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Abstract The lysine-specific histone demethylase 1 A (LSD1) is involved in antitumor immunity; however, its role in shaping CD8 + T cell (CTL) differentiation and function remains largely unexplored. Here, we show that pharmacological inhibition of LSD1 (LSD1i) in CTL in the context of adoptive T cell therapy (ACT) elicits phenotypic and functional alterations, resulting in a robust antitumor immunity in preclinical models in female mice. In addition, the combination of anti-PDL1 treatment with LSD1i-based ACT eradicates the tumor and leads to long-lasting tumor-free survival in a melanoma model, complementing the limited efficacy of the immune or epigenetic therapy alone. Collectively, these results demonstrate that LSD1 modulation improves antitumoral responses generated by ACT and anti-PDL1 therapy, providing the foundation for their clinical evaluation.

Abstract This research addresses the issue of the heritage preventive conservation in the perspective of energy sustainability, for contributing to the achievement of the Sustainable Development Goals (SDGs) and towards the EU Green Deal. The study analyses and compares four cases associated with different microclimate thresholds as suggested by the standard EN 16893:2018 (Cases 1–3) and as derived from the outputs of three degradation models for preserving paper, wood, and canvas paintings (Case 4). Weather-based indices (degree and gram days) were calculated to estimate trends in the potential energy demand of collection facilities in three European cities belonging to different Köppen-Geiger climate zones (Cfb, Csa, and Dfb), under recent past (1981–2010) and near/far future climate scenarios (2021–2050 and 2071–2100) from two Shared Socioeconomic Pathways (SSP2-4.5 and SSP5-8.5). The findings suggest that adapting facilities’ management strategies to focus on collections preservation can facilitate the achievement of 5 out of 17 SDGs, offering a viable alternative to costly energy retrofits and encouraging the development of shared solutions for similar facilities in the same climate zone. The results can contribute to inform the revision of EN 16893 and to face major challenges such as the preservation of paper collections in southern latitudes.

After Jeanette Wing in 2006 described computational thinking (CT) as a fundamental skill for everyone just like reading or arithmetic, it has become a widely discussed topic all over the world. Computational thinking is a problem-solving skill set that is used to tackle problems in computer science. However, these skills, such as pattern recognition, decomposition, abstraction, generalization, and algorithmic thinking, are useful in other domains, as well. This study focuses on the use of CT skills to approach complex linguistic learning tasks in the foreign language classroom. To foster these problem-solving skills, an innovative method is used. The authors take advantage of computer science (CS) models (e.g. Unified Modeling Language -- UML) and transform them into a teaching and learning tool. This paper describes the design and implementation of a survey used to detect students' use of learning strategies that are linked to computational thinking. This survey is an instrument used in a multiple-case study and was administered at the beginning of the interventions. The participants of the study were learners of English and Spanish (n=66) from two secondary schools. Results indicated that the students were medium to low users of learning strategies that demand problem-solving skills related to computational thinking. Differences by gender were also found, with females reporting higher use of learning strategies than males. To conclude, the study showed a low use of strategies among students and highlighted the importance of introducing students to learning strategies and fostering skills needed for future professional life.

ABSTRACT: Efficient poultry production can be accomplished using combined technologies. A combination of in ovo and ethno-veterinary technologies can deliver significant benefits, including reduced labour and production costs. This study evaluated the effect of in ovo administration of soursop leaf extract (SLE) on the hatching performance and physiology of Noiler chicks. A total of 550 eggs were incubated, and 460 fertile eggs were randomly distributed into 4 groups with 3 replicates on the 18th d of incubation. The eggs were then injected with 0.75 µg SLE, 1.5 µg SLE, and saline solution (negative control) at a rate of 0.2 ml in the air space. The noninjected group served as the positive control. At the end of the hatching period, the various groups were evaluated for embryo mortality, hatchability, hatch duration, organ weight, serum biochemistry, and chick quality. The results showed no significant differences (P > 0.05) in embryonic mortality, hatchability, organ weight, total protein, albumin, globulin, aspartate aminotransferase, alanine aminotransferase, and glucose among the treatment groups. However, chick weight, chick quality, and serum triglyceride levels were significantly (P < 0.05) higher in the extract-injected group. Additionally, incubation and hatch times were significantly lower (P < 0.05) in the SLE group compared to the other groups. In ovo administration of soursop leaf extract resulted in reduced incubation duration, hatch time, and embryo mortality. In conclusion, the in ovo injection of SLE improved hatch performance and chick quality.

Customer satisfaction with the provided transport services is closely related to the ability of management to respond flexibly to process changes and maintain the required quality. QRQC is also considered as a method for troubleshooting and it can be applicable in many different areas along rail transport. The innovative qualitative approach QRQC highlights the principle of thorough analysis of the causes of problems. After a problem situation occurs in a traffic operation, it is necessary to proceed according to the specified sequence in order to reduce the undesirable influence in the shortest possible time. The article deals with the possibility of applying this method to rail transport processes.

Abstract Background Soil structure is a key indicator of the functioning of soil processes in grasslands, which is influenced by site conditions and management. Methods In this study, we investigated soil structure and its relationship with root growth in 31 Leptosols under different grassland management intensities using X‐ray microcomputed tomography. A close relationship between land use intensity, soil structure, and root growth was observed. Results Our results show that land use type affects root development and soil structure. Pastures had more developed roots and more structured soils than meadows and mown pastures. However, all pastures were unfertilized, while meadows and mown pastures had both fertilized and unfertilized plots. Although no significant differences were found in the unfertilized plots, sample size was limited. In particular, fertilization negatively affected root growth and soil structure, resulting in significant differences between fertilized and unfertilized grasslands. Mowing frequency also had an effect on soil physics, but to a much lesser extent than fertilization. Conclusions Increased land use intensity, characterized by increased fertilization and more frequent mowing, reduces root growth and adversely affects soil structure. Therefore, X‐ray microcomputed tomography is a suitable method to investigate the relationship between soil structure and roots in the soil.

Newborns admitted to neonatal intensive care units (NICU) are at increased risk of health care-associated infections. Serratia marcescens represent the third most common pathogen in NICU outbreaks. Here we present an outbreak investigation performed using Whole Genome Sequencing (WGS) analyses and the control measures implemented to limit the spread of S. marcescens in the NICU of an Italian hospital. In February 2023 S. marcescens was isolated from six newborns, when in 2022 this pathogen was isolated only from two samples in the same ward. Measures for infection prevention were adopted. Routinary surveillance screening, performed with rectal swabs collected at admission and weekly thereafter, was implemented to search for S. marcescens presence. Environmental samples were collected. All the isolates, obtained from the conjunctival swab of six newborns, from rectal swab of two newborns who did not develop infections, as well as from the aerators of two faucets, were sequenced. WGS analyses showed no correlation between the isolates from newborns and environmental isolates. The implementation of the measures for infection prevention and control had enabled us to successfully control the outbreak within a short period. WGS analyses proved to be crucial in outbreak investigation to limit the spreading of the pathogens.

Diese Arbeit widmet sich der Integration und den Auswirkungen von generativer künstlicher Intelligenz (KI) im Bildungswesen. Es werden eine Vielzahl von praktischen Anwendungsfällen vorgestellt, in denen KI den Unterricht unterstützen kann – von der Unterrichtsvorbereitung über die Arbeit mit Texten, bis hin zur Förderung von Kreativität und Sprachunterricht. Zudem wird auf die Notwendigkeit einer kritischen Auseinandersetzung mit KI und die Entwicklung unterstützender Maßnahmen für eine verantwortungsvolle Integration in den Bildungsalltag hingewiesen. Abschließend wird hervorgehoben, dass der Einsatz von KI im Bildungsbereich das Potenzial hat, den Unterricht zu bereichern und individuelle Lernwege zu unterstützen. Weiters wird betont, dass die Integration von KI in das Bildungswesen eine kritische und verantwortungsvolle Herangehensweise erfordert. Die Autorinnen unterstreichen die zentrale Rolle der Lehrkräfte bei der Nutzung des Potenzials von KI, während gleichzeitig die Herausforderungen und ethischen Bedenken berücksichtigt werden müssen.

Background Good oral hygiene is crucial for preventing dental caries and periodontal diseases. However, proper and regular application of oral hygiene practices requires adequate knowledge. In recent years, the internet has become one of the most popular places to find health-related information, necessitating studies that analyze the quality of the content available online. The purpose of the present study was to analyze the content quality and reliability of YouTube™ videos on the topic of adult oral hygiene practices and to guide oral health care professionals who use this platform for patient education. Methods A YouTube™ search was performed of the most frequent search term, ‘dental hygiene’. A total of 150 videos were screened, and 51 were included in the final study. The characteristics, sources, and content of the videos were analyzed using the Global Quality Score (GQS) and DISCERN reliability indices. The IBM SPSS 25 program was used for statistical analyses. Results Most of the included videos were uploaded by oral health care professionals (63%). GQS revealed only 17.6% of the videos were excellent quality whereas 23.5% of them were poor quality. In the content analysis, 62.7% of the videos were deemed moderately useful. Video duration, total content score, and interaction indices were all significantly higher in the useful and very useful groups compared to the slightly useful group (p = 0.020, p < 0.001, p = 0.040). GQS had a positive, low-medium statistically significant correlation with both video duration and total content scores (r = 0.235, r = 0.517; p < 0.05). DISCERN score also had a positive, low-medium statistically significant correlation with total content score (r = 0.500; p < 0.05). Conclusion The study concluded that most YouTube™ videos on oral hygiene practices for adults are moderately useful. When using YouTube™ for patient education, oral health care professionals and organizations should be aware of low-quality videos and seek out accurate, useful videos. There is also a need for quality videos with expanded oral health content.

Abstract Enterobacter asburiae, member of the Enterobacter cloacae complex (ECC) group, shows an increasing clinical relevance being responsible for infections like pneumonia, urinary tract infections and septicemia. The aim of the present study was the investigation of the genomic features of two XDR E. asburiae ST229 clinical strains co-carrying blaNDM-1 and blaVIM-1 determinants, collected in October 2021 and in June 2022, respectively. Two E. asburiae strains were collected from rectal swabs of as many patients admitted to the cardiopulmonary intensive care unit of Fondazione I.R.C.C.S. “Policlinico San Matteo” in Pavia, Italy. Based on the antibiotic susceptibility profile results, both isolates showed an XDR phenotype, retaining susceptibility only to fluoroquinolones. Both isolates shared identical resistome, virulome, plasmid content, and belonged to ST229, a rarely reported sequence type. They co-harbored blaNDM-1 and blaVIM-1 genes, that resulted located on transferable plasmids by conjugation and transformation. Moreover, both strains differed in 24 SNPs and showed genetic relatedness with E. asburiae ST709 and ST27. We described the first case of ST229 E. asburiae co-harboring blaNDM-1 and blaVIM-1 in Italy. This study points out the emergence of carbapenemases in low-risk pathogens, representing a novel challenge for public health, that should include such types of strains in dedicated surveillance programs. Antimicrobial susceptibility testing was carried out using Thermo Scientific™ Sensititre™ Gram Negative MIC Plates DKMGN. Both strains underwent whole-genome sequencing (WGS) using Illumina Miseq platform. Resistome, plasmidome, virulome, MLST, plasmid MLST and a SNPs-based phylogenetic tree were in silico determined.

There are numerous findings, based solely on media and other reports, on the as yet unidentified number of Bosnians who, during the 1991-1996 aggression against the Republic of Bosnia and Herzegovina, were forcibly fled and forcibly displaced from the Republic of Bosnia and Herzegovina to the Federal Republic of Yugoslavia. (hereinafter: the Republic of Serbia), were illegally detained and on that occasion numerous forms of crimes against humanity and international law were (committed) against them. A number of victims stayed in camps (or “collection centers”, as they were officially named by the authorities of the Republic of Serbia), which were located in both a number of known and a number of unknown locations. The scientific and general public is not yet disillusioned with the number and locations of camps in the Republic of Serbia, and the number of detained victims of aggression against the Republic of Bosnia and Herzegovina, as well as the relationship between Serbian authorities and direct perpetrators of crimes against detained victims. The main goal of this research is to answer the central question: were these collection centers of a humanitarian nature or camps where crimes were (committed), and if crimes were committed, to determine their character? Under international humanitarian law, any illegal detention of civilians is considered a violation of that right and is a crime against humanity and international law. The detention of civilians and civilians is a crime that, from appearance to appearance, can be of varying intensity and character: from violations of human rights to freedom of movement, through various forms of torture of victims to executions. Illegal apprehension of civilians and civilians and their placing under political and military or police control of enemy forces, depending on the goals and character of the conflict, can have a variety of intentions: from preventing able-bodied persons from participating in hostilities to intending to do so (ex) exterminates members of a particular group with the characteristics of the group as such.

Although linseed oil (LO) has been used in wood protection for centuries, research continues to develop new and more effective formulations and treatment approaches. In the future, growing interest in LO use could be expected due to its cost and environmental friendliness. This review summarizes recent research (from 2000 onwards) on the use of LO in wood protection, published in peer-reviewed scientific journals and included in the online publication databases Scopus or Web of Science. The studies cover surface and impregnation treatments of various wood substrates using different LO formulations, including chemically modified LO and the use of LO as a base for the development of biofinish and as a medium for thermal modification of wood, as well as research into the mechanisms behind the changes in wood properties due to treatment methods and interaction with LO formulations. Although the improvement of wood hydrophobicity and biodurability dominates, other aspects such as weathering and color stability, adhesion, and environmental safety are included in these studies. In general, almost all of the studies show a greater or lesser potency of the proposed approaches to provide benefits in wood protection; however, the level of innovation and practical feasibility varies.

„Habe Mut, dich deines eigenen Verstandes zu bedienen!“ (Kant 1968) – Kants Leitspruch wurde 1784 zu einem wichtigen Wegweiser der Aufklärung und rund 240 Jahre später erlebt er seine Renaissance im Zuge der aufgeklärten Medienpädagogik. Angesichts der rasanten Entwicklungen der generativen Künstlichen Intelligenz (KI) erscheint Kants Aufforderung aktueller denn je. KI ist zwar im Stande Text zu generieren, doch braucht es eine kompetente und kritische Überprüfung des Outputs. Dieser Beitrag beschreibt eine Integration von generativer KI in den schulischen Kontext unter dem Gesichtspunkt der aufgeklärten Medienpädagogik. Beginnend mit einer Einführung in generative KI, betont die Arbeit die Bedeutung einer reflektierten Auseinandersetzung mit neuen Technologien. Die Diskussion erstreckt sich über technische Aspekte von KI bis hin zu den gesellschaftlichen und ethischen Auswirkungen von KI-Output. Weiters wird eine Roadmap für die Erstellung eines projektbezogenen Unterrichts über generative KI mit generativer KI beschrieben. Dazu wird ein Arbeitsauftrag präsentiert, der Schüler*innen ermutigen soll, individuelle KI-generierte Kunstwerke zu erstellen und in einen kritischen Kontext zu setzen. Die Teamarbeit und Präsentation der entstandenen Werke erfolgen in Form einer virtuellen Kunstgalerie. Durch diese praxisorientierte Herangehensweise werden Schüler*innen nicht nur in die Technologie der generativen KI eingeführt, sondern auch dazu angeregt, ihre Medienkompetenz und kritisches Bewusstsein zu schärfen. Die Arbeit schließt mit einer Reflektion über den Prozess, sowie Implikationen für die medienpädagogische Praxis und mögliche Richtungen für zukünftige Forschung.

ABSTRACTHypervirulent Klebsiella pneumoniae (hvKp) can cause infections in clinically healthy people, such as young and immunocompetent patients. Genes involved in the capsule synthesis or those encoding the siderophores have been adopted as predictors of hvKp. Certain sequence types, such as ST23 and ST86, have been associated with hvKp strains, too. The aim of this study was to investigate the presence of hvKp among 354 K. pneumoniae strains isolated from clinical samples of patients admitted to an Italian 900-bed hospital between 21 May 2021 and April 2022. All the isolates were screened by PCR for the amplification of virulence loci. Whole genome sequencing was performed in strains tested positive for at least one target gene. Thirteen out of 354 (3.7%) were hvKp. Five were wild type and belonged to the hypervirulent clones ST23, ST86, ST5, and ST375 and to the new clone ST6310. Six strains carried the blaKPC gene: three belonged to ST101, two to ST512, and one to ST395. Two isolates were ST147 and carried the blaNDM gene. Although hvKp isolation is not frequent, their presence should be systematically investigated to avoid the spreading of both virulent strains and strains with combined increase in virulence and resistance to antibiotics. PCR-based protocols are essential for surveillance of these strains, which do not always show a recognizable phenotype. Moreover, hvKp strains were isolated also from patients without history of recent foreign travels, indicating an increased spreading of these strains as well as an underestimated of their circulation so far.IMPORTANCEKlebsiella pneumoniae is a healthcare-associated pathogen frequently resistant to antibiotics. Hypervirulent strains of pneumoniae (hvKp) can spread from the primary site of infection to multiple sites causing life-threatening infections also in young otherwise healthy individuals. This study described the isolation of 13 isolates of K. pneumoniae with increased virulence in a large tertiary hospital over a 1-year period. Among them, eight strains were multidrug resistant and hypervirulent. Although these hypervirulent strains are still rare in Italy, their presence is particularly concerning since they can cause difficult-to-treat life-threatening infections. Moreover, not all the hypervirulent isolates were positive by the string test, so hvKp isolates were not always phenotypically detectable. Molecular biology techniques such as PCR amplification and next generation sequencing are therefore necessary for the detection of hvKp isolates, and surveillance programs exploiting molecular techniques are highly desirable.

Pharmacological and nutritional benefits of plant leaf extracts can be harnessed to address the problem of poor chick quality, performance and high mortality, which affect both hatchery and farm managers. This study sought to evaluate the in ovo effect of Soursop leaf extract (SLE) on the hatching and post-hatch performance of Noiler chicks. A total of 640 fertile eggs were randomly distributed into four groups of five replicates: (0.25 µg SLE), (0.5 µg SLE), (0.75 µg SLE) and a non-injected control. On day 18 of incubation, 0.2 ml of SLE was injected into the airspace of the eggs. At hatch, embryonic mortality, hatchability, and chick quality were evaluated. Hatched chicks were reared to assess feed intake, weight gain, feed conversion ratio (FCR) and mortality. Results showed no significant difference (p > 0.05) in embryonic mortality, hatchability and weight gain among the treatment groups. Chick weight and feed intake were significantly higher (p

Erysipelothrix rhusiopathiae is a facultative anaerobe Gram-positive bacillus, which is considered a zoonotic pathogen. E. rhusiopathiae causes erysipeloid, mainly in occupational groups such as veterinarians, slaughterhouse workers, farmers, and fishermen. Two cutaneous forms (localised and generalised) and a septicaemic form have been described. Here, we report the isolation of a strain of E. rhusiopathiae from a 56-year-old immunocompetent obese male admitted to Fondazione IRCCS Policlinico San Matteo Pavia (Italy). Blood cultures were collected and Gram-positive bacilli were observed. E. rhusiopathiae grew and was identified. Antimicrobial susceptibility tests were performed and interpreted with EUCAST breakpoints (PK-PD). The strain was susceptible to all the antibiotics tested, while it was intrinsically resistant to vancomycin. The clinical diagnosis of E. rhusiopathiae can be challenging, due to the broad spectrum of symptoms and potential side effects, including serious systemic infections such as heart diseases. In the case described, bacteraemia caused by E. rhusiopathiae was detected in a immunocompetent patient. Bacteraemia caused by E. rhusiopathiae is rare in immunocompetent people and blood cultures were proven to be essential for the diagnosis and underdiagnosis of this pathogen, which is possible due to its resemblance to other clinical manifestations.

Boas Práticas de Fabricação nas agroindústrias são necessárias para controlar a multiplicação de microrganismos e prevenir a ocorrência de doenças veiculadas por alimentos. Dentre os diversos alimentos que podem ser contaminados pela manipulação intensiva, destacam-se os produtos cárneos, como a linguiça frescal. Com base no exposto, objetivou-se avaliar o nível de contaminação de linguiças frescais produzidas no município de Alegrete (RS) no âmbito da fiscalização do SIM/SISBI entre 2014 e 2016 e correlacionar ao atendimento das Boas Práticas de Fabricação (questionários, orientações e trei[1]namentos). Amostras regulares foram coletadas em 10 estabelecimentos da cidade e testadas para coli[1]formes termotolerantes, Clostridium sulfito redutor, Staphylococcus coagulase positiva e Salmonella spp. A quantificação microbiana de coliformes termotolerantes, Clostridium sulfito redutor, Staphylococcus coagulase positiva e Salmonella spp. diminuiu significativamente, indicando que as intervenções contri[1]buíram para melhorar o perfil microbiológico da linguiça frescal produzida na cidade.

Class switch recombination (CSR) is a process by which B cells switch their immunoglobulin isotype and develop pathogen-eliminating antibodies. Here, the authors show that a protein kinase DYRK1A is required for protection from viral infection through the regulation of CSR and effective clonal expansion.

Mitochondria are involved in many vital functions in living cells, including the synthesis of ATP by oxidative phosphorylation (OXPHOS) and regulation of nuclear gene expression through retrograde signaling. Leigh syndrome is a heterogeneous neurological disorder resulting from an isolated complex I deficiency that causes damage to mitochondrial energy production. The pathogenic mitochondrial DNA (mtDNA) variant m.13513G>A has been associated with Leigh syndrome. The present study investigated the effects of this mtDNA variant on the OXPHOS system and cell retrograde signaling. Transmitochondrial cytoplasmic hybrid (cybrid) cell lines harboring 50% and 70% of the m.13513G>A variant were generated and tested along with wild-type (WT) cells. The functionality of the OXPHOS system was evaluated by spectrophotometric assessment of enzyme activity and high-resolution respirometry. Nuclear gene expression was investigated by RNA sequencing and droplet digital PCR. Increasing levels of heteroplasmy were associated with reduced OXPHOS system complex I, IV, and I + III activities, and high-resolution respirometry also showed a complex I defect. Profound changes in transcription levels of nuclear genes were observed in the cell lines harboring the pathogenic mtDNA variant, indicating the physiological processes associated with defective mitochondria.