Purpose The purpose of the 2023 SFR data challenge was to invite researchers to develop artificial intelligence (AI) models to identify the presence of a pancreatic mass and distinguish between benign and malignant pancreatic masses on abdominal computed tomography (CT) examinations. Materials and methods Anonymized abdominal CT examinations acquired during the portal venous phase were collected from 18 French centers. Abdominal CT examinations were divided into three groups including CT examinations with no lesion, CT examinations with benign pancreatic mass, or CT examinations with malignant pancreatic mass. Each team included at least one radiologist, one data scientist, and one engineer. Pancreatic lesions were annotated by expert radiologists. CT examinations were distributed in balanced batches via a Health Data Hosting certified platform. Data were distributed into four batches, two for training, one for internal evaluation, and one for the external evaluation. Training used 83 % of the data from 14 centers and external evaluation used data from the other four centers. The metric (i.e., final score) used to rank the participants was a weighted average of mean sensitivity, mean precision and mean area under the curve. Results A total of 1037 abdominal CT examinations were divided into two training sets (including 500 and 232 CT examinations), an internal evaluation set (including 139 CT examinations), and an external evaluation set (including 166 CT examinations). The training sets were distributed on September 7 and October 13, 2023, and evaluation sets on October 15, 2023. Ten teams with a total of 93 members participated to the data challenge, with the best final score being 0.72. Conclusion This SFR 2023 data challenge based on multicenter CT data suggests that the use of AI for pancreatic lesions detection is possible on real data, but the distinction between benign and malignant pancreatic lesions remains challenging.

BACKGROUND:Low-dose thoracic protocols were developed massively during the COVID-19 outbreak. PURPOSE:To study the impact on image quality (IQ) and the diagnosis reliability of COVID-19 low-dose chest computed tomography (CT) protocols. MATERIAL AND METHODS:COVID-19 low-dose protocols were implemented on third- and second-generation CT scanners considering two body mass index (BMI) subgroups (<25 kg/m2 and >25 kg/m2). Contrast-to-noise ratios (CNR) were compared with a Catphan phantom. Next, two radiologists retrospectively assessed IQ for 243 CT patients using a 5-point Linkert scale for general IQ and diagnostic criteria. Kappa score and Wilcoxon rank sum tests were used to compare IQ score and CTDIvol between radiologists, protocols, and scanner models. RESULTS:In vitro analysis of Catphan inserts showed in majority significantly decreased CNR for the low dose versus standard acquisition protocols on both CT scanners. However, in vivo, there was no impact on the diagnosis: sensitivity and specificity were ≥0.8 for all protocols and CT scanners. The third-generation scanner involved a significantly lower dose compared to the second-generation scanner (CTDIvol of 1.8 vs. 2.6 mGy for BMI <25 kg/m2 and 3.3 vs. 4.6 mGy for BMI >25 kg/m2). Still, the third-generation scanner showed a significantly higher IQ with the low-dose protocol compared to the second-generation scanner (30.9 vs. 28.1 for BMI <25 kg/m2 and 29.9 vs. 27.8 for BMI >25 kg/m2). Finally, the two radiologists had good global inter-reader agreement (kappa ≥0.6) for general IQ. CONCLUSION:Low-dose protocols provided sufficient IQ independently of BMI subgroups and CT models without any impact on diagnosis reliability.

A 15 year child is presented with transfusion dependent chronic anemia. The clinical and laboratory features suggested a chronic nonspherocytic hemolytic anemia (CNSHA) with bone marrow suggestive of congenital dyserythropoietic anemia (CDA). DNA studies revealed the underlying novel mutation in the PKLR gene responsible for pyruvate kinase deficiency.

Epicardial adipose tissue (EAT) is localized between the myocardial surface and visceral layer of the pericardium. It is a metabolically active organ that secretes several cytokines which modulate cardiovascular morphology and function. EAT may interact locally with coronary arteries through paracrine secretion mechanisms. Cytokines from peri-adventitial EAT may pass through the coronary wall by diffusion from the outside to the inside, interacting with cells. An additional potential mechanism by which EAT interacts locally with coronary arteries may be the vasocrine secretion.EAT may play a significant role as a modulator of cardiac functions. In physiologic conditions, EAT has biochemical cardio-protective properties, secreting anti-atherosclerosis substances; in metabolic disease states, EAT secretes bioactive molecules that may play an important role in the pathogenesis of coronary artery disease and cardiac arrhythmias by promoting atherosclerosis. EAT has been evaluated both in the general population and in metabolic disease states that are characterized by inflammation, such as cardiovascular diseases and chronic kidney disease.This review focuses on the current state of knowledge on EAT as a reliable new parameter for cardiovascular risk stratification in high risk populations.

The presence of pre-existing abdominal wall defect (AWD) could represent a potential contraindication for peritoneal dialysis (PD) treatment. We report the results of our 6-year experience involving simultaneous repair of pre-existing AWD and catheter insertion for PD.Patients with estimated glomerular filtration rate (e-GFR) 7-10 ml/min attending a single nephrology clinic between January 2008 and December 2014 were evaluated. Simultaneous AWD repair and catheter placement was performed. For inguinal (IH) or umbilical hernia (UH), a prolene mesh repair technique was adopted. Except for one case of total anaesthesia, the surgical procedure was performed under either spinal or local anaesthesia. Ceftazidime alone or in association with quinolones was administered 1 h before surgery in a single dose. Patients were discharged 2 days after surgery, and returned to the clinic twice during the 1st week for peritoneum washing (first volume of peritoneal dialysis solution: 300 ml). From week 3, volume (2000 ml) and dwells were personalized according to the patient's clinical condition; options were: incremental PD, standard PD, or continuous cycling PD. Surgical follow-up was planned at 1, 6, and 12 months.Peritoneal catheters were inserted in 170 patients. IH, UH and incisional hernia were found in 18, 2 and 1 patients, respectively. IH was bilateral in 4 patients; concomitant IH and UH occurred in 1 patient. There were no deaths, nor intra-operative complications apart from scrotal haematoma in 1 patient. Over a mean follow-up of 551 days (range 342-1274) no hernia recurrence was registered and the peritoneal catheter continued functioning without problems.Simultaneous AWD repair and peritoneal catheter placement seems a reliable and safe surgical procedure that allows patients with AWD to benefit from PD treatment.

Hereditary hemolytic anemias (HHAs) embrace a highly heterogeneous group of chronic disorders with a highly variable clinical picture. HHA encompass (1) hyporegenerative anemias (HAs), as congenital dyserythropoietic anemias (CDAs); (2) hemolytic anemias due to red cell membrane defects (HAMDs), as hereditary spherocytosis (HS) and hereditary stomatocytosis (HST). Although the workflow to diagnose these conditions is a normal clinical practice, differential diagnosis, classification, and patient stratification among HHAs are often very difficult. Beyond achieving a definitive diagnosis, knowing the genetic basis of these patients can be valuable also for guiding treatment. Next generation sequencing (NGS) refers to non-Sanger-based high-throughput DNA sequencing technologies. This technology plays a major role either in disease gene discovery or in clinical use for establishing a genetic diagnosis. Particularly, the major current application of NGS in diagnostics is through design of disease specific panel, named targeted (t)-NGS, in which a selected fraction of genes is sequenced. The primary aim of our study was the development of a fast, accurate, reliable and cost effective diagnostic/prognostic tool for HHAs based on t-NGS. In order to assess the reliability of this approach we created a t-NGS gene panel, named RedPlex, composed by 34 loci causative or candidates of HHAs. In silico design was performed by Agilent SureDesign web tool. For each locus, all coding regions, 5’ and 3’UTRs, and 100 bp flanking splice junctions were included. Sequence length was set at 150×2 nucleotides, and the predicted target size amounted to 538 regions (239.764 kb). Targeted enrichment was performed on 32 patients from 27 unrelated families by HaloPlex Target Enrichment System. High-throughput sequencing was performed by Illumina NextSeq 500. SureCall software was used for bioinformatic and computational analyses. RedPlex panel showed high sensitivity and specificity. It was able to capture at least 99.4% of 538 target regions with high and uniform coverage. We were able to obtain a conclusive diagnosis in approximately 72% of cases. In addition, a lot of patients (39%) showed multiple disease-associated variants suggesting complex inheritance. Indeed, t-NGS approach also allows the identification of “polygenic” genotypes, which may account for the phenotypic variability among HHA patients. Thus, the secondary aim of this project was the study of the interaction between mutated genes in HHA patients. We particularly focused on the functional interaction between two CDA-related genes, GATA1 and SEC23B. The demonstration of the direct interaction of GATA1 transcription factor on the SEC23B promoter provided also an explanation of the variability of phenotypes GATA1-related by means of the crosstalk of this gene with its target SEC23B.

Multicellular organisms have an immune system, which is essential for the survival of living beings. Interest in the immune system has been expanded since common characteristics of innate immunity between Drosophila melanogaster (Meigen, 1830) and mammals were discovered in the 1980. Since then, immunology has mainly focused on the adaptive immune system that seems to be restricted to vertebrates. Unlike the innate immunity, the adaptive one is acquired after exposure to a specific antigen (Ag) and includes: antigen-presenting cells such as macrophages, proliferation of B and T lymphocytes, Ag-specific antibody/cytokine production and immunological memory. Innate immunity is instead a process of cellular defense at low specificity, which is designed to prevent and combat infectious agents that penetrate at the tissue level, and may be the only form of immunity present in invertebrates such as sea urchins. The immune system of invertebrates acts through (i) cellular components (cell-mediated immunity) in which the effectors of defense reactions are represented by immune cells; (ii) soluble factors (humoral immunity), secreted by the immune cells, such as lectins, agglutinins, lysins, antimicrobial peptides and the prophenoloxidase (proPO) activating system, which act in parallel with the immune cells to fight pathogens and other foreign substances. Here we aim to deepen the study on humoral immunity of invertebrates, especially referring to the phylum Echinodermata because of its features shared with protostomes and other deuterostomes, and suggesting a key step during evolution.

Secondary Hyperparathyroidism is an important concurrent cause of cardiovascular and osteo-articular events, as well as, high morbidity and mortality for patients suffering from chronic kidney disease in conservative therapy and dialysis. The usual therapies, such as the vitamin D active metabolites and the phosphate binders did not always demonstrate effective in SHP control. New drugs, such as the calcimimetics, are available, resulting beneficial in highly reducing PTH levels. The only calcimimetic drug clinically used is cinacalcet, whose use is planned only in patients undergoing dialysis (peritoneal and extracorporeal). We describe the clinical case of a caucasian woman of 82 yrs old, with chronic kidney disease and secondary hyperparathyroidism resistant to usual therapies, in conservative treatment, which is prescribed cinacalcet (off-label). At first we found a worsening of the indices of renal function secondary to the effects of the drug on the hydrosaline balance. Increasing the hydrosaline intake we have seen the reduction and the subsequent stability of exams. Cinacalcet was effective in controlling the levels of parathyroid hormone and has contributed significantly to the achievement of optimal calcium-phosphorus balance. In view of these data, there is no doubt in taking in consideration the use of this drug also in the earliest stages of IRC.

Anadenanthera colubrina var. cebil is an important tree species for its cultural, economic, and medicinal uses in South America. In order to characterize A. colubrina populations, we collected fruits from four different sites (San Bernardo, El Cebilar, Metán and El Gallinato) within the species distribution area in Salta Province, Northwestern Argentina. For this, a total of 75 fruits and seeds per site were collected and described using morphological (fruits size and weight; seed weight and number per fruit) and genetic descriptors (ribosomic DNA extraction and PCR; nucleotide alignment and phylogenetic analysis) with standard protocols. Our results showed that the San Bernardo population had the heaviest fruits and seeds (7.89 +/- 0.2g and 0.19 +/- 0.002, respectively), and the Cebilar population the lightest (6.25 +/- 0.18g and 0.15 +/- 0.002g, respectively). Fruits and seeds from Metán and El Gallinato showed similar and intermediate values. The proportion viable (39 to 55%) and aborted (43 to 57%) seeds was different, while the proportion of predated (1.7 to 4.2%) seeds was similar among populations. The genetic analysis showed variability of ITS sequences within the especies, and also when compared with the same Brazilian species. Both, morphologic and genetic descriptors showed a high level of similarity between San Bernardo and Metán, and between El Cebilar and El Gallinato populations. Further studies are needed to assess levels of phenotypic and genetic variability within and between populations of different plant species, since this information is crucial for biodiversity and germplasm long-term conservation.

Fish hemoglobins have been extensively studied, not only for their structural and functional properties, but also because they offer the possibility of investigating functional differentiation and molecular adaptations in marine and freshwater species living in a large variety of environmental conditions. The number of available amino-acid sequences of fish hemoglobins yields enough material to study evolutionary, structural, and functional aspects. Unlike most mammals, including humans, fish often exhibit hemoglobin multiplicity, due to gene-related heterogeneity and gene-duplication events. Here, we review and discuss some new insights about hemoglobin functional differentiation in fish. In this context, the contributions of structural biology extend well beyond the elucidation of mechanisms and hemoglobin-structure/function relationships.

Collision warning and collision avoidance systems are emerging automotive safety technologies that assist drivers in avoiding rear-end collisions. Their function is to allow the driver enough time to avoid the crash and yet avoid annoying the driver with alerts perceived as occurring too early or unnecessary. The aim of this paper was analyzing the driver's behavior in order to define effective driver assistance systems which can be readily accepted by the driver. A study was performed with an interactive fixed-base driving simulator. A sample of 32 drivers drove on a two-lane rural road. Four different driving traffic conditions were implemented. The data recorded during the tests were analyzed to assess the safety distances required by the driver during a car-following situation. Based on the risk perception of the driver a new collision warning algorithm was developed.

Since haemoglobins of all animal species have the same haem group, differences in their properties, including oxygen affinity, electrophoretic mobility and pH sensitivity, must result from the interaction of the prosthetic group with specific amino-acid residues in the primary structure. For this reason, fish globins have been the subject of extensive studies in recent years, not only for their structural characteristics, but also because they offer the possibility to investigate the evolutionary history of these ancient molecules in marine and freshwater species living in a great variety of environmental conditions. This review summarizes the current knowledge on the structure, function and phylogeny of haemoglobins of notothenioid fishes. On the basis of crystallographic analysis, the evolution of the Root effect is analysed. Adaptation of the oxygen transport system in notothenioids seems to be based on evolutionary changes, involving levels of biological organization higher than the structure of haemoglobin. These include changes in the rate of haemoglobin synthesis or in regulation by allosteric effectors, which affect the amount of oxygen transported in blood. These factors are thought to be more important for short-term response to environmental challenges than previously believed.

This review highlights some aspects of the biochemistry of cold-adapted hemoproteins in fish and bacteria, without claiming to be exhaustive. Heme hexacoordination where the sixth ligand is provided by an internal amino-acid residue, in cold-adapted hemoproteins will be discussed.

OBJECTIVE To report an ataxic variant of Alzheimer disease expressing a novel molecular phenotype. DESIGN Description of a novel phenotype associated with a presenilin 1 mutation. SETTING The subject was an outpatient who was diagnosed at the local referral center. PATIENT A 28-year-old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe beta-amyloid (Abeta) deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A presenilin 1 gene (PSEN1) S170F mutation was detected. MAIN OUTCOME MEASURES We analyzed the processing of Abeta precursor protein in vitro as well as the Abeta species in brain tissue. RESULTS The PSEN1 S170F mutation induced a 3-fold increase of both secreted Abeta(42) and Abeta(40) species and a 60% increase of secreted Abeta precursor protein in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N-terminally truncated Abeta species ending at both residues 40 and 42. CONCLUSION These findings define a new Alzheimer disease molecular phenotype and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the Abeta aggregates' composition.

A stability indicating high performance liquid chromatography procedure has been developed for the simultaneous determination of guaifenesin (GUA), methyl p-hydroxybenzoate (MHB) and propyl p-hydroxybenzoate (PHB) in a commercial cough syrup dosage form. The method was specific and stability indicating as chromatographic conditions were selected to provide adequate separation of GUA, MHB and PHB from the putative degradation products guaiacol (GUAI) and p-hydroxybenzoic acid (HBA) as well as from excipients. The isocratic separation and quantitation were achieved within 17 min on a 150-mm column with an ether-linked phenyl stationary phase and a hydrophilic endcapping. The mobile phase was constituted of eluant A: aqueous phosphate buffer (pH 3.0, 10 mM)/acetonitrile 25/75 (v/v) and eluant B:methanol; the A:B ratio was 85:15 (v/v) with a flow rate 1 ml min-1 and detection of analytes at 254 and 276 nm. The method showed good linearity for the GUA-MHB-PHB mixture in the 95-285, 4-12, and 1-3 microg ml-1 ranges, respectively, being all the square of the correlation coefficients greater than 0.999. The interday R.S.D.s were 1.17, 1.14, and 0.91%, for GUA, MHB, and PHP, respectively. The method demonstrated also to be accurate; indeed the average recoveries, at 100% of the target assay concentration, were 100.5, 100.3, and 100.7% with relative standard deviations of 0.8, 0.7, and 0.4% for GUA, MHB, and PHB, respectively, from laboratory prepared samples. The applicability of the method was evaluated in commercial dosage form analysis as well as in stability studies.

Mutations of Presenilin 1 gene (PSEN1) account for the majority of early–onset familial Alzheimer's disease (FAD) cases and they lead to an increased β–amyloid (Aβ) 42/40 ratio. The relative increased production of Aβ42 species is consequently believed the major cause of Aβ accumulation and deposition occurring in FAD. PSEN1 mutations express a wide clinical and pathologic phenotype, suggesting that other factors influence the rate of Aβ42 accumulation and its neurotoxicity. To report a cerebellar variant of Alzheimer's disease expressing a novel pathological and molecular phenotype. A 28–year–old man presented with psychiatric symptoms and cerebellar signs, followed by cognitive dysfunction. Severe Aβ deposition was accompanied by neurofibrillary tangles and cell loss in the cerebral cortex and by Purkinje cell dendrite loss in the cerebellum. A novel PSEN1 S170F mutation was detected. We analyzed the processing of β–amyloid precursor protein (APP) in vitro as well as the Aβ species in brain tissue. The PSEN1 S170F mutation induced a 3–fold increase of both secreted Aβ42 and Aβ40 species, and a 60% increase of secreted β–amyloid precursor protein (βAPPs) in transfected cells. Soluble and insoluble fractions isolated from brain tissue showed a prevalence of N–terminally truncated Aβ species ending at both residues 40 and 42. These findings define a new Alzheimer's disease (AD) phenotype, and support the concept that the phenotypic variability associated with PSEN1 mutations may be dictated by the composition of Aβ aggregates.Molecular Mechanisms of Neurodegeneration Presenilins