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Abstract The inversion of petrophysical parameters from seismic data represents a fundamental step in the process of characterizing the subsurface, with applications ranging from subsurface resource exploration to geothermal, carbon capture and storage, and hydrogen storage. We propose a novel, data‐driven approach, named Seis2Rock, that utilizes optimal basis functions learned from well‐log information to create a direct link between pre‐stack seismic data and so‐called band‐limited petrophysical reflectivities. Seis2Rock is composed of two stages: training and inference. During training, a set of optimal basis functions are identified by performing singular value decomposition on one or more synthetic amplitude variation with offset gathers created from measured or rock‐physics synthesized elastic well logs. In inference, seismic pre‐stack data are first projected into a set of band‐limited petrophysical reflectivities using the previously computed basis functions; this is followed by regularized post‐stack seismic inversion of the individual properties. In this work, we apply the Seis2Rock methodology to a synthetic data set based on the Smeaheia reservoir model and to the open Volve field data set. Our numerical results reveal the ability of the proposed method in recovering accurate porosity, shale content, and water saturation models. Finally, the proposed methodology is applied in the context of reservoir monitoring to invert time‐lapse, pre‐stack seismic data for water saturation changes.

Drug repurposing is considered a valid approach to accelerate therapeutic solutions for rare diseases. However, it is not as widely applied as it could be, due to several barriers that discourage both industry and academic institutions from pursuing this path. Herein we present the case of an academic multicentre study that considered the repurposing of the old drug guanabenz as a therapeutic strategy in amyotrophic lateral sclerosis. The difficulties encountered are discussed as an example of the barriers that academics involved in this type of study may face. Although further development of the drug for this target population was hampered for several reasons, the study was successful in many ways. Firstly, because the hypothesis tested was confirmed in a sub-population, leading to alternative innovative solutions that are now under clinical investigation. In addition, the study was informative and provided new insights into the disease, which are now giving new impetus to laboratory research. The message from this example is that even a repurposing study with an old product has the potential to generate innovation and interest from industry partners, provided it is based on a sound rationale, the study design is adequate to ensure meaningful results, and the investigators keep the full clinical development picture in mind., 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 Ambrosini, Dalla Bella, Ravasi, Melazzini and Lauria.)

Introduction: Non-operative management (NOM) of uncomplicated acute appendicitis is a well-established alternative to upfront surgery. The administration of intravenous broad-spectrum antibiotics is usually performed in hospital, and only one study described outpatient NOM. The aim of this multicentre retrospective non-inferiority study was to evaluate both safety and non-inferiority of outpatient compared to inpatient NOM in uncomplicated acute appendicitis., Methods: The study included 668 consecutive patients with uncomplicated acute appendicitis. Patients were treated according to the surgeon's preference: 364 upfront appendectomy, 157 inpatient NOM (inNOM), and 147 outpatient NOM (outNOM). The primary endpoint was the 30-day appendectomy rate, with a non-inferiority limit of 5%. Secondary endpoints were negative appendectomy rate, 30-day unplanned emergency department (ED) visits, and length of stay., Results: 30-day appendectomies were 16 (10.9%) in the outNOM group and 23 (14.6%) in the inNOM group (p = 0.327). OutNOM was non-inferior to inNOM with a risk difference of-3.80% 97.5% CI (- 12.57; 4.97). No difference was found between inNOM and outNOM groups for the number of complicated appendicitis (3 vs. 5) and negative appendectomy (1 vs. 0). Twenty-six (17.7%) outNOM patients required an unplanned ED visit after a median of 1 (1-4) days. In the outNOM group, the mean cumulative in-hospital stay was 0.89 (1.94) days compared with 3.94 (2.17) days in the inNOM group (p < 0.001)., Conclusions: Outpatient NOM was non-inferior to inpatient NOM with regard to the 30-day appendectomy rate, while a shorter hospital stay was found in the outNOM group. Further, studies are required to confirm these findings., (© 2023. The Author(s).)

Charities investing on rare disease research greatly contribute to generate ground-breaking knowledge with the clear goal of finding a cure for their condition of interest. Although the amount of their investments may be relatively small compared to major funders, the advocacy groups' clear mission promotes innovative research and aggregates highly motivated and mission-oriented scientists. Here, we illustrate the case of Fondazione italiana di ricerca per la Sclerosi Laterale Amiotrofica (AriSLA), the main Italian funding agency entirely dedicated to amyotrophic lateral sclerosis research. An international benchmark analysis of publications derived from AriSLA-funded projects indicated that their mean relative citation ratio values (iCite dashboard, National Institutes of Health, U.S.) were very high, suggesting a strong influence on the referring international scientific community. An interesting trend of research toward translation based on the "triangle of biomedicine" and paper citations (iCite) was also observed. Qualitative analysis on researchers' accomplishments was convergent with the bibliometric data, indicating a high level of performance of several working groups, lines of research that speak of progression toward clinical translation, and one study that has progressed from the investigation of cellular mechanisms to a Phase 2 international clinical trial. The key elements of the success of the AriSLA investment lie in: (i) the clear definition of the objectives (research with potential impact on patients, no matter how far), (ii) a rigorous peer-review process entrusted to an international panel of experts, (iii) diversification of the portfolio with ad hoc selection criteria, which also contributed to bringing new experts and younger scientists to the field, and (iv) a close interaction of AriSLA stakeholders with scientists, who developed a strong sense of belonging. Periodic review of the portfolio of investments is a vital practice for funding agencies. Sharing information between funding agencies about their own policies and research assessment methods and outcomes help guide the international debate on funding strategies and research directions to be undertaken, particularly in the field of rare diseases, where synergy is a relevant enabling factor., Competing Interests: SG, MR, TZ, MM, and AA were employed by the company Fondazione AriSLA ETS. DB, SP, and AA were employed by the company Fondazione Telethon ETS., (Copyright © 2023 Guareschi, Ravasi, Baldessari, Pozzi, Zaffino, Melazzini and Ambrosini.)

Background: COVID-19 outbreak deeply impacted on mental health, with high rate of psychological distress in healthcare professionals, patients and general population. Current literature on trauma showed no increase in ICU admissions for deliberate self-inflicted injuries in the first weeks after the beginning of COVID-19., Objectives: We tested the hypothesis that self-inflicted injuries/harms of any method requiring ICU admission increased in the year following COVID-19 outbreak., Methods: Retrospective cohort single-center study comparing admissions to ICU the year before and the year after the pandemic start. All patients admitted to polyvalent ICUs-Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy from February 21st, 2019 to February 21st, 2020 (pre-COVID) and from February 22nd, 2020 to February 22nd, 2021 (post-COVID) were enrolled., Results: We enrolled 1038 pre-COVID and 854 post-COVID patients. In post-COVID, the incidence of self-inflicted injuries was 32/854 (3.8% [2.5-5.1]), higher than in pre-COVID (23/1038, 2.2%-p = 0.0014-relative increase 72.7%). The increase was more relevant when excluding COVID-19 patients (suicide attempts 32/697 (4.6% [3.0-6.2])-relative increase 109.1%; p < 0.0001). Both in pre-COVID and post-COVID, the most frequent harm mean was poisoning [15 (65.2%) vs. 25 (78.1%), p = 0.182] and the analysed population was younger than general ICU population (p = 0.0015 and < 0.0001, respectively). The distribution of admissions for self-inflicted injuries was homogeneous in pre-COVID along the year. In post-COVID, no admissions were registered during the lockdown; an increase was observed in summer with pandemic curve at minimal levels., Conclusions: An increase in ICU admissions for self-inflicted injuries/harms was observed in the year following COVID-19 outbreak., (© 2023. The Author(s).)

Introduction: Extracorporeal membrane oxygenation (ECMO)-associated hemolysis still represents a serious complication. The present study aimed to investigate those predictive factors, such as flow rates, the use of anticoagulants, and circuit connected dialysis, that might play a pivotal role in hemolysis in adult patients., Methods: This is a retrospective single-center case series of 35 consecutive adult patients undergoing veno-venous ECMO support at our center between April 2014 and February 2020. Daily plasma-free hemoglobin (pfHb) and haptoglobin (Hpt) levels were chosen as hemolysis markers and they were analyzed along with patients' characteristics, daily laboratory findings, and corresponding ECMO system variables, as well as continuous renal replacement therapy (CRRT) when administered, looking for factors influencing their trends over time., Results: Among the many settings related to the ECMO support, the presence of CRRT connected to the ECMO circuit has been found associated with both higher daily pfHb levels and lower Hpt levels. After correction for potential confounders, hemolysis was ascribable to circuit-related variables, in particular the membrane oxygenation dead space was associated with an Hpt reduction (B = -215.307, p = 0.004). Moreover, a reduction of ECMO blood flow by 1 L/min has been associated with a daily Hpt consumption of 93.371 mg/dL ( p = 0.001)., Conclusions: Technical-induced hemolysis during ECMO should be monitored not only when suspected but also during quotidian management and check-ups. While considering the clinical complexity of patients on ECMO support, clinicians should not only be aware of and anticipate possible circuitry malfunctions or inadequate flow settings, but they should also take into account the effects of an ECMO circuit-connected CRRT, as an equally important key factor triggering hemolysis.

In physical acoustic laboratories, wave propagation experiments often suffer from unwanted reflections at the boundaries of the experimental setup. We propose using multidimensional deconvolution (MDD) to post-process recorded experimental data such that the scattering imprint related to the domain boundary is completely removed and only the Green's functions associated with a scattering object of interest are obtained. The application of the MDD method requires in/out wavefield separation of data recorded along a closed surface surrounding the object of interest, and we propose a decomposition method to separate such data for arbitrary curved surfaces. The MDD results consist of the Green's functions between any pair of points on the closed recording surface, fully sampling the scattered field. We apply the MDD algorithm to post-process laboratory data acquired in a two-dimensional acoustic waveguide to characterize the wavefield scattering related to a rigid steel block while removing the scattering imprint of the domain boundary. The experimental results are validated with synthetic simulations, corroborating that MDD is an effective and general method to obtain the experimentally desired Green's functions for arbitrary inhomogeneous scatterers.

The preterm birth of a child is a sudden event that can disturb the overall family system and its functioning. Many studies have been conducted with the aim of exploring how and the degree to which this event affects the early mother-infant dyadic relationship and maternal well-being, with often mixed findings. The present study investigates the combined effect of preterm birth and parenting stress on mind-mindedness, a parenting dimension that captures how parents represent and treat their children as separate individuals with their own mental states and activities. A hundred and ten mothers and their three-month-old infants (preterm = 54; full-term = 56) participated in the study. Mind-mindedness was assessed by coding mothers' comments about infant's mental states during dyadic face-to-face interaction. Parenting stress was evaluated with the Parenting Stress Index Short Form questionnaire. Mothers of preterm infants reported similar levels of appropriate and non-attuned mind-related comments to mothers of full-term infants. The reported parenting stress levels were also comparable. Interestingly, only mothers of preterm infants who reported higher stress in parenting showed more non-attuned comments during the interaction. The results underline the need to address preterm birth as a complex event, going beyond group differences and considering its interplay with other risk or protective factors in shaping children's and parents' adjustments and well-being.

Femoropopliteal arteries (FPAs) are subjected to a wide range of deformations, mainly determined by leg movement. FPAs are often affected by atherosclerotic plaque development, presumably influenced by the biomechanics of surrounding tissues. Although abnormal hemodynamics in FPAs appears to be an important factor in driving plaque development, to date it has been investigated in few studies, in which the leg was modeled in either fixed straight or bent configuration. Hence, the current work investigates the impact of leg movement on FPA hemodynamics. An idealized model of FPA was created to perform moving-boundary computational fluid dynamics analyses. By mimicking hip rotation, knee flexion and complete movement of walking, the hemodynamics was compared between moving- and fixed-boundary models. Moreover, additional features affecting the hemodynamics (e.g. flow-rate curve amplitude, walking speed) were examined. Significant hemodynamic differences were found between the moving- and fixed-boundary models, with the leg movement inducing higher time-averaged wall shear stress (TAWSS) (up to 66%). The flow-rate amplitude and walking period were the most influential parameters (differences in TAWSS up to 68% and 74%, respectively). In conclusion, this numerical approach highlighted the importance of considering leg movement to investigate FPA hemodynamics, and it could be employed in future patient-specific analyses., Competing Interests: Declaration of competing interest None., (Copyright © 2020 IPEM. Published by Elsevier Ltd. All rights reserved.)

Mesenchymal stem cells (MSCs) are adult bone marrow-derived stem cells actually proposed indifferently for the therapy of neurological diseases of both the Central (CNS) and the Peripheral Nervous System (PNS), as a panacea able to treat so many different diseases by their immunomodulatory ability and supportive action on neuronal survival. However, the identification of the exact mechanism of MSC action in the different diseases, although mandatory to define their real and concrete utility, is still lacking. Moreover, CNS and PNS neurons present many different biological properties, and it is still unclear if they respond in the same manner not only to MSC treatment, but also to injuries. For these reasons, in this study we compared the susceptibility of cortical and sensory neurons both to toxic drug exposure and to MSC action, in order to verify if these two neuronal populations can respond differently. Our results demonstrated that Cisplatin (CDDP), Glutamate, and Paclitaxel-treated sensory neurons were protected by the co-culture with MSCs, in different manners: through direct contact able to block apoptosis for CDDP- and Glutamate-treated neurons, and by the release of trophic factors for Paclitaxel-treated ones. A possible key soluble factor for MSC protection was Glutathione, spontaneously released by these cells. On the contrary, cortical neurons resulted more sensitive than sensory ones to the toxic action of the drugs, and overall MSCs failed to protect them. All these data identified for the first time a different susceptibility of cortical and sensory neurons, and demonstrated a protective action of MSCs only against drugs in peripheral neurotoxicity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Infants born preterm are at high risk for the onset of cognitive dysfunctions at school age. The aim of this study was to investigate the association between early neurodevelopmental assessment and the risk of adverse cognitive outcome in extremely low birth weight children. We enrolled all newborns (January 2002 - April 2007) consecutively admitted to our Institution, with a birthweight < 1000 g. Exclusion criteria were genetic abnormalities, severe neurofunctional impairment, and/or neurosensory disabilities. Ninety-nine children were assessed at 1 year of corrected age using the Griffiths Mental Development Scales Revised. The same children were re-assessed at school age through the Wechsler Intelligence Scale for Children. Children with impaired Griffiths General Quotient (i.e., <1 SD) at 1 year of corrected age showed a significantly lower Full Scale Intelligence Quotient at 7 years of chronological age when compared to children who scored in the normal range at 1 year ( p < 0.01). Considering the Griffiths Sub-quotients separately, a poor score in the Performance or in the Personal-Social Sub-quotients at 1 year was associated with significantly worse cognitive outcomes both in the Verbal and in the Performance Intelligence Quotients at 7 years ( p < 0.01 and p < 0.05, respectively). A score <1 SD in the Locomotor or in the Eye and Hand Coordination Sub-quotients were specifically associated with poorer Performance or Verbal Intelligence Quotients, respectively ( p < 0.05). Our findings suggest that a poor score on the Griffiths Scales at 1 year is associated with a higher risk of cognitive impairment at school age. Larger confirmation studies are needed.

Background/aim: Peripheral neurotoxicity is a dose-limiting factor of many chemotherapeutic agents, including cisplatin. Mesenchymal stem cells are promising for the treatment of several neurological disorders, and our aim was to verify the neuroprotective potential of human mesenchymal stem cells (hMSCs) on dorsal root ganglia (DRG) exposed to cisplatin., Materials and Methods: DRG were exposed to different cisplatin concentrations and then co-cultured with hMSCs or with hMSC-conditioned medium., Results: hMSCs showed a neuroprotective effect on cisplatin-induced death of DRG, mediated by direct contact. Moreover, DRG exhibited an MSC-dependent promotion of neurite outgrowth, in particular at early time points. For this effect, the expression of Neurite Outgrowth Inhibitor (NOGO) and Myelin Associated Glycoprotein (MAG) by hMSCs was pivotal., Conclusion: hMSCs are a promising tool for reducing the neurotoxic effect of cisplatin., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Neurobasal medium (NBM) is a widely used medium for neuronal cultures, originally formulated to support survival of rat hippocampal neurons, but then optimized for several other neuronal subtypes. In the present study, the toxic effect of NBM on long-term cortical neuron cultures has been reported and investigated. A significant neuronal cell loss was observed 24 h after the total medium change performed at days in vitro 10. The neurotoxic effect was specifically because of NBM-A, a commercially derived modification of classic NBM, as neurons exposed to minimum essential medium for 24 h did not show the same mortality rate. We showed that the toxic effect was mediated by the N-methyl-D-aspartate receptor (NMDAr) as its inactivation partly prevented NBM-induced neuronal loss, and the addition of NMDAr activators, such as L-cysteine or glycine to minimum essential medium, reproduced the same toxicity rate observed in NBM. Besides the toxicity associated with NMDAr activation, the decreased antioxidative defenses also worsen (because of glutathione depletion) neuronal death, thus amplifying the effect of excitotoxic amino acids. Indeed, glutathione supplementation by the addition of its precursor N-acetyl-cysteine resulted in an increase in neuronal survival that partially prevented NBM-A toxicity. These results evidenced, on the one hand, the unsuitability of NBM-A for long-term neuronal culture, and on the other, they highlight the importance of selection of more suitable culture conditions.