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Background: MRI fusion prostate biopsy has improved the detection of clinically significant prostate cancer (CSC). Continued refinements in predicting the pre-biopsy probability of CSC are essential for optimal patient counseling. We investigated potential factors related to improved cancer detection rates (CDR) of CSC in patients with PI-RADS ≥ 3 lesions. Methods: The pathology of 980 index lesions in 980 patients sampled by transrectal mpMRI-targeted prostate biopsy across four medical centers between 2017–2020 was reviewed. PI-RADS lesion distribution included 291 PI-RADS-5, 374 PI-RADS-4, and 315 PI-RADS-3. We compared CDR of index PI-RADS ≥ 3 lesions based on location (TZ) vs. (PZ), PSA density (PSAD), and history of prior negative conventional transrectal ultrasound-guided biopsy (TRUS). Results: Mean age, PSA, prostate volume, and level of prior negative TRUS biopsy were 66 years (43–90), 7.82 ng/dL (5.6–11.2), 54 cm3 (12–173), and 456/980 (46.5%), respectively. Higher PSAD, no prior history of negative TRUS biopsy, and PZ lesions were associated with higher CDR. Stratified CDR highlighted significant variance across subgroups. CDR for a PI-RADS-5 score, PZ lesion with PSAD ≥ 0.15, and prior negative biopsy was 77%. Conversely, the CDR rate for a PI-RADS-4 score, TZ lesion with PSAD < 0.15, and prior negative biopsy was significantly lower at 14%. Conclusions: For index PI-RADS ≥ 3 lesions, CDR varied significantly based on location, prior history of negative TRUS biopsy, and PSAD. Such considerations are critical when counseling on the merits and potential yield of prostate needle biopsy.

Abstract Background Cost-effectiveness analyses rarely offer useful insights to policy decisions unless their results are compared against a benchmark threshold. The cost-effectiveness threshold (CET) represents the maximum acceptable monetary value for achieving a unit of health gain. This study aimed to identify CET values on a global scale, provide an overview of using multiple CETs, and propose a country-specific CET framework specifically tailored for Egypt. The proposed framework aims to consider the globally identified CETs, analyze global trends, and consider the local structure of Egypt’s healthcare system. Methods We conducted a literature review to identify CET values, with a particular focus on understanding the basis of differentiation when multiple thresholds are present. CETs of different countries were reviewed from secondary sources. Additionally, we assembled an expert panel to develop a national CET framework in Egypt and propose an initial design. This was followed by a multistakeholder workshop, bringing together representatives of different governmental bodies to vote on the threshold value and finalize the recommended framework. Results The average CET, expressed as a percentage of the gross domestic product (GDP) per capita across all countries, was 135%, with a range of 21 to 300%. Interestingly, while the absolute value of CET increased with a country’s income level, the average CET/GDP per capita showed an inverse relationship. Some countries applied multiple thresholds based on disease severity or rarity. In the case of Egypt, the consensus workshop recommended a threshold ranging from one to three times the GDP per capita, taking into account the incremental relative quality-adjusted life years (QALY) gain. For orphan medicines, a CET multiplier between 1.5 and 3.0, based on the disease rarity, was recommended. A two-times multiplier was proposed for the private reimbursement threshold compared to the public threshold. Conclusion The CET values in most countries appear to be closely related to the GDP per capita. Higher-income countries tend to use a lower threshold as a percentage of their GDP per capita, contrasted with lower-income countries. In Egypt, experts opted for a multiple CET framework to assess the value of health technologies in terms of reimbursement and pricing.

Assessing toxicity of complex mixtures of contaminants from industrial sites with historic and ongoing contamination remains a challenge for risk assessors. Groundwater from a pesticide packaging site in Canada containing a complex mixture of known and unknown contaminants was examined in male rats to determine the target organ toxicity. This study determined the time-course of toxicity (7, 14, 28, and 60 days) following ad libitum oral exposure to 0.05% v/v contaminated groundwater compared to tap water (control) in male Sprague Dawley rats (n=5 /group/time). Exposure to groundwater resulted in inflammation, indicated by a statistically significant increase in plasma lymphocyte and neutrophil counts on days 7 and 60, respectively, but a reduction in the plasma alpha 2 macroglobulin levels by day 60. Gonadotoxicity was indicated by a reduced Johnsen score (grading spermatogenesis) in all exposed groups at all time points, while seminiferous epithelial height was reduced on days 7, 14, and 28 compared to controls. Plasma testosterone was reduced in exposed groups on days 7 and 28, accompanied by elevated testicular lipid peroxidation at all time points compared to control. In contrast, lipid peroxidation in the lungs from exposed rats was elevated on days 7, 14, and 28. Plasma symmetric dimethylarginine was elevated on day 14 in the exposed group indicating renal impairment. Taken together, these results indicate that testes, kidney, immune and lung are target organs for the contaminated groundwater from this industrial site. The current study highlights the challenge in hazard assessment for complex mixtures and highlights the need for effects-directed analysis and the continued, albeit limited, use of animal models in toxicity testing.

Abstract The rough set (RS) and multi-granulation rough set (MGRS) theories have been successfully extended to accommodate preference analysis by substituting the equivalence relation (ER) with the dominance relation (DR). On the other hand, bipolarity refers to the explicit handling of positive and negative aspects of data. In this paper, with the help of bipolar fuzzy preference relation (BFPR) and bipolar fuzzy preference $$\delta $$ δ -covering (BFP $$\delta $$ δ C), we put forward the idea of BFP $$\delta $$ δ C based optimistic multi-granulation bipolar fuzzy rough set (BFP $$\delta $$ δ C-OMG-BFRS) model and BFP $$\delta $$ δ C based pessimistic multi-granulation bipolar fuzzy rough set (BFP $$\delta $$ δ C-PMG-BFRS) model. We examine several significant structural properties of BFP $$\delta $$ δ C-OMG-BFRS and BFP $$\delta $$ δ C-PMG-BFRS models in detail. Moreover, we discuss the relationship between BFP $$\delta $$ δ C-OMG-BFRS and BFP $$\delta $$ δ C-PMG-BFRS models. Eventually, we apply the BFP $$\delta $$ δ C-OMG-BFRS model for solving multi-criteria decision-making (MCDM). Furthermore, we demonstrate the effectiveness and feasibility of our designed approach by solving a numerical example. We further conduct a detailed comparison with certain existing methods. Last but not least, theoretical studies and practical examples reveals that our suggested approach dramatically enriches the MGRS theory and offers a novel strategy for knowledge discovery, which is practical in real-world circumstances.

Abstract Background Multidisciplinary team meeting (MDTM) has become an increasingly important part of disease management model, particularly in cancer care. MDTM consists of a group of doctors to provide independent opinions on diagnostic and treatment decisions, as well as personalized therapeutic plan for patients. By selecting the most suitable treatment for patients from multiple perspectives, management by multidisciplinary team (MDT) have been shown to have advantages over traditional treatment models. The objective of this study is to determine the impact of MDTM on the management of uro-oncological cases and adherence to MDTM plans. Methods We retrospectively collected patients’ clinical information discussed in MDTM from 1st January 2021 to 31st December 2022 at our institution. The pre-MDTM treatment plan by the clinicians and the MDTM consensus plans were compared to assess the overall MDTM impact on patient management. Adherence to MDTM recommendations was also analyzed. Results Data on 432 patients discussed in MDTM from 1st January 2021 to 31st December 2022 were collected and analyzed. Prostate cancer was the most common type of cancer discussed (n = 212, 48.8%). MDTM had a significant impact on decision-making in 276 (63.6%) cases, with changes to patient management being observed in more than half of all cases. Adherence to MDTM outcomes was high with 383 (90.5%) of patients eventually had treatment according to the MDTM recommendation. Conclusion The study highlights the importance of MDTM in the management of genitourinary malignancies, particularly in cases where no original plan exists. Patient’s compliance and adherence to the MDTM consensus plan are also very encouraging.

The study of twisted light is an imperative field of exploration in both the classical electromagnetics and quantum regimes. So, in this manuscript, using the Generalized Lorenz-Mie theory (GLMT), the electromagnetic efficiencies and differential scattering on a homogeneous and isotropic dielectric sphere have been investigated in the presence of a vortex Gaussian beam (VGB) with Gaussian field profile. To do this, a mathematical model is proposed for analyzing the scattering characteristics of the VGB from a dielectric sphere. Electromagnetic fields are expressed in the context of the spherical vector wave-functions (SVWFs). The unknown field coefficients regarding scattered fields and the internal fields are calculated by the implementation of continuous boundary conditions (BCs) at the surface of the dielectric sphere. Scattering efficiency, extinction efficiency, absorption efficiency as well as differential scattering of an isotropic dielectric sphere are numerically studied. The influence of various parameters like as orbital angular momentum (OAM) mode number, beam waist radius, and the relative refractive index for efficiency factors and differential scattering has been computed and numerically analyzed. Our research offers a more comprehensive investigation of the scattering of structured light towards scattering media.

In order to eventually reach the net-zero carbon target, the low carbon transition demands substantial growth in the penetration of renewable generation in energy systems. It is essential to have enough flexible resources to prevent the curtailment of energy systems with high intermittent renewable output to run consistently. Therefore, this study focuses on the multi-objective optimal dispatching model of combined cooling, heating, and power (CCHP) microgrid with power-to-gas (P2G). The structure of the CCHP microgrid and the working principle of P2G are studied and analyzed. First, briefly described the multi-objective optimal dispatch model of the CCHP microgrid with P2G established with the goal of operational and environmental cost. Second, a hybrid gravitational search algorithm and random forest regression (GSA-RFR) are introduced to find out the optimal values. The proposed model verifies that P2G improves the wind abandonment capacity of the CCHP microgrid operation system. Furthermore, it reduces environmental costs and transforms environmental values into economic benefits during system operation. Noting that, the GSA-RFR improves the system economy by 7.13% comparatively.

With the emergence of fiber-reinforced polymer (FRP) reinforcement as a substitute for conventional steel reinforcement, different design codes have been developed to account for the different mechanical properties of the FRP, specifically the elastic modulus. The ACI 440.11-22, CSA/S806-12, and JSCE-97 are well-known standards for FRP-reinforced concrete structures. In particular, these design standards show significant variations in estimating the punching shear resistance and accounting for the elastic modulus. This study provides a statistical and machine learning-based evaluation of the punching shear models in design standards. An Artificial neural network (ANN) framework is used to develop a generalized punching resistance model of flat slabs reinforced with steel and FRP bars utilizing a large experimental dataset with 539 tests. The study presents a parametric study to examine the effect of different factors on the punching shear strength. The parametric study provided a graphical presentation and comparison between the design models and the developed ANN model.

In this work, the vibration analysis of a layered, cylinder-shaped shell is undertaken. The structure of the shell layers is composed of functionally graded and isotropic materials. The vibrations of four-layered cylindrical shells with a ring support along the axial direction are investigated in this research. The two internal layers are composed of isotropic materials, and the external two layers are composed of functionally graded materials. The outer functionally graded material layers considered are stainless steel, zirconia, and nickel. The inner two isotropic layers considered are aluminum and stainless steel. The shell frequency equation is acquired by employing the Rayleigh–Ritz method under the shell theory of Sanders. The trigonometric volume fraction law is used to sort the functionally graded material composition of the FGM layers. The natural frequencies are attained under two boundary conditions, namely simply supported–simply supported and clamped–clamped.

In the fields of numerical analysis and applied science, approximating the roots of nonlinear equations is a fundamental and intriguing challenge. With the rapid advancement of computing power, solving nonlinear equations using numerical techniques has become increasingly important.Numerical methods for nonlinear equations play a critical role in many areas of research and industry, enabling scientists and engineers to model and understand complex systems and make accurate predictions about their behavior. This paper aims to propose novel fourth- and fifth-order iterative schemes for approximating solutions to nonlinear equations in coupled systems using Adomian decomposition methods. The proposed method’s convergence is examined and numerical examples are provided to demonstrate the effectiveness of the new schemes. We compare these iterative techniques with some previous schemes in the literature, and our results show that the new schemes are more efficient. Our findings represent a significant improvement over previously reported results. Polynomiography is an important tool for visualizing the roots of complex polynomials. It is widely used by researchers, mathematicians and engineers, as it provides a way to visualize complex equations understand their behavior. Our proposed method is capable of generating polynomiographs of complex polynomials, revealing interesting patterns that provide clear visual representations of the roots of complex polynomials.

The enumeration of fuzzy subgroups is a complex problem. Several authors have computed results for special instances of groups. In this paper, we present a novel algorithm that is designed to enumerate the fuzzy subgroups of a finite group. This is achieved through the computation of maximal chains of subgroups. This approach is also useful for writing a program to compute the number of fuzzy subgroups. We provide further elucidation by computing the number of fuzzy subgroups of the groups $ Q_8 $ and $ D_8 $.

Background Peer-assisted learning has been shown to be constructive in numerous aspects of undergraduate medical education. The purpose of this study was to evaluate the effectiveness of peer-assisted teaching of medical English skills to non-native English-speaking students. Methods A medical English conversation course was conducted at Damascus University by a group of students. Targeted participants were intermediate level fellow students from the same program. A longitudinal study was carried out between 1st to 31st March 2019 to assess changes in self-assessment of English language skills among course participants. Pre- and post-course appraisal involved a review of previous experience with medical English language, a self-assessment of five English language skills, and an objective measurement of medical English knowledge. In addition, participants were requested to respond to a set of statements related to the importance and the usefulness of peer-assisted teaching of medical English skills. Paired-sample Student t-test was used to compare pre- and post-course appraisal results. Results 42 students attended the course and completed pre- and post-course appraisals in full. Data analyses showed a statistically significant increase in participants’ confidence in speaking medical English in public (p

Abstract Inflammatory bowel diseases (IBD), including ulcerative colitis, are chronic autoimmune conditions characterized by inflammation of the digestive system. The exact cause of IBD is unknown, but they often start during adolescence or early adulthood with symptoms such as urgency, rectal bleeding, diarrhea, abdominal pain and tenesmus. Primary sclerosing cholangitis and autoimmune hepatitis are recognized as co‐occurring conditions associated with ulcerative colitis. However, the combination of ulcerative colitis, primary sclerosing cholangitis, liver cirrhosis, and celiac disease occurring concurrently has only been reported once before in a female patient. Here, we present the exceptional case of a Syrian adult male with all four of these conditions. This highlights the importance of screening for both celiac disease and cirrhosis in patients with ulcerative colitis and primary sclerosing cholangitis together, despite this combination of comorbidities is rare.

Lie algebra plays an important role in the study of singularity theory and other fields of sciences. Finding numerous invariants linked with isolated singularities has always been a primary interest in the field of classification theory of isolated singularities. Any Lie algebra that characterizes simple singularity produces a natural question. The study of properties such as to find the dimensions of newly defined algebra is a remarkable work. Hussain, Yau and Zuo have found a new class of Lie algebra Lk(V), k≥1, i.e., Der (Mk(V),Mk(V)) and proposed a conjecture over its dimension δk(V) for k≥0. Later, they proved it true for k up to k=1,2,3,4,5. In this work, the main concern is whether it is true for a higher value of k. According to this, we first calculate the dimension of Lie algebra Lk(V) for k=6 and then compute the upper estimate conjecture of fewnomial isolated singularities. Additionally, we also justify the inequality conjecture δk+1(V)<δk(V) for k=6. Our calculated results are innovative and serve as a new addition to the study of singularity theory.

IntroductionThe lived experiences of chronic pain (CP) among Arabic-speaking populations remain underexplored. A better understanding of these experiences and their associations with attention difficulties, coping mechanisms, and treatment options could lead to improved support for this group.MethodsThis qualitative study utilised a descriptive design and involved one-to-one interviews with 51 participants with CP who had just completed two attention tasks. Interviews were conducted using a semi-structured topic guide, transcribed verbatim and translated from Arabic to English before agreeing on the coding framework. Themes and subthemes were extracted using a framework analysis approach.ResultsThe study identified six main themes: Factors contributing towards developing or exacerbating CP, the impact of CP on psychosocial functions, including attention, the perceived role of social support, coping strategies for managing CP, perceptions about available treatments and recommendations for interventions.DiscussionCP significantly impacts individuals’ physical and psychosocial functions, and it is reciprocally associated with attentional difficulties. Despite using various approaches to manage their CP, none of the participants used psychological interventions or counselling. Understanding the diverse impacts of CP and the coping strategies employed to develop culturally sensitive interventions, review current related policies, and improve healthcare services is crucial to managing CP among this population.

Complex fuzzy (CF) sets (CFSs) play an important role in modeling two-dimensional information challenges. Researchers exploring decision-making systems have recently become interested in CFS extensions. The complex T-spherical fuzzy (CT-SF) set (CT-SFS) is a recent extension of the CFSs. The present study aims to devise the Frank operational laws for the CT-SF environment and to verify their required properties. Subsequently, some CT-SF Frank aggregation operators are explored, such as CT-SF Frank weighted averaging (CT-SFFWA) operator, CT-SF Frank weighted geometric (CT-SFFWG) operator, CT-SF Frank ordered weighted averaging (CT-SFFOWA) operator, and CT-SF Frank ordered weighted geometric (CT-SFFOWG) operator, CT-SF Frank hybrid averaging (CT-SFFHA) operator, CT-SF Frank hybrid geometric (CT-SFFHG) operator, and their peculiar cases are examined. Based on the devised operators, a novel multi-criteria group decision-making (MCGDM) methodology is investigated to tackle MCGDM problems under the CT-SF environment. Lastly, the practicality and effectiveness of the presented methodology are conducted by parameter analysis and comparative exploration.

Ergot alkaloids are secondary metabolites that exist in two configurations, the C-8-R-isomer (R-epimer), and the C-8-S-isomer (S-epimer). Toxic effects of ergot, such as vasoconstriction, have been primarily attributed to the R-epimer bioactivity, as compared to the S-epimer. Recent studies demonstrated potential bioactivity of S-epimers. Therefore, further cost-effective investigations of the S-epimers are needed. The present study investigated the S-epimer - vascular receptor binding relationship. An in silico molecular docking approach, utilizing AutoDock Vina and DockThor, was used to determine if the S-epimer (ergocristinine) binds to vascular receptors and to compare the binding affinity and interactions to the corresponding R-epimer (ergocristine) and a structural analogue (lysergic acid amide). The binding energy (kcal/mol) of ergocristinine was − 9.7 or − 11.0 to the serotonin (5-HT) 2 A receptor and − 8.7 or − 11.4 to the alpha 2 A adrenergic receptor, depending on the software used. A hydrogen bond was formed between ergocristinine and amino acid residues of the 5-HT 2 A and alpha 2 A adrenergic receptor binding sites, with bond lengths of 3.10 Å and 3.28 Å, respectively. Binding affinities and molecular interactions among the ligands to each receptor differed. Different affinities and interactions may relate to differences in the chemical structures. The binding affinities and strong molecular interactions of the S-epimer to vascular receptors may contribute to the observed physiological manifestations that occur after ergot alkaloid exposure. The results of the present study suggest further investigation on the receptor binding of the S-epimers of ergot alkaloids.

Abstract Background Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. Methods We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P

Background Sodium‐glucose cotransporter‐2 (SGLT2) inhibitors reduce atherosclerotic cardiovascular disease (ASCVD) events in patients with prior ASCVD and type 2 diabetes; however, this benefit is uncertain in patients without established ASCVD. Methods and Results Large‐scale cardiovascular outcome randomized controlled trials or their prespecified subgroup analyses were selected, evaluating SGLT2 inhibitors versus placebo for primary prevention of ASCVD (inception, March 2023). The primary outcome was atherosclerotic major adverse cardiovascular events (MACEs), which was a composite of cardiovascular mortality, myocardial infarction, and stroke. The secondary outcomes were individual components of MACEs and all‐cause mortality. The outcomes were reported as random‐effect relative risk (RR) with a 95% CI. This analysis, comprising 23 987 patients enrolled in 5 randomized controlled trials with a mean follow‐up duration of ≈135 weeks, found no significant reduction in atherosclerotic MACEs with SGLT2 inhibitors in comparison to placebo (RR, 0.85 [95% CI, 0.71–1.01]; P=0.07; I2=44). There were no significant differences in cardiovascular mortality (RR, 0.93 [95% CI, 0.77–1.14]; P=0.50; I2=0), myocardial infarction (RR, 0.88 [95% CI, 0.69–1.11]; P=0.28; I2=23), and stroke (RR, 0.84 [95% CI, 0.62–1.16]; P=0.29; I2=46). SGLT2 inhibitors significantly improved all‐cause mortality (RR, 0.85 [95% CI, 0.72–1.0]; P=0.04; I2=23). On subgroup analyses, the use of SGLT2 inhibitors led to significant reductions in MACEs (RR, 0.74 [95% CI, 0.61–0.89]; P=0.001), myocardial infarction (RR, 0.67 [95% CI, 0.47–0.97]; P=0.03), and stroke (RR, 0.61 [95% CI, 0.41–0.91]; P=0.01) primarily in patients with chronic kidney disease along with type 2 diabetes, whereas these benefits were not observed in patients with type 2 diabetes without chronic kidney disease. Conclusions SGLT2 inhibitors significantly reduced atherosclerotic MACEs in subjects having both chronic kidney disease and type 2 diabetes without established ASCVD.

Introduction:Galactosemia (GAL) is a genetic disorder that results in disturbances in galactose metabolism and can lead to life-threatening complications. However, the underlying pathophysiology of long-term complications in GAL remains poorly understood.Methods: In this study, a metabolomics approach using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was used to investigate metabolomic changes in dried blood spots of 15 patients with GAL and 39 healthy individuals.Results: The study found that 2,819 metabolites underwent significant changes in patients with GAL compared to the control group. 480 human endogenous metabolites were identified, of which 209 and 271 were upregulated and downregulated, respectively. PA (8:0/LTE4) and ganglioside GT1c (d18:0/20:0) metabolites showed the most significant difference between GAL and the healthy group, with an area under the curve of 1 and 0.995, respectively. Additionally, the study identified potential biomarkers for GAL, such as 17-alpha-estradiol-3-glucuronide and 16-alpha-hydroxy DHEA 3-sulfatediphosphate.Conclusion: This metabolomics study deepened the understanding of the pathophysiology of GAL and presented potential biomarkers that might serve as prognostic biomarkers to monitor the progression or support the clinical diagnosis of GAL.

Abstract We describe a case series of five infants (age range: 1–90 days; 4 females and 1 male) who presented to Al Jalila Children’s intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all five patients and their parents within the hospital’s genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive findings were a homozygous pathogenic variant in POMT1 gene causing muscular dystrophydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing Pallister-Killian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase deficiency and Wolman disease. The rWGS analysis provided fast and precise diagnostic findings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-month-old infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pediatric intensive care setting, in a diverse population that has long been underserved in genomic services. Significant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients.

Abstract Background The pro-neural transcription factor ASCL1 is a master regulator of neurogenesis and a key factor necessary for the reprogramming of permissive cell types to neurons. Endogenously, ASCL1 expression is often associated with neuroblast stem-ness. Moreover, ASCL1-mediated reprogramming of fibroblasts to differentiated neurons is commonly achieved using artificially high levels of ASCL1 protein, where ASCL1 acts as an “on-target” pioneer factor. However, the genome-wide effects of enhancing ASCL1 activity in a permissive neurogenic environment has not been thoroughly investigated. Here, we overexpressed ASCL1 in the neuronally-permissive context of neuroblastoma (NB) cells where modest endogenous ASCL1 supports the neuroblast programme. Results Increasing ASCL1 in neuroblastoma cells both enhances binding at existing ASCL1 sites and also leads to creation of numerous additional, lower affinity binding sites. These extensive genome-wide changes in ASCL1 binding result in significant reprogramming of the NB transcriptome, redirecting it from a proliferative neuroblastic state towards one favouring neuronal differentiation. Mechanistically, ASCL1-mediated cell cycle exit and differentiation can be increased further by preventing its multi-site phosphorylation, which is associated with additional changes in genome-wide binding and gene activation profiles. Conclusions Our findings show that enhancing ASCL1 activity in a neurogenic environment both increases binding at endogenous ASCL1 sites and also results in additional binding to new low affinity sites that favours neuronal differentiation over the proliferating neuroblast programme supported by the endogenous protein. These findings have important implications for controlling processes of neurogenesis in cancer and cellular reprogramming.

Theory of m-polar fuzzy set deals with multi-polar information. It is used when data comes from m factors (m≥2). The primary objective of this work is to explore a generalized form of m-polar fuzzy subsemigroups, which is m-polar fuzzy ternary subsemigroups. There are many algebraic structures which are not closed under binary multiplication that is a reason to study ternary operation of multiplication such as the set of negative integer is closed under the operation of ternary multiplication but not closed for the binary multiplication. This paper, presents several significant results related to the notions of m-polar fuzzy ternary subsemigroups, m-polar fuzzy ideals, m-polar fuzzy generalized bi-ideals, m-polar fuzzy bi-ideals, m-polar fuzzy quasi-ideals and m-polar fuzzy interior ideals in ternary semigroups. Also, it is proved that every m- polar fuzzy bi-ideal of ternary semigroup is an m-polar fuzzy generalized bi-ideal of ternary semigroup but converse is not true in general. Moreover, this paper characterizes regular and intra-regular ternary semigroups by the properties of m-polar fuzzy ideals, m-polar fuzzy bi-ideals.

Due to the distributed and non-integrated nature of the healthcare systems which results from the application-centric view it leads to a challenging task to manage healthcare data exchange (heterogeneity problem). On the other hand, Blockchain technologies are emerging as promising and cost-effective means to meet some of these requirements due to their inherent design properties, such as secure cryptography and a resilient peer-to-peer network. Likewise, Blockchain-based applications can benefit the healthcare domain via their properties of asset sharing, and audit trails of data access. Existing work mainly pays attention to centralized and blockchain-based mechanisms. But it doesn’t realize the increase need for better data interoperability amount multiple healthcare systems and services. This requires shifting from the application-centric solutions toward the patient-centric solutions. This paper presents A secure and efficient framework based on Blockchain, Cloud, and IoT named Patient-Centric Healthcare Framework (PCH) for better healthcare systems interoperability. A tiered-based architecture (5 tiers) with collaboration is designed for the feasible realization of PCH. Also, the design and implementation aspects start from the layering diagram, system context, and detailed reference architecture that emphasizes the detailed component topology and interactions within the framework. An electronic medical record is used to show how healthcare data is processed with the required security considerations. Then, an evaluation of PCH against the existing Blockchain-based healthcare frameworks is conducted. The results analysis demonstrates that PCH offers practical solutions to protect healthcare data and support efficient data sharing with better interoperability.

Urothelial melanosis is an exceptionally rare diagnosis, with less than 25 cases being reported in the literature. Melanosis of the urothelium is characterized by abnormal melanin deposition within tissues, producing a black, velvety appearance to the urothelial mucosa. We present a 67-year-old male undergoing cystoscopy during a routine percutaneous nephrolithotomy (PCNL), who was found to have diffuse bladder melanosis extending up the ureter and into the renal pelvis. To our knowledge, this is the first reported case of synchronous melanosis of upper and lower urinary tract.

This study investigates the composition and corrosion of a lead ossuary excavated from the archaeological cemetery located on the site of the Queen Alia International Airport, Jordan. It also presents its conservation treatment using the potentiostatic reduction method. X-ray fluorescence (XRF) and scanning electron microscopy/ energy dispersive X–ray spectroscopy (SEM/EDX) analyses showed that the ossuary was made from a relatively pure lead metal. Examination of the corrosion products using X–ray diffraction (XRD) and SEM/EDX analyses indicated the presence oxides, carbonates and chlorides of lead as the main corrosion products on the ossuary. The metallographic examination showed a cast α-Pb dendritic microstructure. A linear sweep voltammetry (LSV) scan for a small fragment from the ossuary in a sodium sulfate solution allowed identifying the working conditions to reduce the corrosion products to lead metal. Chronoamperometry (CA) techniques helped to monitor the reduction process and determine its completion. The potentiostatic methods showed an excellent effectiveness in determining treatment parameters and monitoring the reduction process of the corrosion products on the ossuary and to prevent over-treatment. The reduced ossuary was finally coated with Paraloid B72 to prevent corrosion reoccurrence in the poor environmental conditions of the storage area.

The aim of this research work is to put forward fuzzy models of granular computing based on fuzzy relation and fuzzy indiscernibility relation. Thanks to fuzzy information granulation to provide multi-level visualization of problems that include uncertain information. In such a granulation, fuzzy sets and fuzzy graphs help us to represent relationships among granules, groups or clusters. We consider the fuzzy indiscernibility relation of a fuzzy knowledge representation system (I). We describe the granular structures of I, including discernibility, core, reduct and essentiality of I. Then we examine the contribution of these structures to granular computing. Moreover, we introduce certain granular structures using fuzzy graph models and discuss degree based model of fuzzy granular structures. Granulation of network models based on fuzzy information effectively handles real life data which possesses uncertainty and vagueness. Finally, certain algorithms of proposed models are developed and implemented to solve real life problems involving uncertain granularities. We also present a concise comparison of the models developed in our work with other existing methodologies.

Abstract Premise Sorghum is a multi‐use crop, the efficient breeding of which requires the development of new genetic tools. One such tool could be the genetic assessment of free microspores, which are released just after the tetrad stage of pollen development. Microspores are ideal for DNA isolation as they have underdeveloped cell walls and can be readily lysed as natural protoplasts. Methods Four cultivars of Sorghum bicolor (ʻAchi Turi’, ʻDale’, ʻLocal’, and ʻTopper 76‐6’) were grown in a greenhouse until flowering (7.7–11.5 cm flag leaf internode length), after which 30 immature microspores were isolated from each line. Plant height, time to flowering, boot radius, and spikelet maturation were recorded for each cultivar. The exine development of the microspores was observed under an inverted Nikon microscope, and those with underdeveloped exine were subjected to whole‐genome amplification and sequencing. Results Microspores in the early uninucleate to early binucleate stages had underdeveloped exine, and were therefore ideal for DNA extraction. High‐quality DNA was obtained from these single‐cell gametophytes. The average DNA concentration was 2902 ng/µL, with fragment sizes comparable to those obtained from leaf tissue extractions. Discussion Harvesting panicles with immature microspores means the entire gametic population is accessible for DNA analyses. This is the first amplification of whole‐genome DNA fragments from sorghum single‐cell microspores isolated during gametogenesis.

Neuroblastoma is a pediatric tumour that accounts for more than 15% of cancer-related deaths in children. High-risk tumours are often difficult to treat, and patients’ survival chances are less than 50%. Retinoic acid treatment is part of the maintenance therapy given to neuroblastoma patients; however, not all tumours differentiate in response to retinoic acid. Within neuroblastoma tumors, two phenotypically distinct cell types have been identified based on their super-enhancer landscape and transcriptional core regulatory circuitries: adrenergic (ADRN) and mesenchymal (MES). We hypothesized that the distinct super-enhancers in these different tumour cells mediate differential response to retinoic acid. To this end, three different neuroblastoma cell lines, ADRN (MYCN amplified and non-amplified) and MES cells, were treated with retinoic acid, and changes in the super-enhancer landscape upon treatment and after subsequent removal of retinoic acid was studied. Using ChIP-seq for the active histone mark H3K27ac, paired with RNA-seq, we compared the super-enhancer landscape in cells that undergo neuronal differentiation in response to retinoic acid versus those that fail to differentiate and identified unique super-enhancers associated with neuronal differentiation. Among the ADRN cells that respond to treatment, MYCN-amplified cells remain differentiated upon removal of retinoic acid, whereas MYCN non-amplified cells revert to an undifferentiated state, allowing for the identification of super-enhancers responsible for maintaining differentiation. This study identifies key super-enhancers that are crucial for retinoic acid-mediated differentiation.

Ergot sclerotia produce toxic secondary metabolites, ergot alkaloids, that infect cereal crops and grasses. Ergot alkaloids have two isomeric configurations: the C-8-R-isomer (R-epimer), and the C-8-S-isomer (S-epimer). Ergot contaminated matrices, such as cereal grains or grasses, may be stored for extended periods at various temperatures before being analyzed, utilized, or consumed. This study assessed the concentration of six common ergot alkaloids in both configurations found in naturally contaminated wheat over time (one, two, and four months) at different temperatures (room temperature, +4 °C, and −20 °C) using ultra-high-performance liquid chromatography–tandem mass spectrometry. The data indicate that the total ergot concentration within a natural contaminated sample varies over time at room temperature, +4 °C, and −20 °C. The total ergot concentration increased until month two, and decreased at month four, independent of temperature (p < 0.05). The total R-epimer concentration appeared to be less stable over time than the total S-epimer concentration. The changes in the total R and total S-epimer concentrations may have been caused by changes in the ergocristine and ergocristinine concentrations, respectively. Time and temperature should be considered when storing potentially contaminated matrices in a laboratory or practical agriculture situations. Quantification of ergot contaminated matrices should occur prior to their use to ensure the most reliable estimates of the concentration of ergot.

A bimodal double log-normal distribution on the real line is proposed using the random sign mixture transform. Its associated statistical inferences are derived. Its parameters are estimated by the maximum likelihood method. The performance of the estimators and the corresponding confidence intervals is checked by simulation studies. Application of the proposed distribution to a real data set from a DNA microarray is presented.

Abstract Background The COVID-19 pandemic has had a major impact on people’s lives globally. The outbreak in Saudi Arabia worsened when the number of cases and deaths rose in March and April of 2020, leading to a national lockdown. This study aimed to assess the factors associated with mental health symptoms in a sample of people residing in Saudi Arabia during the COVID-19 pandemic. Methods We conducted an observational cross-sectional study using an online survey distributed via social media, completed by 3032 respondents from all Saudi regions. We collected demographic data, illness history, and scores of validated self-report scales to assess mental health symptoms, intolerance of uncertainty, and coping strategies. Results In total, respondents indicated moderate to very severe symptoms during the pandemic as follows: 20.9% for depression, 17.5% for anxiety, and 12.6% for stress. Younger age, female gender, and history of mental illness were associated with higher levels of depression, anxiety, stress, and insomnia. Intolerance of uncertainty and certain coping strategies (such as denial or self-blame) were associated with more severe symptoms. Conclusions Mental health is a key concern during the COVID-19 pandemic, especially for the identified vulnerable groups. Agencies concerned with mental health during crises may use the studied associated factors of mental health symptoms to generate targeted policies or interventions.

Nonclassical correlations dynamics of local quantum Fisher information, trace-norm measurement-induced nonlocality, and log-negativity are investigated in a symmetric spin–orbit model. This model is described by a Heisenberg XYZ two-spin system exposed to the magnetic field and Kaplan–Shekhtman–Entin-Wohlman–Aharony (KSEA) interaction under the intrinsic decoherence effects. To evaluate the resourcefulness of this model for the generation and preservation of quantum correlations, we consider two qubits that are initially prepared in two different states, namely uncorrelated and maximally correlated states. The magnetic field is discovered to be effective at generating and preserving nonclassical correlations. Besides, we find that the KSEA interaction can alter the generation, preservation, and revival features of nonclassical correlations in the two-qubit system. However, the bipartite nonclassical correlations become extremely fragile when intrinsic decoherence effects appear.

In this work, we demonstrate that the thermal nonclassical correlations can enhance and become more stable under the magnetic field and second-order spin–orbit interaction effect. Also, we show that the local quantum uncertainty measure can reveal purely quantum correlations beyond other quantifiers of correlations. Our analytical model describes a Heisenberg XYZ two-spin system with an inhomogeneous magnetic field and spin–orbit interaction. A special emphasis is devoted to local quantum uncertainty, concurrence, and Bell-nonlocality measures to investigate the correlations of the bipartite-system at the equilibrium temperature. Our results indicate that temperature, magnetic field, and magnetic field inhomogeneity with DMI and Kaplan–Shekhtman–Entin-Wohlman–Aharony (KSEA) exchanges all play a role in determining the degree of correlation between the quantum spins to some extent. The KSEA interaction greatly enhances the quantum correlation in the system whereas quantum quantifiers are more stable under the influence of the external magnetic field, especially when inhomogeneous and homogeneous magnetic field are near to zero. Furthermore, these findings suggest that the thermal LQU captures a stronger quantum correlation than the Bell-nonlocality and entanglement measures.

The numerical procedure for turbulence fluid flow and heat transfer in a twisted flat tube is presented in this work. For the cross-section of the flat tube, three different geometries are investigated. Water is a working fluid with constant thermophysical properties. The Reynolds number ranges from 5000 to 20000. Results show that by using twisted flat tubes, the efficiency has increased nearly 70% compared to the smooth tubes with the same surface area and hydraulic diameter. Also, the alternating helical direction has caused almost 60%, which seems to be a good choice. Due to the effect of helical pitch that affects the flow path, the alternating geometry was better in some Reynolds and not others. The results are explained using flow characteristics contours such as turbulent kinetic energy, tangential velocity, and temperature. Moreover, the results are presented in numbers and plots for a more accurate comparison.

Asphalt mixture comprising waste glass as an aggregate is referred to as “glasphalt”. Limited studies have been oriented to investigate the Marshall test results of dense-graded glasphalt mixes considering a wide range of variables. This study aims to utilize the artificial neural networks (ANNs) to develop predictive models for Marshall stability and Marshall flow of dense glasphalt mixes based on a large experimental database collected from the literature. Eight independent variables covering the material and mix properties were utilized as inputs in the models. The proposed models resulted in an experimental-to-predicted ratio of 1.00 and 1.00, coefficient of variation of 8.6% and 8.7%, RMSE of 1.63 kN and 0.54 mm, and R-squared of 93.6% and 85.7% for the glasphalt stability and flow models, respectively. Comprehensive parametric analyses have been conducted to further validate the models by investigating the sensitivity of their parameters to the predicted stability and flow values. The analyses revealed some desirable design values that could be considered for a better performance of dense glasphalt mixes. The results indicate that 4% is the desired design air void content of glasphalt mixes. High stability value can be achieved for glasphalt mixes containing a crushed aggregate of 12.5 mm maximum size and 50% glass cullet of 4.75 mm maximum size. Lower viscosity asphalt binder would provide uniformly compacted mixes. Furthermore, glasphalt flow increases as the maximum size of ingredient particles, the penetration grade of asphalt cement, asphalt cement content, and VMA% increase.

It is a natural question to ask whether there is any Lie algebra that completely characterize simple singularities? The higher Nash blow-up derivation Lie algebras Lkl(V) associated to isolated hypersurface singularities defined to be the Lie algebra of derivations of the local Artinian algebra Mnl(V):=Ol/⟨F,Jn⟩, i.e., Lkl(V)=Der(Mnl(V)). In this paper, we construct a new conjecture for the complete characterization of simple hypersurface singularities using the Lie algebras Lkl(V) under certain condition and prove it true for Lkl(V) when k,l=2.

Abstract We discuss the current state of genomic medicine in Arab countries of the Middle East, a region with outsized contribution to Mendelian genetics due to inbreeding yet has poor representation in global variome datasets. We focus on genomic testing, clinical genetics, and genetic counseling services along with associated training and research programs. Finally, we highlight opportunities for improvement in genomic medicine services in this region.

A new inclusion called total inclusion relation has improved the existing dissimilarity measure for q-rung orthopair fuzzy sets (qROFSs). For qROFSs, the modified axiomatic definition of dissimilarity measure is proposed. The modified Hamming and Euclidean dissimilarity measures are defined. An algorithmic procedure for a robust VIKOR method based on modified dissimilarity measures is established. The application of the robust VIKOR method in Mass Vaccination Campaigns (MVCs) in the COVID-19 situation is given.

Abstract We highlight the current lack of representation of the Middle East from large genomic studies and emphasize the expected high impact of cataloging its variation. We discuss the limiting factors and possible solutions to generating and accessing research and clinical sequencing data from this part of the world.

Nationwide databases have implicated an increased incidence of renal cell carcinoma (RCC). The Pennsylvania (PA) Cancer Registry was queried to better define incidence, geographic distribution, and statewide trends of new RCC cases over a 27-year period. JoinPoint Trend Analysis Software modeled average annual percent changes (APCs) in age-adjusted rates (AAR). Maps plotting county-level incidence rates and stage distribution of disease across the state in 5-year time intervals were created using R 4.0.2 software. Overall, 59,628 cases of RCC were recorded in PA from 1990 to 2017. Eighty six percent of patients were >50 years of age, 61% were males, and 89% were Caucasian. Stage distribution using the SEER staging system included 64% local, 17% regional, and 16% distant. Over the study interval, AAR of all RCC cases increased from 9.9 to 18.0 patients per 100,000 population with an APC of 2.3% (p < 0.01). AAR of local disease increased from 5.4 to 12.7 patients per 100,000 population with an APC of 3.2% (p < 0.01). AAR of regional disease also increased from 1.9 to 2.9 patients per 100,000 population with an APC of 1.0% (p = 0.01). Younger patients (

Background Life expectancy has been higher for Hispanic versus non‐Hispanic White (NHW) individuals; however, data are limited on cardiovascular disease (CVD) mortality. Method and Results Using the Centers for Disease Control and Prevention’s Wide‐Ranging Online Data for Epidemiologic Research death certificate database (1999–2018), we compared age‐adjusted mortality rates for total CVD and its subtypes (ischemic heart disease, stroke, heart failure, hypertensive heart disease, other CVD), and average annual percentage changes among Hispanic and NHW adults. The age‐adjusted mortality rate per 100 000 was lower for Hispanic than NHW adults for total CVD (186.4 versus 254.6; P

In this paper, we provide a generalized form of ideals that is k-ideals of semirings with the combination of a bipolar fuzzy set (BFS). The BFS is a generalization of fuzzy set (FS) that deals with uncertain problems in both positive and negative aspects. The main theme of this paper is to present the idea of α,β-bipolar fuzzy k-subsemiring (k-BFSS), α,β-bipolar fuzzy k-ideals (k-BFIs), and α,β-bipolar fuzzy k-bi-ideals (k-BFbIs) in semirings by applying belongingness ∈ and quasi-coincidence q of the bipolar fuzzy (BF) point. After that, upper and lower parts of k-product of BF subsets of semirings are introduced. Lastly, the notions of k-regular and k-intraregular semirings in terms of ∈,∈∨q-k–BFIs and ∈,∈∨q-k–BFbIs are characterized.

In practise, intuitionistic fuzzy numbers (IFNs) are particularly useful for describing ambiguous data. We look at multicriteria decision-making (MCDM) problems with a prioritising relationship between the parameters. The concept of a priority degree is presented. The aggregation operators (AOs) are formed by assigning nonnegative real numbers to stringent priority levels, known as priority degrees. As a result, we construct “intuitionistic fuzzy prioritized averaging operator with priority degrees” and “intuitionistic fuzzy prioritized geometric operator with priority degrees,” which are both prioritized operators. The attributes of the existing method are frequently compared to those of other current approaches, stressing the superiority of the provided work over other methods now in use. In addition, the impact of priority degrees on the overall result is thoroughly investigated. Furthermore, in the intuitionistic fuzzy set (IFS) context, a decision-making strategy is proposed based on these operators. To highlight the efficacy of the proposed approach, an illustrative example relating to the selection of the best choice is considered.

Background Evaluating premature (90th percentile were distributed in the Southern states, and those with mortality

Due to the absence of a neutral function, there are drawbacks to the existing definition of an intuitionistic fuzzy graph (Int-FG). In that definition of Int-FG, membership function and nonmembership function are involved. In this study, lower truncation (Low-T) and upper truncation (Up-T) are applied to picture fuzzy graphs (Pic-FGs). Pic-FG has an additional neutral membership function. Furthermore, Low-T and Up-T of subdivision of the picture fuzzy line graph (Pic-FLnG) are also discussed. The degree of an edge in both Up-T and Low-T of Pic-FG is discussed. Some related theorems related to the degree of Up-T and Low-T of Pic-FG are discussed.

The dual hesitant fuzzy linguistic term set (DHFLTS) is defined by two functions that express the grade of membership and the grade of non-membership using a set of linguistic terms. In the present work, we first quote an example to point out that the existing complement operation of DHFLTS is on the wrong track. Meanwhile, we redefine this operation to fill the holes in the existing ones. Next, the notion of information energy under a dual hesitant fuzzy linguistic background is provided in order to build the criteria weight determination model. To further facilitate the theory of DHFLTS, we propose two vector similarity measures, i.e., Jaccard and Dice similarity measures, and their weighted forms for DHFLTS. In addition, we pioneer some generalized similarity measures of DHFLTSs and indicate that the Dice similarity measures are particular instances of the generalized similarity measures for some parameter values. Afterward, the similarity measures-based model with unknown weight information under the background of dual hesitant fuzzy linguistic environment is constructed. Lastly, an illustrated example is included to validate the method’s application, along with sensitivity analysis and comparative analysis, demonstrating the practicality and validity of its results.

Abstract Background The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) clinical variant interpretation guidelines established criteria for different types of evidence. This includes the strong evidence codes PS3 and BS3 for “well-established” functional assays demonstrating a variant has abnormal or normal gene/protein function, respectively. However, they did not provide detailed guidance on how functional evidence should be evaluated, and differences in the application of the PS3/BS3 codes are a contributor to variant interpretation discordance between laboratories. This recommendation seeks to provide a more structured approach to the assessment of functional assays for variant interpretation and guidance on the use of various levels of strength based on assay validation. Methods The Clinical Genome Resource (ClinGen) Sequence Variant Interpretation (SVI) Working Group used curated functional evidence from ClinGen Variant Curation Expert Panel-developed rule specifications and expert opinions to refine the PS3/BS3 criteria over multiple in-person and virtual meetings. We estimated the odds of pathogenicity for assays using various numbers of variant controls to determine the minimum controls required to reach moderate level evidence. Feedback from the ClinGen Steering Committee and outside experts were incorporated into the recommendations at multiple stages of development. Results The SVI Working Group developed recommendations for evaluators regarding the assessment of the clinical validity of functional data and a four-step provisional framework to determine the appropriate strength of evidence that can be applied in clinical variant interpretation. These steps are as follows: (1) define the disease mechanism, (2) evaluate the applicability of general classes of assays used in the field, (3) evaluate the validity of specific instances of assays, and (4) apply evidence to individual variant interpretation. We found that a minimum of 11 total pathogenic and benign variant controls are required to reach moderate-level evidence in the absence of rigorous statistical analysis. Conclusions The recommendations and approach to functional evidence evaluation described here should help clarify the clinical variant interpretation process for functional assays. Further, we hope that these recommendations will help develop productive partnerships with basic scientists who have developed functional assays that are useful for interrogating the function of a variety of genes.

Background: Inflammatory bowel diseases (IBD) are chronic, relapsing-remitting inflammatory conditions with a substantial negative impact on health-related quality of life and work productivity. Treatment of IBD has been revolutionized by the advent of biologic therapies, initially with anti-TNF agents and more recently with multiple alternatives targets, and yet more under development. Objectives: Approximatively one third of patients do not respond to biologic therapy and more importantly a significant proportion experiences partial response or loss of response during treatment. The latter are common clinical situations and paradoxically are not addressed in the commercial drug labels and available guidelines. There is therefore a clinical need for physicians to understand when and how eventually to optimize the biologic therapy. Design: This consensus using a Delphi methodology was promoted and supported by the Emirates Society of Gastroenterology and Hepatology to close this gap. Data Sources and Methods: Following an extensive systematic review of over 60,000 studies, 81 studies with dose escalation and five addressing drug monitoring were selected and in addition five systematic reviews and three guidelines. Results and Conclusion: after three rounds of voting 18 statements were selected with agreement ranging from of 80% to 100%