Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

There has been significant increase of studies investigating plasma biomarkers of Alzheimer’s and their relationship to cognitive functioning. The impact of ethnicity on this relationship has not been extensively studied. The current research investigated the relationship between the plasma biomarkers of total tau, Aβ40, Aβ42 and NfL and neuropsychological test performance in a bi-ethnic sample of cognitively unimpaired, older community dwelling adults. The 1326 cognitively unimpaired participants drawn from The Health & Aging Brain Study – Health Disparities (HABS-HD) study included 765 Mexican American participants and 860 non-Hispanic White participants with complete plasma biomarkers and neuropsychological testing. Plasma samples were assayed using Simoa technology. Significant differences in concentrations were found for all of the plasma biomarkers. NHWs had significantly higher levels of each of the biomarkers with a lower Aβ42/ Aβ40. With none of the biomarkers related to performance on any of the neuropsychological tests. For MAs, Aβ40 was the only biomarker that was significantly related to neuropsychological test performance. Aβ40 levels were negatively related to performance on Trails A, Trails B and Digit Symbol Substitution. Results suggest that the relationship of these biomarkers to cognitive functioning is impacted by ethnicity and may be domain specific.

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop of new, disease-modifying drugs to treat AD and PD, thereby decreasing the social and economic burdens linked to these NDs.

Ecuador is an important center of biodiversity of the plant family Amaryllidaceae, specially the subfamily Amaryllidoideae, known as a source of important bioactive molecules. The aim of this study was to assess the chemical and biological potential of four different species of Amaryllidoideae collected in Ecuador: Urceolina formosa, Urceolina ruthiana, Clinanthus incarnatus, and Stenomesson aurantiacum. Sixteen alkaloids were identified in the bulb extract of these species by GC-MS, which the extract of S. aurantiacum exhibiting the greatest structural diversity. The potential of these three genera against Alzheimer’s disease was evaluated by measuring their AChE and BuChE inhibitory activity, revealing that C. incarnatus and U. formosa (from Sucumbíos province) showed the best results with IC50 values of 1.73 ± 0.25 and 30.56 ± 1.56 g·ml-1, respectively. Molecular dynamic assays were conducted to elucidate the possible interactions that occurs among 2-hydroxyanhydrolycorine and AChE enzyme, suggesting some similarity with those observed for galanthamine. This study enhances our understanding of the biodiversity of Amaryllidoideae species from Ecuador, highlighting their potential as a source of chemical compounds with pharmaceutical potential.

Alzheimer's Disease (AD) presents a significant challenge in the wake of its multifaceted nature, characterized by cognitive decline, memory impairment, and neuroinflammation. Despite extensive research, effective pharmacological interventions remain elusive, prompting exploration into non-pharmacological approaches. Microcurrent therapy (MC), utilizing imperceptible currents, has emerged as a potent clinical protocol. While previous studies have focused on its therapeutic effects, this study investigates its impact on neuronal damage and neuroinflammation in an AD mouse model, specifically addressing potential side effects. Utilizing 5xFAD transgenic mice, we examined the effects of MC therapy on neuronal integrity and inflammation. Our findings suggest that MC therapy attenuates memory impairment and reduces neurodegeneration, as evidenced by improved performance in memory tests and preservation of neuronal structure. Additionally, MC therapy significantly decreases amyloid-beta (Aβ) plaque deposition and inhibits apoptosis, indicating its potential to mitigate AD pathology. Our study discovered that MC therapy effectively reduces glial activation by inhibiting the TLR4-MyD88-NFκB pathway, consequently leading to decreased levels of inflammatory factors TNF-α, IL-1β, and IL-6, thus implicating TLR4 in neurodegenerative disease-related neuroinflammation. Furthermore, while our study did not observe significant adverse effects, further clinical trial into potential side effects and neuroinflammatory responses associated with MC therapy is warranted.

In this work we looked for a stable and accurate procedure to perform feature selection in datasets with a much higher number of predictors than individuals, as in Genome-Wide Association Studies. Due to the instability in feature selection when many potential predictors are measured, a variable selection procedure is proposed that combines several replications of shrinkage regression models. A weighted formulation is used to define the final predictors. The procedure is applied to investigate Single Nucleotide Polymorphisms (SNPs) predictors associated to Alzheimer’s disease in the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset. Two data scenarios are investigated: one considering only the set of SNPs and another with the covariates age, sex, educational level and APOE4 genotype. The SNP rs2075650 and the APOE4 genotype are given as risk factors for AD, which is in line with the literature, and other four new SNPs are pointed, opening new hypotheses for in vivo analyses. These experiments demonstrate the potential of the new method for stable feature selection.

Cholinesterase (ChE) and secretase (BACE) inhibitors, and fibril- and β-amyloid-suppressing medicines are used to treat Alzheimer's disease (AD) symptomatically. The prevalence and complex nature of AD have increased the urgent need for multi-targeted directed ligands (MTDLs). This is because MTDLs can prevent potential drug-drug interactions during poly-therapy and have a better therapeutic profile than single targeted agents. Using piperazine linker or spacer and two primary scaffolds, benzofuran and 8-hydroxyquinoline, a unique class of multi-targeted medicines was recently reported by our group. These compounds showed re-markable effectiveness in inhibiting Aβ1-42 aggregation and acting as iron chelators.The results prompted us to synthesize an additional series of compounds as multimodal anti-AD agents and investigate its inhibitor activities to ChE (AChE/BChE) and BACE1 enzymes. The resulting in-hibitory effects suggested that the compounds under study might be used to improve cognitive function. The docking analysis' findings revealed that the compounds bind to AChE and BChE by forming H-bond interactions with amino acid residues at binding sites and µ-stacking inter-actions with aromatic residues, whereas the binding to BACE1 only revealed H-bond interac-tions with amino acid residues at binding sites.

The editorial explores the realm of emerging translational research in neurology and psychiatry, providing insights into various subjects, including neurodegenerative disorders and innovative therapeutic methods. The main objective is to study neurological and psychiatric disorders, such as Alzheimer's disease, with a particular emphasis on techniques for neural regeneration and repair. The editorial highlights the importance of taking a comprehensive approach to studying and treating complex neurological and psychiatric conditions. This involves thoroughly reviewing research papers on the causes, development, biomarkers, and treatment options for these conditions. The editorial emphasizes the necessity of using multidisciplinary and integrative methods to gain a deeper understanding and improve the treatment of these conditions. The development of an animal model for recurrent primary dysmenorrhea showcases the innovative techniques employed in the investigation of gynecological disorders, illustrating the capacity of translational research to connect fundamental scientific knowledge with practical medical applications. The cooperative endeavors of researchers and clinicians emphasized in this editorial lay the foundation for revolutionary advancements that hold the potential to enhance outcomes for individuals afflicted with neurological and psychiatric disorders globally.

(1) Background: Alzheimer’s disease (AD) presents a significant challenge in terms of discovering novel diagnostic methods and therapies. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate the mechanism of action of Apelin-13 in an in vivo model of AD induced by streptozocin (STZ); (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. The Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests. The main methods included behavioral assessment, histological analysis, and biochemical assays to evaluate synaptic plasticity and oxidative stress signaling pathways; (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated through the enhancement of synaptic plasticity and attenuation of oxidative stress signaling pathways; (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions.

This study aimed to investigate the relationship between sleep duration, dementia severity, age, and ANS regulation. This cross-sectional pilot study included 27 older patients with probable Alzheimer’s disease, hospitalized at a psychiatric center. We measured heart rate variability to assess ANS regulation at night, evaluated dementia severity using the Clinical Dementia Rating scale, and obtained sleep duration data from sleep diaries maintained by psychiatric nurses. The data were analyzed using repeated-measures generalized linear models with age, sex, dementia severity, and medication (antipsychotics) as covariates. A sleep duration of 7–8 h per night was associated with better ANS regulation than other sleep durations, as indicated by sympathovagal balance (p = 0.005). ANS dysregulation was characterized by a 20.7% increase in sympathetic nervous system activity and a 14.8% decrease in parasympathetic nervous system (PSNS) activity. We found a significant correlation between dementia severity and PSNS activity (p = 0.04) and observed an inverted U-shaped association between sleep duration and ANS regulation. This pilot study demonstrated that a sleep duration of 7–8 h per night may be critical in maintaining optimal ANS regulation. Bidirectional associations between sleep duration, inadequate sleep duration, aging, and ANS regulation warrant further investigation.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

Background: Critical states present scale-free dynamics, optimizing neuronal complexity. We explored electroencephalogram (EEG) criticality in amnesic Mild Cognitive Impairment (aMCI) patients with clinical improvement in working memory, verbal memory, verbal fluency and overall executive functions after the completion of a 6-month prospective memory training. (2) Methods: We compared “before” and “after” stationary resting-state EEG records of right-handed MCI patients (n = 17; 11 females), using the method of critical fluctuations and Haar wavelet analysis. (3) Results: Significant criticality enhancement was present in frontotemporal electrodes [mean dif: 0.10; Z = 7, p = .019] and isolated electrodes T6 [mean dif: 0.204; t (10) = - 2.3, p = .044] and F4 [mean dif: 0.0194; t (10) = - 2.82; p = .018]. (4) Conclusions: EEG criticality agreed with clinical improvement, consisting a possible monitoring biomarker in MCI and Alzheimer’s disease. Further evaluation is needed in patients under cognitive training or even drug-modifying therapies.

The introduction of anti-amyloid monoclonal antibodies against Alzheimer’s disease (AD) is of high importance. However, even though treated patients show very little amyloid pathology, there is only a modest effect on the rate of cognitive decline. Although this effect possibly can increase over time, there is still a need for alternative treatments that will improve the cognitive function in patients with AD. Therefore, the purpose of this study was to characterize the triazinetrione ACD856, a novel pan-Trk positive allosteric modulator, in multiple models to address its neuroprotective and potential disease modifying effects. The pharmacological effect of ACD856 was tested in recombinant cell lines, primary cortical neurons or animals. We demonstrate that ACD856 enhanced NGF-induced neurite outgrowth, increased the levels of the pre-synaptic protein SNAP25 in PC12 cells and increased the degree of phosphorylated TrkB in SH-SY5Y cells. In primary cortical neurons, ACD856 led to increased levels of phospho-ERK1/2, showed neuroprotective effect against amyloid-beta or energy-deprivation induced neurotoxicity, and increased the levels of brain derived neurotrophic factor (BDNF). Consequently, administration of ACD856 resulted in a significant increase of BDNF in the brains of 21-months old mice. Furthermore, repeated administration of ACD856 resulted in a sustained anti-depressant effect which lasted up to seven days, suggesting effects that go beyond merely symptomatic effects. In conclusion, the results confirm ACD856 as a cognitive enhancer, but more importantly, they provide substantial in vitro and in vivo evidence of neuroprotective and long-term effects that contribute to neurotrophic support and increased neuroplasticity. Presumably, the described effects of ACD856 may improve cognition, increase resilience, and promote neurorestorative processes, thereby leading to a healthier brain in patients with AD.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

The multifactorial nature of some diseases, and in particular neurodegenerative diseases such as Alzheimer’s disease, frequently requires the use of several drugs. These drug cocktails are not without drawbacks in terms of increased adverse effects, drug-drug interactions or adherence to treatment. The concept of pleiotropic drugs, which combine, within a single molecule, several activities directed against distinct therapeutic targets, makes it possible to overcome some of these problems. In addition, these pleiotropic drugs, generally, lead to the expression of a synergy of effects, sometimes greater than that observed with a combination of drugs. This article will review, through recent examples, the different kinds of pleiotropic drugs being studied or already present on the market of medicines.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

Inhibition of acetylcholinesterase (AChE) enzyme is a known procedure to treat severe Alzheimer's disease through increasing the acetylcholine level in the brain and thus slowing down the progression of Alzheimer's symptoms. The approved medications are only considered as palliative and addressed some reported deficiencies. Therefore, the demand for safe and effective compounds is substantially increasing. A newly series of coumaryl 1,3-selenazoles derivatives was synthesized in four steps. Then, their antioxidant activities were evaluated using DPPH, ABTS cation radical scavenging assay and cupric reducing antioxidant capacities (CUPRAC). The anticholinesterase activities were evaluated using the Ellman method. Then, the docking studies were carried out to explain the possible correlation between in vitro anticholinesterase activity results and the ligand-receptor interactions. Ten new coumaryl 1,3-selenazoles (5a-5d series and 6a-6f series) derivatives were successfully synthesized. The DPPH radical scavenging assay showed that all tested compounds have IC50 value > 200 μM, for ABTS cation radical scavenging assay the IC50 value > 1000 μM and for CUPRAC assay the IC50 value > 200 μM. Compound 5c was found to be the most active compound against AChE and BChE in its series with IC50 value for AChE is 99.76 μM and IC50 for BChE is 140.28 μM while 6b exhibited the most potent inhibition in its series with IC50 value for AChE is 56.01 μM and IC50 for BChE is 121.34 μM. Besides, the docking studies showed that compound 5c and 6b formed π-π stacking interaction with aromatic residues at the active site of AChE and BChE, which is responsible for inhibiting the enzymes. This shows that the synthesized compounds contain skeletal structures that can interact and inhibit within the enzymes active site.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

Our previous research provides evidence that vergence eye movements may significantly influence cognitive processing and could serve as a reliable measure of cognitive issues. The rise of consumer-grade eye tracking technology, which uses sophisticated imaging techniques in the visible light spectrum to determine gaze position, is noteworthy. In our study, we explored the feasibility of using webcam-based eye tracking to monitor the vergence eye movements of patients with Mild Cognitive Impairment (MCI) during a visual oddball paradigm. We simultaneously recorded eye positions using a remote infrared-based pupil eye tracker. Both tracking methods demonstrated more pronounced cognitive vergence responses for targets as opposed to distractors. In summary, the use of a consumer-grade webcam to record cognitive vergence shows potential. This method could potentially lay the groundwork for future research aimed at creating an affordable screening tool for mental health care.

In this work the seismic resilience of the Emergency Department of a real Hospital complex, located in Tuscany (Italy), has been quantified, with special reference to its nonstructural components and organizational features. Special attention has been paid to the ceilings, whose importance stood out in past earthquakes. A comprehensive meta-model has been set, able to relate all the considered parameters to the assumed response quantity, i.e. the waiting time of the red-code patients arriving to the Emergency Department in the hours immediately after the seismic event. The seismic resilience of the Emergency Department has been measured with reference to earthquakes compatible to the seismic hazard of the area.

We present a modified version of the Szilard Engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer’s original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that to approach a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer’s principle that is completely independent from the Second Law of Thermodynamics.

One of the most common forms of dementia is Alzheimer’s disease (AD), which leads to progressive mental deterioration. Unfortunately, there is no definitive diagnosis and cure that can stop the condition progressing. The diagnosis is often performed based on the clinical history and neuropsychological data, including magnetic resonance imaging (MRI). Deep neural networks (DNN) algorithms are gaining popularity for medical diagnosis, and have been used widely for the analysis of MRI data. DNNs can extract hidden features from thousands of training images automatically. However, they cannot judge how confident they are about their predictions. To use DNNs in safety-critical applications such as medical diagnosis, uncertainty quantification of DNNs predictions is crucial. For this purpose, Monte Carlo dropout (MCD) has been widely used, however, it may lead to overconfident and miss calibrated results. This paper proposes a framework in which the MCD algorithm’s hyper-parameters are optimized during training using Bayesian optimization for the first time. The conducted optimization leads to assigning high predictive entropy to erroneous predictions and making it possible to recognize risky predictions. The proposed framework is used for AD diagnosis, which has not been done before. We compare our method with some existing methods in the literature based on different uncertainty quantification criteria. The results of comprehensive experiments on the Kaggle dataset using a deep model pre-trained on the ImageNet dataset show that the proposed algorithm can quantify uncertainty much better than the existing methods.

This study aimed at investigating the quality statuses of graduates’ sustainable core competences development and the causes behind the identified competence statuses by applying the core competencies’ model. The study employed case study design with thematic analysis involving seven interviewees. This study used tracer study findings and national exit exam results as exhibits. The study revealed “very good” and “excellent” quality statuses for the graduates’ core competence development of College of medicine and Health Sciences (CMHS). Similarly, this study identified “Good +” statuses for the quality of graduates’ core competence development in College of Agriculture and Environmental Sciences ( CAES) and College of Science (CS). Furthermore, the study identified "good" - and +” statuses for the quality of graduates’ competence development at the Faculty of Social Sciences (FSS) and Faculty of Humanities (FH). Improved instruction with a balance of theory and practice, task-oriented deans’ leadership behavior with fairness and shared vision- mission identity, handling internal conflicts, and external ethnic-based war influences were the major reasons for the identified higher competence quality statuses in CMHS, CAES, and CS, whereas the opposite direction decline of these factors were the causes for the low statuses of FSS and FH. Sustainable graduates’ core competence development leads to sustainable employability, labor force, and individual to nation-wide holistic sustainable development

The conformity assessment of products or a measured value with the given standards is carried out based on the global risk of producers and consumers calculation. A product may conform to specifications but be falsely rejected as non-conforming. This is about the producer's risk. If a product doesn't meet the requirements but is falsely accepted as conforming, that poses a risk to the consumer. The conventional approach to risk assessment, which yields only a single numerical value for the global risk of producers and consumers, is naturally extended, and utilized for assessing risk in measurement models with linear regression. The outcomes of the two-dimensional extension, along a moderate scale, are the parabolas with an opening upwards. Risk surfaces were obtained through three-dimensional extension over the area limited by the moderate scale and guard band axes. Four models with different ranges of tolerance intervals were used to test this innovative method of risk assessment in linear regression. The corresponding standard measurement uncertainties are determined by applying a simplified measurement model with the use of comprehensive data on the measurement performance and by determining measurement uncertainty derived from consideration of the functional relationship obtained by linear regression analysis. Models that utilize information from linear regression analysis to determine measurement uncertainty are biased towards risks at the edges of the moderate scale. Testing the model's performances with metrics related to the confusion matrix, such as the F1 score, further substantiated this assertion. The diagnostic odds ratio has been proven to be extremely effective in identifying the curve along the guard band axis, along which the global risks of producers and consumers are at their lowest.

Escalation of commitment explains the choice for investing in an option for which great investments have previously been made even though better choices became available. The last 25 years of producing innumerous versions of Alzheimer Disease animal models with virtually no predictive validity should have exposed the fact that using animals for studying AD is clearly a failing course of action and as such should have been abandoned long ago, giving room to other alternatives to flourish. In this assay, I explore the idea that the investment in new animal models for studying Alzheimer (AD) represents a classic case of escalation of commitment, and sunk cost dilemma, in the biomedical research.

Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/ or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here we review current knowledge of tauopathies listing known genetic and important sporadic forms of this disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tool and usage of epigenetic therapy strategies for these diseases.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. Alzheimer's disturbs the life of at least five million persons in the USA. CD4+ T cells could both exacerbate and reduce AD symptoms. Regulating CD4+ T cells homing to the leaky blood-brain barrier (BBB) constitutes a new hope for enhancing AD prognosis. Alzheimer's drugs such as Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) and memantine are known to play an important part in regulating the neurotransmitters mechanisms. However, little is known about the effect of these drugs on CD4+ T cells homing. In this review, we focus on current and new drugs that could modulate CD4+ T cells interactions with the BBB in AD.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date Alzheimer's and Parkinson's disease are the most common NDs. The risk of developing NDs increases dra-matically with age, and genetic and environmental factors can be crucial in their progression. The main feature of NDs is the abnormal presence of specific proteins that can lead to neuronal death, proteotoxic stress, and alteration of catabolic systems, which are major players in the processes of neurodegeneration and neuroinflammation. Despite research efforts to date, the therapies cur-rently in use for the treatment of NDs provide marginal therapeutic benefit, so the focus is now being direct toward the search of natural products that could be a valuable aid in combating these diseases, including the natural compound Andrographis paniculata (Ap) and especially its main constituent Andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap is capable to modulate neuroinflammatory and neurodegenerative responses, determining a reduction in inflammatory markers and oxidative stress in various NDs. Therefore, in this review we will focus on the molecular mechanisms through which Ap and Andro are able to modulate the processes of neurodegeneration and neuroinflammation that are major causes of neuronal death and cognitive decline.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

Background and objective: Symptoms of most neurodegenerative diseases, including Parkinson’s disease (PD), usually do not occur until substantial neuronal loss occurs. This makes the process of early diagnosis very challenging. Hence, this research used variant call format (VCF) analysis to detect variants and novel genes that could be used as prognostic indicators in the early diagnosis of prodromal PD. Materials and Methods: Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI), and we analyzed prodromal patients with gVCF data collected in the 2021 cohort. A total of 304 participants were included, including 100 healthy controls, 146 prodromal genetic individuals, 21 prodromal hyposmia individuals, and 37 prodromal RBDs. A pipeline was developed to process the samples from gVCF to reach variant annotation and pathway and disease association analysis. Results: Novel variant percentages were detected in the analyzed prodromal subgroups. The prodromal subgroup analysis revealed novel variations of 1.0%, 1.2%, 0.6%, 0.3%, 0.5%, and 0.4% for the genetic male, genetic female, hyposmia male, hyposmia female, RBD male, and RBD female, respectively. Interestingly, 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) that were recently detected in PD patients were detected in the prodromal stage of PD. Conclusion: Genetic biomarkers are crucial for the early detection of Parkinson’s disease and its prodromal stage. The novel PD genes detected in prodromal patients could aid in the use of gene biomarkers for early diagnosis of the prodromal stage without relying only on phenotypic traits.

The article proposes asymptotic methods for calculating Sommerfeld integrals, which enable us to calculate the integral using the expansion of a function into an infinite power series at the saddle point, where the role of a rapidly oscillating function under the integral can be fulfilled either by an exponential or by its product by the Hankel function. The proposed types of Sommerfeld integrals are generalized on the basis of integral representations of the Hertz radiator fields in the form of the inverse Hankel transform with the subsequent replacement of the Bessel function by the Hankel function. It is shown that the numerical values of the saddle point are complex. During integration, auxiliary or so-called standard integrals, which contain the main features of the integrand function, were used. As a demonstration of the accuracy of the technique, a previously known asymptotic formula for the Hankel functions was obtained in the form of an infinite series. The proposed method for calculating Sommerfeld integrals can be useful in solving the half-space Sommerfeld problem. An example is the expression in the form of an infinite series for the magnetic field of reflected waves, obtained directly through the Sommerfeld integral (SI).

Additive manufacturing (AM) techniques are widely investigated for the cost-effective use of titanium (Ti) alloys in various aerospace applications. One of the AM techniques developed for such applications is plasma transferred arc solid free-form fabrication (PTA-SFFF). Materials manufactured through AM techniques often exhibit anisotropies in mechanical properties due to the layer-by-layer material build. In this regard, the present study investigates the isothermal directional fatigue of Ti-TiB metal matrix composite (MMC) manufactured by PTA-SFFF. This investigation includes rotating beam fatigue test, electron microscopy, and fatigue calculations. The fatigue experiments were performed at 350 ºC using specimen with the test axis oriented diagonally (45º) and parallel (90º) to the AM builds directions. The fatigue values from the current experiments along with literature data find that Ti MMC manufactured via PTA-SFFF exhibit fatigue anisotropy reporting highest strength in 90º and lowest in perpendicular (0º) AM build directions. Further, the electron microscopy investigations on 0º, 45º, and 90º AM build specimens reveal frequent TiB clusters in all three AM build directions and suggest that the spread of these TiB clusters play a role in fatigue anisotropy. Moreover, the fatigue calculations were performed using both the Paris’ and recently reported modified Paris’ equations. Comparison of R^2 values for these calculations show that modified Paris’ equation predicts the fatigue life of AM Ti-TiB MMC more accurately than the Paris’ equation.

In this paper, I introduce a new concept of representing numbers in base ; in other words, I have found new series for any number similar to series that could be written according to the collatz sequence which is called zi(n) in this article. These series need to end with 1. Then, we use two sets of rules to make a diagram which then proves the existence of such series for any number.In this diagram, by branching numbers into different branches in accordance to the modularity of 4 and continuing branching to the point that their numbers have enough common terms in their collatz series, we could reduce zi(n) to zi(k) so that k<n in any branch by Rule Number One. This diagram shows that zi(n) exists for every number, in other words, this proves the theorem (A) or zi-existence theorem. The proof of zi-existence theorem leads to a proof of the collatz conjecture because the collatz series could be written as a linear combination of such series that all of them end with 1, so the collatz series for any number ends with 1.

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Hamman’s syndrome is a rare condition that mostly affects young males, often with a predisposition of asthma. It includes the presence of free air in the mediastinum and subcutaneous emfysema with no other underlying cause such as trauma or infection. It occurs spontanously and often in association with prolonged valsalva manouvre. This might explain why there are some cases of Hamman syndrome among young females giving birth. Here we present a case report of a 24-year- old primigravida with Hamman’s syndrome. She presented with symptoms a few hours after an uncomplicated vaginal delivery at 40+1 pregnancy week. The symptoms resolved spontanously after a few days of observation. We also give a systemic review of reported cases since 2000 to provide overview on pathomechanism, symptoms, diagnostics, treatment and management of this condition. Hamman’s syndrome is a rare, usually benign, but potentially serious complication that can occur during the second stage of labour. Diagnostics include inquiring about typical symptoms, clinical examination and chest x-ray or CT scan. Treatment is usually conservative with oxygen, bronchodilators and pain relief. The reccurence rate is low and there is no contraindication to vaginal delivery in future pregnancies. However, it is suggested that physicians and midwives be cautious and consider low threshold for instrumental delivery or caesarean section to avoid excessive valsalva manoeuvre.

Malocclusions have a continuously increasing prevalence from a generation to another as a result of climate changes, soil, atmosphere and water pollution. All of these aspects have unfavorable consequences on the nutritional scheme. Thus, nutrition together with other etiopathogenic factors contribute to complex alterations in the somatic development of the entire organism and, implicitly, of the cephalic extremity. The study group included 4147 children from randomly selected schools from Vâlcea County, Romania. The aim of this study is to determine the prevalence of malocclusions in schoolchildren from Vâlcea County, Romania, according to the three main classes of malocclusions (according to Angle’s classification), age groups (from 6 to 10 years old and from 11 to 14 years old), gender (male and female) and place of origin (rural and urban). For Angle class I malocclusions we recorded the highest prevalence (48,78% from the total number of schoolchildren with malocclusions), followed by Angle class II malocclusions (45,85% from the total number of schoolchildren with malocclusions) and for Angle class III malocclusions we found the lowest prevalence (5,37% from the total number of schoolchildren with malocclusions).According to gender, we found the highest prevalence in female gender (29,90% from the total number of female subjects), while in male gender we recorded a prevalence of 27,70% from the total number of male subjects. Regarding the place of origin, there is a higher prevalence of malocclusions in the urban areas (29,16%). The study subgroup included 140 children randomly selected from the total number of subjects from the study group. They were included in a more advanced study. The aim is to find potential associations between the presence of malocclusions and various oral variables. Categorical variables were expressed as numerical values and percentages, and their association was evaluated with either the Chi-square test of association or homogeneity, or the Fisher Exact test. The acquired data were incorporated into a binomial logistic regression model to assess the likelihood of developing malocclusions in relation to the following variables: defective phonation, bruxism, frequency of teeth brushing, onychophagia, oral respiration, infantile deglutition, placing objects between the maxillaries, thumb sucking and salivary aspects. It is also aimed to compare the results obtained with similar ones from the specialized literature.

Driver’s distractions are more prone to occur with automated driving vehicles, which might turn into cancelling some of their advantages. Traffic reports, naturalistic observations and in-lab tests are carried out to determine the influence of driver’s distractions in car crashes and to develop technology to detect and prevent them from happening. One of the best strategies to cope with this problem is education. In this work we propose a simulation environment to design laboratory experiments to study driver’s distractions as well as simple games to train drivers to take over the control of the vehicle when required. The result framework enables drivers to experience driving highly automated cars in their neighborhoods or in places of their choice with different levels of events to check their ability in taking over the control when required.

Background:Caregiving for individuals with neurological disease involves providing physical, emotional, and social support, which can be a challenging and stressful experience. This study aims to compare the caregivers' burden, including the impact on mental and physical health, social support, and quality of life, in different neurodegenerative disorders. Methods:Fifty-five primary caregivers (F=41;mean age=53.07±12.29) of patients with Parkinson's Disease (PD=26), Multiple System Atrophy (MSA=16), and Amyotrophic Lateral Sclerosis (ALS=13), took part in the study. Standardized screening scales for the quality of life (EQ-5D/EQ-VAS and PQoL), levels of the caregiving burden (CBI and FSQ), and the assessment of the anxiety-depressive axis (HADS) were administered. Results: The mean CBI score was higher for caregivers of MSA patients (28.81±21.90) and ALS (25.15±16.23) than for caregivers of PD patients (16.08±10.34; p=0.036). Critical burden (cut-off>36) was present in the caregivers of MSA (31.3%), ALS (23.1%), and PD (19.2%) patients. Caregivers of patients with ALS had a worse perception of quality of life (EQ-5D total score) than caregivers of patients with MSA and PD (p

In this paper, we propose an extension of the Planck distribution function derived from the Boltzmann principle. That is, we consider extending Planck's law with new distribution functions. In addition, using ideas applied to the expansion of the Planck distribution function, Von Koch's inequality is derived without using the Riemann hypothesis, showing that the abc conjecture is negated. We also describe some challenges for the future. Namely, we will discuss that Entropy is related to dynamical systems described by logistic function models, such as the bacterial and the population growth.

This study explores the intricate relationship between the angle of vehicle-to-vehicle (V2V) conflicts and the severity of conflicts at signalized intersections during traffic signal failures, leveraging the advanced capabilities of LiDAR sensor technology. The research delves into the impact of conflict angles on collision outcomes and introduces LiDAR as a novel and precise tool for capturing spatial dynamics during unregulated traffic movements. Findings reveal that as the angle of V2V conflicts increases, indicating a wider approach between vehicles, the severity of conflicts tends to decrease. This reduction in severity is attributed to the detailed spatial data provided by LiDAR, enabling the identification of glancing impacts rather than direct head-on collisions. The mitigation of forces involved in collisions at increased angles contributes to a decreased likelihood of severe consequences, such as extensive vehicle damage and serious injuries to occupants.Conversely, as the angle of V2V conflicts decreases, signifying a narrower approach between vehicles, the potential for severe collisions tends to increase. LiDAR technology facilitates precise measurements of spatial coordinates and temporal dynamics, revealing that collisions occurring at smaller angles involve more direct and concentrated impact forces. This heightened risk of extensive damage to vehicles and increased injury severity is crucially captured by LiDAR, providing valuable insights into the relationship between conflict angles and collision outcomes during traffic signal failures. This study underscores the efficacy of LiDAR sensor technology in understanding the nuanced dynamics of V2V conflicts and highlights its role in developing targeted safety interventions. The integration of LiDAR data into traffic safety analyses offers a sophisticated approach to mitigating the impact of conflicts and enhancing overall safety at signalized intersections during signal failures. The research also highlighted that as the angle of V2P conflicts widens, PET experiences a proportional increase. A larger conflict angle signifies a more complex interaction between vehicles and pedestrians, leading to prolonged PET values. Conversely, a decrease in the angle of V2P conflicts is associated with a reduction in PET during traffic signal failures.The study commences with an examination of traffic characteristics at the E Cold Spring Ln – Hillen Rd intersection in Baltimore City, MD, utilizing a deployed LiDAR sensor. When the signal at this intersection experienced a temporary malfunction on a regular working day in September 2023, the LiDAR captured data related to vehicle and pedestrian volumes, as well as V2V and V2P conflicts. The primary objective of the research is to evaluate the repercussions of traffic signal failures on both traffic flow and safety, specifically V2V and V2P conflicts, occurring during periods of improper signal functionality. Additionally, this investigation delves into various factors that impact traffic signal performance, encompassing traffic demand, geometric layout, pedestrian interactions, and the incorporation of emerging technologies.

Background: Alzheimer's disease causes great changes, with the prefrontal cortex be-ing frequently damaged zones, affecting physical and cognitive behavioural and compromising autonomy and quality of life. Objective: To evaluate the effectiveness of feedback-based tech-nology on the improvement of physical-cognitive capacities in Alzheimer. Methods: Forty pa-tients with Alzheimer were recruited from the Santa Elena Alzheimer's Association, Seville, of which 15 ended up being pilot participants, divided randomly into controls (8) and experi-mental (7). They were evaluated with: Cognitive Mini-Examination Scale, Oddball Test and At-tention Network, Berg Scale, Tinetti, Timed up and Go and Geriatric Deterioration Scale. The experimental group was treated with feedback-based technology under the supervision of physiotherapists, during 16 thirty-minute sessions, twice a week. The control group performed their usual care. Result: A significant improvement was observed in the experimental group (Cognitive Mini-Examination and Tinetti). In the group of control, a worsening of physical and motor skills was evidenced because of the degenerative disease. Discussion/Conclusion: This treatment could be a strategy to keep the patient in early stages for longer, and improve quali-ty of life delaying dependency. It creates intergenerational bonds and use at home to promote treatment adherence.

Probabilistic and parsimony-based arguments regarding available genetics data are used to propose that Hardy and Higgin’s amyloid cascade hypothesis is valid but is commonly interpreted too narrowly to support, incorrectly, the primacy of the amyloid beta peptide (Aβ) in driving Alzheimer’s disease pathogenesis. Instead, increased activity of the βCTF (C99) fragment of APP is likely the critical pathogenic determinant altered by mutations in the APP gene. This model is consistent with the regulation of APP mRNA translation via its 5’ iron responsive element (IRE). Similar arguments support that the pathological effects of familial Alzheimer’s disease mutations in the genes PSEN1 and PSEN2 are not exerted directly via changes in APP cleavage to produce different ratios of Aβ length. Rather, these mutations likely affect the stability of presenilin holoprotein and/or γ-secretase multimers with consequences for γ-secretase activity and other important cellular functions. All fAD mutations in APP, PSEN1, and PSEN2 likely find unity of pathological mechanism in their actions on endolysosomal acidification and mitochondrial function, with detrimental effects on iron homeostasis and promotion of “pseudo-hypoxia” being of central importance. Aβ production is enhanced and distorted by oxidative stress and accumulates due to decreased lysosomal function. It may act as a disease-associated molecular pattern (DAMP) enhancing oxidative stress-driven neuroinflammation during the cognitive phase of the disease. We also discuss fascinating, but largely ignored, data on presenilin biology that may be important in understanding presenilins’ central role in familial Alzheimer’s disease.

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system, and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer among others. Recent data provide compelling evidence that distinct reactive astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the endoscopic and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. Our study included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies performed in these 8 years were matched and compared. We found a statistically significant decrease in stool changes, weight loss, and abdominal pain as presenting symptoms, and in the fecal calprotectin levels. On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. Non-caseating granulomas were found on 9% of oesophageal, 18% of gas-tric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum and descending colon between the first and second biopsies. Our study showed that more than a third of patients had specific endoscopic (36.59%) and histopathologic (32%) findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular endoscopic and histopathological assessments of pediatric CD patients.

ABSTRACTIntroduction and Purpose: Nurses are expected to be competent in practice based on the domain of standards and interpersonal soft skills (ISS). Nurses are faced with inadequate physical assessment 28%, formulating diagnoses 56%, plans 34%, implementation 31%, evaluation 37,5%, and communication skills 41%. Aims to develop an ISS learning model based on transformative learning theory and digitalization (TLTD) to improve nurses’ competencies. Method: Used Explanatory cross-sectional involved 190 practitioner nurses. Variables of individual characters (X1), facilities (X2), Social environment support/SES (X3), TLTD (X4), ISS (X5), and nursing competencies (Y) were measured. Data was collected using a checklist questionnaire, conducted on 6 June to 10 August 2022 at Dili, Baucau, and Maliana hospitals. Used descriptive and inferential analysis with SEM-PLS. Result: Five of the 11 hypotheses of statistical p-value < 0,05 and T-Test > 1,96, including X2>X4, X3>X5, X4>X5, and X5>y, to form ISS learning model. The characteristic of respondents were 81,8% young adults, 67,9% women, 57,8% undergraduates, judging the previous training 35% was unsuccessful, and 45,8% did not meet expectations. Learning facilities that are still lacking include policies 23,7%, curriculum 23,4%, guideline 22,7%, modules 27,9%, infrastructure 20,3%, social environment support 24,2% low, organizational support, 30,0% low peer support and 26,3% low family support. The average TLTD is 25,3% to 34,2%, ISS 22,1% to 30,5%, and nurse competence 25,3% to 30,5%.Suggestion: Result of the study become base to improve nurse’s competencies. Conclusion: Learning model was formed by facilities, SES, TLTD, ISS, and nurses’ competencies.

Background: Takayasu’s arteritis is a rare type of vasculitis, with severe complications like stroke, ischemic heart disease, pulmonary hypertension, secondary hypertension, aneurysms. Diagnosis is conducted by clinical and angiographic criteria. Treatment is medical and surgical, but unfortunately, the outcome is reserved. Case presentation: A 34- year- old Caucasian women had an ischemic stroke (2009). She was diagnosed with Takayasu’s arteritis and she received treatment with methotrexate, prednisolone, antiplatelet agents, with a mild improvement of clinical state. After 5 years (2014) she associated ascending aorta aneurysm, pulmonary hypertension, mild aortic regurgitation. The surgical treatment solved both ascending aorta aneurysm and left carotid artery stenosis (ultrasound in 2009 and computed tomography angiogram in 2014). Morphopathology revealed typical appearance for Takayasu’s arteritis. Tumor necrosis factor inhibitors (TNF-inhibitors) were associated to methotrexate. At 48 years (2023) she developed coronary heart disease (angina, electrocardiogram); echocardiography revealed severe pulmonary hypertension; angiography described normal coronary arteries, abdominal aorta pseudoaneurysm and arterial-venous fistula, with origin in right coronary artery and drainage on medium pulmonary artery. The patient refused surgical/ interventional treatment; she received again TNF- inhibitors, methotrexate, antiplatelet agents, statins. Conclusions: This case report presents us a severe form of Takayasu’s arteritis. We consider that morphopathology had a great importance in revealing to clinicians the typical appearance and the stadialization of inflammatory arterial process: acute or chronic. The verdict of morphopathologist was chronic phase, with acute relapses, so we decided that immunosuppressive treatment was still necessary.

his quantitative study investigates teachers' perceptions of self-efficacy during the COVID-19 pandemic and explores the correlation between these perceptions and the preservice training they received. The research addresses the cognitive connection between teachers' current self-efficacy, particularly their satisfaction with and appreciation of preservice lecturers. Utilizing a retrospective lens, the study reveals a significant correlation between teachers' evaluation of their preservice training, especially their appreciation of lecturers, and their present self-efficacy. The findings highlight that teachers, amidst the challenges of the pandemic, evaluated their self-efficacy at a remarkably high level. This underscores their resilience during a period of unprecedented uncertainty, demanding substantial personal and professional adaptability. The nuanced interplay observed suggests that teachers' sense of self-efficacy serves as a predictive variable of their mental and professional resilience when confronting uncertainty and navigating rapid and profound changes, as exemplified by the exigencies of the COVID-19 pandemic.

Keywords: Parkinson’s disease; sleep disorders; GBA; Parkin

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative illness, responsible for 60-70% of all dementias, affecting over 50 million people worldwide, and nearly 11 million in European countries. Several putative factors are identified in the literature as causative agents or risk factors for the development of AD. The amyloid cascade hypothesis has been the main hypothesis about the pathophysiology of AD for decades. Recent studies raised the possible role of dysbiosis in the development of AD which prevents memory loss. The amyloid-β (Aβ) deposition might be considered as an inflammatory reaction to certain molecular products arising from the altered microbiome. Based on the above observations, it has been suspected, that antibiotic consumption patterns of different antibiotic classes might be associated with the prevalence of AD in European countries. Methods: Antibiotic consumption (ECDC) for 1997-2007, 2008-2018, and as the whole 1997-2018 period, have been compared to the AD prevalence for 2018 expressed in percentage of the population and statistically analyzed by Pearson calculation. Results: A significant positive correlation has been found between the AD prevalence (2018) and the average quinolone consumption for the year 1997-2007 (p: 0.044). A similar association was not observed for the entire 22 years (1997-2018) of the average quinolone consumption, and the years 2008-18, indicating 10-20 years of time-lapse between the antibiotic exposure and the development of AD. The ratio of broad-spectrum and narrow-spectrum antibiotics (B/N) estimated in the ECDC database for the years of 2008-2018 showed a strong positive association with AD prevalence (2018) (p: 0.026) and a positive correlation tendency for the entire 22 years 1997-2018 (p: 0.063), but none for the years 1997-2007 (p: 0.241). Broad-spectrum, beta-lactamase sensitive penicillin (J01CA) consumption showed a positive (non-significant) correlation with the prevalence of AD for the years 2008-2018 (p:0.080).Discussion: Our study indicated the possible sequential role of certain classes of antibiotics in the development of dysbiosis leading to amyloid deposits of AD, which strengthen the possible role of different mediator molecules (short-chain fatty acids, lipopolysaccharides, etc.) produced by the altered microbiome in the development of AD.

Liquorpheresis (CSF filtration) comprises a therapeutical approach that has been proposed to treat several neurological conditions where antibodies, inflammatory mediators or abnormal peptides are the cause or play an important role in the pathogenesis of the disease. CSF replacement may be an alternative approach not explored so far. Here, we review previous experiences in the use of liquorpheresis in autoimmune and degenerative neurological diseases. Then we describe previous developments and provide some new technical innovations in order to design bidirectional CSF shunting systems. These systems can be complemented either with a deposit of artificial CSF or with a CSF filter, allowing CSF replacement or liquorpheresis respectively. Both options would lead to mechanical dilution of the patient’s CSF.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging lymphoma and gut microbiome investigation field.

Systemic lupus erythematosus (SLE) is a prevalent autoimmune condition, yet its alignment with a specific host immunological pathway remains unclear. The THαβ host immunological pathway, recognized for its defense against viruses and prions, has recently emerged as a response to DNA, RNA, and protein pathogens. SLE patients often produce anti-double strand DNA antibodies and anti-nuclear antibodies, suggesting a potential association with the THαβ host immune reaction. Throughout the course of SLE, elevated levels of type 1 interferons, type 3 interferons, interleukin-10, IgG1, and IgA1 are commonly observed. These cytokines and antibody isotypes are indicative of the THαβ host immunological pathway. Similarly, Myasthenia gravis, Grave’s disease, Graft versus host disease, autoimmune hemolytic anemia, immune thrombocytopenia, dermatomyositis, and Sjogren’s syndrome are also linked to THαβ-related type 2 hypersensitivities. Considering the potential association of these diseases with dysregulated THαβ immune responses, therapeutic strategies such as anti-interleukin-10 or anti-interferons α/β could be explored to manage these disorders effectively.

Introduction: While preparing for dive exams, divers are trained to perform rescue exercises. Currently, divers think they will manage and control their body at any time.Methods: At the bottom of the water, the student takes the instructor who simulates a sickness, up to the surface, by controlling the going up. Then, if the exercise is wrong, both divers go down and exercise again. If the exercise is successful, both divers go down to perform another exercise until they are tired or until they have no more air. Results: I discovered that there was a mistake in the preparation of divers for rescue training due to Descartes’ error, “I think, thus I am”, which is part of our collective memory. Going up and going down after a sickness simulation is a repetitive action of the body and going down is therefore part of the automatisms of rescue, which is very dangerous. Conclusions: The body is not necessarily controlled by the present thinking, and if divers forget sickness while going up in a real rescue situation, they will go down automatically because their bodies were trained like this. In addition, it is very easy to forget sickness. Divers should not go down after rescue, they should be on the dive boat or on the land. Descartes’ error has to be reversed: “I am, thus I think” is right. The divers’ rescue exercises must be simplified and divers should never go down after the simulation of a sickness.

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are well defined phenotypes of chronic inflammatory bowel diseases (IBD). A mechanism of inflammation in these diseases is partially controlled by intestinal dendritic cell (DC). In this study we observed a mature CD83+DC in colonic bioptic samples, and its correlation with disease phenotype and activity. Methods: There were 219 subjects included in the study: 100 with UC, 44 with CD and 75 healthy subjects. Colonic biopsy specimens were incubated with primary antibody Anti-CD83. Intraepithelial CD83+DC were counted per 100 enterocytes. Presence of CD83+DC was analysed according type of IBD, histopathologic inflammation activity and treatment outcome. Results: The presence of mature CD83+DCs (0, ≥1) significantly differed among disease types of IBD (p=0.001), histologic inflammation activity (p=0.049) and applied therapy (p=0.001). The odds for CD83+DC presence was 5.2 times higher in CD group than in control/UC group. The odds for CD83+DC presence was 2.6 times higher in subjects without inflammation or chronic inflammation than in acute inflammation. It was also 3.7 times higher in subjects without therapy. The cut-off value 0.5 CD83+DC (Rock analysis area=0.699; SE 0,046;p<0.001;95%CI:0.609-0.788) had been assessed as a differentiation marker between UC and CD. Conclusion: Presence of CD83+DC could be used as a possible parameter in distinction between UC and CD, as well as predictor of inflammation activity and treatment outcome.

Cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) are endemic threats to cassava production. To fill the existing gaps in the understanding of the epidemiology of these diseases in Côte d’Ivoire, nationwide field surveys were conducted in 2016, 2017 and 2020. The leaf samples collected were analysed by PCR. CBSD was not detected in all fields visited. However, an increase of CMD incidence was observed from 45.95% in 2016 to 51.37% in 2020 while CMD severity remained moderate over the years with a mean value of 2.29. Low whiteflies number was observed in field and decreasing over the years. Molecular analysis allowed detection of East African cassava mosaic Cameroon virus (EACMCMV) in single as well as in mixed infection with African cassava mosaic virus (ACMV). Single EACMCMV infection, which was detected only in three agroecological zones of the eastern Côte d’Ivoire in 2016, spread throughout the country in 2017 and became more widespread in 2020 with a preponderance in the central and southern zones, whereas the ACMV+EACMCMV coinfection has spread to the entire zones studied. Knowing the dynamics of the evolution of these viruses across the country, better disease management strategies could be adopted to control the disease.

Coupling the Maxwell tensor to the Riemann-Christoffel curvature tensor is shown to lead to a geometricized theory of electrodynamics. While this geometricized theory leads directly to the classical Maxwell equations, it also extends their physical interpretation by giving charge density, mass density and the four-velocity that describes their motions geometric definitions. Assuming the existence of a conserved energy-momentum tensor, all solutions to the geometricized theory of electrodynamics developed here are shown to be consistent with the emergence of gravity obeying the General Relativity field equation augmented by a term that mimics the properties of dark matter and/or dark energy. Finally, due to the symmetries of the theory, the properties and phenomenology of antimatter emerge in solutions.

This paper identifies preschool teachers' sources of stress, the times they experience high stress, and their ways of coping with stress levels. The study was conducted using a phenomenological design, one of the qualitative research models. The data were collected through semi-structured interviews with 36 preschool teachers working with children aged 0-6 in state and private schools. As a result of the content analysis, stressors were identified primarily at both interpersonal (positive, and effective interactions), and organizational levels (school management, and leadership style). It was also found that intense stress was experienced when children were difficult to control, such as during sleeping, eating, and cleaning. Finally, these results confirmed that the teachers used active/active behavioral, and passive/avoidant coping strategies. However, it was understood that preschool teachers perceived stress negatively, and did not see stress as a personal development situation. These results are discussed in terms of their ramifications for preschool education.

Defining integrals over volume element in curved spacetime together with the mass and energy densities within that region of spacetime is apparently equivalent to the given energy and mass of that body or particle. With this in mind equations involving energies and mass can be rewritten in terms of their densities and the integral over the volume element. The idea find its place in the Hamiltonian formulations, and can be carried over into quantum mechanical frameworks systematically accounting for the effect of spacetime volume structures and gravity on dynamics of quantum systems. This article briefly explores this concept and runs through various frameworks and equations relevant to this idea, particularly the schrodinger-Newton equation and discusses the cosmological constant as a vacuum energy density.

This study examines the impact of executives implicated in fraud on firms' investment decisions using AAERs in the US, aiming to address the underexplored aspect of rationalization within the fraud triangle. Executives implicated in fraud often display abnormal attitudes to justify accounting irregularities, prompting an investigation into how abnormal investment decisions are used for rationalizing fraud, given their critical role in a firm's long-term sustainability. Analysis of AAERs spanning from 1981 to 2013 reveals that implicated executives, particularly CEOs and CFOs, tend to make abnormal investment decisions, and that collusive fraud exacerbates this behavior. Notably, such executives lean towards overinvestment, particularly in R&amp;D expenditures, to hide or justify fraud; the duration of fraud amplifies its impact on investment decisions. By shedding light on the rationalization aspect of the fraud triangle, this research contributes valuable insights for investors, regulators, and academia emphasizing the significance of public disclosure of fraud to enhance transparency in capital markets and the importance of ethics-focused education in accounting to prevent corporate fraud.

Entropy as a mathematical concept is the first of its own kind, and second to none. Barely one or two papers in literature have investigated fractal dimensions of very basic entropies, such as Shannon, Tsallis, and Rényi entropic expressions. This was a thoughtful inspiration to delve into a step forward towards a unified information- theoretic fractal theory. The storytelling of this current paper starts by introducing my third entropy formula, namely Ismail’s entropy, , as a novel generalization to Shannonian entropy with a visionary link to both long- and short-range interactions, (LRIs), (SRIs) respectively. Clearly, this would generate a fourfold unification with statistical mechanics as well as contemporary physics. Hence, this adds more credibility and weight for this study. The fractal dimension of , is identified in this paper. As an essential part of this work, it was influential to spotlight the importance of fractal geometry to space industry as well as education, which is crucial to develop our societies. Thus, some potential fractal applications to CubeSat Technologies and Education are highlighted. So, will the deep search for more ground-breaking research has come to an end. Certainly, not. This was another inspiration to propose new open problems to widen research gates to the scientific community for more research pathways. Consequently, the paper ends with closing remarks combined with some challenging open problems and the next phase of research.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

Hippocrate, the father of medicine, already said:"Wine is a thing wonderfully appropriate to man if, in health as in disease, it is administered with appropriate and just measure according to the individual constitution." wine has always accompanied humanity, for religion or for health. Christians and Jews need wine for the liturgy. For Platon the wine was an indispensable element in society and took all its importance in the symposium. In this second part of the banquet, mixed with water, the wine gave the word. If the french paradox made a lot of ink flow; it was the wine that was originally responsible for it. Many researchers have tried to share the alcohol and polyphenols in order to solve the mystery. Beyond its cardiovascular effects, there are also effects on longevity, metabolism, cancer prevention and neuroprotection, and the list goes on. The purpose of this work is to make an analysis of current knowledge on the subject. Indeed, if the paradigm of the antioxidants is seductive, it is perhaps by their prooxidant effect that the polyphenols could act, by an epigenetic process mediated by nrf2. Wine is a preserve of antioxidants for the winter and it is by this property that the wine acts, in alcoholic solution. A wine without alcohol is pure heresy. By the way, we were not talking about elixir to design all this millennial pharmacopee that made the man was able to heal and prosper on the planet. From Alvise Cornaro to Serge Renaud, nutrition was the key to health and longevity, whether Cretan or Okinawa diet, it is the small dose of alcohol (wine or sake) that allows the bioavailability of polyphenols. Moderate drinking give a protection for diseases and a longevity potential. In conclusion, let’s drink fewer, but drink better to live older.

Parkinson’s disease (PD) is the second most common degenerative disease which may cause blood pressure abnormalities due to autonomic dysfunction. Early morning rise of blood pressure which is called morning surge is found to be related with some cardiovascular diseases when it is exaggerated. We wanted to search the relation of Morning blood pressure surge (MBPS) and inflammation in PD. Method: Ambulatory blood pressure monitoring for 24 hours, fibrinogen to albumin ratio, hs-CRP are used in this retrospective study. Fifty idiopathic PD patients and 50 age and sex matched control cases were included. MBPS, it has been defined as the difference between morning BP (measured 2 hours after awakening) and the lowest night-time BP. Body mass index (BMI) is used as an independent variable. Results: Median value of MBPS for PD group (21,63) was significantly different from the control group values (18,63) (p

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. 2cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning Electron Microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails.

Côte d’Ivoire has substantially neglected crop residues from farms in rural areas. This study aims to provide strategies for the sustainable conversion of crop residues to hydrogen. Using existing data and theoretical approaches, up to 16,801,306 tons of crop residues of 11 crop types were available in Côte d’Ivoire in 2019. A theoretical hydrogen potential of 1,296,424.84 tons was estimated from the crop residues. Technically, 907,497.39 tons of hydrogen is expected annually. Three scenarios of hydrogen project implementation developed indicated that the Ivorian industries can be supplied with 9,026,635 gigajoules of heat. Moreover, 17,910 cars and 4,732 buses can be supported in the transport sector. It is estimated that 817,293.95 tons of green ammonia for farmers can be supplied. Five million, seven hundred twenty-seven thousand, nine hundred ninety-two (5,727,992) households are expected to have access to 1,718.40 gigawatts of electricity. Due to these changes in transport, energy, industry, and agricultural sectors, a reduction of 1,644,722.08 tons of carbon dioxide per year can be achieved theoretically. With the scenarios, some 263,276.87 tons of hydrogen are exportable to other countries. Conversion of crop residues to hydrogen is a promising opportunity with environmental and socio-economic impact. Therefore, this study requires further extensive research.

Cow’s Milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, 'lactase deficient' individuals cannot digest milk's carbohydrate lactose depriving themselves of highly beneficial milk proteins like casein, lactoalbumin and lactoglobulin, due to lactose intolerance (LI), while other individuals develop cow milk allergy specifically against these proteins (CMPA). The management of these conditions is distinctly different and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restriction or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of the nutrients over the genome, proteome and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and so increasing life expectancy. Here, we report the scientific community opinion proposing to replace the approach “one size fits all” with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety, often resulting from the individual perception of this condition as different from a normal state.

Intrusion detection is generally carried out by matching network traffic patterns with known attack patterns or by identifying abnormal network traffic patterns. One statistical methodological approach used in intrusion detection is Statistical Process Control (SPC) by constructing a control chart. Hotelling’s T2 control chart is a multivariate control chart commonly used to monitor the mean process. The performance of the T2 chart in monitoring mean shifts can be increased if a robust estimator is utilized. Based on previous research, T2 based on the Fast-MCD estimator has good performance in monitoring low to medium outlier contaminated data. Therefore, the MRCD estimator can be used to detect intrusion. On the other hand, this research focuses on developing a bootstrap-based robust Hotelling’s T2 charts with Fast-MCD and MRCD estimators for evaluating performance in detecting intrusion on intrusion detection datasets. Based application of UNSW-NB15, the proposed chart has better performance than the conventional T2 and Fast-MCD-based T2 despite the longer execution time.

The work is devoted to the development of methods for constructing asymptotic formulas as x→∞ of a fundamental system of solutions of linear differential equations generated by a symmetric two-term differential expression of odd order. The coefficients of the differential expression belong to classes of functions that allow oscillation (for example, those that do not satisfy the classical Titchmarsh-Levitan regularity conditions). As a model equation, the 5th order equation i2p(x)y′′′′′+p(x)y′′′′′+q(x)y=λy, for which various cases of behavior of the coefficients p(x),q(x), is investigated. New asymptotic formulas are obtained for the case when the function h(x)=−1+p−1/2(x)∉L1[1,∞) significantly influences the asymptotics of solutions to the equation. The case when the equation contains a nontrivial bifurcation parameter is studied.

Culture signifies the customs, language, ceremonies, Indigenous Medical Knowledge (IMK) and other material objects of a tribe. These and many other features are a representation of identity for many Zambian communities. IMK practices are skills inherent by certain individuals in a tribal grouping who are chosen by the spirits (gods) or trained by those who practice. This intrinsic skill is in danger of diminishing as a result of modern medication. This article attempts to understand the role of traditional healers (also known as asing’anga in local language) in preservation of IMK in Chibombo District of Zambia. In so doing, the paper examined methods of preservation used by asing’anga and the challenges faced. Using hermeneutic phenomenology and linear snowball sampling, findings revealed that preservation was done through training. The study found unwillingness, expiration, and spirituality as challenges in the process of preserving IMK. The study recommended that the Lenje Cultural Association consider documenting and disseminating information to the local people by showcasing what is available in the Mukuni Culture Village Museum and Library. This was seen as a way through which many youths would be encouraged to appreciate the indigenous values in their culture.

Physical activity is especially important of children's everyday life with chronic disease. The aim of the study was to show whether asthma is a barrier to physical activity in our society. The correlation between the severity of the disease, body mass index, and physical activity were analyzed, and, parents' opinion whether children should participate in active sports was assessed. Physical activity of children with asthma was analyzed by questionnaires and activity-measuring armbands. 93 parents and their children were involved in the survey, while 20 children were wearing the armband. The age of children was 12.6±3.5 years (mean±SD), 69.9% were boys, 30.1% were girls. 93.4% of the respondents participated in physical education program and 56.5% also attended sporting activities on a regular basis. 61.2% of the children had mild, 37.6% moderate, and 1.2% severe asthma. 6.5% of the respondents stated that their illness had been consistently or frequently limiting the performance concerning their school or home duties over the past 4 weeks. Twelve percent of parents felt that physical activity was not appropriate in the context of this disease. We conclude, that fear of the consequences of physical activity depends largely on education which should involve their parents, teachers and coaches.

Hippocampal neuronal activity generates dendritic and somatic Ca2+ signals, which depending on stimulus intensity, rapidly propagate to the nucleus and induce the expression of transcription factors and genes with crucial roles in cognitive functions. Soluble Amyloid-beta Oligomers (AβOs), the main synaptotoxins engaged in the pathogenesis of Alzheimer's disease, generate aberrant Ca2+ signals in primary hippocampal neurons, increase their oxidative tone and disrupt structural plasticity. Here, we explored the effects of sub-lethal AβOs concentrations on activity-generated nuclear Ca2+ signals and on the Ca2+-dependent expression of neuroprotective genes. To induce neuronal activity, neuron-enriched primary hippocampal cultures were treated with the GABAA receptor blocker gabazine (GBZ), and nuclear Ca2+ signals were measured in AβOs-treated or control neurons transfected with a genetically encoded nuclear Ca2+ sensor. Incubation (6 h) with AβOs significantly reduced the nuclear Ca2+ signals and the enhanced phosphorylation of cyclic AMP response element binding protein (CREB) induced by GBZ. Likewise, incubation (6 h) with AβOs significantly reduced the GBZ-induced increases in the mRNA levels of Neuronal Per Arnt Sim domain protein 4 (Npas4), Brain-derived Neurotrophic Factor (Bdnf), Ryanodine Receptor type-2 (RyR2), and the antioxidant enzyme NADPH-Quinone-Oxidoreductase (Nqo1). Based on these findings we propose that AβOs, by inhibiting the generation of activity induced nuclear Ca2+ signals, disrupt key neuroprotective gene expression pathways required for hippocampal-dependent learning and memory processes.

A difficult open problem that has never been fully resolved in the literature to date is the behaviour of the (TDCDP) third approximation. As a giant step towards modern control theory, this cutting-edge paper will advance control theory and other relevant inter-disciplinary subjects. Because control theory is important in industry and engineering, this study will be especially beneficial to anyone working in these disciplines who wish to understand more about recent advances in control theory settings. In contrast, the wealth of applications of Fokker Planck Kolmogorov (FPK) equations numerous disciplines As a result, the study instantly gains more taste and credibility. At the end of the paper, there are several challenging open problems, some concluding remarks, and recommendations for further investigation.

Our starting point is the covariant coordinate transformation equation of a relativistic positioning system in Minkowski space-time, which maps the receiver’s emission coordinates (proper times broadcast by the emitters) to its coordinates in some inertial reference frame. Bancroft’s analytical (closed-form) solution to the basic pseudorange navigation equations with four emitters is recovered and the subjacent elements are geometrically interpreted. The case of four static beacons is analized as a clarifying situation.

Educational institutions must identify students who are academically struggling to provide them with necessary support to improve their performance. In this context, recommendation systems powered by deep learning techniques are vital for detecting and categorizing such students. These systems help students plan their future by uncovering patterns in their historical academic data. This study introduces a new deep learning model designed to classify academically underperforming students in educational settings. The model incorporates a Gated Recurrent Neural Network (GRU) and includes specific neural network features like a dense layer, max-pooling layer, and the ADAM optimization algorithm. The model's training and evaluation were conducted using a dataset comprising 15,165 student assessment records from various academic institutions. The performance of the developed GRU model was benchmarked against other educational recommendation systems, including Recurrent Neural Network models, AdaBoost, and the Artificial Immune Recognition System v2. The proposed GRU model demonstrated remarkable accuracy, achieving an overall rate of 99.70%.

Since late December 2021, the Hunga Tonga-Hunga Ha'apai underwater volcano has been erupting in a series of large explosions. On Friday, January 15th, 2022, a particularly significant explosion sent a massive ash cloud high into the atmosphere. This study depicts the modeling of the volcanic ash dispersion from the event while incorporating meteorological data assimilation within the inline Weather Research and Forecasting model coupled with chemistry (WRF-Chem). Two forecast scenarios: one with only meteorology and no chemistry (OMET) and one with gas, aerosol chemistry, and no assimilation (NODA) were undertaken and compared to the third forecast impacting data assimilation to distinguish the Flux Adjusting Surface Data Assimilation System (FASDAS)'s effects. Data assimilation, a process that combines real-time observations with numerical models, plays a pivotal role in enhancing the accuracy of various scientific simulations and predictions.Analysis of different scenarios reveals that the FASDAS result in lessening of planetary boundary layer height (PBLH), downward surface shortwave flux, and 2m temperature by up to 800m, 250 W.m-2 and 6°C on the land portion, respectively, while the opposite is observed nearby the eruption site. Model validation against the observations shows that the inclusion of FASDAS nudging in WRF-Chem significantly enhances the model performance in retrieving meteorological variables. The simulations also revealed significant biases in the concentration of volcanic ash around the ash cloud. Additionally, data analysis from the Copernicus TROPOspheric Monitoring Instrument Sentinel-5 Precursor (TROPOMI-S5P) indicates that total SO2 emissions traveled west. This work demonstrates the significant contribution of data assimilation on the results of operational air quality predictions during violent volcanic eruption events.

Smoker’s paradox usually refers to the common observation of a favourable outcome of smoker patients in acute myocardial infarction. The interpretation of this phenomenon is still controversial and not fully explained. We aimed at assessing whether smoking could be associated with mortality in a large cohort of prospectively enrolled patients with ST segment elevation myocardial infarction (STEMI) referred to primary percutaneous coronary intervention (pPCI). From April 2006 to December 2018 a population of 2456 STEMI patients treated with primary PCI were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data and 1-year follow-up were collected. Among 2546 patients admitted with STEMI 1007 (41%) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5% vs 6%, p&lt;0.0001 and 5% vs 11%, p&lt;0.0001), shorter ischemic time (203 [147-299] vs 220 [154-334] minutes, p=0.002) and shorter decision time (60 [30-135] vs 70 [36-170] minutes, p=0.0063). After propensity-matching, age, cardiogenic shock and low TIMI score were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced death rate at 1-year follow-up (HR 0.54, 95% CI [0.37 - 0.78]; p&lt;0.001). Our data show a protective link between smoking status and mortality in patients with STEMI, the so called “smoker’s paradox”. This could be explained not only by the shorter ischemic time and younger age of the smoking population but also by a specific pathogenetic effect of smoking underlying the onset of STEMI and response to therapies.

Any malocclusion can be associated with various face development patterns, including hyper, neutral and hypodivergent growth patterns. We measured face height ratios, angle formed by Y axis to SN and growth patterns in various malocclusions in a group of patients from Timis county. The pretreatment digital cephalograms of 350 participants were split into three groups based on Angle's classification of dentoalveolar malocclusion. Every cephalogram was digitally traced and analyzed using a composite cephalometric method analysis utilizing the WebCeph imaging cephalometric program, which included two linear and one angular. In general, patients from Timis county have a hypodivergent development pattern. Hypodivergent development pattern predominated in group I, II, and III. Group I hyperdivergent 5.14%, normodivergent 16.01%, hypodivergent 78.85%. Group II hyperdivergent 2.78%, normodivergent 14.44%, hypodivergent 82.78%. Group III hyperdivergent 10.53%, normodivergent 10.53%, hypodivergent 78.94%. In all three groups, the value of the angle formed by Y axis to SN is within normal limits group I 65.4 ±4.34°, group II 63.87± 3.86° and group III 64.66 ±5.28°. A strong negative correlation was found between angle: Y axis to SN and facial height ratio (r= -0,766; p &lt;0.001). In all kinds of malocclusion, patients from Timis county show primarily a hypodivergent development pattern.

Background: Parkinson's disease (PD) is a global disease. However, there is a lack of research specifically focused on the AfrAbia population. Climate change, driven mainly by global warming, is linked to detrimental health impacts, including an increased frequency and intensity of heat waves. Neurological diseases, including neurodegenerative syndromes like Alzheimer's disease, Parkinson's disease, and motor neuron illnesses, have been increasingly seen and recorded in scientific literature. Although there is much literature demonstrating the growth in neurodegenerative disorders, the relationship between environmental variables such as global warming, air pollution, heavy metals, and pesticides and the higher occurrence of these illnesses is still unknown. Objective: The current article primarily aims to examine the relationship between climatic changes, air pollution, pesticides, heavy metals, and the occurrence of PD. Initially, we evaluate the influence of exposure to these variables on the cause or origin of Parkinson's disease. In addition, we will investigate how these variables disrupt processes such as excitotoxicity, oxidative stress, and neuroinflammation, all of which are strongly linked to Parkinson's disease (PD). Conclusions: This research presents a plausible rationale for the adverse effects of environmental influences on the brain, which are pivotal in the progression or onset of Parkinson's disease from an AfrAbian standpoint.

The early detection of cognitive decline and timely non-pharmacological management or drug therapy are extremely important in providing care for Parkinson’s disease with dementia (PDD). In this study, we first conducted a discovery study to identify six plasma microRNAs that may allow for the differentiation of PD with or without mild cognitive impairment via NGS. A total of 120 participants were further recruited in a validation cohort and divided into four subgroups, namely, normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI) and PDD. Among the six candidates, miR-203a-3p was successfully detected in the plasma of the validation cohort using droplet digital PCR (ddPCR). Our results show that the ratio of miR-203a-3p/miR-16-5p observed in PDD was significantly increased compared to in PD-MCI (p < 0.001) and PDND (p = 0.041). Moreover, the ratio of miR-203a-3p/miR-16-5p showed a significant correlation with MoCA scores (r = -0.237, p = 0.024) in patients with PD (PwP). The ROC curve of the logistic regression model, consisting of the variables of age, the ratio of miR-203a-3p/miR-16-5p and the UPDRS III score, also demonstrated an average AUC of 0.883 via 5-fold cross-validation. In conclusion, the ratio of miR-203a-3p/miR-16-5p may serve as a potential biomarker for distinguishing cognitive dysfunction from PwP.

: Crohn’s disease (CD) is a multifactorial chronic disorder that involves a combination of factors as genetic, immune response and gut microbiota. Actually, the therapy comprises salicylates, immunosuppressive agents, corticosteroids, biologic drugs. International guidelines don’t recommend the use of antibiotics except for septic complications of CD patients. The increased evidence of the implication of gut bacteria in this chronic disease support the rationale for using antibiotics as primary treatment of active CD. In the last decades several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E.coli) species and Mycobacterium avium paratubercolosis (MAP), aroused the interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment in CD patients but randomized trials of antibiotic treatments against E.coli and MAP did not show prolonged benefits, and only generated conflicting results so much so that several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course and the outcome measures. In this article we attempted to provide an overview and update of the trials on antibiotic treatment in active CD patients taking into account the role of pathogens, the mechanism by which the different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also tried to draw new lines for future studies to use antibiotics to treat active CD patients

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

Pharmacists must acquire the necessary knowledge to provide better drug therapy to patients. In other words, educational programs need to facilitate behavioral changes among pharmacists. Therefore, this study aimed to evaluate how the behavior of pharmacists changed after attending a palliative care educational program. We conducted a web-based questionnaire survey examining the behavior of pharmacists regarding palliative care before participating in the program, two months after participating in the program, and eight months after participating in the program, to determine the behavior and changes over time. For all questions, scores were higher at two and eight months after attending the program than before attending the program (P &lt;0.05). In addition, no significant difference was observed between two and eight months after attending the program for all questions (P =0.504-1.000). The knowledge gained from the educational program was used to repeatedly intervene with patients with cancer, to address the various symptoms they experienced and maintain their behavior. The proven effectiveness of this program serves as a stepping stone for a nationwide rollout across Japan’s 47 prefectures.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

We are losing love. By studying porn movies to understand love, I discovered that love originally comes from the body, from positive emotions and vibrations of the wonderful body, from the heart and all other parts of the body, such as sexual organs. António Damásio made Descartes’ error by postulating that feelings increase their power from homeostasis (mechanisms of life regu-lation from bacteria to humans). He made this mistake unconsciously because many people un-consciously have a very bad opinion of sexual organs. We consider them ugly because they come from the prehistoric period. I have combined António and Hanna Damásio’s work (body emotions, thinking and language). I discovered that porn actors do not talk during sex, and this is striking. Porn actors mirror what happens in society. This means that people come from prehistory, do not talk during sex, and still unconsciously behave like primitive animals during sexual intercourse; we do not respect the body sufficiently during sex. Therefore, love, which comes from the body, is smothered and buried. We must very delicately talk to the wonderful, delicious and respectful body to wake up love feelings, body emotions and vibrations during sex. We must invent talking movies with porn films. Language of positive emotions associated with the language of wonderful and delicious body will warm love feelings and will give envy to love through sexual intercourse because António Damásio discovered that emotions are social.

Polymer electrolyte was used as a medium for testing the performance of microband electrodes under conditions of linear diffusion. Cyclic voltammetry and chronoamperometry experiments were performed in such viscous medium, where diffusion rates are much slower than in fluid solutions. Confirmation of the existence of such conditions from the log i vs. log v or log i vs. log t relationships in the current equation always yielded values lower than the expected value of 0.5. This could indicate impure linear diffusion profile, i. e. some contribution from radial diffusion (edge effect). However, performing these tests in monomeric solvents of similar viscosities, such as glycerol or propylene glycol, gave the desired value of 0.5. These results lead to the conclusion that current equations which are based on Fick’s laws may not be applicable for polymer electrolytes, where various obstruction to diffusion make it a more complicated process than in monomeric solvents.

Chronic Fatigue Syndrome (CFS) can be triggered by different factors and create a complex health situation. In the last decades incidence has been increasing. This situation is a clear example of how humans, viruses, and the environment are all connected. In the 90s cases related to CFS, com-plaints about a feeling of chronic fatigue, inability for everyday tasks, dull pain, cephalalgia, de-pression, anxiety, poor concentration. Clinical tests for EBV, HHV, CMV, IgG, IgM, T4 and T8 subsets were tested, along with hormones and hemogram tests. Most of the cases were women. The timeline of the medical history showed also myomas, breast lumps, premenstrual syndrome previously to CFS development. The nature of these conditions promoted the idea of a possible common link among them and CFS. Some cases also suffered from allergies, food intolerances, candidiasis, intestinal impairment, thyroid implications, endometriosis. As an initial working hypothesis, The Liver Link (TLL) was proposed in order to understand those different conditions affecting body, mind and emotional wellbeing. Considering liver implication can make a differ-ence in treatment and recovery. Low grade inflammatory conditions are related to Th2 predom-inance and liver functions. Functional disharmonies are very important because they usually still do not appear in any conventional tests. In 2002, TLL was presented as a framework to explain the concomitance of CFS and other conditions and the relationship with some viruses such as EBV, HHV, CMV, as a lecture in a congress at the University of Westminster (London). When SARS-CoV-2 outbroke, TLL helped to warn about the post-covid syndrome more likely to occur in specific individuals.

Caused by age or trauma, collapsed connective tissue can cause nerve entrapment and damage within the tarsal tunnel. Tarsal tunnel syndrome is relatively underdiagnosed. This study presents an intervention targeting damaged tissues surrounding the nerves and replacing the structural cushioning with a Wharton’s jelly tissue allograft. The eight selected patients from four clinical sites had tarsal tunnel-related defects. Patient outcomes were tracked on a 90-day calendar utilizing the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster University Arthritis Index (WOMAC). All patients had failed standard care practices for at least six weeks. Each patient received a Wharton’s jelly tissue allograft to sites around the affected tarsal tunnel. No patients experienced adverse reactions. Percent change calculated from the initial application to the 90-day follow-up showed an improvement of 59.43% in NPRS and a 37.58% improvement in WOMAC. This study provides evidence that WJ allograft applications are safe, minimally invasive, and efficacious for patients who have failed standard care treatments for tissue defects associated with Tarsal Tunnel syndrome. Limitations include the small cohort size and nonblinded nature. The results of this study warrant further research to confirm the efficacy, optimal dose, protocol, and durability of Wharton's jelly.

In our investigation of the time evolution of energy states Einstein’s interpretation from more than a century ago is found to have greater internal consistency than that of non-relativistic quantum mechanics. We choose to align more closely with his methods by abandoning the non-relativistic Hamiltonian method, which has been the standard for nearly a century, in favor of a relativistically correct Lagrangian method. Integral equations of motion for the absorption and emission of radiation are derived that underlie and anticipate the differentially motivated Schrödinger equation. This new interpretation applies to a large volume of experimental evidence of both classical and quantum mechanical origin. Among the examples discussed in support are Planck’s law describing black body radiation, matrix mechanics, the function of the simplest quantum mechanical system an electron cyclotron, chaos theory, and evolutionary biology.

Considering bitemark evidence, forensic dentists must give testimony that could have catastrophic consequences. A bitemark is often the only physical evidence on a body, and odontologists' testimony should be powerful and simple to understand. Given that perpetrators may be executed or imprisoned for life, a defective bitemark analysis is comparable to dentists' most crucial clinical decisions regarding diagnosis. Bias affects human bitemark analysis, and forensic dentists must examine its invisible impacts to avoid making mistakes. The aim of this study was to explore the potential of different types of bias in bitemark analysis and methods during analysis by conducting a scoping review. The majority of the 14 articles that were taken into consideration were published in 2019. USA, UK, Australia, New Zealand, and the Netherlands published the most articles. 36% of the publications addressed contextual bias, while 57% acknowledged cognitive bias. Preventive measures have been recommended to address bias in bitemark analysis. These consist of limiting the availability of unrelated data during the research, employing several comparison samples for a more impartial assessment, and repeating the analysis while being blind to past findings. These preventative measures reduce cognitive and contextual bias and improve bitemark analysis in forensic investigations.

Yeast, crucial in beer production, holds promise as a valuable by-product resource, known as brewer's spent yeast (BSY), with potentially beneficial physiological effects. This study aimed to compare the composition and soluble polysaccharide content of Brewer's spent yeast with those of pure cultured yeast strains, namely Saccharomyces cerevisiae (SC) and S. boulardii (SB), to facilitate the utilization of BSY as an alternative source of functional polysaccharides. BSY exhibited significantly higher carbohydrate content and lower crude protein content than SC and SB cells. The residues recovered through autolysis were 53.11%, 43.83%, and 44.99% for BSY, SC, and SB, respectively. Notably, the polysaccharide content of BSY residue (641.90 μg/mg) was higher than that of SC (553.52 μg/mg) and SB (591.56 μg/mg). The yields of alkali-extracted water-soluble polysaccharides were 40%, 30%, and 35% for BSY, SC, and SB, respectively, with BSY comprising a higher proportion of water-soluble saccharides than SC and SB, including 49.3% mannan and 20.1% β-glucan. Furthermore, BSY demonstrated antioxidant activities, including superoxide dismutase (SOD), ABTS, and DPPH scavenging potential, suggesting its ability to mitigate oxidative stress. BSY also exhibited a significantly higher total phenolic compound content, indicating its potential as an effective functional food material.

The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-like family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which reveal significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~ 90 potential genes that participate in the regulation of the hypertrophic environment (or CVD's Environment). Also, the GO analysis showed genes containing the motif CACCC were enriched for multiple CVD’s, in combination with STRING analysis these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

Synanthropic flora (weeds, spontaneously developed plants) are plants that accompany humans, appearing as a result of anthropopressure as well as after its cessation. The potential of synanthropic flora in shaping green areas usually brings many measurable benefits that depend on land management in cities. The study aimed to determine the preferences and attitudes of adults towards synanthropic flora in settlement units. The article presents survey results from 447 city residents. The obtained results were statistically analyzed using the k-means clustering method to identify segments of respondents with similar attitudes and preferences toward synanthropic flora. Mann-Whitney U tests were employed to determine statistical differences in the demographic variables among the analyzed clusters of respondents. Additionally, multiple regression analysis was performed to identify the opinions and attitudes towards synanthropic flora, that may influence their greater acceptance in the vicinity of residential areas. The results obtained in multiple regression allow for the statement that the respondent’s evaluation of the level of support for the introduction of more synanthropic vegetation into urban greenery (Yw) grows with the increase of acceptance of synanthropic plants occurrence in surroundings. Respondents’ opinions on the subject of the presence of synanthropic plants were studied using such variables concerning: synanthropic vegetation found in turfgrasses has a positive impact on the visual attractiveness of a site (X1), synanthropic plant communities present themselves better than others (X2), presence of synanthropic vegetation in an estate improves the quality of life in that location (X3), introduction of synanthropic flora into estate arrangements is a positive (X4), support for the use of synanthropic flora for educational purposes - as elements of playgrounds or in the form of environmental workshops (X5). Residents’ acceptance of synanthropic flora in green areas is at a relatively high level.

I demonstrate that Bell's theorem is based on circular reasoning and thus a fundamentally flawed argument. It unjustifiably assumes the additivity of expectation values for dispersion-free states of contextual hidden variable theories for non-commuting observables involved in Bell-test experiments, which is tautologous to assuming the bounds of ±2 on the Bell-CHSH sum of expectation values. Its premises thus assume in a different guise the bounds of ±2 it sets out to prove. Once this oversight is ameliorated from Bell's argument by identifying the impediment that leads to it and local realism is implemented correctly, the bounds on the Bell-CHSH sum of expectation values work out to be ±2√2 instead of ±2, thereby mitigating the conclusion of Bell's theorem. Consequently, what is ruled out by any of the Bell-test experiments is not local realism but the linear additivity of expectation values, which does not hold for non-commuting observables in any hidden variable theories to begin with.

Diabetic retinopathy (DR), a major complication of prolonged diabetes, poses a significant risk of vision loss. Early detection is critical for effective treatment, yet traditional diagnostic methods by ophthalmologists are time-consuming, costly, and subject to variability. This study introduces a novel approach employing a hybrid Convolutional Neural Network-Radial Basis Function (CNN-RBF) classifier integrated with Multi-Scale Discriminative Robust Local Binary Pattern (MS-DRLBP) features for enhanced DR detection. We implemented advanced image preprocessing techniques, including noise reduction, morphological operations, and Otsu’s thresholding, to optimize blood vessel segmentation from retinal images. Our method demonstrates exceptional performance in screening DR, achieving an average of 96.10% precision, 95.35% sensitivity, 97.06% specificity, and 96.10% accuracy. These results significantly outperform traditional methods and offer a promising tool for remote and efficient screening of DR. Applied to publicly available datasets, this research contributes to the development of accessible, accurate diagnostic methods in ophthalmology, potentially reducing the global burden of diabetic vision loss.

Electrochemotherapy (ECT) is one of the newest therapeutic strategies employed as medical procedure for skin neoplasms’ treatment, especially for Classic Kaposi’s Sarcoma (CKS). The aim of this study was to demonstrate ECT clinical response and local control of CKS disease. Primary endpoint was to value the worth and efficacy of this local therapy in CKS skin lesions’ treatment. Nineteen CKS patients were enrolled, 14 males and 5 females with median age at diagnosis of 72. Complete response (CR) has been gained in 12 patients after first ECT attempt, meanwhile 3 and 4 out of 19 patients obtained a Partial response (PR), so that they underwent to a second and a third ECT treatment, each other. Clinical response was evaluated during all the time of the follow-up, which ranged between 3 months and 4 years with a median of 18 months. CKS skin lesions control still represents a challenge for surgeons and oncologists. Nevertheless, according to this and other authors’ recent experiences, ECT could be considered the gold standard strategy for early-stage patients, but at the same time it could be considered as a valid option in controlling Kaposi’s Sarcoma locally advanced lesions.

Parkinson’s Disease (PD) is a debilitating neurodegenerative disease, causing loss of motor function, and in some instances, cognitive decline and dementia, in those affected. The quality of life can be improved, and disease progression delayed through early interventions, however, current methods of confirming a PD diagnosis are extremely invasive. This prevents their use as a screening tool for the early onset stages of PD. We propose a surface imprinted polymer (SIP) electroimpedance spectroscopy (EIS) biosensor for detecting α-Synuclein (αSyn) and its aggregates, a biomarker that appears in saliva and blood during the early stages of PD as the blood brain barrier degrades. The surface imprinted polymer stamp is fabricated by low temperature melt stamping polycaprolactone (PCL) on interdigitated EIS electrodes. The result is a low-cost, small footprint biosensor that is highly suitable for non-invasive monitoring of the disease biomarker. The sensors were tested with αSyn dilutions in deionized water, and in constant ionic concentration matrix solutions with decreasing concentrations of αSyn to remove the background effects of concentration. The device response confirmed the specificity of these devices to the target protein of monomeric αSyn. The sensor limit of detection was measured to be 5 pg/L and its linear detection range was 5 pg/L – 5 µg/L. This covers the physiological range of αSyn in saliva and makes this a highly promising method of quantifying αSyn monomers for PD patients in the future. The SIP surface was regenerated, and the sensor reused to demonstrate its capability for repeat sensing as a potential continuous monitoring tool for the disease biomarker.