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• Energy efficient recycling approaches are growing in importance. • Effective sorting of halogenated flame retardant plastic wastes is crucial. • The recycling process needs to prevent the release of toxic halogen-based streams. • More sustainable recycling methods for thermoset wastes need to be developed. • Future FR thermoplastic or thermoset should be fully recyclable. Polymers are indispensable to humans in different applications due to their ease of manufacturing and overall performance. However, after a material lifetime, there is a large amount of polymer-based waste, which greatly contributes to the loss of valuable resources and environmental pollution. Thermoplastics may be readily recycled, but because of their flammability, large amounts of flame retardant (FR) additives are required for many applications. This results in a significant volume of FR polymeric wastes too, particularly halogenated plastics, which are subject to severe recycling regulations. In general, thermoplastics containing FRs are raising concerns, as their effective recycling is strongly influenced by the chemical composition, additive content, and physicochemical characteristics of the waste stream. The recycling of FR thermosets is even more challenging due to their crosslinked and cured nature, which makes them resistant to melting and reprocessing. In many cases, traditional mechanical recycling methods, such as grinding and melting, are not applicable to thermosetting polymers. Current recycling methods do not always consider the recovery of the thermosetting/thermoplastic matrix and the presence of toxic FRs in the polymer network. Sorting and solvent washing treatment are important steps, which are usually performed before recycling the FR polymeric waste to reduce contamination in the following steps. Considering all the technical difficulties during recycling, the high cost of sorting and solvent washing, and the increasing demand for more sustainable procedures, the scientific community is fostering the transformation toward more feasible and energy-efficient recycling strategies. Also, many directives are imposing strict disposal and sorting rules, limiting the use of FR halogen-based compounds, and promoting the commercialization of more recyclable polymers. This review aims to provide a general overview of currently applied approaches for recycling FR thermoplastics and thermosets, and possible approaches for designing the next generation of FR polymer-based materials. The existing recycling strategies for FR polymers are summarized. Developments in the manufacturing of covalent adaptable networks as an outlook towards circularity in polymers are also addressed in this review. [Display omitted] [ABSTRACT FROM AUTHOR]

Uterine myomas are the most common gynecological disease in reproductive-aged women, present several symptoms, and require effective medical and/or surgical strategies. This study aimed to compare robotic-assisted laparoscopic myomectomy (RALM) with laparoscopic myomectomy (LM) in terms of operative times, intraoperative estimated blood loss, pre- and post-hemoglobin levels drop, and length of hospital stay. Data from 50 clinical records (25 RALM in Group A and 25 LM in Group B) of patients with uterine fibroids were collected from December 2022 to December 2023 at Gynecological Unit of DAI Materno-Infantile Federico II in Naples, Italy. Patients aged 30–49 years with symptomatic fibroids were included. Data on peri-operative outcomes, including operative time for myomectomy (OTM), overall operative time (OOT), intraoperative estimated blood loss (EBL), pre- and post-operative hemoglobin levels, and length of hospital stay were analyzed. The OTM in the presence of > 5 myomas was 59 [52–65] vs 69 min [61–96] (p< 0.001) for RALM and LM groups, respectively. Moreover, also in presence of ≤ 5 myomas, a difference was observed in the RALM group 48[43–55] compared to the LM group 53[50–61] min (p= 0.07). The OOT was also statistically significant for Group A compared to Group B (83[65–93] vs 72[56–110] min, p< 0.001). There were no significant differences between the two groups in terms of pre- and post-operative hemoglobin levels and EBL (p= 0.178). Group A demonstrated a notably shorter hospital stay 1.2 [1–2] days compared to Group B 2.9[3–3.75] days (p= 0.007). Our study suggests potential advantages of RALM over LM in terms of reduced operative times and shorter hospital stays. The standardized approach and extensive surgical experience likely contributed to the favorable outcomes of RALM.

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1–3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision–language pretraining for pathology7,8by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.

In this work, we present PharmaCore: a new, completely automatic workflow aimed at generating three-dimensional (3D) structure-based pharmacophore models toward any target of interest. The proposed approach relies on using cocrystallized ligands to create the input files for generating the pharmacophore hypotheses, integrating not only the three-dimensional structural information on the ligand but also data concerning the binding mode of these molecules put in the protein cavity. We developed a Python library that, starting from the specific UniProt ID of the protein under investigation as the only element that requires user intervention, subsequently collects and aligns the corresponding structures bearing a known ligand in a fully automated fashion, bringing them all into the same coordinate system. The protocol includes a final phase in which the aligned small molecules are used to produce the pharmacophore hypotheses directly onto the protein structure using a specific software, e.g., Phase (Schrödinger LLC). To validate the entire procedure and highlight the possible applications in the field of drug discovery and repositioning, we first generated pharmacophores for soluble epoxide hydrolase (sEH) and compared with already-published ones. Then, we reproduced the binding profile of a reported selective binder of ATAD2 bromodomain (AM879), testing it against a panel of 1741 pharmacophores related to 16 epigenetic proteins and automatically generated with PharmaCore, finally disclosing putative unprecedented off-targets. The computational predictions were successfully validated with AlphaScreen assays, highlighting the applicability of the proposed workflow in drug discovery and repositioning. Finally, the process was also validated on tankyrase 2 and SARS-CoV-2 MPro, confirming the robustness of PharmaCore.

This article deals with how innovation ecosystems emerge and become established. It focuses on technologies and how they favor interaction among actors, resources, and practices to facilitate an ecosystem's workability from a long-range perspective. The intrinsically complex and systemic nature of an innovation ecosystem is investigated by looking at the social and material issues concerning the organizing of social interactions, technologies, and other resources. This article adopts an action research approach through the combination of theory and practice and the support of actors—including the authors—involved in the empirical context of the Technological District for Cultural Heritage (DATABENC). This article contribute to the innovation ecosystem literature by assuming that innovation ecosystems emerge from the interplay of deliberate and unforeseen processes. Prompted by technologies, three milestones emerge supporting innovation ecosystem viability: 1) setting the socio-material context; 2) establishing interdependencies among actors, activities, and resources; and 3) giving continuity to social- and material-oriented interactions. In this context, technology is not merely an artefact; it takes three different roles: context builder, mediating mechanism, and institutionalization process enabler.

Computational models of fibrosis-mediated, re-entrant left atrial (LA) arrhythmia can identify possible substrate for persistent atrial fibrillation (AF) ablation. Contemporary models use a 1-size-fits-all approach to represent electrophysiological properties, limiting agreement between simulations and patient outcomes.

ABSTRACTSeveral systems have been proposed in recent years for Advanced Traveler Information Systems (ATIS), ranging from personal (mobile application, on-board) navigation to VMS (Variable Message Signs). All these applications are essentially aimed at assisting the travelers in their travel choices by means of technologically dispatched information about traffic network structure and traffic conditions. It is well known that in ATIS applications one of the key issues to be addressed concerns the accuracy of the dispatched information, here intended as the ability of the system in supplying information that can be verified by the travelers to be correct (affected by a small error). This paper aims at proposing some analytical models able to simulate the effects of the (in)accuracy on travelers’ compliance with information.

Natural products have played an indispensable role in the discovery and development of antibiotics, antineoplastics, and therapeutics for other diseases. Natural products are unique among all other small molecules in that they are produced by dedicated enzymatic assembly lines that are the protein products of biosynthetic gene clusters. As the products of chiral macromolecules, natural products have distinct three-dimensional shapes and stereochemistry is often encoded in their structures through the presence of stereocenters, or in the case of molecules that lack a stereocenter, the presence of an axis or plane of chirality. In the latter forms of chirality, if the barrier to rotation about the chiral axis or chiral plane is sufficiently high, stable conformers may exist allowing for isolation of discrete conformers, also known as atropisomers. Importantly, the diverse functions and biological activities of natural products are contingent upon their structures, stereochemistry and molecular shape. With continued innovation in methods for natural products discovery, synthetic chemistry, and analytical and computational tools, new insights into atropisomerism in natural products and related scaffolds are being made. As molecular complexity increases, more than one form of stereoisomerism may exist in a single compound (for example, point chirality, chiral axes, and chiral planes), sometimes creating atypical or noncanonical atropisomers, a term used to distinguish physically noninterconvertable atropisomers from typical atropisomers.

The design of multitarget drugs represents a promising strategy in medicinal chemistry and seems particularly suitable for the discovery of anti-inflammatory drugs. Here, we describe the identification of an indoline-based compound inhibiting both 5-lipoxygenase (5-LOX) and soluble epoxide hydrolase (sEH). In silicoanalysis of an in-house library identified nine compounds as potential 5-LOX inhibitors. Enzymatic and cellular assays revealed the indoline derivative 43as a notable 5-LOX inhibitor, guiding the design of new analogues. These compounds underwent extensive in vitroinvestigation revealing dual 5-LOX/sEH inhibitors, with 73showing the most promising activity (IC50s of 0.41 ± 0.01 and 0.43 ± 0.10 μM for 5-LOX and sEH, respectively). When challenged in vivo in zymosan-induced peritonitis and experimental asthma in mice, compound 73showed remarkable anti-inflammatory efficacy. These results pave the way for the rational design of 5-LOX/sEH dual inhibitors and for further investigation of their potential use as anti-inflammatory agents.

Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes steroidogenic factor 1 (SF1), a key regulatory factor that determines gonadal development and coordinates endocrine functions. Here, we have established a stem cell-based model of human gonadal development and applied it to evaluate the effects of NR5A1during the transition from bipotential gonad to testicular cells. We combined directed differentiation of human induced pluripotent stem cells (46,XY) with activation of endogenous NR5A1expression by conditionally-inducible CRISPR activation. The resulting male gonadal-like cells expressed several Sertoli cell transcripts, secreted anti-Müllerian hormone and responded to follicle-stimulating hormone by producing sex steroid intermediates. These characteristics were not induced without NR5A1activation. A total of 2691 differentially expressed genetic elements, including both coding and non-coding RNAs, were detected immediately following activation of NR5A1expression. Of those, we identified novel gonad-related putative NR5A1targets, such as SCARA5, which we validated also by immunocytochemistry. In addition, NR5A1activation was associated with dynamic expression of multiple gonad- and infertility-related differentially expressed genes. In conclusion, by combining targeted differentiation and endogenous activation of NR5A1we have for the first time, been able to examine in detail the effects of NR5A1in early human gonadal cells. The model and results obtained provide a useful resource for future investigations exploring the causative reasons for gonadal dysgenesis and infertility in humans.

Minimally invasive cardiac surgery is an established approach for the treatment of heart valve pathologies and is associated with excellent technical and early postoperative outcomes. Data from medium– and long–term longitudinal evaluation of patients who underwent mitral valve repair (MVr) through transaxillary approach (TAxA) are still lacking. The aim of this study is to investigate mid–term results in patients who underwent TAxA MVr. Prospectively collected data of patients who underwent first–time MVr for MV regurgitation between 2017 and 2022, were reviewed. A total of 308 patients received TAxA, while in 220 cases, traditional full sternotomy (FS) was performed. Concomitant aortic and coronary artery bypass grafting (CABG) procedures, infective endocarditis or urgent operations were excluded. A propensity match (PS) analysis was used to overcome preoperative differences between the populations. Follow–up data were retrieved from outpatients’ clinic, telephone calls and municipal administration records. After PS–matching, two well–balanced cohorts of 171 patients were analysed. The overall 30–day mortality rate was 0.6% in both cohorts. No statistical difference in postoperative complications was reported. TAxA cohort experienced earlier postoperative extubation (p < 0.001) with a higher rate of extubation performed in the operating theatre (p < 0.001), shorter intensive care unit (ICU) stay (p < 0.001), and reduced hospitalization with 51% of patients discharged home (p < 0.001). Estimated survival at 5 years was 98.8% in TAxA vs. 93.6% in FS cohort (Log rank p = 0.15). The cumulative incidence of reoperation was 2.6% and 4.4% at 5 years, respectively, in TAxA and FS cohorts (Gray test p = 0.49). TAxA approach for MVr was associated with low rates of in–hospital mortality and major postoperative complications being furthermore associated with shorter mechanical ventilation time, shorter ICU stay and reduced hospitalization with a higher rate of patients able to be discharged home. At mid–term, TAxA was associated with excellent survival and low rate of MV reoperation.

The COVID-19 pandemic disrupted traditional in-person engineering education requiring instructors to adapt to a remote-learning environment. Hands-on engineering is a critical component of engineering education, where students learn applications of the industry through physical design. Remote learning provides opportunities for students to think and instructors to evaluate students using online-learning tools that may not be available in an in-person lab setting. This study compares the effectiveness of undergraduate engineering education in Work Design and Ergonomics Laboratory taught in-person pre-pandemic to during-pandemic remote teaching and post-pandemic in-person instruction. Various hypothesis tests reveal mode of instruction’s impact on effectiveness of engineering education. Three lab case studies (Eye Tracker, Lean Lego, and Time Study) and student evaluations (Student Experience of Teaching Surveys (SETs)) of the course and instructor help assess student learning outcomes and experiences. We analyze the barriers to teaching the lab synchronously both in-person and remotely and how to overcome those.

Positive events can reduce depression as well as enhance wellbeing. The role of secure attachment style in moderating the relationship between positive events and wellbeing is examined to further understand wellbeing models. Participants (n= 490) included two midlife groups and a student group from the UK. They completed the online Computerized Life Event Assessment Record (CLEAR), a measure of life events, the Vulnerable Attachment Style Questionnaire (VASQ), and the Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS). Age was associated with higher rates of wellbeing and secure attachment style. A significant relationship was found between number of positive events and wellbeing, number of people close, and secure attachment score. Hierarchical multiple regression indicated a significant interaction between secure attachment style, number of positive life events, and wellbeing. Simple slopes analysis demonstrated the association between positive life events and wellbeing was significant for secure attachment (B= 1.27, p= .003) but not insecure attachment (B = 0.04, non‐significant). This suggests securely attached individuals are better able to take advantage of positive life events than insecurely attached individuals and experience a greater increase in wellbeing.

Sixteen diterpenes (1–16), along with 10 previously described compounds, including four flavonoids and six diterpenes, were isolated from the aerial parts of Psiadia punctulatagrowing in Saudi Arabia. The diterpene structures were elucidated using NMR spectroscopy and mass spectrometry data. Furthermore, a DFT/NMR procedure was used to suggest the relative configuration of several compounds. The labdane-derived skeletons, namely, ent-atisane, ent-beyerene, ent-trachylobane, and ent-kaurene, were identified. The extracts, fractions, and pure compounds were then tested against Staphylococcus aureus, Streptococcus mutans, Treponema denticola, and Lactobacillus plantarum. One diterpenoid, namely, psiadin, showed an additive effect with the antiseptic chlorhexidine, with a fractional inhibitory concentration index of less than 1. Additionally, psiadin showed a prospective inhibition activity for bacterial efflux pumps.

AbstractAt the time of its inception, in 1978, prevention and primary care were set as fundamental pillars of the Italian National Health Service (NHS), emphasizing the collective and social dimension of health. These principles were progressively neglected over the following four decades. Marketization, managed competition and managerialization privileged the individualized, highly specialized healthcare services mainly provided in hospitals, to the detriment of local outpatient and primary care services. After 2008–09, austerity policies exacerbated this situation determining under-financing as well as structural and staff shortages, while increasing tensions arose between the central government and Regions in the decentralized NHS. In 2020–21, the pandemic highlighted these critical issues. The need to develop a universal and strong outpatient, primary and community care system became evident in order to ensure the appropriateness and quality of foundational health services. This requires the State to play a more prominent role in the NHS governance.

AbstractThis paper introduces the FSE special session ‘Healthcare, Covid-19 and the Foundational Economy’, which uses the Foundational Economy (FE) approach to analyze the public health crisis determined by Covid-19. First, the paper briefly presents the FE approach, which consists of two macro-areas. The former, identified as a 'material' foundational economy, comprises the supply of basic goods and services (i.e. water, electricity, gas, food or banking). The latter, defined as a 'providential' foundational economy, comprises services traditionally covered by welfare policies and indispensable to our lives, including healthcare. Subsequently, the introduction illustrates the contributions of the special session, which includes articles on France, Italy, Spain, the US as well as a comparative analysis of the Covid-19 impact in Europe. In presenting these papers, the introduction shows how the FE concepts and methodological tools are relevant and extremely useful to analyze the public health pandemic crisis and its causes.

Seven new terpenoids, namely, guaiane (1–4), eudesmane (5), and bisabolane (6) sesquiterpenoids and a furanone (7), were isolated from the aerial parts of Ammoides atlantica, a herbaceous plant growing in Algeria, together with eight known compounds. All metabolites were characterized by their 1D and 2D NMR and HRESIMS data. A combined DFT/NMR method was applied to study the relative configurations of 1–4, 6, and 7. All compounds, except 2, were assayed against MCF-7, A375, A549, HaCaT, and Jurkat cell lines. Compounds 8, 10, and 11induced a dose-dependent reduction in cell viability with different potency on almost all cell lines used. The most active compounds, 8and 10, were studied to assess their potential apoptotic effects and cell cycle inhibition.

The purpose of this study is to assess the feasibility and the perioperative outcomes of laparoscopic gynecological surgery in regional anesthesia (RA) from the point of view of the surgeon, anesthesiologist and patient. This is a prospective cohort study comprising sixty-six women planned to undergo gynecologic laparoscopy surgery for benign pathology at tertiary care gynecolgical center of the University Federico II of Naples. Women were assigned, according to their preference, to either RA (Group A) or general anesthesia (GA) (Group B). Surgical, anesthesiologic and postoperative recovery data were recorded. Postoperative pain was considered as the primary outcome. Secondary outcomes included mobilization, length of hospital stay, global surgeons and patient satisfaction, intraoperative pain assessment in Group A. Immediate postoperative pain was significantly lower in Group A 0 vs 2 (p< 0.001), with no significant differences at 24 h. The secondary outcome demonstrated early patient’s mobilization (p< 0.001) as well as early discharge (p< 0.001) and greater patient’s satisfaction for the Group A. In these patients, a maximum pain score of 3 points out of 5 was recorded through the entire surgery. RA showed to decrease the impact of surgical stress and to guarantee a quicker recovery without compromising surgical results. Although several surgical approaches can be employed to treat different conditions, RA technique could be a viable option for well-selected patients affected by gynecological diseases.

ABSTRACTBone remodelling after total hip arthroplasty has been largely observed and investigated. Most studies rely on projective images and only few obtain 3D information with limited spatial resolution. This study proposes a method to provide quantitative, 3D high-resolution data about femur bone density variations, by means of CT volume processing. This would offer a tool for further research and clinical studies. Five patients subjected to primary, cementless total hip arthroplasty were considered. Calibrated CT volumes were acquired before, just after surgery and 1 yr later. Bone remodelling hinders accurate alignment of femur volumes acquired after a year; instead, prosthesis stem remains unchanged. Thus, after metal artefact reduction, prosthesis was segmented, and stem-based accurate alignment was obtained. A test to exclude prosthesis migration was performed by considering specific femur anatomical landmarks. Bone density error due to artefact reduction and realignment was estimated. Quantitative differences in bone mineral density were computed for each voxel, providing a resolution of about 1 mm. Preliminary results showed that the femur underwent consistent remodelling after a year. Widespread bone density losses appeared in those areas where strain-adaptive remodelling is normally expected, particularly about the calcar. Conversely, distal areas with clear stem-bone contact showed considerable density gains.