Tracking the epidemiological trends of female breast cancer in Saudi Arabia since 1990 and forecasting future statistics using global burden of disease data, time-series analysis.

BACKGROUND: Female breast cancer stands as the prime type of cancer in the Kingdom of Saudi Arabia (KSA), with a high incidence and mortality rates. This study assessed the burden of female breast cancer in KSA by analyzing and forecasting its incidence, mortality, and disability-adjusted life years (DALYs). METHODS: We retrieved data from the Global Burden of Disease (GBD) about female breast cancer from 1990 to 2021. Time-series analysis used the autoregressive integrated moving average (ARIMA) model to forecast female breast cancer statistics from 2022 to 2026. RESULTS: From 1990 to 2021, KSA reported 77,513 cases of female breast cancer. The age groups with the highest number of cases are 45-49 years, followed by 40-44 years, 50-54 years, and 35-39 years. The analysis also showed fewer cases in the younger age groups, with the lowest number in the less than 20-year-old age group. From 1990 to 2021, KSA reported 19,440 deaths due to breast cancer, increasing from 201 cases in 1990 to 1,190 cases in 2021. The age-standardized incidence rate/100,000 of breast cancer increased from 15.4 (95% confidence interval (CI) 11.2-21.0) in 1990 to 46.0 (95%CI 34.5-61.5) in 2021. The forecasted incidence rate of female breast cancer will be 46.5 (95%CI 45.8-46.5) in 2022 and 49.6 (95%CI 46.8-52.3) in 2026. The age-standardized death rate per 100,000 Saudi women with breast cancer increased from 6.73 (95%CI 6.73-9.03) in 1990 to 9.77 (95%CI 7.63-13.00) in 2021. The forecasted female breast cancer death rate will slightly decrease to 9.67 (95%CI 9.49-9.84) in 2022 and to 9.26 (95%CI 8.37-10.15) in 2026. DALYs increased from 229.2 (95%CI 165.7-313.6) in 1990 to 346.1 (95%CI 253.9-467.2) in 2021. The forecasted DALYs of female breast cancer will slightly decrease to 343.3 (95%CI 337.2-349.5) in 2022 reaching 332.1 (95%CI 301.2-363.1) in 2026. CONCLUSIONS: Female breast cancer is still a significant public health burden that challenges the health system in KSA, current policies and interventions should be fashioned to alleviate the disease morbidity and mortality and mitigate its future burden.

Developing a production workflow for 3D-printed temporal bone surgical simulators.

INTRODUCTION: 3D-printed temporal bone models enable the training and rehearsal of complex otological procedures. To date, there has been no consolidation of the literature regarding the developmental process of 3D-printed temporal bone models. A brief review of the current literature shows that many of the key surgical landmarks of the temporal bone are poorly represented in models. This study aims to propose a novel design and production workflow to produce high-fidelity 3D-printed temporal bone models for surgical simulation. METHODS: Developmental phases for data extraction, 3D segmentation and Computer Aided Design (CAD), and fabrication are outlined. The design and fabrication considerations for key anatomical regions, such as the mastoid air cells and course of the facial nerve, are expounded on with the associated strategy and design methods employed. To validate the model, radiological measurements were compared and a senior otolaryngologist performed various surgical procedures on the model. RESULTS: Measurements between the original scans and scans of the model demonstrate sub-millimetre accuracy of the model. Assessment by the senior otologist found that the model was satisfactory in simulating multiple surgical procedures. CONCLUSION: This study offers a systematic method for creating accurate 3D-printed temporal bone models for surgical training. Results show high accuracy and effectiveness in simulating surgical procedures, promising improved training and patient outcomes.

Investigating industry 4.0 technologies in logistics 4.0 usage towards sustainable manufacturing supply chain.

In the era of Industry 4.0 (I4.0), automation and data analysis have undergone significant advancements, greatly impacting production management and operations management. Technologies such as the Internet of Things (IoT), robotics, cloud computing (CC), and big data, have played a crucial role in shaping Logistics 4.0 (L4.0) and improving the efficiency of the manufacturing supply chain (SC), ultimately contributing to sustainability goals. The present research investigates the role of I4.0 technologies within the framework of the extended theory of planned behavior (ETPB). The research explores various variables including subjective norms, attitude, perceived behavior control, leading to word-of-mouth, and purchase intention. By modeling these variables, the study aims to understand the influence of I4.0 technologies on L4.0 to establish a sustainable manufacturing SC. A questionnaire was administered to gather input from small and medium-sized firms (SMEs) in the manufacturing industry. An empirical study along with partial least squares structural equation modeling (SEM), was conducted to analyze the data. The findings indicate that the use of I4.0 technology in L4.0 influences subjective norms, which subsequently influence attitudes and personal behavior control. This, in turn, leads to word-of-mouth and purchase intention. The results provide valuable insights for shippers and logistics service providers empowering them to enhance their performance and contribute to achieving sustainability objectives. Consequently, this study contributes to promoting sustainability in the manufacturing SC by stimulating the adoption of I4.0 technologies in L4.0.

A Systematic Review on Clinico-Aetiopathological Trends of Nasopharyngeal Cancer in Asia.

BACKGROUND: Nasopharyngeal cancer (NPC) is a type of malignancy that is highly prevalent in Asian countries. Therefore, an understanding between NPC epidemiological trend, the clinico-pathological and aetiological profiles are needed. This systematic review focuses on asian countries demographic and clinico-pathological presentation reported in 9982 NPC cases diagnosed from the year 2010 to 2021. METHODOLOGY: Data were extracted from databases, such as PubMed, Springer Link, Science Direct, Google Scholar and general search engines, by using pre-determined keywords (e.g. clinico-pathological data, age, sex, tumour stage, nasopharyngeal cancer, nasopharyngeal carcinoma, naso-pharynx and cancer in Asia). RESULTS AND CONCLUSION: Findings from our systematic review shows that from 2010 to 2021, males in age range below 50 years old are at a higher risk of developing NPC in Asia. NPC is mostly diagnosed at advanced stage in Asia, which is likely due to the deep-seated location of the cancer. Type III NPC and EBV proteins (EBNA1 and LMP2A) are frequently associated with reported EBV-positive NPC cases in Asian countries. Meanwhile, NPC type I, II, and III are associated with EBV-negative NPC cases in Asia. Human leucocyte antigen (HLA) alleles (A2, B27, and B46) are frequently present in reported EBV-negative NPC cases in Asia. In Asia, males below 50 years old are more prone to NPC and often diagnosed at late stage. EBV-positive and EBV-negative NPC in Asia have unique histological profiles. Systemic approach of this study may help to provide better knowledge on reported NPC cases especially on the risk factors and clinical presentation focusing in Asian countries.

AgScP2S6 van der Waals Layered Crystal: A Material with a Unique Combination of Extreme Nonlinear Optical Properties.

Research in two-dimensional layered materials (2DLMs) has exploded over the past several years for a variety of applications in photonics and optoelectronics. The 2D nature of these materials allows for a very local electronic probe of material as well as flexible integration with other functional components. Herein, using the femtosecond Z-scan technique, we report a giant two photon absorption (TPA) process and its saturation in the van der Waals gapped silver scandium thiophosphate (AgScP2S6) crystal. We have found a TPA coefficient of the order of 104 cm/GW which is orders of magnitude larger compared to many existing semiconductors and nonlinear crystals. Furthermore, we found a TPA cross-section of 103 GM and characterized the optical limiting (OL) response (0.2 mJ/cm2) and the multipulse laser damage threshold (1.09 ± 0.19 J/cm2). The combination of giant TPA, extremely low OL, and very high damage threshold suggests that this material could be extremely useful in applications like optical limiters or switches.

Inhibition of sPLA2 enzyme activity by cell-permeable antioxidant EUK-8 and downregulation of p38, Akt, and p65 signals induced by sPLA2 in inflammatory mouse paw edema model.

The arachidonic acid (AA) metabolic pathway, plays a vital role in the production of eicosanoids by the action of pro-inflammatory secretory phospholipase A2 (PLA2 ). Release of eicosanoids is known to be involved in many inflammatory diseases. Identification of the inhibitory molecules of this AA pathway enzyme along with the regulation of intracellular signaling cascades may be a finer choice to develop as a powerful anti-inflammatory drug. In this regard, we have screened few cell-permeable antioxidant molecules Tempo, Mito-TEMPO, N,N'-Bis(salicylideneamino)ethane-manganese(II) (EUK)-134, and EUK-8 against pro-inflammatory sPLA2 s. Among these, we found EUK-8 is a potent inhibitor with its IC50 value ranges 0.7-2.0 µM for sPLA2 s isolated from different sources. Furthermore, docking studies confirm the strong binding of EUK-8 towards sPLA2 . In vivo effect of EUK-8 was studied in HSF-sPLA2 -induced edema in mouse paw model. In addition to neutralizing the edema, EUK-8 significantly reduces the phosphorylation level of inflammatory proteins such as p38 member of MAPK pathway, Akt, and p65 along with the suppression of pro-inflammatory cytokine (interleukin-6) and chemokine (CXCL1) in edematous tissue. This shows that EUK-8 not only inhibits the sPLA2 activity, it also plays an important role in the regulation of sPLA2 -induced cell signaling cascades. Apart from the sPLA2 inhibition, we also examine the regulatory actions of EUK-8 with other downstream enzymes of AA pathway such as 5-LOX assay in human polymorphonuclear leukocytes (PMNs) and COX-2 expression in carrageenan-λ induced paw edema. Here EUK-8 significantly inhibits 5-LOX enzyme activity and downregulates COX-2 expression. These data indicate that EUK-8 found to be a promising multitargeted inhibitory molecule toward inflammatory pathway. In conclusion, mitochondrial targeted antioxidant EUK-8 is not only the powerful antioxidant, also a potent anti-inflammatory molecule and may be a choice of molecule for pharmacological applications.

Interrogating the Roles of Mutation-Selection Balance, Heterozygote Advantage, and Linked Selection in Maintaining Recessive Lethal Variation in Natural Populations.

For nearly a century, evolutionary biologists have observed chromosomes that cause lethality when made homozygous persisting at surprisingly high frequencies (>25%) in natural populations of many species. The evolutionary forces responsible for the maintenance of such detrimental mutations have been heavily debated-are some lethal mutations under balancing selection? We suggest that mutation-selection balance alone cannot explain lethal variation in nature and the possibility that other forces play a role. We review the potential that linked selection in particular may drive maintenance of lethal alleles through associative overdominance or linkage to beneficial mutations or by reducing effective population size. Over the past five decades, investigation into this mystery has tapered. During this time, key scientific advances have provided the ability to collect more accurate data and analyze them in new ways, making the underlying genetic bases and evolutionary forces of lethal alleles timely for study once more.

Ultrafast Nonlinear Absorption and Second Harmonic Generation in Cu0.33In1.30P2S6 van der Waals Layered Crystals.

The advancement of ultrafast photonics and optoelectronic devices necessitates the exploration of new materials with optical and chemical stability to implement practical applications. Layered quaternary metal-thio/selenophosphate has attracted much interest over the past few years. Ferroelectric CuInP2S6 (CIPS) is an emerging material that belongs to this family. When synthesized with Cu deficiencies, CIPS forms self-assembled in-plane heterostructures, which in turn exhibit properties that are both compositionally and thermally dependent. These characteristics can be explored for applications in nonlinear optoelectronic and photonic devices. Herein, we study the second and third order nonlinear optical behavior of Cu0.33In1.30P2S6 bulk heterostructure. We observed large two photon induced nonlinear absorptions and self-defocusing at 1032 nm pulsed laser excitation using the Z-scan technique. Furthermore, we identified a polarization-dependent second harmonic signal and determined the laser-induced optical damage threshold. Our observations allow for the designing of optoelectronic and ultrafast photonic devices based on these materials.

Screening and Risk Factors for Retinopathy of Prematurity in a Tertiary Care Hospital in Cairo, Egypt.

Purpose: To evaluate the retinopathy of prematurity (ROP) prevalence, risk factors and screening outcome in a tertiary hospital in Cairo, Egypt. Methods: A prospective observational study was done in Neonatal Intensive Care Unit in Ain Shams University Hospital. A total of 159 premature infants were screened for ROP based on the most inclusive criteria reported to date. Screening included premature infants with gestational age (GA) of ≤34 weeks or birth weight (BW) of ≤2000 grams, or GA >34 weeks or BW >2000 grams, with multiple co-morbidities. The prevalence of ROP, plus disease and their correlation with risk factors of interest were studied. Results: The GA of the included infants ranged from 27 to 36 weeks, mean (SD) 31.87 (± 1.81) weeks. The BW ranged from 640 to 3900 grams, mean (SD) 1784.71 (± 560.30) grams. The prevalence of ROP more than stage 0 was 25.8% (41 infants), 7.3% of the cases (11 infants) showed plus disease and 6.3% (10 infants) showed severe ROP requiring treatment. Of those, 2 cases (20%) fell outside the British Guideline's criteria for Screening. There was a highly significant (p < 0.0001) correlation between ROP more than stage 0 and low GA, low BW, mechanical ventilation, respiratory distress syndrome, necrotizing enterocolitis, intraventricular haemorrhage, and blood transfusion. No significant correlation was found between appearance of ROP more than stage 0 and gender (p = 0.911), patent ductus arteriosus (p =0.187), or sepsis (p =0.998). Conclusion: ROP is a significant problem in the premature infants in Egypt. Extremely premature infants with lower BW are more prone to develop ROP. However, cases with higher GA and BW than mentioned in the British guidelines screening criteria especially with multiple comorbidities showed severe ROP requiring intervention, which implies the need to develop a screening guideline for the Egyptian population.

Gene flow biases population genetic inference of recombination rate.

Accurate estimates of the rate of recombination are key to understanding a host of evolutionary processes as well as the evolution of the recombination rate itself. Model-based population genetic methods that infer recombination rates from patterns of linkage disequilibrium in the genome have become a popular method to estimate rates of recombination. However, these linkage disequilibrium-based methods make a variety of simplifying assumptions about the populations of interest that are often not met in natural populations. One such assumption is the absence of gene flow from other populations. Here, we use forward-time population genetic simulations of isolation-with-migration scenarios to explore how gene flow affects the accuracy of linkage disequilibrium-based estimators of recombination rate. We find that moderate levels of gene flow can result in either the overestimation or underestimation of recombination rates by up to 20-50% depending on the timing of divergence. We also find that these biases can affect the detection of interpopulation differences in recombination rate, causing both false positives and false negatives depending on the scenario. We discuss future possibilities for mitigating these biases and recommend that investigators exercise caution and confirm that their study populations meet assumptions before deploying these methods.

Syringol isolated from Eleusine coracana (L.) Gaertn bran suppresses inflammatory response through the down-regulation of cPLA2, COX-2, IκBα, p38 and MPO signaling in sPLA2 induced mice paw oedema.

Eleusine coracana (L.) Gaertn (E. coracana) is one of the highest consuming food crops in Asia and Africa. E. coracana is a plant with several medicinal values including anti-ulcerative, anti-diabetic, anti-viral and anti-cancer properties. However, the anti-inflammatory property of E. coracana remains to be elucidated. Therefore, the objective of present study was to investigate the potential in isolated molecule from E. coracana via a combination of in vitro, in vivo and in silico methods. In this study, we have isolated, purified and characterized an anti-inflammatory molecule from E. coracana bran extract known as syringol. Purification of syringol was accomplished by combination of GC-MS and RP-HPLC techniques. Syringol significantly inhibited the enzymes activity of sPLA2 (IC50 = 3.00 µg) and 5-LOX (IC50 = 0.325 µg) in vitro. The inhibition is independent of substrate concentration, calcium ion concentration and was irreversible. Syringol interacts with purified sPLA2 enzymes as evidenced by fluorescence and molecular docking studies. Further, the syringol molecule dose dependently inhibited the development of sPLA2 and λ-carrageenan induced edema. Furthermore, syringol decreases the expression of cPLA2, COX-2, IκBα, p38 and MPO in edematous tissues as demonstrated by western blots. These studies revealed that syringol isolated from E. coracana bran may develop as a potent anti-inflammatory molecule.

Hypomineralized Primary Teeth in Preterm Low Birth Weight Children and Its Association with Molar Incisor Hypomineralization-A 3-Year-Prospective Study.

The present prospective study was conducted to assess the prevalence of enamel hypomineralization (EH) in primary dentition among preterm low birth weight (PT-LBW) children, incidence of molar incisor hypomineralization (MIH) in the same cohorts, and to determine associations between PT-LBW, hypomineralization in primary second molars, and MIH. A total of 287 PTLBW study subjects and 290 control full-term normal birth weight subjects were followed up for 36 months. Enamel defects were recorded at baseline. The same cohorts were examined after 3 years for MIH using the European Academy of Paediatric Dentistry (EAPD) criteria. Multiple variable logistic regression models were developed. A total of 279 children (48.4%) presented with EH in primary dentition and 207 (35.9%) children presented with MIH. Children with primary second molar hypomineralization had 2.13 (R2 = 0.19, 95% CI = 0.98-4.19, p = 0.005) times higher frequency of MIH. Children with PT-LBW had 3.02 times (R2 = 0.31, 95% CI = 1.01-5.94, p = 0.005) higher frequency of MIH incidence after adjusting for childhood infection, prenatal history, and presence of hypomineralized primary second molars. To conclude, the present study showed significant association between PT-LBW, hypomineralized second primary molars, and incidence of MIH.

Starch engineered with Moringa oleifera seeds protein crosslinked Fe3O4: A synthesis and flocculation studies.

This study aimed to utilize cationic protein extracted from the Moringa oleifera seed in the fabrication of cationic starch crosslinked with magnetic nanoparticles (MagCS). Important synthesis parameters include starch to cationic protein volume ratio, magnetic nanoparticles mass fraction, reaction and crosslinking time, reaction and crosslinking temperature and crosslinker concentration. At optimum synthesis conditions, MagCS yield a 38.55% amide content, 2.46 degree of substitution, 1.1 mmol/g charge density and 78.6% crosslinking, which are much higher compared to other starch derivatives. A series of characterization analyses such as Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, elemental analysis and vibrating sample magnetometer concluded that MagCS was embedded with amide group, has high crystallinity structure, is thermally stable and shows a promising magnetic characteristic. Based on the synthesis parameters and characterization studies, the synthesis mechanism of MagCS was also postulated. The flocculation performance of MagCS was successfully assessed for the treatment of palm oil mill effluent. At optimum dosage, initial pH and settling time of 1.0 g/L, 9.0 and 15 min, the MagCS flocculant was able to remove 90.48, 83.95 and 58.19% of turbidity, color and chemical oxygen demand, respectively. This study provides an alternative eco-friendly materials in the wastewater treatment application.

Intraspecific Genetic Variation for Behavioral Isolation Loci in Drosophila.

Behavioral isolation is considered to be the primary mode of species isolation, and the lack of identification of individual genes for behavioral isolation has hindered our ability to address fundamental questions about the process of speciation. One of the major questions that remains about behavioral isolation is whether the genetic basis of isolation between species also varies within a species. Indeed, the extent to which genes for isolation may vary across a population is rarely explored. Here, we bypass the problem of individual gene identification by addressing this question using a quantitative genetic comparison. Using strains from eight different populations of Drosophila simulans, we genetically mapped the genomic regions contributing to behavioral isolation from their closely related sibling species, Drosophila mauritiana. We found extensive variation in the size of contribution of different genomic regions to behavioral isolation among the different strains, in the location of regions contributing to isolation, and in the ability to redetect loci when retesting the same strain.

Inversions shape the divergence of Drosophila pseudoobscura and Drosophila persimilis on multiple timescales.

By shaping meiotic recombination, chromosomal inversions can influence genetic exchange between hybridizing species. Despite the recognized importance of inversions in evolutionary processes such as divergence and speciation, teasing apart the effects of inversions over time remains challenging. For example, are their effects on sequence divergence primarily generated through creating blocks of linkage disequilibrium prespeciation or through preventing gene flux after speciation? We provide a comprehensive look into the influence of inversions on gene flow throughout the evolutionary history of a classic system: Drosophila pseudoobscura and Drosophila persimilis. We use extensive whole-genome sequence data to report patterns of introgression and divergence with respect to chromosomal arrangements. Overall, we find evidence that inversions have contributed to divergence patterns between D. pseudoobscura and D. persimilis over three distinct timescales: (1) segregation of ancestral polymorphism early in the speciation process, (2) gene flow after the split of D. pseudoobscura and D. persimilis, but prior to the split of D. pseudoobscura subspecies, and (3) recent gene flow between sympatric D. pseudoobscura and D. persimilis, after the split of D. pseudoobscura subspecies. We discuss these results in terms of our understanding of evolution in this classic system and provide cautions for interpreting divergence measures in other systems.

Homage to Felsenstein 1981, or why are there so few/many species?

If there are no constraints on the process of speciation, then the number of species might be expected to match the number of available niches and this number might be indefinitely large. One possible constraint is the opportunity for allopatric divergence. In 1981, Felsenstein used a simple and elegant model to ask if there might also be genetic constraints. He showed that progress towards speciation could be described by the build-up of linkage disequilibrium among divergently selected loci and between these loci and those contributing to other forms of reproductive isolation. Therefore, speciation is opposed by recombination, because it tends to break down linkage disequilibria. Felsenstein then introduced a crucial distinction between "two-allele" models, which are subject to this effect, and "one-allele" models, which are free from the recombination constraint. These fundamentally important insights have been the foundation for both empirical and theoretical studies of speciation ever since.

PseudoBase: a genomic visualization and exploration resource for the Drosophila pseudoobscura subgroup.

Drosophila pseudoobscura is a classic model system for the study of evolutionary genetics and genomics. Given this long-standing interest, many genome sequences have accumulated for D. pseudoobscura and closely related species D. persimilis, D. miranda, and D. lowei. To facilitate the exploration of genetic variation within species and comparative genomics across species, we present PseudoBase, a database that couples extensive publicly available genomic data with simple visualization and query tools via an intuitive graphical interface, amenable for use in both research and educational settings. All genetic variation (SNPs and indels) within the database is derived from the same workflow, so variants are easily comparable across data sets. Features include an embedded JBrowse interface, ability to pull out alignments of individual genes/regions, and batch access for gene lists. Here, we introduce PseudoBase, and we demonstrate how this resource facilitates use of extensive genomic data from flies of the Drosophila pseudoobscura subgroup.

Unusual Presentation of Epstein-Barr Virus-Associated Cholestatic Hepatitis in an Infant.

Epstein-Barr virus (EBV) infections are prevalent in the pediatric population but are subclinical in the majority of cases. Elevated transaminases in the acute setting rarely increase beyond 5 times the normal upper limit. We present a girl aged 1 y with fever, vomiting, and diarrhea. Although initial physical examination was unremarkable, she developed jaundice, hepatomegaly, abdominal distension, and a maculopapular rash during admission. Laboratory investigations revealed marked increase in transaminases (alanine aminotransferase 7,664.5 IU/L, aspartate aminotransferase 12,266 IU/L), elevated γ-glutamyl transferase (224 IU/L), and hyperbilirubinemia (total 130.7 µmol/L, direct 104.9 µmol/L). Abdominal ultrasound reported hepatomegaly with mild ascites. Serology revealed that both Monospot test and EBV immunoglobulin G were positive. With supportive therapy, improvement was noted within a week of symptom onset. We hereby elucidate the importance of considering EBV as a cause of acute cholestatic hepatitis in a very young pediatric patient who develops a rapid elevation of liver enzymes.