Search

The sonication method was used to prepare a new set of CuO and CuO/Ag nanocomposites. The particle size was estimated using XRD and HR-TEM while the morphology of the nanoparticles was investigated with SEM. The average particle sizes of CuO and Ag falls in the 29.32-35.80 nm and 35.13-45.95 nm ranges, respectively. XRD declared that CuO has the space groups C 1 c 1 (9) and C 1 2/c 1 (15), while silver has space group F m -3 m (225). XPS analysis indicated the presence of Ag as Ag 0 and Cu as Cu 2+ . Nano-oxide and nanocomposites were used to synthesis CuO and CuO/Ag doped lithium-zinc borosilicate glass. Physical parameters of the glass samples were calculated including density, V m , V o , V m B , OPD, d B - B , n b , and N, R p , and R i depending on Ag and CuO mole fractions. The physical properties of glass indicated an increase in density and an initial expansion in glass structural network with the addition of silver metal due to its larger size followed by a compression as its molar ratio increase due to its higher C no . XRD measurements were reported for the glass samples doped with nanoparticles, proving the amorphous phase. ESR measurements were determined for all glass samples to detect the nature of the doped nanoparticles when incorporated inside a glassy matrix where CuO was found as tetragonal in octahedral sites and silver can be transformed after melting inside the glass matrix into Ag + to form more stable Ag y x + clusters.The fabricated sample of CuAgB-4 with significant nano silver doping (7.32% mol) has the maximum LAc and effective atomic number. Nano silver content increases the γ -RdSg in the lithium-zinc borosilicate glasses., (© 2024. The Author(s).)

This study investigates the role of dietary Bacillus subtilis and oregano essential oil in mitigating the effects of high stocking density on growth performance, carcass traits, physiological stress indicators, gene expression, and intestinal integrity in broiler chickens. A total of, 1250 one-day-old Ross 308 male broiler chicks were randomly allocated to five experimental groups, where each group had five replicates of 50 chicks. Group 1 (control, LSD): 15 chicks/m 2 fed a basal diet without feed additive, group 2 (HSD): 20 chicks/m 2 fed a basal diet without feed additive, group 3 (BHSD): 20 chicks/m 2 fed a basal diet supplemented with B. subtilis (500 mg/kg diet), group 4 (OHSD): 20 chicks/m 2 fed a basal diet supplemented with oregano essential oil (300 mg/kg diet), group 5 (CHSD): 20 chicks/m 2 fed a basal diet supplemented with oregano essential oil and B. subtilis. At 35 days of age, there was a noticeable improvement in the growth performance of broilers fed CHSD under high stocking density through the increase in body weight gain, dressing percentage, and crude protein digestibility with a decrease in feed conversion rate compared to other groups. Adding CHSD enhanced the state of oxidation and immunity through increasing superoxide dismutase, glutathione peroxidase, and the relative weight of bursa of Fabricius, while decreasing malondialdehyde, in addition to increasing plasma triiodothyronine levels. The microbial structure and morphometric parameters improved in the group that received the CHSD compared to the other groups, where villus height and Lactobacillus population increased, whereas Escherichia coli and Clostridium perfringens population decreased. Glucose transporter 2 (GLUT2), fatty acid transporter 1 (FABP1), and amino acid transferase 1 (CAT1) gene expression levels significantly increased when feeding on oregano essential oil with B. subtilis. In conclusion, combining oregano essential oil and B. subtilis supplements mitigated the effects of high stocking density by enhancing growth performance, antioxidative status, and intestinal integrity, in addition to modifying the genetic expression of genes related to nutrient absorption., (© 2024. The Author(s).)

Objectives: To evaluate the effect of the universal and rapid autoclave cycles on the mechanical properties and surface roughness of nickel-titanium archwires following clinical use., Material and Methods: Thirty-six NiTi archwires (0.016 × 0.022 inch) were equally divided into a control group (Group A) and 2 experimental groups (Group B & C). Wires in group A were tested in the "as-received" form. Wires in the two other groups were installed in patients mouth for 4 weeks, and then autoclaved using the rapid-cycle (Group B) or the universal-cycle (Group C). All wires were subjected to 3-point bending test to calculate the elastic limit, modulus of elasticity, spring-back, yield strength, resilience and toughness. Atomic force microscopy (AFM) was used for surface roughness qualitative and quantitative analysis., Results: Group B showed significantly higher values of elastic limit, modulus of elasticity, resilience, yield strength and toughness than the other two groups. No significant differences were detected between groups A and C (P > 0.05). Group B showed significantly lower average surface roughness than the other two groups, but no significant differences were detected between groups A and C (P > 0.05)., Conclusions: The mechanical properties and surface roughness of clinically used NiTi wires were less affected by the universal-cycle than the rapid-cycle autoclaving. However, the difference between the effect of both autoclave cycles was diminutive., Clinical Relevance: The mechanical properties and surface roughness of the tested NiTi wires were not notably altered by clinical use and autoclaving., (© 2024. The Author(s).)

Aim: An ineffective immune response resulting from dysregulation of cytokine production might encourage viral persistence and cause chronic viral hepatitis to worsen. This study examined the relationship between alterations in interleukin-6 (IL-6) levels and the IL-6 - 174 G > C (rs1800795) polymorphism, as well as how this polymorphism affects the development and progression of chronic hepatitis brought on by hepatitis B (HBV) and hepatitis C (HCV) into hepatocellular carcinoma (HCC)., Patients and Methods: Whole blood samples from 126 Egyptian patients with HCC (111 with HCV and 15 with HBV), as well as 126 age- and sex-matched healthy individuals, were used to extract DNA. Using PCR-based allele-specific amplification (ASA), the existence of the IL-6 G-174C polymorphism was investigated. Additionally, each participant's serum IL-6 levels were determined using an enzyme-linked immunosorbent assay (ELISA)., Results: The primary observations revealed that HCC patients had greater serum levels of IL-6 compared to the control groups (p < 0.001). Patients with the variant (CG and GG) genotype in the HCC group were found to have more disease severity indicated by higher levels of alpha-fetoprotein (AFP) and a higher ascites grade, as well as increased inflammatory activity as defined by higher levels of IL-6 and C-reactive protein (CRP) (p < 0.001 for both) in comparison to patients with the wild-type (CC) genotype (p < 0.001 and p = 0.002, respectively)., Conclusion: The rs1800795 SNP in the IL-6 gene was associated with increased inflammatory activity and high levels of IL-6, indicating that this SNP may play a role in the development of HCC in Egyptian patients with chronic viral hepatitis., (© 2024. The Author(s).)

Biallelic loss of function variants in ESAM (endothelial cell adhesion molecule) have recently been reported in 14 individuals (9 families) presenting with prenatal intracranial hemorrhage. Here, we describe four patients from two unrelated families in whom three of them presented with variable onset encephalopathy and seizures while one only displayed profound delay without seizures. Brain MRI showed variable onset intracranial hemorrhage that evolved to hydrocephalus in 3 patients, whereas hemosiderin deposits, white matter volume loss, and porencephalic cysts were noted in one patient. Unlike the majority of described cases, the youngest brother of the first family did not show microcephaly and failure to thrive. Exome sequencing identified two novel homozygous ESAM variants. A splice variant (c.731-2A>G) was identified in one family which was confirmed by investigating the patient's mRNA to result in exon skipping and early protein truncation. In addition, a missense variant (c.561G>C; p.Trp187Cys) was identified in the other family, which is the first disease causing missense variant to be described in patients with ESAM deficient phenotype. In addition, a maternally inherited pathogenic MC4R variant (c.811T>C; p.Cys271 Arg) was also identified in the youngest brother of the first family. Variants in the MC4R gene are associated with a non-syndromic form of obesity that could explain the unusual macrocephaly and obesity. Our work establishes ESAM as a tight junction gene that can present with variable neuroradiological and clinical phenotypes when mutated. Moreover, it refines the phenotype of this ultrarare syndrome and extends the number and type of variants described to date., (© 2024. The Author(s).)

Biofuel production has emerged as a leading contender in the quest for renewable energy solutions, offering a promising path toward a greener future. This comprehensive state-of-the-art review delves into the current landscape of biofuel production, exploring its potential as a viable alternative to conventional fossil fuels. This study extensively examines various feedstock options, encompassing diverse sources such as plants, algae, and agricultural waste, and investigates the technological advancements driving biofuel production processes. This review highlights the environmental benefits of biofuels, emphasizing their capacity to significantly reduce greenhouse gas emissions compared to those of fossil fuels. Additionally, this study elucidates the role of biofuels in enhancing energy security by decreasing reliance on finite fossil fuel reserves, thereby mitigating vulnerabilities to geopolitical tensions and price fluctuations. The economic prospects associated with biofuel production are also elucidated, encompassing job creation, rural development, and the potential for additional revenue streams for farmers and landowners engaged in biofuel feedstock cultivation. While highlighting the promise of biofuels, the review also addresses the challenges and considerations surrounding their production. Potential issues such as land use competition, resource availability, and sustainability implications are critically evaluated. Responsible implementation, including proper land-use planning, resource management, and adherence to sustainability criteria, is emphasized as critical for the long-term viability of biofuel production. Moreover, the review underscores the importance of ongoing research and development efforts aimed at enhancing biofuel production efficiency, feedstock productivity, and conversion processes. Technological advancements hold the key to increasing biofuel yields, reducing production costs, and improving overall sustainability. This review uniquely synthesizes the latest advancements across the entire spectrum of biofuel production, from feedstock selection to end-use applications. It addresses critical research gaps by providing a comprehensive analysis of emerging technologies, sustainability metrics, and economic viability of various biofuel pathways. Unlike previous reviews, this work offers an integrated perspective on the interplay between technological innovation, environmental impact, and socio-economic factors in biofuel development, thereby providing a holistic framework for future research and policy directions in renewable energy., (© 2024. The Author(s).)

Background: Although numerous mechanisms are involved in vitiligo pathogenesis, few studies correlate N-acetyltransferase 2 to this disease., Aim: To assess the N-acetyltransferase 2 (rs1799929) gene and its serum levels in vitiligo patients., Subjects and Methods: In this case-control study, 65 vitiligo cases were compared to 65 age- and sex-matched healthy controls. Serum NAT2 levels and the NAT2 gene polymorphism (rs1799929) were evaluated using ELISA and real-time PCR, respectively., Results: Serum N-acetyltransferase 2 levels were significantly lower in cases than in controls, 1.24 ± 0.31 vs. 2.01 ± 0.46 ( p  = 0.001). CC genotype was more dominant in controls (58.5%) than in cases (20%). TT and CT genotypes were more dominant in cases (30.8% and 49.2%) than in controls (13.8% and 27.7%), respectively ( p  = 0.001). The C allele was more prominent in controls (72.3%) than in cases (44.6%) while the T allele was more dominant in cases (55.4%) than in controls (27.7%) ( p  = 0.001). N-acetyltransferase 2 slow acetylator phenotype (TT genotype) was higher in cases (30.8%) than in controls (13.8%) and rapid acetylator phenotypes (CC and CT genotypes) were higher in controls (86.2%) than in cases (69.2%) ( p  = 0.035)., Conclusion: Slow acetylator genotype (TT) of NAT2 gene (rs1799929) and low serum levels of NAT2 enzyme might play a role in the susceptibility and pathogenesis of vitiligo.

Collagen VI-related dystrophies (COL6-RD) display a wide spectrum of disease severity and genetic variability ranging from mild Bethlem myopathy (BM) to severe Ullrich congenital muscular dystrophy (UCMD) and the intermediate severities in between with dual modes of inheritance, dominant and recessive. In the current study, next-generation sequencing demonstrated potential variants in the genes coding for the three alpha chains of collagen VI (COL6A1, COL6A2, or COL6A3) in a cohort of Egyptian patients with progressive muscle weakness (n = 23). Based on the age of disease onset and the patient clinical course, subjects were diagnosed as follows: 12 with UCMD, 8 with BM, and 3 with intermediate disease form. Fourteen pathogenic variants, including 5 novel alterations, were reported in the enrolled subjects. They included 3 missense, 3 frameshift, and 6 splicing variants in 4, 3, and 6 families, respectively. In addition, a nonsense variant in a single family and an inframe variant in 3 different families were also detected. Recessive and dominant modes of inheritance were recorded in 9 and 8 families, respectively. According to ACMG guidelines, variants were classified as pathogenic (n = 7), likely pathogenic (n = 4), or VUS (n = 3) with significant pathogenic potential. To our knowledge, the study provided the first report of the clinical and genetic findings of a cohort of Egyptian patients with collagen VI deficiency. Inter- and intra-familial clinical variability was evident among the study cohort., (© 2024. The Author(s).)

Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptors and has a poor prognosis as it is resistant to chemotherapy. A new treatment option for this type of cancer may be by putting these malignant cells into dormancy. The oocyte's embryonic milieu presents a unique tumor reversion microenvironment by inducing growth arrest and changing cells' phenotypes. We conducted an in-silico study to determine the most likely oocyte extract (OE) proteins involved in inducing dormancy using HDock, CluPro, and molecular dynamic (MD) simulation. Results showed low energy scores for complexes between OE proteins and four surface markers: K1C14, CLD3, CLD4, and ITA6. Apolipoprotein A1 (APOA1) and Apolipoprotein C3 (APOC3) showed the highest stability and affinity with these four surface markers: K1C14, CLD3, CLD4, and ITA6. These proteins are involved in key tumor-related pathways such as angiogenesis, proliferation, apoptosis, and migration. This will pave the way for exploring novel therapeutic options to induce dormancy in TNBC cells., (© 2024. The Author(s).)

Biallelic variants in the ERLIN1 gene were recently reported as the cause of two motor neuron degeneration diseases, SPG62 and a recessive form of amyotrophic lateral sclerosis. However, only 12 individuals from five pedigrees have been identified so far. Thus, the description of the disease remains limited. Following the discovery of a homozygous pathogenic variant in a girl with SPG62, presenting with intellectual disability, and epilepsy, we gathered the largest series of SPG62 cases reported so far (13 individuals) to better understand the phenotype associated with ERLIN1. We collected molecular and clinical data for 13 individuals from six families with ERLIN1 biallelic variants. We performed RNA-seq analyses to characterize intronic variants and used Alphafold and a transcripts database to characterize the molecular consequences of the variants. We identified three new variants suspected to alter the bell-shaped ring formed by the ERLIN1/ERLIN2 complex. Affected individuals had childhood-onset paraparesis with slow progression. Six individuals presented with gait ataxia and three had superficial sensory loss. Aside from our proband, none had intellectual disability or epilepsy. Biallelic pathogenic ERLIN1 variants induce a rare, predominantly pure, spastic paraparesis, with possible cerebellar and peripheral nerve involvement., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Significance: As an inflammatory and autoimmune skin condition, psoriasis affects 2-3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis., Objective: The goal of this work is to improve Esc's solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption., Methods: The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by in vitro release and in vivo effectiveness on a rat model of UV-induced psoriasis., Results: Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis., Conclusion: As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis.

Background: FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response., Methods: We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022., Results: Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% ( P =0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment., Conclusion: DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A new series of benzimidazole-oxindole hybrids 8a-x was discovered as dual cyclin-dependent kinase (CDK2) and glycogen synthase kinase-3-beta (GSK-3β) inhibitors with potent anticancer activity. The synthesized hits displayed potent anticancer activity against national cancer institute cancer cell lines in single-dose and five-dose assays. Moreover, the derivatives 8k, 8l, 8n, 8o, and 8p demonstrated potent cytotoxic activity against PANC-1 cells with IC 50  = 1.88-2.79 µM. In addition, the hybrids 8l, 8n, 8o, and 8p displayed potent antiproliferative activity on the MG-63 cell line (IC 50  = 0.99-1.90 µM). Concurrently, the benzimidazole-oxindole hybrid 8v exhibited potent dual CDK2/GSK-3β inhibitory activity with IC 50 values of 0.04 and 0.021 µM, respectively. In addition, 8v displayed more than 10-fold higher selectivity toward CDK2 and GSK-3 β over CDK1, CDK5, GSK-3α, vascular endothelial growth factor receptor-2, and B-rapidly accelerated fibrosarcoma. Screening of the effect of 8n and 8v on the cell cycle and apoptosis of PANC-1 and MG-63 cells displayed their ability to arrest their cell cycle at the G2-M phase and to potentiate the apoptosis of both cell lines. In silico docking of the benzimidazole-oxindole hybrid 8v into the catalytic pocket of both CDK2 and GSK-3β revealed its perfect fitting through the formation of hydrogen bonding and hydrophobic interactions with the key amino acids in the binding sites. In addition, in silico absorption, distribution, metabolism, excretion studies proved that 8a-x exhibit satisfactory drug-likeness properties for drug development., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Two new sets of quinazoline-oxindole 8a-l and quinazoline-dioxoisoindoline 10a-d hybrids were designed as type II angiokinase inhibitors and anticancer agents. The design strategy was adjusted to account for the quinazoline scaffold's placement in the target kinases' hinge region, where it would form hydrogen bonding and hydrophobic interactions with the important amino acids to stabilize it, and the amide group's occupation in the gate region, which would direct the oxindole scaffold toward the hydrophobic back pocket. The two sets of quinazolines 8a-l and 10a-d displayed pronounced inhibitory activity on VEGFR-2 (IC 50  = 0.46-2.20 µM). The quinazoline-oxindole hybrids 8d, 8f, and 8h displayed IC 50  = 0.46, 0.49, and 0.49 µM, respectively. Compound 8f demonstrated potent multikinase activity with IC 50 values of 0.95 and 0.67 µM against FGFR-1 and BRAF, respectively. Additionally, compound 8f showed significant anticancer activity against National Cancer Institute's cancer cell lines, with GI 50 reaching 1.21 µM. Analysis of the impact of compound 8f on the MDA-MB-231 cell line's cell cycle and apoptosis revealed that 8f stalled the cell cycle at the G2/M phase and promoted its necrosis., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Background: Zinc finger protein 1 (ZPR1), encoded by the ZNF259 gene, plays crucial roles in transcriptional regulation and cell cycle progression. Despite its known functions, its specific involvement in Metabolic Syndrome (MetS) remains debated. Genome-wide association studies have identified several genes, including ZNF259, implicated in lipid metabolism and associated with MetS. Single nucleotide polymorphisms (SNPs) in ZNF259 have been linked to altered lipid metabolism during the development of MetS. This study aims to investigate the association between MetS in Egyptian patients and three specific ZNF259 SNPs: rs964184, rs2075294, and rs2075290. The objective is to explore how these SNPs correlate with MetS development, other health outcomes, and their interaction with dyslipidemia biomarkers., Methods: 200 Egyptian participants were enrolled, and divided into two groups: 100 patients diagnosed with dyslipidemia and 100 healthy controls. The study involved comprehensive assessments, including lipid profile analysis, anthropometric measurements, and genotyping of rs964184, rs2075290, and rs2075294 in the ZNF259 gene using Real-Time Polymerase Chain Reaction (PCR)., Results: The findings indicate that rs964184 SNP correlates significantly with elevated plasma triacylglycerol (TG) levels, while rs2075290 and rs2075294 are associated with higher total serum cholesterol (TC) and TG levels. Among these SNPs, rs2075294 showed the highest predictive value (area under the curve of 0.748), followed by rs2075290 (0.738), and rs964184 (0.583), suggesting rs2075294 as the most influential SNP in MetS prediction., Conclusion: This study underscores the predictive role of ZNF259 SNPs in MetS risk among Egyptians. Future research should further explore the implications of ZNF259 in MetS pathogenesis and its potential as a biomarker for personalized health interventions., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Researchers worldwide are looking for molecules that might disrupt the COVID-19 life cycle. Endoribonuclease, which is responsible for processing viral RNA to avoid detection by the host defense system, and helicase, which is responsible for unwinding the RNA helices for replication, are two key non-structural proteins. This study performs a hierarchical structure-based virtual screening approach for NSP15 and helicase to reach compounds with high binding probabilities. In this investigation, we incorporated a variety of filtering strategies for predicting compound interactions. First, we evaluated 756,275 chemicals from four databases using a deep learning method (NCI, Drug Bank, Maybridge, and COCONUT). Following that, two docking techniques (extra precision and induced fit) were utilized to evaluate the compounds' binding affinity, followed by molecular dynamic simulation supported by the MM-GBSA free binding energy calculation. Remarkably, two compounds (90616 and CNP0111740) exhibited high binding affinity values of -66.03 and -12.34 kcal/mol for helicase and NSP15, respectively. The VERO-E6 cell line was employed to test their in vitro therapeutic impact. The CC 50 for CNP0111740 and 90616 were determined to be 102.767 μg/ml and 379.526 μg/ml, while the IC 50 values were 140.176 μg/ml and 5.147 μg/ml, respectively. As a result, the selectivity index for CNP0111740 and 90616 is 0.73 and 73.73, respectively. Finally, these compounds were found to be novel, effective inhibitors for the virus; however, further in vivo validation is needed.Communicated by Ramaswamy H. Sarma.

Background: For decades cancer remained the center of attention in the scientific community as its survival rates are low. Researchers from all around the world wanted to know the core of the problem as to what initiates cancer in a patient and helps with its progression. Many postulations came to light, but Cancer Stem Cells (CSC) was the most appealing and convincing., Main Body: In this review, we shed light on a potential solution to the problem by reviewing CAR-T cells (Chimeric antigen receptor T cells). These specialized T cells are designed to detect specific antigens on cancer cells. We analyse the steps of their formation from the collection of T cells from the patient's bloodstream and modifying it to exhibit specific CAR structures on their surfaces, to reinjecting them back and evaluating their efficacy. We thoroughly investigate the structure of the CAR design with improvements across different generations. The focus extends to the unique properties of CSCs as in how targeting specific markers on them can enhance the precision of cancer therapy., Conclusion: Despite the successes, the review discusses the existing limitations and toxicities associated with CAR-derived therapies, highlighting the ongoing need for research and refinement. Looking ahead, we explore proposed strategies aimed at optimizing CAR-T cell therapy to mitigate adverse effects for improved cancer treatments., (© 2024. The Author(s).)

Purpose: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations., Methods: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies., Results: We characterize a clinically variable disorder with cardinal features including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a -/- mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition., Conclusion: Our studies comprehensively characterise INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: FLVCR1 encodes a solute carrier (SLC) protein implicated in heme, choline, and ethanolamine transport. While Flvcr1 -/- mice exhibit skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia (DBA), biallelic FLVCR1 variants in humans have previously only been linked to childhood or adult-onset ataxia, sensory neuropathy, and retinitis pigmentosa., Methods: We identified individuals with undiagnosed neurodevelopmental disorders and biallelic FLVCR1 variants through international data sharing and characterized the functional consequences of their FLVCR1 variants., Results: We ascertained 30 patients from 23 unrelated families with biallelic FLVCR1 variants and characterized a novel FLVCR1-related phenotype: severe developmental disorders with profound developmental delay, microcephaly (Z-score -2.5 to -10.5), brain malformations, epilepsy, spasticity, and premature death. Brain malformations ranged from mild brain volume reduction to hydranencephaly. Severely affected patients share traits including macrocytic anemia and skeletal malformations with Flvcr1 -/- mice and DBA. FLVCR1 variants significantly reduce choline and ethanolamine transport and/or disrupt mRNA splicing., Conclusion: These data demonstrate a broad FLVCR1-related phenotypic spectrum ranging from severe multiorgan developmental disorders resembling DBA to adult-onset neurodegeneration. Our study expands our understanding of Mendelian choline and ethanolamine disorders and illustrates the importance of anticipating a wide phenotypic spectrum for known disease genes and incorporating model organism data into genome analysis to maximize genetic testing yield., (Copyright © 2024. Published by Elsevier Inc.)

Background: Techniques in endovascular therapy have evolved to offer a promising alternative to medical therapy alone for Type B aortic dissections (TBADs)., Aim: The aim of this meta-analysis was to compare mortality and overall complications between thoracic endovascular aortic repair (TEVAR) and best medical therapy (BMT) in patients with TBADs., Methods: We included randomized control trials and prospective or retrospective cohort studies that compared TEVAR and BMT for the treatment of type B aortic dissection. Multiple electronic databases were searched., Results: Thirty-two cohort studies including 150,836 patients were included. TEVAR was associated with a significantly lower 30-day mortality rate than BMT (RR = 0.79, CI = 0.63, 0.99, P = 0.04), notably in patients ≥ 65 years of age (RR = 0.78, CI = 0.64, 0.95, P = 0.01). The TEVAR group had a significantly prolonged hospital stay (MD = 3.42, CI = 1.69, 5.13, P = 0.0001) and ICU stay (MD = 3.18, CI = 1.48, 4.89, P = 0.0003) compared to the BMT. BMT was associated with increased stroke risk (RR = 1.52, CI = 1.29, 1.79, P < 0.00001). No statistically significant differences in late mortality (1, 3, and 5 years) or intervention-related factors (acute renal failure, spinal cord ischemia, myocardial infarction, respiratory failure, and sepsis) were noted between the groups., Conclusion: Our meta-analysis revealed a significant association between the TEVAR group and a decreased mortality rate of TBAD compared to the medical treatment group, especially in patients aged 65 years or older. Further randomized controlled trials are needed to confirm our findings., (© 2024. The Author(s).)

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear., Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis., Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability (GDD/ID), infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe GDD/ID, absent speech, and autistic features, while seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, in particular in pre-rRNA processing., Conclusion: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of 'ribosomopathies'., (Copyright © 2024. Published by Elsevier Inc.)

Despite extensive research into the genetic underpinnings of neurodevelopmental disorders (NDD), many clinical cases remain unresolved. We studied a female proband with a NDD, mildly dysmorphic facial features, and brain stem hypoplasia on neuroimaging. Comprehensive genomic analyses revealed a terminal 5p loss and a terminal 18q gain in the proband while a diploid copy number for chromosomes 5 and 18 in both parents. Genomic investigations in the proband identified an unbalanced translocation t(5;18) with additional genetic material from chromosome 2 (2q31.3) inserted at the breakpoint, pointing to a complex chromosomal rearrangement (CCR) involving 5p15.2, 2q31.3, and 18q21.32. Breakpoint junction analyses enabled by long-read genome sequencing unveiled the presence of four distinct junctions in the father, who is a carrier of a balanced CCR. The proband inherited from the father both the abnormal chromosome 5 resulting in segmental aneusomies of chr5 (loss) and chr18 (gain) and a der(2) homologue. Evidences suggest a chromoplexy mechanism for this CCR derivation, involving double-strand breaks (DSBs) repaired by non-homologous end joining (NHEJ) or alternative end joining (alt-EJ). The complexity of the CCR and the segregation of homologues elucidate the genetic model for this family. This study demonstrates the importance of combining multiple genomic technologies to uncover genetic causes of complex neurodevelopmental syndromes and to better understand genetic disease mechanisms., (© 2024. The Author(s).)

Background: Oculocutaneous albinism type1 (OCA1) is caused by the TYR gene's homozygous and compound heterozygous variants. TKFC gene variants cause triokinase & FMN cyclase deficiency syndrome with variable multisystemic disorders., Objectives: To determine the potential disease-causing variants in two deceased patients presenting atypical OCA1 features by demonstrating three generations for a single family. The two deceased neonates had severe skeletal abnormalities and fatal hypertrophic cardiomyopathy. We also explored the potential mechanisms for the causative relationship between TKFC and multisystem disorders., Patients and Methods: Due to the new emerging symptoms that weren't reported before with the TYR gene, the following methods were performed: Sanger sequencing for the TYR gene, followed by whole exome sequencing, co-segregation, and computational analyses., Results: Extensive parental consanguinity was found, and consequently an autosomal recessive mode of inheritance was prioritized. Upon performing sequencing and segregation data, the following has been confirmed: positive co-segregation of nonsense homozygous NM&#95;000372.5:c.346C > T p.(Arg116*) variant in TYR gene and multisystem disease-missense homozygous NM&#95;015533.4:c.598G > A p.(Val200Ile) variant in TKFC gene in the two affected index patients who deceased due to hypertrophic cardiomyopathy. Using computational analysis, we found that c.598G > A p.(Val200Ile) pathogenicity has led to the failure of L2-K1 active site closure due to the potential differential fluctuation between valine and isoleucine residues. Subsequently, disruption of endogenous DHA phosphorylation was found. Two potential mechanisms exploring the causative relationship between TKFC gene and multisystem disorders have been suggested., Conclusions: This study presented a first family with the co-existence of biallelic variants in TYR and TKFC genes associating severe skeletal abnormalities and lethal hypertrophic cardiomyopathy. Neither of these genes would have been pursued in the standard genetic counseling. Such discovery is paving the way for more efficient genetic counseling. Comparing TKFC results with literature data showed that our relevant expanded TKFC variant is the 3rd worldwide., (© 2024. The Author(s).)

Objectives: Favism is a metabolic disease while pracaxi oil is a strong antioxidant agent. This study evaluates anti-infertility activity and assists normal male fertilization of pracaxi oil in favism-induced male rats., Methods: A 36 male albino rats of six equal sets were each with 6 rats; Control, Pracaxi oil (1 mL), and Pracaxi oil (2 mL), Favism-induced male rats-, Pracaxi oil (1 mL) + Favism-induced male rats, and Pracaxi oil (2 mL) + Favism-induced male rats groups. Blood parameters, liver function, serum male hormones were determined. Glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, total protein, and cholesterol in testis were estimated. Sodium/potassium-ATPase and antioxidants in the hypothalamus, testis, and sperm were assessed. Sperm count, motility, and abnormality, and sperm monoclonal proliferating antibody Ki-67 were evaluated., Results: Favism decreased blood parameters, liver function, superoxide dismutase, glutathione, serum testosterone and dehydroepiandrosterone sulfate, sperm count and motility, sodium/potassium-ATPase activity while increased malondialdehyde, serum follicle stimulating hormone, sex hormone binding globulin, and luteinizing hormone, glucose-6-phosphatedehydrogenase, 3β-hydroxysteroid dehydrogenase, cholesterol, total protein, sperm abnormality, the percentage of spermatogonia, 1st spermatocyte, 2nd spermatocyte, and spermatid in the testis. Furthermore, two doses of pracaxi oil to favism-induced male rats back all of aforementioned parameters to be close control values where a higher dose of pracaxi oil had an efficient impact than a lower dose., Conclusions: Pracaxi oil protects the hypothalamic-pituitary-gonad axis, and preserves sperm quality in favism-induced male rats., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Organic dyestuff are mostly toxic compounds that pose serious dangers to the environment. Adsorption using low-cost adsorbents is the most favorable method for its economic aspects. Recently, geopolymers have been introduced as an effective adsorbent for dyes and heavy metals. In this investigation, the synthesis of geopolymers from fired brick waste (Homra) was studied with full characterization using X-ray Diffraction, Fourier Transform Infrared Spectroscopy, Brunauer-Emmett-Teller, Energy dispersive X-ray, Scanning electron microscope tests and Transmission electron microscopy. The synthesized nano-Homra geopolymer (NHGP) was then subjected to the removal of one of the most used basic dyes, Methylene Blue (MB). Adsorption optimization was applied using Response surface methodology to study dye adsorption by the synthesized nano-geopolymer. The independent variables studied were: temperature, contact time, and concentration of dye in the elimination process, which were varied in the range of (25-60 ℃), (10-180 min), and (20-300 mg/L) respectively. The results obtained from ANOVA indicated that the maximum removal efficiency of 95% and adsorption capacity of 80.65 mg/g at a temperature of 59 ℃, contact time of 163 min, and an initial concentration of 254 mg/L. The results showed that the data obtained from the adsorption of MB onto NHGP was compatible with the Pseudo second order (R 2  = 0.9838) and Langmuir isotherm model (R 2  = 0.9882)., (© 2024. The Author(s).)

Statement of Problem: Evidence regarding stress evaluations of removable obturators with Aramany class I defects is lacking. Whether the stress distribution on Aramany class I prostheses can be improved by modifying the currently used designs is also unclear., Purpose: The purpose of part II of this study was to evaluate the stress distribution in different designs of Aramany class I obturators using finite element analysis (FEA) and photoelastic stress analysis., Material and Methods: Four finite element and 8 photoelastic models, including 2 acrylic resin base obturators retained with 2 Adams clasps, 2 linear, 2 tripodal, and 2 fully tripodal design obturators, were used in this study. The frameworks were fabricated on the casts obtained from a modified printed model. Vertical and oblique loads were applied on 2 points (anterior and posterior) of the models. The quantitative measurement was done by measuring the fringe orders and von Mises values to compare the influences of occlusal forces on the obturator components and their supporting structures. The qualitative evaluation was done by visual color mapping to identify the stress concentration., Results: In the photoelastic analysis, the anterior abutments of the tripodal showed the highest stress, followed by the fully tripodal obturators, while, in FEA, the anterior abutments of the linear design received the most in both vertical and oblique load. The central incisor received the most stress in photoelastic (3 or more fringe orders) and FEA (687.3 and 150.1 MPa for vertical and oblique loads, respectively), followed by the lateral incisors. Upon posterior loading, the base of the defect of the linear design demonstrated the most stress in photoelastic (3 or more fringes) and FEA (94.3 and 130.5 MPa for vertical and oblique loads, respectively). The acrylic resin base obturator retained with Adams clasps demonstrated the lowest stress distribution in abutments and their supporting bone upon anterior and posterior loads., Conclusions: Upon vertical and oblique load application, the fully tripodal design was comparable with the tripodal in terms of stress distribution. Both designs were better than the linear in response to the same loading. The stress was concentrated at the anterior palatal part of the obturator, the base of the defect, and the junction of the metal and acrylic resin part of the prostheses upon anterior and posterior loading, respectively., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Recently, Egypt had seismic activity. These seismic events have affected the stability of minarets, especially historical ones. Weight is one of the minaret's main stability factors. The main objective of the current research is to perform a three-dimensional (3D) assessment of an existing minaret, determine its accurate spatial model, document its current condition, examine its stability in the event of earthquakes, and identify the requisite measures to safeguard the minaret from any potential damage. The masonry to construct the minaret was used by extracting and examining specimens of this substance to determine its physical characteristics. The current work created three-dimensional models of the Abou-Ghanam El-Bialy minaret using a terrestrial laser scanner (TLS) to document its current condition, as well as minaret was subjected to a free vibration analysis using 3D finite element modeling. Finally, the minaret's seismic behavior was assessed utilizing mode forms, base responses, and normal stresses. The surveying method effectively documented the Minarets' existing case. The 3D seismic analysis showed that the minaret responded dynamically to earthquake loading, with mode shapes, base reactions, and normal stresses being crucial characteristics. Based on these data, we may suggest procedures to protect the minaret during seismic events., (© 2024. The Author(s).)

Because of its low-lying location, urbanization, and inadequate infrastructure, Jakarta (Indonesia) has experienced an increase in annual flooding events, rising from an average of five significant floods per year in the 1990s to over 20 annually (2010-2020). With climate change exacerbating extreme weather events, Jakarta encounters escalating risks of flooding. Although the recurrent flooding is exacerbated by non-point source (NPS) of pollution such as urban runoff and agricultural discharge that contribute to 40% of total pollutants leading to flood-related issues in Jakarta, none has investigated this research gap. To reflect its novelty, this work explores the implications of climate change on the annual flooding in Jakarta by focusing on NPS and analyzes their impacts from social perspectives. This work also underscores the implications of flooding on livelihoods, health, and social cohesion in Jakarta. Focus group discussion with affected residents was used to shed light on the coping strategies employed in response to recurrent floods, ranging from community-based initiatives to reliance on informal networks. The empirical findings show that the implications of flooding extend beyond physical damages. Displacement of communities, loss of livelihoods, disruption of essential services, and increased health risks are among the social impacts experienced by local residents. Vulnerable populations, including low-income communities residing in informal settlements, bear their consequences. Economic losses from flooding amount to USD 500 million annually, impacting over 1 million residents. However, recent interventions have led to a 15% reduction in peak flood levels and a 20% reduction in flood duration in affected areas. Community resilience has also improved, with a 25% increase in flood insurance coverage and a 20% rise in community response initiatives. Overall, this study highlights that climate change exacerbates annual flooding in Jakarta, significantly impacting vulnerable communities through NPS pollution. Addressing the challenges requires integrated approaches combining effective pollution control, resilient infrastructure, and community engagement to mitigate social and long-term environmental impacts. PRACTITIONER POINTS: Climate-induced flooding disproportionately affects vulnerable communities in Jakarta. Non-point source pollution from urban runoff contributes to the severity of flooding in Jakarta. Waterborne diseases, disruption of livelihoods, and reduced access to clean water are major concerns identified in the study. The study highlights the importance of community-based adaptation strategies to mitigate the impact of flooding and pollution., (© 2024 Water Environment Federation.)

The failure of mass production of Spirulina plateaus can be attributed to an imbalance of nutrients (C:N) and an increase in accumulated sodium ions, coupled with the traditional harvesting process. The current study aims at the recovery of stressed and red cultures of Spirulina platensis as well as enhanced phycocyanin accumulation. The stressed Spirulina platensis cultures were obtained from a local Egyptian Spirulina production farms, which were further subjected to water analyses after removing the Spirulina biomass. Optimization was performed within 300-ml water path photobioreactor. Spirulina platensis samples were incubated with Zarrouk medium comparing with those modified using ammonium bicarbonate or ammonium acetate instead of sodium bicarbonate. Continuous batching was performed every 12 days during three sequenced batches. Growth measurements (dry weight and pigments) were performed along the incubation time. It was found that carbon content of the growth medium seems to be more effective in Spirulina growth and biomass characteristics. Under different carbon sources, acetate resulted in the maximum dry weight of 1.48 g·l -1 and recovery percentage of 463.3%. Such effect was extended along the different incubation batches. Various carbon concentrations revealed that moderate concentration of carbon in the form of acetate (0.699 g·l -1 ) leads to the maximum growth under the same nitrogen content. A similar trend was observed with chlorophyll and phycocyanin accumulation, while carotenoids showed the opposite manner., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cardiovascular disease (CVD) is a leading cause of global mortality. Early intervention and prevention of CVD depend on accurately predicting the risk of CVD. This study aimed to investigate the association between the TyG index and the risk of coronary heart disease (CHD), congestive heart failure (CHF), heart attack (HA), stroke, and hypertension (HTN) among patients without diabetes in the United States., Methods: In this retrospective, cross-sectional study, we used data from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2020. We conducted several regression analysis models and calculated the sensitivity and specificity of (TyG) index for predicting the onset of CHD, CHF, HA, stroke, and HTN., Results: A total of 10,937 individuals without diabetes participated in our study. Individuals with a TyG index greater than 8.96 displayed significant increasing in various parameters, including BMI, systolic/diastolic blood pressure, total cholesterol, LDL, and Apo-B levels (p < 0.001). Almost all regression models ensured that a higher TyGI value was associated with higher odds of having CHD, CHF, HA, stroke, and HTN, which patients with a TyGI value higher than 8.96 have odds ratios of 2.24-5.58 for CHD, 1.68-4.42 for stroke, 2.45-3.77 for HA and 1.75-3.93 for HTN comparing than patients with a TyGI value lower than 8.11 (p-value < 0.05).We evaluated the predictive value of the TyG index for each endpoint, obtaining the following area under the curve (AUC) values: 54.75% for CHF (95% CI: 0.542-0.614), 52.32% for stroke (95% CI: 0.529-0.584), 55.67% for HA (95% CI: 0.595-0.646), 55.59% for HTN (95% CI: 0.574-0.597), and 50.31% for CHD (95% CI: 0.592-0.646)., Conclusion: The TyG index showed a strong correlation with cardiovascular risk factors in individuals without diabetes, however it was a poor predictor of almost studied cardiovascular diseases., (© 2024. The Author(s).)

Mitochondrial dynamics have pillar roles in several diseases including cancer. Cancer cell survival is monitored by mitochondria which impacts several cellular functions such as cell metabolism, calcium signaling, and ROS production. The equilibrium of death and survival rate of mitochondria is important for healthy cellular processes. Whereas inhibition of mitochondrial metabolism and dynamics can have crucial regulatory decisions between cell survival and death. The steady rate of physiological flux of both mitochondrial fission and fusion is strongly related to the preservation of cellular bioenergetics. Dysregulation of mitochondrial dynamics including fission and fusion is a critical machinery in cells accompanied by crosstalk in cancer progression and resistance. Many cancer cells express high levels of Drp-1 to induce cancer cell invasion, metastasis and chemoresistance including breast cancer, liver cancer, pancreatic cancer, and colon cancer. Targeting Drp-1 by inhibitors such as Midivi-1 helps to enhance the responsiveness of cancer cells towards chemotherapy. The review showed Drp-1 linked processes such as mitochondrial dynamics and relationship with cancer, invasion, and chemoresistance along with computational assessing of all publicly available Drp-1 inhibitors. Drp1-IN-1, Dynole 34-2, trimethyloctadecylammonium bromide, and Schaftoside showed potential inhibitory effects on Drp-1 as compared to standard Mdivi- 1. This emerging approach may have extensive strength in the context of cancer development and chemoresistance and further work is needed to aid in more effective cancer management., 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 Elsevier Inc. All rights reserved.)

Molecular hybridization between diphenyl urea and benzylidene acetohydrazide was adopted for the design of a new series of FGFR-1 targeting cancer. The designed series was synthesized and submitted to NCI-USA to be screened for their growth inhibitory activity on NCI cancer cell lines. Some of the synthesized hybrids displayed promising growth inhibitory activity on NCI cancer cell lines with a mean GI% between 70.39% and a lethal effect. Compounds 9a, 9i, 9j, and 9n-p were further selected for a five-dose assay and all the tested candidates showed promising antiproliferative activity with GI 50 reaching the submicromolar range. Encouraged by the potent activity of 9a on colon cancer on the one hand and the well-known overexpression of FGFR-1 in it on the other hand, it was further selected as a representative example to be evaluated for its mechanism on the cell cycle and apoptosis of HCT116 cell line. Interestingly, 9a was found to pause the cell cycle of the HCT116 cell line at the G1 phase and induced late apoptosis. In parallel, all the synthesized hybrids 9a-p were examined for their potential to inhibit FGFR-1 at 10 µM. Compounds 9a, 9g, 9h, and 9p were found to have potent inhibitory activity with % inhibition = 63.04%, 58.31%, 60.87% and 79.84%, respectively. Molecular docking simulation of 9a in the binding pocket of FGFR-1 confirms its capability to achieve the characteristic interactions of the type II FGFR-1 inhibitors. Exploration of the ADME properties of 9a-p by SwissADME web tool proved their satisfactory physicochemical properties for the discovery of new anticancer hits., (© 2024 Wiley Periodicals LLC.)

To understand the dynamic nature of the genome, the localization and rearrangement of DNA and DNA-binding proteins must be analyzed across the entire nucleus of single living cells. Recently, we developed a computational light microscopy technique, called high-resolution diffusion (Hi-D) mapping, which can accurately detect, classify and map diffusion dynamics and biophysical parameters such as the diffusion constant, the anomalous exponent, drift velocity and model physical diffusion from the data at a high spatial resolution across the genome in living cells. Hi-D combines dense optical flow to detect and track local chromatin and nuclear protein motion genome-wide and Bayesian inference to characterize this local movement at nanoscale resolution. Here we present the Python implementation of Hi-D, with an option for parallelizing the calculations to run on multicore central processing units (CPUs). The functionality of Hi-D is presented to the users via user-friendly documented Python notebooks. Hi-D reduces the analysis time to less than 1 h using a multicore CPU with a single compute node. We also present different applications of Hi-D for live-imaging of DNA, histone H2B and RNA polymerase II sequences acquired with spinning disk confocal and super-resolution structured illumination microscopy., (© 2024. Springer Nature Limited.)

Enzymatic deficiency in Gaucher disease (GD) may induce oxidative stress. Vitamin E is the nature's most effective lipid-soluble antioxidant. This prospective clinical trial assessed the oxidant-antioxidant status in Egyptian patients with GD and the efficacy and safety and of vitamin E as an adjuvant antioxidant therapy. Forty children and adolescents with GD on stable doses of enzyme replacement therapy (ERT) were enrolled. Abdominal ultrasonography and transient elastography were performed. Malondialdehyde (MDA), vitamin E, and antioxidant enzymes (reduced glutathione [GSH], superoxide dismutase [SOD], glutathione peroxidase [GPx], and peroxiredoxin 2 [PRDX2]) were assessed. Patients were compared with 40 age- and sex-matched healthy controls. Patients with GD were randomized either to receive oral vitamin E for 6 months or not. All patients with GD had significantly higher MDA levels with lower levels of vitamin E and antioxidant enzymes compared with healthy controls (p < 0.001). Vitamin E and PRDX2 were negatively correlated to severity score index (SSI), lyso GL1, and MDA. After 6 months of vitamin E supplementation, SSI and liver and spleen volumes and liver stiffness were significantly lower. Lyso GL1 and MDA were significantly decreased post-vitamin E therapy while antioxidant enzymes were significantly higher compared with baseline levels and with patients without vitamin E therapy. Oxidative stress is related to disease severity in pediatric patients with GD. A 6-month vitamin E supplementation for those patients represents a safe therapeutic adjuvant agent increasing the efficacy of ERT, reducing oxidative stress, and improving outcomes., (© 2024 SSIEM.)

Developmental and epileptic encephalopathies (DEEs) feature altered brain development, developmental delay and seizures, with seizures exacerbating developmental delay. Here we identify a cohort with biallelic variants in DENND5A, encoding a membrane trafficking protein, and develop animal models with phenotypes like the human syndrome. We demonstrate that DENND5A interacts with Pals1/MUPP1, components of the Crumbs apical polarity complex required for symmetrical division of neural progenitor cells. Human induced pluripotent stem cells lacking DENND5A fail to undergo symmetric cell division with an inherent propensity to differentiate into neurons. These phenotypes result from misalignment of the mitotic spindle in apical neural progenitors. Cells lacking DENND5A orient away from the proliferative apical domain surrounding the ventricles, biasing daughter cells towards a more fate-committed state, ultimately shortening the period of neurogenesis. This study provides a mechanism for DENND5A-related DEE that may be generalizable to other developmental conditions and provides variant-specific clinical information for physicians and families., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) is a common primary liver cancer that requires early diagnosis due to its poor prognosis. Recent advances in artificial intelligence (AI) have facilitated hepatocellular carcinoma detection using multiple AI models; however, their performance is still uncertain., Aim: This meta-analysis aimed to compare the diagnostic performance of different AI models with that of clinicians in the detection of hepatocellular carcinoma., Methods: We searched the PubMed, Scopus, Cochrane Library, and Web of Science databases for eligible studies. The R package was used to synthesize the results. The outcomes of various studies were aggregated using fixed-effect and random-effects models. Statistical heterogeneity was evaluated using I-squared (I 2 ) and chi-square statistics., Results: We included seven studies in our meta-analysis;. Both physicians and AI-based models scored an average sensitivity of 93%. Great variation in sensitivity, accuracy, and specificity was observed depending on the model and diagnostic technique used. The region-based convolutional neural network (RCNN) model showed high sensitivity (96%). Physicians had the highest specificity in diagnosing hepatocellular carcinoma(100%); furthermore, models-based convolutional neural networks achieved high sensitivity. Models based on AI-assisted Contrast-enhanced ultrasound (CEUS) showed poor accuracy (69.9%) compared to physicians and other models. The leave-one-out sensitivity revealed high heterogeneity among studies, which represented true differences among the studies., Conclusion: Models based on Faster R-CNN excel in image classification and data extraction, while both CNN-based models and models combining contrast-enhanced ultrasound (CEUS) with artificial intelligence (AI) had good sensitivity. Although AI models outperform physicians in diagnosing HCC, they should be utilized as supportive tools to help make more accurate and timely decisions., 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 Al-Obeidat, Hafez, Gador, Ahmed, Abdeljawad, Yadav and Rashed.)