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Background: Robot-Assisted Simple Prostatectomy (RASP) is recommended for the treatment of large prostate glands. The introduction of the Single-Port (SP) platform in 2018 has enabled transvesical approach to SP-RASP with promising outcomes. Our aim was to describe the functional and urinary continence outcomes of SP-RASP., Methods: Clinical and surgical data from all consecutive patients who underwent transvesical SP-RASP between February 2020 and March 2024 were collected in a prospectively maintained institutional dataset and retrospectively analyzed. All procedures were performed using the da Vinci SP platform without any conversions to open surgery. Postoperative outcomes were gathered and analyzed, with a particular focus on the incidence of urinary incontinence (UI) and the time to continence recovery., Results: Overall, 89 patients underwent SP-RASP, with a median prostate size of 110 grams (90-171.5) and a median PSA level of 5.5 mg/dl (2.77-10.93). All patients were on at least one prostate medication prior to surgery. Preoperative evaluations showed a median International Prostate Symptoms Score (IPSS) of 23 (20-27), Quality of Life (QoL) of 4 (3-5), and Post-voiding Residual (PVR) of 153 ml (60-400). The median operative time was 180 min (164-200), with a median estimated blood loss of 100 ml (30-180). Postoperatively, no patients required continuous bladder irrigation. The median postoperative opioid intake was 6.5 morphine equivalents (0-10), with over 78% not requiring narcotics after discharge. Overall, 77.5% were same day discharged. No Clavien-Dindo > 2 complications were recorded. The median follow-up time was 18 (7-35) months. At the last postoperative urological evaluation, the median IPSS was 5 (3-7), QoL was 1 (0-2), and PVR was 10 ml (0-25). Only 4 patients (4.5%) experienced UI postoperatively, and all were continent within 3 months., Conclusions: The UI incidence rate and functional outcomes of SP-RASP are very encouraging, likely due to precise adenoma and urethra dissection and bladder neck reconstruction. This approach also allows for same-day discharge., Competing Interests: Competing interests Dr. Simone Crivellaro is a consultant for Intuitive, other authors have nothing to disclose. Ethics approval and consent to participate Institutional review board approval (protocol n° 2017-0152 from Office of Vice Chancellor for Research, University of Illinois at Chicago) was obtained previously to data collecting and analysis. This study was conducted in accordance with ethical principles given by the Helsinki Declaration about clinical studies on human participants, and written informed consent was obtained from all subjects., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Synthetic data is becoming a valuable tool for computational pathologists, aiding in tasks like data augmentation and addressing data scarcity and privacy. However, its use necessitates careful planning and evaluation to prevent the creation of clinically irrelevant artifacts.This manuscript introduces a comprehensive pipeline for generating and evaluating synthetic pathology data using a diffusion model. The pipeline features a multifaceted evaluation strategy with an integrated explainability procedure, addressing two key aspects of synthetic data use in the medical domain.The evaluation of the generated data employs an ensemble-like approach. The first step includes assessing the similarity between real and synthetic data using established metrics. The second step involves evaluating the usability of the generated images in deep learning models accompanied with explainable AI methods. The final step entails verifying their histopathological realism through questionnaires answered by professional pathologists. We show that each of these evaluation steps are necessary as they provide complementary information on the generated data's quality.The pipeline is demonstrated on the public GTEx dataset of 650 Whole Slide Images (WSIs), including five different tissues. An equal number of tiles from each tissue are generated and their reliability is assessed using the proposed evaluation pipeline, yielding promising results.In summary, the proposed workflow offers a comprehensive solution for generative AI in digital pathology, potentially aiding the community in their transition towards digitalization and data-driven modeling., Competing Interests: Declaration of generative AI in scientific writing During the preparation of this work the authors used ChatGPT3.5 for grammar and spelling checks, as well as rephrasing to enhance readability. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Global warming and the introduction of non-native fish represent major threats to freshwater biodiversity worldwide, but their effects have usually been investigated separately. Since most fish are ectotherms, their metabolism and feeding behaviour are highly influenced by temperature. Increasing water temperatures may thus exacerbate the impact of non-native fish, particularly those adapted to warmer conditions, on prey populations. Increasing temperature can also result in divergences between the impacts of females and males, especially in sexually dimorphic species.The globally invasive tropical guppy Poecilia reticulata Peters, a popular aquarium fish also used for control of mosquito-borne diseases and as a model species in ecological and evolutionary studies, exhibits strong sexual dimorphism and larvivory. This laboratory study examined prey consumption and prey size selection by guppies fed with chironomid larvae under varying temperature conditions. The effect of sex, pregnancy and prey body size on the guppy's predatory response was also assessed by comparing Functional Responses.The results highlighted four key points: (1) increased temperature led to increased prey consumption in both females and males by decreasing handling time; (2) prey consumption was disproportionately higher in females than males, regardless of temperature; (3) temperature influenced females' prey size selection; and (4) pregnancy reduced prey handling time among females.These findings show that temperature and intraspecific differences influence the feeding response of invasive fish, and they should both be taken into account when investigating and predicting the ecological impact of invasive species on invaded food webs., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Immune checkpoint inhibitors have revolutionized cancer treatment, but they are associated with a range of immune-related adverse events (irAEs), and emerging evidence suggests significant sex differences in the incidence, type, and severity of these toxicities, suggesting an influential factor and understanding sex-related differences in irAEs as crucial for optimizing patient care and improving clinical outcomes. In MOUSEION-07 study, we aimed to assess the association between sex and treatment-related adverse events in cancer patients treated with immunotherapy through a large up-to-date meta-analysis of available clinical trials. The present systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. The protocol was registered with PROSPERO no. CRD42024549518. Sixteen studies encompassing a total of 4658 patients were included, and 2133 adverse effects were highlighted. The analysis observed a not statistically significant difference in terms of immune-related adverse events (irAEs) between males and females (Odds Ratio 1.19; CI 0.88-1.63) and revealed the presence of publication bias (β = -2.53; 95% CI = [-4.03; -1.04]; P = 0.006). Sex differences in immunotherapy-related adverse events are a significant factor in cancer treatment, necessitating a personalized approach to patient care. Further research is needed to fully understand the mechanisms driving these differences and to develop optimized strategies for monitoring and managing irAEs in both females and males., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Abdominal aortic aneurysm consists of a permanent dilation in the abdominal portion of the aorta and, along with its associated pathologies like calcifications and intraluminal thrombi, is one of the most important pathologies of the circulatory system. The shape of the aorta is among the primary drivers for these health issues, with particular reference to all the characteristics which affect the hemodynamics. Starting from the computed tomography angiography of a patient, we propose to summarize such information using tools derived from Topological Data Analysis, obtaining persistence diagrams which describe the irregularities of the lumen of the aorta. We showcase the effectiveness of such shape-related descriptors with a series of supervised and unsupervised case studies., Competing Interests: Competing Interests The authors declare no competing interests. Ethical statement The study has been conducted in accordance with the Declaration of Helsinki and subsequent modifications. It was approved by the ethics committee Comitato Etico Milano Area 2 at the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milan, with protocol number 3457/2023. The need for a signature of a specific informed consent was waived by the same committee as the study was observational and retrospective. No further requirements of clinical trials was necessary for the same reason., (© 2024. The Author(s).)

The temporal resolution of adults' visual attention has been linked to the frequency of alpha-band oscillations in electroencephalogram (EEG) signal, with higher Peak Alpha Frequency (PAF) being associated with better visual temporal processing skills. However, relatively less is known about neural mechanisms underlying individual differences in the temporal resolution of visual attention in infancy. This study investigated the role of PAF in visual temporal processing in early infancy. In a sample of 6-month-old infants (n = 62) we examined the relationship between PAF extracted from resting-state EEG, and saccadic latencies in a predictive cueing task where the appearance of a reward was predicted by higher or lower frequency of two flickering objects. Results showed that higher PAF was associated with shorter saccadic latencies in a condition with higher differences between the two flickering frequencies, speaking for the involvement of PAF in visual temporal attention in early development. Additionally, we found that infants were generally faster to orient to the reward in trials where both peripheral stimuli were flickering at relatively lower frequencies, roughly corresponding to the theta frequency band. Our findings support theoretical accounts highlighting the role of PAF in visual attention processing and extend this framework to early infancy., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Traumatic lesions on human skeletal remains are widely used for reconstructing past accidents or violent encounters and for comparing trauma prevalence across samples over time and space. However, uncertainties in trauma prevalence estimates increase proportionally with decreasing skeletal completeness, as once-present trauma might have gone missing. To account for this bias, samples are typically restricted to skeletal remains meeting a predefined minimum completeness threshold. However, the effect of this common practice on resulting estimates remains unexplored. Here, we test the performance of the conventional frequency approach, which considers only specimens with ≥ 75% completeness, against a recent alternative based on generalized linear models (GLMs), integrating specimen completeness as a covariate. Using a simulation framework grounded on empirical forensic, clinical, and archaeological data, we evaluated how closely frequency- and GLM-based estimates conform to the known trauma prevalence of once-complete cranial samples after introducing increasing levels of missing values. We show that GLM-based estimates were consistently more precise than frequencies across all levels of incompleteness and regardless of sample size. Unlike GLMs, frequencies increasingly produced incorrect relative patterns between samples and occasionally failed to produce estimates as incompleteness increased, particularly in smaller samples. Consequently, we generally recommend using GLMs and their extensions over frequencies, although neither approach is fully reliable when applied to largely incomplete samples., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Scolytinae (Coleoptera: Curculionidae) are one of the most successful groups of invasive species. They are generally moved among continents transported within live plants, timber and wood-packaging materials. The damages caused by these insects, of economic and ecological relevance, can be caused both by the direct action of burrowing within host plant tissues and by the pathogens carried by some species. In order to prevent the introduction of new and potentially harmful species by planning effective monitoring strategies, the knowledge of recorded host plants is essential. This third contribution provides a complete list of host plants, with economic categorization, for 2,193 scolytine species, belonging to 16 tribes: Amphiscolytini, Bothrosternini, Carphodicticini, Chaetophloeini, Crypturgini, Diamerini, Dryocoetini, Hexacolini, Hylesinini, Hyorrhynchini, Hypoborini, Micracidini, Phloeotribini, Phrixosomatini, Scolytini, and Scolytoplatypodini., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The historical restriction of magnetic resonance imaging (MRI) for patients with cardiac implantable electronic devices (CIEDs) has been lifted by certified MRI-conditional systems in recent years. Mixed-brand CIED systems consisting of a generator from one manufacturer and at least one lead from another manufacturer are not certified for MRI. We evaluated the temporal trend in the prevalence of mixed-brand systems in the era of MRI-conditional systems. Data were analyzed on 5853 CIEDs implanted de novo between 2012 and 2022 in 81 Italian centers linked to the nationwide Home Monitoring Expert Alliance network. The percentage of mixed-brand implants was calculated by device type (pacemaker, implantable cardioverter-defibrillator [ICD], cardiac resynchronization therapy [CRT] device) and over time. A mixed-brand system was implanted in 4.1% (95% CI, 3.6-4.6%) of analyzed patients or, by device type, in 4.5% (3.5-5.7%) of pacemaker patients, 1.1% (0.7-1.7%) of ICD patients, and 6.8% (5.7-7.9%) of CRT pacemaker/defibrillator patients (p < 0.001). Prevalence of mixed-brand implants exhibited significant temporal fluctuations, first declining from 6.6% (2012-2014) to 1.3% (2019), and then increasing to 5.1% (2022). Temporal changes were statistically significant for pacemakers (p < 0.001) and CRT devices (p = 0.001), but not for ICDs (p = 0.438). In the decade between 2012 and 2022, mixed-brand CIED systems were more prevalent in patients treated with pacemakers and CRT devices than in ICD recipients. A decline in the prevalence of mixed-brand systems was observed after the introduction of MRI-conditional systems, reaching a minimum in 2019, followed by a progressive increase in the subsequent years., (© 2024. The Author(s).)

Sperm motility is a crucial factor in male fertility. Photobiomodulation (PBM) has been reported to increase sperm motility, but a consistent approach suitable for identifying standardizable protocols is lacking. We collected asthenozoospermic (n = 70) and normozoospermic (n = 20) semen. The asthenozoospermic samples were irradiated with an 810 nm diode laser, in continuous wave mode, at 0.25 W, 0.5 W, 1 W and 2 W for 60 s on a circular area of 1 cm 2  through a novel handpiece with an innovative flat-top profile. Sperm motility was assessed immediately, after 30 and 60 min. A sample size calculator, unpaired t-test and one-way ANOVA with post-hoc Tukey HSD tests were used for statistics. One and 2 W were the most effective outputs in increasing progressive motility compared to control (p < 0.001). The maximum effect was immediately after 1 W-PBM (p < 0.001) and decreased after 60 min (p < 0.001). Time physiologically decreased vitality (p < 0.001), but less in the 1 W-PBM samples (p < 0.05). 1 W-PBM did not affect chromatin condensation. Asthenozoospermic samples displayed an impairment of 80% in oxygen consumption and ATP production and a slight inefficiency of oxidative phosphorylation compared to normozoospermic samples (p < 0.001). 1 W-PBM partially restored the functionality of aerobic metabolism (p < 0.001) by recovery of oxidative phosphorylation efficiency. PBM did not affect lactate dehydrogenase (glycolysis pathway). No irradiated samples increased accumulated malondialdehyde, a marker of lipidic peroxidation. In conclusion, PBM improves progressive motility in asthenozoospermia through increased mitochondrial energetic metabolism without harmful oxidative stress., (© 2024. The Author(s).)

Carcinogenesis results from the sequential acquisition of oncogenic mutations that convert normal cells into invasive, metastasizing cancer cells. Colorectal cancer exemplifies this process through its well-described adenoma-carcinoma sequence, modeled previously using clustered regularly interspaced short palindromic repeats (CRISPR) to induce four consecutive mutations in wild-type human gut organoids. Here, we demonstrate that long-term culture of mismatch-repair-deficient organoids allows the selection of spontaneous oncogenic mutations through the sequential withdrawal of Wnt agonists, epidermal growth factor (EGF) agonists and the bone morphogenetic protein (BMP) antagonist Noggin, while TP53 mutations were selected through the addition of Nutlin-3. Thus, organoids sequentially acquired mutations in AXIN1 and AXIN2 (Wnt pathway), TP53, ACVR2A and BMPR2 (BMP pathway) and NRAS (EGF pathway), gaining complete independence from stem cell niche factors. Quadruple-pathway (Wnt, EGF receptor, p53 and BMP) mutant organoids formed solid tumors upon xenotransplantation. This demonstrates that carcinogenesis can be recapitulated in a DNA repair-mutant background through in vitro selection that targets four consecutive cancer pathways., (© 2024. The Author(s).)

Sleep is integral to cardiovascular health 1,2 . Yet, the circuits that connect cardiovascular pathology and sleep are incompletely understood. It remains unclear whether cardiac injury influences sleep and whether sleep-mediated neural outputs contribute to heart healing and inflammation. Here we report that in humans and mice, monocytes are actively recruited to the brain after myocardial infarction (MI) to augment sleep, which suppresses sympathetic outflow to the heart, limiting inflammation and promoting healing. After MI, microglia rapidly recruit circulating monocytes to the brain's thalamic lateral posterior nucleus (LPN) via the choroid plexus, where they are reprogrammed to generate tumour necrosis factor (TNF). In the thalamic LPN, monocytic TNF engages Tnfrsf1a-expressing glutamatergic neurons to increase slow wave sleep pressure and abundance. Disrupting sleep after MI worsens cardiac function, decreases heart rate variability and causes spontaneous ventricular tachycardia. After MI, disrupting or curtailing sleep by manipulating glutamatergic TNF signalling in the thalamic LPN increases cardiac sympathetic input which signals through the β2-adrenergic receptor of macrophages to promote a chemotactic signature that increases monocyte influx. Poor sleep in the weeks following acute coronary syndrome increases susceptibility to secondary cardiovascular events and reduces the heart's functional recovery. In parallel, insufficient sleep in humans reprogrammes β2-adrenergic receptor-expressing monocytes towards a chemotactic phenotype, enhancing their migratory capacity. Collectively, our data uncover cardiogenic regulation of sleep after heart injury, which restricts cardiac sympathetic input, limiting inflammation and damage., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The mitochondrial calcium uniporter channel (MCUC) mediates mitochondrial calcium entry, regulating energy metabolism and cell death. Although several MCUC components have been identified, the molecular basis of mitochondrial calcium signaling networks and their remodeling upon changes in uniporter activity have not been assessed. Here, we map the MCUC interactome under resting conditions and upon chronic loss or gain of mitochondrial calcium uptake. We identify 89 high-confidence interactors that link MCUC to several mitochondrial complexes and pathways, half of which are associated with human disease. As a proof-of-concept, we validate the mitochondrial intermembrane space protein EFHD1 as a binding partner of the MCUC subunits MCU, EMRE, and MCUB. We further show a MICU1-dependent inhibitory effect of EFHD1 on calcium uptake. Next, we systematically survey compensatory mechanisms and functional consequences of mitochondrial calcium dyshomeostasis by analyzing the MCU interactome upon EMRE, MCUB, MICU1, or MICU2 knockdown. While silencing EMRE reduces MCU interconnectivity, MCUB loss-of-function leads to a wider interaction network. Our study provides a comprehensive and high-confidence resource to gain insights into players and mechanisms regulating mitochondrial calcium signaling and their relevance in human diseases., (© 2024. The Author(s).)

Background: To investigate the presence of silicone oil (SO)-emulsification on the anterior iris surface with anterior segment optical coherence tomography (AS-OCT)., Methods: In this single-center cross-sectional study, vitrectomized eyes with SO tamponade that underwent AS-OCT imaging and gonioscopy examination during the postoperative follow-up visits, were reviewed., Results: 45 eyes of 42 consecutive patients were included. In 35.6% of the eyes (n = 16) emulsified SO droplets were detected in the anterior chamber (AC) angle by gonioscopy and in 55.6% (n = 25) on the anterior iris surface by AS-OCT imaging. The presence of SO emulsifications in the AC-angle correlated with the presence of SO emulsifications on the anterior iris surface (OR = 13.4, 95% CI [2.179-82.130]; p = 0.005). The accuracy of the AS-OCT predicting the presence of SO in the AC-angle was 71.0% and the sensitivity was 87.5%. No significant association between SO droplets in the AC and other clinical parameters including endotamponade-duration or type of silicone oil were found. The presence of emulsified SO droplets on the anterior iris surface detected by AS-OCT was significantly correlated to postoperative IOP rise (p = 0.027)., Conclusion: AS-OCT is a suitable method for the detection of SO on the anterior iris surface. SO droplets on the iris surface correlate with elevated postoperative IOP and with the presence of SO in the AC detected by gonioscopy, therefore AS-OCT might be used as a screening method for the detection of SO migration into the AC., Trial Registration Number: Institutional Review Board of the Hamburg Medical Chamber (Ethik-Kommission der Ärztekammer Hamburg): 2023-300372-WF., (© 2024. The Author(s).)

We present an ultraviolet (UV) - extreme-ultraviolet (XUV) pump-probe beamline with applications in ultrafast time-resolved photoelectron spectroscopy. The UV pump pulses, tuneable between 255 and 285 nm and with µJ-level energy, are generated by frequency up-conversion between ultrashort visible/infrared pulses and visible narrow-band pulses. Few-femtosecond XUV probe pulses are produced by a high-order harmonic generation source equipped with a state-of-the-art time-delay compensated monochromator. Two-colour UV-XUV sidebands are used for a complete in situ temporal characterization of the pulses, demonstrating a temporal resolution of better than 20 fs. We validate the performances of the beamline through a UV-XUV pump-probe measurement on 1,3-cyclohexadiene, resolving the ultrashort dynamics of the first conical intersection. This instrument opens exciting possibilities for investigating ultrafast UV-induced dynamics of organic molecules in ultrashort time scales., (© 2024. The Author(s).)

The phenoconversion trajectory from idiopathic/isolated Rapid eye movement (REM) sleep behavior disorder (iRBD) towards either Parkinson's Disease (PD) or Dementia with Lewy Bodies (DLB) is currently uncertain. We investigated the capability of baseline brain [ 18 F]FDG-PET in differentiating between iRBD patients eventually phenoconverting to PD or DLB, by deriving the denovoPDRBD-related pattern (denovoPDRBD-RP) from 32 de novo PD patients; and the denovoDLBRBD-RP from 30 de novo DLB patients, both with evidence of RBD at diagnosis. To explore [ 18 F]FDG-PET phenoconversion trajectories prediction power, we applied these two patterns on a group of 115 iRBD patients followed longitudinally. At follow-up (25.6 ± 17.2 months), 42 iRBD patients progressed through overt alpha-synucleinopathy (21 iRBD-PD and 21 iRBD-DLB converters), while 73 patients remained stable at the last follow-up visit (43.2 ± 27.6 months). At survival analysis, both patterns were significantly associated with the phenoconversion trajectories. Brain [ 18 F]FDG-PET is a promising biomarker to study progression trajectories in the alpha-synucleinopathy continuum., (© 2024. The Author(s).)

Haemophilia is associated with reduced bone mass and mineral density. Due to the rarity of the disease and the heterogeneity among the studies, the pathogenesis of bone loss is still under investigation. We studied the effects of coagulation factors on bone cells and characterized in a pilot study the osteoclastogenic potential of patients' osteoclast precursors. To evaluate the effect of coagulation factors on osteoclasts, we treated Healthy Donor-Peripheral Blood Mononuclear Cells (HD-PBMC) with Factor VIII (FVIII), von Willebrand Factor (VWF), FVIII/VWF complex, activated Factor IX (FIXa), activated Factor X (FXa) and Thrombin (THB). FVIII, VWF, FVIII/VWF, FXa and THB treatments reduced osteoclast differentiation of HD-PBMC and VWF affected also bone resorption. Interestingly, PBMC isolated from patients with moderate/severe haemophilia showed an increased osteoclastogenic potential due to the alteration of osteoclast precursors. Moreover, increased expression of genes involved in osteoclast differentiation/activity was revealed in osteoclasts of an adult patient with moderate haemophilia. Control osteoblasts treated with the coagulation factors showed that FVIII and VWF reduced ALP positivity; the opposite effect was observed following THB treatment. Moreover, FVIII, VWF and FVIII/VWF reduced mineralization ability. These results could be important to understand how coagulation factors deficiency influences bone remodeling activity in haemophilia., (© 2024. The Author(s).)

Background: Over the past decade, the range of surgical options to benign prostatic obstruction (BPO) has expanded significantly with the advent of minimally invasive surgical therapies (MISTs). Nevertheless, the available evidence in the field is heterogeneous. Efficacy and safety thresholds are yet to be determined., Objective: To evaluate perioperative and long-term complications after MISTs - including Aquablation, steam injection (Rezūm), Transperineal laser ablation of the prostate (TPLA), implantation of a prostatic urethral lift (PUL) and temporary implantable nitinol device (iTIND) - in patients with lower urinary tract symptoms due to BPO., Evidence Acquisition: A systematic literature search was conducted in January 2024 using Medline (via PubMed), Embase (via Ovid), Scopus, and Web of Science. The search strategy used PICO criteria (Patients, Interventions, Comparisons, Outcomes) [1], focusing specifically on patients with BPH-associated LUTS who underwent MIST or other comparative treatments, aiming to assess both perioperative and long-term safety outcomes. Article selection was conducted in accordance with the PRISMA guidelines. The risk of bias and the quality of the articles included were assessed. A dedicated data extraction form was used to collect the data of interest., Evidence Synthesis: The initial electronic search identified 3660 records, of which 24 ultimately met the inclusion criteria and were included in the analysis. Overall, Aquablation was associated with a higher major complications rate of 14% (IQR 6-22), particularly in the case of patients with prostates <70 ml. PUL showed a higher early postoperative acute urinary retention rate (10.9%, IQR 9.2-12.3%), while 1.4% of patients treated with iTIND experienced major perioperative complications. Urinary tract infections were mostly reported in series assessing TPLA and Rezūm., Conclusions: The adoption of MISTs for LUTS due to BPH is associated with a varied spectrum of perioperative and long-term complications. Our findings showed an acceptable safety profile with specific complications dependent on the type of MIST performed, highlighting the importance of individualized patient selection and procedure-specific considerations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this work we introduce GrapheNet, a deep learning framework based on an Inception-Resnet architecture using image-like encoding of structural features for the prediction of the properties of nanographenes. The model is validated on datasets of computed structure/property data on graphene oxide and defected graphene nanoflakes. By exploiting the planarity of quasi-bidimensional systems and through encoding structures into images, and leveraging the flexibility and power of deep learning in image processing, Graphenet achieves significant accuracy in predicting the physicochemical properties of nanographenes. This approach is able to efficiently encode structures composed of hundreds of atoms, scaling efficiently with the size of the model and enabling the prediction of the properties of large systems, which contrasts with the limitations of current atomistic-level representations for deep learning applications. The approach proposed based on image encoding exhibit a significant numerical accuracy and outperforms the computational efficiency of current representations of materials at the atomistic level, with significant advantages especially in the representation of nanostructures and large planar systems., (© 2024. The Author(s).)

Neutron imaging has gained significant importance as a material characterisation technique and is particularly useful to visualise hydrogenous materials in objects opaque to other radiations. Fields of application include investigations of hydrogen in metals as well as metal corrosion, thanks to the fact that neutrons can penetrate metals better than e.g. X-rays and are highly sensitive to hydrogen. However, at interfaces refraction effects sometimes obscure the attenuation image, which is used for hydrogen quantification. Refraction, a differential phase effect, diverts the neutron beam away from the interface in the image leading to intensity gain and intensity loss regions, which are superimposed to the attenuation image, thus obscuring the interface region and hindering quantitative analyses of e.g. hydrogen content in the vicinity of the interface. For corresponding effects in X-ray imaging, a phase filter approach was developed and is generally based on transport-of-intensity considerations. Here, we compare such an approach, that has been adapted to neutrons, with another simulation-based assessment using the ray-tracing software McStas. The latter appears superior and promising for future extensions which enable fitting forward models via simulations in order to separate phase and attenuation effects and thus pave the way for overcoming quantitative limitations at refracting interfaces., (© 2024. The Author(s).)

Broadband Coherent anti-Stokes Raman (BCARS) microscopy is an imaging technique that can acquire full Raman spectra (400-3200 cm -1 ) of biological samples within a few milliseconds. However, the CARS signal suffers from an undesired non-resonant background (NRB), deriving from four-wave-mixing processes, which distorts the peak line shapes and reduces the chemical contrast. Traditionally, the NRB is removed using numerical algorithms that require expert users and knowledge of the NRB spectral profile. Recently, deep-learning models proved to be powerful tools for unsupervised automation and acceleration of NRB removal. Here, we thoroughly review the existing NRB removal deep-learning models (SpecNet, VECTOR, LSTM, Bi-LSTM) and present two novel architectures. The first one combines convolutional layers with Gated Recurrent Units (CNN + GRU); the second one is a Generative Adversarial Network (GAN) that trains an encoder-decoder network and an adversarial convolutional neural network. We also introduce an improved training dataset, generalized on different BCARS experimental configurations. We compare the performances of all these networks on test and experimental data, using them in the pipeline for spectral unmixing of BCARS images. Our analyses show that CNN + GRU and VECTOR are the networks giving the highest accuracy, GAN is the one that predicts the highest number of true positive peaks in experimental data, whereas GAN and VECTOR are the most suitable ones for real-time processing of BCARS images., (© 2024. The Author(s).)

The sorption properties of zeolites are controlled by several factors, i.e. Si/Al ratio of the aluminosilicate framework [AlSiO 4 ] - , the type and position of the extraframework (EF) cations, and the applied temperature. Here we investigate the flexibility of CHA framework as a function of EF cation-content and temperature (20-350 °C). Two CHA forms (Na- and Cu-CHA) with Si/Al = 2 were analysed. The main objectives were: (i) to shed light on the HT behaviour of Na-CHA, for which contrasting results exist in literature; (ii) define the role of temperature and EF cation-type in the response to the heating stimuli. We show that at 75 °C, Na-CHA undergoes a severe contraction of the unit-cell volume (-12%) accompanied by a symmetry lowering (R-3m to I2/m). The transformation is reversible, if the dehydrated Na-CHA is exposed to ambient conditions. In contrast, Cu-CHA experiences a significant different dehydration path, which involves minor changes of the CHA framework, and a net positive thermal-expansion after dehydration. The implications of the observed transformations for gas separation processes are finally discussed., (© 2024. The Author(s).)

The cardiometabolic implications of Non-Functioning Adrenal Incidentaloma (NFAI) is still matter of debate. This study takes a novel approach to analyze this association, accounting for the influence of various confounding factors. We present the findings of a retrospective, cross-sectional, and case-control study. Data from all NFAI patients in primary prevention, referred to the University of Turin between 2000 and 2023, were collected and compared with subjects without adrenal disease, using propensity score matching analysis. A total of 1997 patients were included (906 patients with NFAI; 1091 controls). Adrenal tumor group was associated with high levels of cardiovascular risk scores in both univariate and multiple linear regression analyses (Progetto CUORE: EC 11.00, 95% CI 2.72-44.46, p = 0.001; SCORE: EC 1.97, 95% CI 1.01-3.81, p = 0.046). Regarding cardiometabolic complications, multivariable logistic regression revealed an independent association between NFAI and ascending aorta dilation (OR 4.64, 95% CI 2.24-9.63, p = 0.000), after adjusting for age, sex, smoking status, metabolic syndrome, number of antihypertensive drugs, estimated glomerular filtration rate (eGFR), and normetanephrine levels. Propensity score matching analysis (1:1 matching ratio), based on the same logistic regression model, confirmed the association of NFAI with aortic dilation (β = 0.083, 95% CI 0.008-0.157, p = 0.030). No significant associations were found with metabolic syndrome, type II diabetes, eGFR <60 mL/min/1.73 m 2 , microalbuminuria, atrial fibrillation, or hypertensive heart disease. This study suggests that patients with NFAI face increased cardiometabolic risk and high prevalence of ascending aorta dilation. Routine evaluation of NFAI patients should include thorough cardiovascular assessment and consideration of treatments aimed at reducing cardiovascular risk., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The study aims to analyse ground displacement conditions observed over an Underground Gas Storage (UGS) site located at Hatfield Moors (United Kingdom), with a focus on understanding its implications for decarbonization efforts. The location serves as an active onshore storage site and was used as an analogy to assess ground motion implications around Carbon Capture and Storage (CCS) by the British Geological Survey (BGS) as part of the SENSE (Assuring integrity of CO 2 storage sites through ground surface monitoring) project. Given the value of continuous and real-time monitoring of ground movements induced by gas storage activities, the study leverages satellite Interferometric Synthetic Aperture Radar (InSAR) data to assess the environmental impact of UGS operations. Using free and open-source Sentinel-1 satellite data, ground motion patterns over Hatfield Moors are analysed, highlighting displacements ranging from - 5.0 to -10.0 mm/year within the peat bog. In addition, the Time Series (TS) of ground displacement from January 2018 to December 2022 reveals a seasonality in ground motion, with uplift observed in late winter and subsidence in late summer, showing a periodicity of approximately 1 year and a magnitude of +/-10.0 mm. Through in-depth analysis, the study highlights the need to understand the underlying causes of ground fluctuations at gas storage sites. This paper shows that InSAR has the versatility to integrate seamlessly with different monitoring tools and methodologies, opening avenues for comprehensive and holistic analyses. Cross-correlation analyses further elucidate temporal relationships between different datasets by evaluating InSAR time series, UGS injection/withdrawal data and piezometric data. This involves decomposing the TS into distinct components, including trend, seasonality and residuals. The case of Hatfield Moors shows a significant discrepancy between the UGS data and the InSAR TS, while also demonstrating a clear correlation between the groundwater data and the InSAR TS. By integrating insights from geology, hydrology and remote sensing technologies, the study navigates the complexities inherent in areas of overlapping phenomena. Accurate interpretation is essential for informed decision making, particularly at sites such as Hatfield Moors, where the convergence of natural peat motion and storage operations highlights the need for interdisciplinary analysis to understand the underlying causes of ground fluctuation., (© 2024. The Author(s).)

Animals' ability to orient and navigate relies on selecting an appropriate motor response based on the perception and integration of the environmental information. This is the case, for instance, of the optokinetic response (OKR) in Drosophila melanogaster, where optic flow visual stimulation modulates head movements. Despite a large body of literature on the OKR, there is still a limited understanding, in flies, of the impact on OKR of concomitant, and potentially conflicting, inputs. To evaluate the impact of this multimodal integration, we combined in D. melanogaster, while flying in a tethered condition, the optic flow stimulation leading to OKR with the simultaneous presentation of olfactory cues, based on repellent or masking compounds typically used against noxious insect species. First, this approach allowed us to directly quantify the effect of several substances and of their concentration on the dynamics of the flies' OKR in response to moving gratings by evaluating the number of saccades and the velocity of the slow phase. Subsequently, this analysis was capable of easily revealing the actual effect, i.e. masking vs. repellent, of the compound tested. In conclusion, we show that D. melanogaster, a cost-affordable species, represents a viable option for studying the effects of several compounds on the navigational abilities of insects., (© 2024. The Author(s).)

Objective: Scanty data are available about neonatal systemic vascular resistances (SVR). We aim to provide reference values and nomograms for neonatal SVR., Design: Multicenter, cross-sectional,descriptive study performed in France and Italy. Neonates with complete hemodynamic stability were enrolled. Non-invasive measurements of SVR by electrical cardiometry performed once, after the first 72 h and before the 7th day of postnatal age., Results: We studied 1094 neonates: SVR was correlated with gestational age (ρ = -0.55, adj-r = -0.46, p < 0.001) and birth weight (ρ = -0.59, adj-r = -0.45, p < 0.001) irrespective of newborn sex. The relationships between SVR, gestational age and birth weight were represented by power equations and SVR was decreasing with increasing age and weight. Age- and weight-based SVR nomograms had optimal goodness-of-fit (non-linear R 2 ≥0.74). Similar results were obtained for body surface indexed-SVR., Conclusions: In hemodynamically stable neonates, SVR decrease with increasing gestational age and birth weight. Specific gestational age and birth weight-based nomograms are provided for the clinical interpretation., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

To better understand the impact of Long COVID on an individual, we explored changes in daily wearable data (step count, resting heart rate (RHR), and sleep quantity) for up to one year in individuals relative to their pre-infection baseline among 279 people with and 274 without long COVID. Participants with Long COVID, defined as symptoms lasting for 30 days or longer, following a SARS-CoV-2 infection had significantly different RHR and activity trajectories than those who did not report Long COVID and were also more likely to be women, younger, unvaccinated, and report more acute-phase (first 2 weeks) symptoms than those without Long COVID. Demographic, vaccine, and acute-phase sensor data differences could be used for early identification of individuals most likely to develop Long COVID complications and track objective evidence of the therapeutic efficacy of any interventions.Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT04336020 ., (© 2024. The Author(s).)

Duchenne Muscular dystrophy (DMD), a yet-incurable X-linked recessive disorder that results in muscle wasting and loss of ambulation is due to mutations in the dystrophin gene. Exonic duplications of dystrophin gene are a common type of mutations found in DMD patients. In this study, we utilized a single guide RNA CRISPR strategy targeting intronic regions to delete the extra duplicated regions in patient myogenic cells carrying duplication of exon 2, exons 2-9, and exons 8-9 in the DMD gene. Immunostaining on CRISPR-corrected derived myotubes demonstrated the rescue of dystrophin protein. Subsequent RNA sequencing of the DMD cells indicated rescue of genes of dystrophin related pathways. Examination of predicted close-match off-targets evidenced no aberrant gene editing at these loci. Here, we further demonstrate the efficiency of a single guide CRISPR strategy capable of deleting multi-exon duplications in the DMD gene without significant off target effect. Our study contributes valuable insights into the safety and efficacy of using single guide CRISPR strategy as a potential therapeutic approach for DMD patients with duplications of variable size., (© 2024. The Author(s).)

In swine farming, animals develop diseases that require the use of antibiotics. In-feed antibiotics as growth promoters have been banned due to the increasing concern of antimicrobial resistance. Seaweeds offer bioactive molecules with antibacterial and antioxidant properties. The aim was to estimate the in vitro properties of seaweed extracts: Ascophyllum nodosum (AN), Palmaria palmata (PP), Ulva lactuca (UL), and 1:1 mixes (ANPP, ANUL, PPUL). Escherichia coli strains were used to test for growth inhibitory activity, and chemical-based assays were performed for antioxidant properties. The treatments were 2 (with/without Escherichia coli) × 2 (F4 + and F18 +) × 5 doses (0, 1.44, 2.87, 5.75, 11.50, and 23.0 mg/mL). Bacteria were supplemented with seaweed extracts, and growth was monitored. The antioxidant activity was assessed with 6 doses (0, 1, 50, 100, 200, 500, and 600 mg/mL) × 6 compounds using two chemical assays. Data were evaluated through SAS. The results showed that AN and UL significantly inhibited (p < 0.05) the growth of F4 + and F18 +. PP and mixes did not display an inhibition of the bacteria growth. AN, PP, UL extracts, and mixes exhibited antioxidant activities, with AN showing the strongest dose-response. Thus, AN and UL seaweed extracts reveal promising antibacterial and antioxidant effects and may be candidates for in-feed additives., (© 2024. The Author(s).)

Objective: To report variants in 26 candidate genes and describe the clinical features of Italian patients with keratoconus (KC)., Subjects/methods: Sixty-four patients with a confirmed diagnosis of KC were enrolled in this genetic association study. Patients were classified into two study groups according to whether they had a confirmed diagnosis of progressive or stable KC. A purpose-developed Next Generation Sequencing (NGS) panel was used to identify and analyse the coding exons and flanking exon/intron boundaries of 26 genes known to be associated with KC and corneal dystrophies. Interpretation of the pathogenic significance of variants was performed using in silico predictive algorithms., Result: The targeted NGS research identified a total of 167 allelic variants of 22 genes in the study population; twenty-four patients had stable keratoconus (n. 54 variants) and forty patients had progressive disease (n. 113 variants). We identified genetic variants of certain pathogenic significance in five patients with progressive KC; in addition, eight novel genetic variants were found in eight patients with progressive KC. Mutations of FLG, LOXHD1, ZNF469, and DOCK9 genes were twice more frequently identified in patients with progressive than stable disease. Filaggrin gene variants were found in 49 patients (76% of total), of whom 32 patients (80% of progressive KC group) had progressive disease., Conclusions: Targeted NGS research provided new insights into the causative effect of candidate genes in the clinical phenotype of keratoconus. Filaggrin mutations were found to represent a genetic risk factor for development of progressive disease in Italy., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Background: Surgical treatment of symptomatic benign prostatic hyperplasia (BPH) has seen an evolution during the last decades. On one hand, en-bloc HoLEP emerged as a valid endoscopic treatment regardless prostate size. On the other hand, robot-assisted simple prostatectomy (RASP) has gained attention in larger prostates showing encouraging results. Herein, for the first time in the scientific scenario, we sought to compare the outcomes of RASP and en-bloc HoLEP cases after propensity-score matching (PSM) analysis., Methods: We retrospectively queried our prospectively database of patients treated with HoLEP or RASP between 2017 and 2022 among two high-volume centers. PSM was applied based on the International Prostate Symptom Score (IPSS) questionnaire, prostate volume and max-flow rate. All procedures were performed by a single surgeon per center. Outcomes were assessed at 1, 3, and 6-month postoperatively and therefore annually. Trifecta definition was used to assess "success" in surgical procedures and was defined as the contemporary presence of: a) no postoperative complications within the first postoperative month; b) 1-month postoperative Qmax >15 ml/s and c) no urinary incontinence at 3-month evaluation., Results: Overall, 48 HoLEP and 47 RASPs were matched. Operative time, hospitalization time (median 4 vs 5 days) and catheterization time (median 3 vs 2 day) were found to be shorter in the HoLEP group as compared to the counterpart (p < 0.05). Early postoperative complication rate was also lower in the HoLEP cohort (6.2% vs 12.6%; p = 0.03) as well as postoperative haemoglobine blood level drop (1.4 vs 2.4 g/dL; p = 0.03). On the other hand, postoperative antegrade ejaculation (55.3% vs 6.8%) 1-month max flow (median 28 vs 24 ml/sec) and continence rates (0% vs 20.8%) favored RASP (p < 0.05). Overall, Trifecta rate was similar in the two groups (76.1% vs 82.6%)., Conclusion: Both HoLEP and RASP are safe and effective treatments for symptomatic BPH. HoLEP demonstrated to have lower perioperative risks while is affecting by a higher probability of transient early UI. On the other hand, RASP is more effective in reducing postoperative ejaculatory dysfunction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

There is a lack of knowledge about the effect of flavanols-rich dark chocolate intake on the anatomy and functionality of retinal vessels. The aim of this study prospective, randomized, blind, crossover clinical trial (ClinicalTrials.gov Identifier: NCT05227248, 07/02/2022) was to evaluate the effect of dark-chocolate intake on the functionality and anatomy of the retinal vessels in healthy subjects using dynamic vessel analyzer (DVA) and optical coherence tomography angiography (OCT-A). Twenty eyes of 20 healthy subjects (mean age, 24.4 ± 1.6 years; 12 females) were enrolled. Participants were randomized to consume 20 g of dark chocolate or 7.5 g of milk chocolate. Visual function, DVA and OCT-A parameters were evaluated before chocolate consumption and two hours later. One week later, the same participants were tested before and after consuming the opposite chocolate. Using OCT-A, no differences were disclosed in terms of perfusion density changes after dark-chocolate and milk-chocolate intake analyzing all chorioretinal plexuses (p > 0.09 in all analyses). Using DVA, a significant increase in the arterial dilation percentage after flicker stimulation was disclosed comparing baseline (2.750 ± 2.054%) with values after the dark chocolate intake (4.145 ± 3.055%, p = 0.016). This difference was not disclosed after the milk chocolate intake (p = 0.465). We disclosed that a reasonable amount of flavanols-rich chocolate in healthy subjects has benefic functional short-term effects in retinal vessels measured with DVA. This suggests a potential role of dark chocolate intake on retinal vessels. Further studies with long-term follow-up are warranted to show if the chronic assumption of dark chocolate could play a favorable role in the prevention of retinal diseases., (© 2024. The Author(s).)

Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 10 3 PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes., (© 2024. The Author(s).)

This study critically examines the use of geodetic strain rates for forecasting long-term earthquake rates in a slow-deforming region such as Italy, challenging the prevailing assumption of their temporal stationarity in interseismic stages for seismic hazard analyses. Typically, earthquake-rate models derived from geodesy assume stationary interseismic loading rates, with stress rates in the upper crust proportional to geodetic strain rates, leading to earthquake rates directly proportional to these strain rate tensors. However, our analysis unveils a pronounced correlation between the epicenters of earthquakes that occurred in the past 60-120 years and areas forecasted for higher future earthquake rates based on geodetic strain rates. This correlation appears weak and scattered in analyses of even older earthquakes. To corroborate our findings, we select the 2009 L'Aquila earthquake (m w  = 6.3) to prove that its apparently marginal viscoelastic relaxation significantly alters the time series of adjacent benchmarks for the following ~ 30-60 years, explaining the high correlation between recent earthquakes and strain rate peaks. Our findings require a methodological shift in interpreting geodetic data for earthquake forecasting, emphasizing the two-component (plate-tectonics-driven stationary long-term deformation, and decadal transient viscoelastic relaxation after an earthquake) nature of crustal stress accumulation recorded in geodetic data. We underscore the potential of geodesy-derived forecasts to provide deeper insights into seismic hazards, stressing the importance of acknowledging the long-term temporal variability inherent in geodetic measurements., (© 2024. The Author(s).)

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival., (© 2024. The Author(s).)

Background: To compare conventional internal limiting membrane (ILM) peeling versus inverted flap technique in small idiopathic macular hole., Methods: Retrospective, multicentre cohort study including consecutive eyes with a ≤250 μm idiopathic macular hole treated with primary vitrectomy. The primary outcome was best-corrected visual acuity (BCVA) change and macular hole closure rate. Closure patterns on optical coherence tomography (OCT) and rates of external limiting membrane (ELM) and ellipsoid zone (EZ) recovery were considered as secondary outcomes., Results: A total of 389 and 250 eyes were included in the conventional ILM peeling group and in the inverted flap group, respectively. Hole closure rate was comparable between the two groups (98.5% in the ILM peeling group and 97.6% in the inverted flap group). Mean BCVA was comparable between the two groups at baseline (p = 0.331). At 12 months, mean BCVA was 0.14 ± 0.19 logMAR in the conventional ILM peeling group and 0.17 ± 0.18 logMAR in the inverted flap group (p = 0.08). At 12 months, 73% of eyes had a U-shape closure morphology in the conventional ILM peeling group versus 55% in the inverted flap group. At 12 months, ELM recovery rate was 96% and 86% in the conventional ILM peeling group and in the inverted flap group, respectively (p < 0.001); EZ recovery rate was 78% and 69%, respectively (p = 0.04)., Conclusions: The inverted flap technique provides no advantages in terms of visual outcome and closure rate in small idiopathic macular hole surgery. Additionally, this technique seems to impair postoperative restoration of external retinal layers compared with conventional peeling., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Metabolic disorders such as insulin resistance and type 2 diabetes are associated with brain dysfunction and cognitive deficits, although the underpinning molecular mechanisms remain elusive. Epigenetic factors, such as non-coding RNAs, have been reported to mediate the molecular effects of nutrient-related signals. Here, we investigated the changes of miRNA expression profile in the hippocampus of a well-established experimental model of metabolic disease induced by high fat diet (HFD). In comparison to the control group fed with standard diet, we observed 69 miRNAs exhibiting increased expression and 63 showing decreased expression in the HFD mice's hippocampus. Through bioinformatics analysis, we identified numerous potential targets of the dysregulated miRNAs, pinpointing a subset of genes regulating neuroplasticity that were targeted by multiple differentially modulated miRNAs. We also validated the expression of these synaptic and non-synaptic proteins, confirming the downregulation of Synaptotagmin 1 (SYT1), calcium/calmodulin dependent protein kinase I delta (CaMK1D), 2B subunit of N-methyl-D-aspartate glutamate receptor (GRIN2B), the DNA-binding protein Special AT-Rich Sequence-Binding Protein 2 (SATB2), and RNA-binding proteins Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) and Neuro-oncological ventral antigen 1 (NOVA1) in the hippocampus of HFD mice. In summary, our study offers a snapshot of the HFD-related miRNA landscape potentially involved in the alterations of brain functions associated with metabolic disorders. By shedding light on the specific miRNA-mRNA interactions, our research contributes to a deeper understanding of the molecular mechanisms underlying the effects of HFD on the synaptic function., (© 2024. The Author(s).)

Predicting epidemic evolution is essential for making informed decisions and guiding the implementation of necessary countermeasures. Computational models are vital tools that provide insights into illness progression and enable early detection, proactive intervention, and targeted preventive measures. This paper introduces Sybil, a framework that integrates machine learning and variant-aware compartmental models, leveraging a fusion of data-centric and analytic methodologies. To validate and evaluate Sybil's forecasts, we employed COVID-19 data from several European and U.S. states. The dataset included the number of new and recovered cases, fatalities, and variant presence over time. We evaluate the forecasting precision of Sybil in periods in which there is a change in the trend of the pandemic evolution or a new variant appears. Results demonstrate that Sybil outperforms conventional data-centric approaches, being able to forecast accurately the changes in the trend, the magnitude of these changes, and the future prevalence of new variants., (© 2024. The Author(s).)

We report neutron-scattering measurements of the density of states (DOS) of water and liquid Fomblin in a wide range of temperatures. In the liquid phase, we confirm the presence of a universal low-energy linear scaling of the experimental DOS as a function of the frequency, g ( ω ) = a ( T ) ω , which persists at all temperatures. The low-frequency scaling of the DOS exhibits a sharp jump at the melting point of water, below which the standard Debye's law, g ( ω ) ∝ ω 2 , is recovered. On the contrary, in Fomblin, we observe a continuous transition between the two exponents reflecting its glassy dynamics, which is confirmed by structure measurements. More importantly, in both systems, we find that the slope a(T) grows with temperature following an exponential Arrhenius-like form, a ( T ) ∝ exp ( - ⟨ E ⟩ / T ) . We confirm this experimental trend using molecular dynamics simulations and show that the prediction of instantaneous normal mode (INM) theory for a(T) is in qualitative agreement with the experimental data., (© 2024. The Author(s).)

Radiotherapy (RT) plays a critical role in the management of rhabdomyosarcoma (RMS), the prevalent soft tissue sarcoma in childhood. The high risk PAX3-FOXO1 fusion-positive subtype (FP-RMS) is often resistant to RT. We have recently demonstrated that inhibition of class-I histone deacetylases (HDACs) radiosensitizes FP-RMS both in vitro and in vivo. However, HDAC inhibitors exhibited limited success on solid tumors in human clinical trials, at least in part due to the presence of off-target effects. Hence, identifying specific HDAC isoforms that can be targeted to radiosensitize FP-RMS is imperative. We, here, found that only HDAC3 silencing, among all class-I HDACs screened by siRNA, radiosensitizes FP-RMS cells by inhibiting colony formation. Thus, we dissected the effects of HDAC3 depletion using CRISPR/Cas9-dependent HDAC3 knock-out (KO) in FP-RMS cells, which resulted in Endoplasmatic Reticulum Stress activation, ERK inactivation, PARP1- and caspase-dependent apoptosis and reduced stemness when combined with irradiation compared to single treatments. HDAC3 loss-of-function increased DNA damage in irradiated cells augmenting H2AX phosphorylation and DNA double-strand breaks (DSBs) and counteracting irradiation-dependent activation of ATM and DNA-Pkcs as well as Rad51 protein induction. Moreover, HDAC3 depletion hampers FP-RMS tumor growth in vivo and maximally inhibits the growth of irradiated tumors compared to single approaches. We, then, developed a new HDAC3 inhibitor, MC4448, which showed specific cell anti-tumor effects and mirrors the radiosensitizing effects of HDAC3 depletion in vitro synergizing with ERKs inhibition. Overall, our findings dissect the pro-survival role of HDAC3 in FP-RMS and suggest HDAC3 genetic or pharmacologic inhibition as a new promising strategy to overcome radioresistance in this tumor., (© 2024. The Author(s).)

Spaceborne-based monitoring for environmental purposes has become a well-established practice. The recent progress of synthetic aperture radar (SAR) sensors, including through the European Space Agency's (ESA) Sentinel-1 constellation, has enabled the scientific community to identify and monitor several geohazards, including subsidence ground deformations. A case study in the Tuscany Region, Italy, highlights the effectiveness of interferometric synthetic aperture radar (InSAR) in detecting abrupt increases in ground deformation rates in an industrial area of Montemurlo municipality. In this case, InSAR data enabled prompt identification of the phenomenon, supporting the authorities in charge of environmental management to thoroughly investigate the situation. First, an on-site validation was performed via field surveys confirming the presence of cracks and fissures on some edifices. Further analysis, including water pumping rates, settlement gauge and topographic levelling, corroborated the InSAR data's findings regarding vertical deformation. Integration of collected data allowed for spatial identification and assessment of the subsidence bowl and its source depth recognized by the remote sensing data. The Montemurlo case offers a procedural guideline for managing abrupt accelerations, identified by InSAR data in subsidence-prone areas due to fluid overexploitation. In fact, these data proved useful in helping local authorities responsible for hydrogeomorphological risk management. With the exacerbation of deformation issues in subsidence-prone regions due to climate change, early detection and monitoring of such phenomena are increasingly crucial, with InSAR data playing a central role in achieving this goal., (© 2024. The Author(s).)

Superconductivity involving finite-momentum pairing 1 can lead to spatial-gap and pair-density modulations, as well as Bogoliubov Fermi states within the superconducting gap. However, the experimental realization of their intertwined relations has been challenging. Here we detect chiral kagome superconductivity modulations with residual Fermi arcs in KV 3 Sb 5 and CsV 3 Sb 5 using normal and Josephson scanning tunnelling microscopy down to 30 millikelvin with a resolved electronic energy difference at the microelectronvolt level. We observe a U-shaped superconducting gap with flat residual in-gap states. This gap shows chiral 2a × 2a spatial modulations with magnetic-field-tunable chirality, which align with the chiral 2a × 2a pair-density modulations observed through Josephson tunnelling. These findings demonstrate a chiral pair density wave (PDW) that breaks time-reversal symmetry. Quasiparticle interference imaging of the in-gap zero-energy states reveals segmented arcs, with high-temperature data linking them to parts of the reconstructed vanadium d-orbital states within the charge order. The detected residual Fermi arcs can be explained by the partial suppression of these d-orbital states through an interorbital 2a × 2a PDW and thus serve as candidate Bogoliubov Fermi states. In addition, we differentiate the observed PDW order from impurity-induced gap modulations. Our observations not only uncover a chiral PDW order with orbital selectivity but also show the fundamental space-momentum correspondence inherent in finite-momentum-paired superconductivity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Many individuals with cancer are resistant to immunotherapies. Here, we identify the gene encoding the pyrimidine salvage pathway enzyme cytidine deaminase (CDA) among the top upregulated metabolic genes in several immunotherapy-resistant tumors. We show that CDA in cancer cells contributes to the uridine diphosphate (UDP) pool. Extracellular UDP hijacks immunosuppressive tumor-associated macrophages (TAMs) through its receptor P2Y 6 . Pharmacologic or genetic inhibition of CDA in cancer cells (or P2Y 6 in TAMs) disrupts TAM-mediated immunosuppression, promoting cytotoxic T cell entry and susceptibility to anti-programmed cell death protein 1 (anti-PD-1) treatment in resistant pancreatic ductal adenocarcinoma (PDAC) and melanoma models. Conversely, CDA overexpression in CDA-depleted PDACs or anti-PD-1-responsive colorectal tumors or systemic UDP administration (re)establishes resistance. In individuals with PDAC, high CDA levels in cancer cells correlate with increased TAMs, lower cytotoxic T cells and possibly anti-PD-1 resistance. In a pan-cancer single-cell atlas, CDA high cancer cells match with T cell cytotoxicity dysfunction and P2RY6 high TAMs. Overall, we suggest CDA and P2Y 6 as potential targets for cancer immunotherapy., (© 2024. The Author(s).)

The Cosmic Gems arc is among the brightest and highly magnified galaxies observed at redshift z ≈ 10.2 (ref.  1 ). However, it is an intrinsically ultraviolet faint galaxy, in the range of those now thought to drive the reionization of the Universe 2-4 . Hitherto the smallest features resolved in a galaxy at a comparable redshift are between a few hundreds and a few tens of parsecs (pc) 5,6 . Here we report JWST observations of the Cosmic Gems. The light of the galaxy is resolved into five star clusters located in a region smaller than 70 pc. They exhibit minimal dust attenuation and low metallicity, ages younger than 50 Myr and intrinsic masses of about 10 6 M ⊙ . Their lensing-corrected sizes are approximately 1 pc, resulting in stellar surface densities near 10 5 M ⊙  pc -2 , three orders of magnitude higher than typical young star clusters in the local Universe 7 . Despite the uncertainties inherent to the lensing model, they are consistent with being gravitationally bound stellar systems, that is, proto-globular clusters. We conclude that star cluster formation and feedback likely contributed to shaping the properties of galaxies during the epoch of reionization., (© 2024. The Author(s).)

Similar to systematic reviews (SRs) in clinical fields, preclinical SRs address a specific research area, furnishing information on current knowledge, possible gaps, and potential methodological flaws of study design, conduct, and report. One of the main goals of preclinical SRs is to identify aspiring treatment strategies and evaluate if currently available data is solid enough to translate to clinical trials or highlight the gaps, thus justifying the need for new studies. It is imperative to rigorously follow the methodological standards that are widely available. These include registration of the protocol and adherence to guidelines for assessing the risk of bias, study quality, and certainty of evidence. A special consideration should be made for pediatric SRs, clinical and preclinical, due to the unique characteristics of this age group. These include rationale for intervention and comparison of primary and secondary outcomes. Outcomes measured should acknowledge age-related physiological changes and maturational processes of different organ systems. It is crucial to choose the age of the animals appropriately and its possible correspondence for specific pediatric age groups. The findings of well-conducted SRs of preclinical studies have the potential to provide a reliable evidence synthesis to guide the design of future preclinical and clinical studies. IMPACT: This narrative review highlights the importance of rigorous design, conduct and reporting of preclinical primary studies and systematic reviews. A special consideration should be made for pediatric systematic reviews of preclinical studies, due to the unique characteristics of this age group., (© 2024. The Author(s).)