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Resumen: Las ataxias hereditarias (AH) y paraparesias espásticas hereditarias son enfermedades raras, poco frecuentes en las consultas del neurólogo general. Proponemos una guía práctica y breve de diagnóstico y manejo de estos pacientes, así como un procedimiento para la evaluación integrada del grado de su discapacidad. Se describen por apartados los conceptos y definiciones de AH y AH-plus y paraparesias espásticas hereditarias pura y complicada, la valoración clínica de los pacientes con las principales pruebas complementarias a realizar, las escalas clínicas necesarias para poder graduar la condición física y psíquica de los pacientes, y se resumen los tratamientos disponibles. Esta guía pretende facilitar la asistencia clínica diaria por parte del neurólogo y unificar los criterios médicos y la metodología de evaluación de la discapacidad de los pacientes con AH y paraparesias espásticas hereditarias. Abstract: Hereditary ataxia (HA) and hereditary spastic paraplegia are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and “HA plus,” and “pure” and “complicated” hereditary spastic paraplegia; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and hereditary spastic paraplegia.

Hereditary ataxia (HA) and hereditary spastic paraplegia (HSP) are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and “HA plus,” and “pure” and “complicated” HSP; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and HSP. Resumen: Las ataxias hereditarias (AH) y paraparesias espásticas hereditarias (PEH) son enfermedades raras, poco frecuentes en las consultas del neurólogo general. Proponemos una guía práctica y breve de diagnóstico y manejo de estos pacientes, así como un procedimiento para la evaluación integrada del grado de su discapacidad. Se describen por apartados los conceptos y definiciones de AH y AH-plus y PEH pura y complicada, la valoración clínica de los pacientes con las principales pruebas complementarias a realizar, las escalas clínicas necesarias para poder graduar la condición física y psíquica de los pacientes, y se resumen los tratamientos disponibles. Esta guía pretende facilitar la asistencia clínica diaria por parte del neurólogo y unificar los criterios médicos y la metodología de evaluación de la discapacidad de los pacientes con AH y paraparesias espásticas hereditarias.

In the late stages of the HIV-1 life cycle, membrane localization and self-assembly of Gag polyproteins induce membrane deformation and budding. Release of the virion requires direct interaction between immature Gag lattice and upstream ESCRT machinery at the viral budding site, followed by assembly of downstream ESCRT-III factors, culminating in membrane scission. However, molecular details of upstream ESCRT assembly dynamics at the viral budding site remain unclear. In this work, using coarse-grained (CG) molecular dynamics (MD) simulations, we investigated the interactions between Gag, ESCRT-I, ESCRT-II, and membrane to delineate the dynamical mechanisms by which upstream ESCRTs assemble templated by late-stage immature Gag lattice. We first systematically derived "bottom-up" CG molecular models and interactions of upstream ESCRT proteins from experimental structural data and extensive all-atom MD simulations. Using these molecular models, we performed CG MD simulations of ESCRT-I oligomerization and ESCRT-I/II supercomplex formation at the neck of the budding virion. Our simulations demonstrate that ESCRT-I can effectively oligomerize to higher-order complexes templated by the immature Gag lattice both in the absence of ESCRT-II and when multiple copies of ESCRT-II are localized at the bud neck. The ESCRT-I/II supercomplexes formed in our simulations exhibit predominantly columnar structures, which has important implications for the nucleation pathway of downstream ESCRT-III polymers. Importantly, ESCRT-I/II supercomplexes bound to Gag initiate membrane neck constriction by pulling the inner edge of the bud neck closer to the ESCRT-I headpiece ring. Our findings serve to elucidate a network of interactions between upstream ESCRT machinery, immature Gag lattice, and membrane neck that regulate protein assembly dynamics at the HIV-1 budding site.

Objective: Effective clinical training is essential for healthcare personnel with clinical skill requirements. This studyaimed to identify an effective learning medium for anesthesia residents by comparing text-based and video-based online training. Materials and Methods: This online, randomized, multicenter study was conducted between October 2020 and March 2021. Three Thai institutions were involved: the Faculty of Medicine Siriraj Hospital, Mahidol University; the Faculty of Medicine, Ramathibodi Hospital, Mahidol University; and the Faculty of Medicine, Songklanagarind Hospital, Prince of Songkla University. In all, 126 anesthesia residents were randomized into a “text group” and a “video group.” Four residents were excluded due to contamination of their learning material. The 122 eligible students undertook 3 knowledge and skill assessments (“Pretest,” “24-hour posttest,” and “3-month posttest”). The primary outcome was the gain score after training. This was measured in 2 ways: the difference between the 24-hour posttest and Pretest scores and the difference between the 3-month posttest and Pretest scores. Results: The mean gain scores for Pretest and 24-hour posttest were higher in the text group with no significant difference (P = 0.347). The mean differences between the 3-month posttest and Pretest scores were higher in the text group without a significant difference (P = 0.488). The mean satisfaction score was higher in the video group. Conclusion: Video-based e-learning training provided better satisfaction without significantly improving gain scores compared to text-based e-learning training. Online video-based was beneficial over text-based for ease of understanding in clinical learning points.

Abstract Background Cellular iron homeostasis is regulated by iron regulatory proteins (IRP1 and IRP2) that sense iron levels (and other metabolic cues) and modulate mRNA translation or stability via interaction with iron regulatory elements (IREs). IRP2 is viewed as the primary regulator in the liver, yet our previous datasets showing diurnal rhythms for certain IRE-containing mRNAs suggest a nuanced temporal control mechanism. The purpose of this study is to gain insights into the daily regulatory dynamics across IRE-bearing mRNAs, specific IRP involvement, and underlying systemic and cellular rhythmicity cues in mouse liver. Results We uncover high-amplitude diurnal oscillations in the regulation of key IRE-containing transcripts in the liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light–dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this timepoint still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic. Conclusions Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.

Introduction: Ethical leadership is leadership focused on appropriate behavior through respect for ethics and values, as well as the rights and dignity of others. Ethical leadership can add value to businesses by motivating employees and fulfilling company values. Therefore, the present research was conducted with the aim of analyzing the relationship between ethical leadership and cooperative social responsibility and the moral climate of the organization. Material & Methods: The current research is applied in terms of purpose and descriptive and correlational in terms of data collection method. The statistical population of this research included all employees of Management and Science University (MSU) in Malaysia. Among them, 200 people were selected as the research sample using a simple random sampling method. A standard questionnaire was used to collect data. The data was analyzed by structural equation modeling method. Results: The results of statistical analysis showed that ethical leadership has a direct and positive effect on cooperative social responsibility and ethical climate. Also, moral climate has a direct and positive effect on cooperative social responsibility. At the same time, ethical leadership has an indirect and positive effect on cooperative social responsibility through the mediation of ethical climate. Conclusion: Ethical leadership can affect their social responsibility by inspiring employees to motivate and align with the company's values. The results of this research showed that ethical leadership leads to greater employee satisfaction and collaborative responsibility and leads to the formation of an ethical atmosphere in the organization

Objectives: Impact of frailty towards immunogenicity and reactogenicity of BNT162b2 boosters administered via intramuscular or intradermal routes in a Thai geriatric population Design: Prospective, randomized, open-labeled. Setting: Siriraj Hospital, Thailand. Participants: Geriatric adults aged ≥65 years. Intervention: 10 μg intradermal or 30 μg intramuscular BNT162b2 (Pfizer-BioNTech). Measurements: Anti-SARS-CoV-2 receptor binding domain IgG, neutralizing antibodies (NAb), and interferon-gamma producing cells against Wuhan and Omicron BA.4/5. Analyses were stratified based on participants’ Clinical Frailty Scale. Results: A total of 139 participants were included in the analysis. Two-four weeks post-booster administration, NAb titers against Wuhan but not Omicron BA.4/5 were significantly lower among frail participants than non-frail participants who received intramuscular administration. Spike-specific T cell responses were similar for frail and non-frail participants, regardless of administration route. Frail participants who received intradermal BNT162b2 had fewer local adverse events (AEs), but higher systemic AEs than non-frail participants. Conclusion: Similar immune responses across vaccine routes warrants further evaluation of intradermal BNT162b2 in frail geriatric populations. Frail participants may be more sensitive to reporting systemic AEs. Registration of clinical trials: The parent study was registered under the Thai Clinical Trials Registry (TCTR20220112002).

In this study, we adapted an HP D100 Single Cell Dispenser – a novel low-cost thermal inkjet (TIJ) platform with impedance-based single cell detection – for dispensing of individual cells and one-pot sample preparation. We repeatedly achieved label-free identification of up to 1,300 proteins from a single cell in a single run using an Orbitrap Fusion Lumos Mass Spectrometer coupled to either an Acquity UPLC M-class system or a Vanquish Neo UHPLC system. The developed sample processing workflow is highly reproducible, robust, and applicable to standardized 384- and 1536-well microplates, as well as glass LC vials. We demonstrate the applicability of the method for proteomics of single cells from multiple cell lines, mixed cell suspensions, and glioblastoma tumor spheroids. As additional proof of robustness, we monitored the results of genetic manipulations and the expression of engineered proteins in individual cells. Our cost-effective and robust single-cell proteomics workflow can be transferred to other labs interested in studying cells at the individual cell level.

BackgroundGlioblastoma (GBM) is a poor prognosis grade 4 glioma. After surgical resection, the standard therapy consists of concurrent radiotherapy (RT) and temozolomide (TMZ) followed by TMZ alone. Our previous data on melanoma patients showed that Dendritic Cell vaccination (DCvax) could increase the amount of intratumoral-activated cytotoxic T lymphocytesMethodsThis is a single-arm, monocentric, phase II trial in two steps according to Simon’s design. The trial aims to evaluate progression-free survival (PFS) at three months and the safety of a DCvax integrated with standard therapy in resected GBM patients. DCvax administration begins after completion of RT-CTwith weekly administrations for 4 weeks, then is alternated monthly with TMZ cycles. The primary endpoints are PFS at three months and safety. One of the secondary objectives is to evaluate the immune response both in vitro and in vivo (DTH skin test).ResultsBy December 2022, the first pre-planned step of the study was concluded with the enrollment, treatment and follow up of 9 evaluable patients. Two patients had progressed within three months after leukapheresis, but none had experienced DCvax-related G3-4 toxicities Five patients experienced a positive DTH test towards KLH and one of these also towards autologous tumor homogenate. The median PFS from leukapheresis was 11.3 months and 12.2 months from surgery.ConclusionsThis combination therapy is well-tolerated, and the two endpoints required for the first step have been achieved. Therefore, the study will proceed to enroll the remaining 19 patients. (Eudract number: 2020-003755-15 https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-003755-15/IT)

Data from real systems is an important resource for research in machine diagnostics and prognostics. The demand for data has increased exponentially in recent years due to the growing interest in prognostics and the development of AI technologies for predictive maintenance. When used for fault detection and predictive maintenance, data must be able to provide information about the degradation phenomena that occur in machines. In addition, one goal of prognostics is to predict the remaining useful life (RUL), which requires a large amount of data to apply data-driven techniques or validate physics-based models. Bearings are subject to a wide range of loads and fatigue stresses, and their failure can be catastrophic for the entire machine or plant. The Department of Engineering of the University of Ferrara has carried out an extensive experimental campaign to record the evolution of vibration signals throughout the life of self-aligning double row rolling element bearings. Six accelerated run-to-failure tests were performed, while the acceleration signals were continuously recorded by a uniaxial accelerometer. A radial load was applied to the bearing housing and controlled by a load cell. The shaft speed was kept constant and controlled by an electric motor driven by an inverter. The data set provided contains acceleration signals in the radial direction for the entire duration of the tests and can be used for research or industrial purposes.

Academic interest in understanding the role of financial technology (FinTech) in sustainable development has grown exponentially in recent years. Many studies have highlighted the context, yet no reviews have explored the integration of FinTech and sustainability through the lens of the banking aspect. Therefore, this study sheds light on the literature trends associated with FinTech and sustainable banking using an integrated bibliometric and systematic literature review (SLR). The bibliometric analysis explored publication trends, keyword analysis, top publisher, and author analysis. With the SLR approach, we pondered the theory-context-characteristics-methods (TCCM) framework with 44 articles published from 2002 to 2023. The findings presented a substantial nexus between FinTech and sustainable banking, showing an incremental interest among global scholars. We also provided a comprehensive finding regarding the dominant theories (i.e., technology acceptance model and autoregressive distributed lag model), specific contexts (i.e., industries and countries), characteristics (i.e., independent, dependent, moderating, and mediating variables), and methods (i.e., research approaches and tools). This review is the first to identify the less explored tie between FinTech and sustainable banking. The findings may help policymakers, banking service providers, and academicians understand the necessity of FinTech in sustainable banking. The future research agenda of this review will also facilitate future researchers to explore the research domain to find new insights.

A novel data acquisition system for condition monitoring and predictive maintenance of mechanical parts, machinery, and industrial plants is presented. Current commercial solutions rely on an analog architecture and a star topology, in which all transducers are connected to a centralized acquisition unit. Usually this requires long shielded cables, which are sensitive to electromagnetic disturbances, always present in industrial environments. The proposed solution makes use of a digital bus implemented on an Unshielded Twisted Pair to connect one or more Acquisition Nodes to a data storage system (e.g., a laptop or an industrial computer). The wiring is simplified, cabling cost is reduced, high disturbance rejection is obtained, at the same time ensuring synchronization between all signals, mandatory for the computation of the most advanced diagnostic metrics. The performance and effectiveness of the developed system are proved in comparison with a top-quality, laboratory-grade commercial solution. A 10-days experiment was performed on a radial bearing mounted on a bearing test bench, by employing both systems side-by-side. Early-stage damage identification will be demonstrated with the described solution, despite costing a fraction and offering numerous advantages for industrial applications with respect to products currently available on the market.

Graph neural network (GNN) is a formidable deep learning framework that enables the analysis and modeling of intricate relationships present in data structured as graphs. In recent years, a burgeoning interest has arisen in exploiting the latent capabilities of GNN for healthcare-based applications, capitalizing on their aptitude for modeling complex relationships and unearthing profound insights from graph-structured data. However, to the best of our knowledge, no study has systemically reviewed the GNN studies conducted in the healthcare domain. This study has furnished an all-encompassing and erudite overview of the prevailing cutting-edge research on GNN in healthcare. Through analysis and assimilation of studies, current research trends, recurrent challenges, and promising future opportunities in GNN for healthcare applications have been identified. China emerged as the leading country to conduct GNN-based studies in the healthcare domain, followed by the USA, UK, and Turkey. Among various aspects of healthcare, disease prediction and drug discovery emerge as the most prominent areas of focus for GNN application, indicating the potential of GNN for advancing diagnostic and therapeutic approaches. This study proposed research questions regarding diverse aspects of GNN in the healthcare domain and addressed them through an in-depth analysis. This study can provide practitioners and researchers with profound insights into the current landscape of GNN applications in healthcare and can guide healthcare institutes, researchers, and governments by demonstrating the ways in which GNN can contribute to the development of effective and efficient healthcare systems.

Although edible insects (EIs) are encouraged as a sustainable source of protein, their consumption is not as generalised as other types of food that are internationally accepted. While in some regions of the world, EIs are part of the gastronomic and cultural traditions, in other regions, people are not so receptive to this type of food, and some people even express some disgust towards it. Hence, this research focused on the habits of the participants regarding the consumption of insects as well as their perceptions about EIs being or not a part of the local culture or gastronomic patrimony. A questionnaire survey was implemented in fourteen countries (Brazil, Croatia, Greece, Latvia, Lebanon, Lithuania, Mexico, Poland, Portugal, Romania, Serbia, Slovenia, Spain, and Turkey), and globally, 7222 adult participants responded to the questionnaire. SPSS software (version 28) was used to process the data and carry out chi-square tests and Factor Analyses (FA). The obtained results showed significant differences between countries for all the questions included in the survey, either those regarding the habits of the participants or their opinions about the facts linked with EI tradition or cultural aspects. It was found that participants from Mexico consume EIs more than in all other countries and that strong motivations that would lead to consumption among those who do not consume include curiosity and food shortage. The solution obtained with FA considering the ten statements of the scale consisted of two factors: F1—Culture and Tradition of EIs (α = 0.675) and F2—Acceptance of EIs (α = 0.614). In conclusion, the consumption of EIs and the perceptions of people are highly variable according to geographic location and cultural environment.

Reading is the most basic tool used in learning and acquiring knowledge. Reading skills gained through education plays an active role in gaining different kinds of knowledge and skills in school life. It is very important for students to have sufficient reading skills in the first grades of primary school. Because this skill plays a key role in success when faced with advanced academic education throughout their education. Otherwise, the student is unable to fulfill the overlapping academic responsibilities and develops a negative attitude towards school and education. Qualitative research method was used in the research. The study group consists of 76 classroom teachers working in various primary schools in Izmir in the 2019-2020 academic year. The personal information form questionnaire and open-ended questions developed by the researcher were asked to the study group, the obtained answers were analyzed with the content analysis method and the results were interpreted.

This study aims to develop a measurement tool that will enable the determination of school administrators' and teachers' opinions on educational technologies. The items prepared by scanning the literature were presented to the opinions of the experts. Following the opinions, the 51-item trial form was applied to a total of 406 administrators and teachers, 249 women and 157 men working in the project high schools in the central and districts of Izmir in the 2018-2019 spring term for pre-application. The results of the factor analysis showed that the scale had four factors explaining 55.64% of the total variance. The last application was performed with a total of 636 administrators and teachers, including 385 women and 251 men, and the construct validity of the measurement tool was reevaluated. Exploratory factor analysis was applied, and it was deemed appropriate to continue the analysis with 37 variables and six factors consisting of these variables. It was determined that the six factors obtained explained 60.17% of the total variance. The determined factors are; "Concerns about educational technologies", "opinions about the contribution of educational technologies to education", "opinions about the concept of educational technologies", "criticisms about educational technologies", "benefits related to the use of educational technologies in educational environments" and "opinions about the scope of educational technologies". As a result of the confirmatory factor analysis performed with the data set, it seems that the ratio of the scale's Chi-square Test (?[superscript 2]) to degrees of freedom (X[superscript 2]/df) is 4.1; GFI, 0.88; CFI, 0.95; NFI, 0.95; NNFI, 0.95; IFI, 0.95; RMSEA, 0.08; and SRMR, 0.05. Considering the suggested values in the literature, it is seen that GFI is slightly below the limit, RMSEA and ?[superscript 2]/df are acceptable, while other fit indices are excellent. Since the fit indexes should be evaluated as a whole, the scale can be said to have a good structure. Cronbach Alpha internal consistency coefficient of the scale whose reliability studies were completed was determined as [alpha]=0.89.

Introduction and aimsTreatment-resistant depression (TRD) occurs when at least two different antidepressants, taken at the right dosage, for adequate period of time and with continuity, fail to give positive clinical effects. Esketamine, the S-enantiomer of ketamine, was recently approved for TRD treatment from U.S. Food and Drug Administration and European Medicine Agency. Despite proved clinical efficacy, many misconceptions by clinicians and patients accompany this medication. We aimed to review the most common “false myths” regarding TRD and esketemine, counterarguing with evidence-based facts.MethodsThe keywords “esketamine”, “treatment resistance depression”, “depression”, “myth”, “mythology”, “pharmacological treatment”, and “misunderstanding” were entered in the main databases and combined through Boolean operators.ResultsMisconceptions regarding the TRD prevalence, clinical features and predictors have been found. With respect of esketamine, criteria to start treatment, dissociative symptoms, potential addiction and aspects of administration and monitoring, were found to be affected by false beliefs by clinicians and patients.Discussion and conclusionTRD represents a challenging condition, requiring precise diagnosis in order to achieve patient’s full recovery. Esketamine has been proved as an effective medication to treat TRD, although it requires precautions. Evidence can inform clinical practice, in order to offer this innovative treatment to all patients with TRD.

Abstract Acquired perforating dermatosis (APD) is a disorder of transepidermal elimination of keratin, collagen or elastic fibers. APD is mainly associated with diabetes mellitus and chronic kidney disease. We present the case of a 66‐year‐old male, poorly controlled diabetic with peripheral arterial disease, obesity, arterial hypertension, Cushing's syndrome and chronic kidney disease requiring hemodialysis who develops an acquired perforating dermatosis. Due to the patient's comorbidities, treatment with corticosteroids, cyclosporine and phototherapy is not possible. He does not respond to gabapentinoids or allopurinol. The outbreaks of skin lesions and pruritus were accentuated in situations of renal function deterioration; however, hemodialysis did not improve her dermatosis, causing a great deterioration of her quality of life. It was decided to start treatment with dupilumab with the dosage used in atopic dermatitis, achieving a complete response of both pruritus and skin lesions. With this case, we want to show how dupilumab can be an effective tool to treat acquired perforating dermatosis.

Abstract The transgenic 116C-NOD mouse strain exhibits a prevalent Th17 phenotype, and reduced type 1 diabetes (T1D) compared to non-obese diabetic (NOD) mice. A cohousing experiment between both models revealed lower T1D incidence in NOD mice cohoused with 116C-NOD, associated with gut microbiota changes, reduced intestinal permeability, shifts in T and B cell subsets, and a transition from Th1 to Th17 responses. Distinct gut bacterial signatures were linked to T1D in each group. Using a RAG-2−/− genetic background, we found that T cell alterations promoted segmented filamentous bacteria proliferation in young NOD and 116C-NOD, as well as in immunodeficient NOD.RAG-2−/− and 116C-NOD.RAG-2−/− mice across all ages. Bifidobacterium colonization depended on lymphocytes and thrived in a non-diabetogenic environment. Additionally, 116C-NOD B cells in 116C-NOD.RAG-2−/− mice enriched the gut microbiota in Adlercreutzia and reduced intestinal permeability. Collectively, these results indicate reciprocal modulation between gut microbiota and the immune system in rodent T1D models.

Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials. Resumen: Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH (APEH) en España en 2019. Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde Marzo de 2018 a Diciembre de 2019 en toda España. Resultados: Se obtuvo información de 1.933 pacientes procedentes de 11 Comunidades Autónomas, de 47 neurólogos o genetistas. Edad media: 53,64 años ± 20,51 desviación estándar (DE); 938 varones (48,5%), 995 mujeres (51,1%). En 920 pacientes (47,6%) no se conoce el defecto genético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más frecuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEH recesiva más frecuente es la SPG7. Conclusiones: La prevalencia estimada de APEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clínicos.

Opisthorchis viverrini is a carcinogenic parasite that can cause bile duct cancer called cholangiocarcinoma. A study of the immune response of this parasite in susceptible and non-susceptible hosts may provide a clue to develop vaccines and immunodiagnostic markers, which are currently not available. Here, we compared the antibody response in susceptible Golden Syrian hamsters and non-susceptible BALB/c mice infected by the liver fluke. In mice, the antibody was detected between 1 and 2 weeks post-infection, whereas it was positive between 2 and 4 weeks post-infection in hamsters. Immunolocalization revealed that the antibody from mice reacts strongly with the tegumental surface and gut epithelium of the worm, while hamster antibody showed a weak signal in the tegument and a comparable signal in the gut of the worm. Immunoblot of the tegumental proteins demonstrated that while hamster antibody showed a broad specificity, mice strongly reacted with a single protein band. Mass spectrometry revealed these immunogenic targets. Recombinant proteins of the reactive targets were produced in the bacterial expression system. The immunoblot of these recombinant proteins confirm the reactivity of their native form. In summary, there is a different antibody response against O. viverrini infection in susceptible and non-susceptible hosts. The non-susceptible host reacts quicker and stronger than the susceptible host.

Resume: Introducción: Las ataxias (AT) y paraparesias espásticas hereditarias (PEH) son síndromes neurodegenerativos raros. Nos proponemos conocer la prevalencia de las AT y PEH en España en 2019. Pacientes y métodos: Estudio transversal, multicéntrico, descriptivo y retrospectivo de los pacientes con AT y PEH, desde marzo de 2018 a diciembre de 2019 en toda España. Resultados: Se obtuvo información de 1933 pacientes procedentes de 11 Comunidades Autónomas, de 47 neurólogos o genetistas. Edad media: 53,64 años ± 20,51 desviación estándar (DE); 938 varones (48,5%), 995 mujeres (51,5%). En 920 pacientes (47,6%) no se conoce el defecto genético. Por patologías, 1.371 pacientes (70,9%) diagnosticados de AT, 562 diagnosticados de PEH (29,1%). La prevalencia estimada de AT es 5,48/100.000 habitantes, y la de PEH es 2,24 casos/100.000 habitantes. La AT dominante más frecuente es la SCA3. La AT recesiva más frecuente es la ataxia de Friedreich (FRDA). La PEH dominante más frecuente es la SPG4, y la PEH recesiva más frecuente es la SPG7. Conclusiones: La prevalencia estimada de AT y PEH en nuestra serie es de 7,73 casos/100.000 habitantes. Estas frecuencias son similares a las del resto del mundo. En el 47,6% no se ha conseguido un diagnóstico genético. A pesar de las limitaciones, este estudio puede contribuir a estimar los recursos, visibilizar estas enfermedades, detectar las mutaciones más frecuentes para hacer los screenings por comunidades, y favorecer los ensayos clínicos. Abstract: Introduction: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. Patients and methods: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. Results: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. Conclusions: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Sugars are precursors to the majority of the world’s biofuels. Most of these come from sugar and starch crops, such as sugarcane and corn grain. Lignocellulosic sugars, although more challenging to extract from biomass, represent a large, untapped, opportunity. In response to the increasing attention to renewable energy, fuels, and chemicals, we review and compare two strategies for extracting sugars from lignocellulosic biomass: biochemical and thermochemical processing. Biochemical processing based on enzymatic hydrolysis has high sugar yield but is relatively slow. Thermochemical processing, which includes fast pyrolysis and solvent liquefaction, offers increased throughput and operability at the expense of low sugar yields.

Alzheimer's disease (AD), a prevalent neurological condition, poses a multifaceted challenge affecting millions worldwide. It demands diverse solutions, both pharmaceutical and non-pharmaceutical, to ameliorate symptoms and enhance patients' quality of life across various stages. Tailored intervention strategies are essential for addressing AD's progression, emphasizing the significance of early detection and stage classification. This study underscores the pivotal role of medical imaging, specifically MRI, in AD diagnosis and monitoring. MRI interpretation is often time-consuming and relies on clinical intuition, necessitating more efficient and accurate approaches. In response, a custom convolutional neural network (CNN) model named ALSA-3 and deep learning (DL) techniques are explored for MRI-based alzheimer's disease classification. Various image processing techniques, such as MSE, RMSE, PSNR, and SSIM, enhance image quality. An ablation study systematically adjusts hyperparameters and layer structures. Results showcase the superiority of the proposed ALSA-3 model over traditional methods, achieving an exceptional 99.50% accuracy, with precision, F1-score, and recall values of 100%, 99%, and 99%. Model robustness is evaluated with different k values, reinforcing its efficacy in alzheimer's disease classification. Moreover, the elucidation of the ALSA-3 model incorporates grad-cam and grad-cam++ explainable artificial intelligence (XAI) techniques, to furnish comprehensive explanations elucidating the clarify the reasoning behind model decisions. This study not only advances state-of-the-art in alzheimer's disease classification but also holds the potential to significantly benefit patients, caregivers, and the medical community. The improved accuracy and efficiency of our model promise more accurate and timely diagnosis, thereby enhancing the lives of those affected by alzheimer's disease.

Glioblastoma, also known as grade IV astrocytoma, is an aggressive and quickly developing brain tumor whose median survival period is believed to be between 12 and 18 months. Patients with glioblastoma are at high risk of developing comorbidities like leukemia, atherosclerosis, autism, sudden cardiac death, and pancreatic neoplasms. Identification of influential biomarker genes is crucial to diagnose and design therapeutic targets for cancer. To do this, we considered The Cancer Genome Atlas (TCGA) dataset to identify the significant genes of glioblastoma. Therefore, we pre-processed the dataset and applied the Kruskal-Wallis test and Bonferroni correction methods to select significant biomarker genes. A total of 26 significant dysregulated genes have been identified from 16261 genes, of which 19 are up-regulated and 7 are down-regulated genes. We performed analysis of functional and ontological pathways, protein-protein interactions (PPI), and protein-drug interactions (PDI) to predict the functions of these influential genes. Comorbidities validation was performed using gold benchmark databases. Furthermore, the Cox proportional hazard model and the product-limit (PL) estimator were used to examine the influence of clinical and genetic variables that play an important role in the survival of glioblastoma patients. This study provides the basis of identifying cancer-influencing genes and understanding the impact of glioblastoma on the progression of comorbidities.

Global urbanization and the growing geographic range of Aedes mosquitoes are the leading causes of the increase in Chikungunya infections, and the lack of a particular antiviral therapy for the disease is a cause of great concern. This article represents the research done so far to find small compounds, like natural drug candidates, that could block the activity of envelope glycoprotein and work as an antiviral to treat CHIKV infection. Here, we used a wide range of in-silico drug design techniques, including molecular docking, molecular dynamics simulation, ADME/toxicity, post-docking MM-GBSA, PCA, and DCCM, to discover potential drug candidates targeting the specific protein of interest. Out of 483 natural compounds, 180 compounds passed the ADMET analysis, and the molecular docking identified the top three lead candidates (CID: 439533, CID: 3082330, and CID: 471) with an effective binding affinity of −4.686, −4.663, and −4.594 (kcal/mol), respectively. Both the control ligand and the lead compounds interacted with the common amino acid residues (TYR301, ILE231, PHE164, ILE321, GLN113), which indicates that lead compounds and the control ligand both bind in the common active site of the protein. Negative binding free energy of CID: 439533, CID: 3082330, CID: 471 were −35.07, −34.89, and −32.5 kcal/mol, respectively. These molecules were then further assessed using MD simulation, which verified the molecules!ˋ stability and binding to the targeted protein. The stability of the protein-ligand docking complex structure was evaluated using MD simulation. The ligands assessed in this study, CID: 439533, CID: 3082330, and CID: 471, unveiled the significant stability of the proteins' binding site in the MD simulation study, which also showed a high negative binding free energy value. Three principal components (PC1, PC2, PC3) for the lead compound CID: 3082330 (2′,3,5,7-Tetrahydroxyflavanone) were (50.08%), (22.61%), and (4.41%), respectively, which we can suggest as the best drug candidate, followed by CID: 439533. Both compounds may potentially inhibit CHIKV envelope glycoprotein activity.

BackgroundDysbiotic biliary bacterial profile is reported in cancer patients and is associated with survival and comorbidities, raising the question of its effect on the influence of anticancer drugs and, recently, the suggestion of perichemotherapy antibiotics in pancreatic cancer patients colonized by the Escherichia coli and Klebsiella pneumoniae.ObjectiveIn this study, we investigated the microbial communities that colonize tumours and which bacteria could aid in diagnosing pancreatic and biliary cancer and managing bile-colonized patients.MethodsA retrospective study on positive bile cultures of 145 Italian patients who underwent cholangiopancreatography with PC and EPC cancer hospitalized from January 2006 to December 2020 in a QA-certified academic surgical unit were investigated for aerobic/facultative-anaerobic bacteria and fungal organisms.ResultsWe found that among Gram-negative bacteria, Escherichia coli and Pseudomonas spp were the most frequent in the EPC group, while Escherichia coli, Klebsiella spp, and Pseudomonas spp were the most frequent in the PC group. Enterococcus spp was the most frequent Gram-positive bacteria in both groups. Comparing the EPC and PC, we found a significant presence of patients with greater age in the PC compared to the EPC group. Regarding Candida spp, we found no significant but greater rate in the PC group compared to the EPC group (11.7% vs 1.96%). We found that Alcaligenes faecalis was the most frequent bacteria in EPC than the PC group, among Gram-negative bacterial species.ConclusionsAge differences in gut microbiota composition may affect biliary habitats in our cancer population, especially in patients with pancreatic cancer. Alcaligenes faecalis isolated in the culture of bile samples could represent potential microbial markers for a restricted follow-up to early diagnosis of extra-pancreatic cancer. Finally, the prevalence of Candida spp in pancreatic cancer seems to trigger new aspects about debate about the role of fungal microbiota into their relationship with pancreatic cancer.

Abstract Background Host determinants of HIV-1 viral tropism include factors from producer cells that affect the efficiency of productive infection and factors in target cells that block infection after viral entry. TRIM5α restricts HIV-1 infection at an early post-entry step through a mechanism associated with rapid disassembly of the retroviral capsid. Topoisomerase I (TOP1) appears to play a role in HIV-1 viral tropism by incorporating into or otherwise modulating virions affecting the efficiency of a post-entry step, as the expression of human TOP1 in African Green Monkey (AGM) virion-producing cells increased the infectivity of progeny virions by five-fold. This infectivity enhancement required human TOP1 residues 236 and 237 as their replacement with the AGM counterpart residues abolished the infectivity enhancement. Our previous studies showed that TOP1 interacts with BTBD1 and BTBD2, two proteins which co-localize with the TRIM5α splice variant TRIM5δ in cytoplasmic bodies. Because BTBD1 and BTBD2 interact with one HIV-1 viral tropism factor, TOP1, and co-localize with a splice variant of another, we investigated the potential involvement of BTBD1 and BTBD2 in HIV-1 restriction. Results We show that the interaction of BTBD1 and BTBD2 with TOP1 requires hu-TOP1 residues 236 and 237, the same residues required to enhance the infectivity of progeny virions when hu-TOP1 is expressed in AGM producer cells. Additionally, interference with the expression of BTBD2 in AGM and human 293T target cells increased their permissiveness to HIV-1 infection two- to three-fold. Conclusions These results do not exclude the possibility that BTBD2 may modestly restrict HIV-1 infection via colocation with TRIM5 variants in cytoplasmic bodies.

Abstract Background and aims Ankylosing spondylitis (AS) is a chronic inflammatory disease that chiefly affects the sacroiliac joints and the spine. Galectin-3, a chimera-type member of the galectin family, binds glycoconjugates containing N-acetyllactosamine. Galectins play a role in regulation of embryogenesis, angiogenesis, neurogenesis, and immunity. The aim of the present study was to evaluate the serum galectin-3 level and its possible association with disease activity in AS patients. Forty five AS patients and 35 healthy controls enrolled in this study. All participants with a history of hyperlipidemia, liver, renal, hematological, familial thyroid, neoplastic, autoimmune infectious diseases and using anti-inflammatory drugs were excluded from the study. Serum galectin-3 levels concentration was measured using a commercial chemiluminescent microparticle immunoassay. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score–CRP (ASDAS-CRP) were used to evaluate disease activity in AS patients. Results Serum galectin-3 levels were significantly higher in AS patients compared to the control group (p = 0.04). A correlation was determined between the serum galectin-3 levels and BASDAI and ASDAS-CRP scores in the AS patients (r = 0.49, p

Background and Aim:Using two-dimensional speckle tracking echocardiography (2D-STE), the ventricular functions of hospitalized coronavirus disease-2019 (COVID-19) patients were assessed. However, there is limited information about cardiac functions in the first year after recovery from the intensive care unit (ICU). This research aims to assess the right ventricular functions of COVID-19 patients and their changes within the first year after ICU discharge using 2D-STE.Materials and Methods:The study was conducted prospectively. The study included 68 consecutive patients and 70 control patients. Echocardiography was performed in the ICU and the first year after discharge from the hospital. Right ventricular global longitudinal strain (RVGLS) was measured using the 2D-STE method.Results:The mean age of the study group was 48.67±8.10 and 37 (54.4%) patients were males. There were no substantial differences across the groups, including age, gender, body mass index, heart rate, diabetes, dyslipidemia, and smoking (P > 0.05). A substantially significant positive correlation was detected between right ventricular dimension (RAD) (r = 0.644, P < 0.001), right ventricular diastolic dimension (RVDD) (r = 0.573, P < 0.001), ferritin (r = 0.454, P < 0.001), D-dimer (r = 0.305, P = 0.011) values and RVGLS in the in-hospital and after-discharge first-year groups. The RVGLS values of the control, in-hospital, and after-discharge first-year groups were -20.36±3.06, -16.98±3.78, and -17.58±6.45, indicating a statistically significant difference across the groups (P < 0.001). Tricuspid annular plane systolic excursion was higher in the control group (P < 0.05).Conclusion:RVGLS was found to be depressed during the in-hospital period and showed no improvement in the 1 year post discharge.

The combination of electrophysiology and optogenetics enables the exploration of how the brain operates down to a single neuron and its network activity. Neural probes are in vivo invasive devices that integrate sensors and stimulation sites to record and manipulate neuronal activity with high spatiotemporal resolution. State-of-the-art probes are limited by tradeoffs involving their lateral dimension, number of sensors, and ability to access independent stimulation sites. Here, we realize a highly scalable probe that features three-dimensional integration of small-footprint arrays of sensors and nanophotonic circuits to scale the density of sensors per cross-section by one order of magnitude with respect to state-of-the-art devices. For the first time, we overcome the spatial limit of the nanophotonic circuit by coupling only one waveguide to numerous optical ring resonators as passive nanophotonic switches. With this strategy, we achieve accurate on-demand light localization while avoiding spatially demanding bundles of waveguides and demonstrate the feasibility with a proof-of-concept device and its scalability towards high-resolution and low-damage neural optoelectrodes.

Background: Dysbiosis, influenced by poor diet or stress, is associated with various systemic diseases. Probiotic supplements are recognized for stabilizing gut microbiota and alleviating gastrointestinal issues, like irritable bowel syndrome (IBS). This study focused on the tryptophan pathways, which are important for the regulation of serotonin levels, and on host physiology and behavior regulation. Methods: Nanovesicles were isolated from the plasma of subjects with chronic diarrhea, both before and after 60 days of consuming a probiotic mix (Acronelle®, Bromatech S.r.l., Milan, Italy). These nanovesicles were assessed for the presence of Tryptophan 2,3-dioxygenase 2 (TDO 2). Furthermore, the probiotics mix, in combination with H2O2, was used to treat HT29 cells to explore its cytoprotective and anti-stress effect. Results: In vivo, levels of TDO 2 in nanovesicles were enhanced in the blood after probiotic treatment, suggesting a role in the gut–brain axis. In the in vitro model, a typical H2O2-induced stress effect occurred, which the probiotics mix was able to recover, showing a cytoprotective effect. The probiotics mix treatment significantly reduced the heat shock protein 60 kDa levels and was able to preserve intestinal integrity and barrier function by restoring the expression and redistribution of tight junction proteins. Moreover, the probiotics mix increased the expression of TDO 2 and serotonin receptors. Conclusions: This study provides evidence for the gut–brain axis mediation by nanovesicles, influencing central nervous system function.