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Abstract Background Health systems across Europe are facing a workforce crisis, with some experiencing severe shortages of doctors. In response, many are exploring greater task-sharing, across established professions, such as doctors, nurses, and pharmacists, with patients and carers, and with new occupational groups, in particular ones that can assist doctors and relieve their workload. Case presentation In the early 2000s the United Kingdom created a new occupational role, that of physician assistant. They had a science degree and then underwent a 2-year postgraduate training course. The name soon changed, to physician associate, and the range of roles and responsibilities expanded greatly, although in a largely unregulated manner; by 2024, some were undertaking complex procedures or managing undifferentiated patients in primary care. Catalysed by some high-profile failings, this expansion has generated major concerns, over patient safety and consent, the scope of practice and preferential employment conditions of this group, the adverse consequences for medical training, and the additional medical workload involved in supervision. This has led to a widespread grassroots backlash by the medical profession, often challenging their leaders who had supported this idea. As a consequence, professional bodies that were initially in favour are now expressing serious concerns and it seems likely that the roles and responsibilities of physician associates (and related occupations) will be curtailed. We review published literature and official documentation about this policy to understand the drivers of its development, its benefits, and risks. Conclusions The experience in the UK offers cautionary lessons for other European countries contemplating similar ideas. It underscores the importance of maintaining trust with those affected by change, undertaking a detailed systems analysis with attention to risks of unintended consequences, agreeing clear role definitions, providing adequate regulatory oversight, and the need to avoid damaging training of future doctors. This case study highlights the need for a carefully thought-out approach that considers both the potential benefits and pitfalls of integrating new roles like physician associates into a healthcare system. The failure to do so has created a new occupational group with unrealistic expectations and has further demoralised an already unhappy medical profession.

Abstract Neurofilament light chain (Nf-L) is a biomarker for axonal damage in human neurology but is understudied in cattle. With this study we wanted to determine Nf-L stability at two different storage temperatures and Nf-L levels in healthy cattle and the relationship with age, evaluate whether Nf-L holds diagnostic potential for neurological disorders, and whether an association exists between Nf-L in serum and in cerebrospinal fluid (CSF). To do this, we measured Nf-L levels in CSF and serum samples from 49 healthy and 75 sick cattle. Storage at −80 °C or −20 °C had no impact on Nf-L concentration. Physiological median Nf-L levels were 6.3 pg/mL (serum) and 414 pg/mL (CSF) in calves and 5.5 pg/mL (serum) and 828 pg/mL (CSF) in adult cattle. There was no association between Nf-L levels in CSF and calf age (r2 0.07, p = 0.13), while a weak association was found for Nf-L in serum (r2 0.26, p = 0.01), and a significant association in adult cattle (CSF, r2 0.69, p = 0.0001; serum, r2 0.68, p = 0.0003). CSF Nf-L levels were higher in samples from animals with degenerative (median Nf-L 49971 pg/mL) and infectious central nervous system (CNS) disorders (median Nf-L, age

Background: Ministerial Decree (D.M.) 77/2022 aims to reform Italy’s primary care system by establishing community health centres and integrating digital tools to address healthcare access disparities and workforce shortages. This review focuses on frailty assessment tools, digital health innovations, and workforce challenges in the Autonomous Province of Bolzano, South Tyrol, emphasising interprofessional trust and collaboration issues. Methods: Using a narrative custom review approach guided by the SANRA checklist, this study synthesised findings from PubMed, official health websites, and regional surveys on frailty, workforce dynamics, interprofessional collaboration, and digital infrastructure in South Tyrol. Results: General practitioners (GPs) exhibited high professional motivation but expressed concerns about autonomy and administrative burdens in collaborative care models. Trust issues between GPs and specialists hinder workforce cohesion and care coordination, highlighting the need for structured inter-professional communication. Frailty assessments, such as the PRISMA-7 tool, identify over 33% of community-dwelling individuals aged 75 years and older as frail, necessitating targeted interventions. Digital health adoption, particularly electronic health records and telemedicine, is slow because of workforce shortages and infrastructure limitations. Conclusions: The successful implementation of D.M. 77/2022 in South Tyrol requires addressing workforce challenges, improving interprofessional trust, expanding digital infrastructure, and integrating frailty assessment findings into care strategies. These measures are critical for achieving a more resilient, equitable, and effective primary healthcare system.

Background/Objectives: The use of coercive measures (CMs) and security technologies (STs) in mental healthcare continues to raise ethical and practical concerns, affecting both patient and staff well-being. Mental health nurses (MHNs) and nursing students (NSs) play a key role in the decision-making process regarding these interventions. However, their attitudes, particularly toward STs, remain underexplored in Italy. This study protocol aims to introduce a new conceptual framework and investigate Italian MHNs’ and NSs’ attitudes toward CMs and STs in mental health settings. Additionally, it will explore the influence of sociodemographic and psychological factors, including stress, anxiety, depression, stigma, and humanization on these attitudes. Methods: The research will be conducted in two phases. Phase 1 involves a national survey of a convenience sample of MHNs and NSs to assess their attitudes and related factors. Phase 2 includes qualitative interviews with a purposive sample of MHNs and NSs to explore participants’ perspectives on STs in more depth. Quantitative data will be analyzed using descriptive and inferential statistics, while qualitative data will be examined through thematic analysis. Conclusions: This study protocol seeks to enhance our understanding of MHNs’ and NSs’ attitudes toward the use of CMs and STs in mental health settings, identifying key factors influencing these attitudes. The findings aim to inform policy development, education programs, and clinical practices in both the Italian and international panoramas. Additionally, the proposed conceptual framework could guide future research in this field.

Background: Arterial embolization is a minimally invasive treatment that occludes blood vessels supplying pathological tissue. Developed to control bleeding without surgery, it has evolved over decades and is now applied in musculoskeletal oncology as a preoperative treatment, palliative care, or standalone therapy for select tumors. Recently, its use has expanded globally in treating chronic pain syndromes and osteoarthritis. Materials and Methods: We reviewed the literature on arterial embolization in various musculoskeletal conditions. The focus was on established oncologic indications for primary and metastatic bone or soft tissue tumors, and emerging evidence on degenerative diseases like osteoarthritis, inflammatory musculoskeletal pathology, and intractable pain. Emphasis was placed on leading studies regarding efficacy, complications, and recurrence rates. Discussion: Arterial embolization has progressed from bleeding control to a versatile therapeutic option in musculoskeletal medicine. It offers symptom relief, reduces tumor size, and improves quality of life. Applications include oncologic interventions and management of degenerative and inflammatory conditions. Despite its benefits, variations in complications and recurrence rates highlight the need for standardized protocols and further research. Conclusions: Arterial embolization is a safe and effective minimally invasive tool in the multidisciplinary management of a wide range of musculoskeletal pathologies. Ongoing research is crucial to understand long-term efficacy, optimize protocols, and broaden its applications.

Sodium glucose cotransporter-2 inhibitors (SGLT2i), originally developed for type II diabetes mellitus, have recently been approved for the treatment of heart failure in both diabetic and non-diabetic patients due to their significant cardiovascular benefits. Beyond their established role in diabetes and heart failure management, current research is exploring the potential applications of SGLT2 inhibitors in the field of cardio-oncology. This interest is driven by dual possible benefits: cardioprotection against the adverse effects of antitumor therapies and inherent antitumor properties. Patients affected by cancer often face the challenge of managing cardiovascular toxicity induced by antineoplastic treatments. SGLT2 inhibitors have shown promise in mitigating toxicities, thereby enhancing the cardiovascular health of these patients. Additionally, emerging evidence suggests that SGLT2 inhibitors may possess direct antitumor effects, further contributing to their therapeutic potential in oncology. This review aims to provide a comprehensive overview of the molecular mechanisms through which SGLT2 inhibitors exert their cardioprotective and antitumor effects. Furthermore, we will examine the current body of evidence supporting the use of these inhibitors in a cardio-oncology setting.

Abstract Gaucher Disease (GD) is an autosomal recessive, lysosomal storage disease caused by pathogenic variants in the glucocerebrosidase gene, leading to the loss of β-glucocerebrosidase (GCase) enzymatic activity. Enzyme replacement therapy (ERT) with recombinant GCase is the standard of care in GD patients. Our study investigates the combined use of in silico molecular evolution, synthetic biology and gene therapy approaches to develop a new synthetic recombinant enzyme. We engineered four GCases containing missense mutations in the signal peptide (SP) from four selected mammalian species, and compared them with human GCase without missense mutations in the SP. We investigated transcriptional regulation with CMV and hEF1a promoters alongside a GFP control construct in 293-FT human cells. One hEF1a-driven mutant GCase shows a 5.2-fold higher level of transcription than control GCase. In addition, this mutant exhibits up to a sixfold higher activity compared with the mock-control, and the predicted tertiary structure of this mutant GCase aligns with human GCase. We also evaluated conserved and coevolved residues mapped to functionally important positions. Further studies are needed to assess its functionality in a GD animal model. Altogether, our findings provide in vitro evidence of the potential of this engineered enzyme for improved therapeutic effects for GD. Article highlights. Conservation and coevolution analysis of amino acid frequencies in GBA1 homologs of pathogenic variants associated with Gaucher disease, Parkinson’ disease risk or Dementia with Lewy bodies risk. Graphic Abstract

Abstract Charcoal kilns, old structures used for charcoal production in the forest, preserve a charcoal-enriched topsoil representing a suitable proxy for studying the long-term effect of biochar addition to soil. Two kiln platforms located at Gelbison and Vesole mountain sites in Southern Italy were selected due to their comparable climates but distinct parent rocks. We conducted standard soil chemical analyses and used next-generation sequencing to explore bacterial and fungal microbiome. Anthracology identified charcoal species, while scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS) characterized charcoal particles. Reflectance Fourier transform infrared spectroscopy (DRIFTS) assessed biochar surface oxidation. Additionally, a bioassay with soybean, maize, and Tomato investigated the impact of kiln soil on plant performance. Our results showed that kiln soils did not exhibit higher pH, cation exchange capacity, or greater richness in cations. EDS and FTIR analyses showed that charcoal buried in forest soil for decades undergoes significant oxidation, with increased O/C ratio and the presence of oxygenated functional groups. Charcoal surfaces were selectively enriched with Ca2+ on limestone substrate sites but with Al and Si over sedimentary (flysch) substrate. While differences in the kiln soil and its surroundings were noticeable, they were not drastic in terms of microbial diversity and composition. Surprisingly, the bioassay indicated that the kiln microbiota had a more positive impact on plant growth compared to external forest soil. In conclusion, this study highlights the unique nature of kiln microsites and begins to unveil the enduring effects of charcoal accumulation on soil chemistry and microbiota in forest soil. Graphical Abstract

Abstract Background While people with substance use disorders, including people who inject drugs (PWID), experience increased risk for COVID-19 infection and adverse outcomes, COVID-19 vaccination rates among PWID are consistently lower than those observed in the general population. Offering COVID-19 vaccines at syringe services programs (SSPs) has been proposed as a critical strategy to increase vaccine uptake among this population. We explored the experiences of frontline staff at an SSP in Miami, Florida implementing onsite COVID-19 vaccines. Methods Between June and July 2022, we conducted in-depth semi-structured interviews with 17 staff members of an SSP in Miami, Florida. Data collection and codebook thematic analysis of transcribed interviews were guided by the Consolidated Framework for Implementation Research (CFIR). Results Facilitators and barriers of COVID-19 vaccine implementation at the SSP aligned with all major CFIR domains. Key facilitators included the SSP’s established partnership with the local health department for vaccine distribution, its existing funding sources which could be leveraged for vaccine-related expenses, consensus among staff about the need for new strategies to increase vaccine uptake among PWID, and PWID’s trust in the SSP. Major—but largely modifiable—barriers included lack of participant compensation, limited internal collaboration and communication regarding the vaccine initiative beyond implementation leads and innovation deliverers due to competing priorities and segmented roles and responsibilities, and insufficient involvement of the most participant-facing staff (i.e., the SSP’s peer navigators and outreach workers). Conclusions Implementing onsite COVID-19 vaccines was perceived as feasible and acceptable by frontline staff at the SSP, however contextual factors impeded optimal implementation. Multilevel strategies, such as participant compensation for vaccine completion and internal educational meetings with staff to improve vaccine implementation and reach, are required. As a trusted source of preventative services for PWID, SSPs are an underutilized venue for increasing vaccine uptake among this population, and findings from this study could inform the expansion of low-barrier vaccine services at SSPs nationwide.

Abstract Background As the global aging population expands, understanding older adults’ preferences for place of death becomes pivotal in ensuring person-centered end-of-life care. Objective This study aimed to investigate the influence of sociodemographic, health, and lifestyle-related factors on end-of-life care preferences of older adults in South Tyrol, Italy. Methods Employing a cross-sectional design, a population-based survey was conducted with a stratified probabilistic sample of adults aged ≥ 75 years in South Tyrol (Autonomous Province of Bolzano/Bozen, Italy). From a randomly selected sample of 3,600 older adults, participants were invited to respond to a questionnaire that included items on older adults’ preferences for place of death and socio-demographic and health- and lifestyle-related factors, including frailty (e.g., PRISMA-7). Descriptive and multinomial logistic regression analyses were performed. Results The majority (55.3%) of the 1,695 older adults (participation rate: 47%) expressed a preference for dying at home and 12.7% indicated a desire for specialized end-of-life care in a healthcare facility. However, 27.9% refrained from disclosing their end-of-life care preferences. The factors influencing these preferences concerning the place of death included age, native language, educational level, living situation, and community. Compared to the preference of dying at own home or home of family or friends, older adults aged ≥ 85 years (OR = 0.57, P = 0.002) and living in an urban area (OR = 0.40, P

Abstract Introduction Occupational therapy has been underdeveloped and often neglected in the global health workforce agenda, contrasting with the global rise of population needs for services. The World Federation of Occupational Therapists (WFOT) is utilizing a research-based, multi-step process for developing a Global Strategy for strengthening the occupational therapist workforce. A multi-pronged scoping review, situational analysis, and expert input process enabled the drafting of a provisional Global Strategy. Here, feedback on that draft from representatives of WFOT member organizations was obtained and analyzed as one key intermediate step toward shaping the in-developing Strategy’s content and structure. Methods Two-phased, mixed-methods consultation consisting of: (1) online survey with score ratings and comments on the utility of each strategy and (2) four in-person focus groups discussions on low-scoring items involving a total of 76 representatives of WFOT member organizations. The focus group discussions were analyzed using an inductive thematic analysis approach. Results Strategies involving ‘task shifting/task sharing’ or the ‘harmonization of workforce data-collection requirements’ received the lowest scores in the initial survey and were thereby addressed in the focus groups discussions. The overarching theme of the focus groups was the need to: “clarify, specify, and contextualize the strategies”, including: (1) “clarify the terminology and specify the application”, for example, describe the meaning of task shifting, specify which tasks can (and cannot) be shifted and to whom, to address concerns regarding scope-of-practice, service demand, and safety; and (2) “outline the context of need and the context for the implementation” of the strategies, elucidating why the strategies are needed and how they can be feasibly implemented across the different jurisdictional contexts. Conclusion Within a mixed-methods consultation, WFOT representatives identified challenging topics on the draft workforce strategies and suggested methods to improve the Global Strategy, its acceptability, and implementation. The terms ‘task shifting/task sharing’ raised the greatest discussion among the profession leaders, when the strategy was not sufficiently clarified, specified, or contextualized.

Abstract Background Patients with active cancer and aortic stenosis may be under-referred for valve interventions due to concerns over a prohibitive risk. However, whether active cancer impacts outcomes after transcatheter aortic valve replacement (TAVR) remains unknown. Methods We searched PubMed, Embase, and Cochrane Library in December 2023 for studies comparing the post-TAVR outcomes of patients with versus without active cancer. We pooled odds ratios (OR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) applying a random-effects model. Statistical analyses were performed in R version 4.3.2. Results We included nine observational studies analyzing 133,906 patients, of whom 9,792 (7.3%) had active cancer. Compared with patients without cancer, patients with active cancer had higher short- (OR 1.33; 95% CI 1.15–1.55; p

Abstract Background Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive tumor of the joints, bursa, and tendon sheath that can cause considerable pain and substantial morbidity. Although surgery is the primary treatment for patients with TGCT, surgical resection is associated with high rates of recurrence, particularly for patients with diffuse TGCT. Pexidartinib, a colony-stimulating factor 1 receptor inhibitor, is approved by the US Food and Drug Administration for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Case Description A 32-year-old man presented with intra-articular diffuse TGCT with pain and received noncurative treatment for 5 years (2014–2019). In 2019, the patient was found to have extensive disease accompanied by pain and limited range of motion. The patient’s case was presented to a sarcoma multidisciplinary tumor board, who determined that surgery would cause significant morbidity and macroscopic residual tumor. As a result of the extent of disease, young age, and otherwise good health, treatment with pexidartinib was started through a compassionate use program at 800 mg/day. After dose reductions to pexidartinib at 400 mg/day and then 200 mg/day as a result of creatine phosphokinase elevations, the patient achieved a complete response after 2 years of treatment; pain was reduced and mobility was restored. The patient reported no side effects related to pexidartinib treatment. Treatment was stopped in 2022 for future family planning. After pexidartinib therapy was interrupted, the patient’s wife had a successful pregnancy and delivery; however, the disease showed a slow but constant clinical deterioration, with a reduction in the range of movement of the affected knee and an apparent increase in widespread TGCT nodules. Conclusion Our case is unique because it provides support for pexidartinib use as upfront therapy for TGCT, instead of surgery, in selected cases.

Abstract Background Tobacco use is one of the main risk factors for Lung Cancer (LC) development. However, about 10–20% of those diagnosed with the disease are never-smokers. For Non-Small Cell Lung Cancer (NSCLC) there are clear differences in both the clinical presentation and the tumor genomic profiles between smokers and never-smokers. For example, the Lung Adenocarcinoma (LUAD) histological subtype in never-smokers is predominately found in young women of European, North American, and Asian descent. While the clinical presentation and tumor genomic profiles of smokers have been widely examined, never-smokers are usually underrepresented, especially those of a Latin American (LA) background. In this work, we characterize, for the first time, the difference in the genomic profiles between smokers and never-smokers LC patients from Chile. Methods We conduct a comparison by smoking status in the frequencies of genomic alterations (GAs) including somatic mutations and structural variants (fusions) in a total of 10 clinically relevant genes, including the eight most common actionable genes for LC (EGFR, KRAS, ALK, MET, BRAF, RET, ERBB2, and ROS1) and two established driver genes for malignancies other than LC (PIK3CA and MAP2K1). Study participants were grouped as either smokers (current and former, n = 473) or never-smokers (n = 200) according to self-report tobacco use at enrollment. Results Our findings indicate a higher overall GA frequency for never-smokers compared to smokers (58 vs. 45.7, p-value

A short history of paperback editions, with a focus on the main publishers who created a great number of new readers thanks to their collections.

Abstract Background Thoracotomy is one of the surgical procedures most burdened by chronic post-operative pain. There is poor evidence regarding the possibility that even in pediatric patients, thoracotomy can be followed by post-operative pain. The primary objective of this analysis is to identify associations with home pain therapy, pain intensity, and possible protective factors acting on chronic pain in this population. Methods A retrospective cross-sectional study was conducted at Ospedale Pediatrico Bambino Gesù IRCCS. The study included pediatric patients undergoing thoracotomy. For statistical analyses, a logistic model and a zero-inflated strategy were implemented to explore associations and predict factors related to home-based analgesic therapy and pain intensity. Results Gender and age were identified as significant factors in the assignment of home therapy, with males having over seven times the risk compared to females (OR = 7.06, 95% CI = [2.11, 29.7]). At the last measurement, pain intensity was positively associated with age and the number of pain events during the week. Conclusions The study highlights significant factors influencing post-thoracotomy pain management in pediatric patients. These findings underscore the importance of tailored pain management strategies that consider gender and age to improve post-operative care and outcomes in pediatric thoracotomy patients.

RESUMEN La evaluación funcional de las estenosis coronarias para guiar los procedimientos de intervencionismo coronario percutáneo se realiza frecuentemente midiendo la reserva fraccional de flujo durante la hiperemia inducida por adenosina o trifosfato de adenosina. Las contraindicaciones de estos estímulos hiperémicos y la posibilidad de que se produzca daño vascular con la guía de presión pueden limitar la utilización de la reserva fraccional de flujo. Esta revisión discute los métodos alternativos de evaluación funcional: diferentes agentes hiperémicos, índices no hiperémicos e índices angiográficos.

ABSTRACT Assessment of the functional significance of coronary artery stenoses to guide percutaneous coronary intervention is widely performed using pressure wire fractional flow reserve during adenosine- or adenosine triphosphate-induced hyperemia. However, the use of fractional flow reserve may be limited by the contraindications and adverse effects of this hyperemic stimulus, as well as the potential risk of vessel damage from the pressure wire. This review will discuss alternative evaluation methods, including various hyperemic agents, nonhyperemic pressure ratios, and angiography-based indices.

The discovery of RNA interference in 1998 opened avenues for the manipulation of gene expression, leading to the development of small interfering RNA (siRNA) drugs. Patisiran, the first FDA-approved siRNA medication, targets hereditary transthyretin amyloidosis with polyneuropathy. Givosiran, lumasiran and nedosiran further expand siRNA applications in treating rare genetic diseases, demonstrating positive outcomes. In cardiology, inclisiran, approved for hypercholesterolaemia, showcases sustained reductions in LDL cholesterol levels. However, ongoing research aims to establish its impact on cardiovascular outcomes. Lipoprotein(a), an independent risk factor for atherosclerotic cardiovascular disease, has become a focus of siRNA therapies, precipitating the development of specific siRNA drugs like olpasiran, zerlasiran and lepodisiran, with promising reductions in lipoprotein(a) levels. Research to assess the effectiveness of these medications in reducing events is currently under way. Zodasiran and plozasiran address potential risk factors for cardiovascular diseases, targeting triglyceride-rich lipoproteins. Zilebesiran, which targets hepatic angiotensinogen mRNA, has demonstrated a dose-related reduction in serum angiotensinogen levels, thereby lowering blood pressure in patients with systemic arterial hypertension. The evolving siRNA methodology presents a promising future in cardiology, with ongoing studies assessing its effectiveness in various conditions. In the future, larger studies will provide insights into improvements in cardiovascular outcomes, long-term safety and broader applications in the general population. This review highlights the historical timeline of the development of siRNA-based drugs, their clinical indications, potential side-effects and future perspectives.

Abstract Purpose Implanted devices used in metastatic spine tumor surgery (MSTS) include pedicle screws, fixation plates, fixation rods, and interbody devices. A material to be used to fabricate any of these devices should possess an array of properties, which include biocompatibility, no toxicity, bioactivity, low wear rate, low to moderate incidence of artifacts during imaging, tensile strength and modulus that are comparable to those of cortical bone, high fatigue strength/long fatigue life, minimal or no negative impact on radiotherapy (RT) planning and delivery, and high capability for fusion to the contiguous bone. The shortcomings of Ti6Al4V alloy for these applications with respect to these desirable properties are well recognized, opening the field for an investigation about novel biomaterials that could replace the current gold standard. Previously published reviews on this topic have exhibited significant shortcomings in the studies they included, such as a small, heterogenous sample size and the lack of a cost-benefit analysis, extremely useful to understand the practical possibility of applying a novel material on a large scale. Therefore, this review aims to collect information about the clinical performance of these biomaterials from the most recent literature, with the objective of deliberating which could potentially be better than titanium in the future, with particular attention to safety, artifact production and radiotherapy planning interference. The significant promise showed by analyzing the clinical performance of these devices warrants further research through prospective studies with a larger sample size also taking into account each aspect of the production and use of such materials. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used to improve the reporting of the review. The search was performed from March 2022 to September 2023. Results At the end of the screening process, 20 articles were considered eligible for this study. Polyetheretherketone (PEEK), Carbon-fibre reinforced polyetheretherketone (CFR-PEEK), long carbon fiber reinforced polymer (LCFRP), Polymethylmethacrylate (PMMA), and carbon screw and rods were used in the included studies. Conclusion CFR-PEEK displays a noninferior safety and efficacy profile to titanium implanted devices. However, it also has other advantages. By decreasing artifact production, it is able to increase detection of local tumor recurrence and decrease radiotherapy dose perturbation, ultimately bettering prognosis for patients necessitating adjuvant treatment. Nonetheless, its drawbacks have not been explored fully and still require further investigation in future studies. This does not exclude the fact that CFR-PEEK could be a valid alternative to titanium in the near future.

Abstract In silico prediction of xenobiotic metabolism is an important strategy to accelerate the drug discovery process, as candidate compounds often fail in clinical phases due to their poor pharmacokinetic profiles. Here we present MetaQM, a dataset of quantum-mechanical (QM) optimized metabolic substrates, including force field parameters, electronic and physicochemical properties. MetaQM comprises 2054 metabolic substrates extracted from the MetaQSAR database. We provide QM-optimized geometries, General Amber Force Field (FF) parameters for all studied molecules, and an extended set of structural and physicochemical descriptors as calculated by DFT and PM7 methods. The generated data can be used in different types of analysis. FF parameters can be applied to perform classical molecular mechanics calculations as exemplified by the validating molecular dynamics simulations reported here. The calculated descriptors can represent input features for developing improved predictive models for metabolism and drug design, as exemplified in this work. Finally, the QM-optimized molecular structures are valuable starting points for both ligand- and structure-based analyses such as pharmacophore mapping and docking simulations.

Anthropogenic threats impacting ecological targets should be mitigated and solved using fast and schematic tools useful in conservation strategies. Herein, we suggest a mixed and quick approach implementing coarse-grained (and expert-based) threat analysis with the fine-grained (and analytical) DPSIR (driving forces, pressure, status, impact, and response) framework of indicators, all included in a single causal chain. Both approaches are largely used in conservation but never combined. A simulated example of the application of the set of indicators (status, pressure, impact, and response) on dune ecosystems (and nested targets represented by halo-psammophilous plants) has been included. Due to its schematic format, values as targets, pressures as threats, and responses as conservation strategies have been unified in a single conceptual framework. This synthetic framework can also be used to communicate to academic students the complexities of socio-ecological systems on the conservation front lines using a simplified cause–effect chain.

The Rydberg blockade mechanism is an important ingredient in quantum simulators based on neutral atom arrays. It enables the emergence of a rich variety of quantum phases of matter, such as topological spin liquids. The typically isotropic nature of the blockade effect, however, restricts the range of natively accessible models and quantum states. In this work, we propose a method to systematically overcome this limitation, by developing gadgets, i.e., specific arrangements of atoms, that transform the underlying Rydberg blockade into more general constraints. We apply this technique to realize dimer models on square and triangular geometries. In these setups, we study the role of the quantum fluctuations induced by a coherent drive of the atoms and find signatures of U(1) and Z_{2} quantum spin liquid states in the respective ground states. Finally, we show that these states can be dynamically prepared with high fidelity, paving the way for the quantum simulation of a broader class of constrained models and topological matter in experiments with Rydberg atom arrays.

Objectives To analyse the potential of the Social Health Insurance (SHI) model to support the achievement of Universal Health Coverage (UHC) in Low and Middle-Income Countries (LMICs) through a policy analysis case study of Kenya’s National Health Insurance Fund (NHIF).Design We used an adaptation of the policy triangle framework to perform a retrospective policy analysis of Kenya’s NHIF, drawing from semistructured interviews and analysis of published documents and grey literature.Setting We focused on Kenya’s NHIF as a case study.Participants We conducted 21 interviews with key stakeholders including policy experts, healthcare providers and formal and informal sector workers. We then triangulated the interview findings with document analysis.Results Only 17% of Kenya’s population are currently covered by the SHI as of 2023. Only 27% of the informal economy is covered by the NHIF, implying very low uptake and/or retention rates. We found little stakeholder engagement in the policy implementation process and minimum adoption of expert advice. Our analysis suggest that political affiliations and positions of power heavily influence health financing policies in Kenya. Purchasing and payment of healthcare was found to be riddled with inefficiencies, including slow bureaucratic reimbursement procedures, little expertise by rural hospital clerks, misappropriations and favouritism of specific private healthcare providers. We also found that group-based parallel schemes and penalty payments for defaulted premiums widened the existing inequity gap in healthcare access.Conclusion Although the SHI system is perceived to increase coverage and the quality of health services in Kenya, substantial structural and contextual challenges appear to deter its suitability to finance the attainment of Universal Health Coverage. From Kenya’s experience, we identify little informal sector participation, inefficiencies in purchasing and payment of healthcare services, as well lack of political goodwill, as key bottlenecks for the implementation of SHI schemes in LMICs. LMICs adopting SHI need to also implement co-financing arrangements that do not impose on the population to co-finance, strategic purchasing systems, political goodwill and good governance for the SHI systems to be beneficial.

Italian wh-questions with bare wh-elements are characterized by an exceptional prosodic pattern, whereby the nuclear pitch accent (NPA) is assigned neither to the wh-element nor to the default rightmost position, but it rather falls on the lexical verb, even though this is not semantically interpreted as a focus. Based on evidence from production, in previous work we argue that the NPA assignment is a reflex of the cyclic syntactic derivation, being sensitive to a syntactic [focus] feature borne by the wh-phrase. The striking dissociation between the NPA and focal interpretation that emerges from the production data raises the question of whether Italian hearers are sensitive to this marked prosodic pattern in understanding a question. To address this question, we carried out a comprehension experiment, where we manipulated the position of the NPA in biclausal wh-questions including two verbs: the verb of the matrix clause and the embedded verb. The results of this experiment confirm the psychological reality of our theoretical analysis, suggesting that hearers exploit prosodic cues to parse the sentence and to assign the correct interpretation to structures that only differ at the surface level with respect to the position of the NPA.

This paper investigates the acceptability of wh in-situ expressions in embedded contexts in French. We report on two experiments that tested the acceptability of wh in-situ and ex-situ in embedded clauses of biclausal direct wh-questions and in indirect questions, and how their acceptability is modulated by the presence of the negation in the embedded clause. In Experiment 1, the contexts favored a D-linked interpretation of the wh-element (in the sense of Pesetsky 1987), while the contexts in Experiment 2 disfavored it. Our results show that the in-situ strategy is generally more acceptable (or at least equally acceptable) than the ex-situ strategy in direct questions with long construal, regardless of D-linking and negation. By contrast, the in-situ strategy is significantly less acceptable than the ex-situ one in indirect questions, regardless of D-linking and negation. Our findings indicate that in long construal direct wh-questions, negation fails to selectively block wh in-situ. In this respect, French differs from many other languages (see e.g., Beck & Kim 1997, a.o.). We show that D-linking is not a necessary condition for in-situ in French. We discuss how our findings relate to the current debate between alternative formal analyses of wh in-situ in French.

The purpose of this study was to evaluate the ecotoxicological effects on soils containing associations of the herbicide tebuthiuron (TBT), the insecticide thiamethoxam (TMX), vinasse (VIN), and millet (Pennisetum glaucum) cultivation. We conducted the experiment under greenhouse conditions using a completely randomized design with five replications. Treatments consisted in soil application of tebuthiuron (1000 g ha−1 a. i), thiamethoxam (330 g ha−1 a. i), vinasse (113 m3 ha−1) with or without P. glaucum cultivation. The monitoring extended to 50 days after sowing (DAS) and evaluated the ecotoxicological potential from Lactuca sativa seeds as test-organism. Seed germination and root development determined the germination index (GI) concerning the negative control, which was prepared with water. Thus, P. glaucum highlighted a beneficial influence on soil health, thereby mitigating the ecotoxicological effects of TBT and TMX. Results emphasized the importance of the timing in soil sample collection, where early collections after plant seeding result in higher germination rates and rapid soil health improvements. Furthermore, vinasse reduced the ecotoxicological impact of pesticides and TBT presence presented harmful effects to test-organism. The interaction between P. glaucum growth period and soil sampling had a profound impact on ecotoxicity bioassays, which highlighted the importance of early intervention. Therefore, P. glaucum and vinasse can be valuable components in effective phytoremediation strategies, pointing towards future research and enhancement of approaches for sustainable treatment strategies of agricultural soils with pesticides.

Background: The evidence of the long-term advantages of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) for aortic stenosis (AS) remains scarce. Methods: Patients with EuroSCORE II

ABSTRACTMonkeypox virus (MPXV) infection confirmation needs reliable polymerase chain reaction (PCR) assays; in addition, viral clade attribution is a key factor in containment measures, considering a more severe syndrome in clade I and the possibility of simultaneous circulation. This study evaluates the performance of all-in-one STANDARD M10 MPX/OPX (SD BIOSENSOR, South Korea – M10). Frozen samples from 205 subjects were selected and stratified according to routine test results (RealStar® Orthopoxvirus PCR Kit 1.0, Altona DIAGNOTICS, Germany – RS; RS-1): in detail, 100 negative skin lesions (SL) and 200 positive samples at the variable stage of infection were analysed. Positive samples were retested with RS (RS-2). Positive and Negative Percent Agreements (PPA, NPA) were calculated. The median (IQR) Ct values of RS and M10 (OPXV target) assays were highly similar. The PPA of M10 compared to RS-1 was 89.5% considering system interpretation, and 96.0% when the operator classified results as positive if any target was detected; NPA was 100%. Comparing the RS-2 run and M10, an overall concordance of 95.3% between assays was found; however, considering operator interpretation, M10 returned more positive results than RS-2. The occurrence of False-Negative results was likely associated with the influence of thawing on low viral concentration; no False-Positive tests were observed. All samples collected at the time of Mpox diagnosis were positive and M10 correctly attributed the clade (West-Africa/II). The M10 MPX/OPX assay demonstrated high reliability in confirming MPXV infection and clade attribution.

Per- and polyfluoroalkyl substances (PFASs) are a large class of compounds used in a variety of processes and consumer products. Their unique chemical properties make them ubiquitous and persistent environmental contaminants while also making them economically viable and socially convenient. To date, several reviews have been published to synthesize information regarding the immunotoxic effects of PFASs on the adaptive immune system. However, these reviews often do not include data on the impact of these compounds on innate immunity. Here, current literature is reviewed to identify and incorporate data regarding the effects of PFASs on innate immunity in humans, experimental models, and wildlife. Known mechanisms by which PFASs modulate innate immune function are also reviewed, including disruption of cell signaling, metabolism, and tissue-level effects. For PFASs where innate immune data are available, results are equivocal, raising additional questions about common mechanisms or pathways of toxicity, but highlighting that the innate immune system within several species can be perturbed by exposure to PFASs. Recommendations are provided for future research to inform hazard identification, risk assessment, and risk management practices for PFASs to protect the immune systems of exposed organisms as well as environmental health.

The concept of Nature-based Solutions (NbS) has gained interest as an approach to make significant contributions to the transformation towards more liveable, sustainable, and climate-resilient cities. However, the uptake of NbS into urban development practice is hindered by knowledge and governance barriers. Knowledge plays an essential role in evidence-based decision-making processes and in building the capacity to co-design sustainable pathways. In turn, governance processes can greatly support the acquisition, dissemination and application of knowledge. However, little is known about how these interactions between governance and knowledge manifest in practice. Therefore, we aim to understand the interplay between governance and monitoring & assessment (M&A) and the associated challenges and opportunities for NbS implementation in European and Latin American cities. Considering different socio-economic and cultural contexts allows us to draw from a wider range of practitioners’ experiences in different governance settings. We conducted an explorative qualitative content analysis on ten semi-structured expert interviews with thirteen city experts from local governments and academia based in seven cities: Bogota (CO), Buenos Aires (AR), Santiago (CL), São Paulo (BR), Barcelona (ES), Lisbon (PT) and Turin (IT). Our findings show that M&A provides agency for individual, institutional actors to steer political commitment and can support integrated working. The potential of collaborative M&A with non-governmental actors is still largely untapped, which requires acknowledgement of the capacities of non-governmental actors to contribute to M&A and raise awareness of the value of M&A to civil society. Furthermore, we recommend integrating more reflective learning opportunities in M&A processes, paying more attention to data sharing, and considering of more feasible M&A processes.

Background: Out-of-hospital cardiac arrest (OHCA) is a major health concern in Europe, leading to significant morbidity and mortality. Survivors often suffer from cognitive deficits, anxiety, and depression, that affect significantly their quality of life. Current post-discharge care is inconsistent and frequently overlooks subtle but disabling symptoms. The ENFORCER trial aims to significantly enhance the health and quality of life of OHCA survivors by providing a comprehensive, accessible, and user-friendly internet-based lifestyle intervention. Methods: ENFORCER is a multicentre, parallel group randomized controlled trial involving OHCA survivors aged 18–80 years with cognitive impairment or anxiety/depression measured through validated instruments.Participants will be randomized 1:1 to the intervention or the control group. The intervention group will receive a one-year program via a secure web application, offering cognitive, emotional, and physical rehabilitation support. The control group will receive standard care.The primary outcome is the difference in the proportion of patients without cognitive or emotional symptoms between the two groups after one year.Secondary outcomes include changes in the level of patients’ cognitive and emotional symptoms, quality of life, sleep quality, sexual interest and satisfaction, and caregivers’ burden, quality of life, sleep quality and emotional symptoms in the two groups. Discussion: The trial addresses the need for consistent post-discharge care, and the timely detection and treatment of cognitive and emotional problems. The internet-based approach allows to potentially reach many patients, ensuring cost-effectiveness and high adherence rates.The study results could establish a standard for post-OHCA care, improving long-term recovery and quality of life for survivors.Trial registration.The trial is registered at clinicaltrials.gov (NCT06395558).

Considerando os desafios socioambientais contemporâneos e as mudanças curriculares no cenário educacional brasileiro, os Projetos Integradores, que surgem recentemente para apoiar a melhoria da qualidade da educação, são incipientes no currículo, sendo necessário o preparo docente para implementar essa perspectiva interdisciplinar no contexto educacional. Para isso, a formação docente e o apoio de livros didáticos são fundamentais. A educação CTSA pode fornecer uma base teórica robusta para os propósitos educacionais do currículo do ensino de ciências. Contudo, os livros didáticos também precisam ser avaliados sobre sua capacidade de contribuir para atingir os objetivos educacionais dos currículos nacionais. Desse modo, a presente pesquisa documental, exploratória e qualitativa teve por objetivo investigar as principais vertentes da educação CTSA de um livro didático sobre Projetos Integradores da área das Ciências da Natureza e suas Tecnologias. Adotou-se a análise de conteúdo para discutir possíveis contribuições deste livro didático para a melhoria da qualidade da educação, na perspectiva CTSA. Os principais resultados indicam um predomínio de uma educação CTSA voltada para o letramento científico epistêmico, valorizando a aplicação de conhecimentos científicos e tecnologias para a resolução de problemas, e desvalorizando as dimensões ética e política dos conteúdos, além da ausência da vertente específica sobre a educação ambiental e integração entre ser humano e meio natural. Conclui-se sobre a necessidade de estudos mais aprofundados sobre essa temática, bem como no investimento na formação docente, para que os professores possam adotar este livro didático a partir de perspectivas mais críticas.

Ultrafast fiber lasers (UFLs) have become an attractive alternative to solid‐state lasers (SSL) due to their excellent beam quality, compactness, environmental stability, and easy thermal management. In the last decade, a significant research effort is spent to identify UFL architectures providing pulse energy, duration, and peak power comparable to those of complex and expensive, Ti:sapphire laser systems and semiconductor saturable absorber mirrors mode‐locked, Yb‐doped SSL. Lately, Mamyshev oscillators (MOs), relying on offset spectral filtering combined with nonlinear spectral broadening by self‐phase modulation, emerge as a promising solution and are rapidly becoming the state of the art for high energy/peak power UFLs based on large‐mode‐area (LMA) fibers. The focus of this work is the first demonstration of starting of the mode‐locking regime in an LMA MO with an affordable passively Q‐switched microchip laser. This solution was previously demonstrated only in low‐power MO based on single‐mode fibers, which are intrinsically easier to seed, if compared to high‐gain LMA UFLs, because of the lower amplified spontaneous emission noise floor. This starting technique in an easy‐to‐implement ring LMA MO at 1 μm is tested. The oscillator provides ≈50 nJ pulses at 12 MHz repetition rate with a minimum pulse duration of ≈50 fs after compression, resulting in MW peak power.

Plants shape their surrounding soil, influencing subsequent plant growth in a phenomenon known as plant–soil feedback (PSF). This feedback is driven by chemical and microbial legacies. Here, we cultivated six crops from two functional groups, i.e., three grasses (Lolium, Triticum, and Zea) and three legumes (Glycine, Lens, and Medicago), to condition a living soil. Subsequently, the same species were sown as response plants on conspecific and heterospecific soils. We employed high-throughput sequencing in tandem with soil chemistry, including total organic matter, pH, total nitrogen, electrical conductivity, phosphorus, and macro and micro-nutrients. Our results showed that Glycine exhibited the strongest negative PSF, followed by Triticum and Zea, while Lolium displayed low feedback. Conversely, Lens demonstrated robust positive PSF, with Medicago exhibiting slight positive feedback. Soil chemistry significance indicated only higher Cl content in Triticum soil, while Lens displayed higher Zn and Mn contents. Microbial diversity exhibited no significant variations among the six soils. Although conditioning influenced the abundance of functionally important microbial phyla associated with each plant, no specificity was observed between the two functional groups. Moreover, each crop conditioned its soil with a substantial proportion of fungal pathogens. However, co-occurrence analysis revealed a strong negative correlation between all crop’s biomass and fungal pathogens, except Glycine, which exhibited a strong negative correlation with mutualists such as Arthrobacter and Bacillus. This underscores the complexity of predicting PSFs, emphasizing the need for a comprehensive understanding of plant interactions with both pathogens and mutualists, rather than focusing solely on host-specific pathogens.

This narrative review addresses the integration of health education into school curricula in South Tyrol, an Italian province with significant cultural and linguistic diversity. This review’s objective is to analyze current health education initiatives and propose a strategic framework to enhance school-based health education, aiming to improve student well-being post-pandemic. The review synthesizes global examples and recent local studies, highlighting the importance of comprehensive teacher training, mindfulness-based interventions, culturally sensitive health education, and community engagement. The key findings indicate that current health education programs in South Tyrol are insufficient to meet immediate public health needs, such as low vaccine uptake and mental health challenges exacerbated by the COVID-19 pandemic. The proposed strategic framework seeks to align educational strategies with the diverse needs of South Tyrol’s student population, thereby improving health literacy and behavior and strengthening the region’s public health infrastructure.

The aim of this paper is to reconstruct the main features and historical-political reasons behind the presidentialism proposal advanced by Piero Calamandrei in the Constituent Assembly. The Author illustrates this proposal not only within the context of the Florentine jurist’s thought, but also within the broader field of institutional reforms and the Italian political system, highlighting the factors that undermine the stability of the executive.

This narrative review delves into the evolving landscape of fertility preservation techniques, with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted, and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the ‘flare-up’ effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and the management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.

Abstract Whether disasters serve as focusing events leading to measures that reduce future disaster risks is contested. Here, we study flood disasters in 23 of the world’s most flood-prone countries to assess whether catastrophic floods, those milestone events with the highest fatalities, have been followed by decreasing mortality in subsequent floods. Results from a trend analysis, controlling for flood magnitude and subtypes, find that reductions in mortality rates have rarely followed the most devastating floods.

It is since the beginning of the so-called ‘digital revolution’ in the 1950s that technological tools have been developed to simplify and optimise traditional, time-consuming, and laborious anamnestic collection for many physicians. In recent years, more and more sophisticated ‘automated’ anamnestic collection systems have been developed, to the extent that they can actually enter daily clinical practice. This article not only provides a historical overview of the evolution of such tools, but also explores the ethical and medico-legal implications of the transition from traditional to digital anamnesis, including the protection of data confidentiality, the preservation of the communicative effectiveness of the doctor–patient dialogue and the safety of care in patients with poor digital and health literacy.

Heterospilus sicanus (Marshall, 1888) is redescribed and illustrated based on the holotype of Dendrosoter sicanus Marshall, 1888 and on recently collected material from its type locality (Sicily, Italy). Previous host records for this species are unreliable. Here, the host of H. sicanus, the rare ptinid beetle Gastrallus pubens Fairmaire, 1875, is recorded for the first time, having been reared in a historic library in Palermo, Italy. Heterospilus sicanus is compared with the similar species Telebolus (= Heterospilus) corsicus Marshall, 1888, which was described in the same monograph from Corsica (France), and it is also redescribed and illustrated. Atoreuteus ceballosi Docavo Alberti, 1960, syn. nov. is synonymised under Heterospilus sicanus (Marshall, 1888), and Hormiopterus (= Rhaconotus) ollivieri Giraud var. flava Fahringer, 1931, syn. nov. is a junior synonym of Heterospilus cephi Rohwer, 1925. A key for determination of the Western Palaearctic Heterospilus species with a striate vertex is provided and the distributions of H. sicanus and H. corsicus are discussed.

Abstract Background SMYD3 has been found implicated in cancer progression. Its overexpression correlates with cancer growth and invasion, especially in gastrointestinal tumors. SMYD3 transactivates multiple oncogenic mechanisms, favoring cancer development. Moreover, it was recently shown that SMYD3 is required for DNA restoration by promoting homologous recombination (HR) repair. Methods In cellulo and in vivo models were employed to investigate the role of SMYD3 in cancer chemoresistance. Analyses of SMYD3-KO cells, drug-resistant cancer cell lines, patients’ residual gastric or rectal tumors that were resected after neoadjuvant therapy and mice models were performed. In addition, the novel SMYD3 covalent inhibitor EM127 was used to evaluate the impact of manipulating SMYD3 activity on the sensitization of cancer cell lines, tumorspheres and cancer murine models to chemotherapeutics (CHTs). Results Here we report that SMYD3 mediates cancer cell sensitivity to CHTs. Indeed, cancer cells lacking SMYD3 functions showed increased responsiveness to CHTs, while restoring its expression promoted chemoresistance. Specifically, SMYD3 is essential for the repair of CHT-induced double-strand breaks as it methylates the upstream sensor ATM and allows HR cascade propagation through CHK2 and p53 phosphorylation, thereby promoting cancer cell survival. SMYD3 inhibition with the novel compound EM127 showed a synergistic effect with CHTs in colorectal, gastric, and breast cancer cells, tumorspheres, and preclinical colorectal cancer models. Conclusions Overall, our results show that targeting SMYD3 may be an effective therapeutic strategy to overcome chemoresistance.

Abstract A precise modelling of the dynamics of bubbles nucleated during first-order phase transitions in the early Universe is pivotal for a quantitative determination of various cosmic relics, including the stochastic background of gravitational waves. The equation of motion of the bubble front is affected by the out-of-equilibrium distributions of particle species in the plasma which, in turn, are described by the corresponding Boltzmann equations. In this work we provide a solution to these equations by thoroughly incorporating the non-linearities arising from the population factors. Moreover, our methodology relies on a spectral decomposition that leverages the rotational properties of the collision integral within the Boltzmann equations. This novel approach allows for an efficient and robust computation of both the bubble speed and profile. We also refine our analysis by including the contributions from the electroweak gauge bosons. We find that their impact is dominated by the infrared modes and proves to be non-negligible, contrary to the naive expectations.

Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

The objective of this study was to evaluate the effectiveness of adding yeast culture (Saccharomyces cerevisiae) combined with Lithothamnium to the diet of feedlot steers through weight gain, dry matter (DM) intake, apparent DM digestibility, and carcass ultrasonography: T1 - diet with yeast culture (7g animal day-1); T2 - diet with Lithothamnium (60g animal day-1); T3 - diet with yeast culture (7g animal day1) plus Lithothamnium (60g animal day-1). Thirty-six ½ Angus Nellore steers, intact males, with an average initial weight of 350 kg and an average age of 11 months, were assigned to a completely randomized design composed of three treatments with six replications; each replication was represented by a pen with two animals. The animals were fed ad libitum twice daily, at 6:00 and 17:00 h. The diets consisted of 40% corn silage and 60% concentrate, on a DM basis. The feedlot period was 78 days, with 10 days of adaptation and 68 experimental days divided into two periods of 34 days each. The addition of yeast culture combined or not with Lithothamnium to the diet resulted in greater average daily gain (1.557 and 1.609 versus 1.440 kg day-1), better feed conversion ratio (6.72 and 6.91 versus 7.57 kg DM kg body weight gain-1), and increased the subcutaneous fat thickness (6.69 and 6.71 versus 5.72 mm). This is because of the higher apparent DM digestibility of the diet (71.11 and 69.32 versus 67.51%) compared to the isolated use of Lithothamnium. The addition of yeast culture, combined or not with Lithothamnium in the diet of feedlot steers, is recommended to improve animal performance and increase fat deposition in the carcass.

IntroductionBacterial infection of the central nervous system (CNS) poses a clinical challenge and is a leading cause of neurological disorders in cattle. Human studies have demonstrated an increase in cerebrospinal fluid (CSF) L-lactate levels in bacterial meningitis. The aims of this study were to establish a Reference Interval (RI) for L-lactate in bovine CSF and assess its potential as a biomarker for detecting infectious-inflammatory disorders.MethodsCSF L-lactate was measured in the field using a commercially available lactate monitor. The RI for CSF L-lactate was calculated on healthy animals; univariate and receiver operating characteristic (ROC) analyses were performed to disclose an association between CSF L-lactate levels and interpretation of CSF in sick animals.ResultsTwenty-seven healthy cattle and 86 sick cattle with either CNS infectious-inflammatory disorders (47/86) or CNS disorders of other etiology (39/86) were included in this prospective study. The RI for CSF L-lactate was 1.1–2.4 mmol/L. The concentration was higher in the cattle with neutrophilic pleocytosis and the area under the ROC curve was 0.92 compared to other animals. Based on a cut-off of 3.15 mmol/L, CSF L-lactate had diagnostic sensitivity and specificity for neutrophilic pleocytosis of 93 and 80%, respectively.DiscussionThis is the first study to determine a RI for CSF L-lactate in cattle. Elevated CSF L-lactate levels indicated neutrophilic pleocytosis, which is often manifested in acute bacterial infection. The present findings may aid in diagnosis and correct use of antimicrobial drugs.

Introduction/objectivesThe precise location of the tumor site is essential for the success of surgical treatment. Neoadjuvant chemotherapy (NAC) is a challenge for preoperative tumor and node localization. Thus, the knowledge and attitudes of the affiliated members of the Brazilian Society of Mastology (SBM) regarding breast and axilla marking were evaluated and a consensus regarding management and treatment was reached.MethodsThis was an online survey conducted between June and December 2022. All 1,742 active mastologists affiliated to the SBM were invited anonymously. The online form contained 28 objective questions, of which 22 were formulated on a Likert scale. These questions addressed relevant aspects related to breast and axilla marking in the neoadjuvant setting. Responses that reached 70% agreement were considered consensual. Statistical analysis was performed using the SPSS program version 26.0. Post hoc analysis was performed when appropriate and the significance level was set at p < 0.05. Polychoric regression analyses were conducted using `VGAM` packageResultsIn total, 468 mastologists answered the questionnaire (26.8%), with a predominance of professionals aged between 40–49 years (32.1%). Most professionals were board-certified (84,8%). The indication of tumor marking in the breast prior to NAC was consensual (96.4%) and the metal clip was the preferred method (69.7%). There was no consensus regarding the indication of pre-NAC histologically positive lymph node marking (49.8% disagree and 42.8% agree). However, there was consensus that the clinical and imaging evaluation was insufficient for staging the axilla as N1 (71.6%). The contraindication of breast and node marking in T4b tumors (71.2%) was consensual. There was consensus on the indication of sentinel lymph node biopsy (SLNB) for initially cN1 (92.3%) or cN2 (72.7%) tumors that became cN0 after NAC, with 67.5% opting for dual staining with technetium and patent blue. When

This special issue addresses the challenges of the international economy, focusing on structural change, social inclusion, and environmental sustainability. It brings together contributions from senior and young scholars, many from Latin America, to explore multidimensional issues like inequality, geopolitical tensions, financial instability, environmental crises, and technological asymmetries. The selected papers, initially presented at the 1st International Workshop on Structural Change, Social Inclusion, and Environmental Sustainability, provide diverse perspectives on topics such as economic policy for a fair transition, centre-periphery dynamics, and the intersection of gender, labour, and economic growth. These works aim to foster collaboration between experienced and emerging voices, enriching the conversation around economic development through pluralist approaches.