The pulsatile flow rate (PFR) in the cerebral artery system and shunt ratios in bifurcated arteries are two patient-specific parameters which may affect the hemodynamic characteristics on the pathobiology of cerebral aneurysms (CAs). Accordingly, a systematic study was employed to investigate the effects of the two parameters on hemodynamic characteristics in two internal carotid artery sidewall aneurysms (i.e., ICASA-1 and ICASA-2) models. Numerical results indicate larger PFRs can cause higher WSS in some local regions of the aneurysmal dome that may increase the probability of small/secondary aneurysms generation than under smaller PFRs. The low WSS and relatively high oscillatory shear index (OSI) could appear under a smaller PFR, which has the potential to cause aneurysmal sac growth and rupture. However, the variances in PFRs and bifurcated shunt ratios have rare impacts on the time-average pressure distributions on the aneurysmal sac, although a higher PFR can contribute more to the pressure increase in ICASA-1 dome due to the relatively stronger impingement by the redirected blood stream than in ICASA-2. Simulation results also present the variances of shunt ratios have rare impacts on the hemodynamic characteristics in sacs, mainly because the bifurcated location is not close enough to the sac in present models. Furthermore, it has been found that the vortex location plays a major role in the temporal and spatial distribution of the WSS on the luminal wall, varying significantly with the cardiac period.

Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles Schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end products (AGEs) accumulation, oxidative stress, and mitochondrial function via inhibition of NF-κB activity, in turn through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2''-O-acetylvitexin (8-C-(2''-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in development or disease improvement in patients of DR.

Background: For the past two decades, the Copenhagen Psychosocial Questionnaire (COPSOQ) has been established as a valid instrument to measure psychosocial stress at work. Nowadays, the COPSOQ international network is responsible for the monitoring and improvement of COPSOQ. 2019, a new questionnaire was published, and the Greek version is now being validated. Methods: Measurement qualities of the Greek COPSOQ III have been explored in adherence to the usual requirements of a validation study as defined by DIN EN ISO 10075-3. A sample of observations from 2.189 participants surveyed with the COPSOQ in Greece was used to validate the current version with appropriate statistical analyses. Exploratory factor analysis was used to assess statistical relations for many scales. Results: With its 108 items and 40 scales, the Greek COPSOQ III includes all psychosocial work factors that have been internationally validated and remain compatible with about 72% of the COPSOQ III German version content. Beyond primary results, congruence with widely used theoretical approaches like the Demand-Control(−Support) model (DCM) or the Job Demands-Resources model (JDR) is generally satisfactory. In summary, our validation study for the Greek COPSOQ III version showed adequate reliability and validity, which is in line with the COPSOQ III questionnaire from other European countries, and it is also compatible with the validation of the German COPSOQ III (Lincke, 2021). Our regression analysis showed that the 34 psychosocial work factors (34 “context” scales) could adequately predict the scores of the satisfactory and health scales (6 “outcome” scales). The analysis also indicated the top five (5) predictors (context variables) for each of the six (6) “effect” scales (outcome variables). Conclusions: With the launch of COPSOQ III in Greece, current and new workplace psychosocial aspects could be explored. COPSOQ III(GR) is a beneficial instrument for enterprise research and risk assessment.

Socio-ecologic, socio-economic, and socio-technical transitions are opportunities that require fundamental changes in the system. These will encounter matters associated with security, service adoption by end-users, infrastructure and availability. The purpose of this study is to examine and overcome the risks to take advantage of opportunities through the novel Risky-Opportunity Analysis Method (ROAM). A novel quantitative method is designed to determine when, after making some changes, the risks become acceptable so that the opportunity does not deviate from the objectives. The approach provided a quantitative evaluation of the possible changes in parallel with digitization, towards providing a green Service Supply Chain (SSC). The result of ROAM shows that the most cost-effective change to increase the resilience of the system is a solution (SMS) which is different from that identified by a TOPSIS multi-criteria method. Real-word decisions in change management should tackle the complexity of systems and uncertainty of events during and after transition through a careful analysis of the alternatives. A case-study was carried out to evaluate the alternatives of an ancillary service in the Payment Service Providers (PSP). The comparison of the ROAM results with the traditional TOPSIS of the case-study unveils the priority of the ROAM in practice when the alternatives are Risky-Opportunities. The existing risk assessment tools do not take advantage of risky opportunities. To this aim, the current article introduces the term Risky-Opportunity, and two indexes Stress and Strain of the alternatives that are designed to be employed in the new quantitative ROAM approach.

The literature on the causation of multiple sclerosis (MS), both genetic and environmental, extends over hundreds of years, with no firm conclusions on the exact role of autoimmunity and lifestyle. The epidemiology of MS was the basis for this review, but with a new, extensive examination of genes pertaining to each disorder, and disease of first, and second, degree relatives of those with MS. The author’s motivation was to discover some relationship between MS, and notable familial conditions, as the heredity of MS is concluded to be 30%, and the disorders had a chronic and/or idiopathic nature. This investigation hoped to further understand the randomness of MS- who acquires it, and what symptoms develop- after the author’s decades of observing several incidences of multiple members developing MS in a single family. Online databases for the human genome were used to link genes to MS, and symptoms, including excessive depression, fatigue and suicide rates, in coordination with linking genes for specific familial conditions including seizures, stroke, mental illness, bowel disorders, and thyroid conditions. Interesting associations were found, notably a cluster of Th2 cytokines, known to cure the animal model of MS, important receptors for neurotransmitters and hormones, a gene specific to Epstein Barr Virus, and potential genes for mitochondrial dysfunction. The results surprised the author, showing polygenic regions of chromosome 2 and 5, especially a cluster at loci 5q31-q33, may be dysregulated. The conclusion agrees with past hypotheses MS results not from a single gene, but from various genes, including those expressed in glial cells. The individual theories to the causation of MS, starting with Charcot may be explained by multiple pathways converging into a single disease outcome. In coordination with a sunlight factor, chromosome 2 appears to mediate the immune system, and inflammation, through ultraviolet radiation producing vitamin D3 in the skin, but additionally through peptides formed in the melanocyte stimulating and concentrating hormone class. The impact of stress in MS could be primary, given the loci of several stress-related and stress-modulated genes on these chromosomes, and calls for more appreciation of, and greater care for, the MS patients’ state of mind.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

The Impact of Event Scale-Revised (IES-R) is the most popular measure of post-traumatic stress disorder (PTSD), which has been recently validated in Arabic. This instrumental study aimed to determine optimal cutoff scores of the IES-R and its subscales in Arab samples of psychiatric patients (N = 168, 70.8% females) and healthy adults (N = 992, 62.7% females) from Saudi Arabia during the COVID-19 pandemic as an ongoing collective traumatic event. Based on a cutoff score of 14 of the Depression Anxiety Stress Scale 8-items (DASS-8), receiver operator curve (ROC) analysis revealed two optimal points of 39.5 and 30.5 for the IES-R in the samples (area under the curve (AUC) = 0.86 & 0.91, p values = 0.001, 95% CI: 0.80-0.92 & 0.87 to 0.94, sensitivity = 0.85 & 0.87, specificity = 0.73 & 0.83, Youden index = 0.58 & 0.70, respectively). Different cutoffs were detected for the six subscales of the IES-R, with numbing and avoidance expressing the lowest predictivity for distress. Meanwhile, hyperarousal followed by the irritability expressed stronger predictive capacity for distress than all subscales in both samples. In path analysis, pandemic-related irritability resulted from direct and indirect effects of key PTSD symptoms (intrusion, hyperarousal, and numbing). Irritability contributed to traumatic symptoms of sleep disturbance in both samples while the opposite was not true. The findings suggest usefulness of the IES-R at a score of 30.5 for detecting adults prone to trauma related distress, with higher scores needed for screening in psychiatric patients. Various PTSD symptoms may induce dysphoric mood, which represents a considerable burden that may induce circadian misalignment and more noxious psychiatric problems/ co-morbidities (sleep disturbance) in both healthy and diseased groups.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk‐reducing salpingo‐oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT alleviated menopausal symptoms in BRCA2 carriers and women who were physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in those with a history of cancer. MBSR, on the other hand, was associated with increased intensity of most menopausal symptoms. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level while their need for extensive measures to optimize their psychological wellbeing is ongoing. Adverse effects of MBSR, which are captured in the present study imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in those women.

From a differential geometric perspective, information geometry (IG) aims to characterise the structure of statistical geodesic models. The research done for this paper offers a novel method for modelling the information geometry of a queuing system. From the perspective of IG, the manifold of the transient M/M/infinity queue is described in this context. The Fisher Information matrix (FIM) as well as the inverse of (FIM), (IFIM) of transient M/M/infinity QM are devised. In addition to that, new results that uncovered the significant impact of stability of QM on the existence of (IFIM) are obtained. Moreover, the Geodesic equations of motion of the coordinates of the underlying transient are obtained. Also, it is revealed that stable QM is developable (i.e., has a zero Gaussian curvature) and has a non-zero Ricci Curvature Tensor (RCT). Novel stability dynamics of transient M/M/iInfinity queue manifold is revealed by discovering the mutual dual impact between the behaviour of (RCT) and the stability(instability) phases of M/M/Infinity QM. Furthermore, a new discovery that presents the significant impact of stability of queue manifold and the continuity of the unique representation between M/G/1 queue manifold and Ricci Curvature Tensor (RCT). The information matrix exponential (IME) is devised. Also, it is shown that stability of the devised (IME) enforces the instability of M/M/ Infinity QM. More interestingly, novel relativistic info-geometric queueing theoretic links are revealed .

Increased screen time during the COVID-19 pandemic and the accelerated incorporation of technology into daily practices have directly contributed to the increased prevalence of eye disease. The human eye is not built for continual technological use and must adjust to exposure to digital screens. Overexposure to technology can result in eye strain and an increased risk of eye diseases such as myopia with complications later in life, including retinal tears, cataracts, and macular degeneration. As vision and ocular diseases become more prevalent, the study of eye diseases, including their causes and treatments, is especially relevant. There is a need to prevent ocular diseases before they become a burden to individuals, their families, and their communities by better understanding the pathophysiology of ocular diseases. Several ocular diseases are thought to be caused by imbalances in reactive oxygen species (ROS) and autophagy. ROS refers to a class of highly reactive oxygen-containing molecules that can undergo damaging reactions with other molecules in the cell. Autophagy is a cellular process of self-eating whereby damaged, harmful, or dead material in cells is broken down to maintain cellular homeostasis. This paper discusses the role of ROS and autophagy in the pathogenesis of computer vision syndrome (CVS), digital eye strain (DES), myopia, cataracts, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve crush injury (OCN), optic nerve gliomas, and retinoblastoma. Lifestyle changes such as limiting screen time, ensuring adequate exposure to evening sunlight, and using blue light protection measures or protective eyewear are important in the prevention of eye disease. Nutrition also contributes significantly to eye health. A balanced diet rich in vitamins and antioxidants may help to prevent ROS and autophagy imbalance-induced eye disease. Medical and surgical treatments become necessary when preventative measures fail. This paper also addresses how government measures to decrease the onset of eye disease, including targeted programs to increase access to fresh vegetables and fruits in food deserts, are a critical macro-level avenue to reduce eye disease prevalence in the US, which according to the National Eye Institute, costs $139 billion yearly.

Despite extensive investigations of the Depression Anxiety Stress Scales-21 (DASS-21) since its development in 1995, its factor structure and other psychometric properties still need to be firmly established, with several calls for revising its item structure. Employing confirmatory factor analysis (CFA), this study examined the factor structure of the DASS-21 and five shortened versions of the DASS-21 among psychiatric patients (N = 168) and the general public (N = 992) during the COVID-19 confinement period in Saudi Arabia. Multigroup CFA, Mann Whitney W test, Spearman’s correlation, and coefficient alpha were used to examine the shortened versions of the DASS-21 (DASS-13, DASS-12, DASS-9 (two versions), and DASS-8) for invariance across age and gender groups, discriminant validity, predictive validity, item coverage, and internal consistency, respectively. Compared with the DASS-21, all three-factor structures of the shortened versions expressed good fit, with the DASS-8 demonstrating the best fit and highest item loadings on the corresponding factors in both samples (χ2(16, 15) = 16.5, 67.0; p = 0.420, 0.000; CFI= 1.000, 0.998; TLI = 0.999, 0.997; RMSEA = 0.013, 0.059, SRMR = 0.0186, 0.0203). It expressed configural, metric, and scalar invariance across age and gender groups. Its internal consistency was comparable to other versions (α = 0.94). Strong positive correlations of the DASS-8 and its subscales with the DASS-21 and its subscales (r = 0.97 to 0.81) suggest adequate item coverage and good predictive validity of this version. The DASS-8 and its subscales distinguished the clinical sample from the general public at the same level of significance expressed by the DASS-21 and other shortened versions, supporting its discriminant validity. Neither the DASS-21 nor the shortened versions distinguished patients diagnosed with depression and anxiety from other conditions. The DASS-8 represents a valid short version of the DASS-21, which may be useful in research and clinical practice for quick identification of individuals with potential psychopathologies. Diagnosing depression/anxiety disorders may be further confirmed in a next step by clinician-facilitated examinations. Brevity of the DASS-21 would save time and effort used for filling the questionnaire and support comprehensive assessments by allowing the inclusion of more measures on test batteries.

Information geometry (IG) seeks to characterize the structure of statistical geodesic models from a differential geometric point of view. By considering families of probability distributions as manifolds with coordinate charts determined by the parameters of each individual model, the tools of differential geometry, such as divergences and metric tensors, provide effective means of studying their characteristics. The research undertaken in this paper presents a novel approach to the modelling study of information geometrics of a queueing system. In this context, the manifold of a stable M/G/1queue is characterised from the viewpoint of IG. The Fisher Information matrix (FIM) as well as the inverse of (FIM), (IFIM) of stable M/G/1 queue manifold are devised. In addition to that, new results that uncovered the significant impact of stability of M/G/1 queue manifold on the existence of (IFIM) are obtained. The Kullback’s divergence (KD), and J-divergence (JD).New result has been devised on the significant impact of both server utilization and squared coefficient of variation of the underlying M/G/1 queue manifold on both (KD) and (KD) are devised. Also, it is revealed that stable M/G/1 QM is developable (i.e., has a zero Gaussian curvature) and has a non-zero Ricci Curvature Tensor (RCT). Novel stability dynamics of M/G/1 queue manifold is revealed by discovering the mutual dual impact between the behaviour of (RCT) and the stability and the instability phases of the underlying M/G/1 queue manifold. Furthermore, a new discovery that presents the significant impact of stability of M/G/1 queue manifold and the continuity of the unique representation between M/G/1 queue manifold and Ricci Curvature Tensor (RCT). The information matrix exponential (IME) is devised. It is also shown that the obtained (IME) is unstable. Also, it is shown that stability of the devised (IME) enforces the instability of M/G/1 queue manifold. Unifying IG with Queueing Theory enables the study of dynamics of queueing system from a novel Riemannian Geometric (RG) point of view, leading to the analysis of the stable M/G/1 queue, based on the Theory of Relativity (TR).Extending the study over two new additional divergence measures, namely and together with a complete illustrative numerical results for all these measures including KD, JD. This links Queueing theory, IG with deep machine learning and metric learning. Furthermore, this reveals the revolutionary approach of queue learning. Full analytic study of Gaussian curvatures subject to both Angular and Monge techniques together with the overall stability dynamics impact on these curvatures. Full analytic study of Einestein Tensor and Stress Energy Tensor together with the overall stability dynamics impact on these curvatures. The inclusion of the definitions of Gaussian and Ricci, Ricci scalar curvatures and Einstein Tensor together with their physical interpretations; The proposed novel approach for the pioneer visualization of queueing systems via computational information geometry. The determination of new important links between classical queueing theory and other mathematical disciplines, such as IG, matrix theory Riemannian geometry and the THEORY OF RELATIVITY by providing for first time i) The full detailed derivations of the Gaussian curvature ii) The Ricci curvature tensor and iii) The full physical as well as the geometric interpretation of these new results. The provision of a novel link between Ricci Curvature (RCT) and the stability analysis of the stable M/G/1 QM. The full investigation of the newly introduced QT-IG unifiers together with the impact of stability/ instability of the underlying M/G/1 QM on them. The full investigation of the newly introduced (QIGU) unifiers together with the impact of stability/ instability of the underlying M/G/1 QM on them.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.