Future Perspectives on Radiomics in Acute Liver Injury and Liver Trauma.

Background: Acute liver injury occurs most frequently due to trauma, but it can also occur because of sepsis or drug-induced injury. This review aims to analyze artificial intelligence (AI)'s ability to detect and quantify liver injured areas in adults and pediatric patients. Methods: A literature analysis was performed on the PubMed Dataset. We selected original articles published from 2018 to 2023 and cohorts with ≥10 adults or pediatric patients. Results: Six studies counting 564 patients were collected, including 170 (30%) children and 394 adults. Four (66%) articles reported AI application after liver trauma, one (17%) after sepsis, and one (17%) due to chemotherapy. In five (83%) studies, Computed Tomography was performed, while in one (17%), FAST-UltraSound was performed. The studies reported a high diagnostic performance; in particular, three studies reported a specificity rate > 80%. Conclusions: Radiomics models seem reliable and applicable to clinical practice in patients affected by acute liver injury. Further studies are required to achieve larger validation cohorts.

Quantitative ADC: An Additional Tool in the Evaluation of Prostate Cancer?

Prostate cancer is one of the most common tumors among the male population. Magnetic resonance imaging (MRI), standardized by the PI-RADS version 2.1 scoring system, has a fundamental role in detecting prostate cancer and evaluating its aggressiveness. Diffusion-weighted imaging sequences and apparent diffusion coefficient values, in particular, are considered fundamental for the detection and characterization of lesions. In 2016 the International Society of Urological Pathology introduced a new anatomopathological 5-grade scoring system for prostate cancer. The aim of this study is to evaluate the correlation between quantitative apparent diffusion coefficient values (ADC) derived from diffusion-weighted imaging (DWI) sequences and the International Society of Urological Pathology (ISUP) and PI-RADS groups. Our retrospective study included 143 patients with 154 suspicious lesions, observed on prostate magnetic resonance imaging and compared with the histological results of the biopsy. We observed that ADC values can aid in discriminating between not clinically significant (ISUP 1) and clinically significant (ISUP 2-5) prostate cancers. In fact, ADC values were lower in ISUP 5 lesions than in negative lesions. We also found a correlation between ADC values and PI-RADS groups; we noted lower ADC values in the PI-RADS 5 and PI-RADS 4 groups than in the PI-RADS 3 group. In conclusion, quantitative apparent diffusion coefficient values can be useful to assess the aggressiveness of prostate cancer.

The Role of Coronary CT Angiography in the Evaluation of Dual Left Anterior Descending Artery Prevalence and Subtypes: A Retrospective Multicenter Study.

BACKGROUND: The aim of this multicenter study was to evaluate the prevalence and features of dual left anterior descending artery (LAD) subtypes using coronary CT angiography (CCTA). METHODS: A retrospective multicenter analysis of 2083 CCTA from December 2020 to November 2022 was conducted to search for the presence and morphological features of dual LAD. The two classifications used were the updated classification of Spindola-Franco and the Jariwala classification. Statistical tests were conducted to evaluate the prevalence of dual LADs among sexes and its association with angina in patients without significant coronary stenoses and/or associated cardiac anomalies. RESULTS: Dual LAD was observed in 124 (5.96%) patients analyzed. According to the Spindola-Franco revisited classification, type I dual LAD was the most common (71/124, 57.26%). According to the Jariwala classification, all cases were group I. In the general population, there was a higher prevalence of dual LAD among females (7.3% females vs. 5.1% males; p value: 0.04). No statistically significant difference was found in the prevalence of angina in the dual LAD population compared to the no dual LAD population (2.1% vs. 1.5%; p value: 0.10). CONCLUSIONS: The acknowledgment and reporting of LAD duplication is helpful for an optimal management of coronary patients with this condition. Dual LAD was more frequent in the female population, mainly not related with angina. Myocardial bridge was more frequent in the dual LAD population than in the no dual LAD population.

Twitter Activists' Argumentation Through Subdiscussions: Theory, Method and Illustration of the Controversy Surrounding Sustainable Fashion.

"Why are millions of dollars worth of orders being left unpaid?". With tweets like this questioning brands' policies, activists advocating for sustainable fashion re-discuss material starting points that are assumed by fashion brands, who argue that they are sustainable because they care about their workers' conditions. This paper argues that activists use tweets to open subdiscussions on material starting points to engage citizens and consumers, re-discussing factual data that brands take for granted, such as the fact that they provide fair conditions for their garment workers. Activists justify their opening of subdiscussions, often through an argumentative pattern that includes an argument based on the locus from effects to cause. They argue that if there are negative effects, the brand cannot claim to care about the conditions of its workers. In discussing how subdiscussions are used by fashion activists, this paper also introduces a conceptualization of Twitter argumentation as a discussion that is not isolated, but is part of a polylogical argumentation that takes place in different venues. For this reason, the argumentation used in tweets is reconstructed as a response to a fashion brand's communication campaigns around sustainability, which extend beyond the confines of Twitter. As an empirical illustration, this paper is based on the campaign targeting fashion retailer Primark; the dataset includes the brand's website as well as activists' tweets.

Functional characterization of a novel TP53RK mutation identified in a family with Galloway-Mowat syndrome.

Galloway-Mowat syndrome (GAMOS) is a very rare condition characterized by early-onset nephrotic syndrome and microcephaly with variable neurologic features. While considerable genetic heterogeneity of GAMOS has been identified, the majority of cases are caused by pathogenic variants in genes encoding the four components of the Kinase, endopeptidase, and other proteins of small size (KEOPS) complex, one of which is TP53RK. Here we describe a 3-year-old male with progressive microcephaly, neurodevelopmental deficits, and glomerular proteinuria. He was found to carry a novel homozygous TP53RK missense variant, c.163C>G (p.Arg55Gly), which was considered as potentially disease-causing. We generated a morpholino tp53rk knockdown model in Xenopus laevis showing that the depletion of endogenous Tp53rk caused abnormal eye and head development. This phenotype could be rescued by the expression of human wildtype TP53RK but not by the c.163C>G mutant nor by another previously described GAMOS-associated mutant c.125G>A (p.Gly42Asp). These findings support the pathogenic role of the novel TP53RK variant.

Isogenic GAA-KO Murine Muscle Cell Lines Mimicking Severe Pompe Mutations as Preclinical Models for the Screening of Potential Gene Therapy Strategies.

Pompe disease (PD) is a rare disorder caused by mutations in the acid alpha-glucosidase (GAA) gene. Most gene therapies (GT) partially rely on the cross-correction of unmodified cells through the uptake of the GAA enzyme secreted by corrected cells. In the present study, we generated isogenic murine GAA-KO cell lines resembling severe mutations from Pompe patients. All of the generated GAA-KO cells lacked GAA activity and presented an increased autophagy and increased glycogen content by means of myotube differentiation as well as the downregulation of mannose 6-phosphate receptors (CI-MPRs), validating them as models for PD. Additionally, different chimeric murine GAA proteins (IFG, IFLG and 2G) were designed with the aim to improve their therapeutic activity. Phenotypic rescue analyses using lentiviral vectors point to IFG chimera as the best candidate in restoring GAA activity, normalising the autophagic marker p62 and surface levels of CI-MPRs. Interestingly, in vivo administration of liver-directed AAVs expressing the chimeras further confirmed the good behaviour of IFG, achieving cross-correction in heart tissue. In summary, we generated different isogenic murine muscle cell lines mimicking the severe PD phenotype, as well as validating their applicability as preclinical models in order to reduce animal experimentation.

Retinol binding protein 1 affects Xenopus anterior neural development via all-trans retinoic acid signaling.

BACKGROUND: Retinol binding protein 1 (Rbp1) acts as an intracellular regulator of vitamin A metabolism and retinoid transport. In mice, Rbp1 deficiency decreases the capacity of hepatic stellate cells to take up all-trans retinol and sustain retinyl ester stores. Furthermore, Rbp1 is crucial for visual capacity. Although the function of Rbp1 has been studied in the mature eye, its role during early anterior neural development has not yet been investigated in detail. RESULTS: We showed that rbp1 is expressed in the eye, anterior neural crest cells (NCCs) and prosencephalon of the South African clawed frog Xenopus laevis. Rbp1 knockdown led to defects in eye formation, including microphthalmia and disorganized retinal lamination, and to disturbed induction and differentiation of the eye field, as shown by decreased rax and pax6 expression. Furthermore, it resulted in reduced rax expression in the prosencephalon and affected cranial cartilage. Rbp1 inhibition also interfered with neural crest induction and migration, as shown by twist and slug. Moreover, it led to a significant reduction of the all-trans retinoic acid target gene pitx2 in NCC-derived periocular mesenchyme. The Rbp1 knockdown phenotypes were rescued by pitx2 RNA co-injection. CONCLUSION: Rbp1 is crucial for the development of the anterior neural tissue.

Expression of the double-stranded RNA-dependent kinase PKR influences osteosarcoma attachment independent growth, migration, and invasion.

Osteosarcoma (OS) is a rare, insidious tumor of mesenchymal origin that most often affects children, adolescents, and young adults. While the primary tumor can be controlled with chemotherapy and surgery, it is the lung metastases that are eventually fatal. Multiple studies into the initial drivers of OS development have been undertaken, but few of these have examined innate immune/inflammatory signaling. A central figure in inflammatory signaling is the innate immune/stress-activated kinase double-stranded RNA-dependent protein kinase (PKR). To characterize the role of PKR in OS, U2OS, and SaOS-2 osteosarcoma cell lines were stably transfected with wild-type or dominant-negative (DN) PKR. Overexpression of PKR enhanced colony formation in soft agar (U2OS and SaOS-2), enhanced cellular migration (U2OS), and invasive migration (SaOS-2). In contrast, overexpression of DN-PKR inhibited attachment-independent growth, migration and/or invasion. These data demonstrate a role for inflammatory signaling in OS formation and migration/invasion and suggest the status of PKR expression/activation may have prognostic value.

ROCK2 deprivation leads to the inhibition of tumor growth and metastatic potential in osteosarcoma cells through the modulation of YAP activity.

BACKGROUND: The treatment of metastatic osteosarcoma (OS) remains a challenge for oncologists, and novel therapeutic strategies are urgently needed. An understanding of the pathways that regulate OS dissemination is required for the design of novel treatment approaches. We recently identified Rho-associated coiled-coil containing protein kinase 2 (ROCK2) as a crucial driver of OS cell migration. In this study, we explored the impact of ROCK2 disruption on the metastatic capabilities of OS cells and analyzed its functional relationship with Yes-associated protein-1 (YAP), the main transcriptional mediator of mechanotransduction signaling. METHODS: The effects of ROCK2 depletion on metastasis were studied in NOD Scid gamma (NSG) mice injected with U-2OS cells in which ROCK2 expression had been stably silenced. Functional studies were performed in vitro in human U-2OS cells and in three novel cell lines derived from patient-derived xenografts (PDXs) by using standard methods to evaluate malignancy parameters and signaling transduction. The nuclear immunostaining of YAP and the evaluation of its downstream targets Cysteine Rich Angiogenic Inducer 6, Connective Tissue Growth Factor and Cyclin D1 by quantitative PCR were performed to analyze YAP activity. The effect of the expression and activity of ROCK2 and YAP on tumor progression was analyzed in 175 OS primary tumors. RESULTS: The silencing of ROCK2 markedly reduced tumor growth and completely abolished the metastatic ability of U-2OS cells. The depletion of ROCK2, either by pharmacological inhibition or silencing, induced a dose- and time-dependent reduction in the nuclear expression and transcriptional activity of YAP. The nuclear expression of YAP was observed in 80/175 (46%) tumor samples and was significantly correlated with worse patient prognosis and a higher likelihood of metastasis and death. The use of verteporfin, a molecule that specifically inhibits the TEAD-YAP association, remarkably impaired the growth and migration of OS cells in vitro. Moreover to inhibiting YAP activity, our findings indicate that verteporfin also affects the ROCK2 protein and its functions. CONCLUSIONS: We describe the functional connection between ROCK2 and YAP in the regulation of OS cell migration and metastasis formation. These data provide support for the use of verteporfin as a possible therapeutic option to prevent OS cell dissemination.

Ethical Reasoning Debriefing in Disaster Simulations.

BACKGROUND: With disasters occurring often, nurses must understand and ethically implement disaster management and patient care coordination. Yet these topics are often not discussed in nursing education curricula. Simulations are a potential solution to this ethical educational deficit, allowing students to act as professional nurses in a realistic scenario with minimal threat of harm to themselves or others. AIM: This study investigates the effect of a high fidelity, multiple-casualty disaster simulation followed by a structured faculty-led debriefing session on perceived ethical reasoning confidence on senior Bachelor of Science in Nursing (BSN) students. Additionally, the effect of the intervention on students' perceived importance of ethical reasoning and perceptions of such skills was explored. METHODS: Students were provided with preparatory materials on the START (Simple Triage and Rapid Treatment) System and The Madison Collaborative's Ethical Reasoning in Action Eight Key Questions (8KQ) frameworks one week before the simulation exercise. In total, 90 students worked in pairs during the 15-minute disaster simulation. Participants' ethical reasoning attitudes were measured before and after the exercise, employing the Survey of Ethical Reasoning (SER) to indicate the importance of each of the 8KQ in students' ethical reasoning process using a five-point Likert scale. The SER was administered electronically using Qualtrics and statistical analysis was completed using SPSS. The 8KQ was also used in the debriefing led by faculty. RESULTS: Comparative assessment of pre and post-results demonstrate significant growth in students' ethical reasoning confidence scores (t(89) = -6.609, p < 0.001). CONCLUSIONS: Simulations are shown to be effective educational approaches in developing ethical reasoning confidence and promoting the development of students' ethical preparedness.