Artificial intelligence (AI) in rare diseases: is the future brighter?

The amount of data collected and managed in (bio)medicine is ever-increasing. Thus, there is a need to rapidly and efficiently collect, analyze, and characterize all this information. Artificial intelligence (AI), with an emphasis on deep learning, holds great promise in this area and is already being successfully applied to basic research, diagnosis, drug discovery, and clinical trials. Rare diseases (RDs), which are severely underrepresented in basic and clinical research, can particularly benefit from AI technologies. Of the more than 7000 RDs described worldwide, only 5% have a treatment. The ability of AI technologies to integrate and analyze data from different sources (e.g., multi-omics, patient registries, and so on) can be used to overcome RDs' challenges (e.g., low diagnostic rates, reduced number of patients, geographical dispersion, and so on). Ultimately, RDs' AI-mediated knowledge could significantly boost therapy development. Presently, there are AI approaches being used in RDs and this review aims to collect and summarize these advances. A section dedicated to congenital disorders of glycosylation (CDG), a particular group of orphan RDs that can serve as a potential study model for other common diseases and RDs, has also been included.info:eu-repo/semantics/publishedVersio

the web-based case study of the Immunology and Congenital Disorders of Glycosylation questionnaire (ImmunoCDGQ)

Funding Information: This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. R.F. (SFRH/BD/124326/2016) and C.P. (SFRH/BD/138647/2018) acknowledge the funding from the Fundação para a Ciência e Tecnologia (FCT), Portugal. S.B. was supported by CDG & Allies-PPAIN funding (6th Liliana Scientific Scholarship). Publisher Copyright: © 2022, The Author(s).BACKGROUND: Congenital Disorders of Glycosylation (CDG) are a complex family of rare metabolic diseases. Robust clinical data collection faces many hurdles, preventing full CDG biological and clinical comprehension. Web-based platforms offer privileged opportunities for biomedical data gathering, and participant recruitment, particularly in rare diseases. The immunology and CDG electronic (e-) questionnaire (ImmunoCDGQ) explores this paradigm, proposing a people-centric framework to advance health research and participant empowerment. OBJECTIVE: The objectives of this study were to: (1) Describe and characterize the ImmunoCDGQ development, engagement, recruitment, participation, and result dissemination strategies; (2) To critically compare this framework with published literature and making recommendations. METHODS: An international, multistakeholder people-centric approach was initiated to develop and distribute the ImmunoCDGQ, a multi-lingual e-questionnaire able to collect immune-related data directly from patients and family caregivers. An adapted version was produced and distributed among the general "healthy" population (ImmunoHealthyQ), serving as the control group. Literature screening was performed to identify and analyze comparable studies. RESULTS: The ImmunoCDGQ attained high participation and inclusion rates (94.6%, 209 out of 221). Comparatively to the control, CDG participants also showed higher and more variable questionnaire completion times as well as increased English version representativeness. Additionally, 20% of the CDG group (42 out of 209) chose not to complete the entire questionnaire in one go. Conditional logic structuring guided participant data provision and accurate data analysis assignment. Multi-channel recruitment created sustained engagement with Facebook emerging as the most followed social media outlet. Still, most included ImmunoCDGQ questionnaires (50.7%, 106 out of 209) were submitted within the first month of the project's launch. Literature search and analysis showed that most e-questionnaire-based studies in rare diseases are author-built (56.8%, 25 out of 44), simultaneously addressing medical and health-related quality of life (HRQoL) and/or information needs (79.5%, 35 out of 44). Also, over 68% of the studies adopt multi-platform recruitment (30 out of 44) actively supported by patient organizations (52.3%, 23 out of 44). CONCLUSIONS: The ImmunoCDGQ, its methodology and the CDG Community served as models for health research, hence paving a successful and reproducible road to people-centricity in biomedical research.publishersversionpublishe

the congenital disorders of glycosylation community perspective

BACKGROUND: Congenital disorders of glycosylation (CDG) are a large family of rare genetic diseases for which therapies are virtually nonexistent. However, CDG therapeutic research has been expanding, thanks to the continuous efforts of the CDG medical/scientific and patient communities. Hence, CDG drug development is a popular research topic. The main aim of this study was to understand current and steer future CDG drug development and approval by collecting and analysing the views and experiences of the CDG community, encompassing professionals and families. An electronic (e-)survey was developed and distributed to achieve this goal. RESULTS: A total of 128 respondents (46 CDG professionals and 82 family members), mainly from Europe and the USA, participated in this study. Most professionals (95.0%) were relatively familiar with drug development and approval processes, while CDG families revealed low familiarity levels, with 8.5% admitting to never having heard about drug development. However, both stakeholder groups agreed that patients and families make significant contributions to drug development and approval. Regarding their perceptions of and experiences with specific drug development and approval tools, namely biobanks, disease models, patient registries, natural history studies (NHS) and clinical trials (CT), the CDG community stakeholders described low use and participation, as well as variable familiarity. Additionally, CDG professionals and families shared conflicting views about CT patient engagement and related information sharing. Families reported lower levels of involvement in CT design (25.0% declared ever being involved) and information (60.0% stated having been informed) compared to professionals (60.0% and 85.7%, respectively). These contrasting perceptions were further extended to their insights and experiences with patient-centric research. Finally, the CDG community (67.4% of professionals and 54.0% of families) reported a positive vision of artificial intelligence (AI) as a drug development tool. Nevertheless, despite the high AI awareness among CDG families (76.8%), professionals described limited AI use in their research (23.9%). CONCLUSIONS: This community-centric study sheds new light on CDG drug development and approval. It identifies educational, communication and research gaps and opportunities for CDG professionals and families that could improve and accelerate CDG therapy development.publishersversionpublishe

AMENDMENT OF ORGANIC COMPOST PROPRIETIES THROUGH COMPOSTING-VERMICOMPOSTING INTEGRATION

The aim of the current study is to evaluate the effects of integrating composting-vermicomposting to improve the organic compost as from the physicochemical analyses and by their application on Brachiaria decumbens growth. Experiments carried out in composting unit used 30:1 ratio of nitrogen-rich organic waste (raw vegetables, fruits and cooked food) and carbon (dry grass) in 2 pile configurations (with, or without passive aeration). After 60 days, product was subjected to vermicomposting for 45 days. Composts were analyzed to check their quality (temperature, pH, moisture, organic carbon, nitrogen and phosphorus levels), as well as compared to each other as biofertilizers (10% (w/v)) for B. decumbens growth. Data have suggested that the vermicomposting process improved the compost pile by increasing its nitrogen (1.26% to 1.95%), phosphorus (0.64% to 1.2%) and organic carbon contents (17.1% to 18.9%). B. decumbens growth showed no significant differences between those treatments, which indicates that organic fraction should be increased (>10%) to release their nutrients to plant.  O objetivo desse trabalho foi avaliar os efeitos da integração da vermicompostagem no melhoramento de composto orgânico a partir de análises físico-químicas e da sua aplicação no crescimento de Brachiaria decumbens. Os experimentos foram conduzidos em pátio de compostagem (por 60 dias) utilizando 30:1 de resíduos orgânicos ricos em nitrogênio e carbono em duas configurações de pilhas (sem aeração e com aeração facilitada); seguido de tratamento via vermicompostagem (45 dias). Os compostos foram avaliados quanto à temperatura, umidade, carbono orgânico, nitrogênio e fósforo. Após a vermicompostagem, o vermicomposto e composto das pilhas foram comparados com fertilizante sintético (8N:25P) e controle (solo in natura) quanto ao potencial de fertilização 10% (p/v), a partir do crescimento da B. decumbens (22 dias). Os resultados demonstraram que a vermicompostagem aumentou os teores de nitrogênio (1,26 para 1,95%), fósforo (0,64 para 1,2%) e carbono orgânico (17,1 para 18,9%) das pilhas compostadas. O crescimento da B. decumbens não apresentou diferença significativa entre os tratamentos, o que indica que a concentração dos compostos orgânicos deve ser acrescida (>10%), para assim disponibilizar os nutrientes para a planta

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach

SFRH/BD/124326/2016 SFRH/BD/138647/2018Congenital disorders of glycosylation (CDG) are rare diseases with variable phenotypes and severity. Immunological involvement remains a largely uncharted topic in CDG, mainly due to lack of robust data. To better characterize immune-related manifestations' prevalence, relevance, and quality-of-life (QoL) impact, we developed electronic questionnaires targeting (1) CDG patients and (2) the general "healthy" population. Two-hundred and nine CDG patients/caregivers and 349 healthy participants were included in this study. PMM2-CDG was the most represented CDG (n = 122/209). About half of these participants (n = 65/122) described relevant infections with a noteworthy prevalence of those affecting the gastrointestinal tract (GI) (63.1%, n = 41/65). Infection burden and QoL impact were shown as infections correlated with more severe clinical phenotypes and with a set of relevant non-immune PMM2-CDG signs. Autoimmune diseases had only a marginal presence in PMM2-CDG (2.5%, n = 3/122), all being GI-related. Allergy prevalence was also low in PMM2-CDG (33%, n = 41/122) except for food allergies (26.8%, n = 11/41, of PMM2-CDG and 10.8%, n = 17/158, of controls). High vaccination compliance with greater perceived ineffectiveness (28.3%, n = 17/60) and more severe adverse reactions were described in PMM2-CDG. This people-centric approach not only confirmed literature findings, but created new insights into immunological involvement in CDG, namely by highlighting the possible link between the immune and GI systems in PMM2-CDG. Finally, our results emphasized the importance of patient/caregiver knowledge and raised several red flags about immunological management.publishersversionpublishe

Photodynamic Therapy for the Treatment of American Tegumentary Leishmaniasis: Evaluation of Therapies Association in Experimentally Infected Mice With Leishmania (Leishmania) amazonensis

Introduction: American tegumentary leishmaniasis (ATL) is a zoonotic disease caused by protozoan parasites of the genus Leishmania that affects the skin and mucous membrane. Currently, the available drugs for the treatment are injectable, with side effects, long-term treatment regimen and there is the possibility of drug resistance. Thus, alternative therapies have been tested, including photodynamic therapy (PDT). We evaluated the efficacy of PDT on its own and associated with the prescribed ATL treatment.Methods: BALB/c mice were infected with Leishmania (Leishmania) amazonensis and divided into 6 groups: Gluc+PDT, treated with Glucantime® and photodynamic therapy (PDT) with methylene blue (MB)/red LED (light-emitting diode); Gluc, treated with Glucantime®; PDT, treated with PDT with MB/red LED; Ampho+PDT, treated with amphotericin and PDT with MB/red LED; Ampho, treated with amphotericin; and control, which were infected but not treated. Two treatment cycles were performed. After 165 days of infection, the parasite load was determined.Results: Statistical differences were not found (P > 0.05) between measures of volume and thickness of the infected footpads in the treated groups when compared with the control group. However, there was a significant reduction (P < 0.05) in the parasitic load of the popliteal lymph nodes of the Gluc+PDT, Gluc, PDT and Ampho groups when compared to the control group. In the histological analysis of the infected footpads, the Gluc+PDT group presented a smaller amount of amastigote nests and lower intensity of the mononuclear infiltrate when compared to the Gluc and PDT groups.Conclusion: The results showed that although there is no significant difference in the evaluations of footpad size (thickness and volume), there is a downward measurement tendency in the Gluc+PDT group, as it can be observed by volume data and corroborated by parasite negative load

The bioremediation potential of filamentous fungi in soil contaminated with lead

Population increase resulting from industrial activities has worsened soil contamination with toxic metals. Given the complex dynamics of these pollutants and the complexity of soil matrices, one of the biggest challenges faced by the environmental field lies on developing effective technologies to remediate contaminated soils. Thus, bioremediation may be a decontamination alternative based on using microorganisms. The aims of the current study are to isolate and characterize filamentous fungi with bioremediation potential to be used in soils contaminated with lead. A soil sample was incubated in Sabouraud Caf Agar medium in BOD at 28ºC. CFUs were counted after 72h of incubation; the three most prominently grown colonies were isolated in new plates containing the same medium. Fungi were transferred to liquid submerged fermentation medium with 20 ppm of lead after 24 h of incubation; they remained in shaker incubator at 30°C, 120 rpm, for 120h. Next, the MP-AES analysis was performed to evaluate the final lead concentration. Isolated fungi such as Aspergillus, Penicillium and Trichoderma removed, 56.82%, 66.77% and 75.29% lead ions, respectively, in comparison to the control. Results confirmed the bioremediation potential of these fungi and their possible use in areas contaminated with the herein investigated metal

Estratégias para melhorar a adesão as metas de segurança do paciente / Strategies to enhance patient safety goals

Descrever estratégia para aprimorar o conhecimento dos colaboradores referente às metas de segurança do paciente. Trata-se de relato de experiência realizado em um hospital filantrópico, em abril de 2018. Realizou-se gincana para aprimorar o conhecimento dos colaboradores acerca das metas de segurança do paciente. Formaram-se 24 equipes entre setores assistenciais e administrativos. Sendo selecionadas três equipes, as quais propuseram a elaboração de checklist para checar as identificações dos pacientes a cada verificação de sinais vitais; a realização de concurso de paródia e teatro referente ao tema higienização das mãos; checagem dos medicamentos a beira leito e dispensação de dose unitária do medicamento. A realização de atividades lúdicas e interativas, no caso a gincana, promove a participação positiva dos colaboradores para aprimorar a qualidade do cuidado e, consequentemente a segurança do paciente

Biobanco de acidente cerebrovascular de Joinville: protocolo de estudos e resultados dos primeiros anos

CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOAiming to contribute to studies that use detailed clinical and genomic information of biobanks, we present the initial results of the first Latin American Stroke Biobank. Blood samples were collected from patients included in the Joinville Stroke Registr7512881889CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO183768402396-2013/0