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Abdullah R Alzahrani,1 Doaa I Mohamed,2 Hebatallah H Abo Nahas,3 Dalia Alaa El-Din Aly El-Waseef,4 Abdulmalik S Altamimi,5 Ibrahim H Youssef,6 Ibrahim Abdel Aziz Ibrahim,1 Soha MY Mohamed,7 Yasmine Gamal Sabry,7 Alaa H Falemban,1 Nasser Attia Elhawary,8 Ghazi A Bamagous,1 Mariusz Jaremko,9 Essa M Saied10,11 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 3Zoology Department, Faculty of Science, Port Said University, Port Said, Egypt; 4Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 5Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia; 6Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 7Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 8Department of Medical Genetics, College of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia; 9Smart-Health Initiative and Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia; 10Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt; 11Institute for Chemistry, Humboldt Universität Zu Berlin, Berlin, GermanyCorrespondence: Essa M Saied, Institute for Chemistry, Humboldt Universität zu Berlin, Berlin, 12489, Germany, Email saiedess@hu-berlin.deIntroduction: Pulmonary fibrosis (PF) and tissue remodeling can greatly impair pulmonary function and often lead to fatal outcomes.Methodology: In the present study, we explored a novel molecular interplay of long noncoding (Lnc) RNA CBR3-AS1/ miRNA-29/ FIZZ1 axis in moderating the inflammatory processes, immunological responses, and oxidative stress pathways in bleomycin (BLM)-induced lung fibrosis. Furthermore, we investigated the pharmacological potential of Trimetazidine (TMZ) in ameliorating lung fibrosis.Results: Our results revealed that the BLM-treated group exhibited a significant upregulation in the expression of epigenetic regulators, lncRNA CBR3-AS1 and FIZZ1, compared to the control group (P< 0.0001), along with the downregulation of miRNA-29 expression. Furthermore, Correlation analysis showed a significant positive association between lnc CBR3-AS1 and FIZZ1 (R=0.7723, p< 0.05) and a significant negative association between miRNA-29 and FIZZ1 (R=− 0.7535, p< 0.05), suggesting lnc CBR3-AS1 as an epigenetic regulator of FIZZ1 in lung fibrosis. BLM treatment significantly increased the expression of Notch, Jagged1, Smad3, TGFB1, and hydroxyproline. Interestingly, the administration of TMZ demonstrated the ability to attenuate the deterioration effects caused by BLM treatment, as indicated by biochemical and histological analyses. Our investigations revealed that the therapeutic potential of TMZ as an antifibrotic drug could be ascribed to its ability to directly target the epigenetic regulators lncRNA CBR3-AS1/ miRNA-29/ FIZZ1, which in turn resulted in the mitigation of lung fibrosis. Histological and immunohistochemical analyses further validated the potential antifibrotic effects of TMZ by mitigating the structural damage associated with fibrosis.Discussion: Taken together, our study showed for the first time the interplay between epigenetic lncRNAs CBR3-AS1 and miRNA-29 in lung fibrosis and demonstrated that FIZZ1 could be a downregulatory gene for lncRNA CBR3-AS1 and miRNA-29. Our key findings demonstrate that TMZ significantly reduces the expression of fibrotic, oxidative stress, immunomodulatory, and inflammatory markers, along with epigenetic regulators associated with lung fibrosis. This validates its potential as an effective antifibrotic agent by targeting the CBR3-AS1/miRNA-29/FIZZ1 axis. Keywords: lung fibrosis, long noncoding RNA CBR3-AS1, miRNA-29, FIZZ1, trimetazidine, histopathology

This study aimed to evaluate the fracture resistance of endodontically treated molars restored with ceramic indirect restorations with and without cervical margin relocation. A total of 120 extracted human maxillary molars were used after MOD cavities preparations with the mesial boxes located 2 mm below CEJ. Specimens were randomly assigned to six groups according to the margin location of each indirect restoration type (n = 20); crown without CMR, crown with CMR, endocrown without CMR, endocrown with CMR, onlay without CMR, and onlay with CMR. Mesial proximal boxes of the MOD cavities were elevated with composite resin in cervical margin relocation groups. Each group was further divided according to indirect restoration material (n = 10); CEREC Tessera and Celtra Press. The specimens were subjected to fracture resistance testing in a universal testing machine. Fracture analysis was performed using stereo and scanning electron microscopes. Data were analyzed by using 3-way ANOVA, 1-way ANOVA and the Tukey HSD tests (α = 0.05). The mean fracture resistance values ranged between 2136.57 and 950.47 N. Significantly higher values were detected among Celtra Press than Cerec Tessera in crown restorations. Unrestorable fracture patterns were seen through all study groups. Crown restorations represented the best restorative option in terms of fracture resistance. Cervical margin relocation adversely affected fracture resistance. However, the material of the indirect restorations had no significant impact on fracture resistance.

Abstract Background The incidence of comorbid depression and post-traumatic stress disorder (PTSD) symptoms is higher in snakebite victims. However, the present state and contributing factors of depression and PTSD among Chinese snakebite victims remain unclear. Methods A representative sample of 6837 snakebite victims were assessed with the Post-traumatic Stress Disorder Checklist (Civilian Version) and The Center for Epidemiologic Studies Depression Scale. Multivariate analyses, including network analysis, evaluated the contributing factors of PTSD and depression symptoms caused by snake bites, as well as the bridge symptoms of comorbidity networks. Results Among 6,837 snakebite victims, 79.5% reported PTSD symptoms and 81.4% reported depression symptoms. Comorbidity of PTSD and depression symptoms was found in 75.1%. Key factors included the presence sequelae after snakebite (ORPTSD = 2.31, ORDepression = 1.89), time to medical facilities (6–8 h: ORPTSD = 3.17, ORDepression = 2.46), and marital status (divorced/widowed: ORPTSD = 1.78, ORDepression = 1.76). Symptoms I1 ("Repeated disturbing memories") and D1 ("Bothered by things that don't usually bother me") bridged PTSD and depression networks. Conclusion The primary psychological challenges for snakebite victims in China are PTSD and depression symptoms, which is concerning. Standardized diagnosis and treatments, timely medical care, and stable marital relationships can reduce risks. Additional psychological support and management of negative memories, especially for those with severe bridge symptoms, can be beneficial. Further research should concentrate on understanding victims' psychological states and developing effective interventions.

Abstract Background Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain major public health issues. Although the primary and secondary prevention of RHD through appropriate management of bacterial pharyngitis and ARF are well-described in the literature, few studies address the knowledge, attitude, and practice (KAP) of developing countries. We aimed to evaluate the KAP of the frontline physicians in Egyptian university hospitals regarding pharyngitis and ARF. Methods We employed a cross-sectional design between September 1st, 2022, and January 31st, 2023 using a self-administered questionnaire in 21 Egyptian universities. The questionnaire was developed based on previous studies and recent guidelines and included four domains: sociodemographic data, knowledge, attitude, and practice regarding pharyngitis and ARF. We utilized both online (Google Forms) and paper surveys. Frontline physicians, including interns, residents, and assistant lecturers, were conveniently invited to participate. Furthermore, with the help of participating phycisians in recruiting their colleagues, we utilized the snowball method. Data were analyzed using IBM SPSS version 27 software. Results The final analysis included 629 participants, of whom 372 (59.1%) were males and 257 (40.9%) had direct contact with ARF patients. Most participants (61.5%) had a fair knowledge level while 69.5% had a fair level of practice regarding ARF and pharyngitis. Higher satisfactory knowledge levels were noted regarding pharyngitis (17.1% vs. 11.3%; p-value: 0.036) and ARF (26.8% vs. 18%; p-value: 0.008) among physicians dealing directly with ARF cases compared to physicians in departments not dealing directly with ARF cases. Physicians in Cairo region universities had significantly higher levels of satisfactory knowledge about ARF compared to Delta and Upper Egypt region universities (p = 0.014). Delta region universities showed significantly lower levels of practice compared to Cairo and Upper Egypt region universities (p = 0.027). The most frequently recognized barriers against health promotion were low socioeconomic status (90.3%) and lack of adequate public education (85.8%). Conclusions Despite the fair knowledge and practice levels towards bacterial pharyngitis and ARF among participants, many gaps were still identified that might contribute to RHD prevalence. Educational interventions should be implemented by updating the local guidelines in Egypt for diagnosis and management based on the most recent guidelines.

When the coronavirus pandemic was declared as a Public Health Emergency, educational ministries and institutions unanimously opted for distance education as a solution to carry on teaching and learning worldwide. Flexible hybrid courses (HyFlex) are one of the innovative teaching devices that have emerged since the health crisis and aimed to achieve educational continuity and satisfy learners’ various needs. Based on a research model inspired by the different extensions of the technology acceptance model (TAM), we conducted a study with 249 students from the faculty of medicine and pharmacy affiliated with Mohammed First University in Oujda (Morocco) who learned in a HyFlex environment during the 2020–2021 fall semester. The study addressed students’ perceptions regarding the implementation of blended-learning and its dimensions. It aimed to analyse the perceptions of usefulness and ease of use of the HyFlex model and the facilitating conditions and individual characteristics, chiefly the availability of technological resources and the mastery of the computational tool on the behavioural intention of adopting this approach. The results show that attitude, perceived usefulness, perceived ease of use and availability of technological resources are the main factors favouring the acceptance of e-learning by the surveyed students.

Background: Previous studies have shown that the neutrophils/lymphocytes (NLR) and platelets/lymphocytes (PLR) ratios could be used as markers of inflammatory load as well as prognostic factors in several medical conditions. The current study aimed to compare the effect of using daily tadalafil 5 mg/day versus daily sildenafil 25 mg/day in improving erectile function as well as their ability to reduce NLR and PLR. Methods: One hundred and four participants were recruited. Seventy-four randomized patients with erectile dysfunction were equally divided into 2 groups. Patients in group A used daily tadalafil 5 mg for 2 months while patients in group B used daily sildenafil 25 mg for 2 months. Patients were collected from June 2022 to June 2023. Thirty healthy individuals served as controls. All patients and controls were evaluated using the validated Arabic version of the international index of erectile function (ArIIEF-5) at baseline and after 2 months of medical treatment. Five cc of venous blood sample was obtained before and after 2 months of medical treatment to compare the effect of phosphodiestrase type 5 inhibitors (PDE-5Is) intake for erectile dysfunction on PLR and NLR before and after treatment. Results: The current study showed that there were no statistically significant differences between the cases and the controls apart from the ArIIEF-5 scores. Moreover, there was no significant difference between patients in group A and those in group B regarding PLR and NLR post administration of PDE-5Is. Interestingly, patients in group A demonstrated a highly significant difference between the ArIIEF-5 scores as well as the PLR and the NLR before and 2 months after administration of daily tadalafil 5 mg. On the other hand, patients in group B who were administrated daily sildenafil 25 mg for 2 months demonstrated only a highly significant difference between the ArIIEF-5 scores before and after administration. Meanwhile, patients in group B did not reveal any statistically significant difference in the PLR and the NLR before and 2 months after administration of sildenafil 25 mg. Further regression analysis after adjustment of different variables of the study showed a significant correlation between ArIIEF-5 and PLR in patients who received daily tadalafil 5 mg (r = 0.430, p=0.004). Conclusions: Tadalafil and sildenafil have similar clinical efficacy in treating erectile dysfunction. However, tadalafil is more effective in lowering PLR and NLR compared to sildenafil.

Abstract Novel active DNA transposons, such as Spy transposons from the PHIS superfamily, are identified through bioinformatics in this study. The native transposases cgSpy and cvSpy displayed transposition activities of approximately 85% and 35% compared to the hyperactive piggyBac transposase (hyPB). The cgSpy transposon showed unique characteristics, including a lack of overproduction inhibition and reduced efficiency for insertion sizes between 3.1 to 8.5 kb. Integration preferences of cgSpy are found in genes and regulatory regions, making it suitable for genetic manipulation. Evaluation in T‐cell engineering demonstrated that cgSpy‐mediated chimeric antigen receptor (CAR) modification is comparable to the PB system, indicating its potential utility in cell therapy. This study unveils the promising application of the active native transposase, Spy, from Colletes gigas, as a valuable tool for genetic engineering, particularly in T‐cell manipulation.

Résumé : L’objet de ce travail était d’étudier les paramètres à prendre en compte lors de l’élaboration du formulaire thérapeutique du CHU Pr Bocar Sidy SALL de Kati. Il s’agissait d’une étude transversale descriptive. La collecte des données s’est déroulée sur une période de 6 mois en 2022. Elle a concerné 70% de l’effectif des médecins (n=42) et 30% de l’effectif des Sages-femmes et infirmiers (n=23) dudit établissement à partir des entrevues individuelles. Il ressort des résultats que près de 2/3 des médecins prescripteurs, sages-femmes et 1/2 des infirmiers connaissaient le formulaire thérapeutique. Cependant l’organe qui s’occupe de son élaboration était près que méconnue par les enquêtés. L’ensemble des prescripteurs ont souhaité voir dans le formulaire les informations relatives à la pharmacologie du médicament. Au total 07 critères pharmacologiques, pharmaco-économiques et réglementaires ont été proposés comme base d’inclusion des produits dans le formulaire. Cependant, 06 critères pharmacologiques et pharmaco-économiques ont été proposés quant aux conditions de substitutions des produits dans le formulaire. Cependant 02 conditions réglementaires ont été évoquées pour le retraire d’un produit dans la liste du formulaire. Le choix la périodicité de révision de la liste des médicaments du formulaire allait de 1 à 5 ans. Enfin d’être concis et utilisable, ce travail était nécessaire pour comprendre les attentes des praticiens sur l’outil qui sera mise en place. Pour son succès, un effort d’éducation, de formation et d’information du personnel sanitaire doit être entrepris.

Toxicants with the potential to bioaccumulate in humans and animals have long been a cause for concern, particularly due to their association with multiple diseases and organ injuries. Per- and polyfluoro alkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAH) are two such classes of chemicals that bioaccumulate and have been associated with steatosis in the liver. Although PFAS and PAH are classified as chemicals of concern, their molecular mechanisms of toxicity remain to be explored in detail. In this study, we aimed to identify potential mechanisms by which an acute exposure to PFAS and PAH chemicals can induce lipid accumulation and whether the responses depend on chemical class, dose, and sex. To this end, we analyzed mechanisms beginning with the binding of the chemical to a molecular initiating event (MIE) and the consequent transcriptomic alterations. We collated potential MIEs using predictions from our previously developed ToxProfiler tool and from published steatosis adverse outcome pathways. Most of the MIEs are transcription factors, and we collected their target genes by mining the TRRUST database. To analyze the effects of PFAS and PAH on the steatosis mechanisms, we performed a computational MIE-target gene analysis on high-throughput transcriptomic measurements of liver tissue from male and female rats exposed to either a PFAS or PAH. The results showed peroxisome proliferator-activated receptor (PPAR)-α targets to be the most dysregulated, with most of the genes being upregulated. Furthermore, PFAS exposure disrupted several lipid metabolism genes, including upregulation of fatty acid oxidation genes (Acadm, Acox1, Cpt2, Cyp4a1-3) and downregulation of lipid transport genes (Apoa1, Apoa5, Pltp). We also identified multiple genes with sex-specific behavior. Notably, the rate-limiting genes of gluconeogenesis (Pck1) and bile acid synthesis (Cyp7a1) were specifically downregulated in male rats compared to female rats, while the rate-limiting gene of lipid synthesis (Scd) showed a PFAS-specific upregulation. The results suggest that the PPAR signaling pathway plays a major role in PFAS-induced lipid accumulation in rats. Together, these results show that PFAS exposure induces a sex-specific multi-factorial mechanism involving rate-limiting genes of gluconeogenesis and bile acid synthesis that could lead to activation of an adverse outcome pathway for steatosis.

This paper investigates the transformative potential of Large Language Models (LLMs) within higher education, highlighting their capacity to reshape the academic landscape. By examining the complex impact of LLMs across critical areas of Higher Education Institutions (HEIs), including the role of HEIs as gatekeepers of knowledge, providers of credentials, research centres, incubators of innovation, drivers of social change and employers. In addition to academic integrity, the future of higher education, intellectual property, and public perception. The findings of this paper indicate that LLMs can empower transformation in HEIs by revolutionising various aspects of academia. The aim is to unveil the profound implications of integrating these cutting-edge technologies. The comprehensive study in this paper reveals the significant impacts and challenges associated with using LLMs in academic settings, which is achieved through a detailed analysis of current literature. The core findings suggest that LLMs hold the promise to trigger significant advancements in higher education. This paper also discusses the innovative potential of LLMs, and it outlines a path for their effective use in HEIs, emphasising the importance of a thoughtful approach to maximise their educational benefits. HEIs must address these challenges thoughtfully, ensuring that the integration of LLMs aligns with their fundamental objectives of promoting education, critical thinking, and personal growth.

Objectives: Several factors can cause acute flaccid paralysis cases including non-polio enteroviruses. In Senegal, few studies on non-polio enteroviruses (NPEV) have been performed. Methods: Our study assess the molecular epidemiology of non-polio enteroviruses in Senegal from 2013 to 2021 through the previously existing programs for surveillance of polioviruses. Results: A total of 3815 stool samples and 281 sewage samples were collected. After virus isolation by cell culture, non-polio enteroviruses-positive isolates were confirmed by reverse transcriptase-quantitative polymerase chain reaction. Following this detection, the positive samples were subjected to molecular characterization. Our data showed that 15.22% and 52.66% were positive in cell culture for non-polio enteroviruses in acute flaccid paralysis surveillance and environmental surveillance, respectively. These non-polio enteroviruses-positive isolates were detected all year round but tend to unequal peaks of circulation, and the age group 0-5 years was more vulnerable to infection (84.4%). Genetic characterization revealed the circulation of enteroviruses species infecting humans (Enterovirus A – Enterovirus D): Enterovirus A (29.2%) and Enterovirus B (63.1%) isolates from both the acute flaccid paralysis surveillance and environmental surveillance while Enterovirus C (5.3%) and Enterovirus D (2.4%) were only isolated from the acute flaccid paralysis surveillance. However, the highly prevalent Enterovirus B species from the acute flaccid paralysis surveillance included echovirus 7 and echovirus 13, whereas coxsackievirus A6 was the predominant species from the environmental surveillance. Conclusion: This first 8-year period study of NPEV in Senegal showed that NPEV represent important viral etiologies associated with acute flaccid paralysis cases and circulating in environmental surveillance in Senegal and highlighted the need to promote effective long-term strategies for monitoring of non-polio enteroviruses infections.

This study aims to explore the synergistic effects of co-inoculation with Fusarium solani (F.s), Fusarium oxysporum (F.o), and Penicillium chrysogenum (P.ch) to enhance the digestibility and quality of lignocellulosic biomass for ruminant feeding. Wheat straw (WS), olive pomace (OP), and cedar wood (CW) were assessed as substrates. Results indicated varying impacts on lignin loss (L_loss), cellulose improvement (C_imp), and In Vitro True Digestibility improvement (IVTD_imp). F.o and P.ch co-inoculation exhibited the highest mean L_loss (53.74%), surpassing F.s and P.ch co-inoculation (18.23%) and F.s and F.o co-inoculation (19.23%). F.o_P.ch co-inoculation notably increased cellulose content (C_imp = 29.86 ± 18.19%) and IVTD_imp (40.74% ± 20.51%), while F.o_F.s showed minimal IVTD_imp (0.14 ± 11.42%). Substrates differed in fiber change and dry matter loss, with OP having the highest C_imp (25.6 ± 20.7%). Treatment duration influenced L_loss and IVTD_imp, increasing from 4 to 12 weeks. Co-inoculating F.o and P.ch enhances lignin degradation and biomass digestibility, improving their suitability for ruminant feed. Thoughtful selection of fungal combinations is crucial for optimizing co-inoculation. These findings support the utilisation of lignocellulosic biomass in ruminant feed.

Toxidromes constitute patterns of symptoms and signs caused by specific toxic effects that guide emergency treatments. Computational identification of chemicals that cause different toxidromes allows us to rapidly screen novel compounds and compound classes as to their potential toxicity. The aim of the current study was to create a computational toolset that can map chemicals to their potential toxidromes. Hence, we evaluated the performance of a state-of-the-art deep learning method—the recently developed communicative message passing neural network (CMPNN)—for its ability to overcome the use of small datasets for training deep learning models. Our results indicated that multi-task training—a technique known for its ability to use multiple small datasets to train conventional deep neural networks—works equally well with CMPNN. We also showed that CMPNN-based ensemble learning results in more reliable predictions than those obtained using a single CMPNN model. In addition, we showed that the standard deviations of individual model predictions from an ensemble of CMPNN models correlated with the errors of ensemble predictions and could be used to estimate the reliability of ensemble predictions. For toxidromes that do not have well-defined molecular mechanisms or sufficient data to train a deep learning model, we used the similarity ensemble approach to develop molecular structural similarity-based toxidrome models. We made the toolset developed in this study publicly accessible via a web user interface at https://toxidrome.bhsai.org/.

Purpose: We retrospectively study twenty-nine surgical cases of aggressive vertebral hemangiomas (AVHs) with neurological deficits and extradural compression to determine the optimal surgical treatment strategy for AVHs at a single institution. Methods: Patients with AVHs with neurological deficits who underwent partial tumor resection plus decompression with or without vertebroplasty (VP), and radiotherapy between 2010 and 2021 were included in this study. Clinical characteristics, surgical outcomes, and follow-up data of the patients were reviewed retrospectively. Results: Twenty-nine AVH cases with neurological deficits and spinal instability were included in this study and treated surgically. The mean operation time of patients with decompression surgery plus VP (Groupe A) was 215.9 (120-265 min), shorter than that of decompression surgery without VP (Group B) 240.2 (120-320 min). Intraoperative blood loss was 273.3 (100–550 mL) in group A and 635.3 (200–1600 mL) in group B. In addition, a significant reduction in blood loss was observed in group A compared to the group B (p=0.0001). All patients experienced immediate pain relief and improvement in their neurological symptoms. Neurological function was assessed by the Frankel score, ASIA score, and the visual analogue scale (VAS) pain score decreased from 7.4 (4-9) to 1.3 (0-3). Of twenty-nine patients in this study, only 7% (2/29 patients) showed signs of recurrence. Conclusion: Decompression plus VP achieve good tumor control and decrease surgical complication. Preoperative vascular embolization and VP can reduce intraoperative bleeding in the treatment of AVH surgery. Moreover, postoperative radiotherapy seems to be a good technique to prevent tumor recurrence.

In this paper we propose a new mathematical model describing the deformations of an isotropic nonlinear elastic body with variable exponent in dynamic regime. We assume that the stress tensor \(\sigma^{p(\cdot)}\) has the form \[\sigma^{p(\cdot)}(u)=(2\mu +|d(u)|^{p(\cdot)-2})d(u)+\lambda Tr(d(u)) I_{3},\] where \(u\) is the displacement field, \(\mu\), \(\lambda\) are the given coefficients \(d(\cdot)\) and \(I_{3}\) are the deformation tensor and the unit tensor, respectively. By using the Faedo-Galerkin techniques and a compactness result we prove the existence of the weak solutions, then we study the asymptotic behaviour stability of the solutions.

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors. Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+ T cells, which led to improved antitumor outcomes. Mechanistically, infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation. Overall, we presented a simple, cost-effective, and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

Animal studies are typically utilized to understand the complex mechanisms associated with toxicant-induced hepatotoxicity. Among the alternative approaches to animal studies, in vitro pooled human hepatocytes have the potential to capture population variability. Here, we examined the effect of the hepatotoxicant thioacetamide on pooled human hepatocytes, divided into five lots, obtained from forty diverse donors. For 24 h, pooled human hepatocytes were exposed to vehicle, 1.33 mM (low dose), and 12 mM (high dose) thioacetamide, followed by RNA-seq analysis. We assessed gene expression variability using heat maps, correlation plots, and statistical variance. We used KEGG pathways and co-expression modules to identify underlying physiological processes/pathways. The co-expression module analysis showed that the majority of the lots exhibited activation for the bile duct proliferation module. Despite lot-to-lot variability, we identified a set of common differentially expressed genes across the lots with similarities in their response to amino acid, lipid, and carbohydrate metabolism. We also examined efflux transporters and found larger lot-to-lot variability in their expression patterns, indicating a potential for alteration in toxicant bioavailability within the cells, which could in turn affect the gene expression patterns between the lots. Overall, our analysis highlights the challenges in using pooled hepatocytes to understand mechanisms of toxicity.

IntroductionCurcumin has highly antimicrobial and antioxidant activities but has poor bioavailability and low solubility in water. The current study aimed to assess curcumin nanoparticles (Curcumin-NPs) antibacterial and antioxidant efficacy against some pathogens in chicken fingers at 4 °C/27 days.MethodsCurcumin-NPs with particle sizes of 80 ± 2 nm were synthesized using a planetary ball-mill and chitosan-gelatin nanoparticle (CS-G-NPs) solution and then placed into chicken fingers at three concentrations, (2, 5, and 10 μg g−1). The physicochemical properties, antioxidant activity, and antibacterial capacity were evaluated.Results and discussionCurcumin-NPs showed high phenolic content (67.48 mg GAE g−1) and antioxidant activity (22.47 μg ml−1) at 10 μg g−1 compared to other concentrations and curcumin bulk. Curcumin-NPs showed noticeably greater antibacterial ability (in vitro) against S. aureus (18 mm), E. coli (15 mm), and B. cereus (13 mm). In challenge studies, Curcumin-NPs effectively inhibited the three inoculated pathogens ~3–4 log CFU g−1; in vivo; in chicken fingers kept for up to 27 days, compared to the control. In curcumin-NPs chicken samples, the contents of thiobarbituric acid reactive substances (TBARS) and total volatile base nitrogen (TVB-N) compared to the control were substantially lower (27 days). TEM analysis provided an estimate of the antibacterial mechanism of Curcumin-NPs. The findings demonstrated that Curcumin-NPs at 10 μg g−1 were more successful in reducing microbial load in chicken fingers as well as improving quality parameters, enhancing shelf life, and reducing lipid oxidation in poultry meat products.

While the literature in ecology on conservative plant translocations has developed significantly in recent years, very few studies on the practical conditions for their implementation, including the economic aspects, have been conducted. However, these non-strictly biological factors are important to consider because they can influence the feasibility and efficiency of translocation operations. Through a series of interviews with national botanical conservatories (CBN), one of the major actors in plant translocations, as well as a few complementary actors, we review the regulatory, organizational and economic dimensions of the practice of conservative plant translocations in France. In particular, we collected the economic costs of the involvement of six CBN in 34 translocation operations, associated with three stages that we feel it is interesting to differentiate in a translocation: preparation, the translocation itself, and the post-translocation phase. It is the two phases upstream and downstream of the translocation operation per se that involve the largest share of costs. We also showed that the motivation underlying a translocation operation, that is within or outside the mitigation hierarchy of development projects, did not significantly influence its cost, which suggests an equivalent implication of the actors interviewed (at least economically) in the two cases identified. The analysis of the economic costs of plant translocations, limited to the involvement of the CBN in this article, should now be completed for the other actors involved. The detailed network of the actors involved in translocations as well as the description of the different stages they encounter and that we propose in this article constitute an essential starting point.

Rainwater pollution in urban areas is a real phenomenon globally, particularly in developing countries. This study aims to trace the origin of polycyclic aromatic hydrocarbons (PAHs) in the Abidjan district's rainwater and to evaluate the health risk to the population. Ten water samples were collected at two sites during the dry and rainy seasons over a 2-year period. The use of molecular indices and profiles as well as Spearman's correlation matrix revealed that the pyrolytic sources, such as wood combustion as well as road traffic, remain the main sources of these pollutants in the water. The risk assessment revealed a higher risk of skin cancer in children. HIGHLIGHTS Sources of polycyclic aromatic hydrocarbons (PAHs) in rainwater have been identified.; The C13 isotope to the confirmation of PAH sources in rainwater has been contributed.; Children have a higher risk of skin cancer than adults.; There is a seasonal variation of PAH concentartions in rainwater.; There is an annual variation of PAH concentrations in rainwater.;

An enhancer trap (ET) mediated by a transposon is an effective method for functional gene research. Here, an ET system based on a PB transposon that carries a mini Krt4 promoter (the keratin4 minimal promoter from zebrafish) and the green fluorescent protein gene (GFP) has been used to produce zebrafish ET lines. One enhancer trap line with eye-specific expression GFP named EYE was used to identify the trapped enhancers and genes. Firstly, GFP showed a temporal and spatial expression pattern with whole-embryo expression at 6, 12, and 24 hpf stages and eye-specific expression from 2 to 7 dpf. Then, the genome insertion sites were detected by splinkerette PCR (spPCR). The Krt4-GFP was inserted into the fourth intron of the gene itgav (integrin, alpha V) in chromosome 9 of the zebrafish genome, with the GFP direction the same as that of the itgav gene. By the alignment of homologous gene sequences in different species, three predicted endogenous enhancers were obtained. The trapped endogenous gene itgav, whose overexpression is related to hepatocellular carcinoma, showed a similar expression pattern as GFP detected by in situ hybridization, which suggested that GFP and itgav were possibly regulated by the same enhancers. In short, the zebrafish enhancer trap lines generated by the PB transposon-mediated enhancer trap technology in this study were valuable resources as visual markers to study the regulators and genes. This work provides an efficient method to identify and isolate tissue-specific enhancer sequences.

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.

The objective of the current work is to extract a new mucilage fraction from Astragalus gyzensis Bunge. seeds, which are collected from the El-Oued province (septentrional Algerian Sahara) and evaluated for their antidiabetic potential. The mucilage fraction is obtained using hot water extraction followed by alcoholic precipitation of polysaccharides by cold ethanol (96%). The primary investigation was performed by describing the main structural features of the extract through colorimetric assays, Fourier-transform infrared spectroscopy and thin-layer chromatography analysis using two systems. Biological activity was also monitored by antidiabetic activity by testing the inhibition of α-amylase and α-glucosidase enzymes in vitro. The extraction yield was 20.69%. The chemical composition mainly consisted of 78.60±0.29% carbohydrates, among them 63.92±0.67% neutral sugar, 15.78±0.76% uronic acid, 8.08±0.04% proteins and 2.57±0.05% phenolic compounds. The results obtained by thin-layer chromatography analysis showed the dominance of mannose and galactose. Fourier-transform infrared spectrum showed characteristic bands expected galactomannans. The investigations highlighted the antihyperglycemic effect in a dose-dependent manner by the inhibition of the α-amylase enzyme (IC50=0.8±0.005 mg/mL). These factors make it suitable for the industrial application of dietary supplement fiber made for diabetic individuals. DOI: http://dx.doi.org/10.5281/zenodo.7618530

ABSTRACT. Background: Hearing loss is generally classified as conductive hearing loss (CHL) and sensory-neural hearing loss (SNHL). It has been reported that COVID-19 infection may affect the vestibular-hearing system causing dizziness, tinnitus, vertigo, and hearing impairment. However, other studies reported that COVID-19 did not lead to significant hearing impairment. Many studies in the literature have reported hearing loss as a complication of COVID-19 vaccines. However, no systematic review or meta-analysis summarizes the literature on this topic. Method: We performed a comprehensive search for the following databases: PubMed, Cochrane (Medline), Web of Science, and Scopus. All studies published in English till October 2022 were included. These include case reports, case series, prospective and retrospective observational studies, and clinical trials reporting hearing loss following COVID-19 vaccines. Newcastle Ottawa scale (NOS) was used to assess the risk of bias for observational studies. NIH tools were used for non-controlled before and after clinical trials and case reports and case series. A third author solved any disagreements. We analyzed the data using SPSS Software version 26. Results: A total of 630 patients were identified, with a mean age of 57.3 that ranged from 15 to 93 years old. The majority of the patients were females, 339 (53.8%). In addition, 328 out of 609 vaccinated patients took the Pfizer-BioNTech BNT162b2 vaccine, while 242 (40%) took the Moderna COVID-19 vaccine. The mean time from vaccination to hearing impairment was 6.2, ranging from a few hours to one month after the last dose. Most patients reported unilateral sensorineural hearing loss post-vaccination 593 (94.1%). In order to report the fate of cases, a follow-up was initiated with a mean of 15.6 and a range of 2 to 63 days after the initiation of the treatment. A total of 20 patients were fully recovered, and 11 reported no response. Three out of 328 patients who took the Pfizer-BioNTech BNT162b2 vaccine fully recovered, while five reported partial recovery. According to the chi-squared test, there is a statistically significant difference between patients in terms of fate and the type of COVID-19 vaccination (P-value = 0.001) while reporting no significant difference in dose number prior to the onset of the symptoms (P-value = 0.65) and gender (P-value = 0.4). The ANOVA test was conducted to compare vaccine types and the number of doses in terms of mean time from vaccination to hearing impairment onset. The results found a significant difference between vaccine types (P-value < 0.000) while showing no significance in terms of the number of doses prior to the onset (P-value = 0.6). Conclusion: There is a statistically significant difference between patients in terms of fate and the type of COVID-19 vaccination while reporting no significant difference in dose number prior to the onset of the symptoms and gender. Further, we concluded that there is a significant difference between vaccine types while showing no significance in terms of the number of doses prior to the onset.

Background: A cesarean section (CS) is one of the most common operations globally, with an estimated 18.5 million surgical procedures each year. Accordingly, music therapy has become a trendy possible solution in many clinical conditions and surgical procedures. However, most previous studies have shown conflicting findings regarding the efficacy of music in reducing pain and anxiety in women with cesarean delivery. Therefore, in this meta-analysis, we aimed to investigate whether music intervention has a beneficial effect on preoperative, intraoperative, and postoperative anxiety, pain, and vital signs in women with cesarean section. Method: We conducted a comprehensive search of Scopus, Web of Science, PubMed, and Cochrane Central was conducted for relevant randomized controlled trials (RCTs) from inception until August 2022. Data were extracted from eligible studies and pooled as standardized mean difference (SMD) or mean difference (MD) values in a random-effect model meta-analysis, using RevMan software. All the steps of this study were performed according to the PRISMA statement guidelines. Results: Thirteen RCTs were included in this meta-analysis with a total of 1513 patients. Our study showed that music was superior to control in terms of overall anxiety score (SMD = - 0.26, 95% CI [- 0.39, - 0.14], p

Les aplombs du cheval correspondent à l’orientation des membres sous le corps. Le jeune poulain peut être confronté quelques jours après sa naissance ou durant sa croissance à des déviations angulaires de ces membres entrainant une mauvaise répartition des charges, une usure non homogène au niveau des articulations, des muscles et des ligaments. Ces déviations sont à l’origine de pathologies telles que l’ostéochondrose, de l’ostéo-arthrose, des tendinites ou des fractures, susceptibles d’influencer ses performances et sa carrière par la suite. Ces déviations angulaires concernent principalement les articulations du carpe, du boulet et du jarret. Lors des déviations congénitales, elles sont attribuées à l'immaturité de la structure osseuse, à une laxité des structures péri-articulaires, une croissance osseuse asynchrone ou à une déviation diaphysaire. Dans le cas des déviations acquises, la croissance osseuse disproportionnée des plaques de croissance et des centres d’ossification des épiphyses en sont les responsables. Le traitement de ces déviations, doit être précoce avant la fermeture des plaques de croissance du poulain. Divers traitements sont actuellement disponibles pour corriger ces déviations, il s’agit des mesures conservatrices, de la maréchalerie ou des interventions chirurgicales. Le but de cette mise à jour bibliographique est de recenser les différents traitements non chirurgicaux décris actuellement et de comparer leurs résultats, afin de garantir aux vétérinaires praticiens équins et aux étudiants vétérinaires la meilleure prise en charge thérapeutique de la pathologie. Mot clés: déviations angulaires, traitement, valgus, varus, poulain

In this present study, the toxicity of Cleome arabica L. (Capparidaceae) seed oils was tested on L5 larvae of Schistocerca gregaria, Forsk. (Orthoptera-Acrididae). The forced administration of 60 ?L/individual of this vegetable oil leads to the death of all the treated larvae either before or after a few days of exuviation (imaginal moult). Signs of intoxication were observed a few hours after treatment, i.e. movement disorders, diarrhoea, inability to take food and weight loss. Male L5 larvae seem more sensitive than female L5; the mortality rates being around 90.91% and 36.36% respectively after 16 days. The TL50 recorded in treated L5 larvae is around 11 days.

Abstract The police are the backbone of protecting Iraq from the inside, and its fortified shield and its trustworthy guard provides men and money to protect its land from the inside. You find it in peace. It helps the citizen with natural disasters, forums and events. Mental health and physical fitness are the basic components of police workers and are considered as an important elements to maintain the policeman’s health and physical competence so that he can perform his field duty to the fullest, as it provides him with safety, ability to act, speed of movement and endurance, especially under conditions that require hard or continuous work, whether in the field. Military or offices. Therefore, the research problem lies in the study of mental health and its relationship to the physical performance of police academy The study aimed to: 1- Identify the mental health values ​​of the research sample. 2- Knowing the values ​​of activity and physical performance of the research sample. 3- Identify the relationship between mental health and physical performance in the research sample. The researchers assumed the existence of a significant correlation between mental health and physical performance in the research sample. The researchers used the descriptive approach to suit the nature of the problem and the objectives of the research. The research sample was chosen randomly, represented by students of the Police Academy in Al-Muthanna Governorate, whose number is (50) students out of 250 students, so their percentage from the community = (20%). The two researchers used the tests (endurance of arms strength - transition velocity - endurance test) and the mental health scale, as the translated and codified mental health scale was approved by Abdulaziz Musa from Al-Quds University, which contains 90 paragraphs and its keys are five-pointed (Likred scale) with the highest value The scale has 450 degrees and the lowest value of the scale is 90 degrees, noting that the scale has degrees of validity, stability and objectivity, and the scale keys are (Always - often - sometimes - rarely - never) The two researchers conducted the tests with the help of the working team over two days: The first day: A mental health scale was distributed and a speed and strength test was conducted. The second day was an endurance test. After collecting the data and treating them statistically, the researchers concluded 1- The research sample enjoys good mental health. 2- There is a correlation between mental health and physical performance. So the researchers recommend 1- Paying attention to mental health with its direct impact on physical fitness. 2- Conducting similar studies on other physical and motor abilities. 3- Preparing concepts to improve mental health, as it is one of the important factors for physical numbers.

Alginates extracted from two Moroccan brown seaweeds and their derivatives were investigated for their ability to induce phenolic metabolism in the roots and leaves of tomato seedlings. Sodium alginates (ALSM and ALCM) were extracted from the brown seaweeds Sargassum muticum and Cystoseira myriophylloides, respectively. Low-molecular-weight alginates (OASM and OACM) were obtained after radical hydrolysis of the native alginates. Elicitation was carried out by foliar spraying 20 mL of aqueous solutions (1 g/L) on 45-day-old tomato seedlings. Elicitor capacities were evaluated by monitoring phenylalanine ammonia-lyase (PAL) activity, polyphenols, and lignin production in the roots and leaves after 0, 12, 24, 48, and 72 h of treatment. The molecular weights (Mw) of the different fractions were 202 kDa for ALSM, 76 kDa for ALCM, 19 kDa for OACM, and 3 kDa for OASM. FTIR analysis revealed that the structures of OACM and OASM did not change after oxidative degradation of the native alginates. These molecules showed their differential capacity to induce natural defenses in tomato seedlings by increasing PAL activity and through the accumulation of polyphenol and lignin content in the leaves and roots. The oxidative alginates (OASM and OACM) exhibited an effective induction of the key enzyme of phenolic metabolism (PAL) compared to the alginate polymers (ALSM and ALCM). These results suggest that low-molecular-weight alginates may be good candidates for stimulating the natural defenses of plants.

Acute kidney injury, which is associated with high levels of morbidity and mortality, affects a significant number of individuals, and can be triggered by multiple factors, such as medications, exposure to toxic chemicals or other substances, disease, and trauma. Because the kidney is a critical organ, understanding and identifying early cellular or gene-level changes can provide a foundation for designing medical interventions. In our earlier work, we identified gene modules anchored to histopathology phenotypes associated with toxicant-induced liver and kidney injuries. Here, using in vivo and in vitro experiments, we assessed and validated these kidney injury-associated modules by analyzing gene expression data from the kidneys of male Hartley guinea pigs exposed to mercuric chloride. Using plasma creatinine levels and cell-viability assays as measures of the extent of renal dysfunction under in vivo and in vitro conditions, we performed an initial range-finding study to identify the appropriate doses and exposure times associated with mild and severe kidney injuries. We then monitored changes in kidney gene expression at the selected doses and time points post-toxicant exposure to characterize the mechanisms of kidney injury. Our injury module-based analysis revealed a dose-dependent activation of several phenotypic cellular processes associated with dilatation, necrosis, and fibrogenesis that were common across the experimental platforms and indicative of processes that initiate kidney damage. Furthermore, a comparison of activated injury modules between guinea pigs and rats indicated a strong correlation between the modules, highlighting their potential for cross-species translational studies.

Malaria incidence is generally lower in cities than rural areas. However, reported urban malaria incidence may not accurately reflect the level of ongoing transmission, which has potentially large implications for prevention efforts. To guide mosquito net distribution, we assessed the extent of malaria transmission in Conakry, Guinea, in 2018. We found evidence of active malaria transmission.

The emergence of fast-switching wide-bandgap (GaN, SiC) power electronics devices has enabled motor drive systems to achieve high efficiency, power density, control bandwidth and high-level of integration. However, the fast-switching speed and high switching frequency result in an increased level of motor overvoltage at both motor terminals and stator neutral. This overvoltage increases the stress across the motor winding insulation and bearings. This paper investigates three types of motor overvoltages, i.e., differential mode (DM) (phase-to-phase) motor terminal overvoltage, common mode (CM) (phase-to-ground) motor terminal overvoltage and CM stator neutral overvoltage (motor neutral to ground). Both the high switching speed (high dv/dt) effect and the high switching frequency effect on the motor overvoltage are investigated in this paper, where the high switching frequency effect has not been fully addressed in existing literature. Significant overvoltage is observed when the switching frequency or its multiples coincide with the cable or motor anti-resonant frequency. The anti-resonant behavior in the cable and motor impedance has been used to identify the overvoltage oscillation frequency and to explain the overvoltage observations for the three types of motor overvoltages. The analysis has been tested using a 7.5kW motor setup with and without a four-core cable, driven by a SiC or a GaN three-phase inverter with a switching frequency up to 250kHz and switching speed up to 40kV/ $\mu \text{s}$ . In addition, the motor bearing current, which is a main cause of bearing degradation, has also been tested and the increase of bearing current is observed due to the high frequency effect.

Partial discharge (PD) is a prime cause of premature failure of inverter-fed motor winding insulation. With the emergence of fast-switching wide-bandgap silicon-carbide (SiC) power semiconductor devices, random-wound motors are more vulnerable to highly repetitive PDs due to the high-frequency steep-fronted switching transitions that result in overvoltage oscillations at the motor terminals and non-uniform voltage distribution within the motor winding turns. This article investigates the impact of the applied PWM voltage waveforms on the PD behavior in SiC-based inverter-fed motors, including two-level, three-level, and quasi-three-level PWM waveforms. The electric field distribution inside insulation defects (air cavities) is analysed for the different PWM voltage waveforms to theoretically predict the number and phase of probable PD events within the fundamental cycle. An experimental PD measurement setup is used to validate the theoretical analysis by applying the PWM voltage waveforms, that are generated by SiC-based power converters, on a typical turn-to-turn motor winding insulation system created by a twisted pair of enamelled magnet wire. Phase-resolved PD patterns are generated to assess the PD behavior against the PWM characteristics of each voltage waveform and the associated overvoltage pattern when power cables are used to emulate the voltage reflections in cable-fed motor drives. Detailed experiment specifications are provided in this article involving PD measurement methods and PD data post-processing algorithms. The obtained results are assessed, and conclusions are drawn as a useful and timely reference that enhances the understanding of insulation PD process in SiC-based power electronics applications.

Abstract Background A family of Tc1/mariner transposons with a characteristic DD38E triad of catalytic amino acid residues, named Intruder (IT), was previously discovered in sturgeon genomes, but their evolutionary landscapes remain largely unknown. Results Here, we comprehensively investigated the evolutionary profiles of ITs, and evaluated their cut-and-paste activities in cells. ITs exhibited a narrow taxonomic distribution pattern in the animal kingdom, with invasions into two invertebrate phyla (Arthropoda and Cnidaria) and three vertebrate lineages (Actinopterygii, Agnatha, and Anura): very similar to that of the DD36E/IC family. Some animal orders and species seem to be more hospitable to Tc1/mariner transposons, one order of Amphibia and seven Actinopterygian orders are the most common orders with horizontal transfer events and have been invaded by all four families (DD38E/IT, DD35E/TR, DD36E/IC and DD37E/TRT) of Tc1/mariner transposons, and eight Actinopterygii species were identified as the major hosts of these families. Intact ITs have a total length of 1.5–1.7 kb containing a transposase gene flanked by terminal inverted repeats (TIRs). The phylogenetic tree and sequence identity showed that IT transposases were most closely related to DD34E/Tc1. ITs have been involved in multiple events of horizontal transfer in vertebrates and have invaded most lineages recently (

Trichinella spiralis larvae have very special characters that make them able to completely transform the function of the affected muscle cells towards a self-serving environment, offering them nourishment and protection via what is known as “nurse cells”. This setting may be affected by drugs that are used for the treatment of co-morbidities and co-infections as calcium channel blockers, which are widely used in clinical practice. In the present study, the effects of verapamil, ivermectin (IVM), and their combined administration on the parasitic burden, immuno-pathology and angiogenesis were investigated during experimental trichinellosis. Estimation of intestinal adult parasitic stages and muscle larvae was done. VEGF gene expression and CD31 immunohistochemical local expression were measured to investigate angiogenesis, in addition to histopathological examination to explore the extent of inflammation. Although verapamil did not have an effect on the adult worm count during the intestinal phase, it induced an anti-inflammatory effect on intestinal pathology. During the muscle phase, it was very effective in reducing the larval count by 93.78%. IVM effectively reduced the worm count by 85.34%, and the muscle larval count by 97.84%, while combined verapamil and IVM administration resulted in a significant reduction in both adult parasites by 69.5% and larval stages by 99%. Both verapamil and IVM and their combination induced a potent decrease in local CD31 protein expression and VEGF gene expression. The important role of calcium and calcium channels during the pathology of trichinellosis, in addition to the pivotal role of calcium on biological processes such as immunity and angiogenesis, make calcium-channel blockers promising candidates for drug repurposing in the management of helminthic infection.

AIM: To determine the prevalence and associations of non-retinopathy ocular conditions among older Australian adults with diabetes. METHODS: Multistage random-cluster sampling was used to select 3098 non-indigenous Australians aged 50y or older (46.4% male) and 1738 indigenous Australians aged 40y or older (41.1% male) from all levels of geographic remoteness in Australia. Participants underwent a standardised questionnaire to ascertain diabetes history, and a clinical examination to identify eye disease. We determined the prevalence of uncorrected refractive error, visually significant cataract, cataract surgery, age-related macular degeneration, glaucoma, ocular hypertension, retinal vein occlusion and epiretinal membrane among those with and without self-reported diabetes. RESULTS: Participants with self-reported diabetes had a higher prevalence of cataract surgery than those without diabetes (28.8% vs 16.9%, OR 1.78, 95%CI: 1.35-2.34 among non-indigenous Australians, and 11.3% vs 5.2%, OR 1.62, 95%CI: 1.22-2.14 among indigenous Australians). Diabetic retinopathy (DR) increased the odds of cataract surgery among self-reported diabetic indigenous and non-indigenous Australians (OR 1.89, P=0.004 and OR 2.33, P

We tested for enterovirus D68 in fecal samples collected during June–September 2016 from 567 patients with acute flaccid paralysis in 7 West Africa nations. Children

Abstracts Background Tc1/mariner and Zator, as two superfamilies of IS630-Tc1-mariner (ITm) group, have been well-defined. However, the molecular evolution and domestication of pogo transposons, once designated as an important family of the Tc1/mariner superfamily, are still poorly understood. Results Here, phylogenetic analysis show that pogo transposases, together with Tc1/mariner, DD34E/Gambol, and Zator transposases form four distinct monophyletic clades with high bootstrap supports (> = 74%), suggesting that they are separate superfamilies of ITm group. The pogo superfamily represents high diversity with six distinct families (Passer, Tigger, pogoR, Lemi, Mover, and Fot/Fot-like) and wide distribution with an expansion spanning across all the kingdoms of eukaryotes. It shows widespread occurrences in animals and fungi, but restricted taxonomic distribution in land plants. It has invaded almost all lineages of animals—even mammals—and has been domesticated repeatedly in vertebrates, with 12 genes, including centromere-associated protein B (CENPB), CENPB DNA-binding domain containing 1 (CENPBD1), Jrk helix–turn–helix protein (JRK), JRK like (JRKL), pogo transposable element derived with KRAB domain (POGK), and with ZNF domain (POGZ), and Tigger transposable element-derived 2 to 7 (TIGD2–7), deduced as originating from this superfamily. Two of them (JRKL and TIGD2) seem to have been co-domesticated, and the others represent independent domestication events. Four genes (TIGD3, TIGD4, TIGD5, and POGZ) tend to represent ancient domestications in vertebrates, while the others only emerge in mammals and seem to be domesticated recently. Significant structural variations including target site duplication (TSD) types and the DDE triad signatures (DD29–56D) were observed for pogo transposons. Most domesticated genes are derived from the complete transposase genes; but CENPB, POGK, and POGZ are chimeric genes fused with additional functional domains. Conclusions This is the first report to systematically reveal the evolutionary profiles of the pogo transposons, suggesting that pogo and Tc1/Mariner are two separate superfamilies of ITm group, and demonstrating the repeated domestications of pogo in vertebrates. These data indicate that pogo transposons have played important roles in shaping the genome and gene evolution of fungi and animals. This study expands our understanding of the diversity of pogo transposons and updates the classification of ITm group.

La question de la pauvreté ne cesse de faire des débats tant théoriques qu’empiriques. Elle est considérée comme un élément central des stratégies et politiques de développement. Ses conséquences et son impact sur la croissance font d’elle un phénomène toujours d’actualité et de regain d’intérêt. En effet, la pauvreté, constitue une préoccupation majeure et un défi à toutes les économies. Elle est l’une des problématiques complexes des politiques de développement, du fait de son caractère multidimensionnel et son impact sur la croissance économique, les inégalités sociales, l’économie informelle, la dégradation des ressources naturelles, la délinquance, la débauche…etc. En somme elle est source de problèmes et contraintes qui entravent d’une manière ou d’une autre le développement durable. La grande question qui s’impose reste comment faut-il approcher de manière scientifique la pauvreté ? Comment peut-on la mesurer ? Sur quels indicateurs et déterminants faut-il se baser pour mieux caractériser et cibler le pauvre et la pauvreté et en faire un élément central parmi d’autres dans toute politique de développement ? La plupart des études scientifiques adoptent l’approche monétaire de la pauvreté élaborée par la banque mondiale et qui se base sur le revenu monétaire ou la dépense en s’appuyant sur le seuil de la pauvreté. Actuellement cette approche est dépassée dans la mesure où elle exclut les facteurs non monétaires considérés déterminants dans le phénomène de la pauvreté. De nos jours, la plupart des études se focalisent sur l’approche multidimensionnelle de la pauvreté qui reste plus objective et qui intègre aussi bien les aspects monétaires que non monétaires. Les objectifs de ce travail visent entre autres : v Le diagnostic et l’état des lieux de la pauvreté au Maroc à travers deux approches à savoir l’approche monétaire et l’approche multidimensionnelle ; v L’évolution et la dynamique de la pauvreté au Maroc ; v L’impact de la pauvreté au Maroc ; v Les mesures mises en œuvre pour atténuer l’impact de la pauvreté.

IntroductionIn Senegal, discontinuation due to sides effects of long-acting, reversible contraceptives (LARCs) is relatively low; 5% of new implant acceptors and 11% of new IUD acceptors stop using in their first year because of health or side effect concerns. This study investigated factors associated with LARC discontinuation in the first 12 months of use in Senegal and explored how LARC users cope with side effects.MethodsThis mixed-method study involved quantitative interviews at five time points with LARC acceptors recruited from three service channels between February 2018 and March 2019. Qualitative interviews were conducted in August 2018 with a subset of those who experienced side effects. Logistic regression models identified factors associated with discontinuation due to side effects and discontinuation for any reason. Twelve-month discontinuation rates due to side effects were also estimated using a cumulative incidence function (CIF) approach to account for time to discontinuation.ResultsIn logistic models, method choice (IUD or implant) [OR = 3.15 (95% CI: 1.91–5.22)] and parity [OR = 0.81 (95% CI: 0.7–0.94)] were associated with discontinuation due to side effects; IUD users and women with fewer children were more likely to discontinue. Results for all-cause discontinuation were similar: method choice [OR = 2.39 (95% CI: 1.6–3.58)] and parity [OR = 0.86 (95% CI: 0.77–0.96)] were significant predictors. The 12-month side effect CIF discontinuation rate was 11.2% (95% CI: 7.9–15.0%) for IUDs and 4.9% (95% CI: 3.5–6.6%) for implants. Side effect experiences varied, but most women considered menstrual changes the least acceptable. No statistically significant differences across services channels were observed.ConclusionsIn this study in Senegal, the choice between implants and IUDs had a significant impact on continuation, and women with more children continued LARC methods longer, despite side effects.

La présente étude porte sur l’analyse diachronique, entre 1986 et 2017, de la dynamique spatiale de 20 forêts sacrées du bassin du Haut Niger en république de Guinée. L’interprétation des images satellites Landsat TM (1986, Landsat OLI/TIRS (2017), ainsi que les relevés de terrain, ont été utilisés. L’étude a révélé que malgré leur caractère sacré, la surveillance des sites forestiers étudiés pose problème. L’analyse diachronique de l’évolution spatiale de chacune des 20 forêts étudiées montre, à l’exception d’un seul site, une tendance régressive de l’ensemble des superficies initiales qui, sont passées de 2 581,10 ha en 1986, à 1 206,6 ha en 2017. Durant les trois décennies, la superficie initiale totale des 20 forêts a diminué de 57,5 % en moyenne, avec un taux annuel moyen de 3,8 %. Cette réduction considérable de la superficie est principalement liée à l’agriculture (63%). La pression démographique, la proximité des villages, l’affaiblissement des systèmes traditionnels de gestion et l’influence de l’islam, sont à l’origine de cette déforestation. La gestion foncière des terres dans les terroirs villageois du bassin est nécessaire pour la sauvegarde de ce patrimoine écologique.

Abstract Background Radical surgery of gastric cancer is considered as the only curative treatment; however, its poor long-term survival is often occurred due to its recurrence either local and/or distant metastasis. Thus, early detection of recurrence helps in improving the prognosis. Our aim is to assess the diagnostic role of 18F-FDG PET/CT for detecting postoperative recurrence in gastric cancer patients who have a radiological and/or clinical suspicion of recurrence. Results The study was carried over 31 males (62%) and 19 females (38%) pathologically proven with gastric carcinoma and underwent surgical intervention. All patients underwent PET/CT scan where the site and number of positive FDG activity analyzed. The sensitivity, specificity, and accuracy for locoregional recurrence were 75%, 81.58%, and 85% with p value 0.001; for regional lymph node recurrence were 100%, 100%, and 100% with p value < 0.001; for liver metastasis were 100%, 100%, and 100% with p value < 0.001; for peritoneum metastasis were 100%, 97.38%, and 98% with p value < 0.001; and for distant metastasis were 100%, 85.7%, and 94% with p value < 0.001. Conclusion With agreements to many studies, this study confirms that FDG PET/CT is a highly effective modality for postoperative surveillance detection of recurrent gastric cancer, especially in patients with clinically manifested disease, elevated tumor markers, and an indication of distant metastasis at diagnostic CT.

Summary: Background: Excessive use of digital smart devices, including smartphones and tablet computers, could be a risk factor for myopia. We aimed to review the literature on the association between digital smart device use and myopia. Methods: In this systematic review and meta-analysis we searched MEDLINE and Embase, and manually searched reference lists for primary research articles investigating smart device (ie, smartphones and tablets) exposure and myopia in children and young adults (aged 3 months to 33 years) from database inception to June 2 (MEDLINE) and June 3 (Embase), 2020. We included studies that investigated myopia-related outcomes of prevalent or incident myopia, myopia progression rate, axial length, or spherical equivalent. Studies were excluded if they were reviews or case reports, did not investigate myopia-related outcomes, or did not investigate risk factors for myopia. Bias was assessed with the Joanna Briggs Institute Critical Appraisal Checklists for analytical cross-sectional and cohort studies. We categorised studies as follows: category one studies investigated smart device use independently; category two studies investigated smart device use in combination with computer use; and category three studies investigated smart device use with other near-vision tasks that were not screen-based. We extracted unadjusted and adjusted odds ratios (ORs), β coefficients, prevalence ratios, Spearman's correlation coefficients, and p values for associations between screen time and incident or prevalent myopia. We did a meta-analysis of the association between screen time and prevalent or incident myopia for category one articles alone and for category one and two articles combined. Random-effects models were used when study heterogeneity was high (I2>50%) and fixed-effects models were used when heterogeneity was low (I2≤50%). Findings: 3325 articles were identified, of which 33 were included in the systematic review and 11 were included in the meta-analysis. Four (40%) of ten category one articles, eight (80%) of ten category two articles, and all 13 category three articles used objective measures to identify myopia (refraction), whereas the remaining studies used questionnaires to identify myopia. Screen exposure was measured by use of questionnaires in all studies, with one also measuring device-recorded network data consumption. Associations between screen exposure and prevalent or incident myopia, an increased myopic spherical equivalent, and longer axial length were reported in five (50%) category one and six (60%) category two articles. Smart device screen time alone (OR 1·26 [95% CI 1·00–1·60]; I2=77%) or in combination with computer use (1·77 [1·28–2·45]; I2=87%) was significantly associated with myopia. The most common sources of risk of bias were that all 33 studies did not include reliable measures of screen time, seven (21%) did not objectively measure myopia, and nine (27%) did not identify or adjust for confounders in the analysis. The high heterogeneity between studies included in the meta-analysis resulted from variability in sample size (range 155–19 934 participants), the mean age of participants (3–16 years), the standard error of the estimated odds of prevalent or incident myopia (0·02–2·21), and the use of continuous (six [55%] of 11) versus categorical (five [46%]) screen time variables Interpretation: Smart device exposure might be associated with an increased risk of myopia. Research with objective measures of screen time and myopia-related outcomes that investigates smart device exposure as an independent risk factor is required. Funding: None.

This study aims to assess for the first time the ability of marine polysaccharides and their derivatives to stimulate natural defenses in olive tree leaves. Alginates, ALSM, and ALCM were isolated from the brown algae Sargassum muticum and Cystoseira myriophylloides, respectively. The OASM and OACM fractions were obtained after radical depolymerization of ALSM and ALCM, respectively. Three sulfated polysaccharides, arabinogalactans (AGB and AGP) and fucoidans (FUCCM) were extracted from the green alga Codium decorticatum and the brown seaweed C. myriophylloides, respectively. The extraction yield of different extracts was in the range of 0.82–32% and the average molecular weight (Mw) varied from 3000 Da to 2173 kDa. The M/G ratios of ALSM and ALCM were 0.87 and 1.12, respectively. FUCCM contained 53% of fucose and 12.83% of sulfates. The AGB and AGP fractions were characterized by the presence of a high degree of sulfation and protein (12–23% (w/w)) and were composed mainly of galactose, glucose, and arabinose. The aqueous saccharide solutions were applied to the leaf discs of the olive tree at 0.5 g/L, 1 g/L, and 2 g/L, for 24 h. These molecules triggered defense responses, by showing a differential capacity to induce the activity of the phenylalanine and tyrosine ammonia-lyase (TAL and PAL), polyphenols, and lignin contents in the leaves of the olive tree. Alginates and their derivatives as well as arabinogalactans exhibited an important induction of TAL activity compared to the PAL. The sulfated polysaccharides were more effective compared to the unsulfated polysaccharides (alginates) which were active at a low concentration. The optimum concentration for most of the studied elicitors was 2 g/L. These results suggest the valorization of these molecules derived from marine biomass as inducers of natural defenses of the olive tree to protect against phytopathogens in the context of sustainable development.

The prevalence of food allergy has increased over the last 20-30 years, including cow milk allergy (CMA) which is one of the most common causes of infant food allergy. International allergy experts met in 2019 to discuss broad topics in allergy prevention and management of CMA including current challenges and future opportunities. The highlights of the meeting combined with recently published developments are presented here. Primary prevention of CMA should start from pre-pregnancy with a focus on a healthy lifestyle and food diversity to ensure adequate transfer of inhibitory IgG- allergen immune complexes across the placenta especially in mothers with a history of allergic diseases and planned c-section delivery. For non-breastfed infants, there is controversy about the preventive role of partially hydrolyzed formulae (pHF) despite some evidence of health economic benefits among those with a family history of allergy. Clinical management of CMA consists of secondary prevention with a focus on the development of early oral tolerance. The use of extensive Hydrolysate Formulae (eHF) is the nutrition of choice for the majority of non-breastfed infants with CMA; potentially with pre-, probiotics and LCPUFA to support early oral tolerance induction. Future opportunities are, among others, pre- and probiotics supplementation for mothers and high-risk infants for the primary prevention of CMA. A controlled prospective study implementing a step-down milk formulae ladder with various degrees of hydrolysate is proposed for food challenges and early development of oral tolerance. This provides a more precise gradation of milk protein exposure than those currently recommended.

Abstract Background The Tc1/mariner superfamily might represent the most diverse and widely distributed group of DNA transposons. Several families have been identified; however, exploring the diversity of this superfamily and updating its classification is still ongoing in the life sciences. Results Here we identified a new family of Tc1/mariner transposons, named Incomer (IC), which is close to, but distinct from the known family DD34E/Tc1. ICs have a total length of about 1.2 kb, and harbor a single open reading frame encoding a ~ 346 amino acid transposase with a DD36E motif and flanked by short terminal inverted repeats (TIRs) (22–32 base pairs, bp). This family is absent from prokaryotes, and is mainly distributed among vertebrates (141 species of four classes), including Agnatha (one species of jawless fish), Actinopterygii (132 species of ray-finned fish), Amphibia (four species of frogs), and Mammalia (four species of bats), but have a restricted distribution in invertebrates (four species in Insecta and nine in Arachnida). All ICs in bats (Myotis lucifugus, Eptesicus fuscus, Myotis davidii, and Myotis brandtii) are present as truncated copies in these genomes, and most of them are flanked by relatively long TIRs (51–126 bp). High copy numbers of miniature inverted-repeat transposable elements (MITEs) derived from ICs were also identified in bat genomes. Phylogenetic analysis revealed that ICs are more closely related to DD34E/Tc1 than to other families of Tc1/mariner (e.g., DD34D/mariner and DD × D/pogo), and can be classified into four distinct clusters. The host and IC phylogenies and pairwise distance comparisons between RAG1 genes and all consensus sequences of ICs support the idea that multiple episodes of horizontal transfer (HT) of ICs have occurred in vertebrates. In addition, the discovery of intact transposases, perfect TIRs and target site duplications of ICs suggests that this family may still be active in Insecta, Arachnida, frogs, and fish. Conclusions Exploring the diversity of Tc1/mariner transposons and revealing their evolutionary profiles will help provide a better understanding of the evolution of DNA transposons and their impact on genomic evolution. Here, a newly discovered family (DD36E/Incomer) of Tc1/mariner transposons is described in animals. It displays a similar structural organization and close relationship with the known DD34E/Tc1 elements, but has a relatively narrow distribution, indicating that DD36E/IC might have originated from the DD34E/Tc1 family. Our data also support the hypothesis of horizontal transfer of IC in vertebrates, even invading one lineage of mammals (bats). This study expands our understanding of the diversity of Tc1/mariner transposons and updates the classification of this superfamily.

The use of PET for detection of Aβ in the brain in AD has limitations; studies also indicate that retinal changes, including Aβ deposition, occur in AD. Here the authors demonstrate the potential to use in vivo retinal hyperspectral imaging as a surrogate for brain accumulation of Aβ.

The data of this study revealed that Tigger was found in a wide variety of animal genomes, including 180 species from 36 orders of invertebrates and 145 species from 29 orders of vertebrates. An extensive invasion of Tigger was observed in mammals, with a high copy number. Almost 61% of those species contain more than 50 copies of Tigger; however, 46% harbor intact Tigger elements, although the number of these intact elements is very low. Common HT events of Tigger elements were discovered across different lineages of animals, including mammals, that may have led to their widespread distribution, whereas Helogale parvula and arthropods may have aided Tigger HT incidences. The activity of Tigger seems to be low in the kingdom of animals, most copies were truncated in the mammal genomes and lost their transposition activity, and Tigger transposons only display signs of recent and current activities in a few species of animals. The findings suggest that the Tigger family is important in structuring mammal genomes.

The brown Tunisian seaweed Halopteris scoparia was used as a feedstock for producing renewable bioethanol, biogas, and biodiesel to demonstrate the proof of concept for the North African energy sector. A quantitative and qualitative quantification of H. scoparia composition using different colorimetric methods was completed to highlight its bioconversion potential. These substrate inputs were subjected to anaerobic fermentation by Saccharomyces cerevisiae to produce bioethanol. The materials were also used to generate bio-hydrogen and volatile fatty acids during dark fermentation by a bacterial consortium and using the oleaginous yeast Yarrowia lipolytica. The lipids were extracted and trans-esterified to Fatty Acid Methyl Esters (FAMEs), and their profiles were then analyzed with gas chromatography (GC). A significant ratio of the bioethanol, e.g., 0.35 g ethanol/g DW substrate, was produced without pretreatment, consistent with the theoretical Gay-Lussac yield. The production of the biohydrogen and lipids were up to 1.3 mL H2/g DW substrate and 0.04 g/g DW substrate, respectively, from the raw biomass. These results were higher than those reported for other well-studied seaweeds such as L. japonica. Overall, this work contributes to the current investigations in Tunisia for producing alternative energies from algae and finding new solutions to the current energy situation and environmental challenges in Maghreb.