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1.
Front Immunol ; 15: 1428773, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39161769

RESUMO

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease characterized by inflammation and hyperplasia of the synovial tissues. RA pathogenesis involves multiple cell types, genes, transcription factors (TFs) and networks. Yet, little is known about the TFs, and key drivers and networks regulating cell function and disease at the synovial tissue level, which is the site of disease. In the present study, we used available RNA-seq databases generated from synovial tissues and developed a novel approach to elucidate cell type-specific regulatory networks on synovial tissue genes in RA. We leverage established computational methodologies to infer sample-specific gene regulatory networks and applied statistical methods to compare network properties across phenotypic groups (RA versus osteoarthritis). We developed computational approaches to rank TFs based on their contribution to the observed phenotypic differences between RA and controls across different cell types. We identified 18 (fibroblast-like synoviocyte), 16 (T cells), 19 (B cells) and 11 (monocyte) key regulators in RA synovial tissues. Interestingly, fibroblast-like synoviocyte (FLS) and B cells were driven by multiple independent co-regulatory TF clusters that included MITF, HLX, BACH1 (FLS) and KLF13, FOSB, FOSL1 (B cells). However, monocytes were collectively governed by a single cluster of TF drivers, responsible for the main phenotypic differences between RA and controls, which included RFX5, IRF9, CREB5. Among several cell subset and pathway changes, we also detected reduced presence of Natural killer T (NKT) cells and eosinophils in RA synovial tissues. Overall, our novel approach identified new and previously unsuspected Key driver genes (KDG), TF and networks and should help better understanding individual cell regulation and co-regulatory networks in RA pathogenesis, as well as potentially generate new targets for treatment.


Assuntos
Artrite Reumatoide , Redes Reguladoras de Genes , Membrana Sinovial , Humanos , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Membrana Sinovial/metabolismo , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , Biologia Computacional/métodos , Sinoviócitos/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Regulação da Expressão Gênica , Linfócitos B/imunologia , Linfócitos B/metabolismo , Transcriptoma
2.
Life Sci Alliance ; 7(11)2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39191488

RESUMO

Pediatric acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis and high relapse rate. Current challenges in the identification of immunotherapy targets arise from patient-specific blast immunophenotypes and their change during disease progression. To overcome this, we present a new computational research tool to rapidly identify malignant cells. We generated single-cell flow cytometry profiles of 21 pediatric AML patients with matched samples at diagnosis, remission, and relapse. We coupled a classifier to an autoencoder for anomaly detection and classified malignant blasts with 90% accuracy. Moreover, our method assigns a developmental stage to blasts at the single-cell level, improving current classification approaches based on differentiation of the dominant phenotype. We observed major immunophenotype and developmental stage alterations between diagnosis and relapse. Patients with KMT2A rearrangement had more profound changes in their blast immunophenotypes at relapse compared to patients with other molecular features. Our method provides new insights into the immunophenotypic composition of AML blasts in an unbiased fashion and can help to define immunotherapy targets that might improve personalized AML treatment.


Assuntos
Imunofenotipagem , Leucemia Mieloide Aguda , Análise de Célula Única , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/genética , Criança , Análise de Célula Única/métodos , Feminino , Masculino , Pré-Escolar , Adolescente , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Citometria de Fluxo/métodos , Lactente , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Biologia Computacional/métodos , Prognóstico
3.
PLoS One ; 19(8): e0308800, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39159190

RESUMO

BACKGROUND: Occupational therapy (OT) is an effective evidence-based intervention that positively influences stroke patients'independence recovery, leading to new opportunities for better quality of life outcomes. OBJECTIVES: To explore the effectiveness of an early OT intervention program (EOTIPS) in the process of hospital to home discharge after stroke in Spain. MATERIAL AND METHODS: We conducted a prospective, randomized controlled clinical trial that included 60 adults who suffered a stroke and were discharged home. Participants assigned to the experimental group (n = 30) were included in EOTIPS and compared with a control group (n = 30). Evaluations assessed quality of life (Stroke and Aphasia Quality of Life Scale [SAQOL-39]), functional independence (Modified Rankin Scale [mRS], Barthel Index [BI] and Stroke Impact Scale-16 [SIS-16]), perceptual-cognitive skills (Montreal Cognitive Assessment [MoCA]), upper limb function (Fugl Meyer Assessment [FMA]), mobility (Berg Balance Scale [BBS] and Timed Up & Go [TUG]), communication skills (Communicative Activity Log [CAL]) and mood disorders (Beck Depression Inventory-II [BDI-II] and Hamilton Anxiety Scale [HAM-A]); they were completed within two weeks post-stroke and after three months follow-up. Statistical analysis included intent-to-treat analysis, considering all participants (dropouts as failures), and efficacy analysis, considering only end-of-treatment participants. RESULTS: Participants in the intervention group showed a significant better evolution in the main outcome measure of quality of life (SAQOL-39 p = .029), as well as for independence (mRSp = .004), perceptual-cognitive skills (MoCA p = .012)and symptoms of depression (BDI-II p = .011) compared to the control group. CONCLUSIONS: EOTIPS was effective in improving quality of life, as well as enhancing perceptual-cognitive skills, independence and reducing levels of depression for patients who suffered a stroke in a Spanish cohort and could be considered as an applicable non-pharmacologic therapeutic tool that can lead to patients' positive outcomes after stroke. This study was registered on ClinicalTrials.gov with the identifier NCT04835363.


Assuntos
Terapia Ocupacional , Qualidade de Vida , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Terapia Ocupacional/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Idoso , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/psicologia , Estudos Prospectivos , Espanha , Resultado do Tratamento
4.
Int J Geriatr Psychiatry ; 39(3): e6078, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38470426

RESUMO

OBJECTIVE: This study aimed to explore the interplay between frailty, physical function, physical activity, nutritional status, and their impact on the quality of life and depressive status in older adults with frailty. METHODS: A cross-sectional study involving 235 pre-frail/frail older adults residing in Spanish communities was conducted. Frailty was assessed using Fried's criteria, physical function was evaluated using the Short Physical Performance Battery, and physical activity levels were measured via wrist-worn accelerometers. Nutritional status was determined using the Mini-Nutritional Assessment alongside anthropometric measurements. Quality of life was gauged using the EuroQoL 5-Dimension 5-Level, while depressive status was assessed using the Yesavage 15-item Geriatric Depression Scale. Multivariate linear regression and logistic regression analyses were employed to elucidate the associations of these factors with quality of life and depression. RESULTS: Our findings revealed significant correlations between various factors and quality of life. Notably, reported fatigue (ß = -0.276, p = 0.002), performance in the 4-m gait test (ß = -0.242, p = 0.001), the score on the short version of the Mini-Nutritional Assessment (ß = 0.312, p = 0.002), and engagement in light physical activity (ß = 0.180, p = 0.023) were all found to be associated with quality of life. In terms of depressive symptoms, the Mini-Nutritional Assessment score emerged as a protective factor (Odds ratio, OR: 0.812, p < 0.001), as did participation in moderate physical activity (OR: 0.988, p = 0.028). Conversely, fatigue (OR: 3.277, p = 0.003) and a slow gait speed (OR: 1.136, p = 0.045) were identified as risk factors for depressive symptoms. CONCLUSIONS: This study underscores the detrimental association of fatigue and slow gait speed on both quality of life and depressive status among older adults with frailty. In contrast, engaging in physical activity and addressing malnutrition risk emerge as critical protective factors for enhancing quality of life and ameliorating depressive symptoms in this population. CLINICAL TRIAL REGISTRATION: This is a study that uses cross-sectional data from a trial registered at ClinicalTrials.gov (Identifier: NCT05610605).


Assuntos
Fragilidade , Estado Nutricional , Idoso , Humanos , Estudos Transversais , Depressão , Exercício Físico , Fadiga , Fenótipo , Qualidade de Vida , Ensaios Clínicos como Assunto
5.
bioRxiv ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38234732

RESUMO

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease characterized by inflammation and hyperplasia of the synovial tissues. RA pathogenesis involves multiple cell types, genes, transcription factors (TFs) and networks. Yet, little is known about the TFs, and key drivers and networks regulating cell function and disease at the synovial tissue level, which is the site of disease. In the present study, we used available RNA-seq databases generated from synovial tissues and developed a novel approach to elucidate cell type-specific regulatory networks on synovial tissue genes in RA. We leverage established computational methodologies to infer sample-specific gene regulatory networks and applied statistical methods to compare network properties across phenotypic groups (RA versus osteoarthritis). We developed computational approaches to rank TFs based on their contribution to the observed phenotypic differences between RA and controls across different cell types. We identified 18,16,19,11 key regulators of fibroblast-like synoviocyte (FLS), T cells, B cells, and monocyte signatures and networks, respectively, in RA synovial tissues. Interestingly, FLS and B cells were driven by multiple independent co-regulatory TF clusters that included MITF, HLX, BACH1 (FLS) and KLF13, FOSB, FOSL1 (synovial B cells). However, monocytes were collectively governed by a single cluster of TF drivers, responsible for the main phenotypic differences between RA and controls, which included RFX5, IRF9, CREB5. Among several cell subset and pathway changes, we also detected reduced presence of NKT cell and eosinophils in RA synovial tissues. Overall, our novel approach identified new and previously unsuspected KDG, TF and networks and should help better understanding individual cell regulation and co-regulatory networks in RA pathogenesis, as well as potentially generate new targets for treatment.

6.
Haemophilia ; 30(1): 51-58, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38111119

RESUMO

BACKGROUND: Haemophilia is a haematological disease, although most haemorrhages occur in the locomotor system. Patients are physically disabled from an early age and have a poorer perception of quality of life. In the day-to-day lives of patients and their families, psychosocial well-being, the disease's physical, personal, and social impact, as well as work-related problems are the most complicated aspects of the disease that need to be addressed. OBJECTIVE: To identify the role of occupational therapy in managing patients with haemophilia and to analyse the therapeutic potential of occupational therapy in treating these patients. METHODS: A scoping review was conducted to identify the role of occupational therapy in managing patients with haemophilia and to analyse the therapeutic potential of occupational therapy in treating these patients. The review was registered in the international registry PROSPERO (Id: CRD42022319637). The databases consulted were SCOPUS, PubMed, PsycINFO, Web of Science and Science Direct, including all studies published until 14 August 2023. RESULTS: No single study was found that specifically developed an occupational therapy intervention for patients with haemophilia. Measurement instruments have been identified, specific for patients with haemophilia and generic, that can be useful for the functional evaluation of these patients in the occupational therapy approach. Different studies showed the importance of multidisciplinary treatment, including occupational therapy. CONCLUSIONS: The use of occupational therapy could be effective in improving autonomy and quality of life in haemophilia patients. Therefore, it is of paramount importance to conduct research studies within the field of occupational therapy.


Assuntos
Hemofilia A , Terapia Ocupacional , Humanos , Hemofilia A/tratamento farmacológico , Qualidade de Vida
7.
Life Sci Alliance ; 7(2)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38052461

RESUMO

Gleason grading is an important prognostic indicator for prostate adenocarcinoma and is crucial for patient treatment decisions. However, intermediate-risk patients diagnosed in the Gleason grade group (GG) 2 and GG3 can harbour either aggressive or non-aggressive disease, resulting in under- or overtreatment of a significant number of patients. Here, we performed proteomic, differential expression, machine learning, and survival analyses for 1,348 matched tumour and benign sample runs from 278 patients. Three proteins (F5, TMEM126B, and EARS2) were identified as candidate biomarkers in patients with biochemical recurrence. Multivariate Cox regression yielded 18 proteins, from which a risk score was constructed to dichotomize prostate cancer patients into low- and high-risk groups. This 18-protein signature is prognostic for the risk of biochemical recurrence and completely independent of the intermediate GG. Our results suggest that markers generated by computational proteomic profiling have the potential for clinical applications including integration into prostate cancer management.


Assuntos
Neoplasias da Próstata , Proteômica , Masculino , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Fatores de Risco , Gradação de Tumores
8.
Microorganisms ; 11(12)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38138141

RESUMO

There is still a long way ahead regarding the COVID-19 pandemic, since emerging waves remain a daunting challenge to the healthcare system. For this reason, the development of new preventive tools and therapeutic strategies to deal with the disease have been necessary, among which serological assays have played a key role in the control of COVID-19 outbreaks and vaccine development. Here, we have developed and evaluated an immunoassay capable of simultaneously detecting multiple IgG antibodies against different SARS-CoV-2 antigens through the use of Bio-PlexTM technology. Additionally, we have analyzed the antibody response in COVID-19 patients with different clinical profiles in Cadiz, Spain. The multiplex immunoassay presented is a high-throughput and robust immune response monitoring tool capable of concurrently detecting anti-S1, anti-NC and anti-RBD IgG antibodies in serum with a very high sensitivity (94.34-97.96%) and specificity (91.84-100%). Therefore, the immunoassay proposed herein may be a useful monitoring tool for individual humoral immunity against SARS-CoV-2, as well as for epidemiological surveillance. In addition, we show the values of antibodies against multiple SARS-CoV-2 antigens and their correlation with the different clinical profiles of unvaccinated COVID-19 patients in Cadiz, Spain, during the first and second waves of the pandemic.

9.
Cureus ; 15(9): e45381, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37854761

RESUMO

Situs inversus is a rare congenital disorder where the reversal of some of the major thoracic or abdominal organs is present. In this disorder, alterations in the fetus's organ lateralization lead to a complete reversal in the arrangement of the internal organs. Most of the time, they are found incidentally when having a procedure or imaging modality. Little has been written regarding the challenges encountered while providing critical care to these patients. Here we present the case of a 68-year-old male patient admitted to the intensive care unit (ICU) with hypoxemic respiratory failure secondary to pneumonia who underwent diagnostic bronchoscopy for organism identification and was confirmed to have situs inversus totalis. Situs inversus totalis represents a challenge at different levels of care to these patients, including in the ICU. Limitations in critical care can be seen upon imaging identification, and during routine procedures performed at the ICU. Confusion might appear while performing bedside point of care ultrasound, obtaining vascular access, performing electrocardiogram, and sample identification, among others. The case brings the relevance of being able to recognize this rare disorder, which can be diagnosed even in advanced age since it might present the clinician with challenges at the time of providing care to patients.

10.
Curr Pain Headache Rep ; 27(11): 801-810, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37889466

RESUMO

PURPOSE OF REVIEW: The aim of this narrative review is to analyze the evidence about a peripheral or central origin of a tension headache attack in order to provide a further clarification for an appropriate approach. RECENT FINDINGS: Tension headache is a complex and multifactorial pathology, in which both peripheral and central factors could play an important role in the initiation of an attack. Although the exact origin of a tension headache attack has not been conclusively established, correlations have been identified between certain structural parameters of the craniomandibular region and craniocervical muscle activity. Future research should focus on improving our understanding of the pathology with the ultimate goal of improving diagnosis. The pathogenesis of tension-type headache involves both central and peripheral mechanisms, being the perpetuation over time of the headache attacks what would favor the evolution of an episodic tension-type headache to a chronic tension-type headache. The unresolved question is what factors would be involved in the initial activation in a tension headache attack. The evidence that favors a peripheral origin of the tension headache attacks, that is, the initial events occur outside the brain barrier, which suggests the action of vascular and musculoskeletal factors at the beginning of a tension headache attack, factors that would favor the sensitization of the peripheral nervous system as a result of sustained sensory input.


Assuntos
Cefaleia do Tipo Tensional , Humanos , Cefaleia do Tipo Tensional/diagnóstico , Cefaleia do Tipo Tensional/etiologia , Cefaleia/diagnóstico , Cefaleia/terapia , Cefaleia/complicações , Sistema Nervoso Periférico , Encéfalo , Cognição
11.
Children (Basel) ; 10(8)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37628290

RESUMO

(1) Background: The main activity children engage with is learning through play or formal education. The aim of this systematic review is to analyze the role of occupational therapy in the school setting for children with additional support needs or disabilities. (2) Method: We conducted a systematic review using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. This systematic review was registered in PROSPERO (CDR42022314271). The search was performed in the following databases: ERIC, Dialnet Plus, PubMed, OTseeker, Cochrane, Scopus, CINAHL, and PsycINFO. (3) Results: In total, 1954 studies were identified, from which 18 articles were selected. These studies were heterogeneous and showed different types of intervention of the occupational therapist in school environments. (4) Conclusions: The main conclusions highlighted the effectiveness of the occupational therapist within the school environment, the importance of an interdisciplinary team to cover the special needs students within the school and the need for intrinsic motivation for an active and inclusive participation of the students with special needs. However, there is a need for more homogeneous studies with a larger sample size that specifically focus on the school context and include the involvement of occupational therapists in order to replicate the findings obtained.

12.
Life Sci Alliance ; 6(11)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37640448

RESUMO

Germinal centers (GCs) play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. Although previous works study experimental systems of the immune response with mouse models that are immunized with specific antigens, our study focused on a real-life situation, with an ongoing GC response in a human lymph node (LN) involving multiple asynchronized GCs reacting simultaneously to unknown antigens. We combined laser capture microdissection of individual GCs from human LN with next-generation repertoire sequencing to characterize individual GCs as distinct evolutionary spaces. In line with well-characterized GC responses in mice, elicited by immunization with model antigens, we observe a heterogeneous clonal diversity across individual GCs from the same human LN. Still, we identify shared clones in several individual GCs, and phylogenetic tree analysis combined with paratope modeling suggest the re-engagement and rediversification of B-cell clones across GCs and expanded clones exhibiting shared antigen responses across distinct GCs, indicating convergent evolution of the GCs.


Assuntos
Doenças Autoimunes , Centro Germinativo , Humanos , Animais , Camundongos , Filogenia , Linfonodos , Linfócitos B
13.
J Clin Med ; 12(13)2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37445301

RESUMO

The therapeutic alliance is a fundamental component of rehabilitation in order to achieve effective outcomes. However, what develops, maintains or hinders this relationship has not been sufficiently explored. The aim of this systematic review is to recognize the role of the therapeutic alliance in the neurological rehabilitation process. A search for articles was carried out in the databases PubMed, Web of Science, SCOPUS, CINAHL, APA PsycInfo, OTseeker and Dialnet. They were selected according to the eligibility criteria. Internal quality assessment of the articles was measured with the Consolidated Criteria for Reporting Qualitative Research (COREQ). The systematic review was registered in PROSPERO (ID 346523). The search in the databases identified 1596 articles, from which 9 different studies were finally included in the systematic review, reflecting the limitations of studies in this field. All studies are qualitative, from the point of view of the patients themselves, their relatives and healthcare professionals. The total sample of the included studies is 182 participants (96 health professionals, 76 users and 10 relatives). Semi-structured interviews, focus group discussions and written reflections were mainly used to collect the data. In conclusion, the therapeutic alliance can be an active component in the post-stroke rehabilitation process. Being recognized as a person, collaboration with the therapeutic team, empathy, empowerment, confidence, professional skills, maintenance of hope and the role of the family have been identified as aspects that can have an influence on the therapeutic alliance.

14.
Healthcare (Basel) ; 11(11)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37297764

RESUMO

Biomechanical methods are frequently used to provide information about the kinematics and kinetics of posture and movement during musical performance. The aim of this review was to identify and analyze the biomechanical methods performed on woodwind musicians to understand their musculoskeletal demands. A systemic review was carried out following the guidelines of the document Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). It was registered in PROSPERO (code 430304).The databases PubMed, Cochrane, CINAHL, Scopus, and Web of Science were consulted between January 2000 and March 2022. The search in the databases identified 1625 articles, and 16 different studies were finally included in the review, with a sample size of 390 participants. Pressure sensors, surface electromyography, infrared thermography, goniometry in two dimensions, and ultrasound topometry in three dimensions were biomechanical methods useful to broaden the knowledge of musculoskeletal demands during musical practice. Piezoresistive pressure sensors were the most widely used method. The great heterogeneity of the studies limited the comparability of the results. The findings raised the need to increase both the quantity and the quality of studies in future research.

15.
Front Immunol ; 14: 1123968, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138881

RESUMO

The adaptive immune system has the extraordinary ability to produce a broad range of immunoglobulins that can bind a wide variety of antigens. During adaptive immune responses, activated B cells duplicate and undergo somatic hypermutation in their B-cell receptor (BCR) genes, resulting in clonal families of diversified B cells that can be related back to a common ancestor. Advances in high-throughput sequencing technologies have enabled the high-throughput characterization of B-cell repertoires, however, the accurate identification of clonally related BCR sequences remains a major challenge. In this study, we compare three different clone identification methods on both simulated and experimental data, and investigate their impact on the characterization of B-cell diversity. We observe that different methods lead to different clonal definitions, which affects the quantification of clonal diversity in repertoire data. Our analyses show that direct comparisons between clonal clusterings and clonal diversity of different repertoires should be avoided if different clone identification methods were used to define the clones. Despite this variability, the diversity indices inferred from the repertoires' clonal characterization across samples show similar patterns of variation regardless of the clonal identification method used. We find the Shannon entropy to be the most robust in terms of the variability of diversity rank across samples. Our analysis also suggests that the traditional germline gene alignment-based method for clonal identification remains the most accurate when the complete information about the sequence is known, but that alignment-free methods may be preferred for shorter sequencing read lengths. We make our implementation freely available as a Python library cdiversity.


Assuntos
Linfócitos B , Receptores de Antígenos de Linfócitos B , Células Clonais , Imunoglobulinas/genética , Biblioteca Gênica
16.
Bioinform Adv ; 3(1): vbad016, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37143924

RESUMO

Motivation: Being able to interpret and explain the predictions made by a machine learning model is of fundamental importance. Unfortunately, a trade-off between accuracy and interpretability is often observed. As a result, the interest in developing more transparent yet powerful models has grown considerably over the past few years. Interpretable models are especially needed in high-stake scenarios, such as computational biology and medical informatics, where erroneous or biased models' predictions can have deleterious consequences for a patient. Furthermore, understanding the inner workings of a model can help increase the trust in the model. Results: We introduce a novel structurally constrained neural network, MonoNet, which is more transparent, while still retaining the same learning capabilities of traditional neural models. MonoNet contains monotonically connected layers that ensure monotonic relationships between (high-level) features and outputs. We show how, by leveraging the monotonic constraint in conjunction with other post hoc strategies, we can interpret our model. To demonstrate our model's capabilities, we train MonoNet to classify cellular populations in a single-cell proteomic dataset. We also demonstrate MonoNet's performance in other benchmark datasets in different domains, including non-biological applications (in the Supplementary Material). Our experiments show how our model can achieve good performance, while providing at the same time useful biological insights about the most important biomarkers. We finally carry out an information-theoretical analysis to show how the monotonic constraint actively contributes to the learning process of the model. Availability and implementation: Code and sample data are available at https://github.com/phineasng/mononet. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

17.
NPJ Syst Biol Appl ; 9(1): 8, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927990

RESUMO

Sequencing of B-cell and T-cell immune receptor repertoires helps us to understand the adaptive immune response, although it only provides information about the clonotypes (lineages) and their frequencies and not about, for example, their affinity or antigen (Ag) specificity. To further characterize the identified clones, usually with special attention to the particularly abundant ones (dominant), additional time-consuming or expensive experiments are generally required. Here, we present an extension of a multiscale model of the germinal center (GC) that we previously developed to gain more insight in B-cell repertoires. We compare the extent that these simulated repertoires deviate from experimental repertoires established from single GCs, blood, or tissue. Our simulations show that there is a limited correlation between clonal abundance and affinity and that there is large affinity variability among same-ancestor (same-clone) subclones. Our simulations suggest that low-abundance clones and subclones, might also be of interest since they may have high affinity for the Ag. We show that the fraction of plasma cells (PCs) with high B-cell receptor (BcR) mRNA content in the GC does not significantly affect the number of dominant clones derived from single GCs by sequencing BcR mRNAs. Results from these simulations guide data interpretation and the design of follow-up experiments.


Assuntos
Linfócitos B , Centro Germinativo , Receptores de Antígenos de Linfócitos B/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-36901475

RESUMO

(1) Objective: The aim of this study is to synthesize the effects of physical therapy on pain, frequency, or duration management in the short, medium, and long term in adult patients diagnosed with Tension-type headache (TTH). (2) Background: Tension-type headache (TTH) is the most common headache with migraine and its pathophysiology and treatment has been discussed for years without reaching a consensus. (3) Methods: A systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered in PROSPERO (CRD42020175020). The systematic search for clinical trials was performed in the databases PubMed, CINAHL, Cochrane Central Register of Controlled Trials, PEDro, Scopus, SciELO and Dialnet. Articles were selected according to the inclusion and exclusion criteria, regarding the effectiveness of physical therapy interventions on adult patients with TTH published in the last 11 years with a score ≥ 6 in the PEDro Scale (Physiotherapy Evidence Database). (4) Results: In total, 120 articles were identified, of which 15 randomized controlled trials were finally included in order to determine the inclusion criteria. Changes in pain intensity, headache frequency or headache duration of individual studies were described (5) Conclusions: This systematic review shows that there is no standardized physical therapy protocol for the approach to tension headache, although all the techniques studied to date address in one way or another the cranio-cervical-mandibular region. The approach to the cranio-cervical-mandibular region reports significant effects in terms of decreasing the intensity of pain and frequency of headache episodes in the short and medium term. More long-term longitudinal studies are needed.


Assuntos
Cefaleia do Tipo Tensional , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Cefaleia , Modalidades de Fisioterapia , Dor
19.
Front Public Health ; 11: 1304719, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38249393

RESUMO

Introduction: The Mexican Report Card on Physical Activity for Children and Adolescents aims to assess the prevalence of movement behaviors and opportunities to perform them. Methods: Data on 11 indicators were obtained from national health surveys, census data, government documents, websites, and published studies. Data were compared against established benchmarks, and a grade between 0 and 10 was assigned to each indicator. Results: For Daily Behaviors, we found 34.5% of Mexican children and adolescents meet Physical Activity recommendations (Grade 3), 48.4% participate in Organized Sports (Grade 5), 35-75.8% engage in Active Play outdoors (Grade 4), 54.1% use Active Transportation (Grade 5), 43.6% spend <2 h in Sedentary Behavior per day (Grade 4), and 65-91% meet Sleep recommendations (Grade 7). Girls have lower physical activity levels and sports participation than boys of the same age. For Physical Fitness, we found 56.2-61.8% of children and adolescents have an adequate body mass index for their age (Grade 6). For Sources of Influence, we found 65-67% of parents engage in physical activity or sports in a week (Grade 7), 32.2-53.3% of basic education schools have a physical education teacher (Grade 6), and 37% of neighborhoods in Mexico have sidewalks with trees (Grade 4). Regarding Government, several policies and programs aimed at improving children physical activity were launched but their impact and allocated implementation budget are unknown (Grade 6). Discussion: Mexican children and adolescents engage in low levels of movement behaviors and have limited opportunities to perform such behaviors. The grades and recommendations provided here should be considered to improve such opportunities.


Assuntos
Exercício Físico , Esportes , Masculino , Criança , Feminino , Humanos , Adolescente , México , Aptidão Física , Índice de Massa Corporal
20.
Healthcare (Basel) ; 10(10)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36292558

RESUMO

(1) Background: The aim of this systematic review focused on analyzing the impact of depression on the functional outcome of the elderly stroke victim and how this disorder affects both the female and the male population. (2) Methods: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered in PROSPERO (ID 346284). The systematic search for clinical trials was performed in the databases Pubmed, Otseeker, Scopus, Web of Science, Psycinfo, Medline Complete, ScienceDirect, SciELO, and Dialnet. Articles were selected according to the inclusion and exclusion criteria, including those dealing with post-stroke depression in adults whose psychological status had changed. Studies that only assessed the psychological state of caregivers were excluded. (3) Results: In total, 609 articles were identified, of which 11 randomized controlled trials were finally included in the review. The results indicate that post-stroke depression influences the recovery of functionality and quality of life. In addition, the need to detect the mood of the adult population after the stroke and to provide individualized treatment according to the characteristics of the person is highlighted. (4) Conclusions: This systematic review shows how early detection of post-stroke depressive symptoms can improve the degree of disability and quality of life of the person, especially in women.

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