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Research integrity is fundamental to the validity and reliability of scientific findings, and for ethical conduct of research. As part of PRINTEGER (Promoting Integrity as an Integral Dimension of Excellence in Research), this study explores the views of researchers, research managers, administrators, and governance advisors in Estonia, Italy, Norway and UK, focusing specifically on their understanding of institutional and organisational influences on research integrity. A total of 16 focus groups were conducted. Thematic analysis of the data revealed that competition is pervasive and appeared in most themes relating to integrity. The structural frameworks for research such as funding, evaluation and publication were thought to both protect and, more commonly, undermine integrity. In addition, institutional systems, including workload and research governance, shaped participants' day-to-day work environment, also affecting research integrity. Participants also provided ideas for promoting research integrity, including training, and creating conditions that would be supportive of research integrity. These findings support a shift away from individual blame and towards the need for structural and institutional changes, including organisations in the wider research environment, for example funding bodies and publishing companies.

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. Methods The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater. Results During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. Conclusions For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Material fatigue is extensively discussed and researched within scientific and industrial communities. Fatigue damage poses a significant challenge for both metallic and non-metallic components, often resulting in unexpected failures of in-service parts. Within multiaxial fatigue assessment, critical plane methods have gained importance due to their ability to characterize a component's critical location and detect early crack propagation. However, the conventional approach to calculate critical plane factors is time-consuming, making it primarily suitable for research purposes or when critical regions are already known. In many real-world scenarios, identifying the critical area of a component is difficult due to complex geometries, varying loads, or time limitations. This challenge becomes particularly crucial after topological optimization of components and in the context of lightweight design. Recently, the authors proposed an efficient method for evaluating critical plane factors in closed form, applicable to all cases that necessitate the maximization of specific parameters based on stress and strain components or their combination. This paper presents and validates the proposed methodology, with reference to a rear upright of a FSAE car, which is characterized by a complex geometry and is subjected to non-proportional loading conditions. The efficient algorithm demonstrated a substantial reduction in computation time compared to the standard plane scanning method, while maintaining solution accuracy.

The large majority of electric cars have a single-speed gearbox, because electrified powertrains provide maximal power across a wide operating range, and single-speed simplifies construction and reduces capital costs. Nevertheless, multi-speed transmissions have also been developed for electric cars, and some of them have recently appeared as commercial products. This paper aims to compare, through some practical examples, solutions with single-speed and dual-speed transmissions. In particular, given the very smooth driving of electric cars, for dual-speed solutions, a dual-clutch gearbox was considered. Finally, a continuously variable transmission (CVT) was also used. Different solutions were analyzed from a technical–economic point of view, based on a simulation of the vehicle under standardized driving cycles, thus evaluating the capital and running electricity costs. The obtained results show that the comparison between the two solutions is very open, and in the majority of cases, the advantages in terms of efficiency overcome the disadvantages due to the additional capital costs. For a rather low battery cost of 150 €/kWh, the total cost reduction moves from about 100–150 € up to 1500–2000 €, depending on the electricity cost, along the whole vehicle lifespan.

Fatigue assessment of components subjected to random loads is a challenging task both due to the variability in amplitude and frequency of the loads and for the computational times required to perform classical time domain fatigue analysis. The frequency domain approach to fatigue life assessment offers a solution by utilizing the power spectral density of the random load, requiring minimal computational effort. However, frequency domain methods are limited to stationary Gaussian signals, while real-world loads often exhibit non-Gaussian characteristics. Previous research proposed formulas to extend frequency domain methods to non-Gaussian cases, but they require knowledge of the parameters related to non-Gaussianity of the component's stress (skewness and kurtosis), which would require a time domain analysis of the stress history on the component and a strong reduction of the computational advantages. This paper aims to address this gap by conducting an extensive campaign of numerical simulations to evaluate the influence of various parameters on the degree of non-Gaussianity of the response of a system. A single-dof mass-spring-damper system was subjected to non-Gaussian random loads of different natures, and the response is analyzed to determine the values of skewness and kurtosis. The study investigated the influence on non-normality indexes of the system's output of several input parameters, which include both the characteristics of the input load and the properties of the dynamic system. The findings contribute to a better understanding of non-Gaussianity in dynamic systems and pave the way for conducting efficient fatigue analyses in the frequency domain. Future work will extend the study to non-stationary random loads, further advancing the understanding of non-Gaussianity and non-stationarity in dynamic systems.

This article aims to present the results of a national, cross-sectional, voluntary, online survey on the presence and roles of associations of breast cancer patients and volunteers in Italian specialist breast centres. The survey was developed according to standard methods. The questionnaire was pre-tested by a random sample of three breast centres, loaded onto the SurveyMonkey platform, and piloted by one volunteer breast centre. The breast centre clinical leads were invited to participate via email. A link to the online instrument was provided. No financial incentives were offered. The results were reported using standard descriptive statistics. The response rate was 82/128 (65%). Members of associations were routinely present in 70% Italian breast centres. Breast centres most often reporting their presence were those certified by the European Society of Breast Cancer Specialists. Patient support (reception and information, listening, identification of needs, and psychological support) was the primary area where associations were reported to offer services. The magnitude of this phenomenon warrants a study to investigate the impact of the activities of associations on the quality of life of patients and on the cost–benefit ratio of the service, and the modes of their interactions with the nursing staff and the medical staff.

Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme—which is entirely free—includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service.

Odontomas are benign tumors characterized by slow and limited growth with a rare recurrence. Odontomas are generally detected by radiographic findings in the radiopaque stage, where calcification of the tissues is observed. This article seeks to report the recurrence of a radiologically diagnosed odontoma to show the importance of radiographic controls after enucleation as a diagnostic and follow-up method. Case report: A female patient, 9 years old, attended dental care in 2020 due to malpositioned teeth. In the intraoral clinical examination, she presented stage II mixed dentition with crowding. A radiographic exam showed no associated lesions. The patient reported a history of odontoma removal and a supernumerary tooth in sextant II in 2016. Subsequently, she was referred to orthodontics, where permanent dentition with moderate anterior crowding in the maxilla and mandible was observed. The radiographic examination showed a radiopaque area compatible with odontoma, palatal to teeth 12 and 13. Conclusions: Although recurrence is rare, complete removal in the case of an odontoma is critical. This study demonstrates the importance of performing radiographic controls 5 years after enucleation of an odontoma, considering the stages of evolution.

The automotive industry is currently transforming, primarily due to the rise of electric and hybrid vehicle technologies and the need to reduce vehicle mass and energy losses to decrease consumption, pollution, and raw material usage. Additionally, road surface manufacturers emphasize improving pavement durability and reducing rolling noise. This necessitates precise load condition definitions and drives the need for reliable wheel testing benches. Many current benches use abrasive-coated rollers or synthetic tapes, but devices capable of testing on actual road surfaces are rare. In this work, a novel device for testing tire-pavement interaction is proposed. The system features a cart moving along a closed-track platform, ensuring test repeatability and enabling structural durability tests on uneven surfaces with installed obstacles. The cart is equipped with a cantilever arm capable of supporting either a testing wheel with customizable dimensions and kinematic parameters or a tire integrated with a complete suspension system, moving along a customizable pavement surface. The system includes actuators and sensors for applying vertical loads and adjusting the alignment of the testing wheel (slip angle, camber angle, etc.), allowing the characterization of tire behavior such as wear, fatigue, rolling noise, and rolling resistance. Multibody simulations were performed to evaluate the bench’s feasibility in terms of kinematics, power requirements, and structural loads. Results confirmed how this novel test bench represents a promising advancement in tire testing capabilities, enabling comprehensive studies on tire performance, noise reduction, and the structural dynamics of vehicle subsystems.

Introduction. According to the National Oncological Plan 2023-2027 on the importance of multidisciplinary and interactive e-learning training, the Italian Melanoma Intergroup (IMI) has developed MelaMEd (Melanoma Multimedia Education), a national project for general practitioners (GPs) on the prevention and detection of cutaneous melanoma through an online platform and an online course. MelaMEd enables participants to (1) recognize skin lesions that require specialist dermatological assessment, (2) select patients at high risk of melanoma and (3) be informed of the diagnosis and treatment pathway of patients with melanoma. Methods. A free online platform and online course were developed and launched in June 2022. Before starting the course, enrolled participants fill out a pre-training questionnaire concerning the basic knowledge of the disease and the recognition and management of suspicious lesions. After the course, participants will fill out the same questionnaire again. The online course will end in December 2023. Here we present a preliminary analysis of the pre-training results (January 2023-July 2023). The data have been analyzed descriptively. Results. So far, five healthcare centers have participated in the project for a total of 1320 participants. Of these, 298 compiled the pre-training questionnaire. Forty-seven percent of them were aged

The text discusses the role of general practitioners (GPs) in the prevention and early diagnosis of melanoma, a type of skin cancer. It highlights the need for GPs to be able to recognize suspicious skin lesions and refer patients to specialist dermatology centers. However, many GPs lack comprehensive training in diagnosing melanoma. The text mentions that various training courses have been conducted for GPs, but their impact on clinical practice has been limited. The "MelaMEd Programme" is an e-learning course developed by the Italian Melanoma Intergroup (IMI). The program aims to provide GPs with comprehensive knowledge of melanoma prevention, diagnosis, and treatment. It includes an e-learning section and a dedicated platform called MelaMEd platform, which offers a multimedia atlas of melanoma. The objective of the study is to evaluate the impact of the MelaMEd programme on GPs' diagnostic accuracy, knowledge of melanoma, and management of suspicious lesions. The methodology involves administering pre-training and post-training questionnaires to participants, assessing their diagnostic skills and evaluating the training course's effectiveness. The study aims to demonstrate the effectiveness of the MelaMEd programme in improving GPs' ability to recognize and manage melanoma. It also seeks to identify areas for improvement and recommend interventions to enhance diagnostic accuracy. The results will be analyzed statistically using descriptive, univariate, and multivariate analysis methods.

In women aged ≥70 with low-risk breast cancer (BrC), some major international guidelines recommend against sentinel lymph node biopsy (for example, those from the Society of Surgical Oncology, U.S.) and post-lumpectomy radiotherapy (for example, those from the National Comprehensive Cancer Network, U.S.). We assessed the frequency of both procedures in six National Cancer Institutes (IRCCSs) in the North, the Centre, and the South of Italy. Data on tumour characteristics and treatment were obtained from each centre. Patients aged 70–79 years diagnosed with a pT1–pT2, clinically axillary lymph node-negative, oestrogen and/or progesterone receptor-positive, and human epidermal growth factor receptor 2-negative BrC between 2015 and 2020 were eligible for the study. Factors associated with the omission of the two procedures were evaluated using binary penalised logistic regression models. Axillary staging was omitted in 33/1000 (3.3%) women. After simultaneous adjustment for the centre of treatment and all other key variables, axillary staging was omitted more often in 2015–2016 vs. 2017–2020 (odds ratio (OR): 2.7; 95% CI: 1.0–7.5), in women aged 75–79 vs. 70–74 years (OR: 2.3; 95% CI: 1.1–4.9), and in those who had mastectomy vs. breast-conserving surgery (OR: 3.3; 95% CI: 1.2–9.0). The higher the histological grade was, the less frequent were the omissions (OR for grade 3 vs. grade 1: 0.2; 95% CI: 0.0–0.7). Post-lumpectomy radiotherapy was omitted in 56/651 (8.6%) women with no significant association with age, period, tumour stage, and tumour grade. In conclusion, the omission of axillary staging and post-lumpectomy radiotherapy in low-risk older BrC patients was rare in the Italian IRCCSs. Although women included in the study cannot be considered a nationally representative sample of BrC patients in Italy, our findings can serve as a baseline to monitor the impact of future guidelines. To do that, the recording and storage of hospital-based information should be improved.

Background: The scratch assay is commonly used in cell biology to evaluate cell migration; however, it is not a standardized method; it produces highly variable gap dimensions. We design a printable device, comprising a single wounding tool and a guide, and compared the gap produced by our device and the traditional method. The deviceis printable in a standard 3D printer. Cells were seeded on a 24‐well plate. After reaching full confluency, a gap was created using the traditional method (scratch assay with a pipette tip), a pipette tip and the guide of the device, or the single wounding tool and the guide. The gaps were observed for up to 48 h under a light microscope and analyzed. Results: The results show that the traditional method produces irregular and not straight gaps, and had the worst cell migration rates compared to the other groups. The wounding tool produced scrape signs at the well surface. Conclusion: The guide and pipette tip delivered the best results for the scratch assay. Significance: The use of the guide and the pipette tip for the scratch assay allows allows to perform reproducible cell migration experiments. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide; however, the underlying causes of AF initiation are still poorly understood, particularly because currently available models do not allow in distinguishing the initial causes from maladaptive remodeling that induces and perpetuates AF. Lately, the genetic background has been proven to be important in the AF onset. iPSC-derived cardiomyocytes, being patient- and mutation-specific, may help solve this diatribe by showing the initial cell-autonomous changes underlying the development of the disease. Transcription factor paired-like homeodomain 2 (PITX2) has been identified as a key regulator of atrial development/differentiation, and the PITX2 genomic locus has the highest association with paroxysmal AF. PITX2 influences mitochondrial activity, and alterations in either its expression or function have been widely associated with AF. In this work, we investigate the activity of mitochondria in iPSC-derived atrial cardiomyocytes (aCMs) obtained from a young patient (24 years old) with paroxysmal AF, carrying a gain-of-function mutation in PITX2 (rs138163892) and from its isogenic control (CTRL) in which the heterozygous point mutation has been reverted to WT. PITX2 aCMs show a higher mitochondrial content, increased mitochondrial activity, and superoxide production under basal conditions when compared to CTRL aCMs. However, increasing mitochondrial workload by FCCP or β-adrenergic stimulation allows us to unmask mitochondrial defects in PITX2 aCMs, which are incapable of responding efficiently to the higher energy demand, determining ATP deficiency.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

Self-propelled wheelchairs are challenging to drive on off-road routes or require enormous physical effort in situations where the gradient exceeds 8%. For most people, these situations are too strenuous and therefore impractical. This work presents an innovative plug-and-play system to electrify a manual wheelchair. With the constraint of not irreversibly modifying the original wheelchair, a mechanical system is developed to allow motors to turn the rear wheels by friction. Torque and power requirements have been derived by modeling and simulating in Matlab the physical system. To manufacture a working prototype, a control system using standard components is devised, and object-oriented firmware is developed with the C++ programming language. The result is a plug-and-play portable kit that can be adapted to wheelchairs of any size, and the expandable Human-Machine-Interface (HMI) makes it ready to expand the audience that can use it.

Caveolae constitute membrane microdomains where receptors and ion channels functionally interact. Caveolin-3 (cav-3) is the key structural component of muscular caveolae. Mutations in CAV3 lead to caveolinopathies, which result in both muscular dystrophies and cardiac diseases. In cardiomyocytes, cav-1 participates with cav-3 to form caveolae; skeletal myotubes and adult skeletal fibers do not express cav-1. In the heart, the absence of cardiac alterations in the majority of cases may depend on a conserved organization of caveolae thanks to the expression of cav-1. We decided to focus on three specific cav-3 mutations (Δ62-64YTT; T78K and W101C) found in heterozygosis in patients suffering from skeletal muscle disorders. We overexpressed both the WT and mutated cav-3 together with ion channels interacting with and modulated by cav-3. Patch-clamp analysis conducted in caveolin-free cells (MEF-KO), revealed that the T78K mutant is dominant negative, causing its intracellular retention together with cav-3 WT, and inducing a significant reduction in current densities of all three ion channels tested. The other cav-3 mutations did not cause significant alterations. Mathematical modelling of the effects of cav-3 T78K would impair repolarization to levels incompatible with life. For this reason, we decided to compare the effects of this mutation in other cell lines that endogenously express cav-1 (MEF-STO and CHO cells) and to modulate cav-1 expression with an shRNA approach. In these systems, the membrane localization of cav-3 T78K was rescued in the presence of cav-1, and the current densities of hHCN4, hKv1.5 and hKir2.1 were also rescued. These results constitute the first evidence of a compensatory role of cav-1 in the heart, justifying the reduced susceptibility of this organ to caveolinopathies.

Objective: To assess the tooth survival rates, adverse events, and need for further treatment of teeth previously treated with regenerative endodontics undergoing orthodontic treatment. Material and Methods: A literature search was performed using MEDLINE, EMBASE, Cochrane, Scopus, and Lilacs databases, grey literature, and endodontic journals, and the date of the last search was 20 April 2022. The included studies involved patients undergoing orthodontic treatment and at least one tooth that was previously treated with regenerative endodontics. A narrative synthesis of the findings was made. The risk of bias and evidence quality were assessed using the Effective Public Health Practice Project tool and the GRADE approach. Results: Five case reports included seven patients and eight teeth with a follow-up of 4 to 11 years. The overall risk of bias was high, and the certainty of evidence was very low. The survival rate was 87.5%. Adverse effects included sinus tracts, root resorption, symptomatology, apical periodontitis, and intracanal tissue necrosis. Five out of eight teeth required further intervention after orthodontics. Conclusions: A high prevalence of adverse effects and further intervention is observed in teeth treated with regenerative endodontics undergoing orthodontic treatment. The low quality of evidence highlights the need for comparative studies and evidence-based guidelines for managing these teeth during orthodontic treatment.