HELP: A computational framework for labelling and predicting human common and context-specific essential genes.

Machine learning-based approaches are particularly suitable for identifying essential genes as they allow the generation of predictive models trained on features from multi-source data. Gene essentiality is neither binary nor static but determined by the context. The databases for essential gene annotation do not permit the personalisation of the context, and their update can be slower than the publication of new experimental data. We propose HELP (Human Gene Essentiality Labelling & Prediction), a computational framework for labelling and predicting essential genes. Its double scope allows for identifying genes based on dependency or not on experimental data. The effectiveness of the labelling method was demonstrated by comparing it with other approaches in overlapping the reference sets of essential gene annotations, where HELP demonstrated the best compromise between false and true positive rates. The gene attributes, including multi-omics and network embedding features, lead to high-performance prediction of essential genes while confirming the existence of essentiality nuances.

Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study.

BACKGROUND/AIM: Late vitamin K deficiency bleeding (VKDB) during early infancy is a serious problem worldwide. Vitamin K (VK) deficiency commonly occurs in newborns who are exclusively breastfed. Protein Induced by VK Absence (PIVKA-II) has been identified as an early indicator of subclinical VK deficiency in neonates, surpassing prothrombin time. To assess PIVKA-II levels at 48 h, 1 and 3 months of age in full-term newborns who were exclusively breastfed and received varying VKDB prophylaxis regimens. METHODS: A prospective observational study was conducted in four hospitals, enrolling 105 newborns. PIVKA-II levels were measured using a sandwich-type enzyme-linked immunosorbent assay. RESULTS: At 48 h of age, there was no significant difference in PIVKA-II concentrations between newborns who received intramuscular administration of 1 mg of phylloquinone (VK1) and those who received oral administration of 2 mg of VK1 at birth. At 1 and 3 months of life, infants who received any supplementation regimen between 2 and 14 weeks exhibited significantly lower PIVKA-II concentrations compared to infants who received only 1 mg of intramuscular VK1 at birth. The prophylaxis involving a dose of 1 mg of intramuscular VK1 at birth followed by oral administration of 150 µg/day of VK1 from the 2nd to the 14th week of life showed the lowest PIVKA-II blood concentrations. CONCLUSIONS: Oral supplementation of VK1 after discharge significantly reduced PIVKA-II concentrations in exclusively breastfed term infants. These findings suggest the importance of oral VK1 supplementation in exclusively breastfed infants during their first 3 months of life to avoid the risk of VK insufficiency.

Mixotrophic Cultivation of Arthrospira platensis (Spirulina) under Salt Stress: Effect on Biomass Composition, FAME Profile and Phycocyanin Content.

Arthrospira platensis holds promise for biotechnological applications due to its rapid growth and ability to produce valuable bioactive compounds like phycocyanin (PC). This study explores the impact of salinity and brewery wastewater (BWW) on the mixotrophic cultivation of A. platensis. Utilizing BWW as an organic carbon source and seawater (SW) for salt stress, we aim to optimize PC production and biomass composition. Under mixotrophic conditions with 2% BWW and SW, A. platensis showed enhanced biomass productivity, reaching a maximum of 3.70 g L-1 and significant increases in PC concentration. This study also observed changes in biochemical composition, with elevated protein and carbohydrate levels under salt stress that mimics the use of seawater. Mixotrophic cultivation with BWW and SW also influenced the FAME profile, enhancing the content of C16:0 and C18:1 FAMES. The purity (EP of 1.15) and yield (100 mg g-1) of PC were notably higher in mixotrophic cultures, indicating the potential for commercial applications in food, cosmetics, and pharmaceuticals. This research underscores the benefits of integrating the use of saline water with waste valorization in microalgae cultivation, promoting sustainability and economic efficiency in biotechnological processes.

Molecular mechanisms of oxidative stress-related neonatal jaundice.

Oxidative stress is a pathological condition characterized by an overload of oxidant products, named free radicals, which are not well counteracted by antioxidant systems. Free radicals induce oxidative damage to many body organs and systems. In neonatal red blood cells, free-radical mediated-oxidative stress leads to eryptosis, a suicidal death process of erythrocytes consequent to alteration of cell integrity. Neonatal red blood cells are targets and at the same time generators of free radicals through the Fenton and Haber-Weiss reactions. Enhanced eryptosis in case of oxidative stress damage may cause anemia if the increased loss of erythrocytes is not enough compensated by enhanced new erythrocytes synthesis. The oxidative disruption of the red cells may cause unconjugated idiopathic hyperbilirubinemia in neonates. High levels of bilirubin are recognized to be dangerous for the central nervous system in newborns, however, many studies have highlighted the antioxidant function of bilirubin. Recently, it has been suggested that physiologic concentration of bilirubin correlates with higher antioxidant status while high pathological bilirubin levels are associated with pro-oxidants effects. The aim of this educational review is to provide an updated understanding of the molecular mechanisms underlying erythrocyte oxidant injury and its reversal in neonatal idiopathic hyperbilirubinemia.

Peripheral Saturation and Perfusion Index on the First Day of Life Play a Role in Early Discharge of Healthy Term Newborns.

Introduction: Pulse oximetry screening is a safe, feasible test, effective in identifying congenital heart diseases in otherwise well-appearing newborns. Uncertainties still persist on the most effective algorithm to be used and the timing of screening. The aim of this study was to evaluate the role of the pulse oximetry screening associated with the peripheral perfusion index performed in the first 24 hours of life for the early detection of congenital heart diseases and noncongenital heart diseases in the newborns. Materials and Methods: A prospective observational cohort study was conducted. The enrollment criteria were as follows: term newborns with an APGAR score >8 at 5 minutes. The exclusion criteria were as follows: clinical signs of prenatal/perinatal asphyxia or known congenital malformations. Four parameters of pulse oximetry screening were utilized: saturation less than 90% (screening 1), saturation of less than 95% in one or both limbs (screening 2), difference of more than 3% between the limbs (screening 3), and preductal peripheral perfusion index or postductal peripheral perfusion index below 0.70 (screening 4). The likelihood ratio, sensibility, specificity, and positive and negative predictive values for identification of congenital heart diseases or noncongenital heart diseases (suspicion of perinatal infection and any respiratory diseases) were evaluated. Results: The best predictive results for minor congenital heart disease were obtained combining screening 3 and screening 4 (χ 2 (1) = 15,279; p < 0.05; OR = 57,900 (9,465-354,180)). Screening 2, screening 3, and screening 4 were predictive for noncongenital heart diseases (χ 2 (1) = 11,550; p < 0.05; OR = 65,744 (10,413-415,097)). Combined screenings 2-4 were predictive for both congenital heart disease and noncongenital heart disease (χ 2 (1) = 22,155; p < 0.05; OR = 117,685 (12,972-1067,648)). Conclusions: Combining peripheral saturation with the peripheral perfusion index in the first 24 hours of life shows a predictive role in the detection of minor congenital heart diseases and neonatal clinical conditions whose care needs attention.

Ensemble of rankers for efficient gene signature extraction in smoke exposure classification.

BACKGROUND: System toxicology aims at understanding the mechanisms used by biological systems to respond to toxicants. Such understanding can be leveraged to assess the risk of chemicals, drugs, and consumer products in living organisms. In system toxicology, machine learning techniques and methodologies are applied to develop prediction models for classification of toxicant exposure of biological systems. Gene expression data (RNA/DNA microarray) are often used to develop such prediction models. RESULTS: The outcome of the present work is an experimental methodology to develop prediction models, based on robust gene signatures, for the classification of cigarette smoke exposure and cessation in humans. It is a result of the participation in the recent sbv IMPROVER SysTox Computational Challenge. By merging different gene selection techniques, we obtain robust gene signatures and we investigate prediction capabilities of different off-the-shelf machine learning techniques, such as artificial neural networks, linear models and support vector machines. We also predict six novel genes in our signature, and firmly believe these genes have to be further investigated as biomarkers for tobacco smoking exposure. CONCLUSIONS: The proposed methodology provides gene signatures with top-ranked performances in the prediction of the investigated classification methods, as well as new discoveries in genetic signatures for bio-markers of the smoke exposure of humans.

Rooming-in Reduces Salivary Cortisol Level of Newborn.

BACKGROUND: Rooming-in practice improves breastfeeding and reduces newborn stress reactivity. When this modality is not available, partial rooming-in after birth can be considered. Salivary cortisol levels (SCLs) are considered reliable biomarkers to indicate stress. OBJECTIVE: To test the hypothesis that rooming-in duration impacts neonatal stress response in hospitalized newborns. DESIGN/METHODS: Forty term newborns, enrolled in the Neonatology and Obstetrics Nursing, C.G. Ruesch, Naples, Italy, were divided, according to the mother's choice, into the study (SG; n = 20) and control (CG; n = 20) groups if they received full (24 hs) or partial (14 hs) rooming-in care, respectively. Saliva samples were collected from all babies between 7:00 a.m. and 8:00 a.m. of the 3rd day of life by using oral swab. Salivary cortisol levels were measured using an enzyme immunoassay kit (Salimetrics LLC, PA, USA). RESULTS: A statistically significant difference in the SCLs between SG and CG was found (median: 258 ng/dl versus 488.5 ng/dl; p = 0.048). CONCLUSIONS: Data support the practice of full rooming-in care compared with partial rooming-in. The rooming-in duration clearly reduces SCLs and likely neonatal stress. These lower SCLs may have long-term positive effects reducing the risk of metabolic syndrome, high blood pressure, and cognitive and behavioural changes.

Giant omphalocele with right lung agenesia and bronchial tracheal hypoplasia: A case report.

The omphalocele is an abdominal wall defect at the base of the umbilical cord, with the worldwide prevalence of 2.6 per 10,000 births. Omphalocele contains herniated abdominal organs and is classified in small and giant based on the size of the defect. Omphalocele is associated with several syndromes or structural anomalies. We reported a case of giant omphalocele of 6 cm with right lung agenesis with tracheal and right bronchial hypoplasia. Laryngeal mask stabilized the newborn allowing endotracheal intubation. Due to serious malformations, the newborn died after few hours of life for cardio-respiratory arrest. Early and accurate prenatal diagnosis allows a better intervention strategies in delivery room, improving the chances of survival and reducing complications for infants with omphalocele.

Laryngeal Mask for Minimally-Invasive Surfactant Administration: A Narrative Review.

The cornerstone of treatment for respiratory distress syndrome in preterm infants is surfactant administration, traditionally performed through an invasive procedure involving tracheal intubation and mechanical ventilation. Consequently, there has been a growing interest in exploring less invasive methods of surfactant delivery to mitigate the associated risks. Currently, several techniques are under evaluation, including intratracheal instillation using a thin catheter, aerosolized or nebulized administration, and guided administration by supraglottic airway devices. One such method is surfactant administration through laryngeal or supraglottic airway, which involves placing a laryngeal mask without the need for laryngoscopy and administering surfactant through the device. The simplicity of laryngeal mask insertion could potentially streamline the surfactant delivery process, eliminating the necessity for advanced skills. This narrative review aimed to assess the current evidence in the literature regarding the benefits and risks associated with surfactant administration through a laryngeal supraglottic airway.

Necrotizing Enterocolitis: A Current Understanding and Challenges for the Future.

This perspective reviews the definition and current understanding of necrotizing enterocolitis and evaluates a future prevention approach to this multifactorial disease. An overview of the prevention approach in general is presented, where key aspects and emerging criticisms are identified. In addition, key elements of early diagnosis and treatment are presented, together with some of their challenges and ambiguities. Moreover, it concludes with emerging questions from the global community to reach a consensus on the definition, diagnosis, and management of necrotizing enterocolitis disease.

Analysis of the Fecal Metabolomic Profile in Breast vs. Different Formula Milk Feeding in Late Preterm Infants.

Human milk is the gold standard for infant nutrition, but when it is not available or insufficient to satisfy the needs of the infant, formula milk is proposed as an effective substitute. A prospective observational cohort study was conducted on late preterm infants fed with breast and two different formula milks. On this basis, they were divided into three groups: group FMPB (fed with formula + postbiotic), group FM (fed with standard formula), and group BM (breastfed). Stool samples for a metabolomic study were collected at T0 (5-7 days after birth), T1 (30 days of life), and T2 (90 days of life), giving rise to 74 samples analyzed via liquid chromatography coupled with high-resolution mass spectrometry. The T0, T1, and T2 LC-MS raw data were processed for Partial Least Square Discriminant Analysis (PLS-DA), followed by a statistical analysis. This preliminary study highlighted a good overlapping between the fecal metabolome of breast and substitute feeding systems, confirming the efficacy of the formula preparations as breast milk substitutes. Moreover, several similarities were also detected between the FMPB and BM metabolome, highlighting that the addition of a postbiotic to standard formula milk could be more effective and considered a better alternative to breast milk.

Long-term benefits of exclusive human milk diet in small for gestational age neonates: a systematic review of the literature.

Evidence about feeding practices' consequences in small for gestational age newborns is not well established because they are less likely to initiate and continue breastfeeding than other newborns. Our aim was to study current knowledge about the benefits of exclusive human milk diet after 2 years of age in small for gestational age newborns. A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline criteria. Pubmed and Scopus were searched for studies published from databases inception until June 2, 2023. Included articles were analysed and synthesised. Risk of bias and level of evidence assessments were performed. They were enrolled small for gestational age newborns fed by breastfeeding, breast milk or donor milk. The systematic review included 9 articles which were related to 4 health domains: neurodevelopment, cardiovascular, somatic growth and bone mineralization and atopy. Extracted data support a beneficial effect of breastfeeding on these outcomes. Better quality of evidence and longer follow-up are needed.

Umbilical cord stump medication with a topical dermo protective powder compared to dry care in healthy full-term and near-term newborns: a two-center prospective cohort study.

BACKGROUND: Proper umbilical cord stump care during the first days of life (both in hospital and at home) should not be overlooked to prevent possible complications (e.g., purulent discharge, granulomas, or periumbilical erythema or omphalitis). Despite the known benefits of its correct execution, the care of umbilical cord stump remains controversial, and many different approaches are described. The World Health Organization suggests the use of dry cord stump care (easy and economic technique) in developed countries, but in many cases in the real life various topical antiseptics are used in combination with dry cord stump. The extracts of Arnica Montana (AM) have been reported to possess antibacterial, anti-inflammatory, antifungal, and immunomodulatory activities, very useful in the management of cord stump in full term infants. METHODS: In our study we evaluated the efficacy of a powder containing AM (study group- GrA) versus dry cord stump (control group-GrB) in a population of healthy newborn >35 weeks of gestational age (GA). RESULTS: Three hundred twenty-six neonates (mean GA 39±1 in both groups and body weight 3200 g and 3400±448 g respectively in GrA and GrB) were enrolled in two standard neonatal care units (163 neonates in GrA and 163 in GrB). At T1 (48 hours after discharge) GrA showed significantly reduced incidence of mild complications in toto, in particular a lower rate of wet umbilical cord stump). No differences between the two groups at T2 (1 week after discharge). CONCLUSIONS: The use of a natural topical dermo-protective powder containing AM reduces the risk of minor complications, both nurse and parental workload in the first days after discharge, but does not have an impact on cord detachment and other complications in neonates >35 weeks GA.

Use and Efficacy of I-Gel in Complicated Intubations in Newborn Infants: A Review of Case Reports in the Literature.

INTRODUCTION: Current guidelines for neonatal resuscitation suggest the use of a laryngeal mask when ventilation with both facemask and endotracheal tube has failed in newborns weighing >2000 g or delivered ≥ 34 weeks of gestation age. Paediatric I-gel® is one of the latest supraglottic airway management devices suitable for children and newborns. I-gel® use was effective in guaranteeing adequate ventilation in patients with anatomic abnormalities in case of respiratory impairment or during surgical procedures after the induction of anaesthesia. OBJECTIVE: The purpose of our review was to evaluate the use and efficacy of I-gel® in case of complicated intubations. METHODS: In July 2023, two authors of this paper independently conducted searches of the MEDLINE, Web of Science, and Scopus databases without imposing any time constraints or other restrictions. Three case reports were included, each describing the use of I-gel® device in difficult intubations in newborns with anatomical abnormalities. RESULTS: No difficulties were reported in the insertion of the device, which was placed even by inexperienced clinicians. CONCLUSION: The data collected highlighted the possibility of using I-gel® not only as a rescue device after attempted and failed endotracheal placement but also as a first choice in selected patients. Studies on larger cohorts would be needed. Further research involving larger patient cohorts of multicentre NICUs is necessary to confirm the use of laryngeal masks in neonates weighing less than 2000 grams.

Predictive Role of Reticulocyte Fluorescence for Late Red Blood Cell Transfusion in Very Low Birth Weight Infants.

BACKGROUND: Nearly 58% of very low birth weight (VLBW) infants receive at least one red blood cell transfusion, which is not without risk. Reticulocyte fluorescence (RF) indicates the degree of cell maturation. The greater the fluorescence, the greater the immaturity of the reticulocytes. AIM: To evaluate RF as a marker of reticulocyte maturity and to investigate its predictive value for transfusion requirement in VLBW infants. METHODS: Complete blood count was performed at 1, 7, 14, 21, and 28 d of age in 104 VLBW infants at the University Hospital of Parma. Iron supplementation was started at 15 d of life. The infants were divided into two groups: those who required transfusion after 28 d of life. (Tr) and those who did not (NTr). RESULTS: Twenty-seven of 104 newborns required a red blood cell transfusion after 28 d of life (Tr group). At 14 d of life, the percentage of high fluorescence reticulocyte (HFR) was significantly higher in the r group than in infants who did not receive any transfusion (NTr groups): 18.5 vs. 5%, p = 0.002. The ROC curve (AUC 74%) revealed an HFR cut-off value of 16.5% as a predictor of the need for red blood cell (RBC) transfusion. CONCLUSIONS: Reticulocyte maturation at 14 d of life is clinically useful for estimating the qualitative impairment of erythropoiesis and predicts the risk of RBC transfusion in VLBW infants. The data suggest the need for tailored iron integration in VLBW infants to improve the quality of hematopoiesis and reduce the risk of blood transfusion.

Community Detection in Protein-Protein Interaction Networks and Applications.

The ability to identify and characterize not only the protein-protein interactions but also their internal modular organization through network analysis is fundamental for understanding the mechanisms of biological processes at the molecular level. Indeed, the detection of the network communities can enhance our understanding of the molecular basis of disease pathology, and promote drug discovery and disease treatment in personalized medicine. This work gives an overview of recent computational methods for the detection of protein complexes and functional modules in protein-protein interaction networks, also providing a focus on some of its applications. We propose a systematic reformulation of frequently adopted taxonomies for these methods, also proposing new categories to keep up with the most recent research. We review the literature of the last five years (2017-2021) and provide links to existing data and software resources. Finally, we survey recent works exploiting module identification and analysis, in the context of a variety of disease processes for biomarker identification and therapeutic target detection. Our review provides the interested reader with an up-to-date and self-contained view of the existing research, with links to state-of-the-art literature and resources, as well as hints on open issues and future research directions in complex detection and its applications.

Untangling the Context-Specificity of Essential Genes by Means of Machine Learning: A Constructive Experience.

Gene essentiality is a genetic concept crucial for a comprehensive understanding of life and evolution. In the last decade, many essential genes (EGs) have been determined using different experimental and computational approaches, and this information has been used to reduce the genomes of model organisms. A growing amount of evidence highlights that essentiality is a property that depends on the context. Because of their importance in vital biological processes, recognising context-specific EGs (csEGs) could help for identifying new potential pharmacological targets and to improve precision therapeutics. Since most of the computational procedures proposed to identify and predict EGs neglect their context-specificity, we focused on this aspect, providing a theoretical and experimental overview of the literature, data and computational methods dedicated to recognising csEGs. To this end, we adapted existing computational methods to exploit a specific context (the kidney tissue) and experimented with four different prediction methods using the labels provided by four different identification approaches. The considerations derived from the analysis of the obtained results, confirmed and validated also by further experiments for a different tissue context, provide the reader with guidance on exploiting existing tools for achieving csEGs identification and prediction.

Does high fidelity neonatal resuscitation simulation increase salivary cortisol levels of health care providers?

BACKGROUND: The use of simulation-based medical education is strongly recommended to insure neonatal resuscitation skills for health caregivers. High fidelity simulation was executed to allow the evaluation of technical and non-technical skills. Salivary cortisol level was considered reliable biomarkers of adrenocortical activity and useful tool to learning assessment and stress response. METHODS: Our primary aim was to test changes in salivary cortisol levels before and after the simulation for neonatal resuscitation between high and low fidelity setting. Secondary aim was to evaluate salivary cortisol level in the participants, leader and not leader. Fifty-two health care providers were divided in ratio 1:1 into low-fidelity (LF group) and high-fidelity scenario (HF group) of neonatal resuscitation. In each group the participants assumed the role of team leader or not team leader. Salivary samples were collected from all participants 5 minutes before and after each simulation scenario by using oral swab. Analysis of difference was analyzed by Kruskal Wallis Test. RESULTS: Salivary cortisol levels were significantly higher in HF group (N.=26) than LF group (N.=26) before the performance (5.407 mmol/L vs. 3.090 mmol/L; P=0.018). In the HF group, salivary cortisol levels were significantly lower after simulation than before (P=0.007), moreover not team leader showed higher salivary cortisol levels before of the simulation than after (P=0.003). Team leaders showed higher salivary cortisol levels than not team leader after high-fidelity scenario (P=0.039). CONCLUSIONS: High-fidelity simulation scenario had a great impact on stress level, furthermore leaders showed higher salivary cortisol levels than not team leaders.

Current Concepts of Corticosteroids Use for the Prevention of Bronchopulmonary Dysplasia.

Despite using antenatal steroids, surfactants and protective ventilation, bronchopulmonary dysplasia (BPD) affects 10-89% of preterm infants. Since lung inflammation is central to the BPD pathogenesis, postnatal systemic corticosteroids could reduce the risk of BPD onset in preterm infants, but short and long-term adverse consequences have been underlined in literature after their use (i.e., hyperglycaemia, hypertension, hypertrophic cardiomyopathy, growth failure, gastrointestinal bleeding, cerebral palsy). Alternative therapeutic strategies such as postponing corticosteroid administration, lowering the cumulative dose, giving pulse rather than continuous doses, or individualizing the dose according to the respiratory condition of the infant have been proposed to avoid their adverse effects. Dexamethasone remains the first-line drug for newborns with severe pulmonary disease beyond the second to the third week of life. Hydrocortisone administration in very preterm infants does not appear to be associated with neurotoxic effects, even if its efficacy in preventing and treating BPD has yet been clearly demonstrated. Alternative methods of corticosteroid administration seem promising. A positive effect on BPD prevention occurs when budesonide is nebulized and intratracheally instilled with a surfactant, but more data are required to establish safety and efficacy in preterm newborns. Additional studies are still needed before the chronic lung disease issue, and its related challenges can be solved.