The quinoline derivative, N-(7-chloro-4-morpholinoquinolin-2-yl)benzamide, was synthesized in a conventional three-step procedure from 4,7-dichloroquinoline using N-oxidation reaction/C2-amidation reaction/C4 SNAr reaction sequence. The structure of the compound was fully characterized by FT-IR, 1H‐, 13C-NMR, DEPT-135°, and ESI-MS techniques. Its physicochemical parameters (Lipinski’s descriptors) were also calculated using the online SwissADME database. Such derivatives are relevant therapeutic agents exhibiting potent anticancer, antibacterial, antifungal, and antiparasitic properties.

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.

In this paper, we focus on the influence of Riemann space-time curvature on the laws of electromagnetism, such as Gauss’s law, Maxwell-Amp´ere’s law, and Faraday’s law. Furthermore, we also introduce the work done on the unification of the gravitation and electromagnetic fields.

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.

Background/Objectives: This study aimed to evaluate compliance and accuracy in comparison with traditional PD diaries for tracking motor symptoms using a new smartphone application (My Parkinson’s) and paper diary strategies. Parkinson's disease (PD) is a neurodegenerative disorder with progressive motor symptoms. Treatment becomes more challenging as PD progresses, motor complications in the form of wearing-off phenomenon and levodopa-induced dyskinesia develop. Traditional paper diaries and clinical scales used to evaluate patients may be inadequate in assessing whether the patient is “on” or “off,” resulting in less-than-ideal treatment changes. Methods: A randomized crossover design was utilized to examine 22 advanced PD patients who underwent symptomatic assessment with both diaries during two separate 24-hour periods seven days apart. The compliance and accuracy of data were assessed by comparing diary entries with the clinical examination notes and WhatsApp queries. Latterly, patients' diary preferences were also evaluated.; Results: The digital diary had significantly better compliance and accuracy than the paper diaries, with substantial/almost perfect levels of agreement (κ = 0·615 to 0·818) between logged symptoms and clinical examination notes. 65% of patients preferred the digital diary for follow-ups, and there was no significant difference in ease of use compared to paper diaries. Conclusions: Digital diaries are helpful in the clinical management of PD patients as they minimize recall bias and reduce data errors in appropriately selected patients. Our study suggests a broader adoption of digital health technologies in PD management. Still, additional research is necessary to improve the tools and assess long-term patient outcomes.

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).

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

These counterexamples have shown the relationships between the power of a Pythagorean equation and Pythagorean’s triples. There are three positive integers that satisfy Fermat’s equation when the power n is equal to 2 in the case of the Pythagorean theorem and it’s applicable relationships in right triangles. On the other hand, as the power varies from positive to negative integers or any integers other than 2, such as in the case of Fermat’s last theorem, the hypotenuse z of a right triangle tends to be equal to one of the sides x or y of the triangle and the other side tends to be equal to zero. And the application of this idea describes the behavior of a mass object in motion. Since the total energy of the object is the sum of its energy in motion and its rest energy, at a particular power n, the total energy of the object tends to be equal to either the rest energy or the photon energy.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent and irreversible neurological disorders that primarily affect the aged population. These conditions lead to disability and mortality as there is currently no medication for a complete cure. Existing drugs only provide symptomatic relief of the disease. Inhibition of Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) will reduce the hydroxylation of Acetylcholine, a molecule possessing a significant role in the neurotransmission pathways and is accounted as a remedial objective for the treatment of AD and PD. This study aimed to identify potent lead molecules from plants that could inhibit AChE and BuChE. We employed molecular docking, molecular dynamic simulation, and MMPBSA approaches to screen and evaluate potential compounds. The docking results were analysed based on binding affinity and hydrogen bond interactions at the active-site residues of the targets. From the analysis, four phytocompounds - Tricetin, Luteolin, Withasomniferol C, and Withanolide were identified as potential hits. These compounds demonstrated strong binding affinities of -8.49, -9.85, -25.26, and -24.1 kcal/mol, respectively. The significant binding affinity suggests that these compounds may effectively inhibit the activity of AChE and BuChE, potentially leading to therapeutic benefits for AD and PD. However, further in-vitro analysis is recommended to validate the activity of these compounds. In-vitro experiments will provide a better understanding of their efficacy, safety, and potential as drug candidates for treating AD and PD.

Around 1637, Pierre de Fermat famously wrote in the margin of a book that he had a proof for the equation $a^n + b^n = c^n$ having no positive integer solutions for exponents $n$ greater than 2. This statement, now known as Fermat's Last Theorem, remained unproven for centuries, despite the efforts of countless mathematicians. Andrew Wiles' work in 1994 finally provided a rigorous proof of Fermat's Last Theorem. However, Wiles' proof relied on advanced mathematical techniques that were far beyond the scope of Fermat's time, raising questions about whether Fermat could have truly possessed a proof using the methods available to him. Wiles's achievement was widely celebrated, and he was awarded the Abel Prize in 2016 in recognition of his groundbreaking work. The citation for the award described his proof as a "stunning advance" in mathematics. The present work offers a potential solution to Fermat's Last Theorem that may be more aligned with the original approach that Fermat claimed to have used.

HIGHLIGHTS Mach's principle is linked with inertia and the mass around. Nowadays, physicists believe its effect is infinitesimal, so Mach's principle is simply ignored. This paper looks at the consequence of applying Mach's principle. It could replace dark matter. ABSTRACT After seeing the history of Mach's principle, we will work out a new model of galaxies inspired by Mach’s principle, which is more satisfactory than current dark matter models. This new model is just maths and needs an explanation. One possible explanation is obviously that Mach's principle is at work in a galaxy.

Urban tourism has witnessed significant growth in recent years, driven by various factors that foster the transformation of urban areas into tourist hotspots. These factors include a rising interest in culture and heritage, ongoing urban redevelopment and conversion processes, and the introduction of new experiences and activities. Two particularly influential factors contributing to this growth are low-cost travel, which facilitates more accessible access to urban destinations, and the emergence of new types of accommodation, such as short-term rental (also known as local accommodation or Airbnb-type accommodation). This sudden and continuous growth of this type of tourist accommodation brings new challenges to cities and local communities. On the positive side, it contributes to job opportunities, the dynamism of the local economy, and urban revitalization. On the other hand, it also represents more difficulty in retaining the local population in city centers, as more and more buildings are converted into hostels and tourist apartments. In this context, it becomes essential to conduct studies evaluating the impacts of these dynamics in urban areas and how they influence residents' and visitors' perspectives. Therefore, this study aims to identify the main transformations resulting from short-term rental (STR) development, focusing on the impacts felt by tourists and residents in Porto. A questionnaire was distributed to tourists and residents in Porto's city center in June 2023. The results reveal differences in opinions between tourists and residents, particularly concerning historical heritage preservation, local population relocation, and reduced housing availability for residents. Nevertheless, there is a similarity in their opinions regarding the stimulus that local accommodation brings to the economy and the rehabilitation of buildings and urban areas. This study reinforces the need to pay more attention to the future development of tourist accommodation in city centers, especially regarding local policies and territorial planning, to balance better tourism development and local communities' quality of life.

Although the empirical Kepler’s laws can be proven by applying Newton’s laws to the dynamics of two particles attracted due to the gravitational interaction, there is no explicit formula for the motion as a function of time. In this paper, a quasi-analytical solution for this problem is proposed. It approximates the real behavior of celestial bodies with an acceptable degree of accuracy. All calculations involved require a low computational cost. This problem is closely related to Kepler’s equation, since, the solution for the equations of motion as a function of time gives us the solution to Kepler’s equation as well. The results are presented for each planet of the solar system (including Pluto), and the solution is compared against the real orbits.

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.

The geometry of structural members can influence the fatigue crack growth rate. In the paper, the T-stress depending on the element's geometry is used to quantify the effect of geometry on the fatigue crack growth rate. A series of fatigue tests on three-point bending specimens with different initial crack lengths were conducted. As a result, the dependence of the crack growth rate on the T-stress value was obtained.

We report an unusual case of Terson's syndrome that resulted in the di-agnosis of a right posterior communicating artery aneurysm. Interest-ingly Terson's syndrome presented with Roth spot resembling features accompanied by third nerve palsy in a patient without any disturbance of consciousness. To our knowledge, the association of Terson's syndrome with third nerve palsy has not been described before in the absence of radiologically diagnosed subarachnoid haemorrhage. We present the case of a 48-year old woman who presented in the De-partment of Emergencies of the University Hospital of Patras with right-sided complete pupil-involving third nerve palsy combined with bilateral Terson's syndrome. More precisely, fundoscopy revealed multi-ple scattered intra- and pre-retinal haemorrhages in both eyes while some retinal haemorrhages had a white-centered pattern resembling Roth spots. Neurological examination revealed no nuchal rigidity or any other neurological signs. The Glasgow coma scale was 15/15. A cerebral computed tomography angiography revealed a 5mm aneurysm of the right posterior communicating artery and the patient underwent a mi-crovascular clipping operation after craniotomy. The significant contribution of the ophthalmological consultation to the appropriate and timely diagnosis and management of a life-threatening condition is highlighted.

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.

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.

Background/Objectives: The primary life-threatening complication in Spinal-bulbar muscular atrophy (SBMA) is ventilatory failure, which results from the weakening of the bulbar and respiratory muscles. However, systematic studies assessing respiratory function over the long-term have not been performed. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years, aiming to identify any potential, sustained decline during this time. Furthermore, we explored possible correlations between respiratory function tests and clinical and biochemical serum indices. Methods: We collected data from 9 genetically confirmed SBMA patients and conducted spirometric measurements twice a year for eleven years. The spirometric data included maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)]. Additionally, we measured serum biochemical indices and SBMA functional rating scale (SBMAFRS) for clinical analysis. Results: All three respiratory function tests showed a descending trend. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with the three pulmonary function tests. MIP and MEP correlated with creatine phosphokinase and creatinine levels, and FVC correlated with serum level of transaminases. Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in patients with SBMA. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

We have shown that Newton’s third law does not strictly hold in a system with remote elements, due the finite speed of signal propagation and thus force imbalance occurs at the system’s center of mass. As the said system is affected by a total force for a finite duration, mechanical energy and momentums are gained by the system. In early works we assumed that the bodies were macroscopically charge neutral. Later we removed this restriction, thus analyzing the consequences on a possible electric charged relativistic motor. On the first published paper on this subject we studied this phenomena in general but gave only an example of a system reaching a stationary state, in this paper we shall analyze a charged retarded electromagnetic motor in a more general time dependent setting giving specific examples in which the system never reaches a stationary state yet produces steady linear momentum non the less.

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.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

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.

We are interested in studying alterations in the regulatory circuitry that controls mRNA stability and function, and more specifically in the interactions among miRNAs and mRNAs. We have previously reported transcriptome-wide changes in mRNA expression in an animal model of atherosclerosis (ATS) progression, and reversion upon treatment with an αCD40 specific siRNA. In this work, we have used our data on mRNAs downregulated during these processes to study length dynamics as an adaptive mechanism to thwart miRNA activity. We show that ATS progression was characterized by the lengthening of the 5’UTR and 3’UTR regions of these mRNAs. Furthermore, 3’UTR lengthening (but not that of the 5’UTR) was shown to be partially reversed by the treatment with the αCD40 specific siRNA. Study of the exonic composition of the transcriptome of these mRNAs suggested a role for alternative/cryptic/latent splicing in the generation of length variants. This was confirmed by the detection, during ATS progression, of a transcript variant switching process in which specific isoforms were replaced by others that differed in their pattern of alternative splicing, mainly at their 5’ or 3’UTRs. This work highlights alternative splicing as a mechanism contributing to the generation of 5’/3’UTR length and sequence variability during ATS progression and calls attention on factors regulating alternative splicing as possible targets of therapeutical intervention.

Alzheimer's Disease (AD) and Parkinson's Disease (PD) are two neurodegenerative diseases posing a significant disease burden due to their increasing prevalence and socio-economic cost. Traditional therapeutic approaches for these diseases exist but provide limited symptomatic relief without addressing the underlying pathologies. This review examines the potential of immunotherapy, specifically monoclonal antibodies (mAbs), as disease-modifying treatments for AD and PD. We analyze the pathological mechanisms of AD and PD, focusing on the roles of amyloid-beta (Aβ), tau (τ), and alpha-synuclein (α-syn) proteins. We discuss the latest advancements in mAbs therapies targeting these proteins, evaluating their efficacy in clinical trials and preclinical studies. We also explore the challenges faced in translating these therapies from bench to bedside, including issues related to safety, specificity, and clinical trial design. Additionally, we highlight future directions for research, emphasizing the need for combination therapies, improved biomarkers, and personalized treatment strategies. This review aims to provide insights into the current state and future potential of antibody-based immunotherapy in modifying the course of AD and PD, ultimately improving patient outcomes and quality of life.

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.

The intricate orchestration of molecular events that constitutes life, as we know it, is oftentimes ascribed to an intelligent design motive. It is portrayed as if a paranormal watch maker has engineered the assemblage of parts and events that eventually manifests as the clockwork precision with which ontogeny and evolution operate within the boundary conditions imposed by what we know as life. The debate between those who advocate evolution versus intelligent design as the shaping force for modern life forms persists. However, that is not the motive for this essay. Though there has been several studies and scholarly articles that aspire to decipher and present the complexity of the molecular events that constitutes life in an insular fashion, there is a paucity of resources for undergraduates that summarizes the complexity cogently, as parts of a whole, for appreciating the enormity of the multidimensional nature of biological information and the inherent contradictions that are embedded therein. The fluidity inherent in the way information flows through signalling networks, the way biomolecular architectures maintain homeostasis in the ying-yang of life and the way multicellular complexity evolves through precise cell-cycle control is inherent in the evolution, maintenance and reproduction of biological systems. The matrix of events that encode information at the sequential and structural level across different macromolecules is a fascinating jungle of information. Combining these with how small-molecule metabolites interact with macromolecules in a spatially and temporally coordinated manner to evolve signal over random noise generates a staggering picture of informational organization and relays that, most often, defies human comprehension. This perspective is an attempt to array the various sources of information and put them together in context to appreciate the nuances of how information is stored and relayed within the biological systems. Further, it speculates on how these multitiered organization of biological information could be adapted to guide synthetic biology approaches and the future of information storage and organization.

This paper focuses on the long-standing issue of galactic rotation, i.e. the discrepancy between observed rotation rates and predictions based on Newtonian gravity. While Newton's law holds within the solar system, it fails to explain the higher-than-expected rotation speeds of galaxies, particularly at greater distances from their centers. This study finds that Newton's gravitational formula applies only when gravitational lensing has a negligible impact. We examine the gravitational force on objects farther from the galactic center, where the lensing effect of a supermassive black hole becomes significant. This lensing causes the actual gravitational force to exceed Newtonian predictions, with the discrepancy increasing with distance. This effect offers an alternative explanation for the galactic rotation curve without the need for dark matter. Our findings suggest that Newton's formula requires revision to account for gravitational lensing, a key factor in understanding galactic dynamics and its broader cosmic implications.

This review aimed to identify the risks of cosmetics during the sensitive period of pregnancy. Pregnancy causes many hormonal changes and skin issues, such as red stretch marks, cellulite, and more. These aesthetic concerns can impact both the appearance and health of the pregnant woman. Cosmetics and aesthetic treatments can help improve these problems and positively affect the mental well-being of these women. However, the lack of clinical trials regarding the safety of such treatments during pregnancy has led to the recommendation of only the mildest aesthetic applications. Additionally, professional aestheticians and dermatologists who provide cosmetics and other aesthetic treatments (e.g., laser, ultrasound, radiofrequency) during pregnancy face challenging and sometimes adverse working conditions. They should be treated with respect for their situation, with careful consideration of all the peculiarities associated with pregnancy. Further research and additional recorded data are crucial for better understanding the use of cosmetics and aesthetic treatments during pregnancy.

A 64-year-old woman with primary Sjogren’s syndrome which was not treated, was admitted to our hospital for nasal bleeding, oral bleeding, and purpura on her entire body. On this admission, laboratory findings were as follows: WBC counts, 8,910 /μL; hemoglobin, 9.9 g/dL; and platelet counts, 0.1×10⁴/μL. Although the anti-PLT antibody was positive, other autoimmune antibodies such as anti-DNA were negative. Moreover, cytomegalovirus IgM, Parbovirus B19 IgM, and Helicobacter pyroli IgG antibodies were not detected. No abnormal findings suggestive of infection were identified in the systemic examination. A bone marrow aspiration smear revealed normal bone marrow. Based on these findings, the patient was diagnosed with primary Sjogren’s syndrome-related immune thrombocytopenia. The patient initially received intravenous immunoglobulin, methyl prednisolone pulse therapy, and subsequent high dose prednisolone without significant improvement. Therefore, eltrombopag, a thrombopoietin-receptor agonist, was added. Subsequently, erythromycin was also added, considering its immunomodulatory effects. After initiating the erythromycin treatment, the platelet counts increased. Therefore, add-on eltrombopag and erythromycin treatment was effective; however, the platelet counts gradually decreased with reducing the prednisolone dosage. Instead of increasing the prednisolone dosage again, tacrolimus, a calcineurin inhibitor, was successfully added. Consequently, the prednisolone dosage could be reduced. This case shows that treatment with erythromycin and tacrolimus may be efficacious when conventional immunosuppressants show limited effectiveness in primary Sjogren’s syndrome-related immune thrombocytopenia.

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.

Introduction 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

Variable-Angle Tow (VAT) laminates can improve straight fiber composites mechanical properties thanks to the application of curvilinear fibers. This characteristic allows to achieve ambitious objectives for design and performance purposes. Nevertheless, the wider design space and the higher number of parameters result in a more complex structural problem. Among the various approaches that have been used for VATs study, Carrera’s Unified Formulation (CUF) allows to obtain multiple theories within the same framework, guaranteeing a good compromise between the results accuracy and the computational cost. In this article, the linear buckling behavior of VAT laminates is analyzed through the extension of CUF 2D plate models within the Reissner’s Mixed Variational Theorem (RMVT). Results show that RMVT can better approximate the prebuckling non-uniform stress field of the plate when compared to standard approaches, thus improving the prediction of the linear buckling loads of VAT composites.

Regulation (EU) 2016/429 establishes new extensive guidelines for managing transmissible animal diseases, including zoonoses. The Commission Implementing Regulation 2018/1882 classifies diseases into five categories based on their prevalence and the required response, ranging from eradication to surveillance. Key aspects of the regulations concern emphasis on animal traceability, biosecurity, wildlife pathogen control, sustainable farming, and the reduction of the impact of diseases on both public and animal health, as well as on the environment. These align with the European Green Deal, the Farm to Fork Strategy and the One Health approach. In Italian inner areas—similarly to other European regions that are fragile, remote from major service centers, and often neglected—agropastoral and agri-food activities are beneficial for tourism, commercialization of typical foods, and recreational activities. In these areas including the Molise Region, the activation of optional programmes within the framework of the aforementioned regulations could help control infectious animal diseases that are not subject to mandatory eradication but cause income loss and trade restrictions, such as infectious bovine rhinotracheitis and paratuberculosis, a suspected zoonosis potentially linked to Crohn's disease in humans. These programmes could boost the economic income of local extensive breeding, counteract depopulation, and protect human and animal health.

The United Nations Global Sustainability Agenda 2030 introduces a transformative framework through its Sustainable Development Goals (SDGs), which are designed to achieve equitable, prosperous, and sustainable development globally. Unlike the incremental Millennium Development Goals (MDGs), the SDGs aim for systemic changes across economic, social, and environmental dimensions, ensuring that no one is left behind. This research paper provides a comprehensive examination of Pakistan's progress towards achieving the SDGs under the UN Global Sustainability Agenda 2030. Specifically, it includes an analysis of the prioritization of SDGs in Pakistan, highlights federal and institutional initiatives aimed at promoting sustainable development, and explores the role of the China-Pakistan Economic Corridor (CPEC) in advancing these goals. Additionally, the paper critically analyzes the SDGs in Pakistan’s annual status report, identifies the key challenges faced by the nation in implementing these goals, and offers recommendations for enhancing the effectiveness of SDG implementation. Overall, the focus is primarily on the detailed analysis of the annual status report, the challenges encountered, and strategic recommendations for achieving excellence in SDGs in Pakistan.

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.

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.

4E-BP2 deamidation significantly alters protein production in the brain and nervous system. It maintains the balance of protein production required for a healthy nervous system. Any imbalance in protein production in the brain and nervous system causes all neurodegenerative diseases. Discovering what causes 4E-BP2 deamidation only in neurons will make it possible to control this balance of protein production and cure neurodegenerative diseases such as memory loss, Alzheimer's, and Parkinson's. Alzheimer’s disease is caused by the absence of 4E-BP2 protein in the brain's neurons. This protein undergoes deamidation spontaneously only in the neurons and, in this way, controls the production of proteins in the neurons. This, in turn, determines whether or not Alzheimer’s and Parkinson’s disease start or progress. The purpose of this work is to discover the neurobiological mechanism that causes the deamidation reaction in the 4E-BP2 protein by performing immunoblotting in the retinal ganglia, the optic nerve, the dorsal root ganglia, the sciatic nerve, and the whole brain, extracted via dissection from 2-month-old, Wild-type male mice. The results showed that deamidation mainly occurs in the axons or axon-enriched regions of the optic nerve, the whole brain, and the sciatic nerve, confirming conclusively that axons are the critical factors behind the neurobiological mechanism of 4E-BP2 protein deamidation. The results confirm that they are also the reason why 4E-BP2 deamidation occurs only in neural tissue.

In this paper, we consider the synchronization of chaotic oscillators interconnected via a second order dynamic coupling. The design of the proposed coupling is inspired in the ancient synchronization experiment of synchronized pendulum clocks, as described by the Dutch scientist Christiaan Huygens more than three centuries ago. It is demonstrated that the coupled chaotic systems may exhibit not only complete synchronization, but also mixed synchronization—some states synchronize in anti-phase whereas other states synchronize in-phase. In fact, a transition from complete synchronization to mixed synchronization or viceversa can be induced by just changing a single parameter in the coupling. Additionally, the stability of the synchronous solution is investigated by using the Master Stability Function approach and the largest transverse Lyapunov exponent. The Lorenz system is considered as particular application example. Finally, the performance of the proposed synchronization scheme is illustrated with computer simulations and validated by means of experiments using electronic circuits.

This paper presents a biologically inspired flocking-based aggregation behaviour of a swarm of mobile robots. Aggregation behaviour is essential to many swarm systems, such as swarm robotics systems, in order to accomplish complex tasks that are impossible for a single agent. We developed a robot controller using Reynolds’ flocking rules to coordinate the movements of multiple e-puck robots during the aggregation process. To improve aggregation behaviour among these robots and address the scalability issues in current flocking-based aggregation approaches, we used a K-means algorithm to identify clusters of agents. Using the developed controller, we simulated the aggregation behaviour among the swarm of robots. Five experiments were conducted using Webots simulation software. The performance of the developed system was evaluated under a variety of environments and conditions, such as various obstacles, agent failure, different numbers of robots and arena sizes. The results of the experiments demonstrated that the proposed algorithm is robust and scalable. Moreover, we compared our proposed algorithm with another implementation of the flocking-based self-organizing aggregation behaviour based on Reynolds’ rules in a swarm of e-puck robots. Our algorithms outperformed this method in terms of cohesion performance and aggregation completion time.

Background/Objectives: It is known that balance disorders involve occupational hazards. However, the inverse relationship (between certain occupations and an increased incidence of vertigo or dizziness) has been scarcely studied. The objective of this work was to analyze the occupation of a group of patients with vertigo, compared to economically active general population, and to evaluate the prevalence of occupational noise and/or vibration-exposure in both groups. Methods: A cross-sectional, observational, case-control study was carried out including 461 patients (220: Meniere’s disease; 73: vestibular migraine; 28: vestibular neuritis; 140: BPPV) (310 women and 151 men). These patients were compared to a control group from the general population, obtained from 6th EWCS-Spain (2015). Possible differences regarding sex, age, occupation, exposure to noise, and exposure to mechanical vibrations were analyzed. Results: Differences in distribution of occupations between patients with vertigo and general population were observed (Chi-square, p=6.142 e-30). Patients with vertigo were significantly more exposed to noise (p=8.19 e-12; OR=2,127, CI95% (1.720;2.630)) and vibrations (p=1.11 e-12; OR=2.288, CI95% (1.835;2.853)) than the control group. These differences were observed both between men and women. Conclusions: A relationship between occupational exposure to noise and/or vibrations and the presence of vertigo was observed. Protective and preventive measures could help prevent the occurrence of some diseases involving vertigo.

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients, and healthy subjects with (GBA-C) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn &amp; Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-C and HC were also considered. Clinical assessment included the MDS-UPDRS and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-C (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p&lt;0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p&lt;0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-DHP. Allopregnanolone was the only neurosteroid significantly lower (p&lt;0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

Falls are a frequent and serious problem for older adults and especially those living with Parkinson’s. The relationship between falls and physical activity is complex and people often restrict activity following a fall. Exercise is an important aspect of re-ducing further risk of a fall and a key component of the management of Parkinson’s. The aim of this study was to understand the types of activity that are engaged in, the environments in which they take place and the experience of people with and without Parkinson’s who have fallen. 17 people with Parkinson’s and 13 older adults, who had experienced at least one fall in the previous year, were recruited to this mixed methods study. Activity levels were captured over one week using accelerometers and body worn cameras, allowing the type and location of activity to be recorded and analysed. This information informed an interview. Findings showed that although both groups often achieved up to 10,000 steps per day, this was in very short bouts of activity. Sedentary activity such as watching television dominated the findings. Participants were aware of the benefits of being active but described many barriers to achieving the level of activity they would like to.

The field of epigenetics, which explores how heritable traits or stable alterations of cell functions occur without changes to the DNA sequence and how environmental factors affect gene expression, is rapidly advancing. Epigenetics plays a critical role in memory formation, learning, and cognitive functioning, effectively bridging genetics with environmental influence. Maternal behavior in rats, for instance, can modify the stress response of their offspring through epigenetic mechanisms such as histone acetylation and DNA methylation. Understanding neurodegenerative diseases like Parkinson's disease (PD) depends on comprehending the mechanisms of epigenetic regulation. Epigenetic modifications, which alter proteins and DNA structure without changing the DNA sequence, can activate or suppress gene expression, assisting organisms in adapting to environmental changes. These modifications may influence genes involved in inflammation, synaptic plasticity, and neuroprotection, potentially contributing to cognitive deficits in PD patients. MicroRNAs (miRNAs), histone modifications, and DNA methylation are the epigenetic mechanisms that significantly influence cell differentiation and maintain normal cellular activity. Understanding the intricate molecular processes of epigenetics could lead to more targeted and effective therapies. Despite numerous findings on how epigenetics affects cognitive alterations in PD patients, only some studies coordinate and integrate these results. Here, we summarize recent findings on how epigenetic changes impact gene expression linked to cognitive impairments in 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.

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.

This text deals with exploring random solutions for generalized nonlinear variational inequality problems. Using the Fan-KKM theorem and Aumann's measurable selection theorem, we are able to prove the existence and uniqueness of random solution sets under the conditions of monotonicity and convexity. Additionally, we use Minty's lemma to demonstrate the compactness and convexity of the random solution sets.

Background: Suicidal behavior has been a dilemma in Alzheimer's disease. Many ethical debates have been raised about euthanasia in patients with neurodegenerative diseases, and there is a finding of increased suicide rates in the early stages of dementia. However, little is known about the history of suicide ideations or attempts in people with Alzheimer's disease. We aim to measure questionnaire adequacy and acceptability in this specific study to investigate the history of behaviors and factors associated with suicidal behavior across the lifespan in patients with Alzheimer's disease. Methods: This study is an excerpt from case-control research, where the sample was calculated at 150 participants, 75 for the case group and 75 for the control group. Here, the descriptive statistics of the first third of the case group sample, 25 participants, were made. Adequacy was observed by comprehension of questionnaires, and acceptability was measured by participants' understanding of the study object.Results: The prevalence of suicidal ideation throughout life was 8%, and 4% attempted suicide at some point in their lives. The total score of QLoS had a median of 71, which demonstrated the consideration of a moderate quality of life. The total score of the SAF-quest had a median of 12, which showed a low suicidal behavior history. All patients were included in understanding the questionnaires.Conclusions: This study demonstrated the adequacy, acceptability, and scarcity of suicidality histories throughout life in Alzheimer’s disease patients.

In a systematic explorative study of genetic patterns on chromosome 19, we discovered a pattern comprised of 23 SNP alleles that is significantly associated with late-onset Alzheimer’s disease (AD). This association is validated using two independent data sets. The pattern includes THOP1, which has a long and disputatious relationship with AD. It also spans SLC39A3 and SGTA and is upstream from DIRAS1. We utilized population data to observe the frequencies of this genetic pattern for 11 different ancestries and note that it is highly common for Europeans and relatively infrequent for Africans. This research provides a distinct genetic signature for AD risk as well as insights into the complicated relationship between this disease and THOP1.

To promote of the rural revitalization strategy in China, this study attempts to summarize the gains and losses by the review of the design practice of rural buildings of the People's Commune in the late 1950s. Firstly, from the macro perspective, this paper gleans the relevant commune housing design cases in the Architectural Journal from 1958 to 1960 and summarizes the overall common design policies. Secondly, from the micro perspective, the paper analyzes the process of the investigation and creation through a concrete case. The paper concludes that the actual production and living needs of farmers must be taken into consideration in the process of the implementation of rural modernization, instead of simply putting the focus on standardized construction. Finally, the article points out the two characteristics of "rural modernity" reflected in the process of promoting rural modernization during the early stage of modern China: 1) collective wisdom and efforts; 2) combining local and foreign cultures. This article aims to provide a historical reference for current architects to carry out effective design practices in combination with rural development.

Seaports are critical hubs in global trade, facing increasing pressure to accelerate green transi-tions while navigating evolving economic and environmental landscapes. This research analyses the intricate relationship between port organizational ecosystem resilience and the successful implementation of green transitions, highlighting the challenges and opportunities in moving towards a more sustainable future. The research employed a combined focus group interview and participatory observation methodology to gather insights from experts. Analysis revealed that while technological advancements are a primary driver for greening port operations, a lack of managerial capacity is a significant impediment to the successful integration of these innova-tions. It was identified several challenges, including outdated infrastructure, cybersecurity threats, and the need for ongoing investments in new technologies, along with the need to foster a sustainable behaviour culture. Experts emphasized the importance of developing managerial competencies and continuous learning. The research also highlights the role of strong stake-holder partnerships, including collaboration with government agencies, industry associations, and environmental organizations. This research provides valuable insights for policymakers, port managers, and other stakeholders seeking to navigate the challenges for ensuring a sus-tainable future for the maritime sport organizational ecosystems and maritime industry.

Brewers’ spent grain (BSG) is the major by-product of beer production (70-80% moisture) and the feasibility of its application in foodstuffs depends primarily on its drying. Our objective was to evaluate the effect of physical separation with or without ultrasound application on color, total phenolic content (TPC), antioxidant activity, proximate composition, total dietary fibers, and particles size distribution of BSG powders. From wet BSG (W), two processes, without (A) or with (B) ultrasound, encompassing pressing, convective air-drying, sieving, fraction separation, and milling were evaluated. Powders A1, A2, B1 and B2 were generated. The total color difference compared with W increased throughout both processes, ranging from 1.1 (B1 x A1) to 5.7 (B1 x A2). No significant difference was observed for TPC, while lower antioxidant activity (ABTS+) was observed for process B powders, especially for B2, likely due to the release of antioxidant compounds to the liquid during pressing after ultrasound application. Nevertheless, process B powders showed higher content of total dietary fiber (p < 0.05). In conclusion, process B, with ultrasound application, may be interesting for further extraction of soluble fibers. However, the developed process A may be feasible for industrial and craft brewers, and further studies regarding the effect of their application in foods should be encouraged.

We prove that the probability of “A OR B”, where A and B are events or hypotheses that are recursively dependent (OR is the logico-probabilistic operator) is given by a "Hyperbolic Sum Rule” (HSR) relation isomorphic to the hyperbolic-tangent double-angle formula, and that this HSR is Maximum Entropy (MaxEnt). The possibility of recursive probabilities is excluded by the “Conventional Sum Rule” (CSR) which we also prove MaxEnt (within its narrower domain of applicability). The concatenation property of the HSR is exploited to enable analytical, consistent and scalable calculations for multiple recursive hypotheses: such calculations are not conveniently available for the CSR, and are also intrinsic to current artificial intelligence and machine learning architectures presently considered intractable to analytical study and methodological validation. We also show that it is as reasonable to state that “probability is physical” (it is not merely a mathematical construct) as it is to state that “information is physical” (now recognised as a truism of communications network engineering). We relate this treatment to the physics of Quantitative Geometrical Thermodynamics which is defined in complex hyperbolic (Minkowski) spacetime, and show how the HSR is isomorphic to other physical quantities including certain components important for digital signal processing.

Drawing from literature and Geert Hofstede’s cultural dimensions, this study delves into the impact of cultural factors on family structures, roles, and relationships. Ghana and Latvia have different cultural and social orientations that influence family dynamics. Through a comparative lens, this paper will contribute to understanding how a country’s culture influences family dynamics, highlighting the influence of Power Dynamics of parenting style and Individualism vs. Collectivism on interaction levels within the family.

The appropriate concentration of vitamin D in the athlete’s body is essential for its proper functioning, especially in terms of muscular health, by enhancing recovery and oxygen consumption. Soccer players are required to perform frequent sprints and change of directions during training and competition. The aim of the present study was to establish whether the level of vitamin D (measured by 25-hydroxyvitamin D concentrations- 25(OH)D) in blood serum has any influence on speed (s) and change of direction (COD, s) performance. Material and methods: Twenty male soccer players from the top league in Poland participated in the study. All subjects' were evaluated for the serum concentration of 25(OH)D at the beginning of the preseason. . The linear sprint test was performed at 5m and 30m and COD (time and deficit), was evaluated at 30m at the beginning and after 6 weeks of preparatory period. Results: The results revealed that 50% of soccer players had an insufficient level or a deficit of 25(OH)D (≤ 30 ng/ml), with 20% having a significant deficiency of 30 ng/ml).There were no statistically significant correlations between the training effect for the variables ∆5m (before - after) and ∆30m (before - after). Statistically significant positive correlations were found between the training effect for the variables ∆COD (before - after) (R=0.62/p=0.003) and ∆deficit (before-after) (R=0.47/p=0.039). With a higher concentration of vitamin D in the blood, the training effect for COD and the deficit increased, which was visible in the faster performance of the COD test. No statistically significant differences were found for the mean values of the variables ∆5m (before - after) and ∆30m (before - after) in the group of subjects whose 25(OH)D concentration was 30mg /ml. Significant differences were noticed for the variables ∆COD (m=0.60 [s]) and ∆deficit (m=0.56[s]) in the group of subjects whose 25(OH)D concentration was 30mg /ml. The training effect was significantly higher for the group of subjects whose 25(OH)D concentration was above 30 mg/ml, which was observed by the faster performance of the COD test in this group of subjects. Conclusions: The serum concentration of vitamin D affects training adaptations of muscles. A lower concentration of Vitamin D seems to have a detrimental effect on the change of direction performance. Soccer players whose blood serum 25(OH)D concentrations were >30mg/ml achieved better results in the applied fitness tests.

A relativistic positioning system is a set of four emitters broadcasting their proper times by means of light signals. The four emitter times received at an event constitute the emission coordinates of the event. Covariant quantities associated with relativistic positioning systems are analysed relatively to an observer in Minkowski space-time by splitting them in their relative space-like and time-like components. The location of a user in inertial coordinates from a standard set of emission data (emitted times and satellite trajectories) is solved in the underlying 3+1 formalism. The analytical location solution obtained by Kleusberg for the GPS system is recovered and interpreted in a Minkowskian context.

Recent studies have shown that the endogenous cannabinoid system (ECS) of the brain is essentially involved in the pathogenesis of Parkinson's disease (PD), influencing its symptoms by regulating the level of endogenous cannabinoids and altering the activation of cannabinoid receptors (CBR). Therefore, modulation of ECS with new drugs developed for this purpose may prove to be a promising strategy in the treatment of PD. However, fine regulation of ECS is quite a challenge due to the functional diversity of CBR in the basal ganglia. Our review analyses the effects of ECS modulators on experimental PD models and in patients with PD, as well as presents the outlooks for the development of new cannabinoid drugs for the treatment of motor and non-motor symptoms in PD.

Objective: To explore motivation to exercise, support, and self-management needs among people with Parkinson’s (PwP), family-members and physiotherapists. Methods: Purposeful and maximum difference sampling methods (age, sex, geographical setting, and disease severity) were employed. PwP and family-members were recruited through physiotherapy services and local support groups. Semi-structured interviews with 12 PwP, focus groups with four family-members, and five physiotherapists were conducted. Interview guides were informed by patient-public input, and a recent systematic review. Interviews were recorded, transcribed, and analysed using thematic analysis. Results: Four common themes emerged: 1) The value of an intrinsic connection with exercise: but there are challenges. A greater connection to exercise led to long-term compliance. 2) Tailoring exercise is essential. Preferred exercises and environments were mixed, with differences emerging between sexes. 3) Physiotherapists’ aim to only maintain physical function led to frustration. Limited self-management opportunities, stigma and dehumanisation were discussed. 4) Non-motor symptoms, stigma, fear, and determination. Apathy, pain, and low mood were discussed. Conclusion: Exercise provided physical, emotional, and social rewards. Supports are necessary; however, challenges arise when PwP’s motivation are mismatched to family-members’ and physiotherapists’ goals. Co-created goals, tailored to their preferences, and exercise plans with supported self-management are recommended.

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.

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.

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.

Perimenopause, the transitional phase leading up to menopause, affects millions of women worldwide, yet remains poorly understood and under-addressed in healthcare. This report investigates the significant impact of perimenopause symptoms on women's lives, emphasizing the often debilitating effects such as anxiety, depression, weight gain, and hot flashes, which collectively cost an estimated $1.8 billion annually in lost work time. Despite the availability of treatment options like Hormone Replacement Therapy (HRT) and non-hormonal alternatives, awareness and utilization of these options vary significantly among women. The report highlights the historical neglect of women's health issues and the need for improved communication between patients and healthcare providers. A cross-sectional survey conducted with 1,000 adults from the United States and Canada reveals widespread dissatisfaction with the quality of healthcare communication, underscoring the importance of personalized and comprehensive insights for women's health. The findings advocate for more at-home solutions and resources to empower women in managing perimenopause and menopause, promoting informed decision-making and reducing stigma. This study aims to enhance awareness and support for women during this critical life stage.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

Gilbert's syndrome (GS) is a common hereditary condition characterized by mild increases in serum bilirubin levels due to inherited defects in bilirubin metabolism. This review, based on data from peer-reviewed articles and journals spanning from 1977 to January 2024, provides a comprehensive overview of over four decades of research on GS. Early studies primarily focused on defining the clinical and genetic characteristics of the syndrome, laying the foundation for subsequent investigations. More recent research has delved into the genetic mechanisms underlying the reduced expression of bilirubin UDP-glucuronosyltransferase, which has significantly enhanced our understanding of the pathogenesis of GS. Furthermore, recent studies have shed light on the clinical implications of GS, including its association with non-alcoholic fatty liver disease and mortality risk, highlighting the complex interplay between genetic factors, bilirubin metabolism, and clinical outcomes. Despite its generally benign nature, thorough research is essential to fully understand the impact of GS on patients' lives. This review emphasizes the importance of ongoing research to deepen our understanding of GS and its broader implications.

Alzheimer’s disease (AD) is the most widespread neurodegenerative disorder. Recently, it was found that mucus extract from Cornu aspersum have beneficial effects on memory and cognitive processes in a rat scopolamine model of AD. The present study elucidated mechanisms of action of standardized mucus snail extract (SE) enriched with fraction above 20 kDa on Alzheimer-type dementia in rats. Using proteomic analysis on two-dimensional polyacrylamide gel electrophoresis (2D–PAGE) on rat cortex extracts we compared protein expression in both groups: the first group treated intraperitoneally with scopolamine (Sco, 2 mg/kg, 11 days) and the second (Sco + SE) group treated intraperitoneally with Sco (Sco, 2 mg/kg) and protected by SE (0.5 ml/100 g bw) applied daily orally for 11 days. Brain cortex was separated and the expression of various proteins related to memory and cognitive functions were identified. We found that the expression of Ubiquitin carboxyl-terminal hydrolase isozyme L1, Calbindin, Vacuolar ATP synthase catalytic subunit A, Tropomyosin beta chain, 14-3-3 zeta/delta, Kinesin-1 heavy chain and Stathmin-4 significantly differs in SE-protected rats as compared to non-treated dement animals, and these brain proteins might be potential therapeutic targets for Alzheimer’s type dementia treatment.

Late-onset Alzheimer’s disease (LOAD) is a dementia category disease that starts after the age of 65. Progressive problems in thinking, behaviour, learning etc. are its characteristics. Due to its progressive nature, early diagnosis is crucial. A complex pathway mechanism with different risk factors is involved in LOAD progression. A comprehensive study is done on factors causing LOAD, biomarkers used for diagnosis in clinical and preclinical stage of the disease, ML (Machine Learning) techniques to identify disease stage. We reviewed research papers on clinical and preclinical diagnosis of LOAD using ML techniques from biomarker data: MRI, PET image, MMSE, Genome / Gene expression, DNA / RNA binding sites with protein, Epigenetic expression /DNA, methylation, Speech and text. We have listed improvement scope after finding the gaps and scope of using Generative AI and SMOTE (Synthetic Minority Oversampling Technique) for data augmentation. At the end, we have elaborated current use of DL (Deep Learning) and CNN (‘Convolution Neural Network’) in Alzheimer’s disease (AD) diagnosis.

The samples from lunar farside have great significance for the study of the Moon, and even the solar system. Chang’e-6 landed successfully on the southern mare of the Apollo basin and returned ~2 kg samples from lunar farside. To provide a better understanding for the background of the returned samples, we conducted detailed crater size-frequency distribution (CSFD) measurements in the Chang’e-6 landing region, the southern mare of the Apollo basin. The southern mare is divided into western mare (W region) and eastern mare (E region), and then subdivided into five sub-units (W1, W2, W3, W4, W5) and three units (E1, E2, E3), respectively, according to the elevation, Ti and Fe abundances. Within the W2 and W5 region, more detailed sub-units were divided. The results show that the southern mare generally have two epochs, one of the Imbrian period and the other of the Eratothenian period. The basalt eruption lasted for ~1.7 Ga, from 3.28 Ga of the eastern mare to 1.54 Ga of the western mare. W region is younger than E region, while the three units of E region has an age of ~3.2 Ga. The ages of the western mare basalts range from 2.98 Ga to 1.54 Ga, lasting for 1.4 Ga. It’s worth noting that the age of the basalt at the Chang’e-6 sampling site is ~1.68 Ga, indicating the samples returned may include components with this very young age.

We report the case of a 45-year-old Caucasian man who was treated upfront with brentuximab vedotin (A) and doxorubicin, vinblastine, and dacarbazine (AVD; A+AVD) for advanced-stage classical Hodgkin's lymphoma (cHL). Right after completing the 6th cycle of induction therapy, he developed serotine fever, progressive clinical deterioration, symptomatic splenomegaly and se-vere anemia. Extensive infectious disease evaluations and serial PET scans were conducted to rule out lymphoma progression. Finally, a diagnosis of visceral leishmaniasis (VL) was performed. The patient was treated with parenteral amphotericin B, with rapid and complete resolution of clinical and laboratory abnormalities. We described this rare case of infectious complication after A+AVD delivered for cHL, and we performed a comprehensive review of the literature on the occurrence of VL in the context of non-HL and cHL, since this infection is becoming increasingly prevalent in non-tropical countries.

Aim: Deep brain stimulation (DBS) involves implanting electrodes in specific brain areas. High-frequency Stimulation (HFS) and low-frequency Stimulation (LFS) target motor and non-motor symptoms differently. DBS is crucial in Parkinson's disease treatment for managing medication-resistant symptoms and improving quality of life. This review aims to evaluate the differential impact of high-frequency and low-frequency deep brain stimulation (DBS) on motor symptoms in Parkinson's disease (PD) patients. This systematic review adheres to PRISMA guidelines and focuses on clinical studies involving human subjects. Methods: Systematic search in electronic databases (PubMed, Google Scholar, Science Direct, Cochrane Collaboration Database of Randomized Trials) was performed to identify randomized controlled trials (RCTs) up to 13th July 2024. Results: Among 126 pooled patients from 8 RCTs, it was found that LFS significantly improved gait stability, swallowing, and verbal fluency with minimal adverse effects. Conversely, HFS was effective in reducing rigidity and tremor but was associated with potential side effects such as gait and speech impairment. Conclusion: The review highlights the nuanced effects of STN-DBS frequencies in Parkinson's treatment, suggesting high-frequency improves rigidity and tremor but may cause side effects, while low-frequency enhances gait stability and speech, necessitating further research for optimized, patient-specific therapies.

We report positive correlations between letter frequency and symmetry (more symmetric symbols are more frequent) in English and Russian languages and in four types of numerals (Western, Roman, Arabic, and Chinese) with the coefficients of determination of R2=0.899 (English), R2=0.693 (Russian) and R2=0.740 (numerals). For comparison, we studied "symbol-like" 2D colloidal clusters and found negative correlations between frequency and symmetry (R2=0.814 and R2=0.994). While in human-made systems the frequency of using of a symbol is the driving force which leads to symbols simplification and symmetrizing, in natural system, symmetry leads to lower frequency of occurrence because there are fewer ways of building symmetric clusters than asymmetric ones. We interpret these results as a correlation between the symbol as a type and as a token and we attribute this correlation to the inherent iconicity of symbols

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considerate prevalent among individuals before PD diagnosis and persisting throughout the patient’s life. NMS mainly include loss of taste and smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings showing the impact of Syn deposits on several prodromal NMS and emphasizes the importance of early detection of Syn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.

The excessive and prolonged use of the electronic devices with digital screens may cause some serious health problems. The ocular surface problems particularly Dry Eye Syndrome may be the most common and preventable one of them. In this study, unfavourable and potentially harmful effects of digital screens on lacrimal system and tear functions were evaluated in 221 participants. Their ocular surface conditions were evaluated by Ocular Surface Disease Index (OSDI) scores and their lacrimal functioning was measured by Schirmer’s test.. A reciprocal and statistically significant relationship was found between dry eye symptoms and OSDI scores. This relationship was more prominent especially in long duration use of smartphones with brighter background lights..

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.

Blood biomarkers represent a promising future for studying cognitive impairment, particularly in Alzheimer's Disease (AD), as they offer a non-invasive alternative to cerebrospinal fluid tests and have potential as population screening tools. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations between Amyloid-β, Total Tau, Phosphorylated Tau (p-tau), Neurofilament Light (Nfl), and Glial Fibrillary Acidic Protein (GFAP) with cognition. The reviewed studies are heterogeneous, varying in design and population (mixed, cognitively impaired, or unimpaired), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aβ levels, especially when evaluated through the Aβ42/Aβ40 ratio. In contrast, Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-tau measures tend to show stronger associations with cognitive functions than other biomarkers, no single blood marker has emerged as predominantly associated with a specific cognitive domain. These findings add to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical evaluations of cognition.

The access to cardiac rehabilitation (CR) is contingent upon physician referrals, yet these are often inadequate, particularly in low-resource settings. This multi-method study aimed to translate, culturally adapt, and validate the Portuguese version of the Provider Attitudes toward CR and Referral (PACRR-P) scale, as well as to identify key factors influencing CR referral in a Latin American context for the first time. The PACRR was translated into Brazilian-Portuguese through a rigorous process involving independent translation, back-translation, and expert panel review to ensure face, content, and cross-cultural validity. A total of 44 Brazilian physicians completed the questionnaire, allowing for an assessment of internal consistency, criterion validity, and convergent validity. The findings confirmed the face, content, and cultural validity of the 20 translated items, with a mean item clarity rating of 4.8/5. The final version included 17 of the original 19 PACRR-P items, with a Cronbach’s alpha of 0.73. Referral rates were significantly associated with specific PACRR-P items, supporting the scale's criterion validity, while correlations with ReCaRe scores further supported convergent validity. The most prominent barriers to referral were a lack of familiarity with CR site locations, absence of a standard referral form, and lack of automatic referral processes. The PACRR's validity and reliability among Portuguese-speaking providers are preliminarily supported.

The aim of this study is to characterize the compound extremes of rainfall and temperature in Côte d’Ivoire. For this purpose, we analyzed the outputs of fourteen (14) climate models from the CORDEX-Africa project. Results show an increase (approximately 4.3°C) of the surface temperature and a decrease (5,90 %) of the mean rainfall in the near (2036-2065) and far futures (2071-2100) over Côte d’Ivoire during January-February-March (JFM) period. The analysis of the compound extremes of wet/warm type highlights an increase in the frequency of this climatic hazard in the northern and central parts of the country during January-March (JFM) season in the near and far futures. The dry/warm mode will increase in the central and southern parts of the country during the near future and in the whole country during the far future. These increase in compound extremes could lead to an increase in droughts and natural disasters over the country and could have a negative impact on socio-economic activities, such as transportation and agricultural production. This work could provide decision support for political decision-makers in formulating future public policies for managing agricultural production, food security, and natural disasters.

Patients with inflammatory bowel diseases (IBD), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.