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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.

The validation principles on Quantitative Structure Activity Relationship issued by Organization for Economic and Co‐operation and Development describe three criteria of model assessment: goodness of fit, robustness and prediction. In the case of robustness, two ways are possible as internal validation: bootstrap and cross‐validation. We compared these validation metrics by checking their sample size dependence, rank correlations to other metrics and uncertainty. We used modeling methods from multivariate linear regression to artificial neural network on 14 open access datasets. We found that the metrics provide similar sample size dependence and correlation to other validation parameters. The individual uncertainty originating from the calculation recipes of the metrics is much smaller for both ways than the part caused by the selection of the training set or the training/test split. We concluded that the metrics of the two techniques are interchangeable, but the interpretation of cross‐validation parameters is easier according to their similar range to goodness‐of‐fit and prediction metrics. Furthermore, the variance originating from the random elements of the calculation of cross‐validation metrics is slightly smaller than those of bootstrap ones, if equal calculation load is applied. [ABSTRACT FROM AUTHOR]

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.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

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.

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. [ABSTRACT FROM AUTHOR]

Context In some patients, symptoms may persist after COVID-19, defined as long COVID. Its pathogenesis is still debated and many hypotheses have been raised. Objective Our primary objective was to evaluate the corticotroph and somatotroph functions of patients previously infected with SARS-CoV-2 and experiencing post–COVID-19 syndrome to detect any deficiencies that may explain long COVID. Methods A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a postinfection period of 3 months or less to 15 months, divided into 2 groups. The first group (G1) comprised fully recovered patients, while the second group (G2) included patients experiencing long COVID. The primary outcome was the comparison of corticotroph and somatotroph functions. Results A total of 64 patients were divided into 2 groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1 (P =.045): for the corticotroph axis (G1: 6.3% vs G2: 28.1%) and for the somatotroph axis (G1: 31.3% vs G2: 59.4%). Baseline cortisol level was significantly lower in G2 (G1: 13.37 µg/dL vs G2: 11.59 µg/dL) (P =.045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (P =.01). For the somatotroph axis, the insulin growth factor-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (P =.369). The peak growth hormone level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (P =.041). Conclusion The results showed that long COVID patients in our cohort were more likely to have anterior pituitary deficiencies. The endocrine hypothesis involving anterior pituitary insufficiency can be considered to explain long COVID. [ABSTRACT FROM AUTHOR]

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.