy is an innovative and promising treatment within the field of immunotherapy, which is based on the isolation of patients' own T-cells, genetically modifying these cells to express a CAR for tumor recognition, cultivating and expanding these T cells and infusing them back to the patient. These therapies require several reusable but scarce resources, including special equipment, such as the bioreactor that is used to expand CAR T cells, and medical resources, such as the hospital staff, e.g., doctors and nurses. Considering the stochastic nature of medical procedures and the production of CAR T cells, the scheduling of the therapies and the efficient allocation of the required resources pose a significant challenge inside the hospital environment. Here, we propose a derivative-free policy gradient algorithm that utilizes a simulation model of the therapy, built using real-world data, to obtain efficient control policies for the resource management problem. The proposed method is designed to minimize the expected number of deviations from the therapy protocol as well as the expected overall completion time of the therapies for every patient. The effectiveness of the proposed resource management approach is demonstrated via simulation experiments. [ABSTRACT FROM AUTHOR]

The training of a music teacher's voice, via the examples in his own culture can contribute to getting better results in music education. Therefore, it is believed that transition to Contemporary Turkish Music and then to universal music from our traditional music may be much easier. Accordingly, the use of national resources in voice training is seen to be quite important. In this context, Bursa Folk Songs, whose piano accompanied arrangements were prepared for voice training, and also were trained for one semester by the voice training instructors of three different departments of music education that train music teachers, and then those instructors were interviewed to evaluate the contributions of prepared piano accompanied Bursa Folk Songs for voice training to the field. As a result of the survey, it has been determined that music teacher candidates need to have an extensive repertory, full of examples from their own culture, the repertory of piano-accompanied folk songs is not enough in quantity, and piano accompanied folk songs have both technical and musical contributions during the voice training process.

BACKGROUND: Two jewel beetle species native to Europe, the cypress jewel beetle, Lamprodila (Palmar, Ovalisia) festiva L. (Buprestidae, Coleoptera), and the sinuate pear tree borer, Agrilus sinuatus Olivier (Buprestidae, Coleoptera), are key pests of ornamental thuja and junipers and of orchard and ornamental rosaceous trees, respectively. Although chemical control measures are available, due to the beetles’ small size, agility, and cryptic lifestyle at the larval stage, efficient tools for their detection and monitoring are missing. Consequently, by the time emerging jewel beetle adults are noticed, the trees are typically significantly damaged. METHODS: Thus, the aim of this study was to initiate the development of monitoring traps. Transparent, light green, and purple sticky sheets and multifunnel traps were compared in field experiments in Hungary. RESULTS: Light green and transparent sticky traps caught more L. festiva and A. sinuatus jewel beetles than non-sticky multifunnel traps, regardless of the larger size of the colored surface of the funnel traps. CONCLUSIONS: Although light green sticky sheets turned out to be optimal for both species, using transparent sheets can reduce catches of non-target insects. The key to the effectiveness of sticky traps, despite their reduced suitability for quantitative comparisons, may lie in the behavioral responses of the beetles to the optical features of the traps.

The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination.