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We present MMPred, a software tool that integrates epitope prediction and sequence alignment algorithms to streamline the computational analysis of molecular mimicry events in autoimmune diseases. Starting with two protein or peptide sets (e.g., from human and SARS-CoV-2), MMPred facilitates the generation, investigation, and testing of mimicry hypotheses by providing epitope predictions specifically for MHC class II alleles, which are frequently implicated in autoimmunity. However, the tool is easily extendable to MHC class I predictions by incorporating pre-trained models from CNN-PepPred and NetMHCpan. To evaluate MMPred’s ability to produce biologically meaningful insights, we conducted a comprehensive assessment involving i) predicting associations between known HLA class II human autoepitopes and microbial-peptide mimicry, ii) interpreting these predictions within a systems biology framework to identify potential functional links between the predicted autoantigens and pathophysiological pathways related to autoimmune diseases, and iii) analyzing illustrative cases in the context of SARS-CoV-2 infection and autoimmunity. MMPred code and user guide are made freely available at https://github.com/ComputBiol-IBB/MMPRED.

IntroductionAldo-keto reductase 1B10 (AKR1B10) is a multifunctional enzyme, which is important in cancer development and progression, but the landscape of AKR1B10 in pan-cancers and in tumor microenvironment is unclear.MethodThis study integrated the sequencing data of 33 cancer types, including gastric cancer, from TCGA project to explored the expression pattern and genetic and epigenetic alterations of AKR1B10. The association of AKR1B10 expression with clinical progression of cancers was evaluated by Kaplan-Meier analysis; the potential role of AKR1B10 in tumor microenvironment (TME) and immune-related gene expression were analyzed by PURITY, ESTIMATE, TIMER and CIBERSORT algorithms. The expression of AKR1B10 and immune cell markers in gastric cancer were evaluated with multiplex immunofluorescence staining.ResultResults indicated that AKR1B10 was highly expressed in the gastrointestinal tract in health donors, but the expression of AKR1B10 was significantly changed in most of cancer types, which may be ascribed to DNA methylation in its promoter. The AKR1B10 expression in cancers and its value in disease progression was bidirectional and functionally enriched in metabolism in pan-cancers. In tumor microenvironment, AKR1B10 was significantly correlated with immune cell infiltrations and immune gene expression. In the stomach, along with the diminishing of AKR1B10 expression, CD68+ macrophage increased and CD19+ B cell decreased in gastric cancer.DiscussionThese data indicates that AKR1B10 may be an important factor in the development and progression and a potential therapeutic target for multiple cancers, but plays as a protector in the gastric tissues.

Objetivos: Comparar la validez diagnóstica entre la escala Neuropathy Disability Score (NDS) sin Monofilamento (MF) y NDS modificada con MF frente a Electromiograma (EMG) de extremidades Inferiores. Concordancia entre neuropatía detectada y registrada en Historial Clínico Informatizado (HCI) Metodología: Estudio de concordancia. Duración: 12 meses. Ámbito: Dos centros de Atención Primaria (AP) del Institut Català de Salut. Población diana: Personas con EMG registrado en HCI por sospecha de neuropatía diabética y otras neuropatías de extremidad inferior. Muestreo: Para un coeficiente kappa de 0,8 y precisión de 0,2 necesitamos 104 personas. Criterios de inclusión por Grupos: A: DM con registros del pie de riesgo sin neuropatía. B: DM con diagnóstico de neuropatía. C: Sin neuropatía ni DM conocidas. Selección: Simple, mediante listado de candidatos por centros participantes. Captación: Telefónica y programados en agenda única. Intervenciones: Entrevista clínica (Cuestionario sintomático Neuropathy Symptoms Score) (NSS) (0-9 puntos), Examen clínico: (Valoración sensitivomotora mediante escala NDS modificada (0-5 puntos por pie). Neuropatía si NDS > 6 puntos). Exploraciones: Tres por Enfermería, dos consecutivas y una espaciada 2 semanas. Variables Independientes: Puntuación de NDS y NSS. Dependientes: Factores de Riesgo Cardiovascular. Complicaciones DM. Análisis estadístico: Si la muestra es homogénea, mediante t de Student y ANOVA. Se calculará la fiabilidad y validez inter observador. Concordancia mediante Kappa, sin descartar métodos no paramétricos si la distribución lo aconseja. STATA. Resultados esperados: Disponer de un procedimiento exploratorio que mejore la actual valoración del pie de riesgo en AP. Aplicabilidad: Mejorar el diagnóstico de neuropatía diabética en AP. ABSTRACT Objectives: Compare the diagnostic validity between the Neuropathy Disability Score (NDS) scale without Monofilament (MF) and NDS modified with the MF and Lower Extremity Electromyogram (EMG). Concordance between neuropathy detected and recorded in the Computerized Clinical History (HCI) Methodology: Concordance study. Duration: 12 months. Setting: Two Primary Care (PC) centers of the Institut Català de Salut. Target population: People with EMG recorded in HCI for suspected diabetic neuropathy and other lower extremity neuropathies. Sampling: For a kappa coefficient of 0.8 and precision of 0.2 we need 104 people. Inclusion criteria by Groups: A: DM with risk foot records without neuropathy. B: DM with diagnosis of neuropathy. C: No known neuropathy or DM. Selection: Simple, through a list of candidates by participating centers. Capture: Telephone and scheduled in a single agenda. Interventions: Clinical interview (Neuropathy Symptoms Score) (NSS) symptomatic questionnaire (0-9 points), Clinical examination: (Sensorimotor assessment using modified NDS scale) (0-5 points per foot). Neuropathy if NDS > 6 points. Examinations: Three per Nursing, two consecutive and one spaced 2 weeks apart.Variables Independent: NDS and NSS score. Dependents: Cardiovascular Risk Factors. DM complications. Statistical analysis: If the sample is homogeneous, using Student's t-test and ANOVA. Inter-observer reliability and validity will be calculated. Agreement using Kappa, without ruling out non-parametric methods if the distribution recommends it. STATA. Expected results: To have an exploratory procedure that improves the current assessment of the risk foot in PC. Applicability: Improve the diagnosis of diabetic neuropathy in PC.

Abstract Background Urinary incontinence (UI) is a common geriatric syndrome with high health and socio-economic impacts in nursing home (NH) residents. Objectives To estimate the prevalence and types of UI and its associated factors in older people living in NHs in Central Catalonia (Spain). We also determined the proportion of residents who were receiving behavioural strategies to prevent/manage UI. Design and setting Cross-sectional study in 5 NHs conducted from January to March 2020. Methods We included consenting residents aged 65 + permanently living in the NHs. Residents who were hospitalized, in a coma or palliative care were excluded. UI was assessed using Section H of the Minimum Data Set. Sociodemographic and health-related variables were examined. Descriptive, bivariate, and multivariate (logistic regression) analyses were performed. Results We included 132 subjects (82.6% women), mean age of 85.2 (SD = 7.4) years. The prevalence of UI was 76.5% (95% CI: 68.60-82.93). The most common type was functional UI (45.5%), followed by urgency UI (11.4%). Only 46.2% of residents received at least one behavioural strategy to manage UI. Most sedentary behaviour (SB) variables presented a p-value lower than 0.001 in the bivariate analyses, but none remained in the final model. Moderate-severe cognitive impairment (OR = 4.44, p =.003), anticholinergic activity (OR = 3.50, p =.004) and risk of sarcopenia using SARC-F (OR = 2.75, p =.041) were associated with UI. Conclusions The prevalence of UI was high in this sample of NH residents compared to the literature, yet less than half received prompted voiding as a strategy to prevent/reduce UI.UI was associated with cognitive impairment, anticholinergic activity, and risk of sarcopenia.

Abstract Background Many patients with COVID-19 present the so-called post-acute sequelae of COVID-19 such as fatigue, post-stress discomfort, dyspnea, headache, pain mental impairment, incapacity to perform daily physical tasks ant exercise intolerance. This study aims to investigate the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. Methods The sample will be made up of 120 eligible participants, over the age of 60 years who have had COVID-19 disease and are survivors and present persistent COVID-19 symptomatology diagnosed by the corresponding physician. The participants will be randomly assigned to the experimental groups: supervised endurance group (SEG, n = 30), supervised strength group (SSG, n = 30), supervised concurrent group (SCG, n = 30), which will perform the corresponding exercise program 3 days a week compared to the control group (CG, n = 30), which will not carry out a supervised exercise program. The design of this project will include measurements of four relevant dimensions; 1) Cardiorespiratory fitness; 2) Muscle fitness; 3) Pain and mental health; and 4) Biomarkers of inflammation and oxidative stress. Conclusions The results of this study will provide insights into the effects of different exercise programs on physical and mental fitness, physical condition and biomarkers of the immune system and oxidative stress in older patients with post-COVID-19 sequelae. These findings may be the basis for the formulation of health plans and rehabilitation programs that allow healthy aging and a reduction in the associated morbidity in patients with post-COVID-19 sequelae. Trial registration NCT05848518. Registered on May 8, 2023.

Abstract Introduction Scarce evidence is available about the minimum number of valid days wearing the activPAL3 to obtain a precise estimate of sedentary behaviour (SB) and awake-time movement behaviours (ATMB) in nursing home (NH) residents. The study aimed to determine the minimum number of valid days required for accurately estimate SB and ATMB using the activPAL3 device in NH residents. It also investigated how the starting point of a day (the 24-h period) impacted reliability. Methods Participants wore an activPAL3 for 7 consecutive days. The data was classified in two-time blocks (00:00 Ante Meridiem (AM)—00:00 AM midnight vs 12:00 Post Meridiam (PM) -12:00 PM midday) and the sample was stratified into two groups according to their capacity to stand and walk, to examine if timing of sampling or physical functioning affected minimum wear time. SB, ATMB, sociodemographic, and health-related variables were collected. Sensitivity of the time-blocks were tested through the dispersion frequencies and differences between blocks through Kolmogorov–Smirnov test for normality; parametric variables through two-related means T-test and Wilcoxon test for non-parametric data. Reliability was assessed with the Cronbach's Alpha and the intra-class correlation coefficient (ICC), using a one-factor model estimating the reliability for each measurement day loading in the same latent factor. Results Ninety-five NH residents (81.1% women; age = 85.8 ± 7.2 years) were included. The midnight block had higher reliability, sensitivity and no statistically significant differences between days were found. At least three consecutive days of monitoring were necessary to achieve a reliability of ICC ≥ 0.8 for those NH residents able to stand and walk and six days for those unable. Conclusions NH residents who are able to stand and walk require a minimum of three consecutive days wearing the device, while those who are unable require at least six days due to their highly homogenous daily routines and sensitivity to PA events. Regardless of the activPAL3 recording start time, data processing should reference the midnight time block.

Abstract Oncology treatments require continuous individual adjustment based on the measurement of multiple clinical parameters. Prediction tools exploiting the patterns present in the clinical data could be used to assist decision making and ease the burden associated to the interpretation of all these parameters. The goal of this study was to predict the evolution of patients with pancreatic cancer at their next visit using information routinely recorded in health records, providing a decision‐support system for clinicians. We selected hematological variables as the visit's clinical outcomes, under the assumption that they can be predictive of the evolution of the patient. Multivariate models based on regression trees were generated to predict next‐visit values for each of the clinical outcomes selected, based on the longitudinal clinical data as well as on molecular data sets streaming from in silico simulations of individual patient status at each visit. The models predict, with a mean prediction score (balanced accuracy) of 0.79, the evolution trends of eosinophils, leukocytes, monocytes, and platelets. Time span between visits and neutropenia were among the most common factors contributing to the predicted evolution. The inclusion of molecular variables from the systems‐biology in silico simulations provided a molecular background for the observed variations in the selected outcome variables, mostly in relation to the regulation of hematopoiesis. In spite of its limitations, this study serves as a proof of concept for the application of next‐visit prediction tools in real‐world settings, even when available data sets are small.

Abstract Background Stenosis is one of the most common complications in patients with Crohn’s disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. Methods/design Exploratory study as “proof-of-concept”, multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. Discussion The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD. Trial registration ClinicalTrials.gov NCT 04330846. Registered on 1 April 1 2020. https://clinicaltrials.gov/ct2/home

BackgroundUrogenital schistosomiasis is one of the most prevalent parasitic diseases in sub-Saharan Africa. It is a poverty-related disease conditioned by behavioural practices.MethodsOur objective is to evaluate the awareness, mindset and habits about urogenital schistosomiasis in the community of Cubal (Angola), as well as its association with infection and urinary tract morbidity in pre-school age children. A cross-sectional study of knowledge, attitudes and practices at home was conducted between February and May 2022 with 250 participants.ResultsOverall, 93.6% of those surveyed had some prior knowledge about schistosomiasis and, among all the symptoms associated with this disease, blood in the urine was the best known (54.4%). Nevertheless, 57.6% obtained a medium knowledge score. Regarding attitude, the majority of respondents had a high attitude score (79.2%) with 96.0% willing to participate in mass drug administration campaigns. Laundry in the river was the most common risk practice (61.2%) and 55.2% out of the total were classified with a low practice score.ConclusionLow knowledge about symptoms and transmission by caregivers was the outstanding risk factor for infection in pre-school age children (OR = 16.93, 95%CI: 3.93-72.82), and lack of knowledge that avoiding entering the river prevents schistosomiasis was the main risk factor for morbidity in PSAC (OR = 8.14, 95%CI: 1.14-58.25).