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Abstract Background Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families’ and professionals’ experiences. Results and discussion A questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively. Analysis revealed the lack of seizures as a distinctive feature between PMM2-CDG (11.2%) with Other CDG (57.7%) at symptom onset. Hypotonia and developmental disability were prevalent symptoms across all studied CDG. Feeding problems were identified as an early onset symptom in PMM2-CDG (Cramer’s V (V) = 0.30, False Discovery Rate (FDR) = 3.8 × 10− 9), and hypotonia in all studied CDG (V = 0.34, FDR = 7.0 × 10− 3). The average time to diagnosis has decreased in recent years (now ~ 3.9 years), due to advancements namely the increased use of whole genome and exome sequencing. However, misdiagnoses remain prevalent (PMM2-CDG – 44.9%, non-PMM2-CDG – 64.8%). To address these challenges, we propose adapting medical training to increase awareness of CDG and other rare diseases, ongoing education for physicians, the development of educational resources for relevant medical units, and empowerment of families through patient organizations and support networks. Conclusion This study emphasizes the crucial role of community-centered research, and the insights families can offer to enhance CDG management. By pinpointing existing gaps and needs, our findings can inform targeted interventions and support systems to improve the lives of those impacted by CDG.

Abstract Background Patient and public co-creation and involvement in health initiatives have been witnessing great expansion in recent years. From healthcare to research settings, collaborative approaches are becoming increasingly prevalent and diverse, especially in the field of rare diseases which faces complex challenges. Conference development and implementation, however, have been primarily guided by passive, information-sharing models. There is a need for conferences to evolve towards more inclusive, interactive, collaborative, and problem-solving platforms. Here, we aimed to report on a pioneer model, emphasizing a community partnership approach to conference co-creation that takes the World Conference on Congenital Glycosylation Disorders (CDG) as an exemplary case. Methods To answer the need to overcome the lack of access to high-quality information which limits CDG diagnosis, research and treatment options, the World CDG Organization has been refining a community-centric model for conference co-creation. Focusing on the 5th edition of the conference, data on stakeholders’ preferences was collected using an online survey and a poll to define the conference agenda, guide its development and select optimal dates for an all-stakeholder inclusive, relevant and participatory event. Results We describe the complexities of the community-centric conference co-creation model, detailing its refined methodology and the outcomes achieved. The model is grounded on a participative approach to promote people-centered research and care for CDG patients. The involvement of the public in the conference co-creation and in participatory methods allowed the generation of knowledge on community needs and preferences. Conclusion This paper describes a reliable, highly adaptable conference co-creation model that fosters community-building, disseminates understandable information, and serves as a borderless platform to incentivize multiple stakeholder collaborations towards CDG research and drug development. We argue this is a reproducible model that can be endorsed and more widely adopted by other disease communities and events.

Abstract Background Sleep, sedentary behaviour, and physical activity are essential components within the 24-hour time frame. Existing questionnaires used to measure these behaviours have insufficient measurement properties and are unsuitable for assessing compliance with the WHO Physical Activity and 24-hour Movement Guidelines. To describe the development process of the 24-hour Movement Questionnaire (QMov24h) and its testing. The QMov24h was developed to gather detailed information on sleep, sedentary behaviour, and physical activity. Methods The sample comprised 117 participants (58% women), aged 30.95 ± 13.56 years. The development process of the QMov24h followed the COSMIN guidelines: (i) Construction of items; (ii) Face validity with end-users; (iii) Content validity with experts; (iv) Criterion validity against accelerometry and convergent validity against diary assessments; and (v) 7-day test-retest reliability. Results The QMov24h presented adequate content and face validity. The QMov24h showed moderate criterion validity for sleep (rho=0.343;p

Dialysis plays a crucial role in the purification of nanomaterials but its impact on the structural properties of carbon nanomaterials was never investigated. Herein, a carbon-based nanomaterial generated electrochemically in potassium phosphate buffer, was characterized before and after dialysis against pure water. It is shown that dialysis affects the size of the carbon domains, structural organization, surface functionalization, oxidation degree of carbon, and grade of amorphicity. Accordingly, dialysis drives the nanomaterial organization from discrete roundish carbon domains, with sizes ranging from 70 to 160 nm, towards linear stacking structures of small nanoparticles (

Introduction: Colorectal cancer is the third most prevalent cancer among both men and women with 80% of patients having localized disease enabling curative treatments. Given the low recurrence rate in early-stage disease, there is a growing interest in reviewing follow-up protocols. The aim of this study was to assess the frequency and timing of recurrence in early-stage colon cancer, as well as recurrence patterns. Methods: The data from all patients with colon adenocarcinoma consecutively treated with surgery at the Instituto Português de Oncologia do Porto, EPE, between January 2013 and December 2016, were retrospectively reviewed. Results: A total of 1,372 patients with colon cancer were submitted to surgery during the study period. From this group, 51.4% (n = 705) were early-stage colon cancers. Regarding the pathological stage, 3.5% were stage 0, 37.4% were stage I and 59.1% were stage II. The overall recurrence rate was 6.7%. When considering the group of patients without risk factors, the recurrence rate was 5.6%. The majority of recurrences occurred in the first 3 years of follow-up. The recurrence was diagnosed in the majority of patients through carcinoembryonic antigen elevation, followed by imaging exams. The presence of one or more risk factors (high nuclear grade, vascular invasion, extramural venous invasion, and perineural invasion) showed a statistically significant association with recurrence rate. Conclusion: The recurrence rate was low in early-stage colon cancer, with the majority of recurrences occurring in the first 3 years. Our study results show that surveillance should be tailored according to individual risk factors.

With the purpose of establishing a consensus around clinical orientations for professionals involved in managing patients with sleep breathing disorders (SBD), an interdisciplinary group of scientific societies involved in this field discussed and reviewed all the published international guidelines from the American Dental Association, American Academy of Sleep Medicine, American Academy of Dental Sleep Medicine and the European counterparts. Treatment of SBD is multidisciplinary and should be made in concert with the patient, the sleep physician, and the qualified dentist to solve the individual, social, and economic burden of the disease. This consensus document represents the current thinking of a team of Portuguese experts on managing patients with SBD based on the available evidence.

Objective This study aimed to explore the utility of a high-intensity interval training (HIIT) app as a remote exercise support strategy in children with obesity through assessing adherence, possible effects on obesity-related outcomes, and perceptions of its use to support counseling and improve the treatment of children with obesity. Methods Thirty-seven children (94.6% with obesity; 45.9% girls), with a mean age of 10.4 (±1.8) years and a mean body mass index (BMI) z-score of 3.31 (±1.09) were recruited to use the app during 6 weeks. Assessments were performed at baseline, 6 (end of intervention), and 12 weeks (follow up). Results Thirty-two (86.3%) participants completed both intervention and follow-up assessments and were analyzed. On average, children used the HIIT app 2.5 times per week (95% confidence interval (CI): 1.9 to 3.0), with the highest perceived exertion of 4.1 (95% CI: 3.6 to 4.5). No over-time differences were found in body composition, physical activity, screen time, sleep duration, or water intake after the intervention; however, an over-time decrease in sugary beverages intake (Δ−0.9, 95% CI: −1.6 to −0.1, p = .019). No differences in body composition were found at follow up. Although none of the children or parents perceived impairments in nutritional behavior, general wellbeing, or fitness as a consequence of intervention, most children (64.5%), but not parents, perceived improvements in nutritional behavior and general wellbeing. Conclusion Although feasible, the 6-week effect of HIIT app use is modest or absent regarding body composition, movement, and nutritional behavior change, probably due to its low volume. More studies are needed to explore the utility of HIIT apps as a remote exercise support strategy for children with obesity further.

ABSTRACT Objective: The aim of the present study is to evaluate the occurrence of dentinal defects on the apical surface after rotary instrumentation at different working lengths with Trunatomy Prime system, with or without the use of a glide path file. Methods: Twenty human single-rooted mandibular premolars were selected and divided into 2 experimental groups (n=10). GTP group (Glide Path + Trunatomy Prime), the TP group (Trunatomy Prime). Results: To check the agreement between the examiners, the Kappa test was performed. Subsequently, the results were subjected to the Shapiro-Wilk normality test. The sample showed abnormal behavior and were subjected to the non-parametric Mann Whitney test with a significance level of 5%. No significant difference was found between the groups. Conclusion: It is concluded that there was no causal relationship with the formation of dentin defects with and without the use of glide path files at different limits of instrumentation with Trunatomy files.

Abstract Myxozoa is a class of the Phylum Cnidaria made up of endoparasites from aquatic habitats. The genus Ceratomyxa preferentially infects marine fish, with the gallbladder being the main site parasitized. This study aimed to describe a new species of Ceratomyxa found in this organ in Boulengerella cuvieri using morphological, morphometric characterization and phylogenetic analysis of 18S rDNA gene sequences. Specimens of B. cuvieri were collected, anesthetized, desensitized and biometric measurements were performed. The organs were analyzed under a stereomicroscope and fragments of internal organs were extracted for light microscopy analysis, preserved in 80% ethanol for 18S rDNA gene analysis and fixed in Davidson solution for histological processing. Free spores of Ceratomyxa were observed in the gallbladder, in plasmodia with wave-like movements, with the following dimensions: spore width (24.5 ± 0.4) µm, spore length (5.2 ± 0.3) µm, polar capsule width (1.8 ± 0.2) µm, polar capsule length (2.1 ± 0.3) µm, number of polar tubule turns (4-5) and 100% prevalence. Phylogenetic analysis confirmed that Ceratomyxa matosi n. sp. is a new species, grouped with other freshwater Ceratomyxa species from the Amazon, representing the second description of species of this genus in the state of Amapá.

Abstract The Amazon is the largest river basin in the world and it is home to the greatest diversity of freshwater fish in the world. Mesonauta festivus is a cichlid popularly known as flag cichlid, widely distributed throughout South America. The diversity of parasites in fish from the Amazon region is still underestimated, due to the high fishes diversity. The Myxozoa class has a universal distribution, with some specimens being pathogenic to some fish. The aim of this work was to describe a new species of Hoferellus in M. festivus. The fish were collected in the lake region, municipality of Tartarugalzinho, in the state of Amapá, Brazil. The new species was found parasitizing the urinary bladder of M. festivus. Spores were 11.5 ±1.1 (10.4-12.6) µm long and 10.9 ±1 (9.9-11.9) µm wide, and polar capsules were equally sized, measuring 4.9 ±0.5 (4.4-5.4) µm long and 3.4 ±0.9 (2.5-4.3) µm wide, with a pyriform shape, convergent with the apical region of the spore. The polar filament was wound with 5 to 6 turns. Morphological, morphometric, molecular and phylogenetic analysis proved that it is a new species of Hoferellus in the Amazon region.

The intricate involvement of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in glucose homeostasis and adipogenesis is well-established. However, its role in cancer, particularly luminal bladder cancer, remains debated. The overexpression and activation of PPARγ are implicated in tumorigenesis. Specific gain-of-function mutations (M280I, I290M, and T475M) within the ligand-binding domain of PPARγ are associated with bladder cancer and receptor activation. The underlying molecular pathways prompted by these mutations remain unclear. We employed a dual-basin structure-based model (db-SBM) to explore the conformational dynamics between the inactive and active states of PPARγ and examined the effects of the M280I, I290M, and T475M mutations. Our findings, consistent with the existing literature, reveal heightened ligand-independent transcriptional activity in the I290M and T475M mutants. Both mutants showed enhanced stabilization of the active state compared to the wild-type receptor, with the I290M mutation promoting a specific transition route, making it a prime candidate for further study. Electrostatic analysis identified residues K303 and E488 as pivotal in the I290M activation cascade. Biophysical assays confirmed that disrupting the K303–E488 interaction reduced the thermal stabilization characteristic of the I290M mutation. Our study demonstrates the predictive capabilities of combining simulation and cheminformatics methods, validated by biochemical experiments, to gain insights into molecular activation mechanisms and identify target residues for protein modulation. [ABSTRACT FROM AUTHOR]

Abstract A major drawback in deploying central bank digital currencies (CBDC) is the offline puzzle, which requires that a CBDC must keep the liquidity provision given by cash, and, simultaneously, avoid double‐spending, cloning, and other issues. The puzzle is solved by minting the coins in serial numbers, which are stored on a local blockchain inside a smartphone or EMV card. The local blockchain is strengthened by a two‐stage approval architecture that mitigates attacks and enables non‐repudiation handling. The coins are protected by hardware keys embedded in the microchip and can be continuously mined by the wallet to enhance security. The coins can be either minted as hot coins, which can be retrieved in case of loss, or minted as cold coins, like physical cash.

Background and objectives: Adult-onset leukodystrophies are a rare group of neurological disorders characterized by progressive degeneration of the cerebral white matter. One of these diseases is caused by biallelic pathogenic variants in the AARS2 gene. We describe a patient with late-onset AARS2-related leukoencephalopathy, a milder phenotype and a novel disease-causing variant. Methods: The patient was characterized during routine clinical practice. Results: A 40-year-old male was evaluated for chronic headaches. Six years before, he was hospitalized for a major depression with psychotic features. The first neurological examination was normal, except for a slow downbeat nystagmus. Brain MRI revealed significant hyperintensities in T2 and T2-FLAIR bilaterally in the frontal lobes, with periventricular and corpus callosum involvement, and without restricted diffusion. A multigene panel for leukodystrophies based on whole-exome sequencing identified two heterozygous variants in the AARS2 gene: one previously reported in the literature, already classified as pathogenic, NM_020745.4:c.595C > T (p.(Arg199Cys)), and one novel variant c.730G > A (p.(Val244Ile)), later reclassified as likely pathogenic. Nine years have passed since the first symptoms without clear clinical progression. Discussion: This case underlines that adult-onset leukodystrophy caused by variants in AARS2 may have a wide range of phenotypes and patterns of progression. The new variant c.730G > A (p.(Val244Ile)) herein described may induce a milder clinical picture and a less severe radiological pattern. Practical implications: Adult-onset leukoencephalopathies may present with milder clinical signs than what is generally perceived, and novel disease-causing variants are being identified.

Abstract In aquaculture worldwide, most of the chemotherapeutic agents used for disease control and treatment are unregulated chemical products derived from agriculture. In this study, we investigated the efficacy of therapeutic baths with albendazole against the monogeneans Anacanthorus spathulatus, Notozothecium janauachensis and Mymarothecium boegeri, which infest the gills of Colossoma macropomum, and the hematological and histopathological effects of this anthelmintic agent on these fish. Albendazole at a concentration of 500 mg/L was used in three baths of 24 hours each, with intervals of 24 hours between these baths. Three replications of this treatment were used, and the control group consisted of water from the cultivation tank. Afterwards, hematological, histopathological and parasitological analyses were conducted. We found that the therapeutic baths with albendazole at 500 mg/L presented high efficacy (94.9%) against monogeneans de C. macropomum and caused few physiological or histopathological alterations. Therefore, baths with albendazole at 500 mg/L, as used in this strategy, can be recommended for controlling and treating infections by monogeneans in C. macropomum.

Abstract This study investigated the spatial distribution, parasite interactions, and affinities of Branchiura parasites according to macrohabitat and surface type on fish from the Araguari River, Amapá State, in the Brazilian Amazon. This study presents novel information on the interactions of branchiuran species with host fish, and how the morphology of their attachment structures is associated with different host surface morphologies, with and without scales. A total of 558 fish specimens of 26 species were collected, of which 109 fish (10 species) were parasitized by at least one branchiuran parasite; these were selected for further study. The parasites were collected from the buccal cavity, gills, fins, and integument of the host fish. Parasites with suction discs (Argulus) were mainly associated to hosts with small scales and no scales, while parasites with hooks (Dolops) were mainly associated to hosts with large scales. Overall, parasites with suction discs were more specialized per site than those with hooks.

The increasing prevalence of dementia demands innovative solutions; however, existing technological products often lack tailored support for individuals living with this condition. The Living Lab approach, as a collaborative innovation method, holds promise in addressing this issue by actively involving end-users in the design and development of solutions adapted to their needs. Despite this potential, the approach still faces challenges due to its lack of recognition as a research methodology and its absence of tailored guidelines, particularly in dementia care, prompting inquiries into its effectiveness. This narrative review aims to fill this gap by identifying and analysing digital health Living Labs focusing on dementia solutions. Additionally, it proposes guidelines for enhancing their operations, ensuring sustainability, scalability, and greater impact on dementia care. Fifteen Living Labs were identified and analyzed. Based on trends, best practices, and literature, the guidelines emphasize user engagement, interdisciplinary collaboration, technological infrastructure, regulatory compliance, transparent innovation processes, impact measurement, sustainability, scalability, dissemination, and financial management. Implementing these guidelines can enhance the effectiveness and long-term impact of Living Labs in dementia care, fostering new collaborations globally.

Abstract A critical review of Gonzalo Rodriguez-Pereyra’s Two Arguments for the Identity of Indiscernibles.

This research examines the barriers and facilitators to employers' engagement with higher education institutions. The data were collected through interviews with a set of employers (n = 19) in the Northern region of Portugal, V.N.de Famalicão, in 2019. We begin by exploring employers' engagement activities as a potential solution to address local-level skill problems. Empirical evidence suggests that the engagement activities are mostly passive as firms use higher education largely as a recruitment channel. The differences in organizational goals and culture are the most cited barriers to the lack of more active engagement. Some efforts have recently been made to strengthen the ties between higher education and employers, notably through a local multi-stakeholder partnership as a potential broker. However, it will take time for this to bear fruit and contribute to reducing skill gaps and shortages. The data show that despite employers' apparent willingness, more effort must be made to encourage active engagement.

This pioneering work studied the medieval color palette of four manuscripts produced in the scriptorium of Alfonso X, king of the Crown of Castile (r. 1252-84), including the Songs of Holy Mary (Cantigas de Santa Maria, in Rich Codex and Musicians’ Codex), Lapidary (Lapidario), and Book of Games (Libro de los juegos). Scientific analysis based on fiber-optics reflectance spectroscopy in the visible and Raman spectroscopy showed a color palette based on lapis lazuli, indigo, azurite, vermilion, red lead, orpiment, yellow ochre, two different greens (bottle green and vergaut), lead white, carbon-based black, and most importantly, brazilwood pinks, reds, and purples. So, it is now the first reported use of this lake pigment in European medieval manuscript illumination. The painting technique is also discussed. The diversity of colors and techniques, with the presence of lapis lazuli, brazilwood lake pigments, purple, and gold, demonstrates Alfonso X’s desire to produce sumptuous manuscripts.

In this work, the pyrolysis process and the characteristics of biochar produced using a bench-scale fixed-bed reactor and a prototype-scale auger reactor were studied. Residual forest biomass (RFB) from acacia, broom, gorse, and giant reed was used as feedstock. Besides information on pyrolysis characteristics of these specific biomass species from the Iberian Peninsula, new knowledge on the understanding of how results from small-scale reactors can be used to predict the behavior of higher-scale and continuous-operation reactors is offered. Batch pyrolysis was carried out using 40 g of biomass sample in a fixed-bed reactor with a heating rate of 20 °C∙min−1, pyrolysis temperature of 450 and 550 °C, and a residence time of 30 min, while for the continuous process it was used a prototype of an auger reactor with continuous operation with a biomass flow rate up to 1 kg/h, with temperatures of 450 and 550 °C, and a solids residence time of 5 min. The biochar yield was in the range of 0.26 to 0.36 kg/kg biomass dry basis, being similar for both types of reactors and slightly lower when using the auger reactor. The proximate analysis of the biochar shows volatile matter in the range 0.10 to 0.27 kg/kg biochar dry basis, fixed carbon in the range 0.65 to 0.84 kg/kg biochar dry basis, and ash in the range 0.04 to 0.08 kg/kg biochar dry basis. The carbon, oxygen, and hydrogen content of the biochar was in the range of 0.71 to 0.81, 0.09 to 0.22, and 0.02 to 0.03 kg/kg biochar dry basis, respectively. The results show that the up-scaling of the reactor and regime of operation does not have an important influence on the yield and characteristics of the biochar produced. The biochar obtained in the two types of reactors has characteristics appropriate for environmental applications, such as an additive to improve soil properties. It is possible to see that the characteristics of the biochar are influenced by the type of biomass and the conditions and parameters of the process; therefore, it is of major importance to control and know of these conditions, especially when considering upscaling scenarios.

This research examines regional skill problems and the strategies adopted to reduce skill shortages by a set of employers (n = 16). The data collected in 2019 in a northern region in Portugal indicate considerable and persistent shortages of engineering and IT graduates and non-graduates for operational jobs. The employers implement anticipative strategies interacting with the education system, and the city council has developed a multi-stakeholder partnership. However, the most widespread strategy is remedial and consists of employer-provided training. Employers believe that the partnership has been a fruitful way of expanding economic activities, but further efforts are required to alleviate skill shortages.