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Abstract Mutated KRAS serves as the oncogenic driver in 30% of non-small cell lung cancers (NSCLCs) and is associated with metastatic and therapy-resistant tumors. Focal Adhesion Kinase (FAK) acts as a mediator in sustaining KRAS-driven lung tumors, and although FAK inhibitors are currently undergoing clinical development, clinical data indicated that their efficacy in producing long-term anti-tumor responses is limited. Here we revealed two FAK interactors, extracellular-signal-regulated kinase 5 (ERK5) and cyclin-dependent kinase 5 (CDK5), as key players underlying FAK-mediated maintenance of KRAS mutant NSCLC. Inhibition of ERK5 and CDK5 synergistically suppressed FAK function, decreased proliferation and induced apoptosis owing to exacerbated ROS-induced DNA damage. Accordingly, concomitant pharmacological inhibition of ERK5 and CDK5 in a mouse model of KrasG12D-driven lung adenocarcinoma suppressed tumor progression and promoted cancer cell death. Cancer cells resistant to FAK inhibitors showed enhanced ERK5-FAK signaling dampening DNA damage. Notably, ERK5 inhibition prevented the development of resistance to FAK inhibitors, significantly enhancing the efficacy of anti-tumor responses. Therefore, we propose ERK5 inhibition as a potential co-targeting strategy to counteract FAK inhibitor resistance in NSCLC.

Abstract Platinum (PT)-resistant Epithelial Ovarian Cancer (EOC) grows as a metastatic disease, disseminating in the abdomen and pelvis. Very few options are available for PT-resistant EOC patients, and little is known about how the acquisition of PT-resistance mediates the increased spreading capabilities of EOC. Here, using isogenic PT-resistant cells, genetic and pharmacological approaches, and patient-derived models, we report that Integrin α6 (ITGA6) is overexpressed by PT-resistant cells and is necessary to sustain EOC metastatic ability and adhesion-dependent PT-resistance. Using in vitro approaches, we showed that PT induces a positive loop that, by stimulating ITGA6 transcription and secretion, contributes to the formation of a pre-metastatic niche enabling EOC cells to disseminate. At molecular level, ITGA6 engagement regulates the production and availability of insulin-like growth factors (IGFs), over-stimulating the IGF1R pathway and upregulating Snail expression. In vitro data were recapitulated using in vivo models in which the targeting of ITGA6 prevents PT-resistant EOC dissemination and improves PT-activity, supporting ITGA6 as a promising druggable target for EOC patients.

Abstract Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi‐omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta‐analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR‐binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor–β2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti‐inflammatory and anti‐fibrotic effects of ω3 PUFA on NASH.

Abstract MYC is a key oncogenic driver in multiple tumor types, but concomitantly endows cancer cells with a series of vulnerabilities that provide opportunities for targeted pharmacological intervention. For example, drugs that suppress mitochondrial respiration selectively kill MYC‐overexpressing cells. Here, we unravel the mechanistic basis for this synthetic lethal interaction and exploit it to improve the anticancer effects of the respiratory complex I inhibitor IACS‐010759. In a B‐lymphoid cell line, ectopic MYC activity and treatment with IACS‐010759 added up to induce oxidative stress, with consequent depletion of reduced glutathione and lethal disruption of redox homeostasis. This effect could be enhanced either with inhibitors of NADPH production through the pentose phosphate pathway, or with ascorbate (vitamin C), known to act as a pro‐oxidant at high doses. In these conditions, ascorbate synergized with IACS‐010759 to kill MYC‐overexpressing cells in vitro and reinforced its therapeutic action against human B‐cell lymphoma xenografts. Hence, complex I inhibition and high‐dose ascorbate might improve the outcome of patients affected by high‐grade lymphomas and potentially other MYC‐driven cancers.

Introduction: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown. Materials & methods: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed. Results: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients. Conclusions: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios. [ABSTRACT FROM AUTHOR]

Purpose: Aim of this study is to summarize medical device reports (MDRs) between 2012 and 2022 relating to ureteral stents within the Manufacturer and User Facility Device Experience (MAUDE) database maintained by The Food and Drug Administration (FDA). Methods: MAUDE was analyzed for all MDRs relating to each FDA-approved ureteral stent. Event descriptions were reviewed and characterized into specific event types. Outcome measures include specific ureteral stent and reported events as detailed by the MDRs. Data is presented as number of specific event/total events. Pooled Relative risk was used to compare data. Results: 2652 reports were retrieved in 10 years and a progressive rise in reported events was recorded. 831/2652 (31%) were reported as injury while 1810/2652 (68%) as malfunction of the ureteral stent and 4 events of death. The most frequently reported adverse events (AEs) were stent break (627/2652: 23%); material problems (384/2652: 14%); calcification (222/2652: 8%); difficulty to insert, advance or remove the device (155/2652: 6%). Bard stents were associated with most material problems (19%), Resonance stents were associated with most difficulty to insert, advance or remove the device (9%) and calcification (15%) while filiform double pigtail stent set were associated with most breakage reports (56%) when compared to the other stents (PRR > 1, p < 0,05). Conclusions: According to MAUDE database the most frequent complications related to ureteral stents are breakage, material problems, calcification and difficulty to insert/advance/remove the device. As well Resonance ureteral stents seem to be associated with a higher risk of device problems. [ABSTRACT FROM AUTHOR]

Abstract Lactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. We show herein that lactate fuels GB anaplerosis by replenishing the tricarboxylic acid (TCA) cycle in absence of glucose. Lactate dehydrogenases (LDHA and LDHB), which we found spatially expressed in GB tissues, catalyze the interconversion of pyruvate and lactate. However, ablation of both LDH isoforms, but not only one, led to a reduction in tumor growth and an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OXPHOS) in the LDHA/B KO group which sensitized tumors to cranial irradiation, thus improving mouse survival. When mice were treated with the antiepileptic drug stiripentol, which targets LDH activity, tumor growth decreased. Our findings unveil the complex metabolic network in which both LDHA and LDHB are integrated and show that the combined inhibition of LDHA and LDHB strongly sensitizes GB to therapy.

Middle meningeal artery embolization (MMAE) has emerged as a safe and efficacious alternative to surgery for the treatment of new or recurrent chronic subdural hematoma (CSDH). Several complications such as facial palsy may suddenly occur even in the absence of evident dangerous anastomoses in the angiogram. We herein present a case-report of left facial nerve palsy after MMAE. [ABSTRACT FROM AUTHOR]

Purpose: Pulmonary Embolism (PE) is the third leading cause of cardiovascular death, following myocardial infarction and stroke. The latest European Society of Cardiology (ESC) guidelines on PE recommend short-term prognostic stratification based on right ventricular (RV) overload detected by transthoracic echocardiography (TTE) or contrast-enhanced chest CT. The aim of the study is to find out which of the signs of right ventricular dysfunction best predicts in-hospital mortality (IHM). Methods: This is a monocentric, retrospective study including adult patients admitted from the emergency department with a c-e cCT confirmed diagnosis of PE between January 2018 and December 2022 who underwent a TTE within 48 h. Results: 509 patients (median age 76 years [IQR 67–84]) were included, with 7.1% IHM. At univariate analysis, RV/LV ratio > 1 (OR 2.23, 95% CI 1.1–4.5), TAPSE < 17 mm (OR 4.73, 95% CI 2.3–9.8), the D-shape (OR 3.73, 95% CI 1.71–8.14), and LVEF < 35% (OR 5.78, 95% CI 1.72–19.47) resulted significantly correlated with IHM. However, at multivariate analysis including also haemodynamic instability, PESI class > II, and abnormal hs-cTnI levels, only LVEF < 35% (OR 5.46, 95% CI 1.32–22.61) resulted an independent predictor of IHM. Conclusion: Despite the recognised role of TTE in the early management of patients with circulatory shock and suspected PE, signs of RV dysfunction have been shown to be poor predictors of IHM, whereas severely reduced LVEF is an independent risk factor for in-hospital death. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive multimodal analytical study of an Egyptian ritual Bes-vase, of the 2nd century BCE employing cutting-edge proteomics, metabolomics, genetics techniques, and synchrotron radiation-based Fourier Transformed Infrared microSpectroscopy (SR µ-FTIR) to characterize organic residues of its content. We successfully identified the presence of various functional, bioactive, psychotropic, and medicinal substances, shedding light on the diverse components of a liquid concoction used for ritual practices in Ptolemaic Egypt. Using LC-MS/MS with a new methodological approach, we identified key proteins and metabolites, enabling the identification of botanical sources, confirmed by genetic sequences. Our analyses revealed traces of Peganum harmala, Nimphaea nouchali var. caerulea, and a plant of the Cleome genus, all of which are traditionally proven to have psychotropic and medicinal properties. Additionally, the identification of human fluids suggests their direct involvement in these rituals. Furthermore, metabolomics and SR µ-FTIR analyses also revealed the presence of fermented fruit-based liquid and other ingredients such as honey or royal jelly. The identification of specific chemical compounds, such as alkaloids and flavonoids, provides insight into the psychoactive and therapeutic uses of these in ancient ritual practices. This multidisciplinary study highlights the complexity of ancient cultures and their interactions with psychoactive, medicinal, and bioactive substances. These findings contribute to our understanding of ancient belief systems, cultural practices, and the utilization of natural resources, ultimately enhancing our knowledge of past societies and their connection to the natural world. [ABSTRACT FROM AUTHOR]

Recent methodological developments have contributed to a significant advance in computerised neuropsychological instruments and procedures, including those accessible from remote. In this paper we present Auto-GEMS, a newly developed, web-based, self-administered screening test allowing to quickly estimate an individual's cognitive state also considering their cognitive reserve. Auto-GEMS measures cognitive functioning on eleven items similarly to the in-person paper-and-pencil version (GEMS) and to the remote (phone or video call) version (Tele-GEMS) of the same screening. We collected normative data on a sample of 1308 Italian-speaking participants (age range 18–93) to verify its psychometric properties and computed regression models on demographic variables to establish clinical cut-offs. The psychometric properties of Auto-GEMS have shown good internal consistency, test-retest reliability and convergent validity. This short and user-friendly tool has a number of potential applications. For instance, it can be useful in clinical practice to monitor the cognitive profile of patients or vulnerable individuals, or even administered in a face-to-face, standard clinical setting. It can also be used in research studies to screen participants. The testing materials and the collected data are freely available in a digital archive along with a web App to visualise the test outcome with reference to its normative data. [ABSTRACT FROM AUTHOR]

Intestinal permeability has been related to colorectal cancer (CRC) development. Zonulin, a protein able to regulate tight junction function and intestinal permeability, emerges as a promising marker to elucidate the contribution of bacterial translocation in CRC. An Italian case-control study included 77 CRC cases, 72 intestinal adenoma and 76 healthy controls (for a total of 148 tumor-free subjects), aged 20–85. Serum zonulin levels were quantified by ELISA kit and blood 16S rRNA gene copies by DNA extraction and polymerase chain reaction. We applied logistic regression models adjusted for center, sex, age and education. There was a positive association between zonulin and CRC risk. The odds ratio (OR) of CRC for the highest versus lowest tertile of zonulin as compared to tumor-free subjects was 2.36 (95% confidence interval, 1.14–4.86). The ORs were similar in colon and rectal cancers. The OR of colon cancer for the highest versus lowest levels of both zonulin and 16S rRNA gene copies was 4.55. Circulating levels of zonulin were higher in CRC patients compared to tumor-free controls supporting the hypothesis of an interplay of gut barrier dysfunction and bacterial translocation in colorectal carcinogenesis. Zonulin may interact with 16S rRNA gene copies and serve as a further biomarker in the evaluation of CRC diagnosis. [ABSTRACT FROM AUTHOR]

Background: Macrophages are major effectors in regulating immune response and inflammation. The pro-inflammatory phenotype (M1) is induced by the activation of the Toll-like receptor 4 (TLR4) on the macrophage surface, which recognizes lipopolysaccharide (LPS), a component of Gram-negative bacterial wall, and by the binding of interferon-gamma (IFNγ), a cytokine released by activated T lymphocytes, to its receptor (IFNGR). Among the pathways activated by LPS/IFNγ is the Notch pathway, which promotes the M1 phenotype. Conversely, 17β-estradiol (E2) has been shown to blunt LPS-mediated inflammatory response. While it has been shown that E2 regulates the activity of the Notch1 receptor in human endothelial cells, there is no evidence of estrogen-mediated regulation of Notch1 in macrophages. Methods and results: In this study, RAW 264.7 cells were stimulated with LPS/IFNγ in the presence or absence of E2 and/or N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of γ-secretase, the enzyme involved in Notch activation. The effects of treatment on inducible nitric oxide synthase (iNOS), on components of the Notch pathway, and MAPK (mitogen-activated protein kinase) were assessed by quantitative PCR and Western blotting. We found that E2, through a mechanism involving the inhibition of p38 phosphorylation, reduces the activation of Notch1 induced by LPS/IFNγ. On the contrary, Notch1 exerts a negative control on the estrogen receptor α (ERα) since Notch1 inhibition increases the protein levels of this receptor. Conclusion: In conclusion, we report for the first time a Notch-ERα interaction in macrophages. Our data suggest that E2 may reduce LPS/IFNγ-mediated M1 pro-inflammatory phenotype in macrophages by inhibiting Notch1. This finding encourages further studies on Notch1 inhibitors as novel treatments for inflammation-related diseases. [ABSTRACT FROM AUTHOR]

The paper aims to verify whether volunteering and environmentalism are two phenomena that overlap both conceptually and empirically. The actions for the protection and enhancement of rivers in Italy are taken as a testing ground. Two packages of literature are used to understand the overlap between volunteering and environmentalism, one on neo-institutionalism and the other on new social movements. The starting framework is a general typology of voluntary organisations, which is then adapted to the environmental movement. The hypothesis of growing disintermediation and light commitment by the new generations of volunteers finds original answers in river volunteering. Alongside classic environmentalist militancy, forms of popular action in favour of rivers are emerging that show detachment from politics and attraction to intrinsic benefits, such as the pleasure of recreation and collective memory recovery. This raises new questions about the role of organised civil society in maintaining democracy and helping the ecological transition. [ABSTRACT FROM AUTHOR]

The transition from traditional wastewater treatment plants to biorefineries represents an environmentally and economically sustainable approach to extracting valuable compounds from waste. Sewage sludge produced from wastewater treatment is incinerated or disposed of in specific landfills. Repurposing this waste material to recover valuable resources could help lower disposal costs and reduce environmental impact by producing other beneficial polymers. Microorganisms present in the sewage sludge can ferment organic pollutants, producing volatile fatty acids (VFA), precursors for biopolymers that could be used as an alternative to petroleum-derived plastics. To boost VFA production during sewage sludge fermentation, it is necessary to understand the operating microbial community and its metabolic capacities in anaerobic conditions. This study presents the influence of the headspace volume on the microbial community and the VFA production to define the best operational parameters in a 225 L pilot plant fermenter. The wasted sewage sludge was withdrawn from an oxic-settling-anaerobic plant that collected wastewater from the canteen and dormitory of the UNIPA Campus (Palermo University, Italy) and incubated using a 40% and a 60% headspace volume. The microbial community was analysed before and after the fermentation process through metataxonomic analysis, and VFA yields were determined by gas chromatography analysis. Our results showed that the 40% headspace volume induced a tenfold higher VFA production than the 60% headspace volume, modulating the microbial community's efforts to establish a VFA-producing factory. Notably, at 40% headspace, the relative abundance of bacteria, like Proteobacteria, Firmicutes, Actinobacteria, and Chloroflexi, significantly increased, as well as the relative abundance of Bacteroidetes and Verrucomicrobia decreased during the fermentation process. This result is consistent with the selection of efficient VFA-producing bacteria that lead to increased VFA yields that are not obtained at 60% headspace. Thus, reducing headspace is a promising strategy that can be implemented, even in full-scale plants, to optimise the wastewater reuse process and maximise VFA production to produce bioplastics, like polyhydroxyalkanoate, for the transition from linear wastewater treatment plants to circular biorefineries. [ABSTRACT FROM AUTHOR]

In the past decade, organic mixed ion-electron conductors have been successfully adopted in innovative bioelectronic, neuromorphic, and electro-optical technologies, as well as in multiple energy harvesting and printed electronics applications. However, despite the intense research efforts devoted to these materials, organic mixed conductors have not yet found application in electronic/photonic devices operating in key regions of the electromagnetic spectrum, such as the microwave (>5 GHz) and terahertz (0.1-10 THz) ranges. A possible reason for this technological gap is the widespread notion that organic electronic materials are unsuitable for high-frequency applications. In this work, we demonstrate for the first time the utility of high-performance polymer mixed conductors as electro-active tuning layers in reconfigurable terahertz metasurfaces, achieving modulation performances comparable with state-of-the-art inorganic and 2D semiconductors. Through time-domain terahertz spectroscopy, we show that the large conductivity modulations of these polymers, until now probed only at very low frequencies, are effectively preserved in the terahertz range, leading to optimal metadevice reconfigurability. Finally, we leverage the unique processability of organic materials to develop fully direct-written electrically tuneable metasurfaces onto both rigid and flexible substrates, opening new opportunities for the mass-scale realization of flexible and light-weight terahertz optics with unique mechanical characteristics and environmental footprint. Organic mixed ion-electron conductors are emerging as promising platforms for innovative bioelectronic, neuromorphic, and electro-optical technologies. In this work, authors explore the potential of this class of electronic materials in THz technologies by developing reconfigurable metasurfaces via direct-writing methods. [ABSTRACT FROM AUTHOR]

To develop and validate a novel Comorbidity score for Robotic Surgery (CRS) in predicting severe complications after robot-assisted radical prostatectomy (RARP). Furthermore, we investigated the impact of the surgical platform (Multi-Port – MP vs Single-Port – SP) according to this score. We included 2085 ("development cohort") and 595 ("validation cohort") patients undergoing RARP at two tertiary referral centers between 2014 and March 2024 in a retrospective study. Statistical analyses included validation of the Charlson Comorbidity Index (CCI) to predict 30-day severe complications (Clavien-Dindo ≥ 3a), development and external validation of CRS using calibration plots and decision curve analysis. Lastly, locally weighted scatterplot smoothing (LOWESS) analysis was used to graphically explore the impact of the robotic platform according to novel CRS. CCI exhibited limited predictive ability for severe complications (60% in the validation cohort). In multivariable logistic regression analyses testing the correlation between each condition included in CCI and severe complications, diabetes and myocardial infarction resulted as independent predictors (OR 1.75 [95%CI 1.05–2.82]; OR 1.92 [95%CI 1.26–2.88]) and were subsequently fitted into a multivariable logistic model including age, previous abdominal surgery and obesity (BMI > 30). The resulting predictive model demonstrated superior discrimination and clinical net benefit in predicting severe complications compared to CCI (AUC 64 vs 60%). At LOWESS analysis, SP platform was associated with lower risk of severe complications as CRS increased compared to MP system. The validated CRS showed better accuracy compared to CCI in predicting severe complications after RARP. Additionally, the use of SP robotic platform may reduce the risk of severe complications in highly comorbid patients according to CRS. [ABSTRACT FROM AUTHOR]

Background and Objective: Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of antibiotics including C-reactive protein (C-RP) dynamics could be helpful in predicting the efficacy of antimicrobials. We developed a PK/PD model for assessing the impact of continuous infusion (CI) meropenem PK/PD target attainment on C-RP dynamics in critically ill patients with documented Gram-negative hospital- (HAP) or ventilator-acquired pneumonia (VAP). Methods: Patients were grouped according to the type of antibiotic treatment received [meropenem monotherapy; meropenem plus empirical anti-MRSA (methicillin-resistant Staphylococcus aureus) therapy; meropenem in combination with another anti–Gram-negative active agent; meropenem plus a targeted anti-MRSA therapy]. A one-compartment population PK model of CI meropenem was developed by including all patients. A full C-RP production inhibition model was developed for fitting the PD data by including only patients receiving meropenem monotherapy or meropenem plus empirical anti-MRSA therapy. Monte Carlo simulations explored the relationship between the type of PK/PD target attainment of CI meropenem, defined as optimal (steady-state plasma concentration [Css] to minimum inhibitory concentration [MIC] ratio = 4–8), quasi-optimal (Css/MIC = 1–4) and sub-optimal (Css/MIC < 1) and the magnitude of C-RP production inhibition over time. Results: A total of 64 patients providing 211 meropenem concentrations were included in the PK analysis, whereas 47 patients providing 328 C-RP data were included in the PD model. Simulations showed that optimal PK/PD target attainment was associated with the highest and most rapid C-RP production inhibition (44% and 56% at days 2 and 4, respectively). Conversely, sub-optimal PK/PD target attainment was shown to be almost ineffective (< 5% at day 4 and < 10% at day 10). Conclusion: Our PK/PD model predicted that attaining optimal PK/PD target with CI meropenem may grant prompt and intense C-RP decrease among critically ill patients receiving targeted monotherapy for Gram-negative HAP/VAP, thus anticipating efficacy. [ABSTRACT FROM AUTHOR]

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians. Key Points: Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents the standardized tool for this purpose. Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations. The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is associated with increased morbidity and mortality and exerts an increasingly significant burden on global healthcare resources, with its prevalence rising with an ageing population. Despite a substantial thromboembolic risk, particularly in the period immediately following diagnosis, oral anti-coagulation is frequently not initiated or is delayed. The aim of this study was to evaluate healthcare costs in people with AF, comparing those who were commenced on oral anti-coagulation in the immediate period following the index diagnosis date with those in whom initiation was late and those who never started anti-coagulation. Methods: This retrospective cost analysis used linked Scottish health data to identify adults newly diagnosed with AF between January 1st 2012 and April 30th 2019 with a baseline CHA2DS2-VASc score of ≥ 2. This AF population was sub-divided according to timing of the first prescription of oral anti-coagulant (OAC) during a 2-year follow-up period: never started (OAC never initiated), immediate OAC (OAC prescribed within 60 days of incident AF diagnosis), and delayed OAC (OAC prescribed more than 60 days after incident AF diagnosis). A two-part model was developed, adjusted for key covariates, including age, sex, and frailty, to estimate costs for inpatient admissions, outpatient care, prescriptions, and care home admissions, and overall costs. Results: Of an overall AF population of 54,385, 26,805 (49.3%) never commenced OAC, 7654 (14.1%) initiated an OAC late, and 19,926 (36.6%) were prescribed anti-coagulation immediately. The mean adjusted cost for the overall AF population was £7807 per person per year (unadjusted: £8491). Delayed OAC initiation was associated with the greatest adjusted estimated mean annual cost (unadjusted: £13,983; adjusted: £9763), compared to those that never started (unadjusted: £10,433; adjusted: £7981) and those that received an immediate OAC prescription (unadjusted: £3976; adjusted: £6621). Increasing frailty, mortality, and female sex were associated with greater healthcare costs. Conclusion: AF is associated with significant healthcare resource utilisation and costs, particularly in the context of delayed or non-initiation of anti-coagulation. Indeed, there exists substantial opportunity to improve the utilisation and prompt initiation in people newly diagnosed with AF in Scotland. Interventions to mitigate against the growing economic burden of AF should focus on reducing admissions to hospitals and care homes, which are the principal drivers of costs; prescriptions and outpatient appointments account for a relatively small proportion of overall costs for AF. [ABSTRACT FROM AUTHOR]

Summary: We assessed multiple components of muscle function in ten adults with X-linked hypophosphatemia (XLH) receiving burosumab treatment. Lower limb power (+ 9%), short physical performance battery (SPPB) score (+ 1.2 points), and physical activity (+ 65%) increased following 6 months of treatment, and hand grip increased (+ 10%) between 6 and 12 months of treatment. Purpose: X-linked hypophosphatemia (XLH) is a rare genetic disorder of phosphate metabolism. Burosumab is a monoclonal antibody treatment shown to improve phosphate homeostasis and improve symptoms as well as fracture healing when used as a therapy for XLH in adults. However, little is known about its effects on the large deficits in multiple components of physical function previously reported in XLH. Methods: Ten adults (6 females, age 41.1 ± 15.7 y) were recruited from specialist centres in London and Bristol. During clinical visits for initial burosumab treatment and at 6-month and 12-month follow-up, physical function, and physical activity (PA) assessments were performed. In detail, lower limb power was assessed by mechanography via a countermovement jump, mobility by short physical performance battery (SPPB), functional capacity by 6-min walk test (6MWT), upper limb strength by hand grip dynamometry, and PA via an International Physical Activity Questionnaire (IPAQ). Differences between baseline and 6-month follow-up, and in a subset of 5 patients between 6- and 12-month follow-up, were assessed. Results: Lower limb power increased by 9% (P = 0.049) from baseline to 6 months, as did SPPB score (+ 1.2 points, P = 0.033) and total PA (+ 65%, P = 0.046) although hand grip and 6MWT did not differ. Only for hand grip was a significant improvement (+ 10%, P = 0.023) seen between 6 and 12 months. Conclusions: Burosumab treatment is associated with improved lower limb function and mobility at 6 months, with improvement in hand grip strength at 12 months. Future studies should explore the underlying mechanisms and describe on function and other patient outcomes. [ABSTRACT FROM AUTHOR]

Point cloud registration is a fundamental problem in robotics, critical for tasks such as localization and mapping. Most approaches to this problem use feature-based techniques. However, these approaches have issues when dealing with unstructured environments where meaningful features are difficult to extract. Recently, an innovative global point cloud registration algorithm, PHASER, which does not rely on geometric features or point correspondences, has been introduced. It leverages Fourier transforms to identify the optimal rigid transform that maximizes cross-correlation between source and target point clouds. PHASER can also incorporate additional data channels, like LiDAR intensity, to enhance registration results. Because it does not rely on local features and because of its ability to exploit additional data, PHASER is particularly useful when dealing with very noisy point clouds or with many outliers. For this reason, we propose an extension to PHASER that considers multiple plausible rototranslation hypotheses. Our extended approach outperforms the original PHASER algorithm, especially in challenging scenarios where point clouds are widely separated. We validate its effectiveness on the DARPA SubT, and the Newer College datasets, showcasing its potential for improving registration accuracy in complex environments. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic accuracy of dual-energy CT (DECT) iodine maps in comparison to conventional CT series for the assessment of non-occlusive mesenteric ischemia (NOMI). Material and Methods: We evaluated data from 142 patients (72 men; 50.7%) who underwent DECT between 2018 and 2022, with surgically confirmed diagnosis of NOMI. One board-certified radiologist performed region of interest (ROI) measurements in bowel segments on late arterial (LA) and portal venous (PV) phase DECT iodine maps as well as LA conventional series, in both ischemic and non-ischemic bowel loops, using surgical reports as reference standard, and in a control group of 97 patients. Intra- and inter-reader agreement with a second board-certified radiologist was also evaluated. Receiver operating characteristic (ROC) curve analysis was performed to calculate the optimal threshold for discriminating ischemic from non-ischemic bowel segments. Subjective image rating of LA and PV iodine maps was performed. Results: DECT-based iodine concentration (IC) measurements showed significant differences in LA phase iodine maps between ischemic (median:0.72; IQR 0.52–0.91 mg/mL) and non-ischemic bowel loops (5.16; IQR 3.45–6.31 mg/ml) (P <.0001). IC quantification on LA phase revealed an AUC of 0.966 for the assessment of acute bowel ischemia, significantly higher compared to both IC quantification based on PV phase (0.951) and attenuation values evaluated on LA conventional CT series (0.828). Excellent intra-observer and strong inter-observer agreements were observed for the quantification of iodine concentration. Conversely, weak inter-observer agreement was noted for conventional HU assessments. The optimal LA phase-based IC threshold for assessing bowel ischemia was 1.34 mg/mL, yielding a sensitivity of 100% and specificity of 96.48%. Conclusion: Iodine maps based on LA phase significantly improve the diagnostic accuracy for the assessment of NOMI compared to conventional CT series and PV phase iodine maps. [ABSTRACT FROM AUTHOR]

Transgender and gender diverse individuals experience a gender identity that differs from the sex assigned at birth. Some transgender men may request testosterone to induce virilization; however, its impact on bone health remains to be fully elucidated. The objective of this systematic review and meta-analysis was to evaluate the modifications in bone metabolism over a short-term period among transgender men initiating testosterone therapy. A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library. The articles of interest had to report longitudinal evaluation conducted among transgender men, before starting testosterone and after 12 and 24 months of therapy. The analyzed parameters were BMD, calcium, phosphate, 25OHD, PTH, P1NP, BAP, osteocalcin and CTx. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias. Fourteen studies met the inclusion criteria, including 1484 subjects. In absence of heterogeneity, BMD did not significantly change at lumbar spine, hip, femoral neck, and whole-body evaluations. Calcium, phosphate, 25OHD and PTH remained stable over time. Regarding bone turnover markers, only P1NP showed a statistically significant increase after 12 months of T therapy, in absence of heterogeneity (SMD 0.61 mcg/l; 95% CI: 0.40–0.83; p < 0.0001; I2 = 0%, Pforheterogeneity = 0.48). Testosterone therapy among transgender men seems not to disrupt bone health after 12 and 24 months. A statistically significant elevation in P1NP levels after 12 months of therapy may indicate a positive anabolic effect of testosterone in the short-term. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. Methods: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. Results: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). Conclusions: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients. [ABSTRACT FROM AUTHOR]

Objective: Air leak (AL) is the most frequent adverse event after thoracic surgery. When AL occurs, the concentration of the principal gas in the pleural space should be similar to that of air exhaled. Accordingly, we tried to develop a new method to identify AL by analyzing pCO2 levels in the air flow from the chest drainage using capnography. Methods: This is a prospective observational study of 104 patients who underwent VATS surgery between January 2020 and July 2021. Digital drainage systems were used to detect AL. Results: Eighty-two patients (79%) had lung resection. Among them, 19 had post-operative day 1 air leaks (median 67 ml/min). AL patients had higher intrapleural CO2 levels (median 24 mmHg) (p < 0.001). Median chest drainage duration was 2 days (range 1.0–3.0). Univariable logistic regression showed a linear and significant association between intrapleural CO2 levels and AL risk (OR 1.26, 95% CI 1.17–1.36, p < 0.001, C index: 0.94). The Univariable Gamma model demonstrated that an elevation in CO2 levels was linked to AL on POD1 (with an adjusted mean effect of 7.006, 95% CI 1.59–12.41, p = 0.011) and extended duration of drainage placement (p < 0.001). Conclusions: Intrapleural CO2 could be an effective tool to assess AL. The linear association between variables allows us to hypothesize the role of CO2 in the identification of AL. Further studies should be performed to identify a CO2 cutoff that will standardize the management of chest drainage. [ABSTRACT FROM AUTHOR]

The hippocampal formation is critical for episodic memory, with area Cornu Ammonis 3 (CA3) a necessary substrate for auto-associative pattern completion. Recent theoretical and experimental evidence suggests that the formation and retrieval of cell assemblies enable these functions. Yet, how cell assemblies are formed and retrieved in a full-scale spiking neural network (SNN) of CA3 that incorporates the observed diversity of neurons and connections within this circuit is not well understood. Here, we demonstrate that a data-driven SNN model quantitatively reflecting the neuron type-specific population sizes, intrinsic electrophysiology, connectivity statistics, synaptic signaling, and long-term plasticity of the mouse CA3 is capable of robust auto-association and pattern completion via cell assemblies. Our results show that a broad range of assembly sizes could successfully and systematically retrieve patterns from heavily incomplete or corrupted cues after a limited number of presentations. Furthermore, performance was robust with respect to partial overlap of assemblies through shared cells, substantially enhancing memory capacity. These novel findings provide computational evidence that the specific biological properties of the CA3 circuit produce an effective neural substrate for associative learning in the mammalian brain. [ABSTRACT FROM AUTHOR]

Background: Malignant Distal Biliary Obstruction (MBDO) is a common event occurring along the natural history of both pancreatic cancer and cholangiocarcinoma. Epidemiological and biological features make MBDO one of the key elements of the clinical management of patients suffering for of pancreatic cancer or cholangiocarcinoma. The development of dedicated biliary lumen-apposing metal stents (LAMS) is changing the clinical work up of patients with MBDO. i-EUS is an Italian network of clinicians and scientists with a special interest in biliopancreatic endoscopy, EUS in particular. Methods: The scientific methodology was chosen in line with international guidance and in a fashion similar to those applied by broader scientific associations. PICO questions were elaborated and subsequently voted by a broad panel of experts within a simplified Delphi process. Results and conclusions: The manuscripts describes the results of a consensus conference organized by i-EUS with the aim of providing an evidence based-guidance for the appropriate use of the techniques in patients with MBDO. [ABSTRACT FROM AUTHOR]

Background: Percutaneous endoscopic gastrostomy is commonly used for enteral nutritional access, but gastrocutaneous fistulae (GCF) may persist after tube removal, posing clinical challenges. The use of endoscopic closure devices, including over-the-scope clips (OTSC), has shown promise in managing non-healing fistulae, although data in the pediatric population are limited. Methods: A retrospective multicenter study analyzed pediatric patients who underwent GCF closure following gastrostomy tube removal. Data from seven centers across multiple countries were collected, including patient demographics, procedural details, complications, and outcomes. Closure techniques were compared between OTSC and surgical closure. Results: Of 67 pediatric patients included, 21 underwent OTSC closure and 46 had surgical closure. Surgical closure demonstrated a higher success rate (100%) compared to OTSC closure (61.9%, P < 0.001). While procedural duration was shorter for OTSC closure (25 vs. 40 min, P = 0.002), complications, and scar quality were comparable between techniques. A subsequent sub-analysis did not reveal differences based on center experience. Conclusion: OTSC closure is feasible and safe in pediatric patients, but surgical closure remains superior in achieving sustained GCF closure, although OTSC offers benefits, such as shorter procedural duration, potentially reducing the duration of general anesthesia exposure. Non-operative approaches, including OTSC, may be a valuable alternative to surgical closure. [ABSTRACT FROM AUTHOR]

Mechanical metamaterials consist of specially engineered features designed to tailor and enhance the mechanical properties of their constituent materials. In this context, 2D pantographic fabrics have gained attention for their unique deformation behavior, providing remarkable resilience and damage tolerance. This study explores micro-metric metamaterials with 3D pantographic motifs, aiming to transfer these properties to small scales. 3D micro-metric structures were designed using 2D pantographic fabrics arranged in multiple layers, each featuring unit cells with quasi-perfect pivots. Relatively large specimens of 3D micro-metric pantographs, measuring 158 μ m x 250 μ m x 450 μ m, were fabricated in various configurations using two-photon polymerization. These specimens were mechanically characterized through in-situ scanning electron microscopy microindentation under conditions of cyclic deformation. Structural failures were subsequently assessed via helium-ion microscopy. The 3D micro-metric pantographs exhibited complex mechanical properties, some aligning with those of 2D pantographic fabrics, while new properties, such as a dissipative response and softening, were identified. Nonetheless, the 3D micro-metric pantographs demonstrated great resilience against deformation and enhanced resistance to undesired out-of-plane motions, indicating their potential for novel applications in advanced engineering fields. Additionally, the findings can potentially lead to optimizing and enriching theoretical models describing the mechanical behavior of pantographic metamaterials. [ABSTRACT FROM AUTHOR]

Multiparametric MRI is the optimal primary investigation when prostate cancer is suspected, and its ability to rule in and rule out clinically significant disease relies on high-quality anatomical and functional images. Avenues for achieving consistent high-quality acquisitions include meticulous patient preparation, scanner setup, optimised pulse sequences, personnel training, and artificial intelligence systems. The impact of these interventions on the final images needs to be quantified. The prostate imaging quality (PI-QUAL) scoring system was the first standardised quantification method that demonstrated the potential for clinical benefit by relating image quality to cancer detection ability by MRI. We present the updated version of PI-QUAL (PI-QUAL v2) which applies to prostate MRI performed with or without intravenous contrast medium using a simplified 3-point scale focused on critical technical and qualitative image parameters. Clinical relevance statement: High image quality is crucial for prostate MRI, and the updated version of the PI-QUAL score (PI-QUAL v2) aims to address the limitations of version 1. It is now applicable to both multiparametric MRI and MRI without intravenous contrast medium. Key Points: High-quality images are essential for prostate cancer diagnosis and management using MRI. PI-QUAL v2 simplifies image assessment and expands its applicability to prostate MRI without contrast medium. PI-QUAL v2 focuses on critical technical and qualitative image parameters and emphasises T2-WI and DWI. [ABSTRACT FROM AUTHOR]

Purpose: To create a machine-learning model for estimating the likelihood of post-retrograde intrarenal surgery (RIRS) sepsis. Methods: All consecutive patients with kidney stone(s) only undergoing RIRS in 16 centers were prospectively included (January 2022–August 2023). Inclusion criteria: adult, renal stone(s) only, CT scan (within three months), mid-stream urine culture (within 10 days). Exclusion criteria: concomitant ureteral stone, bilateral procedures. In case of symptomatic infection/asymptomatic bacteriuria, patients were given six days of antibiotics according to susceptibility profiles. All patients had antibiotics prophylaxis. Variables selected for the model: age, gender, age-adjusted Charlson Comorbidity Index, stone volume, indwelling preoperative bladder catheter, urine culture, single/multiple stones, indwelling preoperative stent/nephrostomy, ureteric access sheath, surgical time. Analysis was conducted using Python programming language, with Pandas library and machine learning models implemented using the Scikit-learn library. Machine learning algorithms tested: Decision Tree, Random Forest, Gradient Boosting. Overall performance was accurately estimated by K-Fold cross-validation with three folds. Results: 1552 patients were included. There were 20 (1.3%) sepsis cases, 16 (1.0%) septic shock cases, and three more cases (0.2%) of sepsis-related deaths. Random Forest model showed the best performance (precision = 1.00; recall = 0.86; F1 score = 0.92; accuracy = 0.92). A web-based interface of the predictive model was built and is available at https://emabal.pythonanywhere.com/ Conclusions: Our model can predict post-RIRS sepsis with high accuracy and might facilitate patient selection for day-surgery procedures and identify patients at higher risk of sepsis who deserve extreme attention for prompt identification and treatment. [ABSTRACT FROM AUTHOR]

We present a quantitative strategy to identify all projection neuron types from a given region with statistically different patterns of anatomical targeting. We first validate the technique with mouse primary motor cortex layer 6 data, yielding two clusters consistent with cortico-thalamic and intra-telencephalic neurons. We next analyze the presubiculum, a less-explored region, identifying five classes of projecting neurons with unique patterns of divergence, convergence, and specificity. We report several findings: individual classes target multiple subregions along defined functions; all hypothalamic regions are exclusively targeted by the same class also invading midbrain and agranular retrosplenial cortex; Cornu Ammonis receives input from a single class of presubicular axons also projecting to granular retrosplenial cortex; path distances from the presubiculum to the same targets differ significantly between classes, as do the path distances to distinct targets within most classes; the identified classes have highly non-uniform abundances; and presubicular somata are topographically segregated among classes. This study thus demonstrates that statistically distinct projections shed light on the functional organization of their circuit. The classification of different types of neurons has been a long-standing challenge in neuroscience. Here, the authors present a strategy to quantify all statistically distinct axonal patterns from a brain region based on their anatomical targeting, with this projection-driven neuron classification informing the functional architecture of the circuit. [ABSTRACT FROM AUTHOR]

The relationship between the variations in ovarian hormones (i.e., estrogens and progesterone) and the hypoxic ventilatory response (HVR) remains unclear. HVR is a key adaptive mechanism to high altitude and has been proposed as a predictor for acute mountain sickness (AMS). This study aimed to explore the effects of hormonal changes across the menstrual cycle on HVR. Additionally, it assessed the predictive capacity of HVR for AMS and examined whether a particular menstrual phase could enhance its predictive accuracy. Thirteen eumenorrheic women performed a pure nitrogen breathing test near sea level, measuring HVR and cerebral oxygenation in early follicular, late follicular, and mid-luteal phases. Oxidative stress and ovarian hormone levels were also measured. AMS symptoms were evaluated after spending 14 h, including one overnight, at an altitude of 3,375 m. No differences in HVR, ventilation, peripheral oxygen saturation, or cerebral oxygenation were observed between the three menstrual cycle phases. Moreover, these parameters and the oxidative stress markers did not differ between the women with or without AMS (31% vs 69%), regardless of the menstrual cycle phase. In conclusion, ventilatory responses and cerebral oxygenation in normobaric hypoxia were consistent across the menstrual cycle. Furthermore, these parameters did not differentiate women with or without AMS. [ABSTRACT FROM AUTHOR]

Global functional adaptation after local mechanical stimulation, as in mechanobiology and the mimosa plant, is fascinating and ubiquitous in nature. This is achieved by locally sensing mechanical deformation with precise thresholds, processing this information via biochemical circuits, followed by downstream actuation. The integration of such embodied intelligence allowing for mechano-to-chemo-to-function information-processing remains elusive in man-made systems. By merging the fields of chemical circuits and metamaterials, we introduce adaptive metamaterial hydrogels (meta-gels) that can accurately sense mechanical stimuli (local touch and global strain), transmit this information over long distances via reaction-diffusion signaling, and induce downstream mechanical strengthening by growing nanofibril networks, or soft robotic actuation through competitive swelling. All elements of the sensor-processor-actuator system are embedded in the device, functioning autonomously without external feeding reservoirs. Our concept enables designing advanced life-like materials systems that synergistically combine two worlds – chemical circuits for chemical information-processing and metamaterial unit cells for physical information-processing. 'Functional adaptation after local mechanical stimulation is ubiquitous in nature but remains elusive in artificial systems. Here, the authors describe metamaterial hydrogels to sense mechanical stimuli with sharp force threshold, transmit this information and induce mechanical strengthening by growing nanofibril networks or soft robotic actuation through competitive swelling. [ABSTRACT FROM AUTHOR]

The synthetic lethal effect observed with the use of PARP inhibitors (PARPi) with tumors characterized by the loss of key players in the homologous recombination (HR) pathway, commonly referred to as "BRCAness", is maintaining high interest in oncology. While BRCAness is a well-established feature in breast, ovarian, prostate, and pancreatic carcinomas, our recent findings indicate that up to 15% of colorectal cancers (CRC) also harbor defects in the HR pathway, presenting promising opportunities for innovative therapeutic strategies in CRC patients. We developed a new tool called HRDirect, which builds upon the HRDetect algorithm and is able to predict HR deficiency (HRD) from reference-free tumor samples. We validated HRDirect using matched breast cancer and CRC patient samples. Subsequently, we assessed its efficacy in predicting response to the PARP inhibitor olaparib by comparing it with two other commercial assays: AmoyDx HRD by Amoy Diagnostics and the TruSight Oncology 500 HRD (TSO500-HRD) panel by Illumina NGS technology. While all three approaches successfully identified the most PARPi-sensitive CRC models, HRDirect demonstrated superior precision in distinguishing resistant models compared to AmoyDX and TSO500-HRD, which exhibited overlapping scores between sensitive and resistant cells. Furthermore, we propose integrating HRDirect scoring with ATM and RAD51C immunohistochemical analysis as part of our "composite biomarker approach" to enhance the identification of HRD tumors, with an immediate translational and clinical impact for CRC personalized treatment. [ABSTRACT FROM AUTHOR]

Laser assisted in situ keratomileusis (LASIK) surgery is the leading and most performed refractive surgery nowadays. A possible complication of LASIK surgery is infectious keratitis which can lead to disastrous corneal damage and result in permanent loss of vision. LASIK procedures have become increasingly accessible, and the demand for refractive surgery has risen among patients, challenging the medical field to improve the prevention of post-operative infections. Nevertheless, a wide range of pathogens have been described as responsible for post-LASIK keratitis. However, non-tuberculous mycobacterial keratitis remains an infrequent occurrence and is poorly described in the literature. To the best of our knowledge, this is the first ever reported case of post-LASIK keratitis caused by Mycobacterium wolinskyi. We describe the clinical and microbial characteristics, leading to its challenging treatment choice. [ABSTRACT FROM AUTHOR]

Filial imprinting, a crucial ethological paradigm, provides insights into the neurobiology of early learning and its long-term impact on behaviour. To date, invasive techniques like autoradiography or lesions have been used to study it, limiting the exploration of whole brain networks. Recent advances in fMRI for avian brains now open new windows to explore bird's brain functions at the network level. We developed an fMRI technique for awake, newly hatched chicks, capturing BOLD signal changes during imprinting experiments. While early memory acquisition phases are understood, long-term storage and retrieval remain unclear. Our findings identified potential long-term storage of imprinting memories across a neural network, including the hippocampal formation, the medial striatum, the arcopallium, and the prefrontal-like nidopallium caudolaterale. This paradigm opens up new avenues for exploring the broader landscape of learning and memory in neonatal vertebrates, enhancing our understanding of behaviour and brain networks. Functional MRI of imprinting in awake chicks offers insights into the neural networks for memory acquisition and storage at birth. This discovery opens new avenues for noninvasive studies of neuro-cognitive processes in neonatal vertebrates. [ABSTRACT FROM AUTHOR]

Background: Technetium-99 m-labelled macroaggregated human serum albumin ([99mTc]Tc-MAA) is commonly used for lung perfusion scintigraphy. The European Pharmacopoeia (Eu.Ph.) specifies thin-layer chromatography (TLC) as the only method to assess its radiochemical purity (RCP). Similarly, TLC is the sole method reported in the literature to evaluate the RCP of Gallium-68-labelled MAA [68 Ga]Ga-MAA, recently introduced for lung perfusion PET/CT imaging. Since [68 Ga]Ga-MAA is prepared from commercial kits originally designed for the preparation of [99mTc]Tc-MAA, it is essential to optimize and validate the preparation methods for [68 Ga]Ga-MAA. Results: We tested a novel, simplified method for the preparation of [68 Ga]Ga-MAA that does not require organic solvents, prewash or final purification steps to remove radioactive impurities. We assessed the final product using radio-TLC, radio-UV-HPLC, and radio SDS-PAGE. Overall, our quality control (QC) method successfully detected [68 Ga]Ga-MAA along with all potential impurities, including free Ga-68, [68 Ga]Ga-HSA, unlabeled HSA, which may occur during labelling process and HEPES residual, a non-toxic but non-human-approved contaminant, used as buffer solution. We then applied our QC system to [68 Ga]Ga-MAA prepared under different conditions (25°–40°–75°–95 °C), thus defining the optimal temperature for labelling. Scanning Electron Microscopy (SEM) analysis of the products obtained through our novel method confirmed that most [68 Ga]Ga-MAA particles preserved the morphological structure and size distribution of unlabeled MAA, with a particle diameter range of 25–50 μm, assuring diagnostic efficacy. Conclusions: We optimized a novel method to prepare [68 Ga]Ga-MAA through a QC system capable of monitoring all impurities of the final products. [ABSTRACT FROM AUTHOR]

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Future anxiety (FA), characterized by apprehension about unfavorable changes in the near and distant future, intersects with loneliness and quality of life (QoL). Moreover, it is widely established that aging may influence both loneliness and QoL. Despite acknowledging the impact of FA on QoL, the underlying mechanisms of this relationship are poorly understood. In this study involving 5409 participants (82.12% females), FA, loneliness, and QoL scales were employed to construct a moderated mediation model. FA served as the exogenous variable, QoL as the outcome, and loneliness as the mediator, with age introduced as a moderator. Results showed a direct negative effect of FA on QoL (b=-0.449; p < 0.001) and an indirect effect through loneliness (b=-0.133; p < 0.001). Furthermore, this relationship was negatively moderated by age, suggesting that older individuals, potentially due to greater social connection and support than younger individuals, exhibit a buffering effect, mitigating the impact of future anxiety on their QoL. [ABSTRACT FROM AUTHOR]

Background: Cardiopulmonary resuscitation-associated lung edema (CRALE) is a phenomenon that has been recently reported in both experimental and out-of-hospital cardiac arrest patients. We aimed to explore the respiratory and cardiovascular pathophysiology of CRALE in an experimental model of cardiac arrest undergoing prolonged manual and mechanical chest compression (CC). Oxygen delivery achieved during mechanical or manual CC were also investigated as a secondary aim, to describe CRALE evolution under different hemodynamic supports generated during CPR. Methods: Ventricular fibrillation (VF) was induced and left untreated for 5 min prior to begin cardiopulmonary resuscitation (CPR), including CC, ventilation with oxygen, epinephrine administration and defibrillation. Continuous mechanical and manual CC was performed alternating one of the two strategies every 5 min for a total of 25 min. Unsynchronized mechanical ventilation was resumed simultaneously to CC. A lung computed tomography (CT) was performed at baseline and 1 h after return of spontaneous circulation (ROSC) in surviving animals. Partitioned respiratory mechanics, gas exchange, hemodynamics, and oxygen delivery were evaluated during the experimental study at different timepoints. Lung histopathology was performed. Results: After 25 min of CPR, a marked decrease of the respiratory system compliance with reduced oxygenation and CO2 elimination were observed in all animals. The worsening of the respiratory system compliance was driven by a significant decrease in lung compliance. The presence of CRALE was confirmed by an increased lung weight and a reduced lung aeration at the lung CT, together with a high lung wet-to-dry ratio and reduced airspace at histology. The average change in esophageal pressure during the 25-min CPR highly correlated with the severity of CRALE, i.e., lung weight increase. Conclusions: In this porcine model of cardiac arrest followed by a 25-min interval of CPR with mechanical and manual CC, CRALE was consistently present and was characterized by lung inhomogeneity with alveolar tissue and hemorrhage replacing alveolar airspace. Despite mechanical CPR is associated with a more severe CRALE, the higher cardiac output generated by the mechanical compression ultimately accounted for a greater oxygen delivery. Whether specific ventilation strategies might prevent CRALE while preserving hemodynamics remains to be proved. [ABSTRACT FROM AUTHOR]

One of the physical methods for obtaining magnetite nanoparticles (NPs) is electron beam physical vapor deposition (EB PVD), which requires complex equipment, but allows obtaining a significant amount of pure (ligand-free) NPs. The biomedical application of such NPs is less studied than materials from other synthesis methods. The objective is to study the effect of pure magnetite NPs in the NaCl matrix obtained by EB PVD on hematological indicators, gases, electrolytes and parameters of iron metabolism in the blood of intact animals. The physical characteristics of NPs were studied using high-resolution transmission electron microscopy, scanning transmission electron microscopy, energy-dispersive X-ray spectroscopy mapping, electron energy-loss spectroscopy, selected area electron diffraction and fast Fourier transform. In vivo experiments were conducted on albino male rats, which were injected with solution of magnetite-sodium chloride NPs (1.35 mg Fe/kg). After 3 and 72 h, hematological parameters, blood gases, electrolytes, and serum iron were determined. The synthesized NPs had an average size of 11 nm. They were identified as magnetite, where polycrystals and single crystals were present. The absence of contamination in crystal boundaries, clear orientation and orderliness of atoms in crystals were established. The administration of NPs in the sodium chloride matrix to animals was characterized by a transient increase in the main indicators of red blood accompanied by an increase in the saturation of erythrocytes with hemoglobin and their mean volume after 3 h. It did not worsen blood gases and pH, but decreased blood Na+ content after 72 h. The investigated NPs caused changes in the parameters of serum iron characteristic to iron preparations, which after 3 h were smaller compared to the reference iron drug, and after 72 h—similar to it. More intense rapid effects on hematological parameters at lower serum iron indicate greater activity of the studied pure magnetite NPs obtained by EB PVD syntesis compared to the reference iron preparation. Highlights: Pure magnetite nanoparticles in the NaCl matrix were obtained by EB PVD. They were studied using high-resolution transmission electron microscopy. These nanoparticles had a size of 11 nm, clear orientation and orderliness of atoms in crystals. In healthy animals, they caused a transient increase in red blood indicators. They did not worsen blood gases and pH, but decreased Na+ content in the blood. The nanoparticles caused changes in the serum iron typical to iron preparations. These changes were not toxic and lasting due to compensatory reactions. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 coronavirus emerged in 2019 causing a COVID-19 pandemic that resulted in 7 million deaths out of 770 million reported cases over the next 4 years. The global health emergency called for unprecedented efforts to monitor and reduce the rate of infection, pushing the study of new diagnostic methods. In this paper, we introduce a cheap, fast, and non-invasive COVID-19 detection system, which exploits only exhaled breath. Specifically, provided an air sample, the mass spectra in the 10–351 mass-to-charge range are measured using an original micro and nano-sampling device coupled with a high-precision spectrometer; then, the raw spectra are processed by custom software algorithms; the clean and augmented data are eventually classified using state-of-the-art machine-learning algorithms. An uncontrolled clinical trial was conducted between 2021 and 2022 on 302 subjects who were concerned about being infected, either due to exhibiting symptoms or having recently recovered from illness. Despite the simplicity of use, our system showed a performance comparable to the traditional polymerase-chain-reaction and antigen testing in identifying cases of COVID-19 (that is, 95% accuracy, 94% recall, 96% specificity, and 92% -score). In light of these outcomes, we think that the proposed system holds the potential for substantial contributions to routine screenings and expedited responses during future epidemics, as it yields results comparable to state-of-the-art methods, providing them in a more rapid and less invasive manner. [ABSTRACT FROM AUTHOR]

A recent article in the European Journal of Nuclear Medicine & Molecular Imaging discusses the use of [18F]Fluorocholine PET/CT as a first-line imaging method for localizing parathyroid adenomas in primary hyperparathyroidism. The article emphasizes the importance of considering multiple domains, including technical capacity, diagnostic performance, clinical impact, influence on patient outcome, and cost-effectiveness, when evaluating diagnostic tests. The authors present the results of a cost-effectiveness analysis comparing a one-stop-shop imaging strategy with current standard imaging methods and conclude that first-line [18F]Fluorocholine PET/CT can be cost-effective in Europe and should be integrated into routine clinical practice. The findings suggest that [99mTc]Tc-MIBI scan may become obsolete in primary hyperparathyroidism if [18F]Fluorocholine PET/CT is available. [Extracted from the article]