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Abstract We developed a new seriation merit function for enhancing the visual information of data matrices. A local similarity matrix is calculated, where the average similarity of neighbouring objects is calculated in a limited variable space and a global function is constructed to maximize the local similarities and cluster them into patches by simple row and column ordering. The method identifies data clusters in a powerful way, if the similarity of objects is caused by some variables and these variables differ for the distinct clusters. The method can be used in the presence of missing data and also on more than two-dimensional data arrays. We show the feasibility of the method on different data sets: on QSAR, chemical, material science, food science, cheminformatics and environmental data in two- and three-dimensional cases. The method can be used during the development and the interpretation of artificial neural network models by seriating different features of the models. It helps to identify interpretable models by elucidating clusters of objects, variables and hidden layer neurons. Graphical Abstract

The aim of this study was to determine the prevalence of six viruses, from two families of the order Bunyavirales, in the general population of central Tunisia. Sera collected from 377 asymptomatic blood donors were serologically assayed for Rift Valley fever virus (RVFV), Crimean–Congo hemorrhagic fever virus (CCHFV), and four sandfly-borne phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Cyprus virus (SFCV). Of the 377 subjects enrolled in this study, 17.3% were IgG positive for at least one of the viruses tested. The most frequently detected antibodies were against TOSV (13.3%), followed by SFCV (2.9%), RVFV (1.9%), SFSV (1.3%), and SFNV (1.1%). Only one sample was IgG positive for CCHFV. Dual reactivity was observed in nine cases: SFSV + SFCV in three cases (0.8%) and TOSV + SFNV, TOSV + SFCV, and TOSV + RVFV in two cases (0.5%) each. 15.9% of donors were IgG positive against sandfly-borne phleboviruses. Among the 65 donors IgG positive for phleboviruses, 50.8% were from rural areas compared to 12.3% from urban areas (p < 0.001); 92.3% had animals in their living quarters (p = 0.009); and 70.8% lived in the vicinity of stagnant water (p = 0.062). Seroprevalence was significantly higher among donors living with chronic diseases (p = 0.039). Furthermore, the seroprevalence of phleboviruses was higher in Kairouan, the central governorate, than in the two coastal governorates: Monastir and Sousse, with 33.4%, 24.2%, and 14.9%, respectively. The presence of antibodies in the general population needs further investigation to better assess the extent of these viruses. Only TOSV was known to have an extensive circulation in Tunisia and in North Africa. Continued surveillance and interventions are necessary to detect the emergence of all arboviruses and to prevent further transmission.

Background Immunotherapies are becoming front-line treatments for many advanced cancers, and combinations of two or more therapies are beginning to be investigated. Based on their individual antitumor capabilities, we sought to determine whether combination oncolytic virus (OV) and radiation therapy (RT) may improve cancer outcomes.Methods To investigate the activity of this combination therapy, we used in vitro mouse and human cancer cell lines as well as a mouse model of skin cancer. After initial results, we further included immune checkpoint blockade, whose addition constituted a triple combination immunotherapy.Results Our findings demonstrate that OV and RT reduce tumor growth via conversion of immunologically ‘cold’ tumors to ‘hot’, via a CD8+ T cell-dependent and IL-1α-dependent mechanism that is associated with increased PD-1/PD-L1 expression, and the triple combination of OV, RT, and PD-1 checkpoint inhibition impedes tumor growth and prolongs survival. Further, we describe the response of a PD-1-refractory patient with cutaneous squamous cell carcinoma who received the triple combination of OV, RT, and immune checkpoint inhibitor (ICI), and went on to experience unexpected, prolonged control and survival. He remains off-treatment and is without evidence of progression for >44 months since study entry.Conclusions Effective systemic antitumor immune response is rarely elicited by a single therapy. In a skin cancer mouse model, we demonstrate improved outcomes with combination OV, RT, and ICI treatment, which is associated with mechanisms involving augmented CD8+ T cell infiltration and IL-1α expression. We report tumor reduction and prolonged survival of a patient with skin cancer treated with combination OV, RT, and ICI. Overall, our data provide strong rationale for combining OV, RT, and ICI for treatment of patients with ICI-refractory skin and potentially other cancers.

The aim of the study is to investigate the effects of age, sex, running distance and origin of horse on racing speed for Thoroughbred Arabian horse in Tunisia. Although the occidental type is known to be more successful in racing than the Tunisian type, we undertook this study to try to confirm or deny this supremacy for a sample of racehorses born in Tunisia from occidental father. A total of 333 racing records were considered for race performance. The effects of environmental factors on (sex, age, father’s origin, race distance, number of race seasons) race performance were analyzed using the least-squares method(LSM).The racehorses studied were all Arabian Thoroughbred horses in operation at the racecourse of Ksar Said from 2010 to 2020. They are 180 horses, 90 horses born of a Tunisian father, and 90 horses born in Tunisia ofthe occidentalfather. These horses are the best and most successful in their category. The study revealed that the gender and age effectswere statistically insignificant onracingperformance. Race performance was significantly influenced by the distance and the origin of the father which affirms the improving role of the occidentalhorse in the Tunisian population.

Purpose: The relationship between anxiety or depressive comorbidities, their chronology of onset, and the severity of anorexia nervosa (AN) is not well-studied. We hypothesize that the existence of a comorbidity, particularly before the onset of AN, is associated with greater severity of AN.Methods: One hundred seventy-seven subjects were assessed. The prevalence of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), and social phobia (SP) as well as their chronology of onset were studied. The assessment criteria of AN severity were the overall clinical condition, body mass index (BMI) on admission, lowest BMI, intensity of the eating symptoms, age at the onset of AN, illness duration, number of hospitalizations, and quality of life.Results: Patients with AN had the greatest clinical severity when they had a comorbid disorder over their lifetime, such as MDD, GAD, or SP. These comorbidities along with OCD were associated with a higher level of eating symptoms and a more altered quality of life. A profile of maximum severity was associated with a higher prevalence of MDD and GAD. Concerning the chronology of onset, the age at the start of AN was later in cases of MDD or GAD prior to AN.Conclusion: There seems to be an association between severity of AN and both MDD and GAD. The chronology of onset of the comorbidity did not seem to be associated with the severity.

Abstract Background Anorexia nervosa (AN) is a serious psychiatric illness that begins most of the time during adolescence. An early and efficacious intervention is crucial to minimize the risk of the illness becoming chronic and to limit the occurrence of comorbidities. There is a global consensus on optimal treatment for adolescents suffering from AN: international guidelines recommend single-family therapy that involves the patient and his/her family. Several family therapy approaches have been developed to date. However, these approaches, which imply a direct questioning of intrafamilial dynamics, are not suitable for all patients and families, and the rates of dropout or poor response to treatment remain quite high. A modality of family therapy has been adapted to AN, known as multi-family therapy (MFT), which consists in bringing together several families whose children suffers from the same illness. Objectives of the present randomized clinical trial are to evaluate whether the implementation of MFT in a multi-disciplinary treatment program for adolescents with AN is at least as efficacious as the use of systemic single-family therapy (SFT), with respect to the evolution of body mass index and other clinical outcomes 12 and 18 months after the start of treatment. A cost-efficiency analysis will also be conducted. Methods One hundred fifty patients meeting the inclusion criteria will be randomly assigned to one of the two treatment groups. Patients and their families will receive 10 sessions of therapy spread over 12 months. Body weight, eating disorder and other psychopathology-related symptoms, quality of family relationships, and family satisfaction with treatment will be evaluated during the treatment and at an 18 months follow-up. A cost-efficiency analysis will also be carried out. Discussion We hypothesize that MFT is at least as efficacious as SFT, but at a lesser cost. The identification of possible preferential indications for each technique could help the improvement of therapeutic indications for adolescents suffering from AN and contribute to the earliness of intervention, which is associated with a better outcome. Trial registration ClinicalTrials.gov, NCT03350594. Registered on 22 November 2017. IDRCB number 2016-A00818-43.

The aim of this study was to compare genetically Moroccan (MA) and Tunisian (TN) Barb horses and toe stablish the phylogenic relation between Barb horse and other horse breeds in Morocco by using microsatellites. First, 100 Moroccan barb and 100 Tunisian Barb horses were used. Genetic variability index between and inside the populations were estimated. 133 alleles were detected in the Moroccan population and 125 in the Tunisian. The mean number of alleles was 7.29 and 7.82 respectively for the Tunisian and Moroccan barb horse. The heterozygosity was almost similar in the two groups of Barb horses (TN = 0.716 and MA = 0.714). Fst was estimated at 0.0454 and 0.0780 respectively for TN and MA Barb horses. The Gst was also estimated at 0.012 and the Nei genetic distance at 0.05. The two populations are almost genetically similar and heterogeneous. Finally, 86,5 % of horses were correctly affected to their likelihood population. Secondly, 50 Arabian horses, 50 Arabian-Barb and 50 thoroughbreds and the 200 Barb horses previously studied were used to establish the phylogenic relationships. The use of 17 microsatellites showed that the Barb horses had specific alleles and the highest heterozygosity and the highest genetic distances were obtained with thoroughbred. The two Barb horse populations were highly combined in one side of the phylogenic tree.

Published data on the outcome of maintenance peritoneal dialysis (PD) since the initiation of PD in Tunisia is poor. The purpose of this study is to report long-term clinical outcomes of PD patients through a 10-year experience at a single unit. This is a retrospective review of the medical records of 182 PD patients who were followed up from January 2006 to June 2016. All patients were followed till death, renal transplant, switch over to hemodialysis (HD) or the end of the study in June 2016. The mean age of the incident patients was 43.93 ± 16.95 years. Nineteen (10.4%) were aged >65 years and 59.3% were male. The average duration of follow-up was 27.75 ± 26.18 months. The mean duration of PD treatment was 27.75 ± 26.18 months. There were 186 episodes of peritonitis that occurred over the total study period (54 episodes during the 1st year). The overall incidence of peritonitis during the 10-year study period was 1 per 27.25 patient months. Mechanical complications were noted in 31.2% of cases. Thirty- two (17.6%) patients had catheter displacement. Only 26 cases of hemoperitoneum (14.3%) were recorded. Death occurred in 23.1% of cases. Twenty-two patients (27.5%) were transplanted; 56 patients (70%) were transferred to HD, one patient had renal recovery and one case had voluntarily interrupted PD. In Kaplan–Meier curves of residual renal function (RRF) loss, there was a significant difference between peritonitis group and peritonitis-free group (P = 0.01). Technique and patient survival were associated with diabetes with a significant difference. The main cause of technique failure was peritonitis (61.4%). Moreover, the main repertoried causes of death were cardiovascular and septic causes. The mortality of diabetic and elderly PD patients was higher than mortality in nondiabetic and nonelderly groups, respectively, in our study. Peritonitis was associated with loss of RRF and technique failure.

Facial recognition is a method to identify an individual from his image. It has attracted the intention of a large number of researchers in the field of computer vision in recent years due to its wide scope of application in several areas (health, security, robotics, biometrics...). The operation of this technology, so much in demand in today's market, is based on the extraction of features from an input image using techniques such as SIFT, SURF, LBP... and comparing them with others from another image to confirm or assert the identity of an individual. In this paper, we have performed a comparative study of a machine learning-based approach using several classification methods, applied on two face databases, which will be divided into two groups. The first one is the Train database used for the training stage of our model and the second one is the Test database, which will be used in the test phase of the model. The results of this comparison showed that the SIFT technique merged with the SVM classifier outperforms the other classifiers in terms of identification accuracy rate.

The world was shaken by the arrival of the corona virus (COVID-19), which ravaged all countries and caused a lot of human and economic damage. The world activity has been totally stopped in order to stop this pandemic, but unfortunately until today the world knows the arrival of new wave of contamination among the population despite the implementation of several vaccines that have been made available to the countries of the world and this is due to the appearance of new variants. All variants of this virus have recorded a common symptom which is an infection in the respiratory tract. In this paper a new method of detection of the presence of this virus in patients was implemented based on deep learning using a deep learning model by convolutional neural network architecture (CNN) using a COVID-QU chest X- ray imaging database. For this purpose, a pre-processing was performed on all the images used, aiming at unifying the dimensions of these images and applying a histogram equalization for an equitable distribution of the intensity on the whole of each image. After the pre-processing phase we proceeded to the formation of two groups, the first Train is used in the training phase of the model and the second called Test is used for the validation of the model. Finally, a lightweight CNN architecture was used to train a model. The model was evaluated using two metrics which are the confusion matrix which includes the following elements (ACCURACY, SPECIFITY, PRESITION, SENSITIVITY, F1_SCORE) and Receiver Operating Characteristic (the ROC curve). The results of our simulations showed an improvement after using the histogram equalization technique in terms of the following metrics: ACCURACY 96.5%, SPECIFITY 98.60% and PRESITION 98.66%.

Invasive fungal rhinosinusitis is a rare infection that occurs primarily in immunocompromised patients. The fungal pathogen Alternaria alternata is rarely associated with rhinosinusitis. We report a case of A. alternata rhinosinusitis in an immunocompetent patient. Keywords: Cerebral parenchyma, fungus, mycelian filaments, sinus

We report an observation of facial and upper limb demodicosis, revealing a human immunodeficiency virus infection. After an initial improvement with metronidazole, worsening of skin lesions related to immune reconstitution inflammatory syndrome was observed, requiring the use of steroids. Keywords: Demodex, demodicosis, human immunodeficiency virus, immune reconstitution inflammatory syndrome, metronidazole

Urinary tract infections (UTIs) are common. The diagnosis is confirmed by urine culture which is costly and takes at least 24 hours before results are known. The aim of this study was to determine the diagnostic accuracy of dipstick test for the diagnosis of UTI in symptomatic adult patients. We conducted a cross-sectional study in the department of Infectious Diseases, Sousse-Tunisia during a two-year period. We included all patients with clinical signs of UTI. Urine samples were tested for the presence of leukocyte esterase (LE) and nitrites. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of LE and nitrites were calculated against urine culture as gold standard. Four hundred thirty one patients, 139 men (32%) and 292 women (68%) were included. One hundred sixty six patients (39%) had UTI. The most frequently isolated microorganism was Escherichia coli (75%). LE had a high sensitivity (87%) but a low specificity (64%), while nitrites had a high specificity (95%) but a low sensitivity (48%). Combined positive LE and nitrites had a high PPV (85%) and combined negative LE and nitrites had a high NPV (92%), while positive LE combined with negative nitrites had a low PPV (47%) and a low NPV (53%). In conclusion, in adult patients with UTI symptoms, an alternate diagnosis should be considered if the LE is negative, while an early empirical antibiotic therapy against Enterobacteriaceae should be started if the nitrites are positive.

Ce travail s’est intéressé à la comparaison génétique entre les chevaux Barbes du Maroc et de Tunisie et à l’établissement des relations phylogénétiques entre le cheval Barbe et les autres races de chevaux existantes au Maroc par l’utilisation des microsatellites. Premièrement, 100 chevaux barbes marocains et 100 tunisiens ont été utilisés et les indices de la variabilité intra et inter-population ont été évalués. 133 allèles ont été détectés pour le Barbe marocain contre 125 pour le tunisien. Le NMA était de 7,29 et 7,82 respectivement chez le Barbe tunisien et marocain. Les taux d’hétérozygotie moyens étaient presque similaires chez les deux populations. Le Fst était de 0,0454 et 0,0780 respectivement chez le Barbe de Tunisie et du Maroc. Le Gst était très faible et la distance génétique de Nei était de 0,05. Les deux populations sont donc hétérogènes et pratiquement identiques. 86,5% des individus étudiés ont été affecté convenablement à leur population d’origine. Deuxièmement, 50 chevaux Arabe, 50 Arabe-Barbe et 50 Pur-Sang, en plus des 200 chevaux Barbes préalablement étudiés ont été utilisés. Le cheval barbe a présenté des allèles spécifiques et une forte hétérozygotie avec une distance génétique maximale avec le Pur-Sang. L’arbre phylogénétique a montré, un regroupement très significatif entre les deux populations Barbes d’un côté et les trois autres races de l’autre. Mots clés : cheval, Barbe, analyse génétique, microsatellites, indices de variabilité génétique, arbre phylogénétique

In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1). Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

After publication of our article [1] the authors have notified us of missing to include one name to the authorship list:

La revendication d’un domaine de la « communication publique » constitue une forme d’aboutissement d’un long processus de valorisation d’un domaine de compétence et d’exercice distinct d’autres professions proches et de reconnaissance d’une spécificité et d’un savoir-faire qui justifierait la revendication d’une labellisation en tant que profession. C’est en effet sous les termes de « communication publique » et de « communicants publics » que l’on désigne aujourd’hui en France un secteur d’activités pour l’essentiel constitué de professionnels rattachés aux institutions politiques et administratives. En combinant démarche compréhensive et objectivation, nous reviendrons, dans ce travail, sur les conditions sociopolitiques qui ont permis de poser progressivement, en France, les bases de reconnaissance de l’existence d’une « nouvelle » profession, pour nous intéresser ensuite aux enjeux de l’institutionnalisation des métiers de la communication publique à travers la contribution de la principale association de « professionnels de la communication publique » (Cap’Com), en mettant l’accent sur la portée et les limites de cette action ainsi que les modèles dont elle s’est inspirée pour son travail de légitimation professionnelle. The identification of a specific field of “Public Communication” marks the end of a long process in which the existence of a set of skills quite distinct from those of other related and/or competing professions has finally been recognised. It also acknowledges the specific area of expertise that justifies its claim to be classed as a “profession”. Indeed, in France today the terms “public communication” and “public communicator” are used to denote a sector of the economy that is composed mainly of professional people working for political and administrative institutions. Approaching the subject comprehensively and objectively, this study examines the socio-political conditions that laid the foundations in France for the gradual recognition of a “new” profession. We then consider the issues surrounding the institutionalisation of public communication professions by looking at the contribution made by the principal association of “public communications professionals” (Cap’Com), while emphasising the extent and limits of its activities and the models that provided the inspiration for its work in placing the profession on a legitimate footing.

IFN-λ is the newly established type III IFN with unique immuno-modulatory functions. In contrast to the IFN- family and to some extent IFN-, IFN-λ acts in specific areas of the body to activate resident immune cells and induce local immunity, and is instrumental in preventing infections and keeping transformed cells under control. Mucosal areas of the lung and gastrointestinal tract are now under scrutiny in the elucidation of the immune mechanisms triggered by IFN-λ. New evidence also indicates the crucial role of IFN-λ in promoting viral protection and inducing innate immunity against solid cancers. Based on its unique biological activities among the members of the IFN system, new immunotherapeutic approaches centered around IFN-λ are now emerging for the treatment of cancer, infection, and autoimmune diseases. In the present review, we highlight the recent advances involving IFN-λ immuno-modulatory functions. We also discuss the potential of utilizing IFN-λ as a therapeutic agent.

La trithérapie antirétrovirale a contribué à une baisse considérable de la mortalité liée au VIH. Les causes de décès sont dominées par les infections opportunistes dans les pays en voie de développement et par les maladies cardiovasculaires et les cancers dans les pays développés. L'objectif était de déterminer les causes et les facteurs de risque de décès des patients infectés par le VIH dans le Centre Tunisien. Une étude transversale auprès des patients infectés par le VIH âgés de plus de 15 ans suivis à Sousse et à Monastir entre 2000 et 2014. Le décès était considéré lié au VIH si la cause était un évènement classant SIDA ou s'il était la conséquence d'une infection opportuniste d'étiologie indéterminée avec des CD4 50/mm3, non lié au VIH si la cause n'était pas un évènement classant SIDA, et de cause inconnue si aucune information n'était disponible. Deux cents treize patients, 130 hommes (61%) et 83 femmes (39%), d'âge moyen 4011 ans ont été inclus. Cinquante quatre patients sont décédés, avec une mortalité de 5,4/100 patients-années. La mortalité annuelle a baissé de 5,8% en 2000-2003 à 2,3% en 2012-2014. La survie était de 72% à 5 ans et de 67% à 10 ans. Les décès étaient liés au VIH dans 70,4% des cas. Les causes de décès les plus fréquentes étaient la pneumocystose pulmonaire et la cryptococcose neuroméningée dans 6 cas (11%) chacune. Les facteurs de risque de décès étaient les antécédents d'infections opportunistes, la durée de la trithérapie antirétrovirale = 12 mois et le tabagisme. Le renforcement du dépistage, l'initiation précoce de la trithérapie antirétrovirale, et la lutte contre le tabagisme sont nécessaires afin de réduire la mortalité chez les patients infectés par le VIH en Tunisie.

Les sacroiliites infectieuses sont rares mais peuvent se compliquer de séquelles fonctionnelles invalidantes. Décrire les caractéristiques cliniques et bactériologiques des sacroiliites infectieuses chez les patients suivis à Sousse, Centre Tunisien. Etude rétrospective, descriptive, des cas de sacroiliites infectieuses chez les patients hospitalisés à Sousse entre 2000 et 2015. Le diagnostic a été retenu devant des signes cliniques, d'imagerie, et microbiologiques évocateurs. Vingt-cinq patients, 10 hommes et 15 femmes, d'âge moyen 41 ans (19-78) ont été inclus. Les sacroiliites étaient dues à des bactéries pyogènes dans 14 cas (56%), brucelliennes dans 6 cas (24%), et tuberculeuses dans 5 cas (20%). La durée moyenne d'évolution était de 61, 45 et 402 jours respectivement. Les signes cliniques les plus fréquents étaient les douleurs fessières (92%) et la fièvre (88%). La radiographie standard était anormale dans 75% des cas. La TDM et l'IRM sacro-iliaques dans tous les cas. Le diagnostic a été confirmé bactériologiquement dans 24 cas (96%). La durée moyenne d'antibiothérapie était de 83 jours dans les sacroiliites à pyogènes, et de 102 jours dans les SI brucelliennes. L'évolution était favorable chez 12 patients (48%), 9 patients (36%) ont gardé une douleur sacro-iliaque séquellaire, et 4 patients (16%) sont décédés. Dans notre étude, la durée d'évolution de la sacroiliite infectieuse ne permettait pas de prédire la bactérie responsable, d'où la nécessité d'obtenir une documentation bactériologique afin de prescrire une antibiothérapie appropriée.

The Mogod pony is native of Northwest Tunisia. Its physical characteristics make him well adapted for mountain use. Since the beginning of the 20th century, its number has greatly decreased. To reverse this trend, the breed will have to be better characterized, in particular from the genetic angle, as this might help search into possible relationships between the pony and horse breeds in the area. Electrophoretic systems of albumin (Al), group specific component (Gc), postalbumin (Xk), esterase (Es), transferrin (Tf) and protease inhibitor (Pi) were studied in 47 Mogod ponies by polyacrylamide gel electrophoresis. Allelic frequencies of the six systems were as follows: AlA : 0,36 ; AlB : 0,64 ; GcF : 1,00 ; XkK : 1,00 ; EsI : 0,64 ; EsG : 0,18 ; EsF : 0,17 ; EsS : 0,01 ; TfD : 0,41 ; TfF2 : 0,31 ; TfH : 0,12 ; PiL : 0,35 ; PiU : 0,22 ; PiR ; PiS : 0,09. The blood protein polymorphism of the Mogod pony was compared with that of thoroughbred Arabian horses, Barb horses and Arab-Barb horses based on bibliographic data.

A seroepidemiological survey was carried out on equine viral arteritis in two regions of Tunisia: Ariana and Kasserine. The authors researched specific antibodies against the arteritis virus by the serum neutralization technique in a sample representative of the horse populations in both areas. The sample concerned 199 horses of which 114 were Thoroughbred Arabian from Ariana area and 85 were Barb from Kasserine area; 72 of them were males and 127 females. Results showed that 51 horses (25.6%) were seropositive. Among them 30 (26.3%) were Arabian horses from Ariana and 21 (24.7%) were Barb horses from Kasserine; the difference was not statistically significant. Twelve males (16.66%) and 39 females (30.7%) were positive; the difference was statistically significant. The results are discussed in relation with those obtained by other authors in Tunisia and neighboring countries.

Riluzole, an inhibitor of glutamate release, has shown the ability to inhibit melanoma cell xenograft growth. A phase 0 clinical trial of riluzole as a single agent in patients with melanoma resulted in involution of tumors associated with inhibition of both the mitogen-activated protein kinase (MAPK) and phophoinositide-3-kinase/AKT (PI3K/AKT) pathways in 34% of patients. In the present study, we demonstrate that riluzole inhibits AKT-mediated glycogen synthase kinase 3 (GSK3) phosphorylation in melanoma cell lines. Because we have demonstrated that GSK3 is involved in the phosphorylation of two downstream effectors of transforming growth factor beta (TGFβ), Smad2 and Smad3, at their linker domain, our aim was to determine whether riluzole could induce GSK3β-mediated linker phosphorylation of Smad2 and Smad3. We present evidence that riluzole increases Smad2 and Smad3 linker phosphorylation at the cluster of serines 245/250/255 and serine 204 respectively. Using GSK3 inhibitors and siRNA knock-down, we demonstrate that the mechanism of riluzole-induced Smad phosphorylation involved GSK3β. In addition, GSK3β could phosphorylate the same linker sites in vitro. The riluzole-induced Smad linker phosphorylation is mechanistically different from the Smad linker phosphorylation induced by TGFβ. We also demonstrate that riluzole-induced Smad linker phosphorylation is independent of the expression of the metabotropic glutamate receptor 1 (GRM1), which is one of the glutamate receptors whose involvement in human melanoma has been documented. We further show that riluzole upregulates the expression of INHBB and PLAU, two genes associated with the TGFβ signaling pathway. The non-canonical increase in Smad linker phosphorylation induced by riluzole could contribute to the modulation of the pro-oncogenic functions of Smads in late stage melanomas.

The discovery of the interferon-lambda (IFN-λ) family has considerably contributed to our understanding of the role of interferon not only in viral infections but also in cancer. IFN-λ proteins belong to the new type III IFN group. Type III IFN is structurally similar to type II IFN (IFN-γ) but functionally identical to type I IFN (IFN-α/β). However, in contrast to type I or type II IFNs, the response to type III IFN is highly cell-type specific. Only epithelial-like cells and to a lesser extent some immune cells respond to IFN-λ. This particular pattern of response is controlled by the differential expression of the IFN-λ receptor, which, in contrast to IFN-α, should result in limited side effects in patients. Recently, we and other groups have shown in several animal models a potent antitumor role of IFN-λ that will open a new challenging era for the current IFN therapy.