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With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.

The γ decay of the elusive narrow, near-threshold proton resonance in 11B was investigated at Laboratori Nazionali di Legnaro (INFN) in a particle-γ coincidence experiment, using the 6Li(6Li,pγ) fusion-evaporation reaction and the GALILEO-GALTRACE setup. No clear signature was found for a possible E1 decay to the 1/21−, first-excited state of 11B, predicted by the Shell Model Embedded in the Continuum (SMEC) with a branching of 0.98−69+167×10−3 with respect to the dominant particle-decaying modes. The statistical analysis of the γ-ray spectrum provided an average upper limit of 2.37×10−3 for this γ-ray branching, with a global significance of 5σ. On the other hand, by imposing a global confidence level of 3σ, a significant excess of counts was observed for E=γ9300(20) keV, corresponding to a resonance energy of 11429(20) keV (namely 200(20) keV above the proton separation energy of 11B) and a γ-ray branching of 1.12(35)×10−3. This result is compatible with the SMEC calculations, potentially supporting the existence of a near-threshold proton resonance in 11B.

This article focuses on the varia lectio Ἀγησίλαν provided by cod. B instead of Ἀρκεσίλαν, for Pind. Nem. 11.11. Ἀγησίλαν is usually rejected as unmetrical (Henry) or corrected into Ἁγεσίλαν (Maas), but the comparison with other Pindaric proper names – such as Ἁγησίας, Ἁγησίδαμος and Ἁγησίμαχος – suggests that we print Ἁγησίλαν (Schroeder). This form would provide a metrical responsion between hemm and cho cr which is attested also in Aristoph. Vesp. 274 Æ 282. By adopting Ἁγησίλαν, we should infer that the father of Aristagoras of Tenedos, the young laudandus of Nem. 11, was named Agesilaos: if so, we could not exclude that Aristagoras’ brother was Theoxenus, the other ‘son of Agesilaos’ (υἱὸν Ἁγησίλα) praised in Pind. fr. 123 Maehl., as Schneider first suggested.

OBJECTIVE Our study aims to extend the previous research and compare two diagnostic methods performed on the ulnar nerve to validate the use of the ulnar goniometer in electromyographic diagnostic practice. Comparing the electroneurographic method, obtained through conduction velocity (CV) studies with ultrasound of the ulnar nerve in the area above the elbow and at the wrist, we aim to quantify the reliability of the ulnar goniometer compared to the diagnostic method ultrasound of the nerve. MATERIALS AND METHODS The operator examined with the use of the Ulnar Goniometer, detecting the wrist-below-elbow motor conduction speed and the above-elbow speed (AE), below-elbow speed (BE) and subsequently performed an ultrasound examination of the ulnar nerve in the forearm and elbow. We calculated the degree of homogeneity between measurements. RESULTS Evaluating 30 participants of both genders with typical paresthetic symptoms of ulnar nerve compression at the elbow, 100% of the measurements show that a decrease in Motor Conduction Velocity (MCV) below 50 m/s is associated with an increase in Cross-Sectional Area (CSA). Additionally, in 89% of cases, a reduction in MCV wBE and BEAE by more than 10 m/s is correlated with an increase in CSA. DISCUSSION AND CONCLUSIONS The measurement of the angle below the elbow (BE) and above the elbow (AE) using the Ulnar Goniometer provides us with a slowed Motor Conduction Velocity (MCV) that is by ultrasound data showing an increase in the Cross-Sectional Area (CSA) of the ulnar nerve in that segment, as observed in Cubital Tunnel Syndrome (CTS).

Obbiettivo Il nostro studio mira a estendere la ricerca precedente e confrontare due metodi diagnostici eseguiti sul nervo ulnare per convalidare l'uso del goniometro ulnare nella pratica elettromiografica come strumento ausiliario diagnostico. Confrontando il metodo elettro-neurografico, ottenuto attraverso studi sulla velocità di conduzione (VC), con l'ecografia del nervo ulnare al canale cubitale e in corrispondenza del terzo medio dell’avambraccio, miriamo a quantificare l'affidabilità del goniometro ulnare rispetto al metodo diagnostico dell'ecografia del nervo. Materiali E Metodi l'operatore ha eseguito l'esame con l'uso del Goniometro Ulnare, rilevando la velocità di conduzione motoria dal polso al gomito e la velocità sopra il gomito (AE), sotto il gomito (BE) e successivamente ha eseguito l'ecografia del nervo ulnare nell'avambraccio e nel gomito. Abbiamo calcolato il grado di omogeneità tra le misurazioni. Risultati Valutando 30 partecipanti di entrambi i sessi con sintomi parestesici tipici di compressione del nervo ulnare al gomito, Il 100% delle misurazioni mostra che una diminuzione di MCV al di sotto di 50 m/s è associata a un aumento di CSA. Inoltre, nell'89% dei casi, una riduzione di MCV wBE e BEAE di più di 10 m/s è correlata a un aumento di CSA. Discussione e Conclusioni La misurazione dell'angolo sotto il gomito (BE) e sopra il gomito (AE) utilizzando il Goniometro Ulnare ci fornisce una Velocità di Conduzione Motoria (MCV) rallentata che è in accordo con i dati ecografici che mostrano un aumento della cosiddetta Cross Sectional Area (CSA) ossia la sezione trasversale misurata in mm2 del nervo ulnare in quel segmento, come accade nella Sindrome del Tunnel Cubitale (CTS).

The objective of this study was to characterize hemodynamic changes during trans-vascular stimulation of the renal nerve and their dependence on stimulation parameters. We employed a stimulation catheter inserted in the right renal artery under fluoroscopic guidance, in pigs. Systolic, diastolic and pulse blood pressure and heart rate were recorded during stimulations delivered at different intravascular sites along the renal artery or while varying stimulation parameters (amplitude, frequency, and pulse width). Blood pressure changes during stimulation displayed a pattern more complex than previously described in literature, with a series of negative and positive peaks over the first two minutes, followed by a steady state elevation during the remainder of the stimulation. Pulse pressure and heart rate only showed transient responses, then they returned to baseline values despite constant stimulation. The amplitude of the evoked hemodynamic response was roughly linearly correlated with stimulation amplitude, frequency, and pulse width.

The increasing importance of treatment of lower urinary tract symptoms (LUTS), while avoiding side effects and maintaining sexual function, has allowed for the development of minimally invasive surgical therapies (MISTs). Recently, the European Association of Urology guidelines reported a paradigm shift from the management of benign prostatic hyperplasia (BPH) to the management of nonneurogenic male LUTS. The aim of the present review was to evaluate the efficacy and safety of the most commonly used MISTs: ablative techniques such as aquablation, prostatic artery embolization, water vapor energy, and transperineal prostate laser ablation, and nonablative techniques such as prostatic urethral lift and temporarily implanted nitinol device (iTIND). MISTs are becoming a new promise, even if clinical trials with longer follow-up are still lacking. Most of them are still under investigation and, to date, only a few options have been given as a recommendation for use. They cannot be considered as standard of care and are not suitable for all patients. Advantages and disadvantages should be underlined, without forgetting our objective: treatment of LUTS and re-treatment avoidance.

The present study retrospectively analyzed the infectious agents associated with 829 abortion outbreaks occurring from 2011 to 2021 in northern Italy. Foetuses were subjected to necropsies, and organ samples were analyzed by direct PCR to screen for six swine pathogens. In 42.0% of the examined outbreaks, at least one infectious agent was found. Porcine reproductive and respiratory syndrome virus (PRRSV) (24.9%) and porcine circovirus-2 (PCV2) (11.5%) were the most frequently detected among the known abortion-inducing pathogens. Chlamydia spp. (5.6%), porcine parvovirus (PPV) (4.0%), and Leptospira spp. (2.6%) were less common. Although its role in swine reproductive disorders is still unclear, PCV3 was detected in 19.6% of the cases. Coinfections were detected in 25.0% of positive outbreaks, and the most frequent coinfection was represented by PRRSV and PCV2 (32.2%), followed by PRRSV and PCV3 (23%). PCV2 prevalence showed a slight but consistent reduction during the study period, while PCV3 increased in frequency. Our data suggest an overall reduction in abortion outbreaks during the study period. PRRSV was confirmed as the main abortion agent detected in the examined area, while PCV2 prevalence showed a decline. Conversely, PCV3 detection has been increasing, supporting its potential role as an abortion agent. Our results highlight the importance of implementing a consistent and standardized sampling procedure, as well as a thorough diagnostic protocol, to reduce the incidence of inconclusive diagnoses.

Anodic TiO2 nanotube arrays decorated with Ni, Cu, and NiCu alloy thin films were investigated for the first time for the photocatalytic degradation of paracetamol in water solution under UV irradiation. Metallic co-catalysts were deposited on TiO2 nanotubes using magnetron sputtering. The influence of the metal layer composition and thickness on the photocatalytic activity was systematically studied. Photocatalytic experiments showed that only Cu-rich co-catalysts provide enhanced paracetamol degradation rates, whereas Ni-modified photocatalysts exhibit no improvement compared with unmodified TiO2. The best-performing material was obtained by sputtering a 20 nm thick film of 1:1 atomic ratio NiCu alloy: this material exhibits a reaction rate more than doubled compared with pristine TiO2, enabling the complete degradation of 10 mg L−1 of paracetamol in 8 h. The superior performance of NiCu-modified systems over pure Cu-based ones is ascribed to a Ni and Cu synergistic effect. Kinetic tests using selective holes and radical scavengers unveiled, unlike prior findings in the literature, that paracetamol undergoes direct oxidation at the photocatalyst surface via valence band holes. Finally, Chemical Oxygen Demand (COD) tests and High-Resolution Mass Spectrometry (HR-MS) analysis were conducted to assess the degree of mineralization and identify intermediates. In contrast with the existing literature, we demonstrated that the mechanistic pathway involves direct oxidation by valence band holes.

In this phenomenological case study, we explore how a toddler with autism (Miguel) becomes a member of an early childhood learning community. Drawing on the right to belong and a social-relational model of disability framework, we asked research questions that are fundamental to the rights and agency of the child and how children experience inclusion and belonging in their learning community. By following Miguel during his first year in early care and education, we share depictions of his expressions of interest, initiations, and agency; his ways of relating to children and adults in the classroom; his use of environmental supports and scaffolds to engage with the physical and interpersonal space; and his growing sense of membership in the toddler classroom. In conclusion, we discuss what inclusion means to individual children and the ways in which inclusive practices can unfold in a setting that promotes authentic belonging.

This study followed three preservice student teachers as they navigated a semester-long infant-toddler practicum designed to enact a relationship-based approach to teaching and learning. Selected participants were in particular and contrasting placement settings, which served as a catalyst for engaging in critical reflection in multiple ways. Critical reflection was integrated into all course assignments and highlighted within an interactive journaling process. Throughout the practicum, students met together in a weekly seminar with the course instructor, who also served as their field supervisor. Findings uncover multiple ways that critical self-reflection was stimulated in preservice students and the value and interconnection of multiple mentoring practices, including traditional, collaborative, peer and reverse mentoring. While each preservice student teacher engaged in critical reflection in unique ways, they all benefitted from the supportive infrastructure and socially shared, collective reflection with others. This study highlights how critical reflection supported by collaborative dialogue and mentoring can influence transformative practice in caring for infants. Implications for early childhood teacher education and insights for the field are discussed.

The frequency and length of games, conflicts, and contingency sequences that took place between toddlers as they got to know one another were studied using archival data. The sample consisted of 28 unfamiliar 20- and 30-month-old toddlers (predominantly White, 16 males) who met separately with each of two other toddlers for 18 play dates. The frequency of games increased over time, while the frequency of conflict and contingency sequences decreased. The length of games increased over time while the length of conflicts and contingency sequences were stable. Age and language ability predicted changes in frequency and length of the different types of sequences. Thus, toddlers engage in less structured interactions when they first meet; their interactions become increasingly more organized and positive as the relationship evolves.

Herein, state‐of‐the‐art multiscale modeling methods have been described. This research includes notable molecular, micro‐, meso‐, and macroscale models for hard (polymer, metal, yarn, fiber, fiber‐reinforced polymer, and polymer matrix composites) and soft (biological tissues such as brain white matter [BWM]) composite materials. These numerical models vary from molecular dynamics simulations to finite‐element (FE) analyses and machine learning/deep learning surrogate models. Constitutive material models are summarized, such as viscoelastic hyperelastic, and emerging models like fractional viscoelastic. Key challenges such as meshing, data variability and material nonlinearity‐driven uncertainty, limitations in terms of computational resources availability, model fidelity, and repeatability are outlined with state‐of‐the‐art models. Latest advancements in FE modeling involving meshless methods, hybrid ML and FE models, and nonlinear constitutive material (linear and nonlinear) models aim to provide readers with a clear outlook on futuristic trends in composite multiscale modeling research and development. The data‐driven models presented here are of varying length and time scales, developed using advanced mathematical, numerical, and huge volumes of experimental results as data for digital models. An in‐depth discussion on data‐driven models would provide researchers with the necessary tools to build real‐time composite structure monitoring and lifecycle prediction models.

In recent years, there has been an exponential increase in the generation and accessibility of electronic healthcare data, often referred to as “real-world data”. The landscape of data sources has significantly expanded to encompass traditional databases and newer sources such as the social media, wearables, and mobile devices. Advances in information technology, along with the growth in computational power and the evolution of analytical methods relying on bioinformatic tools and/or artificial intelligence techniques, have enhanced the potential for utilizing this data to generate real-world evidence and improve clinical practice. Indeed, these innovative analytical approaches enable the screening and analysis of large amounts of data to rapidly generate evidence. As such numerous practical uses of artificial intelligence in medicine have been successfully investigated for image processing, disease diagnosis and prediction, as well as the management of pharmacological treatments, thus highlighting the need to educate health professionals on these emerging approaches. This narrative review provides an overview of the foremost opportunities and challenges presented by artificial intelligence in pharmacology, and specifically concerning the drug post-marketing safety evaluation.

BACKGROUND: The generation of induced pluripotent stem cells (iPSC) has been a game-changer in translational and regenerative medicine; however, their large-scale applicability is still hampered by the scarcity of accessible, safe, and reproducible protocols. The porcine model is a large biomedical model that enables translational applications, including gene editing, long term in vivo and offspring analysis; therefore, suitable for both medicine and animal production. AIM: To reprogramme in vitro into pluripotency, and herein urine-derived cells (UDCs) were isolated from porcine urine. METHODS: The UDCs were reprogrammed in vitro using human or murine octamer-binding transcription factor 4 (OCT4), SRY-box2 (SOX2), Kruppel-like factor 4 (KLF4), and C-MYC, and cultured with basic fibroblast growth factor (bFGF) supplementation. To characterize the putative porcine iPSCs three clonal lineages were submitted to immunocytochemistry for alkaline phosphatase (AP), OCT4, SOX2, NANOG, TRA1 81 and SSEA 1 detection. Endogenous transcripts related to the pluripotency (OCT4, SOX2 and NANOG) were analyzed via reverse transcription quantitative real-time polymerase chain reaction in different time points during the culture, and all three lineages formed embryoid bodies (EBs) when cultured in suspension without bFGF supplementation. RESULTS: The UDCs were isolated from swine urine samples and when at passage 2 submitted to in vitro reprogramming. Colonies of putative iPSCs were obtained only from UDCs transduced with the murine factors (mOSKM), but not from human factors (hOSKM). Three clonal lineages were isolated and further cultured for at least 28 passages, all the lineages were positive for AP detection, the OCT4, SOX2, NANOG markers, albeit the immunocytochemical analysis also revealed heterogeneous phenotypic profiles among lineages and passages for NANOG and SSEA1, similar results were observed in the abundance of the endogenous transcripts related to pluripotent state. All the clonal lineages when cultured in suspension without bFGF were able to form EBs expressing ectoderm and mesoderm layers transcripts. CONCLUSION: For the first time UDCs were isolated in the swine model and reprogrammed into a pluripotent-like state, enabling new numerous applications in both human or veterinary regenerative medicine.