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Designing carbonate facies models requires the integration, correlation and conceptual interpretation of multiple geological data sets. Potential significant errors are sourced from uncertain stratigraphic correlations, speculative palaeoecological interpretations and poorly recorded palaeotopographic profiles. The present study explores a methodological workflow to define a well-supported facies model. An exhaustive literature review is presented on sedimentary facies and depositional profiles of Urgonian carbonate platform from SE France and Switzerland (Barremian–Aptian interval). The historical evolution of Urgonian facies models and related sedimentological concepts is investigated to contextualise published models. The presented conceptual model and table of depositional facies shows a consistent, process-based organization of specific elementary facies, facies associations and carbonate system. Within the chronostratigraphic framework, the study of synchronous strata correlations provides quantitative analyses of facies-belt extents and palaeobathymetric estimations. The resulting depositional profile is based on general palaeoecological and sedimentological concepts, facies distribution on palaeogeographic maps and stacking trends. In rare locations in the field, direct lateral facies belt transitions are recorded. Proximal (i.e. emersive and peloidal-foraminiferal) depositional facies are rarely observed; most outcrops record the (i) rudist facies association, which corresponds to distal parts of the inner platform, (ii) coral, ooidal and bioclastic facies associations, which are interpreted to occur on the outer platform, and (iii) calcisiltite, slope and basinal deposits. Key data and concepts allow for the building up of a robust, harmonised facies model that can be used to properly interpret palaeoenvironmental changes, stacking trends and stratigraphic sequence evolution, the resolution of which depends on the available chronostratigraphic framework.

This contribution focuses on the Perisphinctoidea ammonite taxa from the Upper Tithonian at Charens (Drôme, south-east France). Emphasis is laid on five genera that belong to the families Himalayitidae and Neocomitidae. We document the precise vertical range of the index-species Micracanthoceras microcanthum, and a comparative ontogenetic- biometric analysis sheds new light on its range of variation and dimorphism as compared to the bestknown Spanish populations. As herein understood, the lower boundary of the M. microcanthum Zone (base of the Upper Tithonian) is fixed at the FAD of its index species. The faunal assemblages and species distribution of the P. andreaei Zone are rather similar to those described at the key-section of Le Chouet as confirmed by the co-occurrence of the genera Protacanthodiscus, Boughdiriella and Pratumidiscus. New palaeontological evidence supports the view that the basal Neocomitidae Busnardoiceras busnardoi was derived from Protacanthodiscus andreaei in the upper part of the P. andreaei Zone.

This paper presents a methodological approach to develop a user-oriented web tool to support the early stage of the decision making process for energy retrofitting of residential real estates. The tool mixes a simple analytical Urban Building Energy Model (UBEM) to user-oriented feedback interfaces to simulate the retrofitting potential of the residential units. The AUREE tool will be based on a Web – GIS GeoBlog portal with customized interfaces aimed to share the knowledge on urban building heritage and promote participation of stakeholders of the urban community. There are many literature exempla of guidelines or quality protocols on the topic of energy efficiency specified to particular types of buildings or focused on a territorial area, but these are generally not integrated into a geographically based tool. Moreover, the AUREE methodology aims to set interfaces that could use the portal users’ feedback to update the content of the portal itself. After touch on the theoretical context, a summary of the AUREE project is presented, and then the paper focuses on the structures of algorithms and tools adopted on the residential users’ interfaces. The interface mixes the results of an engineering Urban Building Energy Model based on local archetypal approach and standard energy calculation (series UNI 11300 - TS), with participative data provided via user-interactive interfaces to obtain customized retrofitting scenarios and suggestions. At the end of the paper, the main critical aspects and the further step of the research project are pointed

The Upper Cretaceous sedimentary succession cropping out in the Sainte-Baume Massif (Var, southeastern France) is of late Turonian to Campanian age. There, complex imbrication and rapid evolution in space and time of shallow-marine, fluvio-deltaic and lacustrine environments at the front of the North Provence Durancian uplift occur during the Santonian. Marly and/or sandy strata rich in lignite remains and amber grains are interspersed throughout the Santonian series. According to new in situ collections, the features of the amber grains, and their micro-inclusions, are similar to those found in well-known amber-bearing sites from the Bouches-du-Rhône department. This testifies of a widespread resin-producing tree forests in southeastern France at that time.

The presence of “geological” amber (or “succin” in old French monographs) has been reported for several centuries in the Mesozoic deposits of Provence, southeastern France. Diverse amber-bearing sites were inventoried by the authors but their location and stratigraphical context remain unclear for most of them. In the past decades, various data concerning chemistry, palaeontological content and comparison with archaeological discoveries improved our knowledge of the ambers of Provence, but only those of Cretaceous age. The present paper aims at providing a comprehensive description of all the presently known amber-bearing deposits of Provence, including the description of new sites. We highlight the great potential of Provence ambers and allow to consider a wider time range, from the Early Cretaceous to the Miocene.

This paper presents a methodological approach to develop the tool “Urban Abacus of Building Energy performances (Abaco URbano Energetico degli Edifci – AUREE)” for supporting the renovation and energy efficiency enhancement of urban building heritage. The AUREE tool will be based on a Web – GIS GeoBlog portal with some customized interfaces aimed to share the knowledge on urban building heritage and promote the participation of the stakeholders of the urban community. The tool improves citizen and stakeholders awareness on building energy efficiency issues and facilitates the linkage between demand and offer for building companies services via the integration of two main elements: the first is a knowledge layer that represents the actual state of the energy performance of urban building heritage and the second is a spatial based Abacus of the more common building characteristics (structures, plants, uses, ..) and energy retrofitting and renovation technologies. After a touch on the theoretical context, this paper presents a summary of the AUREE general framework and focuses on the methodological approach of the Urban Abacus. The data structure integrates an Urban Building Energy Model (UBEM) in order to support on the energy retrofitting scenario analysis at the level of single building and also for a group of them (city block, district, city). At the end of the paper the furthers research steps have been pointed

Cholangiocytes are the main cell type lining the epithelium of the biliary tree of the liver. This cell type has been implicated not only in diseases affecting the biliary tree but also in chronic liver diseases targeting other hepatic cells such as hepatocytes. However, the isolation and culture of cholangiocytes have been particularly arduous, thereby limiting the development of new therapies. The emergence of organoids has the potential to address in part this challenge. Indeed, cholangiocyte organoids can be established from both the intra- and extrahepatic regions of the biliary tree, providing an advantageous platform for disease modeling and mechanism investigations. Accordingly, recent studies on cholangiocyte organoids, together with the advent of single-cell -omics, have opened the field to exciting discoveries concerning the plastic nature of these cells and their capability to adapt to different environments and stimuli. This review will focus on describing how these plasticity properties could be exploited in regenerative medicine and cell-based therapy, opening new frontiers for treating disorders affecting the biliary tree and beyond., Competing Interests: Declaration of Competing Interest Ludovic Vallier reports a relationship with Definiens AG that includes consulting or advisory and equity or stocks. Ludovic Vallier reports a relationship with Bilitech that includes equity or stocks. Ludovic Vallier reports a relationship with Bit.bio that includes equity or stocks. If there are other authors, they 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily observed in animal models, and their underlying mechanisms are becoming well characterized 1-4 , but technical challenges and ethical aspects are limiting the validation of these results in humans. We decided to address this difficulty with respect to the liver. This organ displays the remarkable ability to regenerate after acute injury, although liver regeneration in the context of recurring injury remains to be fully demonstrated. Here we performed single-nucleus RNA sequencing (snRNA-seq) on 47 liver biopsies from patients with different stages of metabolic dysfunction-associated steatotic liver disease to establish a cellular map of the liver during disease progression. We then combined these single-cell-level data with advanced 3D imaging to reveal profound changes in the liver architecture. Hepatocytes lose their zonation and considerable reorganization of the biliary tree takes place. More importantly, our study uncovers transdifferentiation events that occur between hepatocytes and cholangiocytes without the presence of adult stem cells or developmental progenitor activation. Detailed analyses and functional validations using cholangiocyte organoids confirm the importance of the PI3K-AKT-mTOR pathway in this process, thereby connecting this acquisition of plasticity to insulin signalling. Together, our data indicate that chronic injury creates an environment that induces cellular plasticity in human organs, and understanding the underlying mechanisms of this process could open new therapeutic avenues in the management of chronic diseases., (© 2024. The Author(s).)

Olfactory dysfunction is a prevalent non-motor symptom in Parkinson's disease (PD), affecting approximately 65-90% of subjects. PD patients may also report odor perception in the absence of any external source, often referred to as olfactory hallucinations (OHs) or phantosmia. This study aims to explore the current understanding of OHs in PD and offer a comprehensive overview of their prevalence and characteristics. We conducted a systematic search of the literature published on PubMed from inception to July 2023 regarding OHs in PD, following PRISMA guidelines. From the 2875 studies identified through database searching, 29 studies fulfilled the necessary criteria and underwent data extraction. The frequency of OHs in PD patients varies widely, ranging from 0.5% to 18.2%, with female prevalence ranging from 36% to 75% of the patients. Olfactory experiences may vary widely, ranging from pleasant scents to unpleasant odors. Several studies have indicated the concurrent presence of other types of hallucinations alongside phantosmia, especially visual and auditory hallucinations. OHs in PD are a type of hallucination that has been largely overlooked. To gain a deeper understanding of OHs in PD patients, the next crucial step should involve the development and validation of a dedicated questionnaire.

Currently, Parkinson's Disease (PD) is diagnosed primarily based on symptoms by experts clinicians. Neuroimaging exams represent an important tool to confirm the clinical diagnosis. Among them, Brain Parenchyma Sonography (BPS) is used to evaluate the hyperechogenicity of Substantia Nigra (SN), found in more than 90% of PD patients. In this article, we exploit a new dataset of BPS images to investigate an automatic segmentation approach for SN that can increase the accuracy of the exam and its practicability in clinical routine. This study achieves state-of-the-art performance in SN segmentation of BPS images. Indeed, it is found that the modified U-Net network scores a Dice coefficient of 0.859 ± 0.037. The results presented in this study demonstrate the feasibility and usefulness of SN automatic segmentation in BPS medical images, to the point that this study can be considered as the first stage of the development of an end-to-end CAD (Computer Aided Detection) system. Furthermore, the used dataset, which will be further enriched in the future, has proven to be very effective in supporting the training of CNNs and may pave the way for future studies in the field of CAD applied to PD.

A 74-year-old transgender female presented with urinary difficulty and a painful lesion at her neo-vagina, 47 years after undergoing gender-affirming vaginoplasty. Initial biopsy reported Low-Grade Squamous Intraepithelial Lesion (LGSIL), while MRI revealed no inguinal or pelvic lymphadenopathy. Patient underwent partial neo-vaginectomy with wide local excision and formal urethroplasty. Pathology revealed verrucous carcinoma of the neovagina, a rare neoplasm in transgender female patients. This case highlights the importance of considering squamous cell carcinoma in the differential diagnosis of patients presenting lesions at neo-vagina and the need of screening methods for early detection of such neoplasms., (© 2023 The Authors.)

Introduction: Olfactory impairment and REM sleep behavior disorder (RBD) are common non-motor symptoms in Parkinson's disease (PD) patients, often preceding the onset of the specific motor symptoms and, thus, crucial for strategies directed to anticipate PD diagnosis. In this context, the specific interaction between olfactory impairment and RBD has not been clearly defined., Objective: The aim of this study was to determine the possible role of olfactory impairment and other clinical characteristics as possible predictors of higher scores at RBD screening questionnaire (RBDSQ) in a large population of PD patients., Methods: In this study, 590 PD patients were included from the Parkinson's Progression Markers Initiative. Demographic and clinical features were registered. All participants completed motor and non-motor evaluations at the baseline visit. For motor assessments, the disease severity was evaluated by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pars III. Regarding non-motor symptoms assessment, Montreal Cognitive Assessments (MoCA), University of Pennsylvania Smell Identification Test (UPSIT) and RBD screening questionnaire (RBDSQ) were registered., Results: Among 590 PD patients included in this study, 111 patients with possible RBD were found (18.8%). RBD was less frequent in female PD patients ( p   ≤  0.011). Among patients with or without possible RBD diagnosis, statistically significant differences in MDS-UPDRS III (23.3 ± 11.4 vs. 19.7 ± 9.1, respectively, p   ≤  0.002) and in UPSIT score (19.7 ± 8.3 vs. 22.6 ± 8.0, respectively, p   ≤  0.001) were found. Moreover, significant correlations between RBDSQ versus UPDRS III score and versus UPSIT score were observed. Multivariate linear regression analysis showed that UPSIT was the most significant predictor of higher scores at RBDSQ, while the other significant predictors were UPDRS III and age., Conclusions: The severity of olfactory impairment appears tightly correlated to RBD symptoms, highlighting the role of these biomarkers for PD patients. Additionally, according to this large study, our data confirmed that RBD in PD patients exhibits peculiar gender differences.

Prominent scholars suggested that the impulsive-obsessive compulsive continuum may represent a framework to understand both substance and behavioral addictions. However, the characterization of pathological buying (PB) and problem gambling (PG) within the compulsive-impulsive spectrum has not been extensively investigated. To explore the relationships among PB, PG, alcohol and substance abuse, DSM-5 obsessive-compulsive and related disorders, and impulsive dimensions, a sample of 1,005 Italian community-dwelling adult participants (55.5% female), was administered self-reported measures of PB, PG, and other theoretically-relevant constructs. We expected to observe a multidimensional structure in our data; moreover, DSM-5 obsessive compulsive and related disorders were hypothesized to be accounted for by a common dimension. Three dimensions were identified and replicated across two different, non-redundant methods (i.e., exploratory graph analysis and exploratory factor analysis), namely, substance use and gambling, obsessive and compulsive phenomena, and impulsivity dimensions. Specifically, PG seemed to represent a behavioral variant of addiction vulnerability, PB seemed more akin to obsessive-compulsive spectrum disorders, and disinhibition dimension represented the common core of negative urgency, lack of premeditation, lack of perseverance, sensation seeking (SS), and positive urgency. Our findings may be helpful in improving our knowledge on the similarities and differences between PB and PG., Competing Interests: Declaration of Competing Interest Antonella Somma, Robert F. Krueger, Kristian E. Markon, Giulia Gialdi, Nicole Di Leva, Elena Falcone, Marisole Villa, Claudia Frau, and Andrea Fossati, (Copyright © 2023 Elsevier B.V. All rights reserved.)

To examine the hierarchical structure of psychopathology and dysfunctional personality domains, 2416 Italian community-dwelling adult volunteers were administered a set of psychometrically sound psychopathology measures and the Personality Inventory for DSM-5 Brief Form+ (PID-5-BF+). Parallel analysis, minimum average partial, and very simple structure results suggested that 1-6 principal components (PCs) should be retained. Goldberg's bass-ackwards model of the joint psychopathology measure and PID-5-BF+ ipsatized domain scale correlation matrix evidenced a hierarchical structure that was consistent with the working model proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium. Hierarchical agglomerative cluster analysis around latent variables of the psychopathology indicators and PID-5-BF+ domain scales recovered four latent dimensions, which were akin to the corresponding bass-ackwards components and nicely reproduced the HiTOP Internalizing, Externalizing, Thought Disorder, and Eating Pathology dimensions., (© 2022 John Wiley & Sons Ltd.)

Introduction: Olfactory and cognitive disorders represent important non-motor symptoms in Parkinson's disease (PD). No clear evidence was reported about association of specific cognitive domains and olfactory impairment., Objective: The aim of this study was to evaluate the association between olfactory dysfunction and specific cognitive domains in PD patients compared to controls., Methods: 178 PD patients and 98 controls were enrolled and evaluated for odor threshold (OT), discrimination (OD), identification (OI), and TDI score using the Sniffin' Sticks test. Cognitive function was evaluated using the Montreal Cognitive Assessment scale with six sub-scores: Orientation (OIS), Attention (AIS), Language (LIS), Visuospatial (VIS), Memory (MIS), and Executive index scores (EIS)., Results: Statistically significant correlations were observed between OT versus, LIS, and between TDI score versus EIS. Multivariate linear regression analysis, including age and sex which are well-known predictors of olfactory dysfunction, showed that, among specific cognitive domains, only LIS was significant predictor for OT, VIS was a significant predictor for OD, while both EIS and AIS were significant predictors for OI, and finally only EIS was significant predictor for TDI score., Conclusions: Olfactory disorders in PD patients appear commonly related to dysfunction of specific cognitive domains, with strict association between global olfactory impairment and executive function deficits.

Advances in cellular engineering, as well as gene, and cell therapy, may be used to produce human tissues with programmable genetically enhanced functions designed to model and/or treat specific diseases. Fabrication of synthetic human liver tissue with these programmable functions has not been described. By generating human iPSCs with target gene expression controlled by a guide RNA-directed CRISPR-Cas9 synergistic-activation-mediator, we produced synthetic human liver tissues with programmable functions. Such iPSCs were guide-RNA-treated to enhance expression of the clinically relevant CYP3A4 and UGT1A1 genes, and after hepatocyte-directed differentiation, cells demonstrated enhanced functions compared to those found in primary human hepatocytes. We then generated human liver tissue with these synthetic human iPSC-derived hepatocytes (iHeps) and other non-parenchymal cells demonstrating advanced programmable functions. Fabrication of synthetic human liver tissue with modifiable functional genetic programs may be a useful tool for drug discovery, investigating biology, and potentially creating bioengineered organs with specialized functions., Competing Interests: A.C.-H., K.T., I.J.F., and A.S.-G. are inventors on a provisional international patent application that describes hepatic differentiation of human pluripotent stem cells and liver repopulation (PCT/US2018/018032) and a provisional international patent application that describes the use of human-induced pluripotent stem cells for highly genetic engineering (PCT/US2017/044719). A.S.-G., J.G.-L., A.C.-H., and I.J.F. are co-founders and have a financial interest in Von Baer Wolff, Inc. a company focused on biofabrication of autologous human hepatocytes from stem cells technology. I.J.F. and A.S.-G. are co-founders and have a financial interest in Pittsburgh ReLiver Inc, a company focused on programming liver failure and their interests are managed by the Conflict-of-Interest Office at the University of Pittsburgh in accordance with their policies., (© 2022 The Authors.)

In an online sample of 1054 Italian community-dwelling adults, we assessed the relationships between the frequency of implementation of practices intended to prevent COVID-19 infection, degree of agreement with theories about the origin of the infections, and the frequency of use of different sources of information concerning the COVID-19 pandemic. The results showed that participants' COVID-19-related preventive behaviors and causal beliefs were significantly associated with selected demographic variables and frequency of use of specific sources of information (e.g. scientific journals vs social media).

The only definitive therapy for end-stage liver disease is whole-organ transplantation. The success of this intervention is severely limited by the complexity of the surgery, the cost of patient care, the need for long-term immunosuppression, and the shortage of donor organs. In rodents and humans, end-stage degeneration of hepatocyte function is associated with disruption of the liver-specific transcriptional network and a nearly complete loss of promoter P1-driven hepatocyte nuclear factor 4-alpha (P1-HNF4α) activity. Re-expression of HNF4α2, the predominant P1-HNF4α, reinstates the transcriptional network, normalizes the genes important for hepatocyte function, and reverses liver failure in rodents. In this study, we tested the effectiveness of supplementary expression of human HNF4α2 messenger RNA (mRNA) in primary human hepatocytes isolated from explanted livers of patients who underwent transplant for end-stage irreversibly decompensated liver failure (Child-Pugh B, C) resulting from alcohol-mediated cirrhosis and nonalcoholic steatohepatitis. Re-expression of HNF4α2 in decompensated cirrhotic human hepatocytes corrects the disrupted transcriptional network and normalizes the expression of genes important for hepatocyte function, improving liver-specific protein expression. End-stage liver disease in humans is associated with both loss of P1-HNF4α expression and failure of its localization to the nucleus. We found that while HNF4α2 re-expression increased the amount of P1-HNF4α protein in hepatocytes, it did not alter the ability of hepatocytes to localize P1-HNF4α to their nuclei. Conclusion: Re-expression of HNF4α2 mRNA in livers of patients with end-stage disease may be an effective therapy for terminal liver failure that would circumvent the need for organ transplantation. The efficacy of this strategy may be enhanced by discovering the cause for loss of nuclear P1-HNF4α localization in end-stage cirrhosis, a process not found in rodent studies., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

The use of primary human hepatocytes has been hampered by limited availability of adequate numbers of fresh and viable cells due to the ongoing shortage of liver donors. Thus, there is no surplus of healthy organs from which freshly isolated cells can be prepared when needed. However, primary hepatocytes can be successfully isolated from explanted liver specimens obtained from patients receiving orthotopic liver transplantation for decompensated liver cirrhosis or for metabolic liver disease without end-stage liver disease and are a valuable resource for the pharmaceutical industry research. This review focuses on the isolation, characterization and cryopreservation of hepatocytes derived from therapeutically resected livers with various hepatic diseases.

The prevalence of end-stage liver disease (ESLD) in the US is increasing at an alarming rate. It can be caused by several factors; however, one of the most common routes begins with nonalcoholic fatty liver disease (NAFLD). ESLD is diagnosed by the presence of irreversible damage to the liver. Currently, the only definitive treatment for ESLD is orthotopic liver transplantation (OLT). Nevertheless, OLT is limited due to a shortage of donor livers. Several promising alternative treatment options are under investigation. Researchers have focused on the effect of liver-enriched transcription factors (LETFs) on disease progression. Specifically, hepatocyte nuclear factor 4-alpha (HNF4α) has been reported to reset the liver transcription network and possibly play a role in the regression of fibrosis and cirrhosis. In this review, we describe the function of HNF4α, along with its regulation at various levels. In addition, we summarize the role of HNF4α in ESLD and its potential as a therapeutic target in the treatment of ESLD.