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.

In the paper, by the Faά di Bruno formula, several identities for the Bell polynomials of the second kind, and an inversion theorem, the authors simplify coefficients of two families of nonlinear ordinary differential equations for the generating function of the Catalan numbers and discover inverses of fifteen closely related lower triangular integer matrices.

This work presents a new, original and very interesting approach to a calculus pro-blem of beams with intermediate supports by Transfer-Matrix Method, a very easy method to program to quickly obtain good results. To exemplify the applicability of this approach is given in dentistry, the calculus of a dental bridge on three poles. The dental restorations are very important for improving the general state of health as a result of improving mastication and aesthetic appearance. The approach of this study consists of to present a theoretical study about an indeterminate beam with intermediate support and after, to particularize for an application of a dental restoration case, with a dental bridge on three poles and with two missing teeth between the three poles, assimilated to a simple static indeterminate beam. The results obtained in the presented case study were validated with those obtained by the classical calculation of the Resistance of Materials, with the equation of the three moments of Clapeyron. Due to the ease and elegance of solving various problems with TMM, their approach will continue with other new and original case studies with different modeling and requests, and they will be presented in future research.

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.

Background: Monogenic Alzheimer's disease (AD) has severe health and socioeconomic repercussions. Its rarest cause are presenilin 2 (PSEN2) gene mutations. We present two new cases with presumed PSEN2-AD, with unusual clinical and neuroimaging findings in order to provide more information on the pathophysiology and semiology of these patients. Methods: Women aged 69 and 62 years at clinical onset, marked by prominent behavioral and language dysfunction, progressing to severe dementia within three years. Neuroimaging, laboratory study, genetic testing. In addition, a systematic review of the PSEN2-AD were performed. Results: Neuroimaging revealed pronounced frontal white matter hyperintensities (WMH) and frontotemporal atrophy/hypometabolism. The genetic study unveiled PSEN2 variants: c.772G>A (p.Ala258Thr) and c.1073-2_1073-1del. Both cerebrospinal fluid (CSF) and experimental blood biomarkers shouldered AD etiology. Conclusions: Prominent behavioral and language dysfunction suggesting frontotemporal dementia (FTD) may be underestimated in the literature as a clinical picture in PSEN2 mutations. Thus, it may be reasonable to include PSEN2 in genetic panels when suspecting FTDL. PSEN2 mutations may cause striking WMH, arguably related with myelin disruption induced by amyloid accumulation.

(1) Background: Alzheimer’s Disease (AD) accounts for 70% of dementia cases and with no effective pharmacological treatments, new rehabilitation methods are needed. Motor activities and transcranial direct current stimulation (tDCS) have shown promise in stabilizing and enhancing cognitive functions. Objective: We want to investigate the effects of combined motor or cognitive activity with tDCS on cognitive functions in AD patients. (2) Methods: Patients with mild or moderate AD were randomized into four groups: motor activity or cognitive activity associated with anodic or sham tDCS (MotA, MotS, CogA, CogS). They received two weeks of treatment (45 minutes, 5 days/week), with the first 15 minutes using 2mA tDCS on the dorsolateral prefrontal cortex. Cognitive assessments were conducted pre-treatment (T0), post-treatment (T1), and one week after (T2). (3) Results: Twenty patients were included. Mann-Whitney test showed significant improvements in anodic groups (MotA+CogA) in the global cognitive status (p=.042), in selective attention (p=.012), and sustained attention (p=.012) at T1, but not at T2. In addition, MotA improved in the Picture Recognition Test (p=.027) and in sustained attention (p=.047) at T2. (4) Conclusion: Combined motor or cognitive activity with anodic tDCS could slow cognitive decline in AD patients, with notable improvements in global cognitive state and attention at T1.

The study aims at evaluating the demand of forest bathing in the Northern Italy’s regions underlining the willingness to pay and the potential tourists’ habits and flows on attending alpine contexts. Through the submission of a questionnaire, the sample’s answers have been analyzed employing a stratified sampling methodology considering three different macro areas (Northwest regions, Northeast regions, and Friuli Venezia Giulia region). After analyzing the sample attitudes, the research approached the estimation section by calculating the flow as the number of potential forest bathing hikes per year and the willingness to pay trough the Contingent Valuation Method. The main results indicate that Forest Bathing activity in Northern Italy have a considerable monetary value and it is generally compared with positive feelings, particularly concerning well-being, and fascination factors.

The once near-extinct Russell’s viper has recently come back to the area beyond its historical range. A couple of decades ago, its distribution was confined to 11 districts of Bangladesh. Hence, the study aims to update the distributional map of Russell’s Viper (Daboia russelii) across the country and find out the surges' causal factors. Both primary and secondary data were utilized in this study. It revealed that the distributional range of this snake was expanded from 22 to 33 districts in 2024. The respondents noted that climatic stressors like high humidity accompanied by hot weather, increased salinity, and increased frequency of flooding facilitated the spreading of the viper across the country. The cropping pattern and crop diversification were another major contributing factor. The shifting of the single-cropped area to a multi-cropped area in the Barind tract increased its main prey rats. Contrarily, the killing of natural predators such as foxes, monitor lizards and mongoose led to the rise in the snake population. The destruction of vegetation coverage in the upper part of the Padma Basin facilitated the movement of Russell's vipers downstream.

The Ro60 autoantigen is an RNA-binding protein, and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates quality control and cellular dis-tribution of YRNAs, retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal TLRs and cytoplasmic RNA sensors, which typically sense patho-gen-associated molecular patterns (PAMPs) and mount the first line of defence against invading pathogens. However, recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases including Sjögren's disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for an-ti-drug antibody response among rheumatic patients. Understanding Ro60’s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mecha-nisms of autoimmune conditions.

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

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

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

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

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

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

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

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

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

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

Reviewed the research progress of Newton’s iterative methods for nonlinear equation. Convergence with second order, third order, fourth order, fifth order, sixth order, seventh order, eighth order and ninth order Newton’s iterative methods are given in turn, and the efficiency index of these iterative methods are analyzed. Numerical experiments show that the convergence process of the three Newton iterative methods, and the results indicate that the convergence of the higher-order Newton’s method can be well demonstrated only when the initial point is close to the root.

The following systematic and bibliographic review investigates the intersection between the treatment of cognitive impairments and virtual and augmented reality-based game-oriented applications. The review provides a view into the last 12 years of research. The PubMed Database served as the main source for the review. We defined a comprehensive set of investigation variables and classified three main topics: bibliography, medical, and technical. Of a total of 61 identified articles, 19 were included. The findings from these studies indicate the positive effects of using virtual and augmented reality applications to improve cognitive function and depression. There is also a gap in high-quality evidence since clinical trials have been conducted only with a few patients. Preliminary results indicate positive cognitive and physical well-being effects, but the field demands further investigation to determine the effectiveness. Future research needs to focus on larger studies and the quality of the developed applications. Further, it is important to look at scores like Quality of Living and Satisfaction in Daily Activities to create a functioning environment for the patient.

A sublingual vaccine comprising Poly(I:C) adjuvant and influenza HA antigen was evaluated for safety in both mice and macaque monkeys relative to its intranasal counterpart. Safety was assessed with harmful effects corresponding to upregulation of the inflammation-associated genes: Saa3, Tnf, IL6, IL1b, Ccl2, Timp1, C2, Ifi4, Aif1, Omp, Nos2, and/or Gzmb in mice and SAA2, TNF, IL6, IL1B, CCL2, TIMP, C2, AIF1, and GZMB in macaques. Quantitative gene expression analyses were performed using RT-qPCR with RNA samples from four tissues: olfactory bulb, pons, lung, tongue, and (submandibular) lymph node from both mice and macaques. In mice, the intranasally delivered vaccine markedly upregulated the inflammation-related genes in the olfactory bulb 1 day and 7 days after vaccination. The adverse effects of intranasal vaccination were also observed in macaques, however to a lesser extent than in mice. The intranasal vaccination also upregulated these genes in the pons of both mice and macaques. In contrast, the sublingual vaccine did not adversely affect the olfactory bulb or pons in either mice or macaques. The intranasally administered vaccine significantly upregulated these genes in the lungs only 1 day after vaccination, but not 7 days later, in both mice and macaques. We conclude that intranasal vaccination results in unfavorable side effects corresponding to upregulated inflammatory genes in the brain (olfactory bulb and pons). Sublingual vaccination, however, did not induce these side effects in either mice or macaque and was hence evaluated as safe.

Objective: Fludeoxyglucose F18 positron emission tomography (FDG PET) can give early clues for diagnosing Alzheimer’s disease (AD). Our objective was to use the same scan to predict Apolipoprotein E4 (ApoE4), known to be a risk factor. A second objective was to determine the brain regions and imaging features associated with this gene allele that can potentially help elucidate the mechanisms of the disease and better comprehend the images. Method: We employed data from 112 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). PET and structural MRI data were co-registered with ANTx, and the Freesurfer tool delineated 95 whole brain, 19 hippocampal, and 9 amygdala regions. Using PyRadiomics we extracted 120 radiomic features from these segments. We employed a hybrid feature selection strategy. The HistGradientBoosting (HGB) classifier was evaluated using stratified five-fold cross-validation. Results: The proposed radiomics model predicted the homozygous ApoE4 genotype, with an AUC of 0.945 an accuracy of 0.875, a sensitivity of 0.914, and a specificity of 0.838. Reducing the feature set to seven key features resulted in a slightly decreased performance (AUC: 0.889). The mean values of the features showed statistically significant (p<0.05) incremental deterioration between different groups of homozygous ApoE4 carriers. Conclusion: Our findings underscore the critical role of specific brain regions and associated features in differentiating ApoE4 carriers. The hippocampus, entorhinal cortex, amygdala, thalamus, and pars orbitalis exhibited significant associations with the ApoE4 genotype. By employing SHAP analysis, we identified key features driving model predictions, enhancing interpretability, and providing insights into the underlying pathophysiology.

In this article we have constructed a basic methodology from which important perspectives for both the Collatz conjecture and Beal's conjecture can be derived. We falsified the conjecture we previously developed on Beal's conjecture and made the falsified conjecture usable for Collatz conjecture. In this regard, we have clearly expressed the numbers that can reach 1 in the Collatz conjecture. Then, using this, we created a limit for the numbers that should be considered for the Collatz conjecture. Thanks to the analysis of this limit, we have clearly expressed the recursive Collatz function in an equation. Using this structure, we wrote a function that indicates how many times the Collatz function repeats certain numbers to reach 1.

Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer’s disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to protein’s function and biological integrity, Hcy-thiolactone detoxifying enzymes – PON1, BLMH, BPHL – have evolved. This review provides an account of the biological function of these enzymes and of consequences of their impairments leading to phenotypes characteristic of AD.

Heat waves represents a major concern for the tourism industry in the Mediterranean area. Therefore, it is necessary to deepen the study of the influence of high temperatures and their effects on tourist behavior. This research aims to develop a structural model that allows measuring how heat waves affect the behavior of external tourist demand in coastal destinations. The results are useful for the design by tourist destinations of adaptation measures to climate change. The proposed hypotheses have been contrasted using non-linear structural equations (SEM), estimated with data from the National Institute of Statistics on external demand in Spain. The results confirm lower tourist flows with the increase in high temperatures to the coasts of the Spanish Mediterranean area from traditional source markets, such as the United Kingdom. Furthermore, the tourist flow to the Balearic Islands decreases with high temperatures.

This study investigates how students' well-being relates to sustainable development and education for sustainability at Prince Mohammad Bin Fahd University, Saudi Arabia. The authors endeavor to answer the question "How Does Students' Well-Being Relate to Sustainable Development Via Education for Sustainable Development?" and four sub-questions. Primary data were collected by semi-structured interviews exploring the viewpoints of twenty female and male students (n=26) aged between 18 and 26. The content analysis results have identified additional well-being and education for sustainability factors that influence sustainable education and, therefore, sustainable development. These antecedents include workload, transparency, grading criteria, fairness, belonging, work-life balance, mental health support, missing emotional intelligence factors, factors related to Education for Sustainable Development, such as instructors' role models, institutional commitment, leadership, and collaboration with government. In addition, the study developed a theoretical model for the relationship between antecedents for Education for Sustainable Development, Education for Sustainable Development, and Sustainable Development in the Saudi context. Finally, the study answers four research questions: What factors contribute to education for sustainable development? What are the antecedents of education for sustainable development? How do university educators contribute to sustainable education? How do the antecedents of education for sustainable development, education for sustainable development, and sustainable development relate?

Athlete’s heart is characterised by structural, functional, and electrical remodelling. During an exercise session, the heart increases the use of oxygen, which is associated with decreased vascular resistance in the lungs’ circulation. Left ventricular hypertrophy is an echocardiographic modification especially met in endurance athlete’s heart. Moreover, left atrial dilatation represents another important characteristic of endurance athletes. Electrical modulation in the athletic heart induces neurological modifications leading to sinus arrhythmia, bradycardia, early repolarisation, and first-grade atrioventricular (AV) blocks. Athletes' nutritional status involves the assimilation of macronutrients such as proteins, carbohydrates, and fats. Depending on the duration of physical exercise, ATP can be obtained in aerobic or anaerobic conditions. This systematic review aims to find correlations between different evaluative methods of cardiac adaptation and present the metabolism in performance athletes.

We solve the problem of Apollonius by applying the Lorentz transformation within the frame- work of special relativity to go to a frame of simultaneity, where the solutions are the circum- center. We transform back to get the solutions in a general frame. We show that the solutions in a general frame are the foci of the ellipse going through the centers of the given 3 circles.

Pig farms management is involved in multiple factors such as environmental conditions, animal behavior, weight gaining and others. In all those scenarios, it is fundamental to detect each individual and its development as it grows to reach the shipment phase. Therefore, the objective of this study was to apply an automatic individual pig detection algorithm using Deep Learning Techniques, in frames taken from videos recorded during the weaning phase in real production conditions of small and medium producers in tropical conditions in Colombia. The weaning phase was selected because individual detection in each cage is more difficult due to environmental adaptations that piglets undergo after nursing. Piglets tend to cluster together during this phase, making image processing more challenging compared to the fattening phase, where animals are more isolated. The You Only Look Once (YOLOv7) algorithm and VGG Image Annotator were used to detect individuals in two pens separated by gender. All animal postures, lighting conditions were considered. The Precision, Recall and mAP metrics were used to assess the model performance with different confidence values. A precision of 98.3% in a threshold of 0.9 was reached, Recall of 98.5% in a threshold of 0.85. Data augmentation techniques were important to increase the dataset and to have a more realistic model for individuals’ detection. The method used allowed us to identify all the complete pigs’ bodies under different posture and lighting situations.

Deterministic simulations using the SWAN model were conducted along a stretch of the Tietê-Paraná waterway in the Ilha Solteira dam reservoir, São Paulo, Brazil, to assess the water waves generated by winds. Simultaneously employs a probabilistic metamodeling approach (PCE) and Sobol indices, to quantify uncertainty of the five involved physical parameters (wind velocity and direction, bottom friction (JONSWAP), whitecapping and depth-induced breaking index). In the deterministic part, Janssen’s formulation yielded the most successful and accurate estimations of wave heights. Probabilistic analysis underscored the importance of wind data and the whitecapping parameter in model calibration, with a significant influence of wind speed indicated by Sobol indices. The results not only refined the model calibration process, but also allowed the creation of contour maps for wave height and period that offer practical pre-project applications. This work advances understanding of wind wave hydrodynamics deterministically and probabilistically, with good concordance and performance indices compared to field data, despite being scarce.

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

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

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

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

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

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

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

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

China has formally applied to join the CPTPP. It is a realistic issue to comprehensively assess the possible impact of CPTPP labor provisions on China and explore effective countermeasures and measures. Vietnam, as the only socialist country among CPTPP member states, has revised its domestic labor law internally to build a dual labor union system, concluded FTAs externally and fought for a transitional period in the form of signing side letters to fulfill its obligations under the CPTPP, which has certain reference value for China. In recent years, the economic and trade agreements signed by China have adopted a more open attitude towards labor rules, and the current domestic laws have basically implemented the ILO’s requirements on core labor standards at the level of textual provisions, but there is still a certain gap between the concrete implementation and the substantive requirements of the CPTPP labor rules at the level of dispute settlement. In particular, influenced by the “aggressive interpretation” of labor obligations in the dispute settlement panel report of the EU-Korea labor case, the binding dispute settlement mechanism of the CPTPP may raise the requirements of labor obligations, and China should make thorough and comprehensive risk assessment and preparation for this, and actively participate in a multi-level and differentiated plan based on China’s actual needs, partial freezing and continuous follow-up.

Background: Alzheimer's disease (AD) dementia and Mild Cognitive Impairment (MCI) are currently underdiagnosed in the community. Early detection of cognitive deficits is crucial for timely intervention. FACEmemory®, the first completely self-administered online memory test with voice recognition, has been launched as an accessible tool to detect such deficits. This study aims to correlate FACEmemory subscores with traditional neuropsychological tests and to develop an algorithm to distinguish between cognitively healthy (CH) individuals and those with MCI. Methods: A total of 669 participants (266 CH, 206 with non-amnestic MCI -naMCI-, and 197 with amnestic MCI -aMCI-) were included. Pearson’s correlations were conducted to examine the association between FACEmemory scores, demographics, and cognitive performance on classical neuropsychological tests (the Neuropsychological battery of Ace -NBACE-). Machine learning models were compared to find the best algorithm for distinguishing between CH and MCI (whole MCI, aMCI, and naMCI). Results: FACEmemory scores showed significant correlations (p&lt; 0.001) with memory (r= 0.53), executive functions (r= 0.43), visuospatial/visuoperceptual (r= 0.32), language (r= 0.30), praxis (r= 0.30) and attention (r= 0.26) domains of the NBACE. The best algorithm distinguished between CH and MCI (especially aMCI), with a FACEmemory cutoff score of 44.5, yielding sensitivity and specificity values of 0.81 and 0.72, respectively. Conclusions: FACEmemory is a promising online tool for detecting MCI, particularly aMCI. It could play a key role in reducing underdiagnoses of MCI and AD and supporting early intervention efforts in the community.

We present a simple proof of the well-known axiomatic characterization of state-salient decision rules on the domain of all strict preference profiles, using Pareto property and Global Independence of Irrelevant Alternatives. Our proof appeals to Sen’s Impossibility Theorem and an extract from a proof of the same theorem, that is available in an earlier paper of this author.

Objectives: To evaluate the possible long-term cerebral deposition of amyloid-β in PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and its possible influence on axial and cognitive variables. Methods: Consecutive PD patients treated with bilateral STN-DBS with a long-term follow-up were included. Amyloid-β deposition was evaluated postoperatively through a 18F-flutemetamol positron emission tomography (PET) study. Axial symptoms have been assessed using a standardized clinical-instrumental approach. Speech was assessed by perceptual and acoustic analysis while gait by means of the instrumented timed up and go test (iTUG). Motor severity was evaluated applying the UPDRS part III score and subscores while cognitive functions through a complete neuropsychological assessment. Different stimulation and drug conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, on-stimulation/on-medication conditions (single and dual task). Results: 19 PD patients (male: 11; age: 63.52 years; on-stimulation/on-medication UPDRS-III: 17.05) with a five-year postoperative follow-up were included. Amyloid-β deposition was found in 21% of patients (4/19) with a prevalent involvement of prefrontal, limbic and parietal areas. Compared with patients without amyloid-β deposition, PD patients with positive 18F-flutemetamol PET study showed higher preoperative UPDRS-I (p=.037) score and lower postoperative Raven's matrices scores (p=.05). Conclusions: Our results suggest that in the long-term after STN-DBS a significant percentage of PD patients may present brain amyloid-β deposition. However, larger samples are needed to evaluate the possible role of amyloid-β deposition in the development of axial and cognitive alterations after surgery.

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by symptoms such as tremors, dementia, and bradykinesia. Early non-motor signs, including constipation and hyposmia, suggest a potential connection between PD and the gut. The loss of dopaminergic neurons in the substantia nigra is a hallmark of PD, with unknown causes. While current treatments provide symptom relief, there are no therapies to slow the progression of the disease. The gut microbiota plays a role in inflammatory and immune responses and has been implicated in neurological disorders. The connection between gut microbiota and neurodegenerative disease remains unclear. In this paper, we aim to explore the potential link between gut microbiome dysbiosis in PD, focusing on constipation, which is an early symptom of the disease. Our review will examine the evidence that suggests the possibility of chronic intestinal inflammation that may contribute to the development of Parkinson’s disease and implicate further connections with other neurodegenerative diseases.

Malignant lymphoma is an unusual form of gallbladder neoplasm. Almost all of these tumors are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas. Herein, we report a rare case of a gallbladder Burkitt’s lymphoma (BL) in a child living with HIV. As far as we are concerned, this is the secondfirst report in the pediatric population and the first one in an individual living with HIV. The patient (a five-year-old black female child) attended the Federal Hospital of Lagoa, Rio de Janeiro, Brazil, underwent cholecystectomy and the postoperative pathological analysis of the gallbladder revealed a diagnosis of BL (EBV-positive). Also, HIV serology was performed and returned positive. She was transferred to the Martagão Gesteira Institute of Pediatrics and Childcare for oncological treatment, dying from sepsis and disease progression about 18 months later. Patient did not undergo ART/cART. Previous cases of gallbladder BL were herein described and analyzed to characterize the clinicopathological features and possible similarities. BL can occur in the gallbladder both in the context of HIV infection and in the pediatric population. Biopsy is mandatory in cases with suggestive findings of lymphoma, and an early diagnosis can change the course of the disease. Furthermore, the case highlights the importance of an early initiation of ART/cART in people living with HIV (PLWH).

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n=42) and major NCD (n=164) through DSM-5 criteria on 206 participants aged>65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (=-1.05-p<.0001) and minor NCD (=-0.06-p<.01). In the fully-adjusted multivariate regression model (sex-age-education-multimorbidity-depressive symptoms-antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (=0.09-p<.001). The effect of loneliness on IADL (=-0.26-p<.0001) and ADL (=-0.24-p<.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL:=0.26-p<.0001-ADL:=0.05-p=0.01). Minor NCD displayed different levels of MMSE (=6.68-p<.001), but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill’s test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD.

Nonlinear single unit activity (SUA) characteristics are the useful measures to reveal the information processing and transfer features associated with Parkinson’s disease (PD) in the basal ganglia. Most of the state-of-the-art approaches to compute such parameters in continuous and discrete forms are strongly dependent on SUA recording length, noise level and input parameters. Due to the specificity of SUA data collection (mainly short recordings with relatively low signal-to-noise ratio) new techniques to evaluate neuronal nonlinear properties are needed. We have developed an encoding technique based on a mean interspike interval (ISI) value to calculate spike train discrete nonlinear features. The approach to compute mutual information (MI) of isolated neurons with its unstructured activity was also proposed. The proposed technique of SUA nonlinear features evaluation slightly depends on spike train length, has low correlations with other SUA characteristics (firing rate, coefficient of ISI variance and asymmetry index). The derived entropy measure in the subthalamic nucleus has significant positive correlation with PD severity. The proposed approach provides nonlinear features that are slightly dependent on investigated sample size and independent on input parameters. Also, the developed mean ISI based measures reflect the more complex nature of oscillatory activity in the basal ganglia, than it was thought previously. Moreover, MI, unlike entropy, takes into account the position of the spike train elements, which allows us to investigate the amount of information retained after the occurrence of temporary failures. The developed approach may be useful in describing nonlinear features of basal ganglia activity contributing to PD pathophysiology probably associated with impaired information transfer in movement disorders.

I demonstrate that Bell's theorem is based on circular reasoning and thus a fundamentally flawed argument. It unjustifiably assumes the additivity of expectation values for dispersion-free states of contextual hidden variable theories for non-commuting observables involved in Bell-test experiments, which is tautologous to assuming the bounds of ±2 on the Bell-CHSH sum of expectation values. Its premises thus assume in a different guise the bounds of ±2 it sets out to prove. Once this oversight is ameliorated from Bell's argument by identifying the impediment that leads to it and local realism is implemented correctly, the bounds on the Bell-CHSH sum of expectation values work out to be ±2√2 instead of ±2, thereby mitigating the conclusion of Bell's theorem. Consequently, what is ruled out by any of the Bell-test experiments is not local realism but the linear additivity of expectation values, which does not hold for non-commuting observables in any hidden variable theories to begin with. I also identify similar oversight in the GHZ variant of Bell's theorem, invalidating its claim of having found an inconsistency in the premisses of the argument by EPR for completing quantum mechanics. Conceptually, the oversight in both Bell's theorem and its GHZ variant traces back to the oversight in von~Neumann's theorem against hidden variable theories identified by Grete Hermann in the 1930s.

Glutamate transporter-1 (GLT-1) dynamics are implicated in excitotoxicity and Alzheimer's disease (AD) progression. Early stages of AD are often marked by hyperactivity and increased epileptiform activity preceding cognitive decline. Previously, we identified a direct interaction between GLT-1 and Presenilin 1 (PS1) in the brain, highlighting GLT-1 as a promising target in AD research. This study reports the significance of this interaction and uncovers a novel role of GLT-1 in modulating amyloid-beta (Aβ) production. Overexpression of GLT-1 in cells reduces the levels of Aβ40 and Aβ42 by decreasing γ-secretase activity pertinent to APP processing and induces a more "open" PS1 conformation, resulting in decreased Aβ42/40 ratio. Inhibition of the GLT-1/PS1 interaction using cell-permeable peptides produced an opposing effect on Aβ, highlighting the pivotal role of this interaction in regulating Aβ levels. These findings emphasize the potential of targeting GLT-1/PS1 interaction as a novel therapeutic strategy for AD.

Road safety and the effectiveness of the transportation system as a whole are significantly impacted by driver comfort. Road surface quality can play a significant part in the driver’s comfort experienced on roads in any country. This study employs a Random Forest technique to examine the association between road roughness and drivers' comfort during long-distance driving. Using Random Forest, a dependable machine learning technique that can handle big datasets and detect nonlinear correlations, this work aims to shed light on the complex dynamics between road conditions and driver’s comfort. 1,048,576 rows of data from MIRANDA, an application developed at the University of Gustave Eiffel, were used in this study as part of the data collected from a probe vehicle. The data collected includes an International Roughness Index (IRI). The IRI thresholds offer a simple method for assessing driver comfort and road irregularity. While highlighting how uneven and uncomfortable the road is, the research's findings (Road Roughness: SD – 0.73; Driver's Comfort: - Mean, 10.01, SD – 0.64) also contribute to the standardization of road condition evaluation and maintenance communication. This finding is anticipated to aid in the development of strategies for improving the welfare of long-haul drivers and fixing road infrastructure to comply with standard road index, ultimately leading to the creation of more efficient and sustainable transportation systems.

The energy transition towards Net Zero Emission by 2060 hinges on the renewable energy power plants in Indonesia. Good practices in several countries suggest a peer-to-peer (P2P) energy trading system using blockchain technology, supported by renewable energy (solar panels), an innovation to provide equal access to sustainable electricity while reducing the impact of climate change. The P2P energy trading concept has a higher social potential than the conventional electricity buying and selling approach, such as that of PLN (the grid management concept), but does not have a sharing element. This model implements a solar-powered mini-grid system and produces a Smart Contract that facilitates electricity network users to buy, sell, and trade electricity in rural areas via smartphones. This study aims to analyze the stakeholders' perceptions of the peer-to-peer (P2P) energy trading model using blockchain technology in Gumelar District, Banyumas Regency, Central Java Province, Indonesia. The stakeholders include households, the Ministry of Energy and Mineral Resources (ESDM), the State Electricity Company (PLN), the Institute for Essential Services Reform (IESR), Awina Company, and IPB University. The strength factors of this model are the freedom to generate and sell electricity (0.1) and transparency in electricity usage and sales by disclosing the amount, duration, and price of electricity (0.1). Regarding weakness factors, this model is primarily suitable for the lower middle class residing in rural or remote areas (0.02). Additionally, the intermittent electricity production to meet the substantial demand is a weakness (0.03). The opportunity factor for the model is the increase in public awareness and cooperation in using environmentally friendly, pollution-free electricity (0.12). Furthermore, there is an opportunity for additional income (0.12) and new business investment (0.12). Regarding threat factors, the model faces significant threats from the implementation aspect involving multiple parties (0.04). There is a potential threat in the form of losses for state utilities such as PLN or individuals who have already established electricity infrastructure if this program is implemented on a large scale (0.04). This model is located at the coordinate point (-0.40; 0.31), placing it in quadrant II. This indicates that the model should apply the Stability Strategy and focus on the Selective Maintenance Strategy for improvement. The stability strategy goal is to maintain the current situation by leveraging opportunities and addressing weaknesses. For effectiveness and efficiency, the strategy emphasizes fostering collaboration with PLN, which holds the legal authority as the sole utility company in Indonesia with an extensive electricity network, as well as advocating for regulations that support the independent purchase and sale of solar-powered electricity, particularly in areas without PLN network coverage.

The present study aimed to undertake a detailed investigation of pathological epidemiology and molecular confirmation of Ehrlichia canis among pet dogs in smart city Bhubaneswar, Odisha, a state in eastern India. A total of 178 dogs were screened for Ehrlichiosis on the basis of history, clinical signs, blood, and buffy coat smear examination, resulting in only 56 dogs (31.46%) screening positive. The epidemiological study recorded an increase in incidences among dogs less than one year of age (41%), males (68%), German Shepherds (25%), dogs more than 20 kg body weight (75%), summer months (55%) and dogs housed on pukka houses with exposure to the outside (59%). The majority of the infected dogs had a history of tick infestation (79%) at some point in their life. Clinical signs showed non-typical manifestations like fever, lethargy, diarrhoea, epistaxis, hind limb edema, and corneal opacity. Haematological studies revealed anaemia and thrombocytopenia along with neutrophilia with relative lymphopenia and monocytosis. A decreasing trend was observed in the levels of total protein and albumin with an increase in the levels of globulin, AST, ALT, BUN, and creatinine. The ultrasonography studies revealed hepatosplenomegaly along with hyper-echogenicity in various organs. Pro-teinuria and haematuria were consistent, along with the presence of bile salts in the urine of affected dogs. Molecular confirmation from n-type PCR data using Ehrlichia-specific primers targeting p28 gene (843 bp) was done, and the identified gene sequences submitted to NCBI databases have accession numbers OQ383671-OQ383674 and OP886674-OP886677. Ticks collected from dogs were identified morphologically through microscopy and scanning electron microscopy as Rhipicephalus sanguineus.

This paper presents a co-designed solution aimed at improving community healthcare assistance management. To enhance patients’ self-awareness of their health status, encouraging active participation in care process, and to support nurses in delivering patient-centered care, we have developed an innovative platform with a highly customized app. This platform was designed using a multi-disciplinary bottom-up approach. Patient data collection and processing facilitate the automation of care timeline planning, based on real time patients’ needs and the available resources. To achieve this goal different components have been considered: real-time health data collection and processing, patient care planning, decision support for nurses, secure communication for data transmission, and user-friendly interfaces to ensure easy access to platform functionalities.

In order to reduce the environmental impact of energy enterprises, it is important to promptly identify cases of possible changes in the quality of wastewater generated at power plants, that is cases of exceeding the maximum permissible concentrations of pollutants in wastewater. The goal of the method for detecting complex anomalies in multidimensional time series obtained from smart energy station’s sensor channels is to increase the accuracy of detecting pollution levels in industrial wastewater. To achieve this goal, the following tasks were solved: methods for detecting time series anomalies were analyzed, the method for detecting complex anomalies was developed, software implementation of the algorithm was carried out and experiments were conducted. The developed method is proposed to be used in an smart energy monitoring system.

In the extended malfatti problem, the numbers of circles in the triangle are triangle numbers, because the tangency properties among the internal circles and 3 sides of the triangle have special type of structure. That is, the corner circle tangent to two sides of the triangle and two boundary circles, the boundary circles tangent to one side of the triangle and 4 other circles, and the inner circles always tangent to 6 other circles. The circles we find in extended general Malfatti’s problem has the property that the smallest radius and the largest radius for the circle has big difference. In this paper, we proposed algorithms to solve the problem that the tangency properties among circles and sides of triangle is not fixed, so that the number of circles in the triangle is not necessary a triangle numbers. The purpose of this change is try to find the radii of the circles in the triangle is within a small range.

Crohn’s disease (CD) is a chronic inflammatory disease associated with a significant burden in terms of quality of life and health care costs and is frequently associated with several complications, including the development of intestinal strictures. Stricturing CD requires a careful multidisciplinary approach involving medical therapy and surgery, still posing a continuous management challenge; in this context, endoscopic treatment represents a valuable, in-between opportunity as a minimally invasive strategy, endorsed by extensive yet heterogeneous evidence and evolving research and techniques. This review summarizes current knowledge on the role of therapeutic endoscopy in stricturing CD, focusing on evidence gaps, recent updates, and novel techniques intended for optimizing efficacy, safety, and tailoring of this approach in the view of precision endoscopy.

This study aims to provide an understanding of the preferences of student tourists regarding service attributes related to domestic accommodation. To clarify how lodging firms formulate policies for the student travel market, a “Relative to an Identified Distribution” (RIDIT) analysis in which responses are treated as ordinal data instead of equally spaced data is performed to examine the Likert-scale data obtained from 296 university students in Taiwan. In our RIDIT analytical results, respondents’ preferences are sorted in a descending importance. Of the examined attributes, “Cleanliness of rooms” is the attribute most prioritized by the students, followed by “Located in a safe neighborhood/feeling safe in the room,” and “Close to scenic area for meeting the trip requirement.” The attribute least prioritized by the students is “Interaction with other guests.” This analysis provides conclusions that differ from those obtained through commonly used techniques including the arithmetic average and exploratory factor analysis. The preference rankings indicate that managers should focus on the most prioritized service attributes and implement the necessary measures to enhance their service quality and maximize customer satisfaction.

The green synthesis of metallic nanoparticles is an emerging and promising field owing to its environmentally friendly nature and diverse applications. In this article, a new technology for the green synthesis of functional ultrastable biopolymer gold nanoparticles is introduced. This approach employs thiolated single-stranded DNA (ssDNA-SH) aptamers instead of conventional self-assembled monolayers, resulting in the production of highly stable aptamer-tagged gold-core-shell nanoparticles. A comprehensive discussion on the use of glucose as a simple reducing agent for the green synthesis of Au nanoparticles and the utilization of ssDNA-SH aptamers as smart and biologically functional capping agents is provided. The potential of this innovative approach for the green synthesis of nanoparticles is demonstrated through a case study involving the use of the naked eye for qualitative detection of human fungal infections caused by Candida albicans for women's health.

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

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

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

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

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

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

Inflammatory bowel diseases, comprising Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing and remitting immune-mediated inflammatory diseases affecting the gastrointestinal tract. Ustekinumab (UST) is a monoclonal antibody blocking the p40 subunit of the anti-interleukin (IL) 12/23. Pivotal trials (CERTIFI and UNITI-IM for CD, UNIFI for UC) established the efficacy of UST for the induction and maintenance of remission in both CD and UC, with the most favorable results in naïve patients to biologics. In recent years, a wealth of ‘real-world’ data has emerged supporting positive clinical, endoscopic, and histological outcomes in patients treated with UST, as well as reassuring safety data. More recently, the results of the first head-to-head trials of UST and tumor necrosis factor (TNF) antagonists have been reported. Moreover, a number of studies exploring the role of UST in specific clinical settings, such as perianal CD, postoperative complications and recurrence, extraintestinal manifestations, chronic antibiotic-refractory pouchitis, and pregnancy, have been reported. This review explores results reported to date on UST, including those from pivotal trials, real-world data, and emerging studies regarding therapeutic drug monitoring and immunogenicity. The safety profile of UST was also reviewed.

This paper investigates the adaptability of four state-of-the-art Artificial Intelligence (AI) models to the Australian mammographic context through transfer learning, explores the impact of image enhancement on model performance and analyses the relationship between AI outputs and histopathological features for clinical relevance and accuracy assessment. A total of 1712 screening mammograms (n=856 cancer cases and n=856 matched normal cases) were used in this study. The 856 cases with cancer lesions were annotated by two expert radiologists and the level of concordance between their annotations was used to establish image subsets. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of Globally aware Multiple Instance Classifier (GMIC), Global-Local Activation Maps (GLAM), I&amp;H and End2End AI models, both in the pre-trained and transfer learning modes, with and without applying the Contrast Limited Adaptive Histogram Equalization (CLAHE) algorithm. The four AI models with and without transfer learning in the high-concordance subset outperformed those in the entire dataset. Applying the CLAHE algorithm to mammograms improved the performance of the AI models. In the high-concordance subset with transfer learning and CLAHE algorithm applied, the AUC of the GMIC model was highest (0.912), followed by GLAM model (0.909), I&amp;H (0.893) and End2End (0.875). There were significant differences (P&lt;0.05) in the performances of the four AI models between high-concordance subset and entire dataset. The AI models demonstrated significant differences in malignancy probability concerning different tumour size categories in mammograms. The performance of AI models was affected by several factors such as concordance classification, image enhancement and transfer learning. Mammograms with strong concordance of radiologists’ annotations, applying image enhancement and transfer learning could enhance the accuracy of AI models.

The Einstein’s Boxes paradox was developed by Einstein, de Broglie, Heisenberg, and others to demonstrate the incompleteness of the Copenhagen Formulation of quantum mechanics. I explain the paradox using the Copenhagen Formulation. I then show how a Time-Symmetric Formulation of quantum mechanics resolves the paradox in the way envisioned by Einstein and de Broglie. Finally, I describe an experiment that can distinguish between these two formulations.

Changing the symmetry of spin from SU(2) to the quaternion group, $Q_8$, has many ramifications. In this paper we first summarize the properties of Q-spin and then discuss some of those resulting changes.

Antibodies approved by the FDA are failing to treat neurological disorders, and recently, it was reported that these trials may have violated patient’s rights and subjected them to high, likely lethal risk. The challenge with developing antibodies to treat neurological orders is their almost negligible bioavailability, requiring high dosing that can be toxic. The high potency of these drugs should also be viewed considering the placebo effects since all antibodies have shown severe side effects that are not prevented by the placebo responses. In this critical and urgent advice to the FDA, I am suggesting a guideline amendment to all clinical trials requiring proof of sufficient bioavailability at the site of action, where it is known. For antibodies to cross the blood-brain barrier, there are proven solutions such as conjugating with transferrin protein, making clinical trials in its absence more questionable and unethical.

Single-stranded breaks (SSBs) are the most frequent DNA lesions threatening genomic integrity-understanding how DNA sensor proteins recognize certain SSB types is crucial for studies of the DNA repair pathways. During repair of damaged DNA the final SSB that is to be ligated contains a 5'-phosphorylated end. The present work employed molecular simulation (MD) of DNA with a phosphorylated break in solution to address multiple questions regarding the dynamics of the break site. How does the 5'-phosphate group behave before it initiates a connection with other biomolecules? What is the conformation of the SSB site when it is likely to be recognized by DNA repair factors once the DNA repair response is triggered? And how is the structure and dynamics of DNA affected by the presence of a break? For this purpose, a series of MD simulations of 20 base pair DNAs, each with either a pyrimidine-based or purine-based break, were completed at a combined length of over 20,000 ns simulation time and compared with intact DNA of the same sequence. An analysis of the DNA forms, translational and orientational helical parameters, local break site stiffness, bending angles, 5’-phosphate group orientation dynamics, and the effects of the protonation state of the break site phosphate group provides insights into the mechanism for the break site recognition.

This research arises from the need to rethink children’s play spaces found in the city through new manufacturing methods of Solid Surface materials such as Krion K-Life 1100 from the Porcelanosa Group, which allow the creation of complex ergonomic shapes. The method consisted of an iterative digital fabrication process, in which a series of molds were developed and adjusted to thermoform the Krion, adapting the design in each iteration according to the results obtained. Parametric digital modeling techniques and in-detph curvature analysis were used to optimize the geometry to meet the technical limitations of the material and the thermoforming process. The results showed that, through precise adjustments in the curvature and thickness of the surface, it is possible to thermoform Krion without defects such as folds or wrinkles, obtaining a complex modular and ergonomic surface suitable for children’s play. In conclusions, Krion is a viable material for the generation of complex double-curved geometries, thus opening up a range of possibilities from the creation of new children’s spaces to parametric facades optimized according to their location.

This scoping review aims to systematically examine and analyse the available literature on pure total talar dislocation, focusing on its epidemiology, clinical presentation, imaging techniques, surgical options, rehabilitation protocols, and complications. Following the PRISMA-ScR guidelines, a comprehensive search was conducted across PubMed, Web of Science, and Scopus databases. The search yielded 185 articles, from which 30 met the inclusion criteria, focusing on pure total talar dislocation without fractures. Data from each study were extracted, including patient demographics, injury characteristics, treatment methods, and outcomes. A total of 30 articles were included in this review after screening and quality assessment by five independent reviewers. The studies included case reports, case series, and reviews. Despite the heterogeneity of available studies, key findings suggested that early reduction, careful wound management, and soft tissue preservation are crucial in minimising complications such as avascular necrosis (AVN), post-traumatic arthritis, and infection. Long-term outcomes varied, and the risk of AVN remained high, particularly in cases with compromised blood supply to the talus. Pure total talar dislocation is a rare and challenging condition with no established management protocol. While talar reimplantation and joint fixation offer promising outcomes in preserving function, the risk of complications, particularly AVN, remains significant. Further research is needed to standardise treatment protocols and improve clinical outcomes for this rare but severe injury.

Apple proliferation is among the most important diseases in European fruit production. Early and reliable detection enables farmers to respond appropriately and to prevent further spreading of the disease. Traditional phenotyping approaches by human observers consider multiple symptoms, but these are difficult to measure automatically in the field. Therefore, we investigated the potential of hyperspectral imaging in combination with data analysis by machine learning algorithms to detect the symptoms solely based on the spectral signature of collected leaf samples. In the growing seasons 2019 and 2020, we collected a total of 1,160 leaf samples. Hyperspectral imaging with a dual camera setup in spectral bands from 400 nm to 2500 nm was accompanied with subsequent PCR analysis of the samples to provide reference data for the machine learning approaches. Data processing consists of preprocessing for segmentation of the leaf area, feature extraction, classification and subsequent analysis of relevance of spectral bands. Results show, that imaging multiple leaves of a tree enhances detection results, that spectral indices are a robust means to detect the diseased trees, and that the potentials of the full spectral range can be exploited using machine learning approaches.

(1) Background: This retrospective cohort study aimed to investigate the cephalometric evaluation of facial height ratio (FHR) and growth patterns. (2) Methods: We assessed facial height ratios, Y-axis to SN angle, and growth patterns in 94 participants from Timis county using digital cephalograms. Participants were categorized based on Angle’s classification. Cephalograms were digitally traced and analyzed using WebCeph imaging software. Statistical analysis was conducted using Python version 3.11.9. (3) Results: Significant correlations were observed between FHR and craniofacial development, particularly regarding hypodivergent growth patterns. In a sample of 94, molar classes showed varying patterns: Class I—33.3% hyperdivergent, 61.5% normodivergent, 33.3% hypodivergent. Class II—50% hyperdivergent, 30.8% normodivergent, 52% hypodivergent. Class III—16.7% hyperdivergent, 7.7% normodivergent, 14.7% hypodivergent. Y-axis to SN angle values were within normal limits across groups (Group I: 65.0 (IQR: 61.2-69.0), Group II: 65.0 (IQR: 62.0-69.0), Group III: 67.0 (IQR: 59.7- 69.0). A strong negative correlation was found between Y-axis to SN angle and Jarabak’s ratio (r = -0.72, p &lt; 0.001), highlighting the need for holistic assessment methods in orthodontic practice. (4) Conclusion: Patients from Timis county predominantly exhibit a hypodivergent growth pattern across all malocclusion types. Understanding these patterns is essential for comprehensive orthodontic treatment planning. Further research is needed to explore the implications of these findings on treatment outcomes and patient care.

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body’s oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as "hypoxic pockets." Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson’s disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, entailing several motor-related symptoms that contribute to a reduced quality of life in affected subjects. Recent advances in wearable technologies and computing resources have shown great potential for the assessment of PD-related symptoms. However, the potential applications (e.g., early diagnosis, prognosis and monitoring) and key features of digital biomarkers for motor symptoms of PD (DB-MS-PD) have not been comprehensively studied. This study aims to provide a state-of-the-art review of current digital biomarker definitions for PD, focusing on the use of wearable devices. This review systematically examines research articles from 2012 to 2024, focusing on key features and recent technologies in PD research. A total of 22 studies were included and thoroughly analyzed. Results indicate that DB-MS-PD can accurately distinguish patients with PD (PwPD) from healthy controls (HC), assess disease severity or treatment response, and detect motor symptoms. Large sample sizes, proper validation, non-invasive devices, and ecological monitoring make DB-MS-PD promising for improving PD management. Challenges include sample and method heterogeneity and lack of public datasets. Future studies can leverage evidence of the current literature to provide more effective and ready-to-use digital tools for monitoring PD.

State-of-the-art augmented-reality (AR) glasses record their position and orientation in space, enabling measurements and analyses of clinical gait-and-balance tests. This study’s objective was to evaluate concurrent validity and test-retest reliability for common clinical gait-and-balance tests in people with Parkinson’s disease: the Five Times Sit-To-Stand (FTSTS) and Timed Up-and-Go (TUG) tests. Position and orientation data was collected in 22 participants with Parkinson's disease using HoloLens 2 and Magic Leap 2 AR glasses, from which test-completion durations and durations of distinct sub-parts (e.g., sit-to-stand, turning) were derived and compared to reference systems and over test repetitions. Regarding concurrent validity, for both tests an excellent between-systems agreement was found for position and orientation time series and test-completion durations. Between-systems agreement for FTSTS (sub-)durations were all excellent, while TUG turning sub-durations were excellent (turn 1) and moderate (turn 2). Regarding test-retest reliability, the within-system test-retest variation in test-completion times and sub-durations was always much greater than the between-systems variation, implying that these (sub-)durations may be derived interchangeably from AR and reference-system data. In conclusion, AR data are of sufficient quality to evaluate gait and balance in people with Parkinson's disease, with valid quantification of test-completion durations and sub-durations of distinct FTSTS and TUG sub-parts.

Background: Our study investigates the prevalence and causes of injuries among undergraduate dental students during clinical sessions. Methods: The study was conducted at the Department of Dentistry, National and Kapodistrian University of Athens, focusing on injuries reported from 2021 to 2024. Data were collected through self-reported questionnaires and clinical records. The primary variables assessed included the type of injury, the instrument involved, the clinical procedure being performed, and the immediate actions taken post-injury. Serological testing was conducted on both students and patients to assess the risk of bloodborne pathogen transmission. Results: The findings revealed a high prevalence of injuries, with needles being the most common cause, followed by burs and dental probes. The most frequent injury type was piercing, primarily affecting the fingers. Periodontal treatments, restorative procedures, and endodontic treatments were the main activities leading to injuries. Despite normal medical records for most patients treated by injured students, serological testing showed significant positivity rates for HCV and HBV. It is noteworthy that most injured students demonstrated their commitment to safety by adhering to recommended post-exposure protocols, including wound cleaning, disinfecting, and serological testing. Our study highlights the critical need for enhanced biosafety awareness and training among dental students to reduce injury risks. Conclusions: These findings underline the necessity for integrated safety protocols and continuous education to improve clinical practices and ensure student safety.

The interaction of matter when separated by a distance is a fundamental question, whether such interactions occur through instantaneous action at a distance or retarded interaction (principle of locality)? While the mainstream consensus favors the principle of locality, instantaneous action at a distance offers certain advantages. Previously, instantaneous action at a distance has been viewed as an appearance or representation from specific gauge choices of electromagnetic potentials (retarded). In this paper, we propose a novel approach that combines Weber’s electrodynamics with the concept of vacuum polarization to explore a new possible connection between the two viewpoints: instantaneous action at a distance and the locality principle. This new approach aligns with the observation of locality in signal/energy propagation while retaining the notion of instantaneous action at a distance.

It has been empirically observed that the upper tail of the firm size distribution follows either the Pareto distribution or the Zipf distribution, with both patterns being explained by Gibrat’s law (Gabaix, 1999). This article analyzed firm revenue data from China, spanning from 2005 to 2013, to examine the whole range of the firm size distribution. Our empirical analysis revealed that firm revenue data over these years is well fitted by a three-parameter generalized Pareto distribution, with the fitted parameters indicating a dichotomy: The size distribution of large-sized firms, namely the upper tail, is asymptotically characterized by a Pareto distribution or a Zipf distribution, whereas the size distribution of smaller and medium-sized firms is approximated by an exponential distribution. This finding suggests that Gibrat’s law should be extended to account for the emergence of a generalized Pareto distribution.

Background: Swept-source anterior segment optical coherence tomography (SS-AS- OCT) is a suitable examination for the vitreolenticular interface. Methods: In a prospective study using Anterion (Heidelberg Engineering, Heidelberg, Germany) 102 eyes of 102 patients were examined, in pupil dilation, preoperatively and 6 times over 1-year follow-up. Preoperatively anterior hyaloid membrane (AHM) visibility was determined with Imaging App with high reliability. Postoperatively capsular bag–AHM distance was measured on six points by using Metrics App. Results: The AHM was visible in 18.6% preoperatively and postoperatively as well (Group 1), 49% of the preoperatively adherent AHMs became visible (Group 2A), 32.4% remained attached (Group 2B). Group 1: the average deepest point first day was 782.5 ± 324.1 microns, and it significantly differed from the later follow-up values. Group 2A: the average deepest value was 184.1 ± 220.1 microns, and there was no statistically significant difference between the postoperative visit values. The difference between the groups was statistically significant at every location and at each time points. Conclusions: AS-SS-OCT can be used to check BS both preoperatively(with limitations) and postoperatively.

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

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

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

Sequential properties can violate Bell-type inequalities without direct influence on each other, but only if detected in pairs. This is demonstrated below with theoretical arguments, and with a straightforward toy model. Rotating arrows can have transient qualities that produce maximal Bell violations with predetermined values. Any non-signaling phenomenon (classical, or non-classical) can also be interpreted as local.

There is a great need to develop research-based models for supporting collaboration between educational institutions. Collaboration models are needed, for example, to assist the transition from lower educational level to higher education or from higher education to work life. In this research, collaboration was conducted through a joint upper-secondary school and university course that addressed global challenges by using a project-based learning approach. There is a shortage of research exploring students’ perceptions of collaboration. Therefore, the main purpose of this qualitative case study is to explore the relevance of the joint course for students and university students. The research was guided by the following research question: What kind of relevance did the students experience in the joint project-based learning course? The data was gathered using questionnaires, interviews, and reflective study reports. The data was analyzed via theory-based content analysis where research-oriented relevance model was used as the analysis framework. The analysis framework enabled categorizing experienced relevance on individual, vocational and societal dimensions. Altogether, the analysis produced 7 relevance categories for upper-secondary students and 9 for university students. According to the analysis, upper-secondary school students felt that the course offered the most on an individual relevance dimension whereas university students experienced the vocational relevance dimension most diverse. As the main conclusion, this research produced new insights on the experienced relevance of upper-secondary level and higher education cooperation from the students’ point of view. The acquired knowledge can be useful for everyone developing new cross-institutional cooperation models.

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

Crohn’s disease is a chronic inflammatory bowel disease and despite an increase in the available drug treatments, many patients still require surgery at some point in their disease course. Stricturing and penetrating phenotypes of Crohn’s disease are less likely to respond to our current medical treatment and therefore, surgical intervention may be required. This is most commonly elective, planned surgery, thereby affording the opportunity to optimise medications, nutritional and inflammatory status, steroid use. Poor nutritional status and previous surgery increase the risk of postoperative complications. Preoperative optimisation has three main goals: reduction of postoperative complications, reduction of reoperation rates and reduction of postoperative recurrence rates. In this narrative review, we examine the role of nutritional intervention, medical optimisation pre- and postoperatively and the role of personalised prehabilitation in the reduction of postoperative complications.

This paper analyzes ServiceNow’s overall strategy, business model, mission, vision, and key strategic risks. ServiceNow, a platform-as-a-service provider, has experienced significant growth and is poised for further expansion. The paper identifies strategic risks such as legislative and regulatory challenges, strategy development and execution risks, and competition in the cloud computing industry. Using Porter’s Five Forces framework, the assignment explores these risks and proposes mitigation strategies. Recommendations are made to protect intellectual property, maintain customer loyalty through subscription models, and ensure innovation in response to evolving market demands.

The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn’s disease (CD), where microbiome dysregulation can alter immune responses leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of our recently developed probiotic+amylase blend in the SAMP1/YitFc (SAMP) mouse model of CD-like ileitis. Four groups of SAMP mice were gavaged for 56 days with: 1) probiotic strains + amylase (concentration: 0.25 mg/100 uL PBS); 2) only probiotics; 3) only amylase; PBS (vehicle-treated controls). Ilea were collected for GeoMx Digital Spatial Profiler (DSP) analysis and histological evaluation. Histology assessment for inflammation indicated a significantly reduced level of ileitis in mice administered probiotics+amylase blend. DSP analysis showed decreased abundance of neutrophils and increased abundance of dendritic cells, innate lymphoid cells and macrophages, with a significant enrichment of five intracellular pathways related to apoptosis, in probiotics+amylase treated mice. Increased apoptosis occurrence was confirmed by TUNEL assay. Our data demonstrate a beneficial role of the probiotic and amylase blend, highlighting an increased apoptosis of innate immunity-associated cell subsets, thus promoting the resolution of inflammation. Hence, we suggest that our recently developed probiotic blend may be a therapeutic tool to manage CD and therefore could be a candidate compound to be tested in clinical trials.

Bacillus amyloliquefaciens GL18 has been proven to have good resistance ability and can promote the growth of Avena sativa cultivar ‘Qingyan 1’. Herein, Illumina high-throughput transcriptome sequencing technology was used to analyze the differential expression of genes between the interaction group (LB) and the control group (LCK) when ‘Qingyan 1’ roots interacted with GL18 bacterial suspension or sterile water for 12 h under 4 °C low-temperature stress. The gene function annotation information was obtained using Gene Ontology (GO) functional classification and enrichment analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and annotation of differentially expressed genes was used to explore the related signal transduction pathway of ‘Qingyan 1’ response to cold stress induced by Bacillus GL18. The results showed that after ‘Qingyan 1’ seedlings interacted with GL18 bacterial suspension or sterile water for 12 h, comparing the LB with the LCK or CK (the control group at 26 °C), there were 12,061 and 25,489 differentially expressed genes, respectively. Their functions were mainly related to metabolic process, cellular process, catalytic activity, binding, and cellular parts, and they were significantly enriched in plant tissue growth and development, cell wall, organelle membrane synthesis, thiamine and its compounds, biosynthesis, polyamine decomposition, and other metabolic processes. Signal transduction was detected through KEGG pathway enrichment analysis, and corresponding genes, such as AUXI, PP2C, SNRK2, ABF, BRI1, and PIF4, were expressed. The expression of genes directly involved in plant growth was upregulated in the presence of GL18, as shown by real-time quantitative PCR analysis. It was speculated that the normal growth and development of ‘Qingyan 1’ under low-temperature stress promoted by GL18 is a result of the integration of multiple pathways in terms of regulating endogenous hormone metabolism, secondary metabolite synthesis, and photosynthesis.