Search

Recensione di Valentina Sturli, Professori di desiderio. Seduzione e rovina nel romanzo del Novecento. Carocci, 2024.

Robot-assisted extravesical ureteral reimplantation (REVUR) was described for the first time in 2004. Since then, the surgical approach of vesicoureteral reflux (VUR) has changed dramatically. The benefits of this technique are great when compared to the laparoscopic or traditional open approaches. A literature search of PubMed was performed to identify articles covering any aspect of REVUR in the pediatric population. A total of 108 papers published over the period 2004–2024 were collected. Of these, 40 studies were considered valuable in terms of obtaining a complete overview of the REVUR technique. This review aimed to describe the current state of the art of REVUR and define it as the new standard technique for surgical management of selected patients with VUR.

Abstract The increased intake of ultraprocessed foods (UPFs) in the pediatric age paralleled with the risen prevalence of childhood obesity. The Ultraprocessed Foods in Obesity (UFO) Project aimed at investigating the potential mechanisms for the effects of UPFs in facilitating pediatric obesity, focusing on the direct role of advanced glycation end-products (AGEs) on mitochondrial function, the key regulator of obesity pathophysiology. We comparatively investigated the daily dietary intake of UPFs, energy, nutrients, dietary AGEs [Nε -(carboxymethyl)lysine (CML), Nε -(1-carboxyethyl)lysine (CEL), and Nδ -(5-hydro-5- methyl-4-imidazolon-2-yl)-ornithine (MG-H1)] in 53 obese patients and in 100 healthy controls visiting the Tertiary Center for Pediatric Nutrition of the Department of Translational Medical Science at the University of Naples “Federico II”. AGEs skin accumulation and mitochondrial function in peripheral blood mononuclear cells (PBMCs) were also assessed. A higher intake of UPFs and AGEs, energy, protein, fat, and saturated fatty acids was observed in obese patients. Obese children presented significantly higher skin AGEs accumulation and alterations in mitochondrial metabolism. PBMCs from healthy controls exposed to AGEs showed the same mitochondrial alterations observed in patients. These findings support the UPFs role in pediatric obesity, and the need for dietary strategies limiting UPFs exposure for obesity prevention and treatment.

Context. The study of galaxy cluster mass profiles (M(r)) provides constraints on the nature of dark matter and on physical processes affecting the mass distribution. The study of galaxy cluster velocity anisotropy profiles (β(r)) informs the orbits of galaxies in clusters, which are related to their evolution. The combination of mass profiles and velocity anisotropy profiles allows us to determine the pseudo phase-space density profiles (Q(r)); numerical simulations predict that these profiles follow a simple power law in cluster-centric distance. Aims. We determine the mass, velocity anisotropy, and pseudo phase-space density profiles of clusters of galaxies at the highest redshifts investigated in detail to date. Methods. We exploited the combination of the GOGREEN and GCLASS spectroscopic data-sets for 14 clusters with mass M200 ≥ 1014 M⊙ at redshifts 0.9 ≤ z ≤ 1.4. We constructed an ensemble cluster by stacking 581 spectroscopically identified cluster members with stellar mass M∗ ≥ 109.5 M⊙. We used the MAMPOSSt method to constrain several M(r) and β(r) models, and we then inverted the Jeans equation to determine the ensemble cluster β(r) in a non-parametric way. Finally, we combined the results of the M(r) and β(r) analysis to determine Q(r) for the ensemble cluster. Results. The concentration c200 of the ensemble cluster mass profile is in excellent agreement with predictions from Λ cold dark matter (ΛCDM) cosmological numerical simulations, and with previous determinations for clusters of similar mass and at similar redshifts, obtained from gravitational lensing and X-ray data. We see no significant difference between the total mass density and either the galaxy number density distributions or the stellar mass distribution. Star-forming galaxies are spatially significantly less concentrated than quiescent galaxies. The orbits of cluster galaxies are isotropic near the center and more radial outside. Star-forming galaxies and galaxies of low stellar mass tend to move on more radially elongated orbits than quiescent galaxies and galaxies of high stellar mass. The profile Q(r), determined using either the total mass or the number density profile, is very close to the power-law behavior predicted by numerical simulations. Conclusions. The internal dynamics of clusters at the highest redshift probed in detail to date are very similar to those of lower-redshift clusters, and in excellent agreement with predictions of numerical simulations. The clusters in our sample have already reached a high degree of dynamical relaxation.

Is it possible to interact with the dead? Belief in such encounters is more widespread than we might think. Yet sociologists, unlike other disciplines, have not fully engaged the question. Here, I review both long-standing theoretical objections to such research and recent theories that encourage attention to the issue. Leaning on the latter, I use closed- and open-ended survey data collected from 535 Americans to explore what I call “living-deceased perceived interaction.” My data show that nearly half of my study participants report meaningful and regular interactions with deceased relatives and friends who were important in their lives. I examine the characteristics of such interactions—how and when they are performed and what these experiences mean to respondents. I also investigate the role of one’s social location in initiating interactions with the dead. Finally, I explore the social benefits, if any, these interactions provide for individuals who engage in them.

ABSTRACT: We present the first public data release of the GOGREEN (Gemini Observations of Galaxies in Rich Early Environments) and GCLASS (Gemini CLuster Astrophysics Spectroscopic Survey) surveys of galaxies in dense environments, spanning a redshift range 0.8 < z < 1.5. The surveys consist of deep, multiwavelength photometry and extensive Gemini GMOS spectroscopy of galaxies in 26 overdense systems ranging in halo mass from small groups to the most massive clusters. The objective of both projects was primarily to understand how the evolution of galaxies is affected by their environment, and to determine the physical processes that lead to the quenching of star formation. There was an emphasis on obtaining unbiased spectroscopy over a wide stellar mass range (M ≳ 2 × 1010 M⊙), throughout and beyond the cluster virialized regions. The final spectroscopic sample includes 2771 unique objects, of which 2257 have reliable spectroscopic redshifts. Of these, 1704 have redshifts in the range 0.8 < z < 1.5, and nearly 800 are confirmed cluster members. Imaging spans the full optical and near-infrared wavelength range, at depths comparable to the UltraVISTA survey, and includes Hubble Space Telescope/Wide Field Camera 3 F160W (GOGREEN) and F140W (GCLASS). This data release includes fully reduced images and spectra, with catalogues of advanced data products including redshifts, line strengths, star formation rates, stellar masses, and rest-frame colours. Here, we present an overview of the data, including an analysis of the spectroscopic completeness and redshift quality.

ABSTRACT We study the star formation histories (SFHs) and mass-weighted ages of 331 UVJ-selected quiescent galaxies in 11 galaxy clusters and in the field at 1 < z < 1.5 from the Gemini Observations of Galaxies in Rich Early ENvironments (GOGREEN) survey. We determine the SFHs of individual galaxies by simultaneously fitting rest-frame optical spectroscopy and broad-band photometry to stellar population models. We confirm that the SFHs are consistent with more massive galaxies having on average earlier formation times. Comparing galaxies found in massive clusters with those in the field, we find galaxies with M* < 1011.3 M⊙ in the field have more extended SFHs. From the SFHs we calculate the mass-weighted ages, and compare age distributions of galaxies between the two environments, at fixed mass. We constrain the difference in mass-weighted ages between field and cluster galaxies to $0.31_{^{-0.33}}^{_{+0.51}}$ Gyr, in the sense that cluster galaxies are older. We place this result in the context of two simple quenching models and show that neither environmental quenching based on time since infall (without pre-processing) nor a difference in formation times alone can reproduce both the average age difference and relative quenched fractions. This is distinctly different from local clusters, for which the majority of the quenched population is consistent with having been environmentally quenched upon infall. Our results suggest that quenched population in galaxy clusters at z > 1 has been driven by different physical processes than those at play at z = 0.

We study the stellar mass functions (SMFs) of star-forming and quiescent galaxies in 11 galaxy clusters at 1.0

ABSTRACT We present results on the environmental dependence of the star-forming galaxy main sequence in 11 galaxy cluster fields at 1.0 < z < 1.5 from the Gemini Observations of Galaxies in Rich Early Environments Survey (GOGREEN) survey. We use a homogeneously selected sample of field and cluster galaxies whose membership is derived from dynamical analysis. Using [$\rm{O{\small II}}$]-derived star formation rates (SFRs), we find that cluster galaxies have suppressed SFRs at fixed stellar mass in comparison to their field counterparts by a factor of 1.4 ± 0.1 (∼3.3σ) across the stellar mass range: 9.0 < log (M*/M⊙) < 11.2. We also find that this modest suppression in the cluster galaxy star-forming main sequence is mass and redshift dependent: the difference between cluster and field increases towards lower stellar masses and lower redshift. When comparing the distribution of cluster and field galaxy SFRs to the star-forming main sequence, we find an overall shift towards lower SFRs in the cluster population, and note the absence of a tail of high SFR galaxies as seen in the field. Given this observed suppression in the cluster galaxy star-forming main sequence, we explore the implications for several scenarios such as formation time differences between cluster and field galaxies, and environmentally induced star formation quenching and associated time-scales.

The monitoring of trees is crucial for the management of large areas of forest cultivations, but this process may be costly. However, remotely sensed data offers a solution to automate this process. In this work, we used two neural network methods named You Only Look Once (YOLO) and Mask R-CNN to overcome the challenging tasks of counting, detecting, and segmenting high dimensional Red–Green–Blue (RGB) images taken from unmanned aerial vehicles (UAVs). We present a processing framework, which is suitable to generate accurate predictions for the aforementioned tasks using a reasonable amount of labeled data. We compared our method using forest stands of different ages and densities. For counting, YOLO overestimates 8.5% of the detected trees on average, whereas Mask R-CNN overestimates a 4.7% of the trees. For the detection task, YOLO obtains a precision of 0.72 and a recall of 0.68 on average, while Mask R-CNN obtains a precision of 0.82 and a recall of 0.80. In segmentation, YOLO overestimates a 13.5% of the predicted area on average, whereas Mask R-CNN overestimates a 9.2%. The proposed methods present a cost-effective solution for forest monitoring using RGB images and have been successfully used to monitor $\sim 146\comma\; 500$ acres of pine cultivations.

BackgroundIndocyanine green fluorescence technology (ICG) in pediatric minimally invasive surgery has undergone an important improvement in the last 5 years. However, its use in open surgery is still limited. In this paper, we aim to report our preliminary experience with Rubina® lens ICG fluorescence technology in combination with the IMAGE1 S™ system from KARL STORZ in open excision of masses in children.MethodsThe records of 18 patients undergoing open surgery for head, neck and thorax masses between September and November 2022 were retrospectively reviewed. Rubina® lens ICG fluorescence technology system was used in all the cases. In 10 cases we adopted the holding arm system and in 8 cases the hand-held technique. Data about patients' demographics, surgery and outcomes were collected and analyzed through the following criteria: mass localization, intraoperative time (min), ICG administration (ml), intraoperative complications, postoperative complications.ResultsA total of 18 patients were operated: 4 thyroglossal duct cysts, 3 supraorbital cysts, 2 neck masses, 2 pre-auricular and 2 scalp cysts, 2 gynecomastias, 2 lymphangiomas, 1 nose mass. In all the cases, intralesional injection of 0.5–1 ml of ICG solution was performed peri-operatively. Mean operative time was 58.4 min (35–134 min). Postoperative complications included seroma formation in 2 cases. Surgical pathology reports confirmed complete mass excision in all the cases.ConclusionBased on our preliminary experience, ICG fluorescence guided surgery using Rubina® lens system was very helpful also in open surgery procedures. Rubina® lens system permits to have a very low complication rate, a time-saving surgery, a real time reliability of anatomic structures and an excellent clinical safety. In our experience, holding arm system seems more comfortable than hand-held system. However, further cases need to be performed to evaluate the exact role and to identify new indications of this technique in open pediatric surgical procedures.

Introduction: There are scarce papers about the use of fluorescence-guided surgery (FGS) in the open surgical field. This study aimed to assess the usefulness of FGS in an open setting in the pediatric population and to report our preliminary experience using the Rubina® Lens system. Methods: All patients undergoing ICG fluorescence-assisted open surgery over the period September 2022–September 2023 were enrolled. Each surgical procedure was performed using the Rubina® Lens for ICG fluorescence visualization. Results: A total of 25 patients, 14 boys and 11 girls with a median age at surgery of 5.8 years-old (range 0–15), were enrolled. Surgical indications were dermoid/epidermoid cysts of the head (n = 7), lymphangiomas of the head/neck (n = 2), thyroglossal duct cysts (n = 7), gynecomastia (n = 3), preauricular fistula (n = 2), second branchial cleft fistula (n = 1), fibrolipoma of the shoulder (n = 1) and myofibroma of the gluteal/perineal region (n = 2). In all procedures, an intralesional injection of 2.5 mg/mL ICG solution using a 30-gauge needle was administered. No adverse reactions to ICG occurred. Median operative time was 68.6 min (range 35–189). The visualization of ICG-NIRF with the Rubina® Lens was achieved in all cases. No intraoperative complications were reported. Postoperative complications occurred in 3/25 patients (12%), with gynecomastia (n = 1), thyroglossal duct cyst (n = 1) and neck lymphangioma (n = 1), who developed a fluid collection in the surgical site, requiring needle aspiration in outpatient care (Clavien–Dindo 2). Complete mass excision was confirmed with pathology reports. Conclusions: Based on this initial experience, FGS using the Rubina® Lens was very helpful in open surgery, providing enhanced visualization of anatomy and identification of margins, real-time reliability and low complication rate. It was easy to use, time saving, feasible and clinically safe. Previous experience in MIS is necessary to adopt this technology. The accuracy of the injection phase is important to avoid diffusion of the ICG into the perilesional tissue.

We present results on the rest-frame H-band luminosity functions (LFs) of red-sequence galaxies in seven clusters at 1.0 < z < 1.3 from the Gemini Observations of Galaxies in Rich Early Environments Survey. Using deep GMOS and IRAC 3.6 μm imaging, we identify red-sequence galaxies and measure their LFs down to MH∗ ∼ MH∗ + (2.0 - 3.0) . By stacking the entire sample, we derive a shallow faint-end slope of α ∼ -0.35-0.15+0.15 and MH∗ ∼ -23.520.17+0.15, suggesting that there is a deficit of faint red-sequence galaxies in clusters at high redshift. By comparing the stacked red-sequence LF of our sample with a sample of clusters at z ∼ 0.6, we find an evolution of the faint end of the red sequence over the ∼2.6 Gyr between the two samples, with the mean faint-end red-sequence luminosity growing by more than a factor of 2. The faint-to-luminous ratio of our sample (0.78-0.15+0.19) is consistent with the trend of decreasing ratio with increasing redshift proposed in previous studies. A comparison with the field shows that the faint-to-luminous ratios in clusters are consistent with those in the field at z ∼ 1.15 and exhibit a stronger redshift dependence. Our results support the picture that the buildup of faint red-sequence galaxies occurs gradually over time and suggest that faint cluster galaxies, similar to bright cluster galaxies, already experience the quenching effect induced by the environment at z ∼ 1.15.

Abstract In addition to being novel biomarkers for poor cancer prognosis, members of Lymphocyte antigen-6 (Ly6) gene family also play a crucial role in avoiding immune responses to tumors. However, it has not been possible to identify the underlying mechanism of how Ly6 gene regulation operates in human cancers. Transcriptome, epigenome and proteomic data from independent cancer databases were analyzed in silico and validated independently in 334 colorectal cancer tissues (CRC). RNA mediated gene silencing of regulatory genes, and treatment with MEK and p38 MAPK inhibitors were also tested in vitro. We report here that the Lymphocyte antigen 6G6D is universally downregulated in mucinous CRC, while its activation progresses through the classical adenoma-carcinoma sequence. The DNA methylation changes in LY6G6D promoter are intimately related to its transcript regulation, epigenomic and histological subtypes. Depletion of DNA methyltransferase 1 (DNMT1), which maintains DNA methylation, results in the derepression of LY6G6D expression. RNA-mediated gene silencing of p38α MAPK or its selective chemical inhibition, however, reduces LY6G6D expression, reducing trametinib’s anti-inflammatory effects. Patients treated with FOLFOX-based first-line therapy experienced decreased survival due to hypermethylation of the LY6G6D promoter and decreased p38α MAPK signaling. We found that cancer-specific immunodominant epitopes are controlled by p38α MAPKs signaling and suppressed by DNA methylation in histological variants with Mucinous differentiation. This work provides a promising prospective for clinical application in diagnosis and personalized therapeutic strategies of colorectal cancer.

Postoperative pain presents several challenges in pediatric Minimally Invasive Surgery. The Faces, Legs, Activity, Cry, and Consolability (FLACC) scale is a valid scale for pediatric postoperative pain. The aim of our study was to assess postoperative pain using FLACC scale and to analyze the correlation between FLACC scale score and analgesic requirement in children underwent Minimally Invasive Surgery. We retrospectively analyzed data of 153 children aged 2 months-3 years who underwent Minimally Invasive Surgery in our unit from January 2019 and December 2019. Postoperative pain assessment was established using FLACC scale. In each patient were analyzed the correlation between FLACC score and analgesic requirement. Pain evaluation was assigned immediately after surgery and at 15 and 60 minutes. 36.6% of patients (56 children) were asleep so considered pain free; 21.6% of patients (33 children) had a FLACC score more than 7 so they required analgesics and the pain assessment 15 and 60 minutes after was significantly lower. 41.8% of patients (64 children) had a postoperative FLACC score less than 3, so they didn’t require any analgesic treatment. On the basis of our results, we recommend FLACC scale for postoperative pain assessment in children underwent MIS aged 2 months-3 years. FLACC scale is an effective and precise scale in detection of postoperative analgesic requirement in children and it could be extended in different age groups with further research.

Summary: Ribonucleoprotein (RNP) condensates are crucial for controlling RNA metabolism and splicing events in animal cells. We used spatial proteomics and transcriptomic to elucidate RNP interaction networks at the centrosome, the main microtubule-organizing center in animal cells. We found a number of cell-type specific centrosome-associated spliceosome interactions localized in subcellular structures involved in nuclear division and ciliogenesis. A component of the nuclear spliceosome BUD31 was validated as an interactor of the centriolar satellite protein OFD1. Analysis of normal and disease cohorts identified the cholangiocarcinoma as target of centrosome-associated spliceosome alterations. Multiplexed single-cell fluorescent microscopy for the centriole linker CEP250 and spliceosome components including BCAS2, BUD31, SRSF2 and DHX35 recapitulated bioinformatic predictions on the centrosome-associated spliceosome components tissue-type specific composition. Collectively, centrosomes and cilia act as anchor for cell-type specific spliceosome components, and provide a helpful reference for explore cytoplasmic condensates functions in defining cell identity and in the origin of rare diseases.

Timber extraction is a vital process in forest harvesting, particularly in areas with high slopes where timber harvesting methods are not feasible. In such cases, logging towers employing extraction cables are often the most effective solution. This intricate task involves several phases, with the installation of the tower being one of the most critical. It significantly influences the performance and feasibility of timber extraction. Another crucial phase involves strategically positioning logging lines to minimize the installation time while maximizing the load capacity efficiency. This article presents an integer programming mathematical model for determining the optimal positioning of yarders conditioned to logging lines, the timber logging time, and the logging cycle time. Furthermore, a two-phase heuristic algorithm is introduced to address the problem. Both approaches offer a preliminary proposal for the location of logging towers and the arrangement of logging lines within a two-dimensional spatial plane, thereby streamlining the timber extraction process in challenging terrains. Finally, we compare manually generated approximate planning (referred to as the manual planning approach, MPA) with our presented approaches. Our methods outperform the MPA, and notably, our two-phase approach surpasses solvers commonly used in the industry by up to 38% in real case studies.

Using a sample of four galaxy clusters at 1.35 < z < 1.65 and 10 galaxy clusters at 0.85 < z < 1.35, we measure the environmental quenching timescale, t Q, corresponding to the time required after a galaxy is accreted by a cluster for it to fully cease star formation. Cluster members are selected by a photometric-redshift criterion, and categorized as star-forming, quiescent, or intermediate according to their dust-corrected rest-frame colors and magnitudes. We employ a "delayed-then-rapid" quenching model that relates a simulated cluster mass accretion rate to the observed numbers of each type of galaxy in the cluster to constrain t Q. For galaxies of mass M ∗ 1010.5 M o, we find a quenching timescale of t Q = Gyr in the z ∼ 1.5 cluster sample, and Gyr at z ∼ 1. Using values drawn from the literature, we compare the redshift evolution of t Q to timescales predicted for different physical quenching mechanisms. We find t Q to depend on host halo mass such that quenching occurs over faster timescales in clusters relative to groups, suggesting that properties of the host halo are responsible for quenching high-mass galaxies. Between z = 0 and z = 1.5, we find that t Q evolves faster than the molecular gas depletion timescale and slower than an estimated star formation rate-outflow timescale, but is consistent with the evolution of the dynamical time. This suggests that environmental quenching in these galaxies is driven by the motion of satellites relative to the cluster environment, although due to uncertainties in the atomic gas budget at high redshift, we cannot rule out quenching due to simple gas depletion.

Combining exercise with fasting is known to boost fat mass-loss, but detailed analysis on the consequential mobilization of visceral and subcutaneous WAT-derived fatty acids has not been performed. In this study, a subset of fasted male rats (66 h) was submitted to daily bouts of mild exercise. Subsequently, by using gas chromatography—flame ionization detection, the content of 22 fatty acids (FA) in visceral (v) versus subcutaneous (sc) white adipose tissue (WAT) depots was compared to those found in response to the separate events. Findings were related to those obtained in serum and liver samples, the latter taking up FA to increase gluconeogenesis and ketogenesis. Each separate intervention reduced scWAT FA content, associated with increased levels of adipose triglyceride lipase (ATGL) protein despite unaltered AMP-activated protein kinase (AMPK) Thr172 phosphorylation, known to induce ATGL expression. The mobility of FAs from vWAT during fasting was absent with the exception of the MUFA 16:1 n-7 and only induced by combining fasting with exercise which was accompanied with reduced hormone sensitive lipase (HSL) Ser563 and increased Ser565 phosphorylation, whereas ATGL protein levels were elevated during fasting in association with the persistently increased phosphorylation of AMPK at Thr172 both during fasting and in response to the combined intervention. As expected, liver FA content increased during fasting, and was not further affected by exercise, despite additional FA release from vWAT in this condition, underlining increased hepatic FA metabolism. Both fasting and its combination with exercise showed preferential hepatic metabolism of the prominent saturated FAs C:16 and C:18 compared to the unsaturated FAs 18:1 n-9 and 18:2 n-6:1. In conclusion, depot-specific differences in WAT fatty acid molecule release during fasting, irrelevant to their degree of saturation or chain length, are mitigated when combined with exercise, to provide fuel to surrounding organs such as the liver which is correlated with increased ATGL/ HSL ratios, involving AMPK only in vWAT.

We describe a new Large Program in progress on the Gemini North and South telescopes: Gemini Observations of Galaxies in Rich Early Environments (GOGREEN). This is an imaging and deep spectroscopic survey of 21 galaxy systems at 1 < z < 1.5, selected to span a factor >10 in halo mass. The scientific objectives include measuring the role of environment in the evolution of low-mass galaxies, and measuring the dynamics and stellar contents of their host haloes. The targets are selected from the SpARCS, SPT, COSMOS, and SXDS surveys, to be the evolutionary counterparts of today's clusters and groups. The newred-sensitive Hamamatsu detectors on GMOS, coupled with the nod-and-shuffle sky subtraction, allow simultaneous wavelength coverage over λ ~ 0.6-1.05 μm, and this enables a homogeneous and statistically complete redshift survey of galaxies of all types. The spectroscopic sample targets galaxies with AB magnitudes z' < 24.25 and [3.6] μm < 22.5, and is therefore statistically complete for stellar masses M* ≳ 1010.3M⊙, for all galaxy types and over the entire redshift range. Deep, multiwavelength imaging has been acquired over larger fields for most systems, spanning u through K, in addition to deep IRAC imaging at 3.6 μm. The spectroscopy is ~50 per cent complete as of semester 17A, and we anticipate a final sample of ~500 new cluster members. Combined with existing spectroscopy on the brighter galaxies from GCLASS, SPT, and other sources, GOGREEN will be a large legacy cluster and field galaxy sample at this redshift that spectroscopically covers a wide range in stellar mass, halo mass, and clustercentric radius.

Summary: Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal growth and differentiation, neuronal plasticity, learning, and memory. Using CRISPR/Cas9 technology, we generated a vital Bdnf null mutant line in zebrafish and carried out its molecular and behavioral characterization. Although no defects are evident on a morphological inspection, 66% of coding genes and 37% of microRNAs turned out to be differentially expressed in bdnf−/− compared with wild type sibling embryos. We deeply investigated the circadian clock pathway and confirmed changes in the rhythmic expression of clock (arntl1a, clock1a and clock2) and clock-controlled (aanat2) genes. The modulatory role of Bdnf on the zebrafish circadian clock was then validated by behavioral tests highlighting the absence of circadian activity rhythms in bdnf−/− larvae. The circadian behavior was partially rescued by pharmacological treatment. The bdnf−/− zebrafish line presented here is the first valuable and stable vertebrate model for the study of BDNF-related neurodevelopmental diseases

Pilonidal sinus is a common disease of the natal cleft, which can lead to complications including infection and abscess formation. Various operative techniques are available options for the treatment of this pathology, but the ideal technique is still debatable. Analyzing the literature we found out that more recently minimally invasive approaches have been described. In particular, the mechanism of an endoscopic approach relies on the use of the endoscope without cutaneous tissue damage. Advantages include shorter operative time and time to discharge, which impact resource management in both primary and secondary care: patients undergoing endoscopic technique have a high satisfaction rate, probably due to the low level of postoperative pain and early return to daily activities. Published results of studies of newer approaches have demonstrated a lower short and long-term complication rate compared to open surgery. However, very poor reports are available in literature about pediatric population.

Abstract Background Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. Results We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCOhigh TAMs induce a phenotypic shift towards mesenchymal cellular state of glioma stem cells, promoting both invasive and proliferative activities, as well as therapeutic resistance to irradiation. MARCOhigh TAMs also significantly accelerate tumor engraftment and growth in vivo. Moreover, both MA-TAM master regulators and their target genes are significantly correlated with poor clinical outcomes and are often associated with genomic aberrations in neurofibromin 1 (NF1) and phosphoinositide 3-kinases/mammalian target of rapamycin/Akt pathway (PI3K-mTOR-AKT)-related genes. We further demonstrate the origination of MA-TAMs from peripheral blood, as well as their potential association with tumor-induced polarization states and immunosuppressive environments. Conclusions Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy.

The article proposed in this monographic issue aims to reflect on the process defined as “social construction of emotions”: the possibility of modifying the emotional expressions and the feelings based on the context, the beliefs, the social and the cultural rules that characterize the environment in which we live and act. The sociological analysis will be produced by examining the feature film A particular day (directed by Ettore Scola). It is a sociological work characteristic of the sociology of emotions: the analysis of a media text (filmic, in this case) to critically explain a social process.

Food allergy (FA) is one of the most common chronic conditions in children with an increasing prevalence facilitated by the exposure to environmental factors in predisposed individuals. It has been hypothesized that the increased consumption of ultra-processed foods, containing high levels of dietary advanced glycation end products (AGEs), could facilitate the occurrence of FA. We sought to provide preclinical and clinical evidence on the potential role of AGEs in facilitating the occurrence of FA. Human enterocytes, human small intestine organ culture, and PBMCs from children at risk for allergy were used to investigate the direct effect of AGEs on gut barrier, inflammation, T H 2 cytokine response, and mitochondrial function. Intake of the 3 most common glycation products in Western diet foods, Nε-(carboxymethyl) lysine, Nε-(1-carboxyethyl) lysin, and Nδ-(5-hydro-5- methyl-4-imidazolone-2-yl)-ornithine (MG-H1), and the accumulation of AGEs in the skin were comparatively investigated in children with FA and in age-matched healthy controls. Human enterocytes exposed to AGEs showed alteration in gut barrier, AGE receptor expression, reactive oxygen species production, and autophagy, with increased transepithelial passage of food antigens. Small intestine organ cultures exposed to AGEs showed an increase of CD25+ cells and proliferating crypt enterocytes. PBMCs exposed to AGEs showed alteration in proliferation rate, AGE receptor activation, release of inflammatory and T H 2 cytokines, and mitochondrial metabolism. Significant higher dietary AGE intake and skin accumulation were observed children with FA (n = 42) compared with age-matched healthy controls (n = 66). These data, supporting a potential role for dietary AGEs in facilitating the occurrence of FA, suggest the importance of limiting exposure to AGEs children as a potential preventive strategy against this common condition. [ABSTRACT FROM AUTHOR]

Abstract Background Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically “cold” tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear. Methods We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR and immunofluorescence staining to characterize novel CRC immune biomarkers. The effects of selective antagonists were tested by in vitro assays of long term viability and analysis of kinase active forms using anti-phospho antibodies. Results We identified the lymphocyte antigen 6 complex, locus G6D (LY6G6D) as significantly overexpressed (around 15-fold) in CRC when compared with its relatively low expression in other human solid tumours. LY6G6D up-regulation was predominant in MSS CRCs characterized by an enrichment of immune suppressive regulatory T-cells and a limited repertoire of PD-1/PD-L1 immune checkpoint receptors. Coexpression of LY6G6D and CD15 increases the risk of metastatic relapse in response to therapy. Both JAK-STAT5 and RAS-MEK-ERK cascades act in concert as key regulators of LY6G6D and Fucosyltransferase 4 (FUT4), which direct CD15-mediated immune-resistance. Momelotinib, an inhibitor of JAK1/JAK2, consistently abrogated the STAT5/LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting. Notably, colon cancer cells can evade JAK2/JAK1-targeted therapy by a reversible shift of the RAS-MEK-ERK pathway activity, which explains the treatment failure of JAK1/2 inhibitors in refractory CRC. Conclusions Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human MSS CRC.

Background: Ovarian masses in pediatric populations are the most common abdominal masses in young girls. In neonates, the majority of masses are benign while in children and teen-agers the risk of malignancy exists. The aim of this study is to perform a 25-year experience retrospective analysis of clinical and therapeutic aspects of ovarian tumors in girls, in order to show how the development of minimally invasive technology has changed the management of this pathology. Methods: The records of patients under the age of 18 who were operated in three pediatric surgical units due to ovarian mass, in the last 25 years, were reviewed retrospectively. The study group comprised 147 patients operated between 1996 and 2021 with a diagnosis of ovarian masses. Data involved were demographical, surgical, follow-up and final diagnosis. We analyzed the type of surgical technique, intra-operative data (operative time, the use of different technologies), complications, length of stay and long-term follow-up. Based on these data, we assessed how the surgical approach to ovarian masses has changed in the last 25 years in newborns and young girls. Results: The patients ages ranged between 7 days and 15 years (median, 59 days). All the procedures were completed in laparoscopy or robotics without conversion in open surgery. One-hundred and eleven patients were neonates; they all had follicular cysts and they were all managed in laparoscopy using 1 or 3 trocars. In 80/111 patients (72%), a small part of ovarian parenchyma was saved; in 31/111 patients (28%), in which the ovarian parenchyma was not available, an ovariectomy was performed. Patients in which we saved a small part of ovary, at long term follow-up (minimum follow-up of 12 years) (29/80, 36%), developed a normal ovary at US control. Thirty-six were older patients. They had a histological diagnosis of benign (30) or malign (6) tumors. All the patients (8/36) with a pre-operative suspicion of ovarian malignancy received an ovariectomy and an adnexectomy using sealing devices. In the last 10 years in all the children, except neonates, we adopted sealing devices and, in the last 4 years, in 20 cases, we always adopted ICG fluorescence technology to check ovarian vascularization in case of torsion or to check lympho-nodes condition in case of malignancy. Conclusions: In neonatal ovarian cysts, surgical management remained unchanged and an ovarian sparing procedure is always indicated and the long-term follow-ups confirm this hypothesis. The principal innovation in this age period is the use of ICG fluorescence technology to check ovarian vascularization in case of torsion. In teenagers, the decision-making strategy is based on the tumoral markers and on the morphological aspects of the mass. Robotics cystectomy or ovariectomy now-days represents the safer and faster way to perform this. Sealing devices are essential tools for dissection and resection to avoid bleeding. ICG fluorescence technology in all ages is fundamental to check ovary vascularization after detorsion or to check lympho-node status in case of malignancy. All the suspected lesions have to be removed with an endo-bag.

Background: This study was the second part of a prospective randomized clinical trial and aimed to evaluate the use of a tubular finger oxygen-enriched oil inside-coated dressing device and its effect on the post-operative outcome of children undergoing distal hypospadias repair.Methods: A prospective single-blinded randomized clinical trial was carried out between September 2019 and September 2020. We included all patients with distal hypospadias, who received Snodgrass urethroplasty and preputioplasty. The patients were randomized in two groups according to the type of dressing: tubular finger oxygen-enriched oil inside-coated device (G1) and elastic net bandage with application of oxygen-enriched oil-based gel (G2). The patients were evaluated at 7, 14, 21, 30, and 60 post-operative day (POD).Results: Sixty-four patients (median age 14 months) were included in the study and randomized in two groups, each of 32 patients. Post-operative preputial edema rate was significantly lower in G1 (3/32, 9.3%) compared with G2 (10/32, 31.2%) (p = 0.001). The median duration of preputial edema was significantly shorter in G1 compared with G2 (6 vs. 10.5 days) (p = 0.001). Penile diameter measurements at 4th, 7th, 14th POD proved that entity and duration of post-operative swelling were objectively decreased using the new dressing. The wound healing was significantly faster in G1 compared with G2 (14.2 vs. 18.5 days) (p = 0.001). The post-operative complications rate was significantly lower in G1 (0%) compared with G2 (3/32, 9.3%) (p = 0.001). Foreskin dehiscence occurred in two G2 patients (6.2%) whereas, breakdown of urethroplasty and preputioplasty occurred in one G2 patient (3.1%) due to scratching injuries. The dressing management was subjectively assessed by nurses to be easier in G1 patients compared with G2 ones (median score 1.2 vs. 3.5) (p = 0.001). The median treatment costs were significantly lower in G1 compared with G2 (55 vs. 87 eur) (p = 0.001). No adverse skin reactions occurred.Conclusions: Post-operative dressing using tubular finger oxygen-enriched oil inside-coated device was highly effective, easy to manage, cheaper and associated with a lower rate of foreskin and urethral complications compared with the standard dressing method in pediatric patients undergoing distal hypospadias repair. It was also clinically safe without allergy or intolerance to the product.

Background: Bladder stones (BS) are rare in children. Minimally invasive surgery (MIS) seems to be nowadays the procedure of choice to treat pediatric patients with BS. This study aimed to analyze retrospectively our experience with percutaneous cystolithotomy, endourological treatment with Holmium laser and robotic cystolithotomy in children with BS.Methods: We retrospectively analyzed the data of 13 children (eight boys and five girls) with BS who were treated at our centers between July 2013 and July 2020. The patients received three different MIS procedures for stones removal: five underwent robotic cystolithotomy, five underwent endourological treatment and three received percutaneous cystolithotomy (PCCL). We preferentially adopted endourological approach for stones

Gene-set enrichment analysis is the key methodology for obtaining biological information from transcriptomic space’s statistical result. Since its introduction, Gene-set Enrichment analysis methods have obtained more reliable results and a wider range of application. Great attention has been devoted to global tests, in contrast to competitive methods that have been largely ignored, although they appear more flexible because they are independent from the source of gene-profiles. We analyzed the properties of the Mann–Whitney–Wilcoxon test, a competitive method, and adapted its interpretation in the context of enrichment analysis by introducing a Normalized Enrichment Score that summarize two interpretations: a probability estimate and a location index. Two implementations are presented and compared with relevant literature methods: an R package and an online web tool. Both allow for obtaining tabular and graphical results with attention to reproducible research.

Small non-coding RNAs (ncRNAs) are short non-coding sequences involved in gene regulation in many biological processes and diseases. The lack of a complete comprehension of their biological functionality, especially in a genome-wide scenario, has demanded new computational approaches to annotate their roles. It is widely known that secondary structure is determinant to know RNA function and machine learning based approaches have been successfully proven to predict RNA function from secondary structure information. Here we show that RNA function can be predicted with good accuracy from a lightweight representation of sequence information without the necessity of computing secondary structure features which is computationally expensive. This finding appears to go against the dogma of secondary structure being a key determinant of function in RNA. Compared to recent secondary structure based methods, the proposed solution is more robust to sequence boundary noise and reduces drastically the computational cost allowing for large data volume annotations. Scripts and datasets to reproduce the results of experiments proposed in this study are available at: https://github.com/bioinformatics-sannio/ncrna-deep.

Background: The advent of pediatric endoscopic pilonidal sinus treatment (PEPSiT) has dramatically changed the surgical management of pilonidal sinus disease (PSD) in children and adolescents. This study aimed to report the outcome of our new structurated protocol, including PEPSiT, laser epilation, and oxygen-enriched oil-based gel dressing, for treatment of PSD in pediatric patients and describe tips and tricks of the technique.Methods: We retrospectively reviewed the data of 127 pediatric patients, who underwent PEPSiT for PSD in our institutions over a 36-month period. All patients received laser epilation (LE) before and after surgery. Post-operative dressing was performed using silver sulfadiazine spray and in the last 18 months oxygen-enriched oil-based gel. We divided the patients in two groups according to the protocol adopted: G1 (laser + oxygen-enriched oil-based gel dressing) included 72 patients and G2 (laser + silver sulfadiazine spray dressing) included 55 patients. The two groups were compared regarding success rate, recurrence, wound infection rate, wound healing time, post-operative outcome, time to full daily activities and patient satisfaction.Results: No difference emerged between the two groups regarding the average operative time, the average post-operative pain score, the average analgesic requirement, the average hospitalization and the average time to full daily activities (p = 0.33). No intra- or post-operative complications including wound infection occurred in both groups. The patients required an average number of 7 LE sessions (range 4–10) to achieve complete hair removal. The overall success rate was significantly higher in G1 (n = 71, 98.6%) compared with G2 (n = 50, 90.9%) [p = 0.001]. The recurrence rate was also significantly lower in G1 (n = 1, 1.4%) compared with G2 (n = 5, 9%) [p = 0.001]. Furthermore, G1 reported a faster wound healing (average 21 days) compared with G2 (average 29 days) [p = 0.001] and a higher patient satisfaction score (average 4.9) compared with G2 (average 4.2) [p = 0.001].Conclusions: Based upon our experience, PEPSiT may be considered the standard of care for surgical treatment of PSD in children and adolescents. Our new structurated protocol consisting of pre-operative LE, PEPSiT, and post-operative wound management with oxygen-enriched oil-based gel dressing and LE, allowed to achieve an excellent outcome, with a success rate > 98%.

Background: Indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) has been recently adopted in pediatric minimally invasive surgery (MIS). This study aimed to report our experience with ICG-guided NIRF in pediatric laparoscopy and robotics and evaluate its usefulness and technique of application in different pediatric pathologies.Methods: ICG technology was adopted in 76 laparoscopic and/or robotic procedures accomplished in a single division of pediatric surgery over a 24-month period (January 2018–2020): 40 (37 laparoscopic, three robotic) left varicocelectomies with intra-operative lymphography; 13 (10 laparoscopic, three robotic) renal procedures: seven partial nephrectomies, three nephrectomies, and three renal cyst deroofings; 12 laparoscopic cholecystectomies; five robotic tumor excisions; three laparoscopic abdominal lymphoma excisions; three thoracoscopic procedures: two lobectomies and one lymph node biopsy for suspected lymphoma. The ICG solution was administered into a peripheral vein in all indications except for varicocele and lymphoma in which it was, respectively, injected into the testis body or the target organ. Regarding the timing of the administration, the ICG solution was administered intra-operatively in all indications except for cholecystectomy in which the ICG injection was performed 15–18 h before surgery.Results: No conversions to open or laparoscopy occurred. No adverse and allergic reactions to ICG or other postoperative complications were reported.Conclusions: Based upon our 2 year experience, we believe that ICG-guided NIRF is a very useful tool in pediatric MIS to perform a true imaged-guided surgery, allowing an easier identification of anatomic structures and an easier surgical performance in difficult cases. The most common applications in pediatric surgery include varicocele repair, difficult cholecystectomy, partial nephrectomy, lymphoma, and tumors excision but further indications will be soon discovered. ICG-enhanced fluorescence was technically easy to apply and safe for the patient reporting no adverse reactions to the product. The main limitation is represented by the specific equipment needed to apply ICG-guided NIRF in laparoscopic procedures, that is not available in all centers whereas the ICG system Firefly® is already integrated into the robotic platform.

Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) of the blastocyst. In serum/LIF culture condition, they show variable expression of pluripotency genes that mark cell fluctuation between pluripotency and differentiation metastate. The ESCs subpopulation marked by zygotic genome activation gene (ZGA) signature, including Zscan4, retains a wider differentiation potency than epiblast-derived ESCs. We have recently shown that retinoic acid (RA) significantly enhances Zscan4 cell population. However, it remains unexplored how RA initiates the ESCs to 2-cell like reprogramming. Here we found that RA is decisive for ESCs to 2C-like cell transition, and reconstructed the gene network surrounding Zscan4. We revealed that RA regulates 2C-like population co-activating Dux and Duxbl1. We provided novel evidence that RA dependent ESCs to 2C-like cell transition is regulated by Dux, and antagonized by Duxbl1. Our suggested mechanism could shed light on the role of RA on ESC reprogramming.

Abstract Background Long non-coding RNAs (lncRNAs) represent a novel class of non-coding RNAs having a crucial role in many biological processes. The identification of long non-coding homologs among different species is essential to investigate such roles in model organisms as homologous genes tend to retain similar molecular and biological functions. Alignment–based metrics are able to effectively capture the conservation of transcribed coding sequences and then the homology of protein coding genes. However, unlike protein coding genes the poor sequence conservation of long non-coding genes makes the identification of their homologs a challenging task. Results In this study we compare alignment–based and alignment–free string similarity metrics and look at promoter regions as a possible source of conserved information. We show that promoter regions encode relevant information for the conservation of long non-coding genes across species and that such information is better captured by alignment–free metrics. We perform a genome wide test of this hypothesis in human, mouse, and zebrafish. Conclusions The obtained results persuaded us to postulate the new hypothesis that, unlike protein coding genes, long non-coding genes tend to preserve their regulatory machinery rather than their transcribed sequence. All datasets, scripts, and the prediction tools adopted in this study are available at https://github.com/bioinformatics-sannio/lncrna-homologs.

Mucopolysaccharidoses (MPSs) are inherited metabolic diseases caused by the deficiency of lysosomal enzymes needed to catabolize glycosaminoglycans (GAGs). Four therapeutic options are currently considered: enzyme replacement therapy, substrate reduction therapy, gene therapy, and hematopoietic stem cell transplantation. However, while some of them exhibit limited clinical efficacy and require high costs, others are still in development. Therefore, alternative treatments for MPSs need to be explored. Here we describe an innovative therapeutic approach based on the use of a recombinant protein that is able to bind the excess of extracellular accumulated heparan sulfate (HS). We demonstrate that this protein is able to reduce lysosomal defects in primary fibroblasts from MPS I and MPS IIIB patients. We also show that, by masking the excess of extracellular accumulated HS in MPS fibroblasts, fibroblast growth factor (FGF) signal transduction can be positively modulated. We, therefore, suggest the use of a competitive binding molecule for HS in MPSs as an alternative strategy to prevent the detrimental extracellular substrate storage. Keywords: cell signaling, fibroblast growth factor, glycosaminoglycan, heparan sulfate, lysosomal storage diseases, mucopolysaccharidosis

Abstract Background Recently, supervised learning methods have been exploited to reconstruct gene regulatory networks from gene expression data. The reconstruction of a network is modeled as a binary classification problem for each pair of genes. A statistical classifier is trained to recognize the relationships between the activation profiles of gene pairs. This approach has been proven to outperform previous unsupervised methods. However, the supervised approach raises open questions. In particular, although known regulatory connections can safely be assumed to be positive training examples, obtaining negative examples is not straightforward, because definite knowledge is typically not available that a given pair of genes do not interact. Results A recent advance in research on data mining is a method capable of learning a classifier from only positive and unlabeled examples, that does not need labeled negative examples. Applied to the reconstruction of gene regulatory networks, we show that this method significantly outperforms the current state of the art of machine learning methods. We assess the new method using both simulated and experimental data, and obtain major performance improvement. Conclusions Compared to unsupervised methods for gene network inference, supervised methods are potentially more accurate, but for training they need a complete set of known regulatory connections. A supervised method that can be trained using only positive and unlabeled data, as presented in this paper, is especially beneficial for the task of inferring gene regulatory networks, because only an incomplete set of known regulatory connections is available in public databases such as RegulonDB, TRRD, KEGG, Transfac, and IPA.