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Corrosion has a significant deteriorative effect on fatigue life of aged ship and offshore structures; hence reliable numerical fatigue life analysis of aged ship structures is crucial for safe operation. The reliability of the fatigue damage assessment techniques depends on the quality of the S-N curve which should account for corrosion degradation. In this paper, the different factors affecting the randomness of stress concentration and fatigue life of corroded specimens have been studied. It was demonstrated that the Stress Concentration, which results from the distinctive thickness variation of the corroded specimens, significantly depends on the mean and minimum thickness of the corroded plate. The equivalent thickness of a typical plate, which has the same fatigue strength of the corresponding corroded one under the same cyclic load, was investigated. A time-dependent S-N curve of corroded structures considering the deterioration of material mechanical properties was proposed. The corroded surfaces were modeled using random spatial distributions and the effect of corrosion degradation on the material mechanical properties was taken into account. The numerically estimated fatigue life and the proposed S-N curve were compared with experimental fatigue test results. The comparison showed good agreement between the experimental results and the adopted approaches for fatigue life assessment.

Introduction People with schizophrenia could be more substantially influenced by the emotional stress brought on by the COVID-19 pandemic, resulting in relapses or worsening of an already existing mental health condition because of the high susceptibility to stress. Objectives This study aimed to assess the presence of relapse and its risk factors among patients with schizophrenia during the era of COVID 19 pandemic. Methods This study included 90 adults who met DSM-5 criteria for schizophrenia and were diagnosed by (SCID-I) Arabic version and who are following up at the outpatient psychiatric clinic, Zagazig University Hospital, Egypt, Positive and Negative Syndrome Scale (PANSS) measuring severity of symptoms, Compliance Rating Scale (CRS) and World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). scales were conducted on those patients before COVID-19 pandemic from January to April 2019 and repeated on September to November 2020 during COVID 19 pandemic to compare clinical parameters between those two periods as to detect any deterioration in their clinical state. Results The mean score of compliance rating scale (CRS) was decreased after COVID-19 pandemic compared to before COVID 19 (P

Cervical ectopic pregnancy is implantation of an embryo into the cervical mucosa below the level of the internal os. Cervical pregnancy is an infrequent form of ectopic gestation both in naturally conceived pregnancies and even after assisted reproductive technology (ART). It accounts for less than 1% of all ectopic pregnancies. The Transvaginal ultrasonographic diagnosis rests upon empty uterus, trophoblastic invasion of the cervix below the internal os and enlarged barrel shaped cervix containing a gestational sac present below the level of internal os. Early detection is desirable in order to plan the management early and to avoid serious and often life threatening complications. Management options vary and depend on the gestational age at diagnosis, general condition of the patient and woman’s desire to maintain fertility. Medical treatment with methotrexate is the therapy of choice in early gestation with hemodynamically stable patient. Surgical intervention is indicated in late gestation, unstable cases or failed medical treatment.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are integral to diabetes treatment, facilitating renal glucose excretion and offering benefits in cardiovascular risk reduction, kidney function preservation, and weight management. However, their integration into diabetes care presents challenges due to associated adverse effects. This review assesses the efficacy of SGLT2 inhibitors in diabetes management. A comprehensive literature search using PubMed and Google Scholar yielded pertinent studies. Clinical evidence demonstrates the effectiveness of SGLT2 inhibitors in glycemic control and in reducing cardiovascular risks in diabetes patients. Moreover, these agents exhibit positive effects on cardiovascular and renal functions. Despite their therapeutic promise, careful consideration is warranted when integrating SGLT2 inhibitors into diabetes care. Common adverse effects such as genitourinary infections, hypoglycemia, and sporadic diabetic ketoacidosis necessitate rigorous patient monitoring and education. Nonetheless, SGLT2 inhibitors offer a comprehensive approach to diabetes management, showing efficacy across multiple domains. In summary, SGLT2 inhibitors play a crucial role in diabetes care, offering benefits beyond glycemic control. However, their use requires careful patient selection, education, and monitoring to manage associated risks effectively. Awareness of potential adverse effects is essential for optimizing the therapeutic benefits of SGLT2 inhibitors in T2DM (type 2 diabetes mellitus) management.

Abstract Nortopsentins are a vital class of deep-sea sponge metabolites which can be used as leads for antitumor agents. Although their action has been studied in several diseases’ contexts, their cytotoxic activity against colorectal carcinoma has not yet been fully investigated. Therefore, a series of 2,6-bis(1H-indol-3-yl)-4-(substituted-phenyl)pyridin-5-carbonitriles 4a–j (nortopsentin analogs) was investigated for their cytotoxic activity against colorectal carcinoma. The analog 4i showed the highest antitumor activity via inducing cell cycle arrest at G1 phase. Cell cycle arrest was induced due to expression downregulation of CDK2, CDK4, and CDK6. In addition, 4i suppressed the enzymatic activity of CDK6. The theoretical study of some basic quantum factors and the geometric shape of compound 4i proved that the compound is stable and a soft molecule, in which the EHOMO and ELUMO energies were negative and had a small ∆E gap. 4i also demonstrated a high potential for oral bioavailability due to its adherence to Lipinski’s rule of five. The molecular docking studies of 4i analog showed good binding mode with CDK6 active pocket through the formation of multiple interactions with its key amino acids.

Background: T-LAK cell-originated protein kinase (TOPK), a member of the MEK3/6-related mitogen-activated protein kinase kinase (MAPKK) family, is highly overexpressed in various cancers. This overexpression is linked to the mitotic phase of the cell cycle, highlighting its potential as a prognostic marker and therapeutic target. Unlike many other cancer targets, TOPK exhibits limited expression or is even absent in non-proliferative tissues. Therefore, TOPK inhibitors hold promise for developing anticancer agents with high selectivity and specificity for cancer cells, potentially leading to fewer side effects compared to conventional therapies. This study builds on our previous success in identifying TOPK inhibitors and aims to optimize them for improved potency. Methods: An integrated approach combining computational modeling and organic synthesis was employed. Ninety-two analogs of the lead compound (N2 ,N7 -dibenzyl-9-oxo-9H-fluorene-2,7-disulfonamide) were designed virtually and assessed for binding affinity to TOPK using docking simulations. Eight top-scoring analogs were synthesized and their inhibitory activity against TOPK was evaluated in vitro. Results: The in-silico analysis identified eight promising analogs. However, the most active synthesized analog (compound 10) exhibited moderate inhibitory activity (IC50 = 86 µM) compared to the lead compound (IC50 = 54 µM). Conclusion: While the computational approach identified potential candidates, further optimization of the synthetic analogs is necessary to achieve superior TOPK inhibitory activity. This study highlights the value of a combined computational and synthetic strategy for TOPK inhibitor development. TOPK inhibitory activity. This study highlights the value of a combined computational and synthetic strategy for TOPK inhibitor development.

Abstract Background The current study was aimed at constructing a questionnaire for evaluating the role of variant environmental factors on language acquisition in the three surrounding levels of communication that include familial level, preschool or nursery level, and surrounding social environmental level among children with delayed language development (DLD) due to environmental deprivation. The current study was a retrospective case–control study that was performed on 100 Egyptian Arabic-speaking children aged from 2 to 5 years. The study was carried out among preschool age children in the Mansoura governmental and private preschools (53 males and 47 females). They were divided into 2 groups: Group I (case group) consisted of 50 children with DLD due to environmental deprivation, and group II (control group) consisted of 50 typically developed children. Results The present study demonstrated several factors for prediction of DLD due to environmental deprivation. Univariable analysis revealed multiple factors as number of hours that parents present at home, time of the mother’s job, the relation between the child and the mother, the parents select certain time to talk and play with their child, joint attention of the mother, mother asking her child what he wants, long time using multimedia, divorce as a traumatic stress, bad social performance, and low socioeconomic status. Multivariate analysis revealed that longer time of the mother’s job and less time the mother select to talk and play with her child were the environmental deprivation factors which had the most precipitating effect on predicting DLD. Conclusions The constructed Arabic questionnaire was proved to be valid, reliable, and homogenous and is likely to produce consistent responses in evaluating the variant environmental factors on language development among children with DLD due to environmental deprivation in the three surrounding communications levels.

In this research, we leverage various $ q $-calculus identities to introduce the notion of $ q $-Hermite-Appell polynomials involving three variables, elucidating their formalism. We delve into numerous properties and unveil novel findings regarding these $ q $-Hermite-Appell polynomials, encompassing their generating function, series representation, summation equations, recurrence relations, $ q $-differential formula, and operational principles. Our investigation sheds light on the intricate nature of these polynomials, elucidating their behavior and facilitating deeper understanding within the realm of $ q $-calculus.

Devant son souhait de poursuivre l’entreprise de Pierre Boaistuau, en répondant aux goûts du public de l’époque, François de Belleforest ne se contente pas de traduire les nouvelles de l’Italien Bandello ; il produit une oeuvre d’une grande originalité, en privilégiant la portée exemplaire de ses récits. Paradoxalement, tout en affichant ses préoccupations morales, l’auteur met en scène des personnages emportés par des passions destructrices et complètement gouvernés par le mal. Dans cette étude, on montrera que le conteur opte pour l’authenticité de la représentation, en puisant ses histoires tragiques dans l’actualité ou dans l’Histoire. En outre, il semble primordial, tout en s’interrogeant sur l’efficacité du projet d’édification du lecteur, de mettre en relief l’aspect novateur de l’oeuvre narrative de Belleforest.

Hikmat Abdel-Razeq,1,2 Baha Sharaf,1 Suhaib Khater,1 Huda Jafar Baidoun,2 Hira Bani Hani,1 Ayat Taqash,3 Osama El Khatib,1 Sarah Edaily,1 Mahmoud Abunasser,1 Faris Tamimi,1 Yosra Nabeel Al-Masri,1 Tamer Moh’d Waleed Al-Batsh,1 Anas Zayed,1 Tala Ghatasheh,1 Tala Radaideh1 1Department of Internal Medicine, Section of Hematology and Medical Oncology, King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, the University of Jordan, Amman, Jordan; 3Office of Scientific Affairs and Research. King Hussein Cancer Center, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, Section of Hematology and Medical OncologyKing Hussein Cancer Center, 202 Queen Rania Al Abdullah Street, P.O. Box: 1269, Amman, 11941, Jordan, Tel: +962-6 5300460, Email habdelrazeq@khcc.joBackground: Cyclin-dependent kinase (CDK) 4/6 inhibitors have revolutionized the treatment landscape of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2 −) metastatic breast cancer (MBC). Here, we present the real-world clinical outcomes and toxicity data of patients treated at a single cancer center.Methods: A retrospective analysis was conducted on patients with HR+/HER2− MBC treated with ribociclib plus endocrine therapy (ET). Outcomes measured included progression-free survival (PFS), overall survival (OS), and adverse events.Results: A total of 356 patients (median age 52, range 27– 91 years) were enrolled, all with metastatic disease; 204 (57.5%) had de novo metastasis, and 183 (51.4%) had visceral metastasis. Ribociclib was combined with aromatase inhibitors in 321 patients (90.2%) and with fulvestrant in 35 patients (9.8%). Dose reduction was needed in 101 patients (28.4%), primarily due to neutropenia (21.3%) and abnormal liver enzymes (5.9%). After a median follow-up of 36.3 months, median PFS was 27.3 months (95% CI: 21.3– 31.7). PFS was significantly better in patients receiving ribociclib as first-line therapy (32.1 months, 95% CI: 27.7– 42.1, p < 0.0001) and those with non-visceral metastasis (38.6 months, 95% CI: 29.8–NR, p < 0.0001). Similarly, OS was significantly better in first-line treatment (48.6 months, 95% CI: 39.1–NR) and non-visceral metastasis cases (NR, 95% CI: 40.6–NR, p < 0.0001). No significant differences in 3-year PFS and OS were found between patients with and without dose reductions.Conclusion: In real-world settings, and away from the stringency of controlled clinical trials, endocrine therapy in combination with ribociclib in patients with HR-positive/HER2-negative MBC is an effective and well-tolerated therapy with a manageable toxicity profile and a low drug discontinuation rate. Dose reduction due to toxicity did not worsen the outcome.Keywords: metastatic breast cancer, MBC, CDK4/6 inhibitors, ribociclib, aromatase inhibitors, fulvestrant

Abstract Salinity stress negatively affects the growth and yield of crops worldwide. Onion (Allium cepa L.) is moderately sensitive to salinity. Beneficial microorganisms can potentially confer salinity tolerance. This study investigated the effects of endomycorrhizal fungi (M), Pseudomonas putida (Ps) and their combination (MPs) on onion growth under control (0 ppm), moderate (2000 ppm) and high (4000 ppm) NaCl salinity levels. A pot experiment was conducted with sandy loam soil and onion cultivar Giza 20. Results showed that salinity reduced growth attributes, leaf pigments, biomass and bulb yield while increasing oxidative stress markers. However, individual or combined inoculations significantly increased plant height, bulb diameter and biomass production compared to uninoculated plants under saline conditions. MPs treatment provided the highest stimulation, followed by Pseudomonas and mycorrhizae alone. Overall, dual microbial inoculation showed synergistic interaction, conferring maximum benefits for onion growth, bulbing through integrated physiological and biochemical processes under salinity. Bulb yield showed 3.5, 36 and 83% increase over control at 0, 2000 and 4000 ppm salinity, respectively. In conclusion, combined application of mycorrhizal-Pseudomonas inoculations (MPs) effectively mitigate salinity stress. This approach serves as a promising biotechnology for ensuring sustainable onion productivity under saline conditions.

Abstract Background Abamectin (ABA) is considered a powerful insecticidal and anthelmintic agent. It is an intracellular product of Streptomyces avermitilis; is synthesized through complicated pathways and can then be extracted from mycelial by methanol extraction. ABA serves as a biological control substance against the root-knot nematode Meloidogyne incognita. This investigation is intended to reach a new strain of S. avermitilis capable of producing ABA effectively. Results Among the sixty actinobacterial isolates, Streptomyces St.53 isolate was chosen for its superior nematicidal effectiveness. The mycelial-methanol extract of isolate St.53 exhibited a maximum in vitro mortality of 100% in one day. In the greenhouse experiment, the mycelial-methanol extract demonstrated, for the second-stage juveniles (J2s), 75.69% nematode reduction and 0.84 reproduction rate (Rr) while for the second-stage juveniles (J2s), the culture suspension demonstrated 75.38% nematode reduction and 0.80 reproduction rate (Rr). Molecular identification for St.53 was performed using 16 S rRNA gene analysis and recorded in NCBI Genbank as S. avermitilis MICNEMA2022 with accession number (OP108264.1). LC-MS was utilized to detect and identify abamectin in extracts while HPLC analysis was carried out for quantitative determination. Both abamectin B1a and abamectin B1b were produced and detected at retention times of 4.572 and 3.890 min respectively. Conclusion Streptomyces avermitilis MICNEMA2022 proved to be an effective source for producing abamectin as a biorational agent for integrated nematode management.