Complex Dynamics in Simple Neural Networks: Understanding Gradient Flow in Phase Retrieval

Despite the widespread use of gradient-based algorithms for optimizing high-dimensional non-convex functions, understanding their ability of finding good minima instead of being trapped in spurious ones remains to a large extent an open problem. Here we focus on gradient flow dynamics for phase retrieval from random measurements. When the ratio of the number of measurements over the input dimension is small the dynamics remains trapped in spurious minima with large basins of attraction. We find analytically that above a critical ratio those critical points become unstable developing a negative direction toward the signal. By numerical experiments we show that in this regime the gradient flow algorithm is not trapped; it drifts away from the spurious critical points along the unstable direction and succeeds in finding the global minimum. Using tools from statistical physics we characterize this phenomenon, which is related to a BBP-type transition in the Hessian of the spurious minima

a metaproteomic pipeline to identify newborn mouse gut phylotypes

Abstract In order to characterize newborn mouse gut microbiota phylotypes in very early-life stages, an original metaproteomic pipeline, based on LC–MS 2 -spectra and Mascot driven NCBI non-redundant repository database interrogation was developed. An original computational analysis assisted in the generation of a taxonomic gut architecture from protein hits to operational taxonomic units (OTUs) and related functional categories. Regardless of the mouse's genetic background, a prevalence of Firmicutes (Lactobacillaceae) and Proteobacteria (Enterobacteriaceae) was observed among the entire Eubacteria taxonomic node. However, a higher abundance of Firmicutes was retrieved for Balb/c gut microbiota compared to Rag2 ko mice, the latter was mainly characterized by a Proteobacteria enriched microbiota. The metaproteomic-obtained OTUs were supported, for the identification (ID) of the cultivable bacteria fraction, corroborated by axenic culture-based MALDI-TOF MS IDs. Particularly, functional analysis of Rag2 ko mice gut microbiota proteins revealed the presence of abundant glutathione, riboflavin metabolism and pentose phosphate pathway components, possibly related to genetic background. The metaproteomic pipeline herein presented may represent a useful tool to investigate the highly debated onset of the human gut microbiota in the first days of life, when the bacterial composition, despite its very low diversity (complexity), is still very far from an exhaustive description and other complex microbial consortia. Biological significance The manuscript deals with a "frontier" topic regarding the study of the gut microbiota and the application of a metaproteomic pipeline to unveil the complexity of this fascinating ecosystem at the very early stages of life. Indeed during these phases, its diversity is very low but the bacterial content is highly "instable", and the relative balance between mucosal and fecal bacteria starts its dynamics of "fight" to get homeostasis. However, in the neonatal period, especially immediately after birth, a comprehensive description of this microbial eco-organ is still lacking, while it should be mandatory to highlight its first mechanisms of homeostasis and perturbation, while it co-develops with and within the host species. In order to unravel its low but almost unknown microbial community multiplicity, the newborn mouse gut, characterized by a "very" low complexity, was herein selected as model to design a LC–MS 2 -based shotgun metaproteomic approach, potentially suitable to study onset and shaping in human newborns. A microbiological semi-automatic computational analysis was performed to infer gut phylotypes; such as proof of evidence, related OTUs were compared to axenic-culture-based MALDI-TOF MS IDs showing consistency at family and phyla levels for the bacterial cultivable fraction. This article is part of a Special Issue entitled: Trends in Microbial Proteomics

Giovanni Sartori e la democrazia della Seconda Repubblica

Il saggio ripercorre e analizza criticamente tutti i passaggi istituzionali della cosiddetta Seconda Repubblica, ossia della peculiare democrazia maggioritaria che si imposta in Italia a partire dal 1994. Tali passaggi sono visti all'interno del pensiero di Giovanni Sartori e in particolare della sua teoria della democrazia. Tale pensiero si è manifestato sia attraverso opere scientifiche sia attraverso una continua attività pubblicistica, in particolare dalle colonne, come editorialista, del Corriere della Sera. Dall'esame di questo pensiero emerge una serrata e continua critica dei caratteri istituzionali della peculiare democrazia maggioritaria all'italiana.The essay traces and critically analyzes all the institutional steps of the so-called Italian Second Republic, that is the peculiar majoritarian democracy that is set in Italy since 1994. These steps are seen within the thoughts of Giovanni Sartori and in particular of his theory of democracy . Such thinking has manifested both through scientific works both through continuous publications, in particular from the columns, as a columnist, of the Corriere della Sera. From an examination of this thinking emerges a close and continuous criticism of the institutional character of the distinctive Italian style majoritarian democracy

Mutational and large deletion study of genes implicated in hereditary forms of primary hyperparathyroidism and correlation with clinical features

The aim of this study was to carry out genetic screening of the MEN1, CDKN1B and AIP genes, both by direct sequencing of the coding region and multiplex ligation-dependent probe amplification (MLPA) assay in the largest monocentric series of Italian patients with Multiple Endocrine Neoplasia type 1 syndrome (MEN1) and Familial Isolated Hyperparathyroidism (FIHP). The study also aimed to describe and compare the clinical features of MEN1 mutation-negative and mutation-positive patients during long-term follow-up and to correlate the specific types and locations of MEN1 gene mutations with onset and aggressiveness of the main MEN1 manifestations. A total of 69 index cases followed at the Endocrinology Unit in Pisa over a period of 19 years, including 54 MEN1 and 15 FIHP kindreds were enrolled. Seven index cases with MEN1 but MEN1 mutation-negative, followed at the University Hospital of Cagliari, were also investigated. FIHP were also tested for CDC73 and CaSR gene alterations. MEN1 germline mutations were identified in 90% of the index cases of familial MEN1 (F-MEN1) and in 23% of sporadic cases (S-MEN1). MEN1 and CDC73 mutations accounted for 13% and 7% of the FIHP cohort, respectively. A CDKN1B mutation was identified in one F-MEN1. Two AIP variants of unknown significance were detected in two MEN1-negative S-MEN1. A MEN1 positive test best predicted the onset of all three major MEN1-related manifestations or parathyroid and gastro-entero-pancreatic tumors during follow-up. A comparison between the clinical characteristics of F and S-MEN1 showed a higher prevalence of a single parathyroid disease and pituitary tumors in sporadic compared to familial MEN1 patients. No significant correlation was found between the type and location of MEN1 mutations and the clinical phenotype. Since all MEN1 mutation-positive sporadic patients had a phenotype resembling that of familial MEN1 (multiglandular parathyroid hyperplasia, a prevalence of gastro-entero-pancreatic tumors and/or the classic triad) we might hypothesize that a subset of the sporadic MEN1 mutation-negative patients could represent an incidental coexistence of sporadic primary hyperparathyroidism and pituitary tumors or a MEN1 phenocopy, in our cohort, as in most cases described in the literature

Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP

We analysed calprotectin in sinonasal secretions of different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes to assess its role as a biomarker of non-type 2 inflammation.We included primary diffuse CRSwNP patients (n = 41) and three different control groups [non-allergic rhinitis (NAR) (n = 13), non-allergic eosinophilic syndrome (NARES) (n = 10) and healthy subjects (n = 12)]. Calprotectin levels were detected in nasal secretions using a chemiluminescent immunoassay (CLIA).Calprotectin levels in nasal secretions were significantly higher in all non-type 2 endotypes of CRSwNP compared to healthy controls (p0.05). In contrast, in type-2 CRSwNP calprotectin was significantly lower compared to controls (p0.05). A significant correlation between calprotectin levels and neutrophilic count/HPF was found in CRSwNP (p0.01). Clinically, mean levels of calprotectin and neutrophilia were significantly higher in patients who previously underwent 3 or more endoscopic sinus surgeries (p0.05).Calprotectin in nasal secretions may be a biomarker of non-type 2 inflammation. Low levels of calprotectin are indicative of a type-2 immune response in both CRSwNP and non-allergic rhinitis. We observed that calprotectin levels significantly increased based on the number of previous surgeries.Calprotectina nel secreto nasale: nuovo biomarker di infiammazione non-tipo 2 nella poliposi nasale.Abbiamo analizzato i livelli di calprotectina nelle secrezioni nasali di diversi endotipi di CRSwNP, per valutarne il ruolo di marcatore di infiammazione non-tipo 2.Abbiamo incluso pazienti con CRSwNP diffusa primaria (n = 41) e tre diversi gruppi di controllo [rinite non allergica (NAR) (n = 13), rinite eosinofila non allergica (NARES) (n = 10) e soggetti sani (n = 12)]. I livelli di calprotectina sono stati dosati mediante test di chemoluminescenza.I livelli di calprotectina sono risultati significativamente più alti in tutti gli endotipi non-tipo 2 di CRSwNP, rispetto ai controlli sani (p0,05). Al contrario, nella CRSwNP tipo 2 essa è risultata inferiore rispetto ai controlli (p0,05). È stata riscontrata una correlazione significativa tra i livelli di calprotectina e la conta dei neutrofili/HPF (p0.01). I livelli medi di calprotectina aumentano inoltre nei pazienti in precedenza sottoposti a 3 o più ESS (p0,05).La calprotectina nelle secrezioni nasali può essere considerata un biomarcatore di infiammazione non-tipo 2 mentre bassi livelli di calprotectina sono indicativi di immunoflogosi di tipo 2. Abbiamo infine osservato che i livelli di calprotectina aumentano significativamente in relazione al numero di interventi chirurgici pregressi

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy

Correction: Lung cancer multi-omics digital human avatars for integrating precision medicine into clinical practice: the LANTERN study

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How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice