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Abstract During embryonic and neonatal development, mitochondria have essential effects on metabolic and energetic regulation, shaping cell fate decisions and leading to significant short- and long-term effects on embryonic and offspring health. Therefore, perturbation on mitochondrial function can have a pathological effect on pregnancy. Several shreds of evidence collected in preclinical models revealed that severe mitochondrial dysfunction is incompatible with life or leads to critical developmental defects, highlighting the importance of correct mitochondrial function during embryo-fetal development. The mechanism impairing the correct development is unknown and may include a dysfunctional metabolic switch in differentiating cells due to decreased ATP production or altered apoptotic signalling. Given the central role of mitochondria in embryonic and fetal development, the mitochondrial dysfunction typical of Mitochondrial Diseases (MDs) should, in principle, be detectable during pregnancy. However, little is known about the clinical manifestations of MDs in embryonic and fetal development. In this manuscript, we review preclinical and clinical evidence suggesting that MDs may affect fetal development and highlight the fetal and maternal outcomes that may provide a wake-up call for targeted genetic diagnosis.

Abstract Background Clinical data warehouses provide access to massive amounts of medical images, but these images are often heterogeneous. They can for instance include images acquired both with or without the injection of a gadolinium-based contrast agent. Harmonizing such data sets is thus fundamental to guarantee unbiased results, for example when performing differential diagnosis. Furthermore, classical neuroimaging software tools for feature extraction are typically applied only to images without gadolinium. The objective of this work is to evaluate how image translation can be useful to exploit a highly heterogeneous data set containing both contrast-enhanced and non-contrast-enhanced images from a clinical data warehouse. Methods We propose and compare different 3D U-Net and conditional GAN models to convert contrast-enhanced T1-weighted (T1ce) into non-contrast-enhanced (T1nce) brain MRI. These models were trained using 230 image pairs and tested on 77 image pairs from the clinical data warehouse of the Greater Paris area. Results Validation using standard image similarity measures demonstrated that the similarity between real and synthetic T1nce images was higher than between real T1nce and T1ce images for all the models compared. The best performing models were further validated on a segmentation task. We showed that tissue volumes extracted from synthetic T1nce images were closer to those of real T1nce images than volumes extracted from T1ce images. Conclusion We showed that deep learning models initially developed with research quality data could synthesize T1nce from T1ce images of clinical quality and that reliable features could be extracted from the synthetic images, thus demonstrating the ability of such methods to help exploit a data set coming from a clinical data warehouse.

This paper has been designed in the form of a systematic literature review intended for evaluating the state-of-the-art of discrete-event simulation (DES) usage in the logistics and supply chain management fields under a scientometric perspective. With this primary aim in mind, 127 papers published between 2009 and 2022 are analysed, with the specific purposes of: 1) providing an overview of DES studies in logistics and supply chain management, map the main topics covered within this stream of literature and their evolution in time; 2) providing a robust ranking of the journals and authors in the field; 3) evaluating the rigor in the implementation of DES models in the logistics and supply chain management literature; and finally 4) correlating, through statistical elaborations, all the previous aspects to the success of these papers, measured as the citations received per year, taking inspiration from scientometric disciplines.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a novel term for Non-Alcoholic Fatty Liver Disease (NAFLD), is associated with liver mitochondrial dysfunction. We previously demonstrated that mitochondrial respiratory capacity in peripheral blood mononuclear cells (PBMCs) was significantly reduced in patients with MASLD compared to non-MASLD controls. For MASLD treatment, guidelines recommend behavioral and dietary changes to reduce body weight. A recent 12-month clinical trial demonstrated that ameliorating patients’ lifestyles through improved adherence to the Mediterranean diet and encouraged physical activity results in MASLD remission or regression. Methods: As a sub-study of the 12-month clinical trial, we evaluated the effects of the Mediterranean diet-oriented intervention on PBMC mitochondrial DNA content and respiratory parameters and on various biomarkers associated with MASLD. Results: Contrary to what was found at the baseline, after twelve months of intervention, systemic inflammatory and bioenergetics parameters did not differ between MASLD patients (N = 15) and control subjects (N = 17). PBMCs from MASLD subjects showed rescued basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. The observed recovery coincided with a significant increase in the patients’ adherence to the Mediterranean diet (Medscore). Conclusions: Our findings indicate that a Mediterranean diet-oriented intervention, without calorie reduction, preserves blood cell mitochondrial function in MASLD subjects. Thus, PBMC bioenergetics-based assays might be taken into account not only for diagnosing but also for monitoring therapeutic responses in MASLD.

Nowadays many processes in the food industry are monitored in an automatic way, with the purpose of minimising the need for workforce and of ensuring the proper control of the quality and safety of the foodstuff. All the sensors share data with a centralised management unit, where often a Manufacturing Execution System collects and evaluates them. As reported in recent research, however, a further step that can be undertaken, exploiting Industry 4.0 enabling technologies, is the implementation of digital twin approaches, with the additional aim to prevent possible issues during production. In line with these considerations, this work aims at showing two different digital twin models intended for improving the control of as many real food systems. Liquid and powder fluids are taken as examples for highlighting the differences in the optimization of the two food processes, as well as for fully exploring the potential of the digital twin approach. Finally, based on the real data taken from two pilot plants, a framework for the selection of the best digital twin tool in the food sector is delineated. [ABSTRACT FROM AUTHOR]

This article investigates the impact of the COVID-19 pandemic on logistics and supply chain processes through a two-phase analysis. First, a literature review maps the existing studies, published from 2021 to 2023 (101 papers), offering a view of the multiple challenges faced by supply chains during the pandemic emergency. The literature analysis makes use of descriptive statistics, thematic classifications and cross-analyses to provide a detailed overview of the issues raised by the COVID-19 pandemic and of the related implications. Second, a case study targeting a logistics operator was conducted, to derive practical insights into the real-world implications of pandemic disruptions. The study highlights the importance of proactive risk management strategies and the role of Industry 4.0 technologies to improve supply chain resilience and sustainability. Hence, this research contributes to a deeper understanding of the impact of the COVID-19 pandemic on logistics and supply chain processes and offers valuable guidance for companies, especially those working in the transport and logistics field.

ABSTRACTA literature review on the order picking process in warehouses is presented for delineating the trends in time of research topics in this field. A total of 269 journal papers published between 2007 and 2022 were retrieved from Scopus. After a methodological classification, descriptive analyses were performed on authors, journals, subject area and top publishing countries. Bibliometric tools were used to map the topics covered by the reviewed studies, categorise them and determine possible relationships. Papers’ contents were evaluated in terms of eight categories, including five typical issues of order picking systems, plus three aspects dealing with the characteristics of the application. Insights about the extent to which these aspects have been covered in the literature are derived; relationships between the various aspects of the picking process are also delineated. Suggestions for future research activities are finally deducted, offering researchers and practitioners strong bases for works on order picking systems.

Summary: Mutations in MPV17 are a major contributor to mitochondrial DNA (mtDNA) depletion syndromes, a group of inherited genetic conditions due to mtDNA instability. To investigate the role of MPV17 in mtDNA maintenance, we generated and characterized a Drosophila melanogaster Mpv17 (dMpv17) KO model showing that the absence of dMpv17 caused profound mtDNA depletion in the fat body but not in other tissues, increased glycolytic flux and reduced lifespan in starvation. Accordingly, the expression of key genes of glycogenolysis and glycolysis was upregulated in dMpv17 KO flies. In addition, we demonstrated that dMpv17 formed a channel in planar lipid bilayers at physiological ionic conditions, and its electrophysiological hallmarks were affected by pathological mutations. Importantly, the reconstituted channel translocated uridine but not orotate across the membrane. Our results indicate that dMpv17 forms a channel involved in translocation of key metabolites and highlight the importance of dMpv17 in energy homeostasis and mitochondrial function.

Summary: Here we present a protocol to generate standardized cerebral organoids with hippocampal regional specification using morphogen WNT3a. We describe steps for isolating mouse embryonic (E14.5) neural stem cells from the brain subgranular zone, preparing organoids samples for immunofluorescence, calcium imaging, and metabolic profiling. This protocol can be used to generate mouse brain organoids for developmental studies, modeling disease, and drug screening. Organoids can be obtained in one month, thus providing a rapid tool for high-throughput data validation.For complete details on the use and execution of this protocol, please refer to Ciarpella et al. “Murine cerebral organoids develop network of functional neurons and hippocampal brain region identity”.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

BackgroundManagement of operating rooms is a critical point in health care organizations because surgical departments represent a significant cost in hospital budgets. Therefore, it is increasingly important that there is effective planning of elective, emergency, and day surgery and optimization of both the human and physical resources available, always maintaining a high level of care and health treatment. This would lead to a reduction in patient waiting lists and better performance not only of surgical departments but also of the entire hospital. ObjectiveThis study aims to automatically collect data from a real surgical scenario to develop an integrated technological-organizational model that optimizes operating block resources. MethodsEach patient is tracked and located in real time by wearing a bracelet sensor with a unique identifier. Exploiting the indoor location, the software architecture is able to collect the time spent for every step inside the surgical block. This method does not in any way affect the level of assistance that the patient receives and always protects their privacy; in fact, after expressing informed consent, each patient will be associated with an anonymous identification number. ResultsThe preliminary results are promising, making the study feasible and functional. Times automatically recorded are much more precise than those collected by humans and reported in the organization’s information system. In addition, machine learning can exploit the historical data collection to predict the surgery time required for each patient according to the patient’s specific profile. Simulation can also be applied to reproduce the system’s functioning, evaluate current performance, and identify strategies to improve the efficiency of the operating block. ConclusionsThis functional approach improves short- and long-term surgical planning, facilitating interaction between the various professionals involved in the operating block, optimizing the management of available resources, and guaranteeing a high level of patient care in an increasingly efficient health care system. Trial RegistrationClinicalTrials.gov NCT05106621; https://clinicaltrials.gov/ct2/show/NCT05106621 International Registered Report Identifier (IRRID)DERR1-10.2196/45477

Introduction: Biallelic variants in PITRM1 are associated with a slowly progressive syndrome characterized by intellectual disability, spinocerebellar ataxia, cognitive decline and psychosis. The pitrilysin metallopeptidase 1 (PITRM1) is a mitochondrial matrix enzyme, which digests diverse oligopeptides, including the mitochondrial targeting sequences (MTS) that are cleaved from proteins imported across the inner mitochondrial membrane by the mitochondrial processing peptidase (MPP). Mitochondrial peptidases also play a role in the maturation of Frataxin, the protein affected in Friedreich’s ataxia. Recent studies in yeast indicated that the mitochondrial matrix protease Ste23, which is a homologue of the human insulin-degrading enzyme (IDE), cooperates with Cym1 (homologue of PITRM1) to ensure the proper functioning of the preprotein processing machinery. In humans, IDE could be upregulated by Peroxisome Proliferator-Activated Receptor Gamma (PPARG) agonists.Methods: We investigated preprotein processing, mitochondrial membrane potential and MTS degradation in control and patients’ fibroblasts, and we evaluated the pharmacological effect of the PPARG agonist Pioglitazone on mitochondrial proteostasis.Results: We discovered that PITRM1 dysfunction results in the accumulation of MTS, leading to the disruption and dissipation of the mitochondrial membrane potential. This triggers a feedback inhibition of MPP activity, consequently impairing the processing and maturation of Frataxin. Furthermore, we found that the pharmacological stimulation of PPARG by Pioglitazone upregulates IDE and also PITRM1 protein levels restoring the presequence processing machinery and improving Frataxin maturation and mitochondrial function.Discussion: Our findings provide mechanistic insights and suggest a potential pharmacological strategy for this rare neurodegenerative mitochondrial disease.

Abstract Local livestock breeds play an important role in the food security of smallholders in developing countries in the Global South. They are also a reservoir of potentially valuable genes for adaptation of global animal genetic resources. The Creole cattle population from Pasorapa, Bolivia, is threatened by effects of climate change and unplanned crossbreeding. The aim of this study was to assess the current situation in this population and to evaluate factors to be considered before implementing conservation and genetic improvement programs in order to achieve the sustainable development goals 1, 2, 13 and 15, which refer to no poverty, zero hunger, climate change and life on land, respectively. We examined and analyzed the most important elements related to the production system and farmers’ perceptions that could affect the design of such programs. Open-ended and closed-ended questionnaires and interviews were performed with 81 smallholders from 11 communities in Pasorapa. A rearing system based on two stages and animals feeding mainly on native plants during both, involves a strong interaction between the environment and the production system. A survey of farmers’ perceptions about diseases, mortality causes, and selection criteria revealed that farmers in Pasorapa consider coat color an important trait when selecting breeding and replacement animals. Half of all interviewees perceived an association between coat color and traits such as temperament, milk yield, and beef production. In a SWOT analysis we discussed the vulnerability of the system to climate change impacts and the contribution of this traditional system to rural mitigation. Overall, this work revealed the importance of this local ecotype and identified key factors to consider when developing breeding and conservation programs.

The idea that individuals tend to choose a romantic partner following similarities on personality traits has always attracted much attention in the psychological literature, although results were controversial. We conducted a new data analysis approach to personality traits of 235 newlywed couples. Univariate analysis revealed that a neurotic husband is usually paired with a lesser extrovert and open wife. To figure out if this mating selection pattern may be translated in a mathematical predictive model a twofold approach was employed by using Partial Least Squares regression and machine learning algorithm. The experimental results demonstrate that marital assortment for personality is a multi-trait complementarity process but these data are unable to predict human mating., Author(s): Antonio Cerasa [sup.1] [sup.2] , Emiliano Cristiani [sup.3] , Barbara De Luca [sup.4] , Maria Luisa De Narda [sup.5] , Maria Concetta Cundò [sup.5] , Sara Concetta Bottani [sup.4] [...]

In this monocentric, open label, randomized controlled trial we aimed to compare the efficacy of combined High Flow Nasal Cannula (HFNC) and Non invasive Ventilation (NIV) versus HFNC alone in acute hypoxemic respiratory failure (hARF) in patients affected by Community Acquired Pneumonia (CAP). We enrolled 49 patients affected by CAP with moderate to severe hypoxemic respiratory failure (P/F < 300). The patients were randomized into two groups: one has been treated with HFNC alone (group A) while the other received NIV alternated to HFNC every 3 hours (group B). The primary outcome was P/F change from baseline to 21 hours. Secondary outcomes included variation of pH and pCO2, need to continue HFNC or NIV/HFNC after 45 hours, orotracheal intubation, mortality rate, and the devices comfort. Not statistical significant differences between the two arms were shown in the P/F change at 21 hours since baseline, in pCO2 and pH variation, mortality at hospital and at follow-up. We emphasize the importance of combined HFNC with NIV as a first step for severe pneumonia treatment whereas HFNC might represent as the first step treatment in less severe patients and during the NIV intervals.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a novel term for Non-Alcoholic Fatty Liver Disease (NAFLD), is associated with liver mitochondrial dysfunction. We previously demonstrated that mitochondrial respiratory capacity in peripheral blood mononuclear cells (PBMCs) was significantly reduced in patients with MASLD compared to non-MASLD controls. For MASLD treatment, guidelines recommend behavioral and dietary changes to reduce body weight. A recent 12-month clinical trial demonstrated that ameliorating patients' lifestyles through improved adherence to the Mediterranean diet and encouraged physical activity results in MASLD remission or regression. Methods: As a sub-study of the 12-month clinical trial, we evaluated the effects of the Mediterranean diet-oriented intervention on PBMC mitochondrial DNA content and respiratory parameters and on various biomarkers associated with MASLD. Results: Contrary to what was found at the baseline, after twelve months of intervention, systemic inflammatory and bioenergetics parameters did not differ between MASLD patients (N = 15) and control subjects (N = 17). PBMCs from MASLD subjects showed rescued basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity. The observed recovery coincided with a significant increase in the patients' adherence to the Mediterranean diet (Medscore). Conclusions: Our findings indicate that a Mediterranean diet-oriented intervention, without calorie reduction, preserves blood cell mitochondrial function in MASLD subjects. Thus, PBMC bioenergetics-based assays might be taken into account not only for diagnosing but also for monitoring therapeutic responses in MASLD. [ABSTRACT FROM AUTHOR]

This paper explores the research trends in the literature about supply chain disruptions published over the last 20 years through a comprehensive review and keyword-based analysis. A sample of 4239 papers retrieved from Scopus was analyzed to identify the key themes covered and the shifts in time of those themes. The results highlight a significant rise in the number of publications on supply chain disruptions since 2021, reflecting the dynamic nature of supply chains and the need to adapt them to increasingly complex scenarios. The findings point out the importance of resilience and risk management but also the progressive shift toward technological innovations and digital tools, as a means to enhance supply chain robustness and sustainability in response to recent global disruptions (e.g., the COVID-19 pandemic, the Russia–Ukraine conflict, and the climate change). From the analyses carried out, interesting opportunities for future research directions are delineated. This study represents a unicum in the scientific literature in terms of the number of articles analyzed, the timespan, as well as the scientometric approach adopted. Finally, the paper highlights the main trends in the field of supply chain disruptions, providing valuable insights for future research activities. [ABSTRACT FROM AUTHOR]