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Understanding biomolecular interactions is fundamental to advancing fields like drug discovery and protein design. In this paper, we introduce Boltz-1, an open-source deep learning model incorporating innovations in model architecture, speed optimization, and data processing achieving A lpha F old 3-level accuracy in predicting the 3D structures of biomolecular complexes. Boltz-1 demonstrates a performance on-par with state-of-the-art commercial models on a range of diverse benchmarks, setting a new benchmark for commercially accessible tools in structural biology. By releasing the training and inference code, model weights, datasets, and benchmarks under the MIT open license, we aim to foster global collaboration, accelerate discoveries, and provide a robust platform for advancing biomolecular modeling.

The increase in the world population, which will be almost 10 billion by 2050, will require considerable efforts to significantly increase food production. Despite the considerable progress made in agriculture, this need is becoming an emergency due to desertification, environmental pollution and climate changes. Biotic stresses, such as pathogenic bacteria and fungi, primarily contribute to significant losses in agricultural productivity and compromise food safety. These harmful agents are predominantly managed using large quantities of synthetic pesticides. However, this widespread use has led to substantial environmental pollution, increased pest resistance and toxic residues in agricultural produce, which subsequently enter the food supply, posing severe health risks to humans and animals. These challenges have significantly driven the advancement of integrated pest management strategies to reduce or eliminate synthetic pesticides. A practical and viable alternative lies in biopesticides-methods developed from natural products that are safe for human and animal health. This approach aligns with the strong demand from consumers and public authorities for safer pest control solutions. This review was focused on the isolation, chemical and biological characterization of natural products for the biocontrol of phytopathogenic bacteria and, in some cases, fungi with potential eco-friendly applications.

Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, a bioengineering platform for efficient mRNA loading and functional delivery using bionormal nanoparticles, extracellular vesicles (EVs), is established by expressing a highly specific RNA-binding domain fused to CD63 in EV producer cells stably expressing the target mRNA. The additional combination with a fusogenic endosomal escape moiety, Vesicular Stomatitis Virus Glycoprotein, enables functional mRNA delivery in vivo at doses substantially lower than currently used clinically with synthetic lipid-based nanoparticles. Importantly, the application of EVs loaded with effective cancer immunotherapy proves highly effective in an aggressive melanoma mouse model. This technology addresses substantial drawbacks currently associated with EV-based nucleic acid delivery systems and is a leap forward to clinical EV applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Gastric cancer (GC) incidence has been decreasing over the last decades; however, there are uncertainties in trends and proportional distribution of the diffuse type., Methods: GC incidence data were extracted from the population-based Friuli Venezia Giulia Cancer Registry. GC types (diffuse vs. others) were compared in relation to age at diagnosis, calendar years, and sexes., Results: Between 1995 and 2021, diffuse GC accounted for 10.2% of all GCs. The proportion was greater among individuals aged <45 years, 34.0% in women and 25.7% in men. An increasing proportion over time was observed, in particular in women (from 9.9% in 1995-2000 to 14.10% during 2011-2021). In the last decade (2011-2021), a decreased incidence of all GC was observed, reaching an age-standardized rate (world standard) of 1.4/100,000 for men and 1.2/100,000 for women. Rates of diffuse GC were 0.3/100,000 in younger population., Conclusion: Although the overall GC incidence is decreasing, the percentage of diffuse GC is increasing in the younger population, particularly in women. Reasons for the increased proportion of diffuse-type GC within younger women remain uncertain, possibly related to the decreased exposure to risk factors for other GC histotypes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients., Methods: This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype., Results: A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07)., Conclusion: These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Breast implants are not lifelong, with implant rupture being the third leading cause of revisional surgery in augmented women. Noncontrast MRI is a reliable tool to assess implant integrity; however, false positive and false negative diagnoses have been reported due to an incorrect interpretation of MRI signs. This study aims to investigate the incidence of these misleading results, comparing MRI findings with intraoperative surgical observations and exploring signs of nonunivocal interpretation., Materials and Methods: Between March 2019 and October 2022, our hospital, a referral center for breast cancer care, conducted 139 breast MRI examinations to evaluate implant integrity. Surgical intervention was deemed necessary for patients diagnosed with suspected or confirmed implant rupture at MRI. Those patients who did not undergo any surgical procedure (63 cases) or had surgery at different institutes (11 cases) were excluded., Results: Among the 65 patients who underwent preoperative MRI and subsequent surgery at our institute, surgical findings confirmed the preoperative MRI diagnosis in 48 women. Notably, 17 women exhibited a discordance between MRI and surgical findings: three false negatives, 11 false positives and three possible ruptures not confirmed. Signs of nonunivocal or misleading interpretation were assessed on a patient-by-patient basis. The importance of obtaining detailed information about a patient's breast implant, including fill materials, number of lumens, manufacturer and shape, proved immensely beneficial for interpreting MRI signs accurately., Conclusion: Pre-MRI knowledge of implant details and a meticulous evaluation of non-univocal signs can aid radiologists in accurately assessing implant integrity, reducing the risk of unnecessary revisional surgeries, and potentially averting allegations of medical malpractice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for targeted cancer therapy. The Fc-EVs can be decorated with different types of immunoglobulin G antibody and thus be targeted to virtually any tissue of interest. Following optimization of the engineered EVs by screening Fc-binding and EV-sorting moieties, we show the targeting of EVs to cancer cells displaying the human epidermal receptor 2 or the programmed-death ligand 1, as well as lower tumour burden and extended survival of mice with subcutaneous melanoma tumours when systemically injected with EVs displaying an antibody for the programmed-death ligand 1 and loaded with the chemotherapeutic doxorubicin. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody-drug conjugates., Competing Interests: Competing interests: S.E.A. is a founder of and a consultant for Evox Therapeutics. D.G., J.Z.N. and A.G. are consultants for Evox Therapeutics. O.P.B.W., D.G., J.Z.N., A.G. and S.E.A. have stock interest in Evox Therapeutics. H.S. and A.L. are employees of Evox Therapeutics. The other authors declare no competing interests., (© 2024. The Author(s).)

Wool waste is a huge environmental problem that needs to be addressed in order to avoid the continuous accumulation of biohazardous waste in landfills. In recent years, wool has proven to be an excellent source of keratin that can be used for various purposes. But never before has keratin from wool waste been used as a building block to synthesize a well-known class of biopolymers called nanosponges. Typically, nanosponges are produced by the reaction of cyclodextrins with an appropriate cross-linker to obtain an insoluble hyper-cross-linked polymer, which has applications in various fields. For this reason, a novel, affordable approach for the synthesis of a novel class of nanosponge using wool keratin as the building block has been presented. The keratin nanosponge was synthesized by reacting keratin with pyromellitic dianhydride as a cross-linking agent. The formation of a cross-linked polymer was successfully confirmed by CHNS-elemental analysis, TGA, DSC, FTIR-ATR, SEM, and water absorption capacity measurements. Surprisingly, the keratin-based nanosponge showed ∼50% uptake of heavy metals after only 24 h of contact time. The adsorption kinetics was also evaluated, indicating a pseudo-second-order model fit and the mechanism is predominantly the intraparticle diffusion process. The novel synthesized nanosponge proved to be a possible alternative for wastewater treatment., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Brain Complexity (BC) have successfully been applied to study the brain electroencephalographic signal (EEG) in health and disease. In this study, we employed recurrence entropy to quantify BC associated with the neurophysiology of movement by comparing BC in both resting state and cycling movement. We measured EEG in 24 healthy adults and placed the electrodes on occipital, parietal, temporal and frontal sites on both the right and left sides of the brain. We computed the recurrence entropy from EEG measurements during cycling and resting states. Entropy is higher in the resting state than in the cycling state for all brain regions analysed. This reduction in complexity is a result of the repetitive movements that occur during cycling. These movements lead to continuous sensorial feedback, resulting in reduced entropy and sensorimotor processing., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ferré et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objective: This article uses three different probabilistic convolutional architectures applied to ultrasound image analysis for grading Fatty Liver Content (FLC) in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) patients. Steatosis is a new silent epidemic and its accurate measurement is an impelling clinical need, not only for hepatologists, but also for experts in metabolic and cardiovascular diseases. This paper aims to provide a robust comparison between different uncertainty quantification strategies to identify advantages and drawbacks in a real clinical setting., Methods: We used a classical Convolutional Neural Network, a Monte Carlo Dropout, and a Bayesian Convolutional Neural Network with the goal of not only comparing the goodness of the predictions, but also to have access to an evaluation of the uncertainty associated with the outputs., Results: We found that even if the prediction based on a single ultrasound view is reliable (relative RMSE [5.93%-12.04%]), networks based on two ultrasound views outperform them (relative RMSE [5.35%-5.87%]). In addition, the results show that the introduction of a "not confident" category contributes to increase the percentage of correctly predicted cases and to decrease the percentage of mispredicted cases, especially for semi-intrusive methods., Conclusions: The possibility of having access to information about the confidence with which the network produces its outputs is a great advantage, both from the point of view of physicians who want to use neural networks as computer-aided diagnosis, and for developers who want to limit overfitting and obtain information about dataset problems in terms of out-of-distribution detection., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024 The Author(s).)

Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell-cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine is still limited by existing tools for scaling standardized EV production, single EV tracing and analytics, and thus provide only a snapshot of tissue-specific EV cargo information. Here, we present the Snorkel-tag, for which we have genetically fused the EV surface marker protein CD81, to a series of tags with an additional transmembrane domain to be displayed on the EV surface, resembling a snorkel. This system enables the affinity purification of EVs from complex matrices in a non-destructive form while maintaining EV characteristics in terms of surface protein profiles, associated miRNA patterns and uptake into a model cell line. Therefore, we consider the Snorkel-tag to be a widely applicable tool in EV research, allowing for efficient preparation of EV standards and reference materials, or dissecting EVs with different surface markers when fusing to other tetraspanins in vitro or in vivo., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Background: Surgery is still the standard treatment for breast lesions such as in situ ductal carcinoma (DCIS); however, its survival benefit is minimal, particularly for low-grade DCIS. Surgical complications and related depression status can adversely affect patients' quality of life. Approximately 25% of breast cancer (BC) cases are in situ forms, with DCIS making up 90% of these. Low and intermediate-grade DCIS often grow slowly and do not always progress clinically significant diseases. Identifying non-invasive lesions could help prevent overtreatment. In this context, new diagnostic tools like vacuum-assisted excision (VAE) could enhance the management of these conditions., Methods: The prospective VACIS study explores the role of VAE in ensuring the absence of pathology at subsequent surgery and reducing the diagnostic underestimation of breast biopsies for microcalcifications. Patients with suspicious breast microcalcifications up to 15 mm, who are candidates for stereotactic biopsy, will be enrolled and randomised into two groups. The control group will complete the biopsy with typical sampling, aiming to collect some microcalcifications from the target, while the experimental group will focus on the complete removal of the biopsy target (confirmed by mammography on the biopsy table), followed by a second sequence of cleaning samples. Radiograms will confirm lesion removal. Pathologic outcomes at surgery will be compared between the groups, and the percentage of underestimation will be assessed. The sample size is calculated to be 70 patients per group, using statistical tests and multivariate logistic models to detect a significant difference in the absence of pathology. Data collected will include patient age, lesion characteristics, and details of the biopsy, pathology and surgery., Discussion: Current surgical treatments for low-and sometimes intermediate-grade DCIS offer limited survival benefits and may hurt patients' quality of life due to surgery-related complications and associated depression. These lesions often grow slowly and might not become clinically significant, suggesting a need to avoid overtreatment. Improved diagnostics procedures, such as VAE, could help distinguish non-invasive from potentially invasive lesions, reduce biopsy underestimation, enable personalised management and optimise treatment strategies. This study hypothesises that VAE could be a viable alternative to surgery, capable of removing pathology during the biopsy procedure., Clinical Trial Registration: Clinicaltrials.gov, identifier NCT05932758., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nicosia, Mariano, Latronico, Bozzini, Bellerba, Gaeta, Pesapane, Mazzarol, Fusco, Corso, Sangalli, Giailan, Lazzeroni, Raimondi and Cassano.)

We updated to December 2023 the main findings of the stomach cancer pooling (StoP) project including about 13 000 cases and 31 000 controls from 29 case-control and 5 nested studies. The StoP project quantified more precisely than previously available the positive associations of tobacco smoking, high alcohol consumption, meat intake, selected occupations (e.g. agricultural and miners), gastric ulcer and family history with gastric cancer and the inverse associations with socioeconomic status and selected aspects of diet (fruits, including citrus fruits, vegetables, including allium and mushrooms, and polyphenols). No consistent associations were found with coffee, yoghurt and leisure-time physical activity, metformin or proton pump inhibitors use., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Obsessive-compulsive disorder (OCD), characterized by persistent, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), can significantly impact a child's daily functioning, academic performance, and overall quality of life. As the prevalence of pediatric OCD continues to rise, there is a critical demand for evidence-based treatments that not only alleviate symptoms but also enhance the quality of life for affected children and adolescents. By identifying gaps in knowledge and suggesting directions for future research, this narrative review contributes to the ongoing discourse on pediatric OCD treatments. Ultimately, the synthesis of evidence aims to enhance our understanding and inform best practices in the compassionate and effective management of OCD in children and adolescents. The aim of this study is to provide a comprehensive overview of current trends and emerging strategies in the treatment of pediatric obsessive-compulsive disorder (OCD) and highlights the significance of tailoring treatment approaches to individual patient needs, considering factors such as symptom severity and treatment response. Concentrating on interventions supported by empirical evidence, the review delves into cognitive-behavioral therapy (CBT), pharmacotherapy, the synergistic effects of these modalities, and inventive therapeutic approaches, all while considering the distinctive developmental aspects pertinent to pediatric populations. We conducted this review by searching for titles in the PubMed database from 2013 to present. Our comprehensive literature review focused on advancements in treating pediatric OCD, using keywords like "Obsessive-compulsive disorder," "Pediatric," "treatment," "CBT," "SSRI," "Pharmacotherapy," and "combination therapy." While both pharmacotherapy and CBT show individual efficacy, the combination of these approaches appears to be more effective, especially for medication non-responders with no prior exposure to CBT, despite some mixed findings. These findings contribute significantly to the ongoing discussion on optimizing combined therapy strategies tailored to the complexities of pediatric OCD., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khomami Zadeh et al.)

The brain is understood as an intricate biological system composed of numerous elements. It is susceptible to various physical and chemical influences, including temperature. The literature extensively explores the conditions that influence synapses in the context of cellular communication. However, the understanding of how the brain's global physical conditions can modulate ephaptic communication remains limited due to the poorly understood nature of ephapticity. This study proposes an adaptation of the Hodgkin and Huxley (HH) model to investigate the effects of ephaptic entrainment in response to thermal changes (HH-E). The analysis focuses on two distinct neuronal regimes: subthreshold and suprathreshold. In the subthreshold regime, circular statistics are used to demonstrate the dependence of phase differences with temperature. In the suprathreshold regime, the Inter-Spike Interval are employed to estimate phase preferences and changes in the spiking pattern. Temperature influences the model's ephaptic interactions and can modify its preferences for spiking frequency, with the direction of this change depending on specific model conditions and the temperature range under consideration. Furthermore, temperature enhance the anti-phase differences relationship between spikes and the external ephaptic signal. In the suprathreshold regime, ephaptic entrainment is also influenced by temperature, especially at low frequencies. This study reveals the susceptibility of ephaptic entrainment to temperature variations in both subthreshold and suprathreshold regimes and discusses the importance of ephaptic communication in the contexts where temperature may plays a significant role in neural physiology, such as inflammatory processes, fever, and epileptic seizures., (© 2024. The Author(s).)

The use of renewable resources in composite materials is a vital strategy for enhancing sustainability in material science. Wool fibers are promising due to their unique properties, including thermal insulation and self-extinguishing characteristics. However, a substantial portion of wool is deemed unsuitable for textiles and is often discarded as waste. This review investigates the integration of wool fibers into polymer composites, aiming to improve sustainability and material performance. By analyzing recent advancements, this study highlights the potential of wool fibers to enhance the mechanical, thermal, and acoustic properties of composites. The findings support the development of eco-friendly materials that contribute to waste reduction and promote sustainable practices across various industries.

Introduction: Lymphocytic esophagitis (LyE) and eosinophilic esophagitis (EoE) are immune-mediated esophageal diseases. Clinical characteristics, endoscopic findings, and treatment outcomes of LyE were compared with EoE., Methods: This was an international retrospective study on adults enrolled at 3 centers in Europe. We recorded clinical characteristics and endoscopy findings at baseline and symptoms, histology, and endoscopy outcomes after treatment of patients with LyE and EoE., Results: Demographics, clinical presentation, comorbidities, and endoscopy findings were largely different in 35 patients with LyE compared with 59 patients with EoE. Proton pump inhibitor response was generally lower in LyE., Discussion: LyE is clinically different from EoE, but differences in treatment response need further investigation., (Copyright © 2024 by The American College of Gastroenterology.)

Breast cancer holds the highest diagnosis rate among female tumors and is the leading cause of death among women. Quantitative analysis of radiological images shows the potential to address several medical challenges, including the early detection and classification of breast tumors. In the P.I.N.K study, 66 women were enrolled. Their paired Automated Breast Volume Scanner (ABVS) and Digital Breast Tomosynthesis (DBT) images, annotated with cancerous lesions, populated the first ABVS+DBT dataset. This enabled not only a radiomic analysis for the malignant vs. benign breast cancer classification, but also the comparison of the two modalities. For this purpose, the models were trained using a leave-one-out nested cross-validation strategy combined with a proper threshold selection approach. This approach provides statistically significant results even with medium-sized data sets. Additionally it provides distributional variables of importance, thus identifying the most informative radiomic features. The analysis proved the predictive capacity of radiomic models even using a reduced number of features. Indeed, from tomography we achieved AUC-ROC 89.9 % using 19 features and 92.1 % using 7 of them; while from ABVS we attained an AUC-ROC of 72.3 % using 22 features and 85.8 % using only 3 features. Although the predictive power of DBT outperforms ABVS, when comparing the predictions at the patient level, only 8.7% of lesions are misclassified by both methods, suggesting a partial complementarity. Notably, promising results (AUC-ROC ABVS-DBT 71.8 % - 74.1 % ) were achieved using non-geometric features, thus opening the way to the integration of virtual biopsy in medical routine., (© 2024. The Author(s).)

Background: The social restrictions imposed by the COVID-19 pandemic have disrupted traditional teaching methods and encouraged the development of innovative and safer approaches based on distance learning. Among these novel techniques, digital game-based learning (DGBL) is a method that facilitates learning through the efficient use of interactive software tailored to the user. Methods: In this work, we investigated the effectiveness of the DGBL methodology for remote training using a game-based digital learning software designed about remote neonatal resuscitation. The DGBL approach was validated in 52 anesthesiologist trainees and compared to a homogenous retrospective control group of pediatric trainees with the same prior knowledge, who followed an in-person training course using the digital serious game. Scores obtained during each game session are recorded and used to assess progress in knowledge of the flowchart, decision time, timing of assisted ventilation, and ability to check equipment. Results: The results confirmed the effectiveness of the remote training mode for each of the analyzed features, whereas no statistically significant advantages of using a supervised DGBL were found. Conclusion: In conclusion, the DGBL remote training approach is a valuable tool that can provide users with an interactive, effective, and enjoyable learning experience. Future developments will concern the implementation of multiplayer versions to stimulate interaction between users for the development of inter-professional and teamwork skills.

Introduction: This review explores delirium in critically ill patients in the inpatient setting, focusing on its prevention and management. It evaluates the efficacy of both current pharmacological and non-pharmacological interventions, aiming to provide a comprehensive overview., Methods: A systematic literature search was conducted to identify relevant studies investigating the prevention and management of delirium resulting in a final sample of 26 articles for analysis., Results: Of the 26 articles analyzed for this review ( N  = 8,831 participants) of controlled trials, 16 studies examined the prevention of delirium, 9 explored the treatment of delirium, and 1 investigated both prevention and treatment of delirium., Discussion: Among the reviewed studies, there is evidence that non-pharmacologic methods are effective in the prevention of delirium. Evidence regarding pharmacological interventions for delirium prevention is varied and inconclusive, with some indication that atypical antipsychotics like aripiprazole and quetiapine may reduce the incidence of delirium. Regarding the treatment of delirium, there is limited evidence supporting the use of pharmacological agents. Additional double-blinded, randomized, placebo-controlled clinical trials are needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chan and Corso.)

The limited availability of specialized image databases (particularly in hospitals, where tools vary between providers) makes it difficult to train deep learning models. This paper presents a few-shot learning methodology that uses a pre-trained ResNet integrated with an encoder as a backbone to encode conditional shape information for the classification of neonatal resuscitation equipment from less than 100 natural images. The model is also strengthened by incorporating a reliability score, which enriches the prediction with an estimation of classification reliability. The model, whose performance is cross-validated, reached a median accuracy performance of over 99% (and a lower limit of 73.4% for the least accurate model/fold) using only 87 meta-training images. During the test phase on complex natural images, performance was slightly degraded due to a sub-optimal segmentation strategy (FastSAM) required to maintain the real-time inference phase (median accuracy 87.25%). This methodology proves to be excellent for applying complex classification models to contexts (such as neonatal resuscitation) that are not available in public databases. Improvements to the automatic segmentation strategy prior to the extraction of conditional information will allow a natural application in simulation and hospital settings.

Cancer growth is dependent on angiogenesis, the formation of new blood vessels, which represents a hallmark of cancer. After this concept was established in the 1970s, inhibition of tumor development and metastases by blocking the neoangiogenic process has been an important approach to the treatment of tumors. However, antiangiogenic therapies are often administered when cancer has already progressed. The key to reducing the cancer burden is prevention. We noticed 20 years ago that a series of possible cancer chemopreventive agents showed antiangiogenic properties when tested in experimental models. This article reviews the relevant advances in the understanding of the rationale for targeting angiogenesis for cancer therapy, prevention, and interception and recently investigated substances with antiangiogenic activity that may be suitable for such strategies. Many compounds, either dietary derivatives or repurposed drugs, with antiangiogenic activity are possible tools for cancer angioprevention. Such molecules have a favorable safety profile and are likely to allow the prolonged duration necessary for an efficient preventive strategy. Recent evidence on mechanisms and possible use is described here for food derivatives, including flavonoids, retinoids, triterpenoids, omega fatty acids, and carotenoids from marine microorganisms. As examples, a number of compounds, including epigallocatechin, resveratrol, xanthohumol, hydroxytyrosol, curcumin, fenretinide, lycopene, fucoxanthin, and repurposed drugs, such as aspirin, β blockers, renin-angiotensin-aldosterone inhibitors, carnitines, and biguanides, are reviewed., (©2024 American Association for Cancer Research.)

Recurrence microstates are obtained from the cross recurrence of two sequences of values embedded in a time series, being the generalization of the concept of recurrence of a given state in phase space. The probability of occurrence of each microstate constitutes a recurrence quantifier. The set of probabilities of all microstates are capable of detecting even small changes in the data pattern. This creates an ideal tool for generating features in machine learning algorithms. Thanks to the sensitivity of the set of probabilities of occurrence of microstates, it can be used to feed a deep neural network, namely, a microstate multi-layer perceptron (MMLP) to classify parameters of chaotic systems. Additionally, we show that with more microstates, the accuracy of the MMLP increases, showing that the increasing size and number of microstates insert new and independent information into the analysis. We also explore potential applications of the proposed method when adapted to different contexts., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Physical activity (PA) has an established role in the promotion of health and fitness and the prevention of disease. Expected overall benefits include reduction of all-cause morbidity and death, weight control, improved quality of life, improved bone health and decreased falls of elderly subjects, , deeper cognition, and reduced risk of depression, anxiety, and sleeplessness. Currently, PA is a mainstay in the management of cardiovascular diseases, metabolic syndrome, diabetes, and bone health. Recently, the perception of its role in primary and secondary prevention, interception, and treatment of cancer, however, is also gaining importance. Regular walking, the simplest type of PA, is associated with reduced all-cause and cardiovascular disease mortality, and a role in cancer prevention is of increasing interest. Furthermore, PA improves the quality of life of cancer patients, attenuating side effects of chemotherapy, decreasing sarcopenia, increasing fitness, and inhibiting the recurrence and progression of some cancer types. It promotes emotional and psychological benefits in patients, inducing positive changes. While mechanisms, effective levels and useful amount of PA practice are well established in cardiology, they are yet to be fully determined in oncology. Nevertheless, PA is recommended to reduce cancer risk in the general population, and it has been introduced in programs for the prevention of second cancers. In perspective, it will help as integrative therapy in cancer patients and for cancer survivors. The number of beneficial effects in the cancer continuum is highlighted in this review., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital "Policlinico Riuniti" of Foggia (Italy). COVID-19 patients with a positive ANA test exhibited a significantly lower 30-day survival rate (64.4% vs. 83.0%) and a higher likelihood of severe respiratory complications during hospitalization than those with negative ANA screening (35.4% vs. 17.0%) ( p < 0.001). The association between poor prognosis and ANA status was identified by calculating the HALP score (Hemoglobin-Albumin-Lymphocyte-Platelet), which was lower in COVID-19 patients with a positive ANA test compared to ANA-negative patients (108.1 ± 7.4 vs. 218.6 ± 11.2 AU; p < 0.011). In detail, COVID-19 patients with a low HALP showed a lower 30-day survival rate (99.1% vs. 83.6% vs. 55.2% for high, medium, and low HALP, respectively; p < 0.001) and a higher incidence of adverse respiratory events compared to those with high and medium HALP (13.1% vs. 35.2% vs. 64.6% for high, medium, and low HALP, respectively; p < 0.001). In summary, ANA positivity in COVID-19 patients appears to be linked to a more aggressive disease phenotype with a reduced survival rate. Furthermore, we propose that the HALP score could serve as a valuable parameter to assess prognosis for COVID-19 patients.

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging. They are luminal in molecular subtype, and exhibit estrogen and progesterone receptor positivity and HER2 negativity, thus presenting a more unpredictable response to neoadjuvant therapies. There has been a significant increase in research focused on this distinctive breast cancer subtype, including studies on its pathology, its clinical and surgical management, and the high-resolution definition of its genomic profile, as well as the development of new therapeutic perspectives. This review will summarize the heterogeneous pattern of this unique disease, focusing on challenges in its comprehensive clinical management and on future insights and research objectives., Competing Interests: Declaration of competing interest No financial/personal interest from all Authors with the exception of Prof. Giuseppe Curigliano., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Discrete diffusion or flow models could enable faster and more controllable sequence generation than autoregressive models. We show that na\"ive linear flow matching on the simplex is insufficient toward this goal since it suffers from discontinuities in the training target and further pathologies. To overcome this, we develop Dirichlet flow matching on the simplex based on mixtures of Dirichlet distributions as probability paths. In this framework, we derive a connection between the mixtures' scores and the flow's vector field that allows for classifier and classifier-free guidance. Further, we provide distilled Dirichlet flow matching, which enables one-step sequence generation with minimal performance hits, resulting in $O(L)$ speedups compared to autoregressive models. On complex DNA sequence generation tasks, we demonstrate superior performance compared to all baselines in distributional metrics and in achieving desired design targets for generated sequences. Finally, we show that our classifier-free guidance approach improves unconditional generation and is effective for generating DNA that satisfies design targets. Code is available at https://github.com/HannesStark/dirichlet-flow-matching.

Camera traps became the main observational method of a myriad of species over large areas. Data sets from camera traps can be used to describe the patterns and monitor the occupancy, abundance, and richness of wildlife, essential information for conservation in times of rapid climate and land-cover changes. Habitat loss and poaching are responsible for historical population losses of mammals in the Atlantic Forest biodiversity hotspot, especially for medium to large-sized species. Here we present a data set from camera trap surveys of medium to large-sized native mammals (>1 kg) across the Atlantic Forest. We compiled data from 5380 ground-level camera trap deployments in 3046 locations, from 2004 to 2020, resulting in 43,068 records of 58 species. These data add to existing data sets of mammals in the Atlantic Forest by including dates of camera operation needed for analyses dealing with imperfect detection. We also included, when available, information on important predictors of detection, namely the camera brand and model, use of bait, and obstruction of camera viewshed that can be measured from example pictures at each camera location. Besides its application in studies on the patterns and mechanisms behind occupancy, relative abundance, richness, and detection, the data set presented here can be used to study species' daily activity patterns, activity levels, and spatiotemporal interactions between species. Moreover, data can be used combined with other data sources in the multiple and expanding uses of integrated population modeling. An R script is available to view summaries of the data set. We expect that this data set will be used to advance the knowledge of mammal assemblages and to inform evidence-based solutions for the conservation of the Atlantic Forest. The data are not copyright restricted; please cite this paper when using the data., (© 2024 The Ecological Society of America.)

Pathogenic germline CDH1 mutation confers high risk for developing diffuse gastric and lobular breast cancers in asymptomatic carriers. In these individuals, the estimated gastric cancer risk at 80 years of age is up to 70% for males and 56% for females. Due to this high-risk predisposition, prophylactic total gastrectomy is considered a unique life-saving approach in germline CDH1 carriers, as endoscopy often fails to detect early stage diffuse gastric carcinoma. However, surgical indication is controversial in some clinical contexts, with possible contraindications. This review discusses points against and in favor of a more aggressive surgical approach for consideration during the decision-making process., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

A breast unit is a multidisciplinary center specialized in the management of women with breast diseases, including breast cancer (BC). It represents a care path, passing from screening activities to diagnostic investigations, from surgery to the definition of the therapeutic strategy, from psychophysical rehabilitation to long-term checks (follow-up), and up to genetic counseling. Since 2006, following a resolution issued by the European Parliament to urge member states to activate multidisciplinary breast centers by 2016, work has been underway throughout Italy to improve the management of women with BC. In Italy, the State-Regions agreement was signed on 18 December 2014, sanctioning the establishment of breast units. These centers must adhere to specific quality criteria and requirements. In 2020, the experts of the EUSOMA group (European Society of Breast Cancer Specialists), in their latest document published, expanded the requirements of the breast units. Furthermore, Senonetwork was founded in 2012 with the aim of allowing BC to be treated in breast units that comply with European requirements to ensure equal treatment opportunities for all Italian women. Indeed, the available data indicate that the BC patient has a greater chance of better treatment in the breast units with a multidisciplinary team, thus increasing the survival rate with a better quality of life, compared to those managed in nonspecialized structures. The present review is a perspective on the current Italian reality of breast units, updated with the available literature and the most recent epidemiological data from Senonetwork and AgeNaS., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This literature review evaluates the efficacy and clinical applications of eye movement desensitization and reprocessing (EMDR) therapy for post-traumatic stress disorder (PTSD). The review highlights the effectiveness of EMDR in reducing PTSD symptoms and explores variations in treatment protocols, populations studied, and outcome measures. We conducted systematic searches of multiple databases, supplemented with manual searches and reference list exploration. The inclusion criteria focused on English-language studies published between January 2000 and June 2023, with a specific emphasis on adult psychiatric patients with PTSD receiving EMDR treatment. The review utilized Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for narrative literature reviews. Out of 867 identified studies, 16 met the eligibility criteria. Most studies found that EMDR was superior in relieving PTSD when compared to controls. Eleven of the 16 selected studies demonstrated improvement in PTSD symptoms. An additional three studies noted an improvement in PTSD symptoms when compared to their waitlist control counterparts. One study found EMDR superior in combating depressive symptoms when compared to rapid eye movement desensitization. EMDR therapy is an appropriate treatment for PTSD. Although some studies compared to waitlist controls, and others have a small number of participants, the data supports the use of EMDR for PTSD. Future studies are needed to continue to better understand the mechanism and application in different populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Vereecken et al.)

Domestic chicken farming has been promoted and spread in several Italian municipalities and worldwide as an aid to the self-consumption of domestically produced food. This study investigated the levels of four toxic elements (As, Cd, Hg, and Pb) in eggs from an ethical laying hen farm, comparing the element concentrations with those possibly present in supermarket eggs. A total of 201 eggs, 141 from the farm and produced by different hen genotypes, and 60 from the supermarket, were collected. The levels of the toxic elements were evaluated in the yolk, albumen, and eggshells of all eggs. The results show that the supermarket eggs' yolk and albumen were more contaminated with lead, compared to the rural eggs. Contrarily, the mean content of arsenic was higher in the albumen and eggshells of the rural eggs, compared to the supermarket eggs. The cadmium content was below the LOQ (0.005 mg/kg) in all samples. The mercury content was below or around the LOQ in all rural eggs. Overall, the supermarket egg albumens were significantly more contaminated than the rural ones. No significant differences were found in quality parameters for both types of eggs. The toxic element values that were detected were in line with other studies in the literature. However, despite the concentrations found not representing a risk to the consumers' health, the results of this study raise a potential food safety issue, and it would be desirable to set specific MRLs for eggs for consumers' protection.

Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.

Background: Despite increased awareness of eosinophilic esophagitis (EoE), the diagnostic delay has remained stable over the past 3 decades. There is a need to improve the diagnostic performance and optimize resources allocation in the setting of EoE., Objective: We developed and validated 2 point-of-care machine learning (ML) tools to predict a diagnosis of EoE before histology results during office visits., Methods: We conducted a multicenter study in 3 European tertiary referral centers for EoE. We built predictive ML models using retrospectively extracted clinical and esophagogastroduodenoscopy (EGDS) data collected from 273 EoE and 55 non-EoE dysphagia patients. We validated the models on an independent cohort of 93 consecutive patients with dysphagia undergoing EGDS with biopsies at 2 different centers. Models' performance was assessed by area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV and NPV). The models were integrated into a point-of-care software package., Results: The model trained on clinical data alone showed an AUC of 0.90 and a sensitivity, specificity, PPV, and NPV of 0.90, 0.75, 0.80, and 0.87, respectively, for the diagnosis of EoE in the external validation cohort. The model trained on a combination of clinical and endoscopic data showed an AUC of 0.94, and a sensitivity, specificity, PPV, and NPV of 0.94, 0.68, 0.77, and 0.91, respectively, in the external validation cohort., Conclusion: Our software-integrated models (https://webapplicationing.shinyapps.io/PointOfCare-EoE/) can be used at point-of-care to improve the diagnostic workup of EoE and optimize resources allocation., (Copyright © 2024. Published by Elsevier Inc.)

Importance: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation., Objectives: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival., Design, Setting, and Participants: This single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, with follow-up until January 31, 2023. Women with LBC seen at the European Institute of Oncology were included. Testing for germline CDH1, BRCA1, and BRCA2 genes was performed. Somatic profiling was assessed for germline CDH1 carriers., Main Outcomes and Measures: Accurate estimates of prevalence of germline CDH1 variants among patients with HLBC and the association of somatic sequence alteration with HLBC syndrome. The Kaplan-Meier method and a multivariable Cox proportional hazards regression model were applied for overall and disease-free survival analysis., Results: Of 5429 cases of primary LBC, familial LBC phenotype accounted for 1867 (34.4%). A total of 394 women with LBC were tested, among whom 15 germline CDH1 variants in 15 unrelated families were identified. Among these variants, 6 (40.0%) were P/LP, with an overall frequency of 1.5% (6 of 394). Of the 6 probands with P/LP CDH1 LBC, 5 (83.3%) had a positive family history of BC and only 1 (16.7%) had sporadic juvenile early-onset LBC. No germline BRCA1 and BRCA2 variants were identified in CDH1 carriers. An inactivating CDH1 mechanism (second hit) was identified in 4 of 6 explored matched tumor samples (66.7%) in P/LP germline carriers. The P/LP CDH1 LBC variant carriers had a significantly lower age at diagnosis compared with the group carrying CDH1 variants of unknown significance or likely benign (42.5 [IQR, 38.3-43.0] vs 51.0 [IQR, 45.0-53.0] years; P = .03)., Conclusions and Relevance: In this cohort study, P/LP germline CDH1 variants were identified in individuals not fulfilling the classic clinical criteria for HDGC screening, suggesting that identification of these variants may provide a novel method to test women with LBC with early age at diagnosis and/or positive family history of BC.

Background: Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria., Methods: We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score., Findings: A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P = 0.09) and overall survival (OS) (log-rank P = 0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and 65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n = 17) than in the IDC group (n = 10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population., Interpretation: Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment., Funding: Umberto Veronesi Foundation., Competing Interests: Prof. Giuseppe Curigliano: Grants or contracts from any entity: Merck; Consulting fees: BMS, Roche, Pfizer, Novartis, Lilly, Astra Zeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, Gilead, Menarini; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly, Pfizer, Relay, Gilead, Novartis; Support for attending meetings and/or travel: Daichii Sankyo. Dr. Emilia Montagna: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis., (© 2024 The Authors.)

Background: Ustekinumab (UST) has demonstrated effectiveness in treating patients with Crohn's disease. Monitoring treatment response can improve disease management and reduce healthcare costs. We investigated whether UST trough levels (TLs), serum IL22, and Oncostatin M (OSM) levels could be early indicators of non-response by analysing their correlation with clinical and biochemical outcomes in CD. Methods: Patients with CD initiating UST treatment from October 2018 to September 2020 were enrolled at six Italian centres for inflammatory bowel disease (IBD). Clinical and biochemical data were collected at four time points: baseline, second subcutaneous (SC) dose, fourth SC dose, and 52 weeks. TLs were measured during maintenance, at the second SC dose, and at the fourth SC dose. IL-22 and OSM serum levels were assessed at baseline and the second SC dose. We analysed whether TLs, IL22 levels, and OSM serum levels were associated with clinical response, clinical remission, biochemical remission, and endoscopic remission using the appropriate statistical tests. Results: Out of eighty-four initially enrolled patients, five were lost to follow-up, and eleven discontinued the drug before 52 weeks. At the 52-week time point, 47% achieved biochemical remission based on faecal calprotectin levels, and 61.8% achieved clinical remission. TLs at the second SC dose significantly correlated with biochemical remission at the same time point ( p = 0.011). However, TLs did not correlate with clinical remission. Baseline OSM levels did not correlate with biochemical or clinical remission or response. IL22 levels notably decreased during UST therapy ( p = 0.000), but its values did not correlate with biochemical or clinical remission. Conclusions: UST is an effective therapy for patients with CD. TLs measured at the second SC dose significantly correlated with biochemical remission, emphasising their potential role in treatment monitoring. Levels of OSM and IL-22, despite a significant decrease in the latter during therapy, did not exhibit correlations with clinical or biochemical outcomes in our study. Further studies are needed to confirm these findings.

Purpose: To compare the diagnostic performance (detection, assessment of correct disease extent and multifocality/centricity) of Contrast-Enhanced Mammography (CEM) Versus Breast Magnetic Resonance (MRI) in the study of lobular neoplasms., Methods: We retrospectively selected all the patients who underwent surgery for a lobular breast neoplasm, either an in situ or an invasive tumor, and had undergone both breast CEM and MRI examinations during the pre-surgical planning. Wilcoxon Signed Rank test was performed to assess the differences between size measurements using the different methods and the post-surgical pathological measurements, considered the gold standard. The agreement in identifying multifocality/multicentricity among the different methods and the pathology was assessed using the Kappa statistics., Results: We selected 19 patients, of which one presented a bilateral neoplasm. Then, the images of these 19 patients were analyzed, for a total of 52 malignant breast lesions. We found no significant differences between the post-surgical pathological size of the lesions and the calculated size with CEM and MRI (p-value of the difference respectively 0.71 and 0.47). In all 20 cases, neoplasm detection was possible both with CEM and MRI. CEM and MRI showed an excellent ability to identify multifocal and multicentric cases (K statistic equal to 0.93 for both the procedures), while K statistic was 0.11 and 0.59 for FFDM and US, respectively., Conclusion: The findings of this study suggest that CEM is a reliable imaging technique in the preoperative setting of patients with lobular neoplasm, with comparable results to breast MRI., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Access to medical imaging is pivotal in healthcare, playing a crucial role in the prevention, diagnosis, and management of diseases. However, disparities persist in this scenario, disproportionately affecting marginalized communities, racial and ethnic minorities, and individuals facing linguistic or cultural barriers. This paper critically assesses methods to mitigate these disparities, with a focus on breast cancer screening. We underscore scientific mobility as a vital tool for radiologists to advocate for healthcare policy changes: it not only enhances diversity and cultural competence within the radiology community but also fosters international cooperation and knowledge exchange among healthcare institutions. Efforts to ensure cultural competency among radiologists are discussed, including ongoing cultural education, sensitivity training, and workforce diversification. These initiatives are key to improving patient communication and reducing healthcare disparities. This paper also highlights the crucial role of policy changes and legislation in promoting equal access to essential screening services like mammography. We explore the challenges and potential of teleradiology in improving access to medical imaging in remote and underserved areas. In the era of artificial intelligence, this paper emphasizes the necessity of validating its models across a spectrum of populations to prevent bias and achieve equitable healthcare outcomes. Finally, the importance of international collaboration is illustrated, showcasing its role in sharing insights and strategies to overcome global access barriers in medical imaging. Overall, this paper offers a comprehensive overview of the challenges related to disparities in medical imaging access and proposes actionable strategies to address these challenges, aiming for equitable healthcare delivery.

Imaging plays a key role in the clinical management of Coronavirus disease 2019 (COVID-19) as the imaging findings reflect the pathological process in the lungs. The visual analysis of High-Resolution Computed Tomography of the chest allows for the differentiation of parenchymal abnormalities of COVID-19, which are crucial to be detected and quantified in order to obtain an accurate disease stratification and prognosis. However, visual assessment and quantification represent a time-consuming task for radiologists. In this regard, tools for semi-automatic segmentation, such as those based on Convolutional Neural Networks, can facilitate the detection of pathological lesions by delineating their contour. In this work, we compared four state-of-the-art Convolutional Neural Networks based on the encoder-decoder paradigm for the binary segmentation of COVID-19 infections after training and testing them on 90 HRCT volumetric scans of patients diagnosed with COVID-19 collected from the database of the Pisa University Hospital. More precisely, we started from a basic model, the well-known UNet, then we added an attention mechanism to obtain an Attention-UNet, and finally we employed a recurrence paradigm to create a Recurrent-Residual UNet (R2-UNet). In the latter case, we also added attention gates to the decoding path of an R2-UNet, thus designing an R2-Attention UNet so as to make the feature representation and accumulation more effective. We compared them to gain understanding of both the cognitive mechanism that can lead a neural model to the best performance for this task and the good compromise between the amount of data, time, and computational resources required. We set up a five-fold cross-validation and assessed the strengths and limitations of these models by evaluating the performances in terms of Dice score, Precision, and Recall defined both on 2D images and on the entire 3D volume. From the results of the analysis, it can be concluded that Attention-UNet outperforms the other models by achieving the best performance of 81.93%, in terms of 2D Dice score, on the test set. Additionally, we conducted statistical analysis to assess the performance differences among the models. Our findings suggest that integrating the recurrence mechanism within the UNet architecture leads to a decline in the model's effectiveness for our particular application.

Breast cancer risk models represent the likelihood of developing breast cancer based on risk factors. They enable personalized interventions to improve screening programs. Radiologists identify mammographic density as a significant risk factor and test new imaging techniques. Pathologists provide data for risk assessment. Clinicians conduct individual risk assessments and adopt prevention strategies for high-risk subjects. Tumor genetic testing guides personalized screening and treatment decisions. Artificial intelligence in mammography integrates imaging, clinical, genetic and pathological data to develop risk models. Emerging imaging technologies, genetic testing and molecular profiling improve risk model accuracy. The complexity of the disease, limited data availability and model inputs are discussed. A multidisciplinary approach is essential for earlier detection and improved outcomes.

Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple-areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed.

Metaplastic breast cancer (MpBC) is a rare, aggressive breast cancer (BC) histotype. Scarce information is available about MpBC genetic predisposition. Previous studies, mainly consisting of case reports, retrospective reviews and others on target therapies, pointed to a possible involvement of the BRCA1 gene in increasing MpBC risk, without ever confirming it. In this study, we retrospectively reviewed all BC patients counseled at our Institute for genetic testing of at least BRCA1 or BRCA2 (BRCA) genes and we found that 23 (23/5226 = 0.4%) were affected by MpBC. About 65% (15/23) of MpBC patients harbored a germline pathogenic variant (PV): 13 in BRCA1 (86.7%), including two patients who received genetic testing for known familial PV, one in TP53 (6.7%), and one in MLH1 (6.7%). We observed a statistically different frequency of MpBC in patients who carried a PV in the BRCA genes (13/1114 = 1.2%) vs. all other BC patients (10/4112 = 0.2%) (p = 0.0002). BRCA carriers proved to have an increased risk of developing MpBC compared to all other BC patients who were tested for BRCA genes (OR = 4.47; 95% CI: 1.95-10.23). Notably, MpBCs were diagnosed in 2.1% (13/610) of BRCA1 carriers. No MpBCs were observed in BRCA2 carriers (0/498 = 0%), revealing a statistically significant difference between the prevalence of MpBCs in BRCA1 and BRCA2 carriers (p = 0.0015). Our results confirmed that BRCA1 is involved in MpBC predisposition. Further studies on unselected patients are needed to elucidate the authentic role of BRCA1 and to explore the possible implication of other genes in MpBC predisposition., (© 2023. The Author(s), under exclusive licence to European Society of Human Genetics.)

Background: There is currently no recommendation regarding preferred drugs for active eosinophilic oesophagitis (EoE) because their relative efficacy is unclear. We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE., Methods: We searched MEDLINE, Embase, Embase Classic and the Cochrane Central Register of Controlled Trials from inception to June 2023. We included randomised controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with active EoE. Results were reported as pooled relative risks with 95% CIs to summarise effect of each comparison tested, with drugs ranked according to P score RESULTS: Seventeen RCTs were eligible for systematic review. Of these, 15 studies containing 1813 subjects with EoE reported extractable data for the network meta-analysis. For histological remission defined as ≤6 eosinophils/high-power field (HPF), lirentelimab 1 mg/kg monthly ranked first. For histological remission defined as ≤15 eosinophils/HPF, budesonide orally disintegrating tablet (BOT) 1 mg two times per day ranked first. For failure to achieve symptom improvement, BOT 1 mg two times per day and budesonide oral suspension (BOS) 2 mg two times per day were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE Endoscopic Reference Score, BOT 1 mg two times per day and BOS 1 mg two times per day or 2 mg two times per day were significantly more efficacious than placebo., Conclusions: Although this network meta-analysis supports the efficacy of most available drugs over placebo for EoE treatment, significant heterogeneity in eligibility criteria and outcome measures among available trials hampers the establishment of a solid therapeutic hierarchy., Competing Interests: Competing interests: NdB served as speaker for Reckitt Benckiser, Malesci, Sofar, Alfa-Sigma, Dr Falk and Cadigroup. ES served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots and Unifarco; served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda and Unifarco; received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco and Zeta Farmaceutici.PV, BB, GDC, CB and ACF have no competing interests., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome., Methods: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant., Results: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021)., Conclusions: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The role of inhaled and swallowed aeroallergens in treatment outcomes of adult patients with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of the 6-food elimination diet (SFED) in EoE., Methods: We compared outcomes of patients with EoE who underwent SFED during vs outside of the pollen season. Consecutive adult patients with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Individual pollen sensitization and pollen count data were analyzed to define whether each patient had been assessed during or outside of the pollen season after SFED. All patients had active EoE (≥15 eosinophils/high-power field) before SFED and adhered to the diet under the supervision of a dietitian., Results: Fifty-eight patients were included, 62.0% had positive SPT for birch and/or grass, whereas 37.9% had negative SPT. Overall, SFED response was 56.9% (95% confidence interval, 44.1%-68.8%). When stratifying response according to whether the assessment had been performed during or outside of the pollen season, patients sensitized to pollens showed significantly lower response to SFED during compared with outside of the pollen season (21.4% vs 77.3%; P = 0.003). In addition, during the pollen season, patients with pollen sensitization had significantly lower response to SFED compared with those without sensitization (21.4% vs 77.8%; P = 0.01)., Discussion: Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. The SPT for pollens may identify patients less likely to respond to the diet during the pollen season., (Copyright © 2023 by The American College of Gastroenterology.)

Background and Aims: The monitoring of yearly distributions of HbA 2 measured has been indicated as a reliable indicator of worldwide standardization., Materials and Methods: Measurements/year of HbA 2 have been collected over three consecutive years in 15 Italian laboratories each using the same analytical method over three years period. HbA 2 distributions, cleaned of replicated measurements, were compared by the overlapping area of the raw probability density functions expressed by coefficient eta (η), and by comparing the reference intervals for the central part of each distribution estimated by the indirect method refineR using the R package "refineR"., Results: According to the overlapping areas analysis the distributions/year of the data provided by 4 centers able to perform at least 1000 measurements/year were similar in 2 consecutive years. Moreover, the reference intervals provided by 2 centers using the same analytical methods in two separate locations over the three consecutive years, were very similar. The highest overlap (99.7 %) was observed in one center over two consecutive years. The overlapping areas were very high (93.6-95.7%) in 8 out of 9 inter-comparisons., Conclusion: Despite the limitations of this study the yearly distribution of the HbA 2 measured in various centers appears a reliable tool to test HbA 2 standardization over different centers using different analytical methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)