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Aims. It is now well established that a large amount of heavy (trans-iron) elements are produced during neutron star (NS) mergers. These elements can be detected in the spectra of the kilonova emitted from the post-merger ejected materials. Due to the high level densities that characterize the complex configurations belonging to heavy elements, thus giving rise to millions of absorption lines, the kilonova ejecta opacity is of significant importance. The elements that contribute the most to the latter are those with an unfilled nd subshell belonging to the fifth and the sixth rows of the periodic table, and those with an unfilled nf subshell belonging to the lanthanide and actinide groups. The aim of the present work is to make a new contribution to this field by performing large-scale atomic structure calculations in three specific sixth-row 5d elements, namely hafnium, osmium, and gold, in the first four charge stages (I–IV), and by computing the corresponding opacities, while focusing on the importance of the atomic models used. Methods. The pseudo-relativistic Hartree–Fock (HFR) method, including extended sets of interacting configurations, was used for the atomic structure and radiative parameter calculations, while the expansion formalism was used to estimate the opacities. Results. Theoretical energy levels, wavelengths, and oscillator strengths were computed for millions of spectral lines in Hf I–IV, Os I–IV, and Au I–IV ions, the reliability of these parameters being assessed through detailed comparisons with previously published experimental and theoretical results. The newly obtained atomic data were then used to calculate expansion opacities for typical kilonova conditions expected one day after the NS merger; these are a density of ρ = 10−13 g cm−3 and temperatures ranging from T = 5000 K to T = 15 000 K. Some agreements and differences were found when comparing our results with available data, highlighting the importance of using sufficiently complete atomic models for the determination of opacities. [ABSTRACT FROM AUTHOR]

Introduction: Cancer management in Africa faces diverse challenges due to limited resources, health system challenges, and other matters. Identifying hereditary cancer syndromic cases is crucial to improve clinical management and preventive care in these settings. This study aims to explore the clinicopathological features and genetic factors associated with hereditary cancer in Tunisia, a North African country with a rising cancer burden MATERIALS AND METHODS: Clinicopathological features and personal/family history of cancer were explored in 521 patients. Genetic analysis using Sanger and next-generation sequencing was performed for a set of patients RESULTS: Hereditary breast and ovarian cancer syndrome was the most frequent cluster in which 36 BRCA mutations were identified. We described a subgroup of patients with likely ''breast cancer-only syndrome'' among this cluster. Two cases of Li-Fraumeni syndrome with distinct TP53 mutations namely c.638G>A and c.733G>A have been identified. Genetic investigation also allowed the identification of a new BLM homozygous mutation (c.3254dupT) in one patient with multiple primary cancers. Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes CONCLUSION: Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Recent advances in sequencing technologies have significantly increased our capability to acquire large amounts of genetic data. However, the clinical relevance of the generated data continues to be challenging particularly with the identification of Variants of Uncertain Significance (VUSs) whose pathogenicity remains unclear. In the current report, we aim to evaluate the clinical relevance and the pathogenicity of VUSs in DNA repair genes among Tunisian breast cancer families. Methods: A total of 67 unsolved breast cancer cases have been investigated. The pathogenicity of VUSs identified within 26 DNA repair genes was assessed using different in silico prediction tools including SIFT, PolyPhen2, Align-GVGD and VarSEAK. Effects on the 3D structure were evaluated using the stability predictor DynaMut and molecular dynamics simulation with NAMD. Family segregation analysis was also performed. Results: Among a total of 37 VUSs identified, 11 variants are likely deleterious affecting ATM, BLM, CHEK2, ERCC3, FANCC, FANCG, MSH2, PMS2 and RAD50 genes. The BLM variant, c.3254dupT, is novel and seems to be associated with increased risk of breast, endometrial and colon cancer. Moreover, c.6115G>A in ATM and c.592+3A>T in CHEK2 were of keen interest identified in families with multiple breast cancer cases and their familial cosegregation with disease has been also confirmed. In addition, functional in silico analyses revealed that the ATM variant may lead to protein immobilization and rigidification thus decreasing its activity. We have also shown that FANCC and FANCG variants may lead to protein destabilization and alteration of the structure compactness which may affect FANCC and FANCG protein activity. Conclusion: Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Boujemaa, Nouira, Jandoubi, Mejri, Bouaziz, Charfeddine, Ben Nasr, Labidi, El Benna, Berrazega, Rachdi, Daoud, Benna, Haddaoui, Abdelhak, Samir Boubaker, Boussen and Hamdi.)

Assertiveness is a constructive interpersonal behavior alternative to manipulation and aggression. Medical students (MSs) have daily interpersonal interactions with colleagues, patients and families. Yet, communication deficiencies due to hesitancy to speak-up assertively lead to adverse patient outcomes. This study aimed to assess levels of assertive behaviors (ABs), and to determine its predictors within a sample of first-year Tunisian MSs. This was a cross-sectional survey including 125 first-year MSs from Tunisia. ABs were measured by the Rathus assertiveness scale. Potential independent predictors of AB were evaluated using the following questionnaires: Rosenberg self-esteem scale, interpersonal communication skills inventory short-form-36quality of life questionnaire, and general health questionnaire. In addition, some MSs' characteristics were considered ( eg ; age, sex, living with family, assertiveness training, community work, personal medical field choice, smoking, and alcohol use). Univariate and multivariate analyses were performed. Among the 309 MSs, 125 (40.45%) responded to the survey. AB were found in 36.8% of MSs. Multiple linear regression models revealed that self-esteem global scores, sending clear messages, anxiety/depression and male sex were accountable for 31% in AB scores variance. Targeting self-esteem and interpersonal communication skills (sending clear messages) and identifying subgroups of students with anxiety/depression state would influence ABs.

Introduction: Traumatic life events (TLEs) have been associated with the entire spectrum of psychosis outcomes, including risk and severity of psychotic disorders and psychotic-like experiences (PLEs). In a non-clinical setting, understanding the relationship could help improve prevention services. Objectives: The aim of this study is to establish the relationship between TLEs and PLEs. Methods: A cross-sectional study was conducted in a Tunisan business and engineering school from March 2022 to June 2022. Participants completed the Tunisian dialect version of the Prodromal Questionnaire-Brief (PQ-B), a validated self-report instrument designed to evaluate prodromal symptoms. TLEs such as physical, sexual, and emotional abuse, as well as neglect experiences, lived or witnessed have been assessed along with bullying experiences. Results: The final sample size consisted of 358 participants, with a median age of 22 ± 2.22 years, with a sex ratio (M/F) of 1.41. More than half of the participants (58.6%) reported having experienced TLEs (49% in the preceding 6 months) while 31% had experienced bullying or abuse in school (27.9% in the preceding 6 months). The mean total score of the PQ-B for the study population was 7.27 ± 4.387, 36.3% reached the threshold and were defined as PQ-B-positive subjects. Those with a lifetime history of major life events were more likely to screen positive on the total score PQ-B (p = 0.000), as were those with a lifetime history of bullying or abuse (p = 0.000). Conclusions: Understanding the factors that interact in the significant association between PLEs and TLEs may provide useful information for prevention programs and the improvement of mental health. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Mutational screening of the CDH1 gene is a standard treatment for patients who fulfill Hereditary Diffuse Gastric Cancer (HDGC) testing criteria. In this framework, the classification of variants found in this gene is a crucial step for the clinical management of patients at high risk for HDGC. The aim of our study was to identify CDH1 as well as CTNNA1 mutational profiles predisposing to HDGC in Tunisia. Thirty-four cases were included for this purpose. We performed Sanger sequencing for the entire coding region of both genes and MLPA (Multiplex Ligation Probe Amplification) assays to investigate large rearrangements of the CDH1 gene. As a result, three cases, all with the HDGC inclusion criteria (8.82% of the entire cohort), carried pathogenic and likely pathogenic variants of the CDH1 gene. These variants involve a novel splicing alteration, a missense c.2281G > A detected by Sanger sequencing, and a large rearrangement detected by MLPA. No pathogenic CTNNA1 variants were found. The large rearrangement is clearly pathogenic, implicating a large deletion of two exons. The novel splicing variant creates a cryptic site. The missense variant is a VUS (Variant with Uncertain Significance). With ACMG (American College of Medical Genetics and Genomics) classification and the evidence available, we thus suggest a revision of its status to likely pathogenic. Further functional studies or cosegregation analysis should be performed to confirm its pathogenicity. In addition, molecular exploration will be needed to understand the etiology of the other CDH1- and CTNNA1-negative cases fulfilling the HDGC inclusion criteria.

In light of different challenges associated with the COVID-19 pandemic, university students are considered a particularly vulnerable population to mental health and study engagement issues. The first years at university represent a crucial period for students and are associated with an increase in mental health problems, particularly in healthcare studies. This study aimed (1) to document the current levels of mental health and study engagement among healthcare students in Tunisia, and (2) to investigate the relationships between emotional regulation, optimism, study engagement and common mental health problems (stress, anxiety and depression) among this population. A cross-sectional, electronic survey-based research design was used to draw a sample of 366 health care students from a University in Tunisia. Participants mostly reported mild (34.7%) or moderate (44.3%) levels of depression, moderate (44.7%) or severe (33.6%) levels of anxiety, average (50.8%) or mild (33.8%) levels of stress, and high levels of study engagement (>85%). Through structural equation modelling, the results showed that emotional regulation negatively affected stress, anxiety, and depression. Optimism partially mediated the relationship between emotional regulation, anxiety and depression and fully mediated the relationship between emotional regulation and study engagement. The findings indicated a high prevalence of psychological distress among healthcare university students in Tunisia, and specific protective factors that may be targeted to reduce mental health problems.

Background: Breast cancer is the world's most common cancer among women. It is becoming an increasingly urgent problem in low- and middle-income countries (LMICs) where a large fraction of women is diagnosed with advanced-stage disease and have no access to treatment or basic palliative care. About 5-10% of all breast cancers can be attributed to hereditary genetic components and up to 25% of familial cases are due to mutations in BRCA1 /2 genes. Since their discovery in 1994 and 1995, as few as 18 mutations have been identified in BRCA genes in the Tunisian population. The aim of this study is to identify additional BRCA mutations, to estimate their contribution to the hereditary breast and ovarian cancers in Tunisia and to investigate the clinicopathological signatures associated with BRCA mutations., Methods: A total of 354 patients diagnosed with breast and ovarian cancers, including 5 male breast cancer cases, have been investigated for BRCA1/2 mutations using traditional and/or next generation sequencing technologies. Clinicopathological signatures associated with BRCA mutations have also been investigated., Results: In the current study, 16 distinct mutations were detected: 10 in BRCA1 and 6 in BRCA2 , of which 11 are described for the first time in Tunisia including 3 variations that have not been reported previously in public databases namely BRCA1 _c.915T>A; BRCA2 _c.-227-?_7805+? and BRCA2 _c.249delG. Early age at onset, family history of ovarian cancer and high tumor grade were significantly associated with BRCA status. BRCA1 carriers were more likely to be triple negative breast cancer compared to BRCA2 carriers. A relatively high frequency of contralateral breast cancer and ovarian cancer occurrence was observed among BRCA carriers and was more frequent in patients carrying BRCA1 mutations., Conclusion: Our study provides new insights into breast and ovarian cancer genetic landscape in the under-represented North African populations. The prevalence assessment of novel and recurrent BRCA1/2 pathogenic mutations will enhance the use of personalized treatment and precise screening strategies by both affected and unaffected North African cancer cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hamdi, Mighri, Boujemaa, Mejri, Ben Nasr, Ben Rekaya, Messaoud, Bouaziz, Berrazega, Rachdi, Jaidane, Daoud, Zribi, Ayari, El Benna, Labidi, Ben Hassouna, Haddaoui, Rahal, Benna, Mrad, Ben Ahmed, Boussen, Boubaker and Abdelhak.)

BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity ( Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310_1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hamdi, Boujemaa, Mighri, Mejri, Jaidane, Ben Nasr, Bouaziz, Hassouna, Zribi, Berrazaga, Rachdi, Daoud, El Benna, Labidi, Haddaoui, Rahal, Benna, Boussen, Abdelhak and Boubaker.)

Introduction: Taxanes are widely used in medical oncology. The aim of our study was to report and analyze the toxicity features of these drugs in Tunisian patients and to determine their impact on treatment response., Methods: Our retrospective study concerned 90 patients treated by taxanes in a medical oncology unit, from January 2014 to January 2017. We collected their epidemiologic and anatomo-clinical data and we detailed toxicity features including types grades and impact on tumor response., Results: Median age was 46 years. 80% of patients had breast cancer. Tumors were metastatic in 23.3% of cases. Nail toxicity was observed in 100% of patients. Grade I-II digestive toxicity was observed in 54.4% of cases. Hematological toxicity was noted in 42.2% of patients and it reached grade III-IV in five patients. Neurological toxicity occurred in 31% of patients and was grade III-IV in 6 cases. Alopecia was observed in 60% of patients. Fatigue was noted in 57.8% of patients. Myalgia was observed in 42.2% of patients. Toxicity did not affect the response to treatment., Conclusion: The taxanes' toxicity profile in Tunisian patients is characterized by more frequent digestive and nail toxicities and less frequent hematological toxicities, dose reduction and treatment delays than other populations., (Copyright © 2020 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Temperamental dysregulation may constitute the link between predisposing genetic factors and affective disorders., Aims: Evaluate affective temperaments in bipolar patients, healthy siblings and controls, and address the relationship between affective temperaments and recent life events in these groups., Methods: Sixty bipolar patients, 60 patients' siblings and 60 controls were recruited. Assessment of life events in the last 6 months was performed using the Paykel's interview for recent life events. The Arabic version of Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Auto-questionnaire was used to evaluate affective temperaments., Results: Bipolar patients and siblings showed higher scores in cyclothymic and hyperthymic temperaments compared to controls. There were no significant differences in scores of irritable and anxious temperaments between the three groups.There was a strong relationship between anxious/cyclothymic temperaments and the high number of recent life events in bipolar patients and siblings. Contrary to bipolar patients and siblings, the number of recent life events in controls was not related to any dimension of affective temperament., Conclusions: Cyclothymic and hyperthymic temperaments were associated with bipolarity in patients and they could be characteristic traits of healthy siblings. Anxious/cyclothymic temperament might at least partially explain the high number of recent life events in bipolar patients and in siblings.

Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes., Competing Interests: The authors have declared that no competing interests exist.